Procedural abortion, provider-initiated preterm delivery and survival in pregnant people with cancer: A population-based cohort study.

OBJECTIVE: To assess whether procedural-induced abortion or provider-initiated preterm delivery are associated with improved survival in pregnant people with cancer. DESIGN: Retrospective population-based cohort study. SETTING: Provinces of Alberta and Ontario, Canada, 2003-2016. POPULATION: Females aged 18-50 years diagnosed with cancer at <20 weeks' (for the assessment of procedural-induced abortion) or <37 weeks' gestation (for the assessment of provider-initiated delivery). METHODS: Cox proportional hazard models assessed all-cause mortality in relation to procedural-induced abortion and provider-initiated preterm delivery, adjusting for cancer site, stage at diagnosis and age. Meta-analysis pooled the results across both provinces. MAIN OUTCOME MEASURES: All cause mortality. RESULTS: There were 512 pregnant people diagnosed with cancer at <20 weeks' gestation and 782 diagnosed with cancer at <37 weeks' gestation. Neither procedural-induced abortion (adjusted hazard ratio [aHR] = 1.39, 95% CI: 0.32-6.17) nor provider-initiated preterm delivery (aHR = 1.17, 95% CI: 0.76-1.81) were associated with improved survival following adjustment for age, stage at diagnosis and cancer site. CONCLUSIONS: Neither procedural-induced abortion nor provider-initiated preterm birth was associated with improved survival in pregnant people diagnosed with cancer; however, these obstetric interventions are highly personal decisions best decided by the pregnant person in consultation with their care providers.

Prescription Medication Use in Pregnancy in People with Disabilities: A Population-Based Cohort Study.

Background: Individuals with disabilities may require specific medications in pregnancy. The prevalence and patterns of medication use, overall and for medications with known teratogenic risks, are largely unknown. Methods: This population-based cohort study in Ontario, Canada, 2004-2021, comprised all recognized pregnancies among individuals eligible for public drug plan coverage. Included were those with a physical (n = 44,136), sensory (n = 13,633), intellectual or developmental (n = 2,446) disability, or multiple disabilities (n = 5,064), compared with those without a disability (n = 299,944). Prescription medication use in pregnancy, overall and by type, was described. Modified Poisson regression generated relative risks (aRR) for the use of medications with known teratogenic risks and use of ≥2 and ≥5 medications concurrently in pregnancy, comparing those with versus without a disability, adjusting for sociodemographic and clinical factors. Results: Medication use in pregnancy was more common in people with intellectual or developmental (82.1%), multiple (80.4%), physical (73.9%), and sensory (71.9%) disabilities, than in those with no known disability (67.4%). Compared with those without a disability (5.7%), teratogenic medication use in pregnancy was especially higher in people with multiple disabilities (14.2%; aRR 2.03, 95% confidence interval [CI]: 1.88-2.20). Furthermore, compared with people without a disability (3.2%), the use of ≥5 medications concurrently was more common in those with multiple disabilities (13.4%; aRR 2.21, 95% CI: 2.02-2.41) and an intellectual or developmental disability (9.3%; aRR 2.13, 95% CI: 1.86-2.45). Interpretation: Among people with disabilities, medication use in pregnancy is prevalent, especially for potentially teratogenic medications and polypharmacy, highlighting the need for preconception counseling/monitoring to reduce medication-related harm in pregnancy.

Impact of Antenatal Care Modifications on Gestational Diabetes Outcomes During the COVID-19 Pandemic.

BACKGROUND: Many of the adverse outcomes of gestational diabetes mellitus (GDM) are linked to excessive fetal growth, which is strongly mediated by the adequacy of maternal glycemic management. The COVID-19 pandemic led to a rapid adoption of virtual care models. We aimed to compare glycemic management, fetal growth, and perinatal outcomes before and during the COVID-19 pandemic. METHODS: A retrospective cohort study was conducted between 2017 and 2020. Singleton pregnancies complicated by GDM were included in the study. The cohort was stratified into "before" and "during" COVID-19 subgroups, using March 11, 2020, as the demarcation time point. Women who began their GDM follow-up starting March 11, 2020, and thereafter were allocated to the COVID-19 era, whereas women who delivered before the demarcation point served as the pre-COVID-19 era. The primary outcome was the rate of large-for-gestational-age (LGA) neonates. Secondary outcomes included select maternal and neonatal adverse outcomes. RESULTS: Seven hundred seventy-five women were included in the analysis, of which 187 (24.13%) were followed during the COVID-19 era and 588 (75.87%) before the COVID-19 era. One hundred seventy-one of the 187 women (91.44%) followed during COVID-19 had at least 1 virtual follow-up visit. No virtual follow-up visits occurred before the COVID-19 era. There was no difference in the rate of LGA neonates between groups on both univariate (5.90% vs 7.30%, p=0.5) and multivariate analyses, controlling for age, ethnicity, parity, body mass index, gestational weight gain, chronic hypertension, smoking, and hypertensive disorders in pregnancy (adjusted odds ratio [aOR] 1.11, 95% confidence interval [CI] 0.49 to 2.51, p=0.80). In the multivariate analysis, there was no difference in composite neonatal outcome between groups (GDM diet: aOR 1.40, 95% CI 0.81 to 2.43, p=0.23; GDM medical treatment: aOR 1.20, 95% CI 0.63 to 2.43, p=0.5). CONCLUSIONS: After adjusting for differences in baseline variables, the combined virtual mode of care was not associated with a higher rate of LGA neonates or other adverse perinatal outcomes in women with GDM. Larger studies are needed to better understand the specific impact of virtual care on less common outcomes in pregnancies with GDM.

Long-term Mortality in Individuals Diagnosed With Cancer During Pregnancy or Postpartum.

Importance: Outcomes among patients with pregnancy-associated cancers (diagnosed during pregnancy or 1-year postpartum) other than breast cancer have received relatively little research attention. High-quality data from additional cancer sites are needed to inform the care of this unique group of patients. Objective: To assess mortality and survival in premenopausal women with pregnancy-associated cancers, with a particular focus on cancers other than those of the breast. Design, Setting, and Participants: This population-based retrospective cohort study included premenopausal women (aged 18-50 years) living in 3 Canadian provinces (Alberta, British Columbia, and Ontario) diagnosed with cancer between January 1, 2003, and December 31, 2016, with follow-up until December 31, 2017, or date of death. Data analysis occurred in 2021 and 2022. Exposures: Participants were categorized as being diagnosed with cancer during pregnancy (from conception to delivery), during the postpartum period (up to 1 year after delivery), or during a time that was remote from pregnancy. Main Outcomes and Measures: Outcomes were overall survival at 1 and 5 years and time from diagnosis to death due to any cause. Cox proportional hazard models were used to estimate mortality adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), adjusting for age at cancer diagnosis, cancer stage, cancer site, and days from diagnosis to first treatment. Meta-analysis was used to pool results across all 3 provinces. Results: During the study period there were 1014, 3074, and 20 219 participants diagnosed with cancer during pregnancy, postpartum, and periods remote from pregnancy, respectively. One-year survival was similar across the 3 groups, but 5-year survival was lower among those diagnosed with cancer during pregnancy or postpartum. Overall, there was a greater risk of death due to pregnancy-associated cancer among those diagnosed during pregnancy (aHR, 1.79; 95% CI, 1.51-2.13) and postpartum (aHR, 1.49; 95% CI, 1.33-1.67); however, these results varied across cancer sites. Increased hazard of mortality was observed for breast (aHR, 2.01; 95% CI, 1.58-2.56), ovarian (aHR, 2.60; 95% CI, 1.12-6.03), and stomach (aHR, 10.37; 95% CI, 3.56-30.24) cancers diagnosed during pregnancy, and brain (aHR, 2.75; 95% CI, 1.28-5.90), breast (aHR, 1.61; 95% CI, 1.32-1.95), and melanoma (aHR, 1.84; 95% CI, 1.02-3.30) cancers diagnosed postpartum. Conclusions and Relevance: This population-based cohort study found that pregnancy-associated cancers had increased overall 5-year mortality, though not all cancer sites presented the same risk.

SARS-CoV-2 vaccination, ABO blood group and risk of COVID-19: population-based cohort study.

OBJECTIVE: To compare outcomes between O and non-O blood groups, and by modified RNA (mRNA) and adenovirus-vectored (Ad-V) vaccines. DESIGN: Population-based cohort study. SETTING: All of Ontario, Canada. Linked data sets captured clinical encounters, vaccinations and laboratory testing for SARS-CoV-2. PARTICIPANTS: Individuals aged 12+ years with known ABO blood group and free of SARS-CoV-2 before 15 January 2021. MAIN OUTCOMES MEASURES: The main exposure, first SARS-CoV-2 vaccination, was modelled in a time-varying manner. O and non-O blood group was known prior to vaccination. SARS-CoV-2 infection, and severe COVID-19 (hospitalisation or death), were assessed starting 14 days after vaccination, up to 27 June 2021. RESULTS: 2 472 261 individuals were included. 1 743 916 (70.5%) had at least one vaccination, of which 24.6% were fully vaccinated. Those vaccinated were more likely to be women, older in age, residing in a higher-income area and have higher rates of certain comorbid conditions, like cancer, diabetes and hypertension. Relative to unvaccinated, after receiving their first mRNA (adjusted HR (aHR) 0.46, 95% CI 0.44 to 0.47) or Ad-V (aHR 0.49, 95% CI 0.44 to 0.54) vaccine, the risk of SARS-CoV-2 infection was lower, as was severe COVID-19 (aHR 0.29, 95% CI 0.20 to 0.43 (mRNA); aHR 0.29, 95% CI 0.26 to 0.33 (Ad-V)). Stratifying by blood group produced similar results. For example, after first mRNA vaccination, the aHR of severe COVID-19 was 0.31 (95% CI 0.27 to 0.36) among non-O blood groups, and 0.27 (95% CI 0.22 to 0.32) among O blood groups, relative to unvaccinated. Fully vaccinated individuals had the lowest risk of SARS-CoV-2 and severe COVID-19. CONCLUSIONS: SARS-CoV-2 infection and severe COVID-19 are reduced by vaccination. This effect does not vary by vaccine type or blood group, but is more pronounced among fully, than partially, vaccinated individuals.

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.

Interpregnancy Weight Change Among Mothers of a Child with a Major Congenital Anomaly: A Danish Nationwide Cohort Study.

Background: The mother of an infant with a major congenital anomaly is at a higher risk of premature cardiometabolic disease, possibly from chronic caregiver stress and distraction from self-care, including maintaining a healthy lifestyle and body weight. Objective: To compare the interpregnancy weight gain in women whose first infant had a major congenital anomaly vs those without an affected child. Methods: Multivariable linear regression compared women whose infant had an anomaly vs those whose infant did not, adjusting for interpregnancy time interval, demographics, smoking and health status at the first pregnancy. Results: Of the 199,536 women who had two consecutive singleton births, 4035 (2.0%) had a child with an anomaly at the first birth. The mean (SD) maternal BMI at the start of the first pregnancy was 24.1 (4.7) and 23.7 (4.4) kg/m2 in women with, and without, an anomaly-affected newborn. By the start of the second pregnancy, 3 years later, they had gained a mean (SD) of 2.2 (5.5) and 1.8 (5.2) kg, respectively - an adjusted absolute higher gain of 0.26 kg (95% CI 0.10 to 0.42) in women with an anomaly-affected first-born infant compared to those with an unaffected pregnancy. The adjusted interpregnancy weight gain difference was greatest in women whose first-born infant had a multi-organ anomaly at 0.59 kg (95% CI 0.02 to 1.16). The adjusted odds ratio of moving from a normal BMI category of 18.5-24.9 kg/m2 in the first pregnancy, to an overweight or obese BMI category of 25+ kg/m2 in the second, was 1.18 (95% CI 1.06 to 1.32) comparing mothers with vs without an anomaly-affected child in the first pregnancy. Conclusion: Mothers of an infant with a major congenital anomaly have a modestly higher interpregnancy weight gain and tend to climb to a higher BMI category. The long-term implications of this greater weight trajectory require further study.

Obstetrical and Perinatal Outcomes in Female Survivors of Childhood and Adolescent Cancer: A Population-Based Cohort Study.

BACKGROUND: The likelihood of pregnancy and risk of obstetrical or perinatal complications is inadequately documented in female survivors of pediatric cancer. METHODS: We assembled a population-based cohort of female survivors of cancer diagnosed at age 21 years and younger in Ontario, Canada, between 1985 and 2012. Survivors were matched 1:5 to women without prior cancer. Multivariable Cox proportional hazards and modified Poisson models assessed the likelihood of a recognized pregnancy and perinatal and maternal complications. RESULTS: A total of 4062 survivors were matched to 20 308 comparisons. Median (interquartile range) age was 11 (4-15) years at cancer diagnosis and 25 (19-31) years at follow-up. By age 30 years, the cumulative incidence of achieving a recognized pregnancy was 22.3% (95% confidence interval [CI] = 20.7% to 23.9%) among survivors vs 26.6% (95% CI = 25.6% to 27.3%) among comparisons (hazard ratio = 0.80, 95% CI = 0.75 to 0.86). A lower likelihood of pregnancy was associated with a brain tumor, alkylator chemotherapy, cranial radiation, and hematopoietic stem cell transplantation. Pregnant survivors were as likely as cancer-free women to carry a pregnancy >20 weeks (relative risk [RR] = 1.01, 95% CI = 0.98 to 1.04). Survivors had a higher relative risk of severe maternal morbidity (RR = 2.31, 95% CI = 1.59 to 3.37), cardiac morbidity (RR = 4.18, 95% CI = 1.89 to 9.24), and preterm birth (RR = 1.57, 95% CI = 1.29 to 1.92). Preterm birth was more likely in survivors treated with hematopoietic stem cell transplantation (allogenic: RR = 8.37, 95% CI = 4.83 to 14.48; autologous: RR = 3.72, 95% CI = 1.66 to 8.35). CONCLUSIONS: Survivors of childhood or adolescent cancer are less likely to achieve a pregnancy and, once pregnant, are at higher risk for severe maternal morbidity and preterm birth.

Maternal Schizophrenia, Skin-to-Skin Contact, and Infant Feeding Initiation.

BACKGROUND: The World Health Organization recommends mothers and infants be in direct skin-to-skin contact immediately after birth and initiate breastfeeding as soon as possible. Little is known in women with schizophrenia. METHODS: We conducted a population-based cohort study using administrative health data from Ontario, Canada (2012-2014), comparing women with (n = 471) and without schizophrenia (n = 218 435), and their infants, on the primary outcomes of any skin-to-skin contact and opportunity to initiate breastfeeding within the first 2 h after birth. For dyads with available data, secondary outcomes of intention to breastfeed, breastfeeding support, any breastmilk, and exclusive breastmilk at discharge were assessed. Modified Poisson regression was used to generate relative risks (aRR) and 95% confidence intervals (CI), adjusted for maternal age, parity, neighbourhood income, region of residence, smoking in pregnancy, and maternal medical and non-psychotic psychiatric comorbidity for all outcomes. RESULTS: Maternal schizophrenia was associated with lower likelihood of skin-to-skin contact (65.2% vs 78.1%; aRR 0.88, 95% CI: 0.82-0.94), and breastfeeding initiation post-delivery (38.9% vs 52.6% aRR 0.80, CI: 0.71-0.90) compared to dyads unexposed to maternal schizophrenia. Secondary outcomes followed a similar pattern. The magnitude of the effect was slightly less when restricting the cohort to full-term, vaginal deliveries, not admitted to NICU, and infant not discharged to social services. CONCLUSIONS: Reduced maternal-infant skin-to-skin contact and breastfeeding initiation immediately after birth may significantly impact maternal-child bonding and the establishment breastfeeding in this population. Mothers with schizophrenia may require individualized support to promote these WHO recommended hospital practices in the early post-natal period.

Identifying maternal deaths with the use of hospital data versus death certificates: a retrospective population-based study.

BACKGROUND: Accurate identification of maternal deaths is paramount for audit and policy purposes. Our aim was to determine the accuracy and completeness of data on maternal deaths in hospital and those recorded on a death certificate, and the level of agreement between the 2 data sources. METHODS: We conducted a retrospective population-based study using data for Ontario, Canada, from Apr. 1, 2002, to Dec. 31, 2015. We used Canadian Institute for Health Information (CIHI) databases to identify deaths during inpatient, emergency department and same-day surgery encounters. We captured Vital Statistics deaths in the Office of the Registrar General, Deaths (ORGD) data set. Deaths were considered within 42 days and within 365 days after a pregnancy outcome (live birth, miscarriage, ectopic pregnancy or induced abortion) for all multiple and singleton pregnancies. We calculated agreement statistics and 95% confidence intervals (CIs). RESULTS: Among 1 679 455 live births and stillbirths, 398 pregnancy-related deaths in the ORGD data set were mapped to a birth in CIHI databases, and 77 (16.2%) were not. Among 2 039 849 recognized pregnancies, 534 pregnancy-related deaths in the ORGD data set were linked to CIHI records, and 68 (11.3%) were not. Among live births and stillbirths, after pregnancy-related deaths in the ORGD data set not matched to a maternal death in the CIHI databases were removed, concordance measures between CIHI and ORGD records for maternal death within 42 days after delivery included a κ value of 0.87 (95% CI 0.82-0.91) and positive percent agreement of 0.88 (95% CI 0.83-0.94). The corresponding measures were similar for maternal death within 42 days after the end of a recognized pregnancy. When unlinked pregnancy-related deaths in the ORGD data set were retained, agreement measures declined for death within 42 days after a live birth or stillbirth (κ = 0.68, 95% CI 0.62-0.74). For maternal death within 365 days after a live birth or stillbirth, or after the end of a recognized pregnancy, the concordance statistics were generally favourable when unlinked pregnancy-related deaths in the ORGD data set were removed but were substantially declined when they were retained. INTERPRETATION: Maternal mortality cannot be ascertained solely with the use of hospital data, including beyond 42 days after the end of pregnancy. To improve linkage, we propose including health insurance numbers on provincial and territorial medical death certificates.

Incidence of Pregnancy-Associated Cancer in Two Canadian Provinces: A Population-Based Study.

Pregnancy-associated cancer-that is diagnosed in pregnancy or within 365 days after delivery-is increasingly common as cancer therapy evolves and survivorship increases. This study assessed the incidence and temporal trends of pregnancy-associated cancer in Alberta and Ontario-together accounting for 50% of Canada's entire population. Linked data from the two provincial cancer registries and health administrative data were used to ascertain new diagnoses of cancer, livebirths, stillbirths and induced abortions among women aged 18-50 years, from 2003 to 2015. The annual crude incidence rate (IR) was calculated as the number of women with a pregnancy-associated cancer per 100,000 deliveries. A nonparametric test for trend assessed for any temporal trends. In Alberta, the crude IR of pregnancy-associated cancer was 156.2 per 100,000 deliveries (95% CI 145.8-166.7), and in Ontario, the IR was 149.4 per 100,000 deliveries (95% CI 143.3-155.4). While no statistically significant temporal trend in the IR of pregnancy-associated cancer was seen in Alberta, there was a rise in Ontario (p = 0.01). Pregnancy-associated cancer is common enough to warrant more detailed research on maternal, pregnancy and child outcomes, especially as cancer therapies continue to evolve.

BMI and risk of gestational diabetes among women of South Asian and Chinese ethnicity: a population-based study.

AIMS/HYPOTHESIS: The aim of this study was to examine how BMI influences the association between Asian ethnicity and risk of gestational diabetes (GDM). METHODS: This population-based cohort study included pregnant women without pre-existing diabetes mellitus in Ontario, Canada between 2012 and 2014. Women of Chinese and South Asian ethnicity were identified using a validated surname algorithm. GDM was ascertained using hospitalisation codes. The relationship between ethnicity and GDM was modelled using modified Poisson regression, adjusted for maternal age, pre-pregnancy BMI, parity, previous GDM, long-term residency status, income quintile and smoking status. An interaction term between ethnicity and pre-pregnancy BMI was tested. RESULTS: Of 231,618 pregnant women, 9289 (4.0%) were of South Asian ethnicity and 12,240 (5.3%) were of Chinese ethnicity. Relative to women from the general population, in whom prevalence of GDM was 4.3%, the adjusted RR of GDM was higher among those of South Asian ethnicity (1.81 [95% CI 1.64, 1.99]) and Chinese ethnicity (1.66 [95% CI 1.53, 1.80]). The association between GDM and Asian ethnicity remained significant across BMI categories but differed according to BMI. The prevalence of GDM exceeded 5% at an estimated BMI of 21.5 kg/m2 among South Asian women, 23.0 kg/m2 among Chinese women and 29.5 kg/m2 among the general population. CONCLUSIONS/INTERPRETATION: The risk of GDM is significantly higher in South Asian and Chinese women, whose BMI is lower than that of women in the general population. Accordingly, targeted GDM prevention strategies may need to consider lower BMI cut-points for Asian populations.

Maternal Visceral Adipose Tissue and Risk of Having a Small or Large for Gestational Age Infant.

OBJECTIVE: To determine whether first-trimester visceral adipose tissue (VAT) depth is associated with small-for-gestational-age (SGA; <10th percentile) or large-for-gestational-age (LGA; >90th percentile) birthweight, including when taking into consideration ethnicity-specific birthweight curves. METHODS: We conducted a prospective cohort study involving 452 women with a singleton livebirth. Maternal VAT depth was measured by ultrasound at 11 to 14 weeks gestation. Newborn weight was plotted on population-based and ethnicity-specific birthweight percentile curves. Modelling was performed using linear and logistic regression, adjusting for parity, smoking status, and weight gain. RESULTS: Mean maternal age was 32.9 ± 4.7 years, and mean VAT depth was 4.1 ± 1.7 cm. Using a population-based curve, each 1-cm increase in VAT depth was associated with a 1.5 (95% CI 0.03-3.0) higher birthweight percentile. Taking into account ethnicity-specific curves, a 1-cm higher VAT depth was associated with a 1.7 (95% CI 0.02-3.3) greater birthweight percentile. Using a population-based curve, comparing VAT depth Q4 with VAT depth Q1-3, the adjusted odds ratio (aOR) for LGA was 1.9 (95% CI 0.8-4.1); with ethnicity-specific curves, the aOR for LGA was 1.5 (95% CI 0.7-3.2). The aOR for SGA was 0.8 (95% CI 0.4 to 1.7) comparing Q1 with Q2-4 VAT depth. CONCLUSION: Higher first-trimester maternal VAT depth was associated with a somewhat greater newborn weight percentile, which varies by which birthweight curve is used. There were marginally higher odds of giving birth to an LGA infant for women in highest quartile for VAT depth, with no evident association with SGA.

Reproductive patterns, pregnancy outcomes and parental leave practices of women physicians in Ontario, Canada: the Dr Mom Cohort Study protocol.

INTRODUCTION: Surveys and qualitative studies suggest that women physicians may delay childbearing, be at increased risk of adverse peripartum complications when they do become pregnant, and face discrimination and lower earnings as a result of parenthood. Observational studies enrolling large, representative samples of women physicians are needed to accurately evaluate their reproductive patterns, pregnancy outcomes, parental leave practices and earnings. This protocol provides a detailed research plan for such studies. METHODS AND ANALYSIS: The Dr Mom Cohort Study encompasses a series of retrospective observational studies of women physicians in Ontario, Canada. All practising physicians in Ontario are registered with the College of Physicians and Surgeons of Ontario (CPSO). By linking a dataset of physicians from the CPSO to existing provincial administrative databases, which hold health data and physician billing records, we will be able to retrospectively assess the healthcare utilisation, work practices and pregnancy outcomes of women physicians at the population level. Specific outcomes of interest include: (1) rates and timing of pregnancy; (2) pregnancy-related care and complications; and (3) duration of parental leave and subsequent earnings, each of which will be evaluated with regression methods appropriate to the form of the outcome. We estimate that, at minimum, 5000 women physicians will be eligible for inclusion. ETHICS AND DISSEMINATION: This protocol has been approved by the Research Ethics Board at St. Michael's Hospital in Toronto, Ontario, Canada (#18-248). We will disseminate findings through several peer-reviewed publications, presentations at national and international meetings, and engagement of physicians, residency programmes, department heads and medical societies.

Population-based study of serum ferritin in early pregnancy and adverse perinatal outcomes.

BACKGROUND: Chronic placental inflammation is associated with preterm birth (PTB) and perinatal mortality. Ferritin is often elevated in chronic inflammatory conditions, but prior studies of its relation to PTB were restricted to ferritin measurement within pregnancy, were underpowered to detect rarer outcomes, and did not account for pre-existing maternal inflammatory conditions, such as inflammatory bowel or rheumatological disease. OBJECTIVES: To evaluate whether an elevated ferritin level prior to pregnancy is associated with major adverse pregnancy outcomes. METHODS: A population-based cohort study was completed using Ontario, Canada. Included were all Ontarian women with a hospital livebirth or stillbirth at ≥20 weeks' gestation, 2007-2018, and serum haemoglobin and ferritin measured as an outpatient within 120 days before conception. Excluded were women with a diagnosed iron overload disorder or a ferritin concentration <15 µg/L. The main exposure was a pre-pregnancy serum ferritin ≥95th percentile. Study outcomes included PTB < 37 weeks' gestation, including clinician-initiated and spontaneous PTB; PTB < 32 weeks; chorioamnionitis; and perinatal death. Relative risks (RR) and 95% confidence intervals (CI) were calculated for each study outcome, comparing a serum ferritin concentration ≥95th vs <5th percentile (the referent), while adjusting maternal age, residence, haemoglobin concentration, diabetes mellitus, inflammatory bowel disease, illicit drug/tobacco use, chronic kidney disease, chronic hypertension, sickle-cell disease or thalassaemia, and rheumatological conditions. RESULTS: Among 89 847 births, a preconceptional maternal serum ferritin ≥95th (112.0 µg/L) vs <5th (16.9 µg/L) percentile was associated with an adjusted relative risk (aRR) of 1.34 (95% CI 1.15, 1.57) for PTB, including spontaneous and clinician-initiated PTB. Results were equivocal for chorioamnionitis (aRR 1.23, 95% CI 0.81, 1.86), and there was no association with perinatal mortality (aRR 0.94, 95% CI 0.55, 1.61). CONCLUSION: A high preconceptional ferritin concentration is associated with some adverse perinatal outcomes.

Risk of severe maternal morbidity or death in relation to elevated hemoglobin A1c preconception, and in early pregnancy: A population-based cohort study.

BACKGROUND: The relation between prepregnancy average glucose concentration and a woman's risk of severe maternal morbidity (SMM) is unknown. The current study evaluated whether an elevated preconception hemoglobin A1c (A1c) is associated with SMM or maternal death among women with and without known prepregnancy diabetes mellitus (DM). METHODS AND FINDINGS: A population-based cohort study was completed in Ontario, Canada, where there is universal healthcare. The main cohort included 31,225 women aged 16-50 years with a hospital live birth or stillbirth from 2007 to 2015, and who had an A1c measured within 90 days before conception, including 28,075 women (90%) without known prepregnancy DM. The main outcome was SMM or maternal mortality from 23 weeks' gestation up to 42 days postpartum. Relative risks (RRs) were generated using modified Poisson regression, adjusting for the main covariates of maternal age, multifetal pregnancy, world region of origin, and tobacco/drug dependence. The mean maternal age was 31.1 years. Overall, SMM or death arose among 682 births (2.2%). The RR of SMM or death was 1.16 (95% CI 1.14-1.19; p < 0.001) per 0.5% increase in A1c and 1.16 (95% CI 1.13-1.18; p < 0.001) after adjusting for the main covariates. The adjusted relative risk (aRR) was increased among those with (1.11, 95% CI 1.07-1.14; p < 0.001) and without (1.15, 95% CI 1.02-1.29; p < 0.001) known prepregnancy diabetes, and upon further adjusting for body mass index (BMI) (1.15, 95% CI 1.11-1.20; p < 0.001), or chronic hypertension and prepregnancy serum creatinine (1.11, 95% CI 1.04-1.18; p = 0.002). The aRR of SMM or death was 1.31 (95% CI 1.06-1.62; p = 0.01) in those with a preconception A1c of 5.8%-6.4%, and 2.84 (95% CI 2.31-3.49; p < 0.001) at an A1c > 6.4%, each relative to an A1c < 5.8%. Among those without previously recognized prepregnancy diabetes and whose A1c was >6.4%, the aRR of SMM or death was 3.25 (95% CI 1.76-6.00; p < 0.001). Study limitations include that selection bias may have incorporated less healthy women tested for A1c, and BMI was unknown for many women. CONCLUSIONS: Our findings indicate that women with an elevated A1c preconception may be at higher risk of SMM or death in pregnancy or postpartum, including those without known prepregnancy DM.

Prenatal Biochemical Screening and a Woman's Long-Term Risk of Cancer: A Population-Based Cohort Study.

BACKGROUND: Some hormones measured in pregnancy are linked to certain hormone-sensitive cancers. We investigated whether routine serum screening in pregnancy is associated with a woman's subsequent risk of hormone-sensitive cancer. METHODS: This population-based cohort study included women aged 12-55 years who underwent prenatal screening between 11 weeks + 0 days of gestation to 20 weeks + 6 days of gestation in Ontario, Canada, 1993-2011, where universal health care is available. The hazard ratio of newly diagnosed breast, ovarian, endometrial, and thyroid cancer-arising at 21 weeks + 0 days of gestation or thereafter-was estimated in association with an abnormally low (≤5th) or high (>95th) percentile multiple of the median (MoM) for alpha-fetoprotein (AFP), total human chorionic gonadotropin (hCG), unconjugated estriol, pregnancy-associated plasma protein A, and dimeric inhibin A. RESULTS: Among 677 247 pregnant women followed for a median of 11.0 years (interquartile range = 7.5-16.1), 7231 (1.07%) developed breast cancer, 515 (0.08%) ovarian cancer, 508 (0.08%) endometrial cancer, and 4105 (0.61%) thyroid cancer. In multivariable adjusted models, abnormally high hCG greater than the 95th percentile MoM was associated with a doubling in the risk of endometrial cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.33 to 2.95), and abnormally low AFP at the fifth percentile or less MoM conferred a moderately greater risk of thyroid cancer (aHR = 1.21, 95% CI = 1.07 to 1.38). Abnormally low pregnancy-associated plasma protein A at the fifth percentile or less MoM was not statistically significantly associated with breast cancer after multivariable adjustment (aHR = 1.19, 95% CI = 0.98 to 1.36). CONCLUSIONS: Women with abnormally high levels of serum hCG or low AFP in early pregnancy may be at a greater future risk of certain types of hormone-sensitive cancers.

Characteristics of Women With Gestational Diabetes From Non-Caucasian Compared With Caucasian Ethnic Groups.

OBJECTIVES: Short- and long-term outcomes in women after gestational diabetes mellitus (GDM) vary by ethnicity. Understanding differences in baseline diabetes risk factors is important for informing choice of risk-reducing interventions. We aimed to compare maternal and pregnancy-related characteristics in Caucasian and non-Caucasian women with GDM. METHODS: Using a large multicentre Canadian cohort of women diagnosed with GDM and recruited between 2009 and 2013, we compared demographic, clinical and behavioural characteristics in women with GDM across 7 ethnic groups. Data were obtained from chart reviews and surveys, and logistic and linear regression models were used to compare binary and continuous variables, respectively, between Caucasian and non-Caucasian ethnic groups. RESULTS: Of the 1,332 women with GDM, 911 were eligible for inclusion. Of these, 41.4% were white Caucasian, 17.1% were South Asian, 18.4% were East Asian, 5.8% were black, 8.8% were Filipina, 5.2% were Middle Eastern and 3.3% were Hispanic. Non-Caucasian women were diagnosed with GDM at a younger age and were more likely to have a family history of diabetes compared with Caucasian women. With the exception of East Asians, non-Caucasian women were more likely to be overweight using ethnicity-specific body mass index cutoffs and have higher oral glucose tolerance test values than Caucasian women. Prepregnancy smoking and alcohol consumption prevalence were highest in Caucasian women. CONCLUSIONS: Several important ethnicity-specific differences in clinical and behavioural characteristics of women with GDM were identified. These differences need to be considered when offering interventions for reducing risk of adverse perinatal outcomes and subsequent type 2 diabetes.

Gestational diabetes mellitus is associated with adverse outcomes in twin pregnancies.

BACKGROUND: Among singleton pregnancies, gestational diabetes mellitus is associated with adverse outcomes. In twin pregnancies, this association may be attenuated, given the higher rate of prematurity and the a priori increased risk of some of these complications. OBJECTIVE: Our aim was to test the hypothesis that gestational diabetes mellitus is less likely to be associated with adverse pregnancy outcomes in twin compared with singleton gestations. METHODS: This retrospective cohort study comprised all twin and singleton live births in Ontario, Canada, 2012-2016. Pregnancy outcomes were compared between women with vs without gestational diabetes mellitus, analyzed separately for twin and singleton births. Adjusted risk ratios and 95% confidence intervals were generated using modified Poisson regression, adjusting for maternal age, nulliparity, smoking, race, body mass index, preexisting hypertension, and assisted reproductive technology. RESULTS: A total of 270,843 women with singleton (n = 266,942) and twin (n = 3901) pregnancies met the inclusion criteria. In both the twin and singleton groups, gestational diabetes mellitus was associated with (adjusted risk ratio, [95% confidence interval]) cesarean delivery (1.11 [1.02-1.21] and 1.20 [1.17-1.23], respectively) and preterm birth at <370/7 weeks (1.21 [1.08-1.37] and 1.48 [1.39-1.57]) and at <340/7 weeks (1.45 [1.03-2.04] and 1.25 [1.06-1.47]). In singletons, but not twins, gestational diabetes mellitus was associated with gestational hypertension (1.66 [1.55-1.77]) and preeclampsia. With respect to neonatal outcomes, gestational diabetes mellitus was associated with birthweight greater than the 90th percentile in both twins and singletons, with the risk being 2-fold higher in twins (2.53 [1.52-4.23] vs 1.18 [1.13-1.23], respectively, P = .004). Gestational diabetes mellitus was associated with jaundice in both twins (1.56 [1.10-2.21]) and singletons (1.49 [1.37-1.62) but was associated with the following complications only in singletons: neonatal intensive care unit admission (1.44 [1.38-1.50]), respiratory morbidity (1.09 [1.02-1.16]), and neonatal hypoglycemia (3.20 [3.01-3.40]). CONCLUSION: In contrast to singleton pregnancies, gestational diabetes mellitus in twins was not associated with hypertensive complications and certain neonatal morbidities. Still, the current study highlights that gestational diabetes mellitus is associated with some adverse pregnancy outcomes including accelerated fetal growth also in twin pregnancies.

Hormone Levels in Pregnancy and Subsequent Risk of Maternal Breast and Ovarian Cancer: A Systematic Review.

OBJECTIVE: Some maternal hormone levels in pregnancy are associated with a higher risk of breast and ovarian cancer. This study systematically assessed the association between blood hormone levels measured in pregnancy and future risk of these cancers. METHODS: Two reviewers independently conducted a literature search of MEDLINE and EMBASE databases from January 1970 to August 2017. Studies were included that measured one or more serum hormone levels in pregnancy and later assessed for cancer. Cancer outcomes were considered by cancer type, each in relation to a specific maternal hormone. RESULTS: Eleven studies were included, comprising a total of 57 967 women. The interval between pregnancy and cancer onset varied from 4.1 to 20.5 years. Elevated serum chorionic gonadotropin (two of four studies) and alpha fetoprotein (two of three studies) were each associated with a lower risk of maternal breast cancer, whereas elevated estrone levels suggested a higher risk (one of three studies). Elevated testosterone (one of one study) and androstenedione (one of one study) were each associated with a significantly greater risk of sex-cord stromal ovarian tumours. Higher serum 17-hydroxyprogesterone was associated with an increased risk of sex-cord stromal (one of one study) and epithelial (one of one study) ovarian cancer. CONCLUSION: Observational studies suggest some degree of association between serum hormones measured in pregnancy and a woman's future risk of breast and ovarian cancer. More data are needed to determine sufficiently whether certain blood hormone levels measured in pregnancy are predictive of future cancer risk.