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.

Mode of Delivery and Asthma at School Age in 9 European Birth Cohorts.

Evidence on the association between mode of delivery and asthma at school age is inconclusive. We assessed the associations between specific modes of delivery and asthma in children from 9 European birth cohorts that enrolled participants between 1996 and 2006. Cohort-specific crude and adjusted risk ratios for asthma at ages 5-9 years were calculated using Poisson regression models and pooled. A sensitivity analysis was carried out in children born at term to reduce confounding due to perinatal factors. The study included 67,613 participants. Cohort-specific rates of cesarean delivery varied from 9.4% to 37.5%. Cesarean delivery, as opposed to vaginal delivery, was associated with an increased risk of asthma (adjusted risk ratio (aRR) = 1.22, 95% confidence interval (CI): 1.02, 1.46). Compared with spontaneous vaginal delivery, the adjusted risk ratio was 1.33 (95% CI: 1.02, 1.75) for elective cesarean delivery, 1.07 (95% CI: 0.94, 1.22) for emergency cesarean delivery, and 0.97 (95% CI: 0.84, 1.12) for operative vaginal delivery. In children born at term, the associations were strengthened only for elective cesarean delivery (aRR = 1.49, 95% CI: 1.13, 1.97). The large sample size allowed analysis of the associations between specific modes of delivery and asthma at school age. The increased risk of asthma associated with elective cesarean delivery, especially among children born at term, is relevant in counteracting the increasing use of this procedure, which is often performed without a clear medical indication.

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.

Pregnancy diet and offspring asthma risk over a 10-year period: the Lifeways Cross Generation Cohort Study, Ireland.

OBJECTIVE: The association of maternal pregnancy diet with offspring asthma risk have been reported. However, literature on longitudinal patterns of asthma risk relative to intrauterine nutrient exposure is limited. We aimed to establish whether vegetable, oily fish and vitamin D intake during pregnancy are associated with childhood asthma risk over a 10-year period in the Irish Republic. DESIGN: Mother-child pairs (n=897) from the Lifeways prospective birth cohort, with data on nutrient intake during pregnancy and asthma status, respectively, were eligible for inclusion in the analysis. Data on socioeconomic and morbidity indicators over 10 years of follow-up on mothers and the index child were collected through self-administered questionnaires. Asthma status as diagnosed by the general practitioner at any time point over 10 years was related to maternal vegetable, oily fish and vitamin D intake during pregnancy, while adjusting for gestational age, socioeconomic status, smoking at delivery, breast feeding, season of birth and supplement use. Data were modelled with a marginal model on correlated observations over time within individuals. RESULTS: In the fully adjusted model, asthma was inversely associated with higher daily average intake of oily fish (OR 0.23 per serving/day, 95% CI 0.04 to 1.41) and of vegetables (OR 0.96 per serving/day, 95% CI 0.88 to 1.05), but the confidence limits overlapped 1. A higher daily vitamin D intake was associated with reduced odds of asthma (OR 0.93 per µg/day, 95% CI 0.89 to 0.98). CONCLUSION: This analysis suggests higher daily average intake of vitamin D in pregnancy is associated with asthma risk in offspring over the first 10 years of life.

The Epidemiology of Meningitis among Adults in a South African Province with a High HIV Prevalence, 2009-2012.

INTRODUCTION: Meningitis is a major cause of mortality in southern Africa. We aimed to describe the aetiologies and frequencies of laboratory-confirmed fungal and bacterial meningitis among adults in a South African province with an 11% HIV prevalence, over 4 years. METHODS: We conducted a retrospective, observational study of secondary laboratory data, extracted on all cerebrospinal fluid (CSF) specimens submitted to public-sector laboratories in Gauteng province from 2009 through 2012. We calculated cause-specific incidence rates in the general and HIV-infected populations and used Poisson regression to determine if trends were significant. RESULTS: We identified 11,891 (10.7%) incident cases of meningitis from 110,885 CSF specimens. Cryptococcal meningitis, tuberculous meningitis and pneumococcal meningitis accounted for 62.3% (n = 7,406), 24.6% (n = 2,928) and 10.1% (n = 1,197) of cases over the four-year period. The overall incidence (cases per 100,000 persons) of cryptococcal meningitis declined by 23% from 24.4 in 2009 to 18.7 in 2012 (p <0.001) and decreased by 19% among HIV-infected persons from 178.2 to 144.7 (p <0.001). Tuberculous meningitis decreased by 40% from 11.3 in 2009 to 6.8 in 2012 (p <0.001) and decreased by 36% among HIV-infected persons from 54.4 to 34.9 (p <0.001). Pneumococcal meningitis decreased by 41% from 4.2 in 2009 to 2.5 in 2012 (p <0.001) and decreased by 38% among HIV-infected persons from 28.0 to 17.5 (p <0.001). Among cases of other bacterial meningitis (248/11,891, 2.1%), Neisseria meningitidis (n = 93), Escherichia coli (n = 72) and Haemophilus influenzae (n = 20) were the most common organisms identified. CONCLUSIONS: In this high HIV-prevalence province, cryptococcal meningitis was the leading cause of laboratory-confirmed meningitis among adults. Over a 4-year period, there was a significant decrease in incidence of cryptococcal, tuberculous and pneumococcal meningitis. This coincided with expansion of the national antiretroviral treatment programme, enhanced tuberculosis control programme and routine childhood immunisation with pneumococcal conjugate vaccines.

Fish Intake in Pregnancy and Child Growth: A Pooled Analysis of 15 European and US Birth Cohorts.

IMPORTANCE: Maternal fish intake in pregnancy has been shown to influence fetal growth. The extent to which fish intake affects childhood growth and obesity remains unclear. OBJECTIVE: To examine whether fish intake in pregnancy is associated with offspring growth and the risk of childhood overweight and obesity. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, population-based birth cohort study of singleton deliveries from 1996 to 2011 in Belgium, France, Greece, Ireland, Italy, the Netherlands, Norway, Poland, Portugal, Spain, and Massachusetts. A total of 26,184 pregnant women and their children were followed up at 2-year intervals until the age of 6 years. EXPOSURES: Consumption of fish during pregnancy. MAIN OUTCOMES AND MEASURES: We estimated offspring body mass index percentile trajectories from 3 months after birth to 6 years of age. We defined rapid infant growth as a weight gain z score greater than 0.67 from birth to 2 years and childhood overweight/obesity at 4 and 6 years as body mass index in the 85th percentile or higher for age and sex. We calculated cohort-specific effect estimates and combined them by random-effects meta-analysis. RESULTS: This multicenter, population-based birth cohort study included the 26,184 pregnant women and their children. The median fish intake during pregnancy ranged from 0.5 times/week in Belgium to 4.45 times/week in Spain. Women who ate fish more than 3 times/week during pregnancy gave birth to offspring with higher body mass index values from infancy through middle childhood compared with women with lower fish intake (3 times/week or less). High fish intake during pregnancy (>3 times/week) was associated with increased risk of rapid infant growth, with an adjusted odds ratio (aOR) of 1.22 (95% CI, 1.05-1.42) and increased risk of offspring overweight/obesity at 4 years (aOR, 1.14 [95% CI, 0.99-1.32]) and 6 years (aOR, 1.22 [95% CI, 1.01-1.47]) compared with an intake of once per week or less. Interaction analysis showed that the effect of high fish intake during pregnancy on rapid infant growth was greater among girls (aOR, 1.31 [95% CI, 1.08-1.59]) than among boys (aOR, 1.11 [95% CI, 0.92-1.34]; P = .02 for interaction). CONCLUSIONS AND RELEVANCE: High maternal fish intake during pregnancy was associated with increased risk of rapid growth in infancy and childhood obesity. Our findings are in line with the fish intake limit proposed by the US Food and Drug Administration and Environmental Protection Agency.

Body mass index is associated with the maternal lines but height is heritable across family lines in the Lifeways Cross-Generation Cohort Study.

OBJECTIVES: Overweight and obesity is a problem in children in particular and determining pathways of transmission is important in prevention. We aimed to examine associations for body mass index (BMI) across three generations of the same families. PARTICIPANTS: Members of 556 families in the Lifeways Cross-Generation Cohort Study 2001-2014. SETTING: Community-based study with linkage to health records in the Republic of Ireland. METHODS: Employing a novel mixed-method approach which adjusts for age and familial group, BMI correlations were estimated at three ages of the index child, that is, at birth and at ages 5 and 9. Height was also examined for comparative purposes. RESULTS: Correlation of offspring's BMI with that of the mother increased with age (correlation coefficient 0.15 increasing to 0.28, p value <0.001 in all cases) while no consistent pattern was seen with offspring and fathers. There was an association also with each parent and their own mother. Offspring's BMI was correlated to a lesser extent with that of the maternal grandmother while for girls only there was an association with that of the paternal grandmother at ages 0 and 5 (correlation coefficients 0.25, 0.28, p values 0.02, 0.01, respectively). In contrast, height of the child was strongly associated with those of all family members at age 5, but at birth and at age 9 only there was an association with those of the parents and the paternal grandfather. Correlation of offspring's height with those of the mother and father increased with age. CONCLUSIONS: The results suggest that BMI is predominantly associated with the maternal line, possibly either with intrauterine development, or inherited through the X chromosome, or both, while height is a more complex trait with genetic influences of the parents and that of the paternal grandfather predominating.

Longitudinal follow-up of the relationship between dietary intake and growth and development in the Lifeways cross-generation cohort study 2001-2013.

In this paper we will review evidence on the early life and familial influences on childhood growth and development, with particular reference to the Lifeways cross-generation cohort study in the Republic of Ireland. The Lifeways cross-generation cohort study was established in 2001-2013 through two maternity hospitals in the Republic of Ireland and was one of many new cohort studies established worldwide in the millennium period. Mothers were recruited at first booking visit, completing a self-administered questionnaire, which included a 147 item semi-quantitative FFQ. Longitudinal follow-up is ongoing in 2013, with linkage data to hospital and general practice records and examination of children when aged 5 and 9 years. The study is one of very few containing data on grandparents of both lineages with at least one grandparent recruited at baseline. There have been consistent associations between parental and grandparental health status characteristics and children's outcomes, including infant birth-weight, BMI when child was aged 5 years and childhood wheeze or asthma when child was aged 3 and aged 5 years. In conclusion, empirical evidence to date shows consistent familial and cross-generational patterns, particularly in the maternal line.

Fish intake during pregnancy, fetal growth, and gestational length in 19 European birth cohort studies.

BACKGROUND: Fish is a rich source of essential nutrients for fetal development, but in contrast, it is also a well-known route of exposure to environmental pollutants. OBJECTIVE: We assessed whether fish intake during pregnancy is associated with fetal growth and the length of gestation in a panel of European birth cohort studies. DESIGN: The study sample of 151,880 mother-child pairs was derived from 19 population-based European birth cohort studies. Individual data from cohorts were pooled and harmonized. Adjusted cohort-specific effect estimates were combined by using a random- and fixed-effects meta-analysis. RESULTS: Women who ate fish >1 time/wk during pregnancy had lower risk of preterm birth than did women who rarely ate fish (≤ 1 time/wk); the adjusted RR of fish intake >1 but <3 times/wk was 0.87 (95% CI: 0.82, 0.92), and for intake ≥ 3 times/wk, the adjusted RR was 0.89 (95% CI: 0.84, 0.96). Women with a higher intake of fish during pregnancy gave birth to neonates with a higher birth weight by 8.9 g (95% CI: 3.3, 14.6 g) for >1 but <3 times/wk and 15.2 g (95% CI: 8.9, 21.5 g) for ≥ 3 times/wk independent of gestational age. The association was greater in smokers and in overweight or obese women. Findings were consistent across cohorts. CONCLUSION: This large, international study indicates that moderate fish intake during pregnancy is associated with lower risk of preterm birth and a small but significant increase in birth weight.