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Acta Pediatr 85: 1327-30. 1996 Fetal iron status in maternal anemia PN Singla', M Tyagi', R Shankar', D Dash' and A Kumarl Singla PN. Tyagi M. Shankar R, Dash D, Kuniar A. Fetal iron status in maternal xnemia. Acta Pxdiatr 1996:85: 1327-30. Stockholm. ISSN 0803-5253 Hemoglobin, serum iron, transferrin saturation and ferritin were measured on paired m;itcrniil aid cord blood samples in 54 anemic (hemoglobin < 1 10 g/L) and 22 non-anemic (hemoglobin 2 1 10 g/L) pregnant women ;it term gestation. The levels of hemoglobin, serum iron, transferrin saturation and ferritin were significantly low in the cord blood of anemic women, suggesting that iron supply to the lttus was reduced in maternal anemia. The linear relationships of these parameters with both maternal hemoglobin and maternal serum ferritin indicated that the fetus extracted iron in amounts proportionit1 to the levels available in the mother. Infants of mothers with inoderate and severe iiiieiiiiii had signilicuntly lower cord serum ferritin levels and hence poor iron stores at birth. It is concludcd that iron deficiency anemia during pregnancy adversely affects the iron endowment of tho infant at birth. 3 Fcwiiiii, ,fi't~iI iroir .st~ifii,s, nirrrerrrol cmeniicr PA' Siiiglu, Dcyxirtiliozt of' Pdiulrics, Iiistitutr~ of' Mcrlical Scicvicvs, Boiitirtrs Hirrrhi Ciiiwr.sii,i,, Vrir(itiuxi -721 00.5. Ititlitr Iron deficiency anemia remains a significant public health problem in developing countries. Recent reports indicate that 87.5% of pregnant women in India suffer from anemia, mostly due to iron deficiency (I). It has been believed for a long time that maternal iron defi- ciency has little or no effect on the acquisition of iron by the fetus (2-7). However, a number of investigators (8- 15) have found a positive relation between maternal and newborn iron status, suggesting that the fetus is vulnerable to iron deficiency during intrauterine life. Poor iron stores at birth may predispose these infants to iron deficiency anemia in early infancy, which in turn may liave long lasting effects on their cognitive development ( 16). Furthermore, iron deficiency may impair the cell- mediated immune function ( 17). Thus, the consequences of iron deficiency during pregnancy are of particular concern for those societies where its prevalence is high. The earlier studies (2-4) in the literature did not include sufficient numbers of women with severe preg- nancy anemia, and some of them (7) also did not exclude women with infection. In our earlier communications (8. 9). we presented the effect of severe pregnancy anemia on cord blood hemoglobin and cord serum iron levels. This study evaluates the effect of severe maternal iron deficiency anemia on the iron status of the fetus at term gestation. with special reference to iron stores, as measured by cord serum ferritin assay. Subjects and methods Paired maternal and cord blood samples were obtained from 54 anemic (hemoglobin <I IOg/L) and 22 non-anemic (hemoglobin 2 1 10 g/L) pregnant women, selected randomly from the University Hospital, Banaras Hindu University, Varanasi, India. All these women had singleton live births at Icrm gestation (37-41 weeks). The gestational age of the newborns was confirmed by the Dubowitz method (18). All anemic women belonged to the poor socioeconomic status and none received antenatal care or iron siipplc- mentation. Women with preterm delivery (<37 weeks), antepartum hemorrhage, toxemia of pregnancy, infec- tion, diabetes mellitus, and liver or kidney disorders were excluded from the study. Blood samples were collected from the mother's antecubital vein during the first stage of lobour and from the placental end of the umbilical cord without milking just after the second stage for the estimation of hemoglobin (l9), serum iron (20). unsaturated iron binding capacity (21) and serum ferritin by the ELISA method (Ferrizyme, Abbott Laboratories. Chicago, 111, USA) (22). Blood samples were contained in iron-free plastic tubes and were stored at -20' C until analysis. Informed consent was obtained from each mother before enrolment in the study. The study was approved by the Institute Ethics Committee. Stutisticul atiulysis Statistical comparisons of maternal serum ferritin values were made using Mann-Whitney test, iis serum ferritin levels were highly skewed. Other tests included Student's t-test, correlation (r) and Spearman's rank correlation coefficient (rs). A p value <0.05 was regarded as significant. ( Scandinavian Universitv P r w 1996. ISSN 0803-5253

Fetal iron status in maternal anemia

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Acta Pediatr 85: 1327-30. 1996

Fetal iron status in maternal anemia PN Singla', M Tyagi' , R Shankar', D Dash' and A Kumarl

Singla PN. Tyagi M. Shankar R, Dash D, Kuniar A. Fetal iron status in maternal xnemia. Acta Pxdiatr 1996:85: 1327-30. Stockholm. ISSN 0803-5253

Hemoglobin, serum iron, transferrin saturation and ferritin were measured on paired m;itcrniil a i d cord blood samples in 54 anemic (hemoglobin < 1 10 g/L) and 22 non-anemic (hemoglobin 2 1 10 g /L) pregnant women ;it term gestation. The levels of hemoglobin, serum iron, transferrin saturation and ferritin were significantly low in the cord blood of anemic women, suggesting that iron supply to the l t tus was reduced in maternal anemia. The linear relationships of these parameters with both maternal hemoglobin and maternal serum ferritin indicated that the fetus extracted iron i n amounts proportionit1 to the levels available in the mother. Infants of mothers with inoderate and severe iiiieiiiiii

had signilicuntly lower cord serum ferritin levels and hence poor iron stores at birth. I t is concludcd that iron deficiency anemia during pregnancy adversely affects the iron endowment of tho infant at birth. 3 Fcwiiiii, ,fi't~iI iroir .s t~if i i ,s , nirrrerrrol cmeniicr

PA' Siiiglu, Dcyxirtiliozt of' Pdiulrics, Iiistitutr~ of' Mcrlical Scicvicvs, Boiitirtrs Hirrrhi Cii iwr.si i , i , , Vrir(itiuxi -721 00.5. Ititlitr

Iron deficiency anemia remains a significant public health problem in developing countries. Recent reports indicate that 87.5% of pregnant women in India suffer from anemia, mostly due to iron deficiency ( I ) . It has been believed for a long time that maternal iron defi- ciency has little or no effect on the acquisition of iron by the fetus (2-7). However, a number of investigators (8- 15) have found a positive relation between maternal and newborn iron status, suggesting that the fetus is vulnerable to iron deficiency during intrauterine life. Poor iron stores at birth may predispose these infants to iron deficiency anemia in early infancy, which in turn may liave long lasting effects on their cognitive development ( 16). Furthermore, iron deficiency may impair the cell- mediated immune function ( 17). Thus, the consequences of iron deficiency during pregnancy are of particular concern for those societies where its prevalence is high.

The earlier studies (2-4) in the literature did not include sufficient numbers of women with severe preg- nancy anemia, and some of them (7) also did not exclude women with infection. In our earlier communications (8. 9). we presented the effect of severe pregnancy anemia on cord blood hemoglobin and cord serum iron levels. This study evaluates the effect of severe maternal iron deficiency anemia on the iron status of the fetus at term gestation. with special reference to iron stores, as measured by cord serum ferritin assay.

Subjects and methods Paired maternal and cord blood samples were obtained from 54 anemic (hemoglobin < I IOg/L) and 22

non-anemic (hemoglobin 2 1 10 g /L) pregnant women, selected randomly from the University Hospital, Banaras Hindu University, Varanasi, India. All these women had singleton live births at Icrm gestation (37-41 weeks). The gestational age o f the newborns was confirmed by the Dubowitz method (18). All anemic women belonged to the poor socioeconomic status and none received antenatal care or iron siipplc- mentation. Women with preterm delivery (<37 weeks), antepartum hemorrhage, toxemia of pregnancy, infec- tion, diabetes mellitus, and liver or kidney disorders were excluded from the study.

Blood samples were collected from the mother's antecubital vein during the first stage of lobour and from the placental end of the umbilical cord without milking just after the second stage for the estimation of hemoglobin (l9), serum iron (20). unsaturated iron binding capacity (21) and serum ferritin by the ELISA method (Ferrizyme, Abbott Laboratories. Chicago, 111, USA) (22). Blood samples were contained in iron-free plastic tubes and were stored at -20' C until analysis. Informed consent was obtained from each mother before enrolment in the study. The study was approved by the Institute Ethics Committee.

Stutisticul atiulysis Statistical comparisons of maternal serum ferritin values were made using Mann-Whitney test, iis serum ferritin levels were highly skewed. Other tests included Student's t-test, correlation ( r ) and Spearman's rank correlation coefficient ( r s ) . A p value <0.05 was regarded as significant.

( S c a n d i n a v i a n Un ive r s i tv P r w 1996. ISSN 0803-5253

Page 2: Fetal iron status in maternal anemia

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Page 3: Fetal iron status in maternal anemia

Results Concentrations o f cord blood hemoglobin, serum iron. transferrin saturation and fcrritin were signifi- cantly low in newborns of anemic women and showed ;I d i rcc t co r re1 a t i o n bv i t h mat ern a 1 hem og 1 o hi n (Tablc I ). Furthcrmore, maternal serum ferritin was found to be significantly correlated with cord blood hemoglobin ( r , = +0.390, p < O . O l ) , cord serum iron ( r , = +0.354. p < 0.01). transferrin saturation (r,. = +0.399. p < 0.01) and cord serum ferritin ( r , = t0.523. 11 < 0.001).

Discussion The linear relationships of cord blood hemoglobin, cord scruin iron. transferrin saturation and fcrritin with maternal hemoglobin found in this study suggest that iron supply to the fetus was adversely affected in maternal anemia. This is further supported by the finding of significant correlations of these parameters i n cord blood with maternal serum ferritin levels. These findings are in agreement with those of previous studies ( 10 ~~ 13. 14, 15) including our earlier observa- tions (8, 9, 13). showing an adverse influence of mater- nal iron deficiency on the acquisition of iron by the fetus. However. these are contrary to the observations o f other investigators (2-4) who found that iron accre- tion in the fetus was independent of maternal iron status. This could be due t o the fact that these studies did not include women with severe pregnancy anemia. The significantly lower cord serum ferritin levels in newborns of mothers with moderate and severe anemia in this study further indicated that maternal anemia accounted for reduced iron stores in these infants. Consequently, such infants are at greater risk of developing iron deficiency anemia in early infancy.

Transfer of iron from the mother to the fetus is an active process ( 2 3 ) , involving binding of transferrin iron with transferrin receptors in the placenta, from where i t is rapidly transported to the fetus (24). In iron deficiency, there is upregulation of transferrin receptor synthesis which enables placenta to compete more effectively for circulating transferrin iron, with erythroid marrow of the pregnant woman (24). This explains why serum iron, transferrin saturation and ferritin were higher in cord blood than in maternal blood, even in severe maternal anemia. However, the fetus is not endowed with unlimited ability to extract iron from the mother. Rather, it takes up iron in direct proportion to the levels available in the mother as indicated by the positive correlations of the parameters of iron nutriture in cord blood with maternal hemo- globin and maternal serum ferritin.

The present study demonstrated little influence of mild degree of maternal anemia on iron accretion in the fetus. However, with increasing severity of maternal

anemia. the fetus accumulated less and less iron. ;IS

corroborated by the finding of markedly low levels of sc r im iron. transferrin saturation and fcrritin i n llic cord blood of severely anemic women. Thus i r appcars that there is a limit to the otherwisc highly-ellicicnt mechanism w h ic h trans por t s i ron from nio t he r to fetus, below which the fetus is born with less than optimal iron endowment.

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12ccei\ed J a n . 22. 1996. Accepted iii I-