Table 4.
Associations of circulating folate, vitamin B12 and homocysteine concentrations with gestational age acceleration (subgroup analysis)
| Bohlin | Knight | |||||||
|---|---|---|---|---|---|---|---|---|
| Raw accelerationa | Residual accelerationb | Raw accelerationa | Residual accelerationb | |||||
| Difference (95% CI) in weeks | P value | Difference (95% CI) | P value | Difference (95% CI) in weeks | P value | Difference (95% CI) | P value | |
| Early pregnancy | ||||||||
| Folate, SDS | − 0.01 (− 0.11, 0.10) | 0.89 | 0.02 (− 0.04, 0.08) | 0.50 | − 0.01 (− 0.15, 0.13) | 0.88 | 0.02 (− 0.10, 0.14) | 0.75 |
| Total B12, SDS | 0.02 (− 0.08, 0.12) | 0.71 | 0.03 (− 0.03, 0.09) | 0.36 | − 0.03 (− 0.17, 0.12) | 0.71 | − 0.01 (− 0.14, 0.11) | 0.82 |
| Active B12, SDS | − 0.03 (− 0.14, 0.08) | 0.60 | 0.01 (− 0.05, 0.08) | 0.72 | − 0.07 (− 0.22, 0.08) | 0.36 | − 0.04 (− 0.17, 0.10) | 0.60 |
| Homocysteine, SDS | 0.04 (− 0.07, 0.16) | 0.47 | − 0.04 (− 0.11, 0.03) | 0.25 | − 0.02 (− 0.16, 0.12) | 0.79 | − 0.08 (− 0.20, 0.04) | 0.20 |
| Cord blood | ||||||||
| Folate, SDS | − 0.09 (− 0.19, 0.02) | 0.11 | − 0.04 (− 0.10, 0.03 | 0.24 | 0.05 (− 0.09, 0.18) | 0.52 | 0.08 (− 0.04, 0.20) | 0.18 |
| Total B12, SDS | − 0.10 (− 0.20, 0.00) | 0.06 | − 0.03 (− 0.09, 0.03) | 0.37 | − 0.16 (− 0.30, − 0.02) | 0.02* | − 0.10 (− 0.22, 0.02) | 0.12 |
| Active B12, SDS | − 0.11 (− 0.21, 0.00) | 0.06 | − 0.05 (− 0.11, 0.01) | 0.12 | − 0.15 (− 0.29, − 0.01) | 0.04* | − 0.10 (− 0.23, 0.02) | 0.10 |
| Homocysteine, SDS | − 0.00 (− 0.10, 0.09) | 0.93 | − 0.01 (− 0.06. 0.05) | 0.78 | − 0.00 (− 0.14, 0.14) | 0.97 | − 0.01 (− 0.13, 0.12) | 0.91 |
*This association at nominal significance did remain if we applied a Bonferroni correction, adjusting for four exposures (0.05/4)
This analysis included 380 newborns of mothers with optimal pregnancy dating based on a regular menstrual cycle and gestational age determined by last menstrual period. For the analysis using Bohlin’s epigenetic clock we included 378 of these newborns, after excluding 2 newborns with missing data for some CpGs required for the DNA methylation gestational age calculation. Values represent regression coefficients (95% confidence interval) and reflect the difference in raw and residual gestational age acceleration at birth per increase of 1 standard deviation score in exposure variable. Results are based on the main models, which were adjusted for maternal age, education, pre-pregnancy BMI, parity and smoking, child sex, batch effects (by including plate number), cell types, and additionally for gestational age at blood sampling in early pregnancy models. Folate and homocysteine concentrations were measured in plasma and total and active B12 concentrations were measured in serum
CI confidence interval, SDS standard deviation score
aRaw gestational age acceleration (in weeks) was obtained by subtracting the clinical estimate of gestational age from DNA methylation gestational age
bResidual gestational age acceleration (no unit) was calculated from the residuals from a regression model of DNA methylation gestational age on clinical gestational age