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Antibiotic use during pregnancy and childhood overweight: A population-based nationwide cohort study.

ABSTRACT: Studies in mice suggest that early life represents a critical time window, where antibiotics may exert profound and lasting effects on the gut microbiota and metabolism. We aimed to test the hypothesis that prenatal antibiotic exposure is associated with increased risk of childhood overweight in a population-based cohort study. We linked 43,365 mother-child dyads from a nationwide cohort of pregnant women and their offspring to the Danish National Prescription Registry. Linear and logistic regression models were used to examine associations between prenatal exposure to antibiotics and BMI z-score and overweight (including obesity) at age seven and 11 years. Prenatal antibiotic exposure and childhood overweight were both associated with high pre-pregnancy BMI, maternal diabetes, multi-parity, smoking, low socioeconomic status, high paternal BMI, and short duration of breastfeeding. After adjustment for confounders, no associations were observed between prenatal antibiotic exposure and odds of overweight at age seven and 11 years. Whereas no association was observed between broad-spectrum antibiotics and overweight at age 11 years, exposure to broad-spectrum antibiotics was associated with higher odds of overweight at age seven years with an odds ratio of 1.27 (95% CI, 1.05-1.53) for ampicillin and an odds ratio of 1.56 (95% CI, 1.23-1.97) for amoxicillin. As we did not account for underlying infections, the observed associations with early childhood overweight could be explained by confounding by indication. In conclusion, our population-based study suggests that prenatal exposure to narrow-spectrum antibiotics is not associated with overweight in offspring. Exposure to some broad-spectrum antibiotics may increase the odds of overweight in early childhood, but the association does not persist in later childhood.

SUBMITTER: Jess T

PROVIDER: S-EPMC6687733 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Antibiotic use during pregnancy and childhood overweight: A population-based nationwide cohort study.

Jess Tine T Morgen Camilla S CS Harpsøe Maria C MC Sørensen Thorkild I A TIA Ajslev Teresa A TA Antvorskov Julie C JC Allin Kristine H KH

Scientific reports 20190808 1

Studies in mice suggest that early life represents a critical time window, where antibiotics may exert profound and lasting effects on the gut microbiota and metabolism. We aimed to test the hypothesis that prenatal antibiotic exposure is associated with increased risk of childhood overweight in a population-based cohort study. We linked 43,365 mother-child dyads from a nationwide cohort of pregnant women and their offspring to the Danish National Prescription Registry. Linear and logistic regre ...[more]

PMID: 31395930

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Project description:Objective To investigate the association between in utero exposure to antidepressants and risk of psychiatric disorders.Design Population based cohort study.Setting Danish national registers.Participants 905 383 liveborn singletons born during 1998-2012 in Denmark and followed from birth until July 2014, death, emigration, or date of first psychiatric diagnosis, whichever came first. The children were followed for a maximum of 16.5 years and contributed 8.1×106 person years at risk.Exposures for observational studies Children were categorised into four groups according to maternal antidepressant use within two years before and during pregnancy: unexposed, antidepressant discontinuation (use before but not during pregnancy), antidepressant continuation (use both before and during pregnancy), and new user (use only during pregnancy).Main outcome measure First psychiatric diagnosis in children, defined as first day of inpatient or outpatient treatment for psychiatric disorders. Hazard ratios of psychiatric disorders were estimated using Cox regression models.Results Overall, psychiatric disorders were diagnosed in 32 400 children. The adjusted 15 year cumulative incidence of psychiatric disorders was 8.0% (95% confidence interval 7.9% to 8.2%) in the unexposed group, 11.5% (10.3% to 12.9%) in the antidepressant discontinuation group, 13.6% (11.3% to 16.3%) in the continuation group, and 14.5% (10.5% to 19.8%) in the new user group. The antidepressant continuation group had an increased risk of psychiatric disorders (hazard ratio 1.27, 1.17 to 1.38), compared with the discontinuation group.Conclusions In utero exposure to antidepressants was associated with increased risk of psychiatric disorders. The association may be attributable to the severity of underlying maternal disorders in combination with antidepressant exposure in utero. The findings suggest that focusing solely on a single psychiatric disorder among offspring in studies of in utero antidepressant exposure may be too restrictive.

Project description:BackgroundMaternal hypertensive disorders during pregnancy (HDP) have been suggested to contribute to the development of offspring cardiovascular disease later in life, but empirical evidence remains inconsistent. This study was aimed to assess the association of maternal overall and type-specific HDPs with diabetes in offspring from childhood to early adulthood.MethodsUsing Danish national health registers, a total of 2,448,753 individuals born in Denmark from 1978 to 2018 were included in this study. Maternal HDP included chronic hypertension, gestational hypertension, and preeclampsia. The outcome of interest was diabetes in offspring (including type 1, type 2, and gestational diabetes). The follow-up of offspring started at birth and ended at the first diagnosis of diabetes, emigration from Denmark, death, or time end on 31 December 2018, whichever came first. Cox proportional hazards regression was used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) of the association between maternal HDP and diabetes (including type 1, type 2, and gestational diabetes) in offspring from birth to young adulthood (up to 41 years), with the offspring's age as the time scale.ResultsDuring a follow-up of up to 41 (median: 19.3) years, 1247 offspring born to mothers with HDP and 23,645 offspring born to mothers without HDP were diagnosed with diabetes. Compared with offspring born to mothers without HDP, those born to mothers with HDP had an increased risk for overall diabetes (HR=1.27, 95% CI=1.20-1.34), as well as for type 2 diabetes (HR=1.57, 95% CI=1.38-1.78) and gestational diabetes (HR=1.37, 95% CI=1.25-1.49). We did not observe obvious increased risk for type 1 diabetes (HR=1.08, 95% CI=0.98-1.18). Offspring of mothers with gestational hypertension (HR=1.37, 95% CI=1.00-1.88) or preeclampsia (HR=1.62, 95% CI=1.41-1.87) had higher risks of type 2 diabetes. The strongest association was observed for severe preeclampsia, with a 2-fold risk of type 2 diabetes (HR=2.00, 95% CI=1.42-2.82). The association between maternal HDP and type 1 diabetes did not reach statistical significance, except for maternal gestational hypertension (HR=1.41, 95%CI=1.17-1.71). In addition, we found that offspring born to mothers with any subtypes of maternal HDP had higher risk of gestational diabetes, and the corresponding HRs (95%CIs) for chronic hypertension, gestational hypertension, and preeclampsia were 1.60 (1.06-2.41), 1.29 (1.04-1.59), and 1.38 (1.24-1.53), respectively. We also observed stronger associations among offspring of mothers with HDP and comorbid diabetes (HR=4.64, 95%CI=3.85-5.60) than offspring of mothers with HDP or diabetes alone.ConclusionsOffspring of mothers with HDP, especially mothers with comorbid diabetes, had an increased risk of diabetes later in their life. Our findings suggest that timely and effective prevention of HDP in women of childbearing age should be taken into consideration as diabetes prevention and control strategies for their generations.

Project description:BackgroundPolycystic Ovary Syndrome (PCOS) is an endocrine disorder that affects women in reproductive age and represents an unfavourable risk factor for several pregnancy and perinatal outcomes. Despite, no guidelines or pharmaceutical strategies for treating PCOS during pregnancy are available. The aim of this study is to determine the association between polycystic ovary syndrome with or without metformin and the pregnancy, perinatal outcomes as well as the risk of obesity in children born to these mothers.MethodsIn this nationwide population-based cohort study based in Swedish population, all singleton births (n = 1,016,805) from 686,847 women since 2006 up to 2016 were included. Multivariable logistic and Cox regression modelling with odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals were used to study the association between the exposure of maternal PCOS, metformin during pregnancy (or the combination of both) and: 1) Pregnancy outcomes: preeclampsia, gestational diabetes, caesarean section, and acute caesarean section, 2) Perinatal outcomes: preterm birth, stillbirth, low birth weight, macrosomia, Apgar < 7 at 5 min, small for gestational age and large for gestational age, and 3) Childhood Obesity.ResultsPCOS in women without metformin use during pregnancy was associated with higher risks of preeclampsia (OR = 1.09, 1.02-1.17), gestational diabetes (OR = 1.71, 1.53-1.91) and caesarean section (OR = 1.08, 1.04-1.12), preterm birth (OR = 1.30, 1.23-1.38), low birth weight (OR = 1.29, 1.20-1.38), low Apgar scores (OR = 1.17, 1.05-1.31) and large for gestational age (OR = 1.11, 1.03-1.20). Metformin use during pregnancy (in women without PCOS) was associated with a 29% lower risks of preeclampsia (OR = 0.71, 0.51-0.97), macrosomia and large for gestational age. Obesity was more common among children born to mothers with PCOS without metformin (HR = 1.61, 1.44-1.81); and those with metformin without PCOS (HR = 1.67, 1.05-2.65). PCOS with metformin was not associated with any adverse outcome.ConclusionPCOS was associated with increased risks of adverse pregnancy and perinatal outcomes and childhood obesity. Metformin appears to reduce these risks in mothers with polycystic ovary syndrome and their children; but may increase the risk of childhood-obesity in children form women without PCOS.

Project description:PurposeWe described the medication use during pregnancy in the French population using the French Pregnancy Cohort (FPC).MethodsThe FPC was built with the sampling of all pregnant women included in the French Echantillon généraliste des bénéficiaires (EGB), which is a 1/97th representative sample of the population covered by the French health insurance. The EGB includes anonymized information on the socio-demographic and medical characteristics of beneficiaries, and the health care services they have received such as diagnoses and procedure codes as well as data on filled reimbursed medication; EGB also includes data on hospital stays in all public and private French health facilities. Each filled prescription record contains information on drug brand and generic names, date of prescription and date of dispensing, quantity dispensed, mode of administration, duration of prescription, dosage, and prescribing physician specialty. FPC includes data on all pregnancies of women in the EGB (2010-2013). Date of entry in the FPC is the first day of pregnancy regardless of pregnancy outcome (spontaneous abortions or planned abortions (with or without medical reasons), deliveries), and data on women are collected retrospectively for a period of one year before pregnancy, and prospectively during pregnancy, and up to one year after delivery. The prevalence of prescribed medications before, during and after pregnancy was compared; comparison was also done between trimesters. Pregnancy outcomes are described and include spontaneous and planned abortions, livebirths, and stillbirths.ResultsFPC includes data on 36,065 pregnancies. Among them, 27,253 (75.6%) resulted in a delivery including 201 stillbirths (0.7%). The total number of spontaneous abortions was 6,718 (18.6%), and planned abortions 2,094 (5.8%). The prevalence of filled medication use was 91.1%, 89.9%, and 95.6% before, during and after pregnancy, respectively. Although there was a statistically significant decrease in the proportion of use once the pregnancy was diagnosed (first trimester exposure, 76.4% vs. exposure in the year prior to pregnancy, 91.1% (p < .01)), post-pregnancy medication use was above the pre-pregnancy level (95.6%). Maternal depression was the most prevalent comorbidity during pregnancy (20%), and post-partum depression was higher in those who delivered a stillborn infant (38.8%) as well as in those with a spontaneous (19.5%) or planned abortion (22.4%) compared to those with a liveborn (12.0%).ConclusionFPC is an excellent tool for the study of the risk and benefit of drug use during the perinatal period. FPC has the advantage of including a representative sample of French pregnant women, and study medications only available in France in addition to others available worldwide.

Dataset Information

Antibiotic use during pregnancy and childhood overweight: A population-based nationwide cohort study.

Publications

Antibiotic use during pregnancy and childhood overweight: A population-based nationwide cohort study.

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