Correction: Burden of disease and risk factors for mortality amongst hospitalized newborns in Nigeria and Kenya.

[This corrects the article DOI: 10.1371/journal.pone.0244109.].

Time to full enteral feeds in hospitalised preterm and very low birth weight infants in Nigeria and Kenya.

BACKGROUND: Preterm (born < 37 weeks' gestation) and very low birthweight (VLBW; <1.5kg) infants are at the greatest risk of morbidity and mortality within the first 28 days of life. Establishing full enteral feeds is a vital aspect of their clinical care. Evidence predominantly from high income countries shows that early and rapid advancement of feeds is safe and reduces length of hospital stay and adverse health outcomes. However, there are limited data on feeding practices and factors that influence the attainment of full enteral feeds among these vulnerable infants in sub-Saharan Africa. AIM: To identify factors that influence the time to full enteral feeds, defined as tolerance of 120ml/kg/day, in hospitalised preterm and VLBW infants in neonatal units in two sub-Saharan African countries. METHODS: Demographic and clinical variables were collected for newborns admitted to 7 neonatal units in Nigeria and Kenya over 6-months. Multiple linear regression analysis was conducted to identify factors independently associated with time to full enteral feeds. RESULTS: Of the 2280 newborn infants admitted, 484 were preterm and VLBW. Overall, 222/484 (45.8%) infants died with over half of the deaths (136/222; 61.7%) occurring before the first feed. The median (inter-quartile range) time to first feed was 46 (27, 72) hours of life and time to full enteral feeds (tFEF) was 8 (4.5,12) days with marked variation between neonatal units. Independent predictors of tFEF were time to first feed (unstandardised coefficient B 1.69; 95% CI 1.11 to 2.26; p value <0.001), gestational age (1.77; 0.72 to 2.81; <0.001), the occurrence of respiratory distress (-1.89; -3.50 to -0.79; <0.002) and necrotising enterocolitis (4.31; 1.00 to 7.62; <0.011). CONCLUSION: The use of standardised feeding guidelines may decrease variations in clinical practice, shorten tFEF and thereby improve preterm and VLBW outcomes.

Stunting in the first year of life: Pathway analysis of a birth cohort.

Malnutrition among infants aged below 6 months has been largely overlooked creating gaps in our understanding of factors underlying stunting in early infancy. Recent evidence suggests that pre-natal and early childhood factors may contribute more to driving childhood stunting than previously appreciated. The study was set up to examine pathways including parental and household characteristics, birth size and gestation, and illness in infancy with stunting at birth and months 3, 6 and 12 using an a priori hypothesized framework. It was a secondary analysis of a birth cohort of 1017 infants recruited from four health facilities in Burkina Faso and followed up for one year. Structural equation models (SEM) were generated to explore pathways to stunting at birth and months 3, 6 and 12. The prevalence of being stunted at birth and months 3, 6 and 12 was 7.4%, 23%, 20% and 18% respectively. The fractions of month 12 stunting attributable to being stunted at birth, months 3 and 6 were 11% (95%CI 5.0‒16%), 32% (95%CI 22‒41%) and 40% (95%CI 31‒49%) respectively. In the structural equation model, male sex and maternal characteristics had direct effects on stunting at birth and at 3 months, but not subsequently. Premature birth, twin birth and being stunted at a previous time point were directly associated with stunting at months 3, 6 and 12. Both maternal and paternal characteristics were directly associated with preterm birth. Non-exclusive breastfeeding had borderline positive direct effect on stunting at month 6 but not at month 12. The direct and indirect pathways identified in this study highlight the complex interlinks between child, maternal, paternal and household characteristics. Interventions tackling preterm birth, in utero growth, exclusive breastfeeding and maternal wellbeing may reduce stunting in the first year of life.

Stunting of Growth in Developing Countries.

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Anthropometric criteria for best-identifying children at high risk of mortality: a pooled analysis of twelve cohorts.

OBJECTIVE: To understand which anthropometric diagnostic criteria best discriminate higher from lower risk of death in children and explore programme implications. DESIGN: A multiple cohort individual data meta-analysis of mortality risk (within 6 months of measurement) by anthropometric case definitions. Sensitivity, specificity, informedness and inclusivity in predicting mortality, face validity and compatibility with current standards and practice were assessed and operational consequences were modelled. SETTING: Community-based cohort studies in twelve low-income countries between 1977 and 2013 in settings where treatment of wasting was not widespread. PARTICIPANTS: Children aged 6 to 59 months. RESULTS: Of the twelve anthropometric case definitions examined, four (weight-for-age Z-score (WAZ) <-2), (mid-upper arm circumference (MUAC) <125 mm), (MUAC < 115 mm or WAZ < -3) and (WAZ < -3) had the highest informedness in predicting mortality. A combined case definition (MUAC < 115 mm or WAZ < -3) was better at predicting deaths associated with weight-for-height Z-score <-3 and concurrent wasting and stunting (WaSt) than the single WAZ < -3 case definition. After the assessment of all criteria, the combined case definition performed best. The simulated workload for programmes admitting based on MUAC < 115 mm or WAZ < -3, when adjusted with a proxy for required intensity and/or duration of treatment, was 1·87 times larger than programmes admitting on MUAC < 115 mm alone. CONCLUSIONS: A combined case definition detects nearly all deaths associated with severe anthropometric deficits suggesting that therapeutic feeding programmes may achieve higher impact (prevent mortality and improve coverage) by using it. There remain operational questions to examine further before wide-scale adoption can be recommended.

Trends in inpatient and post-discharge mortality among young infants admitted to Kilifi County Hospital, Kenya: a retrospective cohort study.

OBJECTIVES: To describe admission trends and estimate inpatient and post-discharge mortality and its associated exposures, among young infants (YI) admitted to a county hospital in Kenya. DESIGN: Retrospective cohort study. SETTING: Secondary level hospital. PARTICIPANTS: YI aged less than 60 days admitted to hospital from January 2009 to December 2019: 12 271 admissions in 11 877 individuals. YI who were resident within a Kilifi Health and Demographic Surveillance System (KHDSS): n=3625 with 4421 admissions were followed-up for 1 year after discharge. PRIMARY AND SECONDARY OUTCOME MEASURES: Inpatient and 1-year post-discharge mortality, the latter in KHDSS residents. RESULTS: Of 12 271 YI admissions, 4421 (36%) were KHDSS-resident. Neonatal sepsis, preterm complications and birth asphyxia accounted for 83% of the admissions. The proportion of YI among under-5s admissions increased from 19% in 2009 to 34% in 2019 (Ptrend=0.02). Inpatient case fatality was 16%, with 66% of the deaths occurring within 48 hours of admission. The introduction of free maternity care in 2013 was not associated with a change in admissions or inpatient mortality among YI. During 1-year post-discharge, 208/3625 (5.7%) YI died, 64.3 (95% CI 56.2 to 73.7) per 1000 infant-years. 49% of the post-discharge deaths occurred within 1 month of discharge, and 49% of post-discharge deaths occurred at home. Both inpatient and post-discharge deaths were associated with low admission weight. Inpatient mortality was associated with clinical signs of disease severity, while post-discharge mortality was associated with the length of hospitalisation, leaving against advice and referral to a specialised hospital. CONCLUSIONS: YIs accounted for an increasing proportion of paediatric admissions and their overall mortality remains high. Post-discharge mortality accounts for a lower proportion of deaths but mortality rate is higher than among children aged 2-59 months. Services to address post-discharge mortality are needed and should focus on infants at higher risk.

How do children with severe underweight and wasting respond to treatment? A pooled secondary data analysis to inform future intervention studies.

Children with weight-for-age z-score (WAZ) <-3 have a high risk of death, yet this indicator is not widely used in nutrition treatment programming. This pooled secondary data analysis of children aged 6-59 months aimed to examine the prevalence, treatment outcomes, and growth trajectories of children with WAZ <-3 versus children with WAZ ≥-3 receiving outpatient treatment for wasting and/or nutritional oedema, to inform future protocols. Binary treatment outcomes between WAZ <-3 and WAZ ≥-3 admissions were compared using logistic regression. Recovery was defined as attaining mid-upper-arm circumference ≥12.5 cm and weight-for-height z-score ≥-2, without oedema, within a period of 17 weeks of admission. Data from 24,829 children from 9 countries drawn from 13 datasets were included. 55% of wasted children had WAZ <-3. Children admitted with WAZ <-3 compared to those with WAZ ≥-3 had lower recovery rates (28.3% vs. 48.7%), higher risk of death (1.8% vs. 0.7%), and higher risk of transfer to inpatient care (6.2% vs. 3.8%). Growth trajectories showed that children with WAZ <-3 had markedly lower anthropometry at the start and end of care, however, their patterns of anthropometric gains were very similar to those with WAZ ≥-3. If moderately wasted children with WAZ <-3 were treated in therapeutic programmes alongside severely wasted children, we estimate caseloads would increase by 32%. Our findings suggest that wasted children with WAZ <-3 are an especially vulnerable group and those with moderate wasting and WAZ <-3 likely require a higher intensity of nutritional support than is currently recommended. Longer or improved treatment may be necessary, and the timeline and definition of recovery likely need review.

Anthropometric deficits and the associated risk of death by age and sex in children aged 6-59 months: A meta-analysis.

Risk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6-59 months by age and sex. We categorised children into younger (6-23 months) and older (24-59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC < 125 mm; RR 1.35, p = 0.272 for WHZ < -2). For underweight and stunting, absolute risk of death was higher in younger (RR 2.57, p < 0.001) compared with older children (RR 2.83, p < 0.001). For all deficits, there were no differences in mortality risk for girls compared with boys. There were no differences in the risk of mortality between younger and older wasted children, supporting continued inclusion of all children under-five in wasting treatment programmes. The risk of mortality associated with underweight and stunting was higher among younger children, suggesting that prevention programmes might be justified in focusing on younger children where resources are limited. There were no sex differences by age in mortality risk for all deficits.

Evaluating the role of breastfeeding peer supporters' intervention on the inpatient management of malnourished infants under 6 months in Kenyan public hospitals.

BACKGROUND: The 2013 WHO guidelines for nutritional rehabilitation of malnourished infants under six months (u6m) focus on inpatient re-establishment of exclusive breastfeeding and recommends discharge when infant is gaining weight on breastmilk alone. Guided by a breastfeeding support tool, breastfeeding peer supporters (BFPS) can support implementation of these guideline by providing continuous individualised breastfeeding counselling to mothers of malnourished infants u6m. Recording and sharing information plays an important role in shaping in-patient care but little is known about recording practices for inpatient nutrition rehabilitation of infants u6m or how such practices affect care. We set out to explore introduction of BFPS into hospitals, and how it shaped the recording and practices of care for acutely malnourished infants u6m. METHODS: We applied a descriptive, exploratory design involving a pre and during intervention audit of the infant u6m inpatient records in two hospitals in Kenya, as well as pre- and post-intervention in-depth interviews with health workers involved in the care of admitted infants u6m. We developed an audit tool and used it to extract routine data on patient information from hospital records. Data were entered into a REDCap database and analyzed using STATA 17.0 software. We conducted thirty in-depth interviews with health workers exploring their care practices and their perceived effect of the presence of the BFPS on health workers treatment practices. We analysed interview data using thematic framework approach. RESULTS: A total of 170 and 65 inpatient files were available for the audit during the pre- and post-intervention period respectively. The presence of the BFPS seemed to have encouraged the recording of (i) breastfeeding status upon admission, (ii) breastfeeding management plan and (iii) reporting of its implementation and progress during treatment. The breastfeeding peer support intervention had a positive impact on breastfeeding recording and reporting practices. Health workers reported that the BFPS facilitated the recording of observed breastfeeding data and how their records influenced final inputs of breastfeeding support provided in the inpatient file. CONCLUSIONS: Guideline implementation tools facilitate effective application of guidelines and should accompany any guideline formulation process and have their effectiveness at recording and monitoring progress evaluated.

Enteral Feeding Practices for Very Preterm and Very Low Birth Weight Infants in Nigeria and Kenya.

Background: Optimizing nutrition in very preterm (28-32 weeks gestation) and very low birth weight (VLBW; 1,000 g to <1,500 g) infants has potential to improve their survival, growth, and long-term health outcomes. Aim: To assess feeding practices in Nigeria and Kenya for very preterm and VLBW newborn infants. Methods: This was a cross-sectional study where convenience sampling was used. A standard questionnaire was sent to doctors working in neonatal units in Nigeria and Kenya. Results: Of 50 respondents, 37 (74.0%) were from Nigeria and 13 (26.0%) from Kenya. All initiated enteral feeds with breastmilk, with 24 (48.0%) initiating within 24 h. Only 28 (56.0%) used written feeding guidelines. Starting volumes ranged between 10 and 80 ml/kg/day. Median volume advancement of feeds was 20 ml/kg/day (IQR 10-20) with infants reaching full feeds in 8 days (IQR 6-12). 26 (52.0%) of the units fed the infants 2 hourly. Breastmilk fortification was practiced in 7 (14.0%) units, while folate, iron, calcium, and phosphorus were prescribed in 42 (84.0%), 36 (72.0%), 22 (44.0%), 5 (10.0%) of these units, respectively. No unit had access to donor breastmilk, and only 18 (36.0%) had storage facilities for expressed breastmilk. Twelve (24.0%) used wet nurses whilst 30 (60.0%) used formula feeds. Conclusion: Feeding practices for very preterm and VLBW infants vary widely within Nigeria and Kenya, likely because of lack of locally generated evidence. High quality research that informs the feeding of these infants in the context of limited human resources, technology, and consumables, is urgently needed.

Prospective observational study of the challenges in diagnosing common neonatal conditions in Nigeria and Kenya.

OBJECTIVES: Accurate and timely diagnosis of common neonatal conditions is crucial for reducing neonatal deaths. In low/middle-income countries with limited resources, there is sparse information on how neonatal diagnoses are made. The aim of this study was to describe the diagnostic criteria used for common conditions in neonatal units (NNUs) in Nigeria and Kenya. DESIGN: Prospective observational study. Standard case report forms for suspected sepsis, respiratory disorders, birth asphyxia and abdominal conditions were co-developed by the Neonatal Nutrition Network (https://www.lstmed.ac.uk/nnu) collaborators. Clinicians completed forms for all admissions to their NNUs. Key data were displayed using heatmaps. SETTING: Five NNUs in Nigeria and two in Kenya comprising the Neonatal Nutrition Network. PARTICIPANTS: 2851 neonates, which included all neonates admitted to the seven NNUs over a 6-month period. RESULTS: 1230 (43.1%) neonates had suspected sepsis, 874 (30.6%) respiratory conditions, 587 (20.6%) birth asphyxia and 71 (2.5%) abdominal conditions. For all conditions and across all NNUs, clinical criteria were used consistently with sparse use of laboratory and radiological criteria. CONCLUSION: Our findings highlight the reliance on clinical criteria and extremely limited use of diagnostic technologies for common conditions in NNUs in sub-Saharan Africa. This has implications for the management of neonatal conditions which often have overlapping clinical features. Strategies for implementation of diagnostic pathways and investment in affordable and sustainable diagnostics are needed to improve care for these vulnerable infants.

Anthropometric Criteria for Identifying Infants Under 6 Months of Age at Risk of Morbidity and Mortality: A Systematic Review.

BACKGROUND: There is increasing global focus on small and nutritionally at-risk infants aged <6 months (<6 m). Current WHO guidelines recommend weight-for-length z-score (WLZ) for enrolment to malnutrition treatment programmes but acknowledge a weak evidence-base. This review aims to inform future guidelines by examining which anthropometric criteria best identify infants <6 m at high risk of mortality/morbidity. METHODS: We searched Medline, EMBASE, CINAHL, Global Health, Cochrane Library and POPLINE for studies conducted in low- and middle-income countries and published between 1990 and October 2020. We included studies reporting anthropometric assessment of nutritional status in infants <6 m and assessed the association with subsequent morbidity or mortality. RESULTS: A total of 19 studies were included in the final review, covering 20 countries, predominantly in sub-Saharan Africa. WLZ had poor reliability and poor prognostic ability to identify infants at risk of death. Mid-upper arm circumference (MUAC) and weight-for-age z-score (WAZ) were better at identifying infants at risk of mortality/morbidity. MUAC-for-age z-score did not perform better than using a single MUAC cut-off. Suggested MUAC cut-offs for this age group varied by context, ranging from 10.5 to 11.5 cm. The assessment for reliability showed that length was difficult to measure, making WLZ the least reliable indicator overall. CONCLUSION: Evidence from our review suggests that a change in current practice is necessary. To better identify small and nutritionally at-risk infants <6 m WAZ and/or MUAC rather than WLZ should be used. Future research should explore possible benefits for programme coverage, impact and cost-effectiveness. Research should also examine if context-specific MUAC thresholds are needed.

Maternal BMI is positively associated with human milk fat: a systematic review and meta-regression analysis.

BACKGROUND: Lack of robust estimates of human-milk nutrient composition and influential maternal factors, such as body composition, are barriers to informing nutrition policies and programs. OBJECTIVE: The objective was to understand the relation between maternal BMI and human-milk energy, fat, and/or total protein. METHODS: Four electronic databases (MEDLINE, Embase, CINAHL, and Web of Science) were searched. Outcomes assessed were human-milk energy (kcal/L), fat (g/L), and total protein (g/L) from mothers 1 to 6 mo postpartum. Studies with data on maternal BMI or weight and height that quantified human-milk energy, fat, or protein between 1 and 6 mo postpartum were eligible. Random-effects meta-regression weighted by the inverse of the study-level SE was completed for each of the 3 outcomes. The certainty of evidence for each outcome was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. RESULTS: A total of 11,373 titles and abstracts were identified, and after full-text screening, 69 articles of 66 studies were included. Meta-regression results showed a positive association between maternal BMI and human-milk fat (ß: 0.56 g/L; 95% CI: 0.034, 1.1; P = 0.04; I2 = 93.7%, n = 63 datapoints). There was no significant association between maternal BMI and human-milk energy (ß: 3.9 kcal/L; 95% CI: -1.6, 9.5; P = 0.16, I2 = 93.3%, n = 40 datapoints) or total protein (ß: 0.13 g/L; 95% CI: -0.16, 0.41; P = 0.37, I2 = 99.1%, n = 40 datapoints). The certainty of evidence for human-milk energy was low and the certainty of evidence for fat and total protein was very low. CONCLUSIONS: Meta-regression analysis of available literature suggested an association between maternal BMI and human-milk fat between 1 and 6 mo postpartum. Future studies are needed to confirm the relation between maternal BMI; variation in human-milk energy, fat, and protein content; and the implications for child growth and development. This review is registered with International Prospective Register of Systematic Reviews (PROSPERO 2018 CRD42018098808) at https://www.crd.york.ac.uk/prospero/.

Infant malnutrition treatment in Kenya: Health worker and breastfeeding peer supporter experiences.

Acute malnutrition in infants under 6 months (u6m) is increasingly recognised as a global public health problem. The World Health Organisation (WHO) guidelines for inpatient nutritional rehabilitation of infants u6m is re-lactation: the re-establishment of exclusive breastfeeding. Evidence suggests these guidelines are rarely followed in many low-income settings. Two studies of infant nutritional rehabilitation undertaken in three public hospitals in coastal Kenya employed breastfeeding peer supporters (BFPSs) to facilitate WHO guideline implementation. To explore the acceptability of the strategy to health workers (HWs) and the BFPSs, in-depth interviews were conducted with 20 HWs and five BFPSs in the three study hospitals. The HWs reported that the presence of the BFPSs changed the way infant nutritional rehabilitation was managed, increasing efforts at relactation and decreasing reliance on supplemental milk. BFPSs were said to help address staff shortages and had dedicated time to support and assist the mothers. Key to the success of the BFPSs was the social relationships they were able to establish with the mothers due to the similarity in their experiences and backgrounds. Despite the success of the BFPSs, human resource management and infrastructure challenges remained. BFPSs can successfully be employed to facilitate the implementation of the WHO guidelines for the nutritional rehabilitation of acutely malnourished infants u6m in hospitals in Kenya, establishing supportive social relationships and trust with the mothers of the acutely malnourished infants and helping to address the issue of human resource shortages.

Burden of disease and risk factors for mortality amongst hospitalized newborns in Nigeria and Kenya.

OBJECTIVE: To describe the patient population, priority diseases and outcomes in newborns admitted <48 hours old to neonatal units in both Kenya and Nigeria. STUDY DESIGN: In a network of seven secondary and tertiary level neonatal units in Nigeria and Kenya, we captured anonymised data on all admissions <48 hours of age over a 6-month period. RESULTS: 2280 newborns were admitted. Mean birthweight was 2.3 kg (SD 0.9); 57.0% (1214/2128) infants were low birthweight (LBW; <2.5kg) and 22.6% (480/2128) were very LBW (VLBW; <1.5 kg). Median gestation was 36 weeks (interquartile range 32, 39) and 21.6% (483/2236) infants were very preterm (gestation <32 weeks). The most common morbidities were jaundice (987/2262, 43.6%), suspected sepsis (955/2280, 41.9%), respiratory conditions (817/2280, 35.8%) and birth asphyxia (547/2280, 24.0%). 18.7% (423/2262) newborns died; mortality was very high amongst VLBW (222/472, 47%) and very preterm infants (197/483, 40.8%). Factors independently associated with mortality were gestation <28 weeks (adjusted odds ratio 11.58; 95% confidence interval 4.73-28.39), VLBW (6.92; 4.06-11.79), congenital anomaly (4.93; 2.42-10.05), abdominal condition (2.86; 1.40-5.83), birth asphyxia (2.44; 1.52-3.92), respiratory condition (1.46; 1.08-2.28) and maternal antibiotics within 24 hours before or after birth (1.91; 1.28-2.85). Mortality was reduced if mothers received a partial (0.51; 0.28-0.93) or full treatment course (0.44; 0.21-0.92) of dexamethasone before preterm delivery. CONCLUSION: Greater efforts are needed to address the very high burden of illnesses and mortality in hospitalized newborns in sub-Saharan Africa. Interventions need to address priority issues during pregnancy and delivery as well as in the newborn.

Growth monitoring and mortality risk in low birthweight infants: a birth cohort study in Burkina Faso.

Background: Wasting and underweight in infancy is an increasingly recognised problem but consensus on optimum assessment is lacking. In particular, there is uncertainty on how to interpret anthropometry among low birth weight (LBW) infants who may be growing normally. This research aimed to determine growth of infants from birth to two months (around age of vaccination) and the mortality risk of underweight LBW infants compared to normal birth weight (NBW) infants at two and six months age. Methods: A secondary analysis of a birth cohort of 1103 infants in Burkina Faso was conducted. Anthropometry was performed monthly from 0 to 12 months. We assessed associations with mortality using Cox proportional hazards models and assessed discriminatory values using area under receiver operating characteristics curves. Results: Eighty-six (7.8%) children died by age one year, 26/86 (30%) and 51/86 (59%) within two and six months, respectively. At age two months, weight gain since birth did not better discriminate mortality risk than current weight-for-age (P=0.72) or mid-upper arm circumference (P=0.21). In total, 227 (21%) LBW infants had increased risk of mortality: adjusted hazards ratio (aHR) 3.30 (95%CI 2.09 to 4.90). Among infants who were underweight at two and six months, LBW infants (64% and 49%, respectively) were not at reduced risk of death compared to NBW infants (aHR 2.63 (95%CI 0.76 to 9.15) and 2.43 (95%CI 0.74 to 7.98), respectively). Conclusion: Assessing weight gain since birth does not offer advantages over immediate anthropometry for discriminating mortality risk. LBW infants who are later identified as underweight require care to help prevent mortality.