Maternal Iron Status in Pregnancy and Child Health Outcomes after Birth: A Systematic Review and Meta-Analysis

Abstract

In pregnancy, iron deficiency and iron overload increase the risk for adverse pregnancy outcomes, but the effects of maternal iron status on long-term child health are poorly understood. The aim of the study was to systematically review and analyze the literature on maternal iron status in pregnancy and long-term outcomes in the offspring after birth. We report a systematic review on maternal iron status during pregnancy in relation to child health outcomes after birth, from database inception until 21 January 2021, with methodological quality rating (Newcastle-Ottawa tool) and random-effect meta-analysis. (PROSPERO, CRD42020162202). The search identified 8139 studies, of which 44 were included, describing 12,7849 mother–child pairs. Heterogeneity amongst the studies was strong. Methodological quality was predominantly moderate to high. Iron status was measured usually late in pregnancy. The majority of studies compared categories based on maternal ferritin, however, definitions of iron deficiency differed across studies. The follow-up period was predominantly limited to infancy. Fifteen studies reported outcomes on child iron status or hemoglobin, 20 on neurodevelopmental outcomes, and the remainder on a variety of other outcomes. In half of the studies, low maternal iron status or iron deficiency was associated with adverse outcomes in children. Meta-analyses showed an association of maternal ferritin with child soluble transferrin receptor concentrations, though child ferritin, transferrin saturation, or hemoglobin values showed no consistent association. Studies on maternal iron status above normal, or iron excess, suggest deleterious effects on infant growth, cognition, and childhood Type 1 diabetes. Maternal iron status in pregnancy was not consistently associated with child iron status after birth. The very heterogeneous set of studies suggests detrimental effects of iron deficiency, and possibly also of overload, on other outcomes including child neurodevelopment. Studies are needed to determine clinically meaningful definitions of iron deficiency and overload in pregnancy.

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

“…Despite the low prevalence of homozygosis for HFE gene mutations in our study population (only 4.8% for H63D genotype), the prevalence of having any HFE gene mutation is around 46% in the Mediterranean population [ 34 , 60 ], which turn it into an important risk factor to consider when prescribing iron supplementation. There are some indications from observational studies that not only iron deficiency but also iron excess negatively affects the child’s neurodevelopment [ 18 , 32 , 33 , 35 , 36 ] and, based on that, some main researchers in this field have proposed to adapt the prenatal iron supplementation to the individual’s requirements to mitigate the potential damage from any maternal iron imbalance [ 22 , 23 , 25 , 41 ]. However, few studies have tested this hypothesis, obtaining inconsistent results [ 37 , 61 ].…”

“…In this regard, it is important to highlight that the overall prevalence of HFE gene alterations in our population is quite high [ 34 ]. After some authors have concluded that both iron deficit and excess may injure the child’s cognitive and motor development [ 32 , 35 , 36 ], they advise that prenatal iron supplementation should be individualized considering maternal iron stores, as well as other lifestyle and biological conditions [ 37 , 38 ]. We supported this advice after having shown by a community-based Randomized Clinical Trial (RCT) the effectiveness of adapting iron doses to maternal haemoglobin (Hb) levels early in pregnancy in preventing iron deficiency, anaemia, and haemoconcentration [ 39 ].…”

Ethnic differences in adverse iron status in early pregnancy: a cross-sectional population-based study

“…Serum ferritin was measured by an electrochemiluminescence immunoassay (ECLIA) on the Cobas e411 analyser (Roche, Almere, The Netherlands). Based on the most commonly applied definitions during pregnancy, iron deficiency was defined as ferritin <15 μg/l and iron overload as ferritin >150 μg/l ( 3 , 18 , 19 ) . Ferritin is a positive acute-phase protein, that is elevated in the presence of infection or inflammation, regardless of iron status ( 20 , 21 ) .…”

Iron Status in Pregnant Women in Latvia: An Epidemiological, Cross-Sectional, Multicenter Study According to WHO and UK Criteria

“…Maternal ID with or without anaemia during pregnancy is reported to negatively affect the mother and the foetus/newborn [ 3 , 4 ]. Mothers with ID often experience increased levels of fatigue and reduced physical and mental performance [ 5 ].…”