Associations of screen use with cognitive development in early childhood: the ELFE birth cohort.

BACKGROUND: The associations of screen use with children's cognition are not well evidenced and recent, large, longitudinal studies are needed. We aimed to assess the associations between screen use and cognitive development in the French nationwide birth cohort. METHODS: Time and context of screen use were reported by parents at ages 2, 3.5 and 5.5. Vocabulary, non-verbal reasoning and general cognitive development were assessed with the MacArthur-Bates Communicative Development Inventory (MB) at age 2, the Picture Similarities subtest from the British Ability Scales (PS) at age 3.5 and the Child Development Inventory (CDI) at ages 3.5 and 5.5. Outcome variables were age-adjusted and standardized (mean = 100, SD = 15). Multiple imputations were performed among children (N = 13,763) with ≥1 screen use information and ≥1 cognitive measures. Cross-sectional and longitudinal associations between screen use and cognitive development were assessed by linear regression models adjusted for sociodemographic and birth factors related to the family and children, and children's lifestyle factors competing with screen use. Baseline cognitive scores were further considered in longitudinal analysis. RESULTS: TV-on during family meals at age 2, not screen time, was associated with lower MB scores at age 2 (ß [95% CI] = -1.67 [-2.21, -1.13]) and CDI scores at age 3.5 (-0.82 [-1.31, -0.33]). In cross-sectional analysis, screen time was negatively associated with CDI scores at ages 3.5 (-0.67 [-0.94, -0.40]) and 5.5 (-0.47 [-0.77, -0.16]), and, in contrast, was positively associated with PS scores (0.39 [0.07, 0.71]) at age 3.5. Screen time at age 3.5 years was not associated with CDI scores at age 5.5 years. CONCLUSIONS: Our study found weak associations of screen use with cognition after controlling for sociodemographic and children's birth factors and lifestyle confounders, and suggests that the context of screen use matters, not solely screen time, in children's cognitive development.

SARS-CoV-2 seroprevalence in French 9-year-old children and their parents after the first lockdown in 2020.

Introduction: Children have been significantly less affected by COVID-19 than adults and presented with milder and less symptomatic forms of the disease. However, there has been suggestion that children older than 10 years and adolescents exhibits features closer to that of young adults. Most studies combine children in different age-groups and lack sufficient numbers to explore in detail age specificities. We report data on a population-based sample of 2,555 children at the pivotal age of 9 years. Methods: In April 2020, the participants in two French nationwide cohorts of children, Elfe and Epipage2, were invited to take part into an online survey about Covid related symptoms and family life during the lockdown. A second questionnaire was sent on May 5. This questionnaire also proposed to the child included in the cohort and to one of his/her parents to take part into a capillary blood collection for Covid serology. Families who agreed to the serological survey were sent kits for dried blood spots self-sampling (DBS) with instructions. Samples were processed with a commercial Elisa test (Euroimmun®, Lübeck, Germany) to detect anti-SARS-CoV-2 antibodies (IgG) directed against the S1 domain of the spike protein of the virus. Results: Children's acceptance rate for the serological survey was around 60%. 2,555 serological results were analyzed. The weighted prevalence of a positive Elisa Spike serology was 2.8% in 9 yr-old children (95% CI: 1.7%-4.0%). Positive serology was found in 8.6% (7.4%-9.7%) of parents who provided blood. There was a significant association (p < 0.001) between serology of the child and parent from the same household with an odds ratio of 13.8 (7.9-24.2). Discussion: We have shown that 9-yr old children had a lower susceptibility to SARS-Cov2 infection than adults with the initial Chinese strain, similar to younger children and estimated that around 3% of them have developed antibodies against SARS-Cov2 in France after the first wave of the Covid-19 epidemics.

Longitudinal sleep multi-trajectories from age 1 to 5.5 years and their early correlates: results from the Étude Longitudinale Française depuis l'Enfance birth cohort study.

STUDY OBJECTIVES: To identify sleep multi-trajectories in children from age 1 to 5.5 years and their early correlates. METHODS: We collected early family, maternal, and child characteristics, including children's nighttime sleep duration (NSD) and daytime sleep duration (DSD), night waking (NW), and sleep-onset difficulties (SOD), by parental phone interviews at age 2 months and 1-, 2-, 3.5-, and 5.5 years. Group-based multi-trajectory modeling identified sleep multi-trajectory groups. Multinomial logistic regression assessed associations with early factors. RESULTS: We identified five distinct sleep multi-trajectory groups for NSD, DSD, NW, and SOD in 9273 included children. The "Good sleepers" (31.6%) and "Long sleepers" (31.0%) groups had low NW and SOD prevalence and shorter NSD but longer DSD in "Good sleepers" than in "Long sleepers." The "Good sleepers but few SOD" group (10.3%) had long NSD and DSD but a SOD peak at age 3.5 years; the "Improving NW and SOD" group (9.6%) showed short but rapidly increasing NSD to a plateau and high but decreasing NW and SOD; the "Persistent NW and SOD" group (17.5%) had persistent high NW and SOD. Maternal depression during pregnancy and sleep habits at age 1 (e.g. parental presence or feeding to fall asleep, sleeping at least part of the night away from own bed) were common risk factors associated with the most disordered sleep multi-trajectory groups. CONCLUSIONS: We identified distinct sleep multi-trajectory groups and early life-associated factors in preschoolers. Most of the factors associated with the most sleep-disordered multi-trajectory groups are likely modifiable and provide clues for early prevention interventions.

Child health screening program in French nursery schools: Results and related socioeconomic factors.

Objectives: The study aims to describe the output of routine health screening performed in French nursery schools by the maternal and child health services among children aged 3-4 years and to quantify the level of early socioeconomic health disparities. Methods: In 30 participating départements, data on screening for vision and hearing impairments, overweight and thinness, dental health, language, psychomotor development, and immunizations were collected for children born on specific dates in 2011 and enrolled in nursery school in 2014-2016. Information was collected on the children, their socioeconomic characteristics and on the school attended. Odds of abnormal screening results were compared for each socioeconomic factor by logistic regressions adjusted for age, sex, prematurity and bilingualism. Results: Among the 9,939 children screened, prevalence of disorders was 12.3% for vision, 10.9% for hearing, 10.4% for overweight, 7.3% for untreated caries, 14.2% for language and 6.6% for psychomotricity. Newly detected visual disorders were more frequent in disadvantaged areas. Children with unemployed parents were three time more likely to have untreated caries and twice as likely to present language or psychomotor impairments; 52% were referred to a health professional following screening compared to 39% of children with employed parents. Except for children in disadvantaged areas, vaccine coverage was lower among disadvantaged groups. Conclusion: The prevalences of impairments, which are higher among disadvantaged children, highlight the potential preventive impact of systematic screening under the comprehensive maternal and child healthcare program. These results are important to quantify early socioeconomic inequalities in a Western country known for its generous social welfare system. A more holistic approach to child health is needed with a coherent system involving families and aligning primary care, local child health professionals, general practitioners, and specialists. Further results are needed to evaluate its impact on later child development and health.

Whispers of change in preschool asthma phenotypes: Findings in the French ELFE cohort.

RATIONALE: Early life asthma phenotyping remains an unmet need in pediatric asthma. In France, severe pediatric asthma phenotyping has been done extensively; however, phenotypes in the general population remain underexplored. Based on the course and severity of respiratory/allergic symptoms, we aimed to identify and characterize early life wheeze profiles and asthma phenotypes in the general population. METHODS: ELFE is a general population based birth cohort; which recruited 18,329 newborns in 2011, from 320 maternity units nationwide. Data was collected using parental responses to modified versions of ISAAC questionnaire on eczema, rhinitis, food allergy, cough, wheezing, dyspnoea and sleep disturbance due to wheezing at 3 time points: post-natal (2 months), infancy (age 1) and pre-school (age 5). We built a supervised trajectory for wheeze profiles and an unsupervised approach was used for asthma phenotypes. Chi squared (χ2) test or fisher's exact test was used as appropriate (p < 0.05). RESULTS: Wheeze profiles and asthma phenotypes were ascertained at age 5. Supervised wheeze trajectory of 9161 children resulted in 4 wheeze profiles: Persistent (0.8%), Transient (12.1%), Incident wheezers at age 5 (13.3%) and Non wheezers (73.9%). While 9517 children in unsupervised clusters displayed 4 distinct asthma phenotypes: Mildly symptomatic (70%), Post-natal bronchiolitis with persistent rhinitis (10.2%), Severe early asthma (16.9%) and Early persistent atopy with late onset severe wheeze (2.9%). CONCLUSION: We successfully determined early life wheeze profiles and asthma phenotypes in the general population of France.

Parents' depression and anxiety associated with hyperactivity-inattention and emotional symptoms in children during school closure due to COVID-19 in France.

Several risk factors of children's mental health issues have been identified during the pandemic of COronaVIrus Disease first appeared in 2019 (COVID-19). This study aims to fill the knowledge gap regarding the association between parents' and children's mental health issues during the COVID-19 school closure in France. We conducted a cross-sectional analysis of data collected in the SAPRIS-ELFE study during the COVID-19 pandemic in France. Using multinomial logistic regressions, we estimated associations between parents' and children's mental health issues. Symptoms of anxiety were assessed by the General Anxiety Disorder-7 (GAD-7) and depression by the Patient Health Questionnaire-9 (PHQ-9) for the parents. Hyperactivity/inattention and emotional symptoms in children were assessed by the Strengths and Difficulties Questionnaire (SDQ). The sample included 3496 children aged 8 to 9 years, of whom 50.0% were girls. During the school closure, 7.1% of responding parents had moderate to severe levels of anxiety and 6.7% had moderate to severe levels of depression. A total of 11.8% of the children had an abnormal hyperactivity/inattention score and 6.6% had an abnormal emotional symptoms score. In multivariate regression models, parental moderate to severe level of anxiety and moderate to severe level of depression were associated with abnormal hyperactivity-inattention score (adjusted Odds Ratio (aOR) 3.31; 95% Confidence Interval (CI) 2.33-4.70 and aOR 4.65; 95% CI 3.27-6.59, respectively) and abnormal emotional symptoms score in children (aOR 3.58; 95% CI 2.33-5.49 and aOR 3.78; 95 CI 2.47-5.78 respectively). Children whose parents have symptoms of anxiety and/or depression have an increased likelihood of symptoms of hyperactivity/inattention and emotional symptoms during school closures in France due to COVID-19. Our findings suggest that public health initiatives should target parents and children to limit the impact of such crises on their mental health issues.

Paternity leave uptake and parental post-partum depression: findings from the ELFE cohort study.

BACKGROUND: Several countries are expanding their paternity leave policies, which can have positive effects on parental mental health. We examined whether 2 weeks of paid paternity leave are associated with post-partum depression in mothers and fathers at 2 months after the birth of their child. METHODS: We used data from the Etude Longitudinale Française depuis l'Enfance (ELFE) cohort study. Participating mothers gave birth in 2011 in a representative sample of 320 maternity hospitals in mainland France. Inclusion criteria were single or twin livebirths born after at least 33 weeks' gestation; mother's age at least 18 years; no plans to leave metropolitan France within 3 years. Mothers were interviewed face-to-face shortly after the child's birth. Fathers and mothers were both interviewed by telephone 2 months after the child's birth, reporting whether the father had the right to paternity leave and if yes, if he had taken or intended to take it. We used the Edinburgh Postnatal Depression Scale to assess post-partum depression among fathers and mothers at 2 months. Logistic regression models, using survey-weighted data and adjusted for confounders using inverse probability weights, yielded odds ratios (ORs). FINDINGS: We included 10 975 fathers and 13 075 mothers with reported information on paternity leave and post-partum depression at 2 months in the statistical analyses. Fathers had a median age of 32·6 years (IQR 36·9-22·6) and mothers had a median age of 30·5 years (34·0-27·1) at the time of the ELFE child's birth. The prevalence of depression in fathers according to paternity leave status was 4·5% among those who used paternity leave, 4·8% among those who intended to use paternity leave, and 5·7% among those who did not use paternity leave. For mothers, the prevalence of post-partum depression was 16·1% among those whose partner used paternity leave, 15·1% among those whose partner intended to use paternity leave, and 15·3% among those whose partner did not use paternity leave. Fathers who took paternity leave had reduced odds of post-partum depression (OR 0·74 [95% CI 0·70-0·78]) as did fathers who intended to take paternity leave (0·76 [0·70-0·82]) compared with fathers who did not take paternity leave. However, we did not find such beneficial effects for mothers whose partners took (1·13 [1·05-1·20]) or intended to take paternity leave (1·02 [0·96-1·08]). INTERPRETATION: Taking and intending to take 2-weeks' paid paternity leave was associated with a reduced likelihood of reporting post-partum depression in fathers. However, offering 2-weeks' paternity leave might place mothers at a greater risk of post-partum depression, suggesting that optimal length and timing of the leave, among other factors, need further investigation. FUNDING: The French National Research Agency.

Determinants of incomplete vaccination in children at age two in France: results from the nationwide ELFE birth cohort.

Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries, but its determinants are poorly understood. Their identification is necessary to design target actions that can improve vaccination uptake. Our aim was to assess the determinants of incomplete vaccination in two-year-old children in France. Among the 18,329 children included in the 2011 ELFE French nationwide population-based birth cohort, we selected those for whom vaccination status was available at age two years. Incomplete vaccination was defined as ≥ 1 missing dose of recommended vaccines. Potential determinants of incomplete vaccination were identified by using logistic regression, taking into account attrition and missing data. Of the 5,740 (31.3%) children analyzed, 46.5% (95% confidence interval [CI] 44.7-48.0) were incompletely vaccinated. Factors independently associated with incomplete vaccination were having older siblings (adjusted odds ratio 1.18, 95% CI [1.03-1.34] and 1.28 [1.06-1.54] for one and ≥ 2 siblings, respectively, vs. 0), residing in an isolated area (1.92 [1.36-2.75] vs. an urban area), parents not following health recommendations or using alternative medicines (1.81 [1.41-2.34] and 1.23 [1.04-1.46], respectively, vs. parents confident in institutions and following heath recommendations), not being visited by a maternal and child protection service nurse during the child's first two months (1.19 [1.03-1.38] vs. ≥ 1 visit), and being followed by a general practitioner (2.87 [2.52-3.26] vs. a pediatrician). CONCLUSIONS: Incomplete vaccination was highly prevalent in the studied pediatric population and was associated with several socio-demographic, parental, and healthcare service characteristics. These findings may help in designing targeted corrective actions. WHAT IS KNOWN: • Incomplete vaccination in the pediatric population is a growing public health issue in high-income countries. • The partial understanding of the determinants of incomplete vaccination precludes the design of effective targeted corrective actions. WHAT IS NEW: • High prevalence of incomplete vaccination at age two years in France. • Incomplete vaccination was independently associated with several socio-demographic, parental, and healthcare service characteristics.

Longitudinal impact of psychosocial status on children's mental health in the context of COVID-19 pandemic restrictions.

Emerging research suggests that the prevalence of child and adolescent mental health problems has increased considerably during the COVID-19 crisis. However, there have been few longitudinal studies on children's mental health issues according to their social determinants in this context, especially in Europe. Our aim was to investigate the association between family socioeconomic status (SES) and children' mental health during the period of school closure due to COVID-19. Longitudinal data came from 4575 children aged 8-9 years old in 2020 and participating in the ELFE population-based birth cohort that focuses on children's health, development and socialization. Parents completed the Strengths and Difficulties Questionnaire (SDQ) when children were (a) 5 years of age and (b) 9 years of age, which corresponded to the period of school closure due to the COVID-19 pandemic in France. We retrieved data from the ELFE cohort collected on children from birth to age 5 years (birth, 1 year, 2 years, 3,5 years and 5 years). Socioeconomic status (SES) was measured based on information obtained when the child was 5 years old. Data were analyzed using multinomial logistic regression models. Children's elevated levels of symptoms of Attention-deficit/Hyperactivity disorder (ADHD) during the period of school closure were significantly associated with prior low family SES (aOR 1.26, 95% CI 1.08-1.48). Children's elevated symptoms of hyperactivity/inattention and of emotional symptoms were associated with decline in income during the COVID crisis (respectively, aOR 1.38, 95% CI 1.16-1.63 and aOR 1.23, 95% CI 1.01-1.51). Moreover, when testing interactions, a low prior SES was significantly associated with a higher risk of emotional symptoms aOR 1.54 (1.07-2.21), only for children whose families experienced a decline in income, while gender, parental separation and prior mental health difficulties were not associated. This study underlines the impact of the financial crisis related to the COVID-19 epidemic on children's mental health. Both pre-existing family SES before lockdown and more proximal financial difficulties during the COVID crisis were negatively associated with children's psychological difficulties during the period of school closure. The pandemic appears to exacerbate mental health problems in deprived children whose families suffer from financial difficulties.

Sociodemographic and behavioural factors of adherence to the no-screen guideline for toddlers among parents from the French nationwide Elfe birth cohort.

BACKGROUND: Excessive screen time in infancy and childhood has been associated with consequences on children's development and health. International guidelines call for no screen time before age 2 years, whereas in France, the most prominent guidelines recommend no screen before age 3 years. However, data are lacking on parental adherence to the no-screen guideline for toddlers and factors of adherence in France. Using data from the French nationwide Elfe birth cohort, we estimated adherence to the no-screen guideline at age 2 years and examined related factors, including sociodemographic characteristics, parental leisure activities and screen time. METHODS: In 2011, 18,329 newborns and their parents were enrolled in 349 randomly selected maternity units across mainland France. At age 2 years, screen exposure of 13,117 toddlers was reported by parents in phone interviews. Data on sociodemographic characteristics, parental leisure activities and screen time were collected from both parents. Three patterns of parental leisure activities were derived by principal component analysis: literate (e.g.,reading), screen-based, and physical/artistic activities. Multivariable logistic regression models were used to examine the associations of sociodemographic characteristics, parental leisure activities and parental screen time with adherence to the no-screen guideline for toddlers. RESULTS: Overall, 1809/13,117 (13.5%) families adhered to the no-screen guideline for toddlers. Adherence was reduced with maternal age < 40 years, low parental education, single-parent household and parental migration status. After adjusting for sociodemographic characteristics, adherence to the guideline was positively associated with a parental literate activity pattern (mothers: odds ratio [95% confidence interval]: 1.15 [1.08, 1.22]); fathers: 1.15 [1.07, 1.23]) and negatively with a screen-based activity pattern (mothers: 0.73 [0.69, 0.77]; fathers: 0.81 [0.76, 0.87]). With each additional hour of parental screen time, mothers and fathers were less likely to adhere to the guideline (mothers: adjusted odds ratio 0.80 [0.77, 0.83]; fathers: 0.88 [0.85, 0.91]). CONCLUSIONS: Adherence to the no-screen guideline for toddlers in France was low. Parental leisure activities and parental screen time are major factors of adherence to the no-screen guideline and could be considered in targeted public health interventions.

The external validation of the asthma prediction tool in the French ELFE cohort.

BACKGROUND: Existing predictive scores for early identification of children at high risk of developing asthma include invasive procedures, and hence have limited utility in a primary care setting. The Leicestershire respiratory cohort (LRC) has developed a noninvasive asthma prediction tool (APT) for children with promising results. We aimed to perform its external validation in the French general population Étude Longitudinale Française depuis l'Enfance (ELFE) cohort. METHODS: Predictive scores were determined at Age 1 and the primary outcome of asthma was defined as parental reporting of "asthma ever or "wheezing in the past 12 months" at Age 5. Logistic regression was used to calculate the odds ratio (OR) and performance measures, and discriminative performance was reported using the receiver operating curve and area under curve (AUC). Calibration was assessed using Hosmer-Lemeshow goodness-of-fit test and visualized with a calibration plot. Overall performance was determined using Brier scores. RESULTS: Of the 10,689 children analyzed: 84.9% were at low, 13.1% medium, and 2% at high risk of developing asthma at Age 5. Children in the medium-risk category were three times more likely to develop asthma (OR = 3.3, 95% confidence interval [CI] = 2.97-3.78) whereas 13 times more likely in the high-risk category (OR = 13.8, 95% CI = 10.2-18.8). The tool's AUC was comparable: LRC 0.74 versus ELFE 0.68; as were the Brier scores LRC 0.16 versus ELFE 0.14. The tool's performance was robust to changes in inclusion criteria and outcome definitions. CONCLUSIONS AND RELEVANCE: Results of the present study and previous validation studies performed in high-risk populations provide a comprehensive measure of the effectiveness of the APT, providing encouragement for its application by general practitioners.

Testing the assumptions of customized intrauterine growth charts using national birth studies.

INTRODUCTION: Customized intrauterine growth charts are widely used for growth monitoring and research. They are based on three assumptions: (1) estimated fetal weight (EFW) has a normal distribution with a constant coefficient of variation at all gestational ages; (2) Hadlock's growth curve accurately describes the relation between EFW and gestational ages; (3) associations between EFW and the fetal and maternal characteristics included in the customization model (fetal sex, pre-pregnancy weight, height, parity) are proportional throughout pregnancy. The aim of this study was to test whether these underlying assumptions are verified. MATERIAL AND METHODS: Data came from (1) the French Longitudinal Study of Children (ELFE) cohort, which recruited births after 32 weeks' gestation in 349 maternity hospitals in France in 2011, and (2) the National Perinatal Survey, which included births from all French maternity hospitals in 2016. The study population included, respectively, 6 920 and 8 969 singleton non-malformed term live births with data on customization characteristics and EFW. We computed the coefficient of variation by gestational age and then modeled the association of gestational age, maternal and fetal characteristics with EFW at the second and third trimester ultrasound and with birthweight using linear regression. To assess the proportionality of the impact of maternal and fetal characteristics, we computed the percent change in weight associated with these characteristics at these three time points. RESULTS: The coefficient of variation was close to 12% at each gestational age, but EFW was not normally distributed, leading to small but systematic underestimation of fetuses under the 10th percentile. Weights representing the 50th and 10th percentiles based on Hadlock's growth trajectory were lower than observed or predicted weights. Most characteristics more strongly impacted weight at birth than during pregnancy. In the French Longitudinal study of Children (ELFE) cohort, boys were 1.8% (95% confidence interval [CI] 1.3-2.4) heavier than girls in the third trimester, whereas this percentage was 4.6% (95% CI 4.0-5.2) at birth. In the National Perinatal Survey, these percentages were 2.3% (95% CI 1.8-2.8) and 4.3% (95% CI 3.8-4.8). CONCLUSIONS: These results from two independent sources revealed discrepancies between routine clinical EFW data used for growth monitoring and the customized growth model's assumptions.

Enrichment of Formula in Probiotics or Prebiotics and Risk of Infection and Allergic Diseases up to Age 5.5 Years in the Nationwide Etude Longitudinale Française depuis l'Enfance (ELFE) Cohort.

BACKGROUND: An increasing number of infant and follow-on formulas are enriched with probiotics and/or prebiotics; however, evidence for health effects of such enrichment in early childhood remains inconclusive. OBJECTIVES: The present study aimed to assess whether the consumption of formula enriched with probiotics or prebiotics was associated with the risk of infection and allergic diseases in early childhood. METHODS: Analyses involved data for 8389 formula-fed children from the Etude Longitudinale Française depuis l'Enfance (ELFE) cohort. Enrichment of the formula with probiotics or prebiotics that was consumed from the age of 2-10 mo was identified by the formula ingredient list. Lower respiratory tract infection (LRTI), upper respiratory tract infection (URTI), gastrointestinal infection, wheezing, asthma, food allergy, and itchy rash were prospectively reported by parents up to the age of 5.5 y. Adjusted logistic regression models were used to assess associations between the consumption of enriched formula and risk of infection and allergic diseases. RESULTS: Aged 2 mo, more than half of formula-fed infants consumed the probiotic-enriched formula and only 1 in 10 consumed the prebiotic-enriched formula. Consumption of the Bifidobacterium lactis-enriched formula at 2 mo was associated with a lower risk of LRTI [OR (95% CI) = 0.84 (0.73-0.96)]. Consumption of the Bifidobacterium breve-enriched formula up to 6 mo was associated with a higher risk of LRTI [OR (95% CI) = 1.75 (1.29-2.38)] and asthma [OR (95% CI) = 1.95 (1.28-2.97)], whereas its consumption from 6 to 10 mo was associated with a lower risk of LRTI [OR (95% CI) = 0.64 (0.48-0.86)] and asthma [OR (95% CI) = 0.59 (0.40-0.88)]. Moreover, the consumption of Streptococcus thermophilus from 6 to 10 mo was associated with a higher risk of asthma [OR (95% CI) = 1.84 (1.29-2.63)]. No significant association was found for gastrointestinal infection, food allergy, and itchy rash. Overall, the consumption of prebiotic-enriched formula was not significantly associated with infection and allergy risk. CONCLUSIONS: Associations between the consumption of probiotic-enriched formula and risk of respiratory symptoms differ according to the strain considered and consumption period. Further well-designed studies are needed to confirm these results.

Enrichment of Formula in Probiotics or Prebiotics and Risk of Infection and Allergic Diseases up to Age 5.5 Years in the Nationwide Etude Longitudinale Française depuis l'Enfance (ELFE) Cohort.

BACKGROUND: An increasing number of infant and follow-on formulas are enriched with probiotics and/or prebiotics; however, evidence for health effects of such enrichment in early childhood remains inconclusive. OBJECTIVES: The present study aimed to assess whether the consumption of formula enriched with probiotics or prebiotics was associated with the risk of infection and allergic diseases in early childhood. METHODS: Analyses involved data for 8389 formula-fed children from the Etude Longitudinale Française depuis l'Enfance (ELFE) cohort. Enrichment of the formula with probiotics or prebiotics that was consumed from the age of 2-10 mo was identified by the formula ingredient list. Lower respiratory tract infection (LRTI), upper respiratory tract infection (URTI), gastrointestinal infection, wheezing, asthma, food allergy, and itchy rash were prospectively reported by parents up to the age of 5.5 y. Adjusted logistic regression models were used to assess associations between the consumption of enriched formula and risk of infection and allergic diseases. RESULTS: Aged 2 mo, more than half of formula-fed infants consumed the probiotic-enriched formula and only 1 in 10 consumed the prebiotic-enriched formula. Consumption of the Bifidobacterium lactis-enriched formula at 2 mo was associated with a lower risk of LRTI [OR (95% CI) = 0.84 (0.73-0.96)]. Consumption of the Bifidobacterium breve-enriched formula up to 6 mo was associated with a higher risk of LRTI [OR (95% CI) = 1.75 (1.29-2.38)] and asthma [OR (95% CI) = 1.95 (1.28-2.97)], whereas its consumption from 6 to 10 mo was associated with a lower risk of LRTI [OR (95% CI) = 0.64 (0.48-0.86)] and asthma [OR (95% CI) = 0.59 (0.40-0.88)]. Moreover, the consumption of Streptococcus thermophilus from 6 to 10 mo was associated with a higher risk of asthma [OR (95% CI) = 1.84 (1.29-2.63)]. No significant association was found for gastrointestinal infection, food allergy, and itchy rash. Overall, the consumption of prebiotic-enriched formula was not significantly associated with infection and allergy risk. CONCLUSIONS: Associations between the consumption of probiotic-enriched formula and risk of respiratory symptoms differ according to the strain considered and consumption period. Further well-designed studies are needed to confirm these results.

Early postnatal growth and subsequent neurodevelopment in children delivered at term: The ELFE cohort study.

BACKGROUND: Despite the limited evidence, accelerated early postnatal growth (EPG) is commonly believed to benefit neurodevelopment for term-born infants, especially those small for gestational age. OBJECTIVES: To investigate the existence of critical time windows in the association of EPG with neurodevelopment, considering birth size groups. STUDY DESIGN: In the French ELFE birth cohort, 12,854 term-born neonates were classified as small, appropriate or large for gestational age (SGA, AGA, LGA, respectively). Parents reported their child's development by using the Child Development Inventory (CDI-score) at age 12 months and the MacArthur-Bates Development Inventory (MAB-score; 100 score units) assessing language ability at age 24 months. Predictions of individual weight, body mass index (BMI), length, and head circumference (HC) from birth to age 24 months were obtained from repeated measurements fitted with the Jenss-Bayley mixed-effects model. For each infant, conditional gains (CG) in these growth parameters were generated at four-time points (3, 6, 12 and 24 months) representing specific variations in growth parameters during 0-3, 3-6, 6-12, 12-24 months, independent of previous measures. Using multivariable linear regression models, we provided the estimate differences of the neurodevelopmental scores according to variation of each growth parameter CG, by birth size group. RESULTS: For SGA infants, the MAB-score differed by 5.8 (95% confidence interval [CI] -0.2, 11.8), 6.7 (95% CI -0.1, 13.3), and 9.7 (95% CI 1.9, 17.5) score units when CG in BMI, weight, and HC at 3 months varied from -2 to 1 standard deviation, respectively. For all infants, MAB-score was linearly and positively associated with length conditional gains at 12 months, with stronger magnitude for SGA infants. Results for the CDI-score were overall consistent with those for MAB-score. CONCLUSIONS: For term-born SGA infants, moderate catch-up in HC, BMI and weight within the first 3 months of life may benefit later neurodevelopment, which could guide clinicians to monitor EPG.

Neurodevelopmental outcomes at age 5 among children born preterm: EPIPAGE-2 cohort study.

OBJECTIVES: To describe neurodevelopment at age 5 among children born preterm. DESIGN: Population based cohort study, EPIPAGE-2. SETTING: France, 2011. PARTICIPANTS: 4441 children aged 5½ born at 24-26, 27-31, and 32-34 weeks MAIN OUTCOME MEASURES: Severe/moderate neurodevelopmental disabilities, defined as severe/moderate cerebral palsy (Gross Motor Function Classification System (GMFCS) ≥2), or unilateral or bilateral blindness or deafness, or full scale intelligence quotient less than minus two standard deviations (Wechsler Preschool and Primary Scale of Intelligence, 4th edition). Mild neurodevelopmental disabilities, defined as mild cerebral palsy (GMFCS-1), or visual disability ≥3.2/10 and <5/10, or hearing loss <40 dB, or full scale intelligence quotient (minus two to minus one standard deviation) or developmental coordination disorders (Movement Assessment Battery for Children, 2nd edition, total score less than or equal to the fifth centile), or behavioural difficulties (strengths and difficulties questionnaire, total score greater than or equal to the 90th centile), school assistance (mainstream class with support or special school), complex developmental interventions, and parents' concerns about development. The distributions of the scores in contemporary term born children were used as reference. Results are given after multiple imputation as percentages of outcome measures with exact binomial 95% confidence intervals. RESULTS: Among 4441 participants, 3083 (69.4%) children were assessed. Rates of severe/moderate neurodevelopmental disabilities were 28% (95% confidence interval 23.4% to 32.2%), 19% (16.8% to 20.7%), and 12% (9.2% to 14.0%) and of mild disabilities were 38.5% (33.7% to 43.4%), 36% (33.4% to 38.1%), and 34% (30.2% to 37.4%) at 24-26, 27-31, and 32-34 weeks, respectively. Assistance at school was used by 27% (22.9% to 31.7%), 14% (12.1% to 15.9%), and 7% (4.4% to 9.0%) of children at 24-26, 27-31, and 32-34 weeks, respectively. About half of the children born at 24-26 weeks (52% (46.4% to 57.3%)) received at least one developmental intervention which decreased to 26% (21.8% to 29.4%) for those born at 32-34 weeks. Behaviour was the concern most commonly reported by parents. Rates of neurodevelopment disabilities increased as gestational age decreased and were higher in families with low socioeconomic status. CONCLUSIONS: In this large cohort of children born preterm, rates of severe/moderate neurodevelopmental disabilities remained high in each gestational age group. Proportions of children receiving school assistance or complex developmental interventions might have a significant impact on educational and health organisations. Parental concerns about behaviour warrant attention.

Diet during pregnancy: Influence of social characteristics and migration in the ELFE cohort.

Better adherence to dietary guidelines during pregnancy is supposed to result in healthier perinatal outcomes. We aim to characterize the diets of pregnant women by hypothesis-driven and exploratory approaches and describe potential social determinants. Analyses included 12 048 mothers from the French nationwide ELFE birth cohort. Dietary intake over the last three months of the pregnancy was assessed by a food frequency questionnaire. Two hypothesis-driven scores (the Diet Quality score, based on benchmarks derived from the National Health and Nutrition Program Guidelines, and the PANDiet score, based on nutrient intake) were calculated. Exploratory dietary patterns were also identified by principal component analysis. Multiple linear regressions were used to assess associations of maternal social characteristics with dietary patterns, accounting for the possible effect modification by their migration status. Five dietary patterns were identified: the Western, Balanced, Bread and toppings, Processed products, and Milk and breakfast cereals. Younger maternal age, single motherhood, unemployment and the presence of older children in the household were related to a suboptimal diet during pregnancy. The less acculturated the women were, the healthier and less processed their diets were, independent of their socio-economic position. Several social determinants of the quality of women's diets were however moderated by their migration status. These findings shed light on the relations between indicators of social vulnerability, such as single motherhood and unemployment, and poorer diet quality. Given the reduced diet quality that accompanies the acculturation process, it is of paramount importance to identify the specific factors or obstacles that affect migrant women in maintaining their diet quality advantage over the majority population.

Infant feeding practices and sleep at 1 year of age in the nationwide ELFE cohort.

Sleep problems reported by parents affect 20% to 30% of infants. Few studies focused on the longitudinal association between infant feeding practices and sleep, especially in France. Analyses were based on 8,696 infants from the French national birth cohort ELFE. Collection of feeding practices from birth to 10 months allowed for the identification of trajectories of use of baby cereals and thickened formula by group-based trajectory modelling and calculation of duration of any breastfeeding (BF) and age at complementary feeding introduction (CFI) excluding baby cereals. Total sleep duration (TSD), night waking (NW) and sleep onset difficulties (SOD) were reported at age 1. Associations between feeding and sleep were tested by multinomial logistic regressions. BF duration ≥6 months was associated with parent-reported frequent NW, SOD and TSD ≤ 12 h/24 h at age 1. For TSD and SOD, this association was no longer significant after accounting for parental sleep-related practices. Early use of baby cereals (≤5 months) was associated with poor sleep. Early CFI (<4 months) was associated with shorter TSD and SOD but not NW. Early use of thickened formula (only <6 months) was related to poor sleep at age 1 (NW and SOD), whereas late (around 6 months) use of thickened formula was associated with better sleep. BF duration ≥6 months was related to poor sleep at age 1 but not after adjustment on 1-year parental sleep-related practices except for NW. The use of baby cereals or early CFI was not related to better sleep at age 1.

Pregnancy outcomes in women with preexisting thyroid diseases: a French cohort study.

Women with thyroid diseases at the beginning of pregnancy may have suboptimal thyroid hormone levels because of potential difficulties in compensating for the physiological thyroid hormone changes occurring in pregnancy. Our objective was to study the association between preexisting thyroid diseases, pregnancy complications, and neonatal anthropometry. In total, 16,395 women from the ELFE French longitudinal birth cohort were included, and 273 declared pre-pregnancy thyroid diseases. Associations were investigated with multivariable regression models, with adjustment for relevant potential confounders. Body mass index (BMI) was additionally adjusted for in a second stage. As compared with other women, women with pre-pregnancy thyroid diseases were more frequently obese (19.6% vs. 9.8%) and had greater odds of gestational diabetes development (odds ratio [OR] = 1.58 [95% confidence interval [CI] 1.08, 2.30]) or had undergone treatment for infertility (OR = 1.57 [95% CI 1.07, 2.31]). After adjustment for BMI, the association with gestational diabetes was no longer significant (OR = 1.27 [95% CI 0.86, 1.88]). After excluding women with another medical history, those with pre-pregnancy thyroid diseases had increased odds of premature rupture of membranes (OR = 1.51 [95% CI 1.01, 2.25]). Children born from mothers with hypothyroidism before conception due to a disease or as a potential side effect of treatment had a smaller head circumference at birth than other children (ß = -0.23 [95% CI -0.44, -0.01] cm). In conclusion, pre-pregnancy thyroid diseases were associated with risk of infertility treatment, gestational diabetes, and premature rupture of membranes. The association between history of hypothyroidism and moderate adverse effects on fetal head circumference growth needs replication.

Indoor Microbiome: Quantification of Exposure and Association with Geographical Location, Meteorological Factors, and Land Use in France.

The indoor microbial community is a mixture of microorganisms resulting from outdoor ecosystems that seed the built environment. However, the biogeography of the indoor microbial community is still inadequately studied. Dust from more than 3000 dwellings across France was analyzed by qPCR using 17 targets: 10 molds, 3 bacteria groups, and 4 mites. Thus, the first spatial description of the main indoor microbial allergens on the French territory, in relation with biogeographical factors influencing the distribution of microorganisms, was realized in this study. Ten microorganisms out of 17 exhibited increasing abundance profiles across the country: Five microorganisms (Dermatophagoïdes pteronyssinus, Dermatophagoïdes spp., Streptomyces spp., Cladosporium sphaerospermum, Epicoccum nigrum) from northeast to southwest, two (Cryptococcus spp., Alternaria alternata) from northwest to southeast, Mycobacteria from east to west, Aspergillus fumigatus from south to north, and Penicillium chrysogenum from south to northeast. These geographical patterns were partly linked to climate and land cover. Multivariate analysis showed that composition of communities seemed to depend on landscapes, with species related to closed and rather cold and humid landscapes (forests, located in the northeast) and others to more open, hot, and dry landscapes (herbaceous and coastal regions, located in the west). This study highlights the importance of geographical location and outdoor factors that shape communities. In order to study the effect of microorganisms on human health (allergic diseases in particular), it is important to identify biogeographic factors that structure microbial communities on large spatial scales and to quantify the exposure with quantitative tools, such as the multi-qPCR approach.