Search

Background: Maternal obesity is associated with stillbirth, but uncertainty persists around the effects of higher obesity classes. We sought to compare the risk of stillbirth associated with maternal obesity alone versus maternal obesity and additional or undiagnosed factors contributing to high-risk pregnancy. Methods: We conducted a retrospective cohort study using the Better Outcomes Registry and Network (BORN) for singleton hospital births in Ontario between 2012 and 2018. We used multivariable Cox proportional hazard regression and logistic regression to evaluate the relationship between prepregnancy maternal body mass index (BMI) class and stillbirth (reference was normal BMI). We treated maternal characteristics and obstetrical complications as independent covariates. We performed mediator analyses to measure the direct and indirect effects of BMI on stillbirth through major common-pathway complications. We used fully adjusted and partially adjusted models, representing the impact of maternal obesity alone and maternal obesity with other risk factors on stillbirth, respectively. Results: We analyzed data on 681 178 births between 2012 and 2018, of which 1956 were stillbirths. Class I obesity was associated with an increased incidence of stillbirth (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.35–1.78). This association was stronger for class III obesity (adjusted HR 1.80, 95% CI 1.44–2.24), and strongest for class II obesity (adjusted HR 2.17, 95% CI 1.83–2.57). Plotting point estimates for odds ratios, stratified by gestational age, showed a marked increase in the relative odds for stillbirth beyond 37 weeks' gestation for those with obesity with and without other risk factors, compared with those with normal BMI. The impact of potential mediators was minimal. Interpretation: Maternal obesity alone and obesity with other risk factors are associated with an increased risk of stillbirth. This risk increases with gestational age, especially at term. [ABSTRACT FROM AUTHOR]

Objective: Gestational weight gain (GWG) outside recommended ranges can negatively impact both the woman and child. The long-term effects of below-recommended or above-recommended GWG on the child are unclear. Methods: This retrospective cohort study used a population-based birth registry of 258,005 live births to evaluate the relationship between maternal GWG and paediatric health service use. Results: The results suggest below recommended GWG in underweight women in particular is associated with an increased rate of hospitalizations and specialist visits for the child in the first 24 months. Conclusion: Findings indicate that GWG may impact paediatric outcomes in ways that depend on pre-pregnancy body mass index, as derived from maternal height and weight measures. Significance: The findings of this study are significant as they expand previously published research and suggest that gestational weight gain below recommended levels in underweight women contributes to pediatric health service utilization as the child grows. These findings have important implications and should influence prenatal counselling on gestational weight gain in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Common postpartum mental health (PMH) disorders such as depression and anxiety are preventable, but determining individual-level risk is difficult. Aims: To create and internally validate a clinical risk index for common PMH disorders. Method: Using population-based health administrative data in Ontario, Canada, comprising sociodemographic, clinical and health service variables easily collectible from hospital birth records, we developed and internally validated a predictive model for common PMH disorders and converted the final model into a risk index. We developed the model in 75% of the cohort (n = 152 362), validating it in the remaining 25% (n = 75 772). Results: The 1-year prevalence of common PMH disorders was 6.0%. Independently associated variables (forming the mnemonic PMH CAREPLAN) that made up the risk index were: (P) prenatal care provider; (M) mental health diagnosis history and medications during pregnancy; (H) psychiatric hospital admissions or emergency department visits; (C) conception type and complications; (A) apprehension of newborn by child services (newborn taken into care); (R) region of maternal origin; (E) extremes of gestational age at birth; (P) primary maternal language; (L) lactation intention; (A) maternal age; (N) number of prenatal visits. In the index (scored 0–39), 1-year common PMH disorder risk ranged from 1.5 to 40.5%. Discrimination (C-statistic) was 0.69 in development and validation samples; the 95% confidence interval of expected risk encompassed observed risk for all scores in development and validation samples, indicating adequate risk index calibration. Conclusions: Individual-level risk of developing a common postpartum mental health disorder can be estimated with data feasibly collectable from birth records. Next steps are external validation and evaluation of various cut-off scores for their utility in guiding postpartum individuals to interventions that reduce their risk of illness. [ABSTRACT FROM AUTHOR]

Background: Maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) above or below recommendations have been associated with increased paediatric health service utilization as well as increased risk of adverse birth outcomes, including small for gestational age (SGA) and preterm birth (PTB). SGA and PTB are associated with numerous adverse health outcomes in the child, including delayed growth, motor and cognitive impairment. Previous research has identified birth weight and gestational age on the causal pathway in the association between maternal pre-pregnancy BMI and child hospital admissions, there are no studies to date to quantify this relationship across other areas of health service utilization, nor the impact of gestational weight gain. This study aimed to assess if SGA or PTB partially explain the association between maternal weight and paediatric health service utilization. Methods: The study population consisted of all women who delivered a singleton, live infant in Ontario between 2012 and 2014, and was assembled from data contained in the provincial birth registry. Health service utilization over the first 24 months following birth was examined by linking data from the registry with other provincial health administrative databases housed at ICES. The mediating roles of PTB and SGA were assessed using the Baron-Kenny method and causal mediation analysis. Results: A total of 204,162 infants were included in the analysis of maternal pre-pregnancy BMI and 171,127 infants were included in the GWG analysis. The small magnitude of association between maternal BMI and paediatric health service utilization impacted our ability to estimate the indirect effect of maternal BMI through adverse birth outcomes (adjusted indirect effect = 0.00). 56.7% of the association between below recommended GWG and increased hospitalizations was attributed to PTB, while 6.8% of the association was attributed to SGA. Conclusion: Paediatric hospitalizations may be partially attributable to PTB and SGA in children born to mothers with below-recommended GWG. However, maternal weight also appears to be related to increased paediatric health service utilization independent of PTB and SGA. [ABSTRACT FROM AUTHOR]

Background: Cannabis use during pregnancy is increasing, but the contribution of cannabis legalization to these trends is unclear. We sought to determine whether health service utilization related to cannabis use during pregnancy increased after the legalization of nonmedical cannabis in October 2018 in Ontario, Canada. Methods: In this population-based, repeated cross-sectional study, we evaluated changes in the number of pregnant people who received acute care (emergency department visit or admission to hospital) between January 2015 and July 2021 among all people eligible for the province's public health coverage. We used segmented regression to compare changes in the quarterly rate of pregnant people with acute care related to cannabis use (primary outcome) with the quarterly rates of acute care for mental health conditions or for noncannabis substance use (control conditions). We identified risk factors associated with acute care for cannabis use and the risk of adverse neonatal outcomes using multivariable logistic regression models. Results: The mean quarterly rate of acute care for cannabis use during pregnancy increased from 11.0 per 100 000 pregnancies before legalization to 20.0 per 100 000 pregnancies after legalization (incidence rate ratio [IRR] 1.82, 95% confidence interval [CI] 1.44–2.31), while acute care for mental health conditions decreased (IRR 0.86, 95% CI 0.78–0.95) and acute care for noncannabis substance use did not change (IRR 1.03, 95% CI 0.91–1.17). Legalization was not associated with an immediate change, but the quarterly change in rates of pregnancies with acute care for cannabis use increased by 1.13 (95% CI 0.46–1.79) per 100 000 pregnancies after legalization. Pregnant people with acute care for cannabis use had greater odds of having received acute care for hyperemesis gravidarum during their pregnancy than those without acute care for cannabis use (30.9% v. 2.5%, adjusted odds ratio [OR] 9.73, 95% CI 8.01–11.82). Pregnancies with acute care for cannabis use had greater odds of newborns being born preterm (16.9% v. 7.2%, adjusted OR 1.93, 95% CI 1.45–2.56) and of requiring care in the neonatal intensive care unit (31.5% v. 13.0%, adjusted OR 1.94 95% CI 1.54–2.44) than those without acute care for cannabis use. Interpretation: The rate of acute care related to cannabis use during pregnancy almost doubled after legalization of nonmedical cannabis, although absolute increases were small. These findings highlight the need to consider interventions to reduce cannabis use during pregnancy in jurisdictions pursuing legalization. [ABSTRACT FROM AUTHOR]

Background: This study aims to evaluate the impact of socioeconomic status (SES) on the risk of congenital heart disease (CHD) since previous studies have yielded inconsistent results. Methods: We conducted a population-based retrospective cohort study, including all singleton live and still births in Ontario hospitals from April 1, 2012, to March 31, 2018. We used linked records from the Better Outcomes Registry & Network Information System, the Canadian Institute for Health Information databases, and the Ontario Marginalization Index (ON_Marg). ON_Marg was estimated at a dissemination area level using Canadian Census 2016 data and categorized into quintiles. Multivariable logistic regression models were performed to examine the relationships between four ON_Marg indices (material deprivation, dependency, ethnic concentration, residential instability), as proxies for maternal SES and the risk of infant CHD. We adjusted for maternal age at birth, assisted reproductive technology, obesity, pre-existing health conditions, substance use during pregnancy, mental health conditions before and during pregnancy, rural residence, and infant's sex in the analysis. Results: Among the cohort of 776,799 singletons, 9,359 infants had a diagnosis of CHD. Of those, 3,069 were severe CHD and 493 cases were single ventricle CHD. The prevalence of all infant CHD types was higher for males relative to females. Compared to mothers living in neighbourhoods with the lowest material deprivation, mothers with highest material deprivation had a 27% (adjusted OR = 1.27; 95% CI: 1.18–1.37) higher odds of having an infant diagnosed with CHD. Mothers living in neighbourhoods with the highest minority ethnic and immigrant concentration tend to have infants with 11% lower odds of CHD (adjusted OR = 0.89; 95% CI: 0.82–0.97) as compared to those living in the least ethnically diverse communities. Maternal dependency and residential stability quintiles were not significantly associated with the risk of CHD. Conclusion: Higher maternal material deprivation was associated with increasing odds of infant CHD, whereas neighbourhood minority ethnic concentration was inversely associated with the odds of infant CHD. Our study further confirms that poverty is associated with CHD development. Future investigations might focus on the causal pathways between social deprivation, immigrant status, ethnicity, and the risk of infant CHD. [ABSTRACT FROM AUTHOR]

Background: Around 2% of births in Ontario, Canada involve the use of assisted reproductive technology (ART), and it is rising due to the implementation of a publicly funded ART program in 2016. To better understand the impact of fertility treatments, we assessed perinatal and pediatric health outcomes associated with ART, hormonal treatments, and artificial insemination compared with spontaneously conceived births. Methods: This population-based retrospective cohort study was conducted using provincial birth registry data linked with fertility registry and health administrative databases in Ontario, Canada. Live births and stillbirths from January 2013 to July 2016 were included and followed to age one. The risks of adverse pregnancy, birth and infant health outcomes were assessed by conception method (spontaneous conception, ART – in vitro fertilization and non-ART – ovulation induction, intra-uterine or vaginal insemination) using risk ratios and incidence rate ratios with 95% confidence intervals (CI). Propensity score weighting using a generalized boosted model was applied to adjust for confounding. Result(s): Of 177,901 births with a median gestation age of 39 weeks (IQR 38.0–40.0), 3,457 (1.9%) were conceived via ART, and 3,511 (2.0%) via non-ART treatments. There were increased risks (adjusted risk ratio [95% CI]) of cesarean delivery (ART: 1.44 [1.42–1.47]; non-ART: 1.09 [1.07–1.11]), preterm birth (ART: 2.06 [1.98–2.14]; non-ART: 1.85 [1.79–1.91]), very preterm birth (ART: 2.99 [2.75–3.25]; non-ART: 1.89 [1.67–2.13]), 5-min Apgar < 7 (ART: 1.28 [1.16–1.42]; non-ART: 1.62 [1.45–1.81]), and composite neonatal adverse outcome indicator (ART: 1.61 [1.55–1.68]; non-ART: 1.29 [1.25–1.34]). Infants born after fertility treatments had increased risk of admission to neonatal intensive care unit (ART: 1.98 [1.84–2.13]; non-ART: 1.59 [1.51–1.67]) and prolonged birth admission (≥ 3 days) (ART: 1.60 [1.54–1.65]; non-ART: 1.42 [1.39–1.45]). The rate of emergency and in-hospital health services use within the first year was significantly increased for both exposure groups and remained elevated when limiting analyses to term singletons. Conclusion(s): Fertility treatments were associated with increased risks of adverse outcomes; however, the overall magnitude of risks was lower for infants conceived via non-ART treatments. [ABSTRACT FROM AUTHOR]

Background: Education is considered one of the most robust determinants of health. However, it is unclear whether maternal education and paternal education have differential impacts on perinatal health outcomes. We assess maternal and paternal education differences and their association with adverse birth outcomes in a large birth cohort from Ontario, Canada. Methods: The OaK Birth Cohort recruited patients from Ontario, Canada, between October 2002 and April 2009. We recruited mothers were recruited between 12 and 20 weeks’ gestation and collected both mother and infant data. The final sample size of the cohort was 8,085 participants. We use logistic regression to model the probability of preterm birth (less than 34 and 37 weeks’ gestation), small-for-gestational-age (SGA), or stillbirth as a function of maternal and paternal educational attainment. We adjust for household-level income, maternal and paternal race and ethnicity, and compare the strength of the association between maternal and paternal education on outcomes using Wald tests. Results: 7,928 mother-father-offspring triads were available for the current analysis. 75% of mothers and fathers had college or university level education, and 8.7% of mothers experienced preterm delivery. Compared to mothers with college or university education, mothers with a high school education had an odds ratio of 1.37 (95% CI: 1.01–1.87) for SGA. Paternal education was not associated with infant outcomes. Comparing the odds ratios for maternal education and paternal education showed a stronger association than paternal education at the high school level for SGA birth (difference in odds ratio: 1.95, 95% CI: 1.13–3.36, p = .016) among women at least 25 years old. Conclusion: Maternal education was associated with SGA, and this effect was more robust than paternal education, but both associations were weaker than previously reported. [ABSTRACT FROM AUTHOR]

Background: The risk of congenital heart disease (CHD) has been found to vary by maternal socioeconomic status (SES) and rural-urban residence. In this study, we examined associations of CHD with two maternal SES indicators and stratified the analysis by maternal rural-urban residence.Methods: This was a population-based retrospective cohort study. We included all singleton stillbirths and live hospital births from April 1, 2012 to March 31, 2018 in Ontario, Canada. We linked the BORN Information System and Canadian Institute for Health Information databases. Multivariable logistic regression models were used to examine associations of CHD with material deprivation index (MDI), social deprivation index (SDI), and maternal residence while adjusting for maternal age at birth, assisted reproductive technology, obesity, pre-pregnancy maternal health conditions, mental health illness before and during pregnancy, substance use during pregnancy, and infant's sex. MDI and SDI were estimated at a dissemination area level in Ontario and were categorized into quintiles (Q1-Q5).Results: This cohort study included 798,173 singletons. In maternal urban residence, the p trend (Cochran-Armitage test) was less than 0.0001 for both MDI and SDI; while for rural residence, it was 0.002 and 0.98, respectively. Infants living in the most materially deprived neighbourhoods (MDI Q5) had higher odds of CHD (aOR: 1.21, 95% CI: 1.12-1.29) compared to Q1. Similarly, infants living in the most socially deprived neighbourhoods (SDI Q5) had an 18% increase in the odds of CHD (aOR: 1.18, 95% CI: 1.1-1.26) compared to Q1. Rural infants had a 13% increase in the odds of CHD compared to their urban counterparts. After stratifying by maternal rural-urban residence, we still detected higher odds of CHD with two indices in urban residence but only MDI in rural residence.Conclusion: Higher material and social deprivation and rural residence were associated with higher odds of CHD. Health interventions and policies should reinforce the need for optimal care for all families, particularly underprivileged families in both rural and urban regions. Future studies should further investigate the effect of social deprivation on the risk of CHD development. [ABSTRACT FROM AUTHOR]

Introduction: Racial differences in adverse maternal and birth outcomes have been studied in other countries, however, there are few studies specific to the Canadian population. In this study, we sought to examine the inequities in adverse perinatal outcomes between Black and White pregnant people in Ontario, Canada. Methods: We conducted a population-based retrospective cohort study that included all Black and White pregnant people who attended prenatal screening and had a singleton birth in any Ontario hospital (April 1st, 2012-March 31st, 2019). Poisson regression with robust error variance models were used to estimate the adjusted relative risks of adverse perinatal outcomes for Black people compared with White people while adjusting for covariates. Results: Among 412,120 eligible pregnant people, 10.1% were Black people and 89.9% were White people. Black people were at an increased risk of gestational diabetes mellitus, preeclampsia, placental abruption, preterm birth (<37, <34, <32 weeks), spontaneous preterm birth, all caesarean sections, emergency caesarean section, low birth weight (<2500g, <1500g), small-for-gestational-age (<10th percentile, <3rd percentile) neonates, 5-minute Apgar score <4 and <7, neonatal intensive care unit admission, and hyperbilirubinemia requiring treatment but had lower risks of elective caesarean section, assisted vaginal delivery, episiotomy, 3rd and 4th degree perineal tears, macrosomia, large-for-gestational-age neonates, and arterial cord pH≤7.1, as compared with White people. No difference in risks of gestational hypertension and placenta previa were observed between Black and White people. Conclusion: There are differences in several adverse perinatal outcomes between Black and White people within the Ontario health care system. Findings might have potential clinical and health policy implications, although more studies are needed to further understand the mechanisms. [ABSTRACT FROM AUTHOR]

Objective: To develop and internally validate a deep-learning algorithm from fetal ultrasound images for the diagnosis of cystic hygromas in the first trimester. Methods: All first trimester ultrasound scans with a diagnosis of a cystic hygroma between 11 and 14 weeks gestation at our tertiary care centre in Ontario, Canada were studied. Ultrasound scans with normal nuchal translucency were used as controls. The dataset was partitioned with 75% of images used for model training and 25% used for model validation. Images were analyzed using a DenseNet model and the accuracy of the trained model to correctly identify cases of cystic hygroma was assessed by calculating sensitivity, specificity, and the area under the receiver-operating characteristic (ROC) curve. Gradient class activation heat maps (Grad-CAM) were generated to assess model interpretability. Results: The dataset included 289 sagittal fetal ultrasound images;129 cystic hygroma cases and 160 normal NT controls. Overall model accuracy was 93% (95% CI: 88–98%), sensitivity 92% (95% CI: 79–100%), specificity 94% (95% CI: 91–96%), and the area under the ROC curve 0.94 (95% CI: 0.89–1.0). Grad-CAM heat maps demonstrated that the model predictions were driven primarily by the fetal posterior cervical area. Conclusions: Our findings demonstrate that deep-learning algorithms can achieve high accuracy in diagnostic interpretation of cystic hygroma in the first trimester, validated against expert clinical assessment. [ABSTRACT FROM AUTHOR]

Background: In Canada, as is found globally, women of reproductive age are a growing demographic of persons living with HIV. Combination antiretroviral therapy (cART) treatment enables women living with HIV (WLWH) to become pregnant without perinatal transmission, and they are increasingly planning to become pregnant. Since 2014, Canadian guidelines no longer recommend routine elective cesarean birth (CB) for women who are virally suppressed and receiving cART. It is unknown whether their obstetric care has changed since this update. Our objective was to describe trends in cesarean births among WLWH in Ontario, Canada, over a 12‐year period. Methods: Our research is co‐led and codesigned with WLWH. We conducted a retrospective population‐level cohort study using linked health administrative databases at ICES (formally, the Institute for Clinical and Evaluative Sciences). Participants were all women who gave birth in Ontario, between 2006/07 and 2017/18. We assessed their intrapartum characteristics and used multivariable regression to determine an association between HIV status and CB, controlling for sociodemographic and clinical variables. Results: Since 2014, the overall proportion of CB among WLWH remained stable and was higher than among women without HIV (39.9% vs 29.0%, P < 0.001). In addition, the proportion of primary CB decreased between 2006 and 2010 and between 2014 and 2018 (28.5%‐19.3%), whereas the proportion of repeat CB increased (13.1%‐20.5%, P = 0.013). Conclusions: Because of decreasing HIV‐related indications for CB, more practitioners may be following the guidelines for first‐time mothers. Currently, no guidelines exist for care of WLWH with a previous CB, and opportunities for vaginal birth may be missed in this population. [ABSTRACT FROM AUTHOR]

Background: The emergence of cell-free fetal DNA (cfDNA) testing technology has disrupted the landscape of prenatal screening for trisomies 21 (T21) and 18 (T18). Publicly funded systems around the world are grappling with how to best integrate this more accurate but costly technology, as there is limited evidence about its incremental value in real-world conditions. The objectives of this study were to describe the population-based performance of Ontario's prenatal screening program, which incorporates publicly funded cfDNA screening for specific indications, and the effect of cfDNA testing on the screening and diagnostic choices made by pregnant people.Methods: We conducted a retrospective, descriptive cohort study using routinely collected data from Better Outcomes & Registry Network (BORN) Ontario, which captures linked population data for prenatal and neonatal health encounters across Ontario. We included all singleton pregnancies with an estimated due date between Sept. 1, 2016, and Mar. 31, 2019, that underwent publicly funded prenatal screening in Ontario, and a comparison cohort from Apr. 1, 2012, and Mar. 31, 2013. We assessed performance of the screening program for the detection of T21 or T18 by calculating sensitivity, specificity, positive predictive value and negative predictive value against diagnostic cytogenetic results or birth outcomes. We assessed the impact of the program by calculating the proportion of T21 screen-positive pregnancies undergoing subsequent cfDNA screening and invasive prenatal diagnostic testing.Results: The study cohort included 373 682 pregnancies. The prenatal screening program had an uptake of 69.9%, a screen-positive rate and sensitivity of 1.6% and 89.9% for T21, and 0.2% and 80.5% for T18, respectively. The test failure rate for cfDNA screening was 2.2%. Invasive prenatal diagnostic testing decreased from 4.4% in 2012-2013 to 2.4% over the study period; 65.2% of pregnant people who received a screen-positive result from cfDNA testing went on to have invasive prenatal diagnostic testing.Interpretation: This publicly funded screening program, incorporating cfDNA analysis for common aneuploidies, showed robust performance, a substantial reduction in invasive prenatal diagnostic testing and that pregnant people exercise autonomy in their choices about prenatal screening and diagnosis. [ABSTRACT FROM AUTHOR]

Cell-free fetal DNA screening is routinely offered to pregnant individuals to screen for aneuploidies. Although cell-free DNA screening is consistently more accurate than multiple-marker screening, it sometimes fails to yield a result. These test failures and their clinical implications are poorly described in the literature. Some studies suggest that a failed cell-free DNA screening result is associated with increased likelihood of cytogenetic abnormalities. This study aimed to assess the association between a failed cell-free DNA test and common aneuploidies. The objectives were to determine: (1) the proportion of test failures on first and subsequent attempts, and (2) whether a failed cell-free DNA screen on first attempt is associated with increased likelihood of common aneuploidies (trisomies 21, 18, and 13, and sex chromosome aneuploidies). This was a population-based retrospective cohort study using data from Ontario's prescribed maternal and child registry, Better Outcomes Registry and Network Ontario. The study included all singleton pregnancies in Ontario with an estimated date of delivery from September 1, 2016 to March 31, 2019 that had a cell-free DNA screening record in the registry. Specific outcomes (trisomies 21, 18, and 13, and sex chromosome aneuploidies) of pregnancies with a failed cell-free DNA screen on first attempt were compared with those of pregnancies with low-risk cell-free DNA-screening results using modified Poisson regression adjusted for funding status (publicly funded vs self-paid), gestational age at screening, method of conception, and maternal age for autosomal aneuploidies. Our cohort included 35,146 pregnancies that had cell-free DNA screening during the study period. The overall cell-free DNA screening failure rate was 4.8% on first attempt and 2.2% after multiple attempts. An abnormal cytogenetic result for trisomies 21, 18, and 13, or sex chromosome aneuploidies was identified in 19.4% of pregnancies with a failed cell-free DNA screening for which cytogenetic testing was performed. Pregnancies with a failed cell-free DNA screen on first attempt had a relative risk of 130.3 (95% confidence interval, 64.7–262.6) for trisomy 21, trisomy 18, or trisomy 13, and a risk difference of 5.4% (95% confidence interval, 2.6–8.3), compared with pregnancies with a low-risk result. The risk of sex chromosome aneuploidies was not significantly greater in pregnancies with a failed result compared with pregnancies with a low-risk result (relative risk, 2.7; 95% confidence interval, 0.9–7.9; relative difference, 1.2%; 95% confidence interval, −0.9 to 3.2). Cell-free DNA screening test failures are relatively common. Although repeated testing improves the likelihood of an informative result, pregnancies with a failed cell-free DNA screen upon first attempt remain at increased risk for common autosomal aneuploidies, but not sex chromosome aneuploidies. [ABSTRACT FROM AUTHOR]

Population-based COVID-19 vaccine coverage estimates among pregnant individuals are limited. We assessed temporal patterns in vaccine coverage (≥1 dose before or during pregnancy) and evaluated factors associated with vaccine series initiation (receiving dose 1 during pregnancy) in Ontario, Canada. We linked the provincial birth registry with COVID-19 vaccination records from December 14, 2020 to December 31, 2021 and assessed coverage rates among all pregnant individuals by month, age, and neighborhood sociodemographic characteristics. Among individuals who gave birth since April 2021—when pregnant people were prioritized for vaccination—we assessed associations between sociodemographic, behavioral, and pregnancy-related factors with vaccine series initiation using multivariable regression to estimate adjusted risk ratios (aRR) and risk differences (aRD) with 95% confidence intervals (CI). Among 221,190 pregnant individuals, vaccine coverage increased to 71.2% by December 2021. Gaps in coverage across categories of age and sociodemographic characteristics decreased over time, but did not disappear. Lower vaccine series initiation was associated with lower age (<25 vs. 30–34 years: aRR 0.53, 95%CI 0.51–0.56), smoking (vs. non-smoking: 0.64, 0.61–0.67), no first trimester prenatal care visit (vs. visit: 0.80, 0.77–0.84), and residing in neighborhoods with the lowest income (vs. highest: 0.69, 0.67–0.71). Vaccine series initiation was marginally higher among individuals with pre-existing medical conditions (vs. no conditions: 1.07, 1.04–1.10). COVID-19 vaccine coverage among pregnant individuals remained lower than in the general population, and there was lower vaccine initiation by multiple characteristics. [ABSTRACT FROM AUTHOR]

Increasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years). We conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012–2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE)). We linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944–1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953–1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903–1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833–0.948, per 0.06 increase in park proximity index), when adjusted for air pollution. This study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD. • We linked 8643 pairs of mother-child (aged 2–6 years) with 1554 autism cases. • We investigated prenatal exposure to greenspace metrics and autism in offspring. • Residential park proximity decreased risk of autism development in children. • Low population density neighborhood amplified protective effect of park proximity. [ABSTRACT FROM AUTHOR]

• Serum markers for aneuploidy screening are influenced by maternal characteristics. • Adjustments are needed before marker measurements can be used for risk estimation. • Appropriate adjustments will improve the accuracy of multiple marker screening. • New adjustment factors were generated for race, smoking, and insulin-dependent diabetes. The concentrations of maternal serum markers for aneuploidy screening are influenced by maternal characteristics such as race, smoking, insulin dependent diabetes mellitus (IDDM), and in vitro fertilization (IVF). Accurate risk estimation requires adjustment of initial values for these characteristics. This study aims to update and validate adjustment factors for race, smoking, and IDDM. The study included singleton pregnancies that received multiple marker screening in Ontario, Canada between January 2012, and December 2018, and had their information collected in the Better Outcomes Registry & Network (BORN) Ontario. Serum markers assessed included first trimester pregnancy-associated plasma protein A (PAPP-A), free β and total human chorionic gonadotropin (hCG), placental growth factor (PlGF) and αlpha-fetoprotein (AFP); second trimester AFP, unconjugated estriol (uE3), total hCG and inhibin A. The Mann-Whitney U test was used to assess the differences in the median multiple of the median (MoM) of serum markers between study and reference groups. New adjustment factors were generated by dividing the median MoM of a particular race, individuals who smoke tobacco, or have IDDM by those of the reference groups. The study included 624,789 pregnancies. There were statistically significant differences in serum marker concentrations among pregnant individuals who were Black, Asian, or First Nations compared to a White group, those who smoked compared to Non-smoking individuals, and those with IDDM compared to Non-IDDM group. New adjustment factors for race, smoking, and IDDM were validated by comparing median MoM of serum markers corrected using the current adjustment factors and new adjustment factors generated in this study. The adjustment factors generated in this study can adjust the effects of race, smoking, and IDDM on serum markers more accurately. [ABSTRACT FROM AUTHOR]

Objectives: Investigations about cesarean delivery (CD) on maternal request (CDMR) and infant infection risk frequently rely on administrative data with poorly defined indications for CD. We sought to determine the association between CDMR and infant infection using an intent-to-treat approach., Methods: This was a population-based cohort study of low-risk singleton pregnancies with a term live birth in Ontario, Canada between April 2012 and March 2018. Subjects with prior CD were excluded. Outcomes included upper and lower respiratory tract infections, gastrointestinal infections, otitis media, and a composite of these 4. Relative risk and 95% CI were calculated for component and composite outcomes up to 1 year following planned CDMR versus planned vaginal deliveries (VDs). Subgroup and sensitivity analyses included age at infection (≤28 vs. >28 days), type of care (ambulatory vs. hospitalisation), restricting the cohort to nulliparous pregnancies, and including individuals with previous CD. Last, we re-examined outcome risk on an as-treated basis (actual CD vs. actual VD)., Results: Of 422 134 pregnancies, 0.4% (1827) resulted in a planned CDMR. After adjusting for covariates, planned CDMR was not associated with a risk of composite infant infections (adjusted relative risk 1.02; 95% CI 0.92-1.11). Findings for component infection outcomes, subgroup, and sensitivity analyses were similar. However, the as-treated analysis of the role of delivery mode on infant risk for infection demonstrated that actual CD (planned and unplanned) was associated with an increased risk for infant infections compared to actual VD., Conclusions: Planned CDMR is not associated with increased risk for neonatal or infant infections compared with planned VD. Study design must be carefully considered when investigating the impact of CDMR on infant infection outcomes., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Importance: Ultrasonographic measurement of fetal nuchal translucency is used in prenatal screening for trisomies 21 and 18 and other conditions. A cutoff of 3.5 mm or greater is commonly used to offer follow-up investigations, such as prenatal cell-free DNA (cfDNA) screening or cytogenetic testing. Recent studies showed a possible association with chromosomal anomalies for levels less than 3.5 mm, but extant evidence has limitations., Objective: To evaluate the association between different nuchal translucency measurements and cytogenetic outcomes on a population level., Design, Setting, and Participants: This population-based retrospective cohort study used data from the Better Outcomes Registry & Network, the perinatal registry for Ontario, Canada. All singleton pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, were included. Data were analyzed from March 17 to August 14, 2023., Exposures: Nuchal translucency measurements were identified through multiple-marker screening results., Main Outcomes and Measures: Chromosomal anomalies were identified through all Ontario laboratory-generated prenatal and postnatal cytogenetic tests. Cytogenetic testing results, supplemented with information from cfDNA screening and clinical examination at birth, were used to identify pregnancies without chromosomal anomalies. Multivariable modified Poisson regression with robust variance estimation and adjustment for gestational age was used to compare cytogenetic outcomes for pregnancies with varying nuchal translucency measurement categories and a reference group with nuchal translucency less than 2.0 mm., Results: Of 414 268 pregnancies included in the study (mean [SD] maternal age at estimated delivery date, 31.5 [4.7] years), 359 807 (86.9%) had a nuchal translucency less than 2.0 mm; the prevalence of chromosomal anomalies in this group was 0.5%. An increased risk of chromosomal anomalies was associated with increasing nuchal translucency measurements, with an adjusted risk ratio (ARR) of 20.33 (95% CI, 17.58-23.52) and adjusted risk difference (ARD) of 9.94% (95% CI, 8.49%-11.39%) for pregnancies with measurements of 3.0 to less than 3.5 mm. The ARR was 4.97 (95% CI, 3.45-7.17) and the ARD was 1.40% (95% CI, 0.77%-2.04%) when restricted to chromosomal anomalies beyond the commonly screened aneuploidies (excluding trisomies 21, 18, and 13 and sex chromosome aneuploidies)., Conclusions and Relevance: In this cohort study of 414 268 singleton pregnancies, those with nuchal translucency measurements less than 2.0 mm were at the lowest risk of chromosomal anomalies. Risk increased with increasing measurements, including measurements less than 3.5 mm and anomalies not routinely screened by many prenatal genetic screening programs.

Objective: The impact of gestational weight loss (GWL) on fetal growth among women with obesity remains unclear. This study aimed to examine the association between weight loss during pregnancy among women with body mass index (BMI) ≥ 30 kg/m 2 and the risk of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) neonates., Methods: We conducted a retrospective, population-based cohort study of women with pre-pregnancy obesity that resulted in a singleton live birth in 2012-2017, using birth registry data in Ontario, Canada. Women with pregnancy complications or health conditions which could cause weight loss were excluded. GWL is defined as negative gestational weight change (≤0 kg). The association between GWL and fetal growth was estimated using generalized estimating equation models and restricted cubic spline regression analysis. Stratified analysis was conducted by obesity class (I:30-34.9 kg/m 2 , II:35-39.9 kg/m 2 , and III + : ≥40 kg/m 2 )., Results: Of the 52,153 eligible women who entered pregnancy with a BMI ≥ 30 kg/m 2 , 5.3% had GWL. Compared to adequate gestational weight gain, GWL was associated with an increased risk of SGA neonates (aRR:1.45, 95% CI: 1.30-1.60) and a decreased risk of LGA neonates (aRR: 0.81, 95% CI:0.73-0.93). Non-linear L-shaped associations were observed between gestational weight change and SGA neonates, with an increased risk of SGA observed with increased GWL. On the contrary, non-linear S-shaped associations were observed between gestational weight change and LGA neonates, with a decreased risk of LGA observed with increased GWL. Similar findings were observed from the stratified analysis by obesity class., Conclusion: These findings highlight that GWL in women with obesity may increase the risk of SGA neonates but reduce the risk of LGA neonates. Recommendations of GWL for women with obesity should be interpreted with caution., (© 2023. The Author(s).)

During the rapid deployment of COVID-19 vaccines in 2021, safety concerns may have led some pregnant individuals to postpone vaccination until after giving birth. This study aimed to describe temporal patterns and factors associated with COVID-19 vaccine series initiation after recent pregnancy in Ontario, Canada. Using the provincial birth registry linked with the COVID-19 vaccine database, we identified all individuals who gave birth between January 1 and December 31, 2021, and had not yet been vaccinated by the end of pregnancy, and followed them to June 30, 2022 (follow-up ranged from 6 to 18 months). We used cumulative incidence curves to describe COVID-19 vaccine initiation after pregnancy and assessed associations with sociodemographic, pregnancy-related, and health behavioral factors using Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Among 137,198 individuals who gave birth in 2021, 87,376 (63.7%) remained unvaccinated at the end of pregnancy; of these, 65.0% initiated COVID-19 vaccination by June 30, 2022. Lower maternal age (<25 vs. 30-34 y aHR: 0.73, 95%CI: 0.70-0.77), smoking during pregnancy (vs. nonsmoking aHR: 0.68, 95%CI: 0.65-0.72), lower neighborhood income (lowest quintile vs. highest aHR: 0.79, 95%CI: 0.76-0.83), higher material deprivation (highest quintile vs. lowest aHR: 0.74, 95%CI: 0.70-0.79), and exclusive breastfeeding (vs. other feeding aHR: 0.81, 95%CI: 0.79-0.84) were associated with lower likelihood of vaccine initiation. Among unvaccinated individuals who gave birth in 2021, COVID-19 vaccine initiation after pregnancy reached 65% by June 30, 2022, suggesting persistent issues with vaccine hesitancy and/or access to vaccination in this population.

Background: Cannabis use during pregnancy is increasing, but the contribution of cannabis legalization to these trends is unclear. We sought to determine whether health service utilization related to cannabis use during pregnancy increased after the legalization of nonmedical cannabis in October 2018 in Ontario, Canada., Methods: In this population-based, repeated cross-sectional study, we evaluated changes in the number of pregnant people who received acute care (emergency department visit or admission to hospital) between January 2015 and July 2021 among all people eligible for the province's public health coverage. We used segmented regression to compare changes in the quarterly rate of pregnant people with acute care related to cannabis use (primary outcome) with the quarterly rates of acute care for mental health conditions or for noncannabis substance use (control conditions). We identified risk factors associated with acute care for cannabis use and the risk of adverse neonatal outcomes using multivariable logistic regression models., Results: The mean quarterly rate of acute care for cannabis use during pregnancy increased from 11.0 per 100 000 pregnancies before legalization to 20.0 per 100 000 pregnancies after legalization (incidence rate ratio [IRR] 1.82, 95% confidence interval [CI] 1.44-2.31), while acute care for mental health conditions decreased (IRR 0.86, 95% CI 0.78-0.95) and acute care for noncannabis substance use did not change (IRR 1.03, 95% CI 0.91-1.17). Legalization was not associated with an immediate change, but the quarterly change in rates of pregnancies with acute care for cannabis use increased by 1.13 (95% CI 0.46-1.79) per 100 000 pregnancies after legalization. Pregnant people with acute care for cannabis use had greater odds of having received acute care for hyperemesis gravidarum during their pregnancy than those without acute care for cannabis use (30.9% v. 2.5%, adjusted odds ratio [OR] 9.73, 95% CI 8.01-11.82). Pregnancies with acute care for cannabis use had greater odds of newborns being born preterm (16.9% v. 7.2%, adjusted OR 1.93, 95% CI 1.45-2.56) and of requiring care in the neonatal intensive care unit (31.5% v. 13.0%, adjusted OR 1.94 95% CI 1.54-2.44) than those without acute care for cannabis use., Interpretation: The rate of acute care related to cannabis use during pregnancy almost doubled after legalization of nonmedical cannabis, although absolute increases were small. These findings highlight the need to consider interventions to reduce cannabis use during pregnancy in jurisdictions pursuing legalization., Competing Interests: Competing interests: Daniel Myran reports a speaker fee from McMaster University for presenting at a research conference on nonmedical cannabis legalization. Mark Walker sits on the board of directors for the Children’s Hospital of Eastern Ontario (CHEO) Research Institute. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Introduction: Cannabis use in pregnancy and post partum is increasing. Accessibility to cannabis has expanded due to the legalisation of cannabis in Canada. Therefore, there is a critical need to monitor the impact of cannabis on pregnancy outcomes and infant neurodevelopment. This pilot study will assess the feasibility of modern recruitment and data collection strategies adapted to the current cannabis environment and inform the design of a multicentre prospective birth cohort., Methods and Analysis: We will establish a pregnancy and birth cohort of 50 cannabis users and 50 non-users recruited before delivery. We will follow the participants at regular visits from recruitment to 12 weeks post partum. Participants will provide demographic and socioeconomic data, report their cannabis use patterns, and provide biological samples. Biological samples include maternal and infant urine and blood, breastmilk/chestmilk, cord blood, cord tissue, placenta and meconium. All samples will be processed and stored at -80°C until analysis by immunoassay or liquid chromatography-tandem mass spectrometry to determine the presence of cannabis metabolites. In addition, partners will be invited to provide additional socioeconomic and substance use data., Ethics and Dissemination: Ethics was obtained from Ottawa Health Science Network Research Ethics Board through Clinical Trials Ontario (3791). Our findings will be published in peer-reviewed journals, presented at scientific conferences and shared broadly with patients, healthcare decision-makers, and project partners online and through social media., Trial Registration Number: NCT05309226.Cite Now., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In February 2018, Canada's National Advisory Committee on Immunization (NACI) recommended tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccination during pregnancy to protect newborns against pertussis infection. We sought to describe pre- and postrecommendation trends in Tdap vaccination coverage among pregnant Ontario residents., Methods: Using linked health administrative databases, we conducted a population-based retrospective cohort study of all pregnant individuals who gave birth in Ontario hospitals between April 2012 and March 2020. We described Tdap vaccination patterns in pregnancy for the entire study period and before and after the NACI recommendation. We used log-binomial regression to identify characteristics associated with Tdap vaccination during pregnancy., Results: Among the 991 850 deliveries included, 7.0% of pregnant individuals received the Tdap vaccination during pregnancy. Vaccine coverage increased from 0.4% in 2011/12 to 29.2% in 2019/20. Coverage was highest among individuals who were older, had no previous live births, had adequate prenatal care and received maternity care primarily from a family physician. After adjustment, characteristics associated with lower coverage included younger maternal age, having a multiple birth, residing in a rural location and higher area material deprivation. In 2019/20, 71.0% of vaccinated individuals received the Tdap vaccination during the recommended gestational window (27-32 wk). Stratified analyses of the pre- and postrecommendation cohorts yielded similar findings to the main analyses with a few gradient differences after adjustment., Interpretation: During pregnancy, Tdap vaccination coverage increased substantially in Ontario between 2011/12 and 2019/20, most notably after recommendations for universal Tdap vaccination during pregnancy began in Canada. To further improve vaccine coverage in the obstetric setting, public health strategies should consider tailoring their programs to reach subpopulations with lower vaccine coverage., Competing Interests: Competing interests: Scott Halperin has received research grants or contracts from and has served on ad hoc advisory boards for GlaxoSmithKline, Sanofi Pasteur, Pfizer, Merck, Janssen, Medicago, Entos IMV, CanSino, VBI, Moderna, Precision Nanosystems, AstraZeneca, Seqirus, Novavax and Dynavax (all unrelated to this study). Manish Sadarangani has been an investigator on projects funded by Pfizer, Merck, Moderna, Sanofi Pasteur, Seqirus, Symvivo, VBI Vaccines and GlaxoSmithKline (all unrelated to this study). All funds have been paid to his institute, and he has not received any personal payments. He is chair/deputy chair of 2 data safety monitoring boards for SARS-CoV-2 vaccine trials, involving different vaccines. Kumanan Wilson is the CEO of CANImmunize Inc. and served as a member of the independent data monitoring committee for the Medicago SARS-CoV-2 vaccine trial (all unrelated to this study)., (© 2022 CMA Impact Inc. or its licensors.)

Objective: To assess the risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy., Design: Population based retrospective cohort study., Setting: Ontario, Canada, 1 May to 31 December 2021., Participants: All liveborn and stillborn infants from pregnancies conceived at least 42 weeks before the end of the study period and with gestational age ≥20 weeks or birth weight ≥500 g., Main Outcome Measures: Using Cox regression, hazard ratios and 95% confidence intervals were estimated for preterm birth before 37 weeks (overall and spontaneous preterm birth), very preterm birth (<32 weeks), small for gestational age at birth (<10th centile), and stillbirth. Vaccination against covid-19 was treated as a time varying exposure in the outcome specific risk window, and propensity score weighting was used to adjust hazard ratios for potential confounding., Results: Among 85 162 births, 43 099 (50.6%) occurred in individuals who received one dose or more of a covid-19 vaccine during pregnancy-42 979 (99.7%) received an mRNA vaccine. Vaccination during pregnancy was not associated with any increased risk of overall preterm birth (6.5% among vaccinated v 6.9% among unvaccinated; adjusted hazard ratio 1.02, 95% confidence interval 0.96 to 1.08), spontaneous preterm birth (3.7% v 4.4%; 0.96, 0.90 to 1.03), or very preterm birth (0.59% v 0.89%; 0.80, 0.67 to 0.95). No increase was found in risk of small for gestational age at birth (9.1% v 9.2%; 0.98, 0.93 to 1.03) or stillbirth (0.25% v 0.44%; 0.65, 0.51 to 0.84). Findings were similar by trimester of vaccination, mRNA vaccine product, and number of doses received during pregnancy., Conclusion: The findings suggest that vaccination against covid-19 during pregnancy is not associated with a higher risk of preterm birth, small for gestational age at birth, or stillbirth., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the Public Health Agency of Canada through the Vaccine Surveillance Reference Group and the COVID-19 Immunity Task Force; SEH and LO were partly funded by the Norwegian Research Council. KW is chief executive officer of CANImmunize, which hosts a national digital immunisation record, and is a member of the independent data safety board for the Medicago covid-19 vaccine trial. There are no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine the population-level impact of COVID-19 pandemic-related obstetric practice changes on maternal and newborn outcomes., Methods: Segmented regression analysis examined changes that occurred 240 weeks pre-pandemic through the first 32 weeks of the pandemic using data from Ontario's Better Outcomes Registry & Network. Outcomes included birth location, length of stay, labour analgesia, mode of delivery, preterm birth, and stillbirth. Immediate and gradual effects were modelled with terms representing changes in intercepts and slopes, corresponding to the start of the pandemic., Results: There were 799 893 eligible pregnant individuals included in the analysis; 705 767 delivered in the pre-pandemic period and 94 126 during the pandemic wave 1 period. Significant immediate decreases were observed for hospital births (relative risk [RR] 0.99; 95% CI 0.98-0.99), length of stay (median change -3.29 h; 95% CI -3.81 to -2.77), use of nitrous oxide (RR 0.11; 95% CI 0.09-0.13) and general anesthesia (RR 0.69; 95% CI 0.58- 0.81), and trial of labour after cesarean (RR 0.89; 95% CI 0.83-0.96). Conversely, there were significant immediate increases in home births (RR 1.35; 95% CI 1.21-1.51), and use of epidural (RR 1.02; 95% CI 1.01-1.04) and regional anesthesia (RR 1.01; 95% CI 1.01-1.02). There were no significant immediate changes for any other outcomes, including preterm birth (RR 0.99; 95% CI 0.93-1.05) and stillbirth (RR 1.11; 95% CI 0.87-1.42)., Conclusion: Provincial health system changes implemented at the start of the pandemic resulted in immediate clinical practice changes but not insignificant increases in adverse outcomes., (Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Importance: There is conflicting evidence on the association between intrapartum epidural analgesia and risk of autism spectrum disorder (ASD) in offspring., Objective: To evaluate the association between intrapartum epidural analgesia and the risk of ASD in offspring., Design, Setting, and Participants: This population-based cohort study was conducted in Ontario, Canada, using the health and administrative records of singleton live births by vaginal delivery between April 1, 2006, and March 31, 2014. Neonates with less than 24 weeks' gestation or weighing less than 500 g were excluded. Offspring were followed up from 18 months of age until ASD diagnosis, loss to follow-up, or the end of the study (December 31, 2020), whichever occurred first. Exposure, covariate, and outcome data were obtained using provincial health administrative databases., Exposures: Any intrapartum exposure to epidural or combined spinal-epidural analgesia., Main Outcomes and Measures: The primary outcome was ASD diagnosis after 18 months of age. Inverse probability of treatment weighting (IPTW) of Cox proportional hazards regression models was used to estimate the hazard ratio (HR) of intrapartum epidural analgesia and ASD in offspring. Offspring head injury was used as a control outcome. Models were adjusted for maternal sociodemographic factors, health behaviors, and medical and obstetrical history as well as labor, delivery, and offspring characteristics. Post hoc analyses included restriction to term neonates, a conditional within-mother analysis, exclusion of records with concomitant intrapartum pain management exposures, a complete case analysis, use of an alternative ASD definition, and estimation of the average treatment effect in the treated group., Results: Among the 650 373 mother-offspring pairs included in the study, 418 761 (64.4%) were exposed to intrapartum epidural analgesia. The mean (SD) maternal age at delivery was 29.7 (5.5) years; the offspring had a mean (SD) gestational age at delivery of 39.1 (1.6) weeks and included 329 808 male newborns (50.7%). The exposed and unexposed groups were similar in all maternal and newborn characteristics after IPTW (standardized difference <0.10). Autism spectrum disorder was diagnosed in 7546 offspring (1.8%) of mothers who received intrapartum epidural analgesia (incidence rate, 18.8 [95% CI, 18.4-19.3] per 10 000 person-years) compared with 3234 offspring (1.4%) who were unexposed (incidence rate, 14.4 [95% CI, 13.9-14.9] per 10 000 person-years). The crude HR for ASD associated with intrapartum epidural analgesia was 1.30 (95% CI, 1.25-1.36), and the IPTW-adjusted HR was 1.14 (95% CI, 1.08-1.21). Results did not qualitatively differ in post hoc analyses., Conclusions and Relevance: Results of this study showed that intrapartum epidural analgesia was associated with a small increase in risk for ASD in offspring. The biological plausibility of this association, however, remains unclear, and the finding must be interpreted with caution.

Importance: There is limited comparative epidemiological evidence on outcomes associated with COVID-19 vaccination during pregnancy; monitoring pregnancy outcomes in large populations is required., Objective: To evaluate peripartum outcomes following COVID-19 vaccination during pregnancy., Design, Setting, and Participants: Population-based retrospective cohort study in Ontario, Canada, using a birth registry linked with the provincial COVID-19 immunization database. All births between December 14, 2020, and September 30, 2021, were included., Exposures: COVID-19 vaccination during pregnancy, COVID-19 vaccination after pregnancy, and no vaccination., Main Outcomes and Measures: Postpartum hemorrhage, chorioamnionitis, cesarean delivery (overall and emergency cesarean delivery), admission to neonatal intensive care unit (NICU), and low newborn 5-minute Apgar score (<7). Linear and robust Poisson regression was used to generate adjusted risk differences (aRDs) and risk ratios (aRRs), respectively, comparing cumulative incidence of outcomes in those who received COVID-19 vaccination during pregnancy with those vaccinated after pregnancy and those with no record of COVID-19 vaccination at any point. Inverse probability of treatment weights were used to adjust for confounding., Results: Among 97 590 individuals (mean [SD] age, 31.9 [4.9] years), 22 660 (23%) received at least 1 dose of COVID-19 vaccine during pregnancy (63.6% received dose 1 in the third trimester; 99.8% received an mRNA vaccine). Comparing those vaccinated during vs after pregnancy (n = 44 815), there were no significantly increased risks of postpartum hemorrhage (incidence: 3.0% vs 3.0%; aRD, -0.28 per 100 individuals [95% CI, -0.59 to 0.03]; aRR, 0.91 [95% CI, 0.82-1.02]), chorioamnionitis (0.5% vs 0.5%; aRD, -0.04 per 100 individuals [95% CI, -0.17 to 0.09]; aRR, 0.92 [95% CI, 0.70-1.21]), cesarean delivery (30.8% vs 32.2%; aRD, -2.73 per 100 individuals [95% CI, -3.59 to -1.88]; aRR, 0.92 [95% CI, 0.89-0.95]), NICU admission (11.0% vs 13.3%; aRD, -1.89 per 100 newborns [95% CI, -2.49 to -1.30]; aRR, 0.85 [95% CI, 0.80-0.90]), or low Apgar score (1.8% vs 2.0%; aRD, -0.31 per 100 newborns [95% CI, -0.56 to -0.06]; aRR, 0.84 [95% CI, 0.73-0.97]). Findings were qualitatively similar when compared with individuals who did not receive COVID-19 vaccination at any point (n = 30 115)., Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, COVID-19 vaccination during pregnancy, compared with vaccination after pregnancy and with no vaccination, was not significantly associated with increased risk of adverse peripartum outcomes. Study interpretation should consider that the vaccinations received during pregnancy were primarily mRNA vaccines administered in the second and third trimester.

Objective: To investigate the interrelationships between maternal socioeconomic status (SES), race and congenital heart diseases (CHD) among infants., Design: Retrospective cohort study., Study Setting: Ontario, Canada., Study Population: All singleton stillbirths and live births born in hospitals between 1 April 2012 and 31 March 2018 in Ontario, Canada (n=804 292)., Outcome: CHD., Analysis: Multivariable logistic regression models were performed to assess associations between maternal neighbourhood household income, education level, race and CHD while adjusting for maternal age at birth, assisted reproductive technology, obesity, pre-existing health conditions, substance use during pregnancy, maternal rural residence and infant's sex., Results: Compared with infants whose mothers lived in the highest median household income neighbourhoods, infants whose mothers lived in the lowest median income neighbourhoods had a higher likelihood of having CHD (adjusted OR 1.15, 95% CI 1.06 to 1.24). Compared with infants whose mothers lived in neighbourhoods with more people with a university or higher degree, those infants whose mothers lived in neighbourhoods with less people with a university or higher degree had a higher chance of developing CHD (adjusted OR 1.26, 95% CI 1.16 to 1.36). Compared with white mothers, black mothers had a higher odds of giving birth to a child with CHD (adjusted OR 1.40, 95% CI 1.27 to 1.54). No association was detected between White and Asian mothers and CHD among infants., Conclusions: Our study indicates that there are inequities in CHD burden by maternal SES and race in Ontario, Canada. Further investigation is needed to examine racial variation in CHD using more detailed ethnic data., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In Canada, as is found globally, women of reproductive age are a growing demographic of persons living with HIV. Combination antiretroviral therapy (cART) treatment enables women living with HIV (WLWH) to become pregnant without perinatal transmission, and they are increasingly planning to become pregnant. Since 2014, Canadian guidelines no longer recommend routine elective cesarean birth (CB) for women who are virally suppressed and receiving cART. It is unknown whether their obstetric care has changed since this update. Our objective was to describe trends in cesarean births among WLWH in Ontario, Canada, over a 12-year period., Methods: Our research is co-led and codesigned with WLWH. We conducted a retrospective population-level cohort study using linked health administrative databases at ICES (formally, the Institute for Clinical and Evaluative Sciences). Participants were all women who gave birth in Ontario, between 2006/07 and 2017/18. We assessed their intrapartum characteristics and used multivariable regression to determine an association between HIV status and CB, controlling for sociodemographic and clinical variables., Results: Since 2014, the overall proportion of CB among WLWH remained stable and was higher than among women without HIV (39.9% vs 29.0%, P < 0.001). In addition, the proportion of primary CB decreased between 2006 and 2010 and between 2014 and 2018 (28.5%-19.3%), whereas the proportion of repeat CB increased (13.1%-20.5%, P = 0.013)., Conclusions: Because of decreasing HIV-related indications for CB, more practitioners may be following the guidelines for first-time mothers. Currently, no guidelines exist for care of WLWH with a previous CB, and opportunities for vaginal birth may be missed in this population., (© 2021 Wiley Periodicals LLC.)

Background: Gastroschisis is a congenital anomaly of the abdomen in which the intestines are found outside of the body at birth. While no clear causative factors have been identified, it is strongly associated with young maternal age. Other reported associations include low maternal socioeconomic status, low maternal body mass index (BMI), and smoking., Methods: This is a retrospective review of epidemiologic data relating to cases of gastroschisis in Ontario from 2012-2018 in the Better Outcomes Registry & Network (BORN) Ontario database, which is the province's prescribed maternal-newborn registry. We describe the epidemiology of gastroschisis in Ontario with respect to birth prevalence, maternal age, health, exposures, and geography., Results: The birth prevalence of gastroschisis is 2.31 cases/10,000 births. There was no apparent change in birth prevalence over the study period and there was no difference between male and female infants. Gastroschisis was associated with younger maternal ages and was inversely correlated with maternal BMI. Gastroschisis was associated with first completed pregnancy. Maternal diabetes was associated with a lower birth prevalence of gastroschisis than average. Mothers of babies with gastroschsis were more likely to report use of tobacco, alcohol, and drugs during pregnancy than those without gastroschisis, with marijuana use showing the largest increase in birth prevalence of gastroschisis. Mothers living in rural areas were more likely to have a baby with gastroschisis than those in urban centers, even after controlling for maternal age., Conclusions: This Ontario registry study reveals that mothers with babies with gastroschisis are more likely to be young and thin, live in rural areas, and report prenatal smoking, alcohol use, and drug use than women whose pregnancies do not have gastroschsis., (© 2021 Wiley Periodicals LLC.)

Background: The emergence of cell-free fetal DNA (cfDNA) testing technology has disrupted the landscape of prenatal screening for trisomies 21 (T21) and 18 (T18). Publicly funded systems around the world are grappling with how to best integrate this more accurate but costly technology, as there is limited evidence about its incremental value in real-world conditions. The objectives of this study were to describe the population-based performance of Ontario's prenatal screening program, which incorporates publicly funded cfDNA screening for specific indications, and the effect of cfDNA testing on the screening and diagnostic choices made by pregnant people., Methods: We conducted a retrospective, descriptive cohort study using routinely collected data from Better Outcomes & Registry Network (BORN) Ontario, which captures linked population data for prenatal and neonatal health encounters across Ontario. We included all singleton pregnancies with an estimated due date between Sept. 1, 2016, and Mar. 31, 2019, that underwent publicly funded prenatal screening in Ontario, and a comparison cohort from Apr. 1, 2012, and Mar. 31, 2013. We assessed performance of the screening program for the detection of T21 or T18 by calculating sensitivity, specificity, positive predictive value and negative predictive value against diagnostic cytogenetic results or birth outcomes. We assessed the impact of the program by calculating the proportion of T21 screen-positive pregnancies undergoing subsequent cfDNA screening and invasive prenatal diagnostic testing., Results: The study cohort included 373 682 pregnancies. The prenatal screening program had an uptake of 69.9%, a screen-positive rate and sensitivity of 1.6% and 89.9% for T21, and 0.2% and 80.5% for T18, respectively. The test failure rate for cfDNA screening was 2.2%. Invasive prenatal diagnostic testing decreased from 4.4% in 2012-2013 to 2.4% over the study period; 65.2% of pregnant people who received a screen-positive result from cfDNA testing went on to have invasive prenatal diagnostic testing., Interpretation: This publicly funded screening program, incorporating cfDNA analysis for common aneuploidies, showed robust performance, a substantial reduction in invasive prenatal diagnostic testing and that pregnant people exercise autonomy in their choices about prenatal screening and diagnosis., Competing Interests: Competing interests: Nan Okun reports funding from Roche Diagnostic, outside the submitted work. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)