Recent Immigrants With Inflammatory Bowel Disease Have Significant Healthcare Utilization From Preconception to Postpartum: A Population Cohort Study.

INTRODUCTION: Immigrants with inflammatory bowel disease (IBD) may have increased healthcare utilization during pregnancy compared with non-immigrants, although this remains to be confirmed. We aimed to characterize this between these groups. METHODS: We accessed administrative databases to identify women (aged 18-55 years) with IBD with a singleton pregnancy between 2003 and 2018. Immigration status was defined as recent (<5 years of the date of conception), remote (≥5 years since the date of conception), and none. Differences in ambulatory, emergency department, hospitalization, endoscopic, and prenatal visits during 12 months preconception, pregnancy, and 12 months postpartum were characterized. Region of immigration origin was ascertained. Multivariable negative binomial regression was performed for adjusted incidence rate ratios (aIRRs) with 95% confidence intervals (CIs). RESULTS: A total of 8,880 pregnancies were included, 8,304 in non-immigrants, 96 in recent immigrants, 480 in remote immigrants. Compared with non-immigrants, recent immigrants had the highest rates of IBD-specific ambulatory visits during preconception (aIRR 3.06, 95% CI 1.93-4.85), pregnancy (aIRR 2.15, 95% CI 1.35-3.42), and postpartum (aIRR 2.21, 1.37-3.57) and the highest rates of endoscopy visits during preconception (aIRR 2.69, 95% CI 1.64-4.41) and postpartum (aIRR 2.01, 95% CI 1.09-3.70). There were no differences in emergency department and hospitalization visits between groups, although those arriving from the Americas were the most likely to be hospitalized for any reason. All immigrants with IBD were less likely to have a first trimester prenatal visit. DISCUSSION: Recent immigrants were more likely to have IBD-specific ambulatory care but less likely to receive adequate prenatal care during pregnancy.

Miscarriage after SARS-CoV-2 vaccination: A population-based cohort study.

OBJECTIVE: To evaluate the risk of miscarriage following SARS-CoV-2 vaccination, while accounting for the competing risk of induced abortion. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women aged 15-50 years with a confirmed pregnancy at ≤19 completed weeks' gestation. METHODS: Exposure to first SARS-CoV-2 vaccination, handled in a time-varying manner, was defined as (i) unvaccinated, (ii) remotely vaccinated >28 days before the estimated conception date or (iii) recently vaccinated ≤28 days before conception and up to 120 days after conception. MAIN OUTCOME MEASURES: The outcome was miscarriage, occurring between the estimated date of conception and up to 19 completed weeks of pregnancy. Fine-Grey hazard models, accounting for the competing risk of induced abortion, generated hazard ratios (aHR), adjusted for socio-demographic factors, comorbidities, and biweekly periods. RESULTS: Included were 246 259 pregnant women, of whom 34% received a first SARS-CoV-2 vaccination. Miscarriage occurred at a rate of 3.6 per 10 000 person-days among remotely vaccinated women and 3.2 per 10 000 person-days among those recently vaccinated, in contrast to a rate of 1.9 per 10 000 person-days among unvaccinated women, with corresponding aHR of 0.98 (95% confidence interval [CI] 0.91-1.07) and 1.00 (95% CI 0.93-1.08). CONCLUSIONS: SARS-CoV-2 vaccination was not associated with miscarriage while accounting for the competing risk of induced abortion. This study reiterates the importance of including pregnant women in new vaccine clinical trials and registries, and the rapid dissemination of vaccine safety data.

Temporal Trends in Gestational Diabetes Mellitus and Associated Risk Factors in Ontario, Canada, 2012-2020: A Population-Based Cohort Study.

OBJECTIVES: The prevalence of gestational diabetes mellitus (GDM) has been increasing globally over recent decades; however, underlying reasons for the increase remain unclear. We analyzed trends in GDM rates and evaluated risk factors associated with the observed trends in Ontario, Canada. METHODS: We conducted a retrospective population-based cohort study using the Better Outcomes Registry and Network Ontario, linked with the Canadian Institute for Health Information Discharge Abstract Database. All pregnant individuals who had a singleton hospital delivery from 1 April 2012 to 31 March 2020 were included. We calculated rates and 95% CIs for GDM by year of delivery and contrasted fiscal year 2019/20 with 2012/13. Temporal trends in GDM were quantified using crude and adjusted risk ratios by modified Poisson regression. We further quantified the temporal increase attributable to changes in maternal characteristics by decomposition analysis. RESULTS: Among 1 044 258 pregnant individuals, 82 896 (7.9%) were diagnosed with GDM over the 8 years. GDM rate rose from 6.1 to 10.4 per 100 deliveries between fiscal years 2012/13 and 2019/20. The risk of GDM in 2019/20 was 1.53 times (95% CI 1.50-1.56) higher compared with 2012/13. 27% of the increase in GDM was due to changes in maternal age, 8 BMI, and Asian ethnicity. CONCLUSIONS: The GDM rate has been consistently increasing in Ontario, Canada. The contribution of increasing maternal age, pre-pregnancy obesity, and Asian ethnicity to the recent increase in GDM is notable. Further investigation is required to better understand the contributors to increasing GDM.

A Population-Based Test-Negative Matched Case-Control Analysis of SARS-CoV-2 Vaccine Effectiveness Among Pregnant People in Ontario, Canada.

OBJECTIVE: Pregnancy is a risk factor for severe SARS-CoV-2 infection, which can result in adverse pregnancy outcomes, thus making understanding vaccine effectiveness (VE) in this population important. This study aimed to assess the VE of mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infection and COVID-19-related hospitalization in pregnant people. METHODS: Population-based matched test-negative case-control study of pregnant people aged 18-49 years, of 12 or more weeks gestation in Ontario, Canada, symptomatic with possible SARS-CoV-2 infection, and having at least 1 positive (n = 1842) or negative (n = 8524) real-time polymerase chain reaction (RT-PCR) SARS-CoV-2 test between December 14, 2020, and December 31, 2021. The exposure was receipt of ≥1 dose of mRNA COVID-19 vaccine versus no vaccination. Exposure was further stratified by number and recency of doses. The primary outcome was a positive SARS-CoV-2 RT-PCR test. As a secondary outcome, VE for COVID-19-related hospitalization was assessed. RESULTS: In the primary outcome analysis, there were 1821 positive cases, matched to 1821 negative controls. The mean (SD) maternal age was 31 (5) years. When compared to those unvaccinated, receipt of ≥1 dose was associated with an estimated VE of 39% (95% CI 29%-48%) for symptomatic infection, and 85% (95% CI 72%-92%) for COVID-19 hospitalization. VE estimates demonstrated waning with increased time since last vaccination. CONCLUSIONS: mRNA COVID-19 vaccines provide protection against symptomatic COVID-19 illness and are highly effective at preventing severe illness in pregnant people. The observed effect of vaccine waning highlights the importance of booster doses to provide optimal protection for pregnant people.

Relationship Between Gestational Weight Gain and Health Service Utilization in Early Childhood: A Retrospective Cohort Study.

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.

Effectiveness of maternal influenza vaccination during pregnancy against laboratory-confirmed seasonal influenza among infants under 6 months of age in Ontario, Canada.

BACKGROUND: Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited. METHODS: We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010-2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders. RESULTS: Among 23,806 infants tested for influenza, 1,783 (7.5%) were positive and 1,708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI]: 50%-74%). VE was similar by trimester of vaccination (1st/2nd: 66%, 40%-80%; 3rd: 63%, 46%-74%), infant age at testing (0-<2 months: 63%, 46%-75%; 2-<6 months: 64%, 36%-79%), and gestational age at birth (≥37 weeks: 64%, 50%-75%; < 37 weeks: 61%, 4%-86%). VE against influenza hospitalization was 67% (95%CI: 50%-78%). CONCLUSIONS: Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available.

Pregnancy Status at the Time of Coronavirus Disease 2019 Vaccination and Incidence of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Pregnant women are recommended to receive coronavirus disease 2019 (COVID-19) vaccines; however, relative effectiveness of vaccination by pregnancy status is unclear. METHODS: We compared the relative effectiveness of messenger RNA (mRNA) COVID-19 vaccines according to whether women received both doses while pregnant (n = 7412), 1 dose while pregnant (n = 3538), both doses while postpartum (n = 1856), or both doses while neither pregnant nor postpartum (n = 6687). We estimated risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection starting 14 days after the second dose using Cox regression, reporting hazard ratios (HRs) and 95% confidence intervals (CIs). Second, we examined relative effectiveness of a third (booster) dose while pregnant compared to outside pregnancy. The major circulating variant during the study period was the Delta variant. RESULTS: Fifty-four percent of women received 2 doses of the BNT162b2 vaccine, 16% received 2 doses of the mRNA-1273 vaccine, while 30% received 1 dose of both vaccines. Compared to women who received both doses while neither pregnant nor postpartum, the adjusted HR for a positive SARS-CoV-2 polymerase chain reaction test was similar if the woman received both doses while pregnant (1.04 [95% CI, .94-1.17]), 1 dose while pregnant and 1 dose before or after pregnancy (1.03 [95% CI, .93-1.14]), or both doses while postpartum (0.99 [95% CI, .92-1.07]). The findings were similar for BNT162b2 (Pfizer-BioNTech Comirnaty) and mRNA-1273 (Moderna Spikevax), and during Delta- and Omicron-dominant periods. We observed no differences in the relative effectiveness of the booster dose according to pregnancy status. CONCLUSIONS: We observed similar effectiveness of mRNA vaccines against SARS-CoV-2 infection among women regardless of pregnancy status at the time of vaccination.

Prenatal maternal stress, child internalizing and externalizing symptoms, and the moderating role of parenting: findings from the Norwegian mother, father, and child cohort study.

BACKGROUND: Few studies have examined how parenting influences the associations between prenatal maternal stress and children's mental health. The objectives of this study were to examine the sex-specific associations between prenatal maternal stress and child internalizing and externalizing symptoms, and to assess the moderating effects of parenting behaviors on these associations. METHODS: This study is based on 15 963 mother-child dyads from the Norwegian Mother, Father, and Child Cohort Study (MoBa). A broad measure of prenatal maternal stress was constructed using 41 self-reported items measured during pregnancy. Three parenting behaviors (positive parenting, inconsistent discipline, and positive involvement) were assessed by maternal report at child age 5 years. Child symptoms of internalizing and externalizing disorders (depression, anxiety, attention-deficit hyperactivity disorder, conduct disorder, and oppositional-defiant disorder) were assessed by maternal report at age 8. Analyses were conducted using structural equation modeling techniques. RESULTS: Prenatal maternal stress was associated with child internalizing and externalizing symptoms at age 8; associations with externalizing symptoms differed by sex. Associations between prenatal maternal stress and child depression, and conduct disorder and oppositional-defiant disorder in males, became stronger as levels of inconsistent discipline increased. Associations between prenatal maternal stress and symptoms of attention-deficit hyperactivity disorder in females were attenuated as levels of parental involvement increased. CONCLUSIONS: This study confirms associations between prenatal maternal stress and children's mental health outcomes, and demonstrates that these associations may be modified by parenting behaviors. Parenting may represent an important intervention target for improving mental health outcomes in children exposed to prenatal stress.

Associations between prenatal maternal stress, maternal inflammation during pregnancy, and children's internalizing and externalizing symptoms throughout childhood.

BACKGROUND: Maternal immune activation is a potential mechanism underlying associations between maternal stress during pregnancy and offspring mental health problems. This study examined associations between prenatal maternal stress, maternal inflammation during pregnancy, and children's internalizing and externalizing symptoms from 3 to 10 years of age, and whether maternal inflammation mediated the associations between prenatal maternal stress and children's internalizing and externalizing symptoms. METHODS: This study comprised 4,902 mother-child dyads in the Generation R study. Prenatal maternal stress was assessed using self-reported data collected during pregnancy and analyzed as a latent variable consisting of four stress domains. Maternal inflammation during pregnancy was assessed using serum concentrations of C-reactive protein (CRP) measured at a median of 13.5 weeks' gestation. Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist (CBCL) by maternal report at ages 3 years, 5 years, and 10 years; paternal-reported CBCL data were also available at 3 years and 10 years. RESULTS: Prenatal maternal stress was associated with maternal-reported internalizing and externalizing symptoms of the child at 3, 5, and 10 years of age, and with paternal-reported internalizing and externalizing symptoms at 3 and 10 years. Prenatal maternal stress was associated with maternal CRP concentrations prior to, but not after, covariate adjustment. Maternal CRP concentrations during pregnancy were associated with paternal-reported internalizing symptoms of offspring at 10 years of age prior to, but not after, covariate adjustment. There was no evidence that CRP concentrations mediated the associations between prenatal maternal stress and children's internalizing or externalizing symptoms. CONCLUSIONS: Maternal stress during pregnancy is associated with higher levels of internalizing and externalizing symptoms in children, but this association is not because of differences in maternal immune activation linked to maternal stress. Replication of these findings in other cohorts is required; examination of other biomarkers or variation in immune activity during pregnancy would also benefit from further exploration.

Impact of national recommendations for routine pertussis vaccination during pregnancy on infant pertussis in Ontario, Canada: a population-based time-series study.

BACKGROUND: In February 2018, Canada's National Advisory Committee on Immunization (NACI) recommended antenatal tetanus-diphtheria-acellular pertussis (Tdap) immunization in every pregnancy regardless of previous Tdap immunization history. We examined the impact of the NACI recommendation on rates of infant pertussis in Ontario, Canada. METHODS: We conducted a population-based time-series study of all live births in Ontario between August 1, 2011 and February 28, 2020. We used interventional autoregressive integrated moving average models to examine the impact of the NACI recommendation on monthly rates of pertussis among infants ≤ 3 months of age. RESULTS: We observed 675 incident cases of pertussis among 1,368,024 infants 3 months of age or less between August 2011 and February 2020. The average monthly percent change in infant pertussis during the period up to and including publication of the NACI guidance and the period following publication were 0.0% (95% CI: -0.4-0.3%) and - 0.8% (95% CI -2.3% to -0.1%), respectively. Following interventional ARIMA modelling, publication of the NACI guidance was not associated with a statistically significant decrease in the monthly pertussis incidence trend (-0.67 cases per 100,000 infants; p = 0.73). CONCLUSION: Publication of national recommendations for antenatal Tdap immunization in every pregnancy did not significantly reduce infant pertussis rates. This may reflect the persistently low rate of antenatal vaccination following publication of the recommendations. Expanding the scope of practice of allied health care providers to include antenatal Tdap immunization and patient education regarding antenatal pertussis immunization should be considered to further optimize uptake of vaccination.

Perinatal and pediatric outcomes associated with the use of fertility treatment: a population-based retrospective cohort study in Ontario, Canada.

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.

Comparison of adverse maternal and perinatal outcomes between induction and expectant management among women with gestational diabetes mellitus at term pregnancy: a systematic review and meta-analysis.

BACKGROUND: Induction at 38-40 weeks of gestation has been broadly suggested for women with gestational diabetes mellitus (GDM), yet its benefits and risks remain unclear. This study aimed to systematically review and meta-analyze existing evidence on the effect of induction at term gestation among women with GDM. METHODS: We searched MEDLINE, EMBASE, Cochrane Libraries, and Web of Science from inception to June 2021. We included randomized controlled trials (RCTs) and observational studies comparing induction with expectant management among GDM term pregnancies. Primary outcomes included caesarean section (CS) and macrosomia. All screening and extraction were conducted independently and in duplicates. Meta-analyses with random-effects models were conducted to generate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) using the Mantel-Haenszel method. Methodological quality was assessed independently by two reviewers using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale for observational studies. RESULTS: Of the 4,791 citations, 11 studies were included (3 RCTs and 8 observational studies). Compared to expectant management, GDM women with induction had a significantly lower odds for macrosomia (RCTs 0.49 [0.30-0.81]); observational studies 0.64 [0.54-0.77]), but not for CS (RCTs 0.95 [0.64-1.43]); observational studies 1.03 [0.79-1.34]). Induction was associated with a lower odds of severe perineal lacerations in observational studies (0.59 [0.39-0.88]). No significant difference was observed for other maternal or neonatal morbidities, or perinatal mortality between groups. CONCLUSIONS: For GDM women, induction may reduce the risk of macrosomia and severe perineal lacerations compared to expectant management. Further rigorous studies with large sample sizes are warranted to better inform clinical implications.

Fresh Compared With Frozen Embryo Transfer and Risk of Severe Maternal Morbidity: A Study of In Vitro Fertilization Pregnancies in Ontario, Canada.

OBJECTIVES: To quantify the risk of severe maternal morbidity (SMM) in fresh versus frozen-thawed embryo transfers (ETs) among pregnancies conceived by in vitro fertilization (IVF) and to assess SMM risk according to the number of fresh ETs prior to the index pregnancy. METHODS: Retrospective cohort study using the provincial birth registry in Ontario, Canada. We included 13 929 individuals aged 18-55 years who conceived via IVF between January 1, 2013, and March 5, 2018, and delivered a live or stillborn infant ≥20 weeks gestation. We compared the primary outcome, a composite of SMM or death, between fresh and frozen ETs. RESULTS: A total of 174 individuals who conceived via fresh ETs had SMM (30.7 per 1000), compared with 280 among individuals who received frozen ETs (33.9 per 1000); adjusted risk ratio (aRR) 0.85 (95% CI 0.70-1.04). Compared with frozen ET, fresh ET was associated with a lower risk of severe hemorrhage (aRR 0.63; 95% CI 0.48-0.82) but no difference in risk of preeclampsia. Among individuals with 1 (n = 211) or ≥2 (n = 88) prior fresh cycles, the risk of SMM was not increased compared with having no prior cycles; aRR 0.96 (95% CI 0.78-1.18) and 0.91 (95% CI 0.67-1.25), respectively. CONCLUSION: Fresh ET was associated with a lower risk of severe hemorrhage compared with frozen ET. These findings may be partly explained by the increased popularity of a freeze-all strategy, reserving fresh ETs for patients with fewer comorbidities.

Positive maternal mental health attenuates the associations between prenatal stress and children's internalizing and externalizing symptoms.

Positive maternal mental health can improve perceptions of stressful situations and promote the use of adaptive coping strategies. However, few studies have examined how positive maternal mental health affects children's development. The aims of this study were to examine the associations between positive maternal mental health and children's internalizing and externalizing symptoms, and to ascertain whether positive maternal mental health moderated the associations between prenatal stress and children's internalizing and externalizing symptoms. This study is based on the Norwegian Mother, Father, and Child Cohort Study (MoBa), and comprised 36,584 mother-child dyads. Prenatal stress was assessed using 41 self-reported items measured during pregnancy. Positive maternal mental health (self-efficacy, self-esteem, and enjoyment) was assessed by maternal report during pregnancy and postpartum. Child internalizing and externalizing symptoms were assessed by maternal report at age 5. Structural equation modeling was used for analysis. Maternal self-efficacy, self-esteem, and enjoyment were negatively associated with internalizing and externalizing symptoms in males and females. The association between prenatal stress and internalizing symptoms in males was stronger at low than at high levels of maternal self-esteem and enjoyment, whereas for females, the association was stronger at low than at high levels of maternal self-esteem and self-efficacy. This study provides evidence of associations between positive maternal mental health and children's mental health, and suggests that higher positive maternal mental health may buffer against the impacts of prenatal stress. Positive maternal mental health may represent an important intervention target to improve maternal-child well-being and foster intergenerational resilience.

SARS-CoV-2 Infection During Pregnancy and Associated Perinatal Health Outcomes: A National US Cohort Study.

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with increased risk of adverse perinatal health outcomes, few large-scale, community-based epidemiological studies have been conducted. METHODS: We conducted a national cohort study using deidentified administrative claims data for 78 283 pregnancies with estimated conception before 30 April 2020 and pregnancy end after 11 March 2020. We identified SARS-CoV-2 infections using diagnostic and laboratory testing data, and compared the risk of pregnancy outcomes using Cox proportional hazard models treating coronavirus disease 2019 (COVID-19) as a time-varying exposure and adjusting for baseline covariates. RESULTS: Of the pregnancies, 2655 (3.4%) had a documented SARS-CoV-2 infection. COVID-19 during pregnancy was not associated with risk of miscarriage, antepartum hemorrhage, or stillbirth, but was associated with 2-3 fold higher risk of induced abortion (adjusted hazard ratio [aHR], 2.60; 95% confidence interval [CI], 1.17-5.78), cesarean delivery (aHR, 1.99; 95% CI, 1.71-2.31), clinician-initiated preterm birth (aHR, 2.88; 95% CI, 1.93-4.30), spontaneous preterm birth (aHR, 1.79; 95% CI, 1.37-2.34), and fetal growth restriction (aHR, 2.04; 95% CI, 1.72-2.43). CONCLUSIONS: Prenatal SARS-CoV-2 infection was associated with increased risk of adverse pregnancy outcomes. Prevention could have fetal health benefits.

Attention-deficit hyperactivity disorder in children born to mothers with infertility: a population-based cohort study.

STUDY QUESTION: Is the risk of attention-deficit hyperactivity disorder (ADHD) increased in children born to mothers with infertility, or after receipt of fertility treatment, compared to mothers with unassisted conception? SUMMARY ANSWER: Infertility itself may be associated with ADHD in the offspring, which is not amplified by the use of fertility treatment. WHAT IS KNOWN ALREADY: Infertility, and use of fertility treatment, is common. The long-term neurodevelopmental outcome of a child born to a mother with infertility, including the risk of ADHD, remains unclear. STUDY DESIGN, SIZE, DURATION: This population-based cohort study comprised all singleton and multiple hospital births in Ontario, Canada, 2006-2014. Outcomes were assessed up to June 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Linked administrative datasets were used to capture all hospital births in Ontario, maternal health and pregnancy measures, fertility treatment and child outcomes. Included were all children born at ≥24 weeks gestation between 2006 and 2014, and who were alive at age 4 years. The main exposure was mode of conception, namely (i) unassisted conception (reference group), (ii) infertility without fertility treatment (history of an infertility consultation with a physician within 2 years prior to conception but no fertility treatment), (iii) ovulation induction (OI) or intrauterine insemination (IUI) and (iv) IVF or intracytoplasmic sperm injection (ICSI). The main outcome was a diagnosis of ADHD after age 4 years and assessed up to June 2020. Hazard ratios (HRs) were adjusted for maternal age, income quintile, rurality, immigration status, smoking, obesity, parity, any drug or alcohol use, maternal history of mental illness including ADHD, pre-pregnancy diabetes mellitus or chronic hypertension and infant sex. In addition, we performed pre-planned stratified analyses by mode of delivery (vaginal or caesarean delivery), infant sex, multiplicity (singleton or multiple), timing of birth (term or preterm <37 weeks) and neonatal adverse morbidity (absent or present). MAIN RESULTS AND THE ROLE OF CHANCE: The study included 925 488 children born to 663 144 mothers, of whom 805 748 (87%) were from an unassisted conception, 94 206 (10.2%) followed infertility but no fertility treatment, 11 777 (1.3%) followed OI/IUI and 13 757 (1.5%) followed IVF/ICSI. Starting at age 4 years, children were followed for a median (interquartile range) of 6 (4-8) years. ADHD occurred among 7.0% of offspring in the unassisted conception group, 7.5% in the infertility without fertility treatment group, 6.8% in the OI/IUI group and 6.3% in the IVF/ICSI group. The incidence rate (per 1000 person-years) of ADHD was 12.0 among children in the unassisted conception group, 12.8 in the infertility without fertility treatment group, 12.9 in the OI/IUI group and 12.2 in the IVF/ICSI group. Relative to the unassisted conception group, the adjusted HR for ADHD was 1.19 (95% CI 1.16-1.22) in the infertility without fertility treatment group, 1.09 (95% CI 1.01-1.17) in the OI/IUI group and 1.12 (95% CI 1.04-1.20) in the IVF/ICSI group. In the stratified analyses, these patterns of risk for ADHD were largely preserved. An exception was seen in the sex-stratified analyses, wherein females had lower absolute rates of ADHD but relatively higher HRs compared with that seen among males. LIMITATIONS, REASONS FOR CAUTION: Some mothers in the isolated infertility group may have received undocumented OI oral therapy, thereby leading to possible misclassification of their exposure status. Parenting behaviour, schooling and paternal mental health measures were not known, leading to potential residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: Infertility, even without treatment, is a modest risk factor for the development of ADHD in childhood. The reason underlying this finding warrants further study. STUDY FUNDING/COMPETING INTEREST(S): This study was made possible with funding from the Canadian Institutes of Health Research, Grant number PJT 165840. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Examining the role of pre-pregnancy weight and gestational weight gain in allergic disease development among offspring: A population-based cohort study in Ontario, Canada.

BACKGROUND: Studies suggest maternal weight and weight gain during pregnancy may influence foetal immunological development. However, their role in the aetiology of allergic disease is unclear. OBJECTIVES: We sought to examine the impact of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) on the incidence of four common paediatric allergic diseases. METHODS: We conducted a retrospective, population-based cohort study of all singleton live births in Ontario, Canada between 2012 and 2014, using maternal-newborn records from the provincial birth registry linked with health administrative databases. Neonates were followed up to 7 years for anaphylaxis, asthma, dermatitis and rhinitis, identified through validated algorithms based on healthcare encounters. We multiply imputed missing data and employed Cox proportional-hazards models to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI). To test the robustness of our findings, we also conducted several sensitivity analyses, including probabilistic bias analyses for exposure and outcome misclassification. All methods were prespecified in a published protocol. RESULTS: Of the 248,017 infants followed, 52% were born to mothers with a pre-pregnancy BMI in the normal range and only 19% were born to mothers with adequate weight gain during pregnancy. Incidence rates (per 100,000 person-days) for anaphylaxis, asthma, dermatitis and rhinitis were 0.22, 6.80, 12.41 and 1.54, respectively. Compared with normal BMI, maternal obesity was associated with increased hazards of asthma in offspring (aHR 1.08, 95% CI 1.05, 1.11), but decreased hazards of anaphylaxis (aHR 0.83, 95% CI 0.69, 0.99) and dermatitis (aHR 0.97, 95% CI 0.94, 0.99). In contrast, maternal underweight was associated with increased hazards of dermatitis (aHR 1.06, 95% CI 1.02, 1.10). We found no associations between pre-pregnancy BMI and rhinitis or GWG and any allergic outcome, and no evidence of effect measures modification by infant sex. CONCLUSIONS: These findings provide support for the involvement of maternal pre-pregnancy BMI in paediatric allergic disease development.

Comorbid conditions as risk factors for West Nile neuroinvasive disease in Ontario, Canada: a population-based cohort study.

West Nile neuroinvasive disease (WNND) is a severe neurological illness that can result from West Nile virus (WNV) infection, with long-term disability and death being common outcomes. Although WNV arrived in North America over two decades ago, risk factors for WNND are still being explored. The objective of this study was to identify WNND comorbid risk factors in the Ontario population using a retrospective, population-based cohort design. Incident WNV infections from laboratory records between 1 January 2002 - 31 December 2012 were individually-linked to health administrative databases to ascertain WNND outcomes and comorbid risk factors. WNND incidence was compared among individuals with and without comorbidities using risk ratios (RR) calculated with log binomial regression.Three hundred and forty-five individuals developed WNND (18.3%) out of 1884 WNV infections. West Nile encephalitis was driving most associations with comorbidities. Immunocompromised (aRR 2.61 [95% CI 1.23-4.53]) and male sex (aRR 1.32 [95% CI 1.00-1.76]) were risk factors for encephalitis, in addition to age, for which each 1-year increase was associated with a 2% (aRR 1.02 [95% CI 1.02-1.03]) relative increase in risk. Our results suggest that individuals living with comorbidities are at higher risk for WNND, in particular encephalitis, following WNV infection.

The impact of maternal and geographical factors on the uptake of non-invasive prenatal testing: A retrospective cohort study.

OBJECTIVES: The objectives of this study were to investigate recent trends in non-invasive prenatal testing (NIPT) utilisation, including factors associated with geographical variation, and to determine whether maternal or regional characteristics are associated with uptake the of NIPT. METHODS: This retrospective cohort study included pregnant individuals in Ontario with an expected date of delivery from August 1st, 2016 to March 31st, 2020. Modified Poisson regression was used to estimate rate ratios for NIPT use adjusted for maternal and healthcare covariates. RESULTS: We found substantial variation in NIPT uptake between regions within the province. The highest uptake was found in urban areas, highest quintile of neighbourhood income and education, for those who were ≥40 years of age and had a history of previous aneuploidy, for those with a prenatal care visit in the first trimester, multiple pregnancy, multigravidity and body mass index within the normal range (18.5-24.9 kg/m2 ). CONCLUSION: Our study demonstrated significant regional and maternal differences in NIPT uptake across Ontario. Given the large sample size and diverse population, our study may have implications for other jurisdictions with large, socio-demographically and geographically diverse populations.

COVID-19 pandemic and population-level pregnancy and neonatal outcomes in general population: A living systematic review and meta-analysis (Update#2: November 20, 2021).

INTRODUCTION: Conflicting reports of increases and decreases in rates of preterm birth (PTB) and stillbirth in the general population during the coronavirus disease 2019 (COVID-19) pandemic have surfaced. The objective of our study was to conduct a living systematic review and meta-analyses of studies reporting pregnancy and neonatal outcomes by comparing the pandemic and pre-pandemic periods. MATERIAL AND METHODS: We searched the PubMed and Embase databases and reference lists of articles published up until November 20, 2021, and included English language studies that compared outcomes between the COVID-19 pandemic time period with pre-pandemic time periods. Risk of bias was assessed using the Newcastle-Ottawa scale. We conducted random-effects meta-analysis using the inverse variance method. RESULTS: Fifty-two studies with low-to-moderate risk of bias, reporting on 2 372 521 pregnancies during the pandemic period and 28 518 300 pregnancies during the pre-pandemic period, were included. There was significant reduction in unadjusted estimates of PTB (43 studies, unadjusted odds ratio [uaOR] 0.95, 95% CI 0.93-0.98), but not in adjusted estimates (five studies, adjusted OR [aOR] 0.94, 95% CI 0.74-1.19). This reduction was noted in studies from single centers/health areas (29 studies, uaOR 0.90, 95% CI 0.85-0.94) but not in regional/national studies (14 studies, uaOR 0.99, 95% CI 0.99-1.01). There was reduction in spontaneous PTB (nine studies, uaOR 0.91, 95% CI 0.88-0.94) but not in induced PTB (eight studies, uaOR 0.90, 95% CI 0.79-1.01). There was no difference in the odds of stillbirth between the pandemic and pre-pandemic time periods (32 studies, uaOR 1.07, 95% CI 0.97-1.18 and three studies, aOR 1.18, 95% CI 0.86-1.63). There was an increase in mean birthweight during the pandemic period compared with the pre-pandemic period (nine studies, mean difference 21 g, 95% CI 13-30 g). The odds of maternal mortality were increased (five studies, uaOR 1.15, 95% CI 1.05-1.26); however, only unadjusted estimates were available, and the result was mostly influenced by one study from Mexico. There was significant publication bias for the outcome of PTB. CONCLUSIONS: The COVID-19 pandemic may be associated with a reduction in PTB; however, referral bias cannot be excluded. There was no statistically significant difference in stillbirths between pandemic and pre-pandemic periods.