Maternal and Paternal Dietary Quality and Dietary Inflammation Associations with Offspring DNA Methylation and Epigenetic Biomarkers of Aging in the Lifeways Cross-Generation Study.

BACKGROUND: Early-life nutritional exposures may contribute to offspring epigenetic modifications. However, few studies have evaluated parental dietary quality effects on offspring DNA methylation (DNAm). OBJECTIVES: We aim to fill this gap by elucidating the influence of maternal and paternal whole-diet quality and inflammatory potential on offspring DNAm in the Lifeways Cross-generation cohort. METHODS: Families (n = 1124) were recruited around 16 weeks of gestation in the Republic of Ireland between 2001 and 2003. Maternal dietary intake during the first trimester and paternal diet during the 12 previous months were assessed with an FFQ. Parental dietary inflammatory potential and quality were determined using the energy-adjusted Dietary Inflammatory Index (E-DII), the Healthy Eating Index-2015 (HEI-2015), and the maternal DASH score. DNAm in the saliva of 246 children at age nine was measured using the Illumina Infinium HumanMethylationEPIC array. DNAm-derived biomarkers of aging, the Pediatric-Buccal-Epigenetic clock and DNAm estimator of telomere length, were calculated. Parental diet associations with the DNAm concentrations of 850K Cytosine-phosphate-guanine sites (CpG sites) and with DNAm-derived biomarkers of aging were examined using an epigenome-wide association study and linear regressions, respectively. RESULTS: Maternal HEI-2015 scores were inversely associated with DNAm at CpG site (cg21840035) located near the PLEKHM1 gene, whose functions involve regulation of bone development (ß = -0.0036, per 1 point increase in the score; P = 5.6 × 10-8). Higher paternal HEI-2015 score was related to lower methylation at CpG site (cg22431767), located near cell signaling gene LUZP1 (ß = -0.0022, per 1 point increase in the score, P = 4.1 × 10-8). There were no associations with parental E-DII and DASH scores, and no evidence of major effects on biomarkers of aging. CONCLUSIONS: Parental dietary quality in the prenatal period, evaluated by the HEI-2015, may influence offspring DNAm during childhood. Further research to improve our understanding of parental nutritional programming is warranted.

An association between maternal weight change in the year before pregnancy and infant birth weight: ELFE, a French national birth cohort study.

BACKGROUND: Weight-control interventions in pregnant women with overweight or obesity have limited effectiveness for fetal growth and birth outcomes. Interventions or prevention programs aiming at the pre-pregnancy period should be considered. However, how the woman's weight change before pregnancy affects fetal growth is not known. We investigated the association between weight change over the year before pregnancy and birth weight. METHODS AND FINDINGS: We used the inclusion data of 16,395 women from the ELFE French national birth cohort, a nationally representative cohort in which infants were enrolled at birth with their families in 2011. Maternal weight change was self-reported and classified into 3 groups: moderate weight variation or stable weight, weight loss > 5 kg, and weight gain > 5 kg or both weight loss and gain > 5 kg. Multiple linear regression models were used to investigate the association between pre-pregnancy weight change and a birth weight z-score calculated according to the French Audipog reference, adjusted for a large set of maternal characteristics. The analyses were stratified by maternal body mass index (BMI) at conception (<25 versus ≥25 kg/m2) and adjusted for BMI within these categories. We used the MacKinnon method to test the mediating effect of gestational weight gain (GWG) on these associations. Mother's mean age was 30.5 years, 87% were born in France, and 26% had overweight or obesity. For women in either BMI category at conception, GWG was more than 2 kg higher, on average, for women with weight loss before pregnancy than for women with stable weight or moderate weight variation. For women with BMI < 25 kg/m2 at conception, birth weight was significantly higher with weight loss than stable weight before pregnancy (ß = 0.08 [95% CI 0.02; 0.14], p = 0.01), and this total effect was explained by a significant mediating effect through GWG. For women with BMI ≥ 25 kg/m2 at conception, birth weight was not associated with pre-pregnancy weight loss during the year before pregnancy. Mediation analysis revealed that in these women, the direct effect of pre-pregnancy weight loss that would have resulted in a smaller birth weight z-score (ß = -0.11 [95% CI -0.19; -0.03], p = 0.01) was cancelled out by the GWG. The mediating effect of GWG was even higher when weight loss resulted from a restrictive diet in the year before pregnancy. Weight gain before pregnancy was not associated with birth weight. Although we included a large number of women and had extensive data, the only potential cause of pre-pregnancy weight loss that was investigated was dieting for intentional weight loss. We have no information on other potential causes but did however exclude women with a history of pre-pregnancy chronic disease. Another limitation is declaration bias due to self-reported data. CONCLUSIONS: Health professionals should be aware that GWG may offset the expected effect of weight loss before conception on fetal growth in overweight and obese women. Further studies are required to understand the underlying mechanisms in order to develop weight-control interventions and improve maternal periconceptional health and developmental conditions for the fetus.

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).

Social patterning of childhood overweight in the French national ELFE cohort.

An inverse social gradient in early childhood overweight has been consistently described in high-income countries; however, less is known about the role of migration status. We studied the social patterning of overweight in preschool children according to the mother's socio-economic and migration background. For 9250 children of the French ELFE birth cohort with body mass index collected at age 3.5 years, we used nested logistic regression to investigate the association of overweight status in children with maternal educational level, occupation, household income and migration status. Overall, 8.3% (95%CI [7.7-9.0]) of children were classified as overweight. The odds of overweight was increased for children from immigrant mothers (OR 2.22 [95% CI 1.75-2.78]) and descendants of immigrant mothers (OR 1.35 [1.04-2.78]) versus non-immigrant mothers. The highest odds of overweight was also observed in children whose mothers had low education, were unemployed or students, or were from households in the lowest income quintile. Our findings confirm that socio-economic disadvantage and migration status are risk factors for childhood overweight. However, the social patterning of overweight did not apply uniformly to all variables. These new and comprehensive insights should inform future public health interventions aimed at tackling social inequalities in childhood overweight.

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.

Weight Changes, Nutritional Intake, Food Contaminants, and Supplements in Women of Childbearing Age, including Pregnant Women: Guidelines for Interventions during the Perinatal Period from the French National College of Midwives.

Adequate maternal nutrition is crucial for a healthy pregnancy and optimal fetal growth. Many women in France of childbearing age start their pregnancy in an unfavorable nutritional status. Recent studies highlight the value of paying attention to weight issues from the preconceptional period. It is important to call attention to the need for folate supplementation and to promote a varied and balanced diet throughout pregnancy to cover essential nutritional needs.

Maternal Glycaemic and Insulinemic Status and Newborn DNA Methylation: Findings in Women With Overweight and Obesity.

CONTEXT: Maternal dysglycaemia and prepregnancy obesity are associated with adverse offspring outcomes. Epigenetic mechanisms such as DNA methylation (DNAm) could contribute. OBJECTIVE: To examine relationships between maternal glycaemia, insulinemic status, and dietary glycemic indices during pregnancy and an antenatal behavioral-lifestyle intervention with newborn DNAm. METHODS: We investigated 172 women from a randomized controlled trial of a lifestyle intervention in pregnant women who were overweight or obese. Fasting glucose and insulin concentrations and derived indices of insulin resistance (HOMA-IR), ß-cell function (HOMA-%B), and insulin sensitivity were determined at baseline (15) and 28 weeks' gestation. Dietary glycemic load (GL) and index (GI) were calculated from 3-day food diaries. Newborn cord blood DNAm levels of 850K CpG sites were measured using the Illumina Infinium HumanMethylationEPIC array. Associations of each biomarker, dietary index and intervention with DNAm were examined. RESULTS: Early pregnancy HOMA-IR and HOMA-%B were associated with lower DNAm at CpG sites cg03158092 and cg05985988, respectively. Early pregnancy insulin sensitivity was associated with higher DNAm at cg04976151. Higher late pregnancy insulin concentrations and GL scores were positively associated with DNAm at CpGs cg12082129 and cg11955198 and changes in maternal GI with lower DNAm at CpG cg03403995 (Bonferroni corrected P < 5.99 × 10-8). These later associations were located at genes previously implicated in growth or regulation of insulin processes. No effects of the intervention on cord blood DNAm were observed. None of our findings were replicated in previous studies. CONCLUSION: Among women who were overweight or obese, maternal pregnancy dietary glycemic indices, glucose, and insulin homeostasis were associated with modest changes in their newborn methylome. TRIAL REGISTRATION: ISRCTN29316280.

Association between dietary patterns reflecting one-carbon metabolism nutrients intake before pregnancy and placental DNA methylation.

The preconception period represents an important window for foetal and epigenetic programming. Some micronutrients (B vitamins, choline, betaine, methionine) implicated in one-carbon metabolism (OCM) are essential for major epigenetic processes that take place in early pregnancy. However, few studies have evaluated the implication of the micronutrients in placental DNA methylation. We investigated whether intake of OCM nutrients in the year before pregnancy was associated with placental DNA methylation in the EDEN mother-child cohort. Maternal dietary intake was assessed with a food-frequency questionnaire. Three dietary patterns, 'varied and balanced diet,' 'vegetarian tendency,' and 'bread and starchy food,' were used to characterize maternal OCM dietary intake. The Illumina Infinium HumanMethylation450 BeadChip was used to measure placental DNA methylation of 573 women included in the analyses. We evaluated the association of dietary patterns with global DNA methylation. Then, we conducted an agnostic epigenome-wide association study (EWAS) and investigated differentially methylated regions (DMRs) associated with each dietary pattern. We found no significant association between the three dietary patterns and global DNA methylation or individual CpG sites. DMR analyses highlighted associations between the 'varied and balanced' or 'vegetarian tendency' pattern and DMRs located at genes previously implicated in functions essential for embryonic development, such as neurodevelopment. The 'bread and starchy food' pattern was associated with regions related to genes whose functions involve various metabolic and cell synthesis-related processes. In mainly well-nourished French women without major deficiencies, OCM intake before pregnancy was not associated with major variation in DNA methylation.

Intervention during the Perinatal Period: Synthesis of the Clinical Practice Guidelines from the French National College of Midwives.

These clinical practice guidelines from the French National College of Midwives (CNSF) are intended to define the messages and the preventive interventions to be provided to women and co-parents by the different professionals providing care to women or their children during the perinatal period. These guidelines are divided into 10 sections, corresponding to 4 themes: 1/ the adaptation of maternal behaviors (physical activity, psychoactive agents); 2/ dietary behaviors; 3/ household exposure to toxic substances (household uses, cosmetics); 4/ promotion of child health (breastfeeding, attachment and bonding, screen use, sudden unexplained infant death, and shaken baby syndrome). We suggest a ranking to prioritize the different preventive messages for each period, to take into account professionals' time constraints.

Maternal Dietary Quality and Dietary Inflammation Associations with Offspring Growth, Placental Development, and DNA Methylation.

The 'Developmental Origins of Health and Diseases' hypothesis posits that prenatal maternal diet influences offspring growth and later life health outcomes. Dietary assessment has focused on selected nutrients. However, this approach does not consider the complex interactions between foods and nutrients. To provide a more comprehensive approach to public health, dietary indices have been developed to assess dietary quality, dietary inflammation and risk factors for non-communicable diseases. Thus far, their use in the context of placental development is limited and associations with offspring outcomes have been inconsistent. Although epidemiological studies have focused on the role of maternal diet on foetal programming, the underlying mechanisms are still poorly understood. Some evidence suggests these associations may be driven by placental and epigenetic changes. In this narrative review, we examine the current literature regarding relationships between key validated diet quality scores (Dietary Inflammatory Index [DII], Mediterranean diet [MD], Healthy Eating Index [HEI], Alternative Healthy Eating Index [AHEI], Dietary Approaches to Stop Hypertension [DASH], Glycaemic Index [GI] and Glycaemic Load [GL]) in pregnancy and birth and long-term offspring outcomes. We summarise findings, discuss potential underlying placental and epigenetic mechanisms, in particular DNA methylation, and highlight the need for further research and public health strategies that incorporate diet quality and epigenetics.

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.

Association between Dietary Intake of One-Carbon Metabolism Nutrients in the Year before Pregnancy and Birth Anthropometry.

Few studies have evaluated the role of methylation-pathway nutrients involved in fetal growth (B vitamins, choline, betaine, and methionine). These one-carbon metabolism (OCM) nutrients are essential for DNA methylation in the periconception period. We aimed to characterize dietary patterns of 1638 women from the EDEN mother-child cohort in the year before pregnancy according to the contribution of OCM nutrients and to study the association of such patterns with anthropometric measurements at birth. Dietary intake before pregnancy was assessed by using a semi-quantitative food frequency questionnaire. We used the reduced-rank regression (RRR) method to identify dietary patterns using OCM nutrients as intermediate variables. We ran linear regressions models to study the association between dietary patterns scores and birth weight, length, head circumference, gestational age, and sex-specific z-scores, adjusting for maternal characteristics and vitamin supplementation before and during pregnancy. Three patterns, "varied and balanced", "vegetarian tendency", and "bread and starchy food" were identified, explaining 58% of the variability in OCM nutrient intake. Higher scores on the "varied and balanced" pattern tended to be associated with higher birth length and weight. In mainly well-nourished young French women, we did not find evidence that variability in OCM nutrient intake has major effects on fetal growth.

Healthcare professional perceptions of family-centred rounds in French NICUs: a cross-sectional study.

OBJECTIVE: To assess the perceptions of healthcare professionals (HCPs) regarding parental presence at medical rounds in French neonatal intensive care units (NICUs). We hypothesised that HCPs would perceive barriers against allowing parental participation in round discussions. METHODS: This cross-sectional study approached 304 HCPs from three groups; group 1: French professionals that attended an annual French-speaking meeting of the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP); group 2: NICU professionals from a tertiary care academic hospital in western France; and group 3: paediatric residents from six French universities. We invited all HCPs to complete a questionnaire about medical round practices and their perceptions towards parent participation in family-centred rounds (FCRs). RESULTS: Of the 176 (58%) questionnaires returned, 159 were included in the analysis. The majority of medical rounds took place at the bedside for groups 1 and 3 (68%, 95% CI 54 to 80 and 71%, 95% CI 56 to 84, respectively) and in a conference room for group 2 (65%, 95% CI 51 to 78). Overall, respondents positively perceived FCR for themselves, parents and students. However, most respondents agreed with the following claims: 'Parental attendance at medical rounds prevents some discussions between health professionals' (66%, 95% CI 57 to 73), 'FCR increases round durations' (63%,95% CI 55 to 71) and 'Some decisions made during medical rounds may be stressful for parents' (51%, 95% CI 42 to 59). Nevertheless, responses varied significantly according to NIDCAP training and NICU experience and consequently group 1 displayed a significantly more positive attitude than other groups (p<0.001); they expressed less concern about potentially inhibiting discussions between HCPs (p<0.001), the feasibility (p=0.02) and prolonged round durations (p<0.001). Several difficulties and facilitators of FCR implementation were variously reported, but all groups agreed that routine workload was an important difficulty and that medical leadership would be an important facilitator. CONCLUSION: French HCPs expressed rather positive perceptions towards parental presence in NICU rounds. However, some concerns need to be addressed.