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JOURNAL OF PAEDIATRICS, OBSTETRICS & GYNAECOLOGY
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JOURNAL WATCH
ISSN 1016-0124
(INDONESIA)
GYNAECOLOGY
Endometriosis
OBSTETRICS
Hyperemesis,
Gastrointestinal &
Liver Disorders in
Pregnancy
PAEDIATRICS
The Limping Child:

An Approach
to Diagnosis &
Management
CME ARTICLE
Current Management of
2 SK
P
Antenatal Hydronephrosis
An Update
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MAY/JUN 2012
Vol. 38 No. 3
Journal Watch
89 Herpes simplex vaccine

Pertuzumab and trastuzumab in breast cancer
Harms from breast cancer screening
90 Overdiagnosis from screening mammography
Frequency of bone density testing in older women
Neoadjuvant chemotherapy plus bevacizumab for breast cancer
91 Hydatidiform mole, hCG concentrations, and chemotherapy
89 Effectiveness of trained traditional birth attendants
92 Home vs hospital birth in England
Extended nevirapine for breastfeeding infants of HIV-infected mothers
91
Editorial Board Professor Biran Affandi Dr Tak-Yeung Leung Dr Raman Subramaniam

University of Indonesia Chinese University of Hong Kong Fetal Medicine and Gynaecology Centre, Malaysia
Board Director, Paediatrics Dr Karen Kar-Loen Chan Professor Tzou-Yien Lin Professor Walfrido W Sumpaico
Professor Pik-To Cheung The University of Hong Kong Chang Gung University, Taiwan MCU-DFT Medical Foundation, Philippines
Associate Professor Associate Professor Oh Moh Chay Professor Somsak Lolekha Professor Cheng Lim Tan
Department of Paediatrics KK Womens and Childrens Hospital, Ramathibodi Hospital, Thailand KK Womens and Childrens Hospital, Singapore
and Adolescent Medicine Singapore Professor Lucy Chai-See Lum Associate Professor Kok Hian Tan
The University of Hong Kong
Associate Professor Anette Jacobsen University of Malaya, Malaysia KK Womens and Childrens Hospital, Singapore
Board Director, Obstetrics and Gynaecology KK Womens and Childrens Hospital, Singapore Professor SC Ng Dr Surasak Taneepanichskul
Professor Pak-Chung Ho Professor Rahman Jamal National University of Singapore Chulalongkorn University, Thailand
Head, Department of Universiti Kebangsaan Malaysia Professor Hextan Yuen-Sheung Ngan Professor Eng-Hseon Tay
Obstetrics and Gynaecology The University of Hong Kong Thomson Womens Cancer Centre, Singapore
The University of Hong Kong Dato Dr Ravindran Jegasothy
Hospital Kuala Lumpur, Malaysia Professor Carmencita D Padilla Professor PC Wong
University of the Philippines Manila National University of Singapore
Associate Professor Kenneth Kwek
KK Womens and Childrens Hospital, Singapore Professor Seng-Hock Quak Dr George SH Yeo
National University of Singapore KK Womens and Childrens Hospital, Singapore
Dr Siu-Keung Lam
Dr Tatang Kustiman Samsi Professor Hui-Kim Yap
Kwong Wah Hospital, Hong Kong
University of Tarumanagara, Indonesia National University of Singapore
Professor Terence Lao Professor Perla D Santos Ocampo Professor Tsu-Fuh Yeh
Chinese University of Hong Kong University of the Philippines China Medical University, Taiwan
Dr Kwok-Yin Leung Associate Professor Alex Sia
The University of Hong Kong KK Womens and Childrens Hospital, Singapore
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MAY/JUN 2012
Vol. 38 No. 3
Review Articles
Gynaecology
93 Endometriosis
Endometriosis is a very complex gynaecological condition characterized by the presence of ectopic
endometrial tissue outside the uterine cavity and is frequently associated with debilitating pelvic pain
and infertility. The management of endometriosis can be challenging and should be tailored to each
individuals circumstances.
Francesca Raffi, Saad Amer
93 Review Articles
Obstetrics
105 Hyperemesis, Gastrointestinal and Liver Disorders in Pregnancy

This review aims to discuss some of the common and serious conditions of the gastro-intestinal,
hepatic and biliary tracts in pregnancy.
Clare Cuckson, Sarah Germain
105
Publisher
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Indonesia
MAY/JUN 2012
Vol. 38 No. 3
Review Articles
Paediatrics
117 The Limping Child: An Approach to Diagnosis and Management

Investigating a child with a limp requires careful consideration because the differential diagnoses
are broad. The condition is rarely an emergency, but it can be serious and debilitating.
Angela Cox, Roger Allen
P
Continuing Medical Education 2 SK
117 125 Current Management of Antenatal HydronephrosisAn Update

Antenatal hydronephrosis (ANH) is the most commonly diagnosed congenital urinary tract anomaly,
which is detected by prenatal screening in 15% of all pregnancies. In the early years of routine fetal
ultrasound screening, almost all cases of ANH were subjected to invasive imaging studies postnatally,
followed by a pre-emptive surgical approach. The management of ANH has trended towards a more
conservative approach over the past two decades.
Yap Te-Lu, Anette Sundfor Jacobsen
125
The Journal of Paediatrics, Obstetrics and Gynaecology contains articles under licence from UBM Media LLC. The articles
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Review Articles Case Studies

Comprehensive reviews Interesting cases seen in general
Hyperemesis,
providing the latest clinical practice and their management. Gastrointestinal &
information on all aspects Liver Disorders in Pregnancy
of the management of medical Pictorial Medicine 2012 UBM Medica
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For more information, please refer to the Instructions for Authors on our website www.jpog.com, or contact:
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JPOG MAY/JUN 2012 iii

Peer Reviewed Journal Watch
HSV-1 genital disease. Against HSV-1, infection Harms from breast cancer
GYNAECOLOGY with or without disease, efficacy was 35%. There screening
was no efficacy (-8%) against HSV-2 infection.
Herpes simplex vaccine The HSV-2 vaccine was effective against
HSV-1 genital disease but not against HSV-2 infec-
tion; the reasons are unexplained. An HSV vaccine
suitable for general use is not yet available.
Belshe RB et al. Efficacy results of a trial of a herpes simplex vaccine.

NEJM 2012; 366: 3443.
Pertuzumab and trastuzumab in

breast cancer
About 20% of breast cancers are human epidermal

growth factor receptor 2 (HER2) positive. Treat-
ment with the humanized monoclonal anti-HER2
antibody, trastuzumab, improves outcomes. A new
anti-HER2 antibody, pertuzumab, binds to a differ- The Forrest Report of the 1980s led to the introduc-
ent part of HER2 and could add to the effectiveness tion of UKs breast screening programme. Later, a
Herpes simplex viruses 1 (HSV-1) and 2 (HSV-2) of trastuzumab. Now, a phase III trial has demon- Cochrane review showed that for every 2,000 wom-
both cause genital infections, and HSV-1 infec- strated this increased effectiveness. At 204 centres en invited for screening over a 10-year period, only
tions are increasingly prevalent. Transmission in 25 countries, a total of 808 women with meta- one would have her life prolonged and ten false-
from mother to newborn infant may cause severe static HER2-positive breast cancer were random- positive women would be treated unnecessarily.
disease. Trials of an HSV-2 glycoprotein D-based ized to treatment with trastuzumab and docetaxel More than 200 women would suffer significant
subunit vaccine have shown around 75% efficacy with or without pertuzumab. Progression-free sur- psychological distress because of false-positive
against HSV-2 disease among women seronegative vival was 18.5 months (pertuzumab) vs 12.4 months results. Now, a new analysis has updated the For-
for both HSV-1 and HSV-2 antibodies. Now, a trial (controls), a significant 38% advantage with pertu- rest Report by presenting data in terms of quality-
in the USA and Canada has surprisingly shown ef- zumab. At an interim analysis of overall survival, adjusted life-years (QALYs).
ficacy against HSV-1 genital disease but not HSV-2 there had been 69 deaths in the pertuzumab group Using data from trial meta-analyses and
disease. and 96 in the control group, an insufficient differ- 1985 English data for breast cancer mortality and
The trial included 8,323 women aged 1830 ence to stop the trial at that point. Toxicity was surgery, two cohorts of 100,000 women aged 50
years who were doubly seronegative (HSV-1 and similar in the two groups. were followed by computer modelling. One cohort
HSV-2). Randomization was to the HSV-2 glycopro- The addition of pertuzumab to trastuzumab was invited for mammographic screening and the
tein D vaccine with alum and 3-0-deacylated mo- and docetaxel improved progression-free survival. other was not. Mortality was reduced, and surgery
nophosphoryl lipid A as an adjuvant or hepatitis A increased in the screening group according to avail-
Baselga J et al. Pertuzumab plus trastuzumab and docetaxel for metastatic
vaccine, at months 0, 1, and 6. The HSV-2 vaccine breast cancer. NEJM 2012; 366: 109119; Gradishar WJ. HER2 therapy able data. The cumulative net QALYs gained from
an abundance of riches. Ibid: 176178 (editorial).
induced ELISA and neutralizing antibodies to HSV- screening were explored in five scenarios. Adding
2. The vaccine efficacy was only 20% against any harms in one of these scenarios halved the gains
genital herpes simplex infection but 58% against in QALYs. Subsequent scenarios showed negative
JPOG MAY/JUN 2012 89
JPOG_MayJun12_COMBINE_FINAL.indd 89 6/11/12 5:36 PM

QALYs during the first 7 years after screening. estimation of rates of overdiagnosis among women These investigators conclude that osteopo-
Among women aged 6070, a greater reduction in aged 5069 in Isre, France, between 1991 and rosis would develop in < 10% of older postmeno-
mortality led to a higher gain in QALYs only in the 2006. Overdiagnosis accounted for 1.5% of cases pausal women with rescreening intervals of about
longer term. Varying the data in the model altered of invasive cancer and 28% of cases of carcinoma 15 years for those with an initially normal BMD or
the QALY results, but a pattern of low or negative in situ diagnosed either clinically or at screening mild osteopenia, 5 years for those with moderate
net QALYs in the early years after starting screen- mammography. With analysis restricted to screen- osteopenia, and 1 year for those with advanced
ing remained. ing mammography cases, the estimated overdiag- osteopenia.
According to this computer model, screen- nosis rates were 3.3% and 31.9%, respectively.
Gowlay ML et al. Bone-density testing interval and transition to
ing has a negative effect on quality of life in the The estimated overdiagnosis rates in this osteoporosis in older women. NEJM 2012; 366: 225233.
early years, followed by a net gain in QALYs but at study were smaller than expected.
a slower rate than had been expected.
Seigneurin A et al. Overdiagnosis from non-progressive cancer detected
by screening mammography: stochastic simulation study with calibration
Raftery J, Chorozoglou M. Possible net harms of breast cancer screening: to population based registry data. BMJ 2012; 344 (Jan 14): 15 (d7017);
updated modelling of Forrest Report. BMJ 2012; 344 (Jan 14): 14 (343: d Hackshaw A. Benefits and harms of mammography screening. Ibid: 7 Neoadjuvant chemotherapy plus
7627); Hackshaw A. Benefits and harms of mammography screening. Ibid: (d8279).
344:7 (d8279) (editorial). bevacizumab for breast cancer
In three studies, bevacizumab, a monoclonal an-

Frequency of bone density testing tibody against vascular endothelial growth factor
Overdiagnosis from screening in older women A, has been shown to improve outcomes when
mammography added to chemotherapy for the treatment of human
US guidelines recommend bone density screening epidermal growth factor receptor (HER)2-negative
for women aged 65 years or older, but the optimum metastatic breast cancer. Now, two successive
frequency of screening is uncertain. A US longitudi- reports in the New England Journal of Medicine
nal cohort study has provided more guidance. have shown that adding bevacizumab to neoadju-
The study included 4.957 women (99% vant chemotherapy significantly increased the rate
white) aged 67 or older at four sites in the USA. of complete pathological response in early HER2-
They had bone mineral density (BMD) assessment negative breast cancer.
with dual-energy X-ray absorptiometry scanning at A total of 1,948 patients with early HER2-
baseline and at follow-up over a period of 15 years. negative breast cancer were randomized to treat-
None had a history of hip or clinical vertebral frac- ment with neoadjuvant chemotherapy (epirubicin
ture or treatment for osteoporosis, and none had and cyclophosphamide followed by docetaxel) with
osteoporosis on the baseline BMD screening. The or without bevacizumab. Complete pathological
estimated BMD testing interval (time to the devel- response (absence of invasive and intraductal dis-
opment of osteoporosis before hip or clinical verte- ease in the breast and the axillary lymph nodes)
bral fracture in 10% of women) was 16.8 years with occurred in 18.4% with bevacizumab and 14.9%
a normal baseline BMD, 17.3 years with mild osteo- without bevacizumab, a significant 29% improve-
Although screening mammography results in re- penia, 4.7 years with moderate osteopenia, and 1.1 ment with bevacizumab. Breast-conserving surgery
duced mortality from breast cancer among women years with advanced osteopenia (normal = T score was possible in 66.6% of patients in each of the
aged 5070, there are disadvantages, including at femoral neck and total hip of -1.00 or higher; two groups. Grade 3 or 4 toxic effects (febrile neu-
anxiety from false-positive results, low-dose ra- mild osteopenia = t score -1.01 to -1.49; moderate tropenia, mucositis, the handfoot syndrome, in-
diation, and overdiagnosis. Workers in France have osteopenia = T score -1.50 to -1.99; advanced os- fection, or hypertension) were more frequent with
reported a stochastic simulation model study with teopenia = T score -2.00 to -2.49). bevacizumab. The addition of bevacizumab signifi-

Peer Reviewed Journal Watch
cantly increased the rate of complete pathological this suggestion.

response, most significantly in patients with triple- The study included 13,960 women with a
negative tumours. diagnosis of hydatidiform mole between January
In North America, a total of 1,206 patients 1993 and May 2008. Among these women, 76 (<
with early HER2-negative breast cancer were ran- 1%) had persistently high (> 5 IU/L) hCG levels at
domized to neoadjuvant therapy with docetaxel 6 months. Sixty-six of these patients continued un-
alone or with either gemcitabine or capecitabine der surveillance, and hCG levels returned to normal
for four cycles followed by doxorubicincyclo- without chemotherapy in 65 (98%). The one patient
phosphamide for four cycles. At the same time, whose hCG levels remained high had chronic renal
they were also randomized to bevacizumab or failure as a cause of the high levels and remained
no bevacizumab. The addition of either gem- otherwise well. Ten patients received chemother-
citabine or capecitabine to docetaxel did not sig- apy, and hCG levels returned to normal in eight of
nificantly improve rates of complete pathological them (80%). The remaining two patients had per-
response, and both gemcitabine and capecitabine sistent, slightly high (611 IU/L) levels, but there
were associated with increased toxicity. Adding were no associated clinical problems off treatment.
bevacizumab increased the rate of complete There were no deaths, and outcomes were similar
pathological response from 28.2% to 34.5%, a with or without chemotherapy.
significant effect. Bevacizumab was associated These researchers conclude that a policy
with increased rates of hypertension, left ventricu- of continued surveillance without chemotherapy
lar systolic dysfunction, the handfoot syndrome, seems acceptable for patients with raised (not
and mucositis. younger (< 16 years) and older (> 45 years) women. very high) but falling hCG levels at 6 months after
Adding bevacizumab to neoadjuvant chemo- Molar pregnancies present with vaginal bleeding evacuation of a hydatidiform mole.
therapy increased the rate of complete pathologi- in the first trimester, and levels of human chorionic
Agarwal R et al. Chemotherapy and human chorionic gonadotropin
cal response in both these studies. gonadotropin (hCG) in serum and urine are raised. concentrations 6 months after uterine evacuation of molar pregnancy: a
retrospective cohort study. Lancet 2012; 379: 130135; Cheung ANY, Chan
Following dilatation and curettage, hCG levels re- KKL. Perplexing hCG profile after evacuation of hydatidiform mole. Ibid:
Von Minckwitz G et al. Neoadjuvant chemotherapy and bevacizumab for 98100 (comment).
HER2-negative breast cancer. NEJM 2012; 366: 299309; Bear HD et turn to normal in about 92% of cases. Malignant
al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer.
Ibid: 310320; Montero AJ, Vogel C. Fighting fire with fire: rekindling the transformation occurs in about 15% of cases af-
bevacizumab debate. Ibid: 374375 (editorial).
ter complete hydatidiform mole and 0.51% after
partial hydatidiform mole. Chemotherapy, usually Effectiveness of trained
with methotrexate or dactinomycin, is then neces- traditional birth attendants
sary. All women with a hydatidiform mole in the UK
OBSTETRICS are referred for hCG monitoring and surveillance to Traditional birth attendants are in charge at many
one of three national centres in Dundee, Sheffield, births in developing countries, and giving them
and London. Post-mole gestational trophoblastic extra training and resources can improve obstet-
Hydatidiform mole, hCG neoplasia is suspected when hCG levels plateau ric and neonatal outcomes. A meta-analysis of six
concentrations, and or increase or remain raised at 6 months although randomized controlled trials and seven non-ran-
chemotherapy they are falling. Evidence suggests, however, that domized studies has confirmed that training these
an increased but falling hCG level at 6 months after workers results in improved results.
In the UK, hydatidiform moles constitute between 1 uterine evacuation may not necessarily necessitate A total of 138,549 patients were included in
and 3 of every 1,000 pregnancies, but they are more chemotherapy. A retrospective study at a single the randomized trials that assessed the effects of
common in east Asia. They are more common in hospital in London, England. has added support to training and support for traditional birth attendants.

Meta-analysis showed significant reductions of come events was greater for planned home deliver-
24% in perinatal mortality and 21% in neonatal ies (9.3 per 1,000) than for deliveries planned on an
mortality after such training and support. The non- obstetric unit (5.3 per 1,000) or on a midwifery unit
randomized trials included 72,225 patients. Meta- (4.5 per 1,000). Transfers from home or midwifery
analysis showed significant reductions of 30% in unit to an obstetric unit were necessary, more often
perinatal mortality and 39% in neonatal mortality. for nulliparous women. Operative and instrumen-
Meta-analysis of six studies of maternal mortal- tal deliveries were more frequent for deliveries
ity showed a non-significant reduction of 20% planned to be in an obstetric unit.
after training and support of traditional birth at- For low-risk pregnancies in multiparous
tendants. women, home birth or birth in an obstetric unit is
Training and support of traditional birth at- generally safe and there is a lower risk of obstetric
tendants in developing countries improves out- intervention. Among nulliparous women, there is a
comes according to the type and extent of training higher risk of poor outcomes with home birth.
and support provided. Perinatal, neonatal, and ma-
Birthplace in England Collaborative Group. Perinatal and maternal
ternal mortalities may all be improved. outcomes by planned place of birth for healthy women with low risk
pregnancies: the Birthplace in England national prospective cohort study.
BMJ 2012; 344 (Jan 21): 17 (2011; 343: d7400).
Wilson A et al. Effectiveness of strategies incorporating training and
support of traditional birth attendants on perinatal and maternal mortality:
meta-analysis. BMJ 2012; 344 (Jan 21): 16 (2011; 343: d7102); Hodnett
E. Traditional birth attendants are an effective resource. Ibid: 9 (e365)
(editorial).
ceived oral nevirapine suspension for the first 6

Home vs hospital birth in England PAEDIATRICS weeks. Those who were HIV-negative at 6 weeks
were then randomized to continued nevirapine, or
A national prospective cohort study in England has placebo, until the age of 6 months or until stop-
confirmed the safety of planned home birth for low- Extended nevirapine for ping breastfeeding. Between the ages of 6 weeks
risk women. breastfeeding infants of HIV- and 6 months, HIV-1 infection was acquired by
The study included 64,538 women with infected mothers 1.1% in the extended nevirapine group and 2.4%
low-risk pregnancies with delivery between April in the placebo group, a significant 54% improve-
2008 and April 2010. The primary outcome was Although breastfeeding is essential in sub-Saharan ment with extended nevirapine. At 6 months of age,
a composite of perinatal death, and intrapartum Africa for the infants nutrition and protection from mortality, combined mortality and HIV-1 infection,
morbidity (stillbirth during labour, early neonatal infection, prolonged breastfeeding may lead to and severe adverse event rates were similar in the
death, neonatal encephalopathy, meconium aspira- mother-to-child transmission of human immuno- two groups.
tion syndrome, brachial plexus injury, or fractures deficiency virus (HIV) 1. Antiretroviral therapy is Extended nevirapine prophylaxis given to
of humerus or clavicle). Overall, the incidence of given to protect against antenatal and intrapartum the breastfeeding infant is effective for at least 6
the primary outcome was similar for births planned HIV transmission, but prolonged prophylaxis dur- months. It should be used along with other provi-
at home (4.2 primary outcome events per 1,000 ing breastfeeding has been difficult to achieve in sions such as routine HIV screening in pregnancy,
births), in an obstetric unit (4.4 per 1,000), and in a many countries. Now, successful prophylaxis dur- and antiretroviral interventions during pregnancy,
midwifery unit (3.5 per 1,000). On subgroup analy- ing breastfeeding has been reported from South labour, and delivery.
sis, planned place of birth had no significant effect Africa, Tanzania, Uganda, and Zimbabwe.
Coovadia HM et al. Efficacy and safety of an extended nevirapine regimen
on outcomes among multiparous women. Among The study included 1,527 breastfeeding in infant children of breastfeeding mothers with HIV-1 infection for
prevention of postnatal HIV-1 transmission (HPTN 046): a randomised,
nulliparous women, the incidence of primary out- infants of HIV-1-positive mothers. The infants re- double-blind, placebo-controlled trial. Lancet 2012; 379: 221228.

GYNAECOLOGY I Peer Reviewed
Endometriosis
Francesca Raffi, MBChB, MRCOG; Saad Amer, MBChB, MSc, MRCOG, MD
INTRODUCTION
Endometriosis is a common gynaecological condition affecting about 610% of women

of reproductive age and can be a debilitating disease. It is the second most common
reason for surgery in premenopausal patients.
It is defined as the presence of endometrial-like tissue outside the uterine cavity,
leading to a chronic inflammatory reaction. The exact aetiology is unknown, but the
retrograde menstruation model is the most widely accepted theory explaining the devel-
opment of pelvic endometriosis. According to this model, menstrual blood containing en-
dometrial fragments passes through the fallopian tubes into the pelvic cavity, resulting
in the formation of peritoneal endometrial deposits. There are three distinctive patho-
logical types of pelvic endometriosis: superficial peritoneal implants, ovarian endome-
triomas, and deep infiltrating nodular lesions. The extent of the disease is very variable
and often does not correlate with the severity of symptoms. Although it can sometimes
be asymptomatic (in about 20% of cases), endometriosis is frequently associated with
severe pain and infertility. Several management options exist for endometriosis and the
choice depends on several factors such as age, fertility, severity of the symptoms, and
extent of the disease.
This review presents three different cases of endometriosis with different com-
plexities and presentations. The diagnosis and various medical and surgical treatment
options available to the clinician will be discussed.
Pathological Types of Endometriosis

Superficial peritoneal endometriosis: peritoneal implants consist of glandular and
stromal tissue and respond to the hormonal changes associated with the menstrual

GYNAECOLO GY
cycle showing cyclical changes similar but not iden- CASE 1

tical to the normal endometrium. These implants
heal by fibrosis. A 17-year-old patient presented to her general
Deep infiltrating (adenomatous) endome- practitioner with a 6-month history of severe and
triosis: this type of endometriosis is characterized excruciating dysmenorrhoea. Pelvic examination re-
by proliferative fibromuscular tissue with sparse vealed no abnormality, and a diagnosis of primary
endometrial glandular and stromal tissue (similar to physiological dysmenorrhoea was made. The gen-
adenomyosis), with no surface epithelium. Unlike eral practitioner prescribed painkillers in the form
the peritoneal endometriosis, deep endometriosis of non-steroidal anti-inflammatory drugs, which
does not show significant changes during the men- provided some benefit. However, the dysmenor-
strual cycle. These nodules are typically present in rhoea continued to disrupt the patients life, and
the recto-vaginal space and can involve the utero- she was eventually referred to the gynaecologist.
sacral ligament, the posterior vaginal wall, and the Pelvic examination by the gynaecologist revealed
anterior rectal wall. They can also extend laterally tenderness over the utero-sacral ligaments and on
and affect the ureters. cervical movement. A transvaginal ultrasound scan
Ovarian endometriomas: an endometrioma revealed no pelvic abnormality. The gynaecologist
is an ovarian cyst lined by endometriotic tissue and made a provisional diagnosis of endometriosis and
containing dark brown or chocolate-coloured fluid, prescribed combined oral contraceptive pill (COCP).
which results from recurrent chronic bleeding from Three months later, the patient reported a signifi-
the endometriotic implants. In long-standing en- cant improvement of her pain, but continued to ex-
dometriomas, the endometriotic tissue is gradually perience some degree of dysmenorrhoea. She was
replaced by fibrotic tissue. therefore advised to tricycle the pill.
PRESENTATION
What Are the Main Presenting Symptoms

for Endometriosis?
The main presenting symptoms of endometriosis
Dysmenorrhoea is the include chronic pelvic pain and infertility. Patterns
most common presenting of chronic pelvic pain caused by endometriosis in-
clude dysmenorrhoea, non-cyclical pelvic pain, and
symptom, affecting up
dyspareunia. The pain may also be associated with
to 80% of women other cyclical symptoms, particularly related to the
with endometriosis involvement of the urinary or gastrointestinal (GI)
tract with endometriosis. The severity of these
symptoms does not necessarily correlate with the
extent of the disease when diagnosed at laparos-
copy, as mild disease can cause severe symptoms.
On the other hand, about 20% of women with ad-
vanced endometriosis have no symptoms.

GYNAECOLOGY I GYNAECOLOGY
Peer Reviewed
Dysmenorrhoea: this is the most common Endometriosis is defined as the presence of endometrial-
like tissue outside the uterine cavity, leading to a chronic
presenting symptom, affecting up to 80% of women inflammatory reaction.
with endometriosis. It is often described as severe
and debilitating and does not respond to simple an-
algesia. The pain classically starts 12 weeks be-
fore the onset of menstruation and gradually wors-
ens, reaching a peak in severity during the first 2
days of the menstrual flow. The pain then gradually
lessens until it disappears at the end of the period.
Non-cyclical pelvic pain: this affects up to
a third of patients with endometriosis. It is often
associated with adhesions, large ovarian endome-
triomas, peritoneal inflammation, and bladder or
bowel endometriosis. Pain resulting from pelvic ad-
hesions is usually provoked or worsened by certain
body movements. Other pains may be triggered by
ovulation, bowel movements (dyschezia), or urina-
tion. All types of non-cyclical pains often worsen
around the time of menstruation.
Deep dyspareunia: this affects about a third
of patients with endometriosis and is mainly seen
in advanced disease with deep infiltrating nodules.
It may be severe enough to force the patient to tendance in adolescents is suggestive of endome-
abstain from intercourse. The pain is usually de- triosis. The presence of the classical patterns of
scribed as a stabbing pain on deep penetration. It pain described above has a sensitivity of 76% and
is triggered by pressure on the scarred utero-sacral a specificity of 58% in detecting endometriosis.
ligaments, recto-vaginal nodules or adhesions ob- Around 30% of adolescents with chronic pelvic pain
literating the pouch of Douglas, or involving the have endometriosis. Adolescents with pelvic pain
ovaries. The symptoms are typically worse before not responding to analgesia and/or the COCP have
menstruation. about a 70% prevalence of endometriosis.
Analysing the pattern of pelvic pain is crucial
DIAGNOSIS in establishing the diagnosis of endometriosis in
adolescents. A pain diary documenting the frequen-
How Would You Diagnose Endometriosis in cy and character of the pain will help to determine
Adolescents? whether the pain is cyclical and if it is related to
Symptoms: adolescents with endometriosis of- bowel or bladder function. A family history of en-
ten present with acyclic and/or cyclic pelvic pain. dometriosis is correlated with a higher likelihood of
Bowel and bladder symptoms are also common in endometriosis in these patients.
this group of patients. Chronic pelvic pain severe Although, endometriosis is the commonest
enough to disrupt normal activities and school at- cause of chronic pelvic pain in adolescents, other

GYNAECOLO GY
Box 1. Presenting symptoms scan is useful in detecting endometriomas; howev-

er, endometriomas are rarely seen in adolescents.
Severe dysmenorrhoea Magnetic resonance imaging is of value in identify-
Chronic pelvic pain ing the presence and the extent of deeply infiltrat-
Deep dyspareunia
Cyclical or peri-menstrual symptoms of the bowel or bladder ing lesions. It may also help in detecting bowel and
with possible abnormal bleeding or pain (eg, dyschezia) ureteric involvement.
Infertility Laparoscopy: this is the gold-standard for
the diagnosis of endometriosis. However, in ado-
causes such as sexual abuse, ovarian tumour or lescents, this procedure should only be considered
genital tract anomalies, eg, imperforate hymen in patients with disabling pain not responding to
should be considered. analgesia and/or the COCP. Ideally, a laparoscopic
Examination: pelvic examination, which may surgeon competent in managing endometriosis sur-
not be possible in adolescents, does not usually re- gically should perform the procedure. The surgeon
veal specific signs in most patients with endometri- should also be comfortable operating on adoles-
osis. However, this examination is important mainly cents and be familiar with all the various morpholo-
to rule out other causes of chronic pelvic pain such gies of endometriosis. Clear, red, white, and/or
as ovarian tumour or genital tract anomalies. In yellow-brown lesions are more frequently found in
adolescents who are not sexually active, bimanual adolescents than black or blue lesions. The proce-
rectalabdominal examination may be considered dure carries a 3% risk of minor complications and
as it is better tolerated than a bimanual vaginal a 0.61.8/1,000 risk of major complications such as
abdominal examination. A number of signs can be bowel perforation and vascular damage (Box 1).
detected in some patients with endometriosis, in-
cluding thickening, nodularity and tenderness over MEDICAL TREATMENT OF
the uterosacral ligaments, fixation and retroversion ENDOMETRIOSIS IN ADOLESCENTS
of the uterus, and fullness or a mass in the pouch
of Douglas. What Are the Available Medical Treatment
Differential diagnosis: this includes all gy- Options That You Would Like to Discuss
naecological and non-gynaecological conditions With This Young Patient?
that cause chronic pelvic pain. Gynaecological Non-hormonal medical therapy (analgesia):
disorders include primary dysmenorrhoea, sexual empirical treatment with analgesics for chronic
abuse, ovarian cysts/tumours, and genital tract pelvic pain with a pattern suggestive of endome-
anomalies. In sexually active adolescents, pelvic triosis (without a definitive diagnosis) should be
adhesions should also be considered (due to a considered as a first-line treatment option in ado-
previous pelvic inflammatory infection) in the dif- lescents. Non-steroidal anti-inflammatory drugs
ferential diagnosis. Non-gynaecological diseases to (eg, mefenamic acid or diclofenac) can be effective.
be considered in the differential diagnosis include The administration of these medications should be
irritable bowel syndrome, inflammatory bowel dis- limited to episodes of pains lasting for a few days,
ease, interstitial cystitis, and musculoskeletal pain. eg, dysmenorrhoea.
Imaging: this is of limited value in the diag- Hormonal therapy:
nosis of endometriosis. A transvaginal ultrasound 1. The COCP is a good choice for adolescents with

Peer Reviewed
possible endometriosis and can be used as an alter- Box 2. Factors to consider when planning endometriosis
treatment
nate first-line therapy. It improves dysmenorrhoea
and offers a reliable method of contraception. COCP
Age
is generally well tolerated, safe, and inexpensive.
Need to preserve fertility
Another advantage of the pill is that it can be used Need for contraception
as long-term therapy. Tricycling the pill reduces the Presenting symptoms (pain, infertility)
number of bleeds and the associated pain. Possi- Severity of pain and impact on quality of life
Type, extent and location of endometriotic lesions
ble side effects include weight gain, headaches, Involvement of other non-gynaecological systems
nausea, breast enlargement, and depression. Pa- Expertise of clinician
tients should be warned about the increased risk of Availability of resources
Patients preference
thromboembolism during COCP administration.
Box 3. Management options
Medical
Non-hormonal: simple analgesia (paracetamol, NSAID, codeine)
Hormonal treatment: COCP, progestogens, GnRH analogues
The empirical use of Surgery

Conservative: excision or ablation of endometriotic deposits,
GnRH agonists in adolescents excision or ablation of ovarian endometriomas and excision of
deep infiltrating endometriosis
without a definitive Radical: TAH BSO
diagnosis of endometriosis BSO= bilateral salpingo-oophorectomy; COCP = combined oral contraceptive pill ; GnRH = gonadotrophin-releasing
hormone; NSAID = non-steroidal anti-inflammatory drug; TAH = total abdominal hysterectomy.
is controversial
laparoscopy may be necessary to plan long-term
management of endometriosis, which is potentially
a progressive disease with no cure (Boxes 2 and 3).
CASE 2
A 38-year-old woman presented to the gynaecol-

2. Gonadotrophin-releasing hormone (GnRH) ago- ogy outpatient clinic with a 12-month history of
nists: the empirical use of GnRH agonists in ado- worsening intermittent lower abdominal and pel-
lescents without a definitive diagnosis of endome- vic pain, and severe dyspareunia. The pains were
triosis is controversial. Although, it may help to severe enough to disrupt her life and sexual rela-
avoid laparoscopic surgery, GnRH agonists could tionship. A recent severe episode of the pain led to
adversely affect the final bone density formation, an emergency admission to the hospital. She had
particularly in patients younger than 17 years. Fur- no previous surgery and had completed her family,
thermore, a definitive diagnosis and staging with having had one child delivered vaginally in the past.

GYNAECOLO GY
In the diagnosis of endometriosis, a pelvic examination is important to rule out other causes of chronic pelvic
pain.
Pelvic examination revealed tenderness affecting completion of GnRH agonist therapy, the symptoms
the right adnexa and the pouch of Douglas. She started to recur. The patient returned to clinic re-
underwent a laparoscopy, which revealed widely questing a hysterectomy as a more definitive treat-
spread deposits of active peritoneal endometriosis ment for her pain.
affecting both ovarian fossae, the utero-sacral liga-
ments, the pouch of Douglas, and the utero-vesical MEDICAL MANAGEMENT
peritoneal fold. Extensive adhesions were also What Is the Current Role of GnRH Agonists
present between the bowel and anterior abdominal in Endometriosis?
wall. All endometriotic deposits were ablated with How Do GnRH Agonists Work and What
electro-diathermy, and the adhesions were divided Should You Warn the Patient About?
with scissors. At post-operative follow-up, her pain How Can You Treat Potential Side Effects
and dyspareunia were much improved. However, 6 and How Long Would You Prescribe the
months later she experienced a recurrence of her Treatment for?
symptoms. She was then counselled regarding GnRH agonists are usually offered as a second-line
further management options and decided to take medical therapy for endometriosis in patients with
a 6-month course of GnRH agonist. This improved severe symptoms not responding to analgesics or
her pain dramatically, and she found the side ef- COCP. They are also a good option for women expe-
fects manageable. However, a few months after the riencing persistence or recurrence of severe symp-

Peer Reviewed
toms after conservative surgery as is in our case. majority of patients will experience a recurrence
GnRH agonists cause an initial stimulation of of symptoms few months after discontinuation of
the GnRH receptors on the gonadotrophs of the an- treatment. GnRH agonists are given as injections
terior pituitary gland, followed by inhibition due to either on a monthly or 3-monthly basis. Side effects
loss of these receptors (known as receptor down- include menopausal symptoms of hot flushes, night
regulation). The resulting fall in follicle-stimulating sweats, mood changes, and vaginal dryness. The
hormone leads to a pseudo-menopausal status with most worrying potential side effect is a 56% loss
of bone mineral density. This limits the safe use of
GnRH agonists to 6 months. The bone loss usually
recovers partially after 612 months of discontinu-
ation of GnRH agonists. The hypo-oestrogenic side
effects and bone mineral loss can be significantly
reduced by the daily administration of tibolone
Surgery is more 2.5 mg as an add-back therapy. In some patients,
it may be necessary to continue the GnRH agonist
effective in
therapy beyond 6 months (unlicensed use). It is rec-
reducing pain ommended in these cases to monitor bone density
in patients with on a yearly base.
more advanced
CONSERVATIVE SURGERY
endometriosis
Compared with medical therapy, surgery offers
a more definitive treatment of endometriosis and
tends to achieve longer lasting improvement of
symptoms. The principles of surgical treatment of
endometriosis include ablation, vaporization or ex-
cision of peritoneal implants, excision or ablation
oestrogen deficiency due to ovarian suppression. of endometriomas, excision of deep infiltrating
Prolonged oestrogen deficiency eventually causes nodular endometriosis, and restoration of pelvic
atrophy of the ectopic endometrial tissue with sub- anatomy by adhesiolysis. The reported incidence
sequent relief of pain. The initial stimulation often of disease recurrence at 5-year follow-up is about
causes worsening of the symptoms during the first 20% for surgery compared with about 50% for
2 weeks of treatment. Patients may also experi- medical treatment. However, about 30% of patients
ence irregular bleeding during the first 2 months of will not experience any improvement in symptoms
GnRH agonist therapy, but amenorrhoea then usu- after surgery. Also of note is that surgery is more
ally ensues. About 80% of patients start to experi- effective in reducing pain in patients with more ad-
ence improvement or complete relief of pain about vanced endometriosis.
4 weeks after the initiation of treatment. This im- A laparoscopic approach for endometriosis
provement will continue throughout the 6-month surgery is superior to laparotomy as it allows a
course of GnRH analogue therapy. However, the more thorough inspection of the pelvis with higher

GYNAECOLO GY
Surgery offers a more definitive treatment of endometriosis and atypical forms of pelvic endometriosis. Typical
than medical therapy.
peritoneal implants are pigmented lesions includ-
ing dark powder-burn, black puckered, brown, blue-
black, and yellow deposits. Atypical non-pigment-
ed lesions include clear, white or red polypoid or
flame-like lesions. Other lesions include defects
(windows) in the peritoneum. Ovarian endome-
triomas are thick-walled unilocular or multilocular
cysts of varying sizes (usually < 12 cm in diameter)
containing chocolate-coloured fluid due to repeated
bleeding from the endometriotic tissue. They are
typically associated with advanced endometriosis
A laparoscopic approach
for endometriosis surgery
is superior to laparotomy
as it allows a more
magnification, allowing the detection of subtle en- thorough inspection
dometriotic lesions. In addition, laparoscopic sur-
of the pelvis with
gery minimizes trauma to tissues, resulting in less
post-operative adhesion formation. Laparoscopy is higher magnification
also associated with less blood loss, and with its
magnification it allows good detection and control
of small bleeders. From the patients perspective,
laparoscopic surgery shortens hospital stay and al-
lows quicker return to normal activities.
The stage and severity of endometriosis should
be assessed and documented at laparoscopy by de- and extensive adhesions between the affected
scribing the findings and using the revised Ameri- ovary and pelvic sidewall, back of the uterus, and
can Fertility Society classification system (stages broad ligament. However, about 12% of endometri-
IIV). Systematic inspection of the whole pelvis and omas are not associated with adhesions or severe
abdominal cavity is essential. The laparoscopic sur- disease. Deep infiltrating endometriosis (> 5 mm
geon should be familiar with the different typical depth of infiltration) usually affects the recto-vagi-

Peer Reviewed
nal septum and uterosacral ligaments. Utero-sacral Box 4. Indications for surgery for endometriosis
ligament endometriosis is usually characterized by
thickening and firmness of the ligament with vis- Endometriosis detected during diagnostic laparoscopy
ible scarring. It is therefore necessary to palpate Presence of an endometrioma > 3 cm
Deep infiltrating disease causing significant symptoms
the utero-sacral ligament either with the end of a
Endometriosis associated with severe symptoms in subfertile
blunt laparoscopic probe or by vaginal examination. patients
Obliteration of the pouch of Douglas occurs when After failure of medical treatment to control symptoms
the affected rectum is pulled upwards and becomes
fixed to the back of the uterus, causing partial or
complete obliteration of the pouch of Douglas. CASE 3
Minimal-to-mild peritoneal endometriosis can
either be excised or ablated with electro-coagula- A 26-year-old lady presented with a long-standing
tion or laser vaporization. Care should be taken to history of severe dysmenorrhoea and dyspareunia.
avoid thermal damage to the ureters when treating The pattern of dysmenorrhoea was typical of en-
the pelvic sidewall. Both ablation and excision of dometriosis (as described above). She had been try-
mild endometriotic implants have been shown to be ing to conceive for the previous 15 months without
equally effective in improving post-operative pain. success. She had also been troubled with indiges-
Deep infiltrating endometriosis affecting the tion and constipation. Her GI symptoms gradually
utero-sacral ligaments and/or recto-vaginal septum worsened until she became unable to have solid
should be completely excised. food and survived on fluids only. As a result, her
weight dropped dramatically from 58 to 38 kg over
RADICAL SURGERY a period of 6 months.
Pelvic examination revealed a fixed and ret-
This includes total abdominal hysterectomy with roverted uterus, but no recto-vaginal nodules were
or without bilateral oophorectomy. This treatment found.
option should only be considered in patients who A transvaginal ultrasound scan showed a
have completed their family and have had failed thick-walled, 7-cm, right ovarian cyst with internal
medical or conservative surgical treatments. A pre- echoes, suggestive of an endometrioma. A diagnos-
operative trial of GnRH analogues may be helpful tic laparoscopy was performed and showed grade
in determining whether this treatment will be suc- IV endometriosis with extensive adhesions involv-
cessful and whether oophorectomy should also be ing the bowel and completely covering the pelvic
performed. All deep-seated endometriosis should be organs. Only the superficial part of a right-sided
removed during the hysterectomy to prevent remain- ovarian cyst was seen firmly adherent to the bowel,
ing disease from causing persistent pain. Bilateral uterus, and abdominal wall. The tubes and ovaries
salpingo-oophorectomy may result in a better pain could not be visualized. In view of the extent and
relief with reduced chances of further surgery in severity of the endometriosis and the involvement
the future. However, this benefit has to be balanced of the bowel, no treatment was performed on that
against the disadvantage of inducing menopause occasion.
with the need of hormone replacement therapy Post-operatively, a magnetic resonance imag-
(HRT), especially in patients under 40 (Box 4). ing scan was performed showing an 8-cm multi-

GYNAECOLO GY
Practice points the endometriosis.

Two months after surgery, the patient recov-
ered very well, and all her pain and GI symptoms
Careful assessment of the pattern of chronic pelvic pain
together with laparoscopy is the key to establishing an accurate have completely resolved. She was able to eat nor-
diagnosis of endometriosis. mally and gradually gained weight. At this stage,
Treatment should be tailored according to patients age, disease
she was referred to have in vitro fertilization (IVF)
severity and extent, fertility requirements, contraception, and
patients wishes. treatment.
In adolescents with symptoms of endometriosis, empirical
treatment with analgesics and/or combined oral contraceptive SURGERY FOR EXTENSIVE DISEASE
pill (COCP) is recommended before resorting to laparoscopy.
Gonadotrophin-releasing hormone (GnRH) agonists may
adversely affect the final bone density formation in adolescents What Is the Importance of Pre-operative
especially those under 17. Assessment?
First-line hormonal treatments include the COCP and continuous
Pre-operative assessment helps to achieve an accu-
progestogens.
Second-line medical treatment includes GnRH agonists. rate diagnosis of the stage of the disease and to as-
Conservative surgical treatment reduces pain, improves fertility, sess patients fitness for the surgery. This will help
and offers a more definitive treatment with less chances of to choose the best surgical approach and to antici-
recurrence.
pate possible difficulties. In patients with suspect-
ed deep infiltrating endometriosis, it is important
to exclude ureteric, bladder or bowel involvement.
locular cyst on the right ovary with several pelvic A magnetic resonance imaging scan is of value in
deposits of endometriosis involving the bowel. In determining the extent of deeply infiltrating lesions
view of the bowel involvement with endometrio- and the involvement of bowel and bladder. Other in-
sis and the severe GI symptoms, the patient was vestigations of value may be a contrast enema and
reviewed by a colorectal surgeon who discussed intravenous urogram. The management of deeply
various surgical options for bowel endometriosis. infiltrating lesions is very complex. Patients should
The patient was also counselled about the possible be referred to centres with the necessary expertise
need of a colostomy. and a multidisciplinary team should be involved
The patient was offered conservative surgery in the treatment. Pre-operative bowel preparation
through laparotomy for her extensive endometrio- should be considered.
sis. The procedure was carried out jointly with the
colorectal surgeon. What Is the Association Between Endome-
At laparotomy, extensive adhesiolysis was car- triosis and Infertility and What Treatment
ried out freeing the bowel, uterus, tubes, and ova- Option Should You Offer These Patients?
ries. The right ovarian endometrioma was opened Infertility: 3040% of women with endometriosis
and drained. The cyst wall was then stripped off suffer from infertility. The mechanism of infertil-
and sent for histology. A large segment of the colon ity in mild endometriosis is not fully understood.
was found to be affected by the disease. A hemi- In moderate-to-severe endometriosis, infertility
colectomy was therefore performed. Interestingly, results from anatomical distortion of the fallopian
the histological examination of the resected colon tubes and the tubo-ovarian relationship due to ad-
revealed coexisting Crohns disease in addition to hesions.

Peer Reviewed
Medical treatment of endometriosis does not proaches to endometriomas, including excision or

improve fertility. Surgery, on the other hand can ablation of the cyst wall after drainage and irriga-
improve fertility in women with moderate-to-se- tion. Most surgeons would excise the cyst wall as
vere endometriosis. Subfertile women with severe this has been shown to be superior to ablation with
endometriosis who have minimal or no symptoms fewer recurrences. Excision of the cyst is achieved
are better treated with IVF, which gives them a by stripping the cyst wall off from the underlying
higher pregnancy rate than surgery. On the other ovarian tissue. Bleeding points are then secured
hand, subfertile women with severe symptoms or
who have large endometriomas should be offered
surgery. Post-operative hormonal treatment has no
beneficial effect on pregnancy rates after surgery.
However, down-regulation with GnRH analogues
after debulking surgery for stage IIIIV disease may
be required prior to IVF. If satisfactory anatomical
restoration has been achieved with surgery, the The optimal type of
patient could be advised to try to conceive natu-
surgery for
rally for 612 months before resorting to IVF. If the
anatomical outcome of surgery is suboptimal, IVF endometriomas remains
should be considered shortly after surgery. controversial
How Would You Treat an Endometrioma

Seen on Scan?
The management of endometriomas in patients re-
ceiving fertility treatment is controversial. Whilst
some reproductive specialists believe that endome-
triomas (> 3 cm) should be treated surgically before
assisted reproductive treatment, others argue that with diathermy. Ablation of the cyst could be
surgery could significantly damage ovarian reserve, achieved by laser vaporization or electrocoagula-
which could consequently compromise success of tion of the inner cyst wall. Simple aspiration of the
treatment. On the other hand, advocates of surgery endometrioma is not sufficient as it is associated
claim that untreated endometriomas could adverse- with a high recurrence rate. A biopsy of the cyst
ly affect ovarian response to follicle-stimulating wall should always be sent for histology to exclude
hormone stimulation and could make egg retrieval rare cases of malignancy.
difficult. In addition, inadvertent insertion of the
egg retrieval needle into an endometrioma could How Should Dyspareunia Caused by Severe
cause severe pelvic infection with abscess forma- Recto-vaginal Endometriosis Be Treated?
tion. However, most fertility specialists would sur- Surgery is usually the only effective treatment for
gically treat very large endometriomas (> 8 cm). The women with severe debilitating symptoms due to
optimal type of surgery for endometriomas remains recto-vaginal endometriosis, which do not usu-
controversial. There are two main surgical ap- ally respond to medical therapy. Surgery for recto-

GYNAECOLO GY
vaginal septum endometriosis is very difficult and lostomy may be necessary in severe cases.
requires considerable skill and experience. Tradi-
tionally, this surgery has been performed through CONCLUSION
laparotomy. However, more recently, a laparoscopic
approach has been developed in a few centres. Endometriosis can be a very complex condition to
Whilst laparoscopy offers several advantages over treat, and it is important to tailor the treatment to
open surgery, it takes a considerably longer time, the individual patient. As we have seen, medical
which increases the risk of compartment syndrome treatment may be a very good option for an ado-
(an acute calf muscle ischaemia due to prolonged lescent like Case 1 but would not be appropriate in
pressure within the confined fascial compartment someone seeking to get pregnant like Case 3. More
leading to muscle necrosis). In addition to reducing invasive treatment is necessary if the initial con-
the operating time, open surgery allows careful pal- servative therapy is not effective or if the disease
pation for nodular disease, which is necessary for is more advanced. Again, in these cases, patients
accurate determination of the extent of the disease. wishes must be kept into consideration. A hysterec-
This type of surgery is usually carried out jointly tomy, although a good option for Case 2, would not
with a colorectal surgeon (and sometimes an urolo- be appropriate for Case 1 or 3.
gist) who may not be comfortable performing this
complicated surgery laparoscopically.
The recto-vaginal space is accessed by mobi-
2011 Elsevier Ltd. Initially published in Obstetrics, Gynaecology &
lizing the rectum and the nodules removed until nor- Reproductive Medicine 2011; 21(4):112117.
mal tissue is identified. Depending on the extent of
rectal involvement, removal of endometriotic tissue
from the rectum can be achieved by shaving the an- About the Authors
Francesca Raffi is a Clinical Research Fellow at Royal Derby Hospital,
terior wall, disc resection, anterior wall resection, Derby, UK. Saad Amer is Associate Professor of Obstetrics and Gynae-
or segment resection. Occasionally, a temporary co- cology at Royal Derby Hospital, Derby, UK.

OBSTETRICS I Peer Reviewed
Hyperemesis, Gastrointestinal
and Liver Disorders
in Pregnancy
Clare Cuckson, BA, MB BChir, MRCOG; Sarah Germain, MA, MB BS, DPhil, MRCP
PHYSIOLOGICAL CHANGES IN PREGNANCY
During pregnancy, there is generalized relaxation of smooth muscle resulting in relaxa-

tion of the oesophageal sphincter, reduced gastric peristalsis, and delayed gastric emp-
tying. Small and large bowel transit times are increased.
There is increased blood flow to the liver and increased production of fibrinogen,
transferrin and many other binding proteins. Reference ranges for many liver function
tests are altered. Gestation-specific alkaline phosphatase is increased, mainly from
increased placental production, and aminotransferases and -glutamyltransferase are
reduced.
Nausea, Vomiting and Hyperemesis Gravidarum

Background: nausea is experienced by up to 90% of women during pregnancy, and
50% complain of vomiting. Symptoms can start from 5 weeks and usually resolve by the
end of the first trimester. Persistent vomiting in pregnancy is termed hyperemesis gravi-
darum (HG) when the woman is unable to maintain adequate hydration and nutrition.
The cause of HG is incompletely understood, but hormonal, mechanical and psychologi-
cal factors have been implicated. Biochemical thyrotoxicosis (raised free thyroxine and
suppressed thyroid-stimulating hormone [TSH]) is thought to occur by the stimulatory
action of human chorionic gonadotrophin (hCG) on the thyroid (hCG shares a common
-subunit with TSH).
Features: signs of HG include weight loss, muscle wasting, ptyalism (inability to
swallow saliva resulting in spitting and drooling) tachycardia, and postural hypotension.
Biochemical findings may include hyponatraemia, hypokalaemia, abnormal thyroid func-

Table 1. Differential diagnosis and relevant investigations of nausea and vomiting in pregnancy
Urinary tract infection Mid-stream urine

Renal failure (uraemia) U & Es
Helicobacter pylori antibodies, endoscopy, try empirical
Gastro-oesophageal reflux/gastritis/peptic ulcer disease
proton pump inhibitor
Plain abdominal X-ray (ultrasound can detect bowel
Bowel obstruction
dilatation and bowel tumours)
Amylase, calcium, glucose
Pancreatitis
Abdominal ultrasound, MRCP
Glucose, U & Es, urinalysis for ketones, glucose
Diabetic ketoacidosis
tolerance test
Addisons disease U & Es, early morning cortisol, short synacthen test
Hyperthyroidism TFTs, TSH receptor antibodies
CNS pathology; vestibular disorders, cerebral tumours Neurological examination, CT/MRI brain
CNS = central nervous system; CT = computed tomography; MRCP = magnetic resonance cholangiopancreatography; MRI = magnetic resonance imaging; TFT = thyroid function test; TSH =
thyroid-stimulating hormone; U & Es = urea and electrolytes.
tion and liver function, and metabolic hypochlorae- aspiration of vomitus.

mic alkalosis (loss of HCl from stomach).
Complications: if inadequately treated HG Fetal
can lead to significant maternal and fetal morbidity. Severe HG (abnormal biochemistry and/or Wer-
nickes) can result in intrauterine growth restriction
Maternal or even intrauterine death, but overall there are
Severe hyponatraemia or its over rapid correction lower risks of miscarriage, stillbirth and preterm
can lead to central pontine myelinolysis or osmotic delivery.
myelinolysis (presents with confusion, horizontal Diagnosis & investigations: it is a diag-
gaze paralysis, and spastic quadriplegia). nosis of exclusion, and other causes must be con-
Wernickes encephalopathy (Vitamin B 1 defi- sidered especially if the vomiting starts after the
ciency) can occur in any condition of unbalanced first trimester. The possible differential diagnoses
nutrition, which lasts for 23 weeks. This presents of nausea and vomiting in pregnancy are given in
with a triad of confusion, ataxia, and ophthalmople- Table 1.
gia. It carries a mortality of between 10% and 15%, Management: a protocol for management of
and incomplete recovery can lead to Korsakoffs hyperemesis is given in Table 2. It is important to
psychosis where the patient develops anterograde give the patient adequate reassurance as to the
and retrograde amnesia and confabulation. safety of anti-emetics in pregnancy as poor compli-
Thromboembolism is a risk due to dehydration ance is a major reason for failure of treatment. Mild
and immobility in hospital. cases can be managed as day cases, giving intrave-
Others include vitamin deficiencies and nous rehydration and anti-emetics, and continuing

Table 2. Management of hyperemesis gravidarum
Investigations
Urea and electrolytes, full blood count, liver function tests, thyroid function tests, calcium
Mid-stream urine
Ultrasound scan pelvis
Intravenous fluids
1 L 0.9% normal saline with 20 mmol potassium chloride over 2 hours
1 L 0.9% normal saline with 20 mmol potassium chloride over 4 hours
Followed by
1 L 0.9% normal saline every 8 hours with potassium replacement dependant on serum level
Vitamin supplements
Thiamine PO 50 mg TDS or 100 mg IV in 100 mL normal saline once weekly
or
B vitamins/vitamin C (contains 250 mg thiamine, riboflavin, pyridoxine, nicotinamide, and vitamin C)
Anti-emetics
First-line:
Cyclizine 50 mg PO/IM/IV TDS
Second-line:
Metoclopramide 10 mg PO/IM/IV TDS
Promethazine 25 mg PO Nocte
Domperidone 3060 mg PR BD or 10 mg PO QDS
Prochlorperazine 5 mg PO TDS or 12.5 mg IM/IV TDS; 5 mg TDS PR or 25 mg OD PR
Thromboprophylaxis
Anti-embolic stockings
Low-molecular-weight heparin, eg, enoxaparin 40 mg OD (< 90 kg) or 60 mg OD (> 90 kg)
BD = twice a day; IM = intramuscular; IV = intravenous; nocte = every night; PO = by mouth; PR = per rectum; QDS = four times a day; TDS = three times a day.
with buccal medication, or suppositories then oral ies are present.

once vomiting is under control. It is usual to advise
continuing regular anti-emetics for 7 days follow- Gastric Reflux
ing admission to prevent a recurrence of symptoms. Gastric reflux is a common condition affecting two-
Intravenous thiamine should be given to moder- thirds of pregnant women especially in the third
ate to severe cases. Inpatients should be given trimester. It is exacerbated by changes in pregnan-
anti-embolic stockings and low-molecular-weight cy, including pressure from the enlarging uterus,
heparin, and serum electrolytes should be checked increased gastric transit time, and reduced lower
daily. Refractory cases not responding to conven- oesophageal sphincter pressure. These lead to re-
tional anti-emetics should prompt further investiga- flux of gastric contents into the lower oesophagus
tion for another cause, and a trial of corticosteroids and inflammation of the mucosa. Features include
should be considered. Biochemical thyrotoxicosis retrosternal and epigastric pain, and dyspepsia.
does not require treatment unless there are clinical The differential diagnosis includes peptic ulcer dis-
signs of hyperthyroidism and TSH receptor antibod- ease. Management includes non-pharmacological

The cause of hyperemesis gravidarum is incompletely Peptic Ulcer Disease

understood.
Peptic ulcer disease is uncommon in pregnancy, and
this may in part be owing to a protective effective
of oestrogens and prostaglandins on the gastric mu-
cosa. It usually presents with epigastric pain. Com-
plications such as haemorrhage and perforation are
rare in pregnancy, but significant symptoms such
as haematemesis should be investigated with up-
per gastrointestinal endoscopy, which can be safely
performed in pregnancy. Pharmacological treatment
includes H2-receptor blockers (eg, ranitidine) or pro-
ton-pump inhibitors (eg, omeprazole). Misoprostol
is avoided, and Helicobacter pylori eradication can
usually be delayed until after pregnancy.
Constipation
This is another common condition in pregnancy af-
fecting 40% of women, as physiological changes
lead to decreased colonic motility and pressure of
the gravid uterus on rectosigmoid colon. Risk fac-
tors include dehydration, poor dietary intake, opiate
analgesia, and iron supplements.
Non-pharmacological measures such as in-
creased fluid intake and dietary fibre are usually
sufficient, with temporary cessation of oral iron.
Laxatives may be required if these other measures
fail, and both osmotic (lactulose, magnesium hydro-
chloride) and stimulant (senna, glycerol supposito-
(such as sleeping semi-recumbent and avoiding ries) types are safe.
food and fluids immediately before bed) and phar-
macological measures. Drugs that are safe to use DISORDERS OF THE LIVER AND
in pregnancy are antacids (aluminium salts cause BILIARY TRACT
constipation and magnesium diarrhoea); Antacids
with alginic acid; metoclopramide; sucralfate; H 2- There are several disorders of the liver, which are
receptor blockers (ranitidine is safe but avoid cime- specific to pregnancy and are important to recog-
tidine because of its effect on androgen receptors); nize as they are associated with significant morbid-
and proton-pump inhibitors. Avoid misoprostol as it ity and mortality for the mother and her fetus and
is an abortifacient, and it is also associated with delivery is the only cure. Some pre-existing con-
congenital abnormalities, fetal death, and uterine ditions may only become clinically evident during
perforation. pregnancy, and others such as hepatitis E have a

predilection for pregnant women in whom the prog- Table 3. Swansea criteria for diagnosis of AFLPa six or more of
the following features in the absence of another explanation
nosis is significantly worse.
Liver Disorders Specific to Pregnancy Vomiting

Polydipsia/polyuria
Abdominal pain
Haemolysis Elevated Liver Enzymes and Low Encephalopathy
Platelets (HELLP) Elevated bilirubin (> 14 mol/L)
Background HELLP is thought to be a severe Hypoglycaemia (< 4 mmol/L)
Elevated urate (> 340 mol/L)
form of pre-eclampsia, affecting 520% of these Leucocytosis (> 11109/L)
pregnancies, with one-third post partum. Hepatic Ascites or bright liver on ultrasound scan
damage is thought to occur as a result of increased Microvesicular steatosis on liver biopsy
Elevated ammonia (> 47 mol/L)
sinusoidal pressure, hypovolaemia, and fibrin depo-
Elevated transaminases (aspartate aminotransferase or
sition. alanine aminotransferase > 42 IU/L)
Features and investigations the condition Renal impairment (creatinine > 150 mol/L)
can be asymptomatic or present with right upper Coagulopathy (prothrombin time >14 s or activated partial
thromboplastin time > 34 s)
quadrant or epigastric pain, nausea, vomiting, and
a
Chng CL, Morgan M, Hainsworth I, Kingham JG. Prospective study of liver dysfunction in pregnancy in
general malaise. Southwest Wales. Gut 2002 Dec;51:876880.
In most cases, hypertension and proteinuria

are present, and there is a mild to moderate eleva-
tion of aminotransferases and bilirubin. Blood film Acute Fatty Liver of Pregnancy
will reveal true thrombocytopenia and red cell frag- Background this rare disorder is associated
ments indicative of haemolysis. with abnormalities in mitochondrial oxidation
Complications HELLP is associated with and long-chain 3-hydroxyacyl-CoA dehydrogenase
significant maternal (1%) and perinatal (1060%) (LCHAD) deficiency. There is considerable overlap
mortality. Maternal complications include liver inf- of the symptoms and signs with pre-eclampsia and
arction and rupture, subcapsular liver haematoma, HELLP syndrome. It is more common in multiple
acute renal failure, and placental abruption. pregnancies, primiparae, obese women, and with a
Management the mainstay of management male fetus.
involves stabilizing the patient, including control of Features and investigations the presen-
blood pressure and giving magnesium sulphate for tation is similar to that in HELLP syndrome with
prevention of eclampsia. Prompt delivery is usually nausea, vomiting and abdominal pain, although the
required if it presents antenatally. Clotting times rise in serum transaminases, creatinine and leuco-
should be monitored and correction of thrombocy- cytosis tends to be more marked. Other discriminat-
topenia (platelets, < 50 10 /L) is required to cover
9
ing features are hypoglycaemia and coagulopathy,
delivery. which are much more evident in acute fatty liver of
Studies vary on the recurrence rate of HELLP in pregnancy (AFLP). It may present post partum with
a future pregnancy, with figures of 227% quoted. severe haemorrhage. Table 3 gives the diagnostic
The risk of pre-eclampsia is higher and may be up to criteria for AFLP.
75% if background hypertension is present. Many Complications AFLP carries a high ma-
women choose not to have a further pregnancy. ternal and fetal mortality of between 218% and

758%, respectively. Maternal complications in- with this condition are to the fetus and include pre-
clude disseminated intravascular coagulation, renal term delivery, meconium staining of the liquor, and
failure, pancreatitis, and (transient) diabetes insip- intrauterine fetal death, which is reported to be
idus. There is also a risk of progression to hepatic 212% depending on the studies reviewed. The risk
encephalopathy and fulminant liver failure. of stillbirth is difficult to predict despite cardioto-
Management if AFLP presents antenatally, cography monitoring and ultrasound for fetal well-
then coagulopathy and hypoglycaemia should be being. One prospective cohort study of 693 cases of
treated aggressively and delivery expedited. High OC has shown that the risk to the fetus occurs when
dependency unit and/or intensive therapy unit in- the serum bile acids are above 40 mol/L and that
volvement are/is usually required and early liaison there is a 12% increase in fetal complications for
with a specialist liver unit in case of progression to every 1 mol/L increase in the serum bile acid level.
liver failure.
Post delivery, most women recover quickly,
and management is conservative and supportive.
Liver function may take up to 4 weeks to recover,
and liver transplantation should be considered in
those with liver rupture, severe encephalopathy,
The risk of stillbirth is
or failure of liver recovery. The recurrence rate for
AFLP is around 25%, but many women avoid a fur- difficult to predict despite
ther pregnancy. The baby should be screened for cardiotocography monitoring
LCHAD deficiency.
and ultrasound for fetal
Obstetric Cholestasis wellbeing
Features and investigations Obstetric
cholestasis (OC) is a pregnancy-specific condition,
which occurs in approximately 0.7% of pregnant
women in the UK, and the main features are ma-
ternal pruritus and impaired liver function. In most
cases, the serum bile acids are elevated, but de-
rangement in other markers of liver function such as Management involves excluding other
transaminases, bilirubin and -glutamyltransferase causes for liver function derangement as OC is a
also occurs. Other maternal symptoms include stea- diagnosis of exclusion. Itching can be severe, caus-
torrhoea, pale stools, and dark urine. ing marked skin excoriation, insomnia, and mater-
The aetiology of the condition is incompletely nal distress. It is important to take a proper history
understood but is thought to be due to the chole- in these cases as a rash is not a feature of OC and
static effect of oestrogens, which is supported by the patient will report that the itching preceded the
the higher incidence in twin pregnancy and occur- skin changes. Mild symptoms can be managed with
rence of similar symptoms in some individuals tak- antihistamines and emollients containing 12%
ing the oral contraceptive pill. menthol. For more severe cases, ursodeoxycholic
Complications the major risks associated acid is the most effective treatment for ameliorat-

It is important to recognize the liver disorders that are specific to pregnancy because they are associated with
significant morbidity and mortality for the mother and her fetus.
ing the symptoms and may improve the biochemical limited.

picture. It is not known whether treatment with ur- Maternal liver function tests usually return to
sodeoxycholic acid improves the outcome for the fe- normal post partum with no long-term liver dam-
tus or whether cases in which the serum bile acids age, but should be monitored to ensure this hap-
are below 40 mol/L can be managed expectantly, pens. Women who have had OC should avoid the
and this is the subject of ongoing research. Vitamin combined oral contraceptive pill. Recurrence risk of
K 10 mg orally should be given to the mother from OC in a future pregnancy is high at > 90%.
time of diagnosis to delivery to reduce the risk of
post-partum haemorrhage. Non-pregnancy-specific Liver Disease
Most units advocate delivery at around 3738
weeks, and one study examining 352 pregnancies Gall Bladder Disease (Gallstones and
complicated by OC found that over 90% of intrau- Cholecystitis)
terine deaths occurred after 37 weeks, which sup- Pregnancy increases the risk of gallstone formation,
ports this practice. In resistant cases, rifampicin as oestrogen increases the cholesterol content of
can be used under the guidance of a liver specialist the liver and progesterone increases bile secretion.
although published data on its use in pregnancy is This results in increased saturation of the bile with

Laxatives may be required if increased fluid intake and dietary tion, clotting, glucose, full blood count and oxygen
fibre fail to relieve constipation in pregnancy.
saturation will help to distinguish those needing
intensive care.
Viral Hepatitis
Viral hepatitis is caused by the hepatitis viruses A,
B, C, D and E and by cytomegalovirus, Epstein-Barr
virus and herpes simplex virus (HSV). The course
of these viruses is usually unaffected by pregnancy
except for hepatitis E and HSV where the outcomes
are likely to be more severe. In general, patients
may be asymptomatic or complain of right upper
quadrant pain, nausea and vomiting, and general
malaise. Transaminases are raised typically > 1,000
IU, but alkaline phosphatase is often normal.
cholesterol and gallstone formation. Cholecystitis

should be treated promptly with broad-spectrum
The course of these viruses
intravenous antibiotics and fluids, as it can precipi-
tate pre-term labour. Pancreatitis is another serious is usually unaffected by
complication of gallstones and again management pregnancy except for hepatitis
is usually conservative as discussed below.
E and HSV where the outcomes
Pancreatitis are likely to be more severe
Pancreatitis rarely occurs in pregnancy and is most
commonly due to gallstones. Hypertriglyceridaemia
and hypercalcaemia of primary hyperparathyroidism
are other causes. The presentation and symptoms
are similar to the non-pregnant patient, and the di-
agnosis is usually made when the serum amylase >
1,000 U/L. Management is supportive with intrave-
nous fluids and analgesia. Most cases will resolve Hepatitis A transmission of hepatitis A oc-
spontaneously, but around 10% will develop severe curs by the faecooral route and is common in parts
complications needing intensive therapy unit sup- of Asia, Africa and South America where sanitation
port. Careful assessment of renal and liver func- is poor. It should be suspected if there is a history

of recent travel to these areas. Most cases are self- Table 4. Differential diagnosis of abnormal liver function in
pregnancy
limiting, but fulminant liver failure can occur. Acute
infection is confirmed by the presence of hepatitis
Viral hepatitis (A, B, C, E) Serology
A IgM antibodies in the serum. Vertical transmis- EBV, CMV, HSV
sion at delivery is rare, but if occurs the neonate Autoimmune hepatitis ANA, anti-LKM antibodies
can be treated with normal immunoglobulin. Primary biliary cirrhosis Anti-mitochondrial
Hepatitis B transmission of hepatitis B antibodies, ANF, anti-sm
occurs mainly by sexual contact or infected blood Autoimmune sclerosing Anti-sm, ANCA
cholangitis
products. Acute infection usually presents with
Wilsons disease Serum copper and caerulo-
mild symptoms. Fulminant liver failure can occur plasmin
in around 1%. Usually less than 5% remain as car- Haemochromatosis Ferritin
riers which is associated with a risk of cirrhosis, Gallstones Ultrasound
chronic active hepatitis, and liver cancer. The risk Fatty liver
of vertical transmission is low unless the mother Cirrhosis
ANA = antinuclear antibodies; ANCA = anti-neutrophil cytoplasmic antibodies; ANF = antinuclear factor;
develops the acute infection during the pregnancy CMV = cytomegalovirus; EBV = Epstein-Barr virus; HSV = herpes simplex virus; LKM = liver-kidney
microsome.
(90% in the third trimester). High vertical transmis-
sion rates also occur in mothers who are positive
for the hepatitis B e antigen which is a marker of
high infectivity. Pregnancy has no effect on the disease; how-
Mode of delivery does not alter the vertical ever, patients are more at risk of OC which is often
transmission rate. Invasive procedures in labour, more severe.
such as applying fetal scalp electrodes or fetal The risk of vertical transmission is low if the
blood sampling, should be avoided. Neonates mother has a low viral titre. Mode of delivery and
should be given hepatitis B immunoglobulin and breastfeeding do not influence the rate of neonatal
vaccinated at birth and usually again at 1 month infection.
and 6 months. Giving this combined regimen pro- Hepatitis E Hepatitis E is spread by the fae-
tects against neonatal infection in 93% of cases. cooral route and, in the non-pregnant population,
Breastfeeding should be encouraged as this also is usually a self-limiting illness. Pregnant women
does not alter the risk of neonatal infection pro- are more severely infected with 20% developing
vided vaccination is given. acute liver failure. The maternal mortality rate is
Mothers with hepatitis B should also be 12 times higher than in the non-pregnant popula-
screened for hepatitis C and human immunodefi- tion. Vertical transmission was approximately 30%
ciency virus and have their baseline liver function in one small study with a fetal mortality rate of 50%
checked. in those affected.
Hepatitis C Hepatitis C is a blood-borne in- Herpes Simplex Virus HSV hepatitis occurs
fection and is common amongst intravenous drug more commonly in pregnant women than the gen-
users. At least 85% of infected individuals will eral population and has a maternal mortality rate
develop chronic liver disease with around 30% de- of 39%. It can occur through primary infection or by
veloping cirrhosis after 10 years. Women should be reactivation of a latent disease and can be caused
under the care of a hepatologist. by serotypes HSV 1 and 2. Mucocutaneous lesions

are present in only 50% of cases. Definitive diag- hood. The incidence of ulcerative colitis is higher
nosis is made on liver biopsy, but computed tomo- in women than in men whereas Crohns disease af-
graphic scan is of value, showing multiple low-den- fects both sexes equally. The course of disease is
sity areas within the liver. Treatment with aciclovir usually unaffected by pregnancy, although Crohns
improves survival and should not be delayed if the may flare post partum. Symptoms suggestive of ac-
diagnosis is suspected. tive disease should be investigated with full blood
The differential diagnosis of abnormal liver count, serum albumin level and stool culture, and
function in pregnancy and a guide to investigations sigmoidoscopy or proctoscopy.
are given in Table 4.
PREGNANCY FOLLOWING LIVER

TRANSPLANTATION
The chance of successful pregnancy in women fol-

lowing transplantation is around 70%, although
the risk of complications such as miscarriage, in-
trauterine growth restriction, pre-term delivery
and pre-eclampsia is increased. Ideally, pregnancy The management of
should be deferred until at least 1 year following IBD during pregnancy
liver transplantation to allow the graft function to
is frequently
stabilize and when lower doses of immunosuppres-
sants can be used. Also, there is an increased risk compromised
of infection with cytomegalovirus immediately fol-
low transplantation, which may result in congenital
abnormalities if it occurs in early pregnancy. Graft
function and survival are not affected by pregnan-
cy though. The immunosuppressant agents, tac-
rolimus, prednisolone and ciclosporin, are generally
well tolerated in pregnancy and are not associated
with fetal malformations. Mycophenolate mofetil
is teratogenic in animals, and there are reported Management: obstetric outcome is related
cases of congenital malformations in babies born to disease activity at the time of conception, and
to mothers taking this drug and it therefore should women should be encouraged to conceive during
be avoided. Rates of caesarean section are high periods of remission. Active disease is a risk fac-
amongst this group of women although vaginal de- tor for pre-term delivery and low birth weight. The
livery is not contraindicated. management of IBD during pregnancy is frequently
compromised owing to patient fears regarding con-
Inflammatory Bowel Disease genital malformations and sometimes similar con-
Features and investigations: inflammatory bow- cerns or lack of experience of physicians in dealing
el disease (IBD) usually presents in young adult- with pregnant women. In general, attacks should be

managed the same as in the non-pregnant patient. Practice points

The aminosalicylates, sulfasalazine and me-
salazine, are safe for use throughout pregnancy Hyperemesis gravidarum is a serious condition and requires
and breastfeeding. Sulfasalazine is a dihydrofolate prompt treatment with hydration, anti-emetics and thiamine to
prevent complications.
reductase inhibitor, which blocks the conversion
HELLP syndrome and acute fatty liver of pregnancy are associ-
of folate to its more active metabolites; therefore, ated with high maternal and fetal morbidity, and cases should be
supplementation with 5 mg folic acid is advised managed by senior clinicians.
preconceptually and during pregnancy. Obstetric cholestasis is a diagnosis of exclusion, and other causes
of liver disease should be considered.
Corticosteroids are also safe although there is Hepatitis E and herpes simplex virus can be more severe in preg-
some evidence for an increased risk of cleft lip and nancy.
palate in animals and humans. For acute colonic Inflammatory bowel disease is usually unaffected by pregnancy;
and in general, flares should be managed in the same way as in
disease, topical steroid enemas can be used. Pred-
the non-pregnant patient.
nisolone is the corticosteroid of choice as > 90% Presentation of appendicitis may be atypical in pregnancy and
is metabolized by the placenta, thus lowering the may delay the diagnosis.
amount reaching the fetus.
There is extensive data on the safety of aza-
thioprine in pregnancy, and there are no harmful ef- obtain information from the surgeon to define the
fects on the fetus when adequate doses are used. risks of vaginal delivery.
Second-line immunosuppressants such as 6-mer- Coeliac disease: this is an abnormality of
captopurine as well as metronidazole and vitamin the small intestinal mucosa caused by the inges-
B12 can also be used safely. tion of gluten-containing substances in susceptible
Conversely, methotrexate is contraindicated individuals. Diagnosis is made by jejunal or duode-
because of teratogenicity, and patients should be nal biopsy, which shows subtotal villous atrophy.
advised not to conceive within 3 months of taking Up to 80% of patients are positive for HLA B8, and
this drug. there is a familial link. Features include diarrhoea,
Infliximab is a chimeric monoclonal antibody malabsorption, anorexia, and weight loss. Haema-
against tumor necrosis factor- and has revolution- tological disorders are common, and other compli-
ized the course of refractory IBD. In a case series of cations include osteoporosis and osteomalacia due
96 pregnant women with Crohns disease or rheu- to malabsorption of vitamin D and calcium, muscle
matoid arthritis treated with infliximab, the preg- weakness, peripheral neuropathy, encephalopathy,
nancy outcomes were not different between the and other mineral and vitamin deficiencies (vitamin
two groups or compared with the general popula- B 6, B12, zinc, folate, ferritin).
tion. A small study in breastfeeding mothers has Exacerbation of symptoms may occur in preg-
also shown that infliximab was undetectable in the nancy, and the rates of miscarriage and stillbirth
breast milk and in the sera of newborn infants. are increased in those with untreated disease.
Mode of delivery: most women with IBD can Strict adherence to a gluten-free diet can reduce
deliver normally. Indications for Caesarean section poor fetal outcomes. Careful attention must be paid
include active or severe perianal disease and ile- to replacing essential minerals and vitamins, and
oanal pouch anastomosis. Where surgery has been women should be encouraged to breastfeed as this
performed, it is recommended that the obstetrician can reduce the incidence or delay the onset of coe-

liac disease in the neonate in those with a strong FURTHER READING

family history.
Bottomley C, Bourne T. Management strategies for hyperemesis. Best
Pract Res Clin Obstet Gynaecol 2009;23:549564.
Appendicitis Caprilli R, Gassull MA, Escher JC, et al. European Crohns and Coli-
The incidence of appendicitis in pregnancy is simi- tis Organisation. European evidence based consensus on the
diagnosis and management of Crohns disease: special situa-
lar to that in the non-pregnant population (1 in tions. Gut 2006;55(suppl 1):i36 i58.
5001,500). Presentation may be atypical in preg- Chng CL, Morgan M, Hainsworth I, Kingham JG. Prospective study
of liver dysfunction in pregnancy in Southwest Wales. Gut
nancy and therefore the diagnosis may be delayed. 2002;51:876880.
The appendix is shifted superiorly and therefore Joshi D, James A, Quaglia A, Westbrook RH, Heneghan M. Liver
disease in pregnancy. Lancet 2010;375:594605.
classic pain over McBurneys point may be absent.
McKillop L, Williamson C. Liver disease in pregnancy. Postgrad Med
Vomiting may be the only symptom. Leucocytosis is J 2010;86:160164.
Nelson Piercy C. Handbook of Obstetric Medicine. Informa Health-
common in pregnancy, and symptoms such as fever
care; 2009:241261.
or extreme leucocytosis are suggestive of perfora- Nelson-Piercy C, Williamson C. Gastrointestinal and hepatic disor-
tion. Ultrasound has high sensitivity and specificity ders. In: Greer IA, Nelson-Piercy C, Walters B, eds. Maternal
medicine. London: Churchill Livingstone; 2007:171190.
for the detection of appendicitis although clinical Royal College of Obstetricians and Gynaecologists. Green top guide-
assessment should be used to guide management. line number 43, January 2006.
Sibai BM. Imitators of severe preeclampsia. Obstet Gynecol
Broad-spectrum antibiotics should be given pre-
2007;109:956966.
operatively. Prompt diagnosis and treatment are Williamson C, Hems LM, Goulis DG, et al. Clinical outcome in a
series of cases of obstetric cholestasis identified via a patient
mandatory as the perinatal death rate is 20% in
support group. BJOG 2004;111:676681.
cases of perforation. Pre-term labour occurs in 11%
of cases in the second trimester, and this risk de-
About the Authors
creases considerably in the first week after surgery.
Clare Cuckson is a Specialist Registrar Obstetrics at Queen Charlottes
and Chelsea Hospital, London, UK. Sarah Germain is a Specialist
2011 Elsevier Ltd. Initially published in Obstetrics, Gynaecology & Registrar in Obstetric Medicine/Diabetes and Endocrinology at Queen
Reproductive Medicine 2011;21(3):8085. Charlottes Hospital and St. Thomas Hospital, London, UK.

PAEDIATRICS I Peer Reviewed
The Limping Child: An Approach

to Diagnosis and Management
Angela Cox, MB BS, FRACP; Roger Allen, MB BS, FRACP
T
he child with a limp is a common problem with broad differential diagnoses, of which
few are true emergencies. This review focuses on the clinical evaluation of children
presenting with a limp, including key elements of the history and examination and ap-
propriate diagnostic tests and management. It also focuses on the more common and important
causes of limp in children.
A limp is defined as a deviation from the normal gait pattern expected for a childs
age.1 It is a common complaint in childhood and was reported to account for four in
every 100 visits to one paediatric emergency department in the USA.2 The conditions to
consider in the differential diagnosis will depend in part on the patients age. Common
conditions leading to a limping child include soft tissue or bone injuries; infection of the
bone, soft tissues or joints; and neuromuscular, congenital, developmental, ischaemic
and neoplastic processes.
A prospective study that evaluated 243 children younger than 14 years of age who
presented to a paediatric emergency department with limp and no history of trauma
showed that 3:
the median age of affected children was 4 years
limp was more common in boys (2:1)
limp was painful in 80% of cases, and pain was localized to the hip in 34% and the
knee in 19% of cases
transient synovitis or irritable hip was the most common cause of limp, accounting
for 40% of all cases.
Although the majority of affected children will have benign, self-limiting causes for
limp, a significant proportion of children will require additional diagnostic studies and
subspecialty care to diagnose and manage more serious underlying conditions.

Important aspects of the history of a limping child disorders and is less likely to present acutely. Pain
that is worse in the morning and associated with
stiffness is suggestive of an inflammatory process,
Age
whereas pain that is worse at the end of the day is
Onset of pain and limp: sudden or insidious, time of day
Any history of trauma, including non-accidental injury
Association with pain and its location, including referred pain
Preceding viral illness, which can precede transient synovitis
Aggravating factors
Functional limitations Three major factors will
Constitutional symptoms, such as fever, weight loss or malaise
cause a child to limp
pain, weakness, or
Clinical examination of a limping child mechanical or structural

abnormalities
Carry out a general examination, including temperature and
skin rashes
Observe the childs gait and posture, looking for pelvic tilting
or asymmetry
more likely to be mechanical in nature.
Test muscle strength with a squat, Trendelenburg test, and
heel and toe walk Patients or their parents should be asked about
Inspect extremities, looking for erythema, swelling or rashes the presence of constitutional symptoms. Fever and
Palpate bones and joints, noting any tenderness, masses, chills may suggest an infectious process such as
effusion or warmth
Observe passive and active range of motion in the spine and osteomyelitis or septic arthritis. Patients with juve-
lower extremities nile arthritis or malignancy may present with fever
Measure leg length and calf and thigh circumferences and loss of weight.
Carry out a neurological examination, checking sensation and
reflexes
CLINICAL EXAMINATION
The clinical examination should begin by observing

HISTORY the childs gait pattern or posture if able. Three ma-
jor factors will cause a child to limp pain, weak-
History taking in children can be a challenge, es- ness, or mechanical or structural abnormalities.
pecially in children who are unable to talk or ad- Any asymmetry of the legs, rotation of a foot or
equately localize the site of pain (see the box on other compensatory postures should be noted (see
this page). The parents should be asked what their the box on this page). A general examination is also
concerns are and what problems they have noticed. important to evaluate for signs of systemic disease
The age of the child is important because differ- or rule out causes of referred pain.
ent diagnoses are entertained dependent on the A more focused examination of the lower ex-
childs age. tremities should then be performed. Any erythema,
Is the limp associated with pain? Painless limp rashes, swelling or other deformities should be
is often the result of mechanical or neuromuscular noted, and the bones and joints should be palpated

PAEDIATRICS
to identify areas of tenderness, masses, effusion Investigations of a limping child

or warmth. All lower extremity joints, that is, hips,
knees and ankles, should be examined for range of
Full blood count, including a differential white cell count
movement; the spine should also be included in this Erythrocyte sedimentation rate: can be elevated in infective
examination. This will help in the identification of inflammatory or malignant conditions
any painful or stiff joints or any muscle weakness. C-reactive protein: more sensitive for early infection or inflam-
mation
A neurological examination including sensation, Joint aspiration, if effusion present: followed by a full blood
tone and power reflexes should also be performed count and differential white cell count, Gram stain, and culture
because many neuromuscular problems can present Blood cultures: for causative organism in osteomyelitis or
septic arthritis
with limp.
Imaging: plain X-ray, ultrasound, bone scan, magnetic reso-
nance imaging or computed tomography
INVESTIGATIONS Surgical: arthroscopy
After a thorough history and clinical examination

have been conducted, potential differential diag-
Common causes of limp in children
noses should be identified. Further investigations
can then help to make the diagnosis (see the box on
this page). A full blood count and measurement of Aged 1 to 5 years
C-reactive protein levels and erythrocyte sedimen- Trauma
tation rate should be considered in the assessment Transient synovitis
Osteomyelitis and/or septic arthritis
of the limping child. If an effusion is present and in-
Discitis
fection is suspected, then a joint aspiration should Juvenile idiopathic arthritis
be performed. If the joint is septic, white cell counts Malignancy
will usually be greater than 50,000 cells/mm3 and
Aged 5 to 10 years
will be predominantly neutrophils. Trauma
Imaging may also be useful in determining a Transient synovitis
diagnosis. Plain X-ray is usually of low yield but Osteomyelitis and/or septic arthritis
Perthes disease
can be useful in identifying slipped upper femoral
Juvenile idiopathic arthritis
epiphyses or Perthes disease. Ultrasound is useful Malignancy
for assessing joint effusion in hips or localizing a
collection, for example, an abscess. A bone scan is Aged 10 to 15 years
Trauma
very sensitive but not highly specific. It will high-
Septic arthritis
light areas of increased or decreased metabolic ac- Slipped upper femoral epiphyses
tivity, which may be due to infection, inflammation, Juvenile idiopathic arthritis
Malignancy
trauma, neoplasm or avascular disease.
CAUSES OF LIMPING
Transient Synovitis
The common causes of limp in children are listed in Transient synovitis or irritable hip is the most com-
the box on this page. mon cause of limp in preschool-aged children. It can

Begin the clinical examination by observing the child's gait evated. An ultrasound, if performed, should show a
pattern or posture.
small effusion. Transient synovitis is a self-limited
inflammatory condition that usually resolves within
7 to 10 days. Treatment is rest and analgesia, usu-
ally with a non-steroidal anti-inflammatory drug
(NSAID) such as ibuprofen or naproxen, based on
the severity of the symptoms.
Transient synovitis or
irritable hip is the most
common cause of
limp in preschool-aged
children
Septic Arthritis and Osteomyelitis

Differentiating transient synovitis from septic ar-
occur between 18 months and 12 years of age and thritis can be difficult because both conditions can
is a diagnosis of exclusion. The typical presentation present with a decreased range of movement in the
is of a preschool-aged child, who is otherwise well, hip. The presence of raised inflammatory markers,
limping or refusing to walk, and it is often preceded fever and a history of non-weight-bearing makes
by a mild viral infection. septic arthritis the most likely diagnosis. If a septic
The child will be mostly afebrile or have a low- process is suspected, the joint should be aspirated
grade fever with a mild to moderate decrease in and the fluid sent for cell count, Gram stain, and
range of movement in the affected hip. Inflamma- culture and sensitivities. There is overlap between
tory markers are usually normal or only slightly el- synovial cell counts in infection and inflammatory

PAEDIATRICS
conditions, but if the white blood cell count is more Figure 1. Perthes disease in a 4-year-old boy. Note the
flattening of the left femoral head and sclerosis.
than 50,000 cells/mm3 and predominantly neu-
trophils, infection should be presumed. Treatment
of patients with septic arthritis is surgical drain-
age and use of antibiotics (usually flucloxacillin) to
cover infection with Staphylococcus aureus.
The presentation of osteomyelitis overlaps
with that of septic arthritis, and treatment is simi-
lar with empirical antibiotic therapy, usually with
flucloxacillin. Open surgical drainage and washout
may be required if there is evidence of joint in-
volvement or abscess. Discitis, infection of the disc
space, can also present with limp and should be
suspected in younger children who are refusing to
walk and cry when picked up. They may be tender
in the region of the affected disc, usually L1 to L5.
Perthes Disease
Perthes disease is an avascular necrosis of the
femoral head and is seen commonly between the
ages of 4 and 9 years and more often occurs in
boys (Figure 1). The onset is often insidious with Figure 2. Slipped upper femoral epiphysis in the left hip of a
9-year-old girl.
a painless limp and then the development of hip,
groin, lateral thigh or knee pain. On examination,
the patient may have a leg length discrepancy with
decreased abduction and internal rotation of the
hip. X-ray changes vary depending on the stage
of the disease, but there is usually flattening and
fragmenting of the femoral head. A bone scan may
pick up earlier changes. Treatment of patients with
Perthes disease may vary from close observation to
bracing or surgery with the goal being to maintain
range of movement and containment of the femoral
head within the acetabulum.
Slipped Upper Femoral Epiphysis

Slipped upper femoral epiphysis is a fracture of the
growth plate leading to slippage of the femoral epi-
physes off the femoral neck (Figure 2). It more com-
monly affects teenage boys, particularly those who

Osteosarcomas are the most common type of bone tumour seen rotated and shortened. Surgical treatment is often
in children.
needed with fixation of the femoral epiphyses by
pinning.
There is no one diagnostic

test for juvenile idiopathic
arthritis, and the diagnosis
is made on clinical
grounds and by excluding
other conditions
Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis is the most common
chronic paediatric rheumatological disease. It is
an inflammatory arthritis that affects one or more
joints and presents in children younger than 16
years of age. Symptoms can last for more than 6
weeks, and the condition is classified on the basis
of disease pattern over the first 6 months.
On initial presentation, particularly in patients
with the oligoarticular subtype of the disease,
monoarticular swelling can be present. This is more
likely to involve the knee or ankle, and isolated
hip arthritis is an uncommon presentation of juve-
are overweight and skeletally immature. There is nile idiopathic arthritis. During history taking, it is
also an association with hypothyroidism. The pres- important to ask about early morning stiffness or
entation can be acute or chronic with a limp and any fevers, rashes and other systemic features. Ex-
often pain referred to the knee or thigh. amination should include examination of all joints
On examination, the leg may be externally including asymptomatic ones and checking for com-

PAEDIATRICS
plications of disease, for example, leg length dis- MALIGNANCY

crepancy, muscle wasting or growth failure.
There is no one diagnostic test for juvenile Neoplasms are some of the most concerning causes
idiopathic arthritis, and the diagnosis is made on of limp or limb pain in children. Children may have
clinical grounds and by excluding other conditions. pain or limp caused by a tumour, for example, oste-
Most, but not all, patients will have raised inflam- osarcoma, non-specific pain from leukaemia or gait
matory markers and some will have associated deterioration from a tumour of the central nervous
anaemia and/or thrombocytosis. Depending on the system.
severity of the condition, patients can be treated Pain from leukaemia is often out of proportion
with a range of medications from NSAIDs, oral and to the findings on examination. There may also be
intra-articular corticosteroids to disease-modifying pallor, lymphadenopathy and hepatosplenomegaly,
anti-rheumatic drugs such as methotrexate and the and the white cell count is usually abnormally high
new biologic therapies, such as the tumor necrosis or low with abnormal cells, lymphoblasts, seen on
factor antagonists etanercept and adalimumab. film. A bone marrow aspirate will confirm the di-
agnosis.
Osteosarcomas are the most common type of
The causes of limp in children are diverse, from benign self-
resolving to serious underlying conditions. bone tumour seen in children and commonly present
in older children in the distal femur or proximal tib-
ia. The pain will often be reported as being worse
at night, and a radiolucent defect will be visible on
X-ray. Benign bone tumours can also present with
pain that is worse at night. Osteoid osteomas are
benign tumours of bone that characteristically re-
spond very well to NSAIDs and usually have typical
X-ray findings of a radiolucent nidus surrounded by
sclerotic bone and are hot on bone scan.
WHO TO REFER
Specialist referral is required for children with:

suspected slipped upper femoral epiphyses
suspected Perthes disease
suspected bone or joint infection
suspected juvenile idiopathic arthritis
any persistent musculoskeletal symptom.
CONCLUSION
The limping child is a common clinical presentation

in the primary health-care setting. The causes are

Key points FURTHER READING
Abbassian A. The limping child: a clinical approach to diagnosis. Br J

History, examination and simple laboratory tests can identify Hosp Med (Lon) 2007;68:246250.
most serious causes of limp in children. Cassidy, JT, Petty, RE. Textbook of Pediatric Rheumatology. 5th Ed.
The presence of acute pain, raised inflammatory markers, fever Philadelphia: WB Saunders; 2005.
and non-weight-bearing makes septic arthritis the most likely Lawrence LL. The limping child. Emerg Med Clin North Am
diagnosis. 1998;16:911929, viii.
It is important to remember that muscle weakness and MacEwen GD, Dehne R. The limping child. Pediatr Rev 1991;12:268
274.
malignancy can be causes of limp.
Referred pain may be present, and the pathology may not be
at the site of the pain.
2011 Medicine Today Pty Ltd. Initially published in Medicine Today
September 2011;12(9):3136. Reprinted with permission.
diverse, from benign self-resolving conditions to in-

fections, malignancy, and inflammatory disorders. About the Authors
Dr Cox is a Paediatric Rheumatologist at Monash Childrens Hospital,
Many conditions causing limp can be managed
Melbourne. Declaration of interest: None. Dr Allen is a Paediatric
by the primary care physician. Immediate referral Rheumatologist at The Royal Childrens Hospital, Melbourne, Victoria,
should be made if septic arthritis is suspected, and Australia. Declaration of interest: Dr Allen has been on paediatric
advisory committees for Novartis and Roche and has been a principal
advice should be sought for any musculoskeletal or associate investigator in various drug trials sponsored by Merck,
complaint that is persistent or worrisome. Amgen, Wyeth and Roche.
References
1. Thompson GH. Bone and joint disor- rics. 17th ed. Philadelphia: WB Saunders; bance in 425 pediatric patients. Pediatr ing child: epidemiology, assessment
ders. In: Behrman RE, Kliegman RM, Jen- 2004:22512252. Emerg Care 1985;1:710. and outcome. J Bone Joint Surg Br
son HB, eds. Nelson Textbook of Pediat- 2. Singer JI. The cause of gait distur- 3. Fischer SU, Beattie TF. The limp- 1999;81:10291034.

Continuing Medical Education
P
2 SK
Current Management of Antenatal

HydronephrosisAn Update
Yap Te-Lu, MBBS, FRSC; Anette Sundfor Jacobsen, MB BCh, FRCS, M Med, FAMS
history of ANH and more accurate antenatal the distribution (segmental or general), degree
diagnosis. of calyceal distension or parenchymal thick-
In our current era, the approach to ANH ness. However, this is the most widely adopted
should have the following goals: accurate quantitative parameter in obstetric practice,
antenatal identification of high-risk ANH; especially outside North America.
and minimal postnatal imaging for low-risk As with most numerical threshold values
patients but aggressive and early surgi- for pathological diagnosis, the choice of the
cal intervention for high-risk uropathies. cut-off point involved a fine balance between
Even though prenatal diagnosis allows for sensitivity and specificity. Studies attempting
the planning of appropriate postnatal care, to define the normal range of APD for a fetus
this benefit should be weighed against undue have found that the maximum dimension of a
Ultrasound makes an excellent screening parental anxiety or even distress. normal renal pelvis at any gestational age is
tool for neonates with ANH. less than 5 mm in 92.7% of cases.1 Therefore,
WHAT CONSTITUTES ANH? a level below 4 mm in the second trimester
INTRODUCTION has been identified as the lower acceptable
Two widely accepted systems based on ultra- limit for a likely normal postnatal outcome.
Antenatal hydronephrosis (ANH) is a general sound images are used internationally for However, there is still controversy as to the
term used to describe the dilatation of the fetal grading the severity of renal pelvis dilatation: threshold value for the third trimester to adopt
renal pelvis and/or its calyces. In pelviectasis, the anteroposterior diameter (APD), a quanti- for predicting postnatal pathology, be it 7 or 9
there is only dilatation of the renal pelvis; tative measurement of the dimension of the mm. A strict criterion of 7 mm on a 33-week
while in caliectasis, there is dilatation of the pelvis; and the Society of Fetal Urology (SFU) gestation ultrasound will lead to a 100%
calyces. ANH is the most commonly diagnosed grading, which is a qualitative observation of detection of all hydronephrosis but also a high
congenital urinary tract anomaly, which is the degree of pelvic and calyceal dilatation. false-positive rate of 3080%.2,3 On the other
detected by prenatal screening in 15% of all The degree of renal pelvic dilatation, however, hand, Mallik and Watson4 illustrated that by
pregnancies. may be modified by the fetus gestational age, increasing the APD cut-off for the third trimes-
In the early years of routine fetal ultra- degree of fetal bladder distension, and mater- ter to 10 mm, it will miss out on 25% of cases
sound screening, almost all cases of ANH nal hydration status. with pelviureteric junction obstruction (PUJO)
were subjected to invasive imaging studies and 50% with vesicoureteral reflux (VUR);
postnatally, followed by a pre-emptive surgical APD Measurement conversely, only 23% with benign dilatation
approach. The management of ANH has since The APD system measures the anteroposterior would be included.
trended towards a more conservative approach diameter in millimetres of the renal pelvis on The third-trimester APD has the highest
over the past two decades. This shift is attrib- the transverse plane at its point of exit from positive predictive value in predicting postnatal
uted to the better appreciation of the natural the kidney. It does not take into account all of uropathies.5 It is thus universally agreed upon
JPOG_MayJun12_CME_CurrManagofAntenatal_ID-FINAL.indd 125 6/11/12 5:51 PM

that an APD greater than 15 mm in the third at greater risk of having a postnatal anomaly But only 51% of SFU grades 3 and 4 eventually
trimester would predict severe hydronephrosis as compared with the normal population. 10
stabilized. Most investigators would therefore
and significant postnatal uropathies. Increasing degree of severity of ANH is clearly recommend repeat or serial ultrasounds to be
associated with a higher incidence of and more performed again in the later part of pregnancy,
SFU Grading of Pelvic Dilatation significant uropathies. According to a review as renal and ureteral biometrics are known
This 5-point grading system was first intro- and meta-analysis of 17 studies involving 1,308 to fluctuate. It has been shown by Thornburg
duced by Fernbach et al in 1993 and has been
6
subjects, the respective risks for mild, moder- et al15 that third-trimester ultrasound was a
widely adopted in North America. It takes into ate and severe degrees of ANH for postnatal better predictor of surgically relevant hydrone-
account the degree of calyceal dilatation and pathologies were 56.788%, 10.229.8%, and phrosis than second-trimester ultrasound.
parenchymal thinning in classifying prenatal 1.513.4%, respectively. 11,12
Overall, the risk is It is equally important to be aware of
hydronephrosis. This system has been shown 36% for postnatal pathology of any degree of an atypical group of patients with APD below
to have good intra-rater reliability but only ANH detected in utero. However within each the threshold value of 4 mm and 7 mm for the
modest inter-rater agreement.7 It has been of the groups, there is a different distribution second and third trimesters, respectively, which
proposed recently that this grading system be of the uropathies. would not merit any postnatal investigation. In
fine-tuned by further defining segmental versus In the mild group (APD 79 mm), only a study by Chaviano et al,16 13% of cases in
diffuse cortical thinning. 11.9% of the ANH demonstrated a postna- their Virtual Pediatric Urology Registry of 1,128
tal anomaly. For moderate ANH with APD patients were within this cut-off limit of which
Secondary Sonographic Features between 9 to 15 mm in the third trimester, 20% eventually required extensive urological
In addition to the presence and severity of the incidence of PUJO was higher than that care postnatally. In another prospective cohort
renal pelvic dilatation, antenatal sonogram of VUR (17% vs 11%). A significant propor- study of mild ANH with APD of 59.9 mm, 18%
should also assess the thickness and nature tion of patients in this group have ureteral eventually demonstrated urological anomalies
of the renal parenchyma, ie, the echogenicity, obstruction. In contrast, for the severe group (mostly VUR) and 7.8% presented with urinary
presence of renal cysts, and degree of cortico- with APD greater than 15 mm, most of the tract infection during a median follow-up
medullary differentiation. The best indicator pathology was attributed to PUJO (54.3%). period of 24 months.17
of renal dysplasia and thus compromised In total, 88.3% in this group had significant
function is hyperechoic renal parenchyma postnatal anomalies. Other Ultrasound Parameters/Score
with presence of cortical cysts. It is pivotal
8,9
Coplen et al , in their studies of 257
13
Used for ANH
to estimate the quantity of amniotic fluid and neonates, found that a threshold limit of APD Novel methods have been suggested in
the development of the fetal lungs. A general of 15 mm would differentiate obstruction from attempts to improve the categorization of
assessment of the fetus to detect other non-significant dilatation in 80% of fetuses severity of ANH. One of them is the hydrone-
congenital malformation and amniocentesis with a sensitivity of 73% and specificity of phrosis index: hydronephrosis index (percent-
for chromosomal defects should be undertaken 82%. age) = 100 (total area of the kidney area
if deemed necessary. More refined assess- However, it has been shown that ANH dilated pelvis) / (total area).18 Another attempt
ments of the fetus renal function involve detected in early pregnancy may stabilize to overcome the effects of a distended fetal
identifying the fetal urine biochemistry, eg, or even resolve completely. In a systematic bladder for ANH is to divide the anteroposte-
sodium, chloride, potassium and microglobulin. review of the literature, Sidhu et al docu-14
rior diameter of the renal pelvis by the blad-
mented a resolution rate of 72% for all grades der volume.19 Zhan et al20 devised a prenatal
Predictive Value of APD for Postna- of ANH. Ninety-eight percent of patients with ultrasound score utilizing fetal APD, renal
tal Uropathies SFU grades 1 and 2 of ANH showed stabiliza- parenchyma thickness, and pelvicalyceal
In general, infants with any degree of ANH are tion, resolution or improvement of pelviectasis. morphology. Values of 0 to 3 were assigned

to each kidney studied. The total score ranges In the pre-antenatal screening era, pyelo- ing trend of renal function or progressive renal
from 0 to 9, with the best pathological cut-off plasty was performed mainly for symptomatic dilatation. Randomized trials have so far
value of 6 differentiating between physiologi- kidneys. The concern was that unrelieved indicated that only 1925% of prenatally
cal fetal dilatation and pathological hydrone- obstruction could potentially lead to near-total diagnosed PUJO eventually required surgical
phrosis loss of kidney function. Thus, in the early ante- intervention.26
natal screening period in the 1980s, almost
Fetal Magnetic Resonance Imaging all ANH cases that were diagnosed as pelvi- Transient Hydronephrosis
Although ultrasound remains the modality ureteric junction obstruction were subjected The majority of the patients with ANH
of choice for imaging ANH, fetal magnetic to early pre-emptive pyeloplasty based on (4188%) have a non-pathological dilatation
resonance imaging is beginning to emerge as the treatment philosophy, which was tailored of the kidney that either resolves spontane-
a valuable complementary tool for complex for symptomatic chronic PUJO. The natural ously in the fetus or stabilizes with no further
urological anomalies. It allows for exquisite history of antenatal pelviureteric junction deterioration over time.4,27,28 Therefore, surgi-
demonstration of both normal and abnormal obstruction and the concept of significant cal intervention is not recommended for these
renal anatomy. Fetal magnetic resonance obstruction (ie, obstruction associated with patients. This transient pelvic dilatation, which
imaging is especially valuable in cases when compromised renal functions) soon began to is termed transient hydronephrosis, may be
the ultrasound findings are inconclusive. Its surface in the 1990s. The landmark random-
22
the result of:
use, however, is still fairly limited. ized controlled trial that illustrates the benign 1. Physiologically slow canalization of the
course of antenatal PUJO was published by ureter and maturation of the excretory
AETIOLOGIES OF ANH Dhillon et al from the Great Ormond Street system.
Hospital, London. Patients were randomized
23
2. Transient real impairment to the urinary
The possible postnatal diagnosis of ANH into two arms: 48 children who had pyeloplasty, out-flow giving rise to self-limiting prena-
includes PUJO, transient hydronephrosis, VUR, and 52 who were managed conservatively. tal dilatation. This has been postulated to
non-refluxing megaureter, duplex kidneys with Of the 52 kidneys managed conservatively, result from a delayed maturation of the
ureterocele or ectopic ureter, posterior urethral 9 (17%) had deterioration of function during pelviureteric or vesicoureteric junctions.
valve (PUV), urethral atresia/stenosis, and the observation period. However, 14 showed 3. Extra-renal pelvis.
ureteral obstruction. evidence of resolving obstruction while 29 4. Low-grade transient VUR that resolves
out of 52 (56%) retained stable function spontaneously with no urinary tract infec-
Pelviureteric Junction Obstruction despite radionuclide scans revealing persis- tion episodes.
Pelviureteric junction obstruction is the tent obstruction. Amongst the studies that Even though ureteric canalization is
commonest cause of pathological ANH support initial conservative management were achieved at the end of embryogenesis, matura-
(4060%) with an incidence of 1 in 2,000 those by Koff et al 24,25
on 104 newborns with tion of the ureteric wall continues well beyond
live births. It is three times more common in
21
unilateral severe hydronephrosis who were birth. In a study by Thomas et al29 to monitor
males and may be bilateral in 2025% of cases. managed conservatively. Only 23 required long-term progress of mild pelvic dilatation in
The proposed aetiology includes intramural surgery for decreasing renal function, while 29 children over a mean period of 4.2 years
fibrosis at the pelviureteric junction, abnormally 69% of the hydronephrosis resolved over an (range 1.57.8 years), 69% of the kidneys
high insertion of the ureter, extrinsic compres- average period of 2.5 years with no deteriora- reverted to normal while the remaining 31%
sion from crossing vessels, and adhesion. The tion of renal function. were diminished in size or were unchanged.
classical ultrasound findings are calyceal and The current surgical approach has tended Nevertheless, it remains exquisitely
renal pelvis dilatation in the absence of a towards an initial watchful wait while surgery challenging to differentiate between transient
hydroureter. has been reserved for cases with a deteriorat- hydronephrosis and pathological dilatation

antenatally. The main distinguishing features sally performed for all patients.) value of identifying and treating VUR in infants
of transient hydronephrosis is the mild to Regarding spontaneous resolution of with mild ANH (SFU grades 1 and 2), a cautious
moderate degree of pelvic dilatation in a reflux, patients with VUR diagnosed antena- observational approach is one option.32 But
normal-sized kidney which has no coexisting tally experienced a speedier resolution than parents must be cautious about the risk of
parenchymal compromise. There should also those presented postnatally. urinary tract infection and the need to seek
be no calyceal and ureteric dilatation or blad- In seven published series with 413 ante- early treatment.
der abnormality. As a guide, almost all kidneys natally detected refluxing units, the short- to
with an APD less than 6 mm in the second medium-term resolution rate for VUR grades Non-refluxing Megaureter
trimester or less than 8 mm in the third tend to 13 was 78% while that of grades 4 and 5 was Dilatation of the ureter that is not caused by
be transient hydronephrotic. On the contrary,
4
36%. These differ from the historical resolu-
33
reflux accounts for about 10% of ANH and has
in kidneys with an APD of 12 mm in the third tion nomograms development by the AUA for an incidence of 1 in 6,500 live births.20 The
trimester, only 40% will eventually prove to be symptomatic cohorts. The deviation may be obstruction may be due to a narrowed area
transient hydronephrotic in nature.27,30 explained in part by the delayed maturation of or a localized segment of dysfunction of the
Of note, one must be aware of the wide the sphincter/bladder neck mechanism seen as distal ureter. The suspicion is first raised by
overlap of antenatal APD threshold values for high voiding pressures during early infancy.34
the presence of antenatally detected unilateral
transient hydronephrosis and pathological dila- On the other hand, antenatal diagnosis hydronephrosis, a communicating hydroureter,
tation. may have pre-selected a group of male infants and a normal urinary bladder.
with bilateral high-grade VUR associated with The initial management of non-refluxing
Vesicoureteral Reflux congenital renal dysplasia. This was revealed megaureter is observation, as it has an even
Vesicoureteral reflux is the retrograde flow of by Caione et al in a series of 50 patients with
35
higher resolution rate than PUJO of up to
bladder urine into the upper urinary tract owing antenatally diagnosed bilateral high-grade 72%.38 Shukla et al39 reported a series of 27
to an incompetent vesicoureteric junction. VUR. After a follow-up period of a mean of 6.3 patients with 40 non-refluxing megaureters
This may result in infective, immunological, years (range 116 years), all the patients with managed conservatively over a mean period
biochemical and/or urodynamic insults to the chronic renal impairment were male. This was of 6.8 years. Complete resolution was seen
kidneys. Reflux nephropathy has been docu- confirmed by Assael et al in a similar series
36
in 21 ureters (52.5%) with 19 (47.5%) show-
mented as the cause of end-stage renal failure of 108 patients of which 76 were male. It is ing improvement or stable findings. This was
in 21% of patients under the age of 19 years in this group of patients that mandate long-term confirmed by McLellan et al38 on the follow-up
12 registries from Europe.31 follow-up by the nephrologist because of the of megaureters which showed that SFU grades
The American Urological Association high risk of developing chronic renal failure in 1, 2 and 3 hydronephrosis resolved over 13, 24
(AUA) Pediatric Vesicoureteral Reflux Guide- puberty. and 35 months, respectively. But for degree of
lines Panel in 2010 published a meta-analysis The AUA panel thus recommends that dilatation greater than SFU grade 3 hydrone-
of 34 studies on 4,756 patients with prenatal MCU be performed for all infants with high- phrosis, the resolution period may take up to
hydronephrosis and VUR. They established
32
grade postnatal hydronephrosis (SFU grades 49 months on the average. The patient should,
an APD threshold criterion of 4 mm during the 3 and 4), hydroureter or abnormal bladder, or however, receive prophylactic antibiotics and
second trimester and 7 mm during the third those who develop urinary tract infection while regular ultrasound scans during this watchful
trimester for the diagnosis of ANH at risk for on follow-up. The frequently cited reasons
32
period.40
VUR. The prevalence of VUR in patients with of opponents to the routine performance of Most series reported an operative rate
ANH in the above studies ranges from 7% to MCU for mild ANH include low diagnostic of 1020%. The predictive factors for surgery
35% with an average of 16.2%. (However, rate, complication of MCU, radiation exposure, may include pelvic dilatation of SFU grades 3
micturating cystography [MCU] was not univer- and cost ineffectiveness. Given the unproven
37
and 4, differential renal function of less than

30%, and a ureteral diameter greater than ing lower moiety ureter. If the upper moiety is days, as about 80% of the cases are detected
1.33 cm. We favour a single-stage ureteral
41
of good function, preservation is an option by prenatally. MCU should be performed urgently
re-implantation, likely with ureteral tapering. either cystoscopic incision of the ureterocele at birth to confirm the diagnosis, thus enabling
or resection of the ureterocele followed by early ablation of the PUV or vesicostomy for
Duplex Kidneys With PUJO or Ure- re-implantation of the ureters. Similarly for the decompression of the upper tract. It is essen-
terocele/Ectopic Ureters ectopic ureter, common sheath re-implantation tial that metabolic abnormalities be corrected
Hydronephrosis can affect either the upper or of ipsilateral ureters is the operation of choice as soon as possible and urosepsis should be
lower moiety of the duplex kidney. Obstruction for preservation of the upper moiety. However, prevented.
of the lower moiety is invariably at the level if the upper moiety demonstrates minimal Of those who survive the neonatal
of the pelviureteric junction. The indication for function with a massively dilated ureter, lapa- period, 1730% will eventually develop end-
surgical intervention in this case is similar to roscopic upper hemi-nephroureterectomy is stage renal impairment necessitating dialysis
that of PUJO in a single kidney. The exception proposed. or transplant.44,45 The presence of bilateral VUR
is the technical details of the surgical correc- with recurrent urinary tract infections are poor
tion. For duplex kidneys with low ureteral bifur- PUV and Urethral Atresia prognostic indicators.
cation, the standard dismembered pyeloplasty Posterior urethral valve is the most common
is appropriate. However, for high ureteral bifur- cause of lower urinary tract obstruction in Multicystic Dysplastic Kidney
cation with a short segment of lower moiety neonates, with an incidence of 1 in 5,000 Although strictly not part of the aetiology of
ureter distal to the PUJO, an end-to-side anas- 8,000 live births. The fetus is invariably male.
4
ANH, multicystic dysplastic kidney (MCDK) has
tomosis between the lower moiety pelvis and Typical ultrasound findings are that of bilateral been mistaken for gross hydronephrosis. The
the upper moiety ureter is favoured. hydronephrosis, hydroureters, and distended diagnostic features on ultrasound that must be
Obstruction of the upper moiety of duplex and thick walled urinary bladder with dilata- verified include multiple non-communicating
systems resulting in dilatation of the corre- tion of the posterior urethra. In addition, there randomly distributed cysts of variable sizes,
sponding pelvicalyceal system is caused by is frequently associated renal dysplasia with lack of identifiable renal parenchyma, and
either an ureterocele or a ectopic ureter. The occasional presence of perinephric urinoma a non-dilated ureter. It is well documented
anomaly is identified on antenatal screening or fetal ascites. The high perinatal mortality that MCDK has an excellent potential for
with an incidence of 57%. The diagnosis
4
rate is attributed to the severe oligohydram- spontaneous involution.46 Narchi47 reviewed
can easily be confirmed by the presence of a nios and the resultant pulmonary hypoplasia. 26 published series of MCDK involving 1,115
massively dilated ureter, a duplex kidney, and In the latest annual report of the UK renal children managed conservatively; there were
visualization of a cystic structure within the registry, obstructive uropathy accounted for no cases of malignant change and only six
urinary bladder on ultrasound. Further postna- 16% of children with end-stage renal failure reported cases of hypertension. Ismaili et al48
tal imaging should include micturating cysto- of whom 89% were male with PUV. However,
42
has shown in their study that two successive
gram, dynamic radionuclide scan, and even data from the literature is inconclusive on the normal postnatal ultrasound scans may suffice
magnetic resonance urography. benefit of antenatal drainage. It may increase to rule out clinically significant uropathies of
The condition may emerge as a neona- perinatal survival with improved lung develop- the contralateral kidney.
tal emergency if the ureterocele becomes ment but has not been shown to optimize renal
prolapsed and causes bladder outlet obstruc- prognosis by limiting the degree of congenital POSTNATAL EVALUATION OF
tion. A simple cystoscopic puncture of the renal dysplasia.43 ANH
ureterocele will suffice. Main surgical decision Nevertheless, the classic scenario of
making will depend on the function of the upper neonates with PUV presenting with life- The postnatal evaluation of ANH should follow
moiety and the presence or absence of a reflux- threatening urosepsis is extremely rare nowa- a systematic and comprehensive imaging

protocol that examines both the upper and dure involving per-urethral catheterization and standardize the interpretation of the drainage
lower urinary tract. Nonetheless, one should the instillation of radiopaque contrast media curve. The normal differential function of each
attempt to avoid unnecessary investigation into the urinary bladder. The examination deliv- kidney is in the range of 4555%. Interpreta-
during physiological and low-risk conditions. ers a substantial quantity of radiation to the tion of the kidneys drainage status, however,
abdomen and pelvis, particularly in patients is not always straightforward and equivocal
Ultrasound with complex malformations. Various modifica- results are common. This is because multiple
Ultrasound examination is radiation-free, tions and improvements to its technique have factors, both physiological and pathological,
safe, quick, cheap, and repeatable. It makes arisen following new insights into the impor- may influence the kidneys drainage ability.
an excellent screening tool for neonates with tance of a physiological rate of bladder filling, There may also be over-estimation of the
ANH and for the planning of subsequent post- pitfalls with low-grade VUR, and the need for function of massive hydronephrotic kidney
natal management. In the normal neonate, post-void assessment. leading to supra-normal readings.50
there is relative dehydration with decreased The overall incidence of VUR in the Most surgeons use drainage pattern as
urine output for the first 2448 hours of life. neonates with ANH varies between 8% and well as differential renal function in conjunction
Therefore, too early a postnatal ultrasound 38% in different studies. As neither the degree with serial ultrasound imaging trend to optimize
may miss a borderline hydronephrosis or of ANH nor the gender of the child can help to the prediction for surgical intervention.51
underestimate a severe one. The initial ultra- predict the presence of VUR in children with
sound must assess the degree of dilatation ANH, there is currently no clear evidence to Static Dimercaptosuccinic Acid
of the pelvicalyceal system, any dilatation of support or eliminate postnatal imaging for Renal Scan
the ureters, estimated size of the bladder and VUR. It is widely accepted that MCU should Technetium Tc 99m dimercaptosuccinic acid
thickness of its wall, as well as the status of be offered to infants with postnatal pelvis dila- (DMSA) renal scan is the standard modality
the renal parenchyma (thinning, dysplasia, tation of more than 7 mm in any one of two used for evaluation of the renal parenchyma.
cysts, impaired perfusion). One should be consecutive postnatal ultrasound examina- The radioisotopes bind to the proximal renal
vigilant of any renal duplication with possible tions performed 1 month apart. 37
tubules after intravenous injection. Its radioac-
coexisting ureterocele. Ultrasound assessment tivity pattern is then captured and translated
of the posterior urethra should be the routine Renal Scintigraphy: Dynamic Renal into static images of the kidneys 24 hours
if there are bilateral secondary obstructive Scans later. DMSA is a highly sensitive and accurate
changes. Dynamic or excretory renal scans are used tool for detecting cortical scarring and func-
Additional information can be obtained by to distinguish upper urinary tract obstruction tional renal tissue, and estimating the differen-
combining ultrasound with contrast-enhanced from a dilated but non-obstructed collecting tial function of each kidney.
voiding urosonography to detect VUR. Ultra- system. Either isotopes, mercaptoacetyltri-
sound contrast media utilizing microbubbles glycine (MAG-3) or diethylenetriaminepen- Magnetic Resonance Urography
have gained approval in several countries. The taacetic acid, may be used with or without a Magnetic resonance urography (MRU) provides
latest advancement in ultrasound technology diuretic. MAG-3 is principally cleared from the high-resolution images of the whole urinary
includes duplex Doppler sonography, ampli- kidney by tubular secretion. It generates excel- tract and its surrounding structures with no
tude-coded colour Doppler sonography, three- lent images of both the parenchyma and the exposure to radiation. Its distinct advantages
dimensional ultrasound, and three-dimensional collecting system, thus enabling quantifica- include its three-dimensional reconstructive
ultrasound-based virtual cystoscopy. tion of their excretory function. MAG-3 is the capabilities and quantification of various renal
preferred agent for diuretic scans. functional indexes such as calyceal and renal
Micturating Cystography Guidelines have been formulated by the transit times, glomerular filtration rate and
Micturating cystography is an invasive proce- European Association of Nuclear Medicine to 49
differential renal functions. Nevertheless,

sophisticated computer software is essential infants with mild to moderate pyelectasis when of renal damage from infection and neglect.
for these advanced applications. followed up for 2 years. Therefore, it is impor- An antenatal consultation with a paediatric
MRU has been shown to be superior to tant to follow up even the mild and moderate urologist or surgeon may be the key to better
radionuclide studies in distinguishing between ANH postnatally with at least two ultrasound compliance.
pyelonephritis and scarring.52 It is especially examinations. By repeating the ultrasound,
informative for duplex system with minimal the predictability for significant uropathies CONCLUSION
functioning upper moiety. MRU, therefore, has has been shown to improve to a sensitivity of
the potential to replace ultrasound and renal 96%, specificity of 76%, positive predictive Over the past two decades, the natural history
radionuclide scintigraphy in the investigation value of 72%, and a negative predictive value of ANH has become better understood and
of ANH. The major impediment with MRU is of 97%. appreciated. Prenatal diagnosis has undoubt-
the excessively long image acquisition time However, for infants with moderate to edly improved the survival outcome and
and its extreme sensitivity to motion artifact. severe hydronephrosis, a more intense and reduced the morbidities of most congenital
This translates to the necessity of general sophisticated protocol must be employed, ie,
urological anomalies.
anaesthesia for neonates, infants and even urgent MCU followed by early diuretic renal
However, perfect and cost-effective
younger children. scan.54
management strategy guidelines derived
Conversely, dilatation detected in the
from evidence-based research are not yet
POSTNATAL IMAGING ALGO- second trimester but resolved by the third
available. Understandably, randomized trials
RITHMS FOR ANH trimester may still have a 12% risk of signifi-
in the realm of maternalfetal medicine and
cant anomalies. Therefore, parents should be
paediatrics are at best difficult if not impos-
Controversy still exists in the literature regard- advised on the possibility of late presentation
sible to develop and execute. Therefore,
ing the extent of postnatal imaging for mild of PUJO.
the next best option may be the setting up
ANH (SFU grades 1 and 2). We recommend Prophylactic use of antibiotics is not
of a collaborative registry on ANH between
the European Society of Paediatric Radiology universally agreed upon. Prenatal screening
regional centres and even countries.
imaging recommendations in paediatric urora- has been responsible for a drastic decrease in
diology37: two postnatal ultrasounds 4 weeks urinary tract infection, but occasional infection About the Authors
apart as screening. It has been shown by the still occurs. Dr Yap is Senior Consultant, Department of Paediatric
Surgery, KK Womens and Childrens Hospital, Singapore.
Brussels Free University Perinatal Nephrol- To ensure that antenatal detection and Associate Professor Jacobsen is Senior Consultant,
ogy Study Group that significant nephrou-
53
postnatal follow-up go hand in hand, all efforts Department of Paediatric Surgery, and Chairman, Divi-
sion of Surgery, KK Womens and Childrens Hospital,
ropathies were diagnosed in 39% of their 213 must be made to educate parents on the risk Singapore.
Acknowledgement
This paper was made possible through a collaboration between KK Womens and Childrens Hospital (KKH) and the Journal of Paedi-
atrics, Obstetrics and Gynaecology. KKH is the largest medical facility in Singapore which provides specialized care for women, babies
and children.
References
1. Scott JE, Wright B, Wilson G, et al. Measuring findings with infant outcome. Am J Obstet Gynecol 4. Mallik M, Watson AR. Antenatally detected urinary of systematic screening for minor degrees of fetal
the fetal kidney with ultrasonography. Br J Urol 1991;165:384388. tract abnormalities: more detection but less action. renal pelvis dilatation in an unselected population.
1995;76:769774. 3. Toiviainen-Salo S, Garel L, Grignon A, et al. Fetal Pediatr Nephrol 2008;23:897904. Am J Obstet Gynecol 2003;188:242246.
2. Corteville JE, Gray DL, Crane JP. Congenital hydronephrosis: is there hope for consensus? Pediatr 5. Ismaili K, Hall M, Donner C, et al; Brussels Free A complete list of references can be obtained upon
hydronephrosis: correlation of fetal ultrasonographic Radiol 2004;34:519529. University Perinatal Nephrology study group. Results request to the editor.

CME Questions
Program pendidikan kedokteran berkelanjutan ini dipersembahkan oleh Medical Progress Institute,
sebuah institusi yang didedikasikan untuk pembelajaran CME, bekerjasama dengan Ikatan Dokter
Indonesia.
Setelah membaca artikel Current Management of Antenatal HydronephrosisAn Update, jawab
pertanyaan berikut kemudian kirimkan dengan menggunakan formulir jawaban yang sudah disediakan ke
CME Medical Progress/ Journal of Paediatrics, Obstetrics & Gynaecology, untuk mendapatkan 2 SKP.
P
Artikel CME: 2 SK
Current Management of Antenatal HydronephrosisAn Update

Answer True or False to the questions below.Jawab pertanyaan di bawah ini dengan Benar
atau Salah
1. The APD system takes into account all of the distribution, degree of calyceal distension or parenchymal thickness.
2. The second-trimester APD has the highest positive predictive value in predicting postnatal uropathies.
3. The SFU grading system has been shown to have good intra-rater reliability but only modest inter-rater agreement.
4. It has been shown that ANH detected in early pregnancy may stabilize or even resolve completely.
5. The classical ultrasound findings of PUJO are calyceal and renal pelvis dilatation in the absence of a hydroureter.
6. Surgical intervention is recommended for patients with transient hydronephrosis.
7. The AUA panel recommends that MCU be performed for all infants with both mild and high-grade postnatal
hydronephrosis.
8. Ultrasound is an excellent screening tool for neonates with ANH and for the planning of subsequent postnatal
management.
9. MCU should not be offered to infants with postnatal pelvis dilatation of more than 7 mm in any one of two consecutive
postnatal ultrasound examinations performed 1 month apart.
10. It is important to follow up even the mild and moderate ANH postnatally with at least two ultrasound examinations.

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