Migrant women, especially from Indian and African ethnicity, have a higher risk of stillbirth than native-born populations in high-income countries. Differential access or timing of ANC and the ...uptake of other services may play a role. We investigated the pattern of healthcare utilisation among migrant women and its relationship with the risk of stillbirth (SB)-antepartum stillbirth (AnteSB) and intrapartum stillbirth (IntraSB)-in Western Australia (WA).
A retrospective cohort study using de-identified linked data from perinatal, birth, death, hospital, and birth defects registrations through the WA Data Linkage System was undertaken. All (N = 260,997) non-Indigenous births (2005-2013) were included. Logistic regression analysis was used to estimate odds ratios and 95% CI for AnteSB and IntraSB comparing migrant women from white, Asian, Indian, African, Māori, and 'other' ethnicities with Australian-born women controlling for risk factors and potential healthcare-related covariates. Of all the births, 66.1% were to Australian-born and 33.9% to migrant women. The mean age (years) was 29.5 among the Australian-born and 30.5 among the migrant mothers. For parity, 42.3% of Australian-born women, 58.2% of Indian women, and 29.3% of African women were nulliparous. Only 5.3% of Māori and 9.2% of African migrants had private health insurance in contrast to 43.1% of Australian-born women. Among Australian-born women, 14% had smoked in pregnancy whereas only 0.7% and 1.9% of migrants from Indian and African backgrounds, respectively, had smoked in pregnancy. The odds of AnteSB was elevated in African (odds ratio OR 2.22, 95% CI 1.48-2.13, P < 0.001), Indian (OR 1.64, 95% CI 1.13-2.44, P = 0.013), and other women (OR 1.46, 95% CI 1.07-1.97, P = 0.016) whereas IntraSB was higher in African (OR 5.24, 95% CI 3.22-8.54, P < 0.001) and 'other' women (OR 2.18, 95% CI 1.35-3.54, P = 0.002) compared with Australian-born women. When migrants were stratified by timing of first antenatal visit, the odds of AnteSB was exclusively increased in those who commenced ANC later than 14 weeks gestation in women from Indian (OR 2.16, 95% CI 1.18-3.95, P = 0.013), Māori (OR 3.03, 95% CI 1.43-6.45, P = 0.004), and 'other' (OR 2.19, 95% CI 1.34-3.58, P = 0.002) ethnicities. With midwife-only intrapartum care, the odds of IntraSB for viable births in African and 'other' migrants (combined) were more than 3 times that of Australian-born women (OR 3.43, 95% CI 1.28-9.19, P = 0.014); however, with multidisciplinary intrapartum care, the odds were similar to that of Australian-born group (OR 1.34, 95% CI 0.30-5.98, P = 0.695). Compared with Australian-born women, migrant women who utilised interpreter services had a lower risk of SB (OR 0.51, 95% CI 0.27-0.96, P = 0.035); those who did not utilise interpreters had a higher risk of SB (OR 1.20, 95% CI 1.07-1.35, P < 0.001). Covariates partially available in the data set comprised the main limitation of the study.
Late commencement of ANC, underutilisation of interpreter services, and midwife-only intrapartum care are associated with increased risk of SB in migrant women. Education to improve early engagement with ANC, better uptake of interpreter services, and the provision of multidisciplinary-team intrapartum care to women specifically from African and 'other' backgrounds may reduce the risk of SB in migrants.
Research suggests that offspring of mothers who experience high levels of stress during pregnancy are more likely to have problems in neurobehavioral development. There is preliminary evidence that ...prenatal maternal stress (PNMS) is a risk factor for both autism and attention deficit hyperactivity disorder (ADHD), however most studies do not control for confounding factors and no study has investigated PNMS as a risk factor for behaviors characteristic of these disorders in early childhood. A population cohort of 2900 pregnant women were recruited before their 18th week of pregnancy and investigated prospectively. Maternal experience of stressful life events was assessed during pregnancy. When offspring were age 2 years, mothers completed the child behavior checklist. Multiple regression showed that maternal stressful events during pregnancy significantly predicted ADHD behaviors in offspring, after controlling for autistic traits and other confounding variables, in both males (p = 0.03) and females (p = 0.01). Similarly, stressful events during pregnancy significantly predicted autistic traits in the offspring after controlling for ADHD behaviors and confounding variables, in males only (p = 0.04). In conclusion, this study suggests that PNMS, in the form of typical stressful life events such as divorce or a residential move, show a small but significant association with both autistic traits and ADHD behaviors independently, in offspring at age 2 years, after controlling for multiple antenatal, obstetric, postnatal, and sociodemographic covariates. This finding supports future research using epigenetic, cross-fostering, and gene-environment interaction designs to identify the causal processes underlying this association.
Maternal stressful life events during pregnancy have been associated with immune dysregulation and increased risk for asthma and atopy in offspring. Few studies have investigated whether prenatal ...stress is associated with increased overall or specific infectious diseases in childhood, nor explored sex differences. We sought to examine the relationship between the nature and timing of maternal stress in pregnancy and hospitalisation with infection in offspring.
Between 1989 and 1992, exposure data on stressful life events were collected from pregnant women (Gen1) in the Raine Study at 18 and 34 weeks' gestation and linked to statutory state-wide hospital morbidity data. We examined associations between the number, category and timing of maternal prenatal stress events and overall and clinical groups of offspring (Gen2) infection-related hospitalisation until age 16 years, adjusting for maternal age, education, and smoking in pregnancy in addition to the presence of siblings at birth.
Of 2,141 offspring with complete stress in pregnancy data available, 1,089 had at least one infection-related hospitalisation, with upper respiratory tract infections the most common (n = 556). Each additional stressful life event during pregnancy was associated with increased risk in male offspring for hospitalisation with all infection types. There was little evidence of these associations in girls.
Increased exposure to stressful life events in utero is associated with sex-specific infection-related hospitalisations in childhood. Prenatal stress may adversely affect early immune development for boys and increase the risk of more severe infections. Mechanistic understanding would inform preventative interventions.
Abstract
Context
“Accelerated aging,” assessed by adult DNA methylation, predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether ...epigenetic age acceleration (assessed age, 17 years) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age.
Design
DNA methylation measured in peripheral blood provided two estimates of epigenetic age acceleration: intrinsic (IEAA; preserved across cell types) and extrinsic (EEAA; dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound, and dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors lipids, homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, inflammatory markers were assessed at age 17 years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients per 5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD risk factors, and CVD development.
Results
In 995 participants (49.6% female; age, 17.3 ± 0.6 years), EEAA (per 5 years) was associated with increased body mass index (BMI) of 2.4% (95% CI, 1.2% to 3.6%) and 2.4% (0.8% to 3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3% to 33%) in high-sensitivity C-reactive protein, 10% (4% to 17%) in interferon-γ–inducible protein of 10 kDa, and 4% (2% to 6%) in soluble TNF receptor 2, adjusted for BMI and HOMA-IR. EEAA (per 5 years) results in a 4% increase in hard endpoints of CVD by 47 years of age and a 3% increase, after adjustment for conventional risk factors.
Conclusions
Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle age CVD. Irrespective of whether this is cause or effect, assessing epigenetic age might refine disease prediction.
An estimate of biological age determined from peripheral blood DNA from ∼1000 adolescents may refine prediction of cardiovascular risk above and beyond traditional risk factors.
Background
Cervical cerclage has been used for decades to reduce preterm birth. The Shirodkar and McDonald cerclage are the most commonly used techniques with no current consensus on the preferred ...technique.
Objective
To compare the efficacy of the Shirodkar and McDonald cerclage techniques in preventing preterm birth.
Search Strategy
Studies were sourced from six electronic databases and reference lists.
Selection Criteria
Studies including women with a singleton pregnancy, requiring a cervical cerclage, using either the Shirodkar or McDonald technique that ran comparative analyses between the two techniques.
Data Collection and Analysis
The primary outcome was preterm birth before 37 weeks, with analyses at 28, 32, 34 and 35 weeks. Secondary data were also collected on neonatal, maternal and obstetric outcomes.
Main Results
Seventeen papers were included: 16 were retrospective cohort studies and one was a randomised controlled trial. The Shirodkar technique was significantly less likely to result in preterm birth before 37 weeks than the McDonald technique (relative risk RR 0.91, 95% CI 0.85–0.98). This finding was supported by a statistically significant reduction in rates of preterm birth before 35, 34 and 32 weeks, PPROM, difference in cervical length, cerclage to delivery interval, and an increase in birthweight in the Shirodkar group. No difference was seen in preterm birth rates <28 weeks, neonatal mortality, chorioamnionitis, cervical laceration or caesarean section rates. The RR for preterm birth prior to 37 weeks was no longer significant when sensitivity analyses were performed removing studies with a serious risk of bias. However, similar analyses removing studies that utilised adjunctive progesterone strengthened the primary outcome (RR 0.83, 95% CI 0.74–0.93).
Conclusion
Shirodkar cerclage reduces the rate of preterm birth prior to 35, 34 and 32 weeks’ gestation when compared with McDonald cerclage; however, the overall quality of the studies in this review is low. Further, large, well‐designed randomised controlled trials are required to address this important question to optimise care for women who may benefit from cervical cerclage.
This article includes Author Insights, a video available at: https://players.brightcove.net/3806881048001/default_default/index.html?videoId=6320301629112.
To investigate prevalence rates and the risk of ante- and intrapartum stillbirth in Western Australia with respect to maternal country of birth and ethnic origin.
Whole population retrospective ...cohort analysis of de-identified, linked routinely collected birth, perinatal and mortality data for all births to non-Indigenous women in WA during 2005-2013.
Crude and adjusted odds ratios (aORs) with 95% confidence intervals were estimated by logistic regression and adjusted for confounding factors, for all stillbirths, antepartum stillbirths and intrapartum stillbirths, stratified by migrant status and ethnic background (white, Asian, Indian, African, Māori, other).
Women born overseas were more likely to have a stillbirth than Australian-born women (aOR, 1.26; 95% CI, 1.09-1.37). There was no significant difference for any type of stillbirth between Australian-born women of white and non-white backgrounds, but non-white migrant women were more likely than white migrants to have a stillbirth (OR, 1.42; 95% CI, 1.19-1.70). Compared with Australian-born women, migrants of Indian (aOR, 1.71; 95% CI, 1.17-2.47), African (aOR, 2.12; 95% CI, 1.46-3.08), and "other" ethnic origins (aOR, 1.43; 95% CI, 1.06-1.93) were more likely to have antepartum stillbirths; women of African (aOR, 5.08; 95% CI, 3.14-8.22) and "other" (aOR, 1.86; 95% CI, 1.15-3.00) background were more likely to have an intrapartum stillbirth.
Immigrants of African or Indian background appear to be at greater risk of ante- and intrapartum stillbirth in WA. Specific strategies are needed reduce the prevalence of stillbirth in these communities.
IntroductionMultiple cohort studies have been established to investigate the impact of early life factors on development and health outcomes. In Australia the majority of these studies were ...established more than 20 years ago and, although longitudinal in nature, are inherently susceptible to socioeconomic, environmental and cultural influences which change over time. Additionally, rapid leaps in technology have increased our understanding of the complex role of gene–environment interactions in life course health, highlighting the need for new cohort studies with repeated biological sampling and in-depth phenotype data across the first 1000 days of life from conception.Methods and analysisThe Newcastle 1000 (NEW1000) Study, based in the regional city of Newcastle, New South Wales, was developed after an extensive consultation process involving 3 years of discussion with key stakeholders and healthcare consumer organisations and seven healthcare consumer workshops. This prospective population-based pregnancy cohort study will recruit 500 families per year for 5 years, providing detailed, longitudinal, multisystem phenotyping, repeated ultrasound measures and serial sample collection to investigate healthcare consumer identified health outcomes of priority. Stage 1 will involve recruitment of pregnant participants and their partners at 14 weeks gestation, with dense phenotype data and biological samples collected at 14, 20, 28 and 36 weeks gestation and serial ultrasound measures at 20, 28, 36 and 40 weeks, with postpartum follow-up at 6 weeks and 6 months. Biological samples will be used for biomarker discovery and sequencing of the genome, transcriptome, epigenome, microbiome and metabolome.Ethics and disseminationEthics approval was obtained from Hunter New England Local Health District Ethics Committee (2020/ETH02881). Outcomes will be published in peer-reviewed journals, disseminated to participants through the NEW1000 website, presented at scientific conferences, and written reports to local, state and national government bodies and key stakeholders in the healthcare system to inform policy and evidence-based practice.
The heterogeneity of spontaneous preterm birth (SPTB) requires an interdisciplinary approach to determine potential predictive risk factors of early delivery. The aim of this study was to investigate ...maternal whole blood gene expression profiles associated with spontaneous preterm birth (SPTB, <37 weeks) in asymptomatic pregnant women. The study population was a matched subgroup of women (51 SPTBs, 114 term delivery controls) who participated in the All Our Babies community based cohort in Calgary (n = 1878). Maternal blood at 17-23 (sampling time point 1, T1) and 27-33 weeks of gestation (T2) were collected. Total RNA was extracted and microarray was performed on 326 samples (165 women). Univariate analyses determined significant clinical factors and differential gene expression associated with SPTB. Thirteen genes were validated using qRT-PCR. Three multivariate logistic models were constructed to identify gene expression at T1 (Model A), T2 (Model B), and gene expression fold change from T1 to T2 (Model C) associated with SPTB. All models were adjusted for clinical factors. Model C can predict SPTB with 65% sensitivity and 88% specificity in asymptomatic women after adjusting for history of abortion and anaemia (occurring before T2). Clinical data enhanced the sensitivity of the Models to predict SPTB. In conclusion, clinical factors and whole blood gene expression are associated with SPTB in asymptomatic women. An effective screening tool for SPTB during pregnancy would enable targeted preventive approaches and personalised antenatal care.
The onset of preterm labor is associated with inflammation. Previous studies suggested that this is distinct from the inflammation observed during term labor. Our previous work on 44 genes ...differentially expressed in myometria in term labor demonstrated a different pattern of gene expression from that observed in preterm laboring and nonlaboring myometria. We found increased expression of inflammatory genes in preterm labor associated with chorioamnionitis, but in the absence of chorioamnionitis observed no difference in gene expression in preterm myometria regardless of laboring status, suggesting that preterm labor is associated with different myometrial genes or signals originating from outside the myometrium. Given that a small subset of genes were assessed, this study aimed to use RNA sequencing and bioinformatics to assess the myometrial transcriptome during preterm labor in the presence and absence of chorioamnionitis.
This study aimed to comprehensively determine protein-coding transcriptomic differences between preterm nonlaboring and preterm laboring myometria with and without chorioamnionitis.
Myometria were collected at cesarean delivery from preterm patients not in labor (n=16) and preterm patients in labor with chorioamnionitis (n=8) or without chorioamnionitis (n=6). Extracted RNA from myometrial tissue was prepared and sequenced using Illumina NovaSeq. Gene expression was quantified by mapping the sequence reads to the human reference genome (hg38). Differential gene expression analysis, gene set enrichment analysis, and weighted gene coexpression network analysis were used to comprehensively interrogate transcriptomic differences and their associated biology.
Differential gene expression analysis comparing preterm patients in labor with chorioamnionitis with preterm patients not in labor identified 931 differentially expressed genes, whereas comparing preterm patients in labor without chorioamnionitis with preterm patients not in labor identified no statistically significant gene expression changes. In contrast, gene set enrichment analysis and weighted gene coexpression network analysis demonstrated that preterm labor with and without chorioamnionitis was associated with enrichment of pathways involved in activation of the innate immune system and inflammation, and activation of G protein-coupled receptors. Key genes identified included chemotactic CYP4F3, CXCL8, DOCK2, and IRF1 in preterm labor with chorioamnionitis and CYP4F3, FCAR, CHUK, and IL13RA2 in preterm labor without chorioamnionitis. There was marked overlap in the pathways enriched in both preterm labor subtypes.
Differential gene expression analysis demonstrated that myometria from preterm patients in labor without chorioamnionitis and preterm patients not in labor were transcriptionally similar, whereas the presence of chorioamnionitis was associated with marked gene changes. In contrast, comprehensive bioinformatic analysis indicated that preterm labor with or without chorioamnionitis was associated with innate immune activation. All causes of preterm labor were associated with activation of the innate immune system, but this was more marked in the presence of chorioamnionitis. These data suggest that anti-inflammatory therapy may be relevant in managing preterm labor of all etiologies.
We hypothesised that antenatal exposure to ubiquitous phthalates may lead to an earlier menarche and a lower prevalence of polycystic ovarian syndrome (PCOS) and polycystic ovarian morphology (PCO) ...in adolescence. The Western Australian Pregnancy Cohort (Raine) Study recruited 3000 women at 18 weeks of gestation in 1989-1991, 1377 had antenatal serum stored without thawing at -80 °C. An unselected subset was evaluated in the early follicular phase for PCO and PCOS by ultrasound and serum evaluation in adolescence. Serum was analysed for anti-Müllerian hormone (AMH), inhibin B, sex hormone binding globulin (SHBG), testosterone, androstenedione and DHEAS. Four hundred microlitres of the frozen maternal serum underwent isotope-diluted liquid chromatography-tandem mass spectrometry, with preceding enzymatic deconjugation followed by solid-phase extraction to determine phthalate exposure. Two hundred and forty four girls attended assessment and most common phthalate metabolites were detectable in the majority of the 123 samples available. Several phthalates were negatively associated with maternal SHBG, and associations with maternal androgens were less consistent. The sum of the metabolites of di-(2-ethylhexyl) phthalate was associated with a non-significant tendency towards an earlier age at menarche (P=0.069). Uterine volume was positively associated with mono-(carboxy-iso-octyl) phthalate (P=0.018). Exposure to monoethyl phthalate (MEP) and the sum of all phthalate metabolites (Σall phth.m) were protective against PCOS in adolescence (P=0.001 and P=0.005 respectively). There were negative associations of MEP with PCO (P=0.022) and of MEP with serum AMH (P=0.031). Consequently, our data suggest that antenatal exposure to environmental phthalates may be associated with oestrogenic and/or anti-androgenic reproductive effects in adolescent girls.
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