{"id":37168,"date":"2021-03-30T10:52:56","date_gmt":"2021-03-30T10:52:56","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=37168"},"modified":"2021-04-09T06:12:47","modified_gmt":"2021-04-09T06:12:47","slug":"relationship-between-maternal-and-cord-blood-iron-status-in-women-and-their-new-born-pairs","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol14no1\/relationship-between-maternal-and-cord-blood-iron-status-in-women-and-their-new-born-pairs\/","title":{"rendered":"Relationship between Maternal and Cord Blood Iron Status in Women and their New Born Pairs"},"content":{"rendered":"<p style=\"text-align: justify;\"><strong>Introduction<\/strong><\/p>\n<p style=\"text-align: justify;\">Maternal micronutrient deficiency and more often iron deficiency\u00a0 are matters of concern in most of the developing countries <sup>[1]<\/sup>. Iron is thought to have a role in tuning child immune mechanisms. Maternal iron is said to have a direct effect on infants T lymphocyte and natural cell populations <sup>[2]<\/sup>. In addition to the need of well-regulated fetal iron stores for immune system, normal level is also essential to provide iron to developing fetal organ systems <sup>[1,3]<\/sup> ,\u00a0 both of which would be disturbed in maternal iron deficiency anemia. Anemia is common problem in pregnancy, occurrence rate ranging from 5.4% in developed countries to more than 80% in developing countries <sup>[4]<\/sup>. Several studies indicate that iron stores in the neonates born to mothers with deficient iron stores may be compromised<sup> [5]<\/sup>. Maternal iron deficiency anemia is significantly associated with the risk of preterm labor and low birth weight .Preterm labor and low birth weight are associated with fetal and neonatal morbidity and mortality, impairment of growth and development and chronic diseases later in life. Neonates born less than 38 weeks gestation may be at risk of insufficient iron endowment <sup>[6,7]<\/sup>. Iron-deficiency may also place neonates at high risk for cognitive, motor, social-emotional, and neuro developmental impairment <sup>[8]<\/sup>. Moreover, requirement of iron is particularly high for rapid growth and differentiation of the fetus and thus a well-balanced iron homeostasis is required. This balance can be threatened in neonates born to iron compromised mothers <sup>[9,10]<\/sup>.<\/p>\n<p style=\"text-align: justify;\">Simultaneously, \u00a0since antioxidant capacity in preterm infants will not be fully developed and neither will they be fully equipped with sufficient iron binding proteins, if these neonates have increased iron they will be at risk of oxidative effect of free iron, and therefore, cautious\u00a0 treating with\u00a0 iron supplementation\u00a0 in neonates is imperative <sup>[11,12]<\/sup>.<\/p>\n<p style=\"text-align: justify;\">Some studies have suggested that the fetus reflects maternal iron status, but this concept is still being debated as few other studies show contrasting results <sup>[13]<\/sup>. To draw consensus regarding the same, more studies, that will look into\u00a0 the role of maternal iron status on fetal stores and factors involved in maternal and fetal iron transfer are required <sup>[14]<\/sup>.<\/p>\n<p style=\"text-align: justify;\">Proper understanding of the relationship between maternal and neonatal iron indices will aid in formulating protocols that is required to improve the maternal and neonatal outcome. Investigating\u00a0 the effects of maternal iron on fetal iron indices \u00a0can be of great value, so that early intervention\u00a0 to prevent or reverse the detrimental effects of iron deficiency on development issues much before \u00a0iron deficiency effects\u00a0 becomes severe can be instituted <sup>[15,16]<\/sup>.<\/p>\n<p style=\"text-align: justify;\">Therefore, this study was planned to evaluate the relationship of iron indices \u00a0between maternal and cord blood collected from mother and infant pairs at the time of delivery irrespective of gestational age , and to explore the association of maternal anemia on the iron status indicators of\u00a0 cord blood.<\/p>\n<p style=\"text-align: justify;\"><strong>Material and methods <\/strong><\/p>\n<p style=\"text-align: justify;\"><strong>Ethical issues<\/strong><\/p>\n<p style=\"text-align: justify;\">This prospective study was conducted in a tertiary care center in south India from July 2012 to October 2014. The protocol was approved by the Institutional Ethical Committee Reference ID:2012-01340. Sixty mothers ranging from the age group of 21-35 years and their infant pairs were recruited for the study after obtaining informed consent form the participants.<\/p>\n<p style=\"text-align: justify;\"><strong>Inclusion criteria<\/strong><\/p>\n<p style=\"text-align: justify;\">All pregnant women and their newborn pairs who had given consent to participate \u2265 26 weeks gestation were recruited for the study.<\/p>\n<p style=\"text-align: justify;\"><strong>Exclusion criteria <\/strong><\/p>\n<p style=\"text-align: justify;\">Pregnant women who presented with medical problems such as gestational diabetes, hypertension, hypothyroidism, epilepsy, renal diseases, cardiorespiratory diseases, immunodeficiency syndromes, antepartum hemorrhage history of blood transfusion in antenatal period were excluded from the study. Babies with major congenital anomalies, pathological jaundice and twin deliveries were excluded.<\/p>\n<p style=\"text-align: justify;\"><strong>Methodology<\/strong><\/p>\n<p style=\"text-align: justify;\">Sixty mothers ranging from the age group of 21-35 years and their infant pairs were recruited for the study. Required information and pregnancy outcomes was recorded in a standard proforma. Maternal blood and cord blood samples were collected from mother and neonate pairs. Maternal venous blood samples were collected 1.5 h \u00b1 20 min before the delivery. 5 ml of cord blood was collected following \u00a0child birth after \u00a0clamping the cord with two clamps placed 4-5 inches apart. \u00a0Diamine Tetra acetic acid was used as anticoagulant and plasma obtained on centrifugation was used to estimate iron and ferritin and whole blood was used for the estimation of hemoglobin. The enrolled mother-infant pairs were grouped based on maternal hemoglobin levels. Mothers with \u00a011g\/dl and more were\u00a0 considered non-anemic <sup>[17]<\/sup>.<\/p>\n<p style=\"text-align: justify;\">The hemoglobin concentration was determined by the standard spectrophotometric cyanometh-haemaglobin method.<\/p>\n<p style=\"text-align: justify;\">Plasma Iron was assayed using Abcam iron assay kit without deprotenisation of the sample. \u00a0This assay kit is based one the\u00a0 principle\u00a0 were in\u00a0\u00a0 ferric carrier protein will dissociate ferric into solution in the presence of an acid buffer. After reduction to the ferrous form, iron reacts with an iron chromogen to produce a stable colored complex with absorbance at 593 nm. Values are expressed as mM\/L<\/p>\n<p style=\"text-align: justify;\">Plasma ferritin\u00a0 was analysed using human Ferritin Enzyme linked\u00a0 immune assay( ELISA) \u00a0kits from Abcam following manufacturers instruction. Assay was based on solid phase direct sandwich principle, the results were obtained from standard curve and expressed as ng\/ml.<\/p>\n<p style=\"text-align: justify;\"><strong>Statistical Analysis<\/strong><\/p>\n<p style=\"text-align: justify;\">All the values are expressed as mean \u00b1 standard deviation. Paired Students t test\u00a0 was used to analyse and compare the data and p-value of less than 0.05 was considered statistically significant.<\/p>\n<p style=\"text-align: justify;\">Descriptive statistics was used for baseline variables. Correlation between maternal iron indices and cord blood iron indices was done by multivariate regression analysis, using SPSS software. r =0.87, p&lt;0.05 was considered as significant as positive linear correlation.<\/p>\n<p style=\"text-align: justify;\"><strong>Results<\/strong><\/p>\n<p style=\"text-align: justify;\">Sixty mother-infant pairs were recruited for the study and their data was included for the final analysis. Thirty of the women were anemic mothers (Hb less than 11gm\/dL) and 30 were non-anemic (Hb more than\u00a0 or equal to 11gm\/dL). Amongst the newborns, 46.6% (n=28) were males \u00a0and 53.4% (n = 32) were\u00a0 females. The mean gestational age of the neonates enrolled was 33.50\u00b15.38 weeks, and the mean birth weight was 2679.25\u00b1457.9 g.<\/p>\n<p style=\"text-align: justify;\">Mean \u00b1SD of measured iron indices in \u00a0maternal \u00a0and cord blood and the p values obtained on comparing \u00a0the data between anemic and non-anemic groups are shown\u00a0 in (Table 1). Hb , iron , ferritin were found to be\u00a0 significantly lower in anemic mothers\u00a0 compared to non-anemic mothers \u00a0(p&lt; 0.05 ).<\/p>\n<p style=\"text-align: justify;\">The iron indices of neonates born to mothers with Hb &lt;11 g\/dL were compared with those with Hb \u226511g\/dL. Lower values with \u00a0significant difference \u00a0\u00a0(p &lt; 0.05) was observed in iron indices (Hb, Ferritin, iron )\u00a0 in\u00a0 cord blood of neonates born to anemic mothers (Table 1).<\/p>\n<p style=\"text-align: justify;\"><strong>Table 1: student t-test, Mean \u00b1SD and p values: group 1 values were compared with group 2.<\/strong> <strong>\u00a0p &lt; 0.05 was considered as significant.\u00a0 <\/strong><\/p>\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td style=\"text-align: center;\" width=\"119\"><strong>Parameters<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"96\"><strong>Overall Mean \u00b1SD<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"102\"><strong>Group 1 (Anemic )<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"96\"><strong>Group 2<\/strong><\/p>\n<p><strong>( Non Anemic)<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"78\"><strong>P Value<\/strong><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"119\">Hb (mother )<\/td>\n<td style=\"text-align: center;\" width=\"96\">11.16\u00b12.51<\/td>\n<td style=\"text-align: center;\" width=\"102\">9.38\u00b10.691<\/td>\n<td style=\"text-align: center;\" width=\"96\">12.94\u00b11.15<\/td>\n<td style=\"text-align: center;\" width=\"78\">0.01<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"119\">Iron (mother )<\/td>\n<td style=\"text-align: center;\" width=\"96\">41.07\u00b113.86<\/td>\n<td style=\"text-align: center;\" width=\"102\">31.26\u00b14.26<\/td>\n<td style=\"text-align: center;\" width=\"96\">50.87\u00b114.49<\/td>\n<td style=\"text-align: center;\" width=\"78\">0.02<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"119\">Ferritin (mother)<\/td>\n<td style=\"text-align: center;\" width=\"96\">59.73\u00b119.61<\/td>\n<td style=\"text-align: center;\" width=\"102\">45.87\u00b19.29<\/td>\n<td style=\"text-align: center;\" width=\"96\">73.60\u00b19.06<\/td>\n<td style=\"text-align: center;\" width=\"78\">0.02<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"119\">Cord Hb<\/td>\n<td style=\"text-align: center;\" width=\"96\">16.84\u00b12.43<\/td>\n<td style=\"text-align: center;\" width=\"102\">15.11\u00b11.19<\/td>\n<td style=\"text-align: center;\" width=\"96\">18.56\u00b12.75<\/td>\n<td style=\"text-align: center;\" width=\"78\">0.00<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"119\">Cord iron<\/td>\n<td style=\"text-align: center;\" width=\"96\">58.39\u00b152.11<\/td>\n<td style=\"text-align: center;\" width=\"102\">21.53\u00b115.50<\/td>\n<td style=\"text-align: center;\" width=\"96\">95.24\u00b122.79<\/td>\n<td style=\"text-align: center;\" width=\"78\">0.001<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"119\">Cord ferritin<\/td>\n<td style=\"text-align: center;\" width=\"96\">150.23\u00b119.7<\/td>\n<td style=\"text-align: center;\" width=\"102\">136.30\u00b110.22<\/td>\n<td style=\"text-align: center;\" width=\"96\">164.17\u00b112.76<\/td>\n<td style=\"text-align: center;\" width=\"78\">0.00<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p style=\"text-align: justify;\">Multivariate regression analysis was done to correlate\u00a0 maternal\u00a0 Hb\u00a0 with maternal and cord iron indices . A positive linear correlation was observed between maternal Hb and maternal\u00a0 iron, between maternal Hb and cord Hb, between maternal Hb and cord ferritin with r =0.87, p&lt;0.05. However, correlation between maternal Hb and maternal ferritin , between maternal Hb \u00a0and cord iron was not significant. \u00a0(Table 2, Fig 1 ).<\/p>\n<p style=\"text-align: justify;\"><strong>Table 2: Multivariate\u00a0 linear\u00a0 Correlation between\u00a0Maternal Hb with Maternal iron status,\u00a0<\/strong><strong>Maternal Hb with Cord blood Hb and Iron status.<\/strong><\/p>\n<table style=\"width: 95%;\" border=\"1\" cellspacing=\"0\" cellpadding=\"4\">\n<tbody>\n<tr>\n<td style=\"text-align: center;\" width=\"307\"><strong>Variables<\/strong><\/td>\n<td style=\"text-align: center;\" width=\"84\"><strong>\u00a0\u00a0\u00a0\u00a0 p-Value<\/strong><\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"307\"><strong>Maternal Hb\u00a0\u00a0 <\/strong>Vs\u00a0\u00a0 Maternal\u00a0 Iron<\/td>\n<td style=\"text-align: center;\" width=\"84\">0.01*<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"307\"><strong>Maternal Hb\u00a0\u00a0 <\/strong>Vs\u00a0\u00a0 Maternal Ferritin<\/td>\n<td style=\"text-align: center;\" width=\"84\">0.06<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"307\"><strong>Maternal Hb\u00a0\u00a0 <\/strong>Vs\u00a0 Cord Hb<\/td>\n<td style=\"text-align: center;\" width=\"84\">0.000*<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"307\"><strong>Maternal Hb\u00a0 <\/strong>\u00a0Vs\u00a0 Cord Iron<\/td>\n<td style=\"text-align: center;\" width=\"84\">0.63<\/td>\n<\/tr>\n<tr>\n<td style=\"text-align: center;\" width=\"307\"><strong>Maternal Hb\u00a0 <\/strong>\u00a0Vs\u00a0 Cord Ferritin<\/td>\n<td style=\"text-align: center;\" width=\"84\">0.003*<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>&nbsp;<\/p>\n<table style=\"width: 70%;\" border=\"1\" cellpadding=\"5\">\n<tbody>\n<tr>\n<td><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2021\/02\/Vol14No1_Rel_Gri_fig1.jpg\"><img decoding=\"async\" class=\"alignnone size-thumbnail wp-image-37169\" src=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2021\/02\/Vol14No1_Rel_Gri_fig1-150x150.jpg\" alt=\"Vol14No1_Rel_Gri_fig1\" width=\"150\" height=\"150\" srcset=\"https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2021\/02\/Vol14No1_Rel_Gri_fig1-150x150.jpg 150w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2021\/02\/Vol14No1_Rel_Gri_fig1-256x256.jpg 256w, https:\/\/biomedpharmajournal.org\/staging\/wp-content\/uploads\/2021\/02\/Vol14No1_Rel_Gri_fig1.jpg 455w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/><\/a><\/td>\n<td><strong>Figure 1: C<\/strong><strong>orrelation between maternal Hb and maternal ferritin,\u00a0<\/strong><strong style=\"font-family: inherit; font-size: inherit;\">between maternal Hb \u00a0and cord iron<\/strong><\/p>\n<p><a href=\"https:\/\/biomedpharmajournal.org\/wp-content\/uploads\/2021\/02\/Vol14No1_Rel_Gri_fig1.jpg\" target=\"_blank\">Click here to view figure<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p style=\"text-align: justify;\"><strong>Discussion<\/strong><\/p>\n<p style=\"text-align: justify;\">One of the common nutritional deficiency seen in pregnant women\u00a0 is iron deficiency. Maternal iron deficiency has detrimental effects on development of the fetal and on pregnancy outcomes <sup>[18]<\/sup>. Results of our study suggests that cord\u00a0 Hb and iron is lowered\u00a0 in neonates born to anemic mothers, results also reveal that\u00a0 \u00a0maternal Hb has a positive linear\u00a0 correlation \u00a0with cord Hb and cord ferritin. However we did not find statistically significant positive correlation between maternal Hb and cord iron. Additionally, maternal\u00a0 Hb did not positively correlate\u00a0 with maternal ferritin suggesting that some of the anemic mothers may have\u00a0 lowered circulating iron levels\u00a0 with normal iron stores. Other similar studies like ours also suggest that mothers with\u00a0 lowered\u00a0 Hb levels may compromise\u00a0 iron homeostasis in\u00a0 their neonates <sup>[10]<\/sup>.<\/p>\n<p style=\"text-align: justify; line-height: 150%;\">Serum \/plasma ferritin is a well-established marker for body iron stores <sup>[19]<\/sup>. Lower values of cord ferritin in neonates born to anemic mothers positively correlated with maternal Hb suggesting that iron stores may be reduced in neonates of anemic mothers.<\/p>\n<p style=\"text-align: justify;\">It is known that a protein synthesized by fetal liver\u00a0 called Hepcidin serves as\u00a0 a regulator of iron homeostasis in early gestation as it helps the fetus to regulate placental iron uptake. \u00a0Synthesis of Hepcidin is said to be regulated by maternal \u00a0iron stores, \u00a0inflammation, hypoxia, and RBC synthesis <sup>[20]<\/sup>. This suggests that several maternal factors are\u00a0\u00a0 involved in tuning the neonates iron status pointing towards need for designing studies involving thorough search of each of the factors involved in fetal iron homeostasis.<\/p>\n<p style=\"text-align: justify;\">Results of our study shows that, though maternal Hb correlates to cord Hb and cord ferritin\u00a0 it does not correlate well with cord iron. This may be because several factors and complex mechanisms may be involved in iron homeostasis in the fetus. However, our results\u00a0 certainly\u00a0 points that iron status indicators are\u00a0 \u00a0reduced\u00a0 in neonates born to anemic mothers\u00a0 which is\u00a0\u00a0 indicative of insufficient iron reserves in the neonates \u00a0at birth. Similar finding have been reported earlier as well <sup>[21, 22]<\/sup>. However some studies have reported that maternal iron status is not reflected \u00a0in the neonates and iron status of fetus is independent of\u00a0 iron status in the mothers <sup>[23,24]<\/sup>. Few other studies suggest that \u00a0the\u00a0 fetus receives iron from mothers as per its requirements irrespective of maternal stores <sup>[6,25] \u00a0<\/sup>thus contradicting the results of our study.<\/p>\n<p style=\"text-align: justify;\">Transport of\u00a0maternal iron to maternal side of syncytiotrophoblast is aided by serum transferrin binding to transferrin receptor and expression of transferrin \u00a0receptors is reported to be upregulated in maternal iron deficiency <sup>[25]<\/sup>, while other studies show that upregulation of receptors \u00a0in iron deficiency fail to provide enough \u00a0iron to fetus <sup>[21]<\/sup>.<\/p>\n<p style=\"text-align: justify;\">Our results make it evident that neonates delivered from anemic mothers show low Hb levels. And that it is\u00a0 important to understand that Hb is primarily required for oxygen and carbon-dioxide transport and as a body buffer and many other functions <sup>[26]<\/sup>. Decreased Hb in the\u00a0 neonates will place the neonates at a risk for upper respiratory tract infections and sepsis , apart from negatively\u00a0 affecting\u00a0 the normal functions attributed by Hb <sup>[27]<\/sup>.<\/p>\n<p style=\"text-align: justify;\">Further studies are required for definitive conclusion to be drawn as to whether iron available in the mother has any influence on the iron transferred across the placenta. Inherent challenges in the interpretation of Hb, Iron and Fe status in umbilical cord blood, exposes a requirement\u00a0 for\u00a0 larger cohort studies so as to obtain conclusive data on the relationship\u00a0 and the effect of maternal\u00a0 iron status on fetal iron\u00a0 homeostasis. Need for sufficient number studies to deduce reference values\u00a0 for iron indices in cord blood are\u00a0 highlighted in our study.<\/p>\n<p style=\"text-align: justify;\"><strong>Conclusions<\/strong><\/p>\n<p style=\"text-align: justify;\">Maternal anemia can effect neonatal iron stores. Hemoglobin, Iron and ferritin was significantly lower in cord blood of neonates born to anemic mothers compared\u00a0 to those born to non-anemic mothers . Additionally neonate\u2019s hemoglobin and ferritin concentration had a significant correlation with hemoglobin concentration of the mother. Based on our results we conclude that maternal anemia may have an effect on the neonates Hb and iron stores. Our findings, combined with a review of the published literature, indicate a need for further analysis of the relations between multiple iron indices to assess iron and hematologic status at birth. Our study also indicates the\u00a0\u00a0 need for further studies that will explore mechanisms involved in iron transfer between the mother and fetus.<\/p>\n<p style=\"text-align: justify;\"><strong>Acknowledgement<\/strong><\/p>\n<p style=\"text-align: justify;\">None.<\/p>\n<p style=\"text-align: justify;\"><strong>Conflict of Interest<\/strong><\/p>\n<p style=\"text-align: justify;\">No conflict of interest between any of the authors.<\/p>\n<p style=\"text-align: justify;\"><strong>Funding\u00a0Source<\/strong><\/p>\n<p style=\"text-align: justify;\">This project was funded by Medicity Diagnostics and Health Care Center , Karnataka , India.<strong>\u00a0 <\/strong><\/p>\n<p style=\"text-align: justify;\"><strong>References<\/strong><\/p>\n<ol>\n<li style=\"text-align: justify;\">Lozoff B, Beard J, Connor J, Barbara F, Georgieff M, Schallert T. Longlasting neural and behavioral effects of iron deficiency in infancy\u201d. 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