04-galal-_Opmaak 1 19/09/12 14:11 Pagina 175 FVV inObGyn, 2012, 4 (3): 175-187 Review Postterm pregnancy M. Galal1, i. SyMOndS2, H. MuRRay3, F. PetRaGlia4, R. SMitH5 1Consultant/Conjoint Senior Lecturer in Obstetrics & Gynaecology, John Hunter Hospital, University of Newcastle, New South Wales, Australia. 2Professor of Obstetrics & Gynaecology, University of Newcastle, New South Wales, Australia. 3Consultant in Obstetrics, John Hunter Hospital, Newcastle, NSW, Australia. 4Professor of Obstetrics and Gynecology, University of Siena, Policlinico “S. Maria alle Scotte”, Viale Bracci, 53100Siena, Italy. 5Professor of Endocrinology, Director of Mother and Baby Unit, Hunter medical research Institute, Newcastle, New South Wales, Australia. Correspondence at: [email protected] or [email protected] Abstract Postterm pregnancy is a pregnancy that extends to 42 weeks of gestation or beyond. Fetal, neonatal and maternal complications associated with this condition have always been underestimated. It is not well understood why some women become postterm although in obesity, hormonal and genetic factors have been implicated. The management of postterm pregnancy constitutes a challenge to clinicians; knowing who to induce, who will respond to induction and who will require a caesarean section (CS). The current definition and management of postterm pregnancy have been challenged in several studies as the emerging evidence demonstrates that the incidence of complications associated with postterm pregnancy also increase prior to 42 weeks of gestation. For example the incidence of still- birth increases from 39 weeks onwards with a sharp rise after 40 weeks of gestation. Induction of labour before 42weeks of gestation has the potential to prevent these complications; however, both patients and clinicians alike are concerned about risks associated with induction of labour such as failure of induction and increases in CS rates. There is a strong body of evidence however that demonstrates that induction of labour at term and prior to 42weeksof gestation (particularly between 40 & 42 weeks) is associated with a reduction in perinatal complications without an associated increase in CS rates. It seems therefore that a policy of induction of labour at 41 weeks in postterm women could be beneficial with potential improvement in perinatal outcome and a reduction in maternal complications. Key words:Body mass index, induction of labour, perinatal complications, postterm pregnancy, ultrasound. Introduction tion of labour including uterine hyper-stimulation, failed induction and increased Caesarean section Post term pregnancy is associated with an increased rates. Postterm pregnancy is also associated with risk of fetal and neonatal mortality and morbidity increased costs related to antenatal fetal monitoring (Olesen et al., 2003a;2003b) as well as an increased and induction of labour (allen et al., 2005; Fonseca maternal morbidity (Caughey et al., 2007). ante - et al., 2003) and can be a source of significant partum stillbirth at and beyond term (37-43 weeks anxiety for the pregnant woman (aCOG, 1997). gestation) is a major public health problem accoun- Optimisation of these conflicting pressures is a ting for a greater contribution to perinatal mortality clinical challenge. than either deaths from complications of prematurity or the sudden infant death syndrome (Cotzias et al., Definitions 1999). increased fetal mortality from postterm preg- nancy could therefore be prevented by induction of Postterm pregnancy is defined as pregnancy that has labour (iOl) at term, however, both clinicians and extended to or beyond 42 weeks of gestation patients alike are concerned about the risks of induc- (294days), or estimated date of delivery (edd) + 175 04-galal-_Opmaak 1 24/09/12 13:03 Pagina 176 14days (ACOG, 2004). The terms prolonged preg- uterus as estimated by bimanual examination in the nancy, postdates and postdatism are synonymously first trimester, the perception of fetal movements, used to describe the same condition. The terms post- auscultation of fetal heart tones, and fundal height date and prolonged pregnancy are ill-defined and in a singleton pregnancy. best avoided (ACOG, 2004). When postterm pregnancy truly exists the cause Postmaturity, postmaturity syndrome and dysma- is usually unknown. Common risk factors include turity are not synonymous terms to postterm preg- primiparity, previous postterm pregnancy (Alfirevic nancy. They are often used to describe the features and Walkinshaw, 1994; Mogren et al., 1999; Olesen of a neonate who appears to have been in utero et al., 1999), male fetus (Divon et al., 2002), obesity longer than 42 weeks of gestation. They describe the (Usha Kiran et al., 2005; Stotland et al., 2007), effects of intrauterine growth restriction (IUGR) hormonal factors and genetic predisposition secondary to utero-placental insufficiency encoun- (Laursen et al., 2004). tered in a postterm pregnancy (Shime et al., 1986). It is not known how body mass index (BMI) affects the duration of pregnancy and timing of Epidemiology delivery, but interestingly obese women have a higher incidence of postterm pregnancy (Usha Kiran The incidence of postterm pregnancy is about 7% of et al., 2005), while women with low BMI have a all pregnancies (Martin et al., 2007). The prevalence higher incidence of preterm labour (delivery before varies depending on population characteristics and 37 weeks of gestation) (Hickey et al., 1997). Because local management practices. Population characteris- adipose tissue is hormonally active (Baranova et al., tics that affect the prevalence include: the percentage 2006), and because obese women may have an of primigravidas in the studied population, the pre- altered metabolic status, it is possible that endocrine valence of obesity, a prior postterm pregnancy as factors involved in the initiation of labour are altered well as genetic predisposition. The proportion of in obese women. women with pregnancy complications and the fre- Perhaps amongst all the factors which could in- quency of spontaneous preterm labour also influence fluence the incidence of postterm pregnancy obesity the rate of postterm pregnancy. The link between is the one modifiable risk factor which could theo- ethnicity and overall duration of pregnancy is not retically improve by dietary and exercise behaviou- well established (Collins et al., 2001; Caughey et al., ral modifications before or during pregnancy. Such 2009). modifications would have an impact on other health Local management practices such as scheduled outcomes as well, but because postterm pregnancy IOL, differences in the use of early ultrasound (US) is associated with a number of perinatal complica - for pregnancy dating, and elective Caesarean section tions, its prevention would be clearly beneficial (CS) rates will affect the overall prevalence of post- (Ingemarsson and Kallen, 1997). term pregnancy. In the United States for example, Using a number needed to treat calculation, it was the increase in the incidence of IOL in the last found that for approximately every 20 women who decade was associated with a drop in the number of successfully decreased BMI below the obesity range, pregnancies continued beyond 41 and 42 weeks one fewer woman would go past 41 weeks of gesta- from 18%&10% respectively in 1998 (Ventura et al., tion (adjusted odds ratio of 1.26; based on baseline 1998) to 14%& 4% respectively in 2005 (Martin et risk of reaching 41 weeks gestation of approximately al., 2005). Similarly, the use of early US for preg- 20%) (Caughey et al., 2009). nancy dating has been associated with a significant Altered levels of circulating hormones that are reduction in the incidence of postterm pregnancy thought to play a role in spontaneous labour may from 12% to 3% (Savitz et al., 2002). also play a role in the causation of postterm preg- nancy. Placental sulphatase deficiency for example, Aetiology and risk factors is a rare X-linked recessive disorder that can prevent spontaneous labour due to a defect in placental sul- The most common cause of prolonged pregnancies phatase activity and the resulting decreased oestriol is inaccurate dating (Neilson, 2000; Crowley, 2004). levels (E3). Fetal adrenal insufficiency and fetal The use of standard clinical criteria to determine the adrenal hypoplasia as well as fetal anencephaly (in estimated delivery date (EDD) tends to overestimate the absence of polyhydramnios), despite being gestational age and consequently increases the inci- rare, are all associated with postterm pregnancies dence of postterm pregnancy (Gardosi et al., 1997; (Doherty and Norwitz, 2008). Taipale and Hiilermaa, 2001). Clinical criteria which Genetic factors may be involved with prolonga- are commonly used to confirm gestational age in- tion of pregnancy. Women who were themselves clude last menstrual period (LMP), the size of the products of a prolonged pregnancy are at higher risk 176 FVV INOBGyN 04-galal-_Opmaak 1 19/09/12 14:11 Pagina 177 of postterm pregnancy (relative risk is 1.3) (Mogren CRH can directly stimulate fetal adrenal produc- et al., 1999). Women with prior prolonged pregnancy tion of dHeas, the precursor for placental oestriol have an increased risk of subsequent postterm preg- synthesis (Smith et al., 1998). Maternal plasma CRH nancy (27% with one prior prolonged pregnancy & concentrations correlate with oestriol concentrations 39% with 2 prior prolonged pregnancies) (Kistka et (Smith et al., 2009). the rising oestriol driven by al., 2007). twin studies also support a genetic pre- CRH increases at the end of gestation more rapidly disposition. Rates of prolonged pregnancy are inc- than oestradiol levels leading to an increase in the reased in women whose twin sister has had a oestriol to oestradiol ratio which has been postulated previous postterm birth. this association is greater to produce an estrogenic environment in the last in monozygotic than in dizygotic twins (laursen et weeks of pregnancy. Concurrently the rise in mater- al., 2004). there also appears to be a paternal role in nal plasma progesterone concentrations that occurs the recurrence risk of prolonged pregnancy. the risk across gestation slows at the end of pregnancy or of recurrence of postterm pregnancy was reduced even falls. this may be due to CRH inhibition of from 19.9% to 15.4% when the father of the baby placental progesterone synthesis (yang et al., 2006). changed between the first and second pregnancy thus the pro-pregnancy effect of progesterone (Olesen et al., 2003). (promoting relaxation) is declining as the pro-labour actions of oestriol (promoting contraction) are inc- Pathogenesis reasing. these changes in ratios have been observed in preterm births, singletons delivering at term and the pathogenesis of postterm pregnancy is not cle- in twin gestations (Smith et al., 2009). the situation arly understood. as demonstrated above some risk in postterm pregnancies is unknown. it is likely to factors associated with postterm pregnancy were be similar in postterm women who go into spontane- identified with some possible explanations, however, ous labour or those who respond to iOl, based on one the pathogenesis of the condition is not yet clear. study of postterm women (torricelli et al., 2011). despite improved understanding of parturition in recent years, we still lack clarity about the exact Complications of postterm pregnancies mechanisms which initiate labour and allow its progression. to have a better understanding of the Postterm pregnancies are associated with increased pathogenesis of postterm pregnancy it is essential to fetal and neonatal motality and morbidity as well as shed some lights on the pathophysiology of parturi- maternal morbidity. these risks are greater than it tion and try to understand why these mechanisms fail was originally thought. Risks have been under- to be triggered in postterm pregnancies or conversely estimated in the past for two reasons. First, earlier are triggered earlier in preterm labour. it seems studies on postterm pregnancy were published before logical that a common ground or a link does exist the routine use of ultrasound for pregnancy dating. between these three conditions. the mechanisms of as a result many pregnancies included in the studies parturition include interactions between hormonal, were not actually postterm. the second reason rests mechanical and inflammatory processes, in which within the definition of stillbirth itself. Stillbirth rates placenta, mother and fetus each play a vital role. were traditionally calculated using pregnancies de- Placental production of the peptide corticotrophin livered at a given gestational age rather than ongoing releasing hormone (CRH) has been related to the (undelivered) pregnancies. this would lower the still- length of gestation (Mclean et al., 1995). Synthesis birth rates in postterm pregnancies as once the fetus of CRH by the placenta increases exponentially as is delivered it is no longer at risk of intra- uterine fetal pregnancy advances and peaks at the time of labour. death (iuFd). the appropriate denominator is there- in women who deliver prematurely the exponential fore not all deliveries at a given gestational age but rise is more rapid than those delivering at term, while ongoing (undelivered) pregnancies (Rand et al., 2000; in women who deliver postterm the rate of rise is slo- Smith, 2001; Caughey et al., 2003). wer (ellis et al., 2002; torricelli et al., 2006). this One retrospective study of over 170,000 singleton data suggests that postterm delivery is due to a births, using the appropriate denominator demon- change in the biological mechanisms regulating the strated a 6-fold increase in stillbirth rates in postterm length of gestation. this may be due to an inherited pregnancies from 0.35 to 2.12 per 1000 ongoing predisposition due to polymorphisms in the genes on pregnancies (Hilder et al., 1998). the physiological pathway linking CRH to birth. it is also possible that the maternal phenotype may Fetal and neonatal complications change the response of maternal tissues to the usual hormonal signals to birth as may occur in the obese the perinatal mortality rate, defined as stillbirths woman. plus early neonatal deaths, at 42 weeks of gestation POStteRM PReGnanCy – Galaletal. 177 04-galal-_Opmaak 1 19/09/12 14:11 Pagina 178 (yoder et al., 2002). Conventional interventions such as amnio-infusion (Hofmeyr, 2002; Fraser et al., 2005)) or routine nasopharyngeal and oro-pharyn- geal suction of meconium at the perineum at the time of delivery, have made very little contribution to this improvement (Vain et al., 2004). Postterm infants are larger than term infants and have a higher incidence of fetal macrosomia (2.5- 10% in postterm versus 0.8-1% at term) (Spellacy et al., 1985; Rosen and dickinson, 1992). Fetal macro- somia, defined as an estimated fetal weight ≥ 4.5 kg (aCOG, 2000), is associated with prolonged labour, cephalo-pelvic disproportion and shoulder dystocia. Shoulder dystocia is associated with risk of orthopa- edic injury (e.g. fractured humerus and clavicle) as (cid:0)Stillbirth (cid:0)neonatal death (cid:0)post neonatal death. well as neurological injury such as brachial plexus injury and cerebral palsy (Spellacy et al., 1985; Fig. 1.— Perinatal mortality per 1000 ongoing pregnancies. Reproduced from bJOG Volume 105 (Hilder l, et al., 1998). Rosen and dickinson, 1992). However, there is no evidence that iOl as a preventative measure in these cases is associated with a reduction in complication is twice as high as that at term (4-7 versus 2-3 per rates or improvement in perinatal outcome (aCOG, 1000 deliveries, respectively). it increases 4-fold at 2004). 43 weeks and 5-7-fold at 44 weeks (bakketeig and about 20% of postterm fetuses have dysmaturity bergsjo, 1989; Feldman, 1992; Hilder et al., 1998; syndrome, which refers to infants with characteris- Cotzias et al., 1999). these data also demonstrate tics resembling chronic intrauterine growth restric- that when calculated per 1000 ongoing pregnancies, tion from utero-placental insufficiency (Vorherr, fetal and neonatal mortality rates increase sharply 1975; Mannino, 1988). this includes thin wrinkled after 40 weeks (Hilder et al., 1998) (Fig. 1). it is be- peeling skin (excessive desquamation), thin body lieved that utero-placental insufficiency, meconium (malnourishment), long hair and nails, oligohydram- aspiration and intrauterine infection are the underly- nios and frequently passage of meconium. these ing causes of the increased perinatal mortality rates pregnancies are at increased risk of umbilical cord in these cases (Hannah, 1993). compression from oligohydramnios, meconium as- Fetal morbidity is also increased in postterm piration, and short-term neonatal complications such pregnancies and pregnancies that progress beyond as hypoglycemia, seizures, and respiratory insuffi- 41 weeks gestation. this includes passage of meco- ciency. they also have an increased incidence of nium, meconium aspiration syndrome, macrosomia non-reassuring antepartum and intrapartum fetal and dysmaturity. Post term pregnancy also is an in- testing (Knox et al., 1979). Whether such infants are dependent risk factor for low umbilical cord pH le- at increased risk of long-term neurologic sequelae is vels (neonatal acidaemia), low 5-minute apgar not clear. in a large, prospective, follow-up study of scores (Kitlinski et al., 2003), neonatal encephalo- children at ages 1 and 2 years, the general intelli- pathy (badawi et al., 1998), and infant death in the gence quotient, physical milestones, and frequency first year of life (Hilder et al., 1998; Cotzias et al., of intercurrent illnesses were not significantly diffe- 1999; Rand et al., 2000). although some of these rent between normal infants born at term and those infant deaths clearly result from peripartum compli- born postterm (Shime et al., 1986). cations such as meconium aspiration syndrome, although much of the work above has been most have no known cause. conducted in postterm pregnancies, some risks such Meconium aspiration syndrome refers to respira- as stillbirth, passage of meconium, and neonatal tory compromise with tachypnea, cyanosis, and re- acidaemia have been described as being greater at duced pulmonary compliance in newborn infants 41 and even 40 weeks of gestation as compared to exposed to meconium in utero. it is seen in higher 39weeks gestation (Caughey et al., 2005; Caughey rates in postterm neonates (Kabbur et al., 2005). in and Musci, 2004). a study from Scotland published the united States the incidence of meconium aspira- in 2010 demonstrated increased risk of stillbirth tion syndrome has shown a 4-fold reduction between (both overall and unexplained stillbirth) as preg- 1990 and 1998 (from 5.8% to 1.5% in infants more nancy advances especially after 39 weeks of gesta- than 37 weeks; P < 0.003). this has been attributed tion (Sutan et al., 2010) (Fig. 2). yudkin et al. (1987) primarily to a reduction in postterm pregnancy rates also demonstrated that the risk of unexplained 178 FVV inObGyn 04-galal-_Opmaak 1 24/09/12 13:02 Pagina 179 Fig. 2.— Risk of Stillbirth by week of gestation (rate calculated Fig. 3.— Relationship between stillbirth and gestational age per 1000 ongoing pregnancies) (Sutan et al. 2010). (Yudkin et al., 1987). stillbirth rises fourfold after 39 weeks to a maximum Similar to neonatal outcomes, maternal morbidity at 41 weeks (Fig. 3). The rates of meconium aspira- also increases in term pregnancies before 42 weeks tion and neonatal acidaemia both increase as term of gestation. Complications such as chorioamnioni- pregnancies progress beyond 38 weeks (Bruckner et tis, severe perineal lacerations, Caesarean delivery, al., 2008). Neonatal morbidity including birth inju- postpartum haemorrhage, and endomyometritis all ries seems to nadir at around 38 weeks and increase increase progressively after 39 weeks of gestation in a continuous fashion thereafter (Nicholson et (Yoder et al., 2002; Caughey and Bishop, 2006; al., 2006). Therefore, 42 weeks of gestation does Heimstad et al., 2006; Caughey et al., 2007; not represent a thershold below which risks are Bruckner et al., 2008;). uniformly distributed. Hence, the definition and A large retrospective study (Caughey et al., 2007), management of postterm pregnancy have been ques- which included 119,254 singleton-low risk pregnan- tioned and challenged in several studies in recent cies, demonstrated a statistically significant increase years (Caughey et al., 2007; Doherty et al., 2008). in the rate of maternal complications beyond 40weeks of gestation and even beyond 39 weeks’ Maternal risks gestation for some morbidities. The study also showed that the increase in Postterm pregnancy is associated with significant maternal complications persisted at statistically and risks to the mother. There is an increased risk of: clinically significant levels even allowing for the 1)labour dystocia (9-12% versus 2-7% at term); increase in operative deliveries. This is true for all 2)severe perineal lacerations (3rd& 4thdegree tears), of the trends except for the rate of endomyometritis related to macrosomia (3.3% versus 2.6% at term); among women undergoing vaginal delivery. For this 3) operative vaginal delivery; and 4) doubling in complication alone, the increase in and among caesarean section (CS) rates (14% versus 7% at women experiencing caesarean deliveries accounted term) (Rand et al., 2000; Campbell et al., 1997; for the bulk of the increase by gestational age Alexander et al., 2000; Treger et al., 2002). (Caughey et al., 2007). Caesarean delivery is associated with higher i ncidence of endometritis, haemorrhage, and thrombo- Management of postterm pregnancy embolic disease (Alexander et al., 2001; Eden et al., 1987). A) Pregnancy Dating The emotional impact of prolonged pregnancy should not be underestimated either. In one rando- Accurate pregnancy dating is crucial to the diagnosis mised controlled trial of women at 41 weeks of and management of postterm pregnancy (Mandruzzato gestation, women who were induced desired the et al., 2010). Last menstrual period has traditionally same management 74% of the time, whereas women been used to calculate the expected date of delivery with serial antenatal monitoring desired the same (EDD). But many inaccuracies could exist because management only in 38% of the time (P < 0.001) of cycle irregularity, recent use of hormonal contra- (Heimstad et al., 2007). ception or because of bleeding early in pregnancy. POSTTERM PREGNANCY – GALALETAL. 179 04-galal-_Opmaak 1 19/09/12 14:11 Pagina 180 Routine ultrasound examination for pregnancy have been recommended. this includes membrane dating demonstrated a reduction in the rate of false sweeping, unprotected sexual intercourse, nipple positive diagnosis and thereby the overall rate of stimulation and acupuncture. postterm pregnancy from 10-15% to approximately Membrane sweeping or stripping is a relatively 2-5%, and thereby minimized unnecessary interven- simple technique usually performed without admis- tion (bennett et al., 2004; Caughey et al., 2008a; sion to hospital. it has the potential to initiate labour 2009). a Cochrane systematic review in 2000 found by increasing local production of prostaglandins and, a similar reduction in the overall rates of induction thus, reduce pregnancy duration or pre-empt formal of labour for postterm pregnancy (OR, 0.68; 95% Ci, induction of labour with either oxytocin, prostaglan- 0.57-0.82) among women who underwent sono- dins or amniotomy. graphic gestational age assessment before 24weeks Some studies show that membrane sweeping may of gestation (neilson, 2000). reduce the interval to spontaneous onset of labour When using ultrasound for dating it is necessary and in turn the proportion of women with postterm to understand the margin of error reported at various pregnancy. However, there is no consistent evidence times during gestation. the variation by ultrasono- that it reduces the incidence of operative vaginal graphy generally is ± 7 days up to 20 weeks of delivery, Caesarean section rates, maternal or gestation, ± 14 days between 20 and 30 weeks of neonatal complications (Kashanian et al., 2006; de gestation, and ± 21 days beyond 30 weeks of Miranda et al., 2006). gestation (aCOG, 2004). a Cochrane review (boulvain et al., 2005) on a calculated gestational age by ultrasound must membrane sweeping for induction of labour in 2010 be therefore considered as an estimate and must take concluded that sweeping of the membranes, perfor- into account the range of possibilities. if the med as a general policy in women at term, was estimated gestational age by a patient’s last associated with reduced duration of pregnancy and menstrual period differs from the ultrasound esti- reduced frequency of pregnancy continuing beyond mate by more than these accepted variations, the ul- 41 & 42 weeks. to avoid one formal induction of trasound estimate of gestational age should be used labour, sweeping of membranes must be performed instead of the patient’s menstrual cycle estimate in eight women (nnt = 8). there was no evidence (aCOG, 2004). of a difference in the risk of maternal or neonatal due to the lower margin of error first trimester ul- infection . discomfort during vaginal examination trasonography seems to be superior to mid-trimester and other adverse effects (bleeding, irregular con- ultrasound for pregnancy dating (Mandruzzato et al., tractions) were more frequently reported by women 2010). in a small prospective randomised controlled allocated to sweeping. Studies comparing sweeping trial, routine first trimester ultrasound for pregnancy with prostaglandin administration are of limited dating reduced the incidence of postterm pregnancy sample size and do not provide evidence of benefit. from 13% to 5% when compared with second Sexual intercourse is widely believed to facilitate trimester ultrasound (bennett et al., 2004). another the onset of labour (Schaffir, 2002). the action of study of this issue, showed that prolonged pregnancy sexual intercourse in stimulating labour is unclear, it is less common in women dated by ultrasound before may in part be due to the physical stimulation of the 12 weeks compared with women scanned between lower uterine segment, endogenous release of 12 and 24 weeks (2.7 versus 3.7% respectively; oxytocin as a result of orgasm, uterine activity which P=0.02). another interesting finding of this study is thought to be provoked by orgasm (Chayen et al., was that better dating revealed a greater difference 1986), or from the direct action of prostaglandins in in the rate of perinatal complications between semen (taylor and Kelly, 1974) as human semen is term and postterm pregnancies (Caughey et al., the biological source that is presumed to contain the 2008a). highest prostaglandin concentration. Some studies show that unprotected sexual intercourse results in b) Prevention of postterm pregnancy earlier onset of labour, reduction in postterm pregnancy rates and fewer interventions with labour Prevention of postterm pregnancies seems to be the induction (tan et al., 2006). However, a Cochrane best management. induction of labour at term is the review concluded that the role of sexual intercourse most decisive way of prevention. However, clini- as a method of induction of labour is uncertain and cians and patients alike are concerned about risks as- that further studies of sufficient power are needed to sociated with induction of labour including an assess its value (Kavanagh et al., 2001). another increased caesarean section rate. to avoid formal in- study in 2009 reported that women who had coitus duction and encourage spontaneous onset of labour were less likely to go into spontaneous labour prior at term, several minimally invasive interventions to their scheduled induction date (tan et al., 2009). 180 FVV inObGyn 04-galal-_Opmaak 1 19/09/12 14:11 Pagina 181 acupuncture has long been used in China and has been proposed. despite the lack of evidence other asian countries for pregnancy-related conditi- demonstrating a beneficial effect, antenatal fetal sur- ons, including breech presentation (tiran, 2004), veillance is often performed during this period. labour pains (Qu and Zhou, 2007), and hyperemesis Some studies report a greater complication rate gravidarum (Helmreich et al., 2006). the Shanghai among women giving birth during the latter half of College of traditional Medicine recommends acu- this 2-week period (bochner et al., 1988; Guidetti et puncture for labour induction (John ed O’Conner, al., 1989; alexander et al., 2000; alexander et al., 1981), and it is used routinely for labour induction 2001; treger et al., 2002). although the data arein- in some societies (West, 1997). additionally, there consistent, there is a suggestion that antenatal testing do not appear to be significant maternal or fetal risks at 40 to 42 weeks of gestation may be associated associated with acupuncture (neri et al., 2002; with improvements in perinatal outcome. in one Scharf et al., 2003). a Cochrane review on this issue retrospective study, women with routine antenatal concluded that fewer women receiving acupuncture testing from 41 weeks had lower rates of caesarean required induction compared to standard care (RR delivery for non-reassuring fetal testing than women 1.45, 95% Ci 1.08, 1.95; three trials) (Smith and in whom testing was started at 42 weeks (2.3% vs. Crowther, 2004). in conclusion, acupuncture cannot 5.6%, respectively; P < 0.01) (bochner et al., 1988). be definitely assessed because of the paucity of trial Furthermore, the group with delayed antenatal data and the need for further evaluation (Rabl et al., testing experienced 3 stillbirths and 7 other neonatal 2001; Smith and Crowther, 2004). morbidity events as compared with none in the 41- breast stimulation is thought to promote labour week antenatal testing group (P < 0.05). However, onset and has been suggested as a means of inducing no randomized controlled trial has demonstrated an labour. it is a non-medical intervention allowing improvement in perinatal outcome attributable to women greater control over the induction process. a fetal surveillance between 40 and 42 weeks of Cochrane review on breast stimulation for cervical gestation (usher et al., 1988). ripening and induction of labour (Kavanagh et al., the literature is inconsistent regarding both the 2005) concluded that breast stimulation appears type and frequency of antenatal surveillance among beneficial in reducing the number of women not in postterm patients (Cardozo et al., 1986; Martin et al., labour after 72 hours, and reducing postpartum 1989; Hannah et al., 1992; almstrom et al., 1995; haemorrhage rates. However, until safety issues have Crowley, 2004). Options for evaluating fetal well- been fully evaluated it should not be used in high- being include nonstress testing (CtG), biophysical risk women. Further studies are required before profile (bPP) or modified bPP (CtG plus amniotic recommending its adoption in practice. fluid volume estimation), contraction stress testing, and a combination of these modalities. Practices vary C) Antepartum fetal surveillance widely and no single method has been shown to be superior (Crowley, 2004). Women who reached 42 weeks gestation and opt to ultrasound assessment of amniotic fluid volume continue their pregnancy with conservative manage- appears to be important. delivery should be consid- ment should undergo antenatal fetal surveillance. ered if there is evidence of fetal compromise or despite the fact that there is no evidence to suggest oligohydramnios (Crowley et al., 1984; Phelan et that antepartum fetal surveillance in postterm preg- al., 1985). adverse pregnancy outcome (e.g. non- nancies decreases perinatal mortality, antenatal fetal reassuring fetal heart rate tracing, neonatal intensive surveillance has become a common practice in these care unit admission, low apgar score) is more cases on the basis of universal acceptance. the common when oligohydramnios is present (bochner reasons are: 1) data suggest a gradual increase in et al., 1987; tongsong and Srisomboon, 1993). perinatal morbidity and mortality during this period Oligohydramnios may result from feto-placental (Fig. 3) (Hilder et al., 1998); 2) there is no evidence insufficiency or increased renal artery resistance (Oz that antenatal fetal monitoring adversely affects post- et al., 2002) and may predispose to umbilical cord term women; 3) the published studies are of insuffi- compression, thus leading to intermittent fetal cient power to demonstrate a benefit of monitoring hypoxemia, meconium passage, or meconium in these cases; 4) because of ethical and medico- aspiration. Frequent (twice weekly) screening in legal considerations, no studies have included post- postterm pregnancies is suggested because amniotic term patients who were not monitored, and it is fluid can become drastically reduced within 24 to unlikely that any future studies will do so. 48hours (Clement et al., 1987). However, there is Women who have passed their edd but who have no consistent definition of oligohydramnios in the not yet reached 42 weeks of gestation constitute an- postterm pregnancy. Options include 1) largest ver- other group for whom antenatal fetal surveillance tical fluid pocket < 2 cm in depth or 2) amniotic fluid POStteRM PReGnanCy – Galaletal. 181 04-galal-_Opmaak 1 19/09/12 14:11 Pagina 182 index (aFi) <5cm (Crowley et al., 1984; Chamberlin ment of women with postterm pregnancy that are at et al., 1984). a prospective, double blind, cohort risk of unsuccessful induction, such as women with study of 1584 women after 40 weeks of gestation an unfavourable cervix. in one study, e3/e2 ratio found that aFi < 5cm, but not largest vertical fluid was presented as a biochemical marker to predict the pocket < 2cm, was associated with birth asphyxia responsiveness to iOl (torricelli et al., 2011) and meconium aspiration, although the sensitivity it was found that maternal serum e3/e2 ratio is for adverse outcome was low (Morris et al., 2003). significantly higher in women responding to iOl umbilical artery doppler velocimetry has no (torricelli et al., 2011). these data was in accord proven benefit in monitoring the postterm fetus and with other studies (Walsh et al., 1984; al-Shawarby is not recommended for this indication (Guidetti et et al., 2006). the study suggested that when preg- al., 1987; Stokes et al., 1991). although no firm nancy is approaching labour the levels of oestriol recommendation can be made on the basis of pub- and oestradiol change in maternal circulation caus- lished research regarding the frequency of antenatal ing an increase in their ratio (e3/e2 ratio). these surveillance among postterm women, it seems that data also suggested that oestrogen activation in twice-weekly testing is widely acceptable by many human parturition is mediated at the functional level clinicians (aCOG, 2004). it also seems that testing, by an increase in myometrial oestrogen responsive- using CtG and aF volume assessment, constitutes ness. the study concluded that a combination of ul- an acceptable standard by many clinicians. trasound assessment of cervical length and the e3/e2 ratio shows a good performance in the prediction of d) Induction of labour successful iOl in postterm pregnancy (torricelli et al., 2011). induction of labour is indicated when the benefits of delivery outweighs the risks associated with induc- Induction of labour in women with a favourable tion. the main concern around induction of labour cervix in postterm low risk pregnancies is related to uterine overstimulation, fetal distress, failure of induction Clinicians are less concerned about iOl in women and increase in caesarean section rates. there are with a favourable cervix; these women are more also risks associated with induction in particular likely to go into spontaneous labour on their own, groups of patients with specific risk factors such as and if induced, induction is more likely to succeed. risk of uterine rupture in women with previous it seems therefore that iOl in this group could be caesarean section. induction of labour is more likely less cost effective as the intervention might not be to succeed when the cervix is favourable. Several required in the first place. Most studies of postterm techniques have been evaluated to assess cervical pregnancy comparing outcomes of labour induction favourability and to predict the likelihood of success with those of expectant management excluded in women undergoing labour induction. these in- women with a favourable cervix (dyson et al., 1987; clude digital cervical examination (bishop score), Heden et al., 1991; Hannah et al., 1992; Shaw et al., ultrasound assessment of cervical length and more 1992; niCHHd, 1994). Moreover, when women in recently biochemical markers (oestriol/oestradiol the expectant management group experienced a ratio). spontaneous change in their cervical status, expectant a favourable cervix is defined as a cervix with management ceased and labour was induced bishop score of ≥ 6. digital cervical assessment has (augensen et al., 1987; Witter et al., 1987; niCHHd, been shown to be superior to trans-vaginal ultra- 1994). sound assessment of cervical length at term to in postterm pregnancy studies in which women predict the time interval from iOl to delivery with a favourable cervix were managed expectantly, (Rozenberg et al., 2005). However, digital cervical there was no indication that expectant management assessment remains subjective and could lack repro- had a deleterious effect on the outcome of the preg- ducibility. nancy, but results were not stratified according to the Oestrogens have been demonstrated to be impor- condition of the cervix (Cardozo et al., 1986; bergsjo tant hormones involved in the regulation of several et al., 1989; James et al., 2001; Chanrachakul and functions during pregnancy (Goodwin, 1999). Herabutya, 2003). When the ongoing risk of still- Oestriol (e3), oestradiol (e2), and the oestriol/ birth is weighted against the very low risk of failed oestradiol ratio in particular play an important role induction in this group, it is suggested that elective in the control of parturition by creating a specific oe- iOl may be a reasonable option for such women at strogenic environment at the onset of labour (Smith 39-41 weeks of gestation. However, such a conclu- et al., 2009). Oestrogens were therefore, studied on sion requires a large well designed trial to determine the basis that they may contribute to a better assess- whether this approach would reduce complications 182 FVV inObGyn 04-galal-_Opmaak 1 19/09/12 14:11 Pagina 183 and improve fetal, neonatal and/or maternal out- primarily related to fewer surgeries performed for comes. at 41-42 weeks of gestation it seems that the non- reassuring fetal heart rate tracings. Patient sa- risks of iOl are outweighed by the benefits and it is tisfaction was significantly higher in women ran- a common practice to offer iOl to such patients domly assigned to labour induction. (Caughey et al., 2008b). a meta-analysis of 19 trials of routine versus se- lective labour induction in postterm patients found Induction of labour in women with a un- that routine induction after 41 weeks of gestation favourable cervix was associated with a lower rate of perinatal morta- lity (OR, 0.2; 95% Ci, 0.06-0.7) and no increase in as many as 80% of women who reach 42 weeks the caesarean delivery rate (OR, 1.02; 95% Ci, 0.75- gestation have an unfavourable cervix (bishop Score 1.38) (2). Routine labour induction also had no effect <6). using cervical ripening prior to induction in on the instrumental delivery rate, use of analgesia, these cases appears to have some advantage in terms or incidence of fetal heart rate abnormality. the risk of outcome regardless of parity or method of induc- of meconium-stained amniotic fluid was reduced, tion. Pre-induction cervical ripening has resulted in but the risks of meconium aspiration syndrome and fewer failed inductions, reduced fetal and maternal neonatal seizures were unaffected (Crowley, 2004). morbidity, reduced medical cost, and possibly a the actual risk of stillbirth during the 41st week of reduced rate of caesarean delivery in the general gestation is estimated at 1.04-1.27 per 1,000 unde- obstetric population (Xenakis et al., 1997; Poma, livered women, compared with 1.55-3.1 per 1,000 1999; Sanchez-Ramos et al., 2002). women at or beyond 42 weeks of gestation (Caughey Cochrane systematic reviews demonstrated that et al., 2008b). taken together, these data suggest that prostaglandins (PGs) improve cervical ripeness and routine induction at 41 weeks of gestation has fetal could initiate uterine contractions (boulvain et al., benefit without incurring the additional maternal 2007; Kelly et al., 2009). However, their value in risks of a higher rate of caesarean delivery (Rand et reducing induction-delivery interval and CS rate in al., 2000; Crowley, 2004). this conclusion has not postterm women is debatable (Rayburn et al., 1988; been universally accepted (Cardozo et al., 1986; Papageorgiou et al., 1992; Sawai et al., 1994). Witter et al., 1987; Heden et al., 1991; niCHHd, although multiple studies have used PG to induce 1994). labour in postterm pregnancies, no standardized dose or dosing interval has been established. Overall, the Induction of labour in postterm women with medications were well tolerated with few reported previous caesarean section side effects. Higher doses of PG (especially PGe1) have been associated with an increased risk of Vaginal birth after caesarean delivery (VbaC) has uterine tachysystole and hyper-stimulation leading been promoted as a reasonable alternative to elective to non-reassuring fetal testing results (How et al., repeat caesarean delivery for some women. the risk 2001). as such lower doses (e.g. 25 microgram of uterine rupture does not appear to increase sub- intravaginal misoprostol) are preferable to 50 micro- stantially after 40 weeks of gestation (Callahan et al., gram (Sanchez-Ramos et al., 2002). When PG is 1999; Zelop et al., 2001), but the risk appears to be used, fetal heart rate monitoring should be performed increased with iOl with prostaglandins or syntoci- routinely to assess fetal well-being because of the non regardless of gestational age (Zelop et al., 2001; risk of uterine hyper-stimulation. lydon-Rochelle, 2001). in a population-based, retro - although postterm pregnancy is defined as a spective cohort analysis, the risk of uterine rupture pregnancy of 42 weeks or more of gestation, several with VbaC was 1.6 per 1000 women with previous large multi-centre randomized studies of manage- one caesarean delivery without labour, 5.2 per 1000 ment of pregnancy beyond 40 weeks of gestation women with spontaneous onset of labour, 7.7 per reported favourable outcomes with routine iOl as 1000 women with iOl without PG, and 24.5 per early as the beginning of 41 weeks of gestation 1000 women with PG induction of labour (lydon- (Hannah et al., 1992; niCHHd, 1994; Crowley, Rochelle, 2001). there is limited evidence on the 2004). the largest study to date randomly assigned efficacy or safety of VbaC after 42 weeks of 3,407 low-risk women with uncomplicated singleton gestation. as such, no firm recommendation can be pregnancies at 41 weeks of gestation to labour made for this particular group (aCOG, 2004). induction (with or without cervical ripening agents) within 4 days of randomization or expectant Conclusion management until 44 weeks of gestation (Hannah et al., 1992). elective induction resulted in a lower Postterm pregnancy is associated with fetal, neonatal caesarean delivery rate (21.2% versus 24.5%), and maternal complications including morbidity and POStteRM PReGnanCy – Galaletal. 183 04-galal-_Opmaak 1 19/09/12 14:11 Pagina 184 perinatal mortality. these risks were originally un- Care in Pregnancy and Childbirth. Oxford: Oxford univer- sity Press, 1989:765-75. derestimated because of inaccurate pregnancy dating baranova a, Gowder SJ, Schlauch K et al. Gene expression of and the denominator used to define stillbirth. the use leptin, resistin, and adiponectin in the white adipose tissue of routine ultrasound for dating in the first trimester of obese patients with non-alcoholic fatty liver disease and has decreased the overall rate of postterm pregnancy insulin resistance. Obes Surg. 2006;16:1118-25. bennett Ka, Crane JM, O’Shea P et al. First trimester ultrasound and demonstrated higher complication rates in post- screening is effective in reducing postterm labor induction term pregnancies due to better distinction between rates: a randomized controlled trial. am J Obstet Gynecol. term and postterm gestation. also the use of ongoing 2004;190:1077-81. bergsjo P, Huang Gd, yu SQ et al. Comparison of induced versus pregnancies as a denominator for stillbirth rather than non-induced labor in postterm pregnancy. a randomized pros- pregnancies delivered has shown a six-fold increase pective study. acta Obstet Gynecol Scand. 1989;68:683-7. in perinatal complications in postterm women. bochner CJ, Medearis al, davis J et al. antepartum predictors of fetal distress in postterm pregnancy. am J Obstet Gynecol. Forty two weeks of gestation does not represent a 1987;157:353-8. threshold under which risks are uniformly distribu- bochner CJ, Williams J 3rd, Castro l et al. the efficacy of ted, and there is emerging evidence that fetal, starting postterm antenatal testing at 41 weeks as compared neonatal and maternal complications do increase with 42 weeks of gestational age. am J Obstet Gynecol. 1988; 159:550-4. before 42 weeks (from 38-39 weeks onwards with boulvain M, Stan C, irion O. Membrane sweeping for induction an obvious rise after 40&41 weeks gestation). of labour. Cochrane database Syst Rev.2005;1:Cd000451. therefore the definition and management of post- boulvain M, Kelly aJ, irion O. intracervical prostaglandins for induction of labour. Cochran database Syst Rev. 2007; term pregnancy have been challenged in several Cd006971. studies in recent years. in the light of the current bruckner ta, Cheng yW, Caughey ab. increased neonatal evidence earlier intervention with iOl at 41 weeks mortality among post-term births in California. am J Obstet Gynecol. 2008;199:421.e1-7. appears appropriate management. Callahan C, Chescheir n, Steiner bd. Safety and efficacy of We conclude that in the light of the current attempted vaginal birth after cesarean beyond the estimated evidence iOl at 41 weeks is justified to minimise date of delivery. J Reprod Med. 1999;44:606-10. both fetal and maternal complications. Campbell MK, Ostbye t, irgens lM. Post-term birth: risk factors and outcomes in a 10-year cohort of norwegian births. Obstet Gynecol.1997;89:543-8. Cardozo l, Fysh J, Pearce JM. Prolonged pregnancy: the References management debate. br Med J. (Clin Res ed) 1986;293: 1059-63. alexander JM, Mcintire dd, leveno KJ. Forty weeks and be- Caughey ab, bishop J. Maternal complications of pregnancy yond: pregnancy outcomes by week of gestation. Obstet Gy- increase beyond 40 weeks of gestation in low risk women. necol.2000; 96:291-4. JPerinatol.2006;26:540-5. alexander JM, Mcintire dd, leveno KJ. Prolonged pregnancy: Caughey ab, Musci tJ. Complications of term pregnancies induction of labor and cesarean births. Obstet Gynecol.2001; beyond 37 weeks of gestation. Obstet Gynecol. 2004;103:57- 97:911. 62. alfirevic Z, Walkinshaw Sa. Management of post-term preg- Caughey ab, nicholson JM, Washington ae. First versus nancy: to induce or not? br J Hosp Med. 1994;52:218-21. second trimester ultrasound: the effect on pregnancy dating allen VM, O’Connell CM, Farrell Sa et al. economic implica- and perinatal outcomes. am J Obstet Gynecol. 2008a; 198: tions of method of delivery. am J Obstst Gynecol. 2005; 703.e1-e5. 193:192-7. Caughey ab, Sengovskikh VV, norwitz eR. Postterm preg- almstrom H, Granstrom l, ekman G. Serial antenatal monito- nancy: How Can We improve Outcomes? Obstet Gynecol ring compared with labor induction in post-term pregnancies. Survey. 2008b;63:715-24. acta Obstet Gynecol Scand. 1995;74:599-603. Caughey ab, Stotland ne, escobar GJ. What is the best meas- al-Shawarby Sa, Connell RJ. induction of labour at term with ure of maternal complications of term pregnancy: ongoing vaginal prostaglandins preparations: a randomized controlled pregnancies or pregnancies delivered? am J Obstet Gynecol. trial of Prostin vs Propess. J Obstet Gynaecol. 2006;26:627- 2003;189:1047-52. 30. Caughey ab, Stotland ne, Washington ae et al. Who is at risk aCOG (american College of Obstetricians and Gynecologists). for prolonged and postterm pregnancy. am J Obstet Gynecol. Management of Postterm Pregnancy. aCOG Practice bulle- 2009;200(6):683e1-683e5. tin no. 6 (1997). int J Gynaecol Obstet. 1998;60:86-91. Caughey ab, Stotland ne, Washington ae et al. Maternal aCOG (american College of Obstetricians and Gynecologists). obstetric complications of pregnancy are associated with Fetal Macrosomia. Washington, dC; aCOG; 2000. aCOG increasing gestational age at term. am J Obstet Gynecol. Practice bulletin #22. 2007;196:155.e1-e6. aCOG (american College of Obstetricians and Gynecologists). Caughey ab, Washington ae, laros RK. neonatal complica- Management of Postterm Pregnancy. aCOG Practice bul- tions of term pregnancies: rates increase in a continuous, not letin no. 55. Obstet Gynecol. 2004;104:639-46. threshold fashion. am J Obstet Gynecol. 2005; 192(1):185- augensen K, bergsjo P, eikeland t et al. Randomised compari- 9. son of early versus late induction of labour in post-term Chamberlain PF, Manning Fa, Morrison i et al. ultrasound eva- pregnancy. br Med J. (Clin Res ed) 1987;294:1192-5. luation of amniotic fluid volume. i. the relationship of mar- badawi n, Kurinczuk JJ, Keogh JM et al. antepartum risk ginal and decreased amniotic fluid volumes to perinatal factors for newborn encephalopathy: the Western australian outcome. am J Obstet Gynecol. 1984;150:245-9. case-control study. br Med J. 1998;317:1549-53. Chanrachakul b, Herabutya y. Postterm with favorable cervix: bakketeig lS, bergsjo P. Post-term pregnancy: magnitude of the is induction necessary? eur J Obstet Gynecol Reprod biol. problem. in: enkin M, Keirse MJ, Chalmers i, eds. effective 2003;106:154-7. 184 FVV inObGyn