Preterm Labor Obstetrics

DEFINITIONS
 Preterm Birth: Any delivery regardless of birth

weight that occurs before 37 completed weeks
from the first day of the last menstrual period
 Beginning at 20 weeks and ending at 36 and 6/7ths
weeks’ gestation
 Low Birthweight (LBW): Infants who weight under

2500 g at birth regardless of gestational age
 Very Low Birthweight (VLBW): those who weight
under 1500 g
INCIDENCE
 Incidence of preterm birth: 11.9% in the United States
(2001)
 In the Philippines: 10.93% among POGS accredited
hospitals (2000)
 Rate of LBW: 7.7% (2001) for singleton and multiple

gestations of all races
 Rate of VLBW: 1.44% (2001)
PERINATAL MORTALITY
 Perinatal death: one that occurs at any time after 22
weeks’ gestation (or above 500 g if gestational age is
not known) through 28 days after delivery
 Perinatal mortality is the sum of fetal stillbirths and

neonatal deaths
PERINATAL MORTALITY
 Perinatal mortality and morbidity are inversely related
to both gestational age and birth weight
 Preterm birth is the leading cause of perinatal

morbidity and neonatal mortality
PERINATAL MORTALITY
 Stillbirths (59.3% average rate), relative risk of 6.7 for
preterm deliveries
 Neonatal deaths (67.58% average rate), relative risk of

7.6 for preterm deliveries
TABLE 42-1. Infant Mortality Rates in the United States in
2013
PERINATAL MORBIDITY
 Respiratory Distress Syndrome (RDS)
 Intraventricular Hemorrhage (IVH)
 Bronchopulmonary Dysplasia
 Patent Ductus Arteriosus
 Necrotizing enterocolitis
 Sepsis
PERINATAL MORBIDITY
 Apnea
 Retinopathy of prematurity
 Hyperbilirubinemia and Jaundice
 Hypoglycemia
 Nutritional difficulties and
 Thermal instability
PERINATAL MORBIDITY
 Incidence of major morbidity
 60% for infants with birth weights between 501-750 g
 50% for infants weighing between 751 and 1000 g

Major short and long term
problems in VLBW infants
Organ system Short term problems Long term problems
Pulmonary Respiratory distress Bronchopulmonary
syndrome, air leak, dysplasia, reactive airway
bronchopulmonary disease, asthma
dysplasia, apnea of
prematurity
Gastrointestnal or Hyperbilirubinemia, Failure to thrive, short
nutritional feeding intolerance, bowel syndrome,
necrotizing enterocolitis, cholestasis
growth failure
Organ or system Short-term problems Long term Problems
Immunological Hospital acquired Respiratory syncytial
infection, immune virus infection,
deficiency, perinatal bronchiolitis
infection
Central nervous system Intraventricular Cerebral palsy,
hemorrhage, hydrocephalus, cerebral
periventricular atrophy,
leukomalacia, neuredevelopmental
hyrocephalus delay, hearing loss
Opthalmological Retinopathy of Blindness, retinal
prematurity detachment, myopia,
strabismus
Organ or system Short term problems Long term Problems
Cardiovascular Hypotension, PDA, Pulmonary Hypertension,

pulmonary Hypertension Hypertension in
adulthood
Renal Water and electrolyte Hypertension in
imbalance,acid-base adulthood
disturbances
Hematological Iatrogenic anemia, need
for frequent transfusions,
anemia of prematurity
Endocrinological Hypoglycemia, Impaired glucose
transiently low thyroxine regulation, increased
levels, cortisol deficiency insulin resistance
 Currently, the threshold of viability lies between 20
and 26 weeks’ gestation.
TABLE 42-4. General Guidelines for Obstetrical Interventions for
Threatened imminent Periviable Delivery.
Parkland Hospital
 traditional fetal indications for cesarean delivery are
practiced in women at 250/7 weeks or beyond.
Cesarean delivery is not offered for fetal indications
before 240/7 weeks.
 At 240/7 weeks, cesarean delivery is not offered unless
fetal weight is estimated at 750 g or greater.
 Aggressive obstetrical management is practiced in
cases of growth restriction, wherein gestational age is
used to guide management rather than fetal size.
Causes of late preterm birth:
 idiopathic spontaneous preterm labor
 prematurely ruptured membranes
CAUSES OF PRETERM BIRTH:
 (1) spontaneous unexplained preterm labor with intact
membranes,
 (2) idiopathic preterm premature rupture of
membranes (PPROM),
 (3) delivery for maternal or fetal indications, and
 (4) twins and higher-order multifetal births.
SPONTANEOUS PRETERM LABOR
Common associated findings are:
multifetal pregnancy,
intrauterine infection,
bleeding,
placental infarction,
premature cervical dilation,
cervical insufficiency,
hydramnios,
uterine fundal abnormalities,
 Fetal anomalies
 Severe maternal illness from
infections,
autoimmune diseases, and
gestational hypertension
Uterine Distension
 Multifetal pregnancy hydramnios are well-recognized
risks for preterm birth. Early uterine distention likely
acts to initiate expression of contraction-associated
proteins (CAPs) in the myometrium.
 Prematurely increased stretch and endocrine activity
may initiate events that shift the timing of uterine
activation, including premature cervical ripening.
Maternal–Fetal Stress
Physiological Psychological
 nutrient restriction  Racial discrimination,
 obesity,  childhood stress,
 infection,  depression,
 diabetes.  posttraumatic stress
syndrome
Cervical Dysfunction
 premature cervical remodeling precedes premature
labor onset (epithelial barrier is critical to prevent
ascending infection),
 enhanced risk of preterm birth from group B
streptococcal colonization may be in part due to the
bacteria’s ability to secrete hyaluronidase. This enzyme
degrades hyaluronic acid in the cervicovaginal
epithelia to aid bacterial ascension
 Second, the mechanical competence of the cervix can
be reduced
Infection:
 Bacteria can gain access to intrauterine tissues
through:
 (1) transplacental transfer of maternal systemic
infection,
 (2) retrograde flow of infection into the peritoneal
cavity via the fallopian tubes, or
 (3) ascending infection with bacteria from the vagina
and cervix.
Infection:
 Intraamnionic infection is a primary cause of preterm
labor in pregnancies with intact membranes accounts
for 25 to 40 percent of preterm births.
 considerable data associate chorioamnionitis with
preterm labor
 With chorioamnionitis, microbes may invade
maternal tissue only and not amnionic fluid. Despite
this, endotoxins can stimulate amnionic cells to secrete
cytokines that enter amnionic fluid
Inflammatory Responses.
 Inflammatory responses drive the pathogenesis of

infection-induced preterm labor.
 Lipopolysaccharide (LPS) or other toxins elaborated
by bacteria are recognized by pattern-recognition
receptors such as toll- like receptors (Janssens, 2003).
Origin of Cytokines.
 Uterine cytokines are likely important for preterm

labor.
 it appears that cytokines produced in maternal
decidua and myometrium will have effects on that
side, whereas cytokines produced in the membranes or
in cells within the amnionic fluid will not be
transferred to maternal tissues.
 with infection, leukocytes—mainly neutrophils,
macrophages, and T lymphocytes—infiltrate the
cervix, lower uterine segment, fundus, and
membranes at the time of labor.
Vaginal Microbiota.
 Lactobacillus species show an enhanced dominance.

 Gardnerella vaginalis and Ureaplasma urealyticum—in
women with preterm birth
 Some specific microorganisms are detected more
frequently than others in amnionic fluid of women
with preterm labor:
 G vaginalis,
 Fusobacterium species,
 Mycoplasma hominis, and
 U urealyticum.
Preterm Premature Rupture of
Membranes
 definition:spontaneous rupture of the fetal

membranes before 37 completed weeks and before
labor onset (ACOG 2016d).
 major predisposing events:
 intrauterine infection,
 oxidative stress-induced DNA damage, and
 premature cellular senescence are major predisposing
events Associated risk factors include lower
socioeconomic status, body mass index <19.8,
nutritional deficiencies, and cigarette smoking. Women
with PPROM carry an enhanced risk for recurrence
during a subsequent pregnancy (Bloom, 2001). Despite
 Associated risk factors include
 lower socioeconomic status,
 body mass index <19.8,
 nutritional deficiencies, and
 cigarette smoking.
 Women with PPROM carry an enhanced risk for
recurrence during a subsequent pregnancy (Bloom,
2001).
 Despite these known risk factors, none is identified in
most cases of preterm rupture.
Preterm Premature Rupture of
Membranes
 Molecular Changes: Increased apoptosis or necroptosis

of membrane cellular components and greater levels of
specific proteases in membranes and amnionic fluid
are related to PPROM. Most tensile strength of the
membranes is provided by the amnionic extracellular
matrix and interstitial amnionic collagens that are
produced in mesenchymal cells (Casey, 1996).
 Infection : bacteria were isolated from amnionic fluid
in a third of cases
Multifetal Pregnancy
 Twins and higher-order multifetal births account for
approximately 3 percent of neonates born in the
United States (Martin, 2017).
 Preterm delivery continues to be the major cause of
the excessive perinatal morbidity and mortality with
multifetal pregnancies.
CONTRIBUTING FACTORS
 Pregnancy Factors
 Lifestyle Factors
 Genetic Factors
 Periodontal Disease
 Interval between Pregnancies
 Prior Preterm Birth
 Infection
Antibiotic Prophylaxis
 antibiotic prophylaxis to prevent preterm birth is not

recommended in women with preterm labor and
intact membranes (Flenady, 2013).
Bacterial Vaginosis
 In this condition, normal, hydrogen peroxide-

producing, lactobacillus-predominant vaginal flora is
replaced with anaerobes
 Using Gram staining, relative concentrations of the
bacterial morphotypes characteristic of bacterial
vaginosis are determined and graded by the Nugent
score or assessed clinically with Amsel criteria.
 has been associated with spontaneous abortion,
preterm labor, PPROM, chorioamnionitis, and
amnionic fluid infection
DIAGNOSIS
Symptoms Cervical change

 Defines preterm labor to be  cervical dilation as a predictor
regular contractions before 37 of increased preterm delivery
weeks that are associated risk (Copper, 1995).
with cervical change.(ACOG)  prenatal cervical
 pelvic pressure, menstrual- examinations in
like cramps, watery vaginal asymptomatic women are
discharge, and lower back neither beneficial nor
pain harmful.
Ambulatory Uterine Monitoring
 An external tocodynamometer belted around the
abdomen and connected to an electronic waist
recorder allows a woman to ambulate while uterine
activity is recorded. Results are transmitted via
telephone daily.
 Women are educated concerning signs and symptoms
of preterm labor, and clinicians are kept apprised of
their progress.
 does not reduce preterm birth rates with the internet
and cellular telephones,
 use of such monitoring is discouraged (ACOG, 2016c).
Fetal Fibronectin
 This glycoprotein is produced in 20 different molecular

forms by various cell types, including hepatocytes,
fibroblasts, endothelial cells, and fetal amnion cells.
 values exceeding 50 ng/mL are considered positive.
 The ACOG does not recommend screening with fFN
tests
Cervical Length Measurement
 When performed by trained operators, cervical length

analysis using transvaginal sonography is safe, highly
reproducible, and more sensitive than transabdominal
sonographic screening (ACOG, The Society for
Maternal-Fetal Medicine (2016b)
 The Society for Maternal-Fetal Medicine (2016b)
recommends transvaginal cervical length screening for
those women with a history of prior spontaneous
preterm birth,
 routine use of these screening tests in this low-risk
population is not recommended.
CERVICAL LENGTH
PRETERM BIRTH PREVENTION
 Cerclage: Indications
 history of recurrent midtrimester losses and who are
diagnosed with cervical insufficiency. A
 women identified during sonographic examination to
have a short cervix.
 “rescue” cerclage, done emergently when cervical
incompetence is recognized in women with threatened
preterm labor.
PRETERM BIRTH PREVENTION
 Prophylaxis with Progestogen Compounds
 ACOG(2016c) and the Society for Maternal-Fetal
Medicine (2017a) approve the use of progestogen therapy
for prevention of preterm birth in select women with
singleton pregnancies.
 Criteria
1. history of prior preterm birth
2. no prior preterm birth but a sonographically identified short
cervix.
 the Society for Maternal-Fetal Medicine (2017a) recently
reaffirmed the use of 17-OHP-C, rather than vaginal
progesterone, for prevention of recurrent preterm birth.
 Thus, vaginal progesterone, but not 17-OHP-C,
appears to benefit women with a sonographically
measured short cervix.
MANAGEMENT OF PRETERM PREMATURE RUPTURE OF
MEMBRANES
ACOG recommendations:
 At 240/7 to 336/7 weeks, expectant management in the
absence of nonreassuring fetal status, clinical
chorioamnionitis, or placental abruption is recommended.
 At 340/7 weeks of gestation or greater, delivery is still
recommended by the College for all women with ruptured
membranes.
 Parkland Hospital : practices are consistent with ACOG
Considerations with Expectant Management
 therapeutic tocolysis—for those with ruptured membranes
and labor—has also not provided significant perinatal
benefit (Garite, 1987).
 23 weeks or less is the threshold for development of lung
hypoplasia
 when contemplating early expectant management,
consideration is also given to oligohydramnios and
resultant limb compression deformities (Chap. 11, p. 232).
 expectant management of women with PPROM and
noncephalic presentation was associated with a higher rate
of umbilical cord prolapse, especially before 26 weeks.
Clinical Chorioamnionitis
 infection is a major concern with membrane rupture.

 While some cases remain subclinical, if
chorioamnionitis is diagnosed, prompt efforts to effect
delivery, preferably vaginally, are initiated.
 Because maternal leukocytosis alone is not a
consistent finding, fever is the only reliable indicator
for the diagnosis of chorioamnionitis.
Antimicrobial Therapy
 The proposed microbial pathogenesis for spontaneous
preterm labor or ruptured membranes has prompted
investigators to give various antimicrobials to forestall
delivery.
 Three outcome benefits:
 (1) fewer women developed chorioamnionitis,
 (2) fewer newborns developed sepsis, and
 (3) pregnancy was more often prolonged 7 days
Antimicrobial
 oral amoxicillin plus erythromycin, every 8 hours for 5
days.
 Antimicrobial-treated women had significantly fewer
newborns with RDS, necrotizing enterocolitis, and
composite adverse outcomes.
 amoxicillin-clavulanate regimen: not recommended,
because of its association with an increased incidence
of neonatal necrotizing enterocolitis
Corticosteroids to Accelerate Fetal Lung
Maturity
 The use of antenatal corticosteroids in the setting of

PPROM was once considered controversial as the
magnitude of the benefits was not as great as when the
membranes were intact.
 Recommendation: A single course of corticosteroids,
for pregnant women with ruptured membranes
between 240/7 and 340/7 weeks’ gestation (ACOG,
2017a).
 Periviability: a single course of corticosteroids as early
as 230/7 weeks in those who are at risk for preterm
delivery within 7 days may be considered (ACOG,
2017e).
 A similar controversy is found at the other end of the
gestational age spectrum, wherein corticosteroid
administration in the late-preterm period is also under
consideration
Membrane Repair
 There are limited reports of sealants in the repair of

fetal membranes.
 Crowley and coworkers (2016) recently reviewed the
available evidence and concluded that data are
currently insufficient to evaluate sealing procedures
for ruptured membranes.
 Parkland Hospital: agents not currently used for this
indication.
MANAGEMENT OF PRETERM LABOR WITH
INTACT MEMBRANES
 Amniocentesis to Detect Infection

 Several tests have been used to diagnose
intraamnionic infection
 Although such infection can be confirmed
with a positive test result, there is little utility
for routine amniocentesis (ACOG ,2017b).
 Corticosteroids for Fetal Lung Maturation
 Corticosteroid therapy was effective in lowering the
incidence of RDS and neonatal mortality rates if birth
was delayed for at least 24 hours after initiation of
betamethasone.
 A single course of corticosteroids is currently
recommended by the ACOG (2017a) for women
between 24 and 34 weeks who are at risk for delivery
within 7 days.
 This recommendation for premature twins has been
challenged (Viteri, 2016).
 For pregnancies at 23 weeks and at risk of delivery
within 7 days, a single course of corticosteroids may be
considered
 Administration of corticosteroids during the
periviable period is linked to a family’s decision
regarding resuscitation and should be considered in
that context (ACOG, 2017e).
 Betamethasone and dexamethasone appear to be
equivalent for fetal lung maturation .
 These two drugs are comparable in reducing rates of
major neonatal morbidities in preterm newborns . A
treatment course may be two 12-mg doses of
betamethasone, and each dose is given
intramuscularly 24 hours apart. With dexamethasone,
6-mg doses are given intramuscularly every 12 hours
for four doses. Because treatment for less than 24
hours may be beneficial and reduce neonatal
morbidity and mortality rates, a first dose of antenatal
corticosteroids is administered regardless of the ability
Betamethasone and dexamethasone appear to be
equivalent for fetal lung maturation .
Betamethasone Dexamethasone
 12 mg IM every 24  6-mg IM doses are
hours for 2 doses given every 12 hours
for four doses.
 Because treatment for less than 24 hours may be
beneficial and reduce neonatal morbidity and
mortality rates, a first dose of antenatal corticosteroids
is administered regardless of the ability to complete
additional doses before delivery (American College of
Obstetricians and Gynecologists, 2017a).
Women at Risk for Late-Preterm
Delivery
 A single course of betamethasone for women between

340/7 and 366/7 weeks has been recommended by
both the American College of Obstetricians and
Gynecologists (2017a) and the Society for Maternal-
Fetal Medicine (2016a).
Repeated Courses
 Single versus additional courses of intramuscular

corticosteroids for lung maturation has been the topic
of two major trials.
 A nonsignificant rise in the cerebral palsy rate was
identified in infants exposed to repeated courses.
 Parkland Hospital: single course therapy as
recommended by the American College of
Obstetricians and Gynecologists (2017a)
Rescue Therapy
 single rescue course of antenatal corticosteroids is

considered in women before 34 weeks whose prior
course was administered at least 7 days
previously.(ACOG,2017a)
 Effects of rescue therapy beyond 34 weeks are
currently unknown.
 Parkland Hospital: currently do not provide
additional courses of corticosteroids beyond the initial
single-course therapy.
Magnesium Sulfate for Neuroprotection
 The ACOG(2012) issued a Patient Safety Checklist for

use of magnesium sulfate for neuroprotection. For
those with PPROM, prophylaxis may similarly be
considered.
 Parkland Hospital: provision of magnesium sulfate for
neuroprotection with threatened preterm delivery
from 240/7 to 276/7 weeks.
Antimicrobials
 Cochrane metaanalysis: antimicrobial prophylaxis

given to women with intact membranes did not reduce
preterm birth rates or affect other clinically important
short-term outcomes (Flenady, 2013).
 fetal exposure to antimicrobials was associated with an
increased cerebral palsy rate at age 7 years compared
with that in children without fetal exposure (Kenyon,
2008b).
 antimicrobial use described here is distinct from that
given for group B streptococcal prophylaxis .
Bed Rest
 The American College of Obstetricians and

Gynecologists (2017d) suggests that, although
frequently prescribed, bed rest is only rarely indicated,
and ambulation should be considered in most cases.
Cervical Pessaries
 Silicone rings, such as the Arabin pessary, are being

used to support the cervix in women with a
sonographically short cervix.
 The Society for Maternal-Fetal Medicine (2017b)
recently recognized the conflicting published reports
and lack of an FDA-approved pessary for the
indication of preterm birth prevention. They currently
recommend pessary prophylaxis only within research
protocols.
Emergency or Rescue Cerclage
 Some evidence supports the concept that cervical

incompetence and preterm labor lie along a spectrum
leading to preterm delivery.
 Nulliparity, membranes extending beyond the external
cervical os, and cerclage before 22 weeks were
associated with a significantly decreased chance of
significant pregnancy continuation.
 it is unclear if such interventions truly confer a benefit
or merely increase the risk of membrane rupture and
infection (Hawkins, 2017).
Tocolysis to Treat Preterm
Labor
Gynecologists (2016b) has concluded that tocolytic
agents do not markedly prolong gestation but may
delay delivery in some women for up to 48 hours.
 Tocolytic agents recommended for short term use
 Beta-adrenergic agonists,
 magnesium sulfate,
 calcium-channel blockers, or
 indomethacin
Tocolysis to Treat Preterm Labor
 β-Adrenergic Receptor Agonist

Gynecologists (2016b) recommends only short-
term inpatient use of terbutaline as a tocolytic or
as acute therapy of uterine tachysystole.
Subcutaneous dosages of 0.25 mg are commonly
used for the latter indication.
Prostaglandin inhibitors
 act by inhibiting prostaglandin synthesis or by
blocking their action on target organs.
 A group of enzymes collectively termed prostaglandin
synthase is responsible for the conversion of free
arachidonic acid to prostaglandins.
 Several drugs block this system, including
acetylsalicylate and indomethacin.
 Indomethacin, a nonselective cyclooxygenase inhibitor,

was first used as a tocolytic agent
Magnesium Sulfate
 can alter myometrial contractility.
 a calcium antagonist, and when given in
pharmacological doses, it may inhibit labor.
 Dose: Intravenous magnesium sulfate, given as a 4-g
loading dose and followed by a continuous infusion of
2 g/hr, usually arrests labor
 Side effect:
 Pulmonary edema
 bone thinning and fractures in fetuses exposed for more
than 5 to 7
 Abandoned at Parkland
 Indomethacin
 is administered orally or rectally.
 Use 24 to 48 hours because of concerns for
oligohydramnios, can develop with therapeutic doses. (
reversible with drug discontinuation).
 Other side effects: intraventricular hemorrhage, patent
ductus arteriosus, sepsis, necrotizing enterocolitis, or
neonatal death.
Nitric Oxide Donors
 These potent smooth-muscle relaxants affect the
vasculature, gut, and uterus. In randomized clinical
trials, nitroglycerin administered orally, transdermally,
or intravenously was ineffective or showed no
superiority over other tocolytics. In addition, maternal
hypotension was a common side effect (Bisits, 2004;
El-Sayed, 1999; Lees, 1999).
Calcium-Channel Blockers
 reduced calcium concentrations inhibit contractions.

Calcium-channel blockers act to inhibit, by various
mechanisms, calcium entry through cell membrane
channels.
 calcium-channel blockers, especially nifedipine, are
safer and more effective tocolytic agents than β-agonist
drugs
Atosiban
 This nonapeptide oxytocin analogue is an oxytocin-

receptor antagonist (ORA). Goodwin and colleagues
(1995) described its pharmacokinetics in pregnant
women. In randomized clinical trials, atosiban failed
to improve relevant neonatal outcomes and was linked
with significant neonatal morbidity (Moutquin, 2000;
Romero, 2000). The FDA has denied approval of
atosiban because of concerns regarding efficacy and
fetal–newborn safety.
Labor
 electronic monitoring.
 Fetal tachycardia, especially with ruptured
membranes, is suggestive of sepsis.
 Low and colleagues (1995) observed that intrapartum
acidosis—umbilical artery blood pH <7.0—had an
important role in neonatal complications
 Group B streptococcal infections are common and
dangerous in the preterm neonate, and antimicrobial
prophylaxis should be provided
Delivery
 In the absence of a relaxed vaginal outlet, an
episiotomy for delivery may be necessary once the fetal
head reaches the perineum.
 Perinatal outcome data do not support routine
episiotomy or forceps delivery to protect the “fragile”
preterm fetal head.
 Staff proficient in resuscitative techniques
commensurate with the gestational age and fully
oriented to any specific problems should be present at
delivery.
Prevention of Intracranial Hemorrhage
 Preterm newborns frequently have intracranial germinal

matrix bleeding that can extend to more serious
intraventricular hemorrhage.
 It was hypothesized that cesarean delivery to obviate
trauma from labor and vaginal delivery might prevent these
complications. This has not been validated by subsequent
studies.
 These hemorrhages correlated with exposure to active-
phase labor. However, they emphasized that avoidance of
active-phase labor is impossible in most preterm births
because decisions for delivery route are not required until
active labor is firmly established.
Thank you
CAUSES OF PRETERM BIRTH
 Medical and Obstetrical Complications (28%)
 Preeclampsia (50%)
 Fetal Distress (25%)
 Fetal growth restriction
 Abruptio placenta (25%)
 Fetal Death
OB complications
Spontaneous labor Spontaneous ROM Hypertension
Placental abruption Placenta previa Fetal complications
Others
1% 2%3%
1%
13%
45%
35%
 Threatened Abortion
 Associated with increased adverse outcomes

 Vaginal bleeding associated with subsequent pregnancy
loss prior to 24 weeks, preterm labor and abruption
 Lifestyle Factors
 Cigarette smoking
 Inadequate maternal weight gain during pregnancy
 Illicit Drug use
 Young or advanced maternal age
 Poverty
 Occupational factors: prolonged walking or standing,
strenuous working conditions and long weekly work
hours
 Psychological and Physical Stress
 Genetic Factors
 Recurrent familial and racial nature of preterm birth
 Gene for decidual Relaxin
 Fetal mitochondrial trifunctional protein defects
 Polymorphism in the interleukin-1 gene complex, β2 –
adrenergic receptor, tumor necrosis factor alpha may be
involved in preterm membrane rupture
 Studies to evaluate gene-environment interactions
 Chorioamnionitis
 Infection of the membranes and amniotic fluid caused

by a variety of microorganisms
Identification of Women at Risk for
Spontaneous Preterm Labor
 RISK-SCORING SYSTEMS
 No benefits with this approach (Hueston and colleagues,
1995)
 Failed to identify most women who deliver preterm
neonates (Mercer and colleagues, 1996)
 OBSTETRICAL HISTORY
 A history of preterm birth confers an increased risk of
early delivery in subsequent pregnancies
 Risk of preterm births rose as the number of prior
preterm births increased
 Risk of preterm birth in subsequent births
First Birth Second Birth Subsequent preterm

Birth (%)
Not preterm 4.4
Preterm 17.2
Not preterm Not preterm 2.6
Preterm Not preterm 5.7
Not preterm Preterm 11.1
Preterm Preterm 28.4

Recurrent spontaneous preterm
births according to prior outcome
Birth outcome Second birth < or = 34 weeks
percent
First birth > or = 35 weeks 5%
First birth < or = 34 weeks 16%
First and second birth 41%
< or = 34 weeks
 Risk Factors for nonrecurrent spontaneous preterm
births
 2nd trimester bleeding
 Abnormal AFV
 Multiple gestation
 Substance abuse
 Trauma
 Risk Factors for recurrent spontaneous preterm births
 Maternal Ethnicity
 Genitourinary infection
 Gestational age of the first preterm birth
 The earlier the birth the greater the likelihood of recurrence
 CERVICAL LENGTH
 The distance between the internal os and external os as
measured with electronic calipers
 Transabdominal sonography (mean 3.2 - 5.3 cm)
 Transvaginal sonography (mean 3.2 - 4.8 cm)
 Most amenable to standardization
 Provides the highest degree of consistency
 Transperineal sonography (mean 2.9 - 3.5 cm)
 CERVICAL LENGTH
 Iams et al (1996) provided cervical measurements in a
large number of pregnant patients at 24 weeks gestation
obtained by TVS:
 75th %tile 40 mm
 5th %tile 22 mm
 1st %tile 13 mm
 CERVICAL LENGTH
 Cervical length as measured by TVS is inversely
proportional and continuously related to the risk of
preterm birth in both singleton and multiple
pregnancies
 A cervical length of 25 mm or less (10th %tile) conferred
a 6.5-fold relative risk of preterm birth before 35 weeks
gestation and a 7.7-fold relative risk of preterm birth
before 32 weeks gestation
 CERVICAL LENGTH
 Also strongly related to a history of spontaneous
preterm birth, especially before 32 weeks’ gestation
 The earlier the gestational age at delivery, the shorter the
cervix in the next pregnancy
 CERVICAL LENGTH
 Related to the risk of recurrent preterm birth
 For women with prior preterm birth there is a 31% likelihood of
preterm birth with a cervical length of 25 mm or less (at 24
weeks)
 16% likelihood of preterm birth if the cervical length was 26-35 mm
 8% likelihood if 36 mm or more
 In contrast to women whose only prior birth(s) were term, the
rate of birth before 35 weeks’ gestation
 8% if the cervix was 25 mm or less
 4% if the cervix was 26-35 mm
 2% when the cervix was 36 mm or more
 CERVICAL LENGTH
 Use of ultrasonographic cervical length measurements
can increase the ability to predict spontaneous birth
before 35 weeks in high risk women
 Currently has no role in the screening of normal-risk
women
 Infection
 Epidemiological, microbiological and clinical evidence
of an association between infections and preterm birth
 Most bacteria identified in the uterus in association with
preterm labor is vaginal in origin
 In women with spontaneous labor with intact
membranes, most commonly identified organisms:
 Ureaplasma urealyticum, Mycoplasma hominis, Gardnerella
vaginalis, Peptostreptococcus, Bacteroides
 Less commonly Chlamydia, Trichomonas, E. coli, group B
Streptoccocci
 Infection
 Bacterial Vaginosis
 Alteration of the maternal vaginal flora in which normally
predominant lactobacilli are largely replaced by gram negative
anaerobic bacteria such Gardnerella vaginalis, Bacteroides sp,
Mobiluncus sp, Mycoplasma sp
 Associated with a 2-fold increase in the risk of spontaneous
preterm birth
 Association is stronger if detected early in pregnancy
 Infection
 Bacterial Vaginosis
 Rates of preterm birth were decreased with antibiotic
treatment in women with prior preterm birth and Bacterial
vaginosis
 No effect on the rate of preterm birth in women with
asymptomatic BV treated with metronidazole
 Infection
 Infections outside the genital tract
 Most commonly urinary tract infection, intraabdominal
infections such as pyelonephritis and appendicitis
 Maternal Periodontal disease
 Fusobacterium necleatum, Capnocytophaga associated with upper
genital infection in women
 7-fold risk of preterm birth
 Research underway to determine whether midpregnancy
identification and treatment of women with periodontal disease
prevents preterm birth
 Infection
 Relationship between infection with vaginal
microorganisms and prematurity is complex
 Ascent of the organisms from the lower to the upper
genital tract
 Even distribution of infection-related preterm births throughout
pregnancy
 Expected increase in the third trimester
 Predominance of infection-related preterm births before
30 weeks not consistent with ascending infection
 Infection
 Evidence show that microorganisms associated with
preterm birth could colonize the endometrial cavity
prior to conception
 Exert their influence by eliciting a maternal and/or fetal
response that leads to hormonal, cytokine and
prostaglandin production
 Leading to cervical ripening, weakening of the
membranes and uterine contractions
 Biochemical Markers
 Fetal Fibronectin
 Glycoprotein produced in different molecular forms by a variety
of cell types, hepatocytes, fibroblasts, endothelial cells and fetal
amnion
 Thought to play a role in intercellular adhesion during
implantation and in the maintenance of placental adhesion to
the decidua
 Detected in cervicovaginal secretions in women with normal
pregnancies and reflects stromal remodeling of the cervix before
labor
 Detection in cervicovaginal secretions prior to membrane
rupture and possible marker for impending preterm birth
 Measured using an Enzyme-linked Immunosorbent Assay
 Values >50 ng/mL are considered positive
 Swamy and colleagues (2001)
 A positive assay result at 22-34 weeks had a positive predictive
value for delivery within 1 week of 30%, within 2 weeks of 41%
 Negative predictive value for delivery within 1 week at 98%,
and delivery within 2 weeks 96%
 Alkaline phosphatase
 Alpha-fetoprotein
 Beta-2-microglobulin
 C-reactive protein
 Ferritin
 IL-6
 Intracellular adhesion molecule-1 (ICAM-1)
 Maternal plasma granulocyte colony stimulating factor
(GCSF)
 Frequency of uterine contraction
 Uterine activity has been studied to identify women who
will enter preterm labor
 Based on the study of 109 women who were monitored
for contraction frequency for 24 hours 2x weekly,
contraction frequency increased throughout gestation
with a diurnal rhythm, peak activity at night
 Frequency of uterine contraction
 Significant individual variability in contraction
frequency in normal pregnancy
 Uterine contractions were significantly more frequent in
women who would deliver preterm, difference was not
clinically useful
 Low sensitivity and positive predictive value
 Salivary Estriol
 Feto-maternal signal which mimics the mothers’ urinary
estriol
 Surge prior to 36 weeks indicates heightened risk for
preterm labor
 Detection of an early estriol surge (3-4 weeks prior to
labor) or an increased quantitative estriol level ≥2.3
ng/mL may help identify women at risk for preterm
labors and births
 Requires further evaluation before it can be
recommended for clinical use
 Signs and Symptoms
 Painful or painless uterine contractions
 Other symptoms: pelvic pressure, menstrual-like
cramps, watery vaginal discharge, pain in the lower back
 Common in normal pregnancy
 Signs and symptoms appeared only within 24 hours of
preterm labor
Recommended Screening
Strategies to Prevent Preterm birth
(ACOG)
 No current data to support use of home uterine –
activity monitoring or bacterial vaginosis screening.
 Screening for risk of preterm labor other than
historical risk factors, is not beneficial in the general
ob population.
 Sonography to determine cervical length and / 0r fetal
fibronectin level measurement may be useful in
determining women at risk of preterm labor. However,
their value may rest primarily with their negative
predictive value given the lack of proven treatment
options.
Prevention of preterm birth
 Elusive goal.
 May be achievable in selected population.
 Use of: progesterone
: cervical cerclage
Progesterone
 Maintain uterine quiescence and block labor
initiation.
 Proposed dosage:
1. weekly intramuscular injection of either inert
oil or 17 alpha hydroxyprogesterone caproate from 16 to
20 weeks through 36 weeks AOG.
2. daily 200 mg progesterone suppositories from
24 weeks to 34 weeks AOG.
Progesterone
 Potential benefit for preventing preterm birth in the
following groups of women:
1. For women with a past history of spontaneous
preterm birth.
2. For women with short cervix identified on
ultrasound.
3. For women with multiple pregnanc y.
4. For women following presentation of threatened
preterm labor
Progesterone
 ACOG recommendation: Progesterone should be
limited to women with a documented history of
previous spontaneous birth at 37 weeks
Major Pathogenic Pathways of Preterm
Delivery
Management of Preterm Labor
 Establish the diagnosis
 Search for treatable conditions that may be triggering
preterm labor
 Decide whether there are any maternal or fetal
contraindications to attempting inhibition of labor
Diagnosis of Preterm Labor
 ACOG (1997)
 Contractions of four in 20 minutes or eight in 60
minutes plus progressive change in the cervix
 Cervical dilatation greater than 1 cm
 Cervical effacement of 80% or greater
 Symptoms are often non-specific and not
necessarily of labor at term
 Signs and symptoms of early preterm labor occur
often in normal pregnancy
 Digital examination of the cervix is imprecise until
significant dilation and effacement have occurred
 Frequency of uterine contractions varies
considerably
 Transvaginal Sonography
 Improve accuracy of preterm labor diagnosis
 Superior to digital examination in predicting preterm
birth in women with acute preterm labor signs and
symptoms
 Cervical length of 30 mm or greater has a very high
negative predictive value for preterm birth in studies of
symptomatic women
 Used to improve the accuracy of diagnosis of preterm
labor
 A positive test result in a patient with contractions and
cervical dilatation of under 3 cm has better sensitivity
(90%) and negative predictive value (97%) for delivery
within 7-14 days than clinical markers but with a positive
predictive value of <20% for birth within 7-14 days
 Establish the diagnosis
 Search for treatable conditions that may be triggering
preterm labor
 Decide whether there are any maternal or fetal
contraindications to attempting inhibition of labor
 Amniocentesis to detect infection
 Amniotic fluid cultures may be positive in 9.1% overall,
22% in those progressing to preterm delivery
 Routine amniocentesis to rule out an infectious cause of
preterm labor has not been proven to be effective
 May be of value in refractory preterm labor
 Amniotic fluid glucose may provide further insight
 AF glucose concentration <14 mg/dL has a sensitivity
87%, positive predictive value of 63% and a negative
predictive value of 98% in the detection of a positive
culture
 Elevated leukocyte count
 High interleukin-6 concentration
 Most sensitive for detection of AF bacteria
 Sensitivity of 82%
 Positive gram stain result
 Negative gram stain was the most reliable test to exclude
amnionic fluid bacteria
 Specificity of 99%
 Not been shown that amniocentesis to diagnose
infection is associated with improved pregnancy
outcomes in women with or without membrane rupture
 Antimicrobials
 Cochrane meta-analysis (King and Flenady, 2000)
 No difference in the rates of newborn respiratory distress
syndrome or of sepsis between placebo and antimicrobial
treated groups
 Increase in perinatal morbidity in the antimicrobial-treated
group
 Antimicrobials
 ORACLE II trial (2001)
 6295 women in spontaneous preterm labor with intact
membranes were randomized to receive amoxcillin-clavulanic
acid, erythromycin, both or placebo
 Primary outcomes of neonatal death, chronic lung disease and
major cerebral abnormality were similar in the groups
 No benefit for supplemental antibiotic therapy
 Recent follow up (2008)
- fetal exposure to antimicrobials in this clinical setting was
associated with increased cerebral palsy rate at age 7 years
compared with that of non-exposed infants.
 Antimicrobials
 Goldenberg (2002)
 Antimicrobial treatment of women with preterm labor for the sole
purpose of preventing delivery is generally not recommended
 Prophylaxis to prevent group B streptococcal infection is

recommended in women with preterm labor who have unknown or
positive anal or vaginal cultures
 In the setting or preterm labor, supplemental antibiotics should

only be used to treat a specific pathogen
Pharmacologic Treatment of Preterm Labor
 Magnesium Sulfate
 Prostaglandin Synthesis inhibitors
 Calcium Antagonists
 Beta-adrenergic agonists
 Elevated concentration of Magnesium sulfate has a
central depressant effect
 Alter nerve transmission by affecting acetylcholine
release and sensitivity at the motor end-plate
 Suppresses contractility in a dose-dependent manner
 Effect is through an increase in cyclic adenosine
monophosphate
 Could also have a competitive antagonist role with
calcium, decreasing the intracellular free calcium
 Pharmacology
 Inhibited when maternal serum levels are 5-8 mg/dL
 Excreted almost entirely by the kidney
 Increases in maternal serum magnesium also result in
hypocalcemia, usually asymptomatic
 Magnesium cross the placenta with fetal and newborn levels
increasing proportionally with maternal levels
 Clinical efficacy
 2 randomized placebo-controlled trials, no demonstrable
benefit for women treated with magnesium sulfate
 Efficacy is comparable to the beta-adrenergic agents but with
fewer adverse maternal side effects
 Meta-analysis done suggested that magnesium offered small
improvements in prolongation of pregnancy without a
demonstrable effect on the neonate
 Maternal effects
 Flushing, a sense of warmth, headache, nystagmus, nausea,
dizziness, dryness of mouth and lethargy (45%)
 Blurred vision or diplopia (75%)
 Fetal effects
 No significant alterations in neurologic stat of APGAR scores
with mean umbilical cord magnesium concentration of 3.6
mg/dL (Green and associates, 1983)
 Respiratory and motor depression observed in infants with
umbilical cord magnesium between 4-11 mg/dL
 Fetal heart variability has been reported to be unchanged,
decreased or increased
 No overall association between magnesium and cerebral palsy
 Dosage and administration
 Initial LD of 4-6 g administered intravenously followed by
maintenance dose of 1-4 g/hour
 IV therapy continued for 12 hours after contractions reduce to
fewer than 4-6 g/hour
 Careful observation of intake and output
 May restrict fluid intake
 Constant monitoring of deep tendon reflexes, serum
magnesium and calcium levels
 Prostaglandin Synthesis Inhibitors
 Prostaglandins have a significant stimulatory role in
established labor
 Indomethacin, Naproxen, Fenoprofen depress synthesis
of prostaglandins by inhibiting the cyclooxygenase
enzyme necessary for conversion of arachidonic acid to
prostaglandin G, the precursor of prostagladins E and F
 Indomethacin
 Pharmacology
 Non-specific cyclooxygenase inhibitor
 Absorbed after oral or rectal administration
 Plasma concentrations peaking 1-2 hrs after oral

administration
 Protein bound, eliminated unchanged in pregnant women
 Readily passes the placenta
 Binds in a reversible manner to cyclooxygenase

 Indomethacin
 Clinical Efficacy
 Effective in delaying delivery for at least 48 hours
 Comparison trials with beta-adrenergic agents reveal

comparable tocolytic effectiveness and fewer maternal side
effects
 Indomethacin
 Maternal Effects
 Serious maternal side effects are infrequent
 Associated with postpartum hemorrhage
 Doubled bleeding times
 Gastrointestinal side effects: kept to a minimum if taken with

meals
 Prolonged administration are associated with headaches,
dizziness, depression and psychosis
 Indomethacin
 Fetal Effects
 Constriction of the fetal ductus arteriosus
 Cyclooxygenase-1 (COX-1)-dependent prostaglandins are the

main mediators for ductal arteriosus patency in utero
 Indomethacin inhibits COX-1 and COX-2 enzymes
 Moise and co-workers (1988): antenatal indomethacin

treatment causing ductal arteriosus constriction and
constriction resolving within 24 hours of discontinuing
treatment
 Indomethacin
 Fetal Effects
 Neonatal pulmonary hypertension
 As a result of prolonged diversion of blood away from the

ductus arteriosus and toward the fetal vasculature
 Most cased involved indomethacin treatment longer than
48 hours
 Indomethacin
 Fetal Effects
 Oligohydramnios
 Secondary to decreased fetal urine production
 Unpredictable
 Reversible on cessation of treatment

 Indomethacin
 Fetal Effects
 Intraventricular hemorrhage
 If used after other tocolytic agents have failed
 If used in conjuction with magnesium sulfate
 Necrotizing enterocolitis
 Confliction reports
 Indomethacin
 Dosage and Administration
 50 mg or 100 mg rectal suppository
 50 mg orally as a loading dose, 25-50 mg orally every 6 hours
 Limited to women before 32 weeks of gestation, fetus with no

evidence of IUGR, Amniotic fluid volume is normal
 Treat for 48-72 hours
 Evaluation of amniotic fluid volume and ductus arteriosus

should be considered if treatment is continued longer
 Calcium Channel Blockers
 Nifedipine and Nicardipine
 Act by inhibiting the influx of calcium ions through the cell
membrane, primarily affecting the voltage-dependent calcium
channels
 Pharmacology
 Plasma concentrations of Nifedipine peak in 30-60 minutes
after oral administration
 Eliminated through the kidney and gut
 Nifedipine has been shown to cross the placenta, kinetics of

the transfer and metabolism within the fetus are unreported
 Nicardipine
 Clinical efficacy
 Similar efficacy with magnesium sulfate
 Nifedipine
 Meta-analysis of 13 trials revealed nifedipine to be superior to
beta-adrenergic agents in terms of delaying delivery for 48
hours, reaching 34 weeks of gestation, the incidence of
respiratory distress syndrome of the newborn and neonatal
intensive care admissions
 Cause vasodilatation
 Flushing, headache, nausea
 Transient tachycardia and mild decreases in blood pressure,
with occasional significant hypotension
 Modest increase in blood glucose
 Isolated hepatotoxicity
 Adjunctive treatment with magnesium can result in
neuromuscular blockade
 Fetal Effects
 Significant decreases in fetal arterial PO2 and pH following
maternal administration of nicardipine in rhesus monkeys
probably as a result of decreased uterine blood flow
 Fetal acidemic responses, even fetal demise, have been seen in
sheep
 Doppler studies during treatment in humans have not shown
abnormal fetal or uteroplacental circulations
 Other observational reports have not revealed any alarming
incidence of low APGAR scores or core pH
 Loading dose of 10 mg oral nifedipine, repeated after 20
minutes if contractions persist, may repeat in another 20
minutes
 Sublingual therapy has been discontinued because of
potential hypotension
 Oral therapy continued with 10-20 mg every 4-6 hours
 Duration of treatment not been established
 Beta-Adrenergic Agonists
 Isoxsuprine, hexoprenaline, fenoterol, orciprenaline,
ritodrine, salbutamol, terbutaline
 Derivatives of epinephrine
 Formulated to maximize the beta2 –adrenergic effects on
the uterus although all have some beta1 –adrenergic
activity
 Action mediated via adenyl-cyclase induced increase in
cyclic adenosine monophosphate which inhibits myosin
light chain kinase and this inhibits uterine contractions
 Pharmacology
 Most clinically utilized beta-adrenergic agonists are excreted
unaltered, or are excreted as conjugates by the kidney
 Some agents (ritodrine, terbutaline) cross into the fetus,
others probably cross to a lesser degree
 Pharmacology
 Ritodrine
 Concentration in maternal serum increases with increasing
infusion rates
 Vary from patient to patient
 Intravenous infusion results in peak plasma concentration

within 10 minutes, similar to intramuscular
 Half-life is 2 hours
 Therapeutic blood concentrations not established

 Pharmacology
 Terbutaline
 Intravenous administration results in peak plasma levels
within 10 minutes, similar subcutaneously
 Half-life of 3-4 hours
 Therapeutic blood concentrations not established

 Effectiveness of the different beta-adrenergic drugs used
clinically for tocolysis is comparable
 Can delay delivery for 3 days
 Effect on preterm birth remains controversial

 Have the ability to inhibit uterine activity rapidly and delay delivery
for 3-7 days
 Without proven benefit to the neonate
 Oral administration has not proven useful in near or long term
 Meta-analyses failed to demonstrate any improvement in the
prevention of preterm birth, interval to delivery, recurrence o preterm
labor
 Have the highest rate of serious maternal effects
 Cardiovascular Effects
 Hypotension
 Myocardial ischemia: occur at high heart rates (>120-130
beats/minute)
 Cardiac arrhythmias: asymptomatic, premature nodal and ventricular
contractions, respond to cessation of treatment
 Pulmonary edema: common
 Predisposing factors: twin gestation, HR >130 bpm, anemia <9
g/dL, maternal infection iatrogenic fluid overload
 Close observation of intake and output, fluid restriction
 Metabolic Effects
 Increase in hepatic glycogenolysis
 Maternal hyperglycemia
 Abnormal carbohydrate metabolism increased by

concomitant use of corticosteroids
 Associated with ketoacidosis in insulin-dependent diabetics
 Persists for an indeterminate period of time
 Hypokalemia
 Nausea, emesis, restlessness, general agitation

 Fetal and Neonatal Effects
 Mild fetal tachycardia
 Increase in beat-to-beat variability
 Neonatal hypoglycemia, hypocalcemia, ileus and hypotension

common in infants delivered within 48 hours of treatment
 Normal growth and development at 2 years of age
 Children aged 6 years after exposure found no significant

alterations in anthropometric measurements, neurologic tests or
general behavior, some showed decreased school performance
 Intravenous, Intramuscular, Subcutaneous, Oral
 Ritodrine
 Initial intravenous rate at 0.05-010 mg/min, increased by 0.05
mg/min at 10 to 30 minute intervals
 Potential maximum rate of 0.350 mg/min
 Terbutaline
 Initial intravenous rate at 0.01 mg/min and increased by 0.01
mg/min at 10-30 minute intervals
 Maximum rate at 0.08 mg/min
 Intravenous rate adjusted according to uterine activity or until
adverse maternal effects are noted
 Infusion rate should not be increased further if maternal pulse
rate reaches 130 bpm, systolic pressure <80-90
 Once tocolysis achieved, continued for another 6-24 hours
OR
 Once labor is halted, infusion rate reduced slowly until the lowest
inhibitory rate is established; maintenance rate to continue for 12
hours
 Miscellaneous Tocolytic Drugs
 Atosiban
 Oxytocin antagonists
 Glycerol nitrate
 Nitric oxide donor
 Intravenous nitroglycerin
 Caused hypotension
GLUCOCORTICOID THERAPY
 Corticosteroids accelerated lung maturation in
sheep fetuses
 Liggins and Howie (1972) studied this treatment in
women
 Effective in lowering the incidence of respiratory distress
and neonatal mortality if birth was delayed for at least
24 hours after intitiation of betamethasone
 Effects persisted for up to 7 days after completion
 Benefits
 Reduced neonatal mortality
 Reduction in the incidence of respiratory distress
syndrome
 Significant reduction in the incidence of intraventricular
hemorrhage
 Improvement in the circulatory stability and reduction
in the requirements for oxygen and ventilatory support
 Reduce incidence of necrotizing enterocolitis
 Short-term Adverse effects for the infant
 Greatest concern for infection and adrenal suppression
 Evidence presented shows no increase in infection, or
clinically important adrenal suppression, rapid return of
adrenal function when antenatal steroids are
discontinued
 Long-term Adverse effects for the infant
 Children from 3 large trials have been monitored in
childhood
 Follow-up data have been published on physical growth
and development up to 3 years of age in the US
 None of these studies indicates that antenatal steroid
therapy has any effect on these parameters, nor is there
any evidence that lung growth is affected
 Short and Long-term Adverse Maternal Effects
 Maternal infection
 Maternal Pulmonary edema
 In women treated with corticosteroids in combination with IV
fluids and tocolytics
 Risk factors: Fluid overload, presence of underlying heart
disease, multiple pregnancy
 Type of Corticosteroid
 Dexamethasone and Betamethasone
 Identical in biologic activity
 Readily cross the placenta in their biologically active
form
 Devoid of mineralocorticoid activity, weak
immunosuppressive activity
 Most extensively studied for accelerating fetal lung
maturation
 Two doses of Betamethasone 12 mg given
intramuscularly 24 hours apart
 Dexamethasone 6 mg given intramuscularly 12 hours
apart for 4 doses
 Timing
 Neonatal benefits from a complete course of antenatal
corticosteroids starting at 24 hours and lasting up to 7
days following initial treatment
 Reduction in neonatal mortality, RDS and IVH even
with treatment initiated less than 24 hours prior to
delivery
 Single versus multiple courses
 Randomized NICHD Maternal-Fetal Medicine Units
Network trial of single versus weekly courses of
betamethasone
 Less morbidity in newborns given weekly doses who were
delivered before 32 weeks
 Trial was discontinued because repetitive courses adversely
impacted birthweight and incidence of fetal growth
restriction
 Single versus multiple courses
 Other studies have shown:
 Significantly associated with abnormal psychomotor
development (Esplin and colleagues, 2000)
 Significant reduction in head circumference, lower
birthweight ( Thorp and co-workers 2001)
 Dose-dependent decrease in birthweight and length (Mercer
et al, 2001)
 Recommendations: (NIH, 2001)
 1. All pregnant women between 24-34 weeks’ gestation
who are at risk of preterm delivery within 7 days should
be considered candidates for antenatal treatment with
corticosteroids.
 2. There is no proof of efficacy of any regimen of
antenatal corticosteroid administration other than a
mixture of 6 mg of betamethasone phosphate and 6 mg
of betamethasone acetate (total 12 mg of
betamethasone) given intramuscularly every 24 hours
for 2 doses, or dexamethasone 6 mg given
intramuscularly every 12 hours for 4 doses
 3. Because of insufficient scientific data from
randomized clinical trials regarding efficacy and safety,
repeated courses of corticosteroids should not be used
routinely. In general, repeated courses should be
reserved for patients enrolled in randomized controlled
trials
Glucocorticoid therapy
 Parkland Hospital (2008)
- single course therapy recommended by ACOG
 Which corticosteroid:
- bethamethasone and dexamethasone were
comparable in reducing rates of major neonatal
morbidities in preterm infants.
Management of Preterm Ruptured
Membranes and Preterm Labor
 1. Confirming the Diagnosis
 2. Determining the Gestational Age
 3. Evaluating for the presence of maternal and/or fetal
infection
 4. Establishing the onset of labor
 5. Ruling out fetal distress
 Diagnosis of PROM
 Leakage of fluid from the vagina
 A conclusive diagnosis of ruptured membranes is made
when there is pooling of amniotic fluid in the posterior
fornix or clear fluid passing from the cervical canal on
sterile speculum exam
 Nitrazine Paper
 pH sensitive paper strip that changes color from yellow-green
to dark blue at a pH above 6.0 to 6.5
 pH of the vagina in pregnancy is 4.5-6.0
pH of amniotic fluid is 7.1-7.3
 False-positive results from contamination with blood, semen
or alkaline antiseptics
 Vaginal infections may raise the pH of the vagina
 Ferning test
 Swab of the posterior vaginal fornix should be taken, smeared
on a slide, allowed to dry and examined under a microscope
for the presence of a typical FERNING appearance
 Establishing Gestational Age
 Menstrual dating, prenatal examinations, previous
ultrsonograms reviewed
 Ultrasonography should be performed, if with any
doubts
 Oligohydramnios is usually confirmatory of PROM
 Useful in confirming the presentation
 Ruling out Chorioamnionitis
 Based on clinical signs and symptoms
 Fever (100.4oF), leukocytosis, maternal and fetal
tachycardia, uterine tenderness, malodorous vaginal
discharge
 Laboratory tests: C-reactive protein
 Ruling out Labor
 Presence of regular and painful uterine contractions
 Endovaginal ultrasound may be used to determine
whether cervical dilatation is present
 External electronic fetal monitoring may be applied
 Ruling out Fetal Distress
 PROM increases the risk of umbilical cord prolapse and
cord compression from oligohydramnios
 Fetal heart rate monitoring should be included in the
initial evaluation if the fetus is of viable gestational age
 TOCOLYSIS
 Premature labor is an expected sequela of PROM and
prematurity is the leading cause of perinatal morbidity
and mortality
 Prospective, randomized controlled trials of tocolytic
agents in PPROM have been conducted
 One study showed a prolongation of pregnancy of up to 24 hours
with tocolytic therapy
 2 studies showed no difference
 NONE showed any prolongation of pregnancy beyond that point
or any difference in any index of perinatal morbidity and
mortality measured
 TOCOLYSIS
 Randomized trials of prophylactic oral tocolytics failed
to show pregnancy prolongation
 CORTICOSTEROIDS
 Initial trials of corticosteroids with PPROM did not
show a reduction in the rate or severity of RDS in treated
patients
 Some studies also showed and increase in the risk of
maternal and/or neonatal infections in the patients
randomized to the corticosteroid group
 Meta-analyses have been done with conflicting results
 CORTICOSTEROIDS
 NIH (1994): “the use of corticosteroids to reduce infant
morbidity in the presence of PPROM remains
controversial”
 Steroids reduced the overall incidence of RDS,
magnitude was not as great as when the membranes are
intact
 Reduction in intraventricular hemorrhage (IVH) in
infants younger than 30-32 weeks
 CORTICOSTEROIDS
 Corticosteroids can be used in the earlier gestational
ages (less than 30-32 weeks) where maximum benefit for
RDS, IVH and mortality will be achieved in conjunction
with antibiotics and only a single course should be given
regardless of duration of the latency period
 PROPHYLACTIC ANTIBIOTICS
 Maternal and perinatal risks of infection would be
reduced
 Interval between PROM and delivery might be
prolonged
 PROPHYLACTIC ANTIBIOTICS
 Mercer and Arheart (1995)
 Use of prophylactic antibiotics in patients with PPROM resulted
in a longer latent period and in reductions in maternal infections,
including both chorioamnionitis and endometritis
 Fetal and neonatal benefits include lower rates of sepsis,
pneumonia and intraventricular hemorrhage
 No uniformity in antibiotics chosen or in duration of

therapy
 3-day or 7-day regimens of ampicillin or ampicillin sulbactam
 Erythromycin
 Management aimed at prolonging gestation for the
patient who is not in labor, not infected and not
experiencing fetal distress
 Expectant management
 Most commonly accepted scheme for the patient less
than 36 weeks with PROM but with a viable fetus
 Hospitalization
 Careful observation for signs of infection, labor or fetal
distress
 Monitoring of FHR and uterine contractions
 If labor begins, and infection or fetal distress develops
delivery is warranted
 Daily clinical evaluation, frequent non-stress tests,
Biophysical Profile evaluation
 When the patients reach 36 or 37 weeks’ gestation,
delivery is indicated
Recommended management of
Preterm Ruptured membranes:
Gestational age Management
34 weeks or more Proceed to delivery usually by induction
of labor.
Group B streptococcal prophylaxis is
recommended.
32 weeks to 33 completed weeks Expectant management unless
pulmonary maturity is documented.
recommended.
Corticosteroids- No concensus, but
some experts recommend
Antimicrobials to prolong latency if no
contraindications
Recommended Management of
Preterm Ruptured Membranes
Gestational age Management
24 to 31 completed weeks Expectant management.
recommended
Single course corticosteroid is
recommended.
Tocolytics? NO consensus
Antimicrobials to prolong latency if no
contraindications
Before 24 weeks Patient counselling.

Expectant management or induction of
labor.
Group B strep prophylaxis is not
recommended.
Corticosteroids are not recommended
Antimicrtobials? Incomplete data on
use
Preterm Labor
1. Confirmation of preterm labor.
2. For pregnancies less than 34 weeks in women with
no maternal or fetal indications for delivery, close
observa tion with monitoring of uterine contractions
and FHB is appropriate. Serial examinations are
done to assess cervical changes.
3. For pregnacies less than 34 weeks, corticosteroids are
given for enhancement of fetal lung maturation.
4. Consideration is given for maternal mganesium
sulfate infusion 12 to 24 hours to afford fetal
neuroprotection.
Preterm Labor
5. For pregnancies less than 34 weeks in women who
are not in advanced labor, some practitionaer believe
it is reasonable to attempt inhibition of contractions
to delay delivery while women are given
corticosteroids therapy and group B streptococcal
prophylaxis.
6. For pregnancies 34 weeks and beyond, women with
preterm labor are monitored for labor progression
and fetal well-being.
7. For active labor, an antimicrobial is given for the
prevention of neonatal group B strep infection.
Intrapartum Management
 Labor:
- continuous electronic fetal monitoring.
- Fetal tachycardia ( sepsis)
- antibiotic prophylaxis
 Delivery:
- episiotomy in the absence of a relaxed outlet.
- STAFF proficient in resuscitative techniques
 Risks
 Maternal and fetal risks vary with the gestational age at
membrane rupture
 Include uterine infection and sepsis
 Before 25 weeks, risk of oligohydramnios with resultant
pulmonary hypoplasia and limb compression deformities

Preterm Labor Obstetrics

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Preterm Labor Obstetrics

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DEFINITIONS

 Preterm Birth: Any delivery regardless of birth

 Low Birthweight (LBW): Infants who weight under

 Rate of LBW: 7.7% (2001) for singleton and multiple

 Perinatal mortality is the sum of fetal stillbirths and

 Preterm birth is the leading cause of perinatal

 Neonatal deaths (67.58% average rate), relative risk of

 60% for infants with birth weights between 501-750 g

 50% for infants weighing between 751 and 1000 g

Cardiovascular Hypotension, PDA, Pulmonary Hypertension,

 Inflammatory responses drive the pathogenesis of

 Uterine cytokines are likely important for preterm

 Lactobacillus species show an enhanced dominance.

 definition:spontaneous rupture of the fetal

 Molecular Changes: Increased apoptosis or necroptosis

 antibiotic prophylaxis to prevent preterm birth is not

 In this condition, normal, hydrogen peroxide-

Symptoms Cervical change

 This glycoprotein is produced in 20 different molecular

 When performed by trained operators, cervical length

 infection is a major concern with membrane rupture.

 The use of antenatal corticosteroids in the setting of

 There are limited reports of sealants in the repair of

 Amniocentesis to Detect Infection

 A single course of betamethasone for women between

 Single versus additional courses of intramuscular

 single rescue course of antenatal corticosteroids is

 The ACOG(2012) issued a Patient Safety Checklist for

 Cochrane metaanalysis: antimicrobial prophylaxis

 The American College of Obstetricians and

 Silicone rings, such as the Arabin pessary, are being

 Some evidence supports the concept that cervical

 β-Adrenergic Receptor Agonist

 Indomethacin, a nonselective cyclooxygenase inhibitor,

 reduced calcium concentrations inhibit contractions.

 This nonapeptide oxytocin analogue is an oxytocin-

 Preterm newborns frequently have intracranial germinal

 Associated with increased adverse outcomes

 Infection of the membranes and amniotic fluid caused

First Birth Second Birth Subsequent preterm

Not preterm Not preterm 2.6

Preterm Not preterm 5.7

Not preterm Preterm 11.1

Preterm Preterm 28.4

 Prophylaxis to prevent group B streptococcal infection is

 In the setting or preterm labor, supplemental antibiotics should

 Absorbed after oral or rectal administration

 Plasma concentrations peaking 1-2 hrs after oral

 Readily passes the placenta

 Binds in a reversible manner to cyclooxygenase

 Comparison trials with beta-adrenergic agents reveal

 Associated with postpartum hemorrhage

 Doubled bleeding times

 Gastrointestinal side effects: kept to a minimum if taken with

 Cyclooxygenase-1 (COX-1)-dependent prostaglandins are the

 Moise and co-workers (1988): antenatal indomethacin

 As a result of prolonged diversion of blood away from the

 Secondary to decreased fetal urine production

 Reversible on cessation of treatment

 If used after other tocolytic agents have failed

 If used in conjuction with magnesium sulfate

 50 mg orally as a loading dose, 25-50 mg orally every 6 hours

 Limited to women before 32 weeks of gestation, fetus with no