Extended Risk of Mortality in Children with Inborn Errors of Metabolism: A Longitudinal Cohort Study.

OBJECTIVES: To determine the long-term risk of mortality among children with inborn errors of metabolism. STUDY DESIGN: We conducted a retrospective cohort study of 1750 children with inborn errors of metabolism (excluding mitochondrial disorders) and 1 036 668 children without errors of metabolism who were born in Quebec, Canada, between 2006 and 2019. Main outcome measures included all-cause and cause-specific mortality between birth and 14 years of age. We used adjusted survival regression models to estimate HRs and 95% CIs for the association between inborn errors of metabolism and mortality over time. RESULTS: Mortality rates were greater for children with errors of metabolism than for unaffected children (69.1 vs 3.2 deaths per 10 000 person-years). During 7 702 179 person-years of follow-up, inborn errors of metabolism were associated with 21.2 times the risk of mortality compared with no error of metabolism (95% CI 17.23-26.11). Disorders of mineral metabolism were associated with greater mortality the first 28 days of life (HR 60.62, 95% CI 10.04-365.98), and disorders of sphingolipid metabolism were associated with greater mortality by 1 year (HR 284.73, 95% CI 139.20-582.44) and 14 years (HR 1066.00, 95% CI 298.91-3801.63). Errors of metabolism were disproportionately associated with death from hepatic/digestive (HR 208.21, 95% CI 90.28-480.22), respiratory (HR 116.57, 95% CI 71.06-191.23), and infectious causes (HR 119.83, 95% CI 40.56-354.04). CONCLUSIONS: Children with errors of metabolism have a considerably elevated risk of mortality before 14 years, including death from hepatic/digestive, respiratory, and infectious causes. Targeting these causes of death may help improve long-term survival.

Shifting age of child eating disorder hospitalizations during the Covid-19 pandemic.

BACKGROUND: We studied the effect of the Covid-19 pandemic on child eating disorder hospitalizations in Quebec, Canada. Quebec had one of the strictest lockdown measures targeting young people in North America. METHODS: We analyzed eating disorder hospitalizations in children aged 10-19 years before and during the pandemic. We used interrupted time series regression to assess trends in the monthly number of hospitalizations for anorexia nervosa, bulimia nervosa, and other eating disorders before the pandemic (April 2006 to February 2020), and during the first (March to August 2020) and second waves (September 2020 to March 2021). We determined the types of eating disorders requiring hospital treatment and identified the age, sex and socioeconomic subgroups that were most affected. RESULTS: Hospitalization rates for eating disorders increased during the first (6.5 per 10,000) and second waves (12.8 per 10,000) compared with the period before the pandemic (5.8 per 10,000). The increase occurred for anorexia nervosa as well as other types of eating disorders. The number of girls and boys aged 10-14 years admitted for eating disorders increased during wave 1. Wave 2 triggered an increase in eating disorder admissions among girls aged 15-19 years. Hospitalization rates increased earlier for advantaged than disadvantaged youth. CONCLUSIONS: The Covid-19 pandemic affected hospitalizations for anorexia nervosa as well as other eating disorders, beginning with girls aged 10-14 years during wave 1, followed by girls aged 15-19 years during wave 2. Boys aged 10-14 years were also affected, as well as both advantaged and disadvantaged youth.

The impact of COVID-19 on small business outcomes and expectations.

To explore the impact of coronavirus disease 2019 (COVID-19) on small businesses, we conducted a survey of more than 5,800 small businesses between March 28 and April 4, 2020. Several themes emerged. First, mass layoffs and closures had already occurred-just a few weeks into the crisis. Second, the risk of closure was negatively associated with the expected length of the crisis. Moreover, businesses had widely varying beliefs about the likely duration of COVID-related disruptions. Third, many small businesses are financially fragile: The median business with more than $10,000 in monthly expenses had only about 2 wk of cash on hand at the time of the survey. Fourth, the majority of businesses planned to seek funding through the Coronavirus Aid, Relief, and Economic Security (CARES) Act. However, many anticipated problems with accessing the program, such as bureaucratic hassles and difficulties establishing eligibility. Using experimental variation, we also assess take-up rates and business resilience effects for loans relative to grants-based programs.

Longitudinal risk of maternal hospitalization for mental illness following preterm birth.

BACKGROUND: Preterm birth may affect maternal mental health, yet most studies focus on postpartum mental disorders only. We explored the relationship between preterm delivery and the long-term risk of maternal hospitalization for mental illness after pregnancy. METHODS: We performed a longitudinal cohort study of 1,381,300 women who delivered between 1989 and 2021 in Quebec, Canada, and had no prior history of mental illness. The exposure was preterm birth, including extreme (<28 weeks), very (28-31 weeks), and moderate to late (32-36 weeks). The outcome was subsequent maternal hospitalization for depression, bipolar, psychotic, stress and anxiety, personality disorders, and self-harm up to 32 years later. We used adjusted Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between preterm birth and mental illness hospitalization. RESULTS: Compared with term, women who delivered preterm had a higher rate of mental illness hospitalization (3.81 vs. 3.01 per 1000 person-years). Preterm birth was associated with any mental illness (HR 1.38, 95% CI 1.35-1.41), including depression (HR 1.37, 95% CI 1.32-1.41), psychotic disorders (HR 1.35, 95% CI 1.25-1.44), and stress and anxiety disorders (HR 1.42, 95% CI 1.38-1.46). Delivery at any preterm gestational age was associated with the risk of mental hospitalization, but risks were greatest around 34 weeks of gestation. Preterm birth was strongly associated with mental illness hospitalization within 2 years of pregnancy, although associations persisted throughout follow-up. CONCLUSIONS: Women who deliver preterm may be at risk of mental disorders in the short and long term.

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.

Observational study of birth outcomes in children with inborn errors of metabolism.

BACKGROUND: We examined the birth outcomes of children with inborn errors of metabolism detected at birth or later in life. METHODS: We carried out a retrospective cohort study of 1733 children with inborn errors of metabolism and 1,033,693 unaffected children born in Canada between 2006 and 2019. Primary outcomes included preterm birth, low birth weight, congenital anomalies, and other neonatal complications. We estimated adjusted risk ratios (RR) and 95% confidence intervals (CI) for the association of inborn errors of metabolism with each outcome. RESULTS: Children with inborn errors of metabolism had 2.51 times the risk of preterm birth (95% CI 2.27-2.77) and 3.08 times the risk of low birth weight (95% CI 2.77-3.42) compared with unaffected children. Disorders of mineral and lipoprotein metabolism were more strongly associated with adverse birth outcomes. Inborn errors of metabolism were associated with congenital anomalies (RR 2.62; 95% CI 2.36-2.90), particularly abdominal wall defects (RR 8.35; 95% CI 5.18-13.44). Associations were present for errors of metabolism diagnosed both at birth and later in life. CONCLUSIONS: Children with inborn errors of metabolism, whether detected at birth or later, are at high risk of adverse birth outcomes and congenital anomalies. IMPACT: Inborn errors of metabolism may affect fetal development, but the association with adverse birth outcomes is not well characterized. This study indicates that children with inborn errors of metabolism are at risk of preterm birth, neonatal jaundice, congenital anomalies, and a range of other adverse birth outcomes. Mothers of children with inborn errors of metabolism are at risk of preeclampsia and cesarean delivery. Adverse birth outcomes may be a first sign of inborn errors of metabolism that merit increased screening.

Risk of Severe Maternal Morbidity After Bariatric Surgery: Retrospective Cohort Study.

OBJECTIVE: We assessed whether bariatric surgery before pregnancy lowers the risk of severe maternal morbidity to a level comparable to no obesity. SUMMARY OF BACKGROUND DATA: Obesity is a risk factor for severe maternal morbidity, but the potential for bariatric surgery to reduce the risk has not been studied. METHODS: We analyzed a retrospective cohort of 2,412,075 deliveries between 1989 and 2019 in Quebec, Canada. The main exposure measures were bariatric surgery before pregnancy and obesity without bariatric surgery, compared with no obesity. The outcome was severe maternal morbidity, a composite of life-threatening pregnancy complications. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between bariatric surgery and severe maternal morbidity, adjusted for maternal characteristics. RESULTS: A total of 2654 deliveries (0.1%) were in women who had bariatric surgery, and 70,041 (29.0 per 1000) were in women who had severe maternal morbidity. Risk of severe maternal morbidity was not significantly elevated for bariatric surgery (RR 1.20; 95% CI 0.98-1.46), but was greater for obesity compared with no obesity (RR 1.60; 95% CI 1.55-1.64). Bariatric surgery was not associated with morbidities such as severe preeclampsia, sepsis, and cardiac complications compared with no obesity, but obesity was associated with elevated risks of these and other severe morbidities. Bariatric surgery was associated, however, with intensive care unit admission, compared with no obesity. CONCLUSIONS: Pregnant women with prior bariatric surgery have similar risks as nonobese women for most types of severe maternal morbidity, except for intensive care unit admission.

Effect of publicly funded assisted reproductive technology on maternal and infant outcomes: a pre- and post-comparison study.

STUDY QUESTION: Does publicly funded assisted reproductive technology result in improved maternal and infant outcomes? SUMMARY ANSWER: Publicly funded ART in Quebec was associated with reduced risks of preeclampsia, cesarean delivery, preterm birth, low birth weight and other adverse outcomes. WHAT IS KNOWN ALREADY: Publicly funded ART programs that provide free access to single embryo transfer are known to decrease the rate of multiple pregnancy, but the impact on other pregnancy outcomes is unknown. STUDY DESIGN, SIZE, DURATION: We conducted a pre- and post-comparison study of 597 416 pregnancies conceived between July 2008 and September 2015 in Quebec, Canada, a region where public funding of ART began in August 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included all pregnant women who conceived by ART (n = 14 309) or spontaneously (n = 583 107) and delivered a live or stillborn infant in hospitals of Quebec. The main exposure measure was conception before versus during the publicly funded ART program. Outcomes included measures of maternal and infant morbidity and mortality. We estimated risk ratios (RR) and 95% confidence intervals for the association of publicly funded ART with maternal and infant outcomes using log-binomial regression models adjusted for maternal characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: In this study, 2638 pregnancies were conceived by ART before, and 11 671 were conceived by ART, during public funding. Compared with no public funding, ART funding was associated with reduced risks of severe maternal morbidity (RR 0.64, 95% CI 0.50-0.83), preeclampsia (RR 0.55, 95% CI 0.44-0.68), cesarean delivery (RR 0.83, 95% CI 0.77-0.89), preterm birth (RR 0.67, 95% CI 0.60-0.75), low birth weight (RR 0.63, 95% CI 0.55-0.72), severe neonatal morbidity (RR 0.75, 95% CI 0.57-0.99) and neonatal intensive care unit admission (RR 0.65, 95% CI 0.53-0.78). When multiple pregnancies were excluded, ART funding continued to be associated with a lower risk of preeclampsia (RR 0.61, 95% CI 0.48-0.79) and preterm birth (RR 0.85, 95% CI 0.73-0.99). However, ART funding was associated with increased risk of gestational diabetes. LIMITATIONS, REASONS FOR CAUTION: We had no information on the type of ART, number of in-vitro fertilization cycles or number of embryos transferred. We lacked data on body mass index, ethnicity and smoking and cannot rule out residual confounding. WIDER IMPLICATION OF THE FINDINGS: Our findings suggest that publicly funded ART programs that encourage single embryo transfer may have substantial benefits for a range of maternal and infant outcomes, beyond prevention of multiple births. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grant 6D02363004 from the Public Health Agency of Canada. N.A. acknowledges a career award from the Fonds de recherche du Québec-Santé (34695). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Maternal risk factors for paediatric inguinal hernia.

BACKGROUND: Risk factors for paediatric inguinal hernia are poorly understood. This longitudinal cohort study assessed whether children with a maternal history of inguinal hernia or connective tissue disorders have a higher risk of developing inguinal hernias before 13 years of age. METHODS: The study included children followed up between birth and 13 years of age in Quebec, Canada, 2006-2019. Newborns whose mothers had inguinal hernias or connective tissue disorders were followed over time to identify future hospital admissions for inguinal hernia. Cox proportional hazards regression adjusted for patient characteristics was used to estimate hazard ratios (HRs) and 95 per cent confidence intervals for the association between maternal hernia or connective tissue disorders and future childhood hernias. Associations in girls and boys were examined separately. RESULTS: The study included 786 322 children with 6 186 448 person-years of follow-up. There were 6861 children with inguinal hernias, corresponding to an incidence of 11.1 per 10 000 person-years. Children with a maternal history of inguinal hernia had 2.92 (95 per cent c.i. 2.39 to 3.58) times the risk of having inguinal hernias relative to children whose mothers had no such history. Children with a maternal history of connective tissue disorders had 1.30 (1.00 to 1.68) times the risk. Maternal hernias were strongly associated with risk of inguinal hernias in girls (HR 5.34, 3.82 to 7.47), whereas maternal connective tissue disorders were associated with inguinal hernias in boys (HR 1.35, 1.02 to 1.79). CONCLUSION: Paediatric inguinal hernias may be associated with maternal inguinal hernias and connective tissue disorders, but the underlying reason for this relationship requires further investigation.

In this study of 786 322 children in Canada from 2006 to 2019, it was found that children whose mothers had an inguinal hernia or connective tissue disorder were more at risk of developing a hernia themselves. Repairs for inguinal hernia are among the most common operations performed in children. The results showed that girls whose mothers had an inguinal hernia had more than five times the risk of developing an inguinal hernia before 13 years of age. Boys whose mothers had connective tissue disorders had a 35 per cent greater risk of inguinal hernia. These findings suggest that inguinal hernias may be inherited.

The impact of COVID-19 on pregnancy outcomes: a systematic review and meta-analysis.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) on maternal and newborn health is unclear. We aimed to evaluate the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and adverse pregnancy outcomes. METHODS: We conducted a systematic review and meta-analysis of observational studies with comparison data on SARS-CoV-2 infection and severity of COVID-19 during pregnancy. We searched for eligible studies in MEDLINE, Embase, ClinicalTrials.gov, medRxiv and Cochrane databases up to Jan. 29, 2021, using Medical Subject Headings terms and keywords for "severe acute respiratory syndrome coronavirus 2 OR SARS-CoV-2 OR coronavirus disease 2019 OR COVID-19" AND "pregnancy." We evaluated the methodologic quality of all included studies using the Newcastle-Ottawa Scale. Our primary outcomes were preeclampsia and preterm birth. Secondary outcomes included stillbirth, gestational diabetes and other pregnancy outcomes. We calculated summary odds ratios (ORs) or weighted mean differences with 95% confidence intervals (CI) using random-effects meta-analysis. RESULTS: We included 42 studies involving 438 548 people who were pregnant. Compared with no SARS-CoV-2 infection in pregnancy, COVID-19 was associated with preeclampsia (OR 1.33, 95% CI 1.03 to 1.73), preterm birth (OR 1.82, 95% CI 1.38 to 2.39) and stillbirth (OR 2.11, 95% CI 1.14 to 3.90). Compared with mild COVID-19, severe COVID-19 was strongly associated with preeclampsia (OR 4.16, 95% CI 1.55 to 11.15), preterm birth (OR 4.29, 95% CI 2.41 to 7.63), gestational diabetes (OR 1.99, 95% CI 1.09 to 3.64) and low birth weight (OR 1.89, 95% CI 1.14 to 3.12). INTERPRETATION: COVID-19 may be associated with increased risks of preeclampsia, preterm birth and other adverse pregnancy outcomes.

Ramadan exposure during early pregnancy and risk of stillbirth in Arab women living in Canada.

BACKGROUND: Data on fasting during Ramadan and the risk of preterm birth and child mortality are conflicting, but the association with stillbirth is unknown. OBJECTIVE: We studied the relationship between Ramadan and the risk of stillbirth for Arab women in Quebec, Canada. METHODS: We conducted a retrospective cohort study using birth certificates for Arab women in Quebec, Canada, between 1981 and 2017. The exposure was Ramadan in the first and second trimester (1-27 weeks of gestation), and the outcome was early (<28 weeks) or late (≥28 weeks) stillbirth. We used log-binomial regression models to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association between Ramadan and risk of stillbirth. We adjusted models for maternal characteristics and assessed associations by cause of death. RESULTS: The study included 78,349 live births and 274 stillbirths. There were 3.5 stillbirths per 1,000 pregnancies for women exposed to Ramadan between weeks 1-27 of gestation (95% CI 3.0, 4.0), and 3.4 per 1,000 for unexposed women (95% CI 2.8, 4.1). Compared with no exposure, Ramadan between weeks 1-27 was not associated with the risk of early (RR 1.32, 95% CI 0.76, 2.28) or late stillbirth (RR 0.93, 95% CI 0.70, 1.23) in adjusted models. RRs for early stillbirth were 1.40 for Ramadan between weeks 15-21 (95% CI 0.70, 2.80) and 1.38 for Ramadan between weeks 22-27 (95% CI 0.67, 2.84). Relative to no exposure, Ramadan between weeks 15-21 was associated with early stillbirth due to congenital anomaly (RR 3.96; 95% CI 1.35, 11.57) in unadjusted models. There was no association with other causes of stillbirth. CONCLUSIONS: There is no evidence that Ramadan is associated with the risk of early or late stillbirth overall. Further research is needed to confirm an association with stillbirth due to congenital anomalies.

Precision-engineered Peptide and Protein Analogs: Establishing a New Discovery Platform for Potent GPCR Modulators.

Numerous members of the human G protein-coupled receptor (GPCR) superfamily are receptors of therapeutic interest. GPCRs are considered to be highly tractable for drug discovery, representing the targets of approximately one-third of currently licensed drugs. These successful drug discovery outcomes cover only a relatively small subset of the superfamily, however, and many other attractive receptors have proven to present significant challenges. Among these difficult GPCRs are those whose natural ligands are peptides and proteins. In this review we explain the obstacles faced by GPCR drug discovery campaigns, with particular focus on those related to peptide and protein GPCRs. We describe a novel and promising approach for these targets based on engineering of their natural ligands and describe an integrated discovery platform that allows potent ligand analogs to be discovered rapidly and efficiently. Finally, we present a case study involving the chemokine receptor CCR5 to show that this approach can be used to generate new drugs for peptide and protein GPCR targets combining best-in-class potency with tunable signaling activity.

Maternal Autoimmune Disorders and Risk of Kawasaki Disease in Offspring.

We assessed the association between maternal autoimmune disorders and offspring risk of Kawasaki disease in a longitudinal cohort of 792 108 newborns. We found that maternal autoimmune disorders, especially autoimmune thyroiditis, may be risk factors for Kawasaki disease in children, particularly young children.

Hot weather and risk of drowning in children: Opportunity for prevention.

The link between outdoor temperature and risk of drowning in children is poorly understood. The objective of this study was to determine the association between elevated temperature and the chance of drowning in children and adolescents. We used a case-crossover study design to assess 807 fatal and nonfatal drowning-related hospitalisations among children aged 0 to 19 years in Quebec, Canada between 1989 and 2015. The primary exposure measure was maximum temperature the day of drowning. We estimated odds ratios and 95% confidence intervals (CI) for the association of temperature with drowning by age group (<2, 2-4, 5-9, 10-19 years), adjusted for precipitation, relative humidity, and holidays. Elevated temperature was associated with greater odds of drowning. Compared with 15 °C, a temperature of 30 °C was associated with 6 times the chance of drowning between 0 and 19 years of age (95% CI 4.40-8.16). The association was not modified by characteristics such as age or location of drowning. Relative to 15 °C, a temperature of 30 °C was associated with 3.75 times the odds of drowning in pools (95% CI 1.85-7.63) and 12.44 times the odds of drowning in other bodies of water (95% CI 3.53-43.81). Associations persisted even after implementation of a policy to restrict access to private pools in 2010. These findings suggest that hot weather is strongly associated with the risk of drowning in children aged 0 to 19 years. Interventions to prevent drowning in children should be enhanced during hot days, and not only around pools.

Rapid and low-cost multiplex synthesis of chemokine analogs.

Peptides represent a promising source of new medicines, but improved technologies are needed to facilitate discovery and optimization campaigns. In particular, longer peptides with multiple disulfide bridges are challenging to produce, and producing large numbers of structurally related variants is dissuasively costly and time-consuming. The principal cost and time drivers are the multiple column chromatography purification steps that are used during the multistep chemical synthesis procedure, which involves both ligation and oxidative refolding steps. In this study, we developed a method for multiplex parallel synthesis of complex peptide analogs in which the structurally variant region of the molecule is produced as a small peptide on a 384-well synthesizer with subsequent ligation to the longer, structurally invariant region and oxidative refolding carried out in-well without any column purification steps. To test the method, we used a panel of 96 analogs of the chemokine RANTES (regulated on activation normal T cell expressed and secreted)/CCL5 (69 residues, two disulfide bridges), which had been synthesized using standard approaches and characterized pharmacologically in an earlier study. Although, as expected, the multiplex method generated chemokine analogs of lower purity than those produced in the original study, it was nonetheless possible to closely match the pharmacological attributes (anti-HIV potency, capacity to elicit G protein signaling, and capacity to elicit intracellular receptor sequestration) of each chemokine analog to reference data from the earlier study. This rapid, low-cost approach has the potential to support discovery and optimization campaigns based on analogs of other chemokines as well as those of other complex peptide and small protein targets of a similar size.

Long-Term Risk of Cardiovascular Disease in Women Who Have Had Infants With Heart Defects.

BACKGROUND: The possibility that congenital heart defects signal a familial predisposition to cardiovascular disease has not been investigated. We aimed to determine whether the risk of cardiovascular disorders later in life was higher for women who have had newborns with congenital heart defects. METHODS: We studied a cohort of 1 084 251 women who had delivered infants between 1989 and 2013 in Quebec, Canada. We identified women whose infants had critical, noncritical, or no heart defects, and tracked the women over time for future hospitalizations for cardiovascular disease, with follow-up extending up to 25 years past pregnancy. We calculated the incidence of cardiovascular hospitalization per 1000 person-years, and used Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs) for the association between infant heart defects and risk of maternal cardiovascular hospitalization. Models were adjusted for age, parity, preeclampsia, comorbidity, material deprivation, and time period. RESULTS: Women whose infants had heart defects had a higher overall incidence of cardiovascular hospitalization. There were 3.38 cardiovascular hospitalizations per 1000 person-years for those with critical defects (95% CI, 2.67-4.27), 3.19 for noncritical defects (95% CI, 2.96-3.45), and 2.42 for no heart defects (95% CI, 2.39-2.44). In comparison with no heart defects, women whose infants had critical defects had a hazard ratio of 1.43 (95% CI, 1.13-1.82) for any cardiovascular hospitalization, and women whose infants had noncritical defects had a hazard ratio of 1.24 (95% CI, 1.15-1.34), in adjusted models. Risks of specific causes of cardiovascular hospitalization, including myocardial infarction, heart failure, and other atherosclerotic disorders, were also greater for mothers of infants with congenital heart defects than with no defects. CONCLUSIONS: Women whose infants have congenital heart defects have a greater risk of cardiovascular hospitalization later in life. Congenital heart defects in offspring may be an early marker of predisposition to cardiovascular disease.

Fasting during Ramadan Increases Risk of Very Preterm Birth among Arabic-Speaking Women.

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.

Maternal proximity to extremely low frequency electromagnetic fields and risk of birth defects.

Causes of birth defects are unclear, and the association with electromagnetic fields is inconclusive. We assessed the relationship between residential proximity to extremely low frequency electromagnetic fields from power grids and risk of birth defects. We analyzed a population-based sample of 2,164,246 infants born in Quebec, Canada between 1989 and 2016. We geocoded the maternal residential postal code at delivery and computed the distance to the nearest high voltage electrical transmission line or transformer station. We used log-binomial regression to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association of residential proximity to transmission lines and transformer stations with birth defects, adjusting for maternal and infant characteristics. The prevalence of birth defects within 200 m of a transmission line (579.4 per 10,000 per live births) was only slightly higher compared with distances further away (568.7 per 10,000). A similar trend was seen for transformer stations. Compared with 200 m, a distance of 50 m was not associated with the risk of birth defects for transmission lines (RR 1.00, 95% CI 1.00-1.01) and transformer stations (RR 1.01, 95% CI 1.00-1.03). There was no consistent association when we examined birth defects in different organ systems. We found no compelling evidence that residential proximity to extremely low frequency electromagnetic fields from electrical power grids increases the risk of birth defects. Women residing near electrical grids can be reassured that an effect on the risk of birth defects is unlikely.

Residential exposure to electromagnetic fields during pregnancy and risk of child cancer: A longitudinal cohort study.

OBJECTIVE: We assessed whether exposure to electromagnetic fields during pregnancy increases the risk of childhood cancer. METHODS: We studied a retrospective cohort of 784,944 newborns in Quebec, Canada between 2006 and 2016 who were followed for cancer one decade after birth. The exposures were residential distance to the nearest high voltage power transformer station and transmission line. We determined the incidence of childhood cancer, and estimated hazard ratios and 95% confidence intervals (CI) in Cox proportional hazards regression models adjusted for maternal and birth characteristics. RESULTS: There were 1114 incident cases of cancer during 4,647,472 person-years of follow-up. Residential proximity to transformer stations was associated with a somewhat greater risk of cancer, but there was no association with transmission lines. Compared with 200 m, a distance of 80 m from a transformer station was associated with a hazard ratio of 1.08 (95% CI 0.98, 1.20) for any cancer, 1.04 (95% CI 0.88, 1.23) for hematopoietic cancer, and 1.11 (95% CI 0.99, 1.25) for solid tumours. CONCLUSIONS: Residential proximity to transformer stations is associated with a borderline risk of childhood cancer, but the absence of an association with transmission lines suggests no causal link.

Residential noise exposure and the longitudinal risk of hospitalization for depression after pregnancy: Postpartum and beyond.

OBJECTIVE: Depression is a major public health concern, but the link with the built environment is unclear. We sought to determine the relationship between residential noise during pregnancy and later risk of severe depression in women. METHODS: We analyzed a population-based cohort of 140,456 women with no documented history of mental illness who were pregnant in Montreal between 2000 and 2016. We obtained residential noise estimates (LAeq. 24 h, Lden, Lnight) from land use regression models, and followed the women over time for up to 18 years after pregnancy to identify subsequent hospitalizations for depression or other mental disorders. We used Cox regression to compute hazard ratios and 95% confidence intervals (CI) adjusted for maternal characteristics. RESULTS: There were 8.0 incident hospitalizations for depression and 16.4 for other mental disorders per 10,000 person-years in women exposed to an LAeq. 24 h of 60-64.9 dB(A). The incidence was lower for noise at < 55 dB(A), with 7.4 hospitalizations for depression and 13.8 for other mental disorders per 10,000 person-years. Compared with 50 dB(A), an LAeq. 24 h of 60 dB(A) was associated with 1.16 times (95% CI 0.84-1.62) the risk of depression hospitalization, and 1.34 times (95% CI 1.04-1.74) the risk of other mental disorders. Associations were more prominent for Lnight, with 1.32 times (95% CI 1.08-1.63) the risk of depression hospitalization at 60 dB(A) and 1.68 times the risk (95% CI 1.05-2.67) at 70 dB(A). CONCLUSIONS: Pregnant women exposed to noise, especially nighttime noise, have a greater risk of hospitalization for depression and other mental disorders later in life. Residential noise may be a risk factor for depression after pregnancy.