Maternal Smoking In Pregnancy Research Articles

DNA methylation as a marker for prenatal smoke exposure in adults.

BackgroundPrenatal smoke exposure is known to be robustly associated with DNA methylation among offspring in early life, but whether the association persists into adulthood is unclear. This study aimed to investigate the long-term effect of maternal smoke exposure on DNA methylation in 754 women (mean age 30 years); to replicate findings in the same women 18 years later and in a cohort of 230 men (mean age 53 years); and to assess the extent to which a methylation score could predict prenatal smoke exposure.MethodsWe first carried out an epigenome-wide association analysis for prenatal smoke exposure and performed replication analyses for the top CpG sites in the other samples. We derived a DNA methylation score based on previously identified CpG sites and generated receiver operating characteristic (ROC) curves to assess the performance of these scores as predictors of prenatal smoke exposure.ResultsWe observed associations at 15 CpG sites in 11 gene regions: MYO1G, FRMD4A, CYP1A1, CNTNAP2, ARL4C, AHRR, TIFAB, MDM4, AX748264, DRD1, FTO (false discovery rate <5%). Most of these associations were specific to exposure during pregnancy, were present 18 years later and were replicated in a cohort of men. A DNA methylation score could predict prenatal smoke exposure (30 years previously) with an area under the curve of 0.72 (95% confidence interval 0.69, 0.76).ConclusionsThe results of this study provide robust evidence that maternal smoking in pregnancy is associated with changes in DNA methylation that persist in the exposed offspring for many years after prenatal exposure.

Sex differences in effects of maternal risk and protective factors in childhood and pregnancy on newborn telomere length

Little research has examined determinants of newborn telomere length, a potential biomarker of lifetime disease risk impacted by prenatal exposures. No study has examined whether maternal exposures in childhood influence newborn telomere length or whether there are sex differences in the maternal factors that influence newborn telomere length. We tested whether a range of maternal risk and protective factors in childhood and pregnancy were associated with newborn telomere length among 151 sociodemographically diverse mother-infant dyads. We further examined whether the pattern of associations differed by infant sex. Newborn telomere length was assessed from cord blood collected at birth. Risk/protective factors included maternal health (smoking, body mass index), socioeconomic status (education, income), stress exposures, and mental health (depressive and posttraumatic stress disorder symptoms) in pregnancy as well as maternal experiences of abuse (physical, emotional, sexual) and familial emotional support in childhood. When examined within the whole sample, only maternal smoking in pregnancy and familial emotional support in childhood emerged as significant predictors of newborn telomere length. Male and female newborns differed in their pattern of associations between the predictors and telomere length. Among males, maternal smoking, higher body mass index, and elevated depressive symptoms in pregnancy and maternal sexual abuse in childhood were associated with shorter newborn telomere length; higher maternal educational attainment and household income in pregnancy and greater maternal familial emotional support in childhood were associated with longer newborn telomere length. Together, these factors accounted for 34% of the variance in male newborn telomere length. None of the risk/protective factors were associated with female newborn telomere length. The results suggest that male fetuses are particularly susceptible to maternal exposure effects on newborn telomere length. These findings have implications for elucidating mechanisms contributing to sex disparities in health.

Estimating the health-care costs of children born to pregnant smokers in England: cohort study using primary and secondary health-care data.

Background and aimsLittle is known about the long‐term economic consequences of smoking during pregnancy. We estimated the association between smoking in pregnancy and the costs of delivering health‐care to infants and children in England, and investigated which aspects of care are the key drivers of these costs.MethodsWe used Hospital Episode Statistics (HES) linked with Clinical Practice Research Datalink (CPRD) data in England from January 2003 to January 2015 in children with longitudinal data for at least 1, 5 and 10 years after birth. Poisson regression provided rate ratios (RR) and 95% confidence intervals (CIs) comparing health‐care episode rates between those exposed and not exposed to smoking during pregnancy. Linear regression was used to compare estimated costs between groups (£ sterling, 2015 prices) and generalized linear multivariable (GLM) models adjusted for potentially moderating factors.ResultsA total of 93 152 singleton pregnancies with the required data were identified. Maternal smoking in pregnancy was associated with higher primary care, prescription and hospital in‐patient episode rates, but lower out‐patient visit and diagnostic test rates. Adjusting for year of birth, socio‐economic deprivation, parity, sex of child and delivery method showed that maternal smoking in pregnancy was associated with increased child health‐care costs at 1 year [average cost difference for children of smokers, β = £91.18, 95% confidence interval (CI) = £47.52–134.83 and 5 years of age (β = £221.80, 95% CI = £17.78–425.83], but not at 10 years of age (β = £365.94, 95% CI = –£192.72 to £924.60).ConclusionIn England, maternal smoking in pregnancy is associated with increased child health‐care costs over the first 5 years of life; these costs are driven primarily by greater hospital in‐patient care.

Maternal smoking during pregnancy and offspring overweight: is there a dose-response relationship? An individual patient data meta-analysis.

A number of meta-analyses suggest an association between any maternal smoking in pregnancy and offspring overweight obesity. Whether there is a dose-response relationship across number of cigarettes and whether this differs by sex remains unclear. Studies reporting number of cigarettes smoked during pregnancy and offspring BMI published up to May 2015 were searched. An individual patient data meta-analysis of association between the number of cigarettes smoked during pregnancy and offspring overweight (defined according to the International Obesity Task Force reference) was computed using a generalized additive mixed model with non-linear effects and adjustment for confounders (maternal weight status, breastfeeding, and maternal education) and stratification for sex. Of 26 identified studies, 16 authors provided data on a total of 238,340 mother-child-pairs. A linear positive association was observed between the number of cigarettes smoked and offspring overweight for up to 15 cigarettes per day with an OR increase per cigarette of 1.03, 95% CI = [1.02-1.03]. The OR flattened with higher cigarette use. Associations were similar in males and females. Sensitivity analyses supported these results. A linear dose-response relationship of maternal smoking was observed in the range of 1-15 cigarettes per day equally in boys and girls with no further risk increase for doses above 15 cigarettes.

Spirometry and Impulse Oscillometry in Preschool Children: Acceptability and Relationship to Maternal Smoking in Pregnancy

Comparisons of the technical acceptability of spirometry and impulse oscillometry (IOS) and clinical correlations of the measurements have not been well studied in young children. There are no large studies focused on African American and Hispanic children. We sought to (1) compare the acceptability of spirometry and IOS in 3- to 5-year-old children and (2) examine the relationship of maternal smoking during pregnancy to later lung function. Spirometry and IOS were attempted at 4 sites from the Urban Environmental and Childhood Asthma Study birth cohort at ages 3, 4, and 5 years (472, 471, and 479 children, respectively). We measured forced expiratory flow in 0.5 s (forced expiratory volume in 0.5 seconds [FEV0.5]) with spirometry and area of reactance (AX), resistance and reactance at 5 Hz (R5 and X5, respectively) using IOS. Children were more likely to achieve acceptable maneuvers with spirometry than with IOS at age 3 (60% vs 46%, P < .001) and 5 years (89% vs 84%, P= .02). Performance was consistent among the 4 study sites. In children without recurrent wheeze, there were strong trends for higher FEV0.5 and lower R5 and AX over time. Maternal smoking during pregnancy was associated with higher AX at ages 4 and 5years (P < .01 for both years). There was no significant difference in FEV0.5 between children with and without in utero exposure to smoking. There is a higher rate of acceptable maneuvers with spirometry compared with IOS, but IOS may be a better indicator of peripheral airway function in preschool children.

Characteristics and factors associated with hospitalization in early childhood: 2004 Pelotas (Brazil) birth cohort.

Hospitalization is a frequent event in early childhood. In Brazil, the National Household Sample Survey of 2008 showed a 9% hospitalization rate among children in the first four years of life. The study aimed to describe the characteristics of hospitalization in the first six years of life and analyze the early factors associated with hospitalization in a birth cohort in southern Brazil. A zero-inflated Poisson model was used to simultaneously examine the effects of co-variables for the occurrence of a given event and to count events. The frequency of at least one episode of hospitalization during the study period was 33.4% (95%CI: 31.8-34.9), and was highest in the first year (19.1%; 95%CI: 17.9-20.4), remaining stable at approximately 10% between the first and fourth years, decreasing to 8.4% (95%CI: 7.6-9.4) between the fourth and sixth years. diseases of the respiratory system were among the leading causes of hospitalization, followed by infectious and parasitic diseases. History of prior hospitalization was one of the most important predictors of odds of hospitalization and risk of multiple hospitalizations. In early childhood, birth weight, gestational age, Apgar score, sex, and type of pregnancy were inversely associated with hospitalization, and environmental characteristics such as maternal smoking in pregnancy, mother's skin color, and low family income were associated statistically with number of hospitalizations. The results point to the importance of focusing efforts on reducing hospitalizations from diseases of the respiratory system, especially in children under one year.

Maternal Smoking in Pregnancy and Offspring Depression: a cross cohort and negative control study

Previous reports suggest that offspring of mothers who smoke during pregnancy have greater risk of developing depression. However, it is unclear whether this is due to intrauterine effects. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) from the UK (N = 2,869), the Nord-Trøndelag health study (HUNT) from Norway (N = 15,493), the Pelotas 1982 Birth Cohort Study from Brazil (N = 2,626), and the Swedish Sibling Health Cohort (N = 258 sibling pairs), we compared associations of maternal smoking during pregnancy and mother’s partner’s smoking during pregnancy with offspring depression and performed a discordant sibling analysis. In meta-analysis, maternal smoking during pregnancy was associated with higher odds of offspring depression (OR 1.20, 95% CI:1.08,1.34), but mother’s partner’s smoking during pregnancy was not (OR 1.05, 95% CI:0.94,1.17). However, there was only weak statistical evidence that the odds ratios for maternal and mother’s partner’s smoking differed from each other (p = 0.08). There was no clear evidence for an association between maternal smoking during pregnancy and offspring depression in the sibling analysis. Findings do not provide strong support for a causal role of maternal smoking during pregnancy in offspring depression, rather observed associations may reflect residual confounding relating to characteristics of parents who smoke.

Vitamin C Prevents Offspring DNA Methylation Changes Associated with Maternal Smoking in Pregnancy.

Infants whose mothers smoked during pregnancy demonstrate lifelong decreases in pulmonary function. DNA methylation changes associated with maternal smoking during pregnancy have been described in placenta and cord blood at delivery, in fetal lung, and in buccal epithelium and blood during childhood. We demonstrated in a randomized clinical trial ( ClinicalTrials.gov identifier, NCT00632476) that vitamin C supplementation to pregnant smokers can lessen the impact of maternal smoking on offspring pulmonary function and decrease the incidence of wheeze at 1 year of age. To determine whether vitamin C supplementation reduces changes in offspring methylation in response to maternal smoking and whether methylation at specific CpGs is also associated with respiratory outcomes. Targeted bisulfite sequencing was performed with a subset of placentas, cord blood samples, and buccal samples collected during the NCT00632476 trial followed by independent validation of selected cord blood differentially methylated regions, using bisulfite amplicon sequencing. The majority (69.03%) of CpGs with at least 10% methylation difference between placebo and nonsmoker groups were restored (by at least 50%) toward nonsmoker levels with vitamin C treatment. A significant proportion of restored CpGs were associated with phenotypic outcome with greater enrichment among hypomethylated CpGs. We identified a pattern of normalization in DNA methylation by vitamin C supplementation across multiple loci. The consistency of this pattern across tissues and time suggests a systemic and persistent effect on offspring DNA methylation. Further work is necessary to determine how genome-wide changes in DNA methylation may mediate or reflect persistent effects of maternal smoking on lung function.

The effect of in utero exposure to alcohol, tobacco and cannabis on educational attainment in adolescence: findings from ALSPAC, a UK cohort study

ABSTRACT&#x0D; ObjectivesAlcohol, tobacco and cannabis can cross the placenta, and could have long-lasting effects on the brain of the developing foetus. We examine whether exposure to these substances is associated with educational attainment in adolescence (Key Stage 4 [KS4], aged 16yrs), and consider whether any associations are due to an intrauterine causal mechanism.&#x0D; ApproachWe use two main approaches: (1) a comparison of the risks associated with maternal substance use during pregnancy with the risks associated with paternal substance use at the same time, and (2) Mendelian Randomisation (MR). The population-based sample are from the Avon Longitudinal Study of Parents and Children. Educational attainment at KS4 was determined through linkage to the National Pupil Database: capped score of eight best subjects (converted to percentage). Mothers and their partners reported use of substances during the mother’s pregnancy via questionnaire. In observational complete-case analysis (n=6018), multilevel (child level 1, school level 2) linear models were used to examine the association between maternal and paternal substance use and KS4 attainment adjusted for potential confounders. In MR analysis, genetic markers associated with maternal alcohol (rs1229984) and tobacco (rs1051730) use were used to estimate the unconfounded effect of the exposures.&#x0D; ResultsMaternal substance use in pregnancy was common (72% reported any alcohol, 22% any tobacco, and 2% any cannabis) and socially patterned (tobacco associated with deprivation, moderate alcohol and light cannabis with higher maternal education). In adjusted observational analyses, children of mothers who smoked had lower KS4 percentage scores (β -2.7, 95% CI -3.7 to -1.7) but a similar association was observed for paternal smoking (β -3.0, -3.8 to -2.2). Compared to children of non-drinkers in first trimester, children whose mothers drank ≥7 units per week had lower KS4 scores (β -4.6, -7.9 to -1.4), but children of lighter drinkers did not. The MR analyses were under-powered but provisional results suggest no association between maternal smoking and KS4 score, but that small amounts of alcohol could have a detrimental effect. Neither maternal nor paternal cannabis use was associated with educational attainment in observational analyses, but few mothers in our sample used cannabis regularly in pregnancy.&#x0D; ConclusionsThe negative association in observational analysis between maternal smoking in pregnancy and child KS4 attainment is likely due to residual confounding rather than an intrauterine mechanism. Conversely, residual confounding may be masking a negative association between lower levels of alcohol drinking and KS4 attainment in observational analysis.

Somatic growth in the first six months of life of infants exposed to maternal smoking in pregnancy

BackgroundSome studies suggest a relationship between maternal smoking during pregnancy and not only intrauterine fetal growth restriction or low birth weight, but also with changes in the postnatal growth and development. The objective of the present study was to investigate the effects of smoking during pregnancy on infants growth in the first 6 months of life compared with a control group and a group with idiopathic intrauterine growth restriction.MethodsLongitudinal observational study using a convenience sample of newborns divided into three groups: infants of smoking mothers (tobacco), with idiopathic intrauterine growth restriction (IUGR) and a control group. The sample was selected from two hospitals in Porto Alegre, located in southern Brazil, between 2011 and 2015. Newborns were evaluated at birth, 7 and 15 days, and in the first, third, and sixth month. Anthropometric measures were weight, length and head circumference. The growth indicators used were expressed as z-scores. The analyses were performed using the generalized estimating equation method.ResultsThe sample included 273 mother/newborn pairs: 86 tobacco group, 34 IUGR group, and 153 control group. In terms of weight at birth, all groups differed significantly (p < 0.001). The birth length of tobacco and control groups were similar, but the IUGR group was lower than both (p < 0.001). We found no differences in growth trajectory between tobacco and control group, but there were differences in the growth of the IUGR group when compared with the other groups. At 6 months of age, all groups had similar anthropometric measurements.ConclusionIntrauterine growth restriction had major impact on the growth trajectory of the infants studied, regardless of other factors, such as smoking and diet.

Smoking in Pregnancy and Child ADHD.

There is a well-documented association between maternal smoking during pregnancy and offspring attention-deficit/hyperactivity disorder (ADHD). The degree to which this reflects causal intrauterine effects or is due to unmeasured confounding is not clear. We sought to compare the association between maternal smoking during pregnancy and offspring ADHD with the associations with paternal smoking, grandmother's smoking when pregnant with mother, and maternal smoking in previous pregnancies. Each of these exposures is expected to be influenced by much of the same confounding factors as maternal smoking during pregnancy, but cannot have direct intrauterine effects. A sibling control design was also used. The current study used data from the Norwegian Mother and Child Cohort Study (n > 100 000 children). Mothers and fathers reported on smoking during pregnancy, and mothers reported on smoking in previous pregnancies and their mother's smoking when pregnant with them. Mothers reported on child ADHD symptoms at 5 years of age. Information about child ADHD diagnosis was obtained from the Norwegian Patient Registry. Maternal smoking during pregnancy was not more strongly associated with offspring ADHD diagnosis than was paternal smoking, grandmother's smoking when pregnant with mother, or maternal smoking in previous pregnancies. Sibling control analyses showed no association between maternal smoking in pregnancy and child ADHD symptoms among siblings discordant for maternal smoking. These results suggest that the association between maternal smoking during pregnancy and offspring ADHD is not due to causal intrauterine effects, but reflects unmeasured confounding.

Maternal smoking impacts key biological pathways in newborns through epigenetic modification in Utero.

BackgroundChildren exposed to maternal smoking during pregnancy exhibit increased risk for many adverse health effects. Maternal smoking influences methylation in newborns at specific CpG sites (CpGs). Here, we extend evaluation of individual CpGs to gene-level and pathway-level analyses among 1062 participants in the Norwegian Mother and Child Cohort Study (MoBa) using the Illumina 450 K platform to measure methylation in newborn DNA and maternal smoking in pregnancy, assessed using the biomarker, plasma cotinine. We used novel implementations of bioinformatics tools to collapse epigenome-wide methylation data into gene- and pathway-level effects to test whether exposure to maternal smoking in utero differentially methylated CpGs in genes enriched in biologic pathways. Unlike most pathway analysis applications, our approach allows replication in an independent cohort.ResultsData on 485,577 CpGs, mapping to a total of 20,199 genes, were used to create gene scores that were tested for association with maternal plasma cotinine levels using Sequence Kernel Association Test (SKAT), and 15 genes were found to be associated (q < 0.25). Six of these 15 genes (GFI1, MYO1G, CYP1A1, RUNX1, LCTL, and AHRR) contained individual CpGs that were differentially methylated with regards to cotinine levels (p < 1.06 × 10−7). Nine of the 15 genes (FCRLA, MIR641, SLC25A24, TRAK1, C1orf180, ITLN2, GLIS1, LRFN1, and MIR451) were associated with cotinine at the gene-level (q < 0.25) but had no genome-wide significant individual CpGs (p > 1.06 × 10−7). Pathway analyses using gene scores resulted in 51 significantly associated pathways, which we tested for replication in an independent cohort (q < 0.05). Of those 32 replicated in an independent cohort, which clustered into six groups. The largest cluster consisted of pathways related to cancer, cell cycle, ERα receptor signaling, and angiogenesis. The second cluster, organized into five smaller pathway groups, related to immune system function, such as T-cell regulation and other white blood cell related pathways.ConclusionsHere we use novel implementations of bioinformatics tools to determine biological pathways impacted through epigenetic changes in utero by maternal smoking in 1062 participants in the MoBa, and successfully replicate these findings in an independent cohort. The results provide new insight into biological mechanisms that may contribute to adverse health effects from exposure to tobacco smoke in utero.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3310-1) contains supplementary material, which is available to authorized users.

Aortic Elastic Properties in Preschool Children Born Preterm.

Preterm birth predisposes children to the development of cardiovascular diseases in adulthood. The aim of this study was to characterize elastic properties of the aorta at preschool age and test the hypothesis that prematurity is associated with decreased aortic distensibility and increased stiffness, both of which are predictors of increased cardiovascular risk. In an observational study of 76 five- to seven-year-old children born at a gestational age <32 weeks and 79 term-born controls, elastic parameters of the ascending and descending abdominal aorta were determined noninvasively by means of M mode echocardiographic tracings and calculated using computerized wall contour analysis. Compared with children born at term, the preterm group showed significantly reduced distensibility and increased stiffness of the descending abdominal aorta. These results remained significant under multivariable adjustment for birth weight z score, maternal smoking in pregnancy, maternal education, family history of cardiovascular disease, breastfeeding, childhood nutrition, and current body mass index z score (multivariable odds ratios and 95% confidence intervals 5.1, 1.7-15.9; P=0.005 and 2.8, 1.0-7.9; P=0.046, respectively). Further adjustment for intravenous lipid therapy attenuated the strength of association. Elastic properties of the ascending aorta did not differ between the 2 study groups. Children born preterm are characterized by decreased elastic properties of the descending abdominal aorta potentially attributable to impaired viscoelastic properties of and lipid damage to the aorta. Clinical follow-up of preterm infants with a focus on aortic elastic properties may be useful for tailoring early prevention programs and counteracting cardiovascular risk in adulthood.

Land-use variables and respiratory infections in infancy in the Piccolipiù birth cohort

In birth cohort studies, borderline associations have been reported between traffic-related air pollution and otitis, and pneumonia in children. However, the evidence is still scarce, especially in for infants. We aimed to explore the associations of land-use variables at birth and respiratory infections in infants participating in the ongoing prospective Piccolipiù birth cohort recruited in 5 centers in Italy. Of the 3337 infants enrolled, 2698 were studied at 12 months and 1976 at 24 months of age. Occurrence of recurrent upper respiratory infections (URI) including otitis, lower respiratory infections (bronchiolitis, bronchitis, pneumonia), asthmatic bronchitis, and productive cough between birth and 12 months and 12-24 months was ascertained by questionnaires. We investigated road density (meters of roads in the 100m buffer, recoded in quartiles:108-525 [ref]; 525-675; 675-828; 828-1747), major roads density (meters of major roads in the 100m buffer, 0 [ref]; 3.5-203; 203-1654), and distance from major roads (meters, recoded in quartiles: 0-8 [ref]; 8-80; 80-180; 180-2.643). We performed logistic regression, adjusting for center, parental asthma/allergy, maternal education, maternal smoking in pregnancy, siblings, daycare, exposure to passive smoking, dampness and/or mold. Recurrent URI at 12-24 months were associated with road density (higher quartile adjusted OR: 1.88; 95% CI: 1.17; 3.03) and major road density (OR: 1.66; 95% CI: 1.12; 2.47), while an inverse association was found for distance of major roads (higher quartile OR: 0.60; IC 95%: 0.37; 0.98). All trends were significant (P&lt; 0.015). Having siblings and day care attendance were also consistently associated with URI. No associations were found for other respiratory problems. URI are one of the leading causes of physician visits in young children. These data suggest that living near busy roads increases the risk of recurrent URI between 12 and 24 months of life, in addition to known risk factors.

DNA Methylation Score as a Biomarker in Newborns for Sustained Maternal Smoking during Pregnancy.

Background:Maternal smoking during pregnancy, especially when sustained, leads to numerous adverse health outcomes in offspring. Pregnant women disproportionately underreport smoking and smokers tend to have lower follow-up rates to repeat questionnaires. Missing, incomplete, or inaccurate data on presence and duration of smoking in pregnancy impairs identification of novel health effects and limits adjustment for smoking in studies of other pregnancy exposures. An objective biomarker in newborns of maternal smoking during pregnancy would be valuable.Objectives:We developed a biomarker of sustained maternal smoking in pregnancy using common DNA methylation platforms.Methods:Using a dimension reduction method, we developed and tested a numeric score in newborns to reflect sustained maternal smoking in pregnancy from data on cotinine, a short-term smoking biomarker measured mid-pregnancy, and Illumina450K cord blood DNA methylation from newborns in the Norwegian Mother and Child Cohort Study (MoBa).Results:This score reliably predicted smoking status in the training set (n = 1,057; accuracy = 96%, sensitivity = 80%, specificity = 98%). Sensitivity (58%) was predictably lower in the much smaller test set (n = 221), but accuracy (91%) and specificity (97%) remained high. Reduced birth weight, a well-known effect of maternal smoking, was as strongly related to the score as to cotinine. A three-site score had lower, but acceptable, performance (accuracytrain = 82%, accuracytest = 83%).Conclusions:Our smoking methylation score represents a promising novel biomarker of sustained maternal smoking during pregnancy easily calculated with Illumina450K or IlluminaEPIC data. It may help identify novel health impacts and improve adjustment for smoking when studying other risk factors with more subtle effects.Citation:Reese SE, Zhao S, Wu MC, Joubert BR, Parr CL, Håberg SE, Ueland PM, Nilsen RM, Midttun Ø, Vollset SE, Peddada SD, Nystad W, London SJ. 2017. DNA methylation score as a biomarker in newborns for sustained maternal smoking during pregnancy. Environ Health Perspect 125:760–766; http://dx.doi.org/10.1289/EHP333

Prenatal Tobacco Exposure Shortens Telomere Length in Children.

Preliminary evidence suggests a possible association between prenatal tobacco exposure and telomere length in children. This study was conducted to investigate whether maternal smoking during pregnancy was associated with telomere shortening in their children and whether prenatal and childhood exposure to environmental tobacco had any impact on this association. This is a population-representative study on the association between prenatal tobacco exposure and telomere length in children. Ninety-eight Hong Kong Chinese children aged under 15 years with prenatal tobacco exposure and 98 age- and gender-matched controls were recruited from a population health study with stratified random sampling. Telomere length in children with prenatal tobacco exposure was significantly shorter than in those with no exposure (mean T/S ratio = 24.9 [SD = 8.58] in exposed vs. 28.97 [14.15] in control groups; P = 0.02). A negative dose-response relationship was observed between the T/S ratio and tobacco exposure duration: the longer the duration of maternal smoking in pregnancy, the shorter the child's telomere length. The association between the child's telomere length and prenatal tobacco exposure remained significant after considering the influence of family socioeconomic status and exposure to environmental tobacco smoke during pregnancy and childhood. Prenatal tobacco exposure was associated with telomere shortening in children. As this may impose significant health impacts through fetal genetic programming, more efforts should be made to reduce fetal tobacco exposure by educating pregnant women to not smoke and motivating smokers to quit in early pregnancy. As reflected by telomere shortening, prenatal tobacco exposure in children can cause premature aging and increased health risks, which we suggest is entirely preventable. Not smoking during pregnancy or quitting smoking is critical to improving the health outcome of our future generations as prenatal tobacco exposure may affect children's biological programming.

Gestational influenza and risk of hypomania in young adulthood: prospective birth cohort study

BackgroundPrevious studies have suggested a possible link between exposure to influenza in utero and bipolar disorder in adulthood. Using data from a prospective birth cohort, we aimed to test for an association between exposure to gestational influenza and the experience of hypomania assessed in early adulthood. MethodsWe used data on 2957 participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). The two main outcomes of interest were hypomania, assessed using the Hypomania Checklist (HCL-32) at age 22–23, and ‘hypomania plus previous psychotic experiences (PE)’. Maternally-reported gestational influenza was the exposure of interest. Multivariable logistic regression was used and estimates of association were adjusted for a range of possible confounding factors, including maternal smoking in pregnancy. ResultsRelative to controls, rates of exposure to gestational influenza were higher for participants with hypomania (24.0%) and for participants with ‘hypomania plus PE’ (34.2%), but univariate and multivariable analyses of an association between gestational influenza and hypomania (with and without previous PE) were not significant. LimitationsThe response rate to those who were sent the HCL-32 questionnaire was 36.8%. As a result, some analyses may have been under-powered to detect a true effect. Influenza infection during pregnancy was self-reported by mothers. ConclusionsIn this prospective population study, gestational influenza was not identified as a clear risk factor for lifetime hypomania or for ‘hypomania with PEs’ in young adult offspring. It is possible that previous reports of an association between gestational influenza and bipolar disorder in adulthood have been confounded by factors such as maternal smoking during pregnancy.

Smoking in pregnancy and risk of cancer among young children: A population-based study.

Smoking during pregnancy is a plausible risk factor for childhood cancer, yet previous studies have yielded conflicting results, and few prospective studies have been published. Data on maternal smoking were obtained from California birth certificates. We linked California birth certificates (births 2007-2011) with California Cancer Registry records for childhood cancer cases (diagnosed January 2007-September 2013) that were ages 5 or younger at diagnosis (N cases = 2,021). Controls (N = 40,356) were frequency-matched by birth year and randomly selected from birth certificate records. We used unconditional logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI) to assess the association between smoking during pregnancy and childhood cancer. We observed positive associations for gliomas (OR = 1.8, 95% CI: 1.0-3.4) and retinoblastoma (OR = 3.0, 95% CI: 1.4-6.6), particularly bilateral retinoblastoma (OR = 9.4, 95% CI 3.6-24.7) with maternal smoking in pregnancy. Maternal smoking during pregnancy may be a risk factor for retinoblastoma and certain types of childhood brain tumors.

DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2× 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.

Perinatal Risk Factors for Feeding and Eating Disorders in Children Aged 0 to 3 Years.

To describe the incidence, age at diagnosis, and associations between perinatal risk factors of feeding and eating disorders (FED) diagnosed at hospital in children aged 0 to 3 years. A nationwide cohort of 901 227 children was followed until 48 months of age in the national registers from 1997 to 2010. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) for FED diagnosis according to the International Classification of Diseases and associations with perinatal risk factors. A total of 1365 children (53% girls) were diagnosed with FED at hospital, corresponding to a cumulative incidence of 1.6 per 1000 live births. High risk of FED was seen in children born before gestational week 28 (HR, 3.52; 95% confidence interval [CI], 2.15-5.78). HRs were 3.74 for children small for gestational age ≤3 SD (95% CI, 2.71-5.17) and 4.71 in those with congenital malformations (95% CI, 3.86-5.74). Increased risk of FED was associated with female gender (HR, 1.2; 95% CI, 1.08-1.34), maternal smoking in pregnancy (HR, 1.24; 95% CI, 1.08-1.42), immigrant status (HR, 2.24; 95% CI, 1.92-2.61), and being the firstborn (HR, 1.33; 95% CI, 1.19-1.50). FED in referred children aged 0 to 3 years are associated with perinatal adversities, female gender, maternal smoking in pregnancy, being firstborn, and having immigrant parents. The results suggest complex causal mechanisms of FED and underscore the need for a multidisciplinary approach in the clinical management of young children with persistent problems of feeding, eating, and weight faltering.