Article Type : Research Article
Authors : Agarwal KN, Agarwal DK, Mittal RD and Dewan P
Keywords : Malnutrition; Anthropometric indices; Leucocyte F?AN; Erythrocyte glutamic acid; salivary ferritin; Physical; Neurologic and Cognitive sequelae; Milk; Fermented milk Dahi; Berseem leaves
Identify and Grade the Degree of Malnutrition in Childhood
To identify and grade the degree of childhood
malnutrition, anthropometric indices were developed, given the absence of
nationwide growth data in India. Growth data from affluent Indian children were
collected between 1989 and 1991, covering the period from birth to 5 years in
seven states. The study included only full-term infants with a birth weight of
?2500 g, and assessments were conducted at 3, 6, 9, and 12 months of age, with
a minimum of three readings for each infant (cohort-I). In cohort-II, 1011 boys
and 874 girls were followed from 12 months to 5 years, with a minimum of three
measurements taken for each child every six months up to 72 months of age.
Cross-sectional multicentric data on physical growth and sexual development
were collected from affluent Indian children aged 5-17.5 years in girls and
5-18 years in boys, representing 23 schools across 9 states with a total of
12,893 boys and 10,941 girls [1-4].These data provided the basis for Indian
national growth curves and criteria for categorizing children as normal
healthy, stunted, wasted, and stunted-wasted. Recognizing that body stature
changes take a long time to develop in malnutrition, efforts were made to
explore biochemical tests on body fluids [5]. Biochemical tests revealed
significant findings. For instance, blood leucocytes (with a lifespan of 13-20
days) showed decreased F?AN in hypoproteinaemia [6]. Erythrocytes (with a
lifespan of 100 days) exhibited a significant increase in glutamic acid [7].
Serum and salivary arginase activity, as well as levels of salivary protein and
ferritin, decreased with the severity of protein-energy malnutrition (PEM).
Salivary ferritin, in particular, demonstrated a significant fall even in PEM
grade I, with a marked decrease in grade III compared to normal children. The
innovative, non-invasive salivary ferritin assay proved sensitive in
recognizing the severity and early stages of PEM, making it particularly
relevant for practical use in rural areas [8]. Salivary iron was found to
increase in cases of hypoproteinaemia and iron deficiency [9].
Maternal malnutrition on pregnancy outcome and growth in offspring
A prospective study conducted in K V block of rural
Varanasi, India, focused on the effects of maternal nutrition on pregnancy
outcomes and the growth and development of offspring. Among 3,700 eligible
pregnant women examined at 16, 28, and 36 ± 2 weeks of gestation, 34.6% had a
birth weight <2500g (LBW), and only 8.2% had a birth weight >3000g (10).
Notably, fundal height (FH) was <24.5 cm at 28 weeks of gestation in 1,368
women, associated with higher LBW deliveries. These women exhibited no increase
in FH during 35-39 weeks and gained weight at a rate of 15-53 g/week during
35-43 weeks of gestation, with a total pregnancy weight gain of only 6.0 kg.
This was considerably below the recommended 13-15 kg for normal weight gain
[10].
Offspring’s of intrauterine growth-retarded mothers showed hypertonia in 72% and hypo excitability in 56%. Various reflexes, such as limp posture, poor recoil of limbs, incomplete Moro's, and crossed extensor responses, demonstrated modifications [11]. EEG results indicated a shortening of sleep cycles, with marked reduction in REM sleep for babies weighing <2000g. Inter and intra-hemispheric asymmetry and abnormal paroxysmal discharges suggested brain dysmaturity [12]. Subsequent follow-up studies in the same rural area, where 13% of children experienced severe malnutrition and 50% had moderate to mild malnutrition, revealed impaired growth and development. Gessell's developmental schedule assessments from 4 to 52 weeks of age demonstrated poor development in motor, adaptive, language, and personal-social areas for children with grades II and III malnutrition [13]. Children followed from birth to preschool years (13% severe and 50% moderate to mild malnutrition) showed that under nutrition resulted in impaired growth and development. Those with grades II and III malnutrition showed poor development in all areas of behaviour i.e., motor, adaptive, language and personal social [14].
Effect of malnutrition on social maturity and intelligence
Rural children aged 6–8 years, assessed for social
maturity (Vineland Social Maturity Scale), visuomotor coordination (Bender
Gestalt Test), and memory (free recall of words, pictures, and objects),
displayed deficits associated with malnutrition. These deficits were observed
in social competence, visuomotor coordination, and memory, with a more
pronounced impact on immediate memory. Intelligence assessments using the
Wechsler Intelligence Scale for Children (WISC) showed decreasing IQ scores
with the severity of malnutrition. Performance IQ and specific subtests, such
as information and digit span among verbal subtests, exhibited significant
decreases. The study indicated that, despite a decrease in full-scale IQ,
different neuropsychological functions were affected to varying degrees.
Stunting was associated with delayed development of cognitive functions and
permanent cognitive impairments, with minimal improvement with age. Attention,
executive functions, working memory, and visuospatial functions were more
severely affected by childhood protein-energy malnutrition [15]. Even among
undernourished children with an IQ >90, perceptual maturity and conceptual
grasp were impaired, suggesting learning disabilities [16]. Higher mental
abilities related to personal and current information, orientation, mental
control, logical memory, attention span, visual reproductive and associative
learning were also affected. There was impairment in overall memory function,
including set formation and conditional learning [17]. Reaction time studies
demonstrated effects on perceptual abilities, information processing, and
analytical capabilities. Importantly, even undernourished children who had
achieved normal nutrition in later years continued to exhibit prolonged
reaction times [18]. Soft neurological signs observed in preschool years, which
typically disappear or reduce in school years and adolescence, persisted in
early life undernourished (stunted) children. These signs included impaired
repetitive speed movements with a higher degree of overflow and dysrhythmia
[19]. Stunted-wasted children demonstrated soft neurological signs along with
EEG changes, characterized by slow and sharp waves, particularly in the frontal
lobe but also in the parietal and temporal lobes. Motor deficits were more
pronounced on the contralateral side of EEG changes. Brain MRI revealed
structural changes in both frontal lobes, including a reduction in size
anteriorly and posteriorly, as well as a loss of asymmetry, supporting the EEG
abnormalities observed in the frontal lobes [20-21]. A study on mental
functions in 388 rural anemic primary school children (6-8 years of age)
investigated the impact of nutrition on intelligence, attention, and
concentration. Intelligence, as assessed by WISC and arithmetic tests, was not
significantly affected by anemia, except for the digit span subtest. However,
attention and concentration in arithmetic tests were found to be poor in anemic
children [22]. Follow-up studies on rural adolescent children revealed that,
although their height gain was similar to affluent Indian children, the deficit
in early life height was not corrected during the adolescent growth spurt. No
specific age period could be identified for peak height velocity. Weight gain
was only 38% compared to affluent Indian children. In terms of sexual
development, boys exhibited delayed maturation of genitals by 1.54 years, pubic
hair by 0.82 years, and auxiliary hair by 0.65 years, while testicular volume
remained comparable. Rural girls experienced delayed breast development and
menarche by 2.19 years and 0.82 years, respectively, compared to affluent
Indian girls [4-23]. Throughout school age until 17.5 years, follow-up studies
on these early-life undernourished children demonstrated that they maintained
their vital functions by mobilizing amino acids from body muscles, as evidenced
by increased serum enzyme activities such as LDH, ALP, AST, ALT, CK, CK-MB, and
CK-mm. Phosphorus magnetic resonance spectroscopy revealed increased ?-ATP and
Pi in muscles at the expense of Pcr (Phosphocreatinine). These changes
simulated a myopathic status [24].
Nutrition and/or
iron-folate supplementation during pregnancy and childhood-one study involved
146 children receiving 450-500 calories with 10-12 gm protein in rural primary
schools for 172 days (Mid-day meal) over two years. While height gain did not
differ significantly, weight marginally improved. More supplemented children
remained in grade I malnutrition, in contrast to the control group, which
shifted to grade II malnutrition after two years. Supplemented children showed
a marginal improvement in full-scale, verbal, and performance IQ (WISC), with
significant improvements in all subtests except for comprehension and maze
tests. Unstructured Piagetian development task, conservation of liquid also
improved. The score of arithmetic achievement tests improved by 12-14 points in
the supplemented group [25]. Another study involved a total of 916 pregnant women
receiving nutritional supplementation in the national Integrated Child
Development Programme (ICDS), which provided 600 calories with 18-20 gm
protein. A control group of 1,453 pregnant women received healthcare and
nutrition education, and 1,748 pregnancies from non-ICDS villages received
simple healthcare. The ICDS-supplemented mothers gained 100g more in pregnancy,
with birth weight increasing by 58g. The incidence of preterm and low birth
weight decreased by 12.9% and 29.4%, respectively, compared to unsupplemented
mothers (ICDS). Multiple regression analysis revealed that increased weight
gain in pregnancy, length of gestation, caloric intake, and term haemoglobin
were significantly associated with birth weight [26]. In another study, 418
pregnant women at 16-24 weeks of gestation were selected from six sub-centers
of a rural block in Varanasi district. Pregnant women from three sub-centers
received supplementation of 60 mg elemental iron as ferrous sulfate combined
with 500 micrograms folic acid daily for 100 days (study group). A control
group comprised pregnant women from the other three subcenters without
supplementation. Haemoglobin and serum ferritin levels increased significantly
in the study group. Mean birth weight in the study group was 2.88 +/- 0.41 kg
with a low-birth-weight incidence of 20.4%, compared to control figures of 2.59
+/- 0.34 kg and 37.9%, respectively [27]. Another study involving 40 pregnant
women receiving daily and 40 receiving weekly oral therapy (335 mg of ferrous
sulfate and 500 g folic acid) for 14 weeks found that weekly and daily iron
supplementation were equally effective in treating anemia among pregnant women
[28].
Mechanistic Studies in Animal Models
We investigated the impact of staple diets on
neurological development in animal models. Rat mothers receiving wheat or
lentil diets showed a dissociation of brain growth, affecting both brain and
body growth equally. Fetal and weanling rat neurotransmitters were altered,
only partially reversing on rehabilitation [29-30]. In a latent iron deficiency
rat model, dietary iron depletion in pregnant rats reduced fetal hepatic iron
and selectively reduced brain iron content in various regions. Fetal latent iron
deficiency led to irreversible reductions in neurotransmitters related to
glutamate metabolism, TCA-cycle enzymes, catecholamine metabolism, and
serotonin metabolism. These changes were specific to iron deficiency and were
not reversed with rehabilitation [31-35]. Observations from animal studies
suggested that neurological and cognitive changes could be attributed to
alterations in neurotransmitters. To address malnutrition, studies were
conducted with Actimel (Danone) and Dahi (fermented milk), demonstrating their
effectiveness in controlling diarrhea in hospitals and communities (36). Severe
protein-energy malnutrition (PEM) in children was treated according to the WHO
protocol (milk diet) and compared against fermented milk Dahi with
lactobacillus bulgaricus and streptococcus thermophilus in the WHO regime to
develop a better alternative to milk. Dahi, with immunonutrient properties, was
found to be effective in treating and eradicating malnutrition. Berseem leaves
(Trifolium Alexandria) with a protein content of 18-23% were also identified as
a potential source of nutrition. Leaf protein concentrate (LPC) from Berseem
leaves contained 20% protein and demonstrated immuno-modulating properties to
control malnutrition in developing countries. These studies suggested that the
WHO diet should consider incorporating fermented milk/Dahi instead of milk, and
Berseem leaves (LPC) could be mixed with cereals/lentils to increase protein
and micronutrient content [37-40].
In conclusion, this comprehensive study contributed
significantly to the field of childhood and adolescent nutrition. It resulted
in the development of national growth curves, a rapid and non-invasive test for
malnutrition using salivary ferritin, the identification of sequelae associated
with early-life malnutrition, and the exploration of potential preventative
measures. The study underscored the importance of addressing malnutrition
through interventions such as fermented milk and Berseem leaves.