Nutritional assessment and associated factors in children with congenital heart disease-Ethiopia.

INTRODUCTION: Worldwide, congenital heart disease is the principal heart disease in children and constitutes one of the major causes of infant mortality, particularly in developing countries. Infants and children with congenital heart disease exhibit a range of delays in weight gain and growth. In some instances, the delay can be relatively mild, whereas in other cases, cause the failure to thrive.
OBJECTIVES: To determine the nutritional status and associated factors of pediatric patients with congenital heart disease. MATERIAL AND
METHOD: A cross sectional analytical study conducted over a period of 6 months (Feb to Jul 2020). A total of 228 subjects with congenital heart disease who visited the cardiac center during the study period where included until the calculated sample size attained. Data is collected from patient's card and their care giver. Data was then analyzed using Statistical Package for Social Sciences (SPSS) for windows version 25.0. Odds Ratio with 95% Confidence Interval (CI) was used to determine the effect of the independent variables on the outcome variable and P-value less than 0.05 was considered statistically significant.
RESULTS: A total of 228 children ranging from 3month to 17yrs of age with mean age of 4.7 years (SD = 3.8 years) were included in the study. Most of the subjects had acyanotic heart disease accounting for 87.7%. The overall prevalence of wasting, underweight and stunting were 41.3%, 49.1% and 43% respectively. Children with congenital heart disease and having pulmonary hypertension, were found more likely to develop wasting compared to those without pulmonary hypertension with an odds of 1.9 (95% CI: 1.0-3.4) and also have greater chance of stunting with an odds of 1.9 (95% CI: 1.0-3.4). Children 5 to 10 years of age were 2.3 times more likely to be underweight.
CONCLUSION: Malnutrition is a major problem in pediatric patients with congenital heart disease. Pulmonary hypertension and older age are associated with increased risk of undernutrition.

1. Introduction

1.1. Background

Congenital heart disease (CHD) is a defect in the heart or major blood vessels that are present in children at birth & occurs in approximately 1% of live births. It is usually defined as clinically significant structural heart disease present at birth [1,2].

Worldwide, CHD is the principal heart diseases in children and constitutes one of the major causes of infant mortality, particularly in developing countries [3]. Infants and children with CHD exhibit a range of delays in weight gain and growth. In some instances, the delay can be relatively mild, whereas in other cases, it could be severe causing failure to thrive [4].

Good nutrition is essential for survival, physical growth, mental development, performance, productivity, health and well-being across the entire life span from the earliest stages of fetal development, at birth, and through infancy, childhood, adolescence and on into adulthood [4]. Infants and children are more likely to suffer from poor nutrition than compared to adults. The first reason is newborn infants have low stores of fat and protein. The smaller the child, the fewer reserves of energy they have. This means that they can only cope with starvation for shortened periods. The second reason is high nutritional demands for growth: The amount of nutrition children require is greatest during infancy, because of their rapid growth during this period. The third reason is rapid development in the nervous system: the child’s brain grows rapidly during the last four months of pregnancy and also during the first two years of the life. The connections between the nerve cells in the brain are being formed during this time therefore good nutrition is important to ensure that this occurs properly. The fourth reason is Illness: the child’s nutrition may be compromised following an episode of illness or surgery. The body’s energy requirements are increased; thus intake of food and nutrients should be increased [4-6].

Prevalence of growth failure is estimated to be 64% in children with CHD living in developed countries while this number likely to be higher in those living in developing countries for the reason than malnutrition perse is much more common because of other additional factors.

Multiple factors are mentioned in literatures to answer why would patients with CHD develop malnutrition. These are chromosomal abnormalities, feeding problems causing inadequate nutrition and malabsorption that occurs because of edematous gastrointestinal system in those with chronic heart failure. Chronic cyanosis and heart failure dysfunction body metabolism and the susceptibility to infection again will result higher body metabolism. Those children with CHD and undernutrition have worse prognosis implicated by poor somatic growth, repetitive admissions, unfavorable outcome after intervention and finally they will succumb to death [6].

Anthropometry means the study of human body measurements in comparative bases. It utilizes primarily indices of growth which includes weight, stature (length/height) and head circumference especially for younger children. Triceps skinfold thickness, subscapular skinfold thickness, and mid-upper arm circumference are secondary measures to estimate the body composition [4]. Percentile curves are used to compare the measured values to normal ranges of population data.

1.2. Statement of the problem

Significant percentage of undernutrition and short stature seen in children with congenital heart disease. The presence of malnutrition will prone them for infection and the prognosis is grave even if correction is done later in life. The chance of developing malnutrition increases in those having CHD with cyanosis, multiple heart defects, heart failure, delayed intervention, anemia and pulmonary hypertension. Because of multiple reasons children with CHD in developing countries are not getting the opportunity for corrective intervention which indirectly makes them susceptible to develop malnutrition [7-12].

For the above-mentioned reasons, risk factors and associated comorbidities, malnutrition is a common finding we see in our patients with CHD, complicating the course and outcome of the disease. Despite the significant morbidity and mortality associated with undernutrition in CHD, very little emphasis has been given in the management and prevention of this complication in our clinical practice.

1.3. Significance of the study

The conclusion obtained from such study will help health professionals to emphasis on nutritional assessment of patients with CHD and respective measures either to prevent it or early intervention to avoid additional complications. The results of this study can also be an input to develop nutritional guidelines for infants & children with congenital heart disease to provide adequate calories and protein, considering potentially increased needs, and promote optimal weight gain and growth velocity. Such studies in general are useful for policy makers to have an insight about patients with comorbidities like congenital heart disease are at increased risk of such complication in addition to the primary disease itself.

2. Methodology

2.1. Study area

This study was conducted at pediatrics cardiac clinic of cardiac center—Ethiopia.

2.2. Study design and period

A cross sectional, prospective, analytic study was conducted over a period of 6months (February 2020 to July 2020).

2.3. Source and Study population

2.3.1. Source population

All pediatric patients with congenital heart disease age 0–18yrs seen at outpatient clinic of children’s cardiac center.

2.3.2. Study population

All pediatric patients with congenital heart disease age 0–18yrs seen at outpatient clinic of children’s cardiac center during the study period.

2.4. Inclusion criteria

All pediatric patients age 0–18yrs with congenital heart disease seen at outpatient clinic of children’s cardiac clinic who didn’t undergone intervention.

2.5. Exclusion criteria

All patients with risk factors other than CHD that contribute to malnutrition like genetic disorders, chronic illness, prematurity and low birth weight were excluded.

2.6. Sample size determination and sampling technique

The sample size was determined using the single population proportion formula, taking prevalence (P) of 84% from a research done in Egypt (13), Z = 1.96, and assuming a 10% non-response rate, giving the total sample size to be 228.

Study subjects fulfilling the inclusion criteria were included consecutively until sample size is reached.

2.7. Data collection

Data collection was conducted by a trained general practitioner using a structured data inquiry sheet developed by the primary investigator. The data inquiry sheet included demographic characteristics including age, gender, age of diagnosis, social status of the parents and Other data including cardiac diagnosis at echocardiography, presence of pulmonary hypertension, weight, height, length, and body mass index. Relevant laboratory result like hemoglobin was included.

2.8. Method of data collection, tool and personnel

A convenient sampling technique was used to include subjects that fulfilled the inclusion criteria that visited the cardiac clinic at the time of data collection until the sample size was achieved.

Weight was measured by a single person with the same weight scale.

Height was measured using a tape meter when the patient is lying in supine position flat on a rigid surface for those below two years and for those above two years who can’t stand.

WHO Z- score classification for malnutrition is used to assess and categorize the nutritional status of these children included in our study. Acute malnutrition assessed by weight/length score, chronic malnutrition assessed by length/age score, while poor nutrition assessed by weight/age score.

2.9. Data processing and analysis

Interpretation of anthropometric values was based on the WHO Z-scores, interpreted as moderate and severe wasting if weight for height is <- 2SD to > -3SD and < -3SD respectively.

Moderately and severely underweight if weight for age is <- 2SD to > -3SD and < -3SD respectively.

Moderately and severely stunted if length/height for age was <- 2SD to > -3SD and < -3SD respectively.

Data analysis was done using SPSS version 25 statistical package. Individual questionnaire was checked before data entry into the software. Further data cleaning was performed to check for outliers, missed values and any inconsistencies before the data were analyzed using the software.

Pearson’s chi square and fisher-exact test was used to find the association between categorical variables and For variables with p-value less than 0.20 in univariable logistic regression, multivariable logistic regression analyses were conducted to control the cofounders and to assess the association between independent variables and nutritional status. A p-value of ≤ 0.05 was considered significant.

2.10. Ethical consideration

The study was approved by Institutional research board (IRB) of SPHMMC according to Ethiopian national research guideline. The privacy and confidentiality of all participants was secured, and informed written consent was taken from all study subjects and/or their care givers.

3. Results

A total of 228 children with congenital heart disease were included in the research. The mean age was 4.7years (SD 3.8yrs) and range of 3months to 17yrs (see Table 1).

Table 1

Socio-demographic characteristics of the study participants at the cardiac center Ethiopia.

Variables	Frequency	Percent
Age group
<1 years	35	15.3
1–3 years	73	31.9
3–5 years	44	19.2
5–10 years	74	32.4
>10 years	2	0.9
Gender
Male	102	44.7
Female	126	55.3
Residence
Urban	105	46.1
Rural	123	53.9
Religion
Orthodox	130	57.0
Muslim	74	32.5
Protestant	23	10.1
Catholic	1	0.4
School level
PKG	174	76.3
Grade 1–4	45	19.7
Grade 5–8	7	3.1
Grade 9–12	2	0.9
Parental Marital status
Single	1	0.4
Married	225	98.7
Widowed	2	0.9
Parental Education level
Can’t Read or Write	16	7.0
Read and Write	18	7.9
Below high school	84	36.8
Complete high school	48	21.1
College graduate	62	27.2
Occupation
Farmer	41	18.0
Government employee	54	23.7
Daily laborer	31	13.6
Merchant	19	8.3
Private employee	83	36.4
Monthly income
<1000 birr	38	16.7
1001–3000 birr	109	47.8
3001–5000 birr	42	18.4
>5000 birr	39	17.1

Majority of the study subjects have acyanotic congenital heart disease (200/228) accounting for 87.7%. The age at diagnosis for most of the patients, 93.4% (213), is after 12month. (See Table 2).

Table 2

Clinical characteristics of CHD patients.

Variables	Frequency	Percent
CHD type
Acyanotic	200	87.7
Cyanotic	28	12.3
Age at diagnosis
<01 month	15	6.6
01–12 months	58	25.4
>12 months	155	68.0
Pulmonary hypertension
Yes	68	29.8
No	159	69.7
Anemia
Yes	34	14.9
No	194	85.1
Underweight
No underweight	116	50.8
Moderate	49	21.5
Severe	63	27.6
Wasting
No wasting	134	58.8
Moderate	38	16.7
Severe	56	24.6
Stunting
No stunting	130	57
Moderate	49	21.5
Severe	49	21.5

Overall prevalence of underweight, wasting and stunting among CHD patients was 49.1% (112), 41.3% (94) and 43% (98), respectively.

The commonest congenital heart disease was VSD, occurring alone in 25% and co-exising with other congenital heart defects in 40.8%, followed by PDA (15.4%). The commonest cyanotic CHD is TOF occurring in 9.2% of all the CHDs. See Table 3.

Table 3

Type and prevalence of cardiac defects among CHD patients.

Types of CHD	Frequency	Percent
Acyanotic
VSD	57	25.0
PDA	35	15.4
ASD	22	9.6
AVSD	15	6.6
CoA	1	0.4
PS	12	5.3
AS	10	4.4
VSD+ASD	7	3.1
VSD+PDA	15	6.6
VSD+PDA+CoA	6	2.6
AVSD+PDA	4	1.8
PS+VSD	5	2.2
AS+PDA	9	3.9
Cyanotic
TOF	16	7.0
TOF+PA+PDA	6	2.2
PA+PDA	2	0.9
TGA+VSD	3	1.3
TAPVR	1	0.4

From the 200 study subjects with acyanotic CHD, burden of underweight was 48%, wasting was 41.5% and stunting was 42.5%.

In the cyanotic CHD group, 53% of them were underweight, 35.7% were wasted and 42.8% of them were stunted. (see Table 4).

Table 4

Comparison of CHD patients with and without pulmonary hypertension based on their nutritional status.

Variables	APAH	AWTPAH	X2 (P value)	CPAH	CWTPAH	X2 (P value)
Underweight
No	27	76	5.7 (0.057)	0	13	1.9 (0.17)
Yes	39	57		2	14
Wasting
No	33	83	4.2 (0.12)	1	17	0.2 (0.66)
Yes	33	50		2	9
Stunting
No	31	83	5.6 (0.06)	0	17	2.9 (0.09)
Yes	35	50		2	10

APAH = Acyanotic with pulmonary hypertension, AWTPAH = Acyanotic without pulmonary hypertension, CPAH = Cyanotic with pulmonary hypertension, CWTPAH = Cyanotic without pulmonary hypertension, X2 = Chi square.

Chi-square test was done to check if there is significant difference between CHD patients with PAH and without PAH based on their nutritional status using P<0.05 as significant.

Among Acyanotic patients, PAH looks to have some degree of association with all underweight, wasting and stunting but no significant difference was observed between the two groups (acyanotic vs cyanotic).

Among cyanotic patients, PAH is found to have association with stunting but no significant difference was observed between patients with and without PAH based on their nutritional status.

Bivariate analysis was done to check if; Patient’s sex, age, residence, age at diagnosis, acyanotic CHD, VSD, ASD, PDA, cyanotic CHD and TOF, have significant association with underweight at P<0.2. Multivariable analysis was done to see if there is significant association of factors identified on bivariate analysis with outcome variable at P<0.05.

Children between 5 and 10 years of age were 2.3 times more likely to be underweight than those between the age of 1 and 3 years.

Children with ASD were 70% less likely to be underweight compared to others with CHD but without ASD 70% (95% CI:0.1–0.9) (see Table 5a).

Table 5

a. Bivariate and multivariate analysis for Underweight. b. Bivariate and multivariate analysis for wasting. c. Bivariate and multivariate analysis for stunting.

Variables	Underweight (Yes)	Normal weight	COR (95% CI)	P Value	AOR (95% CI)	P Value
Residence
Rural	59	46	1.7 (1.0–2.9)	0.05*	1.6 (0.9–2.8)	0.11
Urban	53	70	1.0		1.0
Age
<1 yr	27	46	2.0 (0.9–4.6)	0.09*	2.3 (0.9–5.3)	0.053
1–3 yr	19	16	1.0		1.0
3–5 yr	21	23	1.6 (0.7–3.3)	0.3	1.6 (0.7–3.5)	0.2
5–10 yr	44	30	2.5 (1.3–4.8)	0.01*	2.3 (1.1–4.5)	0.02*
>10 yr	1	1	1.0		1.0
ASD
Yes	6	16	0.4 (0.1–0.9)	0.04*	0.3 (0.1–0.9)	0.03*
No	106	100	1.0		1.0
Variables	Wasting (Yes)	Wasting (No)	COR (95% CI)	P Value	AOR (95% CI)	P Value
VSD
Yes	19	38	0.6 (0.3–1.0)	0.16*	0.6 (0.3–1.2)	0.14
No	75	96	1.0		1.0
PDA
Yes	19	16	1.9 (0.9–3.9)	0.09*	1.7 (0.8–3.5)	0.19
No	75	118	1.0		1.0
PAH
Yes	34	34	1.7 (0.9–2.9)	0.08*	1.9 (1.0–3.4)	0.04*
No	60	100	1.0		1.0
Variables	Stunting (Yes)	Stunting (No)	COR (95% CI)	P Value	AOR (95% CI)	P Value
Residence
Rural	53	52	1.8 (1.0–3.0)	0.04*	1.7 (0.9–2.9)	0.06
Urban	45	78	1.0		1.0
ASD
Yes	5	17	0.4 (0.1–1.0)	0.05*	0.3 (0.1–0.9)	0.04*
No	93	113	1.0		1.0
PAH
Yes	37	31	1.9 (1.1–3.4)	0.02*	1.9 (1.0–3.4)	0.03*
No	61	99

Bivariate analysis was done to check if; Patient sex, age, residence, age at diagnosis, Acyanotic CHD, VSD, ASD, PDA, PAH, cyanotic CHD and TOF, have significant association with wasting at P<0.2. Multivariable analysis was done to see if there is significant association of factors identified on bivariate analysis with outcome variable at P<0.05. We are mentioning here only those variables which showed associations.

As described in Table 5b, children with PAH are more likely to have wasting compared to those without PAH with an odds of 1.9 (95% CI: 1.0–3.4) among children with CHD.

Bivariate analysis was done to check if; Patient sex, age, residence, age at diagnosis, Acyanotic CHD, VSD, ASD, PDA, cyanotic CHD and TOF, have significant association with stunting at P<0.2. Multivariable analysis was done to see if there is significant association of factors identified on bivariate analysis with outcome variable at P<0.05.

Children with ASD have decreased chance of being stunted by 70% (95% CI: 0.1–0.9) compared to those with CHD but without ASD.

Children with PAH are more likely to be stunted compared to those without PAH with an odds of 1.9 (95% CI: 1.0–3.4) among children with CHD (see Table 5c).

4. Discussion

Children with CHD usually do not exhibit failure to thrive at the time of birth and during neonatal period unless the CHD is hemodynamically significant during that period. Otherwise, it usually become apparent after few weeks of like when the pulmonary pressure declined to its nadir. The severity and degree of malnutrition rely on mainly additional factors which characterizes the CHD. These are presence of cyanosis, development of heart failure and pulmonary hypertension [13-15].

Indian study of anthropometric data in children with CHD revealed dietary intake, educational level, occupational and socioeconomic status did not affect the chance of being malnourished. In low- and middle-income countries, the prevalence of abnormal preoperative anthropometry is high attributed to late presentation, delays in corrective intervention, and frequent hospitalizations related to respiratory infections [6].

In this study, out of 228 participants the overall burden of underweight was 49.1% (112). Among the acyanotic group 48% (96) were underweight which is lower than the cyanotic group where prevalence reaches 53% [16]. In a similar study done in Uganda, involving 194 children with CHD, underweight assessed for those 0-10years, accounted for 42.5%. [7]. Oday Faris Washeel and his colleagues found out underweight accounted for 32% of the 65 studied subjects, 0-5years with CHD who visited the heart center in Nursing College, Al-Muthanna University, Samawah, Iraq. [5]. On the other hand, an Indian study to identify determinants of malnutrition in children with congenital heart disease (CHD) which involved 476 pre-operative patients, found a higher underweight percentage, 59%. [6].

The overall prevalence of wasting in this study was 41.3% (94). Children with acyanotic CHD were observed to have a higher percentage of wasting as compared to those with cyanotic CHD, accounting 41% and 35%, respectively. This percentage is higher in the Indian and Ugandan study where wasting was detected in 56% and 58% of the children with CHD respectively [6,7]. An even higher percentage was reported from the study in Al-Muthanna University, Samawah, Iraq, 64%, which was attributed to premature delivery and low birth weight [5]. Infants delivered premature and with low birth weight were excluded from this study.

Ninety seven out of the 228 study subjects were found to be stunted which equals 43% (98) and no significant difference was seen between the cyanotic and acyanotic CHD. Comparable result was seen in the Ugandan study with stunting of 45%. [7].

In this study pulmonary hypertension is associated with increased risk of being wasted (OR 1.9 (95% CI: 1.0–3.4)) and stunted (OR 1.9 (95% CI: (1.0–3.4)). Acyanotic patients with PAH looks to have some degree of association with all underweight, wasting and stunting but no significant difference on the risk of malnutrition between acyanotic and cyanotic CHD. But in general children with PAH are more likely to have wasting and stunting compared to those without PAH.

In contrast to ours, findings from the study done by Ijeoma Arodiwe and his colleagues stated that severe malnutrition and stunting were seen more in those with cyanotic CHD and developed pulmonary hypertension in comparison to acyanotic heart disease who were only wasted [4]. In another study by Varan B, Tokel K and Yilmaz G. to compare the development of malnutrition in cyanotic and acyanotic ones in the presence and absence of pulmonary hypertension, they found out those with cyanotic CHD are likely to develop stunting than wasting, and out of which who developed pulmonary hypertension are severely affected [16].

Of the total patients 34 (14.9%) of them had anemia with variable degree of severity from mild to severe and it was not found to have association with increased risk of malnutrition in this study; but in Ugandan study they found out association and those children are with moderate or severe anemia [7,17].

The other finding in this study is the decreased risk of being underweight and stunted (70% (95% CI: 0.1–0.9)) in children with ASD than those CHD without ASD.

In the Indian study, they concluded, among many other risk factors identified, older age at surgical correction of the CHD was associated with increased risk of malnutrition and poor recovery after surgery [6]. Similar conclusion was made in the Nigerian study where they found Children in the older age group and those presenting late are more prone to malnutrition and poor growth [4]. The finding in this study was also similar to the above findings. It was found that children above 5 years (especially 5 to 10 years of age) are 2.3 times more likely to be underweight.

According to 2019 Ethiopia Mini Demographic and Health Survey (EMDHS), 7% of children in Ethiopia are wasted, and 1% are severely wasted (below -3 SD) [18]. While our study identified higher prevalence of wasting in patients with CHD, which is 41.3%. In the same report of EMDHS, results show that 21% of all children are underweight (below-2 SD), while the prevalence is higher in our participants, 49.1%. The presence of such malnutrition will subject them to develop complication related to malnutrition and could also affect the outcome of the intervention, while the long term complications of malnutrition is not forgotten[7-10]. This research might help policy makers and/or nutritionists to come up with new strategies in the prevention and management of malnutrition in such patients who are at higher risk.

5. Limitations of the study

This study failed to assess an important contributing factor to malnutrition in CHD, that is CHF. This was not possible because study subjects were on outpatient follow up only.

The limited no of cyanotic patients included in the study also made comparing the two groups difficult (cyanotic vs acyanotic) and the number of patients with CHD and whose age is above ten years were few which makes difficult to draw any conclusion.

6. Conclusion

Malnutrition is a major problem in children with congenital heart disease. This indicates that proper and routine nutritional assessment should be part of the care while dealing with such patients and appropriate measures need to be undertaken this problem. Subsequent studies with larger sample size may strengthen the findings in this research and also the impact of malnutrition in such patients can further be studied in detail.

(SAV)

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9 Jul 2021

PONE-D-21-07948

Nutritional assessment and associated factors in children with congenital heart disease in Ethiopia.

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Reviewer #2: Partly

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Reviewer #1: Yes

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Reviewer #1: The authors conducted an interesting study with some sort of clinical importance. They assessed the impact of nutritional profile on children with CHF, considering a list of confounders that includes their socio-demographic data. Their statistical tools were sound and results supported their finding and presented in clean way.

Reviewer #2: Dear authors,

1- The current manuscript is written in a class education fasion and this fasion could not be accepted as journal paper. You should rewrite the manuscript and follow carefully the journal's guidelines for authors regarding proper manuscript structure and design.

2- The authors enrolled children from 1 year to 17 year old. Assessing nutritional status in a 2 year old child is not like assessing nutrional status in a 17 year old teenage. The age limit should be re considered.

3- The authors should make a separate and complete analyses using subgroup analyses for different age groups (i.e., <5 yr, from 5 to 12 yr, from 12 to 17 yr).

4- A comparison group composed of healthy children from the same region, same community and same age is needed. This is very important to measure properly the significance of changes in nutritional status.

5- In the methodology and study protocol, calculate the minimal sample size needed to conduct the study.

6- In the analysis, make adjustment for the relevant, significant and confounding variables before concluding the results.

7- The authors includes all types of congenital heart disease (I.e., simple defects and complex defect, treated/corrected and untreated/uncorrected). This point should be clear, revised, defended and properly discussed.

Regards

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Reviewer #1: No

Reviewer #2: Yes: Rami Riziq Yousef Abumuaileq

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1 Oct 2021

Dear Reviewers, we would like to thank you very much for your precious time in revising the paper and for your invaluable comments to enrich the manuscript.

We would like apologies and be thankful for the editorial team as well for our delayed responses as we have postponed the date for our response after informing the editorial team as we have been doing another research which is a continuation of this one that is assessing the impact of corrective intervention in malnourished children with CHD.

Submitted filename: Response to Reviewers.docx

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9 Feb 2022

Submitted filename: Review comments on PONE-D-21-07948_R1.docx

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7 Mar 2022

I have uploaded my response as a separate file. Here again, I have copied my responses.

We would like to extend our gratitude for the reviewers and editors for your time and valuable comments. We have addressed all the comments in three pages and the response is written below each comment accordingly. All revised contents in the new manuscript are highlighted with light blue color.

From one of the reviewers (comment #5) there was also a comment about the use of standard English. While revising the manuscript, we have tried to address some of the errors. We highlighted the corrected part in yellow.

Thanks

Temesgen

Reviewer #2:

The manuscript has been improved. We still have two comments:

1- In the discussion before the limitations section, the authors should highlight the clinical implications of the current study. These clinical implications should be clear and practical.

2- The authors should revise carefully the care checklist of the journal.

Response:

1- As a last paragraph in the discussion (just above “limitation of the study”) we have added a new paragraph which describes the clinical implication of our study.

2- The manuscript is restructured as per PLOS ONE ‘manuscript organization’ guideline. So, we made corrections on the first page and the table of contents as some contents need to be either reshuffled or removed. The correction made in the manuscript are highlighted in light blue color.

- Acronym and abbreviations - rewritten.

- The abstract page reduced to one.

- Abbreviations are removed from the abstract.

- According to manuscript organization, the literature review and objective are removed while the objective in the abstract part has been left as it was.

- Acknowledgment added.

Reviewer #3:

Informed consent

It is shown as “patient’s oral consent” in ethic statement of cover letter. However in the paper text, it is shown as “written consent”. Please harmonize.

Response:

In the abstract there is a phrase stating about consent and it is corrected and rephrased same as the one mentioned in the ‘ethical consideration’ as ‘Data was collected from patient card and care givers of the children included in the study after obtaining their informed written consent using data inquiry sheet.’

I could not find a phrase stating about consent in the cover letter, which I have attached again.

Reviewer #3:

Format and structure of the paper

The paper does not align with a standard journal paper format. For example, rather long introduction with short discussion. Authors should reconcile.

• Introduction sections 1.1 to 1.3 are repetitive. These sections should be consolidated into one section.

Response: We have minimized the introduction part by avoiding repetitive information.

- Section 1.2 and 1.3 are minimized and specially 1.3 is rewritten again.

Reviewer #3:

Format and structure of the paper Authors should remove section 2. literature review. Then, the contents can be integrated into discussion or introduction section.

Response: Literature review part is removed, and it was not even in the PLOS ONE journal manuscript organization format.

• Section 3. Objectives. Authors should not use bullet style format.

Response: According to manuscript organization the objective is removed while it is left in the abstract part as it was.

• Section 4.1. Irrelevant information about hospital. Please reconcile.

Response: Some unnecessary phrases are removed.

• Sections 4.2-4.4: Repetitive, please consolidate

Response: Re-written

• Section 4.10. Irrelevant, please remove

Response: removed

Abstract

• Children age between 5-10? Since Authors revised table. Same applies to conclusion, please update.

Response: corrected as per the comment.

Methodology

Section 4.4. Authors need citation of a research from Egypt to determine sample size.

Response: Reference # 13. Hassan BA, Albanna EA, Morsy SM, Siam AG, Al Shafie MM, Elsaadany HF, Sherbiny HS, Shehab M, Grollmuss O. Nutritional Status in Children with Un-Operated Congenital Heart Disease: An Egyptian Center Experience. Front Pediatr. 2015 Jun 15;3:53. doi: 10.3389/fped.2015.00053. PMID: 26125014; PMCID: PMC4467172.

• Authors conducted bivariate analysis for certain set of variables followed by multivariate analysis. In the table 5.x, authors showed only three variables each without mentioning other variables. Did other variables meet statistically significant associations? Authors should clarify this in the text.

Response: Multivariable analysis was done to see if there is significant association of factors identified on bivariate analysis. We are mentioning here only those variables which showed associations. We put this statement in the result part above the table (highlighted in blue color).

• For bivariate analysis, authors used both Acyanotic CHD and cyanotic CHD. I do not think there were control population. Does this have to be “CHD type”?

Response: We used this quantitative analysis to compare two variables which are CHD types otherwise we don’t have a control group.

Discussion

• In your population or general CHD studies, Do patients who have PAH exhibit more severe condition? Do patients only have ASD exhibit less severe condition? Then, it makes sense for the associations with malnutrition. At least, you want to include in the discussion.

Response: yes. Those patients with PAH are at higher risk of developing malnutrition, especially wasting and stunting as we mentioned it in the result Table 5b and 5c.

The other finding in this study is the decreased risk of being underweight and stunted (70% (95% CI: 0.1-0.9)) in children with ASD than those CHD without ASD.

As per your comment we put the above statements in the discussion as well (page 18 and 19)

Submitted filename: RESPONSE to Reviewers.docx

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29 Mar 2022

10 Apr 2022

Responses to reviewers

Hello Dears,

Thank you again for your time and continuous support.

Responses for the specific comments are highlighted yellow in the revised manuscript. One of the comments from reviewers was the use of standard English. I have gone through the manuscript again and corrected many grammatical errors and words which are shaded with red.

Review Comments to the Author

Reviewer #3: Authors have partly addressed my comments. Authors further need to address the comments below.

Informed consent

Please align to written consent from oral consent in Ethics Statement, which is in 5th page of the PDF manuscript (PONE-D-21-07948_R2)

Response:

Corrected as ‘written consent’.

Introduction:

Page 7 from line 8-12, I do not understand the wording here. Please reword using standard English.

Response:

Addressed accordingly, is highlighted in yellow.

Results:

Authors categorize acyanotic and cyanotic as CHD type in Table 2. Later, authors state both acyanotic CHD and cyanotic CHD have significant associations by bivariate analysis (last line of P15 and two more in P16 and 17). Author confirmed no control group was included. Please remove both “acyanotic CHD” and “cyanotic CHD”, and replace to “CHD type”.

Response: Corrected as per the comment; in the revised manuscript page 16 and 17

Discussion:

Comment: P18, line 1-3, 11 and 20, Authors added parentheses and patient numbers. These are confusing with the citations. Please remove.

Response:

Removed as per the comment. page 14 and 15 highlighted with red.

The last sentence on page 6 is removed because it does not explain specifically why Infants and children are more likely to suffer from poor nutrition compared to adults.

Submitted filename: Response to reviewers.docx

Click here for additional data file.

24 May 2022

Nutritional Assessment and Associated Factors In Children with Congenital Heart Disease - Ethiopia

PONE-D-21-07948R3

Dear Dr. Desta,

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.

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Kind regards,

Laszlo Farkas, MD

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 #3: All comments have been addressed

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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 #3: Yes

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

Reviewer #3: Yes

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

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Reviewer #3: Yes

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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 #3: Yes

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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 #3: I congratulate authors to have a manuscript met PLOS ONE standards. All comments are addressed properly.

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Reviewer #3: No

2 Jun 2022

PONE-D-21-07948R3

Nutritional Assessment and Associated Factors In Children with Congenital Heart Disease - Ethiopia

Dear Dr. Desta:

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.

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on behalf of

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Academic Editor

PLOS ONE