James Neilson

Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: A randomised placebo-controlled trial

BACKGROUND Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate. METHODS Eligible women (n=10141) had not given birth or were 24 h or less postpartum; blood pressure of 140/90 mm Hg or more, and proteinuria of 1+ (30 mg/dL) or more; and there was clinical uncertainty about magnesium sulphate. Women were randomised in 33 countries to either magnesium sulphate (n=5071) or placebo (n=5070). Primary outcomes were eclampsia and, for women randomised before delivery, death of the baby. Follow up was until discharge from hospital after delivery. Analyses were by intention to treat. FINDINGS Follow-up data were available for 10,110 (99.7%) women, 9992 (99%) of whom received the allocated treatment. 1201 of 4999 (24%) women given magnesium sulphate reported side-effects versus 228 of 4993 (5%) given placebo. Women allocated magnesium sulphate had a 58% lower risk of eclampsia (95% CI 40-71) than those allocated placebo (40, 0.8%, vs 96, 1.9%; 11 fewer women with eclampsia per 1000 women). Maternal mortality was also lower among women allocated magnesium sulphate (relative risk 0.55, 0.26-1.14). For women randomised before delivery, there was no clear difference in the risk of the baby dying (576, 12.7%, vs 558, 12.4%; relative risk 1.02, 99% CI 0.92-1.14). The only notable difference in maternal or neonatal morbidity was for placental abruption (relative risk 0.67, 99% CI 0.45-0.89). INTERPRETATION Magnesium sulphate halves the risk of eclampsia, and probably reduces the risk of maternal death. There do not appear to be substantive harmful effects to mother or baby in the short term.ARTICLES Summary Background Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate.

Stillbirths: the way forward in high-income countries

Stillbirth rates in high-income countries declined dramatically from about 1940, but this decline has slowed or stalled over recent times. The present variation in stillbirth rates across and within high-income countries indicates that further reduction in stillbirth is possible. Large disparities (linked to disadvantage such as poverty) in stillbirth rates need to be addressed by providing more educational opportunities and improving living conditions for women. Placental pathologies and infection associated with preterm birth are linked to a substantial proportion of stillbirths. The proportion of unexplained stillbirths associated with under investigation continues to impede efforts in stillbirth prevention. Overweight, obesity, and smoking are important modifiable risk factors for stillbirth, and advanced maternal age is also an increasingly prevalent risk factor. Intensified efforts are needed to ameliorate the effects of these factors on stillbirth rates. Culturally appropriate preconception care and quality antenatal care that is accessible to all women has the potential to reduce stillbirth rates in high-income countries. Implementation of national perinatal mortality audit programmes aimed at improving the quality of care could substantially reduce stillbirths. Better data on numbers and causes of stillbirth are needed, and international consensus on definition and classification related to stillbirth is a priority. All parents should be offered a thorough investigation including a high-quality autopsy and placental histopathology. Parent organisations are powerful change agents and could have an important role in raising awareness to prevent stillbirth. Future research must focus on screening and interventions to reduce antepartum stillbirth as a result of placental dysfunction. Identification of ways to reduce maternal overweight and obesity is a high priority for high-income countries.

Interventions for twin–twin transfusion syndrome: a Cochrane review

We performed a Cochrane review to assess which of the treatments for twin–twin transfusion syndrome (TTTS) improves fetal, childhood and maternal outcomes. This article represents a version of the review which includes additional data to the published version.

Choice and birth method : mixed-method study of caesarean delivery for maternal request

Objective  To explore whether women view decision‐making surrounding vaginal or caesarean birth as their choice.

Antibiotics for preterm rupture of the membranes: A systematic review

OBJECTIVE: We sought to evaluate the administration of antibiotics to pregnant women with preterm rupture of membranes (PROM). DATA SOURCES: We collected data by using the Cochrane Controlled Trials Register and MEDLINE. METHODS OF STUDY SELECTION: We included randomized controlled comparisons of antibiotic versus placebo (14 trials, 6,559 women). TABULATION, INTEGRATION, AND RESULTS: Antibiotics were associated with a statistically significant reduction in maternal infection and chorioamnionitis. There also was a reduction in the number of infants born within 48 hours and 7 days and with the following morbidities: neonatal infection (relative risk [RR] 0.67, 95% confidence interval [CI] 0.52–0.85), positive blood culture (RR 0.75, 95% CI 0.60–0.93), use of surfactant (RR 0.83 95% CI 0.72–0.96), oxygen therapy (RR 0.88, 95% CI 0.81–0.96), and abnormal cerebral ultrasound scan before discharge from hospital (RR 0.82, 95% CI 0.68–0.99). Perinatal mortality was not significantly reduced (RR 0.91, 95% CI 0.75–1.11). A benefit was present both in trials where penicillins and erythromycin were used. Amoxicillin/clavulanate was associated with a highly significant increase in the risk of necrotizing enterocolitis (RR 4.60, 95% CI 1.98–10.72). CONCLUSION: The administration of antibiotics after PROM is associated with a delay in delivery and a reduction in maternal and neonatal morbidity. These data support the routine use of antibiotics for women with PROM. Penicillins and erythromycin were associated with similar benefits, but erythromycin was used in larger trials and, thus, the results are more robust. Amoxicillin/clavulanate should be avoided in women at risk of preterm delivery because of the increased risk of neonatal necrotizing enterocolitis. Antibiotic administration after PROM is beneficial for both women and neonates.

Reproductive health in rural Malawi: a population-based survey.

Objectives To assess pregnancy outcome, maternal mortality and health‐seeking behaviour in a rural African population and to assess the effects on these of womens education, distance from a health centre and household type.

The APPLe Study: A Randomized, Community-Based, Placebo-Controlled Trial of Azithromycin for the Prevention of Preterm Birth, with Meta-Analysis

In a randomized trial in Malawi of azithromycin versus placebo in over 2,000 pregnant women, Jim Neilson and colleagues show no benefit of azithromycin for a number of outcomes including preterm birth and prenatal death.

Interleukin-6, interferon-γ, interleukin-8, and granulocyte-macrophage colony stimulating factor levels in human amniotic fluid at term

Cytokines contribute to the maintenance of successful pregnancy and have also been implicated in the initiation of labour. This study has examined those cytokines which may be involved in normal term parturition. IL-6, IFN-gamma, IL-8 and GM-CSF levels were measured by ELISA in samples of amniotic fluid, peripheral and uterine venous blood plasma, and umbilical artery blood plasma from non-labouring women undergoing elective caesarean section at term and from women in spontaneous labour. IFN-gamma and IL-6 were detected only in amniotic fluid and not in blood plasma samples, unlike IL-8 which was found in all amniotic fluid and plasma samples from both labouring and non-labouring women; GM-CSF was undetectable in all samples examined. Levels of IL-6 were significantly raised in the amniotic fluid of women in labour compared with the control group (P = 0.008). IFN-gamma was detected in the amniotic fluid of both labouring women and the control group, and there was also a significant correlation (P = 0.003) between IFN-gamma and IL-6 levels in individual amniotic fluid samples. The presence of both IFN-gamma and IL-8 in amniotic fluid, as well as IL-6, suggests these cytokines are involved in important immunobiological events relevant to the latter half of gestation.

Antenatal ultrasound screening for fetal abnormalities: a systematic review of studies of cost and cost effectiveness.

Objective To review systematically and critically evidence to derive estimates of costs and cost effectiveness of routine ultrasound screening for fetal abnormalities.

Second trimester serum free β human chorionic gonadotrophin levels as a predictor of pre-eclampsia

BACKGROUND To prospectively assess maternal serum free beta human chorionic gonadotrophin (beta hCG) estimation between 15 and 18 weeks gestation, as a screening test for pre-eclampsia in primigravid women. METHODS A prospective longitudinal study in a University Teaching Hospital. The study population was 430 primigravid women, who had maternal serum free beta hCG levels measured as part of antenatal serum screening for Downs Syndrome in the second trimester, who booked consecutively within the unit and went on to deliver on the units labor ward. These women were followed during their subsequent pregnancy and categorized into those who remained normotensive and those who developed pre-eclampsia on both clinical and biochemical grounds. The beta hCG levels were used to construct a receiver operator characteristics curve (ROC) to assess the screening potential for pre-eclampsia. RESULTS Nineteen (4.4%) women in the study group developed pre-eclampsia. The median second trimester free beta hCG multiples of the median (MOM) was significantly elevated compared to that of the control group (1.52 vs 1.10, p=0.03). The ROC curve shows that for a sensitivity of 79%, the specificity was only 54%. CONCLUSIONS Maternal serum free beta hCG alone measured in the second trimester is not clinically useful as a screening test for pre-eclampsia in primigravid women. It has, however, some predictive value.