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J. Perinat. Med. 38 (2010) 111119 Copyright by Walter de Gruyter Berlin New York. DOI 10.1515/JPM.2010.057
Giampaolo Mandruzzato1,**, Zarko Alfirevic2, Frank dures for cervical ripening should be used, especially in nul-
Chervenak3, Amos Gruenebaum4, Runa Heimstad5, liparous women. Close intrapartum fetal surveillance should
Seppo Heinonen6, Malcolm Levene7, Kjell Salvesen5, be offered, irrespective of whether labor was induced or not.
Ola Saugstad8, Daniel Skupski9 and Baskaran Keywords: Birth weight; body mass index; postterm preg-
Thilaganathan10 nancy; ultrasound.
1
Head of Division of Obstetrics and Gynecology
(emeritus), Instituto per IInfanzia, Trieste, Italy
2
Abbreviations
University of Liverpool, Liverpool, UK
3
Weill Medical College of Cornell University, New York,
PT postterm
NY, USA GA gestational age
4
New York Presbiterian Hospital, New York, NY, USA US ultrasound
5
St. Olavs University Hospital, Trondheim, Norway LMP last menstrual period
6
University Hospital, Kuopio, Finland BMI body mass index
7
University of Leeds, Leeds, UK SB stillbirth
8 IUGR intrauterine growth restriction
University Hospital, Oslo, Norway
9
New York Hospital Queens, New York, NY, USA PNM perinatal mortality
10
St. Georges Healthcare Trust, London, UK BW birth weight
NNM neonatal mortality
SGA small for gestational age
Abstract NICU neonatal intensive care unit
MAS meconium aspiration syndrome
A pregnancy reaching 42 completed weeks (294 days) is CS cesarean section
defined as postterm (PT). The use of ultrasound in early CRL crown rump length
pregnancy for precise dating significantly reduces the num- BPD biparietal diameter
FL femur length
ber of PT pregnancies compared to dating based on the last
RCT randomized controlled trial
menstrual period. Although the fetal, maternal and neonatal
SR systematic review
risks increase beyond 41 weeks, there is no conclusive evi- NNT number needed to treat
dence that prolongation of pregnancy, per se, is the major CTG cardiotocography
risk factor. Other specific risk factors for adverse outcomes NST non-stress test
have been identified, the most important of which are AF amniotic fluid
restricted fetal growth and fetal malformations. In order to AFI amniotic fluid index
prevent PT and associated complications routine induction EDD expected date of delivery
before 42 weeks has been proposed. There is no conclusive IVF in-vitro fertilization
evidence that this policy improves fetal, maternal and neo-
natal outcomes as compared to expectant management. It is Introduction
also unclear if the rate of cesarean sections is different
between the two management strategies. After careful iden-
According to FIGO w4x and ACOG w3x, a pregnancy lasting
tification and exclusion of specific risks, it would seem
42 weeks or more is defined as postterm (PT). Epidemiolog-
appropriate to let women make an informed decision about
ical studies have shown that after 41 weeks, the rate of fetal,
which management they wish to undertake. There is consen-
maternal and neonatal complications increase. As such, man-
sus that the number of inductions necessary to possibly avoid
agement of this condition remains a matter of concern for
one stillbirth is very high. If induction is preferred, proce-
most clinicians. Many national scientific societies have pro-
duced guidelines that are likely to be influenced by the char-
*This paper was produced under the auspices of the World Asso-
ciation of Perinatal Medicine for a consensus on issues in Perinatal acteristics of the local health systems. The aim of this
practice, coordinated by Giampaolo Mandruzzato. document is to offer recommendations based on available
**Corresponding author: evidence. This document particularly emphasizes the find-
Giampaolo Mandruzzato, MD ings of published studies after 1990 to allow for more recent
Via del Lazzaretto Vecchio 9
Trieste changes in obstetric practice, new surveillance tests, induc-
Italy tion techniques and advances in neonatal care. The reported
E-mail: mandruzzatogiampaolo@tin.it level of evidence follows the criteria suggested by ACOG.
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112 Mandruzzato et al., Guidelines for the management of postterm pregnancy
Prevalence and etiology w33x and when unrecognized, is the cause of 10% of perinatal
mortality (PNM) in Europe w78x.
The prevalence of PT is commonly reported as 410%. In Retrospective cohort studies with exclusion of complica-
Europe, the prevalence estimates range from 0.8% to 8.1% tions and careful monitoring of maternal and fetal well-being
w112x. This wide variation is likely to be the consequence have been published w5, 7, 57, 63, 106x. They all conclude
of different policies of labor induction and methods for ass- that in uncomplicated PT there is no increase of SBs or
essing gestational age (GA). Ultrasound (US) dating of PNM. Although these studies are smaller and prone to weak-
pregnancy is more accurate than that based upon the last ness of this particular methodology, the importance of careful
menstrual period (LMP) and the use of routine US dating monitoring is emphasized w48x. However, two prospective
significantly reduces the rate of PT. When pregnancies are hospital-based cohort studies have recently w42, 66x made
routinely dated by US and in the absence of a policy of contradictory observations regarding PNM rates, possibly
induction only 7% of the pregnancies progress beyond 294 reflecting differences in prenatal care between the two cen-
days and 1.4% beyond 301 days w63x. The etiology of PT is ters. Further, large prospective studies should be performed
largely unknown, but both fetal abnormality (e.g., anenceph- with uniform criteria for defining maternal and fetal com-
aly) and placental sulphatase deficiency can be associated plications. However, due to the relatively low prevalence of
with prolongation of pregnancy. It has also been suggested PT-related complications, very large studies would be
that some genetic factors w56x, fetal gender w28x and a high required, decreasing the likelihood that they would be ever
pre-pregnancy body mass index (BMI) can contribute to an carried out.
increased risk for PT w88x. The pathophysiological basis for the increased fetal risk
in uncomplicated PT is unclear, although it has long been
suggested that an underlying tendency for placental senes-
Diagnosis cence exists in PT. Fetal growth appears to be unaffected
until 43 weeks of gestation w26x and uncomplicated PT preg-
The diagnosis is overtly simple: pregnancy duration beyond nancies do not appear to show differences in umbilical artery
42 weeks from the LMP. Unfortunately, even in the presence Doppler indices w58x, fetal heart rate patterns w59x or cord
of regular menstrual cycles, the true GA is different from the blood nucleated red blood cell counts w76x.
estimated GA in a significant number of cases. The most
accurate method for assessing GA is fetal biometry per- Maternal
formed by US in early pregnancy.
A significant increase in the rate of maternal complications
in PT is reported in all studies w7, 15, 49, 57, 63, 71, 106x.
Complications of postterm pregnancy The most common are dysfunctional labor, shoulder dysto-
cia, obstetric trauma and post-partum hemorrhage. These
Fetal complications are associated with increased birth weight
(BW) ()4000 g) and macrosomia ()4500 g) which is
Many epidemiological studies based on birth registries have observed in 22% and 4% of newborns, respectively, at
been published w15, 22, 25, 29, 30, 46, 47, 49, 50, 71, 87x, 41 weeks w63x. It has also been suggested that induction of
but the findings are somewhat inconsistent. In five studies, labor can further increase the risk of labor complications
a significant increase in stillbirth (SB) has been observed w15, w7, 42x, although increased cesarean section (CS) rate has
29, 50, 71, 87x, in particular if the SB risk as a function of only been observed in nulliparous, but not multiparous wom-
ongoing pregnancies rather than SB rate per 1000 total births en w20x. Even though maternal anxiety can increase when
is used w25x. In two studies, increased SB rate has only been pregnancy progresses beyond term, two studies w57, 108x
observed in nulliparous women w47, 50x, whereas four other have suggested that women do not perceive this as a signif-
studies w15, 22, 30, 49x have suggested that risk factors, such icant medical problem.
as intrauterine growth restriction (IUGR) and fetal malfor-
mations outweigh the contribution of prolonged pregnancy Neonatal
to the risk of SB. The weakness of most epidemiological
studies is that they do not describe the causes of death. Fur- Mortality A higher rate of NM is reported in some w20,
thermore, epidemiological data are often drawn from large 22, 46, 50, 71x, but not in other studies w15, 30, 49, 63x.
and distant secular periods. The latter do not take into Where evaluated, both small for gestational age (SGA) and
account the advances in modern obstetrics, particularly in major congenital malformations appear to increase this risk
pregnancy dating and fetal assessment. The contribution of w22, 30x.
poor access and inequity of care is also often overlooked
especially because an increasing migrant population and with Neonatal complications Neonatal complications include
racial differences exist in SB rates w11, 104x. The conclusions low Apgar scores, acidemia, admission to neonatal intensive
of epidemiological studies may vary according to whether care unit (NICU), meconium aspiration syndrome (MAS),
the authors have included risk factors other than GA. The clavicular fracture and Erbs palsy. Meconium stained liquor
most important independent risk factor for SB is IUGR, is a physiological finding in fetal life and should not be
which is associated with SB in 52% of the cases at any GA regarded as a neonatal complication. The frequency of meco-
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Mandruzzato et al., Guidelines for the management of postterm pregnancy 113
nium stained liquor increases with advancing GA and is nations, revision of the GA is not warranted; other expla-
thought to be a consequence of fetal gut maturation w6x. nations, such as IUGR or accelerated growth should be
Occasionally, meconium stained liquor is the consequence considered.
of chronic fetal hypoxemia that is reported to occur in 30% In conclusion, before choosing any kind of management
of IUGR fetuses w60x. MAS, on the other hand, is potentially it is fundamental that the GA is accurately assessed. US
a life threatening condition, which is thought to occur when biometry in early pregnancy is the best available method and
acute hypoxemia during labor causes fetal gasping in the the subsequent management of PT pregnancy should be per-
presence of meconium stained liquor w23x. There is also con- formed on the basis of the US adjusted GA. However, it must
siderable evidence that meconium aspiration may occur be remembered that even the best method has a small margin
before labor, but only manifest as MAS once delivery has of error.
occurred w81, 94x. Apgar scores are reported in six studies
w20, 22, 42, 49, 63, 71x. The difference in low Apgar scores
(-7) between term and PT newborns was not significant in Routine induction vs. expectant management
all the studies. In one study low Apgar and acidemia were
more frequently observed after induction than after sponta- The target of avoiding the prolongation of the pregnancy at
neous onset of labor w42x. Birth trauma is significantly more or beyond 42 weeks is to prevent or reduce fetal, maternal
frequent in PT and is probably associated with increased BW. and neonatal complications. All eight randomized controlled
The increased risks of fetal, maternal and neonatal com- trials (RCTs) published since 1990 compared routine induc-
plications depend on many factors. Fetal size, parity and the tion of labor before 42 weeks and expectant management
presence of malformations all play important roles. In cases w17, 36, 39, 44, 45, 51, 68, 79x. The three most recent meta-
of reduced fetal size, complications due to fetal hypoxemia analyses are evaluated in this document w38, 84, 107x as well
are significantly increased. On the other hand, in cases with as observational prospective w8, 10, 52x, retrospective case/
a normally functioning placenta and large fetal size or control w13, 73, 102x or retrospective cohort w41, 89, 111x
macrosomia, the risk of traumatic delivery is increased w61, studies. Although a case-control study must be retrospective,
80x. a cohort study can be either prospective or retrospective.
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114 Mandruzzato et al., Guidelines for the management of postterm pregnancy
Systematic reviews (SRs) and meta-analysis tion. Seven out of eight RCTs found no differences in CS
rate after routine induction vs. expectant management. An
The principal task of a meta-analysis is to pool data from increased rate of MAS with expectant management was
different RCTs. The possible limitations of SRs and meta- found in one out of eight RCTs and two SRs. Maternal and
analysis have been extensively examined and discussed w27, neonatal traumatic complications are mainly a consequence
34, 74, 93x. The three available SRs on PT management are of fetal macrosomia without evidence from RCTs w37x or SRs
influenced by two types of potential bias: )50% of all RCTs w83x that induction reduces the neonatal complication or CS
were published before 1990 w38, 84, 107x making homoge- rates. Therefore, both management strategies (routine induc-
neity of the studies a problem and the Canadian multicenter tion or expectant management) are acceptable. The choice
PT pregnancy w39x study represents the major contributor to depends on the local capacities to diagnose the conditions
the pooled cases in all SRs, despite concerns regarding the with increased risks and to monitor the fetal well-being if
consistency of the findings in this study (see above). expectant management is preferred.
The results for perinatal outcome are contradictory with
one SR showing improvement w38x and the other two no
reduction in PNM w84, 107x. Fetal assessment in the post-dates period
Two SRs reported lower CS rates in the induction group
w38, 107x whilst the third showed no difference between There is no agreement on a specific GA at which fetal mon-
groups w84x. itoring should start. As the rate of fetal, maternal and neo-
In two reviews a lower prevalence of MAS was observed natal complications are significantly increased beyond 41
in the induction group w38, 107x. weeks, it is reasonable to identify fetuses at high risk at that
One method by which homogeneity may be improved is time.
to only include into SRs the RCTs published after 1990. The
obvious reason for this is that modern obstetrics has changed Fetal
over the last decades in terms of the introduction of routine
US and fetal surveillance. However, the inclusion of the There are no specific fetal surveillance tests for PT pregnan-
Canadian multicenter PT pregnancy which accounts for some cy which are able to predict acute events (e.g., placental
60% of cases will significantly influence the results of a abruption or cord complications). The most commonly used
meta-analysis w39x. Wennerholm et al. w107x performed a tests are cardiotocography (CTG) non-stress test (NST),
sub-analysis after exclusion of the Canadian trial w51x and amniotic fluid (AF) volume assessment wamniotic fluid index
found no significant differences in CS rate. Due to the very (AFI) or deepest pocketx, fetal biophysical profile, US esti-
small PNM rates, estimates are that a definitive study would mation of fetal weight and Doppler studies on umbilical and
require randomization of between 16,000 w38x and 30,000 fetal vessels.
w39x pregnancies. At present no such studies exist, and they
will presumably never be performed. Cardiotocography This is the most commonly used fetal
surveillance test, despite the accepted limitations due to inter-
Observational studies and intra-observer variability. In order to overcome this prob-
lem, computer assisted evaluation of CTG has been used.
These are not homogenous with different study designs and Assessment of the fetal heart rate variability offers a reliable
study populations. The CS rates were significantly increased assessment of fetal hypoxemia and/or acidemia. It has been
with induction of labor compared to spontaneous labor in six shown that reduced fetal heart rate variability on the com-
studies w8, 10, 13, 52, 73, 102x, particularly in nulliparous puterized CTG is associated with fetal distress in labor and
women w41, 111x. Only one study w89x reports a lower CS acidemia w105x. The observation of a reactive CTG or short-
rate in the induction group. term variability )4 ms (computerized CTG) offers good
negative predictive value for SB, except for unpredictable
Numbers needed to treat (NNT) acute events (e.g., placental abruption or cord accidents).
The NNT to avoid one SB or perinatal death varies between
studies. NNT ranges from 100 to infinity w38x and from 500 Ultrasound fetal biometry US can predict SGA defined
to )1000 w64x. These numbers are strongly dependent on as BW below the 10th or the 5th percentile w70x. As SGA and
the estimation of the fetal/neonatal risk. A more recent anal- IUGR are not synonyms, the observed US measurements
ysis presented the NNT according to GA w43x. It was esti- should be compared with the expected curve of growth based
mated that the NNT is reduced with advancing GA from 527 on any previous scans in order to identify the degree of
inductions at day 287 to 195 inductions at day 302. growth restriction. The recognition of IUGR and/or small
fetal size identifies the most important risk factor for sub-
Conclusions sequent fetal and neonatal adverse outcomes. Non-reassuring
fetal tests, before and during labor, are more frequently
The findings are equivocal on the advantages or disadvan- observed in cases of reduced fetal size w90x and rate of com-
tages of routine induction vs. expectant management. The plications in labor is inversely correlated to the BW w85x. US
individual RCTs report no differences in PNM, and only one biometry has limited value in diagnosing large or macroso-
of three SRs indicates a lower PM rate after routine induc- mic fetuses because of the systematic error in estimated fetal
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Mandruzzato et al., Guidelines for the management of postterm pregnancy 115
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116 Mandruzzato et al., Guidelines for the management of postterm pregnancy
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Mandruzzato et al., Guidelines for the management of postterm pregnancy 117
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