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Autism spectrum disorder (ASD) is a developmental disorder characterised by deficits in social interactions and communication, with stereotypical and repetitive behaviours. Recent evidence suggests that maternal immune dysregulation may predispose offspring to ASD. Independent samples t-tests revealed downregulation of IL-17A concentrations in cases, when compared to controls, at both 15 weeks (p = 0.02), and 20 weeks (p = 0.02), which persisted at 20 weeks following adjustment for confounding variables. This adds to the growing body of evidence that maternal immune regulation may play a role in foetal neurodevelopment. [This article was written on behalf of the SCOPE Consortium.]

We assessed whether paternal demographic, anthropometric and clinical factors influence the risk of an infant being born large-for-gestational-age (LGA). We examined the data on 3659 fathers of term offspring (including 662 LGA infants) born to primiparous women from Screening for Pregnancy Endpoints (SCOPE). LGA was defined as birth weight >90th centile as per INTERGROWTH 21st standards, with reference group being infants ⩽90th centile. Associations between paternal factors and likelihood of an LGA infant were examined using univariable and multivariable models. Men who fathered LGA babies were 180 g heavier at birth (P <0.001) and were more likely to have been born macrosomic (P <0.001) than those whose infants were not LGA. Fathers of LGA infants were 2.1 cm taller (P <0.001), 2.8 kg heavier (P <0.001) and had similar body mass index (BMI). In multivariable models, increasing paternal birth weight and height were independently associated with greater odds of having an LGA infant, irrespective of maternal factors. One unit increase in paternal BMI was associated with 2.9% greater odds of having an LGA boy but not girl; however, this association disappeared after adjustment for maternal BMI. There were no associations between paternal demographic factors or clinical history and infant LGA. In conclusion, fathers who were heavier at birth and were taller were more likely to have an LGA infant, but maternal BMI had a dominant influence on LGA. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction.Design: A randomised placebo-controlled trial.Setting: Thirteen maternal-fetal medicine units across New Zealand and Australia.Population: Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks.Methods: Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first).Main Outcome Measures: The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre-eclampsia.Results: Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated, 39/57 (68.4%) placebo-treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23-1.05] and had no effect on abdominal circumference Z-scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil-treated and 47/59 (79.7%) for placebo-treated (adjusted OR 2.50, 95% CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil-treated and 33/59 (55.9%) for placebo-treated (adjusted OR 1.93, 95% CI 0.84-4.45); and new-onset pre-eclampsia was 9/51 (17.7%) for sildenafil-treated and 14/55 (25.5%) for placebo-treated (OR 0.67, 95% CI 0.26-1.75).Conclusions: Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing.Tweetable Abstract: Maternal sildenafil use has no beneficial effect on growth in early-onset FGR, but also no evidence of harm. [ABSTRACT FROM AUTHOR]

Objective: To determine: (1) the association between metabolic syndrome (MetS), time to pregnancy (TTP), and infertility; (2) associations between individual and an increasing number of MetS components, TTP, and infertility; and (3) whether these relationships differ by body mass index (BMI < 30 kg/m2 versus BMI ≥ 30 kg/m2 ).Design: Retrospective cohort study.Setting: Multiple centres (in Australia, Ireland, New Zealand, and the UK).Population: Five thousand five hundred and nineteen low-risk nulliparous pregnant women.Methods: Data on retrospectively reported TTP (number of months to conceive) and a blood sample to assess metabolic health were collected between 14 and 16 weeks of gestation. MetS was defined according to the International Diabetes Federation criteria. Accelerated failure time models with log-normal distribution were conducted to estimate time ratios (TRs) and 95% CIs. Differences in MetS on infertility (TTP > 12 months) were compared using a generalised linear model (Poisson distribution) with robust variance estimates (relative risks, RRs; 95% CIs). All analyses (entire cohort and split by BMI) were controlled for a range of maternal and paternal confounding factors.Main Outcome Measures: Time to pregnancy and infertility.Results: Of the 5519 women included, 12.4% (n = 684) had MetS. Compared with women without MetS, women with MetS had a longer TTP (adjusted TR 1.30; 95% CI 1.15-1.46), which was similar in women who were obese and in women who were not obese. Marginal estimates for median TTP in women with MetS versus without MetS was 3.1 months (3.0-3.3 months) versus 4.1 months (3.6-4.5 months), respectively. Women with MetS were at a 62% greater risk for infertility and were at a greater risk for infertility whether they were obese (adjusted RR 1.62; 95% CI 1.15-2.29) or not (adjusted RR 1.73; 95% CI 1.33-2.23). Reduced high-density lipoprotein cholesterol (HDL-C) and raised triglycerides (TGs) were the main individual components associated with risk for infertility.Conclusion: Metabolic syndrome is associated with longer TTP and infertility, independent of obesity. Additional studies, before pregnancy, are required to support our findings and to determine the applicability of which combinations of metabolic abnormalities pose the greatest risk to delayed fertility, or whether individual components are amenable to modification.Tweetable Abstract: Metabolic syndrome is associated with longer time to pregnancy and infertility, independent of obesity. [ABSTRACT FROM AUTHOR]

Objective: To report maternal sleep practices in women who experienced a stillbirth compared with controls with ongoing live pregnancies at similar gestation.Design: Prospective case-control study.Setting: Forty-one maternity units in the United Kingdom.Population: Women who had a stillbirth after ≥ 28 weeks' gestation (n = 291) and women with an ongoing pregnancy at the time of interview (n = 733).Methods: Data were collected using an interviewer-administered questionnaire that included questions on maternal sleep practices before pregnancy, in the four weeks prior to, and on the night before the interview/stillbirth.Main Outcome Measures: Maternal sleep practices during pregnancy.Results: In multivariable analysis, supine going-to-sleep position the night before stillbirth had a 2.3-fold increased risk of late stillbirth [adjusted Odds Ratio (aOR) 2.31, 95% CI 1.04-5.11] compared with the left side. In addition, women who had a stillbirth were more likely to report sleep duration less than 5.5 hours on the night before stillbirth (aOR 1.83, 95% CI 1.24-2.68), getting up to the toilet once or less (aOR 2.81, 95% CI 1.85-4.26), and a daytime nap every day (aOR 2.22, 95% CI 1.26-3.94). No interaction was detected between supine going-to-sleep position and a small-for-gestational-age infant, maternal body mass index, or gestational age. The population-attributable risk for supine going-to-sleep position was 3.7% (95% CI 0.5-9.2).Conclusions: This study confirms that supine going-to-sleep position is associated with late stillbirth. Further work is required to determine whether intervention(s) can decrease the frequency of supine going-to-sleep position and the incidence of late stillbirth.Tweetable Abstract: Supine going-to-sleep position is associated with 2.3× increased risk of stillbirth after 28 weeks' gestation.Plain Language Summary: Stillbirth, the death of a baby before birth, is a tragedy for mothers and families. One approach to reduce stillbirths is to identify factors that are associated with stillbirth. There are few risk factors for stillbirth that can be easily changed, but this study is looking at identifying how mothers may be able to reduce their risk. In this study, we interviewed 291 women who had a stillbirth and 733 women who had a live-born baby from 41 maternity units throughout the UK. The mothers who had a stillbirth were interviewed as soon as practical after their baby died. Mothers who had a live birth were interviewed during their pregnancies at the same times in pregnancy as when the stillbirths occurred. We did not interview mothers who had twins or who had a baby with a major abnormality. Mothers who went to sleep on their back had at least twice the risk of stillbirth compared with mothers who went to sleep on their left-hand side. This study suggests that 3.7% of stillbirths after 28 weeks of pregnancy were linked with going to sleep lying on the back. This study also shows that the link between going-to-sleep position and late stillbirth was not affected by the duration of pregnancy after 28 weeks, the size of the baby, or the mother's weight. Women who got up to the toilet once or more at night had a reduced risk of stillbirth. This is the largest of four similar studies that have all shown the same link between the position in which a mother goes to sleep and stillbirth after 28 weeks of pregnancy. Further studies are needed to see whether women can easily change their sleep position in late pregnancy and whether changing the position a mother goes to sleep in reduces stillbirth. [ABSTRACT FROM AUTHOR]

Cardiovascular events (CVEs) are prevalent in patients with systemic lupus erythematosus (SLE), and it is the young women who are disproportionately at risk. The risk factors for accelerated cardiovascular disease remain unclear, with multiple studies producing conflicting results. In this paper, we aim to address both traditional and SLE-specific risk factors postulated to drive the accelerated vascular disease in this cohort. We also discuss the more recent hypothesis that adverse pregnancy outcomes in the form of maternal-placental syndrome and resultant preterm delivery could potentially contribute to the CVEs seen in young women with SLE who have fewer traditional cardiovascular risk factors. The pathophysiology of how placental-mediated vascular insufficiency and hypoxia (with the secretion of placenta-like growth factor (PlGF) and soluble fms-tyrosine-like kinase-1 (sFlt-1), soluble endoglin (sEng) and other placental factors) work synergistically to damage the vascular endothelium is discussed. Adverse pregnancy outcomes ultimately are a small contributing factor to the complex pathophysiological process of cardiovascular disease in patients with SLE. Future collaborative studies between cardiologists, obstetricians, obstetric physicians and rheumatologists may pave the way for a better understanding of a likely multifactorial aetiological process. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia and intrauterine fetal growth restriction (IUGR) are two of the most common causes of maternal and perinatal morbidity and mortality. Current methods of predicting those at most risk of these conditions remain relatively poor, and in clinical practice past obstetric history remains the most commonly used tool. Aspirin and, in women at risk of preeclampsia only, calcium have been demonstrated to have a modest effect on risk reduction. Several observational studies and randomised trials suggest that low molecular weight heparin (LMWH) therapy may confer some benefit. Methods/design: This is a multicentre open label randomised controlled trial to determine the effect of the LMWH, enoxaparin, on the prevention of recurrence of preeclampsia and/or IUGR in women at high risk due to their past obstetric history in addition to standard high risk care for all participants. Inclusion criteria: A singleton pregnancy >6+0 and <16+0 weeks gestation with most recent prior pregnancy with duration >12 weeks having; (1) preeclampsia delivered <36+0 weeks, (2) Small for gestational age (SGA) infant <10th customised birthweight centile delivered <36+0 weeks or, (3) SGA infant =3rd customised birthweight centile delivered at any gestation. Randomisation is stratified for maternal thrombophilia status and women are randomly assigned to 'standard high risk care' or 'standard high risk care' plus enoxaparin 40 mg from recruitment until 36+0 weeks or delivery, whichever occurs sooner. Standard high risk care includes the use of aspirin 100 mg daily and calcium 1000-1500 mg daily (unless only had previous SGA with no preeclampsia). The primary outcome is preeclampsia and/or SGA <5th customised birthweight centile. Analysis will be by intention to treat. Discussion: The EPPI trial has more focussed and clinically relevant inclusion criteria than other randomised trials with a more restricted composite primary outcome. The inclusion of standard use of aspirin (and calcium) for all participants will help to ensure that any differences observed in outcome are likely to be related to enoxaparin use. These data will make a significant contribution to future meta-analyses and systematic reviews on the use of LMWH for the prevention of placental mediated conditions. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is the leading cause of neonatal mortality and morbidity in developed countries. Whether continued tocolysis after 48 hours of rescue tocolysis improves neonatal outcome is unproven.Objectives: To evaluate the effectiveness of maintenance tocolytic therapy with oral nifedipine on the reduction of adverse neonatal outcomes and the prolongation of pregnancy by performing an individual patient data meta-analysis (IPDMA).Search Strategy: We searched PubMed, Embase, and Cochrane databases for randomised controlled trials of maintenance tocolysis therapy with nifedipine in preterm labour.Selection Criteria: We selected trials including pregnant women between 24 and 36(6/7)  weeks of gestation (gestational age, GA) with imminent preterm labour who had not delivered after 48 hours of initial tocolysis, and compared maintenance nifedipine tocolysis with placebo/no treatment.Data Collection and Analysis: The primary outcome was perinatal mortality. Secondary outcome measures were intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), infant respiratory distress syndrome (IRDS), prolongation of pregnancy, GA at delivery, birthweight, neonatal intensive care unit admission, and number of days on ventilation support. Pre-specified subgroup analyses were performed.Main Results: Six randomised controlled trials were included in this IPDMA, encompassing data from 787 patients (n = 390 for nifedipine; n = 397 for placebo/no treatment). There was no difference between the groups for the incidence of perinatal death (risk ratio, RR 1.36; 95% confidence interval, 95% CI 0.35-5.33), intraventricular haemorrhage (IVH) ≥ grade II (RR 0.65; 95% CI 0.16-2.67), necrotising enterocolitis (NEC) (RR 1.15; 95% CI 0.50-2.65), infant respiratory distress syndrome (IRDS) (RR 0.98; 95% CI 0.51-1.85), and prolongation of pregnancy (hazard ratio, HR 0.74; 95% CI 0.55-1.01).Conclusion: Maintenance tocolysis is not associated with improved perinatal outcome and is therefore not recommended for routine practice.Tweetable Abstract: Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation. [ABSTRACT FROM AUTHOR]

The CPR is the ratio of the fetal Middle Cerebral Artery Pulsatility index (MCA PI) to the Umbilical Artery Pulsatility index (UA PI) with gestation specific reference centiles available.1 2 A low CPR is now generally accepted as a proxy for late fetal growth restriction (FGR).3 4 This article is protected by copyright. All rights reserved. [ABSTRACT FROM AUTHOR]

Objective To determine maternal and fetal outcomes in women with mechanical heart valves managed with therapeutic dose enoxaparin during pregnancy. Design Retrospective audit. Setting Hospital-based high-risk antenatal clinics. Population Pregnant women with mechanical heart valves attending high-risk antenatal clinics, treated with enoxaparin (1 mg/kg twice daily) during pregnancy. Methods Women with mechanical heart valves treated with enoxaparin at any stage during pregnancy (1997–2008) identified using a database of women with mechanical heart valves attending the high-risk clinics and a prospective database of women prescribed enoxaparin for any indication during pregnancy. Main outcome measures Maternal outcomes included thromboembolic and haemorrhagic complications. Pregnancy and fetal outcomes included miscarriage, stillbirth, baby death and live birth, small-for-gestational-age infants, warfarin embryopathy and warfarin-related fetal loss. Results Thirty-one women underwent 47 pregnancies. In 34 pregnancies (72.3%), anticoagulation was with predominantly enoxaparin and 13 (27.7%) pregnancies women received mainly warfarin, with enoxaparin given in the first trimester and/or peri-delivery. Seven (14.9%) thrombotic complications occurred, of which five (10.6%) were associated with enoxaparin treatment. Non-compliance or sub-therapeutic anti-Xa levels contributed in each case. Antenatal and postpartum haemorrhagic complications occurred in eight (17%) and 15 (32%) pregnancies respectively. Of 35 pregnancies continuing after 20 weeks’ gestation, 96% (22/23) of women taking predominantly enoxaparin had a surviving infant compared with 75% (9/12) in women taking primarily warfarin. Four perinatal deaths occurred, three attributable to warfarin. Conclusions Compliance with therapeutic dose enoxaparin and aspirin during pregnancy in women with mechanical heart valves is associated with a low risk of valve thrombosis and good fetal outcomes, but close monitoring is essential. [ABSTRACT FROM AUTHOR]

Objectives To compare umbilical and uterine artery Doppler waveforms and fetal size at 20 weeks between smokers and nonsmokers. Design Prospective cohort study. Setting Auckland, New Zealand and Adelaide, Australia. Population Nulliparous participants in the Screening for Pregnancy Endpoints (SCOPE) study. Methods Self-reported smoking status was determined at 15 ± 1 weeks’ gestation. At the 20 ± 1 week anatomy scan, uterine and umbilical Doppler resistance indices (RI) and fetal measurements were compared between smokers and nonsmokers. Main outcomes measures Umbilical and mean uterine artery Doppler RI values, abnormal umbilical and uterine Doppler (RI > 90th centile) and fetal biometry. Results Among the 2459 women, 248 (10%) were smokers. Smokers had higher umbilical RI [0.75 (SD 0.06) versus 0.73 (0.06), P < 0.0001] and mean uterine RI [0.59 (0.09) versus 0.56 (0.10), P < 0.0001]. They were twice as likely to have an abnormal umbilical Doppler at 20 weeks compared with nonsmokers [ n = 35 (14.6%) versus n = 156 (7.2%), OR 2.21, 95% CI 1.49–3.27]. This effect remained significant after adjusting for age, ethnicity, marital status, employment and BMI (adjusted OR 1.62, 95% CI 1.03–2.54). Smokers were more likely to have an abnormal mean uterine RI [ n = 33 (13.7%) versus n = 198 (9.2%), OR 1.57, 95% CI 1.06–2.33], but this association was not significant after adjusting for confounders. Fetuses of women who smoked had a small reduction in femur length and estimated weight compared with nonsmokers. Conclusions At 20 weeks’ gestation, women who smoke have higher umbilical artery RI, a surrogate measure for an abnormal placental villous vascular tree. This may contribute to later fetal growth restriction among smokers. Further research is needed to explore the clinical significance of these findings. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate the relationship between blood pressure that is measured with the automated blood pressure monitor, Omron HEM-705CP (Omron Corporation, Tokyo, Japan), and mercury sphygmomanometry in normotensive and preeclamptic pregnant women.Study Design: Healthy pregnant women (n = 101 women) underwent mercury and home Omron HEM-705CP monitor blood pressure measurements at 10 to 14, 19 to 22, 27 to 30, and 35 to 37 weeks of gestation and 5 to 9 weeks after delivery. After routine mercury blood pressure recordings that were taken by midwives, women with preeclampsia (n = 45 women) measured their own blood pressure using an Omron HEM-705CP monitor (n = 212 recordings). In the longitudinal cohort, mean +/- 2 SD were calculated for blood pressure levels throughout pregnancy. Individual variation in home Omron minus office mercury throughout pregnancy was determined. In preeclampsia, back-to-back blood pressure measurements by the two methods were correlated and quantified as being within 5, 10, and 15 mm Hg. Bland-Altman plots were calculated, and the sensitivity of the Omron HEM-705CP monitor to detect hypertension that was identified by mercury sphygmomanometry was evaluated.Results: At 10 to 14, 19 to 22, 27 to 30, and 35 to 37 weeks of gestation, the upper limits for normal systolic blood pressure levels with the use of home Omron HEM-705CP monitor measurements were 132, 130, 133, and 138 mm Hg and for diastolic blood pressure levels were 82, 79, 81, and 88 mm Hg, respectively. For women who were normotensive and had preeclampsia (although group mean blood pressure values by mercury sphygmomanometry and Omron HEM-705CP monitor were similar), there were marked individual differences (90% of mild hypertension (140/90 mm Hg) but missed one third of hypertension with a blood pressure level of >160/100 mm Hg by mercury sphygmomanometry.Conclusion: Clinicians should be aware of the potential differences between blood pressure measurements with mercury sphygmomanometers and Omron HEM-705CP monitors in pregnancy. The Omron HEM-705CP monitor should not be used to monitor hypertension in preeclampsia. [ABSTRACT FROM AUTHOR]

Objectives: This study of the changes in cytokine concentrations in gestational tissues from women with term and preterm labor was undertaken to assess the extent of inflammatory activation associated with spontaneous labor and delivery.Study Design: Extracts of amniotic, chorionic-decidual, and placental tissues from women delivered at term before labor (n = 15), at term after labor (n = 15), and preterm (n = 31) were assayed for interleukin 1beta, interleukin 6, and interleukin 8.Results: In amniotic tissues of women delivered by spontaneous labor at term the median interleukin-6, interleukin-8, and interleukin-1beta concentrations were 3.8 to 5.4 times those of tissues from women delivered at term without labor (P <.05, Mann-Whitney U test). Interleukin-6 and interleukin-8 concentrations were also significantly increased (3. 3-4 times) in chorionic-decidual tissues. Marked increases (approximately 3-6 times) in the concentrations of all 3 cytokines were observed in both amniotic and chorionic-decidual tissues from women with preterm deliveries with respect to those from women with term deliveries after labor. Cytokine concentrations were significantly correlated within amniotic tissues from both women with term delivery after labor and women with preterm delivery and also in preterm chorionic-decidual tissues but not preterm placental tissues. Concentrations of cytokines in the tissues of women delivered preterm were not significantly affected by mode of delivery, treatment with antibiotics, or twin birth. In preterm tissues with evidence of intrauterine infection only amniotic interleukin-1beta concentrations were significantly elevated (P <. 05). Little or no labor-related change in cytokine concentrations was seen within placental tissues.Conclusions: Increased cytokine abundance in gestational membranes associated with labor supports the view that an inflammatory process is involved in both term and preterm labor. This process does not, however, appear to be evident in the villous placenta. [ABSTRACT FROM AUTHOR]