Adapting prenatal iron supplementation to maternal needs results in optimal child neurodevelopment: a follow-up of the ECLIPSES Study

Abstract

Background Prenatal prescription of standard iron supplements to prevent iron deficiency appears not to be appropriate for all women and their children, as some women may be at risk of iron deficiency and others at risk of iron excess early in pregnancy. The present study aimed to assess whether prenatal iron supplementation adapted to the needs of each pregnant woman affects their child’s neurodevelopment. Methods Follow-up of a community-based RCT involving 503 mother–child pairs. Non-anaemic pregnant women recruited in Tarragona (Spain) early in pregnancy were prescribed a daily iron dose based on their initial haemoglobin levels: Stratum 1 (Hb = 110–130 g/L, 80 or 40 mg/d of iron) and Stratum 2 (Hb > 130 g/L, 40 or 20 mg/d of iron). Women receiving 40 mg/d were considered the control group in each Strata . The child’s neurodevelopment was assessed at 40 days of age using the Bayley Scales of Infant Development-III (BSID-III). Adjusted multiple regression models were used. Results Multiple regression analyses showed no association between the intervention and control group within each Strata on the BSID-III scores on any of the developmental scales in children, including cognitive, language, and motor development: Stratum 1 (β 1.46, 95%CI -2.15, 5.07; β 1.30, 95%CI -1.99, 4.59; and β 2.04, 95%CI -3.88, 7.96, respectively) and Stratum 2 (β -4.04, 95%CI -7.27, 0.80; β -0.36, 95%CI -3.47, 2.75; and β -3.76, 95%CI -9.30, 1.78, respectively). Conclusions In non-anaemic women in early pregnancy, no differences were found in the cognitive, language and motor development of children at 40 days of age between the dose of iron tested in each case –adjusted to initial Hb levels– compared to the dose of the control group. Further studies are guaranteed to confirm our findings. Trial registration The ECLIPSES study was registered at www.clinicaltrialsregister.eu as EudraCT number 2012–005,480-28. Supplementary Information The online version contains supplementary material available at 10.1186/s12884-022-05033-y.

Preparatory work for the update of the tolerable upper intake levels for iron

“…When measured shortly (up to 40 days) after birth, multiple regression analyses did not reveal any significant association of the dose of iron supplemented (20-80 mg/day) to pregnant, non-anaemic females with the BSID III-scores of their offspring, which assess cognitive, language, and motor development (Iglesias-Vazquez et al, 2022). In parallel to this finding, when investigating the effect of 20 mg iron/day supplementation to pregnant females from the 20 th week of gestation on the IQ of the 4-year old offspring, no differences were found between the supplementation and the placebo group (Parsons et al, 2008;Zhou et al, 2006).…”

“…A large body of studies support that iron-deficiency anaemia is associated with impaired cognitive development in infants (Idjradinata & Pollitt, 1993;Lozoff et al, 1982;Lozoff et al, 1996;Walter et al, 1989). When supplemented daily with either 2 mg iron/kg BW (Bora et al, 2021), 3 mg iron/ kg BW (Idjradinata & Pollitt, 1993), or 6 mg/ kg BW (Akman et al, 2004) for 6, 4, or 6 months, respectively, developmental delays associated with iron deficiency or iron-deficiency anaemia were found to be reversed.…”

“…A large body of studies support that iron-deficiency anaemia is associated with impaired cognitive development in infants (Idjradinata & Pollitt, 1993;Lozoff et al, 1982;Lozoff et al, 1996;Walter et al, 1989). When supplemented daily with either 2 mg iron/kg BW (Bora et al, 2021), 3 mg iron/ kg BW (Idjradinata & Pollitt, 1993), or 6 mg/ kg BW (Akman et al, 2004) for 6, 4, or 6 months, respectively, developmental delays associated with iron deficiency or iron-deficiency anaemia were found to be reversed. Supplementation of 6 months (Lind et al, 2004b) or 17-19 months (Aukett et al, 1986) old, partly anaemic children with 10 or 24 mg iron for two or 6 months, respectively, improved the scores on the Bayley Scales of Infant Development test or the psychomotor skills in the Denver developmental EFSA Supporting publication 2024:EN-8661…”