Low birth weight and associated factors among HIV positive and negative mothers delivered in northwest Amhara region referral hospitals, Ethiopia,2020 a comparative crossectional study.

BACKGROUND: Even though pregnancy does not affect HIV infection progression, HIV affects the pregnancy outcome. Maternal HIV infection has many untoward effects which include low birth weight which is the major cause of neonatal, infant, and under-five mortality. However, there is controversy and limited information about the effect of HIV status on birth weight around the world including Ethiopia. Therefore, this study aimed to compare the prevalence of LBW and their associated factors among HIV+ and HIV- mothers delivered in Northwest Amhara region referral hospitals.
METHOD: A comparative crossectional study was conducted from September 2016 to September 2019. A simple random sampling technique was used to select 474 participants. Data were collected from the mothers' chart by using a data extraction sheet and then entered into Epi-data and exported into SPSS for analysis. Independent variables with p-values < 0.2 in the bivariable analysis were entered into multivariable logistic regression models with backward logistic regressions method to control confounders and identify the factor. RESULT: The overall prevalence of LBW was 13.9% (95% CI:10.8%-17.1%). The prevalence was higher among HIV+ 17.7% (95% CI:14.1%-22.8%) than HIV- mothers 10.1% (95% CI:6.3%-13.8%). CD4 count < 200 cells/mm3 [AOR 3.2, 95%CI (1.05, 9.84)] and between 200-350 cells/mm3 [2.81, 95% CI (1,08, 7.28)], Mothers with MUAC <23 cm [AOR 3.39, 95% CI (1.41, 8.18)] and gestational age <37 weeks [AOR 7.34, 95% CI (3.02,17.80)] were significantly associated with LBW in HIV+ mothers. While, rural residence [AOR 3.93,95% CI (1.356,11.40)], PROM during current pregnancy [AOR 4.96, 95% CI (2.55, 15.83)] and gestational age <37 week [AOR 8.21, 95% CI (2.60, 25.89)] were significantly associated with LBW in HIV negative mothers.
CONCLUSION: The prevalence of LBW was significantly higher among HIV+ mothers as compared to HIV-mothers and this study suggests to emphasize nutritional supplementation of HIV positive mothers, needs to focus on nutritional counseling during ANC/PMTCT follow up and encourage HIV positive mothers to delay their pregnancy until their immune status improve.

Introduction

Since the beginning of the epidemic, more than 74.9 million people have been infected with HIV globally. By the end of 2018 37.9 million people were living with HIV and 82% of pregnant women’s residing with HIV had access to Anti-Retroviral Treatment (ART) to stop transmission of HIV to their baby globally [1]. According to the World health organization (WHO) report, the African region remains the most severely affected area particularly East and Southern Africa [2]. In Ethiopia by 2018, nearly 690,000 people were living with HIV/AIDS and the adult prevalence rate was 1% and the incidence rate was 0.24% per year [3].

The prevalence of HIV increased from 2005 to 2011 in most of the regions Ethiopia (1.4% in 2005 and 1.5% in 2011), including Dire Dawa, Addis Ababa, Gambella, South Nations, SNNPR, Benishangule Gumuz, and Somali. On the other hand, in the later 5 years duration, 2011 to 2016, the prevalence was decreased in all of the administrative regions, decreasing from 1.5% to 0.9% [4]. the pooled prevalence of HIV in pregnant women in Ethiopia was 5.74%. Besides, subgroup analysis was done based on different regions of Ethiopia and there is significant variation in HIV prevalence between regions, the pooled prevalence among subgroups indicated 9.50% in Amhara, 4.80% in Addis Ababa, 2.14% in SNNP, and 4.48% in the Oromia region [5]. This pooled estimate is higher than the national HIV prevalence among the general population of Ethiopia.

Pregnancy does not affect HIV infection progression [6]. However, HIV affects birth outcomes. Several studies in Africa and other countries revealed that HIV-positive mothers had a high risk of adverse birth outcomes, including, low birth weight babies, stillbirths, and preterm birth [7-10]. In contrast, a study done in India showed no differences between HIV-infected and uninfected mothers with respect to obstetric and birth outcomes [11].

The birth rate of Ethiopia in 2019 was 32.109 births per 1000 people, and it was declined from 2018 by 1.42% [12]. Low birth weight (LBW) is defined as a birth weighing below 2,500 grams irrespective of gestational age. Globally 20.5 million live births suffered from LBW in 2015 and almost half of them in Southern Asia which is 9.8 million and about one-quarter of all LBW newborns are in sub-Saharan Africa [13]. According to the Ethiopian demography health survey (EDHS) 2016, the proportion of births weighing less than 2.5 kg at birth was 13% [14]. LBW is a major risk factor for neonatal, infant, and under-five mortality [15, 16]. Likewise, these children experience more morbidity, both in the short and long term, including suffered from stunted growth, lower Intelligent Quiescent (IQ) and the consequences of low birthweight continue into adulthood, increasing the risk of adult-onset chronic conditions such as obesity and diabetes [17, 18].

Studies revealed that mothers in the teenage age group, age >30 years, and residing from the rural area had a greater risk of having LBW baby [19, 20]. Different studies showed that behavioral factors like alcohol consumption, cigarette smoking, and chewing Khat during pregnancy also increases the risks of LBW [20, 21]. Being anemic during the pregnancy, history of chronic medical conditions, having had urinary tract infection (UTI) during pregnancy, malaria infection, Untreated reproductive tract infection (RTIs), bad obstetric history, and pregnancy-related complications increase the risk of delivering LBW baby [9, 20, 22]. The magnitude of LBW among mothers with mid-upper arm circumference (MUAC) less than 23cm was higher when compared with those with MUAC greater than 23cm [22, 23]. Moreover, mothers whose body mass index (BMI) was below 18.5 were at high risk of LBW [9, 19]

The baseline maternal CD4 counts below 200 cells/mm3, maternal HIV status, maternal exposure to highly active antiretroviral therapy (HAART), advanced-stage HIV disease, intrauterine HIV transmission, and viral load ≥20 000copies/ml are factors influencing the occurrence of adverse birth outcomes [9, 19, 21, 24].

Even though there is an advancement of medical technologies, improvement in utilization of antenatal care (ANC), Prevention of Mother to Child Transmission (PMTCT), and institutional delivery LBW is still a public health problem in Ethiopia. However, there are few studies done related to birth outcomes in HIV-infected women in Ethiopia and even the existing ones can’t conclude regarding the effect of HIV on birth outcomes because the studies focus only on the HIV+ pregnant women and there is no HIV- comparison group. Therefore, this study aims to assess the LBW and associated factors among HIV+ and HIV- women in northwest Amhara region referral hospitals.

Methods and materials

Study design, period, and area

A hospital-based comparative cross-sectional study was conducted among mothers delivered from September 2016 to September 2019 in northwest Amhara region referral hospitals and the data was extracted from March 3 to April 4 and May 5- May 18/ 2020. In the northwest part of the Amhara region, there are 3 referral hospitals such as; University of Gondar comprehensive and specialized Hospital (UoGCSH), Felege Hiwot comprehensive, and specialized hospital (FHCS), and Debre Markos referral hospital. Each referral hospital’s catchment population is estimated to be 5–7 million people. the annual average number of births in each hospital is 6000 per year. The overall incidence rate of new HIV infection from 2015 to 2018 in the Amhara region was 6.9 per1000 tested population. The incidence rate was higher in females (4.1 per1000 population) than in males (2.84 per1000 population) [25]. The Ethiopian government started to implement Option B+ (initiation of antiretroviral therapy for all pregnant mothers) PMTCT service in 2013. Since then, the Option B+ treatment option has been launched in all health facilities and provided without fee. According to the operational plan, under Option B+, all HIV+ pregnant mothers will receive triple antiretroviral therapy (ART) drugs and will continue the treatment for the rest of their lives. Focused antenatal care is provided in those hospitals and this care recognize all pregnant women are at risk of complication, therefore, it provides safe, simple, and cost-effective intervention to all pregnant women to maintain normal pregnancies, save lives by preventing complications or early detection, and treatment of complications.

Population

All mothers delivered from September 2016 to September 2019 in northwest Amhara region referral hospitals were considered to study participants. All mothers delivered from September 2016 –September 2019 in northwest Amhara region referral hospitals with a gestational age of 28 weeks and above were included in the study. However, Mothers who had unknown or unreliable last normal menstrual period (LNMP) with the absence of ultrasound evidence, a mother with unrecorded birth weight.

Sample size determination, Sampling procedure, and study variables

The required sample size was determined by using a double population proportion formula by taking the required statistical assumptions Zα/2 = 1.96, power (β) = 0.84, r = ratio of N2 to N1 which is taken as 1, P1 = Proportion of LBW among HIV positive mothers = 21.4% [9], P2 = Proportion of LBW among HIV negative mothers = 11.9% [26]. The total final estimated sample size was 474 The calculated sample size was distributed equally among the two populations(N1 = 237, N2 = 237). A simple random sampling technique was used to select the study participants. The total sample size was proportionally allocated for the three hospitals. Medical Record Number (MRN) of study participants was filtered first from the logbook of each referral Hospital according to their delivery time and HIV status then we gave a serial number for the remaining participants and select each record for our study using a computer-generated random number. LBW was the outcome variable and sociodemographic factor (age, residence, educational status, history of substance use, including alcohol drinking and smoking), Maternal medical and obstetric related factors (anemia, chronic medical disease, UTI, PIH, APH, and PROM, previous history of abortion, previous history of stillbirth, previous history of low birth weight, parity, gravidity), Nutrition-related factor (nutritional counseling during ANC, iron and folic acid supplementation during pregnancy, pre-pregnancy BMI, MUAC,), HIV related status (CD4 count, viral load, WHO clinical stage of the disease, initiation of ART, time of initiation of ART, time of diagnosis with HIV, types of ARV) were independent variables.

Definition of variables

Low birth weight

A birth weight < 2500 gram irrespective of gestational age [22].

UTI

Defined as a documented clinical/laboratory diagnosis of UTI any time during the pregnancy [27].

Gestational age

determined by clinicians during antenatal visit or delivery using the last normal menstrual period (LNMP), or early ultrasound evidence [9].

APH

defined as any vaginal bleeding in the mother after 28 weeks of gestation as documented in the records by the attending clinician [27].

PIH

defined clinically as a blood pressure of >140/90 mmHg after 20 weeks of gestation with or without proteinuria and/or edema as diagnosed and documented by the attending clinician [27].

Stillbirth

Dead birth after 28th week of gestation and before the expulsion from the uterus [28].

Anemia

Documented Hgb level below 11gm/dl laboratory diagnosis [27].

Data collection instrument, data collection procedures, and quality assurance

Data were collected from mothers’ charts using a structured checklist prepared in English. The data extraction sheet is designed based on study objectives and developed by reviewing national and international literature and by observing charts. Three supervisors having a second degree in clinical midwifery and six data collectors having a first degree in midwifery were involved in the data collection process. A 5% preliminary chart review was conducted in the Gondar university comprehensive and specialized hospital before the actual data collection and amendments were considered based on the result of a preliminary chart review. Data collectors and supervisors were trained for one day regarding the technique and data collection process by the principal investigator before the actual data collection. Frequent and timely supervision of data collectors was undertaken by the supervisor and principal investigator. The collected data was checked out for its completeness during data collection by the principal investigator and supervisor.

Data processing and analysis

Data were coded and then entered, edited, and cleaned using EPI data version 4.6 and exported to SPSS 25 statistical software for analysis. we manage missing data by using replacement technique if less than 20% of value are missed in one variable (E.g. we managed by replacement technique pre-pregnancy BMI, MUAC, ANC follow up, iron duration, anemia.)but if more than 20% of values missed in one variable we discard the variables (E.g. we discard marital status, educational status, occupational status, substance abuse, pregnancy status, pre-pregnancy weight). The outcome variable was dichotomized and coded as ‘0’ and ‘1’, representing those who have birth weight > = 2500 K.g. and have < 2500 K.g. respectively. Descriptive statistics were used to describe the socio-demographic characteristics of the respondents, the magnitude of LBW of HIV+ and HIV- women. Text and tables were used to present the findings. The binary logistic regression model was used to assess the association between dependent and independent variables. Variables with a p-value of less than 0.2 in bivariable logistic regression were considered for multivariable logistic regression analysis. In the multivariable analysis, a P-value of less than 0.05 and an odds ratio with 95% CI were used to declare the presence and the strength of association between the independent and outcome variable. Before conducting the multivariable logistic regression model multicollinearity was checked using variance inflation factor (VIF) and there is no multicollinearity between independent variables. The Hosmer and Lemeshow test was used to diagnose the model fitness and the model were adequate.

Ethical approval and consent to participate

Ethical approval was obtained ethical review committee of the Institute of public health on behalf of the Institutional Review Board (IRB) of University of Gondar. Permission was obtained from the clinical director of each hospital. Since this study uses secondary data to ensure confidentiality Personal Identifiers Were not used on the data collection form, and All data were kept strictly confidential and used only for the study purposes.

Results

Sociodemographic characteristics and nutrition-related factors

During the period of review, 237 HIV+ and 237 HIV- mothers and their newborn characteristics were extracted from ANC and delivery registers and analyzed. Among a total of 474 delivered mothers participated in the study, 80.2% of HIV+ mothers were in the age group 20–34 years with a mean age 30.13 (S.D ±4.5) and 86.9% of HIV- mothers were in the age group 20–34 with a mean age of 27.05 (S.D ± 4.7). Regarding residents of the mother, 97.0% were HIV+ and 69.2% of HIV—women were urban residents.

During antenatal care follow up 99.2% of HIV+ and 97% of HIV- mothers were counseled about dietary intake. More than three-quarters (84%) of HIV+ mothers had MUAC ≥23cm (Table 1).

Table 1

Sociodemographic and nutrition-related characteristics of mothers delivered in Northwest Amhara regional state referral hospitals (N = 474).

Variable	categories	HIV positive		HIV negative
		Frequency	%	Frequency	%
Age	< 20	1	0.4	8	3.4
	20–34	190	80.2	206	86.9
	> = 35	46	19.4	23	9.7
Resident	Urban	230	97.0	157	66.2
	Rural	7	3.0	80	33.8
Iron intake	No	2	0.8	7	3.0
	Yes	235	99.2	230	97.0
Duration of iron	< 3 months	145	61.2	155	65.4
Intake	≥3 months	90	38.0	75	31.6
Nutritional counseling	No	2	0.8	7	3
	Yes	235	99.2	230	97
Pre pregnancy BMI	<18.5	30	15.3
	≥18.5	166	84.7
MUAC	<23cm	38	16.0
	≥23cm	199	84.0

Medical, obstetric related characteristics, Pregnancy and labor-related complications of the mothers

In this study, twenty-five (10.5%) HIV + mothers and eight (3.4%) HIV- mothers were diagnosed with anemia during the current pregnancy. Among the study participants, 82.7% of HIV+ and 59.5% of HIV- mothers had a history of multi-gravidas. Almost all (99.2%) of HIV+ and 97.5% of HIV- mothers had ANC follow up and of which 63.3% of HIV+ and 37.6%of HIV- mothers had four and above ANC follow up respectively. Common pregnancy-related complications retrieved from records were PROM (18.1% Vs 13.9% for HIV- and HIV+ respectively). More than three-quarters of labor in HIV+ and HIV- mothers (85.6% and 81.9% respectively) were initiated spontaneously. About 77.6% HIV + and 63.7% of HIV—mothers current deliveries were spontaneous vaginal delivery (Table 2).

Table 2

Medical, obstetric related characteristics, Pregnancy and labor-related complications of the mothers delivered in Northwest Amhara regional state referral hospitals (N = 474).

Variable	categories	HIV positive		HIV negative
		Frequency	%	frequency	%
Anemia	No	212	89.5	229	96.6
	Yes	25	10.5	8	3.4
History of HTN	No	235	99.2	237	100
	Yes	2	0.8	0	0
History of DM	No	237	100	236	99.6
	Yes	0	0	1	0.4
STI during current pregnancy	No	231	97.5	232	97.9
	Yes	6	2.5	5	2.1
Type of STI	Syphilis	5	2.1	4	1.7
	HBSg	1	0.4	1	0.4
UTI	No	222	93.7	233	98.3
	Yes	15	6.3	4	1.7
Gravidity	Primigravida	41	17.3	96	40.5
	Multigravida	196	82.7	141	59.5
History of LBW	No	230	97.0	233	98.3
	Yes	7	3.0	4	1.7
History of spontaneous abortion	No	202	85.2	210	88.6
	Yes	35	14.8	27	11.4
History of stillbirth	No	223	94.1	226	95.4
	Yes	14	5.9	11	4.6
ANC follow up	No	2	0.8	6	2.5
	Yes	235	99.2	231	97.5
Number of ANC	<4	85	35.9	142	61.5
	> = 4	150	63.3	89	37.6
PIH	No	223	94.1	197	83.1
	Yes	14	5.9	40	16.9
PROM	No	204	86.1	194	81.9
	Yes	33	13.9	43	18.1
APH	No	234	98.7	224	94.5
	Yes	3	1.3	13	5.5
Malpresentation	No	225	94.9	213	89.9
	Yes	12	5.1	24	10.1
Prolonged labor	No	209	88.2	172	72.6
	Yes	11	4.6	41	17.3
	Elective C/S	17	7.2	24	10.1
Labor status	Induced	17	7.2	19	8.0
	Spontaneous	203	85.6	194	81.9
	Elective C/S	17	7.2	24	10.1
Mode of delivery	SVD	184	77.6	151	63.7
	Cesarean section	52	22	75	31.6
	Instrumental delivery	1	0.4	11	4.6

HIV related characteristics of the mother

The majority (81.0%) of HIV + mothers know their HIV status before pregnancy and 99.6% were in WHO clinical stage one. Among HIV+ mothers, almost all (99.2%) were on ART, of which 81.0% started HAART before pregnancy and all of them had good drug adherence. more than half of (73.0%) HIV + mothers CD4 count were ≥ 351mm3 (Table 3).

Table 3

HIV related characteristics of the mother delivered in west Amhara regional state referral hospitals N = 237).

Variable	Categories	HIV positive
		Frequency	%
Time of HIV diagnosis	before pregnancy	192	81.0
	during pregnancy	43	18.2
	during delivery	2	0.8
ART intervention	No	2	0.8
	Yes	235	99.2
Time HAART initiated	before pregnancy	192	81
	during pregnancy	43	19
HAART regimen	1c	62	26.3
	1d	14	6.0
	1e	143	60.9
	Other	16	6.8
HAART adherence	Good	235	100
	Fair	0	0
	Poor	0	0
PMTCT follow up	No	0	0
	Yes	237	100
WHO clinical stage	stage 1	236	99.6
	stage 2	1	0.4
CD4 count	<200	23	9.7
	200–350	41	17.3
	> = 351	173	73.0
viral load	TND	215	91.6
	< 1000	17	7.2
	> = 1000	3	1.2

1c: AZT+3TC+NVP, 1d: AZT+3TC+EFV, 1e: TDF+3TC+EFV, TND: target not detected.

Prevalence of LBW

The finding of this study showed that the overall magnitude of LBW among mothers delivered in west Amhara regional state referral hospitals was 13.9% (95% CI:10.8%-17.1%) with a mean birth weight of 2938.2 gram (S. D±439.1). Based on the mother’s HIV status the magnitude of LBW was higher in HIV- mothers, which is 17.7% (95% CI:14.1%-22.8%) with the mean birth weight of 2837.97 gram (SD±464.885), while among HIV- mothers the prevalence of LBW was 10.1% (95% CI:6.3%—13.8%) with the mean birth weight of 3033.3 gram (SD±395.1) (Table 4)

Table 4

Birth outcome in Northwest Amhara regional state referral hospitals (N = 474).

Variable	Categories	HIV positive		HIV negative		Overall
		Frequency	%	Frequency	%	Frequency %
Birth outcome	Alive	235	99.2	234	98.7	469	98.9
	Still birth	2	0.8	3	1.3	5	1.1
Sex of newborn	Male	125	52.7	132	55.7	257	54.22
	Female	112	47.3	105	44.3	217	45.78
Birth weight	<2500gram	42	17.7	24	10.1	66	13.9
	≥2500gram	195	82.3	213	89.9	408	86.1

Determinants of LBW

Multivariable analysis result of HIV-mothers showed that women with CD4 count less than 200 cells/mm3 and between 200–350 cells/mm3 were 3 times [AOR 3.2, 95%CI (1.05, 9.84)] and 2.8 times [AOR 2.81, 95% CI (1,08, 7.28)] more likely to have LBW baby respectively compared with those have CD4 count greater than 350 cells/mm3. Mothers with MUAC <23 cm were 3 times [AOR 3.39, 95% CI (1.41, 8.18)] more likely to have LBW babies compared with their counterparts. Newborn babies who were delivered before the gestational age of 37 weeks were 7 times [AOR 7.34, 95% CI (3.02,17.80)] higher to become low birth weight When compared to babies born at a gestational age of 37 weeks and more (Table 5).

Table 5

Bivariable and multivariable logistic regressions of factors associated with LBW among HIV positive mothers.

Variables	Response	LBW		COR (95% CI)	AOR (95%)
		No	Yes
Anemia	No	181	31	1	1
	Yes	14	11	4.58(1.91,11.03)	2.67(0.97, 7.34)
PROM	No	173	31	1	1
	Yes	22	11	2.79(1.23,6.32)	1.30(0.45, 3.78)
Number of	> = 4	131	19	1	1
ANC	< 4	63	22	2.41(1.25,4.77)	1.26(0.49, 8.35)
CD4 count	> = 351	151	25	1	1
	200–350	30	7	2.52(1.11,5.73)	2.81(1.08, 7.28) *
	<200	14	10	4.341(1.73, 10.77)	3.22(1.05,9.84) *
MUAC	> = 23cm	172	27	1	1
	<23 cm	23	15	4.15(1.71, 11.40)	3.39(1.41, 8.18) *
Duration of	> = 3 months	79	11	1	1
iron intake	< 3months	115	30	1.874(0.89, 3.96)	1.68(0.71, 3.99)
Gestational	> = 37 weeks	179	24	1	1
Age	< 37 weeks	16	18	8.34(3.78,18.62)	7.34(3.02,17.80) *

*P-value <0.05.

Multivariable analysis result of HIV- mothers revealed that mothers living in a rural area were 4 [AOR 3.93,95% CI (1.356,11.40)] times more likely to have LBW babies when compared to those mothers who live in the urban area. the odds of delivering LBW babies among mothers who had PROM during current pregnancy were 5 [AOR 4.96, 95% CI (2.55, 15.83)] times higher than their counterparts. Newborn babies who were delivered before the gestational age of 37 weeks were 8 [AOR 8.21, 95% CI (2.60, 25.89)] times higher to become low birth weight When compared to babies born at a gestational age of 37 weeks and more (Table 6).

Table 6

Bivariable and multivariable logistic regressions of factors associated with LBW among HIV negative mothers.

Variables	Response	LBW		COR (95%CI)	AOR (95% CI)
		No	Yes
Residence	Urban	148	9	1	1
	Rural	65	15	3.79(1.58, 9,12)	3.93(1.356,11.40) *
PROM	No	181	13	1	1
	Yes	32	11	4.79(2.97, 11.62)	4.96(2.55, 15.83) *
PIH	No	183	14	1	1
	Yes	30	10	4.36(1.77, 9.70)	3.34(0.97, 10.5)
Number of ANC	> = 4	85	4	1	1
	< 4	123	19	3.28(1.078, 9.99)	1.68(0.30, 9.35)
Duration of	> = 3months	72	3	1	1
Iron intake	< 3 months	135	20	3.56(1.02, 12.37)	3.578(0.77,15.57)
Gestational	> = 37	190	10	1	1
Age	< 37	23	14	11.57(4.61, 29.01)	8.21(2.60, 25.89) *

Discussion

This study compares the prevalence of LBW in HIV + and HIV—mothers delivered in northwest Amhara region referral hospitals. The prevalence of LBW in this study shows difference between the two target populations. In which LBW among HIV + was 17.7% (95% CI:14.1%-22.8%) whereas it was 10.1% (95% CI:6.3%—13.8%). in HIV- mothers. This finding is supported by the study conducted in Nigeria 48.3%adverse pregnancy outcome occurs in HIV+ women compared to 30.3% adverse pregnancy outcomes in the HIV-women and in which low birth weight was 9.4% Vs 3.3% in HIV+ and HIV—mothers respectively [29].

A study done in Calabar teaching hospital, Nigeria, stated that there is a higher proportion of LBW among HIV+ mothers(21.7%) compared with HIV- mothers(14.4%)(8). Moreover, the finding of this study also supported by a study done in Ghana based on maternal HIV infection status, the prevalence of LBW was higher among HIV infected mothers (22.5% Vs 14.1%), and a study done in South Africa revealed that LBW was higher in HIV+ mothers (14% Vs 9%) [30, 31]. A meta-analysis of cohort studies revealed that the prevalence of LBW among HIV infected women ranged from 3.4 to 56.0% and 2.5 to 36.9% in HIV uninfected women [24].

The discrepancy of birth weight among HIV+ and HIV- mothers might be due to compromised immune system of the mother increase the risk of opportunistic infections, which contributed to the occurrence of adverse birth outcomes [24] or it might be due to HAART particularly NVP-based HAART increased risk of preterm birth compared with EFV-based HAART [32] or it might be due to undernutrition secondary to chronic medical conditions (HIV) [9], in which malnourished mothers are highly prone to having LBW baby.

However, a study done in India showed that no differences between HIV+ and HIV—mothers with respect to obstetric and birth outcomes [11]. This might be due to the study excluding severely ill women which may lead to adverse birth outcomes or it might be due to the good nutritional status of the mother that may lead to good birth outcomes.

The odds of being LBW in babies born before a gestational age of 37 weeks was 7 times higher in HIV+ and 8 times higher in HIV- mothers when compared to babies born at a gestational age of 37 weeks and more. This finding is consistent with studies done in Gondar [9, 33, 34] Tigray [35], China [21], Iran[36], and Bangladeshi [37]. This could be because the baby deliver before completion of their normal physical development in the womb which leads to LBW [35]

In this study mothers who had a CD4 count below 200 cells/mm3 and between 200–350 cells/mm3 were 3.2- and 2.8-times higher risk of having LBW respectively as compared to those with CD4 level above 350 cells/mm3. This result is similar to the studies carried out in Northwest Ethiopia public hospitals [9], China, Tanzania [38] and Nigeria [29] this might be due to compromised immune system of the mother may increase the risk of opportunistic infections which affect mothers health, nutritional status and intrauterine fetal growth [9].

HIV+ mothers who had MUAC <23 cm had 3.4 folds higher risk of LBW compared to those who had MUAC ≥ 23cm. This finding is in line with studies done in Dessie referral hospital [22] and Kersa district, southern Ethiopia [23]. This might be due to the intergenerational effect of malnutrition [21], which means undernutrition of the mother may increase the risk of intrauterine growth restriction [35].

HIV- mothers residing in rural areas were 3.9 times more likely to have LBW babies compared with mothers residing from urban. This finding is in line with studies done in Tigray [35], Mekelle hospital [39], and Hosana [20]. This could be because mothers who live in rural areas have lower access to medical services and have poor awareness about health, and nutrition [35]. Rural residence of the mother had an effect on birth weight, which increases the risk of neonatal, infant, and under-five mortality, therefore, the concerned body should work on increasing medical service access and improve their awareness about nutrition.

The likelihood of having LBW baby among HIV- Mothers who had PROM during their current pregnancy was found to be 4.9 times higher compared to those who did not have PROM. This result is supported by studies conducted in South Africa [40] and Kenya [41]. This could be due to provider-initiated early termination of pregnancy because of pregnancy-related complications which lead to LBW [42] or it might be due to that labor will spontaneously initiate within a week after preterm PROM [43] which leads to delivery of a baby before completion of normal physical development.

HIV status of the mother was significantly associated with the LBW among all mothers, the odds of delivering LBW baby among HIV positive mothers were 4(AOR 4.2 95% CI [1.89–9.43]) times higher than negative mothers. this finding is in line with studies done in Gondar university hospital [27, 44], Nigeria [29], USA [45], South Africa [46], and meta-analysis conducted in developed and developing countries [24]. This might be due to compromised immune system of the mother increase the risk of opportunistic infection, which contributes to the occurrence of LBW [24, 47] or another possible explanation is ART drugs especially PI-based increase prematurity [48] and NVP-based HAART resulted in an increased risk of preterm birth [33], which might in turn cause LBW. The result of this study indicated that being HIV positive increases the risk of delivering LBW, therefore, it is better to emphasize HIV prevention.

Limitation of study

Since this study is hospital-based, it doesn’t include mothers who gave birth at home. In addition, data used were secondary there may be bias and incomplete information’s.

Conclusion

In our study, the prevalence of LBW was significantly higher among HIV+ mothers than HIV—mothers. CD4 count < 200cells/mm3 and between 200–350 cells/mm3, MUAC <23cm, and gestational age < 37 weeks were important contributing factors for LBW among HIV + mothers. On the other hand, Rural residence, PROM during the current pregnancy, and gestational age < 37 weeks were factors contributing to LBW among HIV- mothers. Therefore, the nutrition program needs to emphasize activities that improve the nutritional status of HIV+ mothers. Health care providers need to focus on nutritional counseling during ANC/PMTCT follow-up and encourage HIV + mothers to delay their pregnancy until their immune status improves.

(ZIP)

Click here for additional data file.

10 Jun 2021

PONE-D-20-40543

Prevalence of Low birth weight and associated factors among HIV positive and negative mothers delivered in northwest Amhara region referral hospitals, Ethiopia,2020 A comparative crossectional study

PLOS ONE

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Reviewer #1: Yes

Reviewer #2: Partly

**********

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Reviewer #1: I Don't Know

Reviewer #2: No

**********

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #2: No

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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: This is an interesting paper which shows important differences in the birth weights of infants born to HIV positive mothers compared to HIV negative mothers.

The paper needs to be edited and adjusted by somebody with experience in writing journal articles. There are numerous grammatical and language issues which need to be corrected. These will not be specifically highlighted here as there too many to mention.

Introduction:

i) It should be made clear that the 74.9 million is worldwide

ii) More information about number of births in Ethiopia per year. Home birth rate etc.

iii) More information about HIV in Ethiopia would be useful. Is it increasing/decreasing? What % of people are on ARVs etc. Incidence should be quoted as 0.24% per year.

iv) The paragraph about LBW in the world needs to be reworked to make it flow better

v) what is chewing 'chat'? Most readers would not know this.

Methods and Materials

i) It's confusing what is meant by data was extracted from March 3 to April 4 and May 5 - May 18.

Results

This could be shortened. Some results are irrelevant (eg: Rh factor) and some tables could be combined. Results that are easily interpreted in the table do not necessarily need to be mentioned in the text also, although it is understandable that some should be emphasized.

Prevalence of LBW.

Perhaps a box and whisker plot to break the monotony of the tables. Don't need so many decimal places (eg: 439.065)

Why include Still births? What is the benefit?

It is also confusing why preterm infants were included. They are obviously much more likely to be LBW but not necessarily growth restricted. Growth restriction is the whole focus of the paper. So these should either be excluded or determined if they are growth restricted using growth charts for gestational age.

No baby HIV results? It would be important to know the transmission rate. HIV positive infants should be a different baby from an HIV exposed but uninfected infant.

Discussion

Some of the points mentioned above need to be mentioned in the discussion. What about emerging evidence that ARVs may cause hypertension in the mothers and therefore may produce smaller babies?

There are some studies from South Africa comparing unexposed to exposed but negative infants. These could also be included.

So all in all, an interesting study, but needs a lot of editing and revision.

Reviewer #2: • There is a lot of effort in collecting medical chart data from an African hospital. So, the authors are commended for pursuing this endeavor. Also, having a comparison group is a plus.

• In the introduction section, the authors make the case that there is controversy in whether contributes to LBW. While some studies have shown no association between HIV and LBW, there have been one systematic review and another meta-analysis on this topic, so the purpose of the investigation and the resulting findings are not new. See for example (Xiao, Peng-Lei, et al. 2015; 15. Brocklehurst, Peter, and Rebecca French 1998). It is important the authors recognize this and summarize the findings of those studies in the manuscript. They are cited but not discussed. Same can be said about the discussion section where the study is compared to other studies.

• The purpose of the study should be expanded. Currently, it sounds like their overall goal is to investigate HIV’s association with LBW. However, a huge part of the study is looking at risk factors for LBW among mothers living with HIV.

• To be able to somewhat confidently conclude that HIV is associated with LBW in their population, statistically, they should use propensity score matching to account for selection bias into the two groups. Currently, the prevalence of LBW is provided for each group, with an associated 95% CI. It is unclear what is driving these differences, since there is such an imbalance in the confounding variables. In addition, it is also not clear where that 95% CI statistic is coming from. Just computing the prevalence is not adequate since the sample is not a randomized selection (that is those who are HIV+ and those who are not—and not necessarily the sample of participants from the hospital)

• The prevalence of HIV is also driven by context—(For example rich countries vs. low income countries, differences in access to ART, and underlying nutritional status). The sample is largely urban and drawn from three tertiary hospitals. Tertiary hospitals see more at risk patients than non-tertiary hospitals, including more mothers living with HIV. As a result, the prevalence of LBW among the two populations could be driven by that. Relatedly, since the study was not nationally representative and only done in three tertiary hospitals, the title of the study should reflect that, so that it is not misleading as a nationally representative study. Moreover, there has to be more detail about the setting. What is the HIV prevalence among pregnant women? What proportion has access to treatment? What PMTCT services are offered?

• There are so many tables in the results section and they can be combined. For example, the demographic variables can be combined.

• Given that they are looking at so many variables, the analysis should account for multi-collinearity, using variance inflation factor.

• Missing data and missing folders are a big problem with medical chart reviews. Without disclosing how much folders were missing and how much data was also missing, is hard to have confidence in the numbers and results. The number of folders would affect the denominator in calculating LBW. This information should be provided for mothers living with and those without HIV.

• The HIV field has moved away from labelling mothers as HIV+ and HIV- to people centered labels like mothers living with HIV.

Introduction

• Antiretroviral therapy access play a significant role in prevalence of LBW and transmission of HIV. The background should discuss this relationship between access and LBW

• In justifying the study, the authors indicate that there have been previous studies conducted in Ethiopia, but they have lacked a comparison group. None of these studies are cited.

Methods

• Are the PMTCT free at the three hospitals?

• What PMTCT model does the hospital provide? Option B? Option B+?

• What is the prevalence of HIV among pregnant women? How does it compare to the general population?

• What is the justification for the 28 weeks criteria for inclusion and exclusion.

• What is the HIV prevalence at these hospitals? It should be included.

• What is the total number of births there? What is the standard of care for the patients. Readers need some context, since they may not all be familiar with the country.

• A key problem with relying on medical records is missing data and folders. The authors should provide details about missing folders and data and describe how that was addressed in the analysis.

• The authors on page 12 lists variables that were treated as independent variables. Wouldn’t those be confounding/covariates variables, since they are comparing HIV to non-HIV+ mothers?

• For the variables, the authors should consider describing the types of measurement variables—that is how they were treated in the analysis (categorical, continuous, etc)).

• Several of the variables in the Tables are not described in the methods, example stillbirth

• There are also several clinical acronyms in the tables and methods that are not defined

Results

• The number of tables are quite excessive. Table 1-3 could be combined.

• The results are impacted but the concerns raised earlier

**********

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Reviewer #1: Yes: Lloyd Tooke

Reviewer #2: No

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12 Aug 2021

Authors’ response to concerns of Editor and Reviewers

Dear Editor and Reviewers, we the authors of this article would be very happy to convey our deepest gratitude for your immense contribution - rigorous editorial and review concerns for which we will go one by one to make our manuscript suitable for publication in PLOS ONE journal. Therefore, we are going to respond the Editor, Reviewer #1 and Reviewer #2 concerns respectively as presented hereunder:

Editor concerns and Authors’ responses

Editor concern: “1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.”

Authors’ response: Dear Editor, in all parts of the revised manuscript, we have used PLOS ONE’s requirements for publication of manuscripts. All the changes have been presented in a manuscript with track changes and without track changes.

Editor concern: “2 We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, please include your amended statements within your cover letter; we will change the online submission form on your behalf.

Authors’ response: Dear Editor, in the revised manuscript, the acknowledgment section of the manuscript is restated, in fact we extend our gratitude to university of Gondar for the contribution of securing ethical clearance fee free because of this we wrongly understand the contribution as financial support. However, there is no direct financial support from university of Gondar. Therefore, all the changes have been presented in a manuscript with track changes and without track changes.

Editor concern: “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.

Authors’ response: Dear Editor, in the revised manuscript, we have been updated data availability and materials, all the relevant data are within the manuscript and its supporting information files. Therefore, all the changes have been included in a manuscript with track changes and without track changes, as well as in the cover letter. And data attached as supporting files.

Editor concern: “4 PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager.

Authors’ response: Dear Editor, have an ORCID iD and that it is validated by Editorial Manager

Editor concern: “5 Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript.

Authors’ response: Dear Editor, in the revised manuscript, the ethical statement it is being moved to the methods part only, and we have presented it in a manuscript with track changes and without track changes.

2. Reviewer #1 concerns and Authors’ responses

Reviewer concern: “1.1 The paper needs to be edited and adjusted by somebody with experience in writing journal articles. There are numerous grammatical and language issues which need to be corrected. These will not be specifically highlighted here as there too many to mention.

Authors’ response: Dear Reviewer, in the revised manuscript, we included an updated English language usage, spelling and grammar. We have given the manuscript for language edition and all the changes have been included in the manuscript with track changes and without track changes

Reviewer concern: “1.2 in the introduction part

I. It should be made clear that the 74.9 million is worldwide

Authors’ response: Dear Reviewer, “Since the beginning of the epidemic, more than 74.9 million people have been infected HIV” in the original manuscript is corrected as “Since the beginning of the epidemic, more than 74.9 million people have been infected HIV globally” in the revised version of the manuscript with track changes and without track changes.

II. More information about number of births in Ethiopia per year. Home birth rate etc.

Authors’ response: Dear Reviewer, we include additional information regarding number of births in Ethiopia per year and home birth rate in the revised version of the manuscript with track changes and without track changes.

III. More information about HIV in Ethiopia would be useful. Is it increasing/decreasing? What % of people are on ARVs etc. Incidence should be quoted as 0.24% per year

Authors’ response: Dear Reviewer, we include additional information regarding HIV in Ethiopia Is increasing or decreasing and “the incidence rate was 0.24%” in the original manuscript is corrected as “the incidence rate was 0.24% per year”. Therefore, all the changes have been included in a manuscript with track changes and without track changes.

IV. The paragraph about LBW in the world needs to be reworked to make it flow better

Authors’ response: Dear Reviewer, the paragraph about LBW in the world in the original manuscript is rewrite in the revised version of the manuscript with track changes and without track changes.

V. what is chewing 'chat'? Most readers would not know this

Authors’ response: Dear Reviewer, the word ‘chat’ in the original manuscript is corrected as “Khat (stimulant drug)” in the revised version of the manuscript with track changes and without track changes.

Reviewer concern: “1.3 in the method part

i) It's confusing what is meant by data was extracted from March 3 to April 4 and May 5 - May 18.

Authors’ response: Dear Reviewer, due to covid 19 the data collection was interrupted that is why we write the data extraction period from March 3 to April 4 and May 5 - May 18.

Reviewer concern: “1.4 in the result part

I. This could be shortened. Some results are irrelevant (eg: Rh factor) and some tables could be combined. Results that are easily interpreted in the table do not necessarily need to be mentioned in the text also, although it is understandable that some should be emphasized

Authors’ response: Dear Reviewer, we delete irrelevant variables (e.g., Rh factor) and we combine Table 2 (Medical and obstetric related characteristics of the mothers delivered in Northwest Amhara regional state referral hospitals) and Table 3 (Pregnancy and labor-related complications of the mothers delivered in west Amhara regional state referral hospitals) in one table in the revised version of the manuscript with track changes and without track changes.

II. Why include Still births? What is the benefit?

It is also confusing why preterm infants were included. They are obviously much more likely to be LBW but not necessarily growth restricted. Growth restriction is the whole focus of the paper. So, these should either be excluded or determined if they are growth restricted using growth charts for gestational age.

Authors’ response: Dear Reviewer, we include still birth to show birth outcome is alive or dead and take it as an independent variable. we can’t exclude preterm infants because the definition of LBW is birth of baby weighting below 2,500 grams irrespective of gestational age

III. No baby HIV results? It would be important to know the transmission rate. HIV positive infants should be a different baby from an HIV exposed but uninfected infant

Authors’ response: Dear Reviewer, we extracted this data from mothers’ chart and in the mother’s chart the babies HIV status is not recorded.

3. Reviewer #2 concerns and Authors’ responses

Reviewer concern: “2.1 in the introduction part

I. Antiretroviral therapy access plays a significant role in prevalence of LBW and transmission of HIV. The background should discuss this relationship between access and LBW

Authors’ response: Dear Reviewer,

II. In justifying the study, the authors indicate that there have been previous studies conducted in Ethiopia, but they have lacked a comparison group. None of these studies are cited

Authors’ response: Dear Reviewer, we cited the study done in Ethiopia “Kebede B, Andargie G, Gebeyehu A. Birth outcome and correlates of low birth weight and preterm delivery among infants born to HIV-infected women in public hospitals of Northwest Ethiopia. 2013” in the original manuscript

Reviewer concern: “2.2 in the method part

I. Are the PMTCT free at the three hospitals?

Authors’ response: Dear Reviewer, the PMTCT services are provided freely in those hospitals and we include in the revised version of the manuscript with track changes and without track changes.

II. What PMTCT model does the hospital provide? Option B? Option B+?

Authors’ response: Dear Reviewer, “The Ethiopian government started to implement the Option B+ (initiation of antiretroviral therapy for all pregnant mothers) PMTCT service in 2013. Since then, the Option B+ treatment option has been launched in all PMTCT health facilities and provided without fee. According to the operational plan, under Option B+, all HIV+ pregnant mothers will receive triple antiretroviral therapy (ART) drugs and will continue the treatment for the rest of their lives” and we include in the revised version of the manuscript with track changes and without track changes.

III. What is the prevalence of HIV among pregnant women? How does it compare to the general population?

Authors’ response: Dear Reviewer, “pooled prevalence of HIV in pregnant women in Ethiopia was 5.74% and the pooled prevalence among subgroups indicated 9.50% in Amhara, 4.80% in Addis Ababa, 2.14% in SNNP and 4.48% in Oromia region. This pooled estimate is higher than the national HIV prevalence among the general population of Ethiopia”. we include this information in the revised version of the manuscript with track changes and without track changes

IV. What is the justification for the 28 weeks criteria for inclusion and exclusion?

Authors’ response: Dear Reviewer, based on Ethiopian ministry of health standard if the gestational age is less than 28 weeks it is abortion and as you know our research is done among mothers who gave birth that is why we exclude gestational age less than 28 weeks of gestation.

V. What is the HIV prevalence at these hospitals? It should be included.

Authors’ response: Dear Reviewer, we can’t get evidence HIV prevalence in each hospital but there is study on Epidemiology of HIV Infection in the Amhara Region of Ethiopia, 2015 to 2018 Surveillance Data Analysis and those hospitals found in Amhara region. The result of this study showed that the overall incidence rate of new HIV infection from 2015 to 2018 in the Amhara region was 6.9 per1000 tested population. The incidence rate was higher in females (4.1 per1000 population) than in males (2.84 per1000 population). we include this information in the revised version of the manuscript with track changes and without track changes.

VI. What is the total number of births there? What is the standard of care for the patients? Readers need some context, since they may not all be familiar with the country

Authors’ response: Dear Reviewer, the annual average number of births in each hospital is 6000 per year. Focused antenatal care is provided in those hospitals and this care recognize all pregnant women are at risk of complication, therefore, it provides safe, simple, and cost-effective intervention to all pregnant women to maintain normal pregnancies, save the lives by preventing complications or early detection and treatment of complications. Moreover, the Option B+ treatment option is provided without fee in those hospitals and we include in the revised version of the manuscript with track changes and without track changes.

VII. A key problem with relying on medical records is missing data and folders. The authors should provide details about missing folders and data and describe how that was addressed in the analysis.

Authors’ response: Dear Reviewer, we manage missing data by using replacement technique if less than 20% of value are missed in one variable ( E.g. we managed by replacement technique pre pregnancy BMI, MUAC, ANC follow up, iron duration, anemia etc.) but if more than 20% of values missed in one variable we discard the variables ( E.g. we discard marital status, educational status, occupational status, substance abuse, pregnancy status, pre pregnancy weight) and we include in the revised version of the manuscript with track changes and without track changes

VIII. The authors on page 12 lists variables that were treated as independent variables. Wouldn’t those be confounding/covariates variables, since they are comparing HIV to non-HIV+ mothers?

Authors’ response: Dear Reviewer, we try to control cofounding variables by using appropriate statical analysis, which means first we check chi-square assumption then bivariable analysis and finally we did multivariable logistic regression by using back ward logistic regression technique

IX. For the variables, the authors should consider describing the types of measurement variables—that is how they were treated in the analysis (categorical, continuous, etc).

Authors’ response: Dear Reviewer, data processing and analysis part shows the outcome variable is categorical and treat in the analysis by using binary logistic regression model.

X. Several of the variables in the Tables are not described in the methods, example stillbirth

Authors’ response: Dear Reviewer, we try to describe variables found in the table on the method part example Stillbirth in the revised version of the manuscript with track changes and without track changes.

XI. There are also several clinical acronyms in the tables and methods that are not defined

Authors’ response: Dear Reviewer, we defined clinical acronyms that is found in the table and method (E.g., DM, HTN, STI) in the revised version of the manuscript with track changes and without track changes.

XII. Given that they are looking at so many variables, the analysis should account for multi-collinearity, using variance inflation factor.

Authors’ response: Dear Reviewer, before conducting the multivariable logistic regression model multicollinearity was checked using variable inflation factor (VIF) and there is no multicollinearity between independent variables and we include in the revised version of the manuscript with track changes and without track changes.

Reviewer concern: “2.3 in the result part

• The number of tables are quite excessive. Table 1-3 could be combined.

Authors’ response: Dear Reviewer, we combine Table 2 (Medical and obstetric related characteristics of the mothers delivered in Northwest Amhara regional state referral hospitals) and Table 3 (Pregnancy and labor-related complications of the mothers delivered in west Amhara regional state referral hospitals) in one table in the revised version of the manuscript with track changes and without track changes.

Reviewer concern: “2.4

The HIV field has moved away from labelling mothers as HIV+ and HIV- to people centered labels like mothers living with HIV.

Authors’ response: Dear Reviewer, labels like mothers living with HIV is corrected as “HIV+ and HIV- mothers” in the revised version of the manuscript with track changes and without track changes.

Reviewer concern: “2.5

• In the introduction section, the authors make the case that there is controversy in whether contributes to LBW. While some studies have shown no association between HIV and LBW, there have been one systematic review and another meta-analysis on this topic, so the purpose of the investigation and the resulting findings are not new. See for example (Xiao, Peng-Lei, et al. 2015; 15. Brocklehurst, Peter, and Rebecca French 1998). It is important the authors recognize this and summarize the findings of those studies in the manuscript. They are cited but not discussed. Same can be said about the discussion section where the study is compared to other studies.

Authors’ response: Dear Reviewer, we try to discuss the cited references on the discussion session and we include the change in the revised manuscript with track change and without track changes. Regarding to the issue raised on “the purpose of the investigation and the resulting findings are not new” yes you are right there are systematic review and metanalysis on this topic but there are few studies done related to birth outcomes in HIV-infected women in Ethiopia even the existing ones can’t show the disparity between HIV+ and HIV- mothers.

Reviewer concern: “2.6

To be able to somewhat confidently conclude that HIV is associated with LBW in their population, statistically, they should use propensity score matching to account for selection bias into the two groups. Currently, the prevalence of LBW is provided for each group, with an associated 95% CI. It is unclear what is driving these differences, since there is such an imbalance in the confounding variables. In addition, it is also not clear where that 95% CI statistic is coming from. Just computing the prevalence is not adequate since the sample is not a randomized selection (that is those who are HIV+ and those who are not—and not necessarily the sample of participants from the hospital)

Authors’ response: Dear Reviewer, to say HIV is statically associated with birth weight we do regression analysis in the overall population (which means taking both HIV positive and negative as one population) by taking HIV status as independent variable and we get being HIV+ increase the risk of delivering low birth weight baby compared with HIV negative mothers at P-value 0.000 (AOR 4.2 95% CI [1.89-9.43]). we include this change in the revised manuscript with and without track change

Submitted filename: Authors response.docx

Click here for additional data file.

26 Nov 2021

10 Jan 2022

Editor concerns and Authors’ responses

Editor concern: “1. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Authors’ response: Dear Editor, we reviewed our Manuscript reference list; it is complete and correct and there is no retracted cited paper

Reviewer #1 concerns and Authors’ responses

Reviewer concern 1: There are still a few grammatical errors such as "is suffered from" LBW and 'Result' instead of results.

Authors’ response: Dear Reviewer, ‘is suffered from’ LBW and 'Result' instead of results is corrected as “suffered from” LBW and “Results” in the revised version of the manuscript with track changes and without track changes.

Reviewer concern 2: It was stated that chewing "chat" would be explained in the text as "khat (stimulant)" but this was not done

Authors’ response: Dear Reviewer, the word ‘chat’ in the original manuscript is corrected as “Khat (stimulant drug)” in the revised version of the manuscript with track changes and without track changes.

Submitted filename: Authors Response 2.docx

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28 Jan 2022

Prevalence of Low birth weight and associated factors among HIV positive and negative mothers delivered in northwest Amhara region referral hospitals, Ethiopia,2020 A comparative crossectional study

PONE-D-20-40543R2

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Reviewers' comments:

2 Feb 2022

PONE-D-20-40543R2

Low birth weight and associated factors among HIV positive and negative mothers delivered in northwest Amhara region referral hospitals, Ethiopia,2020 A comparative crossectional study

Dear Dr. Fentie:

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