Patterns of perinatal polyunsaturated fatty acid status and associated dietary or candidate-genetic factors.

Perinatal exposure to omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) can be characterized through biomarkers in maternal or cord blood, or breast milk. Objectives were to describe perinatal PUFA status combining multiple biofluids, and to investigate how it was influenced by dietary intake during pregnancy and maternal FADS and ELOVL gene polymorphisms. This study involved 1,901 mother-child pairs from the EDEN cohort, with PUFA levels measured in maternal and cord erythrocytes, and colostrum. Maternal dietary PUFA intake during the last trimester was derived from a food frequency questionnaire. Twelve single nucleotide polymorphisms in FADS and ELOVL genes were genotyped from maternal DNA. Principal component analysis incorporating PUFA levels from the three biofluids identified patterns of perinatal PUFA status. Spearman's correlations explored associations between patterns and PUFA dietary intake, and linear regression models examined pattern associations with FADS or ELOVL haplotypes. Five patterns were retained: "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs"; "Omega-6 LC-PUFAs"; "Colostrum LC-PUFAs"; "Omega-6 precursor (LA) and DGLA"; "Omega-6 precursor and colostrum ALA". Maternal omega-3 LC-PUFA intakes were correlated with "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs" (r(DHA) = 0.33) and "Omega-6 LC-PUFAs" (r(DHA) = -0.19) patterns. Strong associations were found between FADS haplotypes and PUFA patterns except for "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs". Lack of genetic association with the "High omega-3 LC-PUFAs, low omega-6 LC-PUFAs" pattern, highly correlated with maternal omega-3 LC-PUFA intake, emphasizes the importance of adequate omega-3 LC-PUFA intake during pregnancy and lactation. This study offers a more comprehensive assessment of perinatal PUFA status and its determinants.

Screening preterm-born infants for autistic traits may help to identify social communication difficulties at five years of age.

AIM: This study compared neurodevelopmental screening questionnaires completed when preterm-born children reached 2 years of corrected age with social communication skills at 5.5 years of age. METHODS: Eligible subjects were born in 2011 at 24-34 weeks of gestation, participated in a French population-based epidemiological study and were free of motor and sensory impairment at 2 years of corrected age. The Ages and Stages Questionnaire (ASQ) and the Modified Checklist for Autism in Toddlers (M-CHAT) were used at 2 years and the Social Communication Questionnaire (SCQ) at 5.5 years of age. RESULTS: We focused on 2119 children. At 2 years of corrected age, the M-CHAT showed autistic traits in 20.7%, 18.5% and 18.2% of the children born at 24-26, 27-31 and 32-34 weeks of gestation, respectively (p = 0.7). At 5.5 years of age, 12.6%, 12.7% and 9.6% risked social communication difficulties, with an SCQ score ≥90th percentile (p = 0.2). A positive M-CHAT score at 2 years was associated with higher risks of social communication difficulties at 5.5 years of age (odds ratio 3.46, 95% confidence interval 2.04-5.86, p < 0.001). Stratifying ASQ scores produced similar results. CONCLUSION: Using parental neurodevelopmental screening questionnaires for preterm-born children helped to identify the risk of later social communication difficulties.

Longitudinal effects of maternal depressive and anxious symptomatology on child hair cortisol and cortisone from pregnancy to 5-years: The EDEN mother-child cohort.

Exposure to maternal depressive and anxious symptomatology in utero and after birth can affect child outcomes. One proposed mechanism is through changes in child stress hormone levels, however current studies present inconsistent findings, and further research is needed to better understand the impact of maternal mental health on child stress response. This study aims to add to the limited literature by analysing longitudinal data ranging from 24 weeks amenorrhea to 5 years postpartum among 281 mother-child pairs from the French EDEN mother-child birth cohort. Hair cortisol and cortisone data were collected from children at four time points: birth, 1, 3, and 5 years. Mothers reported depressive symptomatology via the Center for Epidemiologic Studies Depression Scale (CES-D) (at 24-weeks amenorrhea, 3-, and 5-year follow-up), and the Edinburgh Postnatal Depression Scale (EPDS) (at 4, 8 and 12 months postpartum). Prenatal anxiety symptomatology was measured via the State Anxiety Inventory (STAI) at 24 weeks amenorrhea. Group-based trajectory modelling indicated a 1-cluster classification of longitudinal child hair cortisol, cortisone and cortisol-to-cortisone ratio, as analyses did not reveal a classification by subgroups representing different child profiles. After inverse probability weighting, small effects showed prenatal depressive symptomatology was significantly associated to higher levels of child hair cortisone at one year. Prenatal anxiety symptomatology was significantly linked to higher levels of child cortisol measured at birth and cortisone at birth and at 1 year. Postpartum depressive symptomatology at 8 months was related to higher levels of cortisone among 3-year-olds. These effects were not moderated by child sex or maternal socio-economic status. Further research is needed to understand why there are associations at some time points and not others to determine any potential buffering factors.

Sleep duration in preschool age and later behavioral and cognitive outcomes: an individual participant data meta-analysis in five European cohorts.

Short sleep duration has been linked to adverse behavioral and cognitive outcomes in schoolchildren, but few studies examined this relation in preschoolers. We aimed to investigate the association between parent-reported sleep duration at 3.5 years and behavioral and cognitive outcomes at 5 years in European children. We used harmonized data from five cohorts of the European Union Child Cohort Network: ALSPAC, SWS (UK); EDEN, ELFE (France); INMA (Spain). Associations were estimated through DataSHIELD using adjusted generalized linear regression models fitted separately for each cohort and pooled with random-effects meta-analysis. Behavior was measured with the Strengths and Difficulties Questionnaire. Language and non-verbal intelligence were assessed by the Wechsler Preschool and Primary Scale of Intelligence or the McCarthy Scales of Children's Abilities. Behavioral and cognitive analyses included 11,920 and 2981 children, respectively (34.0%/13.4% of the original sample). In meta-analysis, longer mean sleep duration per day at 3.5 years was associated with lower mean internalizing and externalizing behavior percentile scores at 5 years (adjusted mean difference: - 1.27, 95% CI [- 2.22, - 0.32] / - 2.39, 95% CI [- 3.04, - 1.75]). Sleep duration and language or non-verbal intelligence showed trends of inverse associations, however, with imprecise estimates (adjusted mean difference: - 0.28, 95% CI [- 0.83, 0.27] / - 0.42, 95% CI [- 0.99, 0.15]). This individual participant data meta-analysis suggests that longer sleep duration in preschool age may be important for children's later behavior and highlight the need for larger samples for robust analyses of cognitive outcomes. Findings could be influenced by confounding or reverse causality and require replication.

Symptomatic Upper Extremity Peripheral Artery Disease is Associated With Poor Outcomes and a Broad Spectrum of Etiologies.

The symptomatic upper extremity peripheral artery disease (sUE-PAD) is poorly studied compared with the lower extremity peripheral artery disease (LE-PAD). We aimed to describe sUE-PAD etiologies and outcomes at 2 years. From an observational survey conducted in two French tertiary hospitals, demographic characteristics, etiology, treatment, and outcomes during follow-up were collected on patients with ICD-10 I74.2 code (arterial thrombosis of the upper limbs). We identified 181 patients (53% male, 55 ± 17 years) with hypothenar hammer syndrome (13.8%), cardioembolism (13.3%), atheroma (12.7%), or connective tissue disease (10.5%). No etiology could be found for 16.0% of them. The amputation rate was 13.3%, and lasting symptoms remained at 21.3%. During follow-up, atrial fibrillation occurred in 1 patient and cancer in 4. At 2 years, 59 patients were lost to follow-up, 110 patients were alive, and 12 patients had died. Age and cancer were associated with death. sUE-PAD is not benign, with 20% impaired upper extremity outcome and 10% overall mortality at 2 years. Less frequent than LE-PAD, sUE-PAD presents different characteristics: more women, younger age, and a broad spectrum of etiologies. sUE-PAD requires thorough etiological assessment and is considered to be associated with a severe overall prognosis.

Prenatal dietary exposure to chemicals and allergy or respiratory diseases in children in the EDEN mother-child cohort.

INTRODUCTION: Maternal exposure to food chemicals may increase the risk of allergy and respiratory disorders in offspring. We aimed to assess the association of prenatal dietary exposure to single chemicals and chemical mixtures with allergy or respiratory events reported before age 8 y in children. METHODS: We included 1428 mother-child pairs enrolled in the EDEN mother-child cohort. Maternal dietary exposure to 209 chemicals and eight associated mixtures was investigated. Allergic and respiratory diseases (wheezing, asthma, allergic rhinitis, eczema and food allergy) were reported by parents between birth and age 8 y. Associations with the studied outcomes were evaluated with three approaches based on adjusted logistic regression, estimating odds ratios (ORs) and 95 % confidence intervals (CIs). First, food chemicals were considered individually, with correction for multiple testing. Second, chemicals selected by elastic net regression were considered simultaneously in a multiple exposure model. Third, predefined mixtures were introduced in the same adjusted logistic regression. Results are expressed as odds ratio (OR[95 % CI]). RESULTS: Prenatal single exposure to 74 food chemicals was associated with higher risk of allergic rhinitis. Prenatal single exposure to 11 chemicals was associated with higher risk of wheezing. In the multi-exposure approach, risk of wheezing was associated with the pesticides diazinon and triadimenol, and polycyclic aromatic hydrocarbon 5-methylchrysene. Phytoestrogen resveratrol was negatively associated with lower risk of both wheezing and allergic rhinitis, and mycotoxin monoacetoxyscirpenol was negatively associated with risk of eczema. Finally, a chemical mixture composed mainly of trace elements, furans and polycyclic aromatic hydrocarbons, was associated with higher risk of allergic rhinitis (1.33 [1.02;1.73]). CONCLUSION: Prenatal dietary exposure to chemicals was associated with risk of allergic rhinitis or wheezing up to age 8 y. A few chemicals were associated with other allergic and respiratory diseases. Larger prospective studies are needed to confirm these findings.

Impact of parental lifestyle patterns in the preconception and pregnancy periods on childhood obesity.

Introduction: High prevalence of overweight and obesity already observed in preschool children suggests the involvement of early-life risk factors. Preconception period and pregnancy are crucial windows for the implementation of child obesity prevention interventions with parental lifestyle factors as relevant targets. So far, most studies have evaluated their role separately, with only a few having investigated their potential synergistic effect on childhood obesity. Our objective was to investigate parental lifestyle patterns in the preconception and pregnancy periods and their association with the risk of child overweight after 5 years. Materials and methods: We harmonized and interpreted results from four European mother-offspring cohorts participating in the EndObesity Consortium [EDEN, France; Elfe, France; Lifeways, Ireland; and Generation R, Netherlands] with data available for 1,900, 18,000, 1,100, and 9,500 families, respectively. Lifestyle factors were collected using questionnaires and included parental smoking, body mass index (BMI), gestational weight gain, diet, physical activity, and sedentary behavior. We applied principal component analyses to identify parental lifestyle patterns in preconception and pregnancy. Their association with risk of overweight (including obesity; OW-OB) and BMI z-scores between 5 and 12 years were assessed using cohort-specific multivariable logistic and linear and regression models (adjusted for potential confounders including parental age, education level, employment status, geographic origin, parity, and household income). Results: Among the various lifestyle patterns derived in all cohorts, the two explaining the most variance were characterized by (1) "high parental smoking, low maternal diet quality (and high maternal sedentary behavior in some cohorts)" and, (2) "high parental BMI and low gestational weight gain." Patterns characterized by high parental BMI, smoking, low diet quality or high sedentary lifestyle before or during pregnancy were associated with higher risk of OW-OB in children, and BMI z-score at any age, with consistent strengths of associations in the main cohorts, except for lifeways. Conclusion: This project provides insight into how combined parental lifestyle factors in the preconception and pregnancy periods are associated with the future risk of child obesity. These findings are valuable to inform family-based and multi-behavioural child obesity prevention strategies in early life.

Parental lifestyle patterns around pregnancy and risk of childhood obesity in four European birth cohort studies.

BACKGROUND: A high prevalence of excess weight in children younger than 5 years suggests the involvement of early-life risk factors. The preconception and pregnancy periods are crucial stages for the implementation of interventions to prevent childhood obesity. Most studies so far have evaluated the effects of early-life factors separately, with only a few investigating the combined effect of parental lifestyle factors. Our objective was to fill the literature gap regarding parental lifestyle factors in the preconception and pregnancy periods and to study their association with the risk of overweight in children after the age of 5 years. METHODS: We harmonised and interpreted data from four European mother-offspring cohorts (EDEN [comprising 1900 families], Elfe [comprising 18 000 families], Lifeways [comprising 1100 families], and Generation R [comprising 9500 families]). Written informed consent was obtained from parents of all involved children. Lifestyle factor data collected through questionnaires comprised parental smoking, BMI, gestational weight gain, diet, physical activity, and sedentary behaviour. We applied principal component analyses to identify multiple lifestyle patterns in preconception and pregnancy. Their association with child BMI z-score and risk of overweight (including obesity, overweight and obesity, as defined by the International Task Force reference) between the ages of 5 and 12 years were assessed using cohort-specific multivariable linear and logistic regression models (adjusted for confounders including parental age, education level, employment status, geographic origin, parity, and household income). FINDINGS: Among the various lifestyle patterns identified in all cohorts, the two that better explained variance were high parental smoking plus low maternal diet quality or high maternal sedentary behaviour, and high parental BMI plus low gestational weight gain. Overall, we observed that patterns characterised by high parental BMI, smoking, low-quality diet, or sedentary lifestyle before or during pregnancy were associated with higher BMI z-scores and risk of overweight and obesity in children aged 5-12 years. INTERPRETATION: Our data contribute to a better understanding of how parental lifestyle factors might be associated with the risk of childhood obesity. These findings are valuable to inform future family-based and multi-behavioural child obesity prevention strategies in early life. FUNDING: European Union's Horizon 2020 under the ERA-NET Cofund action (reference 727565) and European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL, EndObesity).

Hydrolysed proteins in infant formula and child neurodevelopment up to the age of 3·5 years: the nationwide Étude Longitudinale Française depuis l'Enfance (ELFE) birth cohort.

While breast-feeding is the recommended feeding mode in infancy, rates are low in some Western societies, and infants are widely fed formula. France, in particular, shows high rates of infant formula use, including formulas with protein hydrolysates. The degree of protein hydrolysis has previously been associated with neurodevelopmental outcomes. The present study examines the associations between the protein's hydrolysis degree in infant formula and child neurodevelopment up to 3·5 years of age in the French nationwide Étude Longitudinale Française depuis l'Enfance (ELFE study). Parents reported on brand and name of the formula used at 2 months, and protein hydrolysis degree was derived from the ingredient list. Analyses were based on 6979 infants (92·2, 6·8 and 1 % consuming non-hydrolysed, partially and extensively hydrolysed formulas, respectively). Neurodevelopment was assessed at age 1 and 3·5 years with the Child Development Inventory (CDI), at age 2 years with the MacArthur-Bates Communicative Development Inventories and at age 3·5 years with the Picture Similarities sub-scale (British Ability Scales). Associations between protein hydrolysis degree and child neurodevelopment were assessed using linear and logistic regression for overall scores and poor CDI sub-domain scores (<25th centile), respectively. Among formula-fed infants, protein hydrolysis degree in infant formula was not associated with overall neurodevelopmental scores up to 3·5 years. Some associations were found with the motor skills CDI sub-domain, but they were not consistent at 1 and 3·5 years as well as across sensitivity analyses. The use of hydrolysed formula appears safe in terms of overall neurodevelopment, and research should further investigate specific neurodevelopmental domains.

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.

Maternal pre-pregnancy obesity and offspring hyperactivity-inattention symptoms at 5 years in preterm and term children: a multi-cohort analysis.

The objective of this study was to determine the relationship between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 5 years, including preterm and term-born children, and to determine whether this association varied with gestational age. Maternal pre-pregnancy BMI and offspring HIS were assessed in 10,898 participants born ≥ 33 weeks of gestation from the ELFE cohort and 2646 children born between 23 and 34 weeks from the EPIPAGE 2 cohort. Reported pre-pregnancy weight (kg) and measured height (m) were collected from mothers at inclusion and used to classify BMI (kg/m2). Child HIS were evaluated using the Strengths and Difficulties Questionnaire around 5 years of age. Logistic regression estimated odds ratios (OR) of a high HIS score (≥ 90th percentile) in the ELFE cohort and generalized estimated equations were used in EPIPAGE 2 to account for non-independence of multiple births. As a negative control, paternal BMI was also considered as an exposure of interest in sensitivity analyses. Maternal pre-pregnancy obesity and overweight were associated with child HIS at 5 years in ELFE (adjusted OR [aOR] for obesity 1.27 [1.06, 1.53]; overweight aOR 1.16 [1.00, 1.36]) and pre-pregnancy obesity was associated with high HIS scores in preterm infants of EPIPAGE 2 (aOR 1.48 [1.06, 2.08]). In ELFE, the magnitude of the association increased with decreasing gestational age (interaction p = 0.02). High maternal pre-pregnancy BMI is associated with greater likelihood of high HIS scores in both at-term and preterm children at 5 years of age.

Maternal diet during pregnancy and child neurodevelopment up to age 3.5 years: the nationwide Étude Longitudinale Française depuis l'Enfance (ELFE) birth cohort.

BACKGROUND: Dietary guidelines available to pregnant women are made to improve maternal health and fetal development. But their adequacy to sustain offspring neurodevelopment has remained understudied. OBJECTIVES: We assessed the association between compliance with nutritional guidelines during pregnancy and neurodevelopment in preschool children. METHODS: The analyses were based on data for 6780 to 11,278 children from the Étude Longitudinale Française depuis l'Enfance (ELFE) study, a nationwide birth cohort. Maternal diet during the last 3 mo of pregnancy was evaluated at delivery by using a validated 125-item FFQ. From this FFQ, food group consumption, a diet quality score (adapted National Health and Nutrition Program Guideline Score), and a nutrient intake score (Probability of Adequate Nutrient intake based Diet quality index) were calculated and dietary patterns were derived by principal component analysis. Child neurodevelopment was reported by parents at 1 and 3.5 y with the Child Development Inventory (CDI-1, CDI-3.5) and at 2 y with the MacArthur-Bates Communicative Development Inventories (MB-2), and assessed by a trained investigator at 3.5 y with the Picture Similarities test (British Ability Scales, PS-3.5). Associations between maternal diet and child neurodevelopment were assessed by multivariable linear regression models on standardized variables. RESULTS: Higher nutrient intake score was associated with higher neurodevelopmental scores from 1 to 3.5 y (ß = 0.04; 95% CI: 0.02, 0.06 for CDI-1; ß = 0.03; 95% CI: 0.01, 0.05 for MB-2; and ß = 0.03; 95% CI: 0.01, 0.05 for CDI-3.5). Higher fruit and vegetables or fish intake and lower pork-meat products intake were related to higher CDI-3.5 scores (ß = 0.03; 95% CI: 0.01, 0.05 for fruit and vegetables; ß = 0.03; 95% CI: 0.01, 0.05 for fish; and ß = -0.02; 95% CI: -0.04, 0.00 for pork-meat products). A higher score on the processed food pattern was associated with poorer neurodevelopmental score at 1 y (ß = -0.05; 95% CI: -0.06, -0.03). CONCLUSIONS: Higher diet quality during pregnancy was associated with higher parent-reported neurodevelopmental scores in early childhood. The negative association of pork-meat products consumption with early neurodevelopmental scores needs to be further confirmed.

Association of Assisted Reproductive Technology With Offspring Growth and Adiposity From Infancy to Early Adulthood.

Importance: People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population. Objective: To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study. Design, Setting, and Participants: This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022. Exposures: Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction). Main Outcomes and Measures: The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups. Results: Up to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units). Conclusions and Relevance: These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.

Cord blood leptin level and a common variant of its receptor as determinants of the BMI trajectory: The EDEN mother-child cohort.

BACKGROUND: Cord blood leptin is an indicator of neonatal fat mass and could shape postnatal adiposity trajectories. Investigating genetic polymorphisms of the leptin receptor gene (LEPR) could help understand the mechanisms involved. OBJECTIVES: We aimed to investigate the association of cord blood leptin level and the LEPR rs9436303 polymorphism, with body mass index (BMI) at adiposity peak (AP) and age at adiposity rebound (AR). METHODS: In the EDEN cohort, BMI at AP and age at AR were estimated with polynomial mixed models, for 1713 and 1415 children, respectively. Multivariable linear regression models allowed for examining the associations of cord blood leptin level and LEPR rs9436303 genotype with BMI at AP and age at AR adjusted for potential confounders including birth size groups. We also tested interactions between cord blood leptin level and rs9436303 genotype. RESULTS: Increased leptin level was associated with reduced BMI at AP and early age at AR (comparing the highest quintile of leptin level to the others). Rs9436303 G-allele carriage was associated with increased BMI at AP and later age at AR but did not modulate the association with leptin level. CONCLUSION: These results illustrate the role of early life body composition and the intrauterine environment in the programming of adiposity in childhood.

Cardiovascular Health at Age 5 Years: Distribution, Determinants, and Association With Neurodevelopment.

Background: Early childhood may represent an opportune time to commence primordial prevention of cardiovascular disease (CVD, i.e., prevention of risk factors onset), but epidemiological evidence is scarce. We aimed to examine the distribution and parental and early life determinants of ideal cardiovascular health (CVH) in children up to 5 years and to compare the level of cognitive development between children with and without ideal CVH at age 5 years. Methods: Using data from the Etude sur les déterminants pré et post natals précoces du Développement psychomoteur et de la santé de l'Enfant (EDEN) study, a French population-based mother-child cohort study, CVH was examined in children at 5 years of age based on the American Heart Association CVH metrics (ideal body mass index, physical activity, diet, blood pressure, cholesterol and glucose levels, and passive smoking, considered in sensitivity analysis only). Children were categorized as having ideal (five to six ideal metrics) or non-ideal CVH (<5 ideal metrics). Intelligence quotient (IQ) at age 5 years was assessed using the French version of the Wechsler Preschool and Primary Scale of Intelligence. Results: Among the 566 children (55% boys), only 34% had ideal CVH. In fully adjusted logistic regression, boys compared to girls (OR = 1.77, 95% CI 1.13-2.78), children with intermediate (1.77, 1.05-2.98) or ideal (2.58, 1.38-4.82) behavioral CVH at age 3 years and children who spent < 30 min/day watching television (1.91, 1.09-3.34) at age 3 years were more likely to have ideal CVH at age 5 years. At age 5 years, there was a significant 2.98-point difference (95% CI 0.64-5.32) in IQ between children with and without ideal biological CVH after adjusting for confounders. Conclusion: This study highlights that only a third of children aged 5 years had ideal CVH and identified modifiable determinants of ideal CVH and is suggestive of an association between CVH and neurodevelopment at a young age.

Maternal Diet Quality during Pregnancy and Allergic and Respiratory Multimorbidity Clusters in Children from the EDEN Mother-Child Cohort.

We investigated the associations between maternal diet quality and allergic and respiratory diseases in children. Analyses were based on 1316 mother-child pairs from the EDEN mother-child cohort. Maternal diet quality during pregnancy was assessed through a food-based score (the Diet Quality), a nutrient-based score (the PANDiet), and the adherence to guidelines for main food groups. Clusters of allergic and respiratory multimorbidity clusters up to 8 years were identified using Latent Class Analysis. Associations were assessed by adjusted multinomial logistic regressions. Four clusters were identified for children: "asymptomatic" (67%, reference group), "asthma only" (14%), "allergies without asthma" (12%), "multi-allergic" (7%). These clusters were not associated with mother diet quality assessed by both scores. Children from mothers consuming legumes once a month or less were at higher risk of belonging to the "multi-allergic" cluster (odds ratio (OR) (95% confidence interval (95%CI)) = 1.60 (1.01;2.54)). No association was found with other food groups or other clusters. In our study, allergic and respiratory multimorbidity in children was described with four distinct clusters. Our results suggest an interest in legumes consumption in the prevention of allergic diseases but need to be confirmed in larger cohorts and randomized control trials.

Predictors of incomplete maternal satisfaction with neuraxial labor analgesia: A nationwide study.

PURPOSE: Neuraxial analgesia is effective and widely used during labour, but little is known about maternal satisfaction with its use. Our objectives were to assess the frequency of incomplete maternal satisfaction with neuraxial labour analgesia and its predictors. METHODS: We extracted data from the 2016 National Perinatal Survey, a cross-sectional population-based study including all births during one week in all French maternity units. This analysis included all women who attempted vaginal delivery with neuraxial analgesia. Maternal satisfaction with analgesia was assessed by a 4-point Likert scale during a postpartum interview. Incomplete satisfaction grouped together women who were fairly, not sufficiently and not at all satisfied. We performed generalised estimating equations analyses adjusted for sociodemographic, obstetric, anaesthetic, and organisational characteristics to compare women with incomplete satisfaction to those completely satisfied. RESULTS: Among the 8538 women included, 35.2% were incompletely satisfied with their neuraxial analgesia. The odds of incomplete satisfaction were higher among women who reported a prenatal preference not to use neuraxial analgesia but subsequently did (adjusted odds ratio 1.21; 95% confidence interval 1.05-1.39) and among those who did not use patient-controlled neuraxial analgesia (1.20; 1.07-1.34); the odds were lower among women who used combined spinal epidural analgesia (0.53; 0.28-0.99) than among those with epidural analgesia. CONCLUSION: Incomplete maternal satisfaction with neuraxial analgesia is a frequent concern in France. Increasing the use of patient-controlled neuraxial analgesia and combined spinal-epidural analgesia, as well as consistency between prenatal preference and actual use of neuraxial analgesia may improve maternal satisfaction.

Routine CYP2C19 Genotyping to Adjust Thienopyridine Treatment After Primary PCI for STEMI: Results of the GIANT Study.

OBJECTIVES: The aim of this study was to evaluate prospectively the clinical impact of routine transmission of CYP2C19 genotype in the management of acute ST-segment elevation myocardial infarction with primary percutaneous coronary intervention. BACKGROUND: Response to clopidogrel differs widely among patients, notably because of CYP2C19 genetic polymorphisms. METHODS: CYP2C19 genotype (6 alleles) was determined centrally and communicated within 4.1 ± 1.9 days of primary percutaneous coronary intervention in 1,445 patients with ST-segment elevation myocardial infarction recruited at 57 centers in France. CYP2C19 metabolic status was predicted from genotype and served to adjust thienopyridine treatment. The primary endpoint was differences in 12-month outcomes (death, myocardial infarction, and stent thrombosis) between patients with the wild-type genotype or gain-of-function allele (class 1, n = 1,118) and those with loss-of-function (LOF) alleles (class 2, n = 272) who received optimized thienopyridine treatment. RESULTS: Detection of LOF alleles resulted in adjustment of P2Y12 inhibition in 85% of patients, with significantly higher use of prasugrel or double-dose clopidogrel. The primary endpoint did not differ between class 1 and class 2 patients (3.31% vs. 3.04%, respectively; p = 0.82). In contrast, carriers of LOF alleles without treatment adjustment had significantly worse outcomes (15.6%; p < 0.05). Bleeding rates were not different between groups. CONCLUSIONS: In a real-world setting, a complete CYPC2C19 genotype can be mostly determined in <7 days using analysis of saliva deoxyribonucleic acid collected during the in-hospital phase among patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Genotype information led to stronger platelet inhibition treatment in the vast majority of LOF allele carriers and to similar clinical outcomes as in patients carrying the wild-type genotype or gain-of-function allele. (Genotyping Infarct Patients to Adjust and Normalize Thienopyridine Treatment [GIANT]; NCT01134380).

Change in Cardiovascular Health and Incident Type 2 Diabetes and Impaired Fasting Glucose: The Whitehall II Study.

OBJECTIVE: Most previous studies on cardiovascular health (CVH) and incident type 2 diabetes (T2D) have used a single measure of CVH, and none have investigated the association with impaired fasting glucose (IFG). We examined the association between changes in CVH and incident T2D and IFG. RESEARCH DESIGN AND METHODS: Within the Whitehall II study, CVH was examined every 5 years from 1991/93 until 2015/16. Subjects with 0-2, 3-4, and 5-6 ideal metrics of CVH from the American Heart Association were categorized as having low, moderate, or high CVH, respectively. RESULTS: There were 6,234 participants (mean age 49.8 ± 6.0 years, 70% male) without prior cardiovascular disease and T2D, including 5,015 who were additionally free from IFG at baseline. Over a median follow-up of 24.8 (interquartile range 24.0-25.2) years, 895 and 1,703 incident cases of T2D and IFG occurred, respectively. Change in CVH between 1991/93 and 2002/04 was calculated among 4,464 participants free from CVD and T2D and among 2,795 participants additionally free from IFG. In multivariate analysis, compared with those with stable low CVH, risk of T2D was lower in those with initially high CVH (hazard ratio [HR] 0.21; 95% CI 0.09, 0.51), those who had persistently moderate CVH or changed from moderate to high CVH (moderate-moderate/high; HR 0.53; 95% CI 0.41, 0.69), low-moderate/high (HR 0.62; 95% CI 0.45, 0.86), and moderate-low (HR 0.74; 95% CI 0.56, 0.98). Results were similar for IFG, but the effect sizes were smaller. CONCLUSIONS: Compared with stable low CVH, other patterns of change in CVH were associated with lower risk of T2D and IFG.

Incidence, Mortality, and Outcome-Predictors of Sudden Cardiac Arrest Complicating Myocardial Infarction Prior to Hospital Admission.

BACKGROUND: Mortality of ST-segment-elevation myocardial infarction (STEMI) decreased drastically, mainly through reduction in inhospital mortality. Prehospital sudden cardiac arrest (SCA) became one of the most feared complications. We assessed the incidence, outcome, and prognosis' predictors of prehospital SCA occurring after emergency medical services (EMS) arrival. METHODS AND RESULTS: Data were taken between 2006 and 2014 from the e-MUST study (Evaluation en Médecine d'Urgence des Strategies Thérapeutiques des infarctus du myocarde) that enrolls all STEMI managed by EMS in the Greater Paris Area, including those dead before hospital admission. Among 13 253 STEMI patients analyzed, 749 (5.6%) presented EMS-witnessed prehospital SCA. Younger age, absence of cardiovascular risk factors, symptoms of heart failure, extensive STEMI, and short pain onset-to-call and call-to-EMS arrival delays were independently associated with increased SCA risk. Mortality rate at hospital discharge was 4.0% in the nonSCA group versus 37.7% in the SCA group ( P<0.001); 26.8% of deaths occurred before hospital admission. Factors associated with increased mortality after SCA were age, heart failure, and extensive STEMI, while male sex and cardiovascular risk factors were associated with decreased mortality. Among patients admitted alive, PCI was the most important mortality-reduction predictor (odds ratio, 0.40; 95% CI, 0.25-0.63; P<0.0001). CONCLUSIONS: More than 1 of 20 STEMI presents prehospital SCA after EMS arrival. SCA occurrence is associated with a 10-fold higher mortality at hospital discharge compared with STEMI without SCA. PCI is the strongest survival predictor, leading to a twice-lower mortality. This highlights the persistently dramatic impact of SCA on STEMI and the major importance of PCI in this setting.