Thesis Abstract

<p> </p><h2>Abstract
</h2><div><p>Severe acute malnutrition (SAM) affects ~4 million infants under 6 months (u6m) worldwide, but evidence underpinning their care is “very low” quality. To inform future research and policy, the objectives of our study were to identify risk factors for infant u6m SAM and describe the clinical and anthropometric outcomes of treatment with current management strategies. We conducted a prospective cohort study in infants u6m in Barisal district, Bangladesh. One group of 77 infants had SAM (weight‐for‐length Z‐score [WLZ] &lt;−3 and/or bipedal oedema); 77 others were “non‐SAM” (WLZ ≥−2 to &lt;+2, no oedema, mid‐upper‐arm circumference ≥125 mm). All were enrolled at 4–8 weeks of age and followed up at 6 months. Maternal education and satisfaction with breastfeeding were among factors associated with SAM. Duration of exclusive breastfeeding was shorter at enrolment (3·9 ± 2.1 vs. 5.7 ± 2.2 weeks, <em>P</em>&nbsp;&lt; 0.0001) and at age 6 months (13.2 ± 8.9 vs. 17.4 ± 7.9 weeks; <em>P</em>&nbsp;= 0.003) among SAM infants. Despite referral, only 13 (17%) reported for inpatient care, and at 6 months, 18 (23%) infants with SAM still had SAM, and 3 (3.9%) died. In the non‐SAM group, one child developed SAM, and none died. We conclude that current treatment strategies have limited practical effectiveness poor uptake of inpatient referral being the main reason. World Health Organization recommendations and other intervention strategies of outpatient‐focused care for malnourished but clinically stable infants u6m need to be tested. Breastfeeding support is likely central to future treatment strategies but may be insufficient alone. Better case definitions of nutritionally at‐risk infants are also needed.</p></div><div><strong>Keywords </strong>breastfeeding, infants under 6 months, moderate acute malnutrition, mortality, risk factors, severe acute malnutrition</div> <br><p></p>

Thesis Overview

<p> </p><div><h2>1. INTRODUCTION</h2><p>Undernutrition is responsible for 45% of all under‐5 child deaths (Black et al., <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0003">2013</a>) and affects progress towards numerous Sustainable Development Goals (Greenslade, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0010">2015</a>). Target 2.2 of Sustainable Development Goals 2 (Zero Hunger) aims to “By 2030, end all forms of malnutrition, including stunting and wasting in children under 5 years of age” (Sustainable Development Goals, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0030">2015</a>).</p><p>Over the last decade, the treatment of malnourished children aged 6–59 months has been revolutionized by a public‐health focused model of care, “Community Management of Acute Malnutrition” (CMAM; Bhutta et al., <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0002">2017</a>; Trehan &amp; Manary, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0031">2015</a>). Yet, despite some 4 million infants worldwide being severely wasted (Kerac et al., <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0015">2011</a>) with a higher risk of death than older children (Grijalva‐Eternod et al., <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0011">2017</a>), malnourished infants aged under 6 months (u6m) have long been neglected (Kerac, Mwangome, McGrath, Haider, &amp; Berkley, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0018">2015</a>). This problem was most recently highlighted in the updated World Health Organization (WHO, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0034">2013</a>) guidelines on “The Management of Severe Acute Malnutrition (SAM) in Infants and Children.” Although this document includes a chapter on infants u6m (for the first time), “very low quality” underlying evidence is acknowledged (WHO, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0034">2013</a>). Others, including 64 national and international experts who contributed to a 2015 Child Health and Nutrition Research Initiative research prioritization exercise, have also highlighted major evidence gaps around this vulnerable patient group (Kerac et al., <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0018">2015</a>). Especially lacking is evidence for the potential safety and effectiveness of home‐based treatment of clinically stable infants u6m with SAM (Kerac et al., <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0018">2015</a>).</p><p>Bangladesh guidelines are typical of almost all current national SAM guidelines (Kerac et al., <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0014">2017</a>) in that they only describe inpatient care (IPHN/DGHS/MoHFW/PRB, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0012">2008</a>). As in the early days of CMAM for older children, a shift to outpatient/community care is a significant paradigm change that is politically and programmatically sensitive (Kerac et al., <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0018">2015</a>).</p><p>To move forward, data on potentially modifiable risk factors and outcomes using current inpatient‐only treatments are needed. This is vital need for researchers, policymakers, and programme managers to design and test better future interventions. Our goal was to address these research gaps. Our first aim was to identify risk factors associated with infant u6m SAM and, second, to describe the clinical and anthropometric outcomes of treatment using current management strategies.</p></div><div><div><a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#">Go to:</a></div><h2>2. PARTICIPANTS AND METHODS</h2><div><h3>2.1. Study design and participants</h3><p>We conducted a prospective cohort study. This involved two groups, each consisting of 77 infants aged 4–8 weeks (the age when future interventions to treat infant u6m SAM will be anticipated to begin; Mwangome, Fegan, Fulford, Prentice, &amp; Berkley, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0024">2012</a>). One group comprised infants with SAM as defined by current WHO guidelines: weight‐for‐length Z‐score (WLZ) &lt;−3 and/or bilateral nutritional oedema (WHO, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0034">2013</a>); the other comprised age‐ and sex‐matched infants who were not severely malnourished (non‐SAM) defined as WLZ ≥−2 to &lt;2 and mid‐upper‐arm circumference (MUAC) ≥125 mm. Exclusions were infants from twin/multiple pregnancies and those with obvious congenital anomalies that could affect feeding (e.g., cleft lip or palate).</p><p>Ethical approval was obtained from the Institutional Review Board of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b; PR14112). Written informed consent was obtained from the infants' parents or legal guardians. The study is registered with the ISRCTN trial registry: <a target="_blank" rel="nofollow" href="http://www.isrctn.com/ISRCTN12494235">http://www.isrctn.com/ISRCTN12494235</a>.</p></div><div><h3>2.2. Variables</h3><p>The primary outcome was the proportion of infants who died or who had SAM (defined as per WHO criteria as WLZ &lt;−3 and/or MUAC &lt;115 mm and/or oedema) at age 6 months (180 completed days). Key secondary outcomes were changes in and absolute values of weight‐for‐length z‐score (WLZ), weight‐for‐age z‐score (WAZ), and length‐for‐age z‐score (LAZ).</p><p>Maternal mental health status was assessed using the WHO Self Reporting Questionnaire 20 (SRQ 20; WHO, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0033">1994</a>). Mothers who had a high total score (≥13) or who answered “Yes” to question no. 17 (“Has the thought of ending your life been on your mind?”) were referred to the outpatient psychiatry department at the nearby Sher‐e‐Bangla Medical College Hospital, Barisal, for appropriate management.</p><p>At cohort end line (age ≥ 6 months), infants' vital status, anthropometry, and dietary history were repeated.</p></div><div><h3>2.3. Data collection procedures</h3><div><p></p><h4>2.3.1. Anthropometry</h4><p>Anthropometric assessments were performed following the standard procedures (SMART, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0028">2017</a>). Length was measured using a portable length measuring board to 0.1 cm (Shorrboard, Weigh and Measure, LLC, Maryland, USA). Weight was measured using a digital scale accurate to 5 g (Digital Kinlee, Taiwan). MUAC was measured with UNICEF measuring tapes to 1 mm. Infants' reported birth date was verified against a birth certificate or immunization card whenever possible. Oedema was assessed by pressing the upper side of both feet by pressing for 3 s. Maternal anthropometry was measured only for the prospective cohort study at enrolment: Weight was measured with a scale accurate to 100 g and height by a height board graduated to the nearest 0.1 cm. Regular checks of weighing scale and length/height board calibration were carried out with a known weight and length, respectively.</p></div><div><p></p><h4>2.3.2. Data collection procedures</h4><p>SAM “case” infants were identified by household visits. Age‐ and sex‐matched controls were also selected by household visits in Barisal district of Bangladesh. Study participants were identified by the set criteria as mentioned above.</p><p>For both parts of the study, data were collected electronically: This enabled immediate validation of key variables. Supervisors also checked incoming data daily for completeness and consistency.</p></div></div><div><h3>2.4. Sample size estimation and statistical analysis</h3><p>Sample size for the prospective cohort study was estimated for comparing outcomes in the exposed group (SAM) and unexposed group (non‐SAM) assuming that 25% of the participants in the SAM group would have SAM at 6 months of age and 6.3% of the participants in the non‐SAM group would have SAM at the same time point (the prevalence of SAM in infants u6m in Bangladesh during designing the survey; NIPORT, Mitra, &amp; ICF, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0027">2013</a>). With 5% level of significance and 80% power, 77 infants were required per group, assuming approximately 25% loss to follow‐up at the end of 6 months. The following formula was used for sample size estimation: [(pA1−pA/κ+pB1−pB]z1−α/2+z1−β/pA−pB2 [available at <a target="_blank" rel="nofollow" href="http://powerandsamplesize.com/Calculators/Compare-2-Proportions/2-Sample-Equality">http://powerandsamplesize.com/Calculators/Compare‐2‐Proportions/2‐Sample‐Equality</a>].</p><p>Anthropometric z‐scores (standard deviation scores) were calculated from raw age, sex, length, and weight data using WHO, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0032">2006</a>&nbsp;growth standards and WHO Anthro software (WHO, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0032">2006</a>). LAZs and WLZs were calculated for infants who were ≥45 cm long (WHO 2005). WAZs were calculated for all infants. Those with extreme values were excluded from analysis following standard WHO “cleaning rules,” WAZ &lt;−6.0 or WAZ &gt;+5.0, LAZ &lt;−6.0 or LAZ &gt;+6.0, and WLZ &lt;−5.0 or WLZ &gt;+5.0 <em>SD</em>&nbsp;(Crowe, Seal, Grijalva‐Eternod, &amp; Kerac, <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-bib-0009">2014</a>).</p><p>Potential explanatory variables were grouped under household characteristics, maternal characteristics, and infant characteristics. Differences between groups were tested using chi‐squared tests for proportions, Student's <em>t</em>&nbsp;test for normally distributed continuous variables, and Mann–Whitney <em>U</em>&nbsp;test for skewed continuous variables. Multivariable logistic regression was performed for adjustments of different variables and potential risk factors for SAM. Multiple linear regression analysis was also used to adjust the potentially confounding variables when different variables were compared for test of significance. The potential confounders were considered to be the age of the infants at the time of enrolment, monthly income, and maternal education. All the tests were considered as significant at <em>P</em>&nbsp;&lt; 0.05. Statistical analysis was done with the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.).</p></div></div><div><div><a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#">Go to:</a></div><h2>3. RESULTS</h2><div><h3>3.1. Sociodemographic characteristics</h3><p>Infants in the SAM group were over a week younger at enrolment than those in the non‐SAM group (5.1 ± 1.2 weeks vs. 6.5 ± 1.2 weeks, <em>P</em>&nbsp;= 0.001). Median household monthly income was significantly lower (<em>P</em>&nbsp;= 0.007) in SAM group, and mothers were less educated (<em>P</em>&nbsp;= 0.005) also. Fewer households in the SAM group had electricity (<em>P</em>&nbsp;= 0.013). Other reported sociodemographic characteristics were comparable between groups (Table <a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/table/mcn12642-tbl-0001/">1</a>).</p><div><h3>Table 1</h3><div><p>Sociodemographic characteristics of the study participants</p></div><div>VariablesSAM (<em>n</em>&nbsp;= 77)Non‐SAM (<em>n</em>&nbsp;= 77)<em>P</em>Age in weeks<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-note-0003">a</a>5.1 ± 1.26.5 ± 1.20.001<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-note-0005">c</a>Female sex, <em>n</em>&nbsp;(%)33 (43)33 (43)1.00Mother's age (year)<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-note-0003">a</a>24.7 ± 5.923.4 ± 4.70.13<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-note-0005">c</a>Maternal education (years)6.4 ± 3.68.1 ± 3.80.005<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-note-0005">c</a>Family income (US$), median (interquartile range)<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-note-0004">b</a>90 (71, 128)115 (83, 192)0.007<a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/#mcn12642-note-0006">d</a>Has electricity, <em>n</em>&nbsp;(%)47 (61)62 (80)0.013Source of drinking water, <em>n</em>&nbsp;(%)0.50Stand pipe2 (3)0 (0)Tube well75 (97)77 (100)Source of water other household purposes, <em>n</em>&nbsp;(%)0.45Piped into dwelling3 (4)8 (10)Stand pipe3 (4)1 (1)Tube well16 (21)16 (21)Surface water55 (71)52 (68)Floor material, <em>n</em>&nbsp;(%)0.11Earth/sand/clay/mud/dung65 (84)56 (73)Cement/concrete12 (16)21 (27)Exterior wall of the house, <em>n</em>&nbsp;(%)0.51Cement/concrete10 (8)16 (12)Bricks4 (3)6 (5)Metal/asbestos sheets76 (58)74 (57)Other (cane/palm/trunks/bamboo/wood planks/shingles)10 (8)4 (3)Source of fuel, <em>n</em>&nbsp;(%)0.26Wood54 (70)63 (82)Straw/shrubs/grass18 (23)9 (11)Other (LPG/gas/kerosense/charcoal/animal dung)5 (7)5 (7)Types of toilet facility for household members, <em>n</em>&nbsp;(%)0.68Flush to septic tank/flush to pit latrine/ventilated improved pit latrine10 (13)15 (20)Pit latrine with slab65 (84)58 (75)Pit latrine without slab/open pit2 (3)4 (5)Practice of hand washing with soap while helping the child after defecation, <em>n</em>&nbsp;(%)0.58Always24 (31)26 (34)Sometimes21 (27)16 (21)Rarely18 (23)24 (31)Never14 (18)11 (14)Practice of hand washing with soap before preparing food, <em>n</em>&nbsp;(%)0.50Always13 (27)15 (20)Sometimes17 (22)10 (13)Rarely17 (22)21 (27)Never30 (39)31 (40)Practice of hand washing with soap after using toilet, <em>n</em>&nbsp;(%)0.59Always50 (65)55 (71)Sometimes16 (21)16 (21)Rarely8 (10)5 (7)Never3 (4)1 (1)</div><div><a target="_blank" rel="nofollow" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586027/table/mcn12642-tbl-0001/?report=objectonly">Open in a separate window</a></div><div><div><p><em>Note</em>. All tests of significance are Pearson chi‐square test, unless mentioned. Level of significance &lt;0.05. SAM: severe acute malnutrition.</p></div><div>aMean ± <em>SD</em>.</div><div>bMedian Interquartile Range.</div><div>cStudent's <em>t</em>&nbsp;test.</div><div>dMann–Whitney <em>U</em>&nbsp;test.</div></div></div></div></div> <br><p></p>