The threshold for population-level optimal red blood cell (RBC) folate concentration among women of reproductive age for the prevention of neural tube defects has been estimated at 906 nmol/L; however, the dose-response relationship between folic acid intake and blood folate concentrations is uncharacterized. To estimate the magnitude of blood folate concentration increase in response to specific dosages of folic acid under steady-state conditions (as could be achieved with food fortification), a systematic review of the literature and meta-analysis was conducted. Of the 14,002 records we identified, 533 were selected for full-text review, and data were extracted from 108 articles. The steady-state concentrations (homeostasis) of both serum/plasma and RBC folate concentrations were estimated using a Bayesian meta-analytic approach and one-compartment physiologically-based pharmacokinetic models. RBC folate concentrations increased 1.78 fold (95% credible interval (CI): 1.66, 1.93) from baseline to steady-state at 375–570 µg folic acid/day, and it took a median of 36 weeks of folic acid intake (95% CI: 27, 52) to achieve steady-state RBC folate concentrations. Based on regression analysis, we estimate that serum/plasma folate concentrations increased 11.6% (95% CI: 8.4, 14.9) for every 100 µg/day folic acid intake. These results will help programs plan and monitor folic acid fortification programs.

Lower cognitive performance is associated with poorer health and functioning throughout the lifespan and disproportionately affects children from lower socioeconomic status (SES) populations. Previous studies reporting positive associations between child home enrichment and cognitive performance generally had a limited distribution of SES. We evaluated the associations of SES and child enrichment with cognitive performance in a population with a wide range of SES, particularly whether enrichment attenuates associations with SES. Children were sampled from a case–control study of small-for-gestational-age (SGA) conducted in a public hospital serving a low SES population (final n = 198) and a private hospital serving a middle-to-high SES population (final n = 253). SES (maternal education and income) and perinatal factors (SGA, maternal smoking and drinking) were obtained from maternal birth interview. Five child home enrichment factors (e.g. books in home) and preschool attendance were obtained from follow-up interview at age 4.5 years. Cognitive performance was assessed with the Differential Ability Scales (DAS), a standardized psychometric test administered at follow-up. SES and enrichment scores were created by combining individual factors. Analyses were adjusted for perinatal factors. Children from the public birth hospital had a significantly lower mean DAS general cognitive ability (GCA) score than children born at the private birth hospital (adjusted mean difference −21.4, 95% CI: −24.0, −18.7); this was substantially attenuated by adjustment for individual SES, child enrichment factors, and preschool attendance (adjusted mean difference −5.1, 95% CI: −9.5, −0.7). Individual-level SES score was associated with DAS score, beyond the general SES effect associated with hospital of birth. Adjustment for preschool attendance and home enrichment score attenuated the association between individual SES score and adjusted mean DAS-GCA among children born at both of the hospitals. The effect of being in the lower compared to the middle tertile of SES score was reduced by approximately a quarter; the effect of being in the upper compared to the middle tertile of SES score was reduced by nearly half, but this comparison was possible only for children born at the private hospital. A child’s individual SES was associated with cognitive performance within advantaged and disadvantaged populations. Child enrichment was associated with better cognitive performance and attenuated the SES influence. Health care providers should reinforce guidelines for home enrichment and refer children with delays to early intervention and education, particularly children from disadvantaged populations.