Impact of Maternal and Early Life Undernutrition/Anemia on Mental Functions

ACTA SCIENTIFIC PAEDIATRICS Volume 2 Issue 2 February 2019 Review Article

Kailash Nath Agarwal* and Dev Kumari Agarwal Health Care and Research Association for Adolescents, Noida, India *Corresponding Author: Kailash Nath Agarwal, Health Care and Research Association for Adolescents, Noida, India. Received: December 14, 2018; Published: January 22, 2019

Abstract

Malnutrition refers to deficiencies, excesses or imbalances in intake of energy, protein and/or other nutrients and refers to both incorporates chronicity, etiology, mechanisms of nutrient imbalance, severity of malnutrition and its impact on outcomes. In growing under nutrition and over nutrition. New classification scheme proposed by American Society for Parenteral and Enteral Nutrition economies both under nutrition as well as over nutrition are observed with associated health consequences. Intrauterine and early life under nutrition result in impairment of growth and development, intelligence, behavioral, conceptual and sensory motor development in preschool years. A child is stunted if the body is proportionate yet when compared to a normal

functions leading to weight loss. A child who is stunted and wasted is both short and thin compared to that of a normal child. Mal- child of the same age, he/she is shorter. In a wasted child, body fat and muscle reserves are broken down to maintain essential

nutrition in childhood affects IQ, cognitive function, persistence of soft neurological signs and affects higher-order thinking skills in adolescents. The changes that occur early in iron deficiency/anemia (pregnancy anemia in Bangladesh 77% and India 86%)) may neurotransmitters, irreversibly. account for much of the long-term impact on decreased cognitive abilities. As anemia or iron deficiency affect brain iron content and Keywords:

Malnutrition; Definition; Maternal; Low Birth Weight; Intrauterine Growth Retardation; Child; Stunted; Wasted; Anemia; Iron Deficiency; Brain Development

Malnutrition

rea, Sudan and Somalia are exposed to bacteria. The bacteria sicken children suffering from malnutrition in the world. The preva- The World Bank estimates that India has highest number of them, and make it hard for children to consume nutrients, which lence of underweight children in India is among the highest in the results in malnutrition. 620 million people in India don’t have a toilet in their house and they use public toilet or defecate in fields - world, and is nearly double that of Subsaharan Africa with dire or any open space (Prime Minister of India has initiated a national and mental development, mortality, productivity and economic programmed “Swatch Bharat” to meet the much needed in sanita consequences for morbidity like retardation of physical growth world. UNICEF is also recognizing the poor sanitation as one of the [1] - tion). In addition, the air quality in India is among the worst in the dia 20th amongst leading countries with a serious hunger situation. reasons for malnutrition. In addition, cost of food, no easy afford- growth. The 2015 Global health Index (GHI) Report ranked In Despite of economic growth in India, India’s hunger is still worse ability of pulses (source of protein for vegetarians) and vegetables/ - fruits make it worse. Women who suffer malnutrition are less likely than North Korea or Sudan. And a child raised in India is more likely edge in nurturing/feeding children. Consequently, newborns/in- biggest reason for India’s malnutrition is poor sanitation, polluted to have healthy babies. Further they generally lack proper knowl to be malnourished than Somalia. Various studies suggest that the fants in early life are unable to get adequate amount of nutrition poor sanitation situation, more children in India than North Ko- from their mothers. water, unclean vegetables, adulteration and illiteracy. Because of

Citation: Kailash Nath Agarwal and Dev Kumari Agarwal. Acta Scientific Paediatrics “Impact of Maternal and Early Life Undernutrition/Anemia on Mental Functions”. 2.2 (2019): 08-14. Impact of Maternal and Early Life Undernutrition/Anemia on Mental Functions

09 The chapter on ‘Malnutrition’ will cover aspects of maternal/ o Illness-related: childhood nutrition and associated health consequences: o Non-illness-related: Secondary Caused to oneby orenvironmental/behavioral more diseases/injury or factors, or both o o Definition of Malnutrition -

Nutrition during Pre-pregnancy, Pregnancy and Lactation ‘Pediatric malnutrition (under nutrition) is defined as an imbal o StagesHealth Consequences of Intrauterine and Childhood Mal- nutrition ance between nutrient requirements and the intake that results in negatively affect growth, development and other relevant out- cumulative deficits of energy, protein, or micronutrients that may o comes’. Effects of Malnutrition and/or Iron Deficiency on Brain Definition of Malnutrition Malnutrition Statistics Malnutrition - [2], malnutrition ing as stunting, wasting, underweight and anemia. Unfortunately, India with surplus food continues to see malnutrition: manifest these indices are on a rise as observed in National Family Health According to the World Health Organization protein and/or other nutrients. - refers to deficiencies, excesses or imbalances in intakes of energy, nutrition survey conducted by the Nandi Foundation, 42 percent Surveys (NFHS) II vs III. According to the 2011 Hunger and Mal

of Indian children under five years old are underweight - almost double the rate of sub-Saharan Africa. This is in spite of the fact that today India is one of the major food producers in the world. The food sector contributes to about 18% of India’s GDP. In terms of world ranking, India stands o - ulation FIRST in the production of cereals, milk and livestock pop o Figure a: o SECOND in producing fruits and vegetables - nuts, tea, coffee, tobacco, spices, sugar and oilseeds [4]. DWHO. WHO Child Growth Standards.th 2014. Available at: Ranks among in the top 5 in producing rice, wheat, ground http://www.who.int/nutrition/media_page/backgrounders_4_ Comparison of Maternal and Child Health Indices en.pdf. Accessed on: August 5 Indicators Indiaa Sri Lankab Bangladeshc Contrary to the common usage, the term ‘malnutrition’ correct- Neonatal Mortality Rate 29 24 ly includes both under nutrition and over nutrition. Infant Mortality Rate 42 8 33 6 o Maternal Mortality Rate 210 39 220

requirements,Under nutrition poor is defined absorption as the and/or result poor of food biological intake Institutional Delivery 98 28 usethat ofis nutrientscontinuously consumed. insufficient It usually to meet results dietary in energyloss of (per 10,000 live births) body weight. Table a: 46 d - causes each year in India o It is estimated that 67,000 women die of puerperal ta Over nutrition refers to a chronic condition where the in- ke of food is in excess of dietary energy requirements. sity. a. UNICEF, UNICEF - India - Statistics, 2014. Available at: http:// Over nutrition usually results in overweight and/or obe www.unicef.org/infoby country /india_statistics.html. Redefining Pediatric Malnutrition: Paradigm Shift towards b. UNICEF, UNICEF - Srilanka - Statistics, 2014. Available at: http:// Etiology-based Definition-American Society for Parenteral www.unicef.org/infoby country /sri_lank a_statistics.html. and Enteral Nutrition (ASPEN) [3] has proposed: statistics.html.3c UNICEF, UNICEF - Bangladesh - Statistics, 2014. Available at: http://www.unicef.org/infoby country /bangladesh_bangladesh_ mechanisms of nutrient imbalance, severity of malnutrition, and New classification scheme incorporates chronicity, etiology, - BMJ. d. Bhowmik S. Child mortality: Will India achieve the 2015 target? its impact on outcomes. Based on its etiology, malnutrition is ei 2013;346:1502. ther:

10 Nutrition during Pre-pregnancy, Pregnancy and Lactation Stages pregnancy nutrition and its impact on pregnancy outcome. These two historical examples illustrate the importance of pre- the importance of maternal nutrition on maternal health and child We will discuss community-based case studies, which outline outcome [5]. Let us now look at the community-based case study - 2. -

In the case study– 1 the impact of maternal under nutrition can We will discuss the impact of ICDS (Integrated Child Develop rural Varanasi be observed from a prospective study conducted in rural setting ment Services) program on maternal nutrition and birth weight in [7]. India’s ICDS (nutrition + education + child care weight pattern in chronic as well as currently undernourished of eastern Uttar Pradesh, Varanasi. The study evaluated the birth program) has been adapted from the Women Infants and Children pregnant women. In the study, anthropometry, hemoglobin, di- (WIC) in USA.

births were seen within 48 hr and their weight was recorded. 5289 pregnancies were registered during 1987-1993. All live etary intake, birth weight, fundal height and abdominal girth data a. of 3700 eligible pregnant women at 16 ± 2, 28 ± 2 and 36 ± 2 weeks supplemented and 1453 were un supplemented, both pattern of newborns. of gestation were recorded. Outcome measure was birth weight groupsIn the received ICDS, 916 healthcare pregnant and womennutrition wereeducation. nutritionally b. and they received simple healthcare. Results indicated that out of 3700 births, 34.6% were of low There were 1748 pregnancies from the non-ICDS villages, birth weight and only 8.2% weighed more than 3000 g. Fundal was associated with higher low-birth-weight deliveries. Fundal - height was <24.5 cm at 28 weeks of gestation (1368 women) and nancy, birth weight increased by 58 g, preterm’s and low birth - The ICDS-supplemented mothers gained 100 g more in preg height did not increase during 35-39 weeks of gestation (was low er by 5 cm as compared to normal). weights reduced by 12.9% and 29.4%, respectively, as compared - to the un supplemented mothers (ICDS). In the un supplemented - With respect to the maternal weight gain, women in later preg ICDS area, preterm and low-birth-weight births reduced by 44.2% gain of 15 - 53 g, only. In contrast, healthy women gained 400 g/ nancy (during 35 - 43 weeks of gestation), showed weekly weight and 22.4%, respectively, as compared to non-ICDS area pregnan - cies. The un supplemented (ICDS) had higher birth weight by 25 g having birth weight over 3000 g in these three areas, respectively. week in the second and third trimesters. Total weight gained dur as compared to the non-ICDS. There were 16.2%, 11.0% and 12.9% [5]. The multiple regression analysis showed that the increased weight ing the entire period of pregnancy was about 6 kg only, whereas - ideallyFor understandingthe gain should the be betweenimportance 13 andof nutrition 18 kg in pregnancy, it gain in pregnancy, length of gestation, caloric intake and term he moglobin were significantly associated with birth weight. is useful to additionally note the data of World War II-famine in pregnant women and lead to better maternal and fetal outcomes. Leningrad (USSR) where women were already undernourished. Thus, nutritional supplementation can benefit undernourished About 50% of the children who were born were low birth weight (LBW) and birth weight fell by 530g. In contrast, during the Dutch Maternal anemia and its consequences famine, only 9% of the infants born to previously well-nourished - famine was imposed on a previously well-nourished population o Dutch women had LBW and birth weight fell by 327g. The Dutch [8,9] shown in table 1. The preva- - The anemia prevalence in three countries, India, Bangla desh and Sri Lanka are ally decreased from 1800 calories in December 1943 to 1400 calo- and the official daily food for the general adult population gradu lence of anemia in pregnancy is 86% and 81% in lactation in India and is responsible for 20-40% maternal deaths ries in October 1944 to below 1000 calories in the late November (MMR > 200). Indian Council Medical Research 2001- showed that 84.7% of mothers are anemic (hemoglobin 1944. December 1944 to April 1945 was the peak of the famine - < 11.0 gm/dl), of these 9.9% are with severe anemia (he during which the official daily ration fell abruptly to about 400- o moglobinAgarwal., et< 7.0al. [8]gm/dl). 800 calories. Even though pregnant and lactating women had ex showed in 7 states pregnancy anemia tra food during the famine, these extra supplies could no longer be - Famine is that it was imposed on a previously well-nourished pop- nancy/lactationwas in 86.1% (severe anemia anemia is a serious in 9.7%); health anemia hazard during for provided at the height of the famine. What is unique about Dutch lactation being 81.7% (severe anemia – 7%). Thus, preg ulation . mother and child in India. Therefore, we must discuss ef-

[6]

11 fects of pregnancy anemia on fetal outcome including brain Maternal anemia and its consequences growth. Intrauterine Growth Low Birth Weight o Anemia is a serious health hazard for mother and child in In- dia. Therefore, we must discuss affects of pregnancy anemia Retardation [15,16] on fetal outcome including brain growth. Fetal growth de- morbidity and mortality [15] impaired mental develop- Increased risk of perinatal Increasedment and risk mortality of morbidity, Itpends, continues to a largeto trap extent, iron aton a the gradient availability even whenof iron fetus from is there- mother. Placenta formation needs iron in the first 2 weeks. [17] moved in animals. Normally, placental iron transfer to fetus neurological and mental growth restriction, higher the impairmentGreater incidence when ofcompared physical, to Greater the severity [18] of infants with appropriate increases 3-4 times during 20-37 weeks of gestation. intrauterine growth mortality risk Countries Anemia in Anemia in

pregnancy lactation [16] development of adult India [8] Global incidence: 30 million metabolicIncreased syndrome risk for [9] — infants every year (nearly 75% 86.1% 81.7 % Maternal suboptimal nutrition during pregnancy results in [8] of these are born in Asia)[16] [17,18] Sri Lanka 16.0% intrauterine growth restriction and the birth of newborns with

Table 1:Bangladesh 77.0% 77.0% . low birth weight[1] Table b In maternalPrevalence anemia, of anemia fetal liver in India, iron Srilankais low resulting and Bangladesh in early- onset anemia. There is an increased gradient in the presence of Childhood Undernutrition but the transport remains proportionate to the degree of mater- maternal iron deficiency for transport of iron from mother to fetus India and Bangladesh have the highest proportion of children - who are underweight. In India, 20% of children are wasted (Table in maternal hypoferremia, and fetal brain iron content and neu- nal hypoferremia. Fetal Liver iron stores are reduced significantly 2). National Family Health Survey in India indicated that 1 in 6 chil rotransmitters are reduced irreversibly, and their receptors are dren aged between 38 and 57 months are wasted. It is encouraging altered [10]. side [11,12]. to note that the corresponding figures in Sri Lanka are on the lower Health Consequences of Intrauterine and Childhood Indicator India Sri Lanka Bangladesh Malnutrition Underweight Maternal suboptimal nutrition during pregnancy results in (moderate and ) severe) weight less than 10th 43.0% (29.4% 29.0% 48.0% Infants born with IUGR (Intra Uterine Growth Retardation-Birth [11,12]. Furthermore, Stunting centile for gestational age) are at an increased (weight for age) when compared to infants with appropriate intrauterine growth, risk of prenatal morbidity and mortality Wasting 48.0% (38.8%) 14.0% 43.0% - (height for age) rological and mental impairment [13] 20.0% (15.0%) infants with IUGR have greater rates of physical (Stunting), neu (weight for . Globally, about 30 million height) [11,12](1 in 6 Children 14.0% 13.0% infants are born in Asia [13]. infants suffer from IUGR every year, and nearly 75% of all affected 38-57 month) Table 2: Underweight, stunted and wasted children

- Low birth-weight infants are at an increased risk of morbidity, tal death is reported to be four times higher in infants who weigh in India, Sri Lanka and Bangladesh. impaired mental development and mortality. The risk of neona 2000-2499 g at birth when compared to those who weigh 2500- 3499 g. The greater the severity of growth restriction within the In parenthesis recent “Rapid survey on children”, UNICEF and [14]. Government of India figures are given 2015. An underweight child has a weight-for-age Z-score that is at low birth-weight category, the higher the risk of mortality - Low birth weight is a strong predictor of size in later life since dards. This condition can result from either chronic or acute mal- least 2 SD below the median for the National Child Growth Stan nutrition, or both. childhood [3]. infants born with IUGR seldom catch-up to normal size during of adult metabolic syndrome. Low-birth-weight babies have an in- Low birth weight increases the risk for development A stunted child has a height-for-age Z-score that is at least 2 hypertension, type 2 diabetes and other chronic diseases [15-18]. creased risk of later life diseases such as coronary heart disease, standard deviations (SD) below the median for the National Child

12 o growth retardation that results from failure to receive adequate time persisted in later years during adolescence. Growth Standards. Chronic malnutrition is an indicator of linear The deficit in higher mental abilities and prolonged reaction o - and chronic illness [14]. These chronic malnourished have seri- orly as well as posteriorly with loss of asymmetry. nutrition over a long period and may be exacerbated by recurrent Brain MRI: Both frontal lobes showed reduction in size anteri ous health consequences i.e. short stature with poor strength and o structural and functional brain damage. higher suggesting neuronal compensation. P3 latency was normal, but the P2 and P3 amplitudes were o Nutrition supplementation in pregnancy, lactation, infancy Stunting Consequences childhood showed improvement in mental functions [28,30].

Iron depletion and brain - tions < 35 mcg/L have abnormal auditory recognition memory, in- Neonatal Period: Infants with cord serum ferritin concentra

from a stranger’s voice [31]. fants do not discriminate a familiar stimulus (e.g. maternal voice) o Figure b [32]. Term infants born to iron deficient anemic mothers also o exhibit alterations in temperament and activity - Evidence from developing countries indicates that being stunt- Mental Functions in Rural Anemic Primary School Chil dren (nutrition controlled) Mental functions in nutrition cognitive performance and lower school achievement in middle controlled 388 (6-8 yr of age), matched for social and ed between 12 and 36 months of age is associated with poorer childhood. educational status were studied by WISC and arithmetic span.test to In assess Arithmetic “Intelligence, test ‘Attention Attention and and Concentration’ Concentration”. was A wasted child has a weight-for-height Z-score that is at least poorAnemia in anemic did not children affect intelligence,[33]. except subtest-digit

o Those anemic in infancy in spite of iron therapy in early life remain poor in school achievements and have pres- 2 SD below the median for the National Child Growth Standards. and may be affected by recent episodes of diarrhea and other acute ence of soft neurological signs. Central conduction time Wasting represents a recent failure to receive adequate nutrition illnesses. - for auditory brain stem responses at 6, 12, 18 months Effects of Malnutrition and/or Iron Deficiency on Brain ness was less mature [34]. were slower. Heart rate variability during sleep/wakeful The intrauterine growth retarded offspring of undernourished mothers [19,20] Anemia and brain iron [35,36] - o : Studies in children 8-12 years of age having anemia (nutrition o ShowedLimp posture, hypotonia poor inrecoil 72% of and limbs, hypo incomplete excitability Moro’s in 56%. and al, serum ferritin < 20ng) or due to thalassemia (serum ferritin > in globus pallidus, caudate and dentate nucleus in both the condi- 1000ng), on brain MRI spectroscopy showed similar iron content o crossed extensor responses. tions. There was an increase in creatinine and aspartate and reduc- - ingTheir < 2000g. EEG hadThere shortening was some inter of sleep and intra cycle hemispheric (REM and NERM), the reduction was marked for REM babies weigh Hutington’s chorea and Alzeimher’s disease. Reduction of choline, - tion in choline concentration. Such changes are also observed in gesting dysmaturity of brain - asymmetry and abnormal paroxysmal discharges; sug - o Malnutrition in childhood [21-30]. in latent iron deficiency is a significant effect. Choline is synthe o Affects IQ, cognitive function and persistence of soft neu- sized in the brain in very small amounts; its uptake is Na+ depen rological signs, impaired repetitive speed movements dent,Latent which Iron requiresdeficiency oxygen. in rat model - with higher degree of overflow and dysrhythmia with patic iron and selectively brain iron content. EEG changes supporting abnormalities in frontal lobe. Dietary iron depletion IN PREGNANT RATS- reduced fetal he

13 Iron content decreased [37] comes.

o pregnant women and lead to better maternal and fetal out- In Cerebral cortex 17%, Cerebellum 18%, Hypothalamus 19%, comesNutritional as shown supplementation by the Varanasi can rural benefit study. Intrauterine undernourished and Mid braino No 21%, change and inCorpus – medulla striatum oblongata 32% and pons. early life under nutrition results in impairment of growth and o Fetal brain iron content did not change after maternal development, intelligence, behavioral, conceptual and sensory motor development in preschool years. Malnutrition in childhood affects IQ, cognitive function, persistence of soft “Fe” supplementation. - adolescents. Low brain “Fe” content was associated with significant altera neurological signs and affects higher-order thinking skills in o tion in brain Cu, Zn, Ca, Mn, Pb and Cd levels. account for much of the long-term impact on decreased cogni- Fetal brain iron reduction and latent iron deficiency in post tiveChanges abilities, that due occur to irreversibleearly in the braincourse iron of ironand neurotransmitdeficiency may- weanling rats altered neurotransmitters, irreversibly [38,39] ter changes.

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Citation: Kailash Nath Agarwal and Dev Kumari Agarwal. Acta Scientific Paediatrics “Impact of Maternal and Early Life Undernutrition/Anemia on Mental Functions”. 2.2 (2019): 08-14.