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Infections in the first trimester of pregnancy can be teratogenic, but the possibility that Covid-19 could lead to birth defects is unclear. We examined whether SARS-CoV-2 infection during pregnancy or exposure to pandemic conditions were associated with the risk of congenital anomalies. We carried out a retrospective study of 420,222 neonates born in Quebec, Canada in two time periods: prepandemic (January 1, 2017 to March 12, 2020) vs. pandemic (March 13, 2020 to March 31, 2022). We classified pandemic births as early (first trimester completed before the pandemic) or late (first trimester during the pandemic), and identified patients with SARS-CoV-2 infections during pregnancy. We applied (1) adjusted log-binomial regression models to assess the association between SARS-CoV-2 infection and congenital anomalies, and (2) autoregressive interrupted time series regression to analyze temporal trends in the monthly number of defects in all patients regardless of infection. In total, 29,263 newborns (7.0%) had a congenital anomaly. First trimester SARS-CoV-2 infections were not associated with a greater risk of birth defects compared with no infection (RR 1.07, 95% CI 0.59–1.95). However, births during the late pandemic period were more likely to be diagnosed with congenital microcephaly compared with prepandemic births (RR 1.44, 95% CI 1.21–1.71). Interrupted time series analysis confirmed that the frequency of microcephaly increased during the late pandemic period, whereas other anomalies did not. We conclude that Covid-19 is likely not teratogenic, but enhanced surveillance of anomalies among late pandemic births may have heightened the detection of infants with microcephaly. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Health outcomes of children in families affected by cancer are poorly understood. The authors assessed the risk of hospitalization in children who have a sibling with cancer. Methods: This was a longitudinal cohort study in which 1600 children who had a sibling with cancer were matched to 32,000 children who had unaffected siblings in Quebec, Canada, from 2006 to 2020. The exposure of interest was having a sibling with cancer. Outcomes included hospitalization for pneumonia, asthma, fracture, and other morbidities any time after the sibling was diagnosed with cancer. The children were followed over time, and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the impact of having a sibling with cancer on the risk of hospitalization before age 14 years, adjusted for patient characteristics. Results: Children who had a sibling with cancer had an increased risk of hospitalization compared with unaffected children (HR, 1.15; 95% CI, 1.02‐1.29). Conditions associated with a greater risk of hospitalization included pneumonia, hemangioma, other skin conditions, sleep apnea, and inflammatory bowel disease. The risk of hospitalization was greatest for children whose older sibling had cancer (HR, 1.16; 95% CI, 1.01‐1.32) and for children whose sibling had hematopoietic cancer (HR, 1.22; 95% CI, 1.01‐1.48). Conclusions: Children who have a sibling with cancer are at risk of hospitalization for conditions such as pneumonia, inflammatory bowel disease, and other morbidities. Families affected by childhood cancer may benefit from additional support to facilitate care for all children in the family. Lay Summary: Little is known about the health of children who have a brother or sister with cancer.The authors studied the types of hospitalization experienced by children who have siblings with cancer.The results indicated that having a sibling with cancer increased the chance of being hospitalized for pneumonia and other conditions that could have been preventable.The results also indicated that children who had an older sibling with cancer or a sibling with blood cancer had a greater chance of being hospitalized.The findings highlight the importance of providing timely care for children in families affected by childhood cancer. Children who have older siblings with cancer or siblings with hematopoietic cancer have an elevated risk of hospitalization. Many hospitalizations may be preventable, underscoring the importance of timely ambulatory care for children in families experiencing cancer. [ABSTRACT FROM AUTHOR]

Aim: This study assessed the self-reported health perception and use of health care by adults born very preterm before 30 weeks of gestation.Methods: The participants were part of a cross-sectional observational study that assessed the global health of young adults aged 18-29 years born very preterm in Quebec, Canada. Health perception was explored from 2011 to 2016 using the second Short-Form 36 Health Survey (SF-36v2), and objective health measures were obtained. Further in-depth open-ended questions were asked in 2018.Results: The 101 preterm subjects had similar perceptions of their health to 105 term-born controls, according to the SF-36v2, despite significantly more adverse health conditions. Their healthcare use was similar. However, the later in-depth questionnaire showed that 23% of 45 preterm subjects and 3% of 34 term-born subjects perceived their health as poorer than the general population. Major factors that could improve their respective health were lifestyle habits (74% vs. 81%) and eliminating specific adverse symptoms (52% vs. 27%). Only 10% of preterm individuals had been asked about their perinatal history by physicians.Conclusion: Adults born very preterm said their health was poorer than the general population and identified specific factors that should be addressed during routine health monitoring. [ABSTRACT FROM AUTHOR]

It is supposed that cesarean birth is implicated in the development of autoimmunity. We evaluated the association between cesarean delivery and the risk of hospitalization for autoimmune disease in children up to 14 years of age. We performed a longitudinal cohort study of 934,873 children born between 2006 and 2019 in Quebec, Canada. The main exposure measure was cesarean delivery versus vaginal delivery (spontaneous or induced). Outcomes included hospitalization for type 1 diabetes, celiac disease, or other autoimmune disorders before 14 years of age. We used Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between cesarean delivery and hospitalization for autoimmune disorders, adjusted for patient characteristics. A total of 248,963 children (27%) were delivered by cesarean. Median length of follow-up was 7.4 years. The hospitalization rate for autoimmune disorders was 69.1 per 100,000 person-years for cesarean and 65.9 per 100,000 person-years for vaginal delivery. Cesarean delivery was not associated with autoimmune disorders overall (HR 1.02, 95% CI 0.96–1.10). There was no association with type 1 diabetes (HR 1.00, 95% CI 0.85–1.17), celiac disease (HR 0.86, 95% CI 0.71–1.04), inflammatory bowel disease (HR 1.15, 95% CI 0.88–1.49), or idiopathic thrombocytopenic purpura (HR 1.01, 95% CI 0.82–1.25). Cesarean delivery was not associated with autoimmune disorders at different ages. Conclusion: This study suggests that cesarean delivery is not associated with the risk of hospitalization for autoimmune disorders before 14 years of age. Delivery mode does not seem to mediate the risk of autoimmunity in childhood. What is Known: • Children born by cesarean may be at risk of abnormal immune development. • The association between cesarean delivery and risk of pediatric autoimmune disorders is unclear. What is New: • In this cohort study of over 900,000 children, cesarean delivery was not associated with the risk of hospitalization for a range of autoimmune disorders before 14 years of age. • Cesarean delivery may not be related to the development of autoimmunity. [ABSTRACT FROM AUTHOR]

Background: Intraventricular hemorrhage is a serious neonatal complication associated with neurodevelopmental disorders, but the relationship with other childhood morbidities is unclear. We sought to assess the association of neonatal intraventricular hemorrhage with the risk of morbidity up to 12 years of age.Methods: We analyzed a cohort of 794,384 infants born between 2006 and 2016 in Quebec, Canada, with 4,269,579 person-years of follow-up. The exposure was grade I to IV intraventricular hemorrhage in the neonatal period. The main outcome measure was childhood hospitalization by cause of admission. In adjusted Cox regression models, we estimated hazard ratios and 95% confidence intervals for the association of intraventricular hemorrhage with future childhood hospitalization.Results: Infants with intraventricular hemorrhage had a higher incidence of childhood hospitalization than infants without hemorrhage (23.8 vs. 5.7 per 100 person-years). Compared with those with no hemorrhage, infants with intraventricular hemorrhage had 1.56 times the risk of hospitalization (95% confidence interval, 1.43-1.70). The risk was 2.81 times higher for grade III/IV hemorrhage (95% confidence interval, 2.23-3.53). Intraventricular hemorrhage at term was associated with 3.19 times the risk of hospitalization (95% confidence interval, 2.55-4.00), whereas preterm intraventricular hemorrhage was associated with 2.06 times the risk before 28 weeks (95% confidence interval, 1.75-2.42) and 1.87 times the risk between 28 and 36 weeks (95% confidence interval, 1.68-2.08), compared with no hemorrhage at term. Primary reasons for hospitalizations included central nervous system, ophthalmologic, musculoskeletal, and cardiovascular disorders.Conclusions: Intraventricular hemorrhage, especially of higher grades and in term neonates, is a predictor of future risk of hospitalization in childhood. [ABSTRACT FROM AUTHOR]

We sought to determine if neonatal phototherapy is associated with a greater risk of childhood cancer. We conducted a retrospective cohort study of 786,998 infants born in hospitals of Quebec, Canada between 2006 and 2016, with 4,660,868 person‐years of follow‐up over an 11‐year period. The exposures were neonatal phototherapy (32,314 or 4.1% of infants) and untreated jaundice (91,855 or 11.7% of infants). The outcome was hospitalization for solid or hematopoietic childhood tumours between 2 months and 11 years of age. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of phototherapy with childhood cancer, adjusted for infant characteristics. The incidence of childhood cancer was higher for infants with phototherapy (25.1 per 100,000 person‐years) and untreated jaundice (23.0 per 100,000) compared to unexposed infants (21.6 per 100,000). Phototherapy appeared to be associated with late onset solid tumours, including brain/central nervous system cancers. Between age 4 and 11 years, children who received neonatal phototherapy had more than 2 times the risk of any solid tumour compared to unexposed children (HR 2.26, 95% CI 1.34–3.81). Results were similar for phototherapy compared against untreated jaundice. A similar trend was however less apparent for hematopoietic cancer. We conclude that neonatal phototherapy may be associated with a slightly increased risk of solid tumours in childhood, but cannot rule out an effect of bilirubin. Minimizing unnecessary exposure to phototherapy through adherence to recommended thresholds for treatment is encouraged. What's new? While phototherapy is widely used to treat neonatal jaundice, it can induce oxidative stress and DNA damage. Whether these factors raise the risk for subsequent development of childhood cancer remains uncertain. Here, associations between phototherapy and childhood cancer risk were investigated among infants born between 2006 and 2016 in Quebec, Canada. Childhood cancer incidence was found to be elevated among phototherapy‐treated infants and infants with untreated jaundice. Phototherapy appeared to be associated in particular with solid tumors that developed later, between ages 4 and 11. Closer study is needed to disentangle the potentially carcinogenic effects of phototherapy from hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Background: Neonatal abstinence syndrome is increasingly prevalent, and may be related to opioid use disorders caused by postoperative prescriptions for pain control. We assessed the association of maternal prepregnancy surgery with risk of neonatal abstinence syndrome from opioid use disorders in future pregnancies.Methods: We conducted a longitudinal retrospective cohort study of 2 182 365 deliveries in Quebec, Canada, between 1989 and 2016. The main exposure was maternal prepregnancy surgery. The main outcome measure was neonatal abstinence syndrome in offspring. We adjusted associations for maternal comorbidity and pregnancy characteristics using log-binomial regression models.Results: The prevalence of neonatal abstinence syndrome in the cohort was 10.7 per 10 000 births. Compared with no surgery, prepregnancy surgery was associated with a risk ratio (RR) of neonatal abstinence syndrome of 1.63 (95% confidence interval [CI] 1.49-1.78). Risk was greater for 3 or more prepregnancy surgeries (RR 2.34, 95% CI 2.07-2.63) and age < 15 years at first surgery (1 surgery: RR 2.08, 95% CI 1.71-2.54; 2 or more surgeries: RR 2.79, 95% CI 2.32-3.37). Nearly all surgical specialties increased the risk of neonatal abstinence syndrome, but associations were strongest for cardiothoracic surgery (RR 4.45, 95% CI 2.87-6.91), neurosurgery (RR 3.00, 95% CI 1.56-5.77) and urologic surgery (RR 3.03, 95% CI 2.16-4.26).Interpretation: Prepregnancy surgery is associated with the risk of neonatal abstinence syndrome in future pregnancies. Prescription opioids for postsurgical pain may result in opioid use disorders during future pregnancies, inadvertently increasing the risk of neonatal abstinence syndrome in offspring. [ABSTRACT FROM AUTHOR]

The possibility that child maltreatment was misclassified as unintentional injury during the COVID-19 pandemic has not been evaluated. We assessed if child maltreatment hospitalizations changed during the pandemic, and if the change was accompanied by an increase in unintentional injuries. This study included children aged 0–4 years who were admitted for maltreatment or unintentional injuries between April 2006 and March 2021 in hospitals of Quebec, Canada. We used interrupted time series regression to estimate the effect of the pandemic on hospitalization rates for maltreatment, compared with unintentional transport accidents, falls, and mechanical force injuries. We assessed if the change in maltreatment hospitalization was accompanied by an increase in specific types of unintentional injury. Hospitalizations for child maltreatment decreased from 16.3 per 100,000 (95 % CI 9.1–23.4) the year before the pandemic to 13.2 per 100,000 (95 % CI 6.7–19.7) during the first lockdown. Hospitalizations for most types of unintentional injury also decreased, but injuries due to falls involving another person increased from 9.0 to 16.5 per 100,000. Hospitalization rates for maltreatment and unintentional injury remained low during the second lockdown, but mechanical force injuries involving another person increased from 3.8 to 8.1 per 100,000. Hospitalizations for child maltreatment may have been misclassified as unintentional injuries involving another person during the pandemic. Children admitted for these types of unintentional injuries may benefit from closer assessment to rule out maltreatment. • Hospitalization rates for child maltreatment decreased during the pandemic. • Falls and unintentional mechanical injuries involving another person increased in parallel. • Some cases of maltreatment may have been misclassified as unintentional injury. • Strategies to identify child maltreatment during a pandemic are needed. [ABSTRACT FROM AUTHOR]

The extent to which child traffic injuries may be attributed to parents who use cannabis before driving is unknown. We investigated whether prenatal cannabis use disorders may predict future road traffic injuries in children. We conducted a cohort study of 792,082 children in Quebec, Canada with 6,280,663 years of follow-up between 2006 and 2019. The main exposure measure was maternal cannabis use disorder before or during pregnancy. The main outcome measure was future hospitalizations for transport-related injuries in children after birth. Using Cox proportional hazards regression models adjusted for potential confounders, we estimated hazard ratios and 95% confidence intervals (CI) for the association of prenatal cannabis use disorders with transport-related injuries in children. Maternal cannabis use disorders before birth were associated with 5.64 times the risk of hospitalization for future motor vehicle crash injuries in children (95% CI 2.61-12.21). The risk increased with the child's age. Prenatal cocaine, opioid, and other drug use disorders were not associated with pediatric transport-related injuries. Maternal cannabis use disorders before birth may be an early predictor of childhood injuries from motor vehicle crashes. [ABSTRACT FROM AUTHOR]

Introduction: Risk factors for accidental drug poisonings in children are poorly understood, including the association with maternal substance use. This study seeks to determine whether maternal substance use disorders before birth are associated with the future risk of accidental drug poisonings in young children.Methods: This study was a longitudinal cohort analysis of 1,032,209 children aged <5 years between 2006 and 2020 in Quebec, Canada. The main exposure included maternal substance use disorders before or during pregnancy. The outcome was hospitalization for drug poisonings before age 5 years, including opioids, cannabis, sedatives/hypnotics, stimulants, and other drugs. Adjusted Cox proportional hazards regression was used to compute hazard ratios and 95% CIs for the association of substance use disorders with child drug poisonings during 4,523,003 person-years of follow-up. Analyses were conducted in 2020.Results: Hospitalization rates for drug poisoning before age 5 years were greater for children of mothers with substance use disorders versus no substance use disorder (84.8 vs 20.7 per 100,000 person-years). Maternal substance use disorders before birth were associated with 2.28 times the risk of future drug poisonings in children (95% CI=1.63, 3.20). The association was stronger for maternal opioid use disorders (hazard ratio=4.16, 95% CI=2.38, 7.27) than other drug use disorders. Associations with child poisonings were stronger between age 1 and 2 years (hazard ratio=3.26, 95% CI=2.09, 5.10) and for poisonings involving opioids, cannabis, and sedative/hypnotic drugs.Conclusions: Maternal substance use disorders before childbirth may be markers of future risk of drug poisonings in young children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Maternal stress and anxiety are associated with adverse pregnancy outcomes, but the association with future childhood injuries is unclear, especially risk of orthopedic fractures. We conducted a longitudinal study of 773,339 newborns in Quebec, Canada between 2006 and 2018. We identified women with stress or anxiety disorders before or after delivery, and computed the incidence of future operative fractures in offspring. We estimated hazard ratios (HR) with 95% confidence intervals (CI) for the association of maternal stress and anxiety disorders with the risk of pediatric fractures, adjusted for maternal and infant characteristics. Incidence of any fracture was higher for maternal stress (20.5 per 10,000 person-years) and anxiety (19.8 per 10,000 person-years) than no disorder (15.3 per 10,000 person-years). Maternal stress was associated with 1.17 times the risk of pediatric fractures (95% CI 1.00–1.38), and anxiety was associated with 1.26 times the risk (95% CI 1.07–1.47), compared with no disorder. Stress was predominantly linked with fall-related fractures (HR 1.26, 95% CI 1.06–1.50), and anxiety with assault-related fractures (HR 2.97, 95% CI 1.50–5.89). The association of stress with fall-related fractures was more prominent after 36 months of age, whereas anxiety was linked with assault-related fractures before 6 months. Stress and anxiety disorders before or after delivery are associated with the future risk of fractures in children. Women with a history of stress or anxiety disorders may benefit from counselling and social support for child fracture prevention. • The possibility of an association of maternal history of stress and anxiety with childhood bone fractures has not been evaluated. • We followed a longitudinal cohort of 773,339 newborns over time for risk of fractures up to 12 years of age. • Maternal stress or anxiety disorders before, during, and after pregnancy were associated with the future risk of fractures in children. • Associations were stronger for fractures due to falls and assault. [ABSTRACT FROM AUTHOR]