The effect of universal maternal antenatal iron supplementation on neurodevelopment in offspring: a systematic review and meta-analysis

Abstract

BackgroundAlthough antenatal iron supplementation is beneficial to mothers, its impact on the neurodevelopment of offspring is controversial. A systematic review and meta-analysis was undertaken to assess whether routine maternal antenatal iron supplementation confers later neurodevelopmental benefit to offspring.MethodsElectronic databases were searched using MESH terms or key words and identified papers were reviewed by two independent reviewers. The study quality was assessed using the Cochrane risk of bias assessment tool. The review was registered in the PROSPERO CRD data base.ResultsSeven publications were identified, based on four randomised trials published between 2006 and 2016. Three of the trials were in the Asian sub-continent. A range of tools were used to evaluate neurodevelopment. Meta-analysis of outcomes from the three RCTs meeting our inclusion criteria showed minimal effect of antenatal iron supplementation on the neurodevelopment of offspring, which was not statistically significant: weighted mean difference of 0.54 (95% CI: -0.67 to 1.75); test for overall effect Z = 0.87; p = 0.38; and heterogeneity 48%. Meta-analysis of outcomes of these RCTs at later stages of development produced similar results.ConclusionsThe benefit of routine antenatal iron supplementation on neurodevelopment in offspring was not statistically significant in this relatively limited set of trials, and some benefit cannot be excluded in areas with a high prevalence of maternal anaemia. A large randomized controlled trial showing significant benefit would be required to modify our conclusions.Electronic supplementary materialThe online version of this article (10.1186/s12887-018-1118-7) contains supplementary material, which is available to authorized users.

Iron Deficiency and Iron Deficiency Anemia: Implications and Impact in Pregnancy, Fetal Development, and Early Childhood Parameters

“…However, it is not entirely clear that maternal iron supplementation during pregnancy can reverse effects of maternal ID during pregnancy on neurodevelopment [77,78]. Two recent systematic reviews found no evidence that iron supplementation during pregnancy improved neurodevelopment in offspring [76,79]. The specific frequency of ID in the populations studied may have contributed to the absence of a statistically significant effect: benefits may have been confined to patients who were iron deficient or had marginal iron stores at the time of treatment [79,80].…”

“…Two recent systematic reviews found no evidence that iron supplementation during pregnancy improved neurodevelopment in offspring [76,79]. The specific frequency of ID in the populations studied may have contributed to the absence of a statistically significant effect: benefits may have been confined to patients who were iron deficient or had marginal iron stores at the time of treatment [79,80]. From a standpoint of newborn anemia/iron status, the evidence appears more clear: studies spanning 60 years that consistently support the concept that maternal ID typically does not reduce fetal iron supply.…”

“…In general, iron supplementation is considered low risk [53], and an iron supplement of 65 mg elemental iron mg/day beginning at or before 20 weeks' gestation generally is adequate to prevent ID during pregnancy [30]. However, one of the arguments against routine iron supplementation, particularly in the less-developed world, is that benefits on infant neurocognitive development (as distinct from benefits on maternal anemia and iron stores) have not been demonstrated clearly, as was discussed earlier [79].…”

Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study

“…More recently, it has been suggested that ID during pregnancy may not only have effects in early life [5,6,[21][22][23][24] but could also be related to long-term alterations in cognitive, behavior, and social development and poorer school performance during childhood and adolescence [3,12,[25][26][27]. Even so, a review concluded that the influence of maternal iron status during pregnancy on the cognitive function of offspring is inconclusive [13,28,29]. Some reasons for these inconsistencies may be related to methodological issues such as different cognitive assessments or to the time when iron status was assessed during pregnancy.…”

“…Although some previous studies have shown that prenatal iron supplementation could improve a child's neuropsychological outcomes [33,34], there is still much controversy and most of the evidence has examined the relationship in small populations, in developing countries, and in the short-term in the first months of life [35][36][37]. A recent meta-analysis concluded that the benefit of routine antenatal iron supplementation for neurodevelopment in offspring was not significant [29]. Moreover, cognitive development can be influenced by multiple factors that must be taken into account, such as obstetrical outcomes, infant breastfeeding, the mother's alcohol and cigarette intake, the mother's intellectual capacity, and the family environment [28,[35][36][37].…”