Skip to main content
Download PDF

Mortality, morbidity and growth among moderately low birthweight infants in India, Malawi, and Tanzania

BMC Pediatrics volume 25, Article number: 316 (2025) Cite this article

Abstract

Background

Despite notable global reductions in infant and under-five mortality over the last two decades, about half of the remaining neonatal deaths occur among low birth weight (LBW) infants. We conducted a prospective study to characterize the mortality risk and morbidity of moderately LBW (MLBW; 1500–2499 g birth weight) infants during the first year of life in India, Malawi, and Tanzania.

Methods

The multi-site Low Birthweight Infant Feeding Exploration (LIFE) study was conducted from September 2019 to July 2021 and followed a cohort of MLBW infants from India, Malawi, and Tanzania from birth to 52 weeks of age. At follow-up visits conducted at 1, 2, 4, 6, 10, 14, 18, 26, 39, and 52 weeks of age, mothers/caregivers were asked to recall the presence of diarrhea, fever, acute respiratory infections, and convulsions during the past week, and infant weight and length were assessed. Generalized estimating equations (GEE) were used to evaluate study site and sociodemographic risk factors for infant morbidity and mortality, and also to assess the relationship between infant morbidity and anthropometric measures.

Results

A total of 1,121 MLBW infants were included in the analysis and 47 (4.2%) deaths were recorded by the age of 12 months. Preterm-appropriate-for-gestational age infants had approximately twice the risk of infant death compared to term-small-for-gestational age infants (RR: 2.09; 95% CI: 1.08, 4.05). Period prevalence of diarrhea and fever increased with infant age and differed by study site (p-values < 0.05). In time-varying analyses, reported diarrhea during the past week was associated with lower length-for-age z-score (LAZ) (mean difference (MD): -0.20; 95% CI: -0.31, -0.09), weight-for-age z-score (WAZ) (MD: -0.25; 95% CI: -0.35, -0.16), and weight-for-length z-score (WLZ) (MD: -0.24; 95% CI: -0.36, -0.12), while fever was associated with lower WAZ (MD: -0.14; 95% CI: -0.21, -0.06), and WLZ (MD: -0.17; 95% CI: -0.26, -0.08) but not LAZ at the concurrent study visit.

Conclusion

The risk of death during the first year of life is high for MLBW, but differs by the contribution of prematurity and size-for-gestational age. Interventions that reduce the incidence of diarrhea and fever may improve the growth of MLBW infants.

Trial registration

The LIFE study was registered with ClinicalTrials.gov (NCT04002908).

Peer Review reports

Introduction

Every year, globally about 35 million newborns are born preterm (< 37 weeks) and/or low birthweight (LBW) (< 2500 g) [1]. This population, referred to as small and vulnerable newborns (SVN), has an increased risk of morbidity and mortality [2]. SVNs include an estimated 12 million preterm, 22 million small-for-gestational age (SGA), and 1.5 million preterm and SGA births. Despite global trends in the reduction of under-five and infant mortality, thereare still an estimated 4.9 million global deaths annually among children under 5 years of age and approximately 47% of these deaths occur in the neonatal period [3, 4]. It is estimated that over half of the 2.4 million neonatal deaths worldwide in 2020 were attributed to SVNs, with the majority of deaths and SVN births occurring in low- and middle-income countries (LMICs) [1].

LBW infants have long been recognized to have an increased risk of neonatal mortality [5]. More recent evidence on SVNs has focused on separating the mortality risk for preterm birth and small-for-gestational age (SGA) newborns. In a recent pooled cohort study of over 200,000 births in LMICs, as compared to the reference of term appropriate-for-gestational age (AGA) births, term-SGA, preterm-AGA and preterm-SGA infants had a median relative risk for neonatal mortality of 2.8, 6.0, and 10.4, respectively [6]. Multiple studies have also found that LBW infants are at greater risk for diarrhea; however, the association with respiratory infections and other morbidities is unclear [7, 8]. Importantly, moderately LBW (MLBW) infants, who are defined by a weight of 1.5 to < 2.5 kg, include more than > 90% of global LBW births as compared with very LBW infants (< 1.5 kg), but data is lacking in this group on morbidity, mortality and growth [9,10,11]. Few studies have evaluated the contribution of preterm birth and SGA to the mortality and morbidity risk among MLBW infants in LMIC settings.

We conducted a secondary analysis of a prospective cohort study to characterize the mortality risk and morbidity patterns among MLBW infants in India, Malawi, and Tanzania during the first year of life. We assessed risk factors for infant death and morbidities including diarrhea, respiratory tract infections, fever, and convulsions. We also assessed the relationship of infant morbidity with infant postnatal growth. The study results are intended to inform the design of interventions to improve survival, reduce morbidity, and improve postnatal growth of MLBW infants.

Methods

The LBW Infant Feeding Exploration (LIFE) study included a multi-site prospective observational cohort of MLBW infants followed in four study sites in India-Karnataka state, India-Odisha state, Malawi, and Tanzania. The study protocol and primary outcome findings on the relationship of feeding practices with infant growth to 6-months of age in the cohort were published previously [12, 13]. Here, we report secondary analyses from the LIFE study focused on mortality, morbidity and growth outcomes during the extended period of follow-up to 1-year postnatal age.

Briefly, the LIFE study was conducted at 12 health facilities including 5 facilities in India-Karnataka state (Belgaum and Davangere), 2 facilities in India-Odisha state (Cuttack), 2 facilities in Malawi (Lilongwe), and 3 facilities in Tanzania (Dar-es-Salaam). The facilities in India-Odisha state, Malawi, and Tanzania sites were public secondary and tertiary facilities while there was a mix of public and private tertiary facilities in India-Karnataka state. The participant inclusion criteria were uniform across study sites and included infants that (i) had a birthweight ≥ 1500 and < 2500 g and (ii) resided within 50 km of the enrollment facility. The exclusion criteria for infants were (i) congenital abnormalities that impacted feeding (cleft lip or palate; hydrocephalus; gastrointestinal tract anomalies including gastroschisis, omphalocele or anal atresia; neural tube defects; congenital cardiac defects; suspected trisomy 21; suspected TORCH infection; infants with severe neonatal encephalopathy jeopardizing early survival were also excluded), (ii) having a twin/triplet who died before enrollment, (iii) having a mother aged less than the site-specific age of consent, or (iv) having a mother who had died before enrollment [12] In terms of sample size, the full power calculations for the primary analyses related to 6-month anthropometric measures are published elsewhere. Briefly, sample size of 300 per study site was calculated on an estimated stunting prevalence of 10% at 6 months of age and a precision of ± 3.6% [12, 13].

Data collection

Participants were screened for eligibility within 72 hours of birth. Birthweight was measured by facility staff and gestational age was determined using an algorithm that preferentially selected the best obstetric estimate based on ultrasound and last menstrual period (LMP) dating from charts, followed by LMP based on maternal report, then gestational age recorded in the chart, and finally a Dubowitz examination if none of the previously stated data were available [12, 13]. Postnatal infant follow-up visits were conducted at 1, 2, 4, 6, 10, 14, 18, 26, 39, and 52 weeks postnatal age. Study visits were conducted in hospital if the infant was admitted. Subsequent visits were conducted at outpatient clinic facilities. If a participant was not able to attend an outpatient clinic visit, study visits in the home or via telephone were attempted. At each follow-up visit, mothers/caregivers were asked to recall the presence of a pre-specified list of infant morbidities during the past 7-days. Symptoms of acute respiratory tract infection (ARI) were defined by the report of cough with fast breathing and/or difficulty breathing. Infant feeding practices were assessed at each study visit using a 7-day recall period. Maternal and household sociodemographic characteristics were assessed at the 1-week study visit and included information on maternal age, maternal education, household water source, and sanitation. Household water and sanitation were classified based on Joint Monitoring Programme (JMP) for Water Supply, Sanitation and Hygiene definitions [14]. At each postnatal follow-up visit, infant recumbent length (Seca 417 length board, Hamburg, Germany) and weight (Seca 334 digital weight scale, Hamburg, Germany) were taken in triplicate using standardized procedures. WHO child growth standards and INTERGROWTH-21st standards were used to calculate length-for-age (LAZ), weight-for-length (WLZ), and weight-for-age (WAZ) z-scores at each visit [15,16,17]. For preterm infants, the INTERGROWTH-21st standards were used up to 26 weeks of age, WHO growth standards corrected for gestational age at 26 weeks of age, and the WHO child growth standards with no correction for gestational age after 26 weeks of age. For term infants, the WHO child growth standards were used throughout.

Statistical analysis

We calculated the neonatal (< 28 days of life) and infant (< 365 days of life) mortality rates in the study population per 1,000 MLBW infants. We then evaluated risk factors for infant death including study site and infant characteristics with generalized estimating equations (GEE) that used exchangeable correlation matrices to account for twins and log links with binomial variance functions to estimate relative risks. Infant characteristics of interest included sex, singleton or twin birth, delivery type (cesarean or vaginal), birthweight (1500 - <2000 g or 2000 - <2500 g), preterm birth (< 37 weeks), SGA (< 10th percentile (SGA), AGA 10-90th percentile, or large-for-gestational age > 90th percentile (LGA)), and the combination of gestational age and size-for-gestational age (term-SGA, preterm-SGA, preterm-AGA, preterm-LGA). Due to the small number of infant deaths, we only conducted univariable analyses for infant mortality risk factors.

We then described the one-week period prevalences of maternal-reported infant diarrhea, fever, ARI symptoms, and convulsions at each study visit stratified by site. Risk factors for maternal-reported diarrhea and fever at each study visit were assessed in repeated measures analyses with GEE models that used exchangeable working covariance matrices to account for twins and log links with binomial variance functions to produce population-averaged relative risks. We did not conduct risk factor analyses for ARI symptoms, and convulsions due to the low number of events. A two-step analytic strategy was used that first examined the relationship of site and infant age with diarrhea and fever and then we evaluated the relationship of sociodemographic and infant characteristics in models adjusted for study site and infant age. Sociodemographic factors of interest included maternal age, parity, maternal education, household water source and household sanitation. Infant characteristics evaluated as risk factors for diarrhea and fever included all variables in the mortality analysis but also included exclusive breastfeeding status as a time-varying predictor. P-values for trend were calculated for wealth quintile and infant age by treating each as a continuous variable.

We then evaluated the association of reported fever and diarrhea with infant growth outcomes. We first assessed the time-varying association of reported diarrhea and fever during the prior week with infant LAZ, WAZ, and WLZ at the same study visit with generalized linear mixed-effects models that included a random intercept and a compound symmetric covariance structure to account for twins. We then evaluated the relationship of the cumulative number of study visits with diarrhea and fever reported during the study period with LAZ, WAZ, and WLZ at the 52-week visit with GEE models. Multivariable models for the relationship of diarrhea and fever with growth outcomes included adjustment for study site, infant age, infant characteristics, and sociodemographic characteristics. P-values < 0.05 were considered statistically significant. Statistical analyses were conducted using SAS version 9.4 (SAS Institute, Cary, North Carolina).

Results

The study enrolled MLBW infants from September 2019 to July 2020. Infant follow-up 52 weeks of age was completed in July 2021. Across the study sites, a total of 2,152 infants were assessed for eligibility of which 1,126 (52.3%) MLBW infants were enrolled (Supplemental Fig. 1) and 1,121 MLBW infants included for analysis. The characteristics of the cohort overall and stratified by site are presented in Table 1. The majority of infants weighed 1500 - <2000 g (74.3%). The study sites in India had a greater proportion of term-SGA MLBW infants as compared to Malawi and Tanzania where over half of MLBW infants were preterm. The majority of infants resided in households with satisfactory water sources (91.5%) and satisfactory sanitation (79.9%). The follow-up visit completion rate to 52 weeks of age was high at 96.3%.

Table 1 Birth characteristics and sociodemographic factors of the moderately low birthweight infant study population
Full size table

A total of 47 infant deaths were recorded (infant mortality rate: 41.9 per 1,000 MLBW live births) and among these deaths, 19 (40.4% of deaths) occurred during the neonatal period. Table 2 presents the association of study site, birth, and infant characteristics with the risk of infant death. There was no statistically significant difference in infant mortality by site.

Table 2 Association of study site and infant characteristics with infant mortality among moderately low birthweight infants
Full size table

In terms of infant characteristics, a birthweight 1500 - <2000 g as compared to 2000 - <2500 g (RR: 2.17; 95% CI: 1.21–3.90) and preterm as compared to term birth (RR: 2.52; 95% CI 1.37, 4.65) were associated with increased risk of infant mortality, while there was no association of size-for-gestational age categories with infant mortality. However, the combination of preterm and size-for-gestational age status was associated with the risk of infant mortality. As compared to term-SGA MLBW infants, preterm-AGA infants had 2.09 times (95% CI: 1.08, 4.05) the risk of infant death, while preterm-SGA infants and preterm-LGA infants had 3.27 times (95% CI: 1.65, 6.48) and 3.33 times (95% CI: 1.01–11.06) the risk of infant death, respectively.

The one-week period prevalences of maternal/caregiver-reported morbidity signs by study site and infant age are presented in Fig. 1 and Supplemental Table 1.

Fig. 1
figure 1

One-week period prevalences of maternal-reported diarrhea, fever and ARI* symptoms among moderately low birthweight infants. *Cough with fast breathing and/or difficulty breathing. Abbreviations: ARI; acute respiratory tract infection

Full size image

The risk for diarrhea and fever significantly increased with infant age and was greater for infants in India-Karnataka, Malawi, and Tanzania sites as compared to the India-Odisha site (Supplemental Tables 2 and 3). There were no reports of ARI symptoms at any site for visits between 1 and 26 weeks and were rarely reported at 39- and 52-week visits. Convulsions were only reported for one infant at the India-Karnataka site. We did not identify any sociodemographic or infant characteristic associated with the risk of diarrhea after adjusting for study site and infant age (Supplemental Table 4). The only risk factor identified for infant fever was unsatisfactory sanitation (RR: 1.45; 95% CI: 1.15, 1.82; Supplemental Table 5). There was no association of time-varying exclusive breastfeeding status with reported diarrhea and fever (Supplemental Tables 4 and 5).

Time-varying analyses of the association of reported diarrhea and fever during the prior week with infant LAZ, WAZ, and WLZ at the same study visit are presented in Table 3. We found that diarrhea during the last 7 days was associated with lower LAZ (mean difference (MD): -0.20; 95% CI: -0.31, -0.09), WAZ (MD: -0.25; 95% CI: -0.35, -0.16), and WLZ (MD: -0.24; 95% CI: -0.36, -0.12). Reported fever during the last week was also associated with lower WAZ (MD: -0.14; 95% CI: -0.21, -0.06), and WLZ (MD: -0.17; 95% CI: -0.26, -0.08), but there was no association with LAZ.

Table 3 Time-varying association of maternal/caregiver-reported diarrhea and fever during the last week with infant anthropometrics
Full size table

We then evaluated the association of the cumulative number of study visits with reported diarrhea and fever per infant with growth outcomes at 52 weeks age presented in Table 4. Infants who had one study visit during infancy with diarrhea recorded had significantly lower WAZ (MD: -0.65; 95% CI: -1.21, -0.08) and WLZ (MD: -0.26; 95% CI: -0.44, -0.08) at 52 weeks compared to infants that did not have diarrhea reported at any visit. Infants with two or more visits with fever recorded had significantly lower WLZ at 52 weeks of age (MD: -0.31; 95% CI: -0.54, -0.07) compared to infants who did not have fever recorded at any visit. There was no association between the number of visits with reported diarrhea or fever with infant LAZ at 52 weeks.

Table 4 Association of study visits with maternal/caregiver reported diarrhea and fever with growth outcomes at 1-year postnatal age
Full size table

Discussion

In this prospective cohort study of MLBW infants in India, Malawi, and Tanzania, the risk of infant mortality was high and was found to vary by the contribution of preterm and size-for-gestational age at birth. Both preterm-SGA and preterm-LGA births had a greater risk of infant death as compared to term-SGA infants. Diarrhea and fever were common among MLBW infants, and the risk of these morbidities generally increased with age. Diarrhea and fever during the last 7 days were found to be associated with lower infant WAZ and WLZ at the same study visit, while diarrhea was associated with lower concurrent LAZ. There was some evidence that a greater number of study visits during infancy with reported diarrhea or fever was associated with reduced ponderal growth at 1-year of age.

The infant mortality rate for this MLBW cohort was high at 41.9 per 1000 livebirths which is higher than the global infant mortality rate among all infants of 28 deaths per 1000 livebirths [18]. In our study, the greatest risk of mortality was among the preterm infant groups; preterm-SGA and preterm-LGA infants, which had 3 times the risk of mortality in comparison to term-SGA infants. A combination of preterm and SGA has previously been shown to have the highest risk of mortality in comparison to term-AGA infants. Globally, the highest rates of LBW have been reported in South Asia and it is well known the rates of SGA and preterm also vary by region [1]. Among LBW infants, SGA births have been reported proportionally more common in South Asia, and preterm births more predominant in SSA [1, 19]. A similar trend was noted in our cohort. Maternal undernutrition has been recognized as a predominant risk factor for SGA [20, 21], while maternal infections such as malaria, urinary tract infections, and pre-eclampsia are leading risk factors for preterm births [22, 23]. The geographical variation for these risk factors may be contributors to the variation and patterns of LBW phenotypes globally. As a result, identification of these risk factors is critical and interventions such as maternal micronutrient supplementation in pregnancy, malaria prophylaxis in endemic areas, and ensuring target antenatal care visits may be crucial to reduce the burden of LBW [20, 24].

In our cohort, the risk of diarrhea increased with infant age with the highest prevalence found at 26 weeks to 52 weeks. This pattern is in line with literature whereby there is an increased risk of diarrhea during weaning from exclusive breastfeeding (generally after 6 months of age), lack of adequate hygiene in preparation of complementary feeds, and waning of maternal antibodies [25,26,27]. The prevalence of reported fever also increased with infant age. The cause of this fever was not established, these reports were not from hospitalization, hence mostly with unestablished cause and severity. Infections are common in the first 2 years of life, particularly in the 6-11month age group [26]. In contrast to reports from South Africa where LBW was a risk factor for respiratory tract infections [28], ARI were uncommon in our cohort, possibly due to recall bias and our use of a 1-week recall. Overall, our findings show that while mortality risk is highest during the first weeks of life, common childhood morbidities like diarrhea and fever tend to become more prevalent with greater infant age. However, it is important to note that infections remain as major causes of early neonatal death [29].

Our analysis also found an association between reported morbidities and suboptimal growth. Reported diarrhea was associated with low WAZ, LAZ and WLZ, which is well established in literature of children’s general population [26, 30]. In our cohort, a report of febrile illness was associated with lower WAZ and WLZ. There are many postulated pathways for the association of fever with poor growth including poor appetite, malabsorption, and diverting nutrients from growth toward metabolism [26]. In our study, we evaluated concurrent reports of infections with growth and therefore it is not clear if morbidity preceded or occurred as a result of poor nutritional status due to the cyclical nature of nutrition and infection [31]. Not all infections affecting growth may be clinically apparent as subclinical infections and environmental enteric dysfunction may also affect growth [32, 33]. Overall, while the relationship between birth phenotypes with mortality is well-characterized, more research is needed to characterize morbidity risk and potential interventions for SVN infants. Nutrition support interventions may be suboptimal for SVN infants to achieve adequate growth and development if there is no incorporation of measures towards infection prevention [34]. Hence more research is needed on feeding, vaccination, water sanitation and hygiene programs, and other interventions that may reduce the infectious disease burden among LBW infants.

Our analysis had some limitations. Firstly, we did not have a reference group of non-LBW infants and analysis used term-SGA infants as a reference group. Term-SGA infants are known to have an increased risk for morbidity and mortality compared to term-AGA non-LBW infants. Secondly, the morbidity data collection relied on 1-week maternal/caregiver recall at variable time points during the first year of life. As a result, we did not have complete coverage of recall time which did not allow us to capture the total number of morbidity episodes during infancy. In addition, we did not include other anthropometric measures (e.g. head circumference or mid upper arm circumference) or neurodevelopment outcomes in this paper; analyses related to these indicators are underway and will be published elsewhere. We also did not analyze the association of receipt and timing of vaccination with morbidity, mortality and growth in this study; we plan to conduct a full analysis of vaccination and child outcomes in a future study. We also were not able to assess the association of exclusive breastfeeding duration and subsequent mortality in our study population as only four deaths occurred after 6 months of age. Thirdly, we conducted the study at three sites in Tanzania, Malawi, and India and therefore our findings may not be generalizable to all settings. Nevertheless, 75% of LBW morbidity and mortality occurs in South East Asia and SSA [20], hence this cohort may be reflective of MLBW infants in these settings.

Conclusions

The risk of infant mortality for MLBW infants is high but differs by the contribution of prematurity and size-for-gestational age, being higher in preterm infants than in term-SGA. Therefore, our study supports the need to stratify SVN into categories by gestational age and size-for gestational age rather than just evaluating the broader contributions of LBW in research and care. Interventions that reduce the incidence of diarrhea and fever may improve the growth of MLBW infants. Overall, the development of new interventions and improved implementation of known interventions are needed to improve the survival and growth of MLBW infants in LMICs.

Data availability

Data are available in a public, open access repository. Deidentified individual participant data (including data dictionaries) used in this manuscript are available through the Harvard Dataverse platform under the BetterBirth Dataverse website. This can be found at: https://dataverse.harvard.edu/dataverse/BetterBirthData.

Abbreviations

AGA:

Appropriate-for-gestational age

ARI:

Acute respiratory tract infection

GEE:

Generalized estimating equations

LAZ:

Length-for-age z-score

LBW:

Low birth weight

LGA:

Large-for-gestational-age

LIFE:

Low Birthweight Infant Feeding Exploration

LMIC:

Low- and middle-income countries

MD:

Mean difference

MLBW:

Moderately low birth weight

SGA:

Small-for-gestational age

SVN:

Small and vulnerable newborns

TSGA:

Term-small-for-gestational age

WAZ:

Weight-for-age z-score

WHO:

World Health Organization

WLZ:

Weight-for-length z-score

References

  1. Lawn JE, Ohuma EO, Bradley E, Okwaraji YB, Yargawa J, Blencowe H, et al. Small babies, big risks: global estimates of prevalence and mortality for vulnerable newborns to accelerate change and improve counting. Lancet. 2023;401(10389):1707–19.

    Article  PubMed  Google Scholar 

  2. Mohiddin A, Semrau KEA, Simon J, Langlois EV, Shiffman J, Nabwera H et al. The ethicconomic, and developmental imperative to prevent small vulnerable newborns and stillbirths: essential actions to improve the country and global response. Lancet. 2023;401(10389):1636–8. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1016/S0140-6736(23)00721-3

  3. Ashorn P, Black RE, Lawn JE, Ashorn U, Klein N, Hofmeyr J, et al. The lancet small vulnerable newborn series: science for a healthy start. Lancet. 2020;396(10253):743–5.

    Article  CAS  PubMed  Google Scholar 

  4. United Nations Children’s Fund (UNICEF). The Demographic and Health Surveys (DHS) Program, ICF. Levels & Trends in Child Mortality. 2024.

  5. McCormick MC. The contribution of low birth weight to infant mortality and childhood morbidity. N Engl J Med. 1985;312(2):82–90.

    Article  CAS  PubMed  Google Scholar 

  6. Hazel EA, Erchick DJ, Katz J, Lee ACC, Diaz M, Wu LSF et al. Neonatal mortality risk of vulnerable newborns: A descriptive analysis of subnational, population-based birth cohorts for 238 143 live births in low- and middle-income settings from 2000 to 2017. BJOG Int J Obstet Gynaecol. 2023;(April):1–12.

  7. Lira PIC, Ashworth A, Morris SS. Low birth weight and morbidity from diarrhea and respiratory infection in Northeast Brazil. J Pediatr. 1996;128(4):497–504.

    Article  CAS  PubMed  Google Scholar 

  8. Etiler N, Velipasaoglu S, Aktekin M. Risk factors for overall and persistent diarrhoea in infancy in Antalya, Turkey: A cohort study. Public Health. 2004;118(1):62–9.

    Article  CAS  PubMed  Google Scholar 

  9. Marete I, Ekhaguere O, Bann CM, Bucher SL, Nyongesa P, Patel AB et al. Regional trends in birth weight in low- and middle-income countries 2013–2018. Reprod Health. 2020;17(3):1–9. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12978-020-01026-2

  10. North K, Marx Delaney M, Bose C, Lee ACC, Vesel L, Adair L, et al. The effect of milk type and fortification on the growth of low-birthweight infants: an umbrella review of systematic reviews and meta-analyses. Matern Child Nutr. 2021;17(3):1–13.

    Article  Google Scholar 

  11. Upadhyay RP, Martines JC, Taneja S, Mazumder S, Bahl R, Bhandari N, et al. Risk of postneonatal mortality, hospitalisation and suboptimal breast feeding practices in low birthweight infants from rural Haryana, India: findings from a secondary data analysis. BMJ Open. 2018;8(6):1–12.

    Article  Google Scholar 

  12. Vesel L, Spigel L, Behera JN, Bellad RM, Das L, Dhaded S et al. methods, descriptive and observational cohort study examining feeding and growth patterns among low birthweight infants in India, Malawi and Tanzania: the LIFE study protocol. 2021;1–11.

  13. Vesel L, Bellad RM, Manji K, Saidi F, Velasquez E, Sudfeld CR et al. Feeding practices and growth patterns of moderately low birthweight infants limited settings: results from in resource- ­ a multisite. Longitud Observational Study. 2023;1–12.

  14. WHO/UNICEF/JMP. FIVE YEARS INTO, The SDGs Progress on household drinking water, sanitation and hygiene. Launch version July 12 Main report Progress on Drinking Water, Sanitation and Hygiene. 2020. 1–164 p. Available from: http://apps.who.int/bookorders

  15. Villar J, Ismail LC, Victora CG, Ohuma EO, Bertino E, Altman DG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the newborn Cross-Sectional study of the INTERGROWTH-21st project. Lancet. 2014;384(9946):857–68.

    Article  PubMed  Google Scholar 

  16. WHO Child Growth Standards. Dev Med Child Neurol. 2009;51(12):1002–1002.

    Article  Google Scholar 

  17. Villar J, Giuliani F, Bhutta ZA, Bertino E, Ohuma EO, Ismail LC, et al. Postnatal growth standards for preterm infants: the preterm postnatal Follow-up study of the INTERGROWTH-21stProject. Lancet Glob Heal. 2015;3(11):e681–91.

    Article  Google Scholar 

  18. United Nations Inter-agency Group for Child Mortality Estimation. United Nations Inter-agency Group for Child Mortality Estimation (UN IGME). Levels & trends in child mortality: report 2022, estimates developed by the united nations Inter-agency group for child mortality estimation, united nations children’s fund. UNICEF Org. 2023. 1–80 p.

  19. Benjamin-Chung J, Mertens A, Colford JM, Hubbard AE, van der Laan MJ, Coyle J, et al. Early-childhood linear growth faltering in low- and middle-income countries. Nature. 2023;621(7979):550–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Imdad A, Bhutta ZA. Nutritional management of the low birth weight/preterm infant in community settings: A perspective from the developing world. J Pediatr. 2013;162(3 SUPPL.):S107–14. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.jpeds.2012.11.060

  21. Muhihi A, Sudfeld CR, Smith ER, Noor RA, Mshamu S, Briegleb C et al. Risk factors for small-for-gestational-age and preterm births among 19,269 Tanzanian newborns. BMC Pregnancy Childbirth. 2016;16(1):1–12. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12884-016-0900-5

  22. He JR, Tikellis G, Paltiel O, Klebanoff M, Magnus P, Northstone K et al. Association of common maternal infections with birth outcomes: a multinational cohort study. Infection. 2024;(0123456789). Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s15010-024-02291-0

  23. Goldenberg RL, Culhane JF, Iams JDRR. Preterm birth: epidemiology and causes of preterm birth. 2020;Lancet 200(January):75–84.

  24. Patel S, Verma NR, Padhi P, Naik T, Nanda R, Naik G, Mohapatra E. Retrospective analysis to identify the association of various determinants on birth weight. J Family Med Prim Care. 2021;10(1):496–501. https://doiorg.publicaciones.saludcastillayleon.es/10.4103/jfmpc.jfmpc_1493_20. Epub 2021 Jan 30. PMID: 34017777; PMCID: PMC8132747.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Motarjemi Y, Kaferstein F, Moy G, Quevedo F. Contaminated weaning food: A major risk factor for diarrhoea and associated malnutrition. Bull World Health Organ. 1993;71(1):79–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Dewey KG, Mayers DR. Early child growth: How do nutrition and infection interact? Matern Child Nutr. 2011;7(SUPPL. 3):129–42.

  27. Niewiesk S. Maternal antibodies: clinical significance, mechanism of interference with immune responses, and possible vaccination strategies. Front Immunol. 2014;5(SEP):1–15.

    CAS  Google Scholar 

  28. Le Roux DM, Nicol MP, Myer L, Vanker A, Stadler JAM, Von Delft E, et al. Lower respiratory tract infections in children in a Well-vaccinated South African birth cohort: spectrum of disease and risk factors. Clin Infect Dis. 2019;69(9):1588–96.

    Article  PubMed  Google Scholar 

  29. Sharrow D, Hug L, You D, Alkema L, Black R, Cousens S et al. Global, regional, and national trends in under-5 mortality between 1990 and 2019 with scenario-based projections until 2030: a systematic analysis by the UN Inter-agency Group for Child Mortality Estimation. Lancet Glob Heal. 2022;10(2):e195–206. Available from: https://doiorg.publicaciones.saludcastillayleon.es/10.1016/S2214-109X(21)00515-5

  30. Checkley W, Buckley G, Gilman RH, Assis AM, Guerrant RL, Morris SS, et al. Multi-country analysis of the effects of diarrhoea on childhood stunting. Int J Epidemiol. 2008;37(4):816–30.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Katona P, Katona-Apte J. The interaction between nutrition and infection. Clin Infect Dis. 2008;46(10):1582–8.

    Article  PubMed  Google Scholar 

  32. Crane RJ, Jones KDJ, Berkley JA. Environmental enteric dysfunction: an overview. Food Nutr Bull. 2015;36(1 0):S76–87.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Goto R, Mascie-Taylor CGN, Lunn PG. Impact of intestinal permeability, inflammation status and parasitic infections on infant growth faltering in rural Bangladesh. Br J Nutr. 2009;101(10):1509–16.

    Article  CAS  PubMed  Google Scholar 

  34. Weisz A, Meuli G, Thakwalakwa C, Trehan I, Maleta K, Manary M. The duration of diarrhea and fever is associated with growth faltering in rural Malawian children aged 6–18 months. Nutr J. 2011;10(25):1–4.

    Google Scholar 

Download references

Acknowledgements

The authors would like to thank clinical leadership and staff at all study facilities for their partnership, support and contribution to this work; the mothers/caregivers and infants for their participation in the study; and all data collectors and study staff for conducting study activities.

Funding

This publication is based on research funded in part by the Bill & Melinda Gates Foundation. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation (OPP1192260 / INV-007326).

Author information

Authors and Affiliations

  1. University of North Carolina Project Malawi, Lilongwe, Malawi

    Tisungane Mvalo, Friday Saidi & Irving F. Hoffman

  2. Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA

    Tisungane Mvalo

  3. Department of Pediatrics, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belgaum, Karnataka, India

    Sangappa M. Dhaded, Roopa Bellad & Bhavana Koppad

  4. Department of Pediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

    Karim P. Manji, Rodrick Kisenge & Sarah Somji

  5. Ariadne Labs, Harvard T.H. Chan School of Public Health / Brigham and Women’s Hospital, Boston, MA, USA

    Linda Vesel, Katherine E.A. Semrau, Danielle E. Tuller & Rana Mokhtar

  6. Department of Pediatrics, Kamuzu Central Hospital (KCH), Ministry of Health, Lilongwe, Malawi

    Msandeni Chiume

  7. Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA

    Friday Saidi

  8. Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA

    Irving F. Hoffman

  9. Department of Physiology, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belgaum, Karnataka, India

    Sunil Vernekar

  10. Department of Pediatrics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Anne C.C. Lee & Krysten North

  11. Brown Alliance for Infant and Maternal Health Research, Warren Alpert Medical School of Brown University, Providence, RI, USA

    Anne C.C. Lee

  12. Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Christopher R. Sudfeld

  13. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Christopher R. Sudfeld

Authors
  1. Tisungane Mvalo
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Sangappa M. Dhaded
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Karim P. Manji
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Linda Vesel
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Katherine E.A. Semrau
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Rodrick Kisenge
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Sarah Somji
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Msandeni Chiume
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Friday Saidi
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Irving F. Hoffman
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Sunil Vernekar
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Roopa Bellad
    View author publications

    You can also search for this author inPubMed Google Scholar

  13. Bhavana Koppad
    View author publications

    You can also search for this author inPubMed Google Scholar

  14. Danielle E. Tuller
    View author publications

    You can also search for this author inPubMed Google Scholar

  15. Rana Mokhtar
    View author publications

    You can also search for this author inPubMed Google Scholar

  16. Anne C.C. Lee
    View author publications

    You can also search for this author inPubMed Google Scholar

  17. Krysten North
    View author publications

    You can also search for this author inPubMed Google Scholar

  18. Christopher R. Sudfeld
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

T.M and C.R.S wrote the first version of the manuscript. C.R.S performed data analysis and interpretation. K.E.A.S, S.M.D, K.M, I.F.H, D.E.T, A.C.L, R.B. and C.R.S were involved in conceptualization and design of the study. Data collection was performed by T.M, S.M.D, K.M, R.K, S.V, R.B and F.S. Data management and cleaning was performed by L.V and R.R.M. All authors reviewed the drafts of the manuscript and approved the final version.

Corresponding author

Correspondence to Tisungane Mvalo.

Ethics declarations

Ethics and approval to participate

This study was approved by 11 ethics committees in India, Malawi, Tanzania and the USA: (1) India Health Ministry’s Screening Committee with Indian Council of Medical Research acting as its secretariat (2019–2674); (2) Directorate of Health and Family Welfare Services, Government of Karnataka which also covers investigators at Women and Children Hospital, Davangere and Chigateri General District Hospital, Davangere (NHM/SPM/04/2019-20); (3) Institutional Ethics Committee of KLE Academy of Higher Education and Research which also covers investigators at JN Medical College, Belagavi and KLES Dr Prabhakar Kore Hospital & Medical Research Center, Belagavi (KAHER/IEC/2019-20/D-2760); (4) Institutional Ethics Review Board of SS Institute of Medical Sciences & Research Centre (IERB/200/2019); (5) Institutional Ethics Committee of JJM Medical College (JJMMC/IEC-01/2019) which also covers investigators at Bapuji Child Health Institute & Research Centre, Davangere, Women & Children Hospital, Davangere and Chigateri General District Hospital, Davangere; (6) Research and Ethics Committee, Directorate of Health Services, Odisha State which also covers investigators at City Hospital Oriya Bazar, Cuttack (155/PMU/187/17); (7) Institutional Ethical Committee, Sriram Chandra Bhanja Medical College, Cuttack (7188); (8) Malawi National Health Sciences Research Committee (NHSRC 2019/Protocol19/03/2250-UNCPM 21905); (9) Tanzania National Institute of Medical Research (NIMR/HQ/R.8a/Vol.IX/3126); (10) Muhimbili University of Health and Allied Sciences (DA.282/298/01.C/); and (11) USA - Harvard T.H Chan School of Public Health (IRB10-0282) which also covers investigators at Boston Children’s Hospital, Brigham and Women’s Hospital, Emory University, PATH and University of North Carolina. Informed consent was obtained from all parents/legally accepted representatives prior to any study procedure or data collection for each study participant.

Consent for publication

Informed consent was obtained directly from patient(s)/ legally accepted representatives.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mvalo, T., Dhaded, S.M., Manji, K.P. et al. Mortality, morbidity and growth among moderately low birthweight infants in India, Malawi, and Tanzania. BMC Pediatr 25, 316 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12887-025-05668-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12887-025-05668-8

Keywords

BMC Pediatrics

ISSN: 1471-2431

Contact us