Maternal and Child Nutrition: First Major Step for Prevention of Cardio-Metabolic Disorders.

Gundu H. R. Rao 1,3 Mangala Bharathi 2

Emeritus Professor 1 Lellehei Heart Institute, University of Minnesota, Minneapolis, Minnesota, USA. Director 3 Research and Development, Genelon Life Sciences,

Director 2 Genelon Life Sciences, Bangalore, India.

South Asians (Indians, Bangladeshis, Pakistanis and Sri Lankans) have the highest incidence of coronary artery disease (CAD), compared to any other ethnic group in the world (1, 2, 3). According the World Diabetic Federation, India has over 65 million diabetics and an equal or more pre-diabetics. To create awareness, develop educational and preventive strategies, I started a professional society, South Asian Society on Atherosclerosis and Thrombosis (www.sasat.org), in Minnesota, in 1993. We have organized international conferences in various parts of the country and published several books on the subject in India. To expand our activities in this area, we also started some sister organizations; International Society For Prevention of Atherosclerosis and Thrombosis (ISPAT), Institute of Preventive Medicine (IPM), Global Alliance of Traditional Health Systems (GATHS), and Mind Body Spirit Society of India (MBSSI). After two decades of organizing educational programs in India, we at IPC Heart Care Center, Mumbai (www.ipcheartcarecenter.com), IPM, SASAT and ISPAT, believe that it is time to start working with the community and develop some novel diagnostic methodologies, and non-traditional approaches, to the management of Cardio-Metabolic Disorders (CMDs). When planning early detection and prevention one frequently asked question is, what is the earliest diagnosis of a disease and how early should we deploy prevention strategies? In the early 1990s, I led a delegation to World Health Organization (WHO), in Geneva, to present our “novel ideas” to the Chief of Non-Communicable Disease Division (Other participants included: Dr Devi Shetty of Narayana Hrudayalaya, Bangalore; Prof Raghavendra Rao, Neonatologist, University of Minnesota, USA; Dr Mahadev Murthy, Program Officer, NIH/USA; and Dr V. S. Pandurangi, Commonwealth Association for Mental Handicap and Developmental Disabilities, UK, who coordinated our visit to Geneva). In that presentation, I defined earliest time for prevention of CMDs, as even before conception of a child or even when one is thinking of having a child. In developing countries, even to this day 30% of the children born are of low birth weight. Seminal studies done over a long period at the Holdsworth Memorial Mission Hospital, Mysore, has demonstrated that these low birth weight children, when they grow into adulthood, develop cardio metabolic disorders. In this overview, we will discuss what is known of this problem, what has been done to alleviate this problem and offer some future strategies and action plans.

The low-birth-weight (LBW) remains a high risk for infant mortality (NEJM 312:82-90, 1985). Collaborative Studies in India, from Medical Research Council (MRC) of United Kingdom (UK), with Mission Hospital Mysore (MHM), and King Edward Memorial (KEM) Hospital, Pune, have demonstrated that over a third of all babies born in India, are of low-birth-weight. Follow up of these LBW babies have demonstrated that they develop a significantly high incidence of elevated blood pressure, obesity, diabetes (type-2) and cardiovascular diseases (CVDs). In view of these findings, MRC has set up an epidemiology resource center at KEM hospital Pune and at Mission Hospital, Mysore. This is not a finding that is unique to the South Asians. Xiao and associates in Beijing, China, studied individuals born between 1921 to 1954, at the Peking Union Medical College Hospital, to estimate the association between birth weight and Metabolic Syndrome (MS). They defined MS, as per the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP111) guidelines. According to their studies, the prevalence of MS was 27%, though 55% of the subjects had as least two components of the MS (4). In the 1980s Barker developed a hypothesis according to which many nutritional events that occur during the intrauterine growth will influence the development of adult diseases (5, 6).

Holdsworth Mission Hospital, Mysore, has kept birth records of all the children born in that hospital since 1934. However, the importance of this meticulous medical record remained unknown till Indian Council of Medical Research (ICMR), India, established a “birth cohort study” in 1969 at five centers: New Delhi, Mumbai, Pune, Mysore and Vellore. These studies were funded for five years by ICMR. Babies were measured in detail at birth and through infancy, child hood and adolescence. In 1993, Medical Research Council of UK established an Epidemiology Resource Center at Mission Hospital, Mysore, and initiated a research program to assess the importance of early life on diseases of this population (Mysore Cohort). These and other studies, have clearly demonstrated the relationship of LBW with elevated blood pressure, obesity, insulin resistance obesity, CAD and stroke (11-25). It has been suggested that in poor nutritional conditions, a pregnant female can modify the development of unborn child such that, it will be prepared for survival in an environment in which the resources are likely to be inadequate, resulting in a thrifty phenotype (8,9). David barker’s group has contributed significantly to our understanding of the ill effects of LBW on the risk for the development of adult on-set diseases (5, 7, 11). They have documented their findings in over 50 publications in the last decade and provided evidence from population studies, that LBW at term and in some case LBW at age 1, are associated with an increased risk for hypertension, CAD, non-insulin dependent diabetes, and autoimmune disorders (17). A brief review of literature demonstrates the complexity of this problem. Maternal nutrition and intra uterine growth is a complex subject, as many experts have found out there is no simple solution (17-56). Extensive studies by Prof Barker and associates, have demonstrated a strong relationship between LBW, and metabolic disease such as hypertension, obesity, CAD and stroke. Some studies have shown evidence for impairment of visual as well as brain development. Added to this complexity, there is some speculation that some of these observed effects may be due to genetic pre-disposition or due to micro environmental influences (48-59). Cohort study from Vellore has shown influence of intergeneration

trends in birth weight across two generations (58). A retrospective study (1948-96) from China has shown that low birth weight may increase the prevalence of and risk for low lung function in adulthood suggesting that development of lung function may by affected by hypogenensis in utero (59). Low birth weight is one of the main predictors of infant mortality. The global incidence of LBW is about 17%, estimates vary from 30% in India to as low as 5-7% in the developed countries of the world. The LBW according to the experts is by and large associated with situations in which intra uterine malnutrition is produced due to alterations in placental circulation as well as the unavailability of essential nutrients. There are many risk factors reported in the literature, the most important being socio economic factors in the resource poor countries as well as maternal lifestyles (60). Although interventions exist and the benefits of few such interventions have been demonstrated, the incidence of LBW has not decreased in South Asian Countries. There is no proven prevention strategy for LBW. Having said that, there are a few interventions that can be planned, like education of the would be parents, better maternal and neonatal nutrition, better prenatal care including ultrasound measurements to determine more precisely the gestational age of the growing baby.

According to a report by the Center for Disease Control (CDC), Atlanta, at the Thirty-fourth World Health Assembly, the Member states of the WHO adopted, as part of the global strategy for health for all by the year 2000, the proportion of infants born with an LBW as one of a number of global indicators with which to monitor progress. After more than a decade, “based on this marker”, there seems to be no significant progress worldwide. In developed countries, most of infants are weighed at birth; in developing countries usually only those born in medical institutions are weighed. Only about one third of the births in developing countries take place in institutions. The incidence of LBW by the region, ranges from 31% in Middle South Asia and 20% for Asia as a whole to 14% in Africa, 10% Latin America and 6% in the Western countries. In Middle South Asia where the problem is acute, there is no significant change. Rates in the incidence of LBW in Middle South Asia remains between 20 % and 50%. In a way it is a global problem and needs immediate attention by the affected communities, as it seems to be one of the causes for so called, “Fetal Origin of Adult Disease (FOAD)” (61).

There is extensive epidemiological evidence to support FOAD hypothesis, In brief the hypothesis suggests that intrauterine environmental exposures and events affect the fetus development and thereby increases the risk of specific diseases in adult life. Barker and colleagues documented initial support for this hypothesis for coronary artery disease (CAD). They standardized the mortality ratios for cardiovascular disease for 16,000 individuals, born in Hertfordshire, UK, from 1911-1930, to birth records for these individuals. The data suggested that low birth weight, small head circumference and low mass/height index at birth was associated with an increase in coronary heart disease in adulthood (62). Studies from this group showed that the low birth weight predisposed these children with LBW for the development of almost all known cardio-metabolic risk factors in adult hood (62-66). They also explored this phenomenon in children born at Mission Hospital Mysore. They studied 517 men and

women born between 1934 and 1954 at this hospital and found that as in the UK study, coronary heart disease was associated with small size at birth, suggesting that its patho-genicity was influenced by events in utero (67). In 1993 Medical Research Council of UK established an Epidemiology Resource Center at the Mission Hospital campus in Mysore, and initiated a research program to assess the importance of early life on diseases of this population (Mysore Cohort). These and other studies, have clearly demonstrated the relationship with LBW with elevated blood pressure, obesity, insulin resistance, dyslipidemia, metabolic syndrome, obesity, CAD and stroke (11-25). An association has been demonstrated by many epidemiological studies between LBW and increased risk later in adulthood, for breast and testicular cancer, end-stage renal disease, osteoporosis, spontaneous hypothyroidism, adult asthma and hearing loss, cardiac hypertrophy, depression, liver cirrhosis, schizophrenia, polycystic ovary syndrome, precocious pubarche, hypospadias, crypt-orchidism, low scores of alertness, neural tube development defects, mood instability, significant differences in academic and professional achievement (6).

Reducing the incidence of LBW neonates by at least one third between the year 2000 and 2010 was one of the major goals of the United Nations resolution, “A World Fit for Children”, and was considered an important contribution towards the Millennium Development Goal (MDG)-4, of reducing child mortality by two thirds by 2015 (68). In a study conducted at JSS Medical College, Mysore, researchers found that more than 50% of the mothers were anemic at some point during their pregnancy. Preterm babies occurred more frequently in mothers who were anemic in their second and third trimesters (69-73). Studies on the “Mysore cohort” showed an association between maternal homocystiene and folate concentrations during pregnancy and childhood insulin resistance (74). The Pune Maternal nutrition studies demonstrated that low maternal vitamin B12 and high folate status contribute to the epidemic of adiposity and type-2 diabetes in India (75) Estimates from the WHO report that from 35% to 75% of pregnant women in developing countries are anemic. Results of over 60 randomized studies with 43 clinical trials involving more than 27,400 pregnant women demonstrated that use of iron and folic acid supplementation was associated with a reduced risk of anemia and iron deficiency during pregnancy and of giving birth to low birth weight babies (76).

Similar to the studies on iron, folate and vitamin B12, clinical trials have been done on the role of multi-micronutrient (MMN) supplementation for women during pregnancy. Cochrane Data Base summarizes the results of nine such trials with more than 15,370 women (2006, 2012). Results indicate that when compared with supplementation of two or less micronutrients or no supplementation or a placebo, multiple-micronutrient supplementation resulted in a statistically significant decrease in number of low birth weight babies. However, these differences lost statistical significance, when multi-micronutrient data were compared with the iron and folic acid supplementation alone (77,78). Haider et al, based on an earlier review concluded, that a significant benefit of MMN supplementation occurs during pregnancy in reducing small-for-gestational age births as compared to iron-folate (79). In spite of several reviews and meta-analysis of various clinical trials on this subject, it is not clear as to what treatment is better, iron -

folate supplementation or MMN? Further studies are needed to develop information regarding what combinations of MMN are essential for substituting currently used iron-folate supplementation.

Poor nutrition is a well-known cause of LBW, especially in developing and resource poor countries (80). According to a classic review by Kramer, maternal nutrition factors both before and during pregnancy account for more than 50% of cases of LBW in these countries (81). In the area of general nutrition, there is a great need to create awareness among women of childbearing age as well as pregnant women, about the nutritional requirements for good health. This is a very complex issue, as it involves policy development and coordination of several multi-disciplinary public health programs. It is clear from many studies, that just caring for the nutrition status of pregnant women may be too narrow a window, to improve the nutritional status. In spite of several studies and policy announcements, rates of anemia have not declined among both pregnant women and non-pregnant women, in most of the developing countries. Therefore, collective thinking of researchers in this field is, to include all women of reproductive age in such studies (80-85). It is also worth considering fortification of food with iron and other nutrients. Significant reduction in LBW has been demonstrated in Chile and Venezuala with fortified foods, including mother’s milk.

Studies have shown that improving food intake during pregnancy effectively reduces LBW, but programs have been less successful because interventions are expensive and difficult to manage (18-26), Each year 20 million children are born with LBW worldwide and more than 95% of them in developing countries. In one of the largest studies on this subject, researchers at the Harvard School of Public Health and Muhimbili University of Dar es Salaam, Tanzania, found that giving daily supplementation of multivitamin supplements to pregnant women significantly reduces risks of low birth weight. These vitamin supplements produced in bulk by the UNICEF cost less than a dollar for the duration of the pregnancy (ww.hsph.haravrd.edu). According to the International Food Policy Institute, the major determinants of intrauterine growth retardation (IUGR) are related to mother’s nutritional status. Priority research recognized by this international think-tank, include interventions that incorporate, zinc, iron, folate, cobalamin, magnesium, and other micronutrients. Typical diet in South Asia is rich in carbohydrates and this puts considerable amount of stress on the endogenous insulin. Furthermore, it has been shown by MRC studies, that high carbohydrate intake in early pregnancy suppresses placental growth, if combined with a low dairy or meat protein intake (29).

Professor Caroline Fall (http://www.mrc.soton.ac.uk/staff/caroline-fall/) of MRC Environmental Epidemiology Unit, Southampton, UK, has been associated with studies on LBW children since 1989, when she started working with the Hertfordshire cohort. Since 1993 she has been working on the fetal origins of cardio-metabolic diseases in Indian populations in 5 different centers; New Delhi, Mumbai, Pune, Mysore and Vellore (86-105). Life Course Unit of MRC maintains a large number of internationally unique cohort resources; some comprise population-based samples of

adults in whom detailed pheno-typing has been undertaken (Hertfordshire cohort study, the Helsinki Cohort Study, and the New Delhi Cohort Study, while others comprise more contemporary mother-offspring studies; Southampton Women’s Survey and the Pune Maternal Study. In spite of the fact that there is so much work going on, globally on this complex problem of great public health importance, no definite guidelines exist as to what is the best approach to alleviate this problem at any given geographical location?

Maternal and child under nutrition was the subject of a Series of papers in The Lancet in 2008. A consortium of scientists led by Professor Robert E Black from Johns Hopkins Bloomberg School of public Health (the Maternal and Child Nutrition Study Group), have reviewed this problem in a systematic way. Maternal and Child Nutrition Study Group: Robert E Black (Johns Hopkins Bloomberg School of Public Health, USA), Harold Alderman (International Food Policy Research Institute, USA), Zulfiqar A Bhutta (Aga Khan University, Pakistan), Stuart Gillespie (International Food Policy Research Institute, USA), Lawrence Haddad (Institute of Development Studies, UK), Susan Horton (University of Waterloo, Canada), Anna Lartey (University of Ghana, Ghana), Venkatesh Mannar (The Micronutrient Initiative, Canada), Marie Ruel (International Food Policy Research Institute, USA), Cesar G Victora (Universidade Federal de Pelotas, Brazil), Susan P Walker (The University of the West Indies, Jamaica), Patrick Webb (Tufts University, USA) rblack@jhsph.edu. The overall finding as summarized in a special edition of the Lancet (June 2013) is that 3.1 million children younger that 5 years of age, die every year from under nutrition; that is a staggering 45% of the total child deaths in 2011, and is not acceptable (106).

According to estimates, fetal growth restriction or being small for gestational age, causes more than 800,000 neonatal deaths. One hundred sixty five million children with stunted growth have compromised cognitive development. Reducing the incidence of LBW neonates by at least one third between the year 2000 and 2010 was one of the major goals of the United Nations resolution, “A World Fit for Children” and was considered an important contribution towards the Millennium Development Goal (MDG)-4, of reducing child mortality by two thirds by 2015. As the end of this expected deadline approaches (2015), the countries and the international community, who signed this resolution, have to agree, that improving the nutrition or alleviating the under nutrition, was one of the great missed opportunities of the past 15 years. Time for concerted action is now, and if the maternal and child nutrition is optimized, the benefits can be reaped for generations to come. Estimated cost to cover a set of needed nutrition interventions worldwide to 90% coverage is USD 9.6 billion per year. A second series on nutrition, published in The Lancet, explicitly shows that the solution to malnutrition lies on a collective effort in which all stakeholders-governments, academia, civil society, UN system organizations, foundations development banks and business–carry out specific roles in ensuring that interventions are delivered equitably and at scale (The Lancet Special issue 2013).

Bhutta and associates as members of the consortium on Maternal and Child Nutrition Group, did a comprehensive update of the evidence-based interventions for improvement of maternal and child nutrition. They concluded that promising

interventions exist, to improve maternal nutrition and reduce fetal growth restriction and small-for-gestational age (SGA) births, in appropriate settings in developing countries. It was recommended that these intervention strategies be scaled up before and during pregnancy. These interventions include, balanced energy intake, protein, calcium, and multiple micronutrient supplementation and preventive strategies for infectious diseases. This group also suggested replacement of iron-folate with multiple micro nutrient supplements, in pregnancy and suggested that this may have additional benefits for reduction of SGA in, at-risk populations. Treatment strategies for severe acute malnutrition with recommended packages of care and ready-to-use therapeutic foods are well established by the World bodies dealing with nutritional issues. While considering the interventions for maternal health, it is important to plan for peri-conceptional folic acid supplementation. A review of five major clinical trials has demonstrated that peri-conceptional folic acid supplementation resulted in 72% reduction in risk of neural tube defects (107).

Food fortification to provide the daily requirements of micronutrients is safe and cost effective and has been used widely in developed countries for more than a century (108-111). According to the International Food Policy Institute, the major determinants of intrauterine growth retardation (IUGR) are related to mother’s nutritional status. Priority research recognized by this international think-tank, include interventions that incorporate, zinc, iron, folate, cobalamin, magnesium, and other micronutrients. Typical diet in South Asia is rich in carbohydrates and this puts considerable amount of stress on the endogenous insulin. Furthermore, it has been shown by MRC studies, that high carbohydrate intake in early pregnancy suppresses placental growth, if combined with a low dairy or meat protein intake (29). Attempts to improve the Indian diet in terms of protein have been not very successful. At least in north India and Nepal, soybeans have apparently been used as foods for centuries. The earliest efforts to popularize their use were made during the 1930s in India by Mahatma Gandhi and by the Britisher Kale, working with the Maharaja of Baroda. Extensive nutritional studies, begun in India in the late 1930s, have continued to the present.

In spite of the fact that in some parts of the country soybean has been consumed as a food, it has not made great impact as a source of protein in the daily diet of common Indian. Scientists at Central Food Technological Research Institute (CFTRI) Mysore, as well as National Institute of Nutrition (NIN) at Hyderabad, continue to look for additional sources for proteins. CFTRI developed baby food formulas, from Buffalos milk proteins. It became commercialized as AMUL Baby Food. In addition to this, deodorized fish floor as well as protein concentrates from peanuts were developed at this institute. CFTRI also developed peanut protein-based yogurt in early 60s. It was popular in the restaurants for a brief period. To this day, there is a continued effort at various research institutions both at the State level as well as National level, to develop a cost effective, acceptable protein supplement.

During mid 60s, Dr. Parpia, the director, of CFTRI in Mysore, estimated that 80% of India's young children suffered from various degrees of protein malnutrition. Moreover, as high yielding wheat acreage expanded, often taking the place of less profitable pulses, both Indian nutritionists and USAID personnel became concerned

about protein deficiencies that might result. Encouraged by these extremely promising findings, in 1967, the All-India Coordinated Research Project on Soybean was started as a team effort, to develop the soybean as a new protein food source. The project, with headquarters at Pant Nagar, was a joint venture between the Indian Council of Agricultural Research (ICAR), the two University of Illinois-assisted Indian universities (G.B. Pant and JANU), USAID, with help from the Indian Ministry of Agriculture.

In 1965 Shurpalekar and co-workers at the Central Food Technological Research Institute, Mysore, published a study on the preparation of a high-protein spray-dried soymilk-type weaning food based on whole soy flour. Prepared in response to the shortage and high cost of cow's milk, it was fortified with methionine, vitamins and minerals, contained 26% protein and 18% fat, and had a PER of 2.47 (99% that of casein). In 1966 Bal-Amul, the first weaning food developed and manufactured in Asia, was launched in India. Commercial soybean production in this region began to grow starting in the late 1960s, with India leading the way, followed by Nepal. Starting in the late 1970s extremely original, creative work with soyfoods, began in Sri Lanka. India and Nepal also have showed increased interest in soyfoods. Foods can be fortified at three levels; mass or universal, targeted (Eg: Maternal Nutrition or Child nutrition), and household. Mass fortification can be mandatory at the regional or national level and has the potential to produce foods and food products that are widely consumed. Fortification of foods, whether mass or targeted, has the greatest potential to improve nutritional status of population in general, or targeted, as in mother and child programs.

In a series of articles published on Maternal and Child nutrition, in The Lancet (June 2013), basic message becomes clear, that the solution to malnutrition lies on a collective effort, in which all stakeholders, governments, academia, civil society, UN system organizations, foundations, development banks and business–carry out specific roles in ensuring that interventions are delivered equitably and at scale (The Lancet Special issue 2013). It is easy to publish scholarly, wise suggestions, or pass resolutions at regional or national levels by the Global Organizations. However, in a country like India for instance, it is difficult to bring these stakeholders on to a common platform. Moreover, in spite of the fact that MRC of UK under the leadership of Professor Caroline Fall is coordinating research on this subject at five major centers in India since 1993, no definite policies have been developed to address these issues. India with the largest number of diabetics already has serious health care burden. In this overview, we are trying to address an issue that may be one of the major causes contributing to the growth of metabolic diseases. Although we know about the dramatic growth of the twin-epidemics, heart disease and type-2 diabetes, in the last two decades, we have not been able to convince the policy makers to develop a national platform to address these issues.

We at SASAT, ISPAT, IPM, IPC Heart Care Center, Mumbai; Public Heath Institute (PHI), and Center for Disease Control (CDC), Rajiv Gandhi University of Health Sciences (RGUHS), Karnataka, would like to work in concert and develop strategies for the prevention of CMDs and initiate some action plans for immediate implementation. Having reviewed briefly the effect of dietary behavior, macro-and

micronutrient deficiencies before and during pregnancy, we feel the need to develop regional and national programs, to address these issues, which lead to the development of pregnancy-associated intrauterine growth retardation. The questions that we need to address immediately are as follows: How and to what extent nutritional deficiencies affect fetal growth (weight, length, head circumference and development of other organ systems)? How can these deficiencies be remedied in order to improve fetal growth and reduce the number of LBW/SGA in future? What is the take home lesson from large-scale public health nutritional interventions? In any preventive program, the first and the foremost steps are to create awareness of the problems and develop appropriate educational programs. We the members of the expert committee at the RGUHS have initiated an education and awareness program for the school going adolescent children. With the help of Nestles Corporation of Nanjangud, near Mysore, we have initiated a bilateral program of educating the young girls of school going age, the basics of hygiene and nutrition. RGUHS has over 20,000 volunteers under the National Social Service Scheme (NSS). Once a workable model is developed, we can implement these programs in the middle and high schools in the State of Karnataka.

We would like to establish working relationship with the five centers in India; New Delhi, Mumbai, Pune, Mysore and Vellore, where studies are in progress on this subject for several decades. We also would like to establish network with key members of the International Consortium on Maternal and Child Nutrition (Prof Robert E. Black, Johns Hopkins School of Public Health, Harold Alderman, International Food Policy Research Institute (IFPRI), Zulfikar Bhutta, Aga Khan University, Pakistan, Stuart Gillespie (IFPRI), Lawrence Haddad, Institute of Development Studies, UK, Venkatesh Mannar, The Micro nutrient Initiative, Canada, Susan P Walker, The University of West Indies and Professor Caroline Fall of MRC Life Sources Unit at Southampton, UK to get their collective input on how to address this complex, country specific, region specific problem and to find out as to what large scale interventions have worked to optimize the nutrition of the pregnant “would be mother” and growing child. Any intervention that is cost-effective and reduces the health care burden of this preventable, malnutrition related problem would be welcome. If the remedies and recommendations come from the collective wisdom of a world body, it would be easier to convince the policymakers and stakeholders the value of deployment of such interventions and remedial measures.

According to nutritionists, fortified foods are indeed beneficial and fill the gaps in nutrition intake. However, fortified foods with recommended dietary allowance (RDA), can be introduced only, by the Governments, or the food industries. The need for fortification arises from deficiencies of vital nutrients such as ascorbic acid, calcium, iron, folate, vitamin A etc. On the other hand, stakeholders can think “out of the box” and develop novel ways of delivering the needed nutrients for the select groups of the society. Prof. Gundu Rao had developed such a proposal few years ago to the US/AID, which was a-tri-sector collaboration, between the University of Minnesota, CFTRI and Madras Diabetes Research Foundation. In brief, the proposal aimed at developing a ready-to-use packet of nutrients, as a daily supplement for

pregnant women. A randomized double blind trial has demonstrated the optimal dosage of multivitamin supplements, to reduce adverse pregnancy outcomes among HIV-infected women in Tanzania (112). Therefore, we feel confident that we can also develop similar easy-to-use, and ready-to-use supplements, that are acceptable and affordable for pregnant women in India.

In conclusion, the incidence of low birth weight (LBW) and small-for-gestational age (SGA) children is quite high in developing and resource poor countries. Several studies done in India and elsewhere, have demonstrated that these under nourished children develop cardio-metabolic disorders such as hypertension, central abdominal obesity, metabolic syndrome, type-2 diabetes and heart disease. In India alone, more than 70, 000 children are born every day. If 30% of these children are LBW/SGA, we are adding a large number of children to the society, who are predisposed to develop CMDs. According to publish reports as well as series of articles published in the Lancet, this condition can be remedied with appropriate interventions. Collective wisdom of Maternal and Child Nutrition Group suggests, that the solution to malnutrition lies on a collective effort, in which all stakeholders-governments, academia, civil society, UN system organizations, foundations, development banks and business–carry out specific roles in ensuring that interventions are delivered equitably and at scale. From our past experience we may or may not be able to apply these suggestions in India. However, interested like-minded groups can work together and develop a working model to address these issues and initiate action plans immediately.

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