Association between Maternal Plasma Ferritin Level and Infants’ Size at Birth: A Prospective Cohort Study in Rural Bangladesh

Abstract

Background : Iron supplementation in pregnancy is recommended by the WHO to prevent a major public health problem, namely, maternal iron deficiency and its consequences. There are gaps in the existing evidence regarding maternal and neonatal benefits and harms of universal iron supplementation. Objective : To evaluate the association between maternal iron status during pregnancy and infant size at birth (birth weight and length). Method : This present prospective cohort study was nested in a food and micronutrient supplementation trial conducted in Matlab (MINIMat study), rural Bangladesh. We randomly selected 573 women recruited into the MINIMat study from January – December 2002 who delivered singletons with available birth anthropometric information. The plasma ferritin of each mother was measured at gestational week 14 (GW14; before the start of micronutrient supplementation) and at week 30 (GW30). Results : Multivariable linear regression revealed no association between plasma ferritin at GW14 and birth weight. However, newborns of women in the highest tertile of plasma ferritin at GW30 (median = 29 µg/L) had on average a 93-gm lower birth weight (95% CI: −172, – 14; p = 0.021) than the newborns of womehemoglobin (Hb) synthesisn in the lowest tertile (median = 8 µg/L). Logistic regression showed that odds of low birth weight were approximately two times higher [odds ratio (OR) = 2.27; 95% CI: 1.40, 3.67] among those with mothers in the highest ferritin tertile than in the lowest tertile at GW30. No association was found between maternal plasma ferritin and birth length. Conclusion : We observed an inverse association between high plasma ferritin in the last trimester (GW30) and birth weight but not birth length. The results suggested that elevated plasma ferritin in pregnancy could have an untoward effect on birth weight.

The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen—a prospective cohort study

“…Furthermore, it has been proposed that the observed ferritin-birth outcome relationship may be due to an adverse effect of iron supplementation on birthweight in iron-replete women, amongst whom supplementation may reduce birthweight [ 6 , 22 , 45 ]. Putative mechanisms may include adverse impacts on foetal growth due to either increased blood viscosity or placental damage from free radicals in supplemented iron-replete women [ 59 , 60 ].…”

“…However, studies assessing relationships between markers of maternal iron reserves and birth outcomes do not consistently report a reduction in adverse outcomes in ironreplete women [42,43]. Recent studies report possible associations of ID during pregnancy with reduced risks of adverse pregnancy outcomes and increases in mean birthweight, as well as associations of iron supplementation during pregnancy with an increased risk of LBW [20,[44][45][46][47][48].…”

“…Several mechanisms to explain the association between an iron-replete state with reductions in birthweight have been proposed [20][21][22]45]. Iron deficiency may lead to decreased reticulocyte numbers, and thus in malariaendemic settings such as PNG, ID may confer a level of protection from P. falciparum infection.…”

“…In settings with high burdens of infectious pathogens and a high burden of iron deficiency, iron supplementation is safe and appears to translate into improvements in birth outcomes when given in combination with SP or SPAZ. Furthermore, it has been proposed that the observed ferritin-birth outcome relationship may be due to an adverse effect of iron supplementation on birthweight in iron-replete women, amongst whom supplementation may reduce birthweight [6,22,45]. Putative mechanisms may include adverse impacts on foetal growth due to either increased blood viscosity or placental damage from free radicals in supplemented iron-replete women [59,60].…”

Iron, iodine and vitamin D deficiencies during pregnancy: epidemiology, risk factors and developmental impacts

“…Far fewer studies have explored associations with indices of iron deficiency, with conflicting evidence to date from those that have, particularly given the confounding impact of inflammation on ferritin (46,47) . Moreover, the U-shaped curve of risk associated with iron status during pregnancy must also be considered, as elevated iron status indices, including ferritin and Hb, particularly in the third trimester, have been associated with an increased risk of some adverse birth outcomes (42,44,48) . Excess iron intakes or elevated iron status during pregnancy is thought to increase blood viscosity, impair placental blood flow and contribute to oxidative stress, further emphasising the caution required when prescribing iron supplementation to pregnant women (44) .…”