Nutrition Publication

NNIW81 - Low-Birthweight Baby: Born Too Soon or Too Small

Editor(s): N. Embleton, J. Katz, E. Ziegler. 81

The 81st Nestlé Nutrition Institute Workshop brought together world class scientists in the area of neonatal care, epidemiology and nutrition management of low birth weight infants. Throughout the three-day workshop, participants heard from leading experts on the latest scientific evidence on catch up and growth acceleration, the short and long term consequences of Low Birth Weight Babies (LBWB) and the importance of different nutrition approaches in the management of LBWB.

Related Articles

Catch-Up Growth and Metabolic and Cognitive Outcomes in Adolescents Born Preterm

Author(s): N. Embleton, T. Skeath

The worldwide rate of premature birth is increasing. Survival has also improved, even for very preterm infants, meaning greater numbers of preterm infants surviving into later life. This has led to greater attention being focused on long-term outcomes. Recent interest in the Developmental Origins of Health and Disease has highlighted the importance of early life growth and nutritional exposures for chronic diseases such as cardiovascular disease, osteoporosis and type 2 diabetes. There is evidence linking preterm birth and poor growth in utero with worse long-term cognitive outcome, but also evidence to link more rapid growth in certain epochs of early life with adverse metabolic outcomes. The current data suggest that a diverse range of metabolic outcomes are affected by preterm birth, and that adult survivors may be more likely to develop certain chronic diseases. There are data to show that catch-up growth during the neonatal period and in infancy may affect these later outcomes, but studies are inconsistent in their findings. In addition, it is clear that lifestyle factors during childhood and adolescence have a major impact on metabolic disease that may be greater in magnitude to the effects of early growth and nutritional exposures.

Catch-Up Growth Basic Mechanisms

Author(s): I. Griffin

The neuroendocrine model of catch-up growth has been well studied in a number of animal models. During nutritional inadequacy, which invariably precedes catch-up growth, growth hormone (GH) levels increase under the influence of the oxygenic ‘hunger signal’ ghrelin. This increase in GH would usually be accompanied by an increase in IGF-1. However, malnutrition also induces the nutritionally responsive proteins sirtuin 1 (SIRT1) and fibroblast growth factor 21 (FGF21) that block GH signal transduction in the liver by blocking the JAK/STAT pathway, limiting IGF-1 production. The result is that GH’s action is shifted from hepatic effects to effects in other tissues (for example muscle and adipose) and shifted away from IGF-1-mediated effects and towards GH-mediated effects. Once nutrients become more available, SIRT1 and FGF21 levels, and hepatic GH sensitivity return to normal, and production of IGF-1 resumes. This shifts GH signaling away from GHmediated effects, and towards IGF-1-mediated effects both in the liver and in other tissues. It presumably leads to greatly increased IGF-1 signaling that would have been expected without the prior episode of nutritional inadequacy. Although much work remains to be done, it does appear that ghrelin is increased in in utero and postnatal malnutrition, that elevations in ghrelin may be prolonged after malnutrition resolves, and that higher ghrelin levels are associated with increased rates of catch-up growth. Prolonged increases in circulating ghrelin and GH, combined with a rapid return in hepatic GH sensitivity would provide an elegant mechanism to drive catch-up growth after periods of nutritional insufficiency.

Feeding the Larger Low-Birthweight Infant in a Resource-Poor Environment

Author(s): G. Kirsten

The high low birthweight prevalence in resource-poor countries (16.5%) places a burden on overstretched resources. Labor ward must have written guidelines to triage these infants for optimal nutritional support to the special care nursery (SCN; 1,500–1,800 g and <34 weeks) and postnatal ward (PW; >1,800 g and ≥ 34 weeks). Separation of mother and infant should be prevented. Initiating breastfeeding and kangaroo mother care (KMC) in labor ward by skilled nurses in the latter group is a priority and continues in the PW. SCN infants receive an intravenous 10% glucose-electrolyte solution and, if stable, commence with expressed colostrum and breast milk (EBM) feeding and intermittent KMC which progresses to continuous KMC and breastfeeding. Enteral feeding is advanced more slowly in unstable infants. Parenteral nutrition is only administered to infants with bowel obstruction or feeding intolerance. EBM of HIV+ mothers in the SCN is pasteurized. The decision to discharge a mother-infant dyad should be individualized. Infants in the SCN are discharged at 34 weeks, a weight of 1,600–1,800 g and are gaining adequate weight. Discharge from the PW usually takes place after 48 h, often before the infant has regained his birthweight but breastfeeding must be established. Multivitamin- and iron-containing syrup is continued for at least 12 months. The clinics in the community must provide postdischarge nutritional support. 

Global Incidence of Preterm Birth

Author(s): J. Tielsch

Estimating the incidence of preterm birth depends on accurate assessment of gestational age and pregnancy outcomes. In many countries, such data are not routinely collected, making global estimates difficult. A recent systematic approach to this problem has estimated a worldwide incidence of 11.1 per 100 live births in 2010. Significant variation in rates by country and region of the world was noted, but this variation is smaller than observed for a number of other important reproductive outcomes. Rates range from approximately 5% in some northern European countries to over 15% in some countries in sub-Saharan Africa and Asia. Time trends suggest that preterm birth incidence is increasing, but much of this change may reflect changes in medically induced early delivery practices as improvements in survival of preterm infants has improved. Whether there have been major changes in spontaneous preterm birth is unknown. New approaches to classifying etiologic heterogeneity have been proposed and offer the promise of developing specific interventions to address the range of underlying causes of this important healthproblem.

Global Prevalence of Small for Gestational Age Births

Author(s): R. Black

Fetal growth restriction is found both in babies who are preterm or full-term, and in either case has important adverse effects on subsequent survival, health, growth and development. Fetal growth restriction is usually assessed by comparing the weight of the newborn with the expected weight for the child’s gestational age using less than the 10th centile of a reference population for fetal growth as the threshold for being called small for gestational age (SGA). We estimate that in 2010 32.4 million babies were born SGA in low- and middle-income countries, constituting 27% of all live births. The estimated prevalence of SGA is highest in South Asia and in Sahelian countries of Africa. India has the world’s largest number of SGA births, 12.8 million in 2010, due to the large number of births and the high proportion, 46.9%, of births that are SGA. The prevalence of SGA births is approximately double the prevalence of low-birthweight births (using the common indicator of <2,500 g birthweight) globally and in the world’s regions. Thus, given the adverse effects of being born SGA, even weighing 2,500 g or more, it is important that maternal, neonatal and child health programs seek and use information on gestational age as well as birthweight to appropriately assess the newborn’s risks and direct care.

Human Milk Fortification in India

Author(s): N. Kler, A. Thakur, M. Modi, A. Kaur, P.Garg, A. Soni, S. Saluja

Human milk fortification in preterm babies has become a standard of care in developed countries. Use of human milk fortifier (HMF) in very-low-birthweight infants is not a routine practice in India. There are concerns about high osmolality, feed intolerance, necrotizing enterocolitis, risk of contamination and added cost associated with use of HMF. There are limited data from India which address the issue of safety and short-term benefits of human milk fortification. This chapter highlights the issues related to human milk fortification in our country.

Human Milk Fortification

Author(s): K. Simmer

Human milk is the feed of choice for preterm infants. However, human milk does not provide enough nutrition, especially protein, for preterm infants to achieve target growth rates similar to those in utero (15–20 g/kg per day). Fortifiers for human milk, manufactured from bovine milk, are commercially available and routinely used for patients born <32 weeks’ gestation prior to discharge home. Recent recommended dietary intakes (RDI) have been revised. Up to 4.2 g of protein and 135 kcal/kg per day is recommended for infants born very preterm. Additional supplements are needed to current commercial fortifiers to achieve these RDI and reduce the incidence of ex-uterine growth failure. A human milk fortifier that is manufactured from donor human milk is available in some developed countries and may confer some clinical benefits, including a reduction in necrotizing enterocolitis. Fortification can be added in a standardized protocol as per manufacturers’ instructions. Human milk composition can be analyzed and fortification individualized to take into account the large variation from mother to mother. Alternatively, fortification can be increased in a stepwise manner based on assumed compositionwhile monitoring blood urea levels for safety. The current aim is to prevent preterm infants dropping percentiles and falling below the 10th percentile at 36 weeks’ corrected gestationalage or discharge home. More data are required on how best to fortify human milk for preterm infants to achieve optimal growth, development and health outcomes in the long term. There is an urgent need for well-designed and informed randomized clinical trials in this vulnerable preterm population.

Mortality Risk among Term and Preterm Small for Gestational Age

Author(s): J. Katz, A. Lee, N. Kozuki, R. Black

Globally, 15% of infants are low birthweight (LBW; <2,500 g) each year. Most LBW infants are either preterm (<37 weeks gestation) and/or growth restricted in utero. These etiologies of LBW have different prevalence, risk factors, health and survival consequences, and are attenuated by different interventions. Birthweight has generally been easier to measure than gestational age in low-resource settings. This is now changing rapidly with access to antenatal care and ultrasound and allows providers, researchers and public health practitioners the opportunity to identify infants born too soon or too small, and to better target interventions to reduce mortality and morbidity associated with these conditions. Understanding the mortality patterns and burden of preterm or small for gestational age (SGA) is important for designing programs to prevent these outcomes and improve survival of these infants. We present here estimates of the increased mortality risk, timing of mortality, and attributable mortality burden associated with these conditions. Such dataprovide estimates of the potential for proven maternal interventions to reduce SGA burden and its associated mortality, as well as identify infants who would most benefit from clinical and public health interventions to improve their survival and health

Nutrient Needs for Catch-Up Growth in Low-Birthweight Infants

Author(s): E. Ziegler

Growth restriction among low-birthweight (LBW) infants occurs prenatally as well as postnatally. Regardless of when and how the growth restriction occurs, growth-restricted infants have the potential for catch-up growth. Catch-up growth has decidedly beneficial effects on later cognition. It also may have adverse effects on cardiovascular and metabolic health. Although the benefits for later cognition are well documented in a number of studies, growth-restricted LBW infants often do not experience catch-up growth and therefore do not enjoy its benefits. One reason is that for catch-up growth to occur, extraordinarily high protein intakes are required. Nutrient intakes have been estimated with the use of the factorial method based on the assumption that catch-up growth comprises essentially a restoration of lean body mass, with restoration of fat mass optional. The basic (no catch-up) nutritional needs of growth-restricted LBW infants are altered to a modest degree, with energy needs increased and protein needs decreased. With catch-up, however, protein needs are increased sharply. Since energy needs are only modestly increased, the protein/energy ratio of requirements is appreciably increased. The high protein needs are difficult to meet with the usual feedings for LBW infants unless special measures are taken to increase protein intakes and to increase the protein/energy ratio. Without the necessary protein intake, catch-up growth is not possible or will be delayed, which may compromise the realization of the long-term benefits on cognition

Nutritional and Reproductive Risk Factors for Small for Gestational Age and Preterm Births

Author(s): N. Kozuki, A. Lee, R. Black, J. Katz

Approximately 32.4 million small for gestational age (SGA) babies and 13.7 million preterm babies are born annually in low- and middle-income countries (LMICs), of whom 2.8 million are both SGA and preterm. These newborns who are born too small and/or too soon not only experience heightened risk of neonatal and infant mortality, but also of long-term morbidities, like adulthood chronic disease. In order to reduce these burdens worldwide, it is critical to identify and understand the epidemiology of the risk factors that contribute to SGA and preterm births. As part of the Child Health Epidemiology Reference Group, we explored nutritional and reproductive health-related maternal risk factors associated with SGA and preterm outcomes in LMICs, including short maternal stature, young/advanced maternal age, low/high parity, and short birth interval. In this chapter, we highlight our findings and relevant existing literature, and also summarize literature on how low/high BMI and low weight gain during pregnancy, respectively, are associated with SGA and/or preterm outcomes.

Prevention of Intrauterine Growth Restriction and Preterm Birth

Author(s): P. Ashorn, H. Vanhala, O. Pakarinen, U. Ashorn, A. De Costa

Intrauterine growth restriction and preterm birth (PTB) account for a large share of global child mortality, morbidity and developmental loss. Of the numerous risk factors for these conditions, maternal infections have been most consistently identified. Our aim was to study if presumptive antibiotic treatment of pregnant women before any signs of the onset of labor would promote fetal growth and reduce the incidence of PTB or low birthweight (LBW). In a systematic literature search, we identified 14 clinical trials of sufficient quality. Eight trials concluded that there was a positive effect on one or both of the conditions, and others found no such association. The trials reporting an effect were typically conducted in Sub-Saharan Africa (6 trials) and with broadest spectrum antibiotics, whereas data from India (2) suggested no intervention effect and trials in the US (5) or Europe (1) yielded both positive and negative findings. We conclude that appropriately chosen presumptive antimicrobial treatment of pregnant women, targeting infections in the reproductive tract but also other maternal infections such as malaria, other parasitic diseases, skin infections, and periodontitis, can in selected contexts promote fetal growth and reduce the incidence of PTB and LBW.

Probiotic Supplementation for Preterm Neonates – What Lies Ahead

Author(s): S. Patole

Systematic reviews of randomized controlled trials indicate that probiotic supplementation significantly reduces the risk of necrotizing enterocolitis (NEC) without adverse effects in preterm very-low-birthweight neonates. A change in practice in favor of probiotic supplementation is justified considering the health burden of NEC in this population. The reduction in the risk of NEC seems to occur even when the baseline incidence of the illness is as low as 5%. Facilitation of feed tolerance is a significant benefit of probiotics considering that optimizing enteral nutrition is a priority in extremely preterm neonates, including those with intrauterine growth restriction, who are at a higher risk for feed intolerance and NEC. The increasing number of reports on routine use of probiotics indicates that difficulty in accessing clinically proven and safe probiotic products is not a significant barrier towards a change in practice. Strategies to address important gaps in knowledge and the impact of routine use of probiotic supplementation are reviewed to prepare for what lies ahead in this field

Role of Specific Nutrients in Low-Birthweight Infants

Author(s): J. Bhatia

Low birthweight (LBW) is defined by the World Health Organization (WHO) as body weight less than 2,500 g at birth based on epidemiological observations that infants with a birthweight less than 2,500 g are 20 times more likely to die than ‘heavier’ babies [1] . Moreover, according to the WHO, a birthweight below 2,500 g contributes to poor health outcomes. Worldwide, the incidence of LBW is estimated to be 15.5% with a range from 7 to 18.6% based on more developed, less developed and least developed countries. In addition to discussing causes and consequences of LBW, this chapter will discuss specific nutrients that need particular attention in this cohort of infants: calcium, phosphorus, magnesium, vitamin D, iron, copper, zinc and issues related to feeding these infants including the use of human milk. Since LBW is an important public health indicator of long-term maternal malnutrition, maternal health, poor prenatal care and, in addition, poses significant challenges in feeding and growth, this large population, globally, deserves particular attention

Should We Promote Catch-Up Growth or Growth Acceleration in Low-Birthweight Infants

Author(s): A. Singhal

The idea that catch-up growth or growth acceleration has adverse effects on long-term health has generated much debate. This pattern of growth is most commonly seen after birth in infants of low birthweight; a global problem affecting over 20 million newborns a year. Faster postnatal growth may have short-term benefits but increases the long-term risk of aging, obesity and metabolic disease. Consequently, the optimal pattern of postnatal growth is unclear and is likely to differ in different populations. In infants born prematurely, faster postnatal growth improves long-term cognitive function but is associated with later risk factors for cardiovascular disease. So, on balance, the current policy is to promote faster growth by increasing nutrient intake (e.g. using higher-nutrient preterm (formulas). Whether the same policy should apply to larger preterm infants is not known. Similarly, in infants from impoverished environments, the short-term benefits of faster postnatal growth may outweigh long-term disadvantages. However, whether similar considerations apply to infants from countries in transition is uncertain. For term infants from developed countries, promoting catch-up growth by nutritional supplementation has few advantages for short- or long-term health. Overall therefore, a ‘one size fits all’ solution for the optimal pattern of postnatal growth is unlikely.

Stunting Persists despite Optimal Feeding Are Toilets Part of the Solution

Author(s): A. Prendergast, J. Humphrey

Children in developing countries have an average length-for-age that is already below the World Health Organization standard at birth and show a further decline in linear growth over the first 24 months of life; however, complementary feeding interventions have only a modest impact on growth. Children living in conditions of poor sanitation and hygiene are frequently exposed to pathogenic microbes through feco-oral transmission. Acute diarrhea represents only the tip of the ‘enteric disease iceberg’, with a substantial underlying burden of chronic, subclinical enteropathy. Environmental enteric dysfunction (EED) is characterized by disturbance in small intestinal structure and impaired gut barrier function, enabling microbial translocation and chronic systemic inflammation, which may impair growth. Gut damage appears to arise early in infancy and markers of intestinal inflammation, intestinal permeability and systemic immune activation are inversely associated with linear growth. Reducing feco-oral microbial transmission by improving water, sanitation and hygiene (WASH) may theoretically prevent or ameliorate EED and improve linear growth; ongoing trials are exploring this hypothesis. Given the complex interplay of factorsleading to stunting, multisectoral interventions are likely required. Improving WASH in addition to infant feeding may be one approach to improve the growth and developmental potential of infants in developing countries