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Background

This abandoned randomised controlled trial assessed the effects of hospitalisation from 24 to 30 weeks gestation for women with a triplet pregnancy on the risk of preterm birth.

Methods

Women with a triplet pregnancy and no other condition necessitating hospital admission were approached for participation in the study, and randomised to either antenatal hospitalisation (hospitalised group), or to routine antenatal care (control group). The randomisation schedule used variable blocks with stratification by parity, and a researcher not involved with clinical care contacted by telephone to determine treatment allocation by opening the next in a series of consecutively numbered, opaque, sealed envelopes. Primary study outcomes were preterm birth (defined as birth less than 37 weeks gestation) and very preterm birth (defined as birth less than 34 weeks gestation), and the development of maternal pregnancy induced hypertension. The trial was ceased prior to achieving the calculated sample size due to difficulties in recruitment. The results of this randomised controlled trial were then combined with the results of another comparing bed rest in women with a triplet pregnancy.

Results

Seven women with a triplet pregnancy were recruited to the trial, with three randomised to the hospitalisation group, and four to the control group. There were no statistically significant differences between the two groups for the primary outcomes birth before 37 weeks (3/3 hospitalisation group versus 4/4 control group; relative risk (RR) not estimable), birth before 34 weeks (3/3 hospitalisation group versus 2/4 control group; RR 2.00 95% Confidence Intervals (CI) 0.75–5.33) and pregnancy induced hypertension (1/3 hospitalisation group versus 1/4 control group; RR 1.33 95%CI 0.13–13.74).

When the results of this trial were incorporated into a meta-analysis with the previous randomised controlled trial assessing hospitalisation and bed rest for women with a triplet pregnancy, (total sample size 26 women and 78 infants), there were no statistically significant differences identified between the two groups.

Conclusion

The results of this trial and meta-analysis suggest no benefit of routine hospitalisation and bed rest for women with a triplet pregnancy to reduce the risk of preterm birth. The adoption or continuation of a policy of routine hospitalisation and bed rest for women with an uncomplicated triplet pregnancy cannot be recommended.

Objective

To determine if exposure to more than one course of antenatal glucocorticoids is associated with changes in infant blood pressure and myocardial wall thickness in the first month after birth.

Design

Prospective cohort study.

Setting

Tertiary neonatal intensive care unit.

Participants

Mothers who were eligible for but declined to enter a randomised trial of repeated doses of antenatal glucocorticoids (ACTORDS)—that is, who had a singleton, twin, or triplet pregnancy at <32 weeks gestation, had received an initial course of glucocorticoids seven or more days previously, and were considered to be at continued risk of preterm birth.

Main outcome measures

Blood pressure daily for the first week then weekly until 4 weeks of age. End diastolic interventricular septal and left ventricular posterior wall (EDIVS and EDLVPW) thickness at 48–72 hours after birth.

Results

Thirty seven women were enrolled and delivered 50 infants. Thirty mothers (39 infants) were exposed to one course of glucocorticoids, and seven mothers (11 infants) to more than one course. Blood pressures were higher in the first week after birth in infants exposed to multiple courses of glucocorticoids, and in infants with a latency between last exposure and delivery of less than seven days. Systolic blood pressure on day 1 was >2SD above published normal ranges in 67% of babies exposed to multiple courses and 24% of babies exposed to a single course of glucocorticoids (p  =  0.04). There was no difference between groups in thickness of the EDIVS or EDLVPW. However, 44/50 (88%) babies had EDIVS and 49/50 (98%) babies had EDLVPW thickness >2 SD above the expected mean for birth weight and gestation. EDIVS but not EDLVPW thickness increased with increasing latency (mean 0.02 mm/day, p  =  0.03).

Conclusion

Future randomised trials should assess the long term effects of exposure to antenatal glucocorticoids, particularly multiple courses, on the cardiovascular status of the infant.

Background

For women who have a caesarean section in their preceding pregnancy, two care policies for birth are considered standard: planned vaginal birth and planned elective repeat caesarean. Currently available information about the benefits and harms of both forms of care are derived from retrospective and prospective cohort studies. There have been no randomised trials, and recognising the deficiencies in the literature, there have been calls for methodologically rigorous studies to assess maternal and infant health outcomes associated with both care policies.

The aims of our study are to assess in women with a previous caesarean birth, who are eligible in the subsequent pregnancy for a vaginal birth, whether a policy of planned vaginal birth after caesarean compared with a policy of planned repeat caesarean affects the risk of serious complications for the woman and her infant.

Methods/Design

Design: Multicentred patient preference study and a randomised clinical trial.

Inclusion Criteria: Women with a single prior caesarean presenting in their next pregnancy with a single, live fetus in cephalic presentation, who have reached 37 weeks gestation, and who do not have a contraindication to a planned VBAC.

Trial Entry & Randomisation: Eligible women will be given an information sheet during pregnancy, and will be recruited to the study from 37 weeks gestation after an obstetrician has confirmed eligibility for a planned vaginal birth. Written informed consent will be obtained. Women who consent to the patient preference study will be allocated their preference for either planned VBAC or planned, elective repeat caesarean. Women who consent to the randomised trial will be randomly allocated to either the planned vaginal birth after caesarean or planned elective repeat caesarean group.

Treatment Groups: Women in the planned vaginal birth group will await spontaneous onset of labour whilst appropriate. Women in the elective repeat caesarean group will have this scheduled for between 38 and 40 weeks.

Primary Study Outcome: Serious adverse infant outcome (death or serious morbidity).

Sample Size: 2314 women in the patient preference study to show a difference in adverse neonatal outcome from 1.6% to 3.6% (p = 0.05, 80% power).

Clinical Trial Registration

ISCTRN5397431

OBJECTIVE: To test the efficacy in terms of birth weight and infant survival of a diet supplement programme in pregnant African women through a primary healthcare system. DESIGN: 5 year controlled trial of all pregnant women in 28 villages randomised to daily supplementation with high energy groundnut biscuits (4.3 MJ/day) for about 20 weeks before delivery (intervention) or after delivery (control). SETTING: Rural Gambia. SUBJECTS: Chronically undernourished women (twin bearers excluded), yielding 2047 singleton live births and 35 stillbirths. MAIN OUTCOME MEASURES: Birth weight; prevalence of low birth weight (< 2500 g); head circumference; birth length; gestational age; prevalence of stillbirths; neonatal and postneonatal mortality. RESULTS: Supplementation increased weight gain in pregnancy and significantly increased birth weight, particularly during the nutritionally debilitating hungry season (June to October). Weight gain increased by 201 g (P < 0.001) in the hungry season, by 94 g (P < 0.01) in the harvest season (November to May), and by 136 g (P < 0.001) over the whole year. The odds ratio for low birthweight babies in supplemented women was 0.61 (95% confidence interval 0.47 to 0.79, P < 0.001). Head circumference was significantly increased (P < 0.01), but by only 3.1 mm. Birth length and duration of gestation were not affected. Supplementation significantly reduced perinatal mortality: the odds ratio was 0.47 (0.23 to 0.99, P < 0.05) for stillbirths and 0.54 (0.35 to 0.85, P < 0.01) for all deaths in first week of life. Mortality after 7 days was unaffected. CONCLUSION: Prenatal dietary supplementation reduced retardation in intrauterine growth when effectively targeted at genuinely at-risk mothers. This was associated with a substantial reduction in the prevalence of stillbirths and in early neonatal mortality. The intervention can be successfully delivered through a primary healthcare system.

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

To determine whether twins born second are at increased risk of perinatal death because of complications during labour and delivery.

Design

Retrospective cohort study.

Setting

Scotland, 1992 and 1997.

Participants

All twin births at or after 24 weeks' gestation, excluding twin pairs in which either twin died before labour or delivery or died during or after labour and delivery because of congenital abnormality, non-immune hydrops, or twin to twin transfusion syndrome.

Main outcome measure

Delivery related perinatal deaths (deaths during labour or the neonatal period).

Results

Overall, delivery related perinatal deaths were recorded for 23 first twins only and 23 second twins only of 1438 twin pairs born before 36 weeks (preterm) by means other than planned caesarean section (P>0.99). No deaths of first twins and nine deaths of second twins (P=0.004) were recorded among the 2436 twin pairs born at or after 36 weeks (term). Discordance between first and second twins differed significantly in preterm and term births (P=0.007). Seven of nine deaths of second twins at term were due to anoxia during the birth (2.9 (95% confidence interval 1.2 to 5.9) per 1000); five of these deaths were associated with mechanical problems with the second delivery following vaginal delivery of the first twin. No deaths were recorded among 454 second twins delivered at term by planned caesarean section.

Conclusions

Second twins born at term are at higher risk than first twins of death due to complications of delivery. Previous studies may not have shown an increased risk because of inadequate categorisation of deaths, lack of statistical power, inappropriate analyses, and pooling of data about preterm births and term births.

What is already known on this topicIt is difficult to assess the wellbeing of second twins during labourDeliveries of second twins are at increased risk of mechanical problems, such as cord prolapse and malpresentation, after vaginal delivery of first twinsIncreased risks of perinatal death in second twins have not been shown, but the methods of these studies were flawedWhat this study addsSecond twins delivered at term are at increased risk of delivery related perinatal deathsIntrapartum anoxia caused 75% of these deaths in second twins, and most of these resulted from mechanical problems after vaginal delivery of first twinsPlanned caesarean section of twins at term may prevent perinatal deaths

Background

Prevention of preterm birth remains one of the most important challenges in maternity care. We propose a randomised trial with: a simple Candida testing protocol that can be easily incorporated into usual antenatal care; a simple, well accepted, treatment intervention; and assessment of outcomes from validated, routinely-collected, computerised databases.

Methods/Design

Using a prospective, randomised, open-label, blinded-endpoint (PROBE) study design, we aim to evaluate whether treating women with asymptomatic vaginal candidiasis early in pregnancy is effective in preventing spontaneous preterm birth. Pregnant women presenting for antenatal care <20 weeks gestation with singleton pregnancies are eligible for inclusion. The intervention is a 6-day course of clotrimazole vaginal pessaries (100 mg) and the primary outcome is spontaneous preterm birth <37 weeks gestation.

The study protocol draws on the usual antenatal care schedule, has been pilot-tested and the intervention involves only a minor modification of current practice. Women who agree to participate will self-collect a vaginal swab and those who are culture positive for Candida will be randomised (central, telephone) to open-label treatment or usual care (screening result is not revealed, no treatment, routine antenatal care). Outcomes will be obtained from population databases.

A sample size of 3,208 women with Candida colonisation (1,604 per arm) is required to detect a 40% reduction in the spontaneous preterm birth rate among women with asymptomatic candidiasis from 5.0% in the control group to 3.0% in women treated with clotrimazole (significance 0.05, power 0.8). Analyses will be by intention to treat.

Discussion

For our hypothesis, a placebo-controlled trial had major disadvantages: a placebo arm would not represent current clinical practice; knowledge of vaginal colonisation with Candida may change participants' behaviour; and a placebo with an alcohol preservative may have an independent affect on vaginal flora. These disadvantages can be overcome by the PROBE study design.

This trial will provide definitive evidence on whether screening for and treating asymptomatic candidiasis in pregnancy significantly reduces the rate of spontaneous preterm birth. If it can be demonstrated that treating asymptomatic candidiasis reduces preterm births this will change current practice and would directly impact the management of every pregnant woman.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12610000607077

Objective To determine the effect of birth order on the risk of perinatal death in twin pregnancies.

Design Retrospective cohort study.

Setting England, Northern Ireland, and Wales, 1994-2003.

Participants 1377 twin pregnancies with one intrapartum stillbirth or neonatal death from causes other than congenital abnormality and one surviving infant.

Main outcome measures The risk of perinatal death in the first and second twin estimated with conditional logistic regression.

Results There was no association between birth order and the risk of death overall (odds ratio 1.0, 95% confidence interval 0.9 to 1.1). However, there was a highly significant interaction with gestational age (P<0.001). There was no association between birth order and the risk of death among infants born before 36 weeks' gestation but there was an increased risk of death among second twins born at term (2.3, 1.7 to 3.2, P<0.001), which was stronger for deaths caused by intrapartum anoxia or trauma (3.4, 2.2 to 5.3). Among term births, there was a trend (P=0.1) towards a greater risk of the second twin dying from anoxia among those delivered vaginally (4.1, 1.8 to 9.5) compared with those delivered by caesarean section (1.8, 0.9 to 3.6).

Conclusions In this cohort, compared with first twins, second twins born at term were at increased risk of perinatal death related to delivery. Vaginally delivered second twins had a fourfold risk of death caused by intrapartum anoxia.

Background

15% of multiple pregnancies ends in a preterm delivery, which can lead to mortality and severe long term neonatal morbidity. At present, no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists. Prophylactic administration of 17-alpha hydroxyprogesterone caproate (17OHPC) has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery. At present, there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies.

Methods/Design

We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies. Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled, double blinded randomised study comparing weekly 250 mg 17OHPC intramuscular injections from 16–20 weeks up to 36 weeks of gestation versus placebo. At study entry, cervical length will be measured. The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 15% to 8%. Analysis will be by intention to treat. We will also analyse whether the treatment effect is dependent on cervical length.

Discussion

This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies.

Trial registration

Current Controlled Trials ISRCTN40512715

Objective To determine the effect of artificial teats (bottle and dummy) and cups on breast feeding in preterm infants.

Design Randomised controlled trial.

Setting Two large tertiary hospitals, 54 peripheral hospitals.

Participants 319 preterm infants (born at 23-33 weeks' gestation) randomly assigned to one of four groups: cup/no dummy (n = 89), cup/dummy (n = 72), bottle/no dummy (n = 73), bottle/dummy (n = 85). Women with singleton or twin infants < 34 weeks' gestation who wanted to breastfeed were eligible to participate.

Interventions Cup or bottle feeding occurred when the mother was unable to be present to breast feed. Infants randomised to the dummy groups received a dummy on entry into the trial.

Main outcome measures Full breast feeding (compared with partial and none) and any breast feeding (compared with none) on discharge home. Secondary outcomes: prevalence of breast feeding at three and six months after discharge and length of hospital stay.

Results 303 infants (and 278 mothers) were included in the intention to treat analysis. There were no significant differences for any of the study outcomes according to use of a dummy. Infants randomised to cup feeds were more likely to be fully breast fed on discharge home (odds ratio 1.73, 95% confidence interval 1.04 to 2.88, P = 0.03), but had a longer length of stay (hazard ratio 0.71, 0.55 to 0.92, P = 0.01).

Conclusions Dummies do not affect breast feeding in preterm infants. Cup feeding significantly increases the likelihood that the baby will be fully breast fed at discharge home, but has no effect on any breast feeding and increases the length of hospital stay.

Background

Obesity is a significant global health problem, with the proportion of women entering pregnancy with a body mass index greater than or equal to 25 kg/m2 approaching 50%. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant, however there is more limited information available regarding effective interventions to improve health outcomes.

The aims of this randomised controlled trial are to assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit gestational weight gain is effective in improving maternal, fetal and infant health outcomes.

Methods/Design

Design: Multicentred randomised, controlled trial.

Inclusion Criteria: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit.

Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0 and 20+0 weeks gestation using a central telephone randomisation service, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth.

Treatment Schedules: Women randomised to the Dietary and Lifestyle Advice Group will receive a series of inputs from research assistants and research dietician to limit gestational weight gain, and will include a combination of dietary, exercise and behavioural strategies.

Women randomised to the Standard Care Group will continue to receive their pregnancy care according to local hospital guidelines, which does not currently include routine provision of dietary, lifestyle and behavioural advice.

Outcome assessors will be blinded to the allocated treatment group.

Primary Study Outcome: infant large for gestational age (defined as infant birth weight ≥ 90th centile for gestational age).

Sample Size: 2,180 women to detect a 30% reduction in large for gestational age infants from 14.40% (p = 0.05, 80% power, two-tailed).

Discussion

This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines.

Trial Registration

Australian and New Zealand Clinical Trials Registry ACTRN12607000161426

Background

Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix) or to determine adverse effects for rare outcomes such as intrauterine death.

Methods/design

We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The primary outcome will be adverse perinatal outcome (a composite measure of perinatal mortality and significant neonatal morbidity). Missing data will be imputed within each original study, before data of the individual studies are pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone treatment in women with twin pregnancies will be estimated by means of a random effects log-binomial model. Analyses will be adjusted for variables used in stratified randomization as appropriate. Pre-specified subgroup analysis will be performed to explore the effect of progestogen treatment in high-risk groups.

Discussion

Combining individual patient data from different randomized trials has potential to provide valuable, clinically useful information regarding the benefits and potential harms of progestogens in women with twin pregnancy overall and in relevant subgroups.

Background

The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) showed that treatment of pregnant women with mild gestational diabetes mellitus is beneficial for both women and their infants. It is still uncertain whether there are benefits of similar treatment for women with borderline gestational diabetes.

This trial aims to assess whether dietary and lifestyle advice and treatment given to pregnant women who screen for borderline gestational diabetes reduces neonatal complications and maternal morbidities.

Methods/design

Design: Multicentre, randomised controlled trial.

Inclusion criteria: Women between 240 and 346 weeks gestation with a singleton pregnancy, a positive oral glucose challenge test (venous plasma glucose ≥7.8 mmol/L) and a normal oral 75 gram glucose tolerance test (fasting venous plasma glucose <5.5 mmol/L and a 2 hour glucose <7.8 mmol/L) with written, informed consent.

Trial entry and randomisation: Women with an abnormal oral glucose tolerance test (fasting venous plasma glucose ≥5.5 mmol/L or 2 hour glucose ≥7.8 mmol/L) will not be eligible and will be offered treatment for gestational diabetes, consistent with recommendations based on results of the ACHOIS trial. Eligible women will be randomised into either the ‘Routine Care Group’ or the ‘Intervention Group’.

Study groups: Women in the ‘Routine Care Group’ will receive routine obstetric care reflecting current clinical practice in Australian hospitals. Women in the ‘Intervention Group’ will receive obstetric care, which will include dietary and lifestyle advice, monitoring of blood glucose and further medical treatment for hyperglycaemia as appropriate.

Primary study outcome: Incidence of large for gestational age infants.

Sample size: A sample size of 682 women will be sufficient to show a 50% reduction in the risk of large for gestational age infants (alpha 0.05 two-tailed, 80% power, 4% loss to follow up) from 14% to 7% with dietary and lifestyle advice and treatment.

Discussion

A conclusive trial outcome will provide reliable evidence of relevance for the care of women with borderline glucose intolerance in pregnancy and their infants.

Trial registration

Australian New Zealand Clinical Trials Registry - ACTRN12607000174482

Objective To compare the perinatal outcome of singleton and twin pregnancies between natural and assisted conceptions.

Design Systematic review of controlled studies published 1985-2002.

Studies reviewed 25 studies were included of which 17 had matched and 8 had non-matched controls.

Main outcome measures Very preterm birth, preterm birth, very low birth weight, low birth weight, small for gestational age, caesarean section, admission to neonatal intensive care unit, and perinatal mortality.

Results For singletons, studies with matched controls indicated a relative risk of 3.27 (95% confidence interval 2.03 to 5.28) for very preterm (< 32 weeks) and 2.04 (1.80 to 2.32) for preterm (< 37 weeks) birth in pregnancies after assisted conception. Relative risks were 3.00 (2.07 to 4.36) for very low birth weight (< 1500 g), 1.70 (1.50 to 1.92) for low birth weight (< 2500 g), 1.40 (1.15 to 1.71) for small for gestational age, 1.54 (1.44 to 1.66) for caesarean section, 1.27 (1.16 to 1.40) for admission to a neonatal intensive care unit, and 1.68 (1.11 to 2.55) for perinatal mortality. Results of the non-matched studies were similar. In matched studies of twin gestations, relative risks were 0.95 (0.78 to 1.15) for very preterm birth, 1.07 (1.02 to 1.13) for preterm birth, 0.89 (0.74 to 1.07) for very low birth weight, 1.03 (0.99 to 1.08) for low birth weight, 1.27 (0.97 to 1.65) for small for gestational age, 1.21 (1.11 to 1.32) for caesarean section, 1.05 (1.01 to 1.09) for admission to a neonatal intensive care unit, and 0.58 (0.44 to 0.77) for perinatal mortality. The non-matched studies mostly showed similar trends.

Conclusions Singleton pregnancies from assisted reproduction have a significantly worse perinatal outcome than non-assisted singleton pregnancies, but this is less so for twin pregnancies. In twin pregnancies, perinatal mortality is about 40% lower after assisted compared with natural conception.

Background

Monochorionic (MC) twins are at increased risk for perinatal mortality and serious morbidity due to the presence of placental vascular anastomoses. Cerebral injury can be secondary to haemodynamic and hematological disorders during pregnancy (especially twin-to-twin transfusion syndrome (TTTS) or intrauterine co-twin death) or from postnatal injury associated with prematurity and low birth weight, common complications in twin pregnancies. We investigated neurodevelopmental outcome in MC and dichorionic (DC) twins at the age of two years.

Methods

This was a prospective cohort study. Cerebral palsy (CP) was studied in 182 MC infants and 189 DC infants matched for weight and age at delivery, gender, ethnicity of the mother and study center. After losses to follow-up, 282 of the 366 infants without CP were available to be tested with the Griffiths Mental Developmental Scales at 22 months corrected age, all born between January 2005 and January 2006 in nine perinatal centers in The Netherlands. Due to phenotypic (un)alikeness in mono-or dizygosity, the principal investigator was not blinded to chorionic status; perinatal outcome, with exception of co-twin death, was not known to the examiner.

Findings

Four out of 182 MC infants had CP (2.2%) - two of the four CP-cases were due to complications specific to MC twin pregnancies (TTTS and co-twin death) and the other two cases of CP were the result of cystic PVL after preterm birth - compared to one sibling of a DC twin (0.5%; OR 4.2, 95% CI 0.5–38.2) of unknown origin. Follow-up rate of neurodevelopmental outcome by Griffith's test was 76%. The majority of 2-year-old twins had normal developmental status. There were no significant differences between MC and DC twins. One MC infant (0.7%) had a developmental delay compared to 6 DC infants (4.2%; OR 0.2, 95% 0.0–1.4). Birth weight discordancy did not influence long-term outcome, though the smaller twin had slightly lower developmental scores than its larger co-twin.

Conclusions

There were no significant differences in occurrence of cerebral palsy as well as neurodevelopmental outcome between MC and DC twins. Outcome of MC twins seems favourable in the absence of TTTS or co-twin death.

Background

There is strong evidence supporting the use of antenatal corticosteroids in women at risk of preterm birth to promote fetal lung maturation and reduce neonatal mortality and morbidity. This audit aimed to assess the use of antenatal corticosteroids prior to preterm birth in the nine hospitals in four South East Asian countries participating in the South East Asia Optimising Reproductive Health in Developing Countries (SEA-ORCHID) Project.

Method

We reviewed the medical records of 9550 women (9665 infants including 111 twins and two triplets) admitted to the labour wards of nine hospitals in four South East Asian countries during 2005. For women who gave birth before 34 weeks gestation we collected information on women's demographic and pregnancy background, the type, dose and use of corticosteroids, and key birth and infant outcomes.

Results

Administration of antenatal corticosteroids to women who gave birth before 34 weeks gestation varied widely between countries (9% to 73%) and also between hospitals within countries (0% to 86%). Antenatal corticosteroids were most commonly given when women were between 28 and 34 weeks gestation (80%). Overall 6% of women received repeat doses of corticosteroids. Dexamethasone was the only type of antenatal corticosteroid used.

Women receiving antenatal corticosteroids compared with those not given antenatal corticosteroids were less likely to have had a previous pregnancy and to be booked for birth at the hospital and almost three times as likely to have a current multiple pregnancy. Exposed women were less likely to be induced and almost twice as likely to have a caesarean section, a primary postpartum haemorrhage and postpartum pyrexia.

Infants exposed to antenatal corticosteroids compared with infants not exposed were less likely to die. Live born exposed infants were less likely to have Apgar scores of < 7 at five minutes and less likely to have any lung disease.

Conclusion

In this survey the use of antenatal corticosteroids prior to preterm birth varied between countries and hospitals. Evaluation of the enablers and barriers to the uptake of this effective antenatal intervention at individual hospitals is needed.

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

Objective

To investigate whether initiating external cephalic version (ECV) earlier in pregnancy might increase the rate of successful ECV procedures, and be more effective in decreasing the rate of non-cephalic presentation at birth and of caesarean section.

Design

An unblinded multicentred randomised controlled trial.

Setting

A total of 1543 women were randomised from 68 centres in 21 countries.

Population

Women with a singleton breech fetus at a gestational age of 330/7 weeks (231 days) to 356/7 weeks (251 days) of gestation were included.

Methods

Participants were randomly assigned to having a first ECV procedure between the gestational ages of 340/7 (238 days) and 356/7 weeks of gestation (early ECV group) or at or after 370/7 (259 days) weeks of gestation (delayed ECV group).

Main outcome measures

The primary outcome was the rate of caesarean section; the secondary outcome was the rate of preterm birth.

Results

Fewer fetuses were in a non-cephalic presentation at birth in the early ECV group (314/765 [41.1%] versus 377/768 [49.1%] in the delayed ECV group; relative risk [RR] 0.84, 95% CI 0.75, 0.94, P = 0.002). There were no differences in rates of caesarean section (398/765 [52.0%] versus 430/768 [56.0%]; RR 0.93, 95% CI 0.85, 1.02, P = 0.12) or in risk of preterm birth (50/765 [6.5%] versus 34/768 [4.4%]; RR 1.48, 95% CI 0.97, 2.26, P = 0.07) between groups.

Conclusion

External cephalic version at 34–35 weeks versus 37 or more weeks of gestation increases the likelihood of cephalic presentation at birth but does not reduce the rate of caesarean section and may increase the rate of preterm birth.

Objective:

To evaluate the risks of pregnancy complications and adverse outcomes associated with increasing maternal age and higher plurality.

Design:

Population-based, historical cohort study.

Setting:

US birth certificates and infant death certificates.

Patients:

Live births of ≥20 weeks gestation between 1995-2000: 22,991,306 singleton, 316,696 twin, and 12,193 triplet pregnancies.

Intervention:

None

Main Outcome Measures:

Pregnancy-associated hypertension, incompetent cervix, tocolysis, premature rupture of membranes, excessive bleeding at delivery, delivery <29 weeks, and infant death.

Results:

Compared to singletons, the risks for all adverse outcomes among multiple pregnancies were significantly elevated and were highest for tocolysis, delivery <29 weeks, and infant mortality. Within pluralities, increasing maternal age was associated with significantly higher risks of pregnancy-associated hypertension, excessive bleeding, and incompetent cervix, but for twin and triplet pregnancies, significantly lower risks for tocolysis (ages ≥40, singleton AOR 0.97, twin AOR 0.67, triplet AOR 0.72), delivery <29 weeks (ages ≥40, singleton AOR 1.55, twin AOR 0.72, triplet AOR 0.52), and infant mortality (ages ≥40, singleton AOR 1.34, twin AOR 0.71, triplet AOR 0.42).

Conclusions:

Older maternal age and higher plurality are each associated with increasing risks for many pregnancy complications, but with significantly lower risks of tocolysis, early preterm birth, and infant mortality.

In a multicentre study on perinatal HIV-I infection including 1493 children born from 1471 pregnancies to 1415 infected mothers, 22 twin pairs and 56 sibships (115 children) were recorded. The frequency of twin pregnancies was 1.5 (22/1471) and 3.9% (56/1415) seropositive women had more than one at risk pregnancy. In 18 twin pairs with a known infection status nine of the 36 children (25%) were infected. Discordance in infection status was present in only one (5.5%) dizygous pair. A high relative risk of infection (23.1) in a twin was observed when the other was infected. Infection was unrelated to gestational age, mode of delivery, or birth weight. Infection status was defined in 41 sibships (84 children including one first born twin pair and one third born child). When the first born was infected, 11/26 (42.3%) second born children were also infected, whereas this happened in only 2/16 (12.5%) second or third born children when the first born was uninfected. Two out of nine first born (22.2%) and 5/21 (23.8%) second born children prospectively followed up from birth acquired the infection. Results of this study demonstrate that neither twin nor second pregnancies are at increased risk of mother to child HIV-I transmission. Overall data suggest that non-casual factors in mother and/or child influence perinatal infection.

Purpose

To determine the relative effect of birth weight and gestational age on retinopathy of prematurity (ROP) using preterm twin pairs discordant for birth weight.

Methods

This study was a retrospective cohort study including 55 consecutive twin pairs of 110 preterm infants (gestational age ≤33 weeks). The outcomes of ROP including occurrence (any stage), severe ROP (stage 3 or more), and clinically significant ROP requiring laser treatment were compared between twins with the lower birth weight from each pair and their co-twins with the higher birth weight. Using twin pairs having different birth weight and identical gestational age, the independent effects of prematurity and intrauterine growth on ROP could be evaluated. Other perinatal morbidities related to prematurity were also compared between twin pairs.

Results

No significant differences in ROP between larger and smaller infants were observed in the twin-paired analysis while analysis on individual infants showed strong association between small birth weight and ROP outcomes. However, in both the larger and smaller infant groups, gestational age of <28 weeks was significantly associated with ROP outcomes. No differences were found between twin pairs regarding other perinatal morbidities including bronchopulmonary dysplasia, respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, and periventricular leukomalacia.

Conclusions

Birth weight is not associated with ROP, while gestational age is in the twin-paired study, suggesting that gestational age is a better predictor of ROP than birth weight. This indicates that maturity is more important in the pathogenesis of ROP than intrauterine growth.

We compared neonatal outcomes in twin pregnancies following moderately preterm birth (MPTB), late preterm birth (LPTB) and term birth. A secondary analysis of a multi-center, randomized controlled trial of multiple gestations was conducted. MPTB was defined as delivery between 320/7 and 336/7 weeks and LPTB between 340/7 and 366/7 weeks. Primary outcome was a neonatal outcome composite consisting of one or more of the following: neonatal death, respiratory distress syndrome, early onset culture-proven sepsis, stage 2 or 3 necrotizing enterocolitis, bronchopulmonray dysplasia, grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, pneumonia, or severe retinopathy of prematurity. Among 552 twin pregnancies, the MPTB rate was 14.5%, LPTB 49.8% and term birth rate 35.7%. The rate of the primary outcome was different between groups: 30.0% for MPTB, 12.8% for LPTB, 0.5% for term (p< 0.001). Compared with term neonates, the primary neonatal outcome composite was increased following MPTB (relative risk [RR] 58.5; 95% confidence interval [CI] 11.3 to 1693.0) and LPTB (RR 24.9; 95% CI 4.8 to 732.2). Twin pregnancies born moderately and late preterm encounter higher rates of neonatal morbidities compared to twins born at term.

Background

Multiple pregnancies are at high risk for preterm birth, and therefore an important cause of infant mortality and morbidity. A pessary is a simple and potentially effective measure for the prevention of preterm birth. Small studies have indicated its effectiveness, but large studies with sufficient power on the subject are lacking. Despite this lack of evidence, the treatment is at present applied by some gynaecologists in The Netherlands.

Methods/Design

We aim to investigate the hypothesis that prophylactic use of a cervical pessary will be effective in the prevention of preterm delivery and the neonatal mortality and morbidity resulting from preterm delivery in multiple pregnancy. We will evaluate the costs and effects of this intervention. At study entry, cervical length will be measured. Eligible women will be randomly allocated to receive either a cervical pessary or no intervention. The cervical pessary will be placed in situ at 16 to 20 weeks, and will stay in situ up to 36 weeks gestation or until delivery, whatever comes first.

The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 7.2% without to 3.9% with a cervical pessary, using a two-sided test with an alpha of 0.05 and a power of 0.80.

Discussion

This trial will provide evidence on whether a cervical pessary will decrease the incidence of early preterm birth and its concomitant bad neonatal outcome in multiple pregnancies.

Trial registration

Current Controlled Trials: NTR 1858

Objective To determine if a low glycaemic index diet in pregnancy could reduce the incidence of macrosomia in an at risk group.

Design Randomised controlled trial.

Setting Maternity hospital in Dublin, Ireland.

Participants 800 women without diabetes, all in their second pregnancy between January 2007 to January 2011, having previously delivered an infant weighing greater than 4 kg.

Intervention Women were randomised to receive no dietary intervention or start on a low glycaemic index diet from early pregnancy.

Main outcomes The primary outcome measure was difference in birth weight. The secondary outcome measure was difference in gestational weight gain.

Results No significant difference was seen between the two groups in absolute birth weight, birthweight centile, or ponderal index. Significantly less gestational weight gain occurred in women in the intervention arm (12.2 v 13.7 kg; mean difference −1.3, 95% confidence interval −2.4 to −0.2; P=0.01). The rate of glucose intolerance was also lower in the intervention arm: 21% (67/320) compared with 28% (100/352) of controls had a fasting glucose of 5.1 mmol/L or greater or a 1 hour glucose challenge test result of greater than 7.8 mmol/L (P=0.02).

Conclusion A low glycaemic index diet in pregnancy did not reduce the incidence of large for gestational age infants in a group at risk of fetal macrosomia. It did, however, have a significant positive effect on gestational weight gain and maternal glucose intolerance.

Trial registration Current Controlled Trials ISRCTN54392969.

Objective

To determine whether twin gestations with an anomalous fetus are at increased risk of preterm delivery (PTD) or intrauterine growth restriction (IUGR) compared to twins with two normal fetuses.

Study Design

Retrospective cohort of twins undergoing ultrasound 15–22 weeks gestation. Groups were defined by the presence of one twin with a major anomaly (discordant) or by twins with no major anomalies (normal). The primary outcomes were PTD (<37 weeks) and IUGR (<10th percentile).

Results

Of 1,977 twin pregnancies, 66 had a twin with a major anomaly. Preterm delivery occurred in 42 (63.6%) discordant twins, compared to 1271 (66.5%) normal twins (risk ratio (RR) 1.0, 95% confidence interval (CI) 0.8–1.2). IUGR was diagnosed in 15 (22.7%) normal co-twins, compared to 406 (21.3%) presenting twins in normal twins (RR 1.1, 95% CI 0.7–1.7).

Conclusion

Twins discordant for major anomalies are not at increased risk of PTD or IUGR compared to twins with no major anomalies.