The duration of sexual relationship and its effects on adverse pregnancy outcomes

This study aims to determine if a short duration of sexual relationship is more common among women who experience adverse pregnancy outcomes including gestational hypertension (GHT), preeclampsia, small for gestational age (SGA) pregnancies and spontaneous preterm birth (sPTB) with or without abnormal uterine artery Doppler compared to women who have uncomplicated pregnancies. 5591 nulliparous women from the Screening for Pregnancy Endpoints (SCOPE) study were included. The risk for pregnancy complications for women who had a duration of sexual relationship of ≤3 months, 4–6 months, 7–9 months, 10–12 months was compared with women who had a duration of sexual relationship of >12 months. Uterine artery Doppler was performed at 20 ± 1 weeks’ gestation. A short duration of sexual relationship (≤3 months) was more common among women with SGA in the presence of abnormal uterine artery Doppler [9.8% vs 3.0%, aOR (95% CI) 3.4 (1.6–7.08] compared to women who had uncomplicated pregnancies. A short duration of sexual relationship (≤3 months) was also more common among women who had abnormal uterine artery Doppler compared to those with normal uterine artery Doppler [6.1% vs 3.1%, aOR (95% CI) = 2.1 (1.4–3.2)]. A short duration of sexual relationship was not associated with preeclampsia after adjusting for confounders. A short duration of sexual relationship is more common among women who deliver SGA infants with features of placental insufficiency as indicated by abnormal uterine artery Doppler.Prabha Andraweera, Claire T. Roberts, Shalem Leemaqz, Lesley McCowan, Jenny Myers, Louise C. Kenny, James Walker, Lucilla Poston, Gus Dekker on behalf of the SCOP

Sex- and growth-specific characteristics of small for gestational age infants: a prospective cohort study

Background: Asymmetric fetal growth and male sex are both associated with adverse neonatal outcome. However, less is known about the influence of asymmetric growth and fetal sex within SGA neonates, a group of infants already at increased risk for adverse neonatal outcomes. The aim of the present study was to provide insight into variance in risk factors for SGA in a fetal sex- and growth symmetry-specific way. Methods: For this prospective, multicenter cohort study, data from the Screening for Pregnancy Endpoints (SCOPE) study were used with 5628 nulliparous participants, of which 633 (11.3%) pregnancies were complicated with SGA and 3376 (60.0%) women had uncomplicated pregnancies. Association between risk factors for SGA, SGA subgroups, and uncomplicated pregnancies were assessed with multivariable analyses. Results: Prevalence of asymmetric growth varied from 45.8% of SGA infants to 5.5% of infants with a customized birthweight > 90th percentile (p < 0.001). Significantly more SGA males had asymmetric growth compared to SGA female infants (51.2% vs 40.4%, p = 0.009). Maternal pre-pregnancy diet and BMI < 20 and ≥ 30 were significantly associated with symmetric SGA but not with asymmetric SGA. Asymmetric SGA infants had not only lower customized birthweight percentile (4.4 (SD 2.8) vs 5.0 (SD 3.0), p < 0.001), but also lower rates of stillbirth (p = 0.041) and less often Apgar scores < 7 (p = 0.060).  Conclusions: Among SGA infants, low customized birthweight percentiles and male sex are associated with asymmetric growth. Only symmetric SGA is significantly associated with maternal risk factors in early pregnancy. There is a substantial variance in risk factors and neonatal outcomes for SGA based on growth symmetry, implying a different pathogenesis

Maternal marijuana use has independent effects on risk for spontaneous preterm birth but not other common late pregnancy complications

Widespread legalisation of marijuana raises safety concerns for its use in pregnancy. This study investigated the association of marijuana use prior to and during pregnancy with pregnancy outcomes in a prospective cohort of 5588 nulliparous women from the international SCOPE study. Women were assessed at 15 ± 1 and 20 ± 1 weeks’ gestation. Cases [278 Preeclampsia, 470 gestational hypertension, 633 small-for-gestational-age, 236 spontaneous preterm births (SPTB), 143 gestational diabetes] were compared separately with 4114 non-cases. Although the numbers are small, continued maternal marijuana use at 20 weeks’ gestation was associated with SPTB independent of cigarette smoking status [adj OR 2.28 (95% CI:1.45–3.59)] and socioeconomic index (SEI) [adj OR 2.17 (95% CI:1.41–3.34)]. When adjusted for maternal age, cigarette smoking, alcohol and SEI, continued maternal marijuana use at 20 weeks’ gestation had a greater effect size [adj OR 5.44 (95% CI 2.44–12.11)]. Our data indicate that increasing use of marijuana among young women of reproductive age is a major public health concern

Haemolysis Detection in MicroRNA-Seq from Clinical Plasma Samples

The abundance of cell-free microRNA (miRNA) has been measured in blood plasma and proposed as a source of novel, minimally invasive biomarkers for several diseases. Despite improvements in quantification methods, there is no consensus regarding how haemolysis affects plasma miRNA content. We propose a method for haemolysis detection in miRNA high-throughput sequencing (HTS) data from libraries prepared using human plasma. To establish a miRNA haemolysis signature we tested differential miRNA abundance between plasma samples with known haemolysis status. Using these miRNAs with statistically significant higher abundance in our haemolysed group, we further refined the set to reveal high-confidence haemolysis association. Given our specific context, i.e., women of reproductive age, we also tested for significant differences between pregnant and non-pregnant groups. We report a novel 20-miRNA signature used to identify the presence of haemolysis in silico in HTS miRNA-sequencing data. Further, we validated the signature set using firstly an all-male cohort (prostate cancer) and secondly a mixed male and female cohort (radiographic knee osteoarthritis). Conclusion: Given the potential for haemolysis contamination, we recommend that assays for haemolysis detection become standard pre-analytical practice and provide here a simple method for haemolysis detection

The association of maternal <i>ACE A11860G</i> with small for gestational age babies is modulated by the environment and by fetal sex: a multicentre prospective casecontrol study

We aimed to determine whether the <i>ACE A11860G</i> genotype is associated with small for gestational age babies (SGA) and to determine whether the association is affected by environmental factors and fetal sex. Overall, 3234 healthy nulliparous women with singleton pregnancies, their partners and babies were prospectively recruited in Adelaide, Australia and Auckland, New Zealand. Data analyses were confined to 2121 Caucasian parent–infant trios, among which 216 were pregnancies with SGA infants and 1185 were uncomplicated pregnancies. Women with the <i>ACE A11860G</i> GG genotype in the combined and Adelaide cohorts had increased risk for SGA [odds ratios (OR) 1.5, 95% confidence interval (CI) 1.1–2.1 and OR 2.0, 95% CI 1.3–3.3, respectively) and delivered lighter babies (<i>P</i> = 0.02; <i>P</i> = 0.007, respectively) compared with those with AA/AG genotypes. The maternal <i>ACE A11860G</i> GG genotype was associated with higher maternal plasma ACE concentration at 15 weeks' gestation than AA/AG genotypes (<i>P</i> < 0.001). When the Adelaide cohort was stratified by maternal socio-economic index (SEI) and pre-pregnancy green leafy vegetable intake, the ACE <i>A11860G</i> GG genotype was only associated with an increased risk for SGA (OR 4.9, 95% CI 1.8–13.4 and OR 3.3, 95% CI 1.6–7.0, respectively) and a reduction in customized birthweight centile (<i>P</i> = 0.006 and <i>P</i> = 0.03) if superimposed on maternal SEI <34 or pre-pregnancy green leafy vegetable intake <1 serve/day. Furthermore, the associations of maternal <i>ACE A11860G</i> with customized birthweight centile observed among Adelaide women with SEI <34 or pre-pregnancy green leafy vegetable intake <1 serve/day were female specific. The current study identified a novel association of maternal <i>ACE A11860G</i> with SGA. More interestingly, this association was modified by environmental factors and fetal sex, suggesting <i>ACE A11860G</i>–environment–fetal sex interactions

Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA

ABSTRACTAltered epigenetic mechanisms have been previously reported in growth restricted offspring whose mothers experienced environmental insults during pregnancy in both human and rodent studies. We previously reported changes in the expression of the DNA methyltransferase Dnmt3a and the imprinted genes Cdkn1c (Cyclin-dependent kinase inhibitor 1C) and Kcnq1 (Potassium voltage-gated channel subfamily Q member 1) in the kidney tissue of growth restricted rats whose mothers had uteroplacental insufficiency induced on day 18 of gestation, at both embryonic day 20 (E20) and postnatal day 1 (PN1). To determine the mechanisms responsible for changes in the expression of these imprinted genes, we investigated DNA methylation of KvDMR1, an imprinting control region (ICR) that includes the promoter of the antisense long non-coding RNA Kcnq1ot1 (Kcnq1 opposite strand/antisense transcript 1). Kcnq1ot1 expression decreased by 51% in growth restricted offspring compared to sham at PN1. Interestingly, there was a negative correlation between Kcnq1ot1 and Kcnq1 in the E20 growth restricted group (Spearman’s ρ = 0.014). No correlation was observed between Kcnq1ot1 and Cdkn1c expression in either group at any time point. Additionally, there was a 11.25% decrease in the methylation level at one CpG site within KvDMR1 ICR. This study, together with others in the literature, supports that long non-coding RNAs may mediate changes seen in tissues of growth restricted offspring