Characteristics and treatment outcomes of malnutrition among infants aged less than 6 months in North – East Nigeria (2019 – 2022)

Recommendations for the management of malnutrition among infants aged less than 6 months (<6 m) are based on limited evidence. This study aimed to describe the characteristics, treatment outcomes and outcome ‐ associated factors among mal-nourished infants <6 m admitted at Médecins Sans Frontières (MSF) inpatient and ambulatory therapeutic feeding centres (ITFC and ATFC) in North – East Nigeria, 2019 – 2022. We conducted a descriptive analysis of the cohorts and logistic regression to measure the association between two selected outcomes — inpatient mortality and defaulting from the ambulatory programme — and possible factors associated. In total, 940 infants <6 m were admitted at ITFC. Most of them presented severe acute malnutrition and comorbidities, with diarrhoea being the most frequent. On discharge, 13.3% ( n = 125) of infants were cured, 72.9% ( n = 684) stabilized (referred to ATFC), 6.5% ( n = 61) left against medical advice and 4.2% ( n = 39) died. The median length of hospital stay was 10 days [IQR 7 – 14]. A hospital stay shorter than 10 days was significantly associated with inpatient mortality (aOR = 12.51, 95% confidence interval [CI] = 3.72 – 42.11, p ≤ 0.01). Among 561 infants followed up at the ATFC, only 2.8% reported comorbidities. On discharge, 80.9% ( n = 429) were cured, 16.2% ( n = 86) defaulted and 1.1% ( n = 6) died. Male sex (aOR = 1.94, 95% CI = 1.15 – 3.27, p = 0.01), internally displaced status (aOR = 1.70, 95% CI = 1.05 – 2.79, p = 0.03) and < − 3 WLZ (aOR = 1.95, 95% CI = 1.05 – 3.63, p = 0.03) were significantly associated with programme defaulting. Stabilization and recovery rates among malnourished infants <6 m in the studied project align with acceptable standards in this humanitarian setting. Notable defaulting rates from outpatient care should be further explored.


| INTRODUCTION
The burden of malnutrition among infants aged less than 6 months (<6 m) has been increasingly recognized globally.It is estimated that 24.5 million infants <6 m are acutely malnourished (defined as weight-for-length [WLZ] <−2 z-score) in 54 low-and middle-income countries (Kerac et al., 2021).About half of the global burden of stunting in early childhood originates during the 500 days between conception and 6 months of age (UNICEF, 2023).Malnutrition among infants <6 m can be triggered by inadequate breastfeeding, but numerous maternal, infant and household risk factors are associated with this complex and multi-faceted problem (Kerac et al., 2019(Kerac et al., , 2021;;Munirul Islam et al., 2019).
Infants are particularly at heightened risk of malnutrition in low-income and humanitarian settings, where conditions negatively affect maternal wellbeing, hinder breastfeeding practice and limit access to food and health care services (Al Gasseer et al., 2004;Dall'Oglio et al., 2020;Hirani et al., 2019).Several studies reporting on nutritional programmes operating in humanitarian settings indicate concerns about a high proportion of malnourished infants <6 m identified and highlight challenges associated with their management.(Dureab et al., 2019;Grijalva-Eternod et al., 2017;Haidar et al., 2017;Oberlin, 2006).The treatment of infants <6 m can be more complex than that of older children, including difficulties in supporting the re-establishment of breastfeeding (Haidar et al., 2017;Oberlin, 2006) and lack of safe therapeutic feeding options, such as the ready-to-use therapeutic food (RUTF) intended for children older than 6 months (Burrell et al., 2020;Munirul Islam et al., 2019).
In 2013, the WHO guidelines for the management of severe acute malnutrition included, for the first time, specific recommendations for infants <6 m.Those-largely based on scarce and lowquality evidence-were focused on inpatient management and outpatient care was mentioned as a possibility for uncomplicated cases, but without indications about how to practically apply it (World Health Organization, 2013).The WHO guidelines have been updated in 2023, including a special section on the management of infants <6 m at risk of poor growth and development-which encompasses malnourished infants <6 m.
The new guidelines incorporate recommendations and good practice statements for programme admission, referral and exit criteria, management of lactation difficulties, milk supplementation and interventions focusing on mothers/caregivers.Yet, the scientific evidence focusing on infants <6 m at risk of poor growth and development remains scarce and of limited quality for most areas, while this paucity of data is especially critical for informing outpatient and community-based management (World Health Organization, 2023).Exploring approaches to treatment implementation and outcomes, and identifying outcome-associated factors among infants <6 m and their caregivers is key to closing the evidence gaps and helping with shaping future recommendations.
The North-East region of Nigeria is considered a protracted humanitarian setting, troubled by a long-standing conflict, internal displacement, disruption of livelihoods and food insecurity, while exposed to drought, flooding and disease outbreaks.Over 1.3 million children under 5 and 152,000 pregnant and lactating women were estimated to be acutely malnourished between January and December 2022 in this region (IPC, 2022).Displacement in this area has been linked to a 57% increase in the likelihood of suffering from acute malnutrition, with notable effects among infants (Iacoella & Tirivayi, 2020).Since 2018, Médecins Sans Frontières (MSF) has run a project in Maiduguri, the capital of Borno State in North-East Nigeria, which focuses on nutrition and also provides outreach health support for internally displaced populations (IDPs).The project provides inpatient and ambulatory care for malnourished children aged 1 month to 10 years, including specific therapeutic management for infants aged <6 m (i.e., 1-5 months).
This study aims to describe the characteristics (demographic, anthropometry, comorbidities) and programmatic outcomes of infants aged 1-5 months admitted at MSF inpatient and ambulatory nutritional programmes in Maiduguri, from 2019 to 2022.It also aims to identify factors associated with selected outcomes (i.e., inpatient mortality and defaulting from the ambulatory programme).

| Study design
This is a hospital-based observational cohort study using previously collected data from an MSF nutrition project in Maiduguri, North-East Nigeria.The study follows the STROBE guidelines for reporting observational studies (STROBE, nd).

Key messages
• We found acceptable stabilization and recovery rates for malnourished infants aged less than 6 months (<6 m) receiving inpatient and ambulatory care in this humanitarian setting.
• There was a considerable proportion of defaulters from the ambulatory programme.Although some potential factors associated with programme defaulting were identified in this study, barriers affecting adherence to ambulatory care should be better explored in the community.
• The factors influencing treatment outcomes among malnourished infants <6 m should be more carefully explored in prospective studies, including additional variables related to infant and maternal characteristics, feeding practices and treatment components.

| Study participants
The eligible participants for this study were children aged 1-5 months admitted to MSF ITFC and ATFC in Maiduguri from 1 July 2019 until 30 June 2022.There were no exclusion criteria.

| Data sources and management
Programmatic data are collected routinely and used to monitor the activities and the overall quality of the services offered.The data were extracted from the existing databases at the MSF project.
ITFC data were obtained from a designated Excel database, routinely filled in by data encoders at the MSF facility using the information recorded on each patient file.Patient records at ATFC are directly entered into an electronic application (EasyNut) which can later be transferred to an Excel file.Data management in the project is supervised regularly by the Data Manager who is supported by an epidemiologist covering projects in the country.
The ITFC and ATFC databases are not linked (i.e., different patient codes are used) and therefore we present them as two separate cohorts.However, both cohorts contain mostly the same infants since all infants admitted at ATFC were referred for follow-up after ITFC discharge.Based on WLZ criteria, 75.2% of infants presented with severe acute malnutrition (<−3 z-score) and 18.5% had moderate acute malnutrition (−3 to <−2 z-score).

| Data analysis
Most infants were diagnosed with comorbidities, with diarrhoea/ gastroenteritis as the most frequent (33.6%), followed by respiratory infections (21.4%).In 23.5% (n = 221) of cases, comorbidities were present but not specified.Through routine screening on admission, 2.8% of infants were diagnosed with malaria, and less than 2% of infants had HIV and tuberculosis.

| ATFC
Over the study period, 561 ATFC admissions of infants aged 1-5 months were registered, accounting for 3% of total ATFC admissions from 1 to 59 months at the MSF facility.Infants' characteristics are presented in Table 4. Comorbidities were only reported in 2.8% of cases.In total, 39 (6.9%) and 29 (5.1%) cases were excluded after the cleaning of WAZ and WLZ variables, respectively.On admission, infants had a median weight of 3.5 kg  4).

| DISCUSSION
This study describes the characteristics and treatment outcomes of infants aged 1-5 months admitted at MSF ITFC and ATFC in Maiduguri, North-East Nigeria, from July 2019 to July 2022.It also reports factors associated with two selected programme outcomes: inpatient mortality and defaulting from the ATFC programme.
T A B L E 2 Characteristics of infants aged 1-5 months admitted at ITFC and factors associated with inpatient mortality (n = 940).Most infants admitted at ITFC were recorded as having acute malnutrition and comorbidities.Diarrhea was the most common, as in other studies (Baazab et al., 2022;Singh et al., 2014;Vygen et al., 2013).The presence of certain conditions, symptoms and signs, as well as unspecified comorbidities, was identified to be factors associated with death at the MSF ITFC.These results are difficult to interpret with incomplete records of the comorbidities and clinical presentation of infants on admission.Reporting should be improved at the project level to allow the identification of critical clinical risk factors among infants <6 m.
The median ITFC length of stay at this facility (10 days) was longer than the one reported in other studies looking at inpatient care for infants <6 m (Baazab et al., 2022;Mwangome et al., 2020).
We observed that ITFC length of stay increased over time in the study setting.This can be explained by progressive efforts to strengthen breastfeeding support in this project, striving for most mothers to achieve exclusive breastfeeding before discharge.The re-establishment of breastfeeding can be a lengthy process, influenced by the infant's age, previous feeding methods, the mother's motivation and skilled support (Amat Camacho, von T A B L E 3 Distribution of ITFC and ATFC admissions overtime, discharge outcomes and length of stay.Schreeb et al., 2023).Our study showed that the duration of inpatient treatment shorter than 10 days was strongly associated with inpatient mortality, as it was recently reported in a similar study.(Baazab et al., 2022).This finding could be interpreted as a case of reverse causality.Yet, Baazab et al. (2022) et al., 2023).Although this approach might be feasible in some contexts, it seems difficult to be implemented in this study setting, given the instability, displacement and food security deterioration, which already overburden the current nutritional programmes covering this region.Nevertheless, the key features contributing to safe and effective outpatient management of malnourished infants <6 m need to be further investigated in this context.
We identified a considerable proportion of defaulters from ATFC, which was above the acceptable threshold in the Sphere Standards (<15%) (Sphere Project, 2018).Our analysis indicated that infants with worse WLZ anthropometric values were more likely to default, and a similar trend was seen in infants with lower MUAC scores, although the latter was not statistically significant.It could be hypothesized that more severely malnourished infants might have abandoned the programme due to the aggravation of their health status and death in the community.Special attention should also be given to the follow-up of IDPs since they were also found more likely to drop out of the programme.The reasons behind defaulting among caregivers with infants <6 m should be more closely explored in this context.For instance, looking at the possible logistic difficulties in attending the facility weekly or whether a longer time of admission within the programme due to slower or stagnant weight gain might be contributing factors.
An important proportion of WAZ and WLZ extreme values were flagged during data cleaning, more prominently in the ITFC cohort.
The difficulties in obtaining reliable WLZ data in young infants have been previously recognized (Grijalva-Eternod et al., 2017).Several authors already advocate for considering alternative anthropometry measurements to better identify malnourished infants <6 m more at risk, since MUAC and WAZ appear better associated with mortality than WLZ (Mwangome et al., 2012(Mwangome et al., , 2017)).Not all infants admitted at the studied MSF facility had their MUAC measurements recorded because this recommendation was not yet included in guidelines focusing on infants <6 m until its latest 2023 version.Moreover, context-specific MUAC thresholds have not been determined for this age group (Hoehn et al., 2021).We did not identify any significant association between different WAZ, WLZ or MUAC cut-offs and mortality with the statistical analysis applied in this cohort.
Considering current evidence, and the lack thereof, anthropometric criteria appear to have limited application in this age group.A broader approach to identifying infants <6 m at risk of poor growth and development should be followed, as recommended by the C-MAMI tool and the latest WHO guidelines, where clinical, feeding and maternal factors should be more critically assessed and considered to guide management actions (ENN et al., 2018;World Health Organization, 2023).Information about these factors could be recorded and encoded in programme databases to allow future comprehensive analyses.
At the study facility, infants <6 m comprised 9.5% of all children aged up to 59 months admitted at the ITFC, and 3% of those followed up at the ATFC.Compared with previous studies, this figure is higher than the proportion of infants <6 m admitted at MSF ITFC found in Niger (3.1%) (Vygen et al., 2013), but lower than the average proportion of young infants reported in a study including different IQR 3-4.3) and a median length of 54.5 cm.MUAC was only measured in 14.9% (n = 84) of infants, and the median MUAC score was 108 cm.A total of 35.9% (n = 191) and 33.2% (n = 177) of infants presented with severe and moderate acute malnutrition, respectively.WAZ was <−3 z-score in 78.9% (n = 412) of infants and the median weight on exit was 4.65 kg (IQR 4-5.3).The median duration of follow-up for infants at the ATFC was 49 days (IQR 35-69).At discharge, 80.9% (n = 429) were cured, 16.2% (n = 86) defaulted and 1.1% (n = 6) died.Logistic regression analysis was done to identify factors associated with defaulting from the ATFC programme.Male sex (aOR = 1.94, 95% CI = 1.15-3.27,p = 0.01), IDP status (aOR = 1.70, 95% CI = 1.05-2.79,p = 0.03) and < −3 WLZ (aOR = 1.95, 95% CI = 1.05-3.63,p = 0.03) were significantly associated with programme defaulting (Table therapeutic feeding programmes in low-income countries (15.9%)(Grijalva-Eternod et al., 2017).Our study could not determine whether the burden of malnutrition among infants <6 m reflects the actual prevalence of malnutrition in the MSF project catchment area.However, the latest DHS survey conducted in Nigeria (2018), estimated a 7% prevalence of acute malnutrition (WLZ <−2 z-score) and a 16.8% prevalence of undernutrition (WAZ <−2 z-score) among infants <6 m in the country (ICF, [NPC] Nigeria, 2019).These figures underline the importance of measures to strengthen available support for mothers and infants <6 m at risk of poor growth and development.Lastly, we observed that the number of overall admissionsincluding those of children aged more than 6 months-increased overtime, with a substantial rise from July 2021.It should be noted that the location of the project within Maiduguri changed during the summer of 2022, which might be linked to the increase in the number of cases.Nevertheless, our results could also mirror recent reports that highlight the overall deterioration of food security in Nigeria and the consequent increase of children at risk of malnutrition.A United Nations report published in January 2023, estimates that over 25 million people in Nigeria could face food insecurity this year, a 47% increase from the 17 million people who were already at risk of going hungry in the previous year, mainly due to the ongoing insecurity, protracted conflicts and the projected rise in food prices (NFSS, 2022; Save The Children, 2023).
Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/mcn.13676,Wiley Online Library on [11/06/2024].See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions)on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License ITFC and ATFC admission and discharge criteria for infants <6 m at the MSF facility in Maiduguri (based on MSF protocol and adapted to the project context).No medical complications or possible to control at home -Caregiver feels prepared for discharge and the family situation is as supportive as possible -WAZ/WLZ ≥−2 on two consecutive visits and MUAC ≥125 mm -Adequate weight gain over at least 2 weeks of approximately 10-20 g/day.-Absence of oedema -Breastfeeding effectively or feeding well with BMS Left against medical advice: Leaves the hospital despite medical advice to continue inpatient treatment Nonrespondent: Exits the programme after 12 weeks of treatment, with stagnant weight, dietary treatment well observed, WLZ >−3 and absence of medical comorbidity Death: Dies while admitted Death: Dies within 2 weeks from the last ATFC visit Abbreviations: ATFC, Outpatient Therapeutic Feeding Centre; BMS, breast milk substitute; ITFC, Inpatient Therapeutic Feeding Centre; MUAC, middle-upper arm circumference; WAZ, weight-for-age z-score; WLZ, weight-for-length z-score.AMAT CAMACHO ET AL. | 3 of 12 17408709, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/mcn.13676,Wiley Online Library on [11/06/2024].See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions)on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License increase supplementation up to 200 kcal/kg/day.Before discharge, the caregiver receives practical health education on how to prepare and give BMS to the infant once at home, safely and appropriately.In parallel to infant treatment, mothers and wet nurses receive adequate nutrition-a balanced diet and two sachets of RUTF daily-During outpatient consultations, infants' weight and length are routinely measured, while occasionally middle-upper arm circumference (MUAC) is also assessed.Caregivers can report infants' comorbidities or feeding difficulties, and they are referred to health promotors or clinical staff for breastfeeding support or inpatient hospitalization if needed.If the infant is not breastfed, caregivers receive enough quantity of infant formula (Nutribio ® ) until the next weekly consultation, according to the infant's weight.All lactating mothers or wet nurses receive two sachets per day of RUTF as nutritional supplements during the follow-up period.
Nigeria, and the MSF Ethics Review Board for a-posteriori analyses of routinely collected data.It was conducted with permission from the Medical Director, Operational Center Brussels, Médecins Sans Frontières.The data set was compiled from routine clinical databases and does not include any patient identifying information, to preserve patient confidentiality.A Data Sharing Agreement was signed between MSF and the University of Piemonte Orientale for the purpose of this research.
(Crowe et al., 2014)they were reported.Weight-for-age z-score (WAZ) and WLZ were automatically calculated using reported weight, height, sex and age, based on the 2006WHO Child Growth   Standards.(WorldHealthOrganization,2006)Severeoutliers of anthropometric values were excluded following recommendations for anthropometric data cleaning (WAZ <−6 or >5 z-scores and WLZ <−5 or >5 z-scores)(Crowe et al., 2014).Categorical variables were summarized as counts and percentages, and mean, median and interquartile range (IQR) were calculated for numerical variables.Logistic regression was employed to measure the association between relevant outcomes (dependent variable) and possible explanatory variables (independent).The selected outcomes, considered as dichotomous variables, were mortality at ITFC (death vs. alive at discharge) and defaulting from the ATFC programme (defaulting vs. nondefaulting).The independent variables were infant age, sex, IDP status, WAZ, WLZ, MUAC, comorbidities, seasonality of admission and length of stay.Univariate analysis was undertaken, obtaining crude odds ratio (OR) with 95% confidence intervals (CI) for each variable.A p < 0.05 was considered statistically significant.For2.6 | Ethical considerationsThis study went through an ethical review and was granted an exemption from the Health Research Ethical Committee in Borno State, Almost all infants (98.5%) were recorded as presenting with a marasmic form of malnutrition.Regarding anthropometry, 204 (21.7%) and 250 (26.5%) cases were excluded when applying data cleaning criteria for WAZ and WLZ values, respectively.Excluding those, the median weight was 3.15 kg (IQR 2.5-3.9) and the median length was 55 cm) on admission.The median MUAC score, encoded for 41.1% of infants, was 100 cm (IQR 88-108).