Introduction
Methods
Study population
Maternal folic acid supplement use
Maternal folate concentrations
Foetal and child head circumference
Covariates
Statistical analyses
Results
Folate-deficient n = 493 (8.4 %) | Normal folate concentrations n = 5373 (91.6 %) |
P
c
| |
---|---|---|---|
Child characteristics | |||
Gender (% girl) | 49.5 | 47.8 | 0.50 |
Gestational age at birth (weeks)d,e
| 39.7 ± 2.2 | 39.9 ± 1.7 | <0.01 |
Maternal characteristics | |||
Age at enrolment (years) | 27.0 ± 5.5 | 30.0 ± 4.9 | <0.001 |
Gestational age at enrolment (weeks)f
| 14.3 ± 2.2 | 13.5 ± 2.0 | <0.001 |
Ethnicity (%) | |||
Dutch | 28.9 | 53.9 | |
Other Western | 7.1 | 9.0 | |
Turkish or Moroccan | 24.8 | 13.7 | <0.001 |
Surinamese or Antillean | 21.1 | 10.6 | |
Other non-Western | 18.1 | 12.8 | |
Education (%) | |||
Higher | 14.5 | 45.8 | |
Secondary | 62.7 | 44.5 | <0.001 |
Primary | 22.8 | 9.7 | |
Family income (%) | |||
>2000 €/month | 23.9 | 60.7 | |
1200–2000 €/month | 25.5 | 19.6 | <0.001 |
<1200 €/month | 50.6 | 19.7 | |
BMI at intake (kg/m2) | 25.5 ± 5.0 | 24.4 ± 4.3 | <0.001 |
Smoking during pregnancy (%) | |||
Never | 62.3 | 75.4 | |
Until pregnancy was known | 6.0 | 8.5 | <0.001 |
Continued throughout pregnancy | 31.7 | 16.1 | |
Alcohol consumption during pregnancy (%) | |||
Never | 62.2 | 43.7 | |
Until pregnancy was known | 13.5 | 14.1 | <0.001 |
Continued throughout pregnancy | 24.3 | 42.2 | |
Parity, primiparae (%) | 42.8 | 58.4 | <0.001 |
Psychopathology in mid-pregnancyg
| 0.42 ± 0.47 | 0.28 ± 0.37 | <0.001 |
Folic acid supplement use during pregnancy (%) | |||
No use | 72.5 | 18.6 | |
Start > 10 weeks pregnancy | 11.0 | 13.0 | <0.001 |
Start ≤ 10 weeks pregnancy | 10.0 | 28.9 | |
Preconceptional start | 6.5 | 39.5 |
Maternal folic acid supplementation and offspring head circumference
Head circumference size (SDS) | ||||||
---|---|---|---|---|---|---|
Basicb
| Adjusted for covariatesc
| |||||
SDSd
| Be (95 % CI) |
P
| SDSd
| Be (95 % CI) |
P
| |
Head size (intercept (SDS) at 20 weeks gestation) and folic acid supplementation (n = 5832 (99.4 %), 11,323 observations) | ||||||
No usef
|
−0.163 | Reference |
−0.003 | Reference | ||
Start > 10 weeks |
−0.135 | 0.028 (−0.069; 0.126) | 0.57 |
−0.004 |
−0.001 (−0.104; 0.101) | 0.98 |
Start ≤ 10 weeks |
−0.075 | 0.088 (0.011; 0.166) | 0.03 | 0.028 | 0.031 (−0.054; 0.115) | 0.48 |
Preconceptional start | 0.058 | 0.221 (0.147; 0.296) | <0.001 | 0.123 | 0.126 (0.037; 0.215) | <0.01 |
Head circumference growth (SDS) | ||||||
---|---|---|---|---|---|---|
Basicb
| Adjusted for covariatesc
| |||||
Bg (95 % CI) |
P
| Bg (95 % CI)) |
P
| |||
Period of head growth and folic acid supplementation | ||||||
Second and third trimester (n = 5832 (99.4 %), 11,323 observations) | ||||||
No usef
| Reference | Reference | ||||
Start > 10 weeks | 0.002 (−0.008; 0.012) | 0.72 | 0.001 (−0.009; 0.011) | 0.84 | ||
Start ≤ 10 weeks | 0.004 (−0.004; 0.012) | 0.31 | 0.002 (−0.007; 0.010) | 0.69 | ||
Preconceptional start | 0.008 (−0.000; 0.016) | 0.05 | 0.002 (−0.007; 0.012) | 0.65 | ||
Birth through 6 years (n = 5515 (94.0 %), 29,976 observations) | ||||||
No usef
| Reference | Reference | ||||
Start > 10 weeks |
−0.000 (−0.000; 0.000) | 0.32 |
−0.000 (−0.000; 0.000) | 0.26 | ||
Start ≤ 10 weeks |
−0.000 (−0.000; 0.000) | 0.45 |
−0.000 (−0.000; 0.000) | 0.39 | ||
Preconceptional start |
−0.000 (−0.000; 0.000) | 0.15 |
−0.000 (−0.000; 0.000) | 0.26 |
Maternal folate concentrations and offspring head circumference
Head circumference size (SDS) | ||||||
---|---|---|---|---|---|---|
Basicd
| Adjusted for covariatese
| |||||
SDSf
| Bg (95 % CI) |
P
| SDSf
| Bg (95 % CI) |
P
| |
Head size (intercept (SDS) at 20 weeks gestation) and folate concentration (n = 5832 (99.4 %), 11,323 observations) | ||||||
Mean folateh,i
|
−0.055 | Reference | 0.074 | Reference | ||
Folate (per SD)j
|
−0.021 | 0.034 (0.007; 0.061) | 0.01 | 0.081 | 0.007 (−0.022; 0.037) | 0.63 |
Normal folatei
|
−0.051 | Reference | 0.077 | Reference | ||
Folate-deficient |
−0.100 |
−0.049 (−0.148; 0.049) | 0.32 | 0.110 | 0.033 (−0.068; 0.134) | 0.52 |
Head circumference growth (SDS) | ||||||
---|---|---|---|---|---|---|
Basicd
| Adjusted for covariatese
| |||||
Bk (95 % CI) |
P
| Bk (95 % CI) |
P
| |||
Period of head growth and folate concentration | ||||||
Second and third trimester (n = 5832 (99.4 %), 11,323 observations) | ||||||
Folate (per SD)h,i
| 0.006 (0.003; 0.009) | <0.001 | 0.004 (0.001; 0.007) | 0.01 | ||
Folate-deficient |
−0.013 (−0.023; −0.002) | 0.02 |
−0.007 (−0.018; 0.004) | 0.19 | ||
Birth through 6 years (n = 5515 (94.0 %), 29,976 observations) | ||||||
Folate (per SD)h,i
|
−0.000 (−0.000; 0.000) | 0.28 |
−0.000 (−0.000; 0.000) | 0.66 | ||
Folate-deficient | 0.000 (−0.000; 0.001) | 0.06 | 0.000 (−0.000; 0.000) | 0.29 |