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Gynaecology
and Reproductive
Medicine
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Philip N Baker FRCOG, FMedSci
Pro-Vice-Chancellor and Head of the College of Medicine, Biological Sciences and Psychology,
Dean of the School of Medicine, University of Leicester, UK
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Alec McEwan BA BM BCh MD MRCOG
Consultant in Fetal and Maternal Medicine, Department of Obstetrics and Gynaecology,
Queens Medical Centre, Nottingham, UK
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Sabaratnam Arulkumaran MBBS MD PhD FRCS (Ed) FRCOG
Professor of Obstetrics and Gynaecology,
Department of Obstetrics and Gynaecology,
St. Georges Hospital Medical School, London, UK
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Catherine Aiken MB/BChir MA PhD MRCP MRCOG
Specialist Registrar (ST5) and Academic Clinical Lecturer in Obstetrics and Gynaecology,
Addenbrookes Hospital, Cambridge, UK
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REVIEW
Antepartum haemorrhage
Nadia Amokrane
E R F Allen
Anna Watereld
Shreelata Datta
Abstract
Antepartum haemorrhage (APH) is bleeding from or into the genital
tract occurring between 24 0 weeks gestation until birth. It complicates 3e5% of pregnancies. The 2006e2008 report of the Condential
Enquiries into Maternal Deaths in the UK (CMACE) reported APH as
the cause of death in four women. The high prevalence of APH, and
its associated perinatal mortality and morbidity makes a thorough understanding of APH is essential for the practising obstetrician. The
objective of this review is to consider the most common causes of
APH (placenta praevia, placental abruption and local causes), together
with their management.
Causes of APH
Cervical and vaginal causes
A common cause of APH is bleeding from the cervix. A cervical
ectropion or erosion is where the columnar epithelium that
lines the cervical canal protrudes further onto vaginal surface of
the cervix. This is more common in pregnancy, and is thought to
be related to high oestrogen levels. The tissue of the ectropion is
very friable and contact bleeding can occur, usually at sexual
intercourse or even on passing hard stools. Ectropion can be
easily diagnosed on speculum examination of the cervix.
Cervicitis (inflammation or infection of the cervix) may be an
under-diagnosed cause of bleeding in pregnancy and may be
caused by sexually transmitted infections (STIs) such as chlamydia and gonorrhoea, which can present with abnormal vaginal
bleeding. A high vaginal swab and screening for STIs should be
undertaken. Treatment of STIs presenting in pregnancy is
important, as they can be associated with preterm labour and
neonatal morbidity. Bleeding or spotting can also occur from the
vagina and vulva secondary to non-sexually transmitted infections such as thrush, folliculitis, and from trauma.
Benign cervical polyps are a further cause of APH. If the
bleeding does not clinically compromise the mother or fetus, and
the polyp appears non-suspicious then these should not usually
be removed in pregnancy.
Cervical carcinoma presenting in pregnancy is uncommon
and a detailed history at booking appointment should assess a
womans smear history and history of previous cervical treatments. If a cervical carcinoma is suspected on assessment of the
cervix then urgent referral to colposcopy is indicated.
Introduction
Bleeding in pregnancy is a common reason for presentation to
labour wards, maternity triage units, GP surgeries and early
pregnancy centres in the UK.
The management of bleeding in pregnancy varies according to
gestation. In this review we specifically address antepartum
haemorrhage (APH) which is defined as bleeding from the genital
tract that occurs from viability onwards, defined here as greater
than 24 weeks gestation. Obstetricians may see women with
genital tract bleeding from 16 to 23 weeks gestation however
management of this group of women may differ.
APH and post-partum haemorrhage (PPH) are the leading
causes of maternal death worldwide. In the UK, maternal deaths
have continued to decrease. The recent MBRRACE-UK report
published in December 2014 showed that maternal mortality in
the UK had decreased from 11:100, 000 women between 2006
and 2008 to 10:10,000 between 2009 and 2012. Between 2009
and 2012, 17 mothers in the UK and Ireland died due to
Placental causes
Placental abruption: abruptio placenta is the premature separation of a normally sited placenta from the uterus. Placental
abruption can lead to maternal and fetal complications, and ultimately mortality. Bleeding occurs when the placenta starts to
separate from the decidua basalis. The presentation of placental
abruption usually includes pain (50%) and bleeding (70e80%)
however, a concealed abruption (20% of cases) can present with
no pain or bleeding. Premature labour is seen in nearly a third of
cases of abruption, however, the contraction pains may be
atypical in nature, with the patient describing severe unremitting
pain.
The incidence of placental abruption is reported between
0.26% and 0.80% in literature depending on the type of study
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and population. The biggest risk factor for abruption is a previous abruption with a 10-fold increased risk of abruption if there
has been an abruption in the previous pregnancy. The risk increases to nearly 25% if a woman has had two previous
abruptions.
Although there is no single aetiology for placental abruption, a
number of risk factors have been identified. These include hypertension and pre-eclampsia. Notably, when examining risk
factors in a control population, chronic hypertension has a
stronger association with abruption (OR 3.13) than preeclampsia (OR 1.73). Smoking is associated with a 90% increase in the risk of abruption. There is a three-fold increased
risk in pregnancies complicated by prolonged rupture of membranes (PROM). Cocaine use has also been linked to a higher rate
of placental abruption. However, despite numerous risk factors
and associations, abruption is usually an unexpected event and
the vast majority will occur in low risk pregnancies.
Placenta praevia, placenta accreta, increta and placenta percreta: placenta praevia is the insertion of the placenta partially or
entirely within the lower segment of the uterus after 32 weeks. If
the placenta does not cover the internal os then it is described as
a minor praevia and if it partially or fully covers the os then it is
classified as a major praevia. A morbidly adherent placenta such
as a placenta accreta, increta or percreta invades through the
decidua basalis. In placenta accreta the chorionic villi attach to
the myometrium. In placenta increta the placenta has invaded
into the myometrium; in placenta percreta the placenta invades
through the myometrium and breaches the uterine serosa.
Placenta percreta may then invade other organs such as the
bladder.
The incidence of low-lying placenta can be up to 28% at the
routine 20 week anomaly ultrasound scan, but the majority of
these will have migrated higher by the following scan, usually at
32 weeks or later. The incidence of true placenta praevia at term
is approximately 3%.
There are several hypotheses about the aetiology of placenta
praevia. One theory is that the position of the placenta depends
on the site of implantation of the discoid trophoblast when the
pregnancy is developing and from where the placenta will arise.
A further theory postulates that areas of deficient endometrium
from procedures such as caesarean sections, surgical management of miscarriage and myomectomies may affect how the
placenta attaches in these cases.
The risk factors for placenta praevia include multiparity,
increasing maternal age, smoking, previous praevia and surgical
procedures that may result in deficient endometrium (Table 1).
The number of previous Caesarean sections also increases the
risk of placenta praevia.
In well-resourced settings such as in the UK, the majority of
placenta praevia cases may be picked up on ultrasound scan at
20 weeks. Currently the UK National Screening Committee does
not recommend screening for placenta praevia however, alongside the RCOG, they support most local practice of identifying
women by ultrasound whose placenta lies near the internal os at
the routine 20 week scan. Evidence shows that at the second
trimester scan about 26e60% of women with a low lying
placenta on abdominal ultrasound would be reclassified with a
more accurate transvaginal scan. There have been no reports to
Other causes
Uterine rupture: uterine rupture is a rare event that is defined as
loss of the full thickness of the uterine wall integrity. It usually
occurs during labour in a woman with a previous Caesarean
section or myomectomy. Within this group the risk is still small;
the incidence of uterine rupture has been estimated at 7 per
10,000 planned vaginal births after Caesarean section. Uterine
rupture may present with CTG abnormalities, pain or APH. Early
recognition and quick stabilisation of the mother and baby is
required as mortality and morbidity is high.
Unexplained APH
Some women will present with bleeding that cannot be attributed
to any of the above causes. The RCOG Greentop Guideline references a number of studies over the last four decades that
demonstrate that pregnancies with unexplained APH are at
higher risk of preterm birth and stillbirth. A recent retrospective,
observational study noted that pregnancies complicated by APH
of unknown aetiology are at a higher risk of preterm birth, lower
birthweight, induction of labour, and neonatal unit admissions.
Repeated presentations with unexplained APH in pregnancy
should raise suspicion and the pregnancy should be monitored as
high risk, with the need for additional ultrasound scans for fetal
growth.
Healthcare providers should be aware that maternal trauma,
including domestic violence, can result in APH, possibly from
placental abruption. A third of domestic violence is known to
start or escalate in pregnancy. A retrospective study of 2070
women subjected to physical violence in pregnancy found an
increased odds ratio of APH in this cohort, compared with controls, of 3.79 (95% CI 1.38e10.40). Women who present with
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multidisciplinary team including a senior obstetrician, anaesthetist, and senior midwife. Input is also frequently required
from blood transfusion technicians, haematologists, neonatologists, and porters. Obstetric units will usually have fixed
protocols for the management of massive obstetric haemorrhage
that should be activated if a woman presents with or develops
massive haemorrhage. These protocols should be actively
rehearsed in annual skills training in order to prepare for such
cases.
The RCOG Greentop Guideline defines the severity of APH, as
outlined in Table 2. However, it should be remembered that the
amount of blood lost can be underestimated, particularly as the
amount of blood seen on vaginal examination may not be an
accurate representation of the total blood lost.
The initial assessment of a woman with APH should include
the ABC approach to stabilise the patient (Table 3) and assess the
total estimated blood loss. However, it is important to remember
that not all blood loss is revealed, so the clinical features of blood
loss are extremely important (e.g. grade of shock) to formulating
appropriate management plans.
Patients with major or massive obstetric haemorrhage should
be managed in left lateral tilt to reduce hypotension secondary to
uterine compression of the inferior vena cava. Resuscitation and
stabilization of the mother is the key priority. Following the
initial survey and after commencing resuscitation, the cause and
extent of the APH should be assessed by history taking and
carrying out a full examination.
Abdominal examination may illicit a woody or tense uterus,
which is characteristically seen in placental abruption or it may
show the patient is contracting and could be in labour. If a patient with known placenta praevia presents with bleeding, then a
digital examination or speculum examination is not necessary. A
digital examination or speculum may be indicated where
placenta praevia has been excluded to check for a cause for the
APH and to assess cervical dilatation. The diagnosis of vasa
praevia should be considered when the APH has been associated
with rupture of membranes.
Placental abruption
Vasa praevia
Uterine rupture
Uterine rupture
Table 1
Investigations
The RCOG guideline recommends that all patients with APH
should have a full blood count (FBC) and a group and save. A
Kleihauer test is also necessary for all Rhesus negative women.
Women who present with major or massive haemorrhage should
also have liver and renal function blood tests and a coagulation
screen including fibrinogen. They also may benefit from a
bedside blood check such as a Hemacue since the FBC may not
give an accurate immediate estimate of blood loss.
Blood volume
Spotting
Minor haemorrhage
Major haemorrhage
Massive haemorrhage
Table 2
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C(irculation)
D(isabilty)
E(xposure)
F(etus)
Management
Check patency
Respiratory rate
Oxygen saturations
10e15L via non rebreathing mask
Heart rate
Capillary refill time
Blood pressure
IV access (consider x 2 16 gauge cannulas)
IV fluid resuscitation crystalloid/colloid/blood
Assess blood loss
Consider catheterisation (input/output monitoring)
Glasgow coma score
Abdominal examination
Speculum
Vaginal examination
CTG
Auscultation FHR
Ultrasound
Table 3
be hospitalised until elective delivery although there is no evidence to support this. In accordance with the RCOG Green-top
guideline, women with placenta praevia in the third trimester
should be counselled about the risks of preterm delivery and
obstetric haemorrhage. The place and package of care should be
individualised to meet the needs of each patient. If care is at
home, the woman should be within close proximity to the hospital, have a constant companion at home, and be aware of when
she should attend hospital immediately.
Blood products
Managing severe antepartum haemorrhage frequently requires
blood transfusion and considering delivery with surgical interventions to arrest the bleeding. If women require blood
transfusion then individually cross-matched blood is ideal.
Rarely, if blood loss is so excessive that the processing time for
this would be clinically unacceptable then Group O Rhesus
negative red cells should be utilised. Commencing red cell
transfusion is based on clinical evaluation and haematological
investigations, if available. If a coagulopathy develops then fresh
frozen plasma (FFP) should be administered before one blood
volume is lost. Haematological investigation and specialist
advice should guide the further use of FFP, cryoprecipitate, and
platelets in massive obstetric haemorrhage. The RCOG Green-top
guideline on blood transfusion in obstetrics advises that cryoprecipitate may be indicated when there is bleeding with
fibrinogen concentration below 1 g/L. The platelet count should
be maintained at above 75 109/L.
It is important that women who will refuse blood products in
an emergency, including Jehovahs witnesses, are identified in
the antenatal period and referred to consultant-led care. These
women are at higher risk of morbidity and mortality in the case
of APH. The healthcare provider and patient should discuss what
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Conclusion
APH can be a traumatic and concerning event for women in
pregnancy. Early recognition and management is therefore vital,
together with a relevant postnatal debrief. The MBRRACE-UK
report highlights that haemorrhage is still a significant contributor to UK maternal morbidity and mortality. Therefore, local
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Twin pregnancy
Emma Long
Emma Ferriman
Time of cleavage
after fertilization
Nature of membranes
Abstract
0e3 days
4e8 days
9e12 days
13 days or more
Twins account for 2e3% of all births. They carry signicant risks to
both mothers and babies. These risks include preterm delivery, intrauterine growth restriction, and pre-eclampsia. In addition, monochorionic gestations confer an even higher rate of perinatal morbidity
and mortality arising from a shared placenta due to placental anastamoses, which may lead to twin-to-twin transfusion syndrome (TTTS). It
is essential that chorionicity is established in the rst trimester in order
to initiate the appropriate antenatal management and surveillance. In
view of the high risk of both maternal and fetal complications, twin
pregnancies are ideally managed in a dedicated clinic according to
agreed protocols with both obstetric, midwifery and neonatal input.
Table 1a
Introduction
Twin pregnancies account for approximately 3% of all live
births, but account for 6.3% of stillbirths and 12.7% of neonatal
deaths. Twins are more at risk of pregnancy complications
(Table 1). Monozygotic twin frequency rates remain relatively
stable worldwide at 3e5/1000 maternities, but dizygotic twins
have a variable rate depending on a number of factors including
geographical location, assisted reproductive techniques and
increasing maternal age. Rates vary from 1.3 to 49/1000 maternities. Monochorionic twin gestations are associated with even
higher perinatal risk. Multiple pregnancies have been described
as a modern epidemic and carry considerable resource implications for health providers. In order to reduce the numbers of twin
pregnancies conceived as a result of assisted conception techniques, a number of strategies have been proposed such as
elective single embryo transfer, selective fetal reduction and
single blastocyst transfer.
Miscarriage
11e23 weeks
Perinatal death
IUGR
Preterm delivery
<32 weeks
Major defects
Singleton
Dichorionic
Monochorionic
1%
2%
10%
0.5%
5%
1%
1.5%
20%
5%
3%
30%
10%
1%
1%
4%
Table 1b
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DIZYGOTIC
(non-identical)
MONOCHORIONIC
DICHORIONIC
Figure 1
the nuchal translucency combined with first trimester measurements of (pregnancy associated plasma protein A (PAPP-A)
and human chorionic gonadotrophin (HCG). The detection rate
variesdepending on the chorionicity of the pregnancy: in monochorionic twins the detection rate should be the same as for
singletons (75e80% with a 3% false positive rate), however, in
dichorionic twins where one baby is affected with aneuploidy,
the detection rate may fall between 40 and 50% with a 3% false
positive rate. Detection rates can be improved further using
additional ultrasound markers such as the presence of the nasal
bone and ductus venosus and tricuspid Doppler waveform analyses. Additional biochemical markers, alpha-fetoprotein (AFP)
and oestriol (uE3), can increase the detection rate further (up to
87%). For women who present beyond 14 weeks the quadruple
test may be offered up to 20 weeks gestation.
Finally the advent of non invasive prenatal testing (NIPT)
offers a further choice in screening with detection rates between
98 and 99% and false positive rates of <0.4%.
Following detection of an increased nuchal translucency, the
option of invasive testing should be discussed. Both amniocentesis
and CVS are possible in twin pregnancy, but these procedures
should be performed in a specialist fetal medicine unit, ideally by
the same specialist, to ensure that the pregnancy is mapped
correctly. The risks of miscarriage and other procedure-related
complications are quoted as around 1 in 50 in twin pregnancies.
Both amniocentesis and chorionic villus sampling are valid options, but there is some evidence to suggest that a double amniocentesis has a lower risk of sampling the same fetus.
Anomaly screening
The frequency of fetal abnormality in dizygotic twins is comparable to that of singleton pregnancies (2e3%). This contrasts
with the increased frequency of anomalies seen in monozygotic
pregnancies where rates of up to 10% have been reported, or 2
e3 times those which occur in dizygotic twinning. Several
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a single puncture but in cases of discordant anomaly, both fetuses should be sampled.
Selective feticide of the affected fetus is only possible in
dichorionic twin pairs due to their separate inter-twin circulations. It is associated with an increased risk of pregnancy loss,
and if not performed in the first trimester, is usually delayed until
the third trimester when viability of the normal twin is more
certain. This must be balanced against the risk of spontaneous
premature labour, especially in cases complicated by polyhydramnios such as anencephaly.
Figure 2 Shows the enlarged bladder of the recipient twin with polyhydramnios in twin to twin transfusion syndrome.
Diagnosis of TTTS
Most commonly, the diagnosis of TTTS is made in the second
trimester following the detection of discordant growth or
discrepant liquor volumes. A stuck twin may be visible, compressed against the uterine wall, where the donor is constricted
by anhydramnios and the tense sac of the polyhydramniotic cotwin. A discrepancy in nuchal translucency measurement in the
first trimester is also said to be an early marker for TTTS. Acute
TTTS may present as sudden onset of maternal discomfort and
increasing girth, following rapid development of polyhydramnios. Mortality is extremely high usually as a consequence of premature delivery, either spontaneous or iatrogenic.
A diagnostic staging system proposed by Quintero describes a
progression from early (stage I) to late (stage V) disease
(Table 2). High stage at diagnosis is associated with increased
neurological morbidity and mortality, but progression of disease
from early to more advanced stage is also important for prognosis. Uncertainty exists regarding the optimum management of
early (stage I) disease, where there is some evidence that
aggressive treatment may confer little benefit.
Management options
Several management options exist for the treatment of TTTS,
including laser ablation of the communicating placental vessels,
serial amnioreduction with or without septostomy, and occlusive
feticide. It may be appropriate to consider conservative or
expectant management, or to offer a termination of pregnancy if
the fetuses are extremely premature or severely compromised.
Pathophysiology
Both superficial and deep placental vascular connections are
present in the monochorionic placenta. Deep anastomoses occur
between arteries and veins. These arteriovenous (AV)
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II
Conjoined twins
Incomplete division of the embryo may result in conjoined twins.
Classification of this anomaly is largely descriptive and dependent on the anatomical areas joined. Conjoined thorax (thoracopagus) and conjoined thorax and abdomen (thoracoomphalopagus) are the commonest subtypes with pelvis and
head (ischiopagus and craniopagus) being less common.
With the advent of improved ultrasound techniques, most
cases are identified in the first trimester, and in view of the significant mortality and morbidity, a significant number of parents
will opt for termination. Survival depends on the organs joined.
50% are stillborn and of the survivors up to 75% may have
inoperable defects. Elective delivery is usually advocated, but
there are reports of vaginal deliveries occurring.
III
IV
V
Table 2
Antenatal management
Women with twin pregnancies should be given the same advice
about diet, lifestyle and nutritional supplements as in routine
standard care. There is a higher incidence of anaemia in women
with twin pregnancies therefore a full blood count should be
performed at 20e24 weeks to identify women who need supplementation of iron or folic acid. This should then be repeated at
28 weeks as in routine antenatal care.
It is vital to offer antenatal care in an appropriate setting
aiming to provide standardised care to all women with multiple
pregnancies. Clinical care for women with twin pregnancies
should be provided by a nominated multidisciplinary team consisting of named specialist obstetricians, specialist midwives and
ultrasonographers, all of whom have experience and knowledge
of managing twin pregnancies. In addition, women should have
access to a perinatal mental health specialist, womens health
physiotherapist, an infant feeding specialist and a dietician. A
dedicated clinic allows the close surveillance required by this
population along with the specialised care they may need in
terms of preparation for birth and psychological support.
Mothers with twin pregnancies are at higher risk of all obstetric
complications and should be counselled appropriately (Table 3).
In general, maternal mortality associated with multiple births is
2.5 times higher than singleton births.
NICE and the RCOG consensus document has recommended
two distinct care pathways for monochorionic and dichorionic
twins (Table 4).
Preterm birth
Twin pregnancies are at higher risk of spontaneous or iatrogenic
preterm delivery. The incidence of preterm delivery prior to 37
weeks can be up to 50%. Delivery at less than 32 weeks appears
to vary with the type of twinning, ranging from 5% for DC and
10% for MC twins compared with 1% for singleton pregnancies.
Recent evidence suggests that progesterone supplementation
does not prevent early preterm labour in twin pregnancies and
the use of untargeted single or multiple courses of corticosteroids
is not recommended.
Hypertension
Women with twin pregnancies may be at higher risk of hypertension. NICE suggest that women with multiple pregnancies
Stage
Table 3
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Delivery
NICE guidance recommends delivery from 37 0 weeks gestation for dichorionic twins and from 36 0 weeks gestations for
monochorionic diamniotic twins, but marked variability in policy
exists in practice. There is growing evidence that perinatal
mortality rates increase after 38 weeks even in uncomplicated
twin pregnancies. Additionally, intervention at 37 weeks does
not appear to be associated with a significant difference in mode
of delivery or maternal complications when compared to
expectant management. For women declining delivery, weekly
monitoring should occur.
Retrospective cohort data suggested that, when compared to
the presenting twin, the second twin is at higher risk of intrapartum mortality due to the complications of vaginal delivery.
However, the publication of the Twin Birth Study in 2013 has
refuted this. The study was a large, prospective, randomized,
controlled trial comparing planned Caesarean section to planned
vaginal birth for twins delivered between 32 and 38 weeks
gestation where the presenting twin was cephalic. It found that
planned Caesarean section did not reduce the risk of fetal or
neonatal death or serious neonatal morbidity when compared
with planned vaginal delivery. There was a higher risk of adverse
perinatal outcomes for the second twin, but this was not reduced
Scans
Delivery
From 37 0 weeks.
Consider steroids for elective caesarean
sections
Table 4
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Conclusions
Multiple pregnancy is a common cause of morbidity for both
mothers and babies. Antenatal care focuses on screening for
anomalies and for early signs of complications such as growth
restriction and TTTS. Accurate diagnosis of chorionicity in the
first trimester is essential, and allows appropriate surveillance to
be planned. Following the results of the Twin birth study there is
no evidence to support a policy of elective Caesarean section for
all twins. Current practice in the UK would be to support vaginal
delivery in uncomplicated dichorionic twins in which the first
baby has a cephalic presentation. For monochorionic twins, this
practice is less clear-cut due to the incidence of acute twin-totwin transfusion occurring in labour (up to 10%).
A
Acknowledgements
Acknowledgements for Dr Kelly Cohen, Dr Medha Rathod and Dr
Elizabeth Bonney, Consultants at The Leeds Teaching Hospitals NHS
Trust.
Practice points
FURTHER READING
Bajoria R, Kingdom J. The case for routine determination of chorionicity and zygosity in multiple pregnancy. Prenat Diagn 1997 Dec;
17: 1207e25.
Barrett Jon FR, Hannah ME, Hutton EK, et al. A randomized trial of
planned Cesarean or vaginal delivery for twin pregnancy. N Engl J
Med 2013; 369: 1295e305.
Fisk NM, Duncombe GJ, Sullivan MH. The basic and clinical science of
twin-twin transfusion syndrome. Placenta 2009 May; 30: 379e90.
Management of monochorionic twin pregnancy. RCOG Green-top
Guideline No. 51 December 2008.
MBRRACE-UK: Perinatal Mortality Surveillance Report: UK Perinatal
deaths for births from January to December 2013. Published June
2015.
Multiple pregnancy: the management of twin and triplet pregnancies in
the antenatal period. National Institute for Health and Clinical
Excellence clinical guideline no 129 (Sept 2011).
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Self-assessment
MCQs
1. With regard to twin pregnancies
a. They account for 3% of all live births
d. Rates of dizygotic twinning are affected by assisted conception techniques, geographical area and primigravid pregnancy
e. The rate of major congenital abnormality is 4 higher in dichorionic twins than in singletons
e. NIPT has a low detection rate and a high false positive rate in twins
d. The Cochrane Collaboration found that survivors of TTTS treated with laser had long term neurological sequelae in 40% of cases F
e. Following the death of a monochorionic co-twin the risk of cerebral palsy is in the order of 15%
4. In monoamniotic twins
a. Cord entanglement is universally seen
d. Vaginal delivery is a safe option when the first twin is a non-cephalic presentation
e. Delayed delivery beyond 38 weeks does not require additional fetal monitoring
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Renal disease in
pregnancy
Matt Hall
Nigel J Brunskill
Abstract
Pregnancy in women with chronic kidney disease (CKD) is associated
with risks of accelerated decline in renal function in the mother and
adverse outcomes for the infant, including prematurity and growth restriction. Managing these risks requires collaboration between patient,
nephrologist, neonatologist and obstetrician. In this review we will
discuss approaches to managing pregnancy in women with CKD.
Introduction
Chronic kidney disease (CKD) is defined as abnormalities in
serum biochemistry, urinary constituents (blood and/or protein)
or renal structure that are present for 3 months or more. The
Kidney Disease Improving Global Outcomes (KDIGO) classification of CKD divides CKD into five stages dependent on the estimated glomerular filtration rate (eGFR, Table 1).
CKD whilst rare in pregnancy, affecting 0.15% of pregnancies,
is encountered with increasing frequency. However, most
affected women have early CKD, stages 1 to 3a, with eGFR >45
ml/minute. Pregnancy may be the first time that blood pressure
and urinalysis are performed for some women and hypertension,
proteinuria or haematuria detected at booking may uncover
previously undiagnosed CKD. The development of hypertension
and urinary dipstick abnormalities later in pregnancy may be a
manifestation of CKD, but more commonly represents preeclampsia. Chronic pyelonephritis is the commonest known
aetiology of CKD in pregnant women (Figure 1).
Proteinuria: proteinuria is an independent predictor of progressive renal failure in patients with CKD and a diagnostic marker of
pre-eclampsia in pregnancy. Traditionally, protein excretion is
quantified by measurement in a 24 hour collection of urine. This
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The Kidney Disease Improving Global Outcomes (KDIGO) classification of chronic kidney disease
CKD stage
Estimated GFR
Comment
G1
G2
G3
90 ml/minute
60e89 ml/minute
30e59 ml/minute
G4
G5
15e29 ml/minute
<15 ml/minute or on dialysis
Table 1
is inconvenient for the patient and collections are often incomplete. Nevertheless, if performed correctly, this remains the most
accurate method available.
In contemporary nephrology practice and obstetric medicine,
the urine protein:creatinine ratio (PCR) or albumin:creatinine
ratio (ACR) are accepted as surrogates for 24 hour urine collections for protein estimation. Assuming steady production and
excretion of creatinine, this method corrects for variations in
urine concentration and correlates closely with complete 24 hour
urine collection data, including in pregnant patients with CKD.
Thus PCR or ACR can be used for quantitative monitoring of
proteinuria during pregnancy.
Fetal outcomes
Adverse fetal outcomes (preterm delivery, SGA, neonatal intensive care admission, persistent congenital disability or death)
Percentage
20
15
10
5
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Figure 1
47
REVIEW
Maternal outcomes
Adverse maternal outcomes for women with CKD include preeclampsia, transient decline in renal function, persistent loss of
renal function, requirement for dialysis and death. As with fetal
outcomes, risks can be stratified according to baseline maternal
renal function, blood pressure control, proteinuria and aetiology
of renal disease.
Pre-eclampsia: the risk of developing pre-eclampsia for mothers
with CKD is greatly increased compared to the general population, and increases with worsening renal function; 20% for patients with mild renal dysfunction (serum creatinine <125 mmol/
litre) and 60e80% with severe impairment (serum creatinine
>180 mmol/litre), compared to approximately 5% in the general
population. These estimates vary between studies as a result of
heterogeneity in study cohorts and variations in diagnostic
criteria used. CKD is commonly associated with proteinuria and
hypertension prior to conception and the diagnosis of superimposed pre-eclampsia relies on arbitrary increases in these
parameters with or without additional clinical features of preeclampsia (Box 1).
Renal function: decline in renal function during pregnancy occurs rarely in patients with mild renal impairment at baseline
(serum creatinine <125 mmol/litre) and often reflects an episode
Box 1
48
REVIEW
Women with a history of recurrent UTI or structural abnormalities should submit a urine sample for culture every month
irrespective of symptoms to identify asymptomatic bacteriuria.
A renal ultrasound is required during pregnancy if:
there is a sudden decline in renal function
there are signs or symptoms suggestive of urinary tract
obstruction or renal stone disease.
As above, mild pelvicalyceal dilatation is commonly identified
during normal pregnancy. Functional ureteric obstruction should
only be suspected if there is progressive dilatation on serial renal
ultrasound scans, suggestive signs and symptoms or obstruction,
or worsening renal function.
Investigations e suspected new diagnosis of CKD: renal disease may be discovered for the first time during pregnancy and
should be suspected in women with any, or combinations of,
hypertension, proteinuria and haematuria identified at booking
or in early pregnancy.
A renal ultrasound is helpful to characterise the aetiology and
chronicity of CKD. Large kidneys on ultrasound may reflect polycystic kidney disease, diabetic nephropathy or chronic urinary tract
obstruction. Focal scarring of kidneys may represent a congenital
abnormality of the kidney and urinary tract (CAKUT) in the mother,
most commonly vesicoureteric reflux. Small kidneys are a nonspecific finding in CKD and further diagnosis may be difficult.
Immunological investigations should be requested if there is
suspicion of intrinsic renal disease e haematuria, proteinuria,
decreased renal function and/or hypertension (Table 2). Aetiology
of intrinsic renal disease may be confirmed by renal biopsy and can
be performed during pregnancy, but should be reserved for:
unexplained decline in kidney function in CKD or acute
kidney injury
newly diagnosed nephrotic syndrome
features suggestive of systemic disease or vasculitis.
A renal biopsy is not indicated to investigate stable CKD, nonnephrotic range proteinuria or pre-eclampsia, or after 32
weeks gestation when the pregnancy should be brought to an end
prior to invasive renal investigations.
Management
Preconception counselling: ideally, all patients with CKD
should be offered counselling prior to conception in order to
evaluate and discuss the risks of proceeding with pregnancy and
the likely outcomes. Medications known to be harmful to the
developing fetus can be discontinued or substituted for safer alternatives (see Tables 3 and 4 below).
Patients with active lupus nephritis or vasculitis, and those
with poorly controlled blood pressure should be advised to wait
until these are optimised before trying to conceive. Similarly,
patients with significant renal dysfunction (serum creatinine
>180 mmol/litre) may not accept the risks associated with proceeding with pregnancy and may be better advised to wait until
they have received a renal transplant (see below).
In the majority of cases, patients need not be discouraged
from trying to conceive as long as the potential risks are understood and the pregnancy is closely monitored.
Investigations e pre-existing CKD: if preconception results are
unavailable, serum creatinine, and either urine PCR/ACR or 24
hour urine collection should be performed early in pregnancy to
determine baseline renal function and urine protein excretion.
Patients should have the following recorded at every subsequent visit:
blood pressure
urine dipstick
urine PCR or ACR, and/or urine culture, if dipstick
positive.
Depending on the level of renal function at baseline the
following should be measured every 6e8 weeks during
pregnancy:
serum creatinine and urea
haemoglobin.
More frequent measurement is required if renal function is
abnormal or deteriorating. Serum ferritin, folate and vitamin B12
should be measured if anaemia is identified; serum albumin,
calcium and vitamin D are indicated in women with heavy proteinuria (PCR >100 mg/mmol) or advanced renal dysfunction
(creatinine >180 mmol/litre).
49
REVIEW
Comments
Associated with connective tissue diseases and SLE. Antibodies against double-stranded DNA (antidsDNA) and extractable nuclear antigens (ENA) should be performed if positive.
Associated with small vessel vasculitis (Churg Strauss disease, granulomatosis with polyangiitis and
microscopic polyangiitis).
Decreased levels are found in active SLE, post-infectious glomerulonephritis, mesangiocapillary
glomerulonephritis, subacute bacterial endocarditis, cryoglobulinaemia and heavy chain-deposition
disease.
Rheumatoid factor, cryoglobulins and C3 nephritic factor measurement may be indicated.
Other tests
Table 2
Venous thromboembolism prophylaxis: pregnancy is a prothrombotic state and this is exacerbated by heavy proteinuria.
Consensus opinion recommends that patients with nephrotic
syndrome should receive prophylactic LMWH during pregnancy
and until 6 weeks post-partum. There is less evidence to support
LMWH prophylaxis for women with heavy proteinuria but
without nephrotic syndrome, or more modest proteinuria.
Nevertheless, many practitioners encourage the use of LMWH
Rarely used
Contraindicated
Nifedipine
Labetalol
Methyldopa
Hydralazine
Beta-blockers
Alpha-blockers
Amlodipine
Verapamil
ACE inhibitors
Angiotensin receptor blockers
Aliskiren
Spironolactone
Moxonidine
Minoxidil (3rd trimester)
Thiazide diuretics
Diltiazem
Likely to be harmful
Anti-thymocyte globulin Rituximab
Contraindicated
Mycophenolate
Sirolimus
Methotrexate
Immunosuppressants
Likely to be safe
Prednisolone
Azathioprine
Ciclosporin
Tacrolimus
ACE, angiotensin converting enzyme.
Table 3
50
REVIEW
Likely to be harmful
Contraindicated
Hydralazine
Nifedipine
Methyldopa
Most beta-blockers
Furosemide
Thiazide diuretics
Minoxidil
Immunosuppressants
Likely to be safe
Prednisolone
Azathioprine
Aliskiren
Most ACE inhibitors
Angiotensin receptor blockers
Likely to be harmful
Mycophenolate
Ciclosporin
Tacrolimus
Anti-thymocyte globulin
Contraindicated
Sirolimus
Rituximab
Methotrexate
Table 4
five to seven times a week. This is feasible for patients on haemodialysis at home but might not be practical for patients dialysing in units.
Management on dialysis
Intensive dialysis and fluid removal can accentuate the haemodynamic changes in pregnancy causing blood pressure instability
and hypotension. However, many dialysis patients have treated
chronic hypertension prior to conception, and medication may
need to be reduced to maintain a diastolic blood pressure
>80 mmHg. Lower blood pressure may contribute to IUGR. Later
in pregnancy blood pressure may rise due to pre-eclampsia
51
REVIEW
Relative indications
Refractory hyperkalaemia
Refractory fluid overload
Refractory metabolic acidosis
Severe uraemia causing
encephalopathy or pericarditis
Table 5
Practice points
C
FURTHER READING
Davison JM, Nelson-Piercy C, Kehoe S, Baker P, eds. Renal disease in
pregnancy. London: RCOG Press, 2008.
Gammill HS, Jeyabalan A. Acute renal failure in pregnancy. Crit Care
Med 2005; 33: S372e84.
McKay DB, Josephson MA. Pregnancy in recipients of solid organs e
effects on mother and child. N Engl J Med 2006; 354: 1281e93.
Williams D, Davison J. Chronic kidney disease in pregnancy. BMJ
2008; 336: 211e5.
52
CASE-BASED LEARNING
Ultrasound in antenatal
diagnosis of structural
abnormalities
Abstract
Prenatal diagnosis commenced in the 1980s as part of routine antenatal care. Since then, the technical improvements and standardization of routine antenatal screening around the country have led to
reliable diagnosis for fetal abnormalities, allowing for appropriate management strategies to be offered in a timely fashion. The National
Screening Committee Fetal Anomaly Screening Program (FASP) recommends screening for eleven fetal conditions with a detection rate
of more than 50%. To achieve uniformity in prenatal diagnosis, this
committee has established a series of routine views, measurements
and images that should be obtained and stored during the anomaly
scan. In this article we will present some of the most common structural abnormalities through a series of case presentations.
Introduction
Ultrasound was introduced in the 1980s in the UK as part of
routine antenatal care. However, uniformity on the timing and
requirements of routine ultrasound scanning has only been
standardized recently across the country. Obstetric ultrasound
has advanced rapidly since its inception, which has aided earlier
and better diagnosis of fetal abnormalities.
Currently, there are two routine ultrasound examinations
offered to all pregnant women, each with different aims. The first
trimester ultrasound is performed between 11 and 14 weeks of
gestational age; its primary objectives are to confirm viability,
date the pregnancy accurately according to the crown-rump
length (CRL) and offer screening for common chromosomal abnormalities. The technological advances of ultrasound have
improved resolution and capabilities to such an extent that has
changed our understanding and ability to visualize early fetal
anatomy. In doing so, structural abnormalities are being detected
at an earlier stage, allowing for early counselling and intervention when required. The second ultrasound scan is performed
between 18 and 21 weeks. The purpose of this scan is to identify
major fetal structural abnormalities. The National Screening
Ana Pinas Carrillo LMS CCT Ob/Gyn (Spain) DipFM (UK) is a Consultant
Obstetrician at St. Georges University Hospitals NHS Foundation
Trust, London, UK. Conicts of interest: none declared.
53
CASE-BASED LEARNING
Detection rate
Anencephaly
Open spina bifida
Cleft lip
Diaphragmatic hernia
Gastroschisis
Exomphalos
Major cardiac abnormalities
Bilateral renal agenesis
Lethal skeletal dysplasia
Edwards syndrome (T18)
Pataus syndrome (T13)
98%
90%
75%
60%
98%
80%
50%
84%
60%
95%
95%
Table 1
54
CASE-BASED LEARNING
55
CASE-BASED LEARNING
Case 4: exomphalos
A 30 year-old woman in her second pregnancy attended for the
routine first trimester scan. Her previous pregnancy was uneventful and she reported no pre-existing medical problems. The
pregnancy was dated at 13 3 weeks according to the CRL and
the nuchal translucency was 2.2 mm (<95th centile). During the
examination of fetal anatomy, a herniation in the abdominal wall
was noted with clear visualization of bowel being covered by a
membrane. She was referred to a Fetal Medicine unit. The finding
of bowel covered by peritoneum and amnion was confirmed and
56
CASE-BASED LEARNING
5 weeks and the risk was low (1 in 3200). During the anomaly
scan, the fetal stomach remained small in size throughout the
examination. Amniotic fluid was normal. No other abnormalities
were detected. She was referred to the Fetal Medicine Unit to
assess the fetal stomach. The stomach was clearly visualized,
although of small size. A unilateral cleft lip was noted on the left
side. On detailed examination, a cleft palate was also noted
(Figure 6). No other structural abnormalities were diagnosed at
this point.
Cleft lip (CL) is the most common facial abnormality. It can
be isolated or associated with a cleft palate (CL/P). Detection
of a cleft of the alveolar ridge is relatively easy, but visualizing
clefts of the hard palate can be notoriously difficult. A cleft in
the alveolar ridge is most often associated with cleft of the hard
palate. The presence of a cleft palate (CP) without a cleft lip is
a separate entity with a different embryological origin. The
incidence of CL/P varies according to the ethnicity. It is higher
in Asian population, 1.5e2 per 1000, lowest in Africans, 0.5
per 1000, and around 1 per 1000 in a white population. However, the incidence of cleft palate alone is similar in all ethnicities. Approximately, 50% of the cases have a combined
cleft lip and palate, 20% isolated cleft lip and 30% isolated cleft
palate. The two first entities are more common in males
whereas the latter is more common in females. It can be unilateral or bilateral, with the unilateral left sided cleft lip the
most common finding. An isolated cleft palate is more difficult
to diagnose.
The presence of a CL/P has been related to rubella infection,
drugs such as antiepileptics, retinoic acid, thalidomide, steroids
and alcohol. A family history is not infrequent.
Prenatal diagnosis is important because of the association
with other anomalies. 18% form part of a syndrome or sequence.
It is associated with at least 100 different syndrome, including
EEC (ectrodactyly, ectodermal dysplasia, clefting syndrome),
Opitz syndrome, Meckels syndrome, Roberts syndrome, Apert
syndrome and Treacher-Collins syndrome, amongst others.
Invasive testing should be offered as up to 10% of CL/P will
have an underlying aneuploidy such as trisomy 13 or 18. This
likelihood of a chromosomal abnormality is much lower in the
absence of other structural abnormalities.
As part of the work-up, the mother was offered an amniocentesis, which showed a normal karyotype. After excluding
other structural abnormalities and chromosomal defects, the
mother was reassured and counselled about the postnatal management. Information about the surgical repair and the possible
feeding problems at birth was provided and follow up scans to
assess fetal growth and amniotic fluid were performed. In these
cases, 3D ultrasound may be useful to assess the degree of the
defect and to prepare the parents for the postnatal appearance of
the defect. They were also informed of the risk of recurrence,
which is approximately 4e7% in cases of combined cleft lip and
palate.
A
In this particular case, there were no other structural abnormalities seen, but invasive testing for karyotyping was offered
due to the strong association with trisomies (40%). The patient
opted to have a chorionic villus sampling and the results (both
karyotype and CGH-array) were normal. The couple opted to
continue the pregnancy and she had a routine anomaly scan at 21
weeks that confirmed the findings of an isolated large exomphalos containing bowel and liver. They were offered serial scans
to ensure appropriate growth and to exclude polyhydramnios
and bowel dilatation.
An appointment with the paediatric surgeons was organized
to discuss postnatal management. Serial growth scans showed
adequate growth, normal Dopplers and normal amniotic fluid
volume.
FURTHER READING
Coady AM, Bower S. Twinings textbook of fetal abnormalities. 3rd edn.
Churchill Livingstone Elsevier, 2014. ISBN: 978-0-7020-4591-2.
Nyberg D. Diagnostic imaging of fetal anomalies. 2nd edn. Lippincott
Williams and Wilkins, 2002. ISBN: 9780781732116.
Figure 6 Cleft lip. The arrow points the unilateral defect on the right
side.
57
CASE-BASED LEARNING
Practice points
C
58
ETHICS/EDUCATION
Designer babies
Ronald T K Pang
P C Ho
Abstract
Designer babies are either created from an embryo selected by preimplantation genetic diagnosis (PGD) or genetically modied in order to inuence the traits of the resulting children. The primary aim of creating
designer babies is to avoid their having heritable diseases coded by mutations in DNA. With the development on mitochondria DNA transfer and
discovery of genome-editing tools, the production of precise genomeedited designer babies is no longer science ction. However, knowledge
on the risk of these editing tools is insufcient especially when modications are heritable. Furthermore, there are ethical concerns as to whether
we should apply these technologies to create designer babies. We
believe that these germline genetic editing methods should still be
considered as experimental procedures and research should continue
to improve the method and to assess its long term safety.
Introduction
Designer babies are babies originated from embryos created by
in-vitro fertilization (IVF) and selected because of the presence or
absence of particular genes or a baby created by genetic interventions into pre-implantation embryos in the attempt to influence the traits the resulting children will have.
59
ETHICS/EDUCATION
while analyzing multiple blastomeres will reduce embryo quality. Thus, potential problems may not surface until after birth.
Ethical considerations
Objections have been raised against mitochondrial transfer or
gene editing for several reasons. First, the safety of these procedures has not been fully established. The potential for harm
is great as the problems may be passed on to future generations. The introduction of these techniques for germline genetic
editing may lead us further down a slippery slope. These
techniques may be used for genetic enhancement and not just
for treatment of genetic diseases. In the case of treatment with
mitochondrial transfer, a healthy oocyte donor is required and
she may suffer from the complications and discomfort of the
oocyte donation procedure such as ovarian hyperstimulation
syndrome (OHSS). The use of germline genetic modifications
may also be considered to be dehumanizing and not acceptable
to some couples.
Conclusion
Many significant advances have been made in the recent few
decades in genetic editing and modifications with successful
cases reported in the literature. However, long term safety of
these procedures is still uncertain. Whether these techniques can
be used for treatment of serious genetic diseases is controversial.
We believe that while the procedures should not be considered to
be ready for clinical applications, research should continue to
improve the technology and to assess the long term safety of
these procedures.
A
Possible solutions
At this moment, the risks and complications of using engineering nuclease or mtDNA replacement therapy in creating
designer babies are still not fully known. In many countries,
these procedures are still prohibited by law. In our opinion,
these procedures should still be considered as experimental
and should not be offered as routine clinical procedures.
Nevertheless, we believe that research in this area should
continue under strict regulations and monitoring to ensure
that women who consent to undergo these procedures have
been fully informed of the procedures, the potential risks and
other alternative treatment. The use of well-established
methods like PGD or IVF, if possible, are better choices for
selecting healthy offspring and the ethical issues are often
considered minimal. Another possible option is the use of
ex vivo correction; the stem cells of the patients are isolated
for gene-editing and the corrected functional cells will then be
used for autologous transplantation. Thus, the edited gene will
FURTHER READING
Amato P, Tachibana M, Sparman M, et al. Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases. Fertil Steril 2014; 101: 31e5.
Kim H, Kim JS. A guide to genome engineering with programmable
nucleases. Nat Rev Genet 2014; 15: 321e34.
Reddy P, Ocampo A, Suzuki K, et al. Selective elimination of mitochondrial mutations in the germline by genome editing. Cell 2015;
161: 459e69.
60
SELF-ASSESSMENT
Self-assessment questions
Questions
Question 1 (SBA)
A 32-year old woman in her first pregnancy attends the
antenatal clinic at 10 weeks gestation. She has a history of
chronic kidney disease secondary to reflux nephropathy. Her
eGFR measured in renal clinic 3 months ago was 40 ml/min.
She takes 10 mg amlodipine daily, which controls her blood
pressure well.
Which one of the following statements is true regarding her
management?
A) Her anti-hypertensive should be stopped and labetalol
started if her blood pressure increases during pregnancy
B) Her eGFR is irrelevant as this measure is not validated in
pregnancy
C) Her risk of developing pre-eclampsia is not elevated above
baseline as her blood pressure is well-controlled
D) She should be advised to have regular blood pressure and
eGFR checks monthly in early pregnancy and more
frequently in the third trimester
E) She is at risk of a post-partum decline in her renal function
Question 2 (SBA)
A 26-year old woman attends the antenatal clinic at 16 weeks
gestation. She underwent a living-donor renal transplant 3
years ago due to IgA nephropathy. Her creatinine has been
stable at 115 mmol/L for the past 2 years. Her blood pressure is
120/70 without medication and she has proteinuria of 600 mg/
d. Which one of the following factors is NOT important in
predicting well-maintained renal function during and after
pregnancy?
A) She does not have hypertension at booking
B) Her proteinuria is <1 g/d
C) Her transplanted kidney came from a living related donor
D) Her renal function has been stable for over a year
E) Her creatinine is <125 mmol/L at booking
Question 3 (EMQ)
For each of the patients described below (ieiii), pick the single
most important first management strategy from the list below:
A) Start low molecular weight heparin
B) Start dialysis
C) Advise to avoid pregnancy
D) Stop statin treatment
E) Switch immunosuppressive regimen to azathioprine and
tacrolimus
F) Commence aspirin
G) Monitor urea, creatinine and haemoglobin every 8 weeks
H) Perform renal ultrasound scan
Question 5 (SBA)
Which of the following biological mechanisms is not an
explanation for phenotypic differences in monozygotic twins?
A) Somatic mosaicism
B) Epigenetic phenomena
C) Meiotic errors
D) Disrupted embryonic migration
E) Variable penetrance
Question 6 (SBA)
Following a routine scan at 24 weeks, one of your patients is
found to have very discordant liquor volumes between her
dichorionic twins. Which of the following is not a possible
explanation;
A) Preterm membrane rupture
B) Fetal VATER syndrome
C) Twin to twin transfusion syndrome
61
SELF-ASSESSMENT
Question 7 (SBA)
A 41-year old woman, who has conceived with the use of IVF,
presents initially at 28 weeks with spontaneous rupture of the
membranes. She is highly anxious because her previous baby
was stillborn following an abruption at 32 weeks. She continues
to smoke during the pregnancy despite advice from her obstetric
team. At 35 weeks, she experiences a sudden onset of severe
abdominal pain and bleeding, and an emergency Caesarean
section is performed. Her neonate requires resuscitation, but is
well enough to leave hospital after a 2-week stay in NICU.
Which of the following is the strongest risk factor for
abruption in this case?
A) Maternal age 41
B) Maternal smoking in pregnancy
C) Preterm prelabour rupture of membranes
D) Previous history of abruption
E) Conception with IVF
Answers
Answer 1
E
This patient has CKD G3b. Estimated glomerular filtration
rate is calculated using equations, most commonly the MDRD
or CKD-EPI formulae. These are based on serum creatinine,
patient age, gender and ethnicity. These calculations are not
validated for use during pregnancy, however preconception
baseline values of eGFR (this womans eGFR result is from
pre-pregnancy) are useful in predicting maternal and fetal
outcomes. Even preconception eGFR >60 ml/min is associated with increased risk of prematurity and intrauterine
growth restriction as compared to the general population,
predominantly, but not entirely, due to an increased risk of
developing pre-eclampsia. Amlodipine is rarely used during
pregnancy, but is unlikely to cause harm. It should be
switched to nifedipine or labetalol rather than stopping antihypertensives altogether, if the patient and clinician are not
happy to continue with it in the absence of good data. Women
who commence pregnancy with an eGFR 45 ml/min are at risk
of long-term decline in their renal function if they develop
significant proteinuria during the pregnancy.
Question 8 (SBA)
A 21-year old woman presents at 32 weeks into her first
ongoing pregnancy with abdominal pain and a small antepartum haemorrhage. Her pregnancy has been uncomplicated
thus far and, although she has missed several midwife appointments, she has had normal scans at 12 and 20 weeks. She
is haemodynamically stable, the CTG is normal and she is
admitted for observation. Which one of the following steps is
appropriate in her management at this point?
A) Colposcopy to examine the cervix
B) Screening for domestic violence
C) Extended clotting studies
D) US to look for vasa praevia
E) US to look for placental abruption
Answer 2
C
The origin of a transplanted kidney is not known to be a
factor predicting subsequent pregnancy outcome. Baseline
diastolic blood pressure >75 mmHg or the use of anti-hypertensive agents may be predictive of accelerated decline in
renal function post-partum. Women with serum creatinine>125 mmol/L have a 25% risk of permanently losing
25% of their kidney function as a result of pregnancy.
Question 9 (EMQ)
For each of the patients described below (ieiii), pick the single
most important first management strategy from the list below:
A) Arrange prophylactic balloon catheter placement
B) Proceed to emergency Caesarean section
C) Perform transvaginal ultrasound scan
D) Rescan at 32 weeks gestation
E) Rescan at 36 weeks gestation
F) Complete advance directive regarding blood products
G) Optimize pre-delivery haemoglobin levels
H) Transfuse packed red blood cells
I) Admit to hospital from 34 weeks
Answer 3
i). A
This patient has all the hallmarks of nephrotic syndrome
and is at high risk of venous thromboembolism. She should be
immediately started on low molecular weight heparin while
the aetiology is investigated.
ii). E
This patient is at moderate risk of a decline in her renal
function or a poor fetal outcome from pregnancy, but not to
the extent where she should be advised not to become pregnant. Her major risk factor at present is the use of mycophenolatemofetil, which is linked to a high incidence of specific
congenital anomalies. This should be changed as soon as
possible, and she should not stop her contraceptive until her
renal function is stable on the new regimen.
iii). H
A sudden jump in a previously stable creatinine mandates
urgent imaging of the transplanted kidney. Graft rejection is a
possibility in this case.
62
SELF-ASSESSMENT
Answer 4
E
The risk of miscarriage (of the entire pregnancy) when
performing double amniocentesis or double CVS should be
quoted as 1 in 50 (2%). A proportion of dichorionic twins are
monozygous, although most are dizygous. For the purposes of
prenatal screening, dichorionic twins are treated as dizygotic,
and an individual risk for Down syndrome is given to each
fetus, depending on its NT. The detection rate of the combined
test falls to 40e50% for a constant false positive rate of 3%
because the shifts in biochemical markers are diluted by the
chemical contribution made by the normal twin. Assuming
dizygosity in this pregnancy, the risk of both twins being
affected will be the age incidence multiplied by the age incidence (ie 1 in 100, multiplied by 1 in 100). The risk of at least
one of the twins being affected is double the normal age related
risk (ie 1 in 100 plus 1 in 100). For a risk to be given for each
twin in a dichorionic twin pregnancy, both NT measurements
must be made.
Answer 8
B
Clinicians should be aware that domestic violence can
result in APH, possibly from placental abruption. A third of
domestic violence is known to start or escalate in pregnancy.
Women who disclose domestic violence should be managed
appropriately by a local safeguarding team. Ultrasound is not
recommended as a diagnostic tool to diagnose abruption as
the reported sensitivity is only between 25 and 50%. While the
RCOG guideline recommends that all patients with APH
should have a full blood count (FBC), group and save and a
Kleihauer test if Rhesus D negative, there is no indication for
extended clotting studies in this case. Women who present
with major or massive haemorrhage should also have liver
and renal function blood tests and a coagulation screen
including fibrinogen.
Answer 9
i). F
This patient needs to be prepared for a large blood loss at
the time of delivery. While optimizing her haemoglobin level
will be important, this is currently within normal range. The
priority is to prepare for an emergency situation, and having a
clear record of her wish for treatment with blood products is
essential. The healthcare provider and patient should discuss
what blood components and blood derivatives (for example
clotting factor concentrates) would be acceptable to the
woman in the event of serious blood loss, and also if autologous transfusion in the form of cell salvage can be used. All
discussions must be clearly documented.
ii). D
This woman is at risk of placenta praevia due to low-lying
placenta at 20 weeks and maternal age. The placental location
should be rechecked at 32 weeks. If it is still low-lying at this
stage, then careful consideration should be given to preparing
for the possibility of major haemorrhage at delivery and to
further investigation to rule out placental invasion (accreta/
percreta).
iii). G
Whatever the aetiology of these repeated bleeds, this patient is clearly at high risk of both significantly preterm delivery and of major blood loss at the time of delivery. While a
number of careful preparations need to be made for this, the
most appropriate from the list is to optimize her haemoglobin
in case of emergency delivery.
Answer 5
C
Meiosis occurs during gametogenesis. An error at this point
will be present in the zygote, from the outset, and will be
found in both twins following division of the embryo.
Answer 6
C
Twin to twin transfusion syndrome does not occur in
dichorionic twins, whatever the zygosity. Preterm membrane
rupture of one sac, autosomal recessive (infantile) kidney
disease in one of the twin pair, and selective fetal growth restriction secondary to placental dysfunction could all cause
one of a twin pair to have markedly reduced liquor volumes.
Oesophageal atresia is a very common feature of VATER
syndrome, a mostly sporadic condition, and this will eventually cause polyhydramnios around the affected twin.
Answer 7
D
All of the above are risk factors for placental abruption with
the exception of conception by IVF. However, the strongest
risk factor for abruption is a previous abruption. There is a 10fold increased risk for mothers who have had one previous
abruption and the risk increases to nearly 25% if a woman has
had two previous abruptions.
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