Dr K. N. Agarwal, Professor Pediatrics
University College Medical Sciences & GTBH, Delhi-110095.
Email: kna_noida@hotmail.com

Pregnancy outcome in anemia : (3,4)
In the case of moderate to severe anemia - breathlessness, edema, congestive heart failure and even cerebral anoxia have been observed. 200 anemic pregnant women observed in the University Hospital, Varanasi, showed reduced gestation, higher incidence of premature labor, preterm , low birth weight and still birth deliveries. In the newborns the Apgar score was low and there were increased number of neonatal deaths. Maternal mortality was 13 out of 200 anemic as compared to 1 in 50 control. Similar findings were reported in other Indian studies. Anemic mothers do not tolerate blood loss ,as little as 150 ml can be fatal. Normally a healthy mother during child birth may tolerate a blood loss of up to 1000 ml.

Magnitude of pregnancy anemia in India: (5,6)
As per ICMR studies (1985-86), 11 states data in 4775 women showed that 87.6% had hemoglobin < 10.9 g/dl. In 1987-89, 6 states data in 1968 women showed hemoglobin < 11.0g/dl in 62.3%, however hematinic response was found in 80%.Even District Nutrition survey data of 1999-2000 by the ICMR showed prevalence of hemoglobin < 11.0g/dl in 61, 79, 84, 91and 97% in the districts of HP, UP, Bihar, Assam and Kashmir respectively. These national data suggest high prevalence of nutritional anemia in pregnancy. The iron- folate supplementation as recommended in the national anemia control programme improved maternal hemoglobin, birth weight and reduced low birth weight deliveries (7).

Effects of iron deficiency on feto placental unit :
Studies by Vahlquist (8), Sturgeon (9) and Rios (10) demonstrated that inspite of maternal hypoferriemia and anemia, the cord blood hemoglobin, iron and ferritin levels do not differ in babies born of anemic and non-anemic mothers. This may be true for women with good iron stores and nutrition in developed countries. Recent studies in UK (11) have also shown that higher hemoglobin gain with iron supplementation could be a risk for increased preterm and low birth weight deliveries. In contrast studies in India have shown that fetus suffers in maternal hypoferriemia. The findings are summarized below:

• Cord serum iron and hemoglobin were reduced in preterm as well as full term. There is an increased gradient in presence of maternal iron deficiency for transport of iron from mother to fetus but the transport remains proportionate to the degree of maternal hypoferriemia (12-14).
• Placenta plays an important role in maintaining iron transport to fetus. This process of iron transport is purely a placental function over which mother and fetus have no control, as placenta continues to trap iron even when fetus is removed in animals (15). Inspite of this efficient protective mechanism the placental iron content reduces significantly in maternal hypoferriemia. The placenta showed qualitative decrease in villous surface area, volume of villi and length of blood vessel, while surface area and volume of intervillous space was increased. These placental changes in anemia did not normalize on rehabilitation- suggesting "Maturational arrest" (16-18).
• Bigger the infant and more advanced the gestational age higher was the amount of iron in fetal liver, spleen and kidney. The tissue iron content increased steeply in last 8 weeks of gestation. Infant born before 36 weeks had half the iron content in hepatic reserve (19).
• Placental iron content reduces significantly in maternal hypoferriemia.
• Breast milk iron content is increased in maternal hypoferriemia (20,21).
  

Iron deficiency and the fetal brain :
Iron deficiency anemia in rat mothers results in low fetal brain content which did not improve inspite of rehabilitation in mid-gestation (22).There were changes in the dopamine, serotonin and gamma aminobutyric acid (GABA) systems in such fetal brains. Further the binding receptors of dopamine D2 decreased and GABA increased (23).

Latent iron deficiency-(No anemia but hepatic iron content reduced): The fetal as well as weanling rat brain iron content decreased irreversibly in maternal hypoferreimia. In the post weaning group iron content decreased in corpus striatum 32%, mid brain 21%, hypothalamus 19%, cerebellum 18%,hippocampus15%, but no change in medulla oblongata. In latent iron deficiency neurotransmitter changes were: a) marked reduction in levels of brain GABA and L-glutamic acid. Enzymes for biosynthesis of GABA and L-glutamate like glutamate decarboxylase and glutamate transaminase were also reduced. b) Binding of GABA receptor increased by 143%, glutamate receptor binding decreased by 63%. These findings indicate that iron plays an important functional role in the both excitatory and inhibitory neurotransmitter receptors and c) Whole brain and corpus striatum showed reduction in catecholamine, dopamine norepinepherine, tyrosine and monoamino oxidase, while tyrosine aminotransferase increased in corpus striatum, inspite of reduction in whole brain suggesting that latent iron deficiency induced irreversible neurotransmitter alterations (24-30). These changes were specific to iron deficiency as neurotransmitter alterations in fetal brain due to malnutrition get normalized partially of completely on rehabilitation (31-32).

Iron deficiency in fetal brain induces permanent neurotransmitter changes. This is an important observation as in pregnancy, anemia particularly the iron deficiency remains a public health problem in our country.