Abstract
BackgroundGestational 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.ResultsUsing 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 < 25 kg/m2, p < .001). There was evidence of an association between male sex and greater gestational age acceleration. Greater gestational age acceleration was associated with higher birthweight, birth length and head circumference of the child (mean differences per week higher gestational age acceleration: birthweight 0.1 kg, 95% CI 0.1 to 0.2, p < .001; birth length 0.4 cm, 95% CI 0.2 to 0.7, p < .001; head circumference 0.2 cm, 95% CI 0.1 to − 0.4, p < .001). There was evidence of an association between gestational age acceleration and mode of delivery (assisted versus unassisted delivery, odds ratio = 0.9 per week higher gestational age acceleration, 95% CI 0.7, 1.3 (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.ConclusionsThe 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.
Highlights
Gestational age at delivery is associated with health and social outcomes
Study sample characteristics The characteristics of the 863 participants from the Accessible Resource for Integrated Epigenomic Studies (ARIES) cohort included in our analysis are displayed in Tables 1 and 2, and Additional file 1: Table S1 describes the differences between these participants and the full Avon Longitudinal Study of Parents and Children (ALSPAC) cohort from which ARIES is a subsample
We elected not to use the model of Knight et al [9] because we were less confident that it would produce meaningful gestational age acceleration (GAA) estimates given its low correlation with Gestational age (GA) in ARIES (r = 0.37) [21]
Summary
Gestational age at delivery is associated with health and social outcomes. Recently, cord blood DNA methylation data has been used to predict gestational age. DNA methylation (DNAm) has been used to predict GA at delivery [9, 10] This method builds on work that used DNAm to predict chronological age [11] and subsequent work, showing that the differences between predicted and chronological age are associated with disease outcomes. Those with DNAm-predicted ages that exceeded their chronological ages (age acceleration, AA) have a higher risk of cancer incidence [12,13,14], Alzheimer’s disease [15] and mortality [15,16,17,18,19,20]. The term AA is commonly used in the literature to describe both positive and negative differences (i.e. predicted ages above or below chronological ages), which could be misleading, but we use the term to be consistent with previous literature
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