PLoS ONE
Public Library of Science
image
A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi
DOI 10.1371/journal.pone.0246267 , Volume: 16 , Issue: 2 , Pages:
Article Type: research-article, Article History
Abstract

Introduction

Moderate to severe acute malnutrition (SAM/MAM) and severe anaemia are important and associated co-morbidities in children aged less than five years. Independently, these two morbidities are responsible for high risk of in-hospital and post-discharge deaths and hospital readmissions. The primary objective of this study is to investigate the risk of death among severely anaemic children with moderate to severe acute malnutrition compared to children with severe anaemia alone.

Methods

This was a retrospective analysis of data collected from a large prospective study that was investigating severe anaemia in children aged less than 5 years old. The study was conducted at Queen Elizabeth Central Hospital in Blantyre and Chikhwawa district hospital in southern Malawi. Children aged less than five years old; with severe anaemia were screened and enrolled. Each child was followed up for eighteen months at one, three, six, twelve and eighteen months after enrolment. Data were analysed using STATA 15.

Results

Between July 2002 and July 2004, 382 severely anaemic children were enrolled in the main study. A total of 52 children were excluded due to missing anthropometric data. Out of the 330 included, 53 children were moderately to severely malnourished and 277 were not. At the end of the 18-month follow period, 28.3% of children with MAM/SAM died compared to 13% of children without MAM/SAM (RR 2.1, CI 0.9–4.2, p = 0.03). Similarly, children with moderate to severe malnutrition reported a significantly higher number of malaria infection cases (33.9%) compared to children with severe anaemia alone (27.9%, p = 0.02). However, the number of hospitalizations and recurrence of severe anaemia was similar and not statistically significant between the two groups (RR 0.8 (0.4–1.4), p = 0.6 and RR 1.1 (0.3–2.8), p = 0.8).

Conclusion

Among children with severe anaemia, those who also had moderate to severe malnutrition had a twofold higher risk of dying compared to those who did not. It is therefore crucial to investigate acute malnutrition among severely anaemic children, as this might be treatable factor associated with high mortality.

Nkosi-Gondwe, Calis, Boele van Hensbroek, Bates, Blomberg, Phiri, and Taylor: A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi

Introduction

Malnutrition is a complex and multifactorial condition that results from deficiencies, excesses, or imbalances in a person’s intake of energy and/or nutrients and presents in two broad forms; undernutrition which includes wasting, stunting and underweight; and micronutrient deficiencies and obesity [1]. Globally, it is estimated that 52 million children under five are wasted, 75% of which are in low- and middle-income countries (LMIC) [2]. The 2016 Malawi demographic and health survey (DHS) reported that 37% of children under five years of age are stunted while 12% are underweight [3], and mortality of up to 42% has been reported among children hospitalised with severe acute malnutrition (SAM) [4, 5]. Such high mortality rate has been attributed to comorbidities such as infections, including HIV, as well as micronutrient deficiencies including anaemia that often affect children with SAM [6, 7].

Severe anaemia is one of the most common causes of admissions and mortality in Sub-Saharan Africa (SSA) and annually affects 9.6 million children globally [8, 9]. In Malawi, it was found that children with severe anaemia alone have a tenfold risk of dying within 18 months after the initial episode compared to children from the hospital and community who did not have severe anaemia [10]. Similar findings have been reported in Kenya and Uganda [11, 12]. Causes of severe anaemia are multifactorial and vary in different settings. In addition to infectious diseases, genetic factors and malignancies, nutritional deficiencies are a major factor [1316].

Severe anaemia and any form of malnutrition are common and associated co-morbidities. Anaemia is the most common manifestation of micronutrient deficiency in malnourished children under 5 years old [17], with up to 67% of severely malnourished children found to be severely anaemic [18, 19]. In Malawi, up to 63% of malnourished children have some form of anaemia signified by a Haemoglobin (Hb) level of <11.0g/dl and of these, 22% are moderate to severely anaemic (Hb <7g/dl). On the other hand, 15.8% of severely anaemia children are found with SAM [2].

Severe anaemia is an important co-morbidity and determinant in the recovery of children with malnutrition, so much so that WHO recommends that children with kwashiorkor or marasmus should be assumed to be severely anaemic [20]. Many studies have reported the in-hospital and post-discharge mortality outcomes among children with SAM [5, 21], and children with severe anaemia [11, 22] separately. However, the added risk of dying when a child has both of these conditions; which we predict would be high has not previously reported. As MAM/SAM is a potentially treatable risk factor [3]; we aimed to evaluate its impact on mortality in severely anaemic children.

Materials and methods

This study was approved by the ethics committees of the College of Medicine, University of Malawi and the Liverpool School of Tropical Medicine, United Kingdom. In the SEVANA cohort study, children with severe anaemia and aged less than five years old were enrolled from Queen Elizabeth Central hospital and Chikhwawa district hospital in southern Malawi. Enrolment procedures have been extensively described elsewhere [14]. In summary, 382 children admitted with severe anaemia (defined as a haemoglobin concentration <5.0 g/dL) were enrolled and matched with one community and one hospital control. Each child was then followed up for 18 months.

In the present study, verbal and written informed consent was obtained from the legal guardians and children with severe anaemia who had a recorded weight, length and met the WHO classification of moderate to severe malnutrition defined as a child whose weight-for-length is less than <2 of the Z-scores and weight for age less that -2 of the z-scores [23]. An additional inclusion criterion was documented haemoglobin at enrolment and a documented date of outcome and status (died, completed, lost-to-follow up or withdrawn).

Information about the child’s age, sex, residence, number of living and dead siblings, 24-hour dietary recall, family history of sickle cell disease (SCD), jaundice, bloody stool and urine, blood transfusion in the last two months, being on any medication, HIV infection and other previous medical history were obtained from the legal guardians at enrolment. Additional information included guardian’s age, occupation and education level.

Other data points collected include physical examination findings at enrolment and laboratory records, which included parasitology, microbiology, haematology and biochemistry.

Power calculation

We did a power calculation to evaluate the statistical power of our study due to the limited sample size. Using open EPI version 3 (www.openepi.com), we computed the 95% two-sided confidence interval, risk ratio (2.1) and the number of children sampled in each study group (53 with MAM/SAM versus 275 without SAM/MAM). We found that our analysis gave us a power of 76.4%.

Statistical analyses

Data were coded, entered and analysed using STATA 15 (StataCorp, College Station, Texas, USA). Categorical variables have been summarized as frequencies and proportions, while continuous variables as means with standard deviations and medians with the interquartile ranges (IQR) reported. Death was our primary outcome. We examined risk of dying by calculating mortality rates in the children with moderate to severe acute malnutrition and those without. We measured time to death by survival analysis, using Kaplan-Meier curves to compare the probability of death between the two groups over the 18-month study period. Significance was calculated with a log-rank test. Incidence rates for the composite outcomes i.e. re-hospitalization, malaria and severe anaemia recurrence were also calculated for each group. For the malaria incidence rate, the time at risk was calculated by subtracting 14 days from the child-years follow-up with each case of clinical malaria treated with Lumefantrine-Artemether (AL). P values and 95% confidence intervals have also been included.

Results

Of the 1141 under-5 children enrolled in the SEVANA study between July 2002 and July 2004, 382 were severe anaemic cases admitted to the paediatric wards of QECH and Chikhwawa district hospital and 759 were hospital or community controls without severe anaemia. Of the 382 children, 330 had their weight and heights measured and were included in the final analysis. A total of 53 children had a weight for height z-scores ≤ -2 (moderate to severe acute malnutrition) and 277 had a weight for height z-scores > -2 (not malnourished). During the follow up period, twenty children were lost to follow up, 51 died and 259 children completed the study (Fig 1).

Study flowchart.
Fig 1
Study flowchart.

The baseline characteristics and examination findings of study participants was comparable between the two groups (Table 1). Moderate to severely malnourished children were significantly older with mean age, 24.3 months (SD 12.1) compared to 19.5 months (SD 12.4). The mean number of days hospitalised was not significantly different, 4.9 days (SD 8.1) compared to 3.9 days (SD 4.1). A higher proportion of non-malnourished children resided in a rural location, 52.4% compared to 45.3% in the malnourished group. The majority of parents of the children had received some formal education and about half of them had employment. A total of 34.0% of malnourished children had a sibling who died compared to 28.2% among children without (p = 0.05).

Table 1
Baseline characteristics of study participants.
CharacteristicModerate to severe malnutritionSevere anaemia aloneP-value
n (%)n (%)
Age <24 months30 (56.6)200 (72.2)0.02 a
Mean age in months n (SD)24.3 (12.1)19.5 (12.4)0.01 a
Mean days in hospital n (SD)4.9 (8.2)3.9 (4.1)0.18
Male gender23 (43.4)129 (46.6)0.67
Rural location24 (45.3)145 (52.4)0.35
One or more dead siblings18 (34.0)78 (28.2)0.05 a
Educated father35 (66.0)172 (62.1)0.72
Teenage mother8 (15.1)71 (25.6)0.15
Uneducated mother5 (9.4)30 (10.8)0.03 a
Jobless parent26 (49.1)164 (59.2)0.03 a
One dead parent5 (9.4)18 (6.5)0.72
Previous blood transfusion9 (17.038 (13.7)0.53
Recent antimalarial use31 (58.5)175 (63.2)0.72
History of bloody stool6 (11.3)19 (6.9)0.45
History of bloody urine1 (1.9)5 (1.8)0.97
Jaundiced6 (11.3)10 (3.6)0.02 a
Splenomegaly33 (62.3)178 (64.3)0.49
Raised CRP (≥10Mg/L)44 (83.0)229 (82.7)0.96
Median CRP n (IQR)111.6 (65.2–183.2)93.6 (37.8–150.5)0.27
Mean Haemoglobin n (SD)3.6 (0.8)3.4 (1.0)0.13
Low Vitamin B12 (<118pmol/L)13 (24.5)71 (25.6)0.97
Iron deficiency14 (26.4)76 (27.4)0.99
Malaria infection at enrolment32 (60.4)164 (59.2)0.87
HIV infected7 (13.2)29 (10.5)0.30
CMV infection3 (1.1)0 (0.0)0.52
EBV infection11 (20.8)63 (22.7)0.66
Bacteraemia4 (7.6)36 (13.0)0.48
Sickle cell disease1 (1.9)3 (1.1)0.88
a P-value which are significant at alpha = 0.05

A total of 196 children (59.4%) had a positive blood smear for P. Falciparum malaria infection on admission, and of these 32 (60.4%) were children with MAM/SAM and 164 (59.2%) were children without MAM/SAM. C-reactive protein (CRP), a common marker of inflammation was raised (≥10Mg/L) among 83% of the children with MAM/SAM compared to 82.7% of those without MAM/SAM. A total of 27.3% of all the children had iron deficiency. A higher proportion of children with vitamin A and vitamin B12 deficiency were those without MAM/SAM.

During the 18-month study period, the mean observation days was 383 in the severely anaemic children with MAM/SAM and 456 days in the severely anaemic alone group respectively (Fig 2 and Table 2).

Kaplan Meier survival curves of severely anemic children with moderate to severe acute malnutrition compared to those with severe anaemia alone.
Fig 2
Kaplan Meier survival curves of severely anemic children with moderate to severe acute malnutrition compared to those with severe anaemia alone.
Table 2
Post-discharge morbidity and mortality among severely anaemic children with moderate to severe malnutrition compared to those with severe anaemia alone.
EventModerate to severe malnutritionSevere anaemia alone
Total eventsIncidence rate (1000 person- days)Total eventsIncidence rate (1000 person- days)Rate ratiop-value
n (CI)
N = 53N = 277
Deaths n (%)15 (28.3)5.436 (13.0)2.62.1 (0.9, 4.2)0.03a
Hospitalisation n (%)9 (3.5)1.576 (4.4)1.80.8 (0.4, 1.7)0.62
Malaria incidence n (%)106 (40.8)17.3573 (32.3)13.01.3 (1.04, 1.6)0.02a
Severe anaemia recurrence n (%)5 (1.6)0.832 (1.6)0.71.1 (0.3, 2.8)0.81
a P-value which are significant at alpha = 0.05

The cumulative proportions of children who died during the entire 18 month study period was 51 (15.4%) with 27 (8.2%) dying within one month of admission. Of the 51 deaths, 15 (28.3%) occurred in children with MAM/SAM compared to 36 (13.0%) who did not. The overall incidence rate of death with the 95% CI was 3.0 (2.2,4.0) children per 1000 person days observed. The incidence rates for death were 5.4 (3.0,9.8) and 2.6 (1.9,3.7) among children with MAS/SAM and those without respectively. This shows that children with MAM/SAM had a twofold risk of dying compared to children who has severe anaemia without MAM/SAM (RR 2.1; CI 0.9–4.2,p = 0.03). Similarly, severely anaemic children who were underweight had almost a 3-fold risk of dying compared to those with severe anaemia alone (RR 2.8; CI 1.5–5.2, p = 0.0006).

The survival curves for the two groups showed a statistically non-significant difference in the two mortality rates (log rank = 2.9, p = 0.098) (Fig 2). However, there was a significant difference in mortality when we compared severely anaemic children who were underweight compared to those who were not, p = 0.001 (Fig 3).

Kaplan Meir survival estimates comparing severely anaemic children who are underweight and those that have severe anaemia alone.
Fig 3
Kaplan Meir survival estimates comparing severely anaemic children who are underweight and those that have severe anaemia alone.

During the follow up period, there were a total of 679 confirmed malaria cases, 16 of which were complicated malaria. There were significantly more children who reported malaria infection among those with MAM/SAM 106 (40.8%) compared to 573 (32.3%) (p = 0.01) with severe anaemia alone (IRR 1.3; CI 1.04–1.6, p = 0.02). There were more hospital readmissions among children who had severe anaemia alone compared to those with moderate to severe acute malnutrition (4.4% versus 3.5%), (IRR 0.8; CI 0.4–1.7,p = 0.62), but this was not statistically significant. In addition, the recurrence of severe anaemia was similarly low between children with moderate to severe malnutrition compared to those who had severe anaemia alone (IRR 1.1, CI 0.3–2.8, p = 0.8) over the entire study period.

Discussion

To our knowledge, no cohort studies investigating mortality outcomes in children with both severe anaemia and MAM/SAM have been conducted in SSA. We found that severely anaemic children with MAM/SAM are two times more likely to die compared to severely anaemic children without MAM/SAM during 18 months follow-up. High mortality rates have been reported among hospitalized children with severe anaemia and MAM/SAM separately in other African countries [24]. However, our findings show a much higher mortality rate than those reported in studies in children with severe anaemia in Ethiopia and Gambia [22, 25]. This higher mortality could be attributed to the fact that children included in our study had both conditions, which independently are major causes of mortality in children.

There are few cohort studies that have investigated mortality outcomes in children with both severe anaemia and MAM/SAM. Most of these have reported varying ranges of the burden of these two co-morbidities but there is limited data on impact. One study in Ethiopia reported that there was no significant difference in recovery among severe malnourished children with anaemia compared to those without anaemia [26]. On the other hand another study in Ethiopia found that children with SAM and anaemia had less chance of recovering compared to those who had SAM and no anaemia [27], which was similar to findings of a study in Kenya (Kwambai et al, Unpublished). However, this study did not have a comparison group. These findings are important because children admitted to hospital with severe anaemia are not routinely screened for MAM/SAM [2830]. This has the implication that these children will not be checked for MAM/SAM, as it may be a treatable factor associated with high mortality.

The interplay between MAM/SAM, severe anaemia and the risk of mortality is multifactorial. It is believed that malnutrition lowers immunity, which leads to susceptibility to infections [31]. In addition, it is also possible that children with MAM/SAM are more likely to have micronutrient deficiency leading to cell damage that makes infections worse and leads to poor outcomes. Studies have attributed poor recovery outcomes in children with either MAM/SAM or severe anaemia to many factors including infections such as malaria [3234]. We found that there was significantly higher malaria incidence among severely anaemic children with moderate to severe acute malnutrition compared to those with severe anaemia alone. The association between malnutrition and malaria has been inconclusive and conflicting [34]. In malaria endemic regions, malaria infection is associated with anaemia although it may not be the primary cause of it [35]. This finding is similar to other studies in Cameroon, Ghana and Gambia, where under-nutrition was associated with increased risk of malaria-associated mortality and multiple malaria infections [3638].

Compared to other studies among children with severe anaemia or malnutrition, we did not find significant differences in hospital re admissions or recurrent severe anaemia. We had few fewer re-hospitalisations to detect meaningful differences. Although we did not make associations with other risk factors, our findings are important for exploring interventions that may reduce the additional burden that exists among severely anaemic children with malnutrition.

Our study had limitations. Our sample size was limited and we collected data from existing data that are now 16 to 18 years old. This might have an effect on the findings and their interpretation within the current context. Considering that mortality is a relatively rare outcome and the number of deaths was small, the confidence intervals for the mortality risks are relatively wide. However, we were able to detect significant and meaningful differences in mortality between the two groups of children.

Conclusions and recommendations

Severe anaemic children who also have moderate to severe malnutrition have a higher risk of death than those with severe anaemia alone, even after discharge from hospital. It is therefore crucial to carefully screen for acute malnutrition in children admitted with severe anaemia, as this may be a treatable factor associated with high mortality. Prospective cohort studies may be utilised to evaluate effects of interventions that may be used to reduce mortality among severely anaemic children with moderate to severe acute malnutrition.

Acknowledgements

We wish to acknowledge the immense contributions of the entire SEVANA team for the data and the children who participated in the main trial.

References

World Health Organization/ United Nations Children’s Fund (UNICEF)/International Bank for Reconstruction and Development/The World Bank: Levels and trends in child malnutrition: Key Findings of the 2020 Edition of the Joint Child Malnutrition Estimates. Geneva, World Health Organization; 2020.

United Nations Children’s Fund (UNICEF) WHO, International Bank for Reconstruction and Development/The World Bank. Levels and trends in child malnutrition: key findings of the 2019 Edition of the Joint Child Malnutrition Estimates. Geneva: World Health Organization.

National Statistical Office (NSO) [Malawi] and ICF International. 2016 Malawi Demographic and Health Survey 2015–16: Key Indicators Report. Zomba, Malawi, and Rockville, Maryland, USA NSO and ICF International.

2020 Global Nutrition Report: Action on equity to end malnutrition. Bristol, UK: Development Initiatives.

BahwereP; MtimuniAngella; SadlerKate; BandaTheresa; CollinsSteve. Long term mortality after community and facility based treatment of severe acute malnutrition: Analysis of data from Bangladesh, Kenya, Malawi and Niger. Journal of Public Health and Epidemiology 2012;4(8):11.

McDonaldCM, OlofinI, FlaxmanS, FawziWW, SpiegelmanD, CaulfieldLE, et al The effect of multiple anthropometric deficits on child mortality: meta-analysis of individual data in 10 prospective studies from developing countries. Am J Clin Nutr. 2013;97(4):896901. doi: 10.3945/ajcn.112.047639

IbrahimMK, ZambruniM, MelbyCL, MelbyPC. Impact of Childhood Malnutrition on Host Defense and Infection. Clinical Microbiology Reviews. 2017;30(4):919 doi: 10.1128/CMR.00119-16

BurchardGD, CramerJP, EhrhardtS, MantelC, BienzleU, MockenhauptFP, et al Malaria, Anemia, and Malnutrition in African Children—Defining Intervention Priorities. The Journal of Infectious Diseases. 2006;194(1):10814. doi: 10.1086/504688

World Health Organization. The global prevalence of anaemia in 2011. Geneva: World Health Organization; 2015.

10 

KassebaumNJ, JasrasariaR, NaghaviM, WulfSK, JohnsN, LozanoR, et al A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014;123(5):615 doi: 10.1182/blood-2013-06-508325

11 

PhiriKS, CalisJ. C., FaragherB., NkhomaE., Ng’omaK., MangochiB., et al Long term outcome of severe anaemia in Malawian children. PLoS ONE. 2008;3(8):11 doi: 10.1371/journal.pone.0002903

12 

AryaAKK, Pramod; MidhaTanu; SinghMahendra. Hematological profile of children with severe acute malnutrition: a tertiary care centre experience. International Journal of Contemporary Pediatrics. 2017;4(5):4.

13 

LackritzEM, HightowerA.W., ZuckerJ.R., RuebushT.K., OnudiC.O., SteketeeR.W.; et al Longitudinal evaluation of severely anemic children in Kenya: the effect of transfusion on mortality and hematologic recovery. AIDS. 1997;11(12):8 doi: 10.1097/00002030-199712000-00013

14 

CalisJC KP, FaragherEB, BrabinBJ, BatesI, CuevasLE, et al Severe anemia in Malawian children. New England Journal of Medicine. 2008;358(9):11.

15 

Boele van HensbroekM, CalisJCJ, PhiriKS, VetR, MunthaliF, KraaijenhagenR, et al Pathophysiological mechanisms of severe anaemia in Malawian children. PloS one. 2010;5(9):e12589e. doi: 10.1371/journal.pone.0012589

16 

DhabangiA, IdroR, JohnCC, DzikWH, OpokaR, SsenyongaR, et al Risk factors for recurrent severe anemia among previously transfused children in Uganda: an age-matched case-control study. BMC Pediatrics. 2019;19(1):27 doi: 10.1186/s12887-019-1398-6

17 

YangW, LiX, LiY, ZhangS, LiuL, WangX, et al Anemia, malnutrition and their correlations with socio-demographic characteristics and feeding practices among infants aged 0–18 months in rural areas of Shaanxi province in northwestern China: a cross-sectional study. BMC Public Health. 2012;12(1):1127 doi: 10.1186/1471-2458-12-1127

18 

MoraledaC, AguilarR, QuintóL, NhampossaT, RenomM, NhabombaA, et al Anaemia in hospitalised preschool children from a rural area in Mozambique: a case control study in search for aetiological agents. BMC Pediatrics. 2017;17:63 doi: 10.1186/s12887-017-0816-x

19 

ThakurN, ChandraJ, PemdeH, SinghV. Anemia in severe acute malnutrition. Nutrition. 2014;30(4):4402. doi: 10.1016/j.nut.2013.09.011

20 

World Health Organization. Management of severe malnutrition: a manual for physicians and other senior health workers. Geneva, 1999.

21 

KeracM, BunnJ, ChagalukaG, BahwereP, TomkinsA, CollinsS, et al Follow-Up of Post-Discharge Growth and Mortality after Treatment for Severe Acute Malnutrition (FuSAM Study): A Prospective Cohort Study. PLOS ONE. 2014;9(6):e96030 doi: 10.1371/journal.pone.0096030

22 

BojangKA, Van HensbroekMB, PalmerA, BanyaWAS, JaffarS, GreenwoodBM. Predictors of mortality in Gambian children with severe malaria anaemia. Annals of Tropical Paediatrics. 1997;17(4):3559. doi: 10.1080/02724936.1997.11747910

23 

World Health Organization. Guideline: Updates on the management of severe acute malnutrition in infants and children. Geneva: World Health Organization; 2013.

24 

CollinsS, DentN, BinnsP, BahwereP, SadlerK, HallamA. Management of severe acute malnutrition in children. The Lancet. 2006;368(9551):19922000. doi: 10.1016/S0140-6736(06)69443-9

25 

GueshG, DeguG, AbayM, BeyeneB, BrhaneE, BrhaneK. Survival status and predictors of mortality among children with severe acute malnutrition admitted to general hospitals of Tigray, North Ethiopia: a retrospective cohort study. BMC Res Notes. 2018;11(1):832-. doi: 10.1186/s13104-018-3937-x

26 

DesyibelewHD, FekaduA, WoldieH. Recovery rate and associated factors of children age 6 to 59 months admitted with severe acute malnutrition at inpatient unit of Bahir Dar Felege Hiwot Referral hospital therapeutic feeding unite, northwest Ethiopia. PLOS ONE. 2017;12(2):e0171020 doi: 10.1371/journal.pone.0171020

27 

WondimA, TigabuB, KelkayMM. Time to Recovery from Severe Acute Malnutrition and Its Predictors among Admitted Children Aged 6–59 Months at the Therapeutic Feeding Center of Pawi General Hospital, Northwest Ethiopia: A Retrospective Follow-Up Study. Int J Pediatr. 2020;2020:8406597 doi: 10.1155/2020/8406597

28 

NaharA, RavindranathY. Approach to severe anemia in children in the emergency room. Therapy. 2008;5(4):9.

29 

ThorneCJ, RobertsLM, EdwardsDR, HaqueMS, CumbassaA, LastAR. Anaemia and malnutrition in children aged 0–59 months on the Bijagós Archipelago, Guinea-Bissau, West Africa: a cross-sectional, population-based study. Paediatrics and international child health. 2013;33(3):15160. doi: 10.1179/2046905513Y.0000000060

30 

RahmanMS, MushfiqueeM, MasudMS, HowladerT. Association between malnutrition and anemia in under-five children and women of reproductive age: Evidence from Bangladesh Demographic and Health Survey 2011. PloS one. 2019;14(7):e0219170e. doi: 10.1371/journal.pone.0219170

31 

GebremichaelDY. Predictors of nutritional recovery time and survival status among children with severe acute malnutrition who have been managed in therapeutic feeding centers, Southern Ethiopia: retrospective cohort study. BMC Public Health. 2015;15(1):1267 doi: 10.1186/s12889-015-2593-5

32 

MassaD, WoldemichaelK., TsehaynehB., & TesfayA. Treatment outcome of severe acute malnutrition and determinants of survival in Northern Ethiopia: A prospective cohort study. International Journal of Nutrition and Metabolism. 2016;8(3):12.

33 

MengeshaMM, DeyessaN, TegegneBS, DessieY. Treatment outcome and factors affecting time to recovery in children with severe acute malnutrition treated at outpatient therapeutic care program. Glob Health Action. 2016;9:30704-. doi: 10.3402/gha.v9.30704

34 

KeerthiwansaJ GS; SivarajaS; SubashiniK.Y. Malnutrition and anaemia among hospitalised children in Vavuniya. Ceylon Medical Journal. 2014;59:3 doi: 10.4038/cmj.v59i4.7869

35 

AkiyamaT, PongvongsaT, PhrommalaS, TaniguchiT, InamineY, TakeuchiR, et al Asymptomatic malaria, growth status, and anaemia among children in Lao People’s Democratic Republic: a cross-sectional study. Malaria journal. 2016;15(1):499-. doi: 10.1186/s12936-016-1548-3

36 

DasD, GraisRF, OkiroEA, StepniewskaK, MansoorR, van der KamS, et al Complex interactions between malaria and malnutrition: a systematic literature review. BMC Med. 2018;16(1):186-. doi: 10.1186/s12916-018-1177-5

37 

SumbeleIUN, BopdaOSM, KimbiHK, NingTR, Nkuo-AkenjiT. Nutritional status of children in a malaria meso endemic area: cross sectional study on prevalence, intensity, predictors, influence on malaria parasitaemia and anaemia severity. BMC public health. 2015;15:1099-. doi: 10.1186/s12889-015-2462-2

38 

CaulfieldLE, RichardSA, BlackRE. Undernutrition as an underlying cause of malaria morbidity and mortality in children less than five years old. The American journal of tropical medicine and hygiene. 2004;71(2 Suppl):5563.

15 Jul 2020

PONE-D-20-12989

A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi

PLOS ONE

Dear Dr. Gondwe,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please be sure to prepare a point-by-point response to the reviewers' comments. In general, they found the manuscript to be of interest but clarifications are required. The biggest concern has to do with the applicability of the findings to today's context. Are the authors able to cite evidence that MAM/SAM might go unnoticed in a severely anemic child who presents to a health clinic?

Please submit your revised manuscript by Aug 29 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Laura E. Murray-Kolb

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: PLOS ONE article review; Manuscript Number: PONE-D-20-12989

Title: A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi

Comments

There are several places where it is not clear whether you are talking about malnutrition in general or MAM/SAM. Such statements should be made more explicit to avoid confusing a reader should your paper be published.

Abstract

Line#41: correct this typo” theses”

Line#44: “Add company name and location for “STATA 15”

Line#48-50: These two sentences should be made clearer. So 15 out of 53 SAM children died vs. 36 out of 275 severely anemic children? 53+275=328, but you had weight and height data for 330 children. 28.3% is a cumulative value across 18 months. What does 53 represent? Is this a cumulative value or the number of SAM children with anemia throughout the study period?

Introduction

After reference 2, “correct the typo in “It”

After reference 3, “…nearly half of all children under five years are

Malnourished…" Given the broad definition of malnutrition in your first sentence, be specific with what malnutrition represents here. For instance, stunting, Stunting + anemia?

Just before reference 8, are community controls here non-anemic healthy children? Anemic children, that are managed at the community level?

Just before reference 16, “… severely malnourished children…”, are these SAM children?

Statistical analysis

First sentence, see comments above under abstract.

The penultimate sentence, what is "AL"? Write the full name on the first appearance.

Page 8: second paragraph, 196 children out of 330? If so, 60.4% (n=118???). Is the total number of malnourished children, not 53?

Discussion

First sentence, does “… our setting ..” here mean Malawi? Sub-Saharan Africa?

The second sentence, add "are" between "malnutrition" and "two."

After reference 19, correct they typo “…higher mortality rate than that…" "that" to "those": Also recheck the references. Reference 21 is the Gambia, not Nigeria.

Page 13: penultimate sentence, correct typo in “Children”.

Second paragraph, “Unpublished, T. Kwambai”.

Check this study from Ethiopia, Int J Pediatr. 2020; 2020: 8406597.

doi: 10.1155/2020/8406597

References

Recheck your all to ensure consistent formatting and style.

Figure 1: Flowchart

52+(53+275) =380. You have not accounted for 2 children.

Figure 2 and Figure 3: Kaplan-Meier plots

The axes should be properly labelled.

Reviewer #2: The authors use old data (2002-2004) from a small sample (n=330) of hospitalized children under five years old in Malawi. Following these children for 18 months, they compare the death rate in children with severe anaemia to the death rate in children with severe anaemia plus at least moderate acute malnutrition (WHZ < -2). Compared to children with severe anaemia alone, children with severe anaemia plus MAM/SAM were twice as likely to die. The authors conclude by recommending that children who are hospitalized with severe anaemia should also be screened for MAM/SAM.

My primary concern is that the findings are not relevant in today’s context. I may be wrong, but it is hard to believe that hospitalized children are not screened for MAM/SAM. I would guess that weight and height are among the first things to be measured when any child is hospitalized. If a child presents with both MAM/SAM and anaemia, they will receive food and iron supplements, two different treatments. A child who presents with MAM/SAM may also be screened for anaemia. It is hard to believe that MAM/SAM would go completely unnoticed by doctors in today’s context. The authors need to address this and justify the relevance of the study using recent evidence. Other minor comments are below.

Abstract

The following sentence is unclear: “Under-five children with severe anaemia were screened and enrolled and of theses children with moderate to severe acute malnutrition; defined as weight-for-height Z-score <-2 were included.” Enrolled and included are distinct? Do you mean included in the analysis? And of course there is a bad typo, “theses”.

Don’t use acronym SAM for moderate to severe malnutrition. SAM is severe (HAZ < -3) and does not include moderate. You could say 53 children were identified as having MAM or SAM.

Introduction

The manuscript is missing line numbers.

The first sentence of the introduction is incorrect. Malnutrition goes much beyond intake. Inadequate or excess intake among other factors can lead to malnutrition.

Change ‘commonest’ to most common.

Methods

Power calculation: can you clarify what the study groups were and what the sample size was for each group? Is it the 53 with MAM/SAM and 275 without MAM/SAM?

What is the acronym AL? Albendazole?

Results

Table 1 – groups need to be labeled better. Severe anaemia + MAM/SAM vs. Severe anaemia alone

Discussion

Do not abbreviate severe anaemia as SA. Avoid abbreviations whenever possible.

The data are 16-18 years old, not 16 years old.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.


12 Nov 2020

Dear PLOS ONE,

Thank you for reviewing our manuscript titled “A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi” for consideration for publication in your esteemed journal. We have revised our manuscript with considerations to the comments and suggestions from the reviewers and ensured that it meets PLOS ONE’s style requirements. We would like to confirm that informed verbal and written consent were obtained from the guardians of all the children who participated in the study and a statement regarding ethical considerations has been added under the methods section. In addition, there are no ethical or legal restrictions on sharing of our data set. The anonymized data set can be found on:

https://figshare.com/articles/dataset/Moderate_to_severe_malnutrition_in_severe_anemia_study_/13061447

Please kindly update our Data availability statement to reflect the availability of data.

Responses to reviewers

Below are point by point responses to each comment raised by the reviewers. Responses are highlighted in bold.

1. There are several places where it is not clear whether you are talking about malnutrition in general or MAM/SAM. Such statements should be made more explicit to avoid confusing a reader should your paper be published.

It is correct that we are referring to MAM/SAM and we have made corrections throughout the manuscript.

2. Abstract

Line#41: correct this typo” theses”

This has been corrected.

3. Line#44: “Add company name and location for “STATA 15”

We have added the company name and location for “STATA 15”.

4. Line#48-50: These two sentences should be made clearer. So 15 out of 53 SAM children died vs. 36 out of 275 severely anemic children? 53+275=328, but you had weight and height data for 330 children. 28.3% is a cumulative value across 18 months. What does 53 represent? Is this a cumulative value or the number of SAM children with anemia throughout the study period?

This has been revised. The correct number of children without MAM/SAM was 277. Revisions to the text and the study flow chart (Figure 1) have been made accordingly.

5. Introduction

After reference 2, “correct the typo in “It”

This has been corrected.

6. After reference 3, “…nearly half of all children under five years are

Malnourished…" Given the broad definition of malnutrition in your first sentence, be specific with what malnutrition represents here. For instance, stunting, Stunting + anemia?

We have revised this in line 81-84. We have defined malnutrition as follow: it is a complex and multifactorial condition that results from deficiencies, excesses, or imbalances in a person’s intake of energy and/or nutrients and presents in two broad forms; undernutrition which includes wasting, stunting and underweight; and micronutrient deficiencies and obesity.

7. Just before reference 8, are community controls here non-anemic healthy children? Anemic children, that are managed at the community level?

Thank you very much. Community controls were children matched for age and sex from the community and hospital who did not have severe anemia. A revision has been made in live 94 to make it clearer.

8. Just before reference 16, “… severely malnourished children…”, are these SAM children?

This is correct. We have revised this to make it clearer.

9. Statistical analysis

First sentence, see comments above under abstract.

We have revised this with a full name of the company and location in line 180-181 under statistical analyses.

10. The penultimate sentence, what is "AL"? Write the full name on the first appearance.

AL is the abbreviation for Artemether-Lumefantrine and it has been written in full in line 192-193.

11. Page 8: second paragraph, 196 children out of 330? If so, 60.4% (n=118???). Is the total number of malnourished children, not 53?

This was 196 out of 330, representing 59.4% with a positive blood smear for P. Falciparum malaria infection on admission, and out of these, 32 ( 60.4%) were children with MAM/SAM and 164 (59.2 %) were children without MAM/SAM. Revisions have been made in line 216-218 to make it clearer.

12. Discussion

First sentence, does “… our setting ..” here mean Malawi? Sub-Saharan Africa?

“Our setting” means Sub-Saharan Africa. We have revised this to reflect the same in line 287.

13. The second sentence, add "are" between "malnutrition" and "two."

This has been corrected in line 288.

14. After reference 19, correct they typo “…higher mortality rate than that…" "that" to "those": Also recheck the references. Reference 21 is the Gambia, not Nigeria.

This has been corrected in line 291. The references have also been corrected in line 292.

15. Page 13: penultimate sentence, correct typo in “Children”.

This has been corrected.

16. Second paragraph, “Unpublished, T. Kwambai”.

Check this study from Ethiopia, Int J Pediatr. 2020; 2020: 8406597.

doi: 10.1155/2020/8406597

Thank you very much. We have reviewed this reference and included it in our text.

17. References.

Recheck your all to ensure consistent formatting and style.

All references have been checked and formatted according to Plos one guidelines

18. Figure 1: Flowchart

52+(53+275) =380. You have not accounted for 2 children.

The flow chart has been revised. The 2 children who were initially omitted had died on admission.

19. Figure 2 and Figure 3: Kaplan-Meier plots

The axes should be properly labelled.

The Kaplan Meier plots have been revised.

20. Reviewer #2: The authors use old data (2002-2004) from a small sample (n=330) of hospitalized children under five years old in Malawi. Following these children for 18 months, they compare the death rate in children with severe anaemia to the death rate in children with severe anaemia plus at least moderate acute malnutrition (WHZ < -2). Compared to children with severe anaemia alone, children with severe anaemia plus MAM/SAM were twice as likely to die. The authors conclude by recommending that children who are hospitalized with severe anaemia should also be screened for MAM/SAM.

My primary concern is that the findings are not relevant in today’s context. I may be wrong, but it is hard to believe that hospitalized children are not screened for MAM/SAM. I would guess that weight and height are among the first things to be measured when any child is hospitalized. If a child presents with both MAM/SAM and anaemia, they will receive food and iron supplements, two different treatments. A child who presents with MAM/SAM may also be screened for anaemia. It is hard to believe that MAM/SAM would go completely unnoticed by doctors in today’s context. The authors need to address this and justify the relevance of the study using recent evidence. Other minor comments are below.

Thank you very much for your comment. We acknowledge that the data are from 16 to 18 years ago and the concern that the findings are not relevant in today’s context. However, our study was done for that particular reason. There are no studies, recent or old that have explored survival of children who have both severe anemia and moderate to severe malnutrition despite that these two conditions are often found together. Our study findings are very relevant even in today’s context, because the burden of these two comorbidities remains high and therefore the mortality risk is still very present. We have made revisions in lines 141-142 to make our rationale clearer. However, we agree that the sample size was limited and therefore we have highlighted that this was a limitation in our study and a larger prospective study should be conducted to confirm our findings. This has been highlighted in the discussion section.

21. Abstract

The following sentence is unclear: “Under-five children with severe anaemia were screened and enrolled and of theses children with moderate to severe acute malnutrition; defined as weight-for-height Z-score <-2 were included.” Enrolled and included are distinct? Do you mean included in the analysis? And of course there is a bad typo, “theses”.

This has been revised extensively to be clearer.

22. Don’t use acronym SAM for moderate to severe malnutrition. SAM is severe (HAZ < -3) and does not include moderate. You could say 53 children were identified as having MAM or SAM.

We have revised the manuscript throughout. Moderate to severe malnutrition have been identified as having MAM/SAM.

23. Introduction

The manuscript is missing line numbers.

We have inserted line numbers.

24. The first sentence of the introduction is incorrect. Malnutrition goes much beyond intake. Inadequate or excess intake among other factors can lead to malnutrition.

This is correct. We have revised the definition of malnutrition to “Malnutrition is a complex and multifactorial condition that results from deficiencies, excesses, or imbalances in a person’s intake of energy and/or nutrients and presents in two broad forms; undernutrition which includes wasting, stunting and underweight; and micronutrient deficiencies and obesity.” in lines 81-84.

25. Change ‘commonest’ to most common.

This has been revised in line 99.

26. Methods

Power calculation: can you clarify what the study groups were and what the sample size was for each group? Is it the 53 with MAM/SAM and 275 without MAM/SAM?

We sampled 53 children who had MAM/SAM and 275 children without MAM/SAM. We have revised the section to make it clearer in lines 177-178.

27. What is the acronym AL? Albendazole?

AL is an acronym for Lumefantrine-Artemether. We have made the correction in line 192-193.

28. Results

Table 1 – groups need to be labeled better. Severe anaemia + MAM/SAM vs. Severe anaemia alone.

Table 1 and 2 has been revised with better labels.

29. Discussion

Do not abbreviate severe anaemia as SA. Avoid abbreviations whenever possible.

We have revised this and spelled severe anemia in full throughout the manuscript.

30. The data are 16-18 years old, not 16 years old.

This is correct. We have made a revision in line 371.

Submitted filename: Responses to reviewers.pdf

18 Jan 2021

A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi

PONE-D-20-12989R1

Dear Dr. Gondwe,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Walter R. Taylor

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Line# 31; SAM/MAM, most part of the manuscript, MAM/SAM was used. See line#118 and other parts. Keep it consistent.

Line#48; correct to follow-up instead of follow.

Line#81; use lower case for haemoglobin

Line#150; 28.2%, remove space

Line# 155; 10mg/L, use lower case for M.

Line# 168; MAS/SAM?

Lines#189, 191, 193; IRR?

Line#218; “However, this study did not have a comparison group.” It is unclear which study this statement refers to, your study or one of the references?

Line#236, re-admissions

References # 4 and 9 are incomplete.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No


22 Jan 2021

PONE-D-20-12989R1

A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi

Dear Dr. Nkosi-Gondwe:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Walter R. Taylor

Academic Editor

PLOS ONE

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

https://www.researchpad.co/tools/openurl?pubtype=article&doi=10.1371/journal.pone.0246267&title=A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi&author=&keyword=&subject=Research Article,Medicine and Health Sciences,Hematology,Anemia,Biology and Life Sciences,Nutrition,Malnutrition,Medicine and Health Sciences,Nutrition,Malnutrition,People and Places,Population Groupings,Age Groups,Children,People and Places,Population Groupings,Families,Children,Biology and Life Sciences,Population Biology,Population Metrics,Death Rates,Medicine and Health Sciences,Medical Conditions,Parasitic Diseases,Malaria,Medicine and Health Sciences,Medical Conditions,Tropical Diseases,Malaria,Medicine and Health Sciences,Epidemiology,Medical Risk Factors,Biology and Life Sciences,Nutrition,Nutritional Deficiencies,Micronutrient Deficiencies,Medicine and Health Sciences,Nutrition,Nutritional Deficiencies,Micronutrient Deficiencies,Medicine and health sciences,Medical conditions,Infectious diseases,Viral diseases,HIV infections,