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BACKGROUND: Low birth weight (LBW) is associated with neonatal mortality and sequelae of lifelong health problems; prioritizing the most promising antenatal interventions may guide resource allocation and improve health outcomes. OBJECTIVE: We sought to identify the most promising interventions that are not yet included in the policy recommendations of the World Health Organization (WHO) but could complement antenatal care and reduce the prevalence of LBW and related adverse birth outcomes in low- and middle-income settings. METHODS: We utilized an adapted Child Health and Nutrition Research Initiative (CHNRI) prioritization method. RESULTS: In addition to procedures already recommended by WHO for the prevention of LBW, we identified six promising antenatal interventions that are not currently recommended by WHO with an indication for LBW prevention, namely: (1) provision of multiple micronutrients; (2) low-dose aspirin; (3) high-dose calcium; (4) prophylactic cervical cerclage; (5) psychosocial support for smoking cessation; and (6) other psychosocial support for targeted populations and settings. We also identified seven interventions for further implementation research and six interventions for efficacy research. CONCLUSION: These promising interventions, coupled with increasing coverage of currently recommended antenatal care, could accelerate progress toward the global target of a 30% reduction in the number of LBW infants born in 2025 compared to 2006-10.

Hypothyroidism is the commonest endocrine disorder of pregnancy, with known adverse feto-maternal outcomes. There is limited data on population-based prevalence, risk factors and outcomes associated with treatment of hypothyroidism in early pregnancy. We conducted analysis on data from an urban and peri-urban low to mid socioeconomic population-based cohort of pregnant women in North Delhi, India to ascertain the burden, risk factors and impact of treatment, on adverse pregnancy outcomes- low birth weight, prematurity, small for gestational age and stillbirth. This is an observational study embedded within the intervention group of the Women and Infants Integrated Interventions for Growth Study, an individually randomized factorial design trial. Thyroid stimulating hormone was tested in 2317 women in early (9–13 weeks) pregnancy, and thyroxin replacement started hypothyroid (TSH ≥2.5mIU/mL). Univariable and multivariable generalized linear model with binomial family and log link were performed to ascertain risk factors associated with hypothyroidism and association between hypothyroidism and adverse pregnancy outcomes. Of 2317 women, 29.2% (95% CI: 27.4 to 31.1) had hypothyroidism and were started on thyroxin replacement with close monitoring. Overweight or obesity was associated with increased risk (adjusted RR 1.29, 95% CI 1.10 to 1.51), while higher hemoglobin concentration was associated with decreased risk (adjusted RR 0.93, 95% CI 0.88 to 0.98 for each g/dL) for hypothyroidism. Hypothyroid women received appropriate treatment with no increase in adverse pregnancy outcomes. Almost a third of women from low to mid socio-economic population had hypothyroidism in early pregnancy, more so if anemic and overweight or obese. With early screening and adequate replacement, adverse pregnancy outcomes may be avoided. These findings highlight the need in early pregnancy for universal TSH screening and adequate treatment of hypothyroidism; as well as for attempts to reduce pre and peri-conception overweight, obesity and anemia. Clinical trial registration: Clinical trial registration of Women and Infants Integrated Interventions for Growth Study Clinical Trial Registry–India, #CTRI/2017/06/008908; Registered on: 23/06/2017, (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies). [ABSTRACT FROM AUTHOR]

Aim: To learn how to achieve high‐quality, effective coverage of Kangaroo Mother Care (KMC), defined as 8 hours or more of skin‐to‐skin contact per day and exclusive breastfeeding in district Sonipat in North India, and to develop and evaluate an implementation model. Methods: We conducted implementation research using a mixed‐methods approach, including formative research, followed by repeated, rapid cycles of implementation, evaluation and refinement until a model with the potential for high and effective coverage was reached. Evaluation of this model was conducted over a 12‐month period. Results: Formative research findings informed the final implementation model. Programme learning was critical to achieve high coverage. The model included improving the identification of small babies, creating KMC wards, modification in hospitalisation criteria, private sector engagement and in‐built programme learning to refine implementation progress. KMC was initiated in 87% of eligible babies. At discharge, 85% received skin‐to‐skin contact care, 60% effective KMC and 80% were exclusively breastfed. At home, 7‐day post discharge, 81% received skin‐to‐skin care and 79% were exclusively breastfed in the previous 24 hours. Conclusion: Achieving high KMC coverage is feasible in the study setting using a model responsive to the local context and led by the Government. [ABSTRACT FROM AUTHOR]

This individually randomized trial was conducted to estimate the effect of promoting community‐initiated kangaroo mother care (ciKMC) in low birthweight (LBW) infants on infant breastfeeding performance. It was designed as a substudy within a larger primary trial on ciKMC and infant survival. Five hundred fifty stable LBW mother‐infant dyads (1500−2250 g) who provided consent, were consecutively enroled for breastfeeding performance assessment. The ciKMC intervention included promotion and support of continuous skin‐to‐skin contact and exclusive breastfeeding (EBF) through home visits during the neonatal period. The primary outcome was effective breastfeeding performance indicated by an infant breastfeeding assessment tool score of ≥10 after the end of the neonatal period. As secondary outcomes, we reported maternal satisfaction related to infant breastfeeding, and EBF after the end of the neonatal period. We completed outcome assessments in 96% of participants. In the ciKMC arm, 92% of the infants showed effective breastfeeding performance against 81% in the control arm [adjusted prevalence ratio (aPR): 1.24, 95% confidence interval (CI): 1.16−1.32]. In the ciKMC arm, 65% of the mothers reported to be very satisfied with their infants' breastfeeding against 51% in the control arm (aPR: 1.22, 95% CI: 1.05−1.41). The proportion of infants practicing EBF was 89% in the ciKMC arm against 45% in the control arm (aPR: 1.62, 95% CI: 1.45−1.81). Our study findings suggest that promotion of ciKMC can improve effective breastfeeding, EBF and maternal satisfaction related to breastfeeding in LBW infants. Key messages: In low birthweight (LBW) infants, breastfeeding can be challenging with low prevalence of exclusive breastfeeding (EBF).Our trial in North India among 550 LBW infants showed that promotion of community‐initiated Kangaroo mother care (ciKMC) can substantially improve infant breastfeeding performance.ciKMC promotion substantially improved EBF prevalence at the end of the neonatal period, number of breastfeeds per day and duration of each breastfeed. It also enhanced mother's satisfaction with their infant's breastfeeding performance. [ABSTRACT FROM AUTHOR]

Despite the high prevalence of inadequate gestational weight gain (GWG) and adverse pregnancy outcomes, very few studies have addressed the association between GWG and pregnancy outcomes in South Asia. Our objectives were to estimate the prevalence of GWG during the second and third trimesters within, below and above the Institute of Medicine (IOM) guidelines, and to estimate the effect of the rate and adequacy of GWG on gestational age at the time of delivery, weight, length, length‐for‐age z‐score (LAZ), weight‐for‐length z‐score (WLZ) and adverse pregnancy outcomes, namely prematurity, small‐for‐gestational age (SGA), low birth weight (LBW), stunting and wasting at birth. We analysed data from the intervention group of the Women and Infants Integrated Interventions for Growth Study (WINGS), which is an ongoing individually randomized factorial design study. Of the 1332 women analysed, 40.2% [95% confidence interval (CI) 37.5 to 42.8] had GWG below the IOM guidelines. For every 100‐g/week increase in GWG, birth weight increased by 61 g, birth length by 0.16 cm, LAZ score by 0.08 SD, WLZ score by 0.14 SD, and gestational age at birth by 0.48 days. Women with GWG below the IOM guidelines had a higher relative risk of adverse pregnancy outcomes (44% for LBW, 27% for SGA, 32% for stunting and 42% for wasting at birth) than women who had GWG within the IOM guidelines, except for prematurity. The association between GWG and LAZ scores at birth was modified by early pregnancy body mass index (BMI). GWG is a strong predictor of newborn anthropometric outcomes and duration of gestation but not prematurity. [ABSTRACT FROM AUTHOR]

Background: Kangaroo mother care (KMC) can substantially enhance overall survival of low birthweight babies. In a large randomized controlled trial, we recently showed that supporting mothers to provide community initiated KMC (ciKMC) can reduce mortality among infants up to 180 days of life by 25% (hazard ratio (HR) 0.75). With the current analysis, we aimed to explore if ciKMC promotion leads to increased inequity in survival. Methods: In the trial we randomized 8402 low birthweight babies to a ciKMC (4480 babies) and a control (3922 babies) arm, between 2015 and 2018 in Haryana, India. We estimated the difference in concentration indices, which measure inequality, between babies in the ciKMC and control arms for survival until 180 days of life. Further, we compared the effect of ciKMC promotion across subgroups defined by socioeconomic status, caste, maternal literacy, infant's sex, and religion. Results: Our intervention did not increase survival inequity, as the concentration index in the ciKMC arm of the trial was 0.05 (95% CI -0.07 to 0.17) lower than in the control arm. Survival impact was higher among those belonging to the lower two wealth quintiles, those born to illiterate mothers and those belonging to religions other than Hindu. Conclusions: We found that ciKMC promotion did not increase inequity in survival associated with wealth. The beneficial impact of ciKMC tended to be larger among vulnerable groups. Supporting mothers to provide KMC at home to low birthweight babies will not increase and could indeed reduce inequities in infant survival. Trial registration: ClinicalTrials.gov, NCT02653534. Registered January 12, 2016—Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Children born with low birth weight (LBW) tend to have lower neurodevelopmental scores compared to term normal birth weight children. It is important to determine factors that influence neurodevelopment in these low birth weight children especially in the first 2–3 years of life that represents a period of substantial brain development. Methods: This secondary data analysis was conducted using data from LBW infants enrolled soon after birth in an individually randomized controlled trial (RCT) and followed up till end of 1st year. Neurodevelopmental assessment was done at 12 months of corrected age by trained psychologists using Bayley Scales of Infant and Toddler Development 3rd edition (Bayley-III). Factors influencing cognitive, motor and language scores were determined using multivariable linear regression model. Results: Linear growth (i.e., length for age z score, LAZ) [cognitive: Standardized ẞ-coefficient = 2.19, 95% CI; 1.29, 3.10; motor: 2.41, 95% CI; 1.59, 3.23; language: 1.37, 95% CI; 0.70, 2.04], stimulation at home [cognitive: 0.21, 95% CI; 0.15, 0.27; motor: 0.12, 95% CI; 0.07, 0.17; language: 0.21, 95% CI; 0.16, 0.25] and number of diarrhoeal episodes [cognitive: -2.87, 95% CI; -4.34, -1.39; motor: -2.62, 95% CI; -3.93, -1.29; language: -2.25, 95% CI; -3.32, -1.17] influenced the composite scores in all three domains i.e., cognitive, language and motor. While increase in LAZ score and stimulation led to increase in composite scores; an increase in number of diarrhoeal episodes was associated with decrease in scores. Weight for height z scores (WHZ) were associated with motor and language but not with cognitive scores. Additionally, a negative association of birth order with cognitive and language scores was noted. Conclusions: The findings indicate the possible importance of promoting nutrition and preventing diarrhoea as well as ensuring optimal stimulation and nurturance at home for enhancing child development in LBW infants. [ABSTRACT FROM AUTHOR]

Background: The period from conception to two years of life denotes a critical window of opportunity for promoting optimal growth and development of children. Poor nutrition and health in women of reproductive age and during pregnancy can negatively impact birth outcomes and subsequent infant survival, health and growth. Studies to improve birth outcomes and to achieve optimal growth and development in young children have usually tested the effect of standalone interventions in pregnancy and/or the postnatal period. It is not clearly known whether evidence-based interventions in the different domains such as health, nutrition, water sanitation and hygiene (WASH) and psychosocial care, when delivered together have a synergistic effect. Further, the effect of delivery of an intervention package in the pre and peri-conception period is not fully understood. This study was conceived with an aim to understand the impact of an integrated intervention package, delivered across the pre and peri-conception period, through pregnancy and till 24 months of child age on birth outcomes, growth and development in children.Methods: An individually randomized controlled trial with factorial design is being conducted in urban and peri-urban low- to mid-socioeconomic neighbourhoods in South Delhi, India. 13,500 married women aged 18 to 30 years will be enrolled and randomized to receive either the pre and peri-conception intervention package or routine care (first randomization). Interventions will be delivered until women are confirmed to be pregnant or complete 18 months of follow up. Once pregnancy is confirmed, women are randomized again (second randomization) to receive either the intervention package for pregnancy and postnatal period or to routine care. Newborns will be followed up till 24 months of age. The interventions are delivered through different study teams. Outcome data are collected by an independent outcome ascertainment team.Discussion: This study will demonstrate the improvement that can be achieved when key factors known to limit child growth and development are addressed together, throughout the continuum from pre and peri-conception until early childhood. The findings will increase our scientific understanding and provide guidance to nutrition programs in low- and middle-income settings.Trial Registration: Clinical Trial Registry - India #CTRI/2017/06/008908; Registered 23 June 2017, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies. [ABSTRACT FROM AUTHOR]

Low-birthweight (LBW) infants are at an increased risk of stunting and poor linear growth. The risk might be additionally higher in these infants when born to short mothers. However, this hypothesis has been less explored. The objective of this secondary data analysis was to determine the risk of linear growth faltering and difference in linear growth velocity in LBW infants born to short mothers (<150 cm) compared to those born to mothers with height ≥150 cm during the first year of life. This analysis uses data from a community-based randomized controlled trial of 2,052 hospital-born term infants with birthweight ≤2,500g from urban low-middle socioeconomic neighbourhoods in Delhi, India. Data on maternal height and infant birth length were available from 1,858 (90.5%) of the infants. Infant anthropometry outcomes were measured at birth, 3, 6, 9, and 12 months of age. We found that infants born to short mothers had around twofold higher odds of stunting and lower attained length-for-age Z scores compared to infants of mothers with height ≥150 cm, at all ages of assessment. Linear growth velocity was significantly lower in infants of short mothers particularly in the first 6 months of life. We conclude that LBW infants born to short mothers are at a higher risk of stunting and have slower postnatal growth velocity resulting in lower attained length-for-age Z scores in infancy. Evidence-based strategies need to be tested to optimize growth velocity in LBW infants especially those born to short mothers. [ABSTRACT FROM AUTHOR]

Background: Low birth weight (LBW) infants constitute a vulnerable subset of infants with impaired immunity in early life. In India, there is scarcity of studies that focus on immunization practices in such infants. This analysis aimed to examine immunization practices in LBW infants with the intention to identify areas requiring intervention.Methods: Data on immunization status of LBW infants enrolled in an individually randomized, double-masked, placebo-controlled trial of neonatal vitamin A supplementation were analysed. Study outcomes were full immunization by one year of age and delayed vaccination with DPT1 and DPT3. Multivariable logistic regression was performed to identify factors associated with the outcome(s).Findings: Out of 10 644 LBW infants enrolled in trial, immunization data were available for 10 517 (98.8%). Less than one-third (29.7%) were fully immunized by one year of age. Lowest wealth quintile (adjusted odds ratio (AOR) 0.39, 95% confidence interval (CI) 0.32-0.47), Muslim religion (AOR 0.41, 95% CI 0.35-0.48) and age of mother <20 years (AOR 0.62, 95% CI 0.52-0.73) were associated with decreased odds of full immunization. Proportion of infants with delayed vaccination for DPT1 and DPT3 were 52% and 81% respectively. Lowest wealth quintiles (AOR 1.51, 95% CI 1.25-1.82), Muslim religion (AOR 1.41, 95% CI 1.21-1.65), mother aged <20 years (AOR 1.31, 95% CI 1.11-1.53) and birth weight <2000 g (AOR 1.20, 95% CI 1.03-1.40) were associated with higher odds of delayed vaccination for DPT-1. Maternal education (≥12 years of schooling) was associated with high odds of full immunization (AOR 2.39, 95% CI 1.97-2.91) and low odds of delayed vaccination for both DPT-1 (AOR 0.59, 95% CI 0.49-0.73) and DPT-3 (AOR 0.57, 95% CI 0.43-0.76).Conclusion: In this population, LBW infants are at a risk of delayed and incomplete immunization and therefore need attention. The risks are even higher in identified subgroups that should specifically be targeted. [ABSTRACT FROM AUTHOR]

Background: Around 70% neonatal deaths occur in low birth weight (LBW) babies. Globally, 15% of babies are born with LBW. Kangaroo Mother Care (KMC) appears to be an effective way to reduce mortality and morbidity among LBW babies. KMC comprises of early and continuous skin-to-skin contact between mother and baby as well as exclusive breastfeeding. Evidence derived from hospital-based studies shows that KMC results in a 40% relative reduction in mortality, a 58% relative reduction in the risk of nosocomial infections or sepsis, shorter hospital stay, and a lower risk of lower respiratory tract infections in babies with birth weight <2000 g. There has been considerable interest in KMC initiated outside health facilities for LBW babies born at home or discharged early. Currently, there is insufficient evidence to support initiation of KMC in the community (cKMC). Formative research in our study setting, where 24% of babies are born with LBW, demonstrated that KMC is feasible and acceptable when initiated at home for LBW babies. The aim of this trial is to determine the impact of cKMC on the survival of these babies.Methods/design: This randomized controlled trial is being undertaken in the Palwal and Faridabad districts in the State of Haryana, India. Neonates weighing 1500-2250 g identified within 3 days of birth and their mothers are being enrolled. Other inclusion criteria are that the family is likely to be available in the study area over the next 6 months, that KMC was not initiated in the delivery facility, and that the infant does not have an illness requiring hospitalization. Eligible neonates are randomized into intervention and control groups. The intervention is delivered through home visits during the first month of life by study workers with a background and education similar to that of workers in the government health system. An independent study team collects mortality and morbidity data as well as anthropometric measurements during periodic home visits. The primary outcomes of the study are postenrollment neonatal mortality and mortality between enrollment and 6 months of age. The secondary outcomes are breastfeeding practices; prevalence of illnesses and care-seeking practices for the same; hospitalizations; weight and length gain; and, in a subsample, neurodevelopment.Discussion: This efficacy trial will answer the question whether the benefits of KMC observed in hospital settings can also be observed when KMC is started in the community. The formative research used for intervention development suggests that the necessary high level of KMC adoption can be reached in the community, addressing a problem that seriously constrained conclusions in the only other trial in which researchers examined the benefits of cKMC.Trial Registration: ClinicalTrials.gov identifier: NCT02653534 . Registered on 26 December 2015 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Burden and risk factors for wasting in the first 6 months of life among Indian children are not well documented. We used data from India's National Family Health Survey 4 to estimate the prevalence of severe wasting (weight for length < ‐3 SD) among 18,898 infants under 6 months of age. We also examined the association of severe wasting with household, maternal, and child‐related factors using multivariable logistic regression analysis. Prevalence of severe wasting among infants less than 6 months of age was 14.8%, ranging from 3.5 to 21% across states. Low birth weight (<2,500 g; adjusted odds ratio [AOR] 1.40, 95% CI [1.19, 1.65]), nonutilization of supplementary nutrition by mother during lactation (AOR 1.23, 95% CI [1.05, 1.43]), and anthropometric assessment during summer (AOR 1.37, 95% CI [1.13, 1.65]) and monsoon months (AOR 1.53, 95% CI [1.20, 1.95]) were associated with higher odds of severe wasting. Infants aged 2 to 3 months (AOR 0.78, 95% CI [0.66, 0.93]) and 4 to 5 months (AOR 0.65, 95% CI [0.55, 0.73]) had lower odds of severe wasting as compared with the 0‐ to 1‐month category. This analysis reveals a high burden of severe wasting in infants less than 6 months in India. Preventive interventions must be targeted at reducing low birth weight due to fatal growth restriction and prematurity. Appropriate care practices at facilities and postdischarge with extra attention to those born small and sick can prevent further deterioration in nutritional status. [ABSTRACT FROM AUTHOR]

Background: Low and middle income countries (LMICs), including India, contribute to a major proportion of low birth weight (LBW) infants globally. These infants require special care. Kangaroo Mother Care (KMC) in hospitals is a cost effective and efficacious intervention. In institutional deliveries, the duration of facility stay is often short. In LMICs, a substantial proportion of deliveries still occur at home and access to health care services is limited. In these circumstances, a pragmatic choice may be to initiate KMC at home for LBW babies. However, evidence is lacking on benefits of community-initiated KMC (cKMC). Promoting KMC at home without an understanding of its acceptability may lead to limited success.Methods: We conducted formative research to assess the feasibility, acceptability and adoption of cKMC with the aim of designing an intervention package for a randomised controlled trial in LBW infants in Haryana, India. Qualitative methods included 40 in-depth interviews with recently delivered women and 6 focus group discussions, two each with fathers and grandfathers, grandmothers, and community health workers. A prototype intervention package to promote cKMC was developed and tested in 28 mother-infant pairs (of them, one mother had twins), using Household (HH) trials.Results: We found that most mothers in the community recognized that babies born small required special care. In spite of not being aware of the practice of KMC, respondents felt that creating awareness of KMC benefits will promote practice. They expressed concerns about doing KMC for long periods because mothers needed rest after delivery. However, the cultural practice of recently delivered women not expected to be doing household chores and availability of other family members were identified as enablers. HH trials provided an opportunity to test the intervention package and showed high acceptability for KMC. Most mothers perceived benefits such as weight gain and increased activity in the infant.Conclusions: Community-initiated KMC is acceptable by mothers and adoption rates are high. Formative research is essential for developing a strategy for delivery of an intervention.Trial Registration: Trial registration number CTRI/2015/10/006267 . Name of Registry: Clinical Trials Registry - India. URL of Registry: http://ctri.nic.in/Clinicaltrials/login.php Date of Registration: 15/10/2015. Date of enrolment of the first participant to the trial: 18/04/2015. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess effects of supplementation with 3 or more micronutrients (multiple micronutrients; MMN) compared to no MMN in human milk-fed preterm and low birth weight (LBW) infants. RESULTS: Data on a subgroup of 414 preterm or LBW infants from 2 randomized controlled trials (4 reports) were included. The certainty of evidence ranged from low to very low. For growth outcomes in the MMN compared to the non-MMN group, there was a small increase in weight- for-age (2 trials, 383 participants) and height-for-age z-scores (2 trials, 372 participants); a small decrease in wasting (2 trials, 398 participants); small increases in stunting (2 trials, 399 participants); and an increase in underweight (2 trials, 396 participants). For neurodevelopment outcomes at 78 weeks, we found small increases in Bayley Scales of Infant Development, Version III (BISD-III), scores (cognition, receptive language, expressive language, fine motor, gross motor) in the MMN compared to the non-MMN group (1 trial, 27 participants). There were no studies examining dose or timing of supplementation. CONCLUSIONS: Evidence is insufficient to determine whether enteral MMN supplementation to preterm or LBW infants who are fed mother's own milk is associated with benefit or harm. More trials are needed to generate evidence on mortality, morbidity, growth, and neurodevelopment. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess effects of enteral "low" dose (daily doses of ≤10 000 international unit) vitamin A supplementation compared with no vitamin A supplementation in human milk-fed preterm and low birth weight (LBW) infants. DATA SOURCES: Cochrane Central Register of Controlled Trials; Medline, Embase, Scopus, Web of Science, CINAHL from inception to 16 March 2021. STUDY SELECTION: Randomized trials were screened. Primary outcomes were mortality, morbidity, growth, neurodevelopment. Secondary outcomes were feed intolerance and duration of hospitalization. We also assessed the dose and timing of vitamin A supplementation. Data were extracted and pooled with fixed and random-effects models. RESULTS: Four trials including 800 very LBW <1.5 kg or <32 weeks' gestation infants were found. At latest follow-up, we found little or no effect on: mortality, sepsis, bronchopulmonary dysplasia, retinopathy of prematurity, duration of hospitalisation. However, we found a increased level of serum retinol mean difference of 4.7 µg/ml (95% CI 1.2 to 8.2, I² =0.00%, one trial, 36 participants,). Evidence ranged from very low to moderate certainty. There were no outcomes reported for length, head circumference or neurodevelopment. LIMITATIONS : Heterogeneity and small sample size in the included studies. CONCLUSIONS: Low-dose vitamin A increased serum retinol concentration among very LBW and very preterm infants but had no effect on other outcomes. More trials are needed to assess effects on clinical outcomes and to assess effects in infants 1.5 to 2.4 kg or 32 to 26 weeks' gestation. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess effects of calcium or phosphorous supplementation compared with no supplementation in human milk-fed preterm or low birth weight infants. METHODS : Data sources include Cochrane Central Register of Controlled Trials, Medline and Embase. We included Randomized controlled trials (RCTs) and non-randomized trials (quasi- randomized). RESULTS: Three studies (4 reports; 162 infants) were included. At latest follow-up (38 weeks), there was reduction in osteopenia (3 studies, 159 participants, relative risk 0.68, 95% confidence interval [CI] 0.46-0.99). At latest follow-up (6 weeks), there was no effect on weight (1 study, 40 participants, mean difference [MD] 138.50 g, 95% CI -82.16 to 359.16); length (1 study, 40 participants, MD 0.77 cm, 95% CI -0.93 to 2.47); and head circumference (1 study, 40 participants, MD 0.33 cm, 95% CI -0.30 to 0.96). At latest follow-up, there was no effect on alkaline phosphatase (55 weeks) (2 studies, 122 participants, MD -126.11 IU/L, 95% CI -298.5 to 46.27, I² = 73.4%); serum calcium (6 weeks) (1 study, 40 participants, MD 0.54 mg/dL, 95% CI -0.19 to 1.27); and serum phosphorus (6 weeks) (1 study, 40 participants, MD 0.07 mg/dL, 95% CI -0.22 to 0.36). The certainty of evidence ranged from very low to low. No studies reported on mortality and neurodevelopment outcomes. CONCLUSIONS: The evidence is insufficient to determine whether enteral supplementation with calcium or phosphorus for preterm or low birth weight infants who are fed mother's own milk or donor human milk is associated with benefit or harm. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Many preterm and low birth weight (LBW) infants have low vitamin D stores. The objective of this study was to assess effects of enteral vitamin D supplementation compared with no vitamin D supplementation in human milk fed preterm or LBW infants. METHODS: Data sources include Cochrane Central Register of Controlled Trials, Medline, and Embase from inception to March 16, 2021. The study selection included randomized trials. Data were extracted and pooled with fixed and random-effects models. RESULTS: We found 3 trials (2479 participants) that compared vitamin D to no vitamin D. At 6 months, there was increase in weight-for-age z-scores (mean difference 0.12, 95% confidence interval [CI] 0.01 to 0.22,1 trial, 1273 participants), height-for-age z-scores (mean difference 0.12, 95% CI 0.02 to 0.21,1 trial, 1258 participants); at 3 months there was decrease in vitamin D deficiency (risk ratio 0.58, 95% CI 0.49 to 0.68, I² = 58%, 2 trials, 504 participants) in vitamin D supplementation groups. However, there was little or no effect on mortality, any serious morbidity, hospitalization, head circumference, growth to 6 years and neurodevelopment. The certainty of evidence ranged from very low to moderate. Fourteen trials (1969 participants) assessed dose and reported no effect on mortality, morbidity, growth, or neurodevelopment, except on parathyroid hormone and vitamin D status. No studies assessed timing. Limitations include heterogeneity and small sample size in included studies. CONCLUSIONS: Enteral vitamin D supplementation improves growth and vitamin D status in preterm and LBW infants. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Iron is needed for growth and development of infants globally, but preterm and low birth weight (LBW) infants are at risk for severe iron deficiencies. To assess the effect of enteral iron supplementation on mortality, morbidity, growth, and neurodevelopment outcomes in preterm or LBW infants fed human milk. Secondary objectives were to assess the effect on biomarkers and dose and timing. METHODS: Data sources include PubMed, Embase and Cochrane Library databases to March 16, 2021. Study Selection includes controlled or quasi experimental study designs. Two reviewers independently extracted data. RESULTS: Eight trials (eleven reports; 1093 participants, 7 countries) were included. No trials reported mortality. At latest follow-up, there was little effect on infection (very low certainty evidence, 4 studies, 401 participants, relative risk [RR] 0.98, 95% confidence interval [95% CI] 0.56 to 1.73, I² = 0.00%) and necrotising enterocolitis (3 studies, 375 participants, RR 1.47, 95% CI 0.68 to 3.20, I² = 0.00%). There was an increase in linear growth (length) (moderate certainty evidence, 3 studies, 384 participants, mean difference 0.69 cm, 95% CI 0.01 to 1.37, I² = 0%) but little effect on weight, head circumference, or cognitive development. There was an improvement in anemia (moderate certainty evidence, 2 studies, 381 participants, RR 0.25, 95% CI 0.10 to 0.62, I² = 0.00%) but no effect on serum ferritin. Limitations include heterogeneity in the included studies. CONCLUSIONS: There are important benefits for human milk-fed preterm and LBW infants from enteral iron supplementation. However, more randomized control trials are required to improve the certainty of evidence. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Evidence on the effect of zinc supplementation on health outcomes in preterm or low birth weight (LBW) infants is unclear. We estimated the effect of enteral zinc versus no zinc supplementation in human milk fed preterm or LBW infants on mortality, growth, morbidities, and neurodevelopment. METHODS: Data sources include PubMed, Cochrane Central and Embase databases through March 24, 2021. Study selection was randomized or quazi-experimental trials. Two reviewers independently screened, extracted data, and assessed quality. We reported pooled relative risks (RR) for categorical outcomes, and mean differences (MD) for continuous outcomes. RESULTS: Fourteen trials with 9940 preterm or LBW infants were included. Moderate to low certainty evidence showed that enteral zinc supplementation had little or no effect on mortality (risk ratio 0.73, 95% confidence interval [CI] 0.46 to 1.16), but increased weight (MD 378.57, 95% CI 275.26 to 481.88), length (MD 2.92, 95% CI 1.53 to 4.31), head growth (MD 0.56, 95% CI 0.23 to 0.90), and decreased diarrhea (RR 0.81; 95% CI 0.68 to 0.97). There was no effect on acute respiratory infections, bacterial sepsis, and psychomotor development scores. The effect of zinc supplementation on mental development scores is inconclusive. There was no evidence of serious adverse events. Eight trials had some concerns or high risk of bias, small-sized studies, and high heterogeneity between trials led to moderate to very low certainty of evidence. CONCLUSIONS: Zinc supplementation in preterm or LBW infants have benefits on growth and diarrhea prevention. Further research is needed to generate better quality evidence. [ABSTRACT FROM AUTHOR]