Assisted Reproductive Technology and Cardiovascular Outcomes in Parents and Offspring.

BACKGROUND: The impact of assisted reproductive technology (ART) on the cardiovascular system is unclear. METHODS: We conducted a retrospective longitudinal cohort study of 1,001,593 pregnancies conceived naturally or through ART from 2008 to 2019 in Québec to assess the association of ART with cardiovascular disease in families. The exposure measure was ART. The outcome included severe maternal cardiovascular morbidity, congenital heart defects in offspring, and long-term risk of cardiovascular hospitalisation in mothers, fathers, and offspring during 11 years of follow-up. We estimated the association between ART and cardiovascular outcomes with the use of adjusted log-binomial regression (risk ratio, 95% confidence interval [CI]) and Cox proportional hazards regression models (hazard ratio [HR]). RESULTS: Compared with natural conception, ART was associated with 2.04 times the risk of severe cardiovascular morbidity in mothers (95% CI 1.86-2.23) and 1.38 times the risk of congenital heart defects in offspring (95% CI 1.26-1.50). ART was not associated with the risk of maternal cardiovascular hospitalisation following pregnancy (HR 1.03, 95% CI 0.88-1.21). However, ART was associated with an increased risk of paternal cardiovascular hospitalisation (HR 1.24, 95% CI 1.11-1.38) and offspring cardiovascular hospitalisation (HR 1.27, 95% CI 1.01-1.61), mainly due to an increased risk of hypertension. CONCLUSIONS: ART is associated with only a small increase in the risk of cardiovascular complications in families. Parents and offspring may be reassured that ART likely has no major impact on the cardiovascular system.

Impact of Covid-19 on risk of severe maternal morbidity.

BACKGROUND: We examined the risk of severe life-threatening morbidity in pregnant patients with Covid-19 infection. METHODS: We conducted a population-based study of 162,576 pregnancies between March 2020 and March 2022 in Quebec, Canada. The main exposure was Covid-19 infection, including the severity, period of infection (antepartum, peripartum), and circulating variant (wildtype, alpha, delta, omicron). The outcome was severe maternal morbidity during pregnancy up to 42 days postpartum. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between Covid-19 infection and severe maternal morbidity using adjusted log-binomial regression models. RESULTS: Covid-19 infection was associated with twice the risk of severe maternal morbidity compared with no infection (RR 2.02, 95% CI 1.76-2.31). Risks were elevated for acute renal failure (RR 3.01, 95% CI 1.79-5.06), embolism, shock, sepsis, and disseminated intravascular coagulation (RR 1.35, 95% CI 0.95-1.93), and severe hemorrhage (RR 1.49, 95% CI 1.09-2.04). Severe antepartum (RR 13.60, 95% CI 10.72-17.26) and peripartum infections (RR 20.93, 95% CI 17.11-25.60) were strongly associated with severe maternal morbidity. Mild antepartum infections also increased the risk, but to a lesser magnitude (RR 3.43, 95% CI 2.42-4.86). Risk of severe maternal morbidity was around 3 times greater during circulation of wildtype and the alpha and delta variants, but only 1.2 times greater during omicron. CONCLUSIONS: Covid-19 infection during pregnancy increases risk of life-threatening maternal morbidity, including renal, embolic, and hemorrhagic complications. Severe Covid-19 infection with any variant in the antepartum or peripartum periods all increase the risk of severe maternal morbidity.

Sex differences in adverse events following seasonal influenza vaccines: a meta-analysis of randomised controlled trials.

BACKGROUND: Despite being a vaccine-preventable disease, influenza remains a major public health threat with vaccine safety concerns reducing vaccine acceptability. Immune responses to vaccines and adverse events may differ between males and females, but most studies do not report results by sex. Using data from clinical trials, we explored sex differences in adverse events following seasonal influenza vaccines. METHODS: We obtained data for phase III randomised controlled trials identified through a systematic review and clinical trials registries, and performed a two-stage meta-analysis. Risk ratios (RR) and 95% confidence intervals (95% CI) comparing solicited reactions in females versus males were pooled using the Mantel-Haenszel method and a random-effects model. We used the ROBINS-I tool to assess risk of bias and the I2 statistic for heterogeneity. Main analysis was stratified by age: 18-64 years and ≥65 years. RESULTS: The dataset for this analysis included 34 343 adults from 18 studies (12 with individual-level data and 6 with aggregate data). There was a higher risk of injection site reactions in females compared with males for both younger and older participants, with RRs of 1.29 (95% CI 1.21 to 1.37) and 1.43 (95% CI 1.28 to 1.60), respectively. Higher risk in females was also observed for systemic reactions, with RRs of 1.25 (95% CI 1.20 to 1.31) and 1.27 (95% CI 1.20 to 1.34) for younger and older participants, respectively. We also observed elevated risks of severe reactions in females, with a higher RR in younger versus older participants for systemic reactions (RRs 2.12 and 1.48, p=0.03, I2=79.7%). RRs were not found to vary between quadrivalent and trivalent vaccines. CONCLUSION: This meta-analysis suggested a higher risk of solicited reactions following influenza vaccines for females compared with males, irrespective of age and vaccine type. Transparent communication of this risk could increase the trust in vaccines and limit vaccine hesitancy. Future studies should report results stratified by sex and explore the role of gender in the occurrence of adverse events.

Severe neonatal birth injury: Observational study of associations with operative, cesarean, and spontaneous vaginal delivery.

AIM: To determine the association of successful and unsuccessful operative vaginal delivery attempts with risk of severe neonatal birth injury. METHODS: We conducted a population-based observational study of 1 080 503 births between 2006 and 2019 in Quebec, Canada. The main exposure was operative vaginal delivery with forceps or vacuum, elective or emergency cesarean with or without an operative vaginal attempt, and spontaneous delivery. The outcome was severe birth injury, including intracranial hemorrhage, brain and spinal damage, Erb's paralysis and other brachial plexus injuries, epicranial subaponeurotic hemorrhage, skull and long bone fractures, and liver, spleen, and other neonatal body injuries. We determined the association of delivery mode with risk of severe birth injury using adjusted risk ratios (RR) and 95% confidence intervals (CI). RESULTS: A total of 8194 infants (0.8%) had severe birth injuries. Compared with spontaneous delivery, vacuum (RR 2.98, 95% CI 2.80-3.16) and forceps (RR 3.35, 95% CI 3.07-3.66) were both associated with risk of severe injury. Forceps was associated with intracranial hemorrhage (RR 16.4, 95% CI 10.1-26.6) and brain and spinal damage (RR 13.5, 95% CI 5.72-32.0), while vacuum was associated with epicranial subaponeurotic hemorrhage (RR 27.5, 95% CI 20.8-36.4) and skull fractures (RR 2.04, 95% CI 1.86-2.25). Emergency cesarean after an unsuccessful operative attempt was associated with intracranial and epicranial subaponeurotic hemorrhage, but elective and other emergency cesareans were not associated with severe injury. CONCLUSIONS: Operative vaginal delivery and unsuccessful operative attempts that result in an emergency cesarean are associated with elevated risks of severe birth injury.

Effect of Vitamin D Supplementation on Bone Mass in Infants With 25-Hydroxyvitamin D Concentrations Less Than 50 nmol/L: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: The dose of supplemental vitamin D needed in infants born with serum 25-hydroxyvitamin D (25[OH]D) concentrations less than 50 nmol/L (ie, 20 ng/mL) is unclear. Objective: To determine whether a higher dose (1000 IU vs 400 IU per day) is required in infants born with 25(OH)D concentrations less than 50 nmol/L for bone mineral accretion across infancy. Design, Setting, and Participants: In this prespecified secondary analysis of a double-blinded randomized clinical trial, conducted from March 2016 to March 2019 in a single center in Greater Montreal, Quebec, Canada, a consecutive sample of 139 healthy term singletons were recruited from 866 infants screened for vitamin D status at birth. Data were analyzed from June 2021 to November 2022. Interventions: Capillary blood was collected 24 to 36 hours after birth to measure serum total 25(OH)D concentrations. Infants with 25(OH)D concentrations less than 50 nmol/L were randomized to receive either 1000 IU or 400 IU per day of oral vitamin D3 supplementation from age 1 to 12 months. Infants with 25(OH)D concentrations of 50 nmol/L or greater formed a reference group. Main Outcomes and Measures: Measures at age 1, 3, 6, and 12 months were preplanned and included whole-body bone mineral content, lumbar spine bone mineral content, and bone mineral density using dual-energy x-ray absorptiometry, and serum 25(OH)D3 using liquid chromatography tandem mass spectrometry. Results: Of 139 included infants, 81 (58.3%) were male, and the median (IQR) gestational age at birth was 39.6 (38.9-40.6) weeks. A total of 49 infants were included in the 1000 IU per day group, 49 infants in the 400 IU per day group, and 41 in the reference group. Mean (SD) whole-body bone mineral content was not different between trial groups over time (1000 IU per day, 173.09 [2.36] g; 400 IU per day, 165.94 [66.08] g). Similarly, no differences were observed in lumbar spine bone mineral content or density. Mean (SD) serum 25(OH)D3 concentrations were significantly higher in the 1000 IU per day group from age 3 to 12 months (3 months, 115.2 [35.3] nmol/L; 6 months, 121.6 [34.4] nmol/L; 12 months, 99.6 [28.8] nmol/L) compared with the 400 IU per day trial group (3 months, 77.4 [23.3] nmol/L; 6 months, 85.1 [18.6] nmol/L; 12 months, 82.3 [14.3] nmol/L). Conclusions and Relevance: In this study, a higher dose of vitamin D supplementation in infants born with 25(OH)D concentrations less than 50 nmol/L did not present advantages to bone mass in infancy. This study supports a standard dose of 400 IU per day of vitamin D supplementation for breastfed infants in Montreal. Trial Registration: ClinicalTrials.gov Identifier: NCT02563015.

Impact of Covid-19 on rates of gestational diabetes in a North American pandemic epicenter.

AIMS: We assessed the impact of Covid-19 on gestational diabetes rates in Quebec, the pandemic epicenter of Canada. METHODS: We conducted a population-based study of 569,686 deliveries in Quebec between 2014 and 2021. We measured gestational diabetes rates in wave 1 (March 1, 2020-August 22, 2020) and wave 2 (August 23, 2020-March 31, 2021), compared with the prepandemic period. We used interrupted time series regression to assess changes in gestational diabetes rates during each wave, and log-binomial regression models to estimate adjusted risk ratios (RR) and 95% confidence intervals (CI) for the association of the pandemic with gestational diabetes. We identified the types of patients that contributed to the change in gestational diabetes rates using Kitagawa's decomposition. RESULTS: Gestational diabetes rates were higher during the first (13.2 per 100 deliveries) and second waves (14.3 per 100 deliveries) than during the prepandemic period (12.4 per 100 deliveries). Risk of gestational diabetes increased both in wave 1 (RR 1.05, 95% CI 1.02-1.09) and wave 2 (RR 1.14, 95% CI 1.10-1.18), compared with the prepandemic period. However, most of the increase in gestational diabetes rates was driven by low-risk women without Covid-19 infections who were socioeconomically advantaged, had no comorbidity, and were 25-34 years of age. CONCLUSIONS: Gestational diabetes rates increased during the pandemic, mainly among women traditionally at low risk of hyperglycemia who did not have Covid-19 infections. Sudden widespread changes in screening or lifestyle can have a large impact on gestational diabetes rates in a population.

Association of Endometriosis and Severe Maternal Morbidity.

OBJECTIVE: To evaluate the association between endometriosis and risk of severe maternal morbidity (SMM). METHODS: We conducted a population-based retrospective cohort study of 2,412,823 deliveries at hospitals in Quebec, Canada, between 1989 and 2019. The exposure was surgically confirmed endometriosis. Patients were classified as having active endometriosis during pregnancy, inactive endometriosis during pregnancy, a diagnosis of endometriosis postpregnancy, or no endometriosis. The outcome was SMM, including by a range of life-threatening maternal conditions during pregnancy or up to 42 days postdelivery. We computed rates of SMM and used log binomial regression to assess the association with endometriosis (risk ratio [RR]; 95% CI), adjusted for maternal characteristics. RESULTS: Severe maternal morbidity occurred in 46.2 of 1,000 patients with endometriosis, compared with 30.7 of 1,000 patients without endometriosis. Relative to no exposure, endometriosis was associated with 1.43 times the risk of SMM (95% CI 1.36-1.51). Patients with endometriosis that was active during pregnancy had a greater risk of SMM (RR 1.93; 95% CI 1.76-2.11). Active endometriosis was associated with the risk of severe preeclampsia and eclampsia, severe hemorrhage, hysterectomy, cardiac complications, embolism, shock, sepsis, and intensive care unit admission. Inactive endometriosis was less strongly associated with these outcomes. CONCLUSION: Pregnant patients with endometriosis, especially active endometriosis, have a greater risk of SMM and may benefit from closer follow-up to prevent severe complications of pregnancy.

Black-White disparity in severe cardiovascular maternal morbidity: A systematic review and meta-analysis.

BACKGROUND: To synthesize existing evidence on Black-White disparities in the prevalence of severe cardiovascular maternal morbidity. METHODS: We searched MEDLINE, EMBASE, and CINAHL for observational studies published before July 31, 2021 that compared the risk of severe cardiovascular maternal morbidity between Black and White women. The outcome was severe cardiovascular maternal morbidity, including acute myocardial infarction, peripartum cardiomyopathy, and stroke during pregnancy, delivery, or postpartum. We extracted relevant information including adjusted and unadjusted effect estimates. We used random-effects models to estimate the pooled association between race and severe cardiovascular maternal morbidity, presented as odds ratios with 95% confidence intervals for the comparison of Black women relative to White women. RESULTS: We included 18 studies that met the eligibility criteria for systematic review and meta-analysis. All studies were conducted in the United States and included a total of 7,656,876 Black women and 26,412,600 White women. Compared with White women, Black women had an increased risk of any severe cardiovascular maternal morbidity (adjusted odds ratio, 1.90; 95% confidence interval, 1.54-2.33). Black women were at risk of acute myocardial infarction (adjusted odds ratio, 1.38; 95% confidence interval, 1.14-1.68), peripartum cardiomyopathy (adjusted odds ratio, 1.71; 95% confidence interval, 1.51-1.94), and stroke (adjusted odds ratio, 2.13; 95% confidence interval, 1.39-3.26). CONCLUSIONS: Black women have a considerably higher risk of severe cardiovascular maternal morbidity than White women, including acute myocardial infarction, peripartum cardiomyopathy, and stroke. Reducing inequality in adverse cardiovascular outcomes of pregnancy between Black and White women should be prioritized.

Association of PCOS with offspring morbidity: a longitudinal cohort study.

STUDY QUESTION: Do children whose mothers have polycystic ovary syndrome (PCOS) have an increased risk of morbidity? SUMMARY ANSWER: Maternal PCOS is associated with an increased risk of infection, allergy and other childhood morbidity. WHAT IS KNOWN ALREADY: PCOS is associated with higher rates of gestational diabetes, pre-eclampsia and preterm delivery, but the long-term impact on child health is poorly understood. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective longitudinal cohort study of 1 038 375 children in Quebec between 2006 and 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 7160 children whose mothers had PCOS and 1 031 215 unexposed children. Outcomes included child hospitalization for infectious, allergic, malignant and other diseases before 13 years of age. We estimated hazard ratios (HRs) and 95% CI for the association of PCOS with childhood morbidity in adjusted Cox proportional hazards regression models. MAIN RESULTS AND THE ROLE OF CHANCE: Children exposed to PCOS were hospitalized at a rate of 68.9 (95% CI 66.2-71.8) per 1000 person-years, whereas unexposed children were hospitalized at a rate of 45.3 (95% CI 45.1-45.5) per 1000 person-years. Compared with no exposure, maternal PCOS was associated with 1.32 times the risk of any childhood hospitalization (95% CI 1.26-1.40), 1.31 times the risk of infectious disease hospitalization (95% CI 1.25-1.38) and 1.47 times the risk of allergy-related hospitalization (95% CI 1.31-1.66). Risk of hospitalization was also elevated for childhood metabolic (HR 1.59, 95% CI 1.16-2.18), gastrointestinal (HR 1.72, 95% CI 1.53-1.92), central nervous system (HR 1.74, 95% CI 1.46-2.07) and otologic disorders (HR 1.34, 95% CI 1.26-1.43). Subgroup analyses suggested that there was little difference in the association of PCOS with hospitalization among boys (HR 1.31, 95% CI 1.24-1.39) and girls (HR 1.34, 95% CI 1.26-1.43). LIMITATIONS, REASONS FOR CAUTION: We analyzed severe childhood morbidity requiring hospitalization, not mild diseases treated in ambulatory clinics. We lacked data on ethnicity, education and physical activity, and cannot rule out residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that maternal PCOS is associated with an increased risk of childhood morbidity. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grant PJT-162300 from the Canadian Institutes of Health Research. N.A. acknowledges a career award from the Fonds de recherche du Québec-Santé (296785). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Assisted reproductive technology and childhood morbidity: a longitudinal cohort study.

OBJECTIVE: To evaluate the association between assisted reproductive technology (ART) and offspring morbidity in the first decade of life. DESIGN: Longitudinal cohort study. SETTING: Provincial health registry in Quebec, Canada. PATIENT(S): A total of 797,654 singleton children born between 2008 and 2019, followed up to 2020. INTERVENTION(S): Retrospective, noninterventional study of any ART procedure vs. no ART. MAIN OUTCOME MEASURE(S): Childhood morbidity, including hospitalization for infectious, allergic, malignant, and other diseases, assessed using adjusted Cox proportional hazards regression to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association with ART. We controlled for unmeasured family-level confounders that were shared among siblings through stratified Cox regression. To do so, we restricted the analysis to 10,097 siblings with discordant exposure to ART and compared the risk of outcomes in exposed vs. unexposed siblings. RESULT(S): Compared with no ART, ART was associated with 1.23 times the risk of any hospitalization (95% CI 1.19-1.27), 1.25 times the risk of infectious disease hospitalization (95% CI 1.21-1.29), and 1.25 times the risk of allergy hospitalization (95% CI 1.14-1.38). When we used a sibling design to control for shared genetic and environmental confounders, ART was not associated with a greater risk of childhood hospitalization (HR 0.92, 95% CI 0.78-1.08). CONCLUSION(S): ART is associated with an elevated risk of hospitalization up to 11 years of age, but discordant sibling analysis suggests that the association may be due to genetic, environmental, or other shared familial confounders.

Black-White Inequality in Outcomes of In Vitro Fertilization: a Systematic Review and Meta-analysis.

This study aims to systematically review disparities in outcomes of in vitro fertilization between Black and White patients. We searched CINAHL, Cochrane Library, EMBASE, Global Health, PsycINFO, PubMed, and Web of Science for observational studies published before August 2021. Outcomes included implantation, clinical pregnancy, spontaneous abortion, and live birth following in vitro fertilization in Black versus White patients. We used random-effects models for meta-analysis and the Mantel-Haenszel method to calculate unadjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between race and in vitro fertilization outcomes, comparing Black relative to White patients. We used the generic inverse variance method to calculate adjusted ORs. Nine observational studies met eligibility criteria, including 696 Black and 7,458 White patients. All were retrospective studies of US cohorts. In unadjusted meta-analyses, Black patients had a greater likelihood of spontaneous abortion (OR 2.08, 95% CI 1.59-2.71) and lower likelihood of live birth (OR 0.67, 95% CI 0.47-0.95) compared with White patients but no difference in implantation (OR 0.95, 95% CI 0.32-2.77) or clinical pregnancy (OR 0.78, 95% CI 0.54-1.12). In adjusted meta-analyses, Black patients had lower odds of live birth (OR 0.57, 95% CI 0.43-0.75) and no difference in clinical pregnancy (OR 0.87, 95% CI 0.51-1.48). This meta-analysis suggests that in vitro fertilization services achieve similar pregnancy rates in Black and White patients. However, Black patients have more spontaneous abortions and fewer live births, suggesting there may be disparities in the quality of achieved pregnancies or other factors associated with pregnancy loss. Systematic review registration: PROSPERO (ID CRD42021256250).

Maternal excess adiposity and serum 25-hydroxyvitamin D < 50 nmol/L are associated with elevated whole body fat mass in healthy breastfed neonates.

BACKGROUND: Vitamin D status of pregnant women is associated with body composition of the offspring. The objective of this study was to assess whether the association between maternal vitamin D status and neonatal adiposity is modified by maternal adiposity preconception. METHODS: Healthy mothers and their term appropriate weight for gestational age (AGA) infants (n = 142; 59% male, Greater Montreal, March 2016-2019) were studied at birth and 1 month postpartum (2-6 weeks). Newborn (24-36 h) serum was collected to measure total 25-hydroxyvitamin D [25(OH)D] (immunoassay); maternal pre-pregnancy BMI was obtained from the medical record. Anthropometry, body composition (dual-energy X-ray absorptiometry) and serum 25(OH)D were measured at 2-6 weeks postpartum in mothers and infants. Mothers were grouped into 4 categories based on their vitamin D status (sufficient 25(OH)D ≥ 50 nmol/L vs. at risk of being insufficient < 50 nmol/L) and pre-pregnancy BMI (< 25 vs. ≥25 kg/m2): insufficient-recommended weight (I-RW, n = 24); insufficient-overweight/obese (I-OW/O, n = 21); sufficient-recommended weight (S-RW, n = 69); and sufficient-overweight/obese (S-OW/O, n = 28). Partial correlation and linear fixed effects model were used while adjusting for covariates. RESULTS: At birth, infant serum 25(OH)D mean concentrations were below 50 nmol/L, the cut-point for sufficiency, for both maternal pre-pregnancy BMI categories; 47.8 [95%CI: 43.8, 51.9] nmol/L if BMI < 25 kg/m2 and 38.1 [95%CI: 33.5, 42.7] nmol/L if BMI ≥25 kg/m2. Infant serum 25(OH)D concentrations at birth (r = 0.77; P < 0.0001) and 1 month (r = 0.59, P < 0.0001) were positively correlated with maternal postpartum serum 25(OH)D concentrations. Maternal serum 25(OH)D concentration was weakly correlated with maternal percent whole body fat mass (r = - 0.26, P = 0.002). Infants of mothers in I-OW/O had higher fat mass versus those of mothers in S-OW/O (914.0 [95%CI: 766.4, 1061.6] vs. 780.7 [95%CI: 659.3, 902.0] g; effect size [Hedges' g: 0.42]; P = 0.04 adjusting for covariates) with magnitude of difference of 220.4 g or ~ 28% difference. CONCLUSIONS: Maternal and neonatal vitamin D status are positively correlated. In this study, maternal adiposity and serum 25(OH)D < 50 nmol/L are dual exposures for neonatal adiposity. These findings reinforce the importance of vitamin D supplementation early in infancy irrespective of vitamin D stores acquired in utero and maternal weight status.

Large-for-Gestational-Age, Leptin, and Adiponectin in Infancy.

CONTEXT: Fetal overgrowth "programs" an elevated risk of obesity and type 2 diabetes in adulthood. Plausibly, adipokines may be involved in programming metabolic health. OBJECTIVE: This work aimed to evaluate whether large-for-gestational-age (LGA), an indicator of fetal overgrowth, is associated with altered circulating leptin and adiponectin levels in infancy, and assess the determinants. METHODS: In the Canadian 3D birth cohort, we studied 70 LGA (birth weight > 90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) infants matched by maternal ethnicity, smoking, and gestational age at delivery. The primary outcomes were fasting leptin, and total and high-molecular-weight (HMW) adiponectin concentrations at age 2 years. RESULTS: LGA infants had higher body mass index (BMI) than OGA infants. However, there were no significant differences in leptin, and total and HMW adiponectin concentrations. Leptin concentrations were positively associated with female sex, weight (z score) gain 0 to 24 months, current BMI, and the sum of triceps and subscapular skinfold thickness, and negatively associated with maternal age and White ethnicity. Female sex was associated with lower total and HMW adiponectin concentrations. Weight (z score) gain 0 to 24 months and current BMI were positively correlated with total and HMW adiponectin concentrations in LGA infants only. CONCLUSION: This study is the first to demonstrate that LGA does not matter for circulating leptin and adiponectin concentrations in infancy, and there may be LGA-specific positive associations between weight gain or current BMI and adiponectin concentrations in infancy, suggesting dysfunction in establishing the adiposity-adiponectin negative feedback loop in LGA individuals.

Premature mortality after pregnancy loss: Trends at 1, 5, 10 years, and beyond.

OBJECTIVE: Little is known on the long-term risk of mortality following pregnancy loss. We assessed risks of premature mortality up to three decades after miscarriage, induced abortion, ectopic or molar pregnancy, and stillbirth relative to live birth. STUDY DESIGN: We carried out a longitudinal cohort study of 1,293,640 pregnant women with 18,896,737 person-years of follow-up in Quebec, Canada, from 1989 to 2018. We followed the women up to 29 years after their last pregnancy event to determine the time and cause of future in-hospital deaths before age 75 years. We used adjusted Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of miscarriage, induced abortion, ectopic pregnancy, molar pregnancy, and stillbirth with premature mortality, compared with live birth. RESULTS: Premature mortality rates were higher for most types of pregnancy loss than live birth. Compared with live birth, pregnancy loss was associated with an elevated risk of premature mortality (HRmiscarriage 1.48, 95% CI 1.33, 1.65; HRinduced abortion 1.50, 95% CI 1.39, 1.62; HRectopic 1.55, 95% CI 1.35, 1.79; and HRstillbirth 1.68, 95%. CI 1.17, 2.41). Molar pregnancy was not associated with premature mortality (HR 0.87, 95% CI 0.33, 2.32). Miscarriage and induced abortion were associated with most causes of death, whereas ectopic pregnancy was associated with cardiovascular (HR 2.18, 95 % CI 1.39, 3.42), cancer (HR 1.38, 95 % CI 1.11, 1.73), and suicide-related mortality (HR 4.94, 95 % CI 2.29, 10.68). Stillbirth was associated with cardiovascular mortality (HR 4.91, 95 % CI 2.33, 10.36). CONCLUSION: Pregnancy loss is associated with an elevated risk of premature mortality up to three decades later, particularly cardiovascular, cancer, and suicide-related deaths.

Pregnancy Outcomes During the COVID-19 Pandemic in Canada, March to August 2020.

OBJECTIVE: Several studies have documented changes in the rates preterm birth and stillbirth during the COVID-19 pandemic. We carried out a study to examine obstetric intervention, preterm birth, and stillbirth rates in Canada from March to August 2020. METHODS: The study included all singleton hospital deliveries in Canada (excluding Québec) from March to August 2020 (and March to August for the years 2015-2019) with information obtained from the Canadian Institute for Health Information. Data for Ontario were examined separately because this province had the highest rates of COVID-19 in the study population. Rates and odds ratios with 95% confidence intervals (CIs) were used to quantify pregnancy-related outcomes. RESULTS: There were 136,445 and 717,905 singleton hospital deliveries in Canada (excluding Quebéc) in from March to August 2020 and between March and August 2015-2019, respectively. Rates of obstetric intervention declined in early gestation in 2020. Odds ratios for labour induction and cesarean delivery at <32 weeks gestation for March-August 2020 versus March-August in 2015 to 2019 were 0.84 (95% CI 0.74-0.95) and 0.92 (95% CI 0.85-1.00), respectively. Preterm birth rates increased in Canada (excluding Québec) from 6.42% in March-August 2015 to 6.74% in March-August 2019 but were unchanged in March-August 2020 (6.74%). Stillbirth rates were stable between March-August 2015 and March-August 2020. However, stillbirth rates peaked in Ontario in April 2020 due to higher rates of stillbirths at 20-27 and 37-41 weeks gestation. CONCLUSION: Changes in labour induction and cesarean delivery at early gestation and other perinatal outcomes during the period of March to August 2020 highlight the need to reconsider the use and impact of obstetric services in pandemics as well as the need for timely perinatal surveillance.

Incidence de la COVID-19 sur les issues de grossesse: examen systématique et méta-analyse.

CONTEXTE: La nature exacte des répercussions de la maladie à coronavirus 2019 (COVID-19) sur la santé maternelle et néonatale reste à préciser. Nous avons cherché à évaluer l'association entre l'infection par le coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) pendant la grossesse et les issues défavorables de la grossesse. MÉTHODES: Nous avons réalisé une revue systématique et une méta-analyse d'études observationnelles fournissant des données comparatives sur l'infection par le SRAS-CoV-2 et la gravité de la COVID-19 pendant la grossesse. Nous avons sélectionné les études admissibles à partir des bases de données MEDLINE, Embase, ClinicalTrials.gov, medRxiv et Cochrane au 29 janvier 2021, en utilisant les Medical Subject Headings (vedettes matière en médecine) et les expressions clés « severe acute respiratory syndrome coronavirus 2 OR SARS-CoV-2 OR coronavirus disease 2019 OR COVID-19 ¼ (coronavirus du syndrome respiratoire aigu sévère 2 ou SRAS-CoV-2 ou maladie à coronavirus 2019 ou COVID-19) AND « pregnancy ¼ (grossesse). Nous avons ensuite évalué la qualité méthodologique de toutes les études retenues avec l'échelle de Newcastle­Ottawa. Les issues primaires étaient la prééclampsie et la naissance prématurée. Les issues secondaires incluaient la mortinaissance et le diabète gestationnel, ainsi que d'autres issues de grossesse. Nous avons calculé des rapports de cotes (RC) sommaires ou des différences moyennes pondérées avec des intervalles de confiance (IC) à 95 % par méta-analyse à effets aléatoires. RÉSULTATS: Nous avons retenu 42 études portant sur 438 548 personnes enceintes. Comparativement à une absence d'infection par le SRAS-CoV-2 pendant la grossesse, le diagnostic de COVID-19 a été associé à la prééclampsie (RC 1,33; IC à 95 % 1,03­1,73), à la naissance prématurée (RC 1,82; IC à 95 % 1,38­2,39) et à la mortinaissance (RC 2,11; IC à 95 % 1,14­3,90). Par rapport à la COVID-19 légère, la COVID-19 grave était fortement associée à la prééclampsie (RC 4,16; IC à 95 % 1,55­11,15), à la naissance prématurée (RC 4,29; IC à 95 % 2,41­7,63), au diabète gestationnel (RC 1,99; IC à 95 % 1,09­3,64) et au faible poids à la naissance (RC 1,89; IC à 95 % 1,14­3,12). INTERPRÉTATION: La COVID-19 pourrait être associée à un risque accru de prééclampsie, de naissance prématurée et d'autres issues défavorables de la grossesse.

Cardiovascular disease and cancer in women with accreta and retained placenta: a longitudinal cohort study.

PURPOSE: The association between placental detachment disorders and risk of chronic disease is unclear. We determined the association of placenta accreta and retained placenta with risk of future maternal cardiovascular disease and cancer. METHODS: We tracked a longitudinal cohort of 541,051 pregnant women over a period of 13 years (2006-2019) in Quebec, Canada. The main exposure measures were placenta accreta and retained placenta in any pregnancy. Outcomes included future hospitalizations for cardiovascular disease and cancer. Using Cox regression models adjusted for maternal characteristics, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of accreta and retained placenta with cardiovascular disease and cancer at 13 years. RESULTS: The incidence of cardiovascular hospitalization was 21.2 per 10,000 person-years for accreta and 23.4 per 10,000 for retained placenta with postpartum hemorrhage, compared with 20.3 per 10,000 for neither placental disorder. Cancer incidence followed a similar pattern, with rates highest for retained placenta with hemorrhage. Retained placenta with hemorrhage was associated with 1.19 times the risk of cardiovascular disease (95% CI 1.03-1.38) and 1.27 times the risk of cancer (95% CI 1.06-1.53). Retained placenta with hemorrhage was associated with heart failure (HR 1.84, 95% CI 1.04-3.27), cardiomyopathy (HR 1.88, 95% CI 1.03-3.43), and cervical cancer (HR 2.03, 95% CI 1.17-3.52). Accreta and retained placenta without hemorrhage were not associated with these outcomes. CONCLUSION: Retained placenta with hemorrhage may be a risk marker for cardiovascular disease and certain cancers later in life.