Antibiotic treatment during early childhood and risk of type 1 diabetes in children: A national birth cohort study.

OBJECTIVE/BACKGROUND: Antibiotics are widely used during childhood infections and influence the composition of the microbiota, which is established during the first years of life. Evidence from animal models of type 1 diabetes shows that antibiotics might accelerate disease progression, and altered intestinal microbiota has been reported in association with type 1 diabetes in humans. We aimed to test the hypothesis that early exposure to antibiotics (0-24 months of age) was associated with an increased risk of childhood type 1 diabetes development. METHODS: We studied 75 615 mother-child dyads from the Danish National Birth Cohort. Information on the use of antibiotics during early childhood and type 1 diabetes development in childhood was available for all children via linkage to the Danish National Prescription Registry and the Danish National Patient Register, respectively. The mean follow-up time was 14.3 years (range 11.5 to 18.4 years, SD 1.4). RESULTS: After adjustment for confounders, we found no association between antibiotic exposure and risk of type 1 diabetes (HR 1.26, 95% CI 0.89-1.79). The number of antibiotic courses during early childhood was not associated with type 1 diabetes development when analyzing for one (HR 1.31, 95% CI 0.87-1.99), two (HR 0.99, 95% CI 0.61-1.63), or 3 or more (HR 1.42, 95% CI 0.95-2.11) courses. Furthermore, no specific types of antibiotics (penicillins/beta-lactam antibacterials, sulfonamide/trimethroprim, or macrolides/lincosamides/streptogramins) were associated with increased risk of type 1 diabetes. CONCLUSION: Our nationwide cohort study suggests that postnatal exposure to antibiotics does not influence the development of childhood type 1 diabetes.

Maternal smoking during pregnancy and offspring overweight: is there a dose-response relationship? An individual patient data meta-analysis.

BACKGROUND/OBJECTIVES: A number of meta-analyses suggest an association between any maternal smoking in pregnancy and offspring overweight obesity. Whether there is a dose-response relationship across number of cigarettes and whether this differs by sex remains unclear. SUBJECT/METHODS: Studies reporting number of cigarettes smoked during pregnancy and offspring BMI published up to May 2015 were searched. An individual patient data meta-analysis of association between the number of cigarettes smoked during pregnancy and offspring overweight (defined according to the International Obesity Task Force reference) was computed using a generalized additive mixed model with non-linear effects and adjustment for confounders (maternal weight status, breastfeeding, and maternal education) and stratification for sex. RESULTS: Of 26 identified studies, 16 authors provided data on a total of 238,340 mother-child-pairs. A linear positive association was observed between the number of cigarettes smoked and offspring overweight for up to 15 cigarettes per day with an OR increase per cigarette of 1.03, 95% CI = [1.02-1.03]. The OR flattened with higher cigarette use. Associations were similar in males and females. Sensitivity analyses supported these results. CONCLUSIONS: A linear dose-response relationship of maternal smoking was observed in the range of 1-15 cigarettes per day equally in boys and girls with no further risk increase for doses above 15 cigarettes.

Parental socioeconomic position and development of overweight in adolescence: longitudinal study of Danish adolescents.

BACKGROUND: An inverse social gradient in overweight among adolescents has been shown in developed countries, but few studies have examined whether weight gain and the development of overweight differs among adolescents from different socioeconomic groups in a longitudinal study. The objective was to identify the possible association between parental socioeconomic position, weight change and the risk of developing overweight among adolescents between the ages 15 to 21. METHODS: Prospective cohort study conducted in Denmark with baseline examination in 1996 and follow-up questionnaire in 2003 with a mean follow-up time of 6.4 years. A sample of 1,656 adolescents participated in both baseline (mean age 14.8) and follow-up (mean age 21.3). Of these, 1,402 had a body mass index (BMI = weight/height2kg/m2) corresponding to a value below 25 at baseline when adjusted for age and gender according to guidelines from International Obesity Taskforce, and were at risk of developing overweight during the study period. The exposure was parental occupational status. The main outcome measures were change in BMI and development of overweight (from BMI < 25 to BMI > = 25). RESULTS: Average BMI increased from 21.3 to 22.7 for girls and from 20.6 to 23.6 in boys during follow-up. An inverse social gradient in overweight was seen for girls at baseline and follow-up and for boys at follow-up. In the full population there was a tendency to an inverse social gradient in the overall increase in BMI for girls, but not for boys. A total of 13.4% developed overweight during the follow-up period. Girls of lower parental socioeconomic position had a higher risk of developing overweight (OR's between 4.72; CI 1.31 to 17.04 and 2.03; CI 1.10-3.74) when compared to girls of high parental socioeconomic position. A tendency for an inverse social gradient in the development of overweight for boys was seen, but it did not meet the significance criteria CONCLUSIONS: The levels of overweight and obesity among adolescents are high and continue to rise. Results from this study suggest that the inverse social gradient in overweight becomes steeper for girls and emerges for boys in late adolescence (age span 15 to 21 years). Late adolescence seems to be an important window of opportunity in reducing the social inequality in overweight among Danish adolescents.

Trends in social inequality in overweight and obesity among adolescents in Denmark 1998-2018.

OBJECTIVES: The aim was to analyze trends in overweight and obesity in relation to socioeconomic position among Danish adolescents in the 20-year period 1998-2018. METHODS: The study used data on self-reported height and weight and parents' occupational social class (OSC) from 11-, 13- and 15-year-old schoolchildren in 1998, 2002, 2006, 2010, 2014 and 2018, n = 22,177. The analyses included absolute social inequality in overweight/obesity (prevalence difference between low and high OSC) and relative social inequality (OR for overweight/obesity). RESULTS: In the total sample, the prevalence of overweight and obesity was 9.7% and 1.4%, respectively, with significantly higher prevalence in low than high OSC. There were significantly increasing trends in both overweight and obesity 1998-2018 in low OSC and no significant increase in high OSC. The OR for overweight was 1.59 (1.42-1.74) in middle and 2.16 (1.89-2.46) in low OSC, OR for obesity 1.74 (1.29-2.34) in middle and 2.97 (2.15-4.11) in low OSC. Associations were not modified by survey year. CONCLUSIONS: There was a persistent absolute and relative social inequality in overweight and obesity 1998-2018 among Danish adolescents.

Association between smoking and the risk of heavy drinking among young women: a prospective study.

AIM: To address the association between smoking habits and the risk of later heavy drinking among young women. METHODS: Repeated assessments of alcohol and smoking habits were obtained in 1991-93 and 1999-2000 in a Danish representative cohort in Copenhagen. A total of 6369 non- to moderate-drinking Danish women, aged 20-29 years at baseline, attended a follow-up examination and were included in the study. The risk of becoming a heavy drinker (more than 14 drinks per week) 8 years after enrolment was analyzed by means of logistic regression. RESULTS: A total of 177 women became heavy drinkers during follow-up. Daily smoking at baseline was associated with an increased risk of becoming a heavy drinker 8 years later. Relative to nonsmokers, the adjusted odds ratios (OR) for becoming a heavy drinker associated with smoking 1-14, 15-24, or more than 24 cigarettes per day were 1.6 (95% confidence intervals (CI) 1.1-2.4), 1.7 (CI 1.1-2.6), and 2.3 (CI 0.9-5.9), respectively. Age at sexual debut modified the effect of smoking, and women with a debut before the age of 15 years had an adjusted OR of 2.9 (CI 1.1-3.9) compared to never-smokers while there seemed to be no effect among women with a sexual debut after the age of 18. In addition, relative to nondrinkers, all of the moderate (1-5 units per week), medium (6-10 units), and large (10-14 units) alcohol consumption at baseline were associated independently with becoming a heavy drinker 8 years later. CONCLUSIONS: This study suggests that smoking is an important predictor of later heavy drinking among young women and that this relatively elevated risk is most pronounced among women with an early sexual debut.

Breastfeeding and complementary feeding in relation to body mass index and overweight at ages 7 and 11 y: a path analysis within the Danish National Birth Cohort.

Background: Infant feeding may play an important role in the development of childhood overweight and obesity. Objective: The objective of this study was to examine whether duration of breastfeeding (BF), timing of introduction of complementary food, and protein intake at age 18 mo are associated with body mass index [BMI (measured in kg/m2)] and overweight at ages 7 and 11 y, independent of BMI during infancy. Design: Children participating in the Danish National Birth Cohort were followed up at ages 7 and 11 y. Information on infant feeding, protein intake at age 18 mo, Ponderal Index at birth, child BMI (at ages 5 mo, 12 mo, 7 y, and 11 y), and several parental factors was available. Path analysis was used to assess the direct and indirect effects of infant feeding on BMI z scores (BMIz) at ages 7 (n = 36,481) and 11 y (n = 22,047). Logistic regression analyses were used to examine associations with overweight. Results: Duration of BF was not associated with childhood BMIz at ages 7 and 11 y. Earlier introduction of complementary food (<4 mo old) was not associated with BMIz at age 7 y, but with a 0.069 (95% CI: 0.021, 0.117, P = 0.005) higher BMIz at age 11 y and increased risk of overweight at age 11 y (OR 1.44; 95% CI: 1.04, 2.00; P = 0.03). Protein intake from dairy products (per 5 g/d) was associated with higher BMIz only at age 7 y (OR: 0.012; 95% CI: 0.003, 0.021; P = 0.007). Protein intake from meat and fish (per 2 g/d) was associated with a 0.010 (95% CI: 0.004, 0.017; P = 0.003) higher BMIz at age 7 y, a 0.013 (95% CI: 0.005, 0.020; P = 0.002) higher BMIz at age 11 y and increased odds of overweight at age 7 y (OR: 1.07; 95% CI: 1.03, 1.10; P < 0.001), but not at age 11 y. Conclusions: Intake of protein from meat and fish at age 18 mo was associated with higher BMIz and risk of overweight in childhood. However, the effect sizes were small. Early introduction of complementary food may be associated with child BMIz and child overweight. This study was registered at www.clinicaltrials.gov as NCT03334760.

Socioeconomic disparities in birth weight and body mass index during infancy through age 7†years: a study within the Danish National Birth Cohort.

BACKGROUND: Socioeconomic inequalities in birth weight and in body mass index (BMI) later in childhood are in opposite directions, which raises questions about when during childhood the change in direction happens. We examined how maternal and paternal education and household income were associated with birthweight z-scores and with BMI z-scores at age 5 and 12 months and 7 years, and we examined the socioeconomic differences in the tracking of these z-scores across infancy and childhood. METHODS: The associations were studied in a cohort of children in the Danish National Birth Cohort, single born between 1997 and 2003, for whom information on body size from at least 1 of 4 time points (n=85 062) was recorded. We examined the associations using linear mixed-effects modelling. RESULTS: Children from families with a low maternal and paternal educational level changed their body size z-scores upwards between birth and age 7 years. At age 5 and 12 months, there were no educational gradient. A low maternal educational level was associated with lower birth weight for gestational age z-scores at birth for boys (-0.199; 95% CI -0.230 to -0.169) and girls (-0.198; 95% CI -0.229 to -0.167) and higher BMI z-scores at age 7 for boys (0.198; 95% CI 0.154 to 0.242) and girls (0.218; 95% CI 0.173 to 0.264). There was not a similarly clear pattern in the tracking between different household income groups. However, a low household income level was associated with higher z-scores of both birth weight and BMI at age 7 years, but with a much weaker gradient at 5 and 12 months. CONCLUSIONS: The educational gradient shifts from positive with birth weight, to none during infancy to inverse with BMI at age 7 years. In contrast, the income gradient was positive at birth and at 7 years and much weaker during infancy.

Comparison of associations of maternal peri-pregnancy and paternal anthropometrics with child anthropometrics from birth through age 7 y assessed in the Danish National Birth Cohort.

BACKGROUND: Maternal prepregnancy adiposity may influence child adiposity beyond the transmitted genetic effects, which, if true, may accelerate the obesity epidemic, but the evidence for this mechanism is inconsistent. OBJECTIVE: The aim was to assess whether the associations of maternal body mass index (BMI) with child anthropometric measurements from birth through infancy and at 7 y of age exceed those of paternal associations. DESIGN: In the Danish National Birth Cohort, information on parental and child anthropometric measures is available for 30,655 trio families from maternal interviews during pregnancy and the postpartum period and from a 7-y follow-up. By using multiple linear and logistic regression models of child SD (z) scores of weight and BMI at birth, 5 mo, 12 mo, and 7 y of age, and of child overweight at age 7 y, we compared associations with maternal prepregnancy and postpartum BMI z scores and with paternal BMI z scores. RESULTS: When comparing maternal-child and paternal-child BMI z score associations, the strongest associations were observed with mothers' BMI at birth [maternal and paternal BMI z scores: 0.143 (95% CI: 0.130, 0.155) and 0.017 (95% CI: 0.005, 0.029), respectively] and throughout infancy, but the relative difference in the associations declined by child age [for BMI z score at child age 7 y per maternal and paternal BMI z scores: 0.208 (95% CI: 0.196, 0.220) and 0.154 (95% CI: 0.143, 0.166), respectively]. At 7 y of age, ORs of child overweight were 2.30 (95% CI: 1.99, 2.67) by maternal overweight and 1.96 (95% CI: 1.74, 2.21) by paternal overweight. There were no differences between the results based on maternal BMI before and after pregnancy or on child's weight adjusted for length or height. CONCLUSIONS: The associations of child weight and BMI with maternal BMI were stronger than with paternal BMI. The differences between the associations were strong at birth but declined with child aging.

Obesity: global trends in the prevalence of overweight and obesity.

A new report provides compelling evidence of the high prevalence of overweight and obesity throughout the world. The prevalence has increased since 1980, but at different rates across ages, times and locations. Studies exploring the causes of these differences could aid development of effective prevention strategies.

Socioeconomic position and the risk of spontaneous abortion: a study within the Danish National Birth Cohort.

OBJECTIVES: To investigate the relationship between different indicators of socioeconomic position and the risk of spontaneous abortion. DESIGN: Cohort study. SETTING: 1996-2002, Denmark. PARTICIPANTS: All first time participants, a total of 89 829 pregnant women, enrolled in the Danish National Birth Cohort were included in the present study. Overall, 4062 pregnancies ended in spontaneous abortion. Information on education, income and labour market attachment in the year before pregnancy was drawn from national registers. MAIN OUTCOME MEASURE: Spontaneous abortion, that is, fetal death within the first 22 weeks of pregnancy, was the outcome of interest. The authors estimated HRs of spontaneous abortion using Cox regression analysis with gestational age as the underlying time scale. RESULTS: Women with <10 years of education had an elevated risk of spontaneous abortion when compared with women with >12 years of education (HR 1.19 (95% CI 1.05 to 1.34)). The HR estimates for the four lowest income quintiles were all increased (HRs between 1.09 and 1.15) as compared with the upper quintile but did not differ considerably from each other. In general, no statistically significant association was found between labour market attachment and the risk of spontaneous abortion; however, the group of women on disability pension had an increased HR of spontaneous abortion when compared with women who were employed (HR 1.32 (95% CI 0.82 to 2.13)). CONCLUSIONS: Educational level and income were inversely associated with the risk of spontaneous abortion. As these factors most likely are non-causally related to spontaneous abortion, the findings indicate that factors related to social position, probably of the environmental and behavioural type, may affect spontaneous abortion risk. The study highlights the need for studies addressing such exposures in order to prevent spontaneous abortions.

Socioeconomic position and the risk of preterm birth--a study within the Danish National Birth Cohort.

BACKGROUND: Low socioeconomic position is generally associated with increased risk of preterm birth, but it remains unclear whether the inequality depends on the socioeconomic measure used, if the associations differ according to the degree of prematurity, and how individual level risk factors mediate the association. METHODS: The hazard ratios (HR) of preterm birth associated with five different measures of socioeconomic position and three degrees of preterm birth were analysed in a dataset of 75 890 singleton pregnancies (1996-2002) from the Danish National Birth Cohort. This, and the mediating role of selected individual level risk factors (smoking, alcohol consumption, binge drinking, pre-pregnancy body mass index, gestational weight gain) were estimated, using Cox regression analyses. RESULTS: Mothers with <10 years of education had an elevated risk of preterm birth compared with mothers with >12 years of education and the association interacted with parity, while income and occupation affected the risk to a lesser degree. The adjusted HR for less educated nulliparous and parous women were 1.22 (95% CI 1.04-1.42) and 1.56 (95% CI 1.31-1.87), respectively, compared with women with >12 years of education. For parous women with <10 years of education inclusion of smoking in the model decreased the HR of preterm birth to 1.43 (95% CI 1.19-1.72). CONCLUSIONS: Maternal educational level was the strongest predictor of preterm birth among five socioeconomic measures and the gradient did not differ significantly according to the degree of preterm birth. For parous women smoking explained some of the educational gradient but in general the selected risk factors only reduced the relative educational gradient in preterm birth marginally.