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Maternal obesity is an important risk factor for childhood obesity and influences the prevalence of metabolic diseases in offspring. As childhood obesity is influenced by postnatal factors, it is critical to determine whether children born to women with obesity during pregnancy show alterations that are detectable at birth. Epigenetic mechanisms such as DNA methylation modifications have been proposed to mediate prenatal programming. We investigated DNA methylation signatures in male and female infants from mothers with a normal Body Mass Index (BMI 18.5–24.9 kg/m 2 ) compared to mothers with obesity (BMI≥30 kg/m 2 ). BMI was measured during the first prenatal visit from women recruited into the Ontario Birth Study (OBS) at Mount Sinai Hospital in Toronto, ON, Canada. DNA was extracted from neonatal dried blood spots collected from heel pricks obtained 24 hours after birth at term (total n = 40) from women with a normal BMI and women with obesity matched for parity, age, and neonatal sex. Reduced representation bisulfite sequencing was used to identify genomic loci associated with differentially methylated regions (DMRs) in CpG-dense regions most likely to influence gene regulation. DMRs were predominantly localized to intergenic regions and gene bodies, with only 9% of DMRs localized to promoter regions. Genes associated with DMRs were compared to those from a large publicly available cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC; total n = 859). Hypergeometric tests revealed a significant overlap in genes associated with DMRs in the OBS and ALSPAC cohorts. PTPRN2 , a gene involved in insulin secretion, and MAD1L1 , which plays a role in the cell cycle and tumor suppression, contained DMRs in males and females in both cohorts. In males, KEGG pathway analysis revealed significant overrepresentation of genes involved in endocytosis and pathways in cancer, including IGF1R , which was previously shown to respond to diet-induced metabolic stress in animal models and in lymphocytes in the context of childhood obesity. These preliminary findings are consistent with Developmental Origins of Health and Disease paradigm, which posits that adverse prenatal exposures set developmental health trajectories.

In this trial comparing less-tight control of hypertension (target diastolic blood pressure, 100 mm Hg) with tight control (85 mm Hg) among pregnant women, rates of pregnancy loss, high-level neonatal care, and serious maternal complications were similar between groups. Almost 10% of pregnant women have hypertension; hypertension is preexisting in 1%, gestational hypertension without proteinuria develops in 5 to 6%, and preeclampsia develops in 2%. 1 Preexisting hypertension and gestational hypertension before 34 weeks are associated with an increased risk of perinatal and maternal complications. 2 – 4 Blood-pressure targets for women with nonsevere hypertension during pregnancy are much debated. Relevant randomized, controlled trials have been small and of moderate or poor quality; tight control (the use of antihypertensive therapy to normalize blood pressure) has been associated with maternal benefits (e.g., a decrease in the frequency of severe hypertension and possibly in . . .

ObjectiveThe study aims to assess the effect of intrauterine metformin exposure on offspring adiposity measures in childhood.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase and Cochrane Central were searched from inception to 4 October 2024.Eligibility criteria for selecting studiesFollow-up studies of randomised-controlled trials and observational studies involving metformin use in pregnancy for any insulin-resistant maternal condition were included.Data extraction and synthesisTwo reviewers independently extracted data and completed risk-of-bias assessments using either Cochrane Risk-Of-Bias tool V.2 or Risk of Bias in Non-Randomised Studies of Exposure depending on study design. Meta-analyses were conducted using the generic inversed variance method in a random-effects model. Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess certainty of evidence.Results18 studies reporting on 7975 children with metformin exposure in utero and over 1 million children without metformin exposure were included. At the oldest age of follow-up reported (weighted mean age of 4.4 years), children with metformin exposure for any maternal indication had comparable body mass index (BMI) with their non-exposed peers (standardised mean difference (SMD) −0.02; 95% CI: −0.11, 0.07; low certainty). When stratified by age at follow-up, while metformin-exposed children had slightly higher BMI at 1–3 years of age (SMD 0.15; 95% CI: 0.04, 0.27; low certainty), no difference remained between the two groups by ages 3–6 and 6–11 years. When stratified by maternal diagnosis, no difference in BMI was found in the diabetes and obesity subgroups, while in the polycystic ovary syndrome subgroup metformin-exposed children were heavier than non-exposed peers (SMD 0.31; 95% CI: 0, 0.62; low certainty). No difference was seen in overweight, obesity or waist circumference.ConclusionsMetformin-exposed children did not differ in adiposity measures compared with their non-exposed peers in later childhood. This adds to the growing body of evidence supporting the long-term safety of metformin use in pregnancy.PROSPERO registration numberCRD42023394464.

Background Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally. Methods This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. Findings We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS. Conclusions The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae.

Background Meaningful performance measurement requires indicators to be scientifically robust and strategically focused. For many circumpolar states, indicators aligned with national strategies may ignore the priorities of northern, remote, or Indigenous populations. The aim of this project was to identify contextually appropriate performance indicators for maternity care in circumpolar regions. Methods Fourteen maternity care and health systems experts participated in a modified Delphi consensus process. The list of proposed indicators was derived from a previously published scoping review. Fourteen participants rated each proposed indicator according to importance, circumpolar relevance, validity, and reliability and suggested additional indicators for consideration. Results Consensus was achieved after two rounds, as measured by a Cronbach’s alpha of 0.87. Eleven indicators, many of which represented physical health outcomes, were ranked highly on all four criteria. Twenty-nine additional indicators, largely focused on social determinants of health, health care responsiveness, and accessibility, were identified for further research. Travel for care, cultural safety and upstream structural determinants of health were identified as important themes. Conclusions This study identified the important gaps between current performance measurement strategies and the context and values that permeate maternal-child health in circumpolar regions. The indicators identified in this study provide an important foundation for ongoing work. We recommend that future work encompass an appreciation for the intersectoral nature of social, structural, and colonial determinants of maternal-child health in circumpolar regions.

Background Angiogenesis is essential for placental growth and development. Improper placental vascular development can reduce blood flow to the fetus and increase the risk of adverse pregnancy and birth outcomes. The objectives of this study were to examine the effect of prenatal vitamin D supplementation on placental angiogenic factors and terminal villi, and associations between angiogenic factors, terminal villi and birth outcomes. Methods This is a secondary analysis using data and specimens from the Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh ( n  = 1298). Participants were enrolled at 17–24 weeks gestation and randomized to receive (IU/week): placebo, 4200, 16,800 or 28,000 vitamin D 3 supplement until birth. Newborns and placentas were measured at birth. We examined a subset of randomly selected placentas ( n  = 80). Tissue sections were evaluated for vascular endothelial growth factor (VEGF-A) and placental growth factor (PlGF) using immunofluorescence. We measured intensity and percent area of expression for angiogenic factors, and total number and surface area of terminal villi. Vitamin D treatment effect was estimated using ANOVA. Regression models were used to assess associations of markers of placental angiogenesis with birth outcomes. Interactions by infant sex were examined. Results The overall mean (SD) percent area of expression was 17.0 (4.0) for VEGF-A and 15.0 (1.9) for PlGF. The mean (SD) number of terminal villi was 39 (15) per 12 in 2 , and surface area was 0.096 (0.040) in 2 . Vitamin D treatment groups were similar to placebo for all outcomes. No associations were observed between angiogenic factors or terminal villi placental and birth outcomes. Conclusions Vitamin D supplementation starting from mid-pregnancy until birth did not affect expression of two key angiogenic factors or terminal villi in the placenta. Placental angiogenic factors or terminal villi did not have an association with birth outcomes. These results do not support a role of maternal vitamin D starting mid-pregnancy in impacting placental development.

Abstract Twin pregnancy is a risk factor for postpartum depression and anxiety. Whether this translates into a higher risk of severe maternal mental illness in the short-term or long-term is unknown. This study was a population-based retrospective cohort study, using linked health administrative databases for the entire province of Ontario, Canada. Included were primiparas aged 15–50 years with a twin vs. singleton hospital livebirth, between January 1, 2003, and March 31, 2019. Propensity-score inverse probability of treatment weights accounted for potential confounding. The primary outcome of severe mental illness comprised a composite of an emergency department visit or hospitalization for mental illness or self-injury, or death by suicide, assessed in the first year after birth, and in long-term follow-up, up to 17 years thereafter. Fifteen thousand twenty-four twin and 796,804 (15,022 weighted) singleton births were included, with a mean (IQR) duration of follow-up of 9 (5–13) years. After weighting, the mean (SD) maternal age was 31.3 (5.5) years. In the first 365 days postpartum, severe mental illness occurred at rates of 10.5 and 8.7 per 1000 person-years in twin and singleton mothers, respectively, corresponding to a hazard ratio (HR) of 1.21 (95% CI 1.07–1.47). From 366 days onward, the corresponding figures were 5.9 and 6.1 per 1000 person-years (HR 0.96, 95% CI 0.89–1.04). Individuals with a twin birth appear to experience an increased risk for severe mental illness in the first year postpartum, but not thereafter. This suggests a potential need for targeted counselling and mental health services for mothers within the first year after birth.

One course of antenatal corticosteroids reduces the risk of respiratory distress syndrome and neonatal death. Weekly doses given to women who remain undelivered after a single course may have benefits (less respiratory morbidity) or cause harm (reduced growth in utero). We aimed to find out whether multiple courses of antenatal corticosteroids would reduce neonatal morbidity and mortality without adversely affecting fetal growth. 1858 women at 25–32 weeks' gestation who remained undelivered 14–21 days after an initial course of antenatal corticosteroids and continued to be at high risk of preterm birth were randomly assigned to multiple courses of antenatal corticosteroids (n=937) or placebo (n=921), every 14 days until week 33 or delivery, whichever came first. The primary outcome was a composite of perinatal or neonatal mortality, severe respiratory distress syndrome, intraventricular haemorrhage (grade III or IV), periventricular leucomalacia, bronchopulmonary dysplasia, or necrotising enterocolitis. Analysis was by intention to treat. All patients and caregivers were unaware of the treatment given. This trial is registered as number ISRCTN2654148. Infants exposed to multiple courses of antenatal corticosteroids had similar morbidity and mortality to those exposed to placebo (150 [12·9%] vs 143 [12·5%]). Those receiving multiple doses of corticosteroids also weighed less at birth than those exposed to placebo (2216 g vs 2330 g, p=0·0026), were shorter (44·5 cm vs 45·4 cm, p<0·001), and had a smaller head circumference (31·1 cm vs 31·7 cm, p<0·001). Multiple courses of antenatal corticosteroids, every 14 days, do not improve preterm-birth outcomes, and are associated with a decreased weight, length, and head circumference at birth. Therefore, this treatment schedule is not recommended. Canadian Institutes of Health Research.

ObjectivesRates of age-associated severe maternal morbidity (SMM) have increased in Canada, and an association with neighbourhood income is well established. Our aim was to examine SMM trends according to neighbourhood material deprivation quintile, and to assess whether neighbourhood deprivation effects are moderated by maternal age.Design, setting and participantsA population-based retrospective cohort study using linked administrative databases in Ontario, Canada. We included primiparous women with a live birth or stillbirth at ≥20 weeks’ gestational age.Primary outcomeSMM from pregnancy onset to 42 days postpartum. We calculated SMM rate differences (RD) and rate ratios (RR) by neighbourhood material deprivation quintile for each of four 4-year cohorts from 1 April 2002 to 31 March 2018. Log-binomial multivariable regression adjusted for maternal age, demographic and pregnancy-related variables.ResultsThere were 1 048 845 primiparous births during the study period. The overall rate of SMM was 18.0 per 1000 births. SMM rates were elevated for women living in areas with high material deprivation. In the final 4-year cohort, the RD between women living in high vs low deprivation neighbourhoods was 3.91 SMM cases per 1000 births (95% CI: 2.12 to 5.70). This was higher than the difference observed during the first 4-year cohort (RD 2.09, 95% CI: 0.62 to 3.56). SMM remained associated with neighbourhood material deprivation following multivariable adjustment in the pooled sample (RR 1.16, 95% CI: 1.11 to 1.21). There was no evidence of interaction with maternal age.ConclusionSMM rate increases were more pronounced for primiparous women living in neighbourhoods with high material deprivation compared with those living in low deprivation areas. This raises concerns of a widening social gap in maternal health disparities and highlights an opportunity to focus risk reduction efforts toward disadvantaged women during pregnancy and postpartum.

A 44-year-old pregnant woman (gravida 6 para 3) received counseling after being bitten by a bat during her 26th week of pregnancy. The patient reported that a bat had flown down and bitten her hand in broad daylight. The patient's partner hit the bat, which fell to the ground. The patient thoroughly washed the wound and sought immediate medical attention. The bat's carcass was kept for testing. The patient was immediately started on a postexposure prophylaxis schedule, including both rabies vaccine and rabies immunoglobulin. The bat was sent to the Canadian Food Inspection Agency Centre of Excellence for Rabies in Ottawa, Ontario, where a direct fluorescent antibody test confirmed that the bat had been rabid. The patient completed treatment -- four doses of rabies vaccine and one dose of rabies immunoglobulin. Two cohort studies that documented the results of rabies postexposure prophylaxis during pregnancy found no negative outcomes.