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2.
J Dev Orig Health Dis ; : 1-9, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31474237

RESUMO

BACKGROUND: Evidence suggests that low birth weight and fetal exposure to extreme maternal undernutrition is associated with cardiovascular disease in adulthood. Hyperemesis gravidarum, a clinical entity characterized by severe nausea and excess vomiting leading to a suboptimal maternal nutritional status during early pregnancy, is associated with an increased risk of adverse pregnancy outcomes. Several studies also showed that different measures related to hyperemesis gravidarum, such as maternal daily vomiting or severe weight loss, are associated with increased risks of adverse fetal pregnancy outcomes. Not much is known about long-term offspring consequences of maternal hyperemesis gravidarum and related measures during pregnancy. We examined the associations of maternal daily vomiting during early pregnancy, as a measure related to hyperemesis gravidarum, with childhood cardiovascular risk factors. METHODS: In a population-based prospective cohort study from early pregnancy onwards among 4,769 mothers and their children in Rotterdam, the Netherlands, we measured childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, preperitoneal fat mass area, blood pressure, lipids, and insulin levels. We used multiple regression analyses to assess the associations of maternal vomiting during early pregnancy with childhood cardiovascular outcomes. RESULTS: Compared with the children of mothers without daily vomiting during early pregnancy, the children of mothers with daily vomiting during early pregnancy had a higher childhood total body fat mass (difference 0.12 standard deviation score [SDS]; 95% confidence interval [CI] 0.03-0.20), android/gynoid fat mass ratio (difference 0.13 SDS; 95% CI 0.04-0.23), and preperitoneal fat mass area (difference 0.10 SDS; 95% CI 0-0.20). These associations were not explained by birth characteristics but partly explained by higher infant growth. Maternal daily vomiting during early pregnancy was not associated with childhood blood pressure, lipids, and insulin levels. CONCLUSIONS: Maternal daily vomiting during early pregnancy is associated with higher childhood total body fat mass and abdominal fat mass levels, but not with other cardiovascular risk factors. Further studies are needed to replicate these findings, to explore the underlying mechanisms and to assess the long-term consequences.

3.
J Am Heart Assoc ; 8(16): e012821, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31405324

RESUMO

Background An adverse fetal environment leads to fetal hemodynamic adaptations with cardiac flow alterations that may subsequently affect cardiac development. We examined the associations of third trimester placental and fetal cardiac hemodynamics with cardiac outcomes in school-age children. Methods and Results We performed a population-based prospective cohort study among 547 mothers and their children. At a gestational age of 30.4 (95% range 28.4-32.7) weeks, we measured umbilical and cerebral artery resistance, cardiac output, and tricuspid and mitral E/A waves with Doppler. At the median age of 10.0 years (95% range 9.4-11.7) we measured cardiac outcomes with cardiac magnetic resonance imaging. Cardiac outcomes included right ventricular end-diastolic volume) and right ventricular ejection fraction, left ventricular end diastolic volume and left ventricular ejection fraction, left ventricular mass, and left ventricular mass-to-volume ratio as left ventricular mass/left ventricular end diastolic volume. Higher third-trimester umbilical artery resistance was associated with higher childhood right ventricular ejection fraction (P value <0.05), but not with other cardiac outcomes. The third-trimester umbilical artery-cerebral artery pulsatility index ratio was not associated with childhood cardiac outcomes. Higher third-trimester fetal left cardiac output was associated with lower childhood left ventricular ejection fraction and higher left ventricular mass-to-volume ratio (P value <0.05). Third-trimester fetal right cardiac output was not associated with childhood cardiac outcomes. A higher third-trimester fetal tricuspid valve E/A ratio was associated with higher childhood right ventricular ejection fraction (P value <0.05). Conclusions Our findings suggest that fetal cardiac fetal blood flow redistribution may have long-term effects on cardiac structure and function. These results should be considered as hypothesis generating and need further replication.

4.
Diabetologia ; 62(10): 1880-1890, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31392381

RESUMO

AIMS/HYPOTHESIS: The study aimed to assess the associations of maternal early-pregnancy blood glucose levels with fetal growth throughout pregnancy and the risks of adverse birth outcomes. METHODS: In a population-based prospective cohort study among 6116 pregnant women, maternal non-fasting glucose levels were measured in blood plasma at a median 13.2 weeks of gestation (95% range 9.6-17.6). We measured fetal growth by ultrasound in each pregnancy period. We obtained information about birth outcomes from medical records and maternal sociodemographic and lifestyle factors from questionnaires. RESULTS: Higher maternal early-pregnancy non-fasting glucose levels were associated with altered fetal growth patterns, characterised by decreased fetal growth rates in mid-pregnancy and increased fetal growth rates from late pregnancy onwards, resulting in an increased length and weight at birth (p ≤0.05 for all). A weaker association of maternal early-pregnancy non-fasting glucose levels with fetal head circumference growth rates was present. Higher maternal early-pregnancy non-fasting glucose levels were also associated with an increased risk of delivering a large-for-gestational-age infant, but decreased risk of delivering a small-for-gestational-age infant (OR 1.28 [95% CI 1.16, 1.41], OR 0.88 [95% CI 0.79, 0.98] per mmol/l increase in maternal early-pregnancy non-fasting glucose levels, respectively). These associations were not explained by maternal sociodemographic factors, lifestyle factors or BMI. Maternal early-pregnancy non-fasting glucose levels were not associated with preterm birth or delivery complications. CONCLUSIONS/INTERPRETATION: Higher maternal early-pregnancy non-fasting glucose levels are associated with decreased fetal growth rates in mid-pregnancy and increased fetal growth rates from late pregnancy onwards, and an increased risk of delivering a large-for-gestational-age infant. Future preventive strategies need to focus on screening for an impaired maternal glucose metabolism from preconception and early pregnancy onwards to improve birth outcomes.

5.
Environ Health Perspect ; 127(8): 87005, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31419153

RESUMO

BACKGROUND: Perturbations in fetal growth may have adverse consequences for childhood and later life health. Organophosphate pesticide (OP) exposure has been associated with reduced birth weight at delivery but results are not consistent. We investigated this question by utilizing ultrasound measures of size in utero in combination with measures from delivery. METHODS: Within Generation R, a population-based prospective cohort conducted between 2002 and 2006 in Rotterdam, Netherlands, we measured dialkyl phosphates (DAPs), OP metabolites, in urine samples from early, middle, and late pregnancy and created a subject-specific average to estimate OP exposure ([Formula: see text]). Ultrasound measures of head circumference, femur length, and estimated fetal weight from middle and late pregnancy and delivery measures were converted to standard deviation scores (SDS). Associations with DAP average were examined in linear mixed effects models that included an interaction term between gestational age at measurement and DAP average to investigate whether the relationship differed over time. Windows of vulnerability to exposure were assessed by modeling urinary DAPs from each visit in relation to growth measurements. RESULTS: A 10-fold increase in average DAPs was associated with a [Formula: see text] SDS decrease in fetal length (95% [Formula: see text], [Formula: see text]) and a [Formula: see text] SDS decrease in estimated fetal weight (95% [Formula: see text], [Formula: see text]) at 20 weeks of gestation. These differences corresponded to 5% and 6% decreases relative to the mean. Effect estimates were greatest in magnitude for DAP concentrations measured early in pregnancy. Associations between average DAPs and growth measures at delivery were positive but not significant for head circumference and length and were null for weight. CONCLUSIONS: Maternal urinary DAPs were associated with decreased fetal weight and length measured during mid-pregnancy, but not at delivery. https://doi.org/10.1289/EHP4858.

6.
Eur J Prev Cardiol ; : 2047487319866022, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31357885

RESUMO

OBJECTIVES: Early life is critical for cardiac development. We examined the associations of longitudinal fetal and childhood growth patterns with childhood right and left ventricular structures measured by cardiac magnetic resonance imaging. METHODS: In a population-based prospective cohort study among 2827 children, we measured growth at 20 and 30 weeks of pregnancy, at birth, 0.5, 1, 2, 6 and 10 years. At 10 years, we measured right ventricular end-diastolic volume, left ventricular end-diastolic volume, left ventricular mass and left ventricular mass-to-volume ratio by cardiac magnetic resonance imaging. RESULTS: Small size for gestational age at birth was associated with smaller right and left ventricular end-diastolic volume relative to current body surface area, but with larger left ventricular mass-to-volume ratio (P < 0.05). Children in the upper 25% of right and left ventricular end-diastolic volume and left ventricular mass at age 10 years were larger at birth and became taller and leaner in childhood (P < 0.05). In contrast, children in the lower 25% of right and left ventricular end-diastolic volume and left ventricular mass were smaller at birth and became shorter and heavier in childhood (P < 0.05). Both fetal and childhood growth were independently of each other associated with childhood right and left ventricular end-diastolic volume and left ventricular mass. CONCLUSION: Children who are larger at birth and grow taller and leaner in childhood have larger hearts relative to body surface area. Small size at birth children, who grow shorter and heavier in childhood, have relatively smaller hearts with larger left ventricular mass-to-volume ratio. Both fetal and childhood growth are important for the development of cardiac dimensions.

7.
Appetite ; 141: 104295, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31128200

RESUMO

INTRODUCTION: Only a few studies have prospectively examined stability of eating behaviors in childhood. These argue that eating behaviors are fairly stable from early childhood onwards, but knowledge on individual patterns across childhood is lacking. Here, we examined patterns of eating behaviors from ages 4-10 years in a population-based sample and aimed to identify parental and earlylife predictors of these patterns. METHODS: Participants were 3514 children from The Generation R Study with repeated assessments of the Child Eating Behavior Questionnaire at ages 4 and 10 years. Patterns of emotional overeating, food responsiveness, enjoyment of food and satiety responsiveness were studied with person-centered Latent Class Growth Analysis with the aim to identify sub-groups of children with distinct eating behavior patterns. Using univariate multinomial logistic and linear regression, parental and early life predictors of eating behavior patterns were examined. RESULTS: We identified three patterns of emotional overeating (stable low (n = 2240); moderately increasing (n = 1028); strongly increasing (n = 246)) and five patterns of food responsiveness (stable low (n = 2343); high decreasing (n = 238); moderately increasing (n = 679); strongly increasing (n = 141); stable high (n = 113)) from 4 to 10 years. For enjoyment of food and satiety responsiveness a similar pattern was identified for all children. Obesogenic eating behavior patterns were associated with a higher birth weight and BMI, emotional and behavioral problems, maternal overweight/obesity and controlling feeding strategies. DISCUSSION: This study suggests that children develop distinct patterns of emotional overeating and food responsiveness across childhood. Parental and early life predictors, particularly a higher weight status and psychiatric problems, are potential correlates of the development and maintenance of unhealthy eating behavior patterns across childhood. This knowledge might help identifying children at risk of developing obesogenic eating behaviors.

8.
Obesity (Silver Spring) ; 27(5): 822-829, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30957987

RESUMO

OBJECTIVE: This study examined the prospective, potentially bidirectional association of aggressive behavior with BMI and body composition across childhood in three population-based cohorts. METHODS: Repeated measures of aggression and BMI were available from the Generation R Study between ages 6 and 10 years (N = 3,974), the Netherlands Twin Register (NTR) between ages 7 and 10 years (N = 10,328), and the Swedish Twin Study of Child and Adolescent Development (TCHAD) between ages 9 and 14 years (N = 1,462). In all samples, aggression was assessed with the Child Behavior Checklist. Fat mass and fat-free mass were available in the Generation R Study. Associations were examined with cross-lagged modeling. RESULTS: Aggressive behavior at baseline was associated with higher BMI at follow-up in the Generation R Study (ß = 0.02, 95% CI: 0.00 to 0.04), in NTR (ß = 0.04, 95% CI: 0.02 to 0.06), and in TCHAD (ß = 0.03, 95% CI: -0.02 to 0.07). Aggressive behavior was prospectively associated with higher fat mass (ß = 0.03, 95% CI: 0.01 to 0.05) but not fat-free mass. There was no evidence that BMI or body composition preceded aggressive behavior. CONCLUSIONS: More aggressive behavior was prospectively associated with higher BMI and fat mass. This suggests that aggression contributes to the obesity problem, and future research should study whether these behavioral pathways to childhood obesity are modifiable.

9.
Hum Reprod ; 34(2): 365-373, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30576447

RESUMO

STUDY QUESTION: Are early-pregnancy urinary bisphenol and phthalate metabolite concentrations associated with placental function markers, blood pressure (BP) trajectories during pregnancy and risk of gestational hypertensive disorders? SUMMARY ANSWER: Early-pregnancy bisphenols and phthalate metabolites were not consistently associated with maternal BP changes or gestational hypertensive disorders, but subclinical, statistically significant associations with placental angiogenic markers and placental hemodynamics were identified. WHAT IS KNOWN ALREADY: In vitro studies suggest that bisphenols and phthalate metabolites may disrupt early placental development and affect the risk of gestational hypertensive disorders. Previous studies investigating effects of bisphenols and phthalate metabolites on gestational hypertensive disorders reported inconsistent results and did not examine placental function or BP throughout pregnancy. STUDY DESIGN, SIZE, DURATION: In a population-based prospective cohort study, bisphenol and phthalate metabolite concentrations were measured in a spot urine sample in early pregnancy among 1396 women whose children participated in postnatal follow-up measurements. PARTICIPANTS/MATERIALS, SETTING, METHODS: After exclusion of women without any BP measurement or with pre-existing hypertension, 1233 women were included in the analysis. Urinary bisphenol and phthalate metabolite concentrations were measured in early-pregnancy [median gestational age 13.1 weeks, inter-quartile range 12.1-14.5]. Molar sums of total bisphenols and of low molecular weight phthalate, high molecular weight (HMW) phthalate, di-2-ethylhexylphthalate, and di-n-octylphthalate metabolites were calculated. Placental angiogenic markers (placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt)-1), placental hemodynamic function measures (umbilical artery pulsatility index (PI), uterine artery resistance index (RI), notching and placental weight), and maternal BP were measured in different trimesters. Information on gestational hypertensive disorders was obtained from medical records. MAIN RESULTS AND THE ROLE OF CHANCE: Each log unit increase in HMW phthalate metabolites was associated with a 141.72 (95% CI: 29.13, 373.21) higher early pregnancy sFlt-1/PlGF ratio (range in total sample 9-900). This association was driven by mono-[(2-carboxymethyl)hexyl]phthalate. In the repeated measurements regression models, each log unit increase in bisphenol A was associated with a 0.15 SD (95% CI: 0.03, 0.26) higher intercept and -0.01 SD (95% CI: -0.01, -0.00) decreasing slope of the umbilical artery PI Z-score and a -1.28 SD (95% CI: -2.24, -0.33) lower intercept and 0.06 SD (95% CI: 0.02, 0.11) increasing slope of the uterine artery RI Z-score. These associations remained significant after Bonferroni correction. Early-pregnancy bisphenols or phthalate metabolites showed no consistent associations with any other outcome. LIMITATIONS, REASONS FOR CAUTION: Information on a large number of potential confounders was available but was partly self-reported. Bisphenols and phthalate metabolites, which typically have a half-life of 24-48 h, were measured via single spot urine samples in early-pregnancy. In addition, at the current sample size, the study was powered to detect an odds ratio of 1.57 for gestational hypertension and 1.78 for pre-eclampsia, but was underpowered to perform multivariable analyses for these outcomes. Further studies combining data from different cohorts may be necessary to increase power. These limitations are possible sources of non-differential misclassification leading to bias toward the null. WIDER IMPLICATIONS OF THE FINDINGS: Bisphenols and phthalate metabolites were not associated with longitudinal changes in BP in pregnancy in our low-risk population. The observed subclinical associations of phthalates with the sFlt-1/PlGF ratio and of bisphenol A with placental hemodynamics may contribute to adverse pregnancy outcomes. Our results are therefore more supportive of an association of early pregnancy bisphenols and phthalate metabolites with risk for pre-eclampsia than with gestational hypertension. STUDY FUNDING/COMPETING INTEREST(S): This analysis was supported by Grant (ES022972) from the National Institutes of Health, USA. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. The authors report no conflicts of interest.

10.
BMC Med ; 16(1): 201, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30396358

RESUMO

BACKGROUND: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies. METHODS: We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape. RESULTS: We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications. CONCLUSIONS: Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

11.
J Dev Orig Health Dis ; : 1-8, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30409238

RESUMO

Adverse exposures during fetal life and the postnatal period influence physical, cognitive and emotional development, and predispose to an increased risk of various chronic diseases throughout the life course. Findings from large observational studies in various populations and experimental animal studies have identified different modifiable risk factors in early life. Adverse maternal lifestyle factors, including overweight, unhealthy diet, sedentary behavior, smoking, alcohol consumption and stress in the preconception period and during pregnancy, are the most common modifiable risk factors leading to a suboptimal in-utero environment for fetal development. In the postnatal period, breastfeeding, infant growth and infant dietary intake are important modifiable factors influencing long-term offspring health outcomes. Despite the large amount of findings from observational studies, translation to lifestyle interventions seems to be challenging. Currently, randomized controlled trials focused on the influence of lifestyle interventions in these critical periods on short-term and long-term maternal and offspring health outcomes are scarce, have major limitations and do not show strong effects on maternal and offspring outcomes. New and innovative approaches are needed to move from describing these causes of ill-health to start tackling them using intervention approaches. Future randomized controlled lifestyle intervention studies and innovative observational studies, using quasi-experimental designs, are needed focused on the effects of an integrated lifestyle advice from preconception onwards on pregnancy outcomes and long-term health outcomes in offspring on a population level.

12.
Int J Obes (Lond) ; 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30232419

RESUMO

BACKGROUND/OBJECTIVES: Maternal obesity and excessive gestational weight gain are associated with an increased risk of obesity in offspring. It remains unclear whether maternal adiposity also affects organ fat, which has important adverse cardiometabolic health consequences and whether the associations reflect intrauterine causal mechanisms. We examined the associations of parental pre-pregnancy body mass index (BMI) and gestational weight gain with general, abdominal, pericardial, and liver fat in 10-year-old children. SUBJECTS/METHODS: In a population-based prospective cohort study among 2354 parents and their children, we obtained pre-pregnancy maternal and paternal BMI and gestational weight gain and offspring BMI, fat mass index (total fat/height4) by dual-energy X-ray absorptiometry, and subcutaneous fat index (subcutaneous fat/height4), visceral fat index (visceral fat/height3), pericardial fat index (pericardial fat/height3), and liver fat fraction by magnetic resonance imaging (MRI) at 10 years. RESULTS: A 1-standard deviation score (SDS) higher maternal pre-pregnancy BMI was associated with higher childhood BMI (difference 0.32 (95% confidence interval (CI) 0.28, 0.36) SDS), fat mass index (difference 0.28 (95% CI 0.24, 0.31) SDS), subcutaneous fat index (difference 0.26 (95% CI 0.22, 0.30) SDS), visceral fat index (difference 0.24 (95% CI 0.20, 0.28) SDS), pericardial fat index (difference 0.12 (95% CI 0.08, 0.16) SDS), and liver fat fraction (difference 0.15 (95% CI 0.11, 0.19) SDS). After conditioning each MRI adiposity measure on BMI at 10 years, higher maternal pre-pregnancy BMI remained associated with higher childhood subcutaneous and visceral fat indices. Smaller but not statistically different effect estimates were observed for paternal BMI. Gestational weight gain was not consistently associated with organ fat. CONCLUSIONS: Higher maternal pre-pregnancy BMI, but not gestational weight gain, was associated with higher general and organ fat. Similar associations of pre-pregnancy maternal and paternal BMI with offspring adiposity suggest a role of family shared lifestyle factors and genetics.

13.
Lancet Child Adolesc Health ; 2(11): 812-821, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30201470

RESUMO

BACKGROUND: Gestational diabetes and gestational hypertensive disorders are associated with offspring obesity, but the role of maternal adiposity in these associations remains unclear. We aimed to investigate whether these pregnancy complications affect the odds of offspring obesity independently of maternal obesity. METHODS: We did an individual participant data (IPD) meta-analysis of mother-offspring pairs from prospective birth cohort studies that had IPD on mothers with singleton liveborn children born from 1989 onwards and had information available about maternal gestational diabetes, gestational hypertension or pre-eclampsia, and childhood body-mass index (BMI). We applied multilevel mixed-effects models to assess associations of gestational diabetes, gestational hypertension, and pre-eclampsia with BMI SD scores and the odds of overweight and obesity throughout childhood, adjusting for lifestyle characteristics (offspring's sex, maternal age, educational level, ethnicity, parity, and smoking during pregnancy). We then explored the extent to which any association was explained by maternal pre-pregnancy or early-pregnancy BMI. FINDINGS: 160 757 mother-offspring pairs from 34 European or North American cohorts were analysed. Compared with uncomplicated pregnancies, gestational diabetes was associated with increased odds of overweight or obesity throughout childhood (odds ratio [OR] 1·59 [95% CI 1·36 to 1·86] for early childhood [age 2·0-4·9 years], 1·41 [1·26 to 1·57] for mid childhood [5·0-9·9 years], and 1·32 [0·97 to 1·78] for late childhood [10·0-17·9 years]); however, these associations attenuated towards the null following adjustment for maternal BMI (OR 1·35 [95% CI 1·15 to 1·58] for early childhood, 1·12 [1·00 to 1·25] for mid childhood, and 0·96 [0·71 to 1·31] for late childhood). Likewise, gestational hypertension was associated with increased odds of overweight throughout childhood (OR 1·19 [95% CI 1·01 to 1·39] for early childhood, 1·23 [1·15 to 1·32] for mid childhood, and 1·49 [1·30 to 1·70] for late childhood), but additional adjustment for maternal BMI largely explained these associations (1·01 [95% CI 0·86 to 1·19] for early childhood, 1·02 [0·95 to 1·10] for mid childhood, and 1·18 [1·03 to 1·36] for late childhood). Pre-eclampsia was associated with decreased BMI in early childhood only (difference in BMI SD score -0·05 SD score [95% CI -0·09 to -0·01]), and this association strengthened following additional adjustment for maternal BMI. INTERPRETATION: Although lowering maternal risk of gestational diabetes, gestational hypertension, and pre-eclampsia is important in relation to maternal and fetal pregnancy outcomes, such interventions are unlikely to have a direct impact on childhood obesity. Preventive strategies for reducing childhood obesity should focus on maternal BMI rather than on pregnancy complications. FUNDING: EU's Horizon 2020 research and innovation programme (LifeCycle Project).

14.
J Am Heart Assoc ; 7(21): e009847, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30608188

RESUMO

Background High blood pressure levels and higher arterial stiffness have been shown to be associated with lower cognition during adulthood, possibly by accumulative changes over time. However, vascular factors may already affect the brain during early life. Methods and Results We examined the relation between cognition and vascular factors within 5853 children from the Generation R Study (mean age 6.2 years) and 5187 adults from the Rotterdam Study (mean age 61.8 years). Diastolic and systolic blood pressure and arterial stiffness were assessed, the latter by measuring pulse-wave velocity and pulse pressure. For cognition, the Generation R Study relied on nonverbal intelligence, whereas the Rotterdam Study relied on a cognitive test battery to calculate the g-factor, a measure of global cognition. In the Generation R Study, standardized diastolic blood pressure showed a significant association with standardized nonverbal intelligence (ß=-0.030, 95% confidence interval=[-0.054; -0.005]) after full adjustment. This association held up after excluding the top diastolic blood pressure decile (ß=-0.042 [-0.075; -0.009]), suggesting that the relation holds in normotensives. Within the Rotterdam Study, standardized cognition associated linearly with standardized systolic blood pressure (ß=-0.036 [-0.060; -0.012]), standardized pulse-wave velocity (ß=-0.064 [-0.095; -0.033]), and standardized pulse pressure (ß=-0.044 [-0.069; -0.020], and nonlinearly with standardized diastolic blood pressure (quadratic term ß=-0.032 [-0.049; -0.015]) after full adjustment. Conclusions Blood pressure and cognition may already be related in the general population during early childhood, albeit differently than during adulthood.

15.
Eur J Endocrinol ; 177(4): 319-327, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28724570

RESUMO

OBJECTIVE: The cardiovascular system is a known target for thyroid hormone. Early-life cardiovascular alterations may lead to a higher risk of cardiovascular disease in adulthood. Little is known about the effects of thyroid hormone on cardiovascular function during childhood, including the role of body composition in this association. DESIGN: Population-based prospective cohort of children (n = 4251, median age 6 years, 95% range: 5.7-8.0 years). METHODS: Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) concentrations were measured to assess thyroid function. Left ventricular (LV) mass was assessed with echocardiography. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (CFPWV). Systolic and diastolic blood pressure (BP) was measured. Body composition was assessed by dual-energy X-ray absorptiometry scan. RESULTS: FT4 was inversely associated with LV mass (P = 0.002), and with lean body mass (P < 0.0001). The association of FT4 with LV mass was partially mediated through variability in lean body mass (55% mediated effect). TSH was inversely associated with LV mass (P = 0.010), predominantly in boys. TSH was positively associated with systolic and diastolic BP (both P < 0.001). FT4 was positively associated with CFPWV and diastolic BP (P < 0.0001, P = 0.008, respectively), and the latter association attenuated after adjustment for CFPWV. CONCLUSIONS: At the age of 6 years, higher FT4 is associated with lower LV mass (partially through effects on lean body mass) and with higher arterial stiffness, which may lead to higher BP. Our data also suggest different mechanisms via which TSH and FT4 are associated with cardiovascular function during early childhood.


Assuntos
Pressão Sanguínea/fisiologia , Composição Corporal/fisiologia , Glândula Tireoide/fisiologia , Tireotropina/sangue , Tiroxina/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Países Baixos/epidemiologia , Vigilância da População/métodos , Estudos Prospectivos , Análise de Onda de Pulso/tendências , Hormônios Tireóideos/sangue
16.
Clin Endocrinol (Oxf) ; 87(6): 799-806, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28666083

RESUMO

OBJECTIVE: Maternal prepregnancy obesity and excessive gestational weight gain are associated with pregnancy complications. Thyroid function is related to differences in body mass index (BMI) in adult populations. We examined the associations of maternal thyroid function in early pregnancy with maternal BMI and weight gain during pregnancy. DESIGN AND METHODS: In a population-based prospective cohort study among 5726 mothers, we measured maternal TSH and FT4 levels at 13.5 weeks of gestation (95% range: 9.7-17.6 weeks). Maternal weight was assessed before pregnancy and in each trimester. RESULTS: Higher maternal TSH levels were associated with higher prepregnancy BMI (difference: 0.18 kg/m2 [95% CI: 0.01, 0.36] per SD increase in maternal TSH level) and higher total gestational weight gain (difference: 0.02 kg/wk [95% CI: 0.01, 0.03] per SD increase in maternal TSH level). Higher maternal FT4 levels were associated with lower prepregnancy BMI (difference: -0.44 kg/m2 [95% CI: -0.63, -0.26] per SD increase in maternal FT4 level) and lower total gestational weight gain (difference: -0.01 kg/wk [95% CI: -0.02, -0.01] per SD increase in maternal FT4 level). The associations of maternal thyroid function with weight gain in early pregnancy were stronger than those with weight gain in mid and late-pregnancy. Maternal hypothyroidism was associated with higher prepregnancy BMI and early pregnancy weight gain, whereas opposite effects were observed for maternal hyperthyroidism (P<.05). CONCLUSIONS: Higher maternal TSH level and lower FT4 level in early pregnancy are associated with higher prepregnancy BMI and higher gestational weight gain. Further studies are needed to explore maternal and foetal consequences.


Assuntos
Obesidade/fisiopatologia , Glândula Tireoide/fisiologia , Ganho de Peso/fisiologia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Obesidade/sangue , Obesidade/epidemiologia , Gravidez , Estudos Prospectivos , Tireotropina/sangue , Adulto Jovem
17.
Eur J Prev Cardiol ; 24(13): 1408-1415, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28604079

RESUMO

Objective Cardiac structure and function are important predictors for cardiovascular disease in adults. Not much is known about tracking of cardiac measures, other than left ventricular mass, from early life onwards. We examined whether and to what extent cardiac measures track from infancy into school-age. Methods We performed a population-based prospective cohort study among 1072 children. Aortic root diameter, left atrial diameter, left ventricular mass, relative wall thickness and fractional shortening were measured repeatedly by echocardiography. We explored tracking between infancy (1.5, six and 24 months) and school-age (six and 10 years). Results Of all cardiac measures, aortic root diameter, left atrial diameter and left ventricular mass were significantly correlated between infancy and school-age ( r = 0.10-0.42, all p-values < 0.01), with the strongest correlations between 24 months and 10 years. Of the different structures, aortic root diameter showed the strongest correlations. Approximately 30% of children who were in the lowest or highest quartile of a measure at the age of 1.5 months remained in that quartile at the age of 10 years. When analysing the effects of the infant cardiac measures on the same outcomes at 10 years in conditional regression models, we observed effect estimates of the same size for the different age windows. Conclusion Our results suggest moderate tracking of structural cardiac measures from early infancy until school-age, which become stronger at older ages, but not of relative wall thickness or fractional shortening. Moderate tracking of cardiac structures suggests that cardiac structures are at least partly determined in early life.


Assuntos
Função Atrial/fisiologia , Doenças Cardiovasculares/diagnóstico , Ecocardiografia/métodos , Átrios do Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Vigilância da População , Função Ventricular/fisiologia , Volume Cardíaco , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Átrios do Coração/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Incidência , Lactente , Masculino , Países Baixos/epidemiologia , Prognóstico , Estudos Prospectivos
18.
Early Hum Dev ; 108: 23-28, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28364636

RESUMO

BACKGROUND: Not much is known about the associations of maternal obesity and excessive gestational weight gain with body fat in infancy. OBJECTIVE: To examine the associations of maternal pre-pregnancy body mass index and gestational weight gain with infant subcutaneous fat. METHODS: In a population-based prospective cohort study among 845 mothers and their infants, we obtained maternal pre-pregnancy body mass index and measured maternal weight during pregnancy. At 1.5, 6 and 24months, we estimated infant total subcutaneous fat (sum of biceps, triceps, suprailiacal and subscapular skinfold thicknesses) and central-to-total subcutaneous fat ratio (sum of suprailiacal and subscapular skinfold thicknesses/total subcutaneous fat). RESULTS: Maternal body mass index was positively associated with higher infant body mass index from 6months onwards. Maternal body mass index was not associated with infant subcutaneous fat measures at 1.5 or 6months. A 1-standard deviation scores (SDS) higher maternal body mass index was associated with a 0.09 (95% Confidence Interval 0.01, 0.17) SDS higher infant total subcutaneous fat at 24months, but not with central-to-total subcutaneous fat ratio. No associations were present for maternal total or period-specific gestational weight gain with infant fat. CONCLUSION: Maternal body mass index was positively associated with infant body mass index and total subcutaneous fat in late infancy. Maternal total and period-specific gestational weight gain were not associated with infant body fat mass measures.


Assuntos
Obesidade/epidemiologia , Complicações na Gravidez/epidemiologia , Gordura Subcutânea/crescimento & desenvolvimento , Ganho de Peso , Adulto , Desenvolvimento Infantil , Feminino , Humanos , Lactente , Masculino , Gravidez
19.
Am J Obstet Gynecol ; 216(5): 512.e1-512.e9, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28188774

RESUMO

BACKGROUND: Nausea and occasional vomiting in early pregnancy is common. Why some women experience severe nausea and occasional vomiting in early pregnancy is unknown. Causes are multifactorial and only symptomatic treatment options are available, although adverse birth outcomes have been described. Helicobacter pylori infection has been implicated in the cause of nausea and occasional vomiting in early pregnancy. OBJECTIVE: The purpose of this study was to investigate the association of H pylori with vomiting severity in pregnancy and its effect on birth outcome. STUDY DESIGN: We assembled a population-based prospective cohort of pregnant women in The Netherlands. Enrolment took place between 2002 and 2006. H pylori serology was determined in mid gestation. Women reported whether they experienced vomiting in early, mid, and late gestation. Maternal weight was measured in the same time periods. Birth outcomes were obtained from medical records. Main outcome measures were vomiting frequency (no, occasional, daily) and duration (early, mid, late gestation), maternal weight gain, birthweight, small for gestational age, and prematurity. Data were analyzed with the use of multivariate regression. RESULTS: We included 5549 Women, of whom 1932 (34.8%) reported occasional vomiting and 601 (10.8%) reported daily vomiting. Women who were H pylori-positive (n=2363) were more likely to report daily vomiting (adjusted odds ratio, 1.44; 95% confidence interval, 1.16-1.78). H pylori-positivity was associated with a reduction of total weight gain in women with daily vomiting (adjusted difference, -2.1 kg; 95% confidence interval, -2.7 to -1.5); infants born to women with H pylori and daily vomiting had slightly reduced birthweight (addjusted difference -60g; 95% confidence interval, -109 - -12) and an increased risk of being small for gestational age (adjusted odds ratio, 1.49; 95% confidence interval, 1.04-2.14). H pylori and daily vomiting did not significantly affect prematurity rate. CONCLUSION: This study suggests that H pylori is an independent risk factor for vomiting in pregnancy. In women with daily vomiting, H pylori is also associated with low maternal weight gain, reduced birth weight, and small for gestational age. Because effective treatments for severe nausea and occasional vomiting in early pregnancy are currently lacking, the effect of H pylori eradication therapy on nausea and occasional vomiting in early pregnancy symptom severity should be the target of future studies.


Assuntos
Infecções por Helicobacter/epidemiologia , Hiperêmese Gravídica/epidemiologia , Êmese Gravídica/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Peso ao Nascer , Estudos de Coortes , Feminino , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Países Baixos/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Ganho de Peso
20.
PLoS Med ; 14(1): e1002221, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28118352

RESUMO

BACKGROUND: It has been suggested that greater maternal adiposity during pregnancy affects lifelong risk of offspring fatness via intrauterine mechanisms. Our aim was to use Mendelian randomisation (MR) to investigate the causal effect of intrauterine exposure to greater maternal body mass index (BMI) on offspring BMI and fat mass from childhood to early adulthood. METHODS AND FINDINGS: We used maternal genetic variants as instrumental variables (IVs) to test the causal effect of maternal BMI in pregnancy on offspring fatness (BMI and dual-energy X-ray absorptiometry [DXA] determined fat mass index [FMI]) in a MR approach. This was investigated, with repeat measurements, from ages 7 to 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 2,521 to 3,720 for different ages). We then sought to replicate findings with results for BMI at age 6 in Generation R (n = 2,337 for replication sample; n = 6,057 for total pooled sample). In confounder-adjusted multivariable regression in ALSPAC, a 1 standard deviation (SD, equivalent of 3.7 kg/m2) increase in maternal BMI was associated with a 0.25 SD (95% CI 0.21-0.29) increase in offspring BMI at age 7, with similar results at later ages and when FMI was used as the outcome. A weighted genetic risk score was generated from 32 genetic variants robustly associated with BMI (minimum F-statistic = 45 in ALSPAC). The MR results using this genetic risk score as an IV in ALSPAC were close to the null at all ages (e.g., 0.04 SD (95% CI -0.21-0.30) at age 7 and 0.03 SD (95% CI -0.26-0.32) at age 18 per SD increase in maternal BMI), which was similar when a 97 variant generic risk score was used in ALSPAC. When findings from age 7 in ALSPAC were meta-analysed with those from age 6 in Generation R, the pooled confounder-adjusted multivariable regression association was 0.22 SD (95% CI 0.19-0.25) per SD increase in maternal BMI and the pooled MR effect (pooling the 97 variant score results from ALSPAC with the 32 variant score results from Generation R) was 0.05 SD (95%CI -0.11-0.21) per SD increase in maternal BMI (p-value for difference between the two results = 0.05). A number of sensitivity analyses exploring violation of the MR results supported our main findings. However, power was limited for some of the sensitivity tests and further studies with relevant data on maternal, offspring, and paternal genotype are required to obtain more precise (and unbiased) causal estimates. CONCLUSIONS: Our findings provide little evidence to support a strong causal intrauterine effect of incrementally greater maternal BMI resulting in greater offspring adiposity.


Assuntos
Adiposidade/genética , Índice de Massa Corporal , Variação Genética , Absorciometria de Fóton , Adolescente , Criança , Inglaterra , Feminino , Humanos , Estudos Longitudinais , Masculino , Análise da Randomização Mendeliana , Análise Multivariada , Gravidez , Análise de Regressão
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