Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Parental infertility and offspring cardiometabolic trajectories: a pooled analysis of three European cohorts.

OBJECTIVE: To assess whether parental infertility is associated with differences in cardiometabolic trajectories in offspring. DESIGN: Pooled observational analysis in three prospective cohorts. SETTING: Three nationwide pregnancy cohorts. PATIENTS: A total of 14,609 singletons from the UK Avon Longitudinal Study of Parents and Children, the Portuguese Geraçao 21, and the Amsterdam Born Children and Their Development study. Each cohort contributed data up to ages 26, 12, and 13 years, respectively. INTERVENTION: Parental infertility is defined as time-to-pregnancy of ≥12 months (n = 1,392, 9.5%). MAIN OUTCOME MEASURES: Trajectories of body mass index (BMI), waist circumference, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C) level, high-density lipoprotein cholesterol (HDL-C) level, triglycerides level, and glucose level were compared in the offspring of couples with and without infertility. Trajectories were modeled using mixed-effects models with natural cubic splines adjusting for cohort, sex of the offspring, and maternal factors (age, BMI, smoking, educational level, parity, and ethnicity). Predicted levels of cardiometabolic traits up to 25 years of age were compared with parental infertility. RESULTS: Offspring of couples with infertility had increasingly higher BMI (difference in mean predicted levels by age 25 years: 1.09 kg/m2, 95% confidence interval [0.68-1.50]) and suggestively higher diastolic blood pressure at age 25 years (1.21 mmHg [-0.003 to 2.43]). Their LDL-C tended to be higher, and their HDL-C values tended to be lower over time (age: 25 years, LDL-C: 4.07% [-0.79 to 8.93]; HDL-C: -2.78% [-6.99 to 1.43]). At age 17 years, offspring of couples with infertility had higher waist circumference (1.05 cm [0.11-1.99]) and systolic blood pressure (age: 17 years; 0.93 mmHg [0.044-1.81]), but these differences attenuated at later ages. No intergroup differences in triglyceride and glucose level trajectories were observed. Further adjustment for paternal age, BMI, smoking, and educational level, and both parents' histories of diabetes and hypertension in the cohort with this information available (Avon Longitudinal Study of Parents and Children) did not attenuate intergroup differences. CONCLUSION: Offspring of couples with infertility relative to those of fertile couples have increasingly higher BMI over the years, suggestively higher blood pressure levels, and tend to have greater values of LDL-C and lower values of HDL-C with age.

Associations between parental and pre-adolescents' physical activity and diet quality: The role of parental child care involvement and child's sex.

BACKGROUND: Research has demonstrated the importance of the family environment in the eating and activity levels of offspring. We examined the cross-sectional associations between moderate-to-vigorous physical activity (MVPA) and diet quality of parents and the MVPA and diet quality of pre-adolescents. Interactions were tested to assess whether the child's sex and the parental level of involvement in daily child care moderated these associations. METHODS: Data from 2467 pre-adolescents (age 11.5 ± 0.2 years; collected in 2015-2016) and their parents or caregivers from a large-scale prospective birth cohort study in Amsterdam (ABCD-study) was used. Parents and pre-adolescents individually reported their diet quality and physical activity. Child care involvement was assessed using the Caregiver Child Interaction Scale. With hierarchical linear regression analyses, we assessed the independent contribution of fathers and mothers. RESULTS: An association between mother-child MVPA was found (ß = 0.013; 95 % CI: 0.006;0.021). The association between father-child MVPA was only significant for highly involved fathers (ß = 0.014; 95 % CI: 0.004;0.023). The child's sex did not change these MVPA associations. Regarding diet quality, associations were found between mother-child diet quality score (DQS) (ß = 0.254; 95 % CI: 0.192;0.316) and father-child DQS, with stronger associations between fathers and sons (ß = 0.234; 95 % CI: 0.169;0.298) than between fathers and daughters (ß = 0.114; 95 % CI: 0.047;0.181). Parental levels of involvement did not change these associations. CONCLUSION: These findings demonstrate that both parental behaviours represent an important factor in physical activity and diet quality in pre-adolescents in a sex-specific manner. As such, it is essential to include both parents in research to obtain the necessary insights for developing effective interventions to promote children's healthy eating and physical activity behaviours.

Differences in birth weight between immigrants' and natives' children in Europe and Australia: a LifeCycle comparative observational cohort study.

OBJECTIVE: Research on adults has identified an immigrant health advantage, known as the 'immigrant health paradox', by which migrants exhibit better health outcomes than natives. Is this health advantage transferred from parents to children in the form of higher birth weight relative to children of natives? SETTING: Western Europe and Australia. PARTICIPANTS: We use data from nine birth cohorts participating in the LifeCycle Project, including five studies with large samples of immigrants' children: Etude Longitudinale Française depuis l'Enfance-France (N=12 494), the Raine Study-Australia (N=2283), Born in Bradford-UK (N=4132), Amsterdam Born Children and their Development study-Netherlands (N=4030) and the Generation R study-Netherlands (N=4877). We include male and female babies born to immigrant and native parents. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is birth weight measured in grams. Different specifications were tested: birth weight as a continuous variable including all births (DV1), the same variable but excluding babies born with over 4500 g (DV2), low birth weight as a 0-1 binary variable (1=birth weight below 2500 g) (DV3). Results using these three measures were similar, only results using DV1 are presented. Parental migration status is measured in four categories: both parents natives, both born abroad, only mother born abroad and only father born abroad. RESULTS: Two patterns in children's birth weight by parental migration status emerged: higher birth weight among children of immigrants in France (+12 g, p<0.10) and Australia (+40 g, p<0.10) and lower birth weight among children of immigrants in the UK (-82 g, p<0.05) and the Netherlands (-80 g and -73 g, p<0.001) compared with natives' children. Smoking during pregnancy emerged as a mechanism explaining some of the birth weight gaps between children of immigrants and natives. CONCLUSION: The immigrant health advantage is not universally transferred to children in the form of higher birth weight in all host countries. Further research should investigate whether this cross-national variation is due to differences in immigrant communities, social and healthcare contexts across host countries.

Early pregnancy triglycerides and not fructosamine are associated with birth weight (with foetal sexual dimorphism).

BACKGROUND: We evaluated whether maternal triglycerides (TGs) or fructosamine (measured in early pregnancy) predominantly contribute to birth weight (BW), in a foetal sexual dimorphism. METHODS: Analysis of data from the Amsterdam Born Children and their Development cohort study (total n = 3514). Maternal nonfasting TGs and fructosamine were determined in early gestation (median 13 weeks). Multivariable linear regression analysis was used to determine whether maternal TGs or fructosamine was associated with BW-small for gestational age (SGA)-large for gestational age (LGA) and whether it was sex-dependent. RESULTS: With each 1 mmol/L increase in TGs, BW increased significantly by 81.7 g. This increase was larger with boys (107.3 g; 95% CI 66-148) than girls (60.5 g; 95% CI 23.6-97.4). No association was found with fructosamine. When including different covariates (gestational age at blood sampling, total duration of pregnancy, maternal height, age, parity, ethnicity, educational level, smoking, alcohol, and pre-pregnancy BMI), 29% of the variance in BW can be explained. Adding fructosamine to this model gave no added value in predicting BW, in contrast to adding TGs (R2 raised from 0.292 to 0.299, p < .001). The odds of a newborn LGA with higher maternal TG were increased (OR 1.6, 95% CI 1.3-2.0), in contrast to fructosamine. CONCLUSIONS: Maternal TGs were more dominant (compared to fructosamine) in its association with BW (measured in early physiological pregnancy) and more prominently present when carrying a male foetus. These remarkable observations warrant more future research, especially in obese patients at risk for gestational diabetes.

Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis.

BACKGROUND: Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia. METHODS: In this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585. FINDINGS: We identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85·6%) women had sufficient data (TSH and FT4 concentrations and TPO antibody status) to be classified according to their thyroid function status. Of these women, 1275 (3·2%) had subclinical hypothyroidism, 933 (2·3%) had isolated hypothyroxinaemia, 619 (1·6%) had subclinical hyperthyroidism, and 337 (0·8%) had overt hyperthyroidism. Compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (2·1% vs 3·6%; OR 1·53 [95% CI 1·09-2·15]). Subclinical hyperthyroidism, isolated hypothyroxinaemia, or TPO antibody positivity were not associated with gestational hypertension or pre-eclampsia. In continuous analyses, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia (p=0·0001). FT4 concentrations were not associated with the outcomes measured. INTERPRETATION: Compared with euthyroidism, subclinical hypothyroidism during pregnancy was associated with a higher risk of pre-eclampsia. There was a U-shaped association of TSH with pre-eclampsia. These results quantify the risks of gestational hypertension or pre-eclampsia in women with thyroid function test abnormalities, adding to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy. These findings have potential implications for defining the optimal treatment target in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies. FUNDING: Arkansas Biosciences Institute and Netherlands Organization for Scientific Research.

Ideal cardiovascular health at age 5-6 years and cardiometabolic outcomes in preadolescence.

BACKGROUND: The American Heart Association (AHA) developed a definition of ideal cardiovascular health (ICH) based on the presence of both ideal health behaviours (diet, physical activity, weight status and smoking) and ideal health factors (glucose, total cholesterol and blood pressure levels). However, research of ICH in the paediatric population is scarce. We aimed to study ICH at age 5-6 years by extending the original ICH score with the health behaviours: sleep duration, screen time and prenatal smoke exposure, and to evaluate its association with cardiometabolic outcomes at age 11-12. METHODS: A total of 1666 children aged 5-6 years were selected from the database of the ABCD-study, a prospective cohort study on the health and development of children born in Amsterdam, the Netherlands. Of these, 846 (50.8%) were boys and 1460 (87.6%) had a healthy weight. Data on self-reported health behaviours and health factors were used to calculate the ICH scores (original and extended) by adding the frequency of scoring 'healthy' on each indicator, based on international cut-offs. The children were followed up for 6 years and cardiometabolic outcomes (carotid intima-media thickness (CIMT), blood pressure, glucose and lipids) were measured. Associations between ICH (both original and extended) and cardiometabolic outcomes were examined using multivariable regression models. RESULTS: At age 5-6 years, 11% scored poor (score 1-5), 56% intermediate (score 6-7) and 33% good (score 8-9) on extended ICH. Healthy diet and normal total cholesterol concentrations were the least prevalent. Neither the original nor the extended ICH scores were associated with CIMT at age 11-12. A higher score on the extended ICH was associated with lower total cholesterol (p for trend < 0.001), lower systolic (p for trend = 0.012) and diastolic blood pressure (p for trend = 0.011), and lower body mass index (BMI) (p < 0.001) at age 11-12. The original ICH score was associated with lower total cholesterol (p < 0.001) and BMI (p < 0.001) only. CONCLUSION: Our findings suggest that extending the ICH score in young children with additional health behaviours improves prediction of some cardiometabolic outcomes, but not CIMT in preadolescence, compared to the original ICH score. We would recommend other researchers to incorporate objective measures of health behaviours and longer follow-up to find out whether associations persist into adulthood.

Early Determinants of Childhood Blood Pressure at the Age of 6 Years: The GECKO Drenthe and ABCD Study Birth Cohorts.

Background There is still uncertainty about the nature and relative impact of early determinants on childhood blood pressure. This study explored determinants of blood pressure at the age of 6 years in 2 Dutch birth cohorts. Methods and Results Results of hierarchical multiple linear regression analyses in GECKO (Groningen Expert Center for Kids With Obesity) Drenthe study (n=1613) were replicated in ABCD (Amsterdam Born Children and Their Development) study (n=2052). All analyses were adjusted for child's age, sex, height, and body mass index (BMI), and maternal education and subsequently performed in the combined sample. No associations were found between maternal smoking during pregnancy and childhood blood pressure. In the total sample, maternal prepregnancy BMI was positively associated with systolic blood pressure (SBP) (ß [95% CI], 0.09 [0.02-0.16] mm Hg) and diastolic blood pressure (ß [95% CI], 0.11 [0.04-0.17] mm Hg). Children of women with hypertension had higher SBP (ß [95% CI], 0.98 [0.17-1.79] mm Hg). Birth weight standardized for gestational age was inversely associated with SBP (ß [95% CI], -6.93 [-9.25 to -4.61] mm Hg) and diastolic blood pressure (ß [95% CI], -3.65 [-5.70 to -1.61] mm Hg). Longer gestational age was associated with lower SBP (ß [95% CI] per week, -0.25 [-0.42 to -0.08] mm Hg). Breastfeeding for 1 to 3 months was associated with lower SBP (ß [95% CI], -0.96 [-1.82 to -0.09] mm Hg) compared with no or <1 month of breastfeeding. Early BMI gain from the age of 2 to 6 years was positively associated with SBP (ß [95% CI], 0.41 [0.08-0.74] mm Hg) and diastolic blood pressure (ß [95% CI], 0.37 [0.07-0.66] mm Hg), but no effect modification by birth weight was found. Conclusions Higher maternal prepregnancy BMI, maternal hypertension, a relatively lower birth weight for gestational age, shorter gestational age, limited duration of breastfeeding, and more rapid early BMI gain contribute to higher childhood blood pressure at the age of 6 years.

Potential determinants during 'the first 1000 days of life' of sleep problems in school-aged children.

STUDY OBJECTIVES: Early life determinants of sleep problems are mostly unknown. The first 1000 days of life (ie, the time between conception and a child's second birthday) is a period where the foundations for optimum health, growth and neurodevelopment are established. The aim of this explorative study is to identify potential early life determinants of sleep problems at age 7-8 years. METHODS: Data from the Amsterdam Born Children and their Development cohort study (n = 2746) were analyzed. Sleep problems at age 7-8 years were reported by the caregiver in the 'Child Sleep Habits Questionnaire'. A higher total score indicates more sleep problems. After multiple imputation (n = 20), we studied multivariable associations between all potential determinants and sleep problems using regression analysis. RESULTS: A higher pre-pregnancy body mass index (BMI) was associated with more sleep problems at age 7-8 years [ß 0.12 (95% CI 0.05, 0.18)]. Children of mothers with symptoms of anxiety during pregnancy [ß 0.06 (95% CI 0.03, 0.09)] and infancy period [ß 0.04 (95% CI 0.00, 0.07)] had more sleep problems. Children of mothers drinking ≥1 glass of alcohol a day around 14 weeks of gestation had a 2 points higher sleep problem score [ß 2.55 (95% CI 0.21, 4.89)] and children of mothers smoking ≥1 cigarette per day in that period had a one point higher score [ß 1.07 (95% CI 0.10, 2.03)]. Infants with relative weight loss (delta BMI-SD) had a higher sleep problem score during childhood [ß -0.32 (95%CI -0.60, -0.04)]. CONCLUSIONS: We identified several potential determinants during pregnancy and infancy associated with childhood sleeping problems. We encourage further research into these and other potential determinants to replicate results and to identify underlying mechanisms.

Peptide hormone ELABELA enhances extravillous trophoblast differentiation, but placenta is not the major source of circulating ELABELA in pregnancy.

Preeclampsia is a frequent gestational hypertensive disorder with equivocal pathophysiology. Knockout of peptide hormone ELABELA (ELA) has been shown to cause preeclampsia-like symptoms in mice. However, the role of ELA in human placentation and whether ELA is involved in the development of preeclampsia in humans is not yet known. In this study, we show that exogenous administration of ELA peptide is able to increase invasiveness of extravillous trophoblasts in vitro, is able to change outgrowth morphology and reduce trophoblast proliferation ex vivo, and that these effects are, at least in part, independent of signaling through the Apelin Receptor (APLNR). Moreover, we show that circulating levels of ELA are highly variable between women, correlate with BMI, but are significantly reduced in first trimester plasma of women with a healthy BMI later developing preeclampsia. We conclude that the large variability and BMI dependence of ELA levels in circulation make this peptide an unlikely candidate to function as a first trimester preeclampsia screening biomarker, while in the future administering ELA or a derivative might be considered as a potential preeclampsia treatment option as ELA is able to drive extravillous trophoblast differentiation.

Association of Exposure to Ambient Air Pollution With Thyroid Function During Pregnancy.

Importance: Air pollutants interact with estrogen nuclear receptors, but their effect on thyroid signaling is less clear. Thyroid function is of particular importance for pregnant women because of the thyroid's role in fetal brain development. Objective: To determine the short-term association of exposure to air pollution in the first trimester with thyroid function throughout pregnancy. Design, Setting, and Participants: In this cohort study, 9931 pregnant women from 4 European cohorts (the Amsterdam Born Children and Their Development Study, the Generation R Study, Infancia y Medio Ambiente, and Rhea) and 1 US cohort (Project Viva) with data on air pollution exposure and thyroid function during pregnancy were included. The recruitment period for the Amsterdam Born Children and Their Development Study was January 2003 to March 2004; for Generation R, April 2002 to January 2006; for Infancia y Medio Ambiente, November 2003 to January 2008; for Rhea, February 2007 to February 2008; and for Project Viva, April 1999 to November 2002. Statistical analyses were conducted from January 2018 to April 2019. Main Outcomes and Measures: Residential air pollution concentrations (ie, nitrogen oxide and particulate matter [PM]) during the first trimester of pregnancy were estimated using land-use regression and satellite-derived aerosol optical depth models. Free thyroxine, thyrotropin, and thyroid peroxidase antibody levels were measured across gestation. Hypothyroxinemia was defined as free thyroxine below the fifth percentile of the cohort distribution with normal thyrotropin levels, following the American Thyroid Association guidelines. Results: Among 9931 participants, the mean (SD) age was 31.2 (4.8) years, 4853 (48.9%) had more than secondary educational levels, 5616 (56.6%) were nulliparous, 404 (4.2%) had hypothyroxinemia, and 506 (6.7%) tested positive for thyroid peroxidase antibodies. Concentrations of nitrogen dioxide and PM with an aerodynamic diameter of 2.5 µm or less (PM2.5) were lower and had less variation in women in the US cohort than those in European cohorts. No associations of nitrogen oxide with thyroid function were found. Higher exposures to PM2.5 were associated with higher odds of hypothyroxinemia in pregnant women (odds ratio per 5-µg/m3 change, 1.21; 95% CI, 1.00-1.47). Although exposure to PM with an aerodynamic diameter of 10 µm or less was not significantly associated with hypothyroxinemia, the coefficient was similar to that for the association of PM2.5 with hypothyroxinemia (odds ratio per 10-µg/m3 change, 1.18; 95% CI, 0.93-1.48). Absorbances of PM2.5 and PM with aerodynamic diameter from 2.5 to 10 µg and were not associated with hypothyroxinemia. There was substantial heterogeneity among cohorts with respect to thyroid peroxidase antibodies (P for heterogeneity, <.001), showing associations of nitrogen oxide and PM with thyroid autoimmunity only in the women in the Generation R Study. Conclusions and Relevance: The findings of this study suggest that first-trimester exposures to PM2.5 were associated with mild thyroid dysfunction throughout pregnancy. The association of PM2.5 exposure with thyroid function during pregnancy is of global health importance because air pollution exposure is widespread and hypothyroxinemia may adversely influence the brain development of offspring.

Radiofrequency electromagnetic fields, screen time, and emotional and behavioural problems in 5-year-old children.

BACKGROUND: Little is known about the exposure of young children to radiofrequency electromagnetic fields (RF-EMF) and potentially associated health effects. We assessed the relationship of RF-EMF exposure from different sources and screen time exposure with emotional and behavioural problems in 5-year-old children. METHODS: Cross-sectional study including 3102 children aged 5 years from the Amsterdam Born Children and their Development (ABCD) study, in the Netherlands. Residential RF-EMF exposure from mobile phone base stations was estimated with a 3D geospatial radio wave propagation model. Residential presence of RF-EMF indoor sources (cordless phone base stations and Wireless Fidelity (WiFi)), children's mobile phone and cordless phone calls and screen time exposure (computer/video game and television watching) was reported by the mother. Teachers (n = 2617) and mothers (n = 3019) independently reported child emotional and behavioural problems using the Strengths and Difficulties Questionnaire. RESULTS: No associations were found between mobile phone and cordless phone calls and emotional and behavioural problems. Children exposed to higher RF-EMF levels from mobile phone base stations showed higher odds of maternal-reported emotional symptoms (OR 1.82, 95%CI 1.07 to 3.09). Children with cordless phone at home had lower odds of teacher-reported problematic prosocial behaviour (OR 0.68, 95%CI 0.48 to 0.97) and of maternal-reported peer relationship problems (OR 0.61, 95% CI 0.39 to 0.96). Children who watched television ≥1.5 h/day had higher odds of maternal-reported hyperactivity/inattention (OR 3.13, 95%CI 1.43 to 6.82). CONCLUSION: Mobile phone and cordless phone calls, which lead to peak RF-EMF exposures to the head, were not associated with any emotional and behavioural problems in 5-year-old children. Environmental RF-EMF exposure from mobile phone base stations and from indoor sources and television watching, which both contribute very little to RF-EMF exposure, were associated with specific emotional and behavioural problems but mainly when reported by the mothers. We cannot, however, discard residual confounding or reverse causality. Further longitudinal research in particular as children will increase the use of telecommunication devices with the age may help to better understand the exact contribution of the different RF-EMF exposure sources if any. Moreover, a thorough control for confounding is essential for a correct interpretation of the studies on screen time and emotional and behavioural problems.

Spatial and temporal variability of personal environmental exposure to radio frequency electromagnetic fields in children in Europe.

BACKGROUND: Exposure to radiofrequency electromagnetic fields (RF-EMF) has rapidly increased and little is known about exposure levels in children. This study describes personal RF-EMF environmental exposure levels from handheld devices and fixed site transmitters in European children, the determinants of this, and the day-to-day and year-to-year repeatability of these exposure levels. METHODS: Personal environmental RF-EMF exposure (µW/m2, power flux density) was measured in 529 children (ages 8-18 years) in Denmark, the Netherlands, Slovenia, Switzerland, and Spain using personal portable exposure meters for a period of up to three days between 2014 and 2016, and repeated in a subsample of 28 children one year later. The meters captured 16 frequency bands every 4 s and incorporated a GPS. Activity diaries and questionnaires were used to collect children's location, use of handheld devices, and presence of indoor RF-EMF sources. Six general frequency bands were defined: total, digital enhanced cordless telecommunications (DECT), television and radio antennas (broadcast), mobile phones (uplink), mobile phone base stations (downlink), and Wireless Fidelity (WiFi). We used adjusted mixed effects models with region random effects to estimate associations of handheld device use habits and indoor RF-EMF sources with personal RF-EMF exposure. Day-to-day and year-to-year repeatability of personal RF-EMF exposure were calculated through intraclass correlations (ICC). RESULTS: Median total personal RF-EMF exposure was 75.5 µW/m2. Downlink was the largest contributor to total exposure (median: 27.2 µW/m2) followed by broadcast (9.9 µW/m2). Exposure from uplink (4.7 µW/m2) was lower. WiFi and DECT contributed very little to exposure levels. Exposure was higher during day (94.2 µW/m2) than night (23.0 µW/m2), and slightly higher during weekends than weekdays, although varying across regions. Median exposures were highest while children were outside (157.0 µW/m2) or traveling (171.3 µW/m2), and much lower at home (33.0 µW/m2) or in school (35.1 µW/m2). Children living in urban environments had higher exposure than children in rural environments. Older children and users of mobile phones had higher uplink exposure but not total exposure, compared to younger children and those that did not use mobile phones. Day-to-day repeatability was moderate to high for most of the general frequency bands (ICCs between 0.43 and 0.85), as well as for total, broadcast, and downlink for the year-to-year repeatability (ICCs between 0.49 and 0.80) in a small subsample. CONCLUSION: The largest contributors to total personal environmental RF-EMF exposure were downlink and broadcast, and these exposures showed high repeatability. Urbanicity was the most important determinant of total exposure and mobile phone use was the most important determinant of uplink exposure. It is important to continue evaluating RF-EMF exposure in children as device use habits, exposure levels, and main contributing sources may change.

Mother's education and offspring asthma risk in 10 European cohort studies.

Highly prevalent and typically beginning in childhood, asthma is a burdensome disease, yet the risk factors for this condition are not clarified. To enhance understanding, this study assessed the cohort-specific and pooled risk of maternal education on asthma in children aged 3-8 across 10 European countries. Data on 47,099 children were obtained from prospective birth cohort studies across 10 European countries. We calculated cohort-specific prevalence difference in asthma outcomes using the relative index of inequality (RII) and slope index of inequality (SII). Results from all countries were pooled using random-effects meta-analysis procedures to obtain mean RII and SII scores at the European level. Final models were adjusted for child sex, smoking during pregnancy, parity, mother's age and ethnicity. The higher the score the greater the magnitude of relative (RII, reference 1) and absolute (SII, reference 0) inequity. The pooled RII estimate for asthma risk across all cohorts was 1.46 (95% CI 1.26, 1.71) and the pooled SII estimate was 1.90 (95% CI 0.26, 3.54). Of the countries examined, France, the United Kingdom and the Netherlands had the highest prevalence's of childhood asthma and the largest inequity in asthma risk. Smaller inverse associations were noted for all other countries except Italy, which presented contradictory scores, but with small effect sizes. Tests for heterogeneity yielded significant results for SII scores. Overall, offspring of mothers with a low level of education had an increased relative and absolute risk of asthma compared to offspring of high-educated mothers.

Outdoor and indoor sources of residential radiofrequency electromagnetic fields, personal cell phone and cordless phone use, and cognitive function in 5-6 years old children.

BACKGROUND: Little is known about the exposure of young children to radiofrequency electromagnetic fields (RF-EMF) and potentially associated health effects. We assessed the relationship between residential RF-EMF exposure from mobile phone base stations, residential presence of indoor sources, personal cell phone and cordless phone use, and children's cognitive function at 5-6 years of age. METHODS: Cross-sectional study on children aged 5-6 years from the Amsterdam Born Children and their Development (ABCD) study, the Netherlands (n=2354). Residential RF-EMF exposure from mobile phone base stations was estimated with a 3D geospatial radio wave propagation model. Residential presence of indoor sources (cordless phone base stations and Wi-Fi) and children's cell phone and cordless phone use was reported by the mother. Speed of information processing, inhibitory control, cognitive flexibility, and visuomotor coordination was assessed using the Amsterdam Neuropsychological Tasks. RESULTS: Residential presence of RF-EMF indoor sources was associated with an improved speed of information processing. Higher residential RF-EMF exposure from mobile phone base stations and presence of indoor sources was associated with an improved inhibitory control and cognitive flexibility whereas we observed a reduced inhibitory control and cognitive flexibility with higher personal cordless phone use. Higher residential RF-EMF exposure from mobile phone base stations was associated with a reduced visuomotor coordination whereas we observed an improved visuomotor coordination with residential presence of RF-EMF indoor sources and higher personal cell phone use. CONCLUSIONS: We found inconsistent associations between different sources of RF-EMF exposure and cognitive function in children aged 5-6 years.

Is first trimester vitamin D status in nulliparous women associated with pregnancy related hypertensive disorders?

OBJECTIVES: this study aimed to explore if maternal vitamin D status in early pregnancy was associated with pre-eclampsia and pregnancy-induced hypertension. Relationships between vitamin D status and blood pressure at the start of pregnancy as well as the occurrence of a mid-pregnancy drop in blood pressure were also explored. This secondary analysis was completed to investigate a possible mechanism for the association between vitamin D status and pregnancy related hypertensive disorders. DESIGN AND SETTING: data were obtained from the Amsterdam Born Children and their Development study, a prospective community-based cohort study based in Amsterdam, The Netherlands. PARTICIPANTS: a total of 2074 nulliparous women without pre-existing hypertension and with a known vitamin D status before 17 weeks gestation were included in the study. Vitamin D status was categorized into four groups: "normal" (≥50nmol/L), "insufficient" (30-49.9nmol/L) "deficient" (20-29.9nmol/L) or "severely deficient" (<20nmol/L). MEASUREMENTS: logistic regression analysis was used to investigate if vitamin D status was related to the odds of experiencing pre-eclampsia or pregnancy-induced hypertension. Models were corrected for maternal age, ethnicity, pre-pregnancy BMI, smoking and socioeconomic status. χ(2) and ANOVA tests were used to investigate relationships between vitamin D status and the blood pressure parameters. FINDINGS: when compared to women with a normal vitamin D status, women who were severely deficient had an increased risk for pre-eclampsia (OR 2.08; 95% CI, 1.05-4.13), but the association was rendered non-significant after correction (OR 1.88; 95% CI 0.79-4.48). There were no associations between vitamin D status and pregnancy-induced hypertension, starting blood pressure or the occurrence of a mid-pregnancy drop in blood pressure. KEY CONCLUSIONS: no strong evidence was found for an association between first trimester vitamin D status and pregnancy related hypertensive disorders in nulliparous women. IMPLICATIONS FOR PRACTICE: at this time, vitamin D supplementation is not warranted for the specific purpose of preventing pregnancy related hypertensive disorders.

Exploring educational disparities in risk of preterm delivery: a comparative study of 12 European birth cohorts.

BACKGROUND: An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data. METHODS: The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22-36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs). RESULTS: Singleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts. CONCLUSIONS: Educational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences.

Smoking overrules many other risk factors for small for gestational age birth in less educated mothers.

BACKGROUND: Although there is convincing evidence for the association between small for gestational age (SGA) and socioeconomic status (SES), it is not known to what extent explanatory factors contribute to this association. AIM: To examine to what extent risk factors could explain educational inequalities in SGA. STUDY DESIGN: In this study fully completed data were available for 3793 pregnant women of Dutch origin from a population-based cohort (ABCD study). Path-analysis was conducted to examine the role of explanatory factors in the relation of maternal education to SGA. RESULTS: Low-educated pregnant women had a higher risk of SGA offspring compared to the high-educated women (OR 1.98, 95% CI 1.35-2.89). In path-analysis, maternal cigarette smoking and maternal height explained this association. Maternal age, hypertension, chronic disease, late entry into antenatal care, neighborhood income, underweight, environmental cigarette smoking, drug abuse, alcohol use, caffeine intake, fish intake, folic acid intake, anxiety, and depressive symptoms did not play a role in the association between maternal education and SGA birth. CONCLUSION: Among a large array of potential factors, the elevated risk of SGA birth among low-educated women appeared largely attributable to maternal smoking and to a lesser extent to maternal height. To reduce educational inequalities more effort is required to include low-educated women especially in prenatal intervention programs such as smoking cessation programs instead of effort into reducing other SGA-risk factors, though these factors might still be relevant at the individual level.

Preterm birth and small for gestational age in relation to alcohol consumption during pregnancy: stronger associations among vulnerable women? Results from two large Western-European studies.

BACKGROUND: Inconsistent data on the association between prenatal alcohol exposure and a range of pregnancy outcomes, such as preterm birth (PTB) and small for gestational age (SGA) raise new questions. This study aimed to assess whether the association between low-moderate prenatal alcohol exposure and PTB and SGA differs according to maternal education, maternal mental distress or maternal smoking. METHODS: The Amsterdam Born Children and their Development (ABCD) Study (N = 5,238) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) (N = 16,301) are both large studies. Women provide information on alcohol intake in early pregnancy, 3 months postpartum and up to 17 years retrospectively. Multivariate logistic regression analyses and stratified regression analyses were performed to examine the association between prenatal alcohol exposure and PTB and SGA, respectively. RESULTS: No association was found between any level of prenatal alcohol exposure (non-daily, daily, non-abstaining) and SGA. The offspring of daily drinkers and non-abstainers had a lower risk of PTB [ABCD: odds ratio (OR) 0.31, 95% confidence interval (CI) 0.13, 0.77; KiGGS: OR 0.75, 95% CI 0.57, 0.99]. Interactions with maternal education, maternal distress or maternal smoking were not significant. CONCLUSIONS: Although these results should be interpreted with caution, both studies showed no adverse effects of low-moderate prenatal alcohol exposure on PTB and SGA, not even in the offspring of women who were disadvantaged in terms of low education, high levels of distress, or smoking during pregnancy.

Infant nutrition in relation to eating behaviour and fruit and vegetable intake at age 5 years.

Infant nutrition may influence eating behaviour and food preferences in later life. The present study explores whether exclusive breast-feeding duration and age at introduction of solid foods are associated with children's eating behaviour and fruit and vegetable intake at age 5 years. Data were derived from the Amsterdam Born Children and their Development study, a prospective birth cohort in the Netherlands, and included 3624 children. During infancy, data on infant nutrition were collected. Child eating behaviour (satiety responsiveness, enjoyment of food, slowness in eating and food responsiveness) was assessed with the Children's Eating Behaviour Questionnaire; and fruit and vegetable intake was calculated from a validated child FFQ. Both questionnaires were filled in by the mothers after their child turned 5 years. Exclusive breast-feeding duration was not associated with later eating behaviour, although longer exclusive breast-feeding was significantly associated with a higher vegetable intake at age 5 years. Compared with the introduction of solid foods at age 6 months, introduction before the age of 4 months was associated with less satiety responsiveness at age 5 years (ß -0·09; 95 % CI -0·16, -0·02). Introducing solid foods after 6 months was associated with less enjoyment of food (ß -0·07; 95 % CI -0·12, -0·01) and food responsiveness (ß -0·04; 95 % CI -0·07, -0·01). Introducing solid foods before the age of 4 months was associated with a higher fruit intake compared with introduction at 6 months. These findings suggest that prolonged breast-feeding and introduction of solid foods between 4 and 6 months may lead to healthier eating behaviour and food preferences at age 5 years.