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Background

Preterm prelabour rupture of membranes (PPROM) complicates up to 2% of all pregnancies and is the cause of 40% of all preterm births. The optimal management of women with PPROM prior to 37 weeks, is not known. Furthermore, diversity in current clinical practice suggests uncertainty about the appropriate clinical management.

There are two options for managing PPROM, expectant management (a wait and see approach) or early planned birth. Infection is the main risk for women in which management is expectant. This risk need to be balanced against the risk of iatrogenic prematurity if early delivery is planned. The different treatment options may also have different health care costs. Expectant management results in prolonged antenatal hospitalisation while planned early delivery may necessitate intensive care of the neonate for problems associated with prematurity.

Methods/Design

We aim to evaluate the effectiveness of early planned birth compared with expectant management for women with PPROM between 34 weeks and 366 weeks gestation, in a randomised controlled trial. A secondary aim is a cost analysis to establish the economic impact of the two treatment options and establish the treatment preferences of women with PPROM close to term.

The early planned birth group will be delivered within 24 hours according to local management protocols. In the expectant management group birth will occur after spontaneous labour, at term or when the attending clinician feels that birth is indicated according to usual care. Approximately 1812 women with PPROM at 34–366 weeks gestation will be recruited for the trial.

The primary outcome of the study is neonatal sepsis. Secondary infant outcomes include respiratory distress, perinatal mortality, neonatal intensive care unit admission, assisted ventilation and early infant development. Secondary maternal outcomes include chorioamnionitis, postpartum infection treated with antibiotics, antepartum haemorrhage, induction of labour, mode of delivery, maternal satisfaction with care, duration of hospitalisation, and maternal wellbeing at four months postpartum.

Discussion

This trial will provide evidence on the optimal care for women with PPROM close to term (34–37 weeks gestation). Consideration of both the clinical and economic sequelae of the management of PPROM will enable informed decision making and guideline development.

In a randomized controlled trial David van der Ham and colleagues investigate induction of labor versus expectant management for women with preterm prelabor rupture of membranes.

Background

At present, there is insufficient evidence to guide appropriate management of women with preterm prelabor rupture of membranes (PPROM) near term.

Methods and Findings

We conducted an open-label randomized controlled trial in 60 hospitals in The Netherlands, which included non-laboring women with >24 h of PPROM between 34+0 and 37+0 wk of gestation. Participants were randomly allocated in a 1∶1 ratio to induction of labor (IoL) or expectant management (EM) using block randomization. The main outcome was neonatal sepsis. Secondary outcomes included mode of delivery, respiratory distress syndrome (RDS), and chorioamnionitis. Patients and caregivers were not blinded to randomization status. We updated a prior meta-analysis on the effect of both interventions on neonatal sepsis, RDS, and cesarean section rate.

From 1 January 2007 to 9 September 2009, 776 patients in 60 hospitals were eligible for the study, of which 536 patients were randomized. Four patients were excluded after randomization. We allocated 266 women (268 neonates) to IoL and 266 women (270 neonates) to EM. Neonatal sepsis occurred in seven (2.6%) newborns of women in the IoL group and in 11 (4.1%) neonates in the EM group (relative risk [RR] 0.64; 95% confidence interval [CI] 0.25 to 1.6). RDS was seen in 21 (7.8%, IoL) versus 17 neonates (6.3%, EM) (RR 1.3; 95% CI 0.67 to 2.3), and a cesarean section was performed in 36 (13%, IoL) versus 37 (14%, EM) women (RR 0.98; 95% CI 0.64 to 1.50). The risk for chorioamnionitis was reduced in the IoL group. No serious adverse events were reported.

Updating an existing meta-analysis with our trial results (the only eligible trial for the update) indicated RRs of 1.06 (95% CI 0.64 to 1.76) for neonatal sepsis (eight trials, 1,230 neonates) and 1.27 (95% CI 0.98 to 1.65) for cesarean section (eight trials, 1,222 women) for IoL compared with EM.

Conclusions

In women whose pregnancy is complicated by late PPROM, neither our trial nor the updated meta-analysis indicates that IoL substantially improves pregnancy outcomes compared with EM.

Trial registration

Current Controlled Trials ISRCTN29313500

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Most pregnancies last around 40 weeks, but in industrialized countries, 5%–10% of babies are born before 37 weeks of gestation (gestation is the period during which a baby develops in its mother's womb). Premature birth is a major cause of infant death in many developed countries, and preterm babies can also have short- and/or long-term health problems such as breathing problems, increased susceptibility to life-threatening infections, and learning and developmental disabilities. There are many reasons why some babies are born prematurely, but preterm prelabor rupture of the membranes (PPROM) accounts for 30%–40% of preterm deliveries. Inside the womb, the baby is held in a fluid-filled bag called the amniotic sac. The amniotic fluid cushions the baby, helps some of its organs develop, and protects both mother and baby from infection. The membranes that form the sac usually break at the start of labor (“water breaking”), but in PPROM, the membranes break before the baby is fully grown. PPROM increases the mother's risk of a womb infection called chorioamnionitis and the baby's risk of neonatal sepsis (blood infection), and can trigger early labor.

Why Was This Study Done?

There is currently no consensus on how to manage women whose membranes rupture between 34 and 37 weeks' gestation. Some guidelines recommend immediate induction of labor if PPROM occurs at or beyond 34 weeks' gestation. Others recommend that labor not be induced unless the mother develops signs of infection such as a high temperature or has not delivered her baby spontaneously by 37 weeks' gestation (expectant management). Before 34 weeks' gestation, expectant management is generally recommended. In this randomized controlled trial, the researchers compare the effects of induction of labor and of expectant management on the rate of neonatal sepsis (the proportion of babies that develop neonatal sepsis; the trial's primary outcome) and on secondary outcomes such as the rates of neonatal respiratory distress syndrome (RDS), cesarean section (surgical delivery), and chorioamnionitis in women with PPROM between 34 and 37 weeks' gestation. The researchers also undertake a meta-analysis of published trials on the effect of both interventions on pregnancy outcomes. A randomized controlled trial compares the effects of different interventions in groups of individuals chosen through the play of chance; meta-analysis is a statistical approach that combines the results of several trials.

What Did the Researchers Do and Find?

In the PPROM Expectant Management versus Induction of Labor (PRROMEXIL) trial, 532 non-laboring women with PPROM between 34 and 37 weeks' gestation were randomly assigned to either immediate induction of labor or expectant management. Neonatal sepsis occurred in seven babies born to women in the induction of labor group and in 11 babies born to women in the expectant management group. This difference was not statistically significant. That is, it could have happened by chance. Similarly, although more babies born to women in the induction of labor group than in the expectant management group developed RDS (21 and 17 babies, respectively), this difference was not significant. Cesarean section rates were similar in both intervention groups, but the risk of chorioamnionitis was slightly reduced in the induction of labor group compared to the expectant management group. Finally, the researchers' meta-analysis (which included these new results) found no significant differences in the risk of neonatal sepsis, RDS, or cesarean section associated with the two interventions.

What Do These Findings Mean?

These findings show that, compared to expectant management, induction of labor did not reduce the incidence of neonatal sepsis in pregnancies complicated by PPROM between 34 and 37 weeks' gestation. However, because fewer babies than expected born to the women in the expectant management group developed neonatal sepsis, this trial was underpowered. That is, too few women were enrolled in the trial to enable the detection of a small difference between the interventions in the neonatal sepsis rate. These findings also show that induction of labor did not substantially affect most of the secondary outcomes measured by the researchers. Given these results and those of their meta-analysis, the researchers conclude that, in women whose pregnancy is complicated by PPROM late in pregnancy, induction of labor does not substantially improve the outcome for either the woman or her baby compared to expectant management.

Additional Information

Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001208.

The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth (in English and Spanish); its News Moms Need blog contains a post on PPROM

Tommy's is a nonprofit organization that funds research and provides information on the causes and prevention of miscarriage, premature birth, and stillbirth

The Royal College of Obstetricians and Gynaecologists guidelines on the diagnosis, investigation, and management of PPROM are available (in English and Russian)

Information about the PPROMEXIL trial is available

Personal stories about PPROM are available on the Austprem web site, a non-profit organization that provides information about prematurity and support for parents of premature babies in Australia

MedlinePlus provides links to other information on premature babies (in English and Spanish)

Objectives

To identify risk factors for spontaneous preterm birth (birth <37 weeks gestation) with intact membranes (SPTB-IM) and SPTB after prelabour rupture of the membranes (SPTB-PPROM) for nulliparous pregnant women.

Design

Prospective international multicentre cohort.

Participants

3234 healthy nulliparous women with a singleton pregnancy, follow up was complete in 3184 of participants (98.5%).

Results

Of the 3184 women, 156 (4.9%) had their pregnancy complicated by SPTB; 96 (3.0%) and 60 (1.9%) in the SPTB-IM and SPTB-PPROM categories, respectively. Independent risk factors for SPTB-IM were shorter cervical length, abnormal uterine Doppler flow, use of marijuana pre-pregnancy, lack of overall feeling of well being, being of Caucasian ethnicity, having a mother with diabetes and/or a history of preeclampsia, and a family history of low birth weight babies. Independent risk factors for SPTB-PPROM were shorter cervical length, short stature, participant’s not being the first born in the family, longer time to conceive, not waking up at night, hormonal fertility treatment (excluding clomiphene), mild hypertension, family history of recurrent gestational diabetes, and maternal family history of any miscarriage (risk reduction). Low BMI (<20) nearly doubled the risk for SPTB-PPROM (odds ratio 2.64; 95% CI 1.07–6.51). The area under the receiver operating characteristics curve (AUC), after internal validation, was 0.69 for SPTB-IM and 0.79 for SPTB-PPROM.

Conclusion

The ability to predict PTB in healthy nulliparous women using clinical characteristics is modest. The dissimilarity of risk factors for SPTB-IM compared with SPTB-PPROM indicates different pathophysiological pathways underlie these distinct phenotypes.

Trial Registration

ACTR.org.au ACTRN12607000551493

Background

Hypertensive disorders, i.e. pregnancy induced hypertension and preeclampsia, complicate 10 to15% of all pregnancies at term and are a major cause of maternal and perinatal morbidity and mortality. The only causal treatment is delivery. In case of preterm pregnancies conservative management is advocated if the risks for mother and child remain acceptable. In contrast, there is no consensus on how to manage mild hypertensive disease in pregnancies at term. Induction of labour might prevent maternal and neonatal complications at the expense of increased instrumental vaginal delivery rates and caesarean section rates.

Methods/Design

Women with a pregnancy complicated by pregnancy induced hypertension or mild preeclampsia at a gestational age between 36+0 and 41+0 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant management for spontaneous delivery. The primary outcome of this study is severe maternal morbidity, which can be complicated by maternal mortality in rare cases. Secondary outcome measures are neonatal mortality and morbidity, caesarean and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be by intention to treat. In total, 720 pregnant women have to be randomised to show a reduction in severe maternal complications of hypertensive disease from 12 to 6%.

Discussion

This trial will provide evidence as to whether or not induction of labour in women with pregnancy induced hypertension or mild preeclampsia (nearly) at term is an effective treatment to prevent severe maternal complications.

Trial Registration

The protocol is registered in the clinical trial register number ISRCTN08132825.

Objective

The objective of this study was to evaluate the risk of funisitis among women with preterm, prelabour rupture of the membranes (PPROM) and subsequent bleeding per vaginam (pv).

Design

Prospective cohort study.

Setting

University Hospital in the United States.

Population

157 women with PPROM, divided into those with bleeding pv during the hospital admission (46) and those without bleeding pv (111).

Methods

Pathologist blinded to bleeding pv status assessed placental pathology for funisitis.

Main Outcome Measures

Funisitis.

Results

Women with bleeding pv were more likely to have funisitis (67.4% vs. 36%, p<0.001) compared to those without bleeding. Logistic regression demonstrated that bleeding pv predicted funisitis after controlling for gestational age at admission, latency period and gestational age of delivery.

Conclusions

Among women with PPROM, those with bleeding pv are more likely to have funisitis than those without bleeding pv.

Background

Preterm labour is the main cause of perinatal morbidity and mortality in the Western world. At present, there is evidence that tocolysis for 48 hours is useful in women with threatened preterm labour at least before 32 weeks. This allows transfer of the patient to a perinatal centre, and maximizes the effect of corticosteroids for improved neonatal survival. It is questionable whether treatment with tocolytics should be maintained after 48 hours.

Methods/Design

The APOSTEL II trial is a multicentre placebo-controlled study. Pregnant women admitted for threatened preterm labour who have been treated with 48 hours corticosteroids and tocolysis will be eligible to participate in the trial between 26+0 and 32+2 weeks gestational age. They will be randomly allocated to nifedipine (intervention) or placebo (control) for twelve days or until delivery, whatever comes first.

Primary outcome is a composite of perinatal death, and severe neonatal morbidity up to evaluation at 6 months after birth. Secondary outcomes are gestational age at delivery, number of days in neonatal intensive care and total days of the first 6 months out of hospital. In addition a cost-effectiveness analysis will be performed. Analysis will be by intention to treat. The power calculation is based on an expected 11% difference in adverse neonatal outcome. This implies that 406 women have to be randomised (two sided test, β 0.2 at alpha 0.05).

Discussion

This trial will provide evidence as to whether maintenance tocolysis reduces severe perinatal morbidity and mortality in women with threatened preterm labour before 32 weeks.

Trial Registration

Clinical trial registration: , NTR 1336, date of registration: June 3rd 2008.

This study aimed to determine if fetal bacteraemia and amniotic fluid infection at the time of membrane rupture reduces the interval between membrane rupture and the onset of labour in pregnancies complicated by preterm prelabour amniorrhexis. Sixty nine pregnancies with preterm prelabour amniorrhexis at 12-36 weeks' gestation that were managed expectantly had spontaneous onset of labour. In all cases cordocentesis and amniocentesis were performed and fetal blood and amniotic fluid were cultured for aerobic and anaerobic bacteria. In the group with negative fetal blood and amniotic fluid cultures (group 1) the median interval from amniorrhexis to delivery was 41 days (range 1-161) and there was an inverse correlation between gestational age at amniorrhexis and delivery interval. In the group with negative fetal blood but positive amniotic fluid cultures (group 2) the median amniorrhexis to delivery interval was nine days (range 1-37), and in the group with positive fetal blood cultures (group 3) the interval was two days (range 1-5). These findings suggest that pregnancies complicated by preterm prelabour amniorrhexis and fetal bacteraemia undergo spontaneous labour within five days of membrane rupture, and if labour does not occur then infection is unlikely.

Objective

To examine whether cervical favourability (measured by cervical length and the Bishop score) should inform obstetricians’ decision regarding labour induction for women with gestational hypertension or mild pre-eclampsia at term.

Design

A post hoc analysis of the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT).

Setting

Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands.

Population

A total of 756 women diagnosed with gestational hypertension or pre-eclampsia between 36 + 0 and 41 + 0 weeks of gestation randomly allocated to induction of labour or expectant management.

Methods

Data were analysed using logistic regression modelling.

Main outcome measures

The occurrence of a high-risk maternal situation defined as either maternal complications or progression to severe disease. Secondary outcomes were caesarean delivery and adverse neonatal outcomes.

Results

The superiority of labour induction in preventing high-risk situations in women with gestational hypertension or mild pre-eclampsia at term varied significantly according to cervical favourability. In women who were managed expectantly, the longer the cervix the higher the risk of developing maternal high-risk situations, whereas in women in whom labour was induced, cervical length was not associated with a higher probability of maternal high-risk situations (test of interaction P = 0.03). Similarly, the beneficial effect of labour induction on reducing the caesarean section rate was stronger in women with an unfavourable cervix.

Conclusion

Against widely held opinion, our exploratory analysis showed that women with gestational hypertension or mild pre-eclampsia at term who have an unfavourable cervix benefited more from labour induction than other women.

Trial registration

The trial has been registered in the clinical trial register as ISRCTN08132825.

Introduction

If left untreated, severe combined immunodeficiency can lead to an acute susceptibility to infection. The intrauterine environment is sterile until the amniotic membranes rupture. The vaginal flora then ascends into the genital tract, thus increasing the risk of chorioamnionitis. An extremely premature and prolonged membrane rupture is associated with a dismal prognosis for an immunocompetent preterm fetus. There are no case reports to date that detail the outcome of an immunocompromised preterm baby following prolonged rupture of membranes.

Case presentation

We present the case of a 32-year-old Indian woman who delivered a 31-week gestational baby who had a severe combined immunodeficiency following premature prelabour prolonged rupture of the membranes at the 14th week of gestation.

Conclusion

Extreme preterm prelabour spontaneous rupture of membranes in an underlying condition of severe combined immunodeficiency does not necessarily lead to an unfavourable outcome.

Objective To determine neonatal outcomes (perinatal mortality and special care unit admission) and maternal outcomes (mode of delivery, delivery complications) of elective induction of labour compared with expectant management.

Design Retrospective cohort study using an unselected population database.

Setting Consultant and midwife led obstetric units in Scotland 1981-2007.

Participants 1 271 549 women with singleton pregnancies of 37 weeks or more gestation.

Interventions Outcomes of elective induction of labour (induction of labour with no recognised medical indication) at 37, 38, 39, 40, and 41 weeks’ gestation compared with those of expectant management (continuation of pregnancy to either spontaneous labour, induction of labour or caesarean section at a later gestation).

Main outcome measures Extended perinatal mortality, mode of delivery, postpartum haemorrhage, obstetric anal sphincter injury, and admission to a neonatal or special care baby unit. Outcomes were adjusted for age at delivery, parity, year of birth, birth weight, deprivation category, and, where appropriate, mode of delivery.

Results At each gestation between 37 and 41 completed weeks, elective induction of labour was associated with a decreased odds of perinatal mortality compared with expectant management (at 40 weeks’ gestation 0.08% (37/44 764) in the induction of labour group versus 0.18% (627/350 643) in the expectant management group; adjusted odds ratio 0.39, 99% confidence interval 0.24 to 0.63), without a reduction in the odds of spontaneous vertex delivery (at 40 weeks’ gestation 79.9% (35 775/44 778) in the induction of labour group versus 73.7% (258 665/350 791) in the expectant management group; adjusted odds ratio 1.26, 1.22 to 1.31). Admission to a neonatal unit was, however, increased in association with elective induction of labour at all gestations before 41 weeks (at 40 weeks’ gestation 8.0% (3605/44 778) in the induction of labour group compared with 7.3% (25 572/350 791) in the expectant management group; adjusted odds ratio 1.14, 1.09 to 1.20).

Conclusion Although residual confounding may remain, our findings indicate that elective induction of labour at term gestation can reduce perinatal mortality in developed countries without increasing the risk of operative delivery.

Objective. To evaluate the management and outcomes of a series of human immunodeficiency virus-(HIV-) infected women whose pregnancies were complicated by preterm premature rupture of membranes (PPROM). Study design. We conducted a retrospective chart review of all women with confirmed HIV infection who had a pregnancy complicated by PPROM remote from term. PPROM remote from term was defined as rupture of membranes prior to 32-week gestation. Collective cases from two centers (Hennepin County Medical Center and The University of Alabama at Birmingham) were reviewed and data on management and outcomes were abstracted. Results. Of the HIV-positive women, we identified 291 pregnancies having occurred in the study interval from two institutions. Of these pregnancies, 7 (2.4%) developed PPROM remote from term with subsequent delivery from 25- to 32-week gestation. Vertical HIV transmission was noted in 2 of 6 children whose long-term followup status was confirmed (33%) of these cases. However, both of these cases occurred in women with either no antepartum/intrapartum antiviral therapy or where only zidovudine monotherapy was used. Importantly, in spite of expectant management, no cases of vertical HIV transmission occurred in women who were receiving either multidrug or highly active antiviral therapy (HAART) at the time of PPROM and who had a cesarean delivery in cases where the predelivery viral load > 1000 copies/mL. Conclusion. Our limited observations raise the question as to whether in the current era of multidrug therapy immediate delivery should be undertaken in HIV+ pregnancies complicated by PPROM at an early gestational age. This case series further suggests that in those pregnancies that lend themselves to expectant management, such a strategy may be considered appropriate.

Objectives. Our objective is to compare maternal plasma procalcitonin concentrations in preterm premature rupture of membranes (pPROM) and premature rupture of membranes (PROM) at term with their levels in uncomplicated pregnancy, and to determine whether these concentrations are useful in the diagnosis of pPROM cases suspected of infection and in the prediction of pPROM-to-delivery interval. Study design. Forty eight patients with pPROM, 30 with PROM at term, 31 healthy women at preterm gestation, and 33 healthy women at term were included. In pPROM group, analysis of procalcitonin concentrations with reference to leucocytosis, serum C-reactive protein, vaginal fluid culture, neonatal infection, histological chorioamnionitis and pPROM-to-delivery interval was carried out. Results. Procalcitonin concentrations in pPROM and PROM at term cases were comparable. However, in both groups procalcitonin values were significantly higher than in healthy controls in approximate gestational age. In pPROM group, procalcitonin concentrations between the patients with and without laboratory indices of infection were comparable, as well as between patients who gave birth to newborns with and without congenital infection, and between patients with and without histological chorioamnionitis. The predictive values of procalcitonin determinations were poor. Conclusion. The value of maternal plasma procalcitonin determinations in the diagnostics of pPROM cases suspected of intraamniotic infection, as well as for the prediction of pPROM-to-delivery interval, newborn's infection or histological chorioamnionitis is unsatisfactory. However, procalcitonin concentrations are elevated, both in patients with preterm and term PROMs in comparison to healthy pregnants, and therefore further evaluations are necessary to establish the role of procalcitonin in the pathophysiology of pregnancy.

Objective: This study was to determine the significance of meconium in the amniotic fluid of pregnancies complicated by preterm premature rupture of membranes (PPROM) without labor.

Methods: A case-control study of 31 pregnancies complicated by PPROM at 27–36 weeks gestation with meconium present (study group) and 93 pregnancies complicated by PPROM but without meconium was performed. The patients were matched for year of delivery, gestational age, race, and parity. Pregnancy and neonatal outcome variables of the 2 groups were compared.

Results: The incidence of early onset neonatal sepsis was significantly increased in the study group (16.1% vs. 1.1%; P < 0.001). Similarly, chorioamnionitis (48.3% vs. 22.5%; P < 0.01), cesarean delivery for a nonreassuring fetal heart rate pattern (19.4% vs. 3.2%; P < 0.01), a 5-min Apgar score < 7 (22.5% vs. 8.6%; P < 0.05), and fetal growth retardation (FGR) (12.9% vs. 2.2%; P < 0.05) were also more common in pregnancies complicated by PPROM with meconium. The mean umbilical cord arterial pH was significantly lower in these pregnancies (7.18 ± 0.07 vs. 7.28 ± 0.08; P < 0.001). After controlling for confounding variables with multiple logistic regression analysis, we found that meconium in the amniotic fluid remained associated with early onset neonatal sepsis.

Conclusions: The presence of meconium in the amniotic fluid of pregnancies complicated by PPROM is associated with an increased incidence of early onset neonatal group B β-hemolytic streptococcus (GBBS) sepsis.

OBJECTIVE: To determine the cost-effectiveness of induction of labour versus serial fetal monitoring while awaiting spontaneous labour in postterm pregnancies. DESIGN: Cost-effectiveness and cost-minimization analyses conducted as part of a Canadian multicentre randomized clinical trial. SETTING: Twenty-two Canadian hospitals, of which 19 were teaching hospitals and 3 were community hospitals. PATIENTS: Women with uncomplicated pregnancies of 41 or more weeks' gestation were randomly assigned to induction of labour or serial antenatal monitoring. Of the 3418 women enrolled, no data were received on 11. Therefore, results were based on data from 1701 women in the induction arm of the study and 1706 women in the monitoring arm. MAIN OUTCOME MEASURES: Perinatal mortality and neonatal morbidity, rates of cesarean section and health care costs. Hospital costing models were developed specifically for the study. Data on use of major resources (e.g., length of hospital stay, surgical procedures, major diagnostic tests and procedures, and medications) for all trial participants were collected and combined with data on minor tests and procedures (e.g., laboratory tests) abstracted from a detailed review of medical records of a sample of patients. RESULTS: Because the results of the clinical trial showed a nonsignificant difference in perinatal mortality and neonatal morbidity between the induction and monitoring arms, the authors conducted a cost-minimization rather than a cost-effectiveness analysis. The mean cost per patient with a postterm pregnancy managed through monitoring was $3132 (95% confidence interval [CI] $3090 to $3174) and per patient who underwent induction of labour was $2939 (95% CI $2898 to $2981), for a difference of $193. The significantly higher (p < 0.0001) mean cost per patient in the monitoring arm was due mainly to the costs of additional monitoring and the significantly higher rates of cesarean section among these patients. Estimated conservatively, the savings resulting from a universal policy of managing postterm pregnancies by induction of labour in Canada may be as high as $8 million a year. CONCLUSIONS: A policy of managing postterm pregnancy through induction of labour not only results in more favourable outcomes than a monitoring strategy but does so at a lower cost.

Objective

To compare the annual incidence rates of caesarean delivery between induction of labour and expectant management in the setting of macrosomia.

Design

This is a retrospective cohort study.

Setting

Deliveries in the USA in 2003.

Population

Singleton births of macrosomic neonates to low-risk nulliparous women at 39 weeks of gestation and beyond.

Methods

Women who had induction of labour at 39 weeks of gestation with a neonatal birthweight of 4000 ± 125 g (3875–4125 g) were compared with women who delivered (either induced or spontaneous labour) at 40, 41 or 42 weeks (i.e. expectant management), assuming an intrauterine fetal weight gain of 200 g per additional week of gestation. Similar comparisons were made at 40 and 41 weeks of gestation. Chi-square test and multivariable logistic regression analysis were used for statistical comparison.

Main outcome measures

Method of delivery, 5-minute Apgar scores, neonatal injury.

Results

There were 132 112 women meeting the study criteria. In women whose labours were induced at 39 weeks and who delivered a neonate with a birthweight of 4000 ± 125 g, the frequency of caesarean was lower compared with women who delivered at a later gestational age (35.2% versus 40.9%; adjusted OR 1.25, 95% CI 1.17–1.33). This trend was maintained at both 40 weeks (36.1% versus 42.6%; adjusted OR 1.31, 95% CI 1.23–1.40) and 41 weeks (38.9% versus 41.8%; adjusted OR 1.16, 95% CI 1.06–1.28) of gestation.

Conclusions

In the setting of known birthweight, it appears that induction of labour may reduce the risk of caesarean delivery. Future research should concentrate on clinical and radiological methods to better estimate birthweight to facilitate improved clinical care. These findings deserve examination in a large, prospective, randomised trial.

The management and outcome of 242 infants delivered between 26 and 34 weeks' gestation in an obstetrical and neonatal regional referral centre as a result of spontaneous preterm labour were recorded prospectively. Results of the survey show that the decision to intervene and delay delivery will depend on the availability of neonatal intensive care facilities. Infants likely to require intensive neonatal care should be transferred in utero to a centre with these facilities. The use of steroids reduces the mortality of preterm infants. The maximum effect occurs between 30 and 32 weeks' gestation, and there is no benefit after 34 weeks. If the weight is over 1500 g the mode of delivery of the preterm infant presenting by the breech does not influence outcome; if under 1500 g a caesarean section improves survival over those infants born by vaginal breech delivery.

Objective

To investigate the effect of maternal obesity on mode of delivery following induction of labour (IOL) for prolonged pregnancy and subsequent intrapartum and neonatal complications.

Design

Retrospective (historical) cohort study.

Setting

Liverpool Women's Hospital NHS Foundation Trust, UK.

Population

A total of 29 224 women with singleton pregnancies between 2004 and 2008 of whom 3076 had a prolonged pregnancy (defined as ≥290 days or 41+3 weeks of gestation) and received IOL.

Methods

Kruskal–Wallis test, chi-square test and multivariable logistic regression.

Main outcome measures

Mode of delivery and risk of delivery and neonatal complications in obese verses non-obese women following IOL.

Results

Obese women had a significantly higher rate of IOL ending in caesarean section compared with women of normal weight following IOL (38.7% versus 23.8% primiparous; 9.9% versus 7.9% multiparous women, respectively); however, length of labour, incidence of postpartum haemorrhage and third-degree tear, rate of low cord blood pH, low Apgar scores and shoulder dystocia were similar in all body mass index categories. Complications included a higher incidence of fetal macrosomia and second-degree, but not third-degree, tear in primiparous women.

Conclusions

Higher maternal body mass index at booking is associated with an increased risk of prolonged pregnancy and increased rate of IOL. Despite this, more than 60% of obese primiparous and 90% of multiparous women with prolonged pregnancies who were induced achieved vaginal delivery and labour complications in the obese women with prolonged pregnancies were largely comparable to those of normal weight women with prolonged pregnancies. Our data suggest that IOL for prolonged pregnancy in obese women is a reasonable and safe management option.

BACKGROUND: As the interval between rupture of the fetal membranes at term and delivery increases, so may the risk of fetal and maternal infection. Recently the TERMPROM (Term Prelabor Rupture of the Membranes) Study Group reported the results of a randomized controlled trial comparing 4 management strategies: induction with oxytocin (IwO), induction with prostaglandin (IwP), and expectant management and induction with either oxytocin (EM-O) or prostaglandin (EM-P) if complications developed. The study found no statistically significant differences in neonatal infection and cesarean section rates between any of the 4 groups. OBJECTIVE: To conduct an economic evaluation comparing the cost of (a) IwO and EM-O, (b) IwP and EM-P and (c) IwO and IwP. DESIGN: An economic analysis, conducted alongside the clinical trial, using a third-party payer perspective. Analysis included all treatment costs incurred for both the mother and the baby. Information on health care utilization and outcomes was collected for all study participants. Three countries (Canada, the United Kingdom and Australia), corresponding to the largest study recruitment, were chosen for calculation of unit costs. For each country, the base, low and high estimates of unit cost for each service item were generated. Intention-to-treat analysis. Extensive statistical and sensitivity analyses were performed. RESULTS: The median cost of IwO per patient was significantly lower statistically than that of EM-O and IwP. This result held in all 3 countries compared -$114 and -$46 in Canada, -113 Pounds and -63 Pounds in the UK, and -A$30 and -A$49 in Australia) and after an extensive sensitivity analysis. There was no statistically significant difference in median cost per patient between IwP and EM-P. CONCLUSION: Although the clinical results of the TERMPROM study did not find IwO to be preferable to the other treatment alternatives, the economic evaluation found it to be less costly. However, these cost differences, even though statistically significant, are not likely to be important in many countries. When this is the case, the authors recommend that women be offered a choice between management strategies.

Background

Preterm prelabor rupture of membrane (PPROM) causes maternal and neonatal complications. Prophylactic antiobiotics were used in the management of PPROM. The objectives of this retrospective study were to compare clinical course and outcome of PPROM managed expectantly with prophylactic antibiotics and antenatal corticosteroids with those without prophylactic antibiotics and antenatal corticosteroids.

Results

A total of 170 cases of singleton pregnant women with gestational age between 28–34 weeks suffering from PROM during January 1998 to December 2009 were included; 119 cases received prophylactic antibiotics and antenatal corticosteroids while 51 cases did not received prophylactic antibiotics and antenatal corticosteroids. Median latency period in the study group was significantly longer than in the control group (89.8 vs. 24.3 hours, P < 0.001). The percentage of patients who did not deliver within 48 hours and within 7 days in the study group were also significantly higher than in control group (64.7 vs. 31.4%, P < 0.001 and 29.4 vs. 7.8%, P = 0.002, respectively). Maternal infectious morbidity was comparable between groups (17.6% vs. 13.7%, P = 0.52). Neonatal infectious morbidity was significantly lesser in study group than control group (21% vs. 35.3%, p = 0.04).

Conclusions

Latency period of PPROM after using prophylactic antibiotics and antenatal corticosteroids increased while neonatal infectious morbidity was low. But maternal infectious morbidity was not increased. This retrospective study confirms the benefit of prophylactic antibiotics and antenatal corticosteroids in management of PPROM.

Background

The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate.

Methods

The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents.

National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England.

Discussion

This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age.

Trial registration

The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660

Background

Gestational Diabetes (GDM) is one of the most common complications of pregnancies affecting around 7% of women. This clinical condition is associated with an increased risk of developing fetal macrosomia and is related to a higher incidence of caesarean section in comparison to the general population. Strong evidence indicating the best management between induction of labour at term and expectant monitoring are missing.

Methods/Design

Pregnant women with singleton pregnancy in vertex presentation previously diagnosed with gestational diabetes will be asked to participate in a multicenter open-label randomized controlled trial between 38+0 and 39+0 gestational weeks. Women will be recruited in the third trimester in the Outpatient clinic or in the Day Assessment Unit according to local protocols. Women who opt to take part will be randomized according to induction of labour or expectant management for spontaneous delivery. Patients allocated to the induction group will be admitted to the obstetric ward and offered induction of labour via use of prostaglandins, Foley catheter or oxytocin (depending on clinical conditions). Women assigned to the expectant arm will be sent to their domicile where they will be followed up until delivery, through maternal and fetal wellbeing monitoring twice weekly. The primary study outcome is the Caesarean section (C-section) rate, whilst secondary measurement4s are maternal and neonatal outcomes. A total sample of 1760 women (880 each arm) will be recruited to identify a relative difference between the two arms equal to 20% in favour of induction, with concerns to C-section rate. Data will be collected until mothers and newborns discharge from the hospital. Analysis of the outcome measures will be carried out by intention to treat.

Discussion

The present trial will provide evidence as to whether or not, in women affected by gestational diabetes, induction of labour between 38+0 and 39+0 weeks is an effective management to ameliorate maternal and neonatal outcomes. The primary objective is to determine whether caesarean section rate could be reduced among women undergoing induction of labour, in comparison to patients allocated to expectant monitoring. The secondary objective consists of the assessment and comparison of maternal and neonatal outcomes in the two study arms.

Trial Registration

The study protocol has been registered in the ClinicalTrials.gov Protocol Registration System, identification number NCT01058772.

To ensure an optimum result in pregnancy it is essential that the physician be alert in the antenatal period to recognize those women and their babies who are at risk during labour. Premature labour, with its attendant risk of respiratory distress syndrome in the newborn, continues to be an important factor in perinatal morbidity and mortality. Early recognition of predisposing factors and the judicious use of myometrial inhibiting agents have helped to reduce the incidence of fetal prematurity in these cases. A long interval between rupture of the membranes and delivery continues to be a danger to both mother and fetus. Delivery is recommended when gestation is beyond 36 weeks or when there are signs of incipient infection, and once labour has begun antibiotics should be used prophylactically. Failure of labour to progress should be recognized and managed aggressively in its early stages. Amniotomy and oxytocin infusion have reduced considerably the incidence of prolonged labour and its risks to both mother and fetus. The role of intrapartum monitoring of the fetal heart rate, measurement of the pH in the fetus's scalp blood and assessment of amniotic fluid is discussed, as is the monitoring of maternal well-being.

Objective. Small for gestational age (SGA) is associated with increased neonatal morbidity and mortality. At present, evidence on whether these pregnancies should be managed expectantly or by induction is lacking. To get insight in current policy we analysed data of the National Dutch Perinatal Registry (PRN). Methods. We used data of all nulliparae between 2000 and 2005 with a singleton in cephalic presentation beyond 36+0 weeks, with a birth weight below the 10th percentile. We analysed two groups of pregnancies: (I) with isolated SGA and (II) with both SGA and hypertensive disorders. Onset of labour was related to route of delivery and neonatal outcome. Results. Induction was associated with a higher risk of emergency caesarean section (CS), without improvement in neonatal outcome. For women with isolated SGA the relative risk of emergency CS after induction was 2.3 (95% Confidence Interval [CI] 2.1 to 2.5) and for women with both SGA and hypertensive disorders the relative risk was 2.7 (95% CI 2.3 to 3.1). Conclusion. Induction in pregnancies complicated by SGA at term is associated with a higher risk of instrumental deliveries without improvement of neonatal outcome. Prospective studies are needed to determine the best strategy in suspected IUGR at term.

Background

Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth). Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth.

Methods/Design

The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks), improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites.

Discussion

OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome.

Trial registration

ISRCTN14568373

Objectives: Steroids, used in pretermpremature rupture of membranes (pPROM), to reduce the risk of morbidity and mortality of the preterm neonate, impair the maternal polymorphonuclear leukocyte (PMN)-based immune system. In spite of combination with antibiotics, prenatal and postnatal bacterial infections of mother and child are frequent. This pilot study focuses on the influence of steroids in pPROM on maternal PMN functional capacity and subsequent infections.

Methods: After opting for expectant management, eight women with pPROM and no signs of infection were treated by steroids (betamethasone 5.7 mg, i.m. every 24 hours, for three days) and antibiotic therapy with either amoxicillin and clavulanic acid, piperacillin or ampicillin i.v. up to delivery. The conventional inflammation parameters of PMN blood count and C-reactive protein (CRP) were measured daily in parallel with PMN migratory capacity towards N-formyl-methionyl-leucyI-phenylalanine stimulation and under blank conditions, estimated by a whole blood membrane filter assay.

Results: In all patients PMN migration decreased during the application of steroids. Three patients showed a decrease in PMN migration below critical values and in spite of antibiotic prophylaxis acute pyelonephritis developed 2–6 days later. PMN count and CRP were not predictive of maternal infection.

Conclusion: Reduced PMN function, caused by steroid treatment in pPROM, is suggested to be a reason for serious bacterial infections in spite of antibiotic prophylaxis. PMN migration reflects individual PMN defensive capacity.