Determinants of dysmenorrhoea among female adolescents: results from a community-based cohort study in Amsterdam.

RESEARCH QUESTION: What is the contribution of sociodemographic, psychosocial, lifestyle and reproductive factors up to the age of 11-12 years to the occurrence of dysmenorrhoea at age 15-16 years within the Amsterdam Born Children and their Development (ABCD) study? DESIGN: Data of 1038 female adolescents were used. Participants' baseline characteristics were obtained using self-reported questionnaires up to the age of 11-12 years, as well as the obstetric information of their mothers during pregnancy. Dysmenorrhoea was assessed at the age of 15-16 years, and was deemed to be present if an adolescent reported menstrual abdominal and/or back pain and therefore took medication and/or hormonal contraception. Using a backward selection approach, potential determinants of dysmenorrhoea were selected and multivariable associations were determined. RESULTS: The overall prevalence of dysmenorrhoea was 49.5% among the participants. Intake of 3-4.5 sugar-sweetened beverages/day (P = 0.035) and higher gynaecological age (i.e. years since menarche) (P < 0.001) were significantly associated with higher occurrence of dysmenorrhoea in the final model, which explained 8.1% of the total variance in the occurrence of dysmenorrhoea. No significant associations were found between the occurrence of dysmenorrhoea and sociodemographic or psychosocial factors. CONCLUSIONS: This investigation of various potential risk factors for dysmenorrhoea suggests that diet and reproductive factors are particularly important predictors of the occurrence of dysmenorrhoea among young adolescents. Specifically, intake of sugar-sweetened beverages and higher gynaecological age were predictive of the occurrence of dysmenorrhoea. Other lifestyle factors were also identified as possible risk factors. Using this knowledge, effective strategies can be developed to reduce the burden of dysmenorrhoea among adolescents, and to provide appropriate care for those suffering from the condition.

Associations of Maternal Educational Level, Proximity to Greenspace During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood: A Proof-of-Concept Federated Analysis in 18 Birth Cohorts.

International sharing of cohort data for research is important and challenging. We explored the feasibility of multi-cohort federated analyses by examining associations between three pregnancy exposures (maternal education, exposure to green vegetation and gestational diabetes) with offspring BMI from infancy to 17 years. We used data from 18 cohorts (n=206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13 and 14-17 years. Associations were estimated using linear regression via one-stage IPD meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z-score comparing low with high education age 2-3 years = 0.03 [95% CI 0.00, 0.05], 4-7 years = 0.16 [95% CI 0.14, 0.17], 8-13 years = 0.24 [95% CI 0.22, 0.26]). Gestational diabetes was positively associated with BMI from 8 years (BMI z-score difference = 0.18 [CI 0.12, 0.25]) but not at younger ages; however associations attenuated towards the null when restricted to cohorts which measured GDM via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age one but not at older ages. Opportunities of cross-cohort federated analyses are discussed.

The effects of hypothetical behavioral interventions on the 13-year incidence of overweight/obesity in children and adolescents.

BACKGROUND: In view of the high burden of childhood overweight/obesity (OW/OB), it is important to identify targets for interventions that may have the greatest effects on preventing OW/OB in early life. Using methods of causal inference, we studied the effects of sustained behavioral interventions on the long-term risk of developing OW/OB based on a large European cohort. METHODS: Our sample comprised 10 877 children aged 2 to < 10 years at baseline who participated in the well-phenotyped IDEFICS/I.Family cohort. Children were followed from 2007/08 to 2020/21. Applying the parametric g-formula, the 13-year risk of developing OW/OB was estimated under various sustained hypothetical interventions on physical activity, screen time, dietary intake and sleep duration. Interventions imposing adherence to recommendations (e.g. maximum 2 h/day screen time) as well as interventions 'shifting' the behavior by a specified amount (e.g. decreasing screen time by 30 min/day) were compared to 'no intervention' (i.e. maintaining the usual or so-called natural behavior). Separately, the effectiveness of these interventions in vulnerable groups was assessed. RESULTS: The 13-year risk of developing OW/OB was 30.7% under no intervention and 25.4% when multiple interventions were imposed jointly. Meeting screen time and moderate-to-vigorous physical activity (MVPA) recommendations were found to be most effective, reducing the incidence of OW/OB by -2.2 [-4.4;-0.7] and -2.1 [-3.7;-0.8] percentage points (risk difference [95% confidence interval]), respectively. Meeting sleep recommendations (-0.6 [-1.1;-0.3]) had a similar effect as increasing sleep duration by 30 min/day (-0.6 [-0.9;-0.3]). The most effective intervention in children of parents with low/medium educational level was being member in a sports club; for children of mothers with OW/OB, meeting screen time recommendations and membership in a sports club had the largest effects. CONCLUSIONS: While the effects of single behavioral interventions sustained over 13 years were rather small, a joint intervention on multiple behaviors resulted in a relative reduction of the 13-year OW/OB risk by between 10 to 26%. Individually, meeting MVPA and screen time recommendations were most effective. Nevertheless, even under the joint intervention the absolute OW/OB risk remained at a high level of 25.4% suggesting that further strategies to better prevent OW/OB are required.

Longitudinal Associations Between Trauma Exposure and Executive Functions in Children: Findings from a Dutch Birth Cohort Study.

This study is the first to distinguish two possible predictive directions between trauma exposure and executive functioning in children in a community sample. The sample consists of 1006 children from two time points with a seven years' time interval of a longitudinal Dutch birth cohort study, the ABCD-study (Van Eijsden et al., 2011). We analyzed the longitudinal associations between trauma exposure and executive functioning using structural equation modeling. The results demonstrated that (after controlling for prenatal substance exposure and mothers' educational level) trauma exposure before age 5 is predictive of poorer executive functioning at age 12 and trauma exposure between age 6 and 12. However, the association between executive functioning at age 5 and trauma exposure between age 6 and 12 was not statistically significant. Our results indicate that early life trauma exposure has a long term impact on later executive functioning and not the other way around. On top of that, trauma exposure seems to accumulate across childhood when children are exposed to a traumatic event before the age of 5. When looking at the potential moderating role of parenting behavior we found no evidence for such a moderating effect of parenting behavior. Our findings showed that children exposed to trauma early in life may experience problems in executive functioning later in life and they seem at higher risk for cumulative trauma exposure. Clinical practice should take this into account in both the way they provide (early) mental health care and in prevention and recognition of early trauma exposure.

Maternal long-chain polyunsaturated fatty acid status during early pregnancy: Association with child behavioral problems and the role of autonomic nervous system activity.

BACKGROUND & AIMS: The prenatal environment, including availability of critical nutrients, has a profound impact on offspring development. The present study examined the association between maternal long-chain polyunsaturated fatty acid (LC-PUFA) status during pregnancy and later child behavioral problems at the age of 5-6 years. In light of evidence of autonomic nervous system (ANS) dysregulation in some behavioral problems, study further tested if the above association is statistically mediated by cardiac ANS activity. METHODS: Data was collected as part of the Amsterdam Born Children and their Development-study and complete data were available for 1717 mothers and their offspring. Maternal LC-PUFA status was assessed during early pregnancy (mean gestation = 12.7, SD = 2.5 weeks) and quantified as levels of docosahexenoic acid (DHA), arachidonic acid (AA), eicosapentaenoic acid (EPA), as well as the ratio of n-6:n-3 fatty acids. Child emotional problems and peer problems (internalizing problems), as well as conduct problems and inattention/hyperactivity (externalizing problems), were assessed using the Strengths and Difficulties Questionnaire as rated by the mother and teacher at 5-6 years. Child cardiac respiratory sinus arrhythmia (RSA), pre-ejection period (PEP), and heart rate (HR) were utilized as measures of ANS activity at 5-6 years. RESULTS: The results confirmed an association between maternal LC-PUFA status and internalizing behavioral problems as rated by the mother, as shown for DHA (ß = -0.11;p < 0.01), EPA (ß = -0.22;p < 0.05), and n-6:n-3 LC-PUFA (ß = 0.17;p < 0.01). Statistical mediation was only demonstrated for HR. No associations were observed between LC-PUFA status and externalizing behavioral problems. CONCLUSIONS: The present results are consistent with a role of maternal LC-PUFA status in internalizing behavioral problems as rated by the mother. These results were not observed when problem behavior was rated by the teacher. Analyses did not yield strong evidence supporting ANS activity as a possible mediator in this relationship.

Gestational diabetes mellitus among Sub-Saharan African and Surinamese women in the Netherlands.

AIM: We assessed the association between ethnicity and the risk of gestational diabetes mellitus (GDM) in the Netherlands. METHODS: A cohort of 7815 women with known GDM status and ethnicity, including women of Sub-Saharan African ethnicity who are currently not identified as high-risk in guidelines. We compared GDM rates among participants of ethnicity to those of ethnic Dutch participants. We employed multivariable regression to correct for possible confounders, including maternal age, pre-pregnancy body mass index (BMI), and education. GDM prevalence and odds ratios based on ethnicity were the main outcome measures. RESULTS: The prevalence rates of GDM according to ethnicity were: Dutch 0.6%, South-Asian Surinamese 6.9%, African-Surinamese 3.5%, Antillean 1.0%, Turkish 1.0%, Moroccan 1.4%, Ghanaian 6.8%, Sub-Saharan African 3.5%, other Western 0.5% and other non-Western 2.8%. After adjustment for age, pre-pregnancy BMI, and education duration, compared with the reference Dutch-ethnicity population, adjusted odds ratios (aOR) for GDM were statistically significantly higher in South-Asian Surinamese (aOR 10.9; 95% Confidence Interval (CI), 4.7-25.0), African-Surinamese (4.3; 2.0-9.2), Ghanaian (6.5; 3.0-14.5), Sub-Saharan African (5.7; 2.0-16.0), and other non-Western women (4.5; 2.2-9.0). GDM was not significantly increased among Antillean (1.4; 0.2-10.3), Turkish (1.4; 0.4-4.2), Moroccan (1.8; 0.8-4.0), and other Western women (0.8; 0.3-2.2). CONCLUSIONS: This study shows for the first time in the Netherlands that women of Ghanaian or other Sub-Saharan African ethnicity have an increased risk of developing GDM than the Dutch. This calls for adaptation of the Dutch guidelines of screening high-risk groups for GDM and more awareness amongst obstetric caregivers.

Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

Prospective associations of age at complementary feeding and exclusive breastfeeding duration with body mass index at 5-6 years within different risk groups.

BACKGROUND: Children with overweight or obesity are at risk for developing obesity in adulthood. Certain maternal characteristics, such as ethnicity, education, body mass index (BMI) or neighbourhood, are determinants for childhood overweight risk. There are large variations in how mothers differing in these characteristics feed their infants. Therefore, associations of age at complementary feeding, exclusive breast feeding duration with childhood overweight may differ in these groups. Understanding these associations would be essential to develop overweight prevention strategies. OBJECTIVES: The objective of this study is to study the associations of age at complementary feeding, exclusive breastfeeding duration with BMI-standard deviation score (SDS) at 5-6 years within risk groups. METHODS: Using data from the Amsterdam Born Children and their Development study, a population-based birth cohort (n = 4495), we formed groups of children at varying risk of overweight according to maternal characteristics of ethnicity, education, pre-pregnancy BMI and neighbourhood. Linear and logistic regression analyses were conducted. RESULTS: Complementary feeding after 5 months of age was associated with lower BMI-SDS in children of mothers of Dutch ethnicity (B: -0.12; 95% CI: -0.21, -0.04), medium-level education (-0.19; -0.30, -0.08), normal BMI (-0.08; -0.16, -0.01) and high-risk neighbourhood (-0.16; -0.29, -0.02). Compared with exclusive breastfeeding for <3 months, exclusive breastfeeding for ≥6 months was associated with lower BMI-SDS in groups of medium-level education (-0.28; 0.44, -0.11), normal BMI (-0.18; -0.29, -0.08) and medium-risk (-0.18; -0.33, -0.04) and high-risk (-0.22; -0.42, -0.02) neighbourhoods. CONCLUSIONS: Associations between infant feeding practices and childhood BMI may differ between risk groups, implying that overweight prevention strategies should be group-specific.

Maternal verbally aggressive behavior in early infancy is associated with blood pressure at age 5-6.

Early life stress has been shown to contribute to alterations in biobehavioral regulation. Whereas many different forms of childhood adversities have been studied in relation to cardiovascular outcomes, very little is known about potential associations between caregivers' verbally aggressive behavior and heart rate and blood pressure in the child. This prospective study examined whether maternal verbally aggressive behavior in early infancy is associated with heart rate or blood pressure at age 5-6. In the Amsterdam Born Children and their Development study, a large prospective, population-based birth cohort, maternal verbally aggressive behavior was assessed by questionnaire in the 13th week after birth. The child's blood pressure and heart rate were measured during rest at age 5-6 (n=2553 included). Maternal verbally aggressive behavior in infancy was associated with a higher systolic blood pressure (SBP) both in supine and sitting position after adjustment for sex, height and age (SBP supine B=1.01 mmHg; 95% CI [0.06; 1.95] and SPB sitting B=1.29 mmHg; 95% CI [0.12; 2.46]). Adjustment for potential confounding variables, such as other mother-infant dyad aspects, family hypertension and child's BMI, only slightly attenuated the associations (SBP supine B=0.99 mmHg; 95% CI [0.06; 1.93] and SPB sitting B=1.11 mmHg; 95% CI [-0.06; 2.27]). Maternal verbally aggressive behavior was not associated with diastolic blood pressure or heart rate at age 5-6. Maternal verbally aggressive behavior might be an important early life stressor with negative impact on blood pressure later in life, which should be further investigated. Possible underlying mechanisms are discussed.

Maternal and paternal family history of diabetes in second-degree relatives and metabolic outcomes at age 5-6 years: The ABCD Study.

AIM: To investigate whether children with a family history of diabetes (FHD) in second-degree relatives (grandparents, aunts/uncles) are at increased risk of developing obesity and diabetes, and whether the risk differs between maternal or paternal transmission. METHODS: In the multiethnic population-based cohort Amsterdam-Born Children and Their Development (ABCD) Study, body mass index (BMI), waist-to-height ratio (WHR), fat percentage (fat%), fasting glucose and C-peptide in 5- or 6-year-old children with no second-degree FHD (n=2226) were compared with children with maternal-only (n=353), paternal-only (n=281) or both maternal and paternal (n=164) second-degree FHD. Children of diabetic mothers or fathers were excluded. RESULTS: None of the children in any of our FHD categories differed in body composition after adjusting for maternal, paternal and childhood lifestyle covariates. However, children with both maternal and paternal second-degree FHD had increased C-peptide levels (0.03nmol, 95% CI: 0.01-0.05) compared with those in the other three study groups. Results were similar when analyses were restricted to only the Dutch children. CONCLUSION: Children with FHD in second-degree relatives on both maternal and paternal sides already have higher C-peptide levels at an early age. This might be the result of a double burden of a shared obesogenic lifestyle, or of more diverse diabetogenic genes compared to children without FHD or with only FHD in one side of the family. In any case, second-degree FHD could be used as a public-health screening tool to identify children at risk of adverse metabolic outcomes and of possible future disease.

Vitamin B12 and folate status in early pregnancy and cardiometabolic risk factors in the offspring at age 5-6 years: findings from the ABCD multi-ethnic birth cohort.

OBJECTIVE: To explore whether maternal vitamin B12 and folate status during early pregnancy are associated with cardiometabolic risk factors in the offspring at age 5-6. DESIGN: Prospective multi-ethnic birth cohort, the Amsterdam Born Children and their Development study (ABCD). SETTING: 12,373 pregnant women living in Amsterdam were approached between 2003 and 2004 for participation in the study. POPULATION: Mother-child pairs for whom information on maternal vitamin B12 or folate status in early gestation and health at age 5-6 years was available (n = 1950). METHODS: Vitamin B12 and folate concentrations were determined in maternal serum at intake in early pregnancy (median 13 weeks' gestation). Anthropometric measurements, blood pressure and fasting blood samples were collected during a health check of children aged 5-6 years. Multiple linear regression was performed to investigate the association between maternal serum concentrations and children's outcomes, corrected for confounders. MAIN OUTCOME MEASURES: Gestational age at birth, birthweight, body mass index (BMI), glucose levels, triglyceride levels, blood pressure and heart rate of the offspring at age 5-6. RESULTS: Low maternal folate levels during early pregnancy were associated with slightly higher BMI in the offspring [decrease per 10 units: ß 0.07 kg/m(2), 95% confidence interval (CI) 0.01, 0.13]. Low maternal vitamin B12 concentrations were associated with higher heart rates (decrease per 100 units: ß 0.49 beats/min, 95% CI 0.11, 0.87). CONCLUSION: This study provides further evidence that maternal nutrition in early pregnancy may possibly program cardiometabolic health of the offspring. TWEETABLE ABSTRACT: Low folate and vitamin B12 levels during pregnancy are associated with higher BMI and heart rate in offspring.

Perinatal outcome in singleton pregnancies complicated with preeclampsia and eclampsia in Ecuador.

Preeclampsia in Ecuador is an understudied subject since available epidemiological data are scarce. The aim of this study was to describe perinatal outcomes among singleton pregnancies complicated with preeclampsia and eclampsia in a sample of low-income Ecuadorian women. Pregnant women complicated with preeclampsia (mild and severe) and eclampsia (defined according to criteria of the ACOG) delivering at the Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil, Ecuador were surveyed with a structured questionnaire containing maternal (socio-demographic) and neonatal data. Perinatal outcomes were compared according to severity of clinical presentation. A total of 163 women with preeclampsia [mild (23.9%), severe (68.7%) and eclampsia (7.4%)] were surveyed. Perinatal mortality and stillbirth rate was similar among studied groups (mild vs. severe preeclampsia/eclampsia cases). However, severe cases displayed higher rates of adverse perinatal outcomes: lower birth Apgar scores, more preterm births, and more low birth weight and small for gestational age infants. Caesarean-section rate and the number of admissions to intensive or intermediate neonatal care were higher in severe cases. A similar trend was found when analysis excluded preterm gestations. In conclusion, in this specific low-income Ecuadorian population perinatal outcome was adverse in pregnancies complicated with severe preeclampsia/eclampsia.

Deviant early pregnancy maternal triglyceride levels and increased risk of congenital anomalies: a prospective community-based cohort study.

OBJECTIVE: The maternal lipid profile could be of importance in congenital anomaly development. This study therefore investigates whether the maternal lipid profile during early pregnancy is associated with major nonsyndromic congenital anomalies (MNCA). DESIGN: Prospective community-based cohort study. SETTING: Amsterdam Born Children and their Development (ABCD) study. POPULATION: A cohort of 3074 pregnant women recruited in 2003-2004 and their offspring. METHODS: Non-fasting blood samples from pregnant women participating in the ABCD-study (median 12.9 weeks of gestation) were analysed for triglycerides (TG), cholesterol (TC), free fatty acids (FFA), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA) (n = 3074). The perinatal outcome (MNCA) was obtained from the Youth Health Care Registration and two questionnaires. Adjustment was made for ethnicity. MAIN OUTCOME MEASURE: MNCA prevalence. RESULTS: The prevalence of MNCA was 2.2% (n = 68: 20 cardiovascular, 25 bone and muscle, and 23 other single anomalies). A nonlinear association was found between maternal TG levels and MNCA prevalence. With a lower or higher level of maternal TG, the estimated probability increased: a TG level of 0.73 mmol/l (5th percentile), of 1.28 mmol/l (50th percentile), and of 2.35 mmol/l (95th percentile) corresponded with an estimated probability of 3.6, 2.1, and 2.9%, respectively. Unadjusted subgroup analyses showed that the U-shaped association was most prominent for cardiovascular congenital anomalies. Other lipids were not associated with MNCA. CONCLUSIONS: Both low and high maternal TG levels during early pregnancy were associated with an increased risk of MNCA in offspring. This suggests that an attempt should be made to normalise TG levels before or during early pregnancy; however, replication of our results is necessary before clinical practice recommendations can be made.

The association of birth weight and infant growth with physical fitness at 8-9 years of age--the ABCD study.

BACKGROUND: Low birth weight and accelerated infant growth are independently associated with childhood obesity. We hypothesized that birth weight and infant growth are associated with physical fitness in childhood, and thereby could act as a link in the developmental origins of obesity. In addition, we assessed whether these associations were mediated by fat-free mass (FFM), moderate-to-vigorous physical activity (MVPA) or sedentary behavior (SB). METHODS: We assessed physical fitness in 194 children of Dutch ethnicity aged 8.6 (±0.35) years from the ABCD cohort. Aerobic fitness was assessed using the 20-meter multistage shuttle run test (20-m MSRT), and neuromuscular fitness using the standing broad jump (SBJ) test and hand grip strength test. MVPA and SB were measured by accelerometry, and FFM by bioelectrical impedance analysis. Low birth weight was defined as below the 10th percentile and accelerated infant growth as an s.d. score weight gain of >0.67 between birth and 12 months. RESULTS: Children with low birth weight and subsequent accelerated infant growth attained a lower 20-m MSRT score than the remainder of the cohort, adjusted for multiple confounders (P<0.01). Birth weight and infant growth were both independently positively associated with hand grip strength, but not after adjusting for current height and body mass index. There was no association of birth weight or infant growth with SBJ. FFM mediated >75% of the association of birth weight and infant growth with hand grip strength, but FFM, MVPA and SB did not mediate the associations with 20-m MSRT. CONCLUSIONS: Our results indicate that low birth weight and accelerated infant growth might negatively affect childhood aerobic and neuromuscular fitness. Differences in FFM largely explain the developmental origins of neuromuscular fitness. Consequently impaired fitness may constitute a link between low birth weight, accelerated infant growth and obesity. Hence, optimization of fitness in these children may affect their obesity and cardiovascular disease risk.

Associations of infant feeding and timing of linear growth and relative weight gain during early life with childhood body composition.

BACKGROUND: Growth and feeding during infancy have been associated with later life body mass index. However, the associations of infant feeding, linear growth and weight gain relative to linear growth with separate components of body composition remain unclear. METHODS: Of 5551 children with collected growth and infant-feeding data in a prospective cohort study (Amsterdam Born Children and their Development), body composition measured using bioelectrical impedance analysis at the age of 5-6 years was available for 2227 children. We assessed how feeding (duration of full breastfeeding and timing of introduction of complementary feeding) and conditional variables representing linear growth and relative weight gain were associated with childhood fat-free mass (FFM) and fat mass (FM). RESULTS: Birth weight was positively associated with both FFM and FM in childhood, and more strongly with FFM than FM. Faster linear growth and faster relative weight gain at all ages in infancy were positively associated with childhood FFM and FM. The associations with FM were stronger for relative weight gain than for linear growth (FM z score: ß coefficient 0.23 (95% con 0.19 to 0.26), P<0.001 and 0.14 (0.11 to 0.17), P<0.001 per s.d. change in relative weight gain and linear growth between 1 and 3 months, respectively). Compared with full breastfeeding <1 month, full breastfeeding >6 months was associated with lower FM (FM z score: -0.17 (-0.28 to -0.05), P=0.005) and lower FFM (FFM z score: -0.13 (-0.23 to -0.03), P=0.015), as was the introduction of complementary feeding >6 months (FM z score: -0.22 (-0.38 to -0.07), P=0.004), compared with <4 months. CONCLUSIONS: Faster infant weight gain is associated with a healthier childhood body composition when it is caused by faster linear growth. Full breastfeeding >6 months and introduction of complementary feeding >6 months are associated with lower childhood FM.

Weight loss in pregnancy and cardiometabolic profile in childhood: findings from a longitudinal birth cohort.

OBJECTIVE: To investigate the consequences of weight loss in pregnancy on pregnancy outcomes and cardiometabolic profile in childhood. DESIGN: Prospective birth cohort (ABCD study). SETTING: Between 2003 and 2004, all pregnant women in Amsterdam were approached for study participation. POPULATION: 7818 pregnant women were included, of which 3165 consented to having their children examined at 5-6 years of age. In 1956 children fasting capillary blood samples were also taken. METHODS: At antenatal booking, women answered questions about their pregnancy and whether they suffered from severe weight loss (SWL; >5 kg). Pregnancy details and outcomes were available through the obstetric caregiver. MAIN OUTCOME MEASURES: At birth main outcome measures were prematurity (<37 weeks) and birthweight. At follow-up, body mass index (BMI), blood pressure, glucose and lipids were assessed. RESULTS: SWL occurred in 6.8% of cases. Women with SWL had similar preterm birth rates compared with women without these complaints (adjusted OR 1.1, 95%CI 0.7, 1.7). Birthweight (adjusted difference - 31 g, 95%CI -76, 15) and BMI at 5-6 years of age (adjusted difference 0.2 kg/m(2) , 95%CI 0.0, 0.5) were similar in children born to mothers with SWL and without SWL, but blood pressure was increased. For diastolic blood pressure this association was independent of confounders (adjusted difference 1.4 mmHg, 95%CI 0.4, 2.4). Lipid and glucose levels were not significantly different between these groups. CONCLUSION: Early pregnancy weight loss, usually occurring as a manifestation of hyperemesis gravidarum, could have long-term consequences for offspring health.

No associations of prenatal maternal psychosocial stress with fasting glucose metabolism in offspring at 5-6 years of age.

Highly prevalent maternal psychosocial complaints are accompanied by increases in glucocorticoid stress hormones, which may predispose the offspring for type 2 diabetes and cardiovascular disease later in adulthood. The aim of the current research is to study whether prenatal maternal psychosocial stress is associated with parameters of blood glucose metabolism in their children aged 5-6 years. The study design was a prospective birth cohort (the Amsterdam Born Children and their Development study, the Netherlands). Depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain were recorded by questionnaire (gestational week 16). A cumulative score was also calculated. Possible sex differences in the associations were considered. The subjects were 1952 mother-child pairs. Outcome measures were fasting glucose (n=1952), C-peptide and insulin resistance (HOMA2-IR) (n=1478) in the children at the age of 5-6 years. The stress scales, single and cumulative, were not associated with glucose/C-peptide/insulin resistance (all P>0.05). We did not find evidence for sex differences. In conclusion, we did not find evidence for an association between psychosocial stress during early pregnancy and parameters of glucose metabolism in offspring at the age of 5-6 years. Differences emerging later in life or in response to a metabolic challenge should not be ruled out.

Increased maternal BMI is associated with infant wheezing in early life: a prospective cohort study.

Rates of obesity are increasing in women of child bearing age with negative impacts on maternal and offspring health. Emerging evidence suggests in utero origins of respiratory health in offspring of obese mothers but mechanisms are unknown. Changes in maternal cortisol levels are one potential factor as cortisol levels are altered in obesity and cortisol is separately implicated in development of offspring wheeze. We aimed to assess whether increased pre-pregnancy maternal body mass index (BMI) was associated with offspring early life wheezing, and whether this was mediated by altered cortisol levels in the mother. In a prospective community-based cohort (Amsterdam Born Children and their Development cohort), women completed questionnaires during pregnancy and at 3-5 months post-delivery regarding self-history of asthma and atopy, and of wheezing of their offspring (n=4860). Pre-pregnancy BMI was recorded and serum total cortisol levels were measured in a subset of women (n=2227) at their first antenatal visit. A total of 20.2% (n=984) women were overweight or obese and 10.3% reported wheezing in their offspring. Maternal BMI was associated with offspring wheezing (1 unit (kg/m2) increase, OR: 1.03; 95% CI: 1.00-1.05), after correction for confounders. Although maternal cortisol levels were lower in overweight mothers and those with a history of asthma, maternal cortisol levels did not mediate the increased offspring wheezing. Pre-pregnancy BMI impacts on baby wheezing, which is not mediated by lower cortisol levels. As the prevalence of obesity in women of child-bearing age is increasing, further studies are needed to investigate modifiable maternal factors to avoid risk of wheezing in young children.