Search

Background: Our objective was to assess whether hyperemesis gravidarum is associated with the risk of endodermal, mesodermal, and ectodermal human chorionic gonadotropin (hCG) receptor+ cancer in women. Methods: We performed a longitudinal cohort study of 1,343,040 women who were pregnant between 1989 and 2019 in Quebec, Canada. We identified women with and without hyperemesis gravidarum and followed them over time to capture incident cancers, grouped by embryonic germ cell layer of origin and organ hCG receptor positivity. We used time-varying Cox regression to model hazard ratios (HR) and 95% confidence intervals (CI) for the association between hyperemesis gravidarum and cancer onset, adjusted for maternal age, comorbidity, multiple gestation, fetal congenital anomaly, socioeconomic deprivation, and time period. Results: Women with hyperemesis gravidarum had a greater risk of endodermal cancer compared with no hyperemesis gravidarum (5.8 vs. 4.8 per 10,000 person-years; HR, 1.36; 95% CI, 1.17–1.57), but not mesodermal or ectodermal cancer. Severe hyperemesis with metabolic disturbance was more strongly associated with cancer from the endodermal germ layer (HR, 1.97; 95% CI, 1.51–2.58). The association between hyperemesis gravidarum and endodermal cancer was driven by bladder (HR, 2.49; 95% CI, 1.37–4.53), colorectal (HR, 1.41; 95% CI, 1.08–1.84), and thyroid (HR, 1.43; 95% CI, 1.09–1.64) cancer. Conclusions: Women with hyperemesis gravidarum have an increased risk of cancers arising from the endodermal germ cell layer, particularly bladder, colorectal, and thyroid cancers. Impact: Future studies identifying the pathways linking hyperemesis gravidarum with endodermal tumors may help improve the detection and management of cancer in women.

OBJECTIVE We studied the association between gestational diabetes mellitus and early versus late childhood cancer. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort study of 1 million children born between 2006 and 2019 in Quebec, Canada. We identified children who were exposed to gestational diabetes mellitus in utero and followed them from birth up to 14 years of age to identify new-onset cancers. We estimated hazard ratios (HRs) for the association between gestational diabetes mellitus and childhood cancer using Cox proportional regression models with adjustment for covariates through inverse propensity score weights. RESULTS A total of 83,626 children (8.2%) were exposed to gestational diabetes mellitus, and 1,702 developed cancer during 7.6 million person-years of follow-up. Children exposed to gestational diabetes mellitus had a higher risk of any cancer (HR 1.19, 95% CI 1.01–1.40), with signals present for blood cancer (HR 1.27, 95% CI 0.92–1.76) and solid tumors (HR 1.14, 95% CI 0.94–1.40). The association between gestational diabetes mellitus and cancer was strongest early in life and decreased with age. Gestational diabetes mellitus was associated with 1.47 times the risk of any cancer (95% CI 1.21–1.79), 1.44 times the risk of solid cancer (95% CI 1.12–1.87), and 1.61 times the risk of blood cancer (95% CI 1.09–2.36) in children age CONCLUSIONS Hyperglycemia may be carcinogenic in utero and may be a novel risk factor for early childhood cancer.

Multisystem inflammatory syndrome in adults (MIS-A) is an increasingly recognized complication of Covid-19. We assessed risk factors, clinical characteristics, and outcomes of patients with MIS-A compared with other inflammatory conditions.We analyzed a cohort of patients ≥21 years hospitalized with MIS-A in Quebec, Canada between February 2020 and March 2021. We included comparison groups that share symptomatology or pathophysiology with MIS-A, including Kawasaki disease, toxic shock syndrome, and other Covid-19 complications. We examined characteristics of men and women at admission, and identified preexisting factors associated with MIS-A through odds ratios (OR) and 95% confidence intervals (CI) from adjusted logistic regression models.Among 22,251 patients in this study, 52 had MIS-A, 90 Kawasaki disease, 500 toxic shock syndrome, and 21,609 other Covid-19 complications. MIS-A was associated with an elevated risk of respiratory failure compared with Kawasaki disease (OR 7.22, 95% CI 1.26-41.24), toxic shock syndrome (OR 4.41, 95% CI 1.73-11.23), and other Covid-19 complications (OR 3.03, 95% CI 1.67-5.50). Patients with MIS-A had a greater risk of cardiac involvement, renal failure, and mortality. The data pointed towards sex-specific differences in presentation, with more respiratory involvement in women and cardiac involvement in men compared with patients that had other Covid-19 complications. Except for allergic disorders and cancer, prior medical risk factors were not associated with a greater likelihood of MIS-A.Patients with MIS-A have an elevated risk of mortality compared with other inflammatory conditions, with women having a predominance of respiratory complications and men cardiovascular complications.

To synthesize existing evidence on Black-White disparities in the prevalence of severe cardiovascular maternal morbidity.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.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).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.

Background : The link between mood disorders and cardiovascular disease in women is unclear. We studied the association of mood disorders around pregnancy with the future risk of cardiovascular disease. Methods : We analyzed a cohort of 1,028,109 women who were pregnant between 1989 and 2012 in Quebec, Canada. We identified women hospitalized for bipolar disorder or depression before, during, or in the 5 years after delivery, and tracked them over time to identify cardiovascular hospitalizations up to 23 years later. We calculated the incidence of cardiovascular hospitalization per 1,000 person-years, and used Cox regression to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association with mood disorders. Results : Incidence of cardiovascular events was higher for bipolar disorder (4.4 per 1,000 person-years) and depression (4.2 per 1,000) than no mental illness (1.8 per 1,000). Compared with no mental disorder, bipolar disorder was associated with 3.0 times the risk of cardiovascular disease (95% CI 1.92–4.73), and depression with 2.3 times the risk (95% CI 1.34–3.99). The risk of cardiovascular disease was elevated for bipolar hospitalization before pregnancy (HR 2.42, 95% CI 1.90–3.09), during pregnancy (HR 3.78, 95% CI 2.32–6.17), in the first year postpartum (HR 2.20, 95% CI 1.54–3.12), and 1–5 years postpartum (HR 2.42, 95% CI 2.04–2.86). Similar associations were found for depression. Limitations : We could only assess mood disorders that required hospitalization, and certain covariates might be underreported. Conclusions : Women with bipolar disorder or depression before, during, or after pregnancy may benefit from early prevention of cardiovascular disease.

Objective Birth outcomes of women with anorexia nervosa are poorly understood. We hypothesized that hospitalization for anorexia nervosa before or during pregnancy is associated with an elevated risk of adverse maternal and infant birth outcomes. Method We performed a retrospective cohort study of 2,134,945 pregnancies in Quebec, Canada, from 1989 to 2016. The main exposure measure was anorexia nervosa requiring hospital treatment before or during pregnancy. Outcome measures included stillbirth, preterm birth, low birth weight, small-for-gestational age birth, preeclampsia, gestational diabetes, cesarean delivery, and other pregnancy disorders. We computed risk ratios and 95% confidence intervals (CI) for the association between anorexia nervosa and birth outcomes adjusted for maternal characteristics. Results Compared with no hospitalization, anorexia nervosa hospitalization was associated with 1.99 times the risk of stillbirth (95% CI 1.20-3.30), 1.32 times the risk of preterm birth (95% CI 1.13-1.55), 1.69 times the risk of low birth weight (95% CI 1.44-1.99), and 1.52 times the risk of small-for-gestational age birth (95% CI 1.35-1.72). The associations with low birth weight and small-for-gestational age birth were more prominent in women hospitalized for anorexia nervosa during pregnancy or within 2 years of delivery. Hospitalization for anorexia nervosa was associated with certain maternal outcomes, including precipitate labor, acute liver failure, and admission to an intensive care unit. Discussion Hospitalization for anorexia nervosa before or during pregnancy is associated with adverse infant and maternal outcomes. Infants are primarily at risk of stillbirth, preterm birth, low birth weight, and small-for-gestational age birth.

BACKGROUND Preterm birth occurs during a critical period of bone mineralization. We assessed whether preterm birth increases the risk of childhood fracture. METHODS We analyzed a cohort of 788,903 infants born between 2006 and 2016 in Quebec, Canada. The exposure was preterm birth (

Children whose mothers have autoimmune disease may be at risk of developing immune-mediated disorders. We assessed the association between maternal autoimmune disease and risk of autoimmune disease, allergy, and cancer in offspring.We analyzed a cohort of 1,011,623 children born in Canada between 2006 and 2019. We identified mothers who had autoimmune diseases and assessed hospitalizations for autoimmune disease, allergy, and cancer in offspring between birth and 14 years of age. We estimated hazard ratios (HR) for the association of maternal autoimmune disease with child hospitalization in adjusted Cox regression models. We used within-sibling analysis to control for genetic and environmental confounders.A total of 20,354 children (2.0%) had mothers with an autoimmune disease. Compared with no autoimmune disease, maternal autoimmune disease was associated with the risk of childhood hospitalization for autoimmune disease (HR 1.96, 95% CI 1.66-2.31) and allergy (HR 1.30, 95% CI 1.21-1.40), but was not significantly associated with cancer (HR 1.31, 95% CI 0.96-1.80). Type 1 diabetes, celiac disease, inflammatory arthritis, and systemic lupus erythematosus were among specific maternal autoimmune diseases most strongly associated with childhood hospitalization for autoimmune disease and allergy. The associations disappeared after controlling for genetic and environmental confounders in the within-sibling analysis.Maternal autoimmune disease is associated with an increased risk of autoimmune disease and allergy hospitalization in offspring, but the relationship appears to be confounded by genetic and environmental factors. Prenatal exposure to immunologic or pharmacologic products is not likely a direct cause of immune-mediated disease in children.

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).

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.

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. 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. 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. Retained placenta with hemorrhage may be a risk marker for cardiovascular disease and certain cancers later in life.

Women who deliver preterm are at risk of cardiovascular disease, but the reason for the association is unclear. We determined whether vascular disorders during pregnancy explain the association between preterm delivery and future maternal cardiovascular disease. We analyzed a longitudinal cohort of 1 199 364 pregnant women with 19 186 983 person-years of follow-up in Quebec between 1989 and 2017. We calculated incidence rates of myocardial infarction, ischemic stroke, and other cardiovascular hospitalizations. We used multivariable Cox regression to estimate adjusted hazard ratios and 95% CIs for the association of very and moderate preterm delivery with maternal cardiovascular hospitalization. We determined the proportion of the association that was due to preeclampsia, acute cardiac events at delivery, antepartum/postpartum hemorrhage, and heart defects. The incidence of maternal cardiovascular hospitalization was greater for very (43.7 per 10 000 person-years) and moderate (39.4 per 10 000) preterm delivery compared with term delivery (26.2 per 10 000). Very preterm delivery was associated with 1.67× the risk of cardiovascular hospitalization (95% CI, 1.56–1.79), and moderate preterm delivery was associated with 1.51× the risk (95% CI, 1.46–1.56). Vascular disorders during pregnancy explained 26.2% of the association of very preterm delivery and 24.0% of the association of moderate preterm delivery, with cardiovascular hospitalization. Preeclampsia was the largest contributor to these proportions. We conclude that vascular disorders during pregnancy, especially preeclampsia, explain up to a quarter of the association between preterm delivery and future maternal cardiovascular hospitalization.

Objective:Infants with neonatal abstinence syndrome have significant morbidity, but the association with birth defects is poorly understood. This study aimed to determine how neonatal abstinence sy...

We sought to determine the relationship between maternal mental illness and the risk of having an infant with a central nervous system defect. We analyzed a cohort of 654,882 women aged less than 20 years between 1989 and 2013 who later delivered a live born infant in any hospital in Quebec, Canada. The primary exposure was mental illness during pregnancy or hospitalization for mental illness before pregnancy. The outcomes were neural and non-neural tube defects of the central nervous system in any offspring. We computed risk ratios (RR) and 95% confidence intervals (CI) for the association between mental disorders and risk of central nervous system defects in log-binomial regression models adjusted for age at delivery, total parity, comorbidity, socioeconomic deprivation, place of residence, and time period. Maternal mental illness was associated with an increased risk of nervous system defects in offspring (RR 1.76, 95% CI 1.64-1.89). Hospitalization for any mental disorder was more strongly associated with non-neural tube (RR 1.84, 95% CI 1.71-1.99) than neural tube defects (RR 1.31, 95% CI 1.08-1.59). Women at greater risk of nervous system defects in offspring tended to be diagnosed with multiple mental disorders, have more than one hospitalization for mental disease, or be 17 or older at first hospitalization. A history of mental illness is associated with central nervous system defects in offspring. Women hospitalized for mental illness may merit counseling at first symptoms to prevent central nervous system defects at pregnancy.

To assess the pregnancy outcomes of women with spina bifida.We analyzed a population-based cohort of 397 pregnant women with spina bifida and 1,083,211 without spina bifida who delivered infants in hospitals in Quebec, Canada, 1989-2013. Outcomes included maternal and infant morbidity and mortality at delivery. We used log-binomial regression models to estimate prevalence ratios (PR) and 95% confidence intervals (CI) for the association of maternal spina bifida with pregnancy outcomes, accounting for maternal characteristics.Women with spina bifida had a higher prevalence of several adverse outcomes compared with women who had no birth defects. Maternal risks were highest for intensive care unit admission during the delivery hospitalization (PR 3.41, CI 95% 1.56-7.43) and respiratory morbidity (PR 9.46, CI 95% 3.31-26.99). Infant risks were greatest for intracranial hemorrhage (PR 6.85, CI 95% 2.23-21.08), birth hypoxia (PR 1.64, CI 95% 1.21-2.22), and hospital length of stay ≥14 days (PR 2.56, CI 95% 1.58-4.15). After adjustment for confounders, maternal spina bifida was associated with risk of oral clefts and abdominal wall defects in infants.Women with spina bifida have an increased risk of severe maternal and infant complications at delivery, compared with no spina bifida. Implications for Rehabilitation A growing number of women with spina bifida achieve pregnancy, but pregnancy outcomes are poorly understood. In a large pregnancy cohort, women with spina bifida had a high risk of severe maternal and infant morbidity at delivery. Women with spina bifida may benefit from enhanced periconceptional counseling and obstetric monitoring by health professionals. Guidelines should be developed for rehabilitation care providers to improve the obstetric management of women with spina bifida.

The risk of cardiovascular disease in women with gestational diabetes is poorly understood. We sought to determine whether gestational diabetes increases the risk of cardiovascular disease more than two decades after pregnancy. We carried out a retrospective cohort study of 1,070,667 women who delivered infants in hospitals within Quebec, Canada, between 1989 and 2013. We followed 67,356 women with gestational diabetes and 1,003,311 without gestational diabetes for a maximum of 25.2 years after the index delivery. The main outcome measures were hospitalization for ischemic heart disease, myocardial infarction, coronary angioplasty, coronary artery bypass graft, and other cardiovascular disorders. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) comparing women with gestational diabetes to no gestational diabetes, adjusted for age, parity, socioeconomic deprivation, time period, and preeclampsia. Women with gestational diabetes had a higher cumulative incidence of hospitalization for cardiovascular disease 25 years after delivery (190.8 per 1000 women) compared with no gestational diabetes (117.8 per 1000 women). Gestational diabetes was associated with a higher risk of ischemic heart disease (HR 1.23, 95% CI 1.12–1.36), myocardial infarction (HR 2.14, 95% CI 1.15–2.47), coronary angioplasty (HR 2.23, 95% CI 1.87–2.65), and coronary artery bypass graft (HR 3.16, 95% CI 2.24–4.47). In this population of pregnant women, gestational diabetes was associated with an increased risk of heart disease 25 years after delivery. Women with gestational diabetes may merit closer monitoring for cardiovascular disease prevention after pregnancy.

OBJECTIVE:To evaluate whether preeclampsia is associated with risk of maternal retinal disease in the decades after pregnancy.METHODS:We carried out a longitudinal cohort study of 1,108,541 women who delivered neonates in any hospital in Quebec, Canada, between 1989 and 2013. We tracked women for la

Background The impact of fasting on risk of preterm birth during Ramadan is unclear. Objectives We evaluated the association between Ramadan fasting during pregnancy and risk of preterm birth for Arab women in Canada. Methods We analyzed birth certificates from 3,123,508 deliveries in Quebec, Canada, from 1981 to 2017. We identified 78,109 births of Arabic-speaking women and determined if Ramadan occurred during any trimester of pregnancy. We calculated rates of extreme (22-27 wk), very (28-31 wk), and late (32-36 wk) preterm birth and estimated RRs and 95% CIs for the association of Ramadan fasting with risk of preterm birth by pregnancy trimester, using log-binomial regression models adjusted for maternal characteristics. Results Arabic speakers had an overall preterm birth rate of 5.53 per 100 births, but rates varied with timing of Ramadan. Among Arabic speakers, fasting during Ramadan between weeks 15-21 of the second trimester was associated with 1.33 times the risk of very preterm birth relative to no fasting (95% CI: 1.06, 1.68). Between weeks 22 and 27 of the second trimester, fasting during Ramadan was associated with 1.53 times the risk of very preterm birth (95% CI: 1.21, 1.93). Ramadan fasting was not associated with extreme or late preterm birth regardless of the trimester of pregnancy. Conclusions In this study of 78,109 births to Arabic-speaking women in Quebec, Ramadan fasting during the second pregnancy trimester was associated with the risk of very preterm birth. Optimal prenatal education about nutritional needs in the second trimester of pregnancy is recommended.

Objective To provide information on the birth outcomes of future intrauterine pregnancies in women whose first pregnancy was ectopic. Design Population-based longitudinal cohort study. Setting All hospitals in Quebec, Canada, 1989–2013. Patient(s) Group surgically treated for an ectopic first pregnancy: 15,823 women; comparison group with an intrauterine first pregnancy: 1,101,748 women. Intervention(s) Not applicable. Main Outcome Measure(s) Repeat ectopic pregnancy, future delivery of a live infant, stillbirth, cesarean delivery, preterm birth, low birth weight, preeclampsia, gestational diabetes, and postpartum hemorrhage as well as other outcomes of pregnancy. Result(s) The overall prevalence of ectopic first pregnancy was 14.2 per 1,000 women, of whom 10% of women with an ectopic first pregnancy had a future ectopic. Regardless of age, women with ectopic first pregnancies had an increased risk of adverse birth outcomes at future intrauterine pregnancies, including 1.27 times the risk of preterm birth (95% confidence interval [CI], 1.18–1.37), 1.20 times the risk of low birth weight (95% CI, 1.10–1.31), 1.21 times the risk of placental abruption (95% CI, 1.04–1.41), and 1.45 times the risk of placenta previa (95% CI, 1.10–1.91). Older women with a prior ectopic pregnancy had particularly elevated risks of placental abruption (risk ratio 1.42; 95% CI, 1.16–1.69). Conclusion(s) Women with ectopic first pregnancies have an increased risk of adverse birth outcomes during subsequent intrauterine pregnancies. These women may benefit from closer clinical management in pregnancy to prevent adverse birth outcomes.

Background Previous studies provide conflicting evidence of a link between maternal substance use and risk of childhood cancer. Methods We analyzed a cohort of 785,438 newborns in Quebec (2006–2016). We identified infants whose mothers had problematic illicit drug, tobacco, or alcohol use before or during pregnancy. The primary outcomes were childhood hematopoietic cancer or solid tumors within 0–5 years of age. Using Cox proportional hazards models, we computed hazard ratios (HR) and 95% confidence intervals (CI) for the association between maternal substance use and childhood cancer, adjusted for potential confounders. Results A total of 925 cases of cancer occurred during 3.5 million person-years of follow-up. Children exposed to any maternal substance use had marginally elevated cancer incidence rates compared with unexposed children (29.4 vs. 26.1 per 100,000 person-years). Maternal illicit drug use was associated with the risk of acute lymphoblastic leukemia (HR 1.63, 95% CI 0.79–3.36) and fibrosarcoma (HR 2.11, 95% CI 0.86–5.16). Maternal tobacco use was associated with acute myeloid leukemia (HR 2.01, 95% CI 0.72–5.60) and fibrosarcoma (HR 2.13, 95% CI 1.05–4.32), but a weak association with neuroblastoma (HR 1.21, 95% CI 0.61–2.40) and renal tumors (HR 1.14, 95% CI 0.42–3.13) also appeared to be present. Conclusions We found a potential association between maternal substance use and certain types of early childhood cancer. Although effects were modest, maternal substance use may contribute to some types of childhood cancer, especially leukemia and fibrosarcoma.

Background The association of takotsubo syndrome with future risk of cardiovascular and noncardiovascular morbidity and mortality is unclear. We assessed the long-term risk of morbidity and mortality in patients with takotsubo syndrome. Methods We performed a matched cohort study of 174 patients with takotsubo syndrome between 1989 and 2006 in Quebec, Canada, with 15 years of follow-up on future hospitalization outcomes. We matched takotsubo patients to 2 comparison groups, including 1736 patients with acute myocardial infarction and 1740 population controls. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of takotsubo syndrome with subsequent in-hospital mortality, cardiovascular morbidity, and other hospitalization outcomes. Results During 15 years of follow-up, patients with takotsubo syndrome had a risk of in-hospital mortality similar to patients with myocardial infarction (HR 1.06; 95% CI, 0.81-1.38), but a lower risk of cardiovascular rehospitalization (HR 0.79; 95% CI, 0.66-0.95). Compared with population controls, however, takotsubo was associated with 1.59 times the risk of in-hospital mortality (95% CI, 1.21-2.09), 2.71 times the risk of cardiovascular rehospitalization (95% CI, 2.24-3.28), and 1.86 times the risk of hospitalization for stress and anxiety disorders (95% CI, 1.21-2.85). Associations were significantly stronger the first few years after the initial admission for takotsubo, and weakened over time. Conclusions Takotsubo syndrome is associated with a risk of mortality similar to that of myocardial infarction after 15 years, but a lower risk of cardiovascular rehospitalization. Patients with takotsubo syndrome nonetheless have more in-hospital mortality and cardiovascular morbidity than population controls.

Importance Bulimia nervosa is associated with short-term cardiovascular complications in women, but its long-term consequences on cardiovascular health are unknown. Objective To study the association of bulimia nervosa with the long-term risk of cardiovascular disease and mortality in women. Design, Setting, and Participants In this longitudinal cohort study, 416 709 women hospitalized in Quebec, Canada, including women hospitalized for bulimia nervosa and those for pregnancy-related events as a comparison group, were followed up for 12 years from 2006 to 2018 to identify incidences of cardiovascular disease and death. Exposures At least 1 hospitalization for bulimia nervosa. Main Outcomes and Measures The study participants were followed up to identify future incidences of cardiovascular disease and deaths. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs to assess the association of bulimia nervosa with future outcomes after adjustment for patient characteristics. Results The study population comprised 818 women who were hospitalized for bulimia nervosa (mean [SD] age, 28.3 [13.4] years) and 415 891 hospitalized for pregnancy-related events (mean [SD] age, 28.3 [5.4] years). Patients were followed up for a total of 2 957 677 person-years. The women hospitalized for bulimia nervosa had a greater incidence of cardiovascular disease compared with those hospitalized for pregnancy-related events (10.34 [95% CI, 7.77-13.76] vs 1.02 [95% CI, 0.99-1.06] per 1000 person-years). Incidence of future cardiovascular disease was even higher for women with 3 or more bulimia admissions (25.13 [95% CI, 13.52-46.70] per 1000 person-years). Women hospitalized for bulimia nervosa had 4.25 (95% CI, 2.98-6.07) times the risk of any cardiovascular disease and 4.72 (95% CI, 2.05-10.84) times the risk of death compared with women hospitalized for pregnancy-related events. Bulimia nervosa was found to be associated with ischemic heart disease (HR, 6.63; 95% CI, 3.34-13.13), atherosclerosis (HR, 6.94; 95% CI, 3.08-15.66), and cardiac conduction defects (HR, 2.99; 95% CI, 1.57-5.71). Bulimia was also associated with 21.93 (95% CI, 9.29-51.74) times the risk of myocardial infarction at 2 years of follow-up and 14.13 (95% CI, 6.02-33.18) times the risk at 5 years of follow-up. Conclusions and Relevance This study’s findings suggest that bulimia nervosa may be associated with the long-term risk of any cardiovascular disease, such as ischemic cardiac events and conduction disorders, as well as with death among women. The findings also suggest that women with a history of bulimia nervosa should be screened regularly for ischemic cardiovascular disease and may benefit from prevention of and treatment for cardiovascular risk factors.

Infants with neonatal abstinence syndrome have significant morbidity, but the association with birth defects is poorly understood. This study aimed to determine how neonatal abstinence syndrome is related to birth defects, including the joint impact of neonatal abstinence syndrome and birth defects on infant morbidity.A population-based cohort of 1,944,804 neonates born in the hospitals of Quebec, Canada (1989-2013), was compiled with data on maternal exposures and infant outcomes after delivery. The prevalence of neonatal abstinence syndrome and birth defects was estimated, including the association with neonatal morbidity and mortality after adjustment for maternal age, parity, morbidity, socioeconomic deprivation, and time period. Joint effects of neonatal abstinence syndrome and birth defects on infant outcomes were assessed.Infants with neonatal abtinence syndrome had a higher prevalence of birth defects (705.7 per 10,000) than infants with no drug exposure (568.9 per 10,000). Compared with no exposure, infants with neonatal abstinence syndrome had 1.35 times the chance of having birth defects (95% confidence interval [1.14, 1.59]). Associations were strongest for central nervous system defects (risk ratio = 6.06, 95% confidence interval [3.93, 9.35]). Neonatal abstinence syndrome combined with birth defects was associated with significantly more infant morbidity and mortality.Infants with neonatal abstinence syndrome have a greater prevalence of birth defects, particularly defects of the central nervous system. Neonatal abstinence syndrome with birth defects may be an underappreciated contributor to infant morbidity.

Background The relationship between childhood asthma and central nervous system defects in offspring is poorly understood. We assessed if childhood asthma was associated with the risk of having an infant with neural tube or other nervous system defects compared with asthma during pregnancy. Methods We analyzed a longitudinal cohort of 128,060 women who were 5 years or less at study entry and later delivered an infant in Quebec, Canada (1989-2014). We identified women hospitalized for asthma before pregnancy, including childhood and adolescence, and determined if asthma was present during pregnancy based on obstetric records. Main outcomes were neural tube and non-neural tube defects in pregnancy. We used log-binomial regression models to determine risk ratios (RR) and 95% confidence intervals (CI) for the association between asthma and risk of nervous system defects, adjusting for patient characteristics. Results Asthma was associated with a greater risk of neural tube defects in offspring (RR 2.39, 95% CI 1.03-5.53) compared with no asthma, but not non-neural tube defects (RR 1.10, 95% CI 0.71-1.71). Women whose asthma resolved before pregnancy had a greater risk of neural tube defects (RR 3.43, 95% CI 1.35-8.69), while women with asthma during pregnancy were at greater risk of non-neural tube defects, especially microcephaly (RR 2.80, 95% CI 1.23-6.40). Conclusions Asthma that resolved before pregnancy was associated with an increased risk of neural tube defects in offspring but not non-neural tube defects. Further investigation is needed to determine the pathophysiology connecting childhood asthma with nervous system defects in offspring.

Background We sought to determine if immune disorders early in life were associated with the later risk of Guillain-Barre syndrome, a neurological disorder thought to be infection-related. Methods We conducted a longitudinal cohort study with 16 108 819 person-years of follow-up for a population of 1 108 541 parous women in Quebec, Canada (1989-2014). The outcome was Guillain-Barre syndrome. We identified women with potential risk factors for future Guillain-Barre syndrome, including immune-mediated and rheumatological diseases, cancer, transfusion, surgical procedures and pregnancy-specific disorders. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of risk factors with later onset of Guillain-Barre syndrome, adjusted for personal characteristics of women. Results The overall incidence of Guillain-Barre syndrome was 1.42 per 100 000 person-years. Incidence was higher for women with immune-mediated (8.79 per 100 000 person-years) and rheumatological disorders (9.84 per 100 000 person-years), transfusion (4.41 per 100 000 person-years), and preeclampsia (2.62 per 100 000 person-years). Immune-mediated disorders were associated with six times the risk of Guillain-Barre syndrome (HR 6.57, 95% CI 3.58 to 12.04), rheumatological disorders with seven times the risk (HR 7.23, 95% CI 3.21 to 16.28), transfusion three times the risk (HR 3.58, 95% CI 1.83 to 6.98) and preeclampsia two times the risk (HR 2.01, 95% CI 1.29 to 3.12). Women with other potential risk factors did not have an increased risk of Guillain-Barre syndrome. Conclusions Immune-related conditions that occur early in life are associated with an increased risk of Guillain-Barre syndrome. The pathophysiology of Guillain-Barre syndrome may extend beyond infectious triggers.

Aims We assessed the long-term risk of cataract following a pregnancy complicated by gestational diabetes. Methods We carried out a longitudinal cohort study of 1,108,541 women who delivered infants between 1989–2013 in Quebec, Canada, with follow-up extending up to 25 years later. The cohort included 71,862 women with gestational diabetes and 5247 with cataracts. We used Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of gestational diabetes with subsequent risk of cataract, adjusted for age, parity, socioeconomic status, time period, comorbidity, and type 2 diabetes. Results Women with gestational diabetes had an elevated incidence of cataract (22.6 per 1000) compared with no gestational diabetes (15.1 per 1000), with 1.15 times the risk (95% CI 1.04–1.28). Women with gestational diabetes who subsequently developed type 2 diabetes had a higher risk of cataract compared with no gestational and type 2 diabetes (HR 3.62, 95% CI 3.01–4.35), but women with gestational diabetes who did not develop type 2 diabetes continued to be at risk (HR 1.12, 95% CI 1.00–1.25). Conclusions Gestational diabetes may be an independent risk factor for cataract later in life, although risks are greatest for women who subsequently develop type 2 diabetes.

Background Pregnancy-related risk factors for cataract are understudied, including the possibility that preeclampsia increases the risk of cataract later in life. Objective We sought to evaluate the long-term risk of cataract extraction following a preeclamptic pregnancy. Study Design We carried out a historic cohort study of 1,108,541 women who delivered at least 1 infant in any hospital in the province of Quebec, Canada, from 1989 through 2013, including 64,350 with preeclampsia and 5732 with cataract extractions. We categorized preeclampsia by onset time and severity, and followed up women for up to 25 years after delivery. We calculated the incidence of inpatient cataract extraction for women with and without preeclampsia, and used Cox proportional hazard models to estimate hazard ratios and 95% confidence intervals for later risk of cataract extraction, adjusting for age at first delivery, total parity, metabolic disease, asthma, socioeconomic deprivation, and time period. Results Women with preeclampsia had a higher incidence of cataract extraction compared with no preeclampsia (21.0 vs 15.9/1000) and 1.20 times the risk (95% confidence interval, 1.08–1.34). Women with early-onset preeclampsia had 1.51 times the risk of cataract extraction compared with no preeclampsia (95% confidence interval, 1.14–2.00), whereas women with late-onset preeclampsia had 1.16 times the risk (95% confidence interval, 1.04–1.30). Risk was elevated by about 20% for both severe and mild preeclampsia. Preeclampsia with diabetes was associated with significantly greater risk (hazard ratio, 4.32; 95% confidence interval, 3.60–5.19). Conclusion Women with preeclampsia, particularly preeclampsia of early onset or with diabetes, may have greater risk of cataract later in life. The underlying pathways linking preeclampsia with cataract require further investigation.

Purpose. Inequality in use of fetal autopsy is poorly understood, despite the importance of autopsy in establishing the cause of stillbirth for future prevention. We examined fetal autopsy rates between linguistic minorities in Quebec, Canada, and assessed trends over three decades. Methods. Using registry data on 11,992 stillbirths from 1981–2011, we calculated fetal autopsy rates for Francophones, Anglophones, and Allophones by decade. Results. We found lower fetal autopsy rates for Allophones (54.4%) than Francophones (68.5%) and Anglophones (63.4%), but rates decreased over time for all language groups. After 2000, Allophones had 25% higher risk of non-autopsy relative to Francophones, with 8.8 fewer autopsies for every 100 stillbirths. Allophones who were not autopsied had 32% higher risk of having an undetermined cause of death. Conclusion. Inequality in use of fetal autopsy may be widespread for minorities in Canada. Efforts to decrease stillbirth in minorities may require policies to increase autopsy rates.

Background Infantile hemangioma is the most common tumor of infancy, but the association with preeclampsia is poorly understood. Objectives We determined the relation between variants of preeclampsia and risk of infantile hemangioma. Methods We carried out a retrospective cohort study of hospital data for all live births between 1989 and 2013 in Quebec, Canada. We identified 14,240 neonates with and 1,930,564 without hemangioma before discharge, and determined whether early or late onset preeclampsia was documented on the maternal chart. We used log-binomial regression to compute prevalence ratios (PR) and 95% confidence interval (CI) for the association between preeclampsia and infantile hemangioma, adjusted for maternal characteristics. Results Prevalence of any hemangioma was higher for preeclampsia than no preeclampsia (81.3 vs. 72.9 per 10,000), with a PR of 1.15 (95% CI 1.06-1.25) after adjustment for maternal characteristics. Preeclampsia with onset before 34 weeks gestation was associated with cutaneous (PR 2.32, 95% CI 1.68-3.21), noncutaneous (PR 3.66, 95% CI 2.49-5.37), and unspecified hemangioma (PR 2.49, 95% CI 1.77-3.49). The association between early onset preeclampsia and hemangioma was however attenuated once long neonatal length of hospital stays was accounted for. There was no association with late onset preeclampsia after 34 weeks, and associations were weaker for other variants including severe preeclampsia and preeclampsia with low birth weight. Conclusions Early onset preeclampsia is associated with increased risk of hemangioma at birth, but detection bias due to longer hospital stays and closer follow-up may be part of the reason. This article is protected by copyright. All rights reserved.

This study examined the spatial variation of potential gastrointestinal pathogens within drinking water sources and home storage containers in four neighborhoods in Maroua, Cameroon. Samples were collected from source (n= 28) and home containers (n= 60) in each study neighborhood. Pathogen contamination was assessed using quantitative polymerase chain reaction, targeting Campylobacter spp., Shiga toxin producing Escherichia coli (virulence genes, stx1 and stx2), and Salmonella spp. Microbial source tracking (MST) targeted three different host-specific markers: HF183 (human), Rum2Bac (ruminant) and GFD (poultry) to identify contamination sources. Staphylococcus aureus and the tetracycline-resistance gene (tetQ) were assessed to measure human hand contact and presence of antibiotic-resistant bacteria. Pathogen/MST levels were compared statistically and spatially, and neighborhood variation was compared with previously collected demographic information. All the test fecal markers and pathogens (except Arcobacter) were detected in home and source samples. Two neighborhoods tested positive for most pathogens/MST while the others only tested positive for one or two. Spatial variation of pathogens/MST existed between sources, storage containers, and neighborhoods. Differing population density and ethno-economic characteristics could potentially explain variation. Future research should explore the influence of demographic and ethno-economic factors on water quality during microbial risk assessments in urban Africa.

ObjectiveWe assessed baseline prevalence, risk factors and outcomes of microcephaly in a large population of neonates.DesignRetrospective cohort study.SettingAll hospitals in the province of Quebec, Canada.Participants794 microcephalic and 1 944 010 non-microcephalic infants born between 1989 and 2012.Main outcome measuresBaseline prevalence of microcephaly and occurrence of other congenital anomalies. We estimated the association of (1) pregnancy risk factors including TORCH infections (toxoplasmosis, rubella, cytomegalovirus, herpes, other), exposure to teratogens, diabetes and maternal congenital anomalies with risk of microcephaly, and (2) microcephaly with risk of infant mortality and severe morbidity, adjusted for maternal characteristics.ResultsThe overall prevalence of microcephaly was 4.1 per 10 000, ranging between 3.0 and 5.3 per 10 000 over time. Only 37% of microcephalic infants presented with other congenital anomalies. Maternal infection during pregnancy was the strongest risk factor, with 32 times the risk of microcephaly (prevalence ratio 32.38; 95% CI 22.42 to 46.75) compared with no infection. Exposure to teratogens was the next most important risk factor, with three times greater risk (prevalence ratio 3.10; 95% CI 2.37 to 4.07). Microcephaly was associated with 20 times the risk of infant mortality compared with no microcephaly (prevalence ratio 20.52; 95% CI 15.57 to 27.04) and significantly greater infant morbidity.ConclusionsIn Canada, infectious exposure during pregnancy is a strong risk factor for microcephaly, and affected infants are at higher risk of poor birth outcomes. Better monitoring of microcephaly is needed in the event that Zika or other novel viruses affect future risk.

Objective To determine the association between recurrent pre-eclampsia and long-term cardiovascular hospitalisation. Methods This study identified cardiovascular hospitalisations up to 25 years after pregnancy for all women who delivered between 1989 and 2013 in Quebec, Canada. Exposures included recurrent and non-recurrent pre-eclampsia in women with two deliveries or more (N=606 820), and pre-eclampsia in women with only one delivery (N=501 761). Incidence, timing and risk of cardiovascular complications were calculated using accelerated failure time models adjusted for age, pre-existing disease, socioeconomic deprivation and period. Outcomes included a range of cardiovascular hospitalisations and procedures. Results Women with recurrent pre-eclampsia had higher incidence of cardiovascular hospitalisation (281.4 per 1000) than women with non-recurrent (167.7 per 1000) or no pre-eclampsia (72.6 per 1000). Mean time to cardiovascular hospitalisation was 10.5 years for recurrent, 11.6 years for non-recurrent and 12.7 years for no pre-eclampsia, a difference of 17.3% for recurrent and 8.7% for non-recurrent relative to no pre-eclampsia. Compared with no pre-eclampsia, recurrent pre-eclampsia was associated with 2 times the risk of heart disease (95% CI 1.69 to 2.29) and 3 times the risk of cerebrovascular disease (95% CI 2.25 to 4.05). Pre-eclampsia in women with one delivery was associated with 3 times greater risk of cardiovascular hospitalisation compared with no pre-eclampsia in women with two deliveries or more (95% CI 2.96 to 3.25). Conclusions Recurrent pre-eclampsia is associated with higher risk of future cardiovascular hospitalisation compared with no pre-eclampsia, and significantly shorter time to first cardiovascular event. Cardiovascular screening should be performed earlier for women with recurrent pre-eclampsia.

To propose three methods to estimate associations between pregnancy exposures and outcomes before term, including the association between preeclampsia and preterm fetal-infant mortality, while avoiding the selection bias found in conventional analytic designs. Population-level analysis of 1,099,839 women who delivered live or stillborn infants in Quebec hospitals from 1989 to 2012, covering nearly a quarter of Canadian births. The exposure of interest was preeclampsia at 20–29, 30–33, 34–36, and ≥37 weeks of gestation. We compared preeclamptic with non-preeclamptic pregnancies in parametric survival models with a Weibull distribution using three analytic designs: (1) fetuses-at-risk; (2) bias correction factors; and (3) analysis of pregnancies at high risk of preterm delivery. Main outcome measures were occurrence of fetal or postnatal infant death before discharge. In models affected by bias due to selection of preterm births, women with preeclampsia early in gestation had paradoxically lower risks of fetal and infant mortality than women without preeclampsia. All three analytic approaches reversed the associations, showing a harmful effect of preeclampsia before term. At 20–29 weeks, for example, preeclampsia was associated with 1.35 times the risk of infant mortality (95 % confidence interval 1.14–1.60) and 1.40 times the risk of stillbirth (95 % confidence interval 1.18–1.67) with the fetuses-at-risk approach. Paradoxically protective benefits of exposures such as preeclampsia before term are artifacts of inappropriate analytic design. Outcomes before term should be analyzed with care, using methods that address bias due to selection of preterm deliveries.

Importance The risk of congenital heart defects in infants of women who had preeclampsia during pregnancy is poorly understood, despite shared angiogenic pathways in both conditions. Objective To determine the prevalence of congenital heart defects in offspring of women with preeclampsia. Design, Setting, and Participants Population-level analysis of live births before discharge, 1989-2012, was conducted for the entire province of Quebec, comprising a quarter of Canada’s population. All women who delivered an infant with or without heart defects in any Quebec hospital were included (N = 1 942 072 neonates). Exposures Preeclampsia or eclampsia with onset before or after 34 weeks of gestation. Main Outcomes and Measures Presence of any critical or noncritical congenital heart defect detected in infants at birth, comparing prevalence in those exposed and not exposed to preeclampsia. Results The absolute prevalence of congenital heart defects was higher for infants of women with preeclampsia (16.7 per 1000 [1219/72 782]) than without it (8.6 per 1000 [16 077/1 869 290]; prevalence ratio [PR], 1.57; 95% CI, 1.48 to 1.67). Infants of preeclamptic women had no increased prevalence of critical heart defects (123.7 vs 75.6 per 100 000 [90/72 782 vs 1414/1 869 290]; PR, 1.25; 95% CI, 1.00 to 1.57; prevalence difference [PD], 23.6 per 100 000; 95% CI, −1.0 to 48.2) but did have an increased prevalence of noncritical heart defects (1538.8 vs 789.2 per 100 000 [1120/72 782 vs 14 752/1 869 290]; PR, 1.56; 95% CI, 1.47 to 1.67; PD, 521.1 per 100 000; 95% CI, 431.1 to 611.0) compared with infants of nonpreeclamptic women. Among specific defects, prevalence was greatest for septal defects. When stratified by variant of preeclampsia, infants of women with early onset ( Conclusions and Relevance In this population-based study, preeclampsia was significantly associated with noncritical heart defects in offspring, and preeclampsia before 34 weeks was associated with critical heart defects. However, the absolute risk of congenital heart defects was low.