The cross-sectional association of parental psychosocial status with children's Body Mass Index z-score and the mediating role of children's energy balance behaviors - the ABCD Study.

OBJECTIVE: Investigate the cross-sectional association between the psychosocial status of mothers and fathers and the BMI z-scores of their 10 to 12-year-old children. Explore whether this association is mediated by children's diet, physical activity, screen time and sleep. Analyze the moderating effect of the educational levels of both the mother and father on the association. DESIGN: In a cross-sectional study design, children's height and weight were measured following a standardized protocol. Parents completed the validated Depression Anxiety and Stress questionnaire, while diet quality, sports participation, time spent in bed and screen time were assessed through child-report using previously validated questions. PARTICIPANTS: The data for this study were obtained from the Amsterdam Born Children and their Development study, involving children aged 10 to 12 years and both of their parents (N = 1315). RESULTS: The majority, 80%, of the parents were highly educated and born in the Netherlands, and 68% of the children had a healthy BMI. Maternal or paternal psychosocial status was not significantly associated with children's BMI z-score (maternal ß -0.0037; 95% CI: -0.008 to 0.0007, paternal ß 0.0028; 95% CI: -0.007 to 0.002). Screen time mediated the association between paternal psychosocial status and children's BMI z-score (ß = 0.010, 95% CI: 0.002; 0.020). Children's diet, physical activity, and sleep did not mediate the association between paternal psychosocial status and children's BMI z-score. Parental educational level was not a moderator. CONCLUSIONS: This research is unique in including four energy balance behaviors and including both mothers and fathers' psychosocial status. Children withfathers experiencing poorer psychosocial status engaged in more screen time which partly explained their higher BMI z-score.

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.

Associations of light exposure patterns with sleep among Dutch children: The ABCD cohort study.

Light exposure affects the circadian system and consequently can affect sleep quality. Only few studies examined this relationship in children. We evaluated associations between light exposure patterns and sleep metrics in children. We measured the sleep parameters of 247 Dutch children, aged between 11 and 13 years and recruited from the ABCD cohort, using actigraphy and sleep records for 7 consecutive nights. Personal light exposures were measured with a light meter during the whole day and night. We applied generalized mixed-effects regression models, adjusted for possible confounders, to evaluate the associations of light exposure patterns on sleep duration, sleep efficiency and sleep-onset delay. In the models mutually adjusted for potential confounders, we found the amount of hours between the first time of bright light in the morning and going to sleep and the duration of bright light to be significantly associated with decreased sleep duration (in min; ß: -2.02 [95% confidence interval: -3.84, -0.25], ß: -8.39 [95% confidence interval: -16.70, -0.07], respectively) and with shorter sleep-onset delay (odds ratio: 0.88 [95% confidence interval: 0.80, 0.97], odds ratio: 0.40 [95% confidence interval: 0.19, 0.87], respectively). Increased light intensities at night were associated with decreased sleep duration (T2 ß: -8.54 [95% confidence interval: -16.88, -0.20], T3 ß: -14.83 [95% confidence interval: -28.04, -1.62]), while increased light intensities before going to bed were associated with prolonged sleep onset (odds ratio: 4.02 [95% confidence interval: 2.09, 7.73]). These findings further suggest that children may be able to influence their sleep quality by influencing the light exposure patterns during day and night.

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.

TSH and FT4 Reference Interval Recommendations and Prevalence of Gestational Thyroid Dysfunction: Quantification of Current Diagnostic Approaches.

CONTEXT: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. METHODS: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. RESULTS: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. CONCLUSION: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Population trajectories and age-dependent associations of obesity risk factors with body mass index from childhood to adolescence across European regions: A two-cohort study.

OBJECTIVE: To investigate population trajectories of behavioural risk factors of obesity from childhood to adolescence and their associations with body mass index (BMI) in children across European regions. METHODS: Data were harmonised between the European multi-centre IDEFICS/I.Family and the Amsterdam Born Children and their Development Cohort. Participants were aged 2.0-9.9 and 5.0-7.5 years at baseline, respectively, and were followed until age 18 years. Behavioural risk factors of interest included diet, physical activity, media use and sleep. Mixed effects models were used for statistical analyses to account for repeated measurements taken from the same child. RESULTS: The study included a total of 14 328 individuals: 4114, 4582, 3220 and 2412 participants from Northern, Southern, Eastern Europe and Amsterdam, respectively. Risk factor means and prevalences changed with age, but the trajectories were mostly similar across regions. Almost no associations between behavioural factors and BMI were found at the age of 6 years. At 11 years, daily sugar-sweetened foods consumption, use of active transport, sports club membership and longer nocturnal sleep duration were negatively associated with BMI in most regions; positive associations were found with media use. Most associations at 11 years of age persisted to 15 years. CONCLUSIONS: Whilst population trajectories of media use and nocturnal sleep duration are similar across European regions, those of other behavioural risk factors like active transport and daily vegetable consumption differ. Also, associations between behavioural risk factors and BMI become stronger with age and show similar patterns across regions.

Modelling individual infancy growth trajectories to predict excessive gain in BMI z-score: a comparison of growth measures in the ABCD and GECKO Drenthe cohorts.

BACKGROUND: Excessive weight gain during childhood is a strong predictor for adult overweight, but it remains unknown which growth measures in infancy (0-2 years of age), besides predictors known at birth, are the strongest predictors for excessive weight gain between 2 and 5-7 years of age. METHODS: The Amsterdam Born Children and their Development (ABCD) study formed the derivation cohort, and the Groningen Expert Center for Kids with Obesity (GECKO) Drenthe study formed the validation cohort. Change (Δ) in body mass index (BMI) z-score between 2 and 5-7 years was the outcome of interest. The growth measures considered were weight, weight-for-length (WfL), and body mass index (BMI). Formats considered for each growth measure were values at 1, 6, 12, and 24 months, at the BMI peak, the change between aforementioned ages, and prepeak velocity. 10 model structures combining different variable formats and including predictors at birth were derived for each growth measure, resulting in 30 linear regression models. A Parsimonious Model considering all growth measures and a Birth Model considering none were also derived. RESULTS: The derivation cohort consisted of 3139 infants of which 373 (11.9%) had excessive gain in BMI z-score (> 0.67). The validation cohort contained 2201 infants of which 592 (26.9%) had excessive gain. Across the 3 growth measures, 5 model structures which included measures related to the BMI peak and prepeak velocity (derivation cohort area under the curve [AUC] range = 0.765-0.855) achieved more accurate estimates than 3 model structures which included growth measure change over time (0.706-0.795). All model structures which used BMI were superior to those using weight or WfL. The AUC across all models was on average 0.126 lower in the validation cohort. The Parsimonious Model's AUCs in the derivation and validation cohorts were 0.856 and 0.766, respectively, compared to 0.690 and 0.491, respectively, for the Birth Model. The respective false positive rates were 28.2% and 20.1% for the Parsimonious Model and 70.0% and 74.6% for the Birth Model. CONCLUSION: Models' performances varied significantly across model structures and growth measures. Developing the optimal model requires extensive testing of the many possibilities.

Carrying an unintended pregnancy to term and long-term maternal psychological distress: Findings from the Dutch prospective Amsterdam Born Children and their Development study.

BACKGROUND: Given the estimated high rate of unintended pregnancies, it is important to investigate long-term effects on psychological distress in women carrying an unintended pregnancy to term. However, research into associations between unintended pregnancies carried to term and psychological distress postpartum is mixed, and especially, evidence on long-term associations is scarce. OBJECTIVE: To examine whether carrying an unintended pregnancy to term is associated with maternal psychological distress later in life, up to 12 years postpartum. DESIGN: This study is based on the population-based birth cohort study 'Amsterdam Born Children and their Development' study, which included pregnant people in 2003 (n = 7784) and followed them up until 12 years postpartum. METHODS: Unintended pregnancy was measured as a multidimensional construct, based on self-reported data around 16 weeks gestation on pregnancy mistiming, unwantedness and unhappiness. Symptoms of maternal psychological distress were assessed around 3 months, 5 years and 12 years postpartum using multiple questionnaires measuring symptoms of depression, anxiety and stress. Multiple structural equation modelling models were analysed, examining the associations between dimensions of unintended pregnancy and maternal psychological distress per time point, while controlling for important co-occurring risks. RESULTS: Pregnancy mistiming and unhappiness were significant predictors of more maternal psychological distress around 3 months postpartum. Around 5 years postpartum, only pregnancy mistiming was positively associated with maternal psychological distress. Dimensions of unintended pregnancy were no longer associated with maternal psychological distress around 12 years postpartum. Strikingly, antenatal psychological distress was a much stronger predictor of maternal psychological distress than pregnancy intention dimensions. CONCLUSION: Those who carried a more unintended pregnancy to term reported more symptoms of psychological distress at 3 months and 5 years postpartum. People carrying an unintended pregnancy to term may benefit from extra support, not because of the pregnancy intentions per se, but because they may be related to antenatal psychological distress.

Carrying an unintended pregnancy to term and maternal psychological distress over timeEvery unintended pregnancy is different, like every person is different. Nevertheless, carrying an unintended pregnancy to term might be stressful, that might impact mental health (e.g. depression or anxiety) of people carrying an unintended pregnancy to term. Research into long-term effects of carrying an unintended pregnancy to term on maternal mental health is scarce. In this study, we investigated effects of carrying an unintended pregnancy to term on maternal mental health up to 12 years postpartum. We used data from 7784 pregnant people living in Amsterdam, who participated in the Amsterdam Born Children and their Development (ABCD) study in 2003. Participants were followed up to 12 years postpartum. During pregnancy, participants answered questions about pregnancy mistiming (did the pregnancy happen at the right time), unwantedness (did they want to become pregnant) and unhappiness (how did they feel when they found out they were pregnant). We investigated these 'dimensions' of unintended pregnancy separately, to grasp to complexity of unintended pregnancy. Furthermore, participants answered multiple questions about experienced symptoms of depressions and anxiety around 3 months, 5 years and 12 years postpartum. People, who reported that their pregnancy was more mistimed, reported more mental health problems up to 5 years postpartum. Furthermore, people who reported more unhappiness with their pregnancy, reported more mental health problems around 3 months postpartum. People with an unintended pregnancy reported no longer more mental health problems around 12 years after birth, compared to people with more intended pregnancy. Strikingly, the mental health of people during pregnancy was more important for their mental health later in life, compared to their unintended pregnancy. Thus, the (emotional) circumstances around the pregnancy might be more influential for mental health later in life, compared to their pregnancy intentions. People carrying an unintended pregnancy to term may benefit from extra support, tailored to their individual needs and circumstances. Nevertheless, our results also showed that people are also resilient to deal with the many events and challenges faced during the periods after birth, since the effect of unintended pregnancy on maternal mental health disappeared over time.

Age-Specific Quantification of Overweight/Obesity Risk Factors From Infancy to Adolescence and Differences by Educational Level of Parents.

Objectives: To explore the age-dependent associations between 26 risk factors and BMI in early life, and differences by parental educational level. Methods: Data of 10,310 children (24,155 measurements) aged 2-16 years participating in a multi-centre European cohort from 2007 to 2014 were utilized. Trajectories of overweight/obesity risk factors and their age-specific associations with BMI were estimated using polynomial mixed-effects models. Results: Exposure to most unfavourable factors was higher in the low/medium compared to the high education group, e.g., for PC/TV time (12.6 vs. 10.6 h/week). Trajectories of various risk factors markedly changed at an age of 9-11 years. Having a family history of obesity, maternal BMI, pregnancy weight gain and birth weight were positively associated with BMI trajectories throughout childhood/adolescence in both education groups; associations of behavioural factors with BMI were small. Parental unemployment and migrant background were positively associated with BMI in the low/medium education group. Conclusion: Associations of risk factors with BMI trajectories did not essentially differ by parental education except for social vulnerabilities. The age period of 9-11 years may be a sensitive period for adopting unfavourable behaviours.

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.

Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis.

AIMS: To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age. METHODS AND RESULTS: Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (-0.53 mmHg; 95% CI:-1.59 to 0.53), DBP (-0.24 mmHg; -0.83 to 0.35), or HR (0.02 beat/min; -0.91 to 0.94). Total cholesterol (2.59%; 0.10-5.07), HDL cholesterol (4.16%; 2.52-5.81), LDL cholesterol (4.95%; 0.47-9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant. CONCLUSION: These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease.

Parental Discontent with Infant Sleep During the First Two Years of Life.

BACKGROUND: Problematic sleep in infants can have a high impact on families. We examined parental discontent with infant sleep in the first six months of life and parent-perceived problematic sleep during the second year of life. METHODS: We used Sarphati Cohort data of 1471 children. During periodic youth health care visits in the first six months of life, professionals registered parental discontent with infant sleep. In the second year of life, parents filled out the Brief Infant Sleep Questionnaire (BISQ), from which we defined parent-perceived problematic sleep and BISQ-defined problematic sleep. We examined the association of parental discontent with infant sleep during the first six months with both BISQ-derived outcomes up to age two, using multivariable logistic regression analysis. RESULTS: 26% of parents were discontented with infant sleep during the first six months of life. During the second year of life, 27% of the parents perceived their child's sleep as problematic, and 9% of the infants had BISQ-defined problematic sleep. Early parental discontent with infant sleep was associated with parent-perceived problematic sleep [adjusted OR 2.50 (95% CI 1.91-3.28)], and BISQ-defined problematic sleep [adjusted OR 1.88 (1.11-3.17)]. CONCLUSIONS: Early registered parental discontent with infant sleep was a predictor of parent-perceived problematic sleep in early toddlerhood. Registering parental discontent during infancy might enable professionals to identify a group of infants at risk for later problematic sleep. We recommend screening and parental support for sleep difficulties in an early stage.

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.

Exposure to natural environments during pregnancy and birth outcomes in 11 European birth cohorts.

Research suggests that maternal exposure to natural environments (i.e., green and blue spaces) promotes healthy fetal growth. However, the available evidence is heterogeneous across regions, with very few studies on the effects of blue spaces. This study evaluated associations between maternal exposure to natural environments and birth outcomes in 11 birth cohorts across nine European countries. This study, part of the LifeCycle project, was based on a total sample size of 69,683 newborns with harmonised data. For each participant, we calculated seven indicators of residential exposure to natural environments: surrounding greenspace in 100m, 300m, and 500m using Normalised Difference Vegetation Index (NDVI) buffers, distance to the nearest green space, accessibility to green space, distance to the nearest blue space, and accessibility to blue space. Measures of birth weight and small for gestational age (SGA) were extracted from hospital records. We used pooled linear and logistic regression models to estimate associations between exposure to the natural environment and birth outcomes, controlling for the relevant covariates. We evaluated the potential effect modification by socioeconomic status (SES) and region of Europe and the influence of ambient air pollution on the associations. In the pooled analyses, residential surrounding greenspace in 100m, 300m, and 500m buffer was associated with increased birth weight and lower odds for SGA. Higher residential distance to green space was associated with lower birth weight and higher odds for SGA. We observed close to null associations for accessibility to green space and exposure to blue space. We found stronger estimated magnitudes for those participants with lower educational levels, from more deprived areas, and living in the northern European region. Our associations did not change notably after adjustment for air pollution. These findings may support implementing policies to promote natural environments in our cities, starting in more deprived areas.

Associations Between Maternal Lipid Blood Levels at the 13th Week of Pregnancy and Offspring's Adiposity at Age 11-12 Years.

CONTEXT: There is increasing evidence that intrauterine lipid metabolism influences the adiposity of the newborn and the first years thereafter. It remains unclear if these effects persist when these children grow older. OBJECTIVE: This study examined the associations between maternal lipid blood levels during the 13th week of pregnancy and an offspring's adiposity, measured at age 11-12, and if these associations were moderated by the child's sex. METHODS: Data were obtained from a community-based birth cohort, the Amsterdam Born Children and their Development (ABCD) study. At a median of 13 weeks' gestation, nonfasting blood samples of triglycerides (TGs), total cholesterol (TC), free fatty acids (FFAs), and apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) were measured. An offspring's body mass index (BMI), subcutaneous fat (SCF), waist-to-height-ratio (WHtR), and fat percentage (fat%) were measured at age 11-12. Mothers with at-term born children were included (n = 1853). Multivariable linear regression analyses were performed to assess the associations between maternal lipids and each offspring's adiposity outcome separately. Sex differences were additionally evaluated. RESULTS: TGs, TC, ApoB/ApoA1, and FFAs were significantly positively associated with BMI, WHtR, and fat% (adjusted for gestational age at blood sampling, child's age, sex, and sexual maturation). After additional adjustments for potential confounders and covariates, only TGs remained significantly associated with WHtR (0.45, 95% CI -0.007; 0.91). There were no associations between maternal lipids and SCF and no clear sex-specific results were found. CONCLUSION: Overall, our results do not strongly support that maternal lipid profile during the 13th week of pregnancy has programming effects on adiposity in preadolescence.

TSH and FT4 Reference Intervals in Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis.

CONTEXT: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. OBJECTIVE: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. METHODS: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. RESULTS: (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. CONCLUSION: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria.

Association of Thyroid Peroxidase Antibodies and Thyroglobulin Antibodies with Thyroid Function in Pregnancy: An Individual Participant Data Meta-Analysis.

Objectives: Thyroid autoimmunity is common in pregnant women and associated with thyroid dysfunction and adverse obstetric outcomes. Most studies focus on thyroid peroxidase antibodies (TPOAbs) assessed by a negative-positive dichotomy and rarely take into account thyroglobulin antibodies (TgAbs). This study aimed at determining the association of TPOAbs and TgAbs, respectively, and interdependently, with maternal thyroid function. Methods: This was a meta-analysis of individual participant cross-sectional data from 20 cohorts in the Consortium on Thyroid and Pregnancy. Women with multiple pregnancy, pregnancy by assisted reproductive technology, history of thyroid disease, or use of thyroid interfering medication were excluded. Associations of (log2) TPOAbs and TgAbs (with/without mutual adjustment) with cohort-specific z-scores of (log2) thyrotropin (TSH), free triiodothyronine (fT3), total triiodothyronine (TT3), free thyroxine (fT4), total thyroxine (TT4), or triiodothyronine:thyroxine (T3:T4) ratio were evaluated in a linear mixed model. Results: In total, 51,138 women participated (51,094 had TPOAb-data and 27,874 had TgAb-data). Isolated TPOAb positivity was present in 4.1% [95% confidence interval, CI: 3.0 to 5.2], isolated TgAb positivity in 4.8% [CI: 2.9 to 6.6], and positivity for both antibodies in 4.7% [CI: 3.1 to 6.3]. Compared with antibody-negative women, TSH was higher in women with isolated TPOAb positivity (z-score increment 0.40, CI: 0.16 to 0.64) and TgAb positivity (0.21, CI: 0.10 to 0.32), but highest in those positive for both antibodies (0.54, CI: 0.36 to 0.71). There was a dose-response effect of higher TPOAb and TgAb concentrations with higher TSH (TSH z-score increment for TPOAbs 0.12, CI: 0.09 to 0.15, TgAbs 0.08, CI: 0.02 to 0.15). When adjusting analyses for the other antibody, only the association of TPOAbs remained statistically significant. A higher TPOAb concentration was associated with lower fT4 (p < 0.001) and higher T3:T4 ratio (0.09, CI: 0.03 to 0.14), however, the association with fT4 was not significant when adjusting for TgAbs (p = 0.16). Conclusions: This individual participant data meta-analysis demonstrated an increase in TSH with isolated TPOAb positivity and TgAb positivity, respectively, which was amplified for individuals positive for both antibodies. There was a dose-dependent association of TPOAbs, but not TgAbs, with TSH when adjusting for the other antibody. This supports current practice of using TPOAbs in initial laboratory testing of pregnant women suspected of autoimmune thyroid disease. However, studies on the differences between TPOAb- and TgAb-positive women are needed to fully understand the spectrum of phenotypes.

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.

Early environmental quality and life-course mental health effects: The Equal-Life project.

BACKGROUND: There is increasing evidence that a complex interplay of factors within environments in which children grows up, contributes to children's suboptimal mental health and cognitive development. The concept of the life-course exposome helps to study the impact of the physical and social environment, including social inequities, on cognitive development and mental health over time. METHODS: Equal-Life develops and tests combined exposures and their effects on children's mental health and cognitive development. Data from eight birth-cohorts and three school studies (N = 240.000) linked to exposure data, will provide insights and policy guidance into aspects of physical and social exposures hitherto untapped, at different scale levels and timeframes, while accounting for social inequities. Reasoning from the outcome point of view, relevant stakeholders participate in the formulation and validation of research questions, and in the formulation of environmental hazards. Exposure assessment combines GIS-based environmental indicators with omics approaches and new data sources, forming the early-life exposome. Statistical tools integrate data at different spatial and temporal granularity and combine exploratory machine learning models with hypothesis-driven causal modeling. CONCLUSIONS: Equal-Life contributes to the development and utilization of the exposome concept by (1) integrating the internal, physical and social exposomes, (2) studying a distinct set of life-course effects on a child's development and mental health (3) characterizing the child's environment at different developmental stages and in different activity spaces, (4) looking at supportive environments for child development, rather than merely pollutants, and (5) combining physical, social indicators with novel effect markers and using new data sources describing child activity patterns and environments.