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Postterm Pregnancy

Author: Aaron B Caughey, MD, PhD, MPH; Chief Editor: David Chelmow
Updated: Oct 22, 2013

Postterm pregnancy is defined as a pregnancy that extends to 42 0/7 weeks and beyond. [1] The
reported frequency of postterm pregnancy is approximately 3-12%. [1, 2] However, the actual biologic
variation is likely less since the most frequent cause of a postterm pregnancy diagnosis is inaccurate
dating.[3, 4, 5, 6] Risk factors for actual postterm pregnancy include primiparity, prior postterm pregnancy,
male gender of the fetus, and genetic factors.[7, 8, 9, 2, 1, 10]
Laursen et al studied monozygotic and dizygotic twins and their subsequent development of
prolonged pregnancies. They found that maternal but not paternal genetic factors influenced the rate
of postterm pregnancies and accounted for the etiology in as many as 30% of these pregnancies. [11] A
more recently described risk factor is obesity, which appears to increase the risk of pregnancies
progressing beyond 41 or 42 weeks of gestation.[12, 13, 14]
Although the last menstrual period (LMP) has been traditionally used to calculate the estimated due
date (EDD), many inaccuracies exist using this method in women who have irregular cycles, have
been on recent hormonal birth control, or who have first trimester bleeding. In particular, women are
more likely to be oligo-ovulatory than polyovulatory, so cycles longer than 28 days are not
uncommonly seen.[4] If such a cycle is 35 days instead of 28 days, a second trimester ultrasound will
not be powerful enough to redate the pregnancy. Thus, not only the LMP date, but the regularity and
length of cycles must be taken into account when estimating gestational age.
Ultrasonographic dating early in pregnancy can improve the reliability of the EDD; however, it is
necessary to understand the margin of error reported at various times during each trimester. A
calculated gestational age by composite biometry from a sonogram must be considered an estimate
and must take into account the range of possibilities.
Estimation range varies. For example, crown-rump length (CRL) is 3-5 days, ultrasonography
performed at 12-20 weeks of gestation is 7-10 days, at 20-30 weeks is 2 weeks, and after 30 weeks is
3 weeks. Thus, a pregnancy that is 35 weeks by a 31-week ultrasound could actually be anywhere
from 32 weeks to 38 weeks (35 wk +/-3 wk). If the calculated ultrasonographic gestational age varies
from the LMP more than the respective range of error, it is used instead to establish the final EDD.
The importance of determining by what method a pregnancy is dated cannot be overemphasized
because this may have significant consequences if the physician delivers a so-called term pregnancy
that is not or observes a so-called term pregnancy that is very postterm.
When determining a management plan for an impending postterm pregnancy (>40 wk of gestation but
< 42 wk), the 3 options are (1) elective induction of labor, (2) expectant management of the
pregnancy, or (3) antenatal testing. Each of these 3 options may be used at any particular time during
this 2-week period.
Note that if the pregnancy is at risk for an adverse outcome from an underlying condition, either
maternal or fetal, inducing labor may proceed without documented lung maturity. Also, an elective
induction of labor may proceed at or after 39 weeks of gestation in the absence of documented lung
maturity provided that 36 weeks have elapsed since documentation of a positive human chorionic
gonadotropin (+hCG) test finding, 20 weeks of fetal heart tones have been established by a fetoscope
or 30 weeks by a Doppler examination, or 39 weeks' gestation have been established by a CRL or by
an ultrasound performed before 20 weeks of gestation consistent with dates by the patient's LMP.

Perinatal outcomes in postterm pregnancies


Recent studies have shown that the risks to the fetus[15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27] and to the mother[24, 28, 29,
30, 31, 32, 33, 34]
of continuing the pregnancy beyond the estimated date of delivery is greater than originally
appreciated.
Risks have traditionally been underestimated for 2 reasons. First, earlier studies were published
before the routine use of obstetric ultrasonography and, as a result, likely included many pregnancies
that were not truly postterm. As noted above, such a misclassification bias would artificially lower the
complication rates of pregnancies designated postterm and increase the complication rates in those
designated term, resulting in a diminution in the difference between term and postterm pregnancies.
The second issue relates to the definition of stillbirth rates. Traditionally, stillbirth rates were calculated
using all pregnancies delivered at a given gestational age as the denominator. However, once a fetus
is delivered, it is no longer at risk of intrauterine fetal demise, and use of this denominator has
traditionally underestimated the risk of stillbirth. The appropriate denominator is not all deliveries at a
given gestational age, but ongoing (undelivered) pregnancies. [19, 20, 34] In one retrospective study of more
than 170,000 singleton births, for example, Hilder et al demonstrated that the stillbirth rate increased
6-fold (from 0.35-2.12 per 1,000 pregnancies) when the denominator was changed from all deliveries
to ongoing (undelivered) pregnancies.[17]

Fetal and neonatal risks


Antepartum stillbirths account for more perinatal deaths than either complications of prematurity
or sudden infant death syndrome.[18] Perinatal mortality (defined as stillbirths plus early neonatal
deaths) at 42 weeks of gestation is twice that at 40 weeks (4-7 vs 2-3 per 1,000 deliveries,
respectively) and increases 4-fold at 43 weeks and 5- to 7-fold at 44 weeks. [16, 17, 18] These data also
demonstrate that, when calculated per 1000 ongoing pregnancies, fetal and neonatal mortality rates
increase sharply after 40 weeks.[17]
Cotzias et al calculated the risk of stillbirth in ongoing pregnancies for each gestational age from 3543 weeks.[18] The risk of stillbirth was 1 in 926 ongoing pregnancies at 40 weeks gestation, 1 in 826 at
41 weeks, 1 in 769 at 42 weeks, and 1 in 633 at 43 weeks. Uteroplacental insufficiency, asphyxia (with
and without meconium), intrauterine infection, and anencephaly all contribute to excess perinatal
deaths, although postterm anencephaly is essentially nonexistent with modern obstetrical care. [35]
A number of key morbidities are greater in infants born to postterm pregnancies as well as
pregnancies that progress to and beyond 41 0/7 weeks gestation including meconium and meconium
aspiration, neonatal acidemia, low Apgar scores, macrosomia, and, in turn, birth injury. For example,
since postterm infants are larger than term infants, with a higher incidence of fetal macrosomia
(defined as estimated fetal weight 4,500 g) [36] , they are, in turn, at greater risk for other
complications.[37, 38] Such complications associated with fetal macrosomia include prolonged labor,
cephalopelvic disproportion, and shoulder dystocia with resultant risks of orthopedic or neurologic
injury.
Approximately 20% of postterm fetuses have fetal dysmaturity (postmaturity) syndrome, which
describes infants with characteristics of chronic intrauterine growth restriction from uteroplacental
insufficiency.[39] These pregnancies are at increased risk of umbilical cord compression from
oligohydramnios, nonreassuring fetal antepartum or intrapartum assessment, intrauterine passage of
meconium, and short-term neonatal complications (such as hypoglycemia, seizures, and respiratory
insufficiency).

Meconium aspiration syndrome refers to respiratory compromise with tachypnea, cyanosis, and
reduced pulmonary compliance in newborns exposed to meconium in utero and is seen in higher
rates in postterm neonates.[40] Indeed, the 4-fold decrease in the incidence of the meconium aspiration
syndrome in the United States from 1990-1998 has been attributed primarily to a reduction in the
postterm delivery rate[22] with very little contribution from conventional interventions designed to protect
the lungs from the chemical pneumonitis caused by chronic meconium exposure, such as
amnioinfusion[41, 42] or routine nasopharyngeal suctioning of meconium-stained neonates. [43]
Postterm pregnancy is also an independent risk factor for neonatal encephalopathy [44] and for death in
the first year of life.[17, 18]
While much of the work above has been conducted in postterm pregnancies. Some of the fetal risks
such as presence of meconium, increased risk of neonatal acidemia, and even stillbirth have been
described as being greater at 41 weeks of gestation and even at 40 weeks of gestation as compared
with 39 weeks gestation.[23, 24] For example, in one study, the rates of meconium and neonatal acidemia
both increased throughout term pregnancies beyond 38 weeks of gestation. In addition to stillbirth
being increased prior to 42 weeks of gestation, one study found that the risk of neonatal mortality also
increases beyond 41 weeks of gestation.[45]Thus, 42 weeks does not represent a threshold below
which risk is uniformly distributed. Indeed, neonatal morbidity (including meconium aspiration
syndrome, birth injury, and neonatal acidemia) appears to be the lowest at around 38 weeks and
increase in a continuous fashion thereafter.[46]
While preterm delivery is a well-established risk factor for cerebral palsy, a recent study suggested
that delivery at 42 weeks or later is also associated with increased risk (RR 1.4, 95% CI, 1.2-1.6 when
compared with delivery at 40 weeks gestation). [47]

Maternal risks and mode of delivery


The maternal risks of postterm pregnancy are often underappreciated. These include an increase
in labor dystocia (9-12% vs 2-7% at term), an increase in severe perineal injury (3 rd and 4th degree
perineal lacerations) related to macrosomia (3.3% vs 2.6% at term) and operative vaginal delivery,
and a doubling in the rate of cesarean delivery (14% vs 7% at term). [19, 28, 29, 30] The latter is associated
with higher risks of complications such as endometritis, hemorrhage, and thromboembolic disease. [29,
48]

In addition to the medical risks, the emotional impact (anxiety and frustration) of carrying a pregnancy
1-2 weeks beyond the estimated due date should not be underestimated. In a randomized, controlled
trial of women at 41 weeks of gestation, women who were induced would desire the same
management 74% of the time, whereas women with serial antenatal monitoring only desired the same
management 38% of the time.[49]
Similar to neonatal outcomes, maternal morbidity also increases in term pregnancies prior to 42
weeks of gestation. Such complications as chorioamnionitis, severe perineal lacerations, cesarean
delivery rates, postpartum hemorrhage, and endomyometritis all increase progressively after 39
weeks of gestation.[24, 31, 32, 33, 22]

Timing of Delivery
The first decision that must be made when managing an impending postterm pregnancy is whether to
deliver. In certain cases (eg, nonreassuring surveillance, oligohydramnios, growth restriction, certain
maternal diseases), the decision is straightforward. In these high-risk situations, the time at which the

risks of remaining pregnant begin to outweigh the risks of delivery may come at an earlier gestational
age (eg, 39 weeks of gestation). However, frequently several options can be considered when
determining a course of action in the low-risk pregnancy. The certainty of gestational age, cervical
examination findings, estimated fetal weight, patient preference, and past obstetric history must all be
considered when mapping a course of action.
The main argument against a policy of routine induction of labor at 41 0/7 to 41 6/7 weeks has been
that induction increases the rate of cesarean delivery without decreasing maternal and/or neonatal
morbidity. Some of the studies that failed to show a reduction in fetal/neonatal morbidity were diluted
by poorly dated pregnancies that were not necessarily postterm. In addition, the potential for
increasing the risk for cesarean delivery with a failed induction is far less likely in the era of safe and
effective cervical ripening agents.
To date, more than 10 studies have been published of elective induction of labor, many of them at 41
weeks of gestation.[50, 35, 51, 52, 53, 54] The preponderance of the evidence from these studies, including
meta-analyses, find that not only is rate of cesarean delivery not increased in women who were
randomized to routine induction of labor, but also more cesarean deliveries were performed in the
noninduction groups, and the most frequent indication was fetal distress. Even with multiple studies,
very few neonatal differences have been demonstrated. However, the reduction in meconium is
statistically significant and the rate of neonatal mortality is lower.
In summary, routine induction at 41 weeks of gestation does not increase the cesarean delivery rate
and may decrease it without negatively affecting perinatal morbidity or mortality. In fact, both the
woman and the neonate benefit from a policy of routine induction of labor in well-dated, low-risk
pregnancies at 41 weeks' gestation. Because it is associated with a lower rate of adverse outcomes,
including shoulder dystocia and meconium aspiration syndrome, this policy may also prove to be
more cost-effective.[55]
A policy of routine induction at 40 weeks' has few benefits, and there are multiple reasons not to allow
a pregnancy to progress beyond 42 weeks.
Prior to 41 weeks of gestation, the evidence becomes more scant with only 3 small, non-US,
randomized, controlled trials comparing elective induction of labor to expectant management of
pregnancy.[53] However, elective induction of labor is increasingly being used as a management
strategy.[56, 57] While this management may be reasonable in a practice that allows 48 hours or more for
the management of the latent phase and the first stage of labor overall, in a setting where induction of
labor is called a failure after 18-24 hours, it will likely further increase the cesarean delivery rate.

Prevention of Postterm Pregnancy


As noted above, the most decisive way to prevent postterm pregnancy is induction of labor prior to 42
weeks gestation. However, since complications rise during 40 and 41 weeks' gestation and both
clinicians and patients are concerned about the risks of induction of labor, it is perceivably better for
women to go into spontaneous labor at 39 weeks of gestation on their own. Several minimally
invasive interventions have been recommended to encourage the onset of labor at term and prevent
postterm pregnancy, including membrane stripping, unprotected coitus, and acupuncture.
Stripping or sweeping of the fetal membranes refers to digital separation of the membranes from the
wall of the cervix and lower uterine segment. This technique, which likely acts by releasing
endogenous prostaglandins from the cervix, requires the cervix to be sufficiently dilated to admit the
practitioners finger. Although stripping of the membranes may be able to reduce the interval to

spontaneous onset of labor, a reduction in operative vaginal delivery, cesarean delivery rates, or
maternal or neonatal morbidity has not been consistently proven. [58, 59, 60]
Unprotected sexual intercourse causes uterine contractions through the action of prostaglandins in
semen and potentially release of endogenous prostaglandins similar to stripping of the membranes.
Indeed, prostaglandins were originally isolated from extract of prostate and seminal vesicle glands,
hence their name. Despite some conflicting data, it appears that unprotected coitus may lead to the
earlier onset of labor, reduction in postterm pregnancy rates, and less induction of labor.[61, 62, 63]
In a small randomized trial that attempted to address this question, women were randomized to a
group advised to have coitus versus a control group that was not. In this study, the women advised to
have coitus did so more often (60% vs 40%), the difference in the rate of spontaneous labor was not
measurable in this underpowered study.[64] Similarly, the efficacy of acupuncture for induction of labor
cannot be definitively assessed because of the paucity of trial data; this requires further examination.
[65, 66]

Cervical Ripening and Intrapartum Management


Once the decision to deliver a patient has been made, the management of the labor induction
depends on the clinical setting, and a brief review of cervical ripening agents and potential
complications of induction of labor is appropriate. A comprehensive review of all available methods for
cervical ripening, indications, contraindications, and dosing is beyond the scope of this article.
As many as 80% of patients who reach 42 weeks' gestation have an unfavorable cervical examination
(ie, Bishop Score < 7). Many options are available for cervical ripening. The different preparations,
indications, contraindications, and multiple dosing regimes of each require practitioners to familiarize
themselves with several of the preparations.
Prostaglandin E2 gel and suppositories for vaginal application were used extensively until the late
1990s when many pharmacies stopped manufacturing them because of the advent of commercially
available and less labor-intensive preparations. Currently available chemical preparations include
prostaglandin E1 tablets for oral or vaginal use (misoprostol), prostaglandin E2 gel for intracervical
application (dinoprostone cervical [Prepidil]), and a prostaglandin E2 vaginal insert (dinoprostone
[Cervidil]). Cervidil contains 10 mg of dinoprostone and has a lower constant release of medication
than Prepidil.[67] In addition, this vaginal insert device allows for easier removal in the event of uterine
hyperstimulation.
Many studies have compared the efficacy and risks of various prostaglandin cervical ripening agents.
Rozenburg et al performed a randomized trial comparing intravaginal misoprostol and dinoprostone
vaginal insert in pregnancies at high risk of fetal distress. They found that both methods were equally
safe for the induction of labor and misoprostol was actually more effective. [68]
Another method for ripening the cervix is by mechanical dilation. These devices may act by a
combination of mechanical forces and by causing release of endogenous prostaglandins. Foley
balloon catheters placed in the cervix, extra-amniotic saline infusions, and laminaria have all been
studied and have been shown to be effective.
Regardless of what method is chosen for cervical ripening, the practitioner must be aware of the
potential hazards surrounding the use of these agents in the patient with a scarred uterus. In addition,
the potential for uterine tachysystole and subsequent fetal distress requires that care be taken to
avoid using too high a dose or too short a dosing interval in an attempt to get a patient delivered

rapidly. Care should also be taken when using combinations of mechanical and pharmacologic
methods of cervical ripening.
Once an induction of labor has begun, watch for the major potential complications associated with
inductions beyond 41 weeks' gestation and have a plan for dealing with each. Complications include
the presence of meconium, macrosomia, and fetal intolerance to labor.
The further the pregnancy progresses beyond 40 weeks, the more likely it is that significant amounts
of meconium will be present. This is due to increased uteroplacental insufficiency, which leads to
hypoxia in labor and activation of the vagal system. In addition, the presence of a smaller amount of
amniotic fluid increases the relative concentration of meconium in utero.
Traditionally, saline amnioinfusion and aggressive nasopharyngeal and oropharyngeal suctioning at
the perineum were used to decrease the risk of meconium aspiration syndrome. Recent studies
contradict this standard practice. Fraser et al performed a prospective, randomized, multicenter study
evaluating the risks and benefits of amnioinfusion for the prevention of meconium aspiration
syndrome.[42] They concluded that in clinical settings, which have peripartum surveillance,
amnioinfusion of thick meconium-stained amniotic fluid did not decrease the risk of moderate-tosevere meconium aspiration syndrome, perinatal death, or other serious neonatal disorders compared
with expectant management. In addition, other recent studies have shown that deep suctioning of the
airway at the perineum does not effectively prevent meconium aspiration syndrome, contrary to
popular belief.
Fetal macrosomia can lead to maternal and fetal birth trauma and to arrest of both first- and secondstage labor. Because the risk of macrosomia increases throughout term and postterm pregnancies,
one of the most important parts of the delivery plan is being prepared for shoulder dystocia in the
event that this unpredictable, anxiety-provoking, and potentially dangerous condition arises. To
prepare such an event, experienced clinicians should be present at the delivery, a stool/step next to
the delivery bed should be placed to help with suprapubic pressure, and the maneuvers to reduce the
shoulder dystocia should be reviewed.
Finally, intrapartum fetal surveillance in an attempt to document fetal intolerance to labor before it
leads to acidosis is critical. Whether continuous fetal monitoring or intermittent auscultation is used,
interpretation of the results by a well-trained clinician is of paramount importance. If the fetal heart rate
tracing is equivocal, fetal scalp stimulation and/or fetal scalp blood sampling may provide the
reassurance necessary to justify continuing the induction of labor. If the practitioner cannot find
reassurance that the fetus is tolerating labor, cesarean delivery is recommended.

Antepartum Fetal Surveillance


Antepartum fetal surveillance is suggested in postterm pregnancies when delivery is not performed.
Although no randomized prospective trials demonstrate a benefit of fetal monitoring, no proof exists
that it negatively affects postterm pregnancies either. Despite a lack of evidence, antepartum fetal
surveillance of postterm pregnancies has become an accepted standard of care despite a lack of
consensus as to a specific regimen of surveillance to be offered. [1]
The perinatal mortality rate increases gradually throughout pregnancy, with the greatest risk affecting
pregnancies continuing past 41 weeks. Therefore, although no evidence can prove that routine
monitoring between 40 and 42 weeks improves perinatal outcome, ACOG states that it is reasonable
to begin antepartum testing after 41 weeks' gestation. [1] In one study of this issue, Bochner et al
demonstrated that initiating monitoring at 41 weeks of gestation led to lower rates of complications. [69]

No single method of antenatal surveillance has been shown to be superior to any other. Options
include a nonstress test, contraction stress test, full biophysical profile, modified biophysical profile
(nonstress test and amniotic fluid index), or a combination of these modalities. Evaluation of the
amniotic fluid level has been shown to be especially important because of demonstrated increased
adverse pregnancy outcomes. Therefore, delivery should be implemented in the event of
oligohydramnios with or without other nonreassuring tests. Doppler ultrasonography has been shown
to provide no proven advantage for evaluating postdate or postterm pregnancies and should not be
routinely used.
A modified biophysical profile has been shown to be as sensitive as a full biophysical profile. Boehm
et al demonstrated that twice-weekly testing of patients at risk for fetal distress was superior to weekly
testing, decreasing the rate of stillbirth from 6.1 per 1000 live births to 1.9 per 1000.
In summary, the use of a nonstress test and an amniotic fluid index 2 times per week for pregnancies
continuing past 41 weeks is reasonable. In addition, if any indication during antepartum surveillance
leads the practitioner to question the intrauterine environment, delivery should be expedited.

Summary
The management of postterm pregnancies is complicated and fraught with complex issues. The
decision of whether to induce labor or to proceed with expectant management with or without
antepartum fetal surveillance is not taken lightly. Data support inducing labor at 41 weeks' gestation in
an accurately dated, low-risk pregnancy, regardless of cervical examination findings. This strategy,
although not without its critics, averts the need for antepartum fetal surveillance and does not increase
the cesarean delivery rate; in fact, it may decrease the cesarean delivery rate.
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http://emedicine.medscape.com/article/261369-overview#a30 post term pregnancy

Post-term birth and the risk of behavioural and


emotional problems in early childhood
1.
2.
3.
4.
5.
6.
7.
8.
9.

Hanan El Marroun1,2,*,
Mijke Zeegers1,3,
Eric AP Steegers4,
Jan van der Ende1,
Jacqueline J Schenk5,
Albert Hofman6,
Vincent WV Jaddoe2,6,7,
Frank C Verhulst1 and
Henning Tiemeier1,6,8
+ Author Affiliations

1.

1.

Department of Child and Adolescent Psychiatry, Erasmus MCSophia,


Rotterdam, The Netherlands, 2The Generation R Study Group, Erasmus MC,
Rotterdam, The Netherlands, 3Pallas Health Research and Consultancy,
Rotterdam, The Netherlands, 4Department of Obstetrics and Gynecology,
Erasmus MC, Rotterdam, The Netherlands, 5Department of Psychology, Erasmus
University Rotterdam, The Netherlands, 6Department of Epidemiology, Erasmus
MC, Rotterdam, The Netherlands, 7Department of Pediatrics, Erasmus MC,
Rotterdam, The Netherlands and 8Department of Psychiatry, Erasmus MC,
Rotterdam, The Netherlands
*Corresponding author. Department of Child and Adolescent Psychiatry, Erasmus MCSophia,
P.O. Box 2060, 3000 CB Rotterdam, The Netherlands. Email:h.marrounel@erasmusmc.nl

Accepted February 23, 2012.


1

Next Section

Abstract
Background Post-term birth, defined as birth after pregnancy duration of 42 weeks,
is associated with increased neonatal morbidity and mortality. The long-term
consequences of post-term birth are unknown. We assessed the association of postterm birth with problem behaviour in early childhood.
Methods The study was performed in a large population-based prospective cohort
study in Rotterdam, The Netherlands. Pregnant mothers enrolled between 2001 and
2005. Of a cohort of 5145 children, 382 (7%) were born post-term, and 226 (4%)
were born preterm. Parents completed a standardized and validated behavioural
checklist (Child Behavior Checklist, CBCL/1.55) when their children were 1.5 and 3
years old. We examined the relation between gestational age (GA) at birth, based on

early fetal ultrasound examination, and problem behaviour with regression analyses,
adjusting for socio-economic and pregnancy-related confounders.
Results A quadratic relationship between GA at birth and problem behaviour
indicates that both preterm and post-term children have higher behavioural and
emotional problem scores than the term born children. Compared with term born
children, post-term born children had a higher risk for overall problem behaviour
[odds ratio (OR)=2.10, 95% confidence interval (CI)=1.323.36] and were almost
two and a half times as likely to have attention deficit / hyperactivity problem
behaviour (OR=2.44, 95% CI=1.384.32).
Conclusions Post-term birth was associated with more behavioural and emotional
problems in early childhood, especially attention deficit / hyperactivity problem
behaviour. When considering expectant management, this aspect of post-term
pregnancy should be taken into account.

Key words

Post-term birth

preterm birth

behavioural and emotional problems

childhood
Previous SectionNext Section

Introduction
Timely onset of labour is important for peri- and post-natal health. Both preterm
(<37 weeks of gestation) and post-term birth (42 weeks of gestation) are
associated with neonatal morbidity and mortality.13 Local management protocols
with regard to elective caesarean delivery and labour induction affect the prevalence
of post-term birth. Overall, labour induction before or at 42 weeks of gestation has
increased,1 but post-term births still occur relatively frequently (up to 510%), even
in industrialized countries.3,4 Accurate pregnancy dating is critical to the diagnosis of
post-term births.3,4 Routine use of ultrasound to confirm pregnancy dating can
decrease occurrence of post-term birth.5 Common risk factors for post-term birth
include obesity, nulliparity and prior post-term birth and rare causes include
placental sulphatase deficiency (an X-linked recessive disorder characterized by low
estriol levels), fetal adrenal hypoplasia or insufficiency and trisomy 16 and 18. 1,2,6,7
The long-term problems associated with preterm birth, such as increased incidence
of cerebral palsy, sensory impairments and behavioural problems are well
known.8 The studies investigating effects of post-term birth have focused on the risks

during pregnancy and delivery.9 Post-term birth increased the risk of neonatal
encephalopathy and death during the first year of life,5,10 but the long-term
consequences are unclear. One of the few studies performed found that post-term
born infants did not differ from controls at age 2 years regarding general intelligence,
physical milestones and illnesses.11 However, a recent study using referral to a
neurologist or psychologist as indicator of developmental problems found that 13%
of children born post-term had a neurological or developmental disorder at the age
of 5 years.12
In this population-based prospective study, we hypothesize that post-term birth is
related to behavioural and emotional problems in preschool children. In order to
examine the specificity of the association between post-term birth and problem
behaviour, we examined specific behavioural and emotional problems including
attention deficit / hyperactivity disorder problems (ADHD), affective problems and
pervasive developmental problems.
Previous SectionNext Section

Materials and methods


This study was embedded within the Generation R Study, a population-based cohort
from fetal life onwards.13 Briefly, pregnant women who were resident in Rotterdam,
The Netherlands, and whose delivery dates were between April 2002 and January
2006, were asked by their midwives and gynaecologists to participate. In the postnatal follow-up of the Generation R cohort, 7484 live born children and their
prenatally recruited mothers participated. Post-natally, 38 children died. The
remaining 7446 children were eligible for the study. Mothers of 477 children withdrew
consent, and mothers of 410 children gave restricted consent (i.e. no participation in
questionnaire studies). The remaining mothers of 6559 children gave full consent for
post-natal follow-up. We excluded twin pregnancies, leaving 6422 children who could
be contacted. Information on child behavioural and emotional problems at 18 and/or
36 months was available for 5145 children (response rate of 78%). Maternal report at
both 18 and 36 months was available for 3840 children, 812 mothers reported at 18
months only and 493 mothers reported at 36 months only. The Medical Ethical
Review Board of the Erasmus Medical Centre, Rotterdam approved the study
protocol. All parents of participating children gave written informed consent.
Ultrasound during the first visit determined gestational age (GA) to the nearest day,
which will be expressed in our analyses in weeks. In total, 4132 women (80%) had
their first ultrasound examination in early pregnancy (median 13.1 weeks, range 5.1
18.0), 868 women (17%) had it in mid-pregnancy (20.4 weeks, 18.125.0) and only
145 women (3%) had their first ultrasound examination in late pregnancy (30.2
weeks, 25.139.2). Crownrump length was used for pregnancy dating until a GA of
12 weeks and 5 days (crownrump length <65mm), and biparietal diameter was
used for pregnancy dating thereafter (GA from 12 weeks and 5 days onwards,
biparietal diameter >23mm). Methods for establishing GA and standard ultrasound
planes for fetal measurements have been described previously. 14 Inter- and intraobserver intra-class correlation coefficients were all >0.98.14

Preterm birth was defined as birth before 37 weeks gestation (N=226) and postterm birth was defined as birth after 42 weeks gestation (N=382). As an additional
comparison group, we defined a group of children born before 35 weeks of gestation
(N=78) which is normally included in cohorts of preterm babies.
The Child Behavior Checklist for toddlers (CBCL/1.55) was used to obtain
standardized parental reports of childrens behavioural and emotional
problems.15,16 The CBCL was a postal questionnaire and sent to be filled out by the
mother when the child was 18 months old and again when the child was 36 months
old. At 36 months of age, we also asked the father to fill out the CBCL. Each item (99
items in total) is scored on a three-point scale (0=not true, 1=somewhat or
sometimes true and 2=very true or often true), based on the childs behaviour
during the preceding 2 months. The sum of all problem items is the Total Problems
score. There are five Diagnostic and Statistical Manual of Mental Disorders (DSM)oriented scales: anxiety problems, affective problems, pervasive developmental
problems, ADHD and oppositional defiant problems. It has been shown that these
DSM-oriented scales provide accurate and supplementary information on clinical
diagnoses.17 Also, good reliability and validity have been reported for the CBCL. 16 We
used the clinical cut-off scores (91st percentile for the Total Problems score and 98th
percentile for the syndrome scales) to classify children as having behavioural
problems in the clinical range.17 When parents filled out the questionnaire, they were
not aware of our research question exploring the relation between post-term birth
and behavioural problems, but parents generally are aware of the GA of their child
and the risks associated with preterm birth. The maternal CBCL Total Problems
ratings at 18 months and 36 months were correlated (r=0.58, P<0.001). Maternal
and paternal CBCL Total Problems ratings at 36 months were correlated (r=0.56, P<
0.001).
Several covariates were considered in the analyses and were chosen based on the
existing literature and effect estimate changes. Maternal weight and height were
measured at intake. We used postal questionnaires to obtain information on mothers
parity, ethnicity and family income. Maternal ethnicity was defined according to the
classification of Statistics Netherlands.18 Educational level was categorized into three
levels: primary, secondary and higher education.19 Information about maternal
smoking and alcohol use was obtained by questionnaires in each trimester. Based on
these questionnaires, maternal smoking or drinking were categorized into no, until
pregnancy was known and continued during pregnancy as described
previously.20 The Brief Symptom Inventory (BSI) was used to assess maternal
psychopathology in mid-pregnancy; the BSI is a validated self-report questionnaire,
which defines a spectrum of psychiatric symptoms.21 Registries provided information
on obstetric variables such as induction, birthweight, mode of delivery, umbilical
artery pH and Apgar scores after 1 and 5min. The post-natal questionnaire
administered at age 6 and 12 months was used to gather information on
breastfeeding and frequency of day care use.
For descriptive analyses, children were categorized in three groups based on GA: (i)
born after 37 weeks of gestation up to and including 41 weeks and 6 days (term,
reference group); (ii) born after <37 weeks of gestation (preterm); and (iii) born after
42+0 weeks of gestation or more (post-term). Chi-square and t-tests were used to

compare maternal and child characteristics. To test the associations between GA and
behavioural problems, we used linear regression models with GA as a continuous
variable. We used the generalized estimating equation (GEE) to analyse the relation
of GA with the behavioural and emotional outcomes measured at different time
points. GEE adjusts for auto-correlation within the same subject. We used an
unstructured correlation matrix, and thus no assumptions were made about the
correlations. The GEE procedure provides a more precise effect estimate and reduces
the error derived from multiple comparisons (Type I error). A quadratic term was
added to the linear regression models to test whether the associations between GA
and behavioural problems were curvilinear. We conducted the primary analyses in all
children, thus also including the children whose GA was assessed in the second and
third trimester. This was done to reduce the risk of potential selection bias.
Furthermore, we reran the analyses including only those children with a GA dating in
early pregnancy (N=4132), because GA dating by ultrasound is assumed to be more
accurate in early pregnancy.5
Moreover, we performed linear regression analyses for maternal ratings at 18 and 36
months separately to assess whether the quadratic association between GA at birth
and child total problems was present at both ages. We also performed the same
linear regression analyses for paternal ratings at 36 months. The results of these
analyses can be found in theSupplementary data, available at IJE online.
Both linear and quadratic analyses were rerun after exclusion of the preterm
children, to ascertain that the relationship between GA and behavioural problems
was not solely driven by the preterm children. In addition, we restricted the analyses
to the children born after 39 weeks of gestation. To check whether results were not
unduly influenced by ethnicity, we reran analyses regarding the Total Problems score
including only the indigenous Dutch children. Gender-specific estimates for the
quadratic association between GA at birth and child behavioural problems are
provided in the Supplementary Table S1, available as Supplementary
data at IJE online.
For logistic regression analyses, scales were dichotomized using the clinical cut-offs.
We further explored the nature of the association between GA and behavioural
problems with the GEE approach, and calculated the odds ratios (ORs) of clinical
problem behaviour for pre- and post-term born children. We analysed only those
scales on which >0.5% of the participants were classified as having clinical
problems; these were the ADHD, affective problems and pervasive developmental
problems scales.
Potential confounders were chosen based on the literature and effect estimate
changes. Both linear and logistic regression models were adjusted for child gender,
maternal age, education, ethnicity, psychopathology, smoking and drinking during
pregnancy, family income and age of the child at the time of assessments of the
CBCL. Maternal weight, height, parity, breastfeeding and day care did not change the
effect estimates (<5%). Maternal age, psychopathology and age of the child were
used as continuous variables. Maternal education, ethnicity, smoking, drinking and
family income were used as categorical variables in the analyses.

Several post-hoc analyses were performed, including only post-term children without
induction, without assisted extraction or no high birthweight (>4000g) to test if
effects were driven by these birth characteristics.
Not all variables were available for each participant, the mean proportion of missing
values was 5.1% and these were imputed. Variables were centred and missing data
were imputed with the mean or, for categorical variables, dummy variables were
made. The association between GA at birth and child behaviour problems of the
imputed and non-imputed data set were compared, and these associations were
similar. Therefore, we only report results of analyses with the imputed data.
For the non-response analysis, we compared maternal and child characteristics of
included participants with participants from whom we did not obtain behavioural
data. Non-responders were lower educated (14.7% primary education vs 6.3%, P<
0.001), younger (maternal age 28.1 vs 31.2 years, P<0.001), more likely to be nonDutch (62.0 vs 35.4%, P<0.001). Excluded infants had a lower birthweight (3313 vs
3431g, P<0.001) and were born after a shorter period of gestation (39.5 vs 39.8
weeks, P<0.001), compared with included infants. The proportion of children born
post-term was lower in the non-response group than in the response group (5.8 vs
6.9%, P<0.001).
Previous SectionNext Section

Results
Table 1 compares demographic and birth characteristics of 5145 children of whom
4537 (88.2%) were born at term, 382 were born post-term (7.4%) and 226 were born
preterm (4.4%).
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Table 1

Maternal and child characteristics in the study population


In Figure 1, the unadjusted associations between the Total Problems scale and GA at
age 18 and 36 months are shown. The curves show a nadir of the Total Problems
score in children born with a GA around 40 weeks, whereas the mean problem scores
are higher in children who are born more preterm or more post-term. In addition, we
present a scatterplot of the correlation between GA at birth and Total Problems score
in theSupplementary data, available at IJE online.

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Figure 1

The unadjusted association between GA at birth and total behavioural and emotional
problem score
For continuous scores on the total problems, ADHD, affective problems scales and
pervasive developmental problems, linear regression analyses showed a curvilinear
relation between GA and behavioural problems, indicating that children with shorter
or longer gestation had higher behavioural problem scores compared with children
born at term (Table 2). After exclusion of the preterm born children, the curvilinear
relations between GA and behavioural problems remained, showing that mean
problem scores were higher in children with a longer GA [Total Problems score GA2
=0.34, 95% confidence interval (CI)= 0.140.54]. When we restricted the analyses
to the children born after 39 weeks of gestation (n=4115), we still observed a linear
association between GA at birth and total child behavioural and emotional problems
(data not shown).
View this table:

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Table 2

Association between GA at birth and behavioural and emotional problem score


(continuous)
Supplementary analyses demonstrated that results were similar when children with
second or third trimester GA dating were excluded (Total Problems score GA2=
0.12, 95% CI=0.060.18). Moreover, analyses on the Total Problems score were
rerun in a smaller subset of Dutch children; the results were somewhat similar ( GA2
=0.08, 95% CI=0.010.12). In addition, there was no interaction between GA and
the two time points of CBCL measurement indicating that effects remained stable
over early childhood (data not shown).
Separate linear regression analyses using the two maternal ratings each
demonstrated that the quadratic association between GA at birth and child
behavioural problems was present at 18 and 36 months (Supplementary Table S2,
available as Supplementary data at IJE online). Analyses using the paternal ratings of

child behavioural and emotional problems also demonstrated a quadratic


relationship between GA at birth and child emotional and behavioural outcomes
(Supplementary Table S3, available as Supplementary data at IJE online).
Table 3 shows that post-term children were almost twice as likely as term born
children to have clinical problem behaviour on the Total Problems scale and were
more likely to have problems in the clinical range on the ADHD scale. Compared with
term born children, post-term children did not have higher ORs on the affective
problems or pervasive developmental problems scales.
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Table 3

Association between GA at birth and behavioural and emotional problems (clinical


cut-off)
The preterm group showed considerably more behavioural or emotional problems
compared with the term group; this group was more likely to develop problems on
the Total Problems scale and the ADHD scale. With a more stringent cut-off for
preterm birth (<35 weeks), we found that these children were more likely to have
problems in the clinical range on the Total Problems scale, ADHD scale and the
pervasive developmental problems scale.
In addition, some groups of children were excluded from the analyses. These
exclusions did not change the results. The risk for developing total problems in
children born post-term remained present after excluding children with induction (OR
=1.77, 95% CI=1.013.10) or after excluding children >4000g of birth weight (OR
=1.83, 95% CI=1.063.15).
Previous SectionNext Section

Discussion
Our study demonstrated that children born post-term were more likely than their
term born peers to have emotional and behavioural problems at both 18 and 36
months after birth.
Post-term delivery and behavioural problems could be explained in several
pathways. First, a larger baby typically has a higher risk for perinatal problems.
Prolonged labour, cephalopelvic disproportion and shoulder dystocia are increased in
post-term children.2 A perinatal lack of oxygen has been associated with behavioural
problems.22 However, our results did not suggest increased fetal stress in the postterm children, as indicated by low Apgar score, low umbilical pH or meconiumstained amniotic fluid. We controlled for several birth characteristics. Moreover,
exclusion of post-term children with induction and >4000g of birth weight did not
change results. A second explanation is uteroplacental insufficiency: a non-optimal
old placenta offers fewer nutrients and less oxygen than a full term fetus

requires.1 The lack of nutrients and oxygen may predispose to abnormal fetal
development and this may lead to abnormal emotional and behavioural
development.23 In our study, we could not distinguish possible effects of
uteroplacental insufficiency from perinatal problems. Thirdly, it is possible that a
disturbance of the placental clock, which controls the length of pregnancy, is
involved. A marker of this clock is the placental secretion of corticotrophin-releasing
hormone (CRH), which is lower in women who deliver post-term than in women
delivering at term.24 CRH is the principal regulator of the maternal and fetal
hypothalamicpituitaryadrenal (HPA) axis.25 It has been suggested that placental
endocrine malfunctioning or maternal stress at critical times during fetal
development may influence the fetal HPA axis, leading to neuroendocrine
abnormalities that could increase the childs vulnerability to emotional and
behavioural problems later in life.26 Finally, the association between post-term birth
and childhood behavioural problems could be explained by underlying causes of
being born post-term. In other words, the cause for post-term could also be the
cause for having behavioural problems, for example neurodevelopmental factors
related to behavioural problems could be involved in the complex process of birth.
This is a population-based study including many post-term children. We measured
problem behaviour with the same validated instrument (CBCL/1.55) at two time
points. As ultrasound gestational dating is thought to be superior to last menstrual
period-based gestational dating,5we decided to use primarily ultrasound dating.
Eighty percent of our sample was dated with ultrasound assessment in early
pregnancy. However, some limitations must be discussed. Firstly, mothers were not
formally blinded for the GA of their children and they might perceive more
behavioural problems in post-term children. However, the notion that a post-term
birth may signal at-risk babies is largely non-existent in the medical profession and
absent in the public debate. Secondly, in the current study, we relied on the CBCL, as
it was not feasible to obtain clinical diagnoses in such a large number of children.
Moreover, these children were too young to be assessed by teachers or other
informants, thus we had to rely on parental ratings that may be biased. Moreover,
the CBCL is not a clinical instrument and cannot provide diagnoses, but addresses
continuous traits in children. However, the DSM-oriented scales provide accurate
information 17 and good reliability and validity have been reported.16
Finally, although we controlled for a large number of confounders, including maternal
smoking, psychopathology and socio-economic characteristics, residual confounding,
for example maternal malnutrition during pregnancy, cannot be ruled out.
Management of prolonged pregnancy follows two approaches: proposing induction
before 42 weeks of gestation or close monitoring of pregnancy after 41 weeks with
selective induction in case of fetal distress or a favourable Bishop score. 4 Pregnancy
and perinatal care are criticized in The Netherlands, as perinatal mortality ranks as
the third worst in Europe.27 Until mid-2008, a woman with a low-risk pregnancy at 42
weeks was referred to a gynaecologist for close monitoring only. The current revised
policy requires a referral at 41 weeks. Although the rate of post-term births went
down after introducing first trimester ultrasound dating of GA,5 post-term delivery
remains common.4

In conclusion, post-term children have a considerably higher risk of clinically relevant


problem behaviour. They are more than twice as likely as term born children to have
clinical ADHD. Further research is needed to determine the causes of post-term birth
to reduce post-term birth rates and to minimize long-term consequences. Also,
longer follow-up is necessary to establish whether the relationship between postterm birth and behavioural problems will persist.
Previous SectionNext Section

Supplementary Data
Supplementary Data are available at IJE online.
Previous SectionNext Section

Funding
The Sophia Childrens Hospital Fund (project number 553) and the WH Krger
Foundation. The first phase of the Generation R Study is made possible by financial
support from the Erasmus Medical Centre, the Erasmus University and The
Netherlands Organization for Health Research and Development (Zon MW, grant
ZonMW Geestkracht 10.000.1003).
Previous SectionNext Section

Acknowledgments
The Generation R Study is conducted by the Erasmus Medical Centre in close
collaboration with the School of Law and Faculty of Social Sciences of the Erasmus
University Rotterdam, the Municipal Health Service Rotterdam area, the Rotterdam
Homecare Foundation and the Stichting Trombosedienst & Artsenlaboratorium
Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of general
practitioners, hospitals, midwives and pharmacies in Rotterdam. H.E.M. checked the
references used in this article for accuracy and completeness. H.T. will act as
guarantor for the article. Someone with an excellent mastery of the English language
has carefully edited the article. This article represents original material and has not
been published previously in whole or in part. In addition, no similar paper is in press
or under review elsewhere.
Conflict of interest: F.C.V. is author and head of the Department of Child and
Adolescent Psychiatry at Erasmus MC, which publishes the Achenbach System of
Empirically Based Assessment (ASEBA) and from which he receives remuneration. All
other authors report no conflicts of interest.
KEY MESSAGES

GA at birth and behavioural and emotional problems in early childhood show a


non-linear quadratic relation indicating that both preterm and post-term children
are at higher risk for problems.

Children born post-term were twice as likely as their term-born peers to have
ADHD in early childhood.

Our results suggest that children born post-term have a neurodevelopmental


delay. However, further research is needed to demonstrate a causal relation.

Published by Oxford University Press on behalf of the International Epidemiological Association


The Author 2012; all rights reserved.
Previous Section

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http://ije.oxfordjournals.org/content/early/2012/04/11/ije.dys043.full

Prolonged and post-term pregnancies:


guidelines for clinical practice from the French
College of Gynecologists and Obstetricians
(CNGOF)
Christophe Vayssire a b
, Jean-Baptiste Haumonte c , Anne Chantry d , Frdric Coatleven e , Marie Pascal
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Abstract
The duration of pregnancy varies between 40+0 and 41+3 weeks. Conventionally, and essentially arbitrarily, a
pregnancy is considered to be prolonged after 41+0 weeks, but the infant is not considered post-term until
42+0 weeks (Professional consensus). A term birth thus occurs during the period from 37+0 to 41+6 weeks.
In France, prolonged pregnancies (41+0weeks) involve 1520% of pregnant women, and post-term pregnancies
(42+0 weeks) approximately 1%. The frequency of post-term pregnancies is very heterogeneous: in Europe and
the United States, it ranges from 0.5% to 10% according to country.
In prolonged pregnancies, the cesarean section rateespecially the emergency cesarean rateis multiplied by
approximately 1.5 (grade B). From 3706 to 4306 weeks, the risk of perinatal mortality increases regularly, from
0.7 to 5.8.
Meconium aspiration syndrome is responsible for substantial morbidity and mortality, and its incidence increases
regularly between 38+0 and 42+6 weeks, from 0.24 to 1.42 (grade B). Similarly, the risks of neonatal acidosis
(grade B), 5-min Apgar scores less than 7 (grade B) and admissions to neonatal intensive care (grade B)
increase progressively between 38+0 and 42+6 weeks. These risks appear to double for post-term growthrestricted newborns (grade C).
Ultrasound dating of the pregnancy makes it possible to reduce the risk that it will be incorrectly considered
prolonged and that labor will therefore be induced unnecessarily. To harmonize practices, if the crown-rump
length (CRL) is correctly measured (this measurement should be taken between 11+0 and 13+6 weeks, when CRL
should measure from 45 to 84mm), ultrasound dating based on it should be used to determine the official date
pregnancy began, regardless of its difference from the date assumed by the patient or estimated based on the
date of the last menstrual period. This rule does not apply to pregnancies by IVF, for which the date pregnancy
began is defined by the date of oocyte retrieval (Professional consensus).
From 3706 to 4306 weeks, the risk of perinatal mortality increases regularly and there is no threshold at which a
clear increase in perinatal mortality becomes visible. Fetal monitoring by cardiotocography (CTG) that begins at
41+0 weeks would cover approximately 20% of women and reduce perinatal morbidity compared with monitoring
that begins at 42+0 weeks (grade C). The frequency recommended for this monitoring ranges between two and
three times a week (Professional consensus).
For ultrasonography assessment, measurement of the largest fluid pocket is recommended, because
measurement of the amniotic fluid index (that is, the sum of the four quadrants) is accompanied by more
diagnoses of oligohydramnios, inductions of labor, and cesareans for fetal distress without any improvement in
neonatal prognosis (grade A). The practice of assessing the Manning biophysical score increases the number of
diagnoses of oligohydramnios and fetal heart rage (FHR) abnormalities and generates an increase in the rates of
inductions and cesareans without improving neonatal prognosis. The use of this biophysical score in monitoring
prolonged pregnancies is therefore not recommended (grade B).

In the absence of a specific disorder, induction of labor can be proposed in patients between 41+0 and 42+6 weeks
(grade B). Nonetheless, the choice of prolongation beyond above 42+0 weeks appears to involve an increase in
fetal risk, which must be explained to the patient and balanced against the potential disadvantages of induction
(Professional consensus).
Stripping the membranes can reduce the duration of pregnancy by increasing the number of patients going into
labor spontaneously during the week afterward (grade B). Compared to an expectant approach, it does not
increase the cesarean section rate (grade A). It reduces recourse to induction by 41% at 41+0 weeks and by 72%
at 42+0 weeks (grade B), without increasing the risk of either membrane rupture or maternal or neonatal infection
(grade B).
Used as a tampon or vaginal gel, prostaglandins E2 (PGE2) are an effective method of inducing labor (grade A).
They can be used to induce labor successfully, regardless of cervical ripeness (grade A). If misoprostol is chosen,
the lowest dose is to be preferred, starting with a vaginal dose of 25g every 36h (grade A). For misoprostol,
more powerful studies remain necessary for better defining the doses, routes of administration, tolerance and
indications. Misoprostol at any dose is contraindicated in women with uterine scars (grade B). Placement of an
intracervical Foley catheter is an effective mechanical means of inducing labor, with less uterine hyperstimulation
than prostaglandins and no increase in the cesarean section rate (grade A). Nonetheless, as the risk of infection
might be increased, this technique requires more robust evaluation before entering general practice (grade B).
In cases of meconium-stained amniotic fluid, pharyngeal aspiration before delivery of the shoulders is not
recommended (grade A). The team managing a post-term newborn with meconium-stained amniotic fluid at birth
must know how to perform intubation and, if the intubation is not helpful, endotracheal aspiration (grade C) and
ventilation with a mask. Routine endotracheal intubation of a vigorous newborn is not recommended (grade A).

2. Definitions and conventions [6]


Depending on the method of calculation, genetic factors and some maternal characteristics, the duration of
gestation ranges from 280 to 290 days from the first day of the last menstrual period (for regular 28-day cycles).
This duration is generally expressed in France as weeks of amenorrhea, which corresponds to the English
expression weeks of gestation. The duration of pregnancy therefore varies between 40+0 and 41+3weeks. Setting
an official due date for women appears illusory, for these vary according to author, mode of calculation and
country. This generally does not present problems, however, for what is essential is that physicians explain to
their patients the date by which specific surveillance for prolonged pregnancy should start and the date at which
induction of labor might be envisioned.
Conventionally, and essentially arbitrarily, a pregnancy is considered to be prolonged after 41+0 weeks, but the
infant is not considered post-term until 42+0 weeks (professional consensus). A term birth thus occurs during the
period from 37+0 to 41+6 weeks ( Fig. 1 ). In view of the moderate, progressive increase in perinatal morbidity
during this period and beyond, the three days (at a maximum) that separate 41+0 weeks from 9 months do not
appear to produce a significant variation in perinatal complications, and this approximation between 41+0 weeks
and 9 months is acceptable (Professional consensus).

3. Frequency of prolonged and postterm pregnancies [7]


In France, prolonged pregnancies (41+0 weeks) involve 1520% of pregnant women, and post-term pregnancies
(42+0 weeks) approximately 1%. This frequency of post-term pregnancies is very heterogeneous: in Europe and
the United States, it ranges from 0.5% to 10%, varying by and within countries (grade B). These variations
simultaneously reflect the diversity of the populations studied and the variations in obstetric practices between
countries: early pregnancy dating by ultrasound and increasingly frequent recourse to induction of labor have
jointly contributed to a progressive diminution in the incidence of prolonged and post-term pregnancies in most
countries (grade B).

4. Maternal complications of prolonged pregnancies [7]


In prolonged pregnancies, the cesarean section rateespecially the emergency cesarean rateis multiplied by
approximately 1.5 (grade B). Nonetheless, the lack of precision in the studies prevents us from being able to
determine whether the increased cesarean risk is linked to the prolonged pregnancy or to policies that promote
induction of labor starting at some specific gestational age. Prolonged pregnancy is also accompanied by a
moderate increase of the risk of third- and fourth-degree perineal lesions, postpartum hemorrhages,
chorioamnionitis and endometriosis (grade C).

5. Fetal and neonatal complications of prolonged pregnancies [8]


From 3706 to 4306 weeks, the risk of perinatal mortality increases regularly, from 0.7 to 5.8 ( Fig. 1 ). In
prolonged pregnancies, the fetus is at increased risk of oligohydramnios (grade C), fetal heart rate abnormalities
(grade A), and meconium-staining in utero (grade B).
The risk of in utero death has dropped considerably in recent decades (grade B). In 2001, its frequency was
estimated at 1.6 to 3.5 births in developed countries (grade B).
Meconium aspiration syndrome is responsible for substantial morbidity and mortality, and its incidence increases
regularly between 38+0 and 42+6 weeks, from 0.24 to 1.42 (grade B). Similarly, the risks of neonatal acidosis
(grade B), 5-min Apgar scores less than 7 (grade B) and admissions to neonatal intensive care (grade B)
increase progressively between 38+0 and 42+6 weeks. These risks appear to double for postterm growth-restricted
newborns (grade C). Post-term newborns have an increased risk of neurologic complications such as neonatal
convulsions (risk multiplied by 1.5) (grade B), anoxic-ischemic encephalopathy (gradeC), cerebral motor
disorders (risk multiplied by 2.4) (grade B), psychomotor developmental disorders (risk multiplied by 2.2) (grade
C) and childhood epilepsy (risk multiplied by 1.9) (grade B), but these complications cannot be directly attributed
to the post-term status. The absolute incidence of these risks nonetheless remains low.
Post-term newborns have a risk of macrosomia five times higher than that of term newborns (grade B), and
macrosomia (including in newborns of mothers without diabetes) increases the risk of hypoglycemia (grade B).
Although their prevalence remains low (less than 1%), post-term newborns are at increased risk of obstetric
injuries related to shoulder dystocia (grade B) and of bone fractures (grade C). Finally, postmaturity is a risk
factor for polycythemia (grade C), and the risk of neonatal sepsis increases by a factor of 1.3 in post-term
newborns (grade B).

6. Pregnancy dating [9]


Ultrasound dating of the pregnancy makes it possible to reduce the risk that it will be incorrectly considered
prolonged and that labor will therefore be induced unnecessarily (grade A). For spontaneous conceptions, it is
routinely recommended to use crown-rump length (CRL) measurement before 14 weeks to determine the date
pregnancy began and to calculate gestational age (grade C). Ideally, this measurement should be taken between
11+0 and 13+6 weeks (when CRL should measure from 45 to 84mm).
To harmonize practices, if the CRL is correctly measured, the ultrasound dating based on it should be used to
determine the official date pregnancy began, regardless of its difference with the date assumed by the patient or
estimated based on the date of the last menstrual period. It should be explained to the patient that this
measurement provides the best determination of the theoretical ultrasound-determined date pregnancy began, to
serve as the reference for monitoring the pregnancy.
If the quality criteria for CRL measurement before 14 weeks are not met, the date pregnancy began should be
determined by the date of the last menstrual period and the usual duration of the patient's cycles. This rule does
not apply to pregnancies by IVF, for which the date pregnancy began is defined by the date of oocyte retrieval
(Professional consensus). Before any intervention for prolonged pregnancy, it should be verified that the best
indicators were used for dating the pregnancy: date of oocyte retrieval, CRL with its quality criteria, or date of last
menstrual period (Professional consensus).
In the absence of a first trimester ultrasound and other information for dating the pregnancy (e.g., when the date
of the last menstrual period is unknown or cycles are irregular), ultrasound head measurements must be chosen
to estimate gestational age (head circumference or biparietal diameter before 18 weeks) (grade B). When
gestational age is still uncertain above 22 weeks, repeating the biometric measurements 1520 days later makes
it possible to reassess the growth process and sometimes to estimate gestational age more accurately
(Professional consensus).

7. At what gestational age should monitoring begin and how


often? [10]
From 3706 to 4306 weeks, the risk of perinatal mortality increases regularly and there is no threshold at which a
clear increase in perinatal mortality becomes visible. Beginning fetal monitoring at 40+0 weeks would require
close monitoring of nearly half of all pregnant women, and nothing indicates that such a policy would reduce
neonatal morbidity or mortality. On the other hand, fetal monitoring that begins at 41+0 weeks would cover
approximately 20% of women and reduce perinatal morbidity compared with monitoring that begins at 42+0 weeks
(grade C). The frequency recommended for this monitoring is 23 times a week (Professional consensus).

7.1. Are there populations that should be particularly monitored? [10]


Fetal mortality among AfricanAmerican women does not rise significantly at the end of pregnancy (grade B).
Nonetheless, no data justify modifying practices for prolonged pregnancies in this population.
The combination of fetal growth restriction and prolonged pregnancy is a risk factor for perinatal mortality (grade
C). Nonetheless, no specific data for this population allow us to define particular management for this situation.

8. What examinations are useful for monitoring prolonged


pregnancies?
8.1. Counting fetal movements? [11]
In prolonged pregnancies, the perceived diminution of fetal movements appears to be associated with an
increased risk of perinatal morbidity (grade C). Current data are nonetheless insufficient to show that asking
parents to count fetal movements in prolonged pregnancies yields any benefits (Professional consensus).
No method for counting these movements in this situation has been assessed.
Despite the sparse data available, it nonetheless appears sensible to recommend that patients consult their
obstetric professional when they perceive a reduction in these movements (Professional consensus). The
investigations to perform in this situation have not yet been clearly established (Professional consensus).

8.2. Amnioscopy [11]


The diagnostic value of amnioscopy for predicting colored or meconium-stained amniotic fluid is mediocre (grade
C). No association has been demonstrated between colored amniotic fluid on amnioscopy and unfavorable
neonatal outcome in prolonged pregnancies (grade C). Amnioscopy is thus not useful in these cases
(Professional consensus).

8.3. Visual or computerized analysis of fetal heart rate (FHR) [12]


Although visual analysis has not been associated with improved perinatal outcome in monitoring prolonged
pregnancies (grade B), recording FHR is the first-line examination for monitoring fetal well-being, and its
integration into monitoring protocols appears ineluctable (Professional consensus).
In computerized FHR analysis, a short-term variation equal to or greater than 4ms may have a negative
predictive value near 100% for predicting fetal acidosis (grade B). Nonetheless, no study has demonstrated the
superiority of this type of analysis over visual FHR analysis in improving perinatal prognosis (grade B). Whether
or not the situation involves prolonged pregnancies, it is nonetheless a potential alternative to visual analysis,
because it offers advantages in terms of organization and development of monitoring protocols, by reducing, in
particular, the duration and repetition of examinations (grade B). It may also be useful in the analysis of
suspicious tracings. The data for computerized FHR analysis, like those for visual analysis, remain insufficient to
demonstrate the value of its use in prolonged pregnancies (grade B).

8.4. Oxytocin tests [12]


Oxytocin tests make it possible to reduce the false-negative rate of FHR recordings but the procedure is long and
has a false-positive rate of the order of 30%. Data are insufficient to recommend its use as a first- or second-line
tool for fetal monitoring in prolonged pregnancies (grade C).

8.5. Ultrasound test for oligohydramnios [13]


In prolonged pregnancies, there is a significant association between oligohydramnios and the onset of FHR
abnormalities, meconium staining, and an increased cesarean section rate. The diagnostic value of
oligohydramnios in predicting unfavorable outcome is nonetheless only moderate (grade C).

For ultrasonography assessment, measurement of the largest fluid pocket is recommended, because
measurement of the amniotic fluid index (that is, the sum of the four quadrants) is accompanied by more
diagnoses of oligohydramnios, inductions of labor, and cesarean sections for fetal distress without any
improvement in neonatal prognosis (grade A).
In view of the risk of oligohydramnios and of increased morbidity and mortality after 41+0 weeks, it seems
reasonable to suggest prenatal ultrasound monitoring of the quantity of amniotic fluid (measurement of the
largest amniotic fluid pocket) starting at 41+0 weeks and thereafter twice a week (Professional consensus). In
cases of oligohydramnios, defined as less than 2cm in the largest pocket, induction can be envisioned
(Professional consensus). In the absence of induction, monitoring must be reinforced (Professional consensus).

8.6. Artery Doppler indexes [13]


Few studies have found a significant association between abnormal Doppler umbilical, cerebral or aortic indexes
and unfavorable outcome in pregnancies equal to or longer than 41+0 weeks. Because the diagnostic value of
these Doppler indexes is very low, their routine use for prolonged pregnancies is not recommended (grade C).

8.7. The biophysical (Manning) score of fetal well-being [13]


The practice of assessing Manning biophysical scores increases the number of diagnoses of oligohydramnios
and FHR abnormalities and generates an increase in the rates of inductions and cesareans without improving
neonatal prognosis. The use of this biophysical score in monitoring prolonged pregnancies is therefore not
recommended (grade B).

9. At what point should delivery be induced? [14]


In the absence of a specific disorder, induction of labor can be proposed to patients between 41+0 and 42+6 weeks
(grade B). The moment of induction will be determined according to the mother's characteristics (local cervical
conditions, uterine scar, parity, body mass index, and age), her preference, and the organization of care in the
maternity unit (Professional consensus).
Nonetheless, the choice of prolongation beyond 42+0 weeks appears to involve an increase in fetal risk and must
therefore be explained to the patient and balanced against the potential disadvantages of induction (Professional
consensus). This comment is especially important in that the generalized use of CRL measurement during the
first trimester to estimate gestational age can increase the proportion of true post-term pregnancies compared
with the proportion in a similar population that includes inadequately dated pregnancies (Professional
consensus).

10. How should delivery be induced? [15]


10.1. Stripping the membranes [15]
Stripping (also called sweeping) the membranes can reduce the duration of pregnancy by increasing the number
of patients going into labor spontaneously during the week afterward (grade B). Compared to an expectant
approach, it does not increase the cesarean section rate (grade A). It reduces recourse to induction by 41% at
41+0 weeks and by 72% at 42+0 weeks (grade B), without increasing the risk of either membrane rupture or
maternal or neonatal infection (grade B). Its inconveniences (contractions, bleeding, and pain) must nonetheless
be clearly explained and accepted before it is practised. In view of these disadvantages, stripping the

membranes should not be performed during a routine examination without advance information and consent
(Professional consensus).

10.2. Oxytocin [15]


Oxytocin administration is currently the reference method for induction of labor with a ripe cervix at 41 weeks and
later (grade A). When the cervix is unfavorable (Bishop score 5), oxytocin can still induce labor but is no longer
the agent of choice (grade A).

10.3. E2 prostaglandins (dinoprostone) [15]


Used as a tampon or vaginal gel, prostaglandins E2 (PGE2) are an effective method of inducing labor (grade A).
They can be used to induce labor successfully, regardless of cervical ripeness (grade A). When cervical
conditions are unfavorable, PGE2 can reduce recourse to oxytocin and diminish the doses needed (grade A).
The use of PGE2 is associated with a risk of tachysystole that may be accompanied by abnormal FHR
(hyperstimulation syndrome) (grade A).

10.4. E1 prostaglandins (misoprostol) [15]


Although misoprostol is not officially approved for prolonged pregnancies, it is an effective and uncomplicated
means of inducing labor, especially for a very unfavorable cervix (grade A). It is not yet clear whether vaginal or
oral administration is optimal, but the vaginal route has been assessed and chosen most often. A risk of
tachysystole with or without FHR modifications is clearly found in all studies with doses of 50g, but these do
not appear to increase the rates of either neonatal morbidity or cesarean delivery (grade A). The lowest doses
are to be preferred, starting with a vaginal dose of 25g every 36h (grade A). The use of this substance
therefore requires an environment where appropriate obstetric monitoring is available in case of FHR
abnormalities. More powerful studies remain necessary for better defining the doses, routes of administration,
tolerance and indications. Misoprostol at any dose is contraindicated in women with uterine scars (grade B).

10.5. Mechanical means [15]


Placement of an intracervical Foley catheter is an effective mechanical means of inducing labor, with less uterine
hyperstimulation than prostaglandins and no increase in the cesarean rate (grade A). Nonetheless, as the risk of
infection might be increased, this technique requires a more robust evaluation before entering general practice
(grade B).

10.6. Other methods [15]


The current data do not show that acupuncture is effective for inducing labor either at term or in prolonged
pregnancies (grade C). Data concerning nipple stimulation and/or sexual activity are contradictory and insufficient
in this indication (grade C). Finally, the use of nitric oxide (NO) donors is under study.

10.7. Special case of the uterine scar


A uterine scar is a particular situation that exposes the woman and her fetus to the risk of uterine rupture, a risk
of the order of 0.5% in cases of spontaneous labor (grade A). This risk is increased, but moderately (0.7%), by
induction with oxytocin and multiplied by five for inductions by prostaglandins (2.45%) (grade A). It is therefore
logical to avoid non-medically indicated inductions in patients with uterine scars, to avoid prostaglandins, and to
take the Bishop score into account for inductions with oxytocin. We note again that misoprostol is contraindicated
in women with uterine scars (grade B).

11. What management for the newborn? [16]


In cases of meconium-stained amniotic fluid, pharyngeal aspiration before delivery of the shoulders is not
recommended (grade A). The team managing a post-term newborn with meconium-stained amniotic fluid at birth
must know how to perform intubation and endotracheal aspiration (grade C) and ventilation with a mask, if the
intubation is not helpful. Routine endotracheal intubation of a vigorous newborn is not recommended (grade A).
Staff managing post-term newborns with perinatal asphyxia must know the initial steps to be taken in the delivery
room, know the indications for controlled hypothermia treatment (grade A) and have established a protocol for
transfer to the neonatal intensive care unit (NICU) (Professional consensus).
Systematic monitoring of blood glucose is recommended for macrosomic post-term newborns (Professional
consensus). Management of hypoglycemia in post-term newborns does not differ from that in other newborns.
The initial clinical examination of macrosomic post-term newborns should routinely include checking for paralysis
of the brachial plexus and clavicle fractures (Professional consensus).

References

[1] C. Vayssiere. Prolonged pregnancy term and beyondmethod and organization. Journal de
Gynecologie, Obstetrique et Biologie de la Reproduction. 2011;40:701-702

[2] HAS. Les recommandations pour la pratique clinique. Base mthodologique pour la ralisation en
France. Available: http://www.has-sante.fr/portail/jcms/c_431294/les-recommandations-pour-la-pratique-cliniquebase-methodologique-pour-leur-realisation-en-france .

[3] ACOG Committee on Practice Bulletin-Obstetrics. ACOG Practice Bulletin. Clinical management
guidelines for obstetricians-gynecologists. Number 55, September 2004 (replaces practice pattern number 6,
October 1997). Management of Postterm Pregnancy. Obstetrics and Gynecology. 2004;104:639-646

[4] Clinical Practice Obstetrics Committee, Maternal Fetal Medicine Committee, M. Delaney, et
al. Guidelines for the Management of pregnancy at 41+0 to 42+0 weeks. Journal of Obstetrics and Gynaecology
Canada. 2008;30:800-823

[5] G. Mandruzzalo, Z. Alfirevic, F. Chervenak, et al. Guidelines for the management of postterm
pregnancy. Journal of Perinatal Medicine. 2010;38:111-119

[6] C. Le Ray, O. Anselem. Definitions of expected date of delivery and postterm delivery. Journal de
Gynecologie, Obstetrique et Biologie de la Reproduction. 2011;40:703-708

[7] A. Chantry. Epidemiology of prolonged pregnancy: incidence and maternal morbidity. Journal de
Gynecologie, Obstetrique et Biologie de la Reproduction. 2011;40:709-716

[8] A. Chantry, E. Lopez. Fetal and neonatal complications related to prolonged pregnancy. Journal de
Gynecologie, Obstetrique et Biologie de la Reproduction. 2011;40:717-725

[9] L.J. Salomon. How to date pregnancy?. Journal de Gynecologie, Obstetrique et Biologie de la
Reproduction. 2011;40:726-733

[10] J.B. Haumonte, C. dErcole. Prolonged pregnancy: when should surveillance be started and what
should be the frequency?. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction. 2011;40:734-746

[11] M.P. Debord. To evaluate the role of fetal movement counting and amnioscopy in the management
of prolonged pregnancies. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction. 2011;40:767-773

[12] F. Coatleven. Place of fetal heart rate monitoring and its computerized analysis during the
surveillance of prolonged pregnancy. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction.
2011;40:774-784

[13] M.V. Senat. Management of postterm pregnancies: the role for AFI, biophysical score and
Doppler. Journal de Gynecologie, Obstetrique et Biologie de la Reproduction. 2011;40:785-795

[14] L. Sentilhes, P.E. Bouet, M. Mezzadri, et al. Assessment of the benefit-harm balance depending on
gestational age to induce delivery for postterm pregnancies. Journal de Gynecologie, Obstetrique et Biologie de
la Reproduction. 2011;40:747-766

[15] N. Winer. Different methods for the induction of labour in posterm pregnancy. Journal de
Gynecologie, Obstetrique et Biologie de la Reproduction. 2011;40:796-811

[16] E. Lopez. Management of postterm neonates. Journal de Gynecologie, Obstetrique et Biologie de


la Reproduction. 2011;40:812-817

Number 579, November 2013

The American College of Obstetricians and Gynecologists Committee on Obstetric


Practice
Society for Maternal-Fetal Medicine
This document reflects emerging clinical and scientific advances as of the date issued and is
subject to change. The information should not be construed as dictating an exclusive course of
treatment or procedure to be followed.

PDF Format

Definition of Term Pregnancy


ABSTRACT: In the past, the period from 3 weeks before until 2 weeks after the estimated date of
delivery was considered term, with the expectation that neonatal outcomes from deliveries in
this interval were uniform and good. Increasingly, however, research has shown that neonatal
outcomes, especially respiratory morbidity, vary depending on the timing of delivery within this 5week gestational age range. To address this lack of uniformity, a work group was convened in late
2012, which recommended that the label term be replaced with the designations early term (37
0/7 weeks of gestation through 38 6/7 weeks of gestation), full term (39 0/7 weeks of gestation
through 40 6/7 weeks of gestation), late term (41 0/7 weeks of gestation through 41 6/7 weeks of
gestation), and postterm (42 0/7 weeks of gestation and beyond) to more accurately describe
deliveries occurring at or beyond 37 0/7 weeks of gestation. The American College of Obstetricians
and Gynecologists and the Society for Maternal-Fetal Medicine endorse and encourage the uniform

use of the work groups recommended new gestational age designations by all clinicians,
researchers, and public health officials to facilitate data reporting, delivery of quality health care,
and clinical research.

Opinion
Gestation in singleton pregnancies lasts an average of 40 weeks (280 days) from the first day of
the last menstrual period to the estimated date of delivery. In the past, the period from 3 weeks
before until 2 weeks after the estimated date of delivery was considered term (1), with the
expectation that neonatal outcomes from deliveries in this interval were uniform and good.
Increasingly, however, research has identified that neonatal outcomes, especially respiratory
morbidity, vary depending on the timing of delivery even within this 5-week gestational age range.
The frequency of adverse neonatal outcomes is lowest among uncomplicated pregnancies
delivered between 39 0/7 weeks of gestation and 40 6/7 weeks of gestation (2, 3). For this reason,
quality improvement projects have focused, for example, on eliminating nonmedically indicated
deliveries at less than 39 0/7 weeks of gestation (4).
In order to facilitate data reporting, delivery of quality health care, and clinical research, it is
important that all clinicians, researchers, and public health officials use both uniform labels when
describing deliveries in this period and a uniform approach to determining gestational age. To
address the lack of uniformity in neonatal outcomes between 37 0/7 weeks of gestation and 42 0/7
weeks of gestation, a work group was convened in late 2012 to determine whether term pregnancy
should be redefined (5). The work group included representatives from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, the American College of
Obstetricians and Gynecologists (the College), the Society for Maternal-Fetal Medicine (SMFM), and
other professional societies and stakeholder organizations. The work group recommended that the
label term be replaced by the designations early term, full term, late term, and postterm to more
accurately describe deliveries occurring at or beyond 37 0/7 weeks of gestation (Box 1). The group
recommended that the use of the label term to describe all deliveries between 37 0/7 weeks of
gestation and 41 6/7 weeks of gestation should be discouraged. Details of the evidence and
rationale that are the foundation of these recommendations can be found in published summaries
of this conference (5).

Box 1. Recommended Classification of Deliveries


From 37 Weeks of Gestation

Early term: 37 0/7 weeks through 38


6/7 weeks
Full term: 39 0/7 weeks through 40 6/7
weeks
Late term: 41 0/7 weeks through 41
6/7 weeks
Postterm: 42 0/7 weeks and beyond
Data from Spong CY. Defining "term" pregnancy:
recommendations from the Defining "Term" Pregnancy
Workgroup. JAMA 2013;309:24456.

The College and SMFM endorse and encourage the uniform use of the work groups recommended
new gestational age designations by all clinicians, researchers, and public health officials to
facilitate data reporting, delivery of quality health care, and clinical research.

Uniform definitions of term are predicated on a uniform method of determining gestational age.
The work group provided a method for determination of gestational age (5) that, like other similar
methods (6), focused on a hierarchy of clinical and ultrasonographic criteria. Individual methods
may differ in the details of when and how ultrasonographic biometry should be used to change
estimated date of delivery based on last menstrual period; however, it is not the purpose of this
document to establish the priority of one method over another. The College and SMFM are working
with other expert groups to establish evidence-based consensus on criteria for determining
gestational age.

References
1.

2.
3.
4.
5.
6.

World Health Organization. ICD-10: International statistical classification of diseases and


related health problems, 10th revision. Volume 2. 2nd ed. Geneva: WHO; 2004. Available
at: http://www.who.int/classifications/icd/ICD-10_2nd_ed_volume2.pdf. Retrieved August 12,
2013.
Tita AT, Landon MB, Spong CY, Lai Y, Leveno KJ, Varner MW, et al. Timing of elective repeat
cesarean delivery at term and neonatal outcomes. Eunice Kennedy Shriver NICHD MaternalFetal Medicine Units Network. N Engl J Med 2009;360:11120. [PubMed] [Full Text]
Reddy UM, Bettegowda VR, Dias T, Yamada-Kushnir T, Ko CW, Willinger M. Term pregnancy:
a period of heterogeneous risk for infant mortality. Obstet Gynecol 2011;117:1279
87. [PubMed] [Obstetrics & Gynecology]
Nonmedically indicated early-term deliveries. Committee Opinion No. 561. American
College of Obstetricians and Gynecologists. Obstet Gynecol 2013;121:911
5. [PubMed] [Obstetrics & Gynecology]
Spong CY. Defining term pregnancy: recommendations from the Defining Term
Pregnancy Workgroup. JAMA 2013;309:24456. [PubMed] [Full Text]
Ultrasonography in pregnancy. ACOG Practice Bulletin No. 101. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2009;113:45161. [PubMed] [Obstetrics &
Gynecology]

Copyright November 2013 by the American College of Obstetricians and Gynecologists, 409 12th
Street, SW, PO Box 96920, Washington, DC 20090-6920. All rights reserved.
ISSN 1074-861X
Definition of term pregnancy. Committee Opinion No. 579. American College of Obstetricians and
Gynecologists. Obstet Gynecol 2013;122:113940.

A comparison of orally administered misoprostol and membrane


sweeping for labour induction in uncomplicated singleton post-term
pregnancies
A O Adeniji, S E Akinola

Department of Obstetrics and Gynaecology, Ladoke Akintola University of Technology Teaching


Hospital, Osogbo, Nigeria
A O Adeniji, MB BS, FWACS, FMCOG
S E Akinola, MB BS, FWACS, FRCOG

Corresponding author: A O Adeniji (tunji1802@yahoo.com; aoadeniji@lautech.edu.ng)

Objectives. This study assessed the efficacy of the two outpatient processes of singledose 50 g oral misoprostol (OM) and membrane sweeping (MS) on the outcome of
labour induction and the possibility of reducing the need for hospital admission for
cervical ripening/labour induction in uncomplicated post-term singleton pregnancies at
a tertiary health institution in south-western Nigeria.
Methods. A total of 100 patients were equally randomised into the two groups between
April 2007 and March 2010. Primary outcome measures were delivery within 48 hours
after the start of induction and route of delivery. Secondary outcome measures were
time interval from induction to onset of labour (latency period), time interval from start
of induction to delivery (duration of labour), need for oxytocin augmentation, labour
complications, Apgar scores at 1 and 5 minutes, and need for neonatal intensive care
unit (NICU) admission.
Results. Both groups were similar at the baseline with regard to age, parity and days
beyond 40 weeks gestation. There was a significantly shorter induction to onset of
labour (latency) interval in the OM group, with a mean of 17.0 hours compared with
31.9 hours in the MS group (p=0.005), with 82.0% of the patients in the OM group in
spontaneous labour within the latency period of 18 hours as opposed to 32.6% of the
MS group (p<0.005). Forty-two patients in the OM group and 40 in the MS group had a
vaginal delivery (84.0% v. 87.0%, p=0.361), with 12 and 20 patients in the OM and MS
groups, respectively, requiring oxytocin augmentation (p=0.023). The duration of
labour was significantly shorter in the OM group, in which 78.6% of those who had a
vaginal delivery achieved it within 9 hours, compared with 57.5% in the MS group
(p=0.036). Overall, neonatal outcomes and need for NICU admission were similar and
comparable in the two groups. On a preference scale, 43% of the women in the MS
group felt positive about the intervention, compared with 92% of the women in the OM
group.
Conclusion. The study demonstrated a shorter latency period, less need for oxytocin
augmentation and shorter duration of labour in patients who received OM. The two
induction agents were similar with regard to neonatal outcomes and need for NICU
admission. Both showed good safety profiles for outpatient care, although further
assessment of the safety profile with larger studies will be needed. More patients felt
positive about the intervention in the OM group than in the MS group.

S Afr J OG 2013;19(1):4-7. DOI:10.7196/SAJOG.584

Post-term pregnancy is fairly common in obstetric practice and is the most common
indication for induction of labour.1 , 2 , 3 , 4 Recent studies have shown that the risks to
the fetus 5 , 6 and to the mother 7 , 8 of continuing pregnancy beyond the estimated
date of delivery are greater than originally thought, and induction of labour remains an
accepted means of achieving vaginal delivery. In some cases the status of the cervix is
unfavourable for labour induction, the success of which depends to a large extent on
the consistency, compliance and configuration of the cervix. 9 Various methods of

cervical ripening, from membrane sweeping (MS) and use of a transcervical Foley
catheter to administration of prostaglandins (PG) and prostaglandin E1 (PGE1)
analogue, are therefore used.
MS involves digital separation of the fetal membranes from the lower segment of the
uterus. It is an established method of promoting the onset of labour without hospital
admission, and is regularly applied to prevent pregnancies extending beyond
term. 10 , 11 This method causes an increase in local PG production, 12 , 13 which
results in ripening of the cervix and ultimately brings about spontaneous onset of
labour. The results of trials on the effectiveness of MS have been
inconsistent, 3 , 8 , 11 possibly owing to methodological differences between studies. A
Cochrane review suggested that routine use of MS between 38 and 40 weeks does not
seem to produce clinically important benefits; 11 however, it may be beneficial in
women with post-term pregnancies. 14 , 15
Misoprostol, a PGE1 analogue, has been reported to be an effective and affordable
cervical ripening and medical induction agent. It can be used intravaginally or orally and
has excellent shelf-life. These factors are immensely advantageous in low-resource
tropical countries. 2 , 4 However, the processes of cervical ripening and labour induction
require admission to hospital, resulting in additional costs in terms of both human and
material resources. Any safe and effective interventions that also cut costs are
therefore desirable. This study explored the comparative efficacy and safety of the two
outpatient techniques of single-dose 50 g oral misoprostol (OM) and MS on the
outcome of labour induction and their effects on reducing the need for hospital
admission for cervical ripening/labour induction in uncomplicated post-term singleton
pregnancies.

Methods
This study was a prospective, randomised controlled trial of a single dose of 50 g OM
and MS in uncomplicated singleton post-term pregnancies. All patients recruited had
had early ultrasound dating of their pregnancy, which was correlated with the expected
delivery date to exclude wrong dates. The study was conducted between April 2007 and
March 2010 at Ladoke Akintola University of Technology Teaching Hospital, Osogbo,
Nigeria. Patients with singleton post-term pregnancies were recruited after giving
informed consent. One hundred sealed opaque envelopes containing papers marked OM
or MS (50 each) were placed in a box, thoroughly mixed and then numerically labelled.
Computer-generated random numbers were used for patient allocation. Patients were
allocated sequential numbers in order of recruitment, and the correspondingly
numbered envelope was opened for randomisation. The institutional ethical review
committee approved the study. Inclusion criteria were a singleton live fetus, post-term
pregnancy from 40 weeks and 1 day to 40 weeks and 9 days, intact fetal membranes,
Bishops score 5 and cephalic presentation. Exclusion criteria were post-term
pregnancies of 40 weeks and 10 days, multiple pregnancies, grand multiparity,
cephalopelvic disproportion, previous caesarean section or a uterine scar, fetal
malpresentation, fetal distress, placenta praevia, antepartum haemorrhage, premature
rupture of the membranes and medical disorders.

Study groups
One hundred patients, randomised to 50 in each group, were studied. The OM group
received a single 50 g misoprostol tablet orally on an outpatient basis, and the MS
group had MS once only at the antenatal clinic. Patients with unyielding cervices
preventing access into the cervical canal were termed failed MS. All patients in both
groups who did not go into spontaneous labour after 48 hours were categorised as
failed labour induction and together with the women with post-term pregnancies of
40 weeks and 10 days managed according to our departmental protocol of cervical
ripening and labour induction (transcervical Foley catheter or intravaginal misoprostol)
to ensure delivery before 42 weeks gestation.
To eliminate bias, attending obstetricians in the labour ward were blinded to the labourinducing agents used in the study groups. Primary outcome measures were delivery
within 48 hours after the start of induction and route of delivery. Secondary outcome
measures were time interval from the start of induction to onset of labour (latency
period), time interval from the start of induction to delivery (duration of labour), need
for oxytocin augmentation, labour complications, Apgar scores at 1 and 5 minutes, and
need for neonatal intensive care unit (NICU) admission.
Data were entered onto a pre-designed sheet and analysed with SPSS version 17. Mean
( standard deviation (SD)), independent t-test, Pearsons chi-square (with Yates
corrections as appropriate), confidence intervals (CIs) and relative risk (RR) were
determined as necessary. The level of significance was set at 0.05.

Results
A total of 100 patients (50 in each group) were recruited for the study; 4 in the MS
group were categorised as failed MS. At baseline the two groups were similar with
regard to mean age, parity and days beyond 40 weeks gestation (Table 1). Table 2
shows that the latency period was significantly shorter in the OM group than in the MS
group, with a mean of 17.0 hours (CI 11.8 - 22.1) as opposed to 31.9 hours (CI 24.7 39.0) in the MS group (p=0.005). Eighty-two per cent of the patients in the OM group
went into labour spontaneously within the latency period of 18 hours, as opposed to
32.6% in the MS group (p<0.005). Two patients in the OM group and 1 in the MS group
went beyond the 48 hours time limit and were categorised as failed induction, but
subsequently had a vaginal delivery after oxytocin augmentation of labour.

Table 1. Socio-demographic characteristics of study patients


Biodata

OM group ( N =50)

MS group ( N =50)

p -value

Age (years), mean (SD)

26.30 (4.9)

25.38 (5.1)

0.830

Parity, mean (SD)

1.70 (0.8)

1.32 (0.9)

Nulliparous, n (%)

3 (6.0)

10 (20.0)

Multiparous, n (%)

47 (94.0)

40 (80.0)

Days beyond 40 weeks,

5.26 (1.6)

5.00 (1.7)

0.071

0.290

mean (SD)

OM = oral misoprostol; MS = membrane sweeping.

Table 2. Comparison of the agents of induction with regard to latency period


Latency period (hours)

OM group ( N =50)
n (%)

MS group ( N =46)
n (%)

p -value

<6

5 (10.0)

4 (8.7)

<0.005

>6 - 12

18 (36.0)

4 (8.7)

>12 - 18

18 (36.0)

7 (15.2)

>18 - 24

4 (8.0)

13 (28.3)

>24 - 48

3 (6.0)

17 (37.0)

>48

2 (4.0)

1 (2.2)

Forty-two patients in the OM group and 40 in the MS group had a vaginal delivery
(84.0% v. 87.0%, p=0.361), with 12 and 20 patients, respectively, requiring oxytocin
augmentation (p=0.023). Of the caesarean sections (8 in the OM group v. 6 in the MS
group), 5 in the OM group were necessitated by presumed fetal distress, compared with
4 in the MS group (Table 3). The duration of labour was significantly shorter in the OM
group, with 33/42 patients (78.6%) who had a vaginal delivery achieving it within 9
hours, compared with 23/40 (57.5%) in the MS group (Table 4).

Table 3. Comparison of events and outcomes of labour in the study groups


Labour events

OM group ( N =50)
n (%)

MS group ( N =46)
n (%)

Oxytocin augmentation

p -value (CI)

0.02 (1.1 - 7.0)

Yes

12 (24.0)

20 (43.5)

No

38 (76.0)

26 (56.5)

Mode of delivery

0.36 (0.1 - 1.8)

Vaginal

42 (84.0)

40 (87.0)

Caesarean section

8 (16.0)

6 (13.0)

Table 4. Comparison of labour duration in the study groups


Duration of labour (hours)

OM group ( N =42)

MS group ( N =40)

n (%)

n (%)

<6

1 (2.4)

4 (10.0)

>6 - 9

32 (76.2)

19 (47.5)

>9 - 10

8 (19.0)

12 (30.0)

>10 - 12

1 (2.4)

5 (12.5)

p -value

0.036

Overall, neonatal outcomes were similar and comparable in the two groups, with more
babies in the OM group (6/50) than in the MS group (3/46) having moderate asphyxia
at the first minute after birth. However, this was statistically insignificant. NICU
admission rates were similar for the two groups. On a preference scale, 43% of the
women in the MS group felt positive about the intervention, compared with 92% of the
women in OM group who said that they would agree to use of the drug in another postterm pregnancy.

Table 5. Neonatal outcomes in the study groups


Neonatal outcome factors

OM group
( N =50)

MS group
( N =46)

p -value (CI)

Birth weight (g), mean (SD)

3 123 (328)

3 089 (302)

Apgar score at 1 minute, mean


(SD)

7.7 (1.0)

7.4 (0.7)

0.150 (-0.1 0.6)

Apgar score at 1 minute


<7, n (%)

6 (12.0)

3 (6.5)

0.358

Apgar score at 5 minutes, mean


(SD)

9.5 (0.6)

9.478 (0.4)

0.867 (-0.2 0.3)

Apgar score at 5 minutes <7

NICU admission, n (%)

2 (4.0)

2 (4.4)

0.930

Discussion
This study randomised 100 patients, with established gestations beyond 40 weeks but
less than 40 weeks and 10 days, into two groups receiving a single-dose 50 g OM
tablet or single MS on an outpatient basis. The intention was to compare the efficacy of
these two methods for induction of labour, evaluate their possible impact on the
number of post-term women requiring hospital admission for induction of labour at our
institution, and compare fetomaternal safety profiles of the two methods. Various

studies have shown individual benefits of MS as opposed to no sweeping, 16 , 17 and of


OM as opposed to intravaginal misoprostol or other labour-inducing
agents. 18 , 19 However, we did not find any study that compared MS with OM, especially
in the outpatient context we adopted in this study. Outpatient management of postterm pregnancies will reduce the financial burden on families by eliminating the cost of
hospital admission. It will also allow women to begin labour at home and only come into
hospital for delivery, which is more like the natural process of labour and involves fewer
interventions.
At baseline the two groups were similar with regard to age distribution and number of
days beyond 40 weeks gestation. Although there were more nulliparous patients in the
MS group, this was not statistically significant. Theoretically it has been argued that MS
may be more effective in multiparous than nulliparous patients. This assumption has
been disputed by de Miranda et al. 16 and could not be substantiated by our study,
although it is noteworthy that 4 patients in our nulliparous group could not have MS
owing to inability to gain access to the cervical canal (failed MS), a technical challenge
in this subset of patients that cannot be overlooked. Previous studies 2 , 4 , 19 , 20 have
demonstrated that intravaginal misoprostol was more effective at improving cervical
effacement and consistency than cervical os dilatation, and also that misoprostol was a
better agent for initiating labour than the transcervical Foley catheter.
Our findings suggest that both 50 g OM and MS, administered on an outpatient basis,
are safe and effective agents for inducing labour in uncomplicated post-term singleton
pregnancies, with OM having the advantages of a shorter latency period, less need for
oxytocin augmentation in labour and shorter duration of labour. Within 12 hours of
initiation of the induction at the clinic, 46.0% of the patients in the OM group (23/50)
reported back in labour, compared with 17.4% in the MS group (8/46). The proportion
increased to 82.0% (41/50) by 18 hours in OM group, whereas it was 32.6% (15/46) in
the MS group. The faster effect of induction in the OM group might be due to the
reported rapid absorption of this agent after oral administration, peaking about 15 - 30
minutes after administration. We also reason that as misoprostol is a PGE1 analogue
and undergoes rapid de-esterification to its active, free acid metabolites, its onset of
action will be speedier than the local PG production via a cascade of synthetic processes
that would be expected in MS. 21 , 22 Studies on misoprostol have demonstrated less
need for oxytocin augmentation than there was with MS, similar to our
findings. 2 , 23 Of our patients 24.0% in the OM group as opposed to 43.5% in the MS
group required oxytocin augmentation (RR 0.5, CI 0.3 - 0.9). This further enhances
acceptability of OM, as women perceive their labour as more natural with less
intervention.
The proportions of vaginal deliveries were similar in the two groups, (83.3% v. 86.7%,
RR 0.1, CI 0.8 - 1.1). When duration of labour was compared, 78.6% of the OM group,
but only 57.5% of the MS group achieved vaginal delivery within 9 hours of onset of
labour (RR 1.2, CI 0.8 - 1.8). Neonatal outcomes in the two groups were similar and
favourable, although the prevalence of moderate birth asphyxia was higher in the OM
group. These episodes occurred in babies of relatively low birth weight and recovery
was recorded by the Apgar score at 5 minutes. All admissions to the NICU in both
groups were for observation only and the infants were discharged within 24 hours.
A major limitation of randomised trials like ours is that they are seldom large enough to
study rare adverse effects. No harmful adverse effects of MS have been reported in

previous studies. 11 Reported adverse effects of misoprostol, such as vomiting,


diarrhoea, tachysystole or hyperstimulation, were not recorded in this study, possibly
because of the single low dose administered. However, 20% of the patients in the MS
group reported that the procedure was uncomfortable and/or painful, similar to earlier
reports, 16 , 24 and 9% had minimal spotting after the procedure, which subsequently
subsided. No case of rupture of the membranes or antepartum haemorrhage was
recorded. On a preference scale, 43% of the women in the MS group felt positive about
the intervention, compared with 92% of the women in the OM group who would agree
to use of the drug in another post-term pregnancy.

Conclusion
This study showed a shorter latency period, less need for oxytocin augmentation and a
shorter duration of labour in patients given single-dose OM compared with MS on an
outpatient basis. The two induction agents were similar with regard to neonatal
outcomes and need for NICU admission, but differences in outcomes cannot be
excluded owing to the small numbers studied. Patient preference for the intervention
was higher in the OM group than in the MS group.
Conflict of interest. We declare that we have no conflict of interest; no funding/grant
was received for this study and there was no commercial relationship. We have full
control of all primary data and agree to allow SAJOG to review our data if requested.

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