Article Type : Short commentary
Authors : Sharma A, Agarwal A and Agarwal KN
Keywords : Anemia; Iron; Pregnancy; Lactation; Fetal; Placental transfer; Brain; Neurotransmitters
As many as 4-5 billion
people, 66-80% of the world's population, may suffer from reduced learning
ability and work capacity due to iron deficiency. Iron deficiency, and
specifically iron deficiency anemia, is one of the most severe and important
nutritional deficiencies in the world. As early as in 1967, Routh & Agarwal
(Indian J Med Res) found that 65% healthy rich population in Delhi, India had
no hepatic iron. Preschool children and women of reproductive age are at a
highest risk. More than 2 billion people, > 30% of the world's population,
are anemic. It is estimated that more than half of the pregnant women in
developing countries are anemic [1].
Several studies have been
carried out to estimate the prevalence of anemia, using the cyanmethemoglobin
method. Agarwal, et al studied in the Indian states of Uttar Pradesh and Bihar;
the national surveys done by the Indian Council Medical Research(ICMR)- covering
11 states; Showed that the prevalence of anemia in pregnant rural women was
87.6% (hemoglobin levels being <10.9g/dl). In 1992, these anemic women were
given different doses of iron 60, 120 and 180 mg with 500 ug folic acid daily
for 90 days in 6 states; however, 62% of them, in spite of taking iron-folate
therapy, continued to be anemic. Thus, indicating that the short-term treatment
as recommended then in the National anemia control program may not be
sufficient to control anemia in pregnancy. However, it was observed that the
birth weight of the babies born to these women improved, and the
low-birth-weight deliveries reduced significantly [2]. The Nutrition Foundation
of India in 2002-2003 found the prevalence of anemia in pregnancy and lactation
in the rural areas (villages) in 7 Indian states (Assam, Himachal Pradesh,
Haryana, Kerala, Madhya Pradesh, Orissa, Tamil Nadu). The prevalence in
Pregnancy in these villages was 84% (severe anemia Hb <7.0g/dl- in 9.2%) and
prevalence in 3 month’s Lactation was 92.2 %( Hb <7.0g/dl in 7.3%). These
data support the findings of the Indian Council of Medical Research (ICMR)
1999-2000, data collected in 11 states
19 districts in the District Nutrition Survey found the pregnancy anemia
prevalence of 84.6% ( severe anemia Hb <7.0 g/dl-in 9.9%). 90% adolescent
girls also had anemia [3] and >87% of children below 3 years of age were
iron deficient [4]. Presently, after 2 decades, the National Family Health
Survey (NFHS-5), showed that 54.3 % of the pregnant women are anemic in the
rural areas in India as compared to 45.7 % in the urban areas. NFHS-5 and NFI
studies used Hemocue and Cyanmetheglobin methods, respectively the former
estimates higher level of hemoglobin. The above studies clearly showed that
prevalence as well as severity of anemia during pregnancy and lactation remains
grave. This is the period when child receives iron for brain (Table 1).
The condition is
prominent in Southeast Asian countries where about half of all global maternal
deaths are due to anemia and India contributes to about 80% of these in South
Asia [5].
Effects
of maternal iron deficiency on feto placental unit
• Normally
Placental Iron transfer to fetus becomes 3 to 4 times during 20-37 wk of
gestation.
a) Cord serum iron and hemoglobin were reduced in preterm as well as fullterm. 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. 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 [6]. In spite of this efficient protective mechanism the placental iron content reduces significantly in maternal hypoferriemia [7]. In contrast,Vahlquist [8] in Swedish and Rios et al [9] in American women had shown that cord iron does not change in iron deficient pregnant women.
Table 1: Percent prevalence of anaemia (Hb<11g%) among pregnant women.
|
NFI Study |
NFHS – 5 |
|
|
Rural |
Rural |
Urban |
India |
84 |
54.3 |
45.7 |
Assam |
93.9 |
55.9 |
41.4 |
Haryana |
91 |
57.2 |
54.6 |
Himachal Pradesh |
68.1 |
43.9 |
* |
Kerala |
57.8 |
27.1 |
35.4 |
Madhya Pradesh |
96.8 |
54.9 |
45.1 |
Orissa |
97 |
62.2 |
59.5 |
Tamil Nadu |
91.5 |
53.1 |
42.6 |
· Iron decreased
‘IRREVERSIBLY’ in all brain parts except medulla oblongata and pons [15,16].
· Susceptibility
to Iron deficiency showed reduction in different parts of the brain:- corpus
striatum-32%, midbrain 21%, hypothalamus 19%, cerebellum 18%, cerebral cortex
17% and Hippocampus 15%.
· Alterations in
brain iron content also induced-Significant alterations in Cu, Zn, Ca, Mn, Pb
and Cd.
Brain ‘Glutamate
metabolism’-(GAD, GDH, and GABA-T)
a) Marked reduction in
levels of brain GABA, L glutamic acid and 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%, but glutamate receptor binding decreased by 63%.
· Brain
‘TCA-cycle’ enzymes-mitochondrial NAD+ linked dehydrogenase significantly
reduced
· Brain
‘Catecholamine metabolism’- Whole brain-dopamine, neonephrine, tyrosine and TAT
significantly reduced; Corpus striatum – same as in whole brain, except TAT
increased.
· Brain ‘5-HT
metabolism’- Tryptophan, 5-HT, 5-HIAA significantly reduced.
The whole brain and
corpus striatum showed reduction in catecholamine, dopamine
nor-epinepherine,tyrosine and monoamino oxidase, while tyrosine amino
transferase increased in corpus striatum, inspite of reduction in whole brain
Suggesting that latent iron deficiency induced irreversible neurotransmitter
Alterations. These changes were specific to iron deficiency as neurotransmitter
alterations in fetal brain due to malnutrition get normalised partially or
completely on rehabilitation. The significant effects on neurotransmitter
receptors (glutamate mediators) during early stages of iron deficiency clearly
indicate the deficits in both excitatory and inhibitory pathways of the central
nervous system [17,18].
Iron deficiency and
thalassemia; both are clinical conditions with anemia but former has no or low
iron content and the later excess of iron in body tissues.
• The
iron content on globus pallidus, caudate and dentate nuclei was similar in both
the clinical conditions.
• There
was an increase in creatinine and aspartate and reduction in choline
concentration. These are very significant findings as choline is synthesized in
the brain in very small amounts; its uptake is Na + dependent, which requires
oxygen. Such changes are also observed in Hutington’s chorea and Alzeimher’s
disease.
• In
contrast in anemia the changes are due to anoxia, irrespective of body iron
status.