Pernille Stemann Larsen

Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research

BACKGROUND During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. METHODS European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. RESULTS In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. CONCLUSION This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.

Maternal complications in pregnancy and wheezing in early childhood: a pooled analysis of 14 birth cohorts

BACKGROUND Evidence on the effect of maternal complications in pregnancy on wheezing in offspring is still insufficient. METHODS A pooled analysis was performed on individual participant data from fourteen European birth cohorts to assess the relationship between several maternal pregnancy complications and wheezing symptoms in the offspring. Exposures of interest included hypertension and preeclampsia, diabetes, as well as pre-pregnancy overweight (body mass index between 25 and 29.9) and obesity (body mass index ≥ 30) compared with normal weight (body mass index between 18.5 and 24.9). Outcomes included both ever and recurrent wheezing from birth up to 12-24 months of age. Cohort-specific crude and adjusted risk ratios (RR) were calculated using log-binomial regression models and then pooled using a random effects model. RESULTS The study included 85509 subjects. Cohort-specific prevalence of ever wheezing varied from 20.0% to 47.3%, and of recurrent wheezing from 3.0% to 14.3%. Adjusted pooled RR for ever and recurrent wheezing were: 1.02 (95% CI: 0.98-1.06) and 1.20 (95% CI: 0.98-1.47) for hypertensive disorders; 1.09 (95% CI: 1.01-1.18) and 1.23 (95% CI: 1.07-1.43) for preeclampsia; 1.04 (95% CI: 0.97-1.13) and 1.24 (95% CI: 0.86-1.79) for diabetes; 1.08 (95% CI: 1.05-1.11) and 1.19 (95% CI: 1.12-1.26) for overweight; 1.12 (95% CI: 1.08-1.17) and 1.16 (95% CI: 0.97-1.39) for obesity. No heterogeneity was found in RR estimates among the cohorts, except for diabetes and recurrent wheezing (P=0.027). CONCLUSIONS Preeclampsia, maternal pre-pregnancy overweight and obesity are associated with an increase risk of wheezing in the offspring.

Occupational lifting and pelvic pain during pregnancy: a study within the Danish National Birth Cohort

OBJECTIVES Pelvic pain during pregnancy is a common ailment, and the disease is a major cause of sickness absence during pregnancy. It is plausible that occupational lifting may be a risk factor of pelvic pain during pregnancy, but no previous studies have examined this specific exposure. The aim of this study was to examine the association between occupational lifting and pelvic pain during pregnancy. METHODS The study comprised 50 143 pregnant women, enrolled in the Danish National Birth Cohort in the period from 1996-2002. During pregnancy, the women provided information on occupational lifting (weight load and daily frequency), and six months post partum on pelvic pain. Adjusted odds ratios for pelvic pain during pregnancy according to occupational lifting were calculated by logistic regression. RESULTS Any self-reported occupational lifting (>1 time/day and loads weighing >10 kg) was associated with an increased risk of pelvic pain during pregnancy as compared to no such lifting. A confounder-adjusted exposure-response relation was observed between self-reported total loads lifted and pelvic pain during pregnancy. Daily lifting of both medium (11-20 kg) and heavy loads (>20 kg) were associated with increased risk, and the highest risk was observed among women who lifted heavy loads independent of exposure to medium loads. CONCLUSION Occupational lifting may increase the risk of pelvic pain during pregnancy.

Occupational lifting during pregnancy and risk of fetal death in a large national cohort study

OBJECTIVE The aim of the present study was to examine the association between occupational lifting and the risk of fetal death according to gestational age. METHODS We used data from the Danish National Birth Cohort (1996-2002). Among 71,500 occupationally active women, 2886 experienced a fetal death. Information on lifting and relevant covariates was collected in interviews around week 16 of pregnancy. The majority of fetal losses (N=2032) happened before the scheduled interview, and exposure data were collected retrospectively from these women. We analyzed early miscarriage (≤12 weeks), late miscarriage (13-21 weeks), and stillbirth (≥22 weeks), using Cox-regression models with gestational age as the underlying time variable. RESULTS The adjusted early miscarriage risk increased with frequency of daily lifts and total burden lifted per day. For example, the hazard ratio was 1.38 [95% confidence interval (95% CI) 1.10-1.74] for a total weight load per day of 101-200 kg and 2.02 (95% CI 1.23-3.33) for a daily load >1000 kg as compared to non-lifters (P for trend <0.0001). Late miscarriage was associated with total daily weight load (P for trend=0.0073) but not with number of lifts per day. There was no association between occupational lifting and stillbirth. CONCLUSIONS In the present study, the risk of miscarriage increased with the number of lifts and total burden lifted per day at work. There may be a case for advising pregnant women against heavy lifting in particular during early pregnancy.

Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review

Learning ObjectivesAfter participating in this activity, learners should be better able to:• Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. AbstractEating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child’s weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating behaviors, mental and physical health, family interactions, and child growth patterns.

Occupational lifting during pregnancy and child’s birth size in a large cohort study

OBJECTIVES It has been suggested that the handling of heavy loads during pregnancy is associated with impaired fetal growth. We examined the association between quantity and frequency of maternal occupational lifting and the childs size at birth, measured by weight, length, ponderal index, small-for-gestational-age (SGA), abdominal circumference, head circumference, and placental weight. METHODS We analyzed birth size from the Danish Medical Birth Registry of 66 693 live-born children in the Danish National Birth Cohort according to the mothers self-reported information on occupational lifting from telephone interviews around gestational week 16. Data were collected in the period 1996-2002. We used linear and logistic regression models and adjusted for confounders. RESULTS In the fully adjusted models, most of the mean differences in birth size measures had values indicating a smaller size of offspring among women with occupational lifting versus women with no lifting, but the differences were very small, and there was a statistically significant trend only for placental weight showing lighter weight with increasing number of kilos lifted per day. In jobs likely to include person-lifting, we found increased odds of SGA among children of women who lifted 501-1000 kilos per day [odds ratio (OR) 1.34, 95% confidence interval (95% CI) 0.98-1.83] and >1000 kilos per day (OR 1.51, 95% CI 0.83-2.76) compared to no lifting. In jobs with no person-lifting, occupational lifting was not associated with SGA. CONCLUSIONS Overall, we observed no strong support for an association between maternal occupational lifting and impaired size at birth. Our data indicated a potential association between lifting and SGA among offspring of women in occupations that are likely to include person-lifting. These results should, however, be interpreted with caution due to limited statistical power, and we suggest that future studies include detailed, individual information on job functions and ergonomic routines of lifting procedures.

What's in a Self‐report? A Comparison of Pregnant Women with Self‐reported and Hospital Diagnosed Eating Disorder

The aim of this study was to examine how similar pregnant women with self-reported lifetime eating disorder (ED) were to pregnant women with a hospital diagnosis of ED. A total of 83 731 pregnant women enrolled in the Danish National Birth Cohort reported on ED, and by linkage to the Danish health registers, hospital diagnoses of ED were obtained. Characteristics of women with self-reported ED, hospital diagnosed ED and without ED were compared using chi-square tests, t-test and logistic regression models with robust standard errors. In total, 4.8% women reported ED, and 0.5% had a hospital diagnosis of ED recorded in the health registers. Women with self-reported ED were comparable with women with hospital diagnosed ED on most reproductive and health characteristics, while they differed from women without ED concerning all characteristics studied. Our findings highlight that women with self-reported ED have impaired function and adverse health outcomes, consistent with diagnosable ED. Copyright

Maternal vegetarianism and neurodevelopment of children enrolled in The Danish National Birth Cohort

Clinical observations suggest that children born to vegan mothers may be at risk of severe neurodevelopmental impairments due to vitamin B12 (1–3), which is to be expected, as this vitamin is exclusively found in food of animal origin (4). Thus, children born to all vegetarians, not just vegans, may be at increased risk of impaired neurodevelopment if they have an insufficient intake of dietary supplements (5). As a result, it has been suggested that mothers should be warned about the impact of vegetarianism, in particular a vegan diet, during childbearing. The aim of this study was to use an existing large-scale populationbased cohort to examine the association between maternal vegetarianism and the risk of impaired neurodevelopment, including more subtle impairments, in children. We initiated this study based on the clinical observations described in Text Box 1 to improve the evidence for dietary counselling of pregnant vegetarians. Our study, which was approved by The Danish Protection Agency, was based on pregnancies enrolled in The Danish National Birth Cohort (DNBC) between 1996 and 2002 (6), and further details of the study can be found at www.dnbc.dk. We used data from 80 743 mother–child dyads of singleton pregnancies with a minimum gestational age of 154 days and information from two pregnancy interviews completed around gestational weeks 16 and 30. The study population was further restricted to observations with either information on impaired neurodevelopment from national registers (n = 77 968), parental reports on the age, in months, when their child sat and walked (n = 55 185), or parental reports on Strengths and Difficulties Questionnaire (SDQ) (n = 47 176). Information on age at sitting and walking and SDQ were collected when the children were 18 months and 7 years of age, respectively. The cohort was linked to the Danish National Patient Register (7) and the Danish Psychiatric Central Research Register (8). These two registers include information on all somatic and psychiatric inand outpatient hospital contacts. Impaired neurodevelopment was defined using the following 10th revision of the International Classification of Diseases codes: seizure disorders/epilepsy (G40-G41), retarded psychomotor development (R62.0), mental retardation (F70–F79), autism spectrum disorder (F84.0, F84.1, F84.5, F84.8, F84.9), developmental disorder of motor function (F82) and attention deficit/hyperactivity disorder (F90.0, F90.1, F90.8, F90.9). We derived information on head circumference at birth, in centimetres, from the Danish Medical Birth Registry (9) and on cerebral palsy from the Danish Cerebral Palsy Registry, a research register of cases that have been validated by a neuropaediatrician (10). All the children were followed in the registers from birth until the age of 7 years, and only diagnoses occurring before this age were included. Information on maternal vegetarianism and intake of multivitamins, folic acid and iron were obtained during pregnancy. The women were asked whether they were vegetarians, and those who answered yes were asked to state what kind of vegetarian diet they followed. This information was recorded as one of three predefined subtypes of vegetarianism by the interviewer: pesco-vegetarians (unfortunately the predefined response category did not distinguish between fish and poultry), lacto-ovo-vegetarians and vegans. The observations were grouped into non-vegetarians and these three subtypes of vegetarianism. Intake of multivitamins, folic acid and iron were categorised based on yes versus no responses. Three combined variables of maternal vegetarianism – non-vegetarian versus vegetarian – were constructed with, and without, the intake of each type of

Parental characteristics in association with disordered eating in 11- to 12-year-olds: A study within the Danish National Birth Cohort

We examined the association between parental characteristics and disordered eating among 11- to 12-year-olds within the Danish National Birth Cohort. Frequency of fasting, purging, and binge eating was obtained by self-report from 37,592 children and combined into a measure of disordered eating (no, monthly, and weekly). Information on parental characteristics was obtained during pregnancy, from the 7-year follow-up, and by linkage to population registers. Data were analysed using multinomial logistic regression models with robust standard errors. In total, 3.1% reported weekly and 4.1% reported monthly disordered eating. Parental young age, low educational level, and overweight/obesity were associated with disordered eating. The relative risk ratios for, respectively, weekly and monthly disordered eating according to maternal eating disorder were 1.01 [0.75, 1.37] and 1.09 [0.84, 1.42]. Disordered eating is common among children and is associated with several parental characteristics. We found social inequality in disordered eating, but our data did not support an association with maternal eating disorder.