Advanced maternal age

The average age of women at childbirth in industrialised nations has been increasing steadily for approximately 30 years. Women aged 35 years or over have an increased risk of gestational hypertensive disease, gestational diabetes, placenta praevia, placental abruption, perinatal death, preterm labour, fetal macrosomia and fetal growth restriction. Unsurprisingly, rates of obstetric intervention are higher among older women. Of particular concern is the increased risk of antepartum stillbirth at term in women of advanced maternal age. In all maternal age groups, the risk of stillbirth is higher among nulliparous women than among multiparous women. Women of advanced maternal age (more than 40 years) should be given low dose aspirin (in the presence of an additional risk factor for pre-eclampsia) and offered serial ultrasounds for fetal growth and wellbeing; given the increased risk of antepartum stillbirth, induction of labour from 39 weeks’ gestation should be discussed with the woman

Discrepancies between registration and publication of randomised controlled trials: an observational study

Abstract OBJECTIVES: To determine the consistency between information contained in the registration and publication of randomised controlled trials (RCTs). DESIGN: An observational study of RCTs published between May 2011 and May 2012 in the British Medical Journal (BMJ) and the Journal of the American Medical Association (JAMA) comparing registry data with publication data. PARTICIPANTS AND SETTINGS: Data extracted from published RCTs in BMJ and JAMA. MAIN OUTCOME MEASURES: Timing of trial registration in relation to completion of trial data collection and publication. Registered versus published primary and secondary outcomes, sample size. RESULTS: We identified 40 RCTs in BMJ and 36 in JAMA. All 36 JAMA trials and 39 (98%) BMJ trials were registered. All registered trials were registered prior to publication. Thirty-two (82%) BMJ trials recorded the date of data completion; of these, in two trials the date of trial registration postdated the registered date of data completion. There were discrepancies between primary outcomes declared in the trial registry information and in the published paper in 18 (47%) BMJ papers and seven (19%) JAMA papers. The original sample size stated in the trial registration was achieved in 24 (60%) BMJ papers and 21 (58%) JAMA papers. CONCLUSIONS: Compulsory registration of RCTs is meaningless if the content of registry information is not complete or if discrepancies between registration and publication are not reported. This study demonstrates that discrepancies in primary and secondary outcomes and sample size between trial registration and publication remain commonplace, giving further strength to the World Health Organisation's argument for mandatory completion of a minimum number of compulsory fields

Interventionist versus expectant care for severe pre-eclampsia between 24 and 34 weeks' gestation.

Background: Severe pre-eclampsia can cause significant mortality and morbidity for both mother and child, particularly when it occurs remote from term, between 24 and 34 weeks' gestation. The only known cure for this disease is delivery. Some obstetricians advocate early delivery to ensure that the development of serious maternal complications, such as eclampsia (fits) and kidney failure are prevented. Others prefer a more expectant approach delaying delivery in an attempt to reduce the mortality and morbidity for the child associated with being born too early. Objectives: The objective of the review was to compare the effects of a policy of interventionist care and early delivery with a policy of expectant care and delayed delivery for women with early onset severe pre-eclampsia. Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 February 2013). Selection criteria: Randomised trials comparing the two intervention strategies for women with early onset severe pre-eclampsia. Data collection and analysis: Two review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. Data were checked for accuracy. Main results: Four trials, with a total of 425 women are included in this review. Trials were at low risk of bias for methods of randomisation and allocation concealment; high risk for blinding; unclear risk for incomplete outcome data and other bias; and low risk for selective reporting. There are insufficient data for reliable conclusions about the comparative effects on most outcomes for the mother. For the baby, there is insufficient evidence for reliable conclusions about the effects on stillbirth or death after delivery (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.69 to 1.71; four studies; 425 women). Babies whose mothers had been allocated to the interventionist group had more intraventricular haemorrhage (RR 1.82, 95% CI 1.06 to 3.14; one study; 262 women), more hyaline membrane disease (RR 2.30, 95% CI 1.39 to 3.81; two studies; 133 women), require more ventilation (RR 1.50, 95% CI 1.11 to 2.02; two studies; 300 women) and were more likely to have a lower gestation at birth in days (average mean difference (MD) -9.91, 95% CI -16.37 to -3.45; four studies; 425 women), more likely to be admitted to neonatal intensive care (RR 1.35, 95% CI 1.16 to 1.58) and have a longer stay in the neonatal intensive care unit (average MD 11.14 days, 95% CI 1.57 to 20.72 days; two studies; 125 women) than those allocated an expectant policy. Nevertheless, babies allocated to the interventionist policy were less likely to be small-for-gestational age (RR 0.30, 95% CI 0.14 to 0.65; two studies; 125 women). Women who had been allocated to the interventionist group were more likely to have a caesarean section (RR 1.09, 95% CI 1.01 to 1.18; four studies; 425 women) than those allocated an expectant policy. There were no statistically significant differences between the two strategies for any other outcomes. Authors' conclusions: This review suggests that an expectant approach to the management of women with severe early onset pre-eclampsia may be associated with decreased morbidity for the baby. However, this evidence is based on data from only four trials. Further large trials are needed to confirm or refute these findings and establish if this approach is safe for the mother

Induction of labour at or near term for suspected fetal macrosomia

Background: Women with a suspected large-for-dates fetus or a fetus with suspected macrosomia (birthweight greater than 4000 g) are at risk of operative birth or caesarean section. The baby is also at increased risk of shoulder dystocia and trauma, in particular fractures and brachial plexus injury. Induction of labour may reduce these risks by decreasing the birthweight, but may also lead to longer labours and an increased risk of caesarean section. Objectives: To assess the effects of a policy of labour induction at or shortly before term (37 to 40 weeks) for suspected fetal macrosomia on theway of giving birth and maternal or perinatal morbidity. Search methods: We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 January 2016), contacted trial authors and searched reference lists of retrieved studies. Selection criteria: Randomised trials of induction of labour for suspected fetal macrosomia. Data collection and analysis: Review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We contacted study authors for additional information. For key outcomes the quality of the evidence was assessed using the GRADE approach. Main results: We included four trials, involving 1190 women. It was not possible to blind women and staff to the intervention, but for other ’Risk of bias’ domains these studies were assessed as being at low or unclear risk of bias.Compared to expectant management, there was no clear effect of induction of labour for suspected macrosomia on the risk of caesarean section (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.76 to 1.09; 1190 women; four trials, moderate-quality evidence) or instrumental delivery (RR 0.86, 95% CI 0.65 to 1.13; 1190 women; four trials, low-quality evidence). Shoulder dystocia (RR 0.60, 95% CI 0.37 to 0.98; 1190 women; four trials, moderate-quality evidence), and fracture (any) (RR 0.20, 95% CI 0.05 to 0.79; 1190 women; four studies, high-quality evidence) were reduced in the induction of labour group. There were no clear differences between groups for brachial plexus injury (two events were reported in the control group in one trial, low-quality evidence). There was no strong evidence of any difference between groups for measures of neonatal asphyxia; low five-minute infant Apgar scores (less than seven) or low arterial cord blood pH (RR 1.51, 95% CI 0.25 to 9.02; 858 infants; two trials, low-quality evidence ; and, RR 1.01, 95% CI 0.46 to 2.22; 818 infants; one trial, moderate-quality evidence, respectively). Mean birthweight was lower in the induction group, but there was considerable heterogeneity between studies for this outcome (mean difference (MD) -178.03 g, 95% CI -315.26 to -40.81; 1190 infants; four studies; I= 89%). In one study with data for 818 women, third- and fourth-degree perineal tears were increased in the induction group (RR 3.70, 95% CI 1.04 to 13.17). For outcomes assessed using GRADE, we based our downgrading decisions on high risk of bias from lack of blinding and imprecision of effect estimates. Authors’ conclusions: Induction of labour for suspected fetal macrosomia has not been shown to alter the risk of brachial plexus injury, but the power of the included studies to show a difference for such a rare event is limited. Also antenatal estimates of fetal weight are often inaccurate so many women may be worried unnecessarily, and many inductions may not be needed. Nevertheless, induction of labour for suspected fetal macrosomia results in a lower mean birthweight, and fewer birth fractures and shoulder dystocia. The unexpected observation in the induction group of increased perineal damage, and the plausible, but of uncertain significance, observation of increased use of phototherapy, both in the largest trial, should also be kept in mind. Findings from trials included in the review suggest that to prevent one fracture it would be necessary to induce labour in 60 women. Since induction of labour does not appear to alter the rate of caesarean delivery or instrumental delivery, it is likely to be popular with many women. In settings where obstetricians can be reasonably confident about their scan assessment of fetal weight, the advantages and disadvantages of induction at or near term for fetuses suspected of being macrosomic should be discussed with parents. Although some parents and doctors may feel the evidence already justifies induction, others may justifiably disagree. Further trials of induction shortly before term for suspected fetal macrosomia are needed. Such trials should concentrate on refining the optimum gestation of induction, and improving the accuracy of the diagnosis of macrosomia

Use of biochemical tests of placental function for improving pregnancy outcome

BACKGROUND: The placenta has an essential role in determining the outcome of pregnancy. Consequently, biochemical measurement of placentally-derived factors has been suggested as a means to improve fetal and maternal outcome of pregnancy. OBJECTIVES: To assess whether clinicians' knowledge of the results of biochemical tests of placental function is associated with improvement in fetal or maternal outcome of pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised, cluster-randomised or quasi-randomised controlled trials assessing the merits of the use of biochemical tests of placental function to improve pregnancy outcome.Studies were eligible if they compared women who had placental function tests and the results were available to their clinicians with women who either did not have the tests, or the tests were done but the results were not available to the clinicians. The placental function tests were any biochemical test of placental function carried out using the woman's maternal biofluid, either alone or in combination with other placental function test/s. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data and assessed trial quality. Authors of published trials were contacted for further information. MAIN RESULTS: Three trials were included, two quasi-randomised controlled trials and one randomised controlled trial. One trial was deemed to be at low risk of bias while the other two were at high risk of bias. Different biochemical analytes were measured - oestrogen was measured in one trial and the other two measured human placental lactogen (hPL). One trial did not contribute outcome data, therefore, the results of this review are based on two trials with 740 participants.There was no evidence of a difference in the incidence of death of a baby (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.36 to 2.13, two trials, 740 participants (very low quality evidence)) or the frequency of a small-for-gestational-age infant (RR 0.44, 95% CI 0.16 to 1.19, one trial, 118 participants (low quality evidence)).In terms of this review's secondary outcomes, there was no evidence of a clear difference between women who had biochemical tests of placental function compared with standard antenatal care for the incidence of stillbirth (RR 0.56, 95% CI 0.16 to 1.88, two trials, 740 participants (very low quality evidence)) or neonatal death (RR 1.62, 95% CI 0.39 to 6.74, two trials, 740 participants, very low quality evidence)) although the directions of any potential effect were in opposing directions. There was no evidence of a difference between groups in elective delivery (RR 0.98, 95% CI 0.84 to 1.14, two trials, 740 participants (low quality evidence)), caesarean section (one trial, RR 0.48, 95% CI 0.15 to 1.52, one trial, 118 participants (low quality evidence)), change in anxiety score (mean difference -2.40, 95% CI -4.78 to -0.02, one trial, 118 participants), admissions to neonatal intensive care (RR 0.32, 95% CI 0.03 to 3.01, one trial, 118 participants), and preterm birth before 37 weeks' gestation (RR 2.90, 95% CI 0.12 to 69.81, one trial, 118 participants). One trial (118 participants) reported that there were no cases of serious neonatal morbidity. Maternal death was not reported.A number of this review's secondary outcomes relating to the baby were not reported in the included studies, namely: umbilical artery pH seven days, pre-eclampsia, eclampsia, and women's perception of care). AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of biochemical tests of placental function to reduce perinatal mortality or increase identification of small-for-gestational-age infants. However, we were only able to include data from two studies that measured oestrogens and hPL. The quality of the evidence was low or very low.Two of the trials were performed in the 1970s on women with a variety of antenatal complications and this evidence cannot be generalised to women at low-risk of complications or groups of women with specific pregnancy complications (e.g. fetal growth restriction). Furthermore, outcomes described in the 1970s may not reflect what would be expected at present. For example, neonatal mortality rates have fallen substantially, such that an infant delivered at 28 weeks would have a greater chance of survival were those studies repeated; this may affect the primary outcome of the meta-analysis.With data from just two studies (740 women), this review is underpowered to detect a difference in the incidence of death of a baby or the frequency of a small-for-gestational-age infant as these have a background incidence of approximately 0.75% and 10% of pregnancies respectively. Similarly, this review is underpowered to detect differences between serious and/or rare adverse events such as severe neonatal morbidity. Two of the three included studies were quasi-randomised, with significant risk of bias from group allocation. Additionally, there may be performance bias as in one of the two studies contributing data, participants receiving standard care did not have venepuncture, so clinicians treating participants could identify which arm of the study they were in. Future studies should consider more robust randomisation methods and concealment of group allocation and should be adequately powered to detect differences in rare adverse events.The studies identified in this review examined two different analytes: oestrogens and hPL. There are many other placental products that could be employed as surrogates of placental function, including: placental growth factor (PlGF), human chorionic gonadotrophin (hCG), plasma protein A (PAPP-A), placental protein 13 (PP-13), pregnancy-specific glycoproteins and progesterone metabolites and further studies should be encouraged to investigate these other placental products. Future randomised controlled trials should test analytes identified as having the best predictive reliability for placental dysfunction leading to small-for-gestational-age infants and perinatal mortality

Surgical intervention versus expectant management for endometrial polyps in subfertile women

BACKGROUND: Endometrial polyps, which are benign growths of the endometrium, may be a factor in female subfertility. Possible mechanisms include physical interference with gamete transport, alteration of the endometrial milieu and unresponsiveness to the cyclical global endometrial changes. As such polyps remain mostly asymptomatic, their diagnosis is often incidental during routine investigations prior to embarking on assisted reproductive treatment. Transvaginal sonography, hysterosalpingography and saline infusion sonography are the diagnostic tools most commonly employed. However, hysteroscopy remains the gold standard for diagnosis, as well as for treatment. Due to the possible effect of endometrial polyps on fertility, their removal prior to any subfertility treatment is widely practiced. OBJECTIVES: To determine the effectiveness and safety of removal of endometrial polyps in subfertile women. SEARCH METHODS: Electronic databases were searched, including the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL and trial registers. The reference lists of identified articles were checked. The last search was performed on 30 July 2014. SELECTION CRITERIA: Only randomised controlled trials, reporting pregnancy or live birth rates and complication rates as primary or secondary outcomes, in which polyps were removed surgically prior to treatment of subfertility were eligible for inclusion. The diagnosis of endometrial polyps was required to be made by transvaginal ultrasound, hysterosalpingography, saline infusion, sono-hysterography or hysteroscopy. Any surgical technique of polyp removal was acceptable, with no intervention in the control groups. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles, abstracts and full articles to assess their suitability for inclusion in this review. Quality assessment was attempted independently by two authors with discrepancies being settled by consensus or consultation with a third review author.No data extraction was performed due to the absence of useable data in the one eligible study. If there had been data to include, two review authors would have independently extracted the data from the studies using a data extraction form designed and pilot tested by the authors. Any disagreements would have been resolved by discussion or by a third review author. MAIN RESULTS: Only one randomised controlled trial of endometrial polypectomy was identified for inclusion. However, a single set of data could not be extracted from this study due to internal inconsistencies of the results reported. Attempts to contact the authors to resolve the issue were unsuccessful, by phone, post and e-mail. AUTHORS' CONCLUSIONS: Removal of endometrial polyps in subfertile women is commonly being performed in many countries with an aim to improve the reproductive outcome. We did not identify any analysable randomised trials which would allow us to reach any sound scientific conclusions on the efficacy of endometrial polypectomy in subfertile women. Well designed, methodologically sound, randomised controlled trials are urgently needed