Search

Introduction: Maternal inflammatory bowel disease (IBD) during pregnancy may be associated with increased susceptibility to infection in offspring. We aimed to assess this association, taking into consideration the mediating role of anti-tumor necrosis factor α (anti-TNFα) agents and adverse birth outcomes., Methods: This population-based cohort study included all live-born singletons born in Denmark during 1995-2016 (n = 1,343,960). The exposure was maternal IBD. Main outcome of interest was offspring infection younger than 5 years, defined by either infection-related hospitalization or systemic antibiotic prescription, whose corresponding risk estimates were hazard ratios (HRs) and incidence rate ratios (IRRs), respectively. We applied an inverse probability-weighted marginal structural model for mediation analysis., Results: Offspring born to mothers with Crohn's disease (CD) had an 18% increased risk of infection-related hospitalization (HR 1.18, 95% confidence interval 1.10-1.26) and a 16% increased frequency of prescribed antibiotics (IRR 1.16, 95% confidence interval 1.11-1.21). Anti-TNFα agents could explain 10% and 3% of the 2 estimated total associations, respectively, while a composite of preterm birth, low birth weight, and small for gestational age could explain 4% and 0%, respectively. The association between prenatal anti-TNFα and frequency of antibiotics attenuated after additional adjustment for maternal CD (IRR from 1.23 [0.98-1.55] to 1.10 [0.87-1.40]). Maternal ulcerative colitis, however, was not associated with offspring infection., Discussion: Maternal CD, but not ulcerative colitis, was associated with an increased risk of infection in offspring younger than 5 years, of which adverse birth outcomes and anti-TNFα had a minor role. The association between anti-TNFα agents and pediatric infection could be partially explained by maternal CD., (Copyright © 2023 by The American College of Gastroenterology.)

Objectives: The study aimed to investigate the association between maternal body mass index (BMI) in early pregnancy and children's intellectual disability (ID) risk in the absence of chromosomal disorders, neurofibromatosis and tuberous sclerosis, taking adverse birth outcomes, maternal hypertension/diabetes and maternal socioeconomic status into consideration., Methods: We conducted a cohort study of singletons without common genetic defects born in Sweden during 1992-2006, and followed them from birth until 31 December 2014 (n=1 186 836). Cox proportional hazards models were used to analyse the association between maternal BMI in early pregnancy and the risk of offspring's ID., Results: The risk of ID was higher in children born to mothers who were underweight (HR=1.21, 95% CI=1.07 to 1.36), overweight (HR=1.28, 95% CI=1.21 to 1.34) or had obesity class I (HR=1.63, 95% CI=1.53 to 1.74), obesity class II (HR=2.08, 95% CI=1.88 to 2.30) and obesity class III (HR=2.31, 95% CI=1.46 to 3.65) than in children born to normal weight mothers. Results remained consistent after excluding children with adverse birth outcome or born to mothers with gestational hypertension/diabetes. Analysis stratified by maternal education and annual household income showed that the association between maternal underweight and children's ID risk was attenuated among children of mothers with tertiary education or with high income., Conclusions: Our findings suggest that maternal underweight or overweight/obesity in early pregnancy was associated with the development of ID in their offspring. This association was independent of the effect of adverse birth outcomes and maternal hypertension/diabetes. High socioeconomic status may attenuate the risk of ID among children of underweight mothers. This study highlights the importance of improving health education before conception to reduce children's ID risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: No previous study has examined the effect of maternal hypothyroidism on a broad spectrum of cardiovascular disease (CVD) endpoints in the offspring., Methods: A nationwide population-based cohort study based on the linkage of several Danish nationwide registries was conducted to explore whether maternal hypothyroidism is associated with offspring's CVD. Altogether 1,041,448 singletons born between the 1st of January 1978 and the 31st of December 1998 were investigated from the age of 8 years to the 31st of December 2016. Exposure was maternal diagnosis of hypothyroidism across lifespan and the outcome of interest was a CVD diagnosis in the offspring. Cox regression models were performed to estimate the hazard ratios (HRs) of CVD., Results: Offspring born to mothers with hypothyroidism had an increased risk of CVD (hazard ratios (HR)=1.23, 95% confidence interval (CI): 1.12-1.35), and of several subcategories of CVD including hypertension, arrhythmia, and acute myocardial infarction in offspring. The magnitude of association was the most pronounced in an exposure occur during pregnancy (HR=1.71, 95% CI: 1.10-2.67), which is consistent across all the subgroup analysis, including sibling analysis., Conclusions: Maternal hypothyroidism is associated with an increased risk of CVD in offspring. Thyroid hormone insufficiency during pregnancy may predominantly contribute to the observed associations; however, the effects of a shared genetic background and a time-stable familial environment/lifestyle factors cannot be excluded., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Miao, Liu, Yuan, Madsen, Yu, László, Liang, Ji and Li.)

Intrauterine malnutrition has a long-term effect on human health. This study aimed to evaluate the associations between exposure to famine in early life and obesity in adulthood in Chinese adults. A total of 5033 participants (22,132 observations) of the China Health and Nutrition Survey (CHNS) in 1991-2015 were classified into three famine exposure groups according to their birth year: unexposed (1963-1966), fetal-exposed (1959-1962) and childhood-exposed (1955-1958). Compared with the unexposed group, the fetal-exposed group had higher levels of body-mass-index (BMI) and waist-circumference (WC), and higher prevalence of overweight and central obesity, whereas the childhood-exposed group had lower levels of the measurements. However, the positive associations of fetal exposure with BMI, WC and prevalence of overweight and central obesity were attenuated by additionally adjusting for age at survey. Stratified analysis showed that the adverse effect of fetal exposure to famine was only observed in subjects at several specific age-groups, and in men living in rural areas and in women living in more severe famine exposed areas ( p for interaction < 0.05). Our results provide evidence for the weak effect of fetal exposure to famine on body measurements in adulthood, and suggest the importance of severity of famine exposure and timing of exposure.

Purpose: To describe recent international trends in antiepileptic drug (AED) use during pregnancy and individual patterns of use including discontinuation and switching., Methods: We studied pregnancies from 2006 to 2016 within linked population-based registers for births and dispensed prescription drugs from Denmark, Finland, Iceland, Norway, Sweden, and New South Wales, Australia and claims data for public and private insurance enrollees in the United States. We examined the prevalence of AED use: the proportion of pregnancies with ≥1 prescription filled from 3 months before pregnancy until birth, and individual patterns of use by trimester., Results: Prevalence of AED use in almost five million pregnancies was 15.3 per 1000 (n = 75 249) and varied from 6.4 in Sweden to 34.5 per 1000 in the publicly-insured US population. AED use increased in all countries in 2006-2012 ranging from an increase of 22% in Australia to 104% in Sweden, and continued to rise or stabilized in the countries in which more recent data were available. Lamotrigine, clonazepam, and valproate were the most commonly used AEDs in the Nordic countries, United States, and Australia, respectively. Among AED users, 31% only filled a prescription in the 3 months before pregnancy. Most filled a prescription in the first trimester (59%) but few filled prescriptions in every trimester (22%)., Conclusions: Use of AEDs in pregnancy rose from 2006 to 2016. Trends and patterns of use of valproate and lamotrigine reflected the safety data available during this period. Many women discontinued AEDs during pregnancy while some switched to another AED., (© 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Overweight and obese pregnant women face higher risk of several critical birth outcomes, including an overall increased risk of congenital abnormalities. Only few studies have focused on associations between maternal overweight and the genital anomalies in boys, cryptorchidism and hypospadias, and results are inconclusive., Methods: We performed a population-based cohort study and assessed the associations between maternal body mass index (BMI) in early pregnancy and occurrence of cryptorchidism and hypospadias. All live-born singleton boys born in Sweden from 1992 to 2012 were included. From the Swedish Patient Register, information on cryptorchidism and hypospadias was available. Data were analysed using Cox proportional hazards regression adjusted for potential confounders. Mediation analyses were performed to estimate how much of the association between BMI and genital anomalies were mediated through obesity-related diseases., Results: Of the 1 055 705 live-born singleton boys born from 1992 to 2012, 6807 (6.4 per 1000) were diagnosed with hypospadias and 16 469 (15.6 per 1000) were diagnosed with cryptorchidism, of which 9768 (9.3 per 1000) underwent corrective surgery for cryptorchidism. We observed dose-response associations between maternal BMI and hypospadias and cryptorchidism. Boys of mothers with BMI ≥40.0 kg/m 2 had the highest adjusted hazard ratios for hypospadias (HR 1.35, 95% confidence interval [CI] 1.04, 1.76) and cryptorchidism (HR 1.25, 95% CI 1.00, 1.58). A substantial proportion of the associations between BMI and the genital anomalies were mediated through preeclampsia., Conclusion: This large register-based study adds to the current literature and indicates that the occurrence of hypospadias and cryptorchidism increase with maternal overweight and obesity severity., (© 2017 John Wiley & Sons Ltd.)

Objectives: The study aimed to investigate the association between maternal body mass index (BMI) in early pregnancy and children's intellectual disability (ID) risk in the absence of chromosomal disorders, neurofibromatosis and tuberous sclerosis, taking adverse birth outcomes, maternal hypertension/diabetes and maternal socioeconomic status into consideration.Methods: We conducted a cohort study of singletons without common genetic defects born in Sweden during 1992-2006, and followed them from birth until 31 December 2014 (n=1 186 836). Cox proportional hazards models were used to analyse the association between maternal BMI in early pregnancy and the risk of offspring's ID.Results: The risk of ID was higher in children born to mothers who were underweight (HR=1.21, 95% CI=1.07 to 1.36), overweight (HR=1.28, 95% CI=1.21 to 1.34) or had obesity class I (HR=1.63, 95% CI=1.53 to 1.74), obesity class II (HR=2.08, 95% CI=1.88 to 2.30) and obesity class III (HR=2.31, 95% CI=1.46 to 3.65) than in children born to normal weight mothers. Results remained consistent after excluding children with adverse birth outcome or born to mothers with gestational hypertension/diabetes. Analysis stratified by maternal education and annual household income showed that the association between maternal underweight and children's ID risk was attenuated among children of mothers with tertiary education or with high income.Conclusions: Our findings suggest that maternal underweight or overweight/obesity in early pregnancy was associated with the development of ID in their offspring. This association was independent of the effect of adverse birth outcomes and maternal hypertension/diabetes. High socioeconomic status may attenuate the risk of ID among children of underweight mothers. This study highlights the importance of improving health education before conception to reduce children's ID risk. [ABSTRACT FROM AUTHOR]

Background: Socioeconomic disparities in infant mortality have persisted for decades in high-income countries and may have become stronger in some populations. Therefore, new understandings of the mechanisms that underlie socioeconomic differences in infant deaths are essential for creating and implementing health initiatives to reduce these deaths. We aimed to explore whether and the extent to which preterm birth (PTB) and small for gestational age (SGA) at birth mediate the association between maternal education and infant mortality.Methods and Findings: We developed a population-based cohort study to include all 1,994,618 live singletons born in Denmark in 1981-2015. Infants were followed from birth until death, emigration, or the day before the first birthday, whichever came first. Maternal education at childbirth was categorized as low, medium, or high. An inverse probability weighting of marginal structural models was used to estimate the controlled direct effect (CDE) of maternal education on offspring infant mortality, further split into neonatal (0-27 days) and postneonatal (28-364 days) deaths, and portion eliminated (PE) by eliminating mediation by PTB and SGA. The proportion eliminated by eliminating mediation by PTB and SGA was reported if the mortality rate ratios (MRRs) of CDE and PE were in the same direction. The MRRs between maternal education and infant mortality were 1.63 (95% CI 1.48-1.80, P < 0.001) and 1.19 (95% CI 1.08-1.31, P < 0.001) for low and medium versus high education, respectively. The estimated proportions of these total associations eliminated by reducing PTB and SGA together were 55% (MRRPE = 1.27, 95% CI 1.15-1.40, P < 0.001) for low and 60% (MRRPE = 1.11, 95% CI 1.01-1.22, P = 0.037) for medium versus high education. The proportions eliminated by eliminating PTB and SGA separately were, respectively, 46% and 11% for low education (versus high education) and 48% and 13% for medium education (versus high education). PTB and SGA together contributed more to the association of maternal educational disparities with neonatal mortality (proportion eliminated: 75%-81%) than with postneonatal mortality (proportion eliminated: 21%-23%). Limitations of the study include the untestable assumption of no unmeasured confounders for the causal mediation analysis, and the limited generalizability of the findings to other countries with varying disparities in access and quality of perinatal healthcare.Conclusions: PTB and SGA may play substantial roles in the relationship between low maternal education and infant mortality, especially for neonatal mortality. The mediating role of PTB appeared to be much stronger than that of SGA. Public health strategies aimed at reducing neonatal mortality in high-income countries may need to address socially related prenatal risk factors of PTB and impaired fetal growth. The substantial association of maternal education with postneonatal mortality not accounted for by PTB or SGA could reflect unaddressed educational disparities in infant care or other factors. [ABSTRACT FROM AUTHOR]

Background: Cerebral palsy (CP) is the most common physical developmental disability in childhood with a prevalence of 2 to 3 per 1000 live births. β2-adrenoreceptor agonist (β2AA) are widely used for the treatment of asthma. Maternal use of β2AAs may increase the risk of adverse neuro-psychiatric health outcomes in the offspring. No study, however, has evaluated the effect of prenatal exposure to β2AAs on the risk of CP. Objective: To examine the association between prenatal exposure to β2AAs and the risk of childhood cerebral palsy. Methods: This population-based cohort study included all live singleton births in Denmark from January 1, 1997 to December 31, 2003. The information on outpatient prescriptions of β2AAs was extracted from Danish National Prescription Registry. Children born to mothers who used β2AAs from 30 days before pregnancy until delivery were categorized as the exposed. To differentiate the effect of β2AAs from the underlying indications, the exposure window was further extended to 2 years before pregnancy and the exposed groups were re-defined to represent different periods of exposure to maternal use of β2AAs (use only before pregnancy, use only during pregnancy, and use both before and during pregnancy). Cases of CP were identified from the Danish Cerebral Palsy Register. Logistic regression was used to estimate incidence odds ratio (OR) of CP. Results: Among all the 442,278 singletons, 19,616 (4.44%) were exposed to β2AAs in utero (from 30 days before pregnancy until delivery). The risk of childhood CP was 0.21% in exposed and 0.19% in unexposed group, yielding an adjusted OR (aOR) 1.12 (95% confidence interval (CI): 0.82, 1.53). When extending the exposure time window to 2 years prior to pregnancy, no overall significant association was observed regardless of the exposure period. However, an increased risk of CP (aOR = 1.41, 95%CI: 0.92, 2.18) for maternal β2AAs use during pregnancy was observed in female offspring, especially in those born at term (aOR = 1.65, 95%CI: 1.02, 2.67). This increase was mainly attributed to an increased risk in those born to mothers who used β2AAs both before and during pregnancy (aOR = 1.81, 95%CI: 0.99, 3.33). Conclusions: We observed an association between maternal β2AAs use during pregnancy and an increased risk of CP in female offspring, but we could not rule out confounding by the underlying indications for β2AAs. [ABSTRACT FROM AUTHOR]