Antenatal magnesium sulphate for the prevention of cerebral palsy in infants born preterm: a double-blind, randomised, placebo-controlled, multi-centre trial.

OBJECTIVE: To study the effect of antenatal magnesium sulphate (MgSO4 ) on cerebral palsy (CP) in a manner that also provides adequate power for a linked trial sequential analysis. DESIGN: Double-blind, randomised, placebo-controlled, multi-centre trial. SETTING: Fourteen Danish obstetric departments. POPULATION: In total, 560 pregnant women at risk for preterm delivery before 32 weeks of gestation were randomised from December 2011 to January 2018. Those women gave birth to 680 children. METHODS: Women were randomised to receive either a loading dose of 5 g MgSO4 followed by 1 g/hour or a placebo in identical volumes. The children were followed up at a corrected age of 18 months or older with a review of their medical charts and with the Ages and Stages Questionnaire. MAIN OUTCOME MEASURE: The primary outcome measure was moderate to severe CP. Secondary outcomes included mortality, neonatal morbidity, blindness and mild CP. RESULTS: The crude rates of moderate to severe CP in the MgSO4 group and the placebo group were 2.0% and 3.3%, respectively. The adjusted odds of moderate to severe CP were lower in the MgSO4 group than in the placebo group (odds ratio 0.61; 95% CI 0.23-1.65). CONCLUSIONS: Antenatal MgSO4 before 32 weeks of gestation decreases the likelihood of moderate to severe CP; these results are entirely consistent with other randomised evidence summarised in the linked trial sequential analysis. TWEETABLE ABSTRACT: Antenatal magnesium sulphate may decrease the risk of moderate to severe cerebral palsy in children born before 32 weeks of gestation.

Low PAPP-A in the first trimester is associated with reduced fetal growth rate prior to gestational week 20.

OBJECTIVE: To evaluate the association between maternal pregnancy-associated plasma protein-A (PAPP-A) and fetal growth from the first to the second trimester. METHODS: A prospective cohort study including 8347 pregnant women attending prenatal care at Aarhus University Hospital were conducted. PAPP-A was measured during 8 to 14 gestational weeks. Fetal growth between the two scans in the first and second trimesters was estimated by (GA(20)- GA(12))/Days(calendar), where GA(12) reflects gestational age in days calculated from crown-rump length at a 12-week scan, GA(20) reflects gestational age in days calculated from biparietal diameter at a 20-week scan, and Days(calendar) reflects the number of calendar days between the two scans. RESULTS: Fetal growth rate from the first to the second trimester was correlated with PAPP-A, with a regression coefficient of 0.009 (95% CI, 0.007-0.012, P < 0.001). PAPP-A below 0.30 MoM was associated with a fetal growth rate below the tenth centile, with an adjusted OR of 2.05 (95% CI, 1.24-3.38). CONCLUSION: Low levels of PAPP-A are associated not only with low birth weight at term but also with slower fetal growth prior to 20 weeks of gestation.

Duration of pregnancy in relation to fish oil supplementation and habitual fish intake: a randomised clinical trial with fish oil.

OBJECTIVE: To examine the effect of fish oil supplementation on duration of pregnancy, conditional on the woman's habitual fish intake. DESIGN: Multicentre 1:1 randomised clinical trial of effect of fish oil in a high-risk population of pregnant women in whom habitual fish intake was assessed at randomisation. SETTING: Nineteen university delivery wards in seven European countries. SUBJECTS: Pregnant women with preterm delivery, intrauterine growth retardation (IUGR), or pregnancy-induced hypertension (PIH) in a previous pregnancy (group 1, n=495); with twin pregnancies (group 2, n=367); or with suspicion of IUGR or threatening preeclampsia in the current pregnancy (group 3, n=106). Women were stratified into low, middle, or high fish consumers. METHODS: The intervention group received fish oil capsules providing 2.7 g long-chain n-3 fatty acids per day (n-3 poly unsaturated fatty acids (PUFA)) from around week 20 (groups 1 and 2) or 6.3 g n-3 PUFA from week 33 (group 3). The control regimen was capsules with olive oil. Effect on timing of spontaneous delivery was examined by Cox regression, assuming elective delivery (occurring in 40%) as a censoring event. Analyses of effect of fish oil were intention to treat, and all analyses were adjusted for maternal smoking, age, and parity. RESULTS: In group 1, fish oil reduced the hazard rate of spontaneous delivery (HR) by 44% (95% confidence interval 14-64%) and 39% (16-56%) in low and middle fish consumers, respectively, with no detectable effect (-56 to 33%) in high fish consumers. In groups 2 and 3, no significant effect of fish oil was detected in any of the sub-strata defined by baseline fish consumption. CONCLUSIONS: In pregnant women with previous pregnancy complications, fish oil supplementation delayed onset of delivery in low and middle, but not in high, fish consumers. SPONSORSHIP: March of Dimes Birth Defects Foundation, Concerted Action (ERB-BMH1-CT92-1906) and PECO (ERB-CIPD-CT94-0235) programmes of the European Commission, and the Danish National Research Foundation. Lube Ltd donated the oil capsules.

Association between raised serum relaxin levels during the eighteenth gestational week and very preterm delivery.

OBJECTIVE: Our aim was to evaluate a possible association between serum relaxin levels in the 18th gestational week and preterm delivery. STUDY DESIGN: We conducted a nested case-control study that was based on serum samples obtained in the 18th week of gestation from 1545 unselected healthy primiparous women. Eleven case subjects were delivered very early (9 spontaneously, 2 by indicated cesarean delivery) and 42 moderately early (41 spontaneously, 1 by indicated cesarean delivery); 123 control subjects (121 having spontaneous labor, 2 undergoing indicated cesarean delivery) were randomly selected among the women with delivery at term. RESULTS: The serum relaxin concentration during the 18th gestational week was 63% higher among subjects with very preterm deliveries than among control subjects (P = .01, Mann-Whitney test). High relaxin levels during the 18th gestational week were associated with an increased risk of very preterm delivery (odds ratio, 11.3; 95% confidence interval, 2.14-59.1) and spontaneous very preterm delivery (odds ratio, 5.5; 95% confidence interval, 1.3-23). There was a negative correlation for case subjects and control subjects between serum relaxin concentrations during the 18th gestational week and gestational age at delivery (P < .05). CONCLUSION: Serum relaxin may be an independent predictor when identification of women at risk of very preterm delivery is attempted in the 18th gestational week.

Flatus and faecal incontinence: prevalence and risk factors at 16 weeks of gestation.

OBJECTIVE: To evaluate the prevalence of anal incontinence at 16 weeks of gestation and to identify possible maternal and obstetrical risk factors. DESIGN: Cross sectional study and cohort study. SETTING: Department of Obstetrics and Gynaecology, Aarhus University Hospital, Denmark. PARTICIPANTS: Cross sectional study: 7,557 women attending antenatal care. Cohort study: a subgroup of 1,726 pregnant women with one previous delivery at our department. RESULTS: The prevalence of anal incontinence within the preceding year was 8.6%. Incontinence of liquid and solid stools was reported in 2.3% and 0.6%, respectively. Isolated flatus incontinence at least once a week was reported in 4.2%. The risk of flatus incontinence at least once a week was increased with age > 35 years (OR 1.6; 95% CI 1.1-2.4) and with previous lower abdominal or urological surgery (OR 1.5, 95% CI 1-1-2.1) in a logistic regression model controlling for maternal factors. Increasing parity did not increase the risk. The risk of flatus incontinence was increased after anal sphincter tear and birthweight > 4,000 g in a logistic regression model controlling for maternal and obstetric variables. Episiotomy was insignificantly associated, while spontaneous perineal tear > 3 cm and a number of other intrapartum factors were not associated. CONCLUSION True faecal incontinence is rare among younger women. However, an age > 35 years and previous lower abdominal or urological surgery increased the risk of flatus incontinence in contrast to increasing parity. This suggests that childbirth plays a minor role compared with age. However, when analysing obstetric variables separately, a birthweight > 4,000 g, and anal sphincter tears were significant risk factors for flatus incontinence.

Urinary incontinence: prevalence and risk factors at 16 weeks of gestation.

OBJECTIVE: To evaluate the prevalence of urinary incontinence at 16 weeks of gestation and to identify possible maternal and obstetric risk factors. DESIGN: Cross-sectional study and cohort study. SETTING: Department of Obstetrics and Gynaecology, Aarhus University Hospital, Denmark. POPULATION: Cross-sectional study: 7795 women attending antenatal care. Cohort study: a sub-group of 1781 pregnant women with one previous delivery at our department. RESULTS: Prevalence and maternal risk factors: the prevalence of urinary incontinence within the preceding year was 8.9% among women at 16 weeks of gestation (nulliparae, 3.9%, para 1, 13.8%, para 2+, 16.2%). Stress or mixed incontinence occurred at least weekly in 3% of all the women. After adjusting for age, parity, body mass index, smoking, previous abortions, and previous lower abdominal or urological surgery in a logistic regression model, primiparous women who had delivered vaginally had higher risk of stress or mixed urinary incontinence than nulliparous women (OR 5.7; 95% CI 3.9-8.3). Subsequent vaginal deliveries did not increase the risk significantly. Young age, body mass index > 30, and smoking were possible risk factors for developing urinary incontinence. Obstetric factors: weight of the newborn > 4000 g (OR 1.9; 95% CI 1.0-3.6) increased the risk of urinary incontinence; mediolateral episiotomy in combination with birthweight > 4000 g also increased the risk (OR 3.5; 95% CI 1.2-10.2); a number of other intrapartum factors did not increase the risk of urinary incontinence. CONCLUSIONS: The first vaginal delivery was a major risk factor for developing urinary incontinence; subsequent vaginal deliveries did not increase the risk significantly. Birthweight > 4000 g increased the risk; episiotomy in combination with birthweight > 4000 g also increased the risk.

Hepatocyte growth factor levels during normal and intra-uterine growth-restricted pregnancies.

Hepatocyte growth factor (HGF), also known as scatter factor, binds the c-met receptor. It has been shown to be involved in mesenchyme-epithelial interactions. HGF is produced by the villous mesenchyme of the placenta throughout pregnancy and its receptor located on the villous cytotrophoblast cells. In this study the levels of HGF were measured in consecutive samples of plasma taken from pregnant women. Normal pregnancies were compared with intrauterine growth restricted (IUGR) pregnancies (below the third centile). In both groups, the levels of HGF were found to increase significantly as pregnancy progressed and then fall post partum. There was a considerable amount of variation found between individual women but no significant difference (P=0.65) between the normal and IUGR pregnancies.

Marine n-3 fatty acid and calcium intake in relation to pregnancy induced hypertension, intrauterine growth retardation, and preterm delivery. A case-control study.

OBJECTIVE: To evaluate whether low intakes in pregnancy of marine n-3 fatty acids or calcium increase the risk of preeclampsia, pregnancy induced hypertension, intrauterine growth retardation, or preterm delivery and whether high intakes of the above nutrients increase the risk of postterm delivery. DESIGN: A case-control nested in cohort study. SUBJECTS AND METHODS: Between 1989 and 1991 a cohort of 9,434 pregnant women was established. Forty-three preeclamptics, 179 women with pregnancy induced hypertension, 182 with intrauterine growth retardation, 153 delivering preterm, and 189 delivering postterm together with 256 controls were sampled for this study. Dietary information was obtained retrospectively between six months and 3 1/2 years after delivery using a semiquantitative food frequency questionnaire, whilst information on potential confounders was obtained from the cohort data base and analyzed by multiple logistic regression. Questions regarding marine n-3 fatty acids and calcium intake provided the basis for categorization into three and five intake groups respectively. RESULTS: For all five pregnancy outcomes and both nutritional factors, none of the confounder-adjusted odds ratios comparing higher intake levels with the lowest intake level were significant. Neither were chi 2-tests for trend calculated for each pregnancy outcome statistically significant (p > 0.20). Odds ratios for highest versus lowest intake levels were for n-3 fatty acids 0.79 ((0.27 to 2.34 (95% CI)) for pregnancy induced hypertension, 1.00 (0.34 to 2.95) for intrauterine growth retardation, and 0.99 (0.35 to 2.74) for preterm delivery; for calcium they were 0.92 (0.33 to 2.60) for pregnancy induced hypertension, 0.77 (0.25 to 2.42) for intrauterine growth retardation, and 1.05 (0.36 to 3.10) for preterm delivery. CONCLUSIONS: No associations could be detected in these data between calcium or fish intake and adverse pregnancy outcome.

Effects of fish oil supplementation in late pregnancy on blood pressure: a randomised controlled trial.

OBJECTIVE: To study the effect of fish oil supplementation on blood pressure during the third trimester of pregnancy. DESIGN: In the 30th week of pregnancy 533 healthy women were randomly assigned in a ratio 2:1:1 to receive fish oil (2.7 g/day n-3 fatty acids (Pikasol)), or a control regimen of either olive oil or no oil supplementation. MAIN OUTCOME MEASURES: Blood pressure measured with an automatic device (Dinamap 1846 SX, Criticon) at baseline and in weeks 33, 37, 39 and subsequently weekly until delivery. RESULTS: Mean blood pressure increased during the third trimester, and this was not influenced by group assignment. No significant effects on either systolic or diastolic blood pressure were seen in the fish oil group compared to the control groups. The proportions of women with a systolic blood pressure above 140 mmHg or a diastolic blood pressure above 90 mmHg were not significantly different in the fish oil group compared with the control groups, although the proportion of women with diastolic above 90 mmHg tended to be lower in the fish oil group compared with the olive oil group. The corresponding relative risk was RR = 0.48 (95% CI 0.22-1.06; P = 0.07). CONCLUSION: 2.7 g/day of marine n-3 fatty acids provided in the third trimester of normal pregnancy showed no effect on blood pressure.