Dataset Information

Epigenetic gestational age acceleration: a prospective cohort study investigating associations with familial, sociodemographic and birth characteristics.

ABSTRACT:

Background

Gestational age at delivery is associated with health and social outcomes. Recently, cord blood DNA methylation data has been used to predict gestational age. The discrepancy between gestational age predicted from DNA methylation and determined by ultrasound or last menstrual period is known as gestational age acceleration. This study investigated associations of sex, socioeconomic status, parental behaviours and characteristics and birth outcomes with gestational age acceleration.

Results

Using data from the Avon Longitudinal Study of Parents and Children (n?=?863), we found that pre-pregnancy maternal overweight and obesity were associated with greater gestational age acceleration (mean difference?=?1.6 days, 95% CI 0.7 to 2.6, and 2.9 days, 95% CI 1.3 to 4.4, respectively, compared with a body mass index 2, p?p?p?p?p?=?.05); caesarean section versus unassisted delivery, odds ratio?=?0.6, 95% CI 0.4 to 0.9 per week higher gestational age acceleration (p?=?.05)). There was no evidence of association for other parental and perinatal characteristics.

Conclusions

The associations of higher maternal body mass index and larger birth size with greater gestational age acceleration may imply that maternal overweight and obesity is associated with more rapid development of the fetus in utero. The implications of gestational age acceleration for postnatal health warrant further investigation.

SUBMITTER: Khouja JN

PROVIDER: S-EPMC6020346 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Epigenetic gestational age acceleration: a prospective cohort study investigating associations with familial, sociodemographic and birth characteristics.

Khouja Jasmine N JN Simpkin Andrew J AJ O'Keeffe Linda M LM Wade Kaitlin H KH Houtepen Lotte C LC Relton Caroline L CL Suderman Matthew M Howe Laura D LD

Clinical epigenetics 20180627

<h4>Background</h4>Gestational age at delivery is associated with health and social outcomes. Recently, cord blood DNA methylation data has been used to predict gestational age. The discrepancy between gestational age predicted from DNA methylation and determined by ultrasound or last menstrual period is known as gestational age acceleration. This study investigated associations of sex, socioeconomic status, parental behaviours and characteristics and birth outcomes with gestational age accelera ...[more]

PMID: 29983833

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Project description:Study questionIs the use of ART, a proxy for infertility, associated with epigenetic age acceleration?Summary answerThe epigenetic age acceleration measured by Dunedin Pace of Aging methylation (DunedinPoAm) differed significantly between non-ART and ART mothers.What is known alreadyAmong mothers who used ART, epigenetic age acceleration may be associated with low oocyte yield and poor ovarian response. However, the difference in epigenetic age acceleration between non-ART and ART mothers (or even fathers) has not been examined.Study design, size, durationThe Norwegian Mother, Father and Child Cohort Study (MoBa) recruited pregnant women and their partners across Norway at around 18 gestational weeks between 1999 and 2008. Approximately 95 000 mothers, 75 000 fathers and 114 000 children were included. Peripheral blood samples were taken from mothers and fathers at ultrasound appointments or from mothers at childbirth, and umbilical cord blood samples were collected from the newborns at birth.Participants/materials, setting, methodsAmong the MoBa participants, we selected 1000 couples who conceived by coitus and 894 couples who conceived by IVF (n = 525) or ICSI (n = 369). We measured their DNA methylation (DNAm) levels using the Illumina MethylationEPIC array and calculated epigenetic age acceleration. A linear mixed model was used to examine the differences in five different epigenetic age accelerations between non-ART and ART parents.Main results and the role of chanceWe found a significant difference in the epigenetic age acceleration calculated by DunedinPoAm between IVF and non-ART mothers (0.021 years, P-value = 2.89E-06) after adjustment for potential confounders. Further, we detected elevated DunedinPoAm in mothers with tubal factor infertility (0.030 years, P-value = 1.34E-05), ovulation factor (0.023 years, P-value = 0.0018) and unexplained infertility (0.023 years, P-value = 1.39E-04) compared with non-ART mothers. No differences in epigenetic age accelerations between non-ART and ICSI fathers were found. DunedinPoAm also showed stronger associations with smoking, education and parity than the other four epigenetic age accelerations.Limitations, reasons for cautionWe were not able to determine the directionality of the causal pathway between the epigenetic age accelerations and infertility. Since parents' peripheral blood samples were collected after conception, we cannot rule out the possibility that the epigenetic profile of ART mothers was influenced by the ART treatment. Hence, the results should be interpreted with caution, and our results might not be generalizable to non-pregnant women.Wider implications of the findingsA plausible biological mechanism behind the reported association is that IVF mothers could be closer to menopause than non-ART mothers. The pace of decline of the ovarian reserve that eventually leads to menopause varies between females yet, in general, accelerates after the age of 30, and some studies show an increased risk of infertility in females with low ovarian reserve.Study funding/competing interest(s)This study was partly funded by the Research Council of Norway (Women's fertility, project no. 320656) and through its Centres of Excellence Funding Scheme (project no. 262700). M.C.M. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement number 947684). The authors declare no conflict of interest.Trial registration numberN/A.

Project description:BACKGROUND:Among highly exposed populations, arsenic exposure in utero may be associated with decreased birth weight, however less is known about potential effects of arsenic exposure in urban communities without contaminated sources such as drinking water. OBJECTIVE:Investigate the association of blood arsenic levels with birth weight-for-gestational age categories within a prospective birth cohort study. DESIGN/METHODS:We analyzed 730 mother-infant dyads within the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) cohort in Mexico City. Total arsenic was measured in maternal blood samples from the 2nd and 3rd trimesters, at delivery, as well as from infant umbilical cord blood samples. Multivariable, multinomial logistic regression models adjusting for maternal age at enrollment, pre-pregnancy body mass index, parity, infant sex, socioeconomic position, and prenatal environmental tobacco smoke exposure were used to calculate odds ratios of small-for-gestational age (<10th percentile, SGA) and large-for-gestational age (>90th percentile, LGA) compared to appropriate-for-gestational age (AGA) per unit increase of log-transformed arsenic. RESULTS:Median (IQR) blood arsenic levels for maternal second trimester were 0.72 (0.33) ?g/L, maternal third trimester 0.75 (0.41) ?g/L, maternal at delivery 0.85 (0.70) ?g/L, and infant cord 0.78 (0.65) ?g/L. Maternal delivery and infant cord blood samples were most strongly correlated (spearman r?=?0.65, p?<?0.0001). Maternal arsenic levels at delivery were associated with significantly higher odds of both SGA (adj. OR?=?1.44, 95% CI: 1.08-1.93) and LGA (adj. OR?=?2.03, 95% CI: 1.12-3.67) compared to AGA. Results were similar for cord blood. There were 130 SGA infants and 22 LGA infants. Earlier in pregnancy, there were no significant associations of arsenic and birth weight-for-gestational age. However, we observed non-significantly higher odds of LGA among women with higher arsenic levels in the 3rd trimester (adj. OR?=?1.46, 95% CI: 0.67-3.12). CONCLUSION:We found that in a Mexico City birth cohort, higher maternal blood arsenic levels at delivery were associated with higher odds of both SGA and LGA. However, sources and species of arsenic were not known and the number of LGA infants was small, limiting the interpretation of this finding and highlighting the importance of future large studies to incorporate arsenic speciation. If our findings were confirmed in studies that addressed these limitations, determining modifiable factors that could be mitigated, such as sources of arsenic exposure, may be important for optimizing fetal growth to improve long-term health of children.

Dataset Information

Epigenetic gestational age acceleration: a prospective cohort study investigating associations with familial, sociodemographic and birth characteristics.

Background

Results

Conclusions

Publications

Epigenetic gestational age acceleration: a prospective cohort study investigating associations with familial, sociodemographic and birth characteristics.

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