Determinants and Outcome of Community-Acquired Late-Onset Neonatal Sepsis in Rural Bangladesh

Abstract

Background. This study examined the sociodemographic as well as other determinants and outcome of community-acquired late-onset neonatal sepsis (LONS) in rural Bangladesh at Matlab. Methods. In this retrospective chart review, we used an unmatched case-control design (1:2 ratio) to evaluate the factors associated with LONS and their outcomes among babies admitted to the neonatal ward of Matlab Hospital of icddr,b, from January 2012 to December 2014. Neonates presenting with any of the clinical signs of serious bacterial infection during 3 to 28 days of life constituted the cases (LONS), and those without LONS constituted the controls. All the data were retrieved from the electronic databases of Matlab Hospital and Matlab Health and Demographic Surveillance System. Results. Among 1482 admitted neonates, 202 were cases and 404 were randomly selected controls. In babies with LONS, case fatality rate (1% vs 0%, P = .037), duration of inpatient stay (4 days vs 2 days, P < .001), and referral to higher center (9% vs 5%, P = .020) were higher. In an adjusted model, undernutrition (weight for length Z score < −2; odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.2-2.94), admission in winter season (OR = 1.62, 95% CI = 1.09-2.41), mother’s schooling <10 years (OR = 1.76, 95% CI = 1.09-2.85), primiparity (OR = 1.55, 95% CI = 1.05-2.29), home delivery (OR = 1.87, 95% CI = 1.07-3.26), and household food insecurity (OR = 2.78, 95% CI = 1.31-5.88) were found to be independently associated with LONS. Conclusion. LONS posed considerable socioeconomic burden to the rural community. Further studies are required to consolidate our findings.

Keywords

community-acquired infections determinants neonates neonatal late-onset sepsis retrospective studies

Introduction

Clinical sepsis in neonates denotes a spectrum of diseases such as septicemia, pneumonia, and meningitis featuring clinical signs of serious infection in the presence or absence of bacteremia in the first 28 days of life.^1-3 On the list of causes of neonatal death, severe infection sits within the top 3,^4-8 which is a major concern for low- and middle-income countries in particular. In resource-poor countries including Bangladesh, sepsis alone contributes to about 7% of the child deaths occurring in the first 28 days of their lives.⁹

Neonatal sepsis can be classified into early-onset sepsis (EONS) and late-onset sepsis (LONS) depending on the time of onset.^10-12 EONS occurs mostly by infections acquired from mother prior to or during childbirth,¹³ while postnatal environment (community or hospital) plays a direct role in the development of LONS.^11,14-18 Globally, incidence of EONS has reduced over decades, whereas the picture is quite opposite for LONS,^19-21 and Bangladesh is not an exception.²²

Evidence suggests that in Matlab, a rural area of Bangladesh, LONS is the single largest contributor to all the deaths occurring in the late neonatal period.²³ Lots of efforts have been made to identify the factors contributing to LONS.^24-26 The majority of these information are based on studies related to neonatal intensive care unit, especially focusing nosocomial infections.^18,27 A prospective study in Switzerland have found that community-acquired LONS contributes to nearly one third of the total burden of LONS.²⁸ However, most studies on the community-acquired LONS, including the lone study in Bangladesh, have focused on pathogen identification,^16,28-31 lacking valid information on sociodemographic influence on community-acquired sepsis, especially LONS and its outcome.²⁹

In this context, the aim of this study was to identify the sociodemographic as well as other determinants and outcome of community-acquired LONS in rural Bangladesh at Matlab.

Methods

Study Setting

Our study population resided in Matlab, a rural subdistrict of the Ganges-Meghna Delta, lying 55 km southeast of the capital city, where the level of poverty was 26%,³² rate of illiteracy was 26.2%, 96% households use tube well water for drinking, and 93% households use solid fuel for cooking.³³

In Matlab, icddr,b has been maintaining an internationally recognized and unique Health and Demographic Surveillance System (HDSS) since 1966 involving 142 villages, comprising a population of 230 000 people. The HDSS area is divided into 2 parts, an icddr,b service area and a comparison (government service) area, each covering a population of about 110 000.³⁴ Matlab Hospital is a primary health facility in Matlab, which offers free-of-cost clinical care to all diarrheal patients, and maternity and child health care to women of reproductive age and children younger than 5 years coming from half of the HDSS area (icddr,b service area).

Study Design, Population, and Data Source

This was a retrospective chart review. For this chart analysis, we used an unmatched case-control design and evaluated the factors associated with LONS in neonates and their outcome between the groups. Data on clinical features and outcome of patients, admitted to the neonatal ward of Matlab Hospital of icddr,b from January 2012 to December 2014, were extracted from Matlab SHEBA, an online database of Matlab Hospital. Neonates with LONS constituted the cases, and those without LONS constituted the controls. Controls were randomly selected from the children without LONS using Stata/PC (version 14.1; StataCorp, College Station, TX) from the personal computerized data source of this study. A 1:2 unmatched case-control ratio was used to increase the statistical power of our analyses. Sociodemographic, maternal, and childbirth-related information were retrieved from the electronic database of HDSS. Case report forms were developed, pretested, and finalized for acquisition of relevant data.

Late-Onset Neonatal Sepsis

LONS was defined as the appearance of any of the clinical signs enlisted in Box 1 between >72 hours (3 days) of birth and first 28 days of life.^10,35 All of these signs indicate serious bacterial infection (sepsis) in neonates.³⁵

Box 1.

Signs of Serious Bacterial Infection (Sepsis) in Neonates^a.

Inability to breastfeed or drink

Lethargy or unconsciousness

Convulsions

Movement only when stimulated or no movement at all

Fast breathing (≥60 breaths per minute)

Severe respiratory distress (eg, grunting, severe chest indrawing)

Central cyanosis or oxygen saturation <90% on pulse oximetry

Raised temperature, >38°C

Hypothermia, <35.5°C

Severe jaundice

Severe abdominal distension

Many or severe skin pustules

Umbilical redness extending to the periumbilical skin

Umbilicus draining pus

Bulging fontanelle

Painful joints, joint swelling, reduced movement, and irritability if these parts are handled

Source: Pocket Book of Hospital Care for Children. Second edition, 2013.³⁵

In our present study, infants with LONS were classified as having community-acquired LONS if neonates who are resident of the region presented with the symptoms of interest between the age of 3 and 28 days, with no history of discharge from any hospital within past 48 hours.¹⁶

Patient Management

Both the cases and control children received standard management including antibiotics if necessary following the World Health Organization (WHO) recommended treatment guideline of neonatal sepsis.³⁵

Determinants of LONS

We presumed several nutritional, maternal, childbirth-related, sociodemographic, and environmental characteristics as potential risk factors for LONS. Characteristics considered and analyzed included age, sex, nutritional status, breastfeeding practice, season of hospital admission, mother’s age, education and parity, place of delivery, mode of delivery, type of birth attendant, socioeconomic status (wealth quintile), family size, household food security, possession of livestock, type of fuel used in cooking, drinking safe water, and use of sanitary latrine. The climate in Bangladesh is characterized by a hot summer from March to May, a rainy monsoon season from June through October, and a cool, dry winter season from November to February.³⁶ Wealth quintile was computed by HDSS as asset score in a 1 to 5 scale, where 1 indicates the lowest. It served as an indicator of household-level wealth consistent with expenditure and income measures. The index was constructed using household asset data via principal component analysis.³³ Household food security was defined by HDSS as the availability of food for all family members, 3 times every day in the previous year.³³ Wood, wood dust, paddy husk, leaves, or straw use with/without kerosene were categorized as solid fuel, and gas and electricity were classified as clean fuel.

Statistical Analysis

All data were first extracted in Microsoft Excel, coded, cleaned, and entered into Stata/PC (version 14.1; StataCorp) for further statistical analyses. Weight for length Z scores was calculated by the WHO Anthro (version 3.2.2; Department of Nutrition, WHO, Geneva, Switzerland). Differences in proportion were compared by the χ² test or Fisher’s exact test as appropriate. Student’s t test was used to compare the means of normally distributed data, and Mann-Whitney test was used for comparison of data that were not normally distributed. P < .05 was considered statistically significant. Strength of association in determining differences in proportion was determined by calculating odds ratio (OR) and their 95% confidence intervals (CIs). In identifying risk factors for LONS, variables were initially analyzed in a univariate model (Table 2), and then factors independently associated with LONS were identified using multiple logistic regression analysis after controlling for the covariates (Table 4). For logistic regression model building, independent variables were selected purposefully based on the method described by Hosmer et al.³⁷ Only the significant variables were retained in the final model.

Ethics and Informed Consent Statement

This study was solely a chart review and did not involve any interviews with patients or their care givers. Data for this study were retrieved from the case records of Matlab Hospital. Data were made anonymous and de-identified prior to analysis. Authors had no access to patient identifying information. Waiver of an ethical approval for this study was taken from the institutional review board (Ethical Review Committee) of icddr,b.

Results

A total of 1482 neonates were admitted during the study period, and among them, 202 were found to be cases and 404 were randomly selected controls (Figure 1).

Figure 1.

Flow chart of the selection of study participants and analytic sample.

Cases have been defined in the Methods section, and common diagnosis of controls are enlisted in Table 1.

Table 1.

Pattern of Diseases Among Controls.

Characteristics	n (%)
Neonatal jaundice (physiological)	153 (38)
Breastfeeding difficulties	81 (20)
Localized umbilical stump redness	57 (14)
Abdominal pain (infantile colic)	40 (10)
Skin rash (erythema toxicum)	32 (8)
Rhinitis (common cold)	20 (5)
Conjunctivitis	12 (3)
Other (oral thrush, watering from eye, constipation, etc)	9 (2)

Median age of the neonates among the cases was 13 days and that of the controls was 10 days (P = .001; Table 2). In bivariate analyses, the cases more often had undernutrition (weight for length Z score < −2), admission in winter season, mother’s schooling <10 years, home delivery, delivery conducted by traditional birth attendants, vaginal delivery, larger family size (>4 members), household food insecurity, possession of livestock, and family’s practice of using solid fuel in cooking compared with the controls (Table 2).

Table 2.

Characteristics of Neonates With (Cases) or Without (Controls) LONS.

Characteristics	Cases (202), n (%)	Controls (404), n (%)	OR	95% CI	P
Age in days (median, IQR)	13 (8, 20)	10 (7, 17)	—	—	.001*
Boy	121 (60)	231 (57)	1.12	0.79-1.58	.522
Undernutrition (WLZ < −2)	49/196 (25)	72/402 (18)	1.53	1.01-2.31	.043*
Not exclusively breastfed	5/200 (3)	9/401 (2)	1.12	0.37-3.38	1.000
Admission in winter season	76 (38)	100 (25)	1.83	1.27-2.65	.001*
Mother’s age >35 years	16 (8)	24 (6)	1.36	0.71-2.63	.355
Mother’s schooling <10 years	163/194 (84)	288/388 (74)	1.83	1.16-2.86	.008*
Primiparity	85 (42)	141 (35)	1.36	0.96-1.92	.085
Home delivery (childbirth)	33 (8)	33 (8)	2.20	1.31-3.69	.002*
Traditional birth attendant	23 (11)	25 (6)	1.95	1.07-3.54	.026*
Cesarean delivery	73 (36)	186 (46)	0.66	0.47-0.94	.020*
Number of family members >4	124 (61)	211 (52)	1.45	1.03-2.05	.033*
Lowest wealth quintile	37 (18)	52 (13)	1.52	0.96-2.41	.074
Household food insecurity	18 (9)	14 (3)	2.73	1.32-5.63	.005*
Possession of livestock	150 (74)	265 (66)	1.51	1.04-2.21	.030*
Using solid fuel in cooking	183 (91)	329 (81)	2.20	1.28-3.76	.003*
Drinking unsafe water	3 (1)	4 (1)	1.51	0.33-6.81	.691
Not using sanitary latrine	150 (74)	275/403 (68)	1.34	0.92-1.96	.127

Abbreviations: LONS, late-onset neonatal sepsis; OR, odds ratio; CI, confidence interval; IQR, interquartile range; WLZ, weight for length Z score.

Statistically significant at 5% level.

The cases more often had longer hospital stay, required referral to higher center, and experienced higher case-fatality rates compared to the controls (Table 3).

Table 3.

Outcome of Neonates With (Cases) or Without (Controls) LONS.

Outcome	Cases (202), n (%)	Controls (404), n (%)	OR	95% CI	P
Hospital stay in days (median, IQR)	4 (3, 5)	2 (1, 3)	—	—	<.001*
Referral to higher center	9 (4)	5 (1)	3.72	1.22-11.33	.020*
Death	3 (1)	0 (0)	—	—	.037*

Abbreviations: LONS, late-onset neonatal sepsis; OR, odds ratio; CI, confidence interval; IQR, interquartile range.

Statistically significant at 5% level.

In an adjusted logistic regression model, undernutrition, admission in winter season, mother’s schooling <10 years, primiparity (a woman who has had one pregnancy that resulted in a fetus that attained a weight of 500 g or a gestational age of 20 weeks, regardless of whether the infant was living at birth or whether it was a single or multiple birth; also written para I or I-para),³⁸ home delivery, and household food insecurity were found to be independently associated with LONS (Table 4).

Table 4.

Results of Multiple Logistic Regression to Explore the Independent Predictors of LONS in Neonates.

Characteristics	OR^a	95% CI	P
Age in days	1.04	1.01-1.07	.002
Undernutrition (WLZ < −2)	1.88	1.20-2.94	.006
Winter season	1.62	1.09-2.41	.016
Mother’s schooling <10 years	1.76	1.09-2.85	.021
Primiparity	1.55	1.05-2.29	.026
Home delivery	1.87	1.07-3.26	.029
Household food insecurity	2.78	1.31-5.88	.008

Abbreviations: LONS, late-onset neonatal sepsis; OR, odds ratio; CI, confidence interval; WLZ, weight for length Z score.

Adjusted OR from multivariable model that includes child’s age in days, nutritional status, season of admission, maternal education and parity, whether the child had home delivery, and household food insecurity.

Discussion

To our knowledge, this is the first study that shed light on the factors, especially sociodemographic factors, contributing to the development of community-acquired LONS in rural Bangladesh. Undernutrition, winter season, mother’s schooling, primiparity, home delivery, and household food insecurity were observed to be the independent determinants of community-acquired LONS.

The observation of independent association of LONS with undernutrition is understandable. Underdeveloped immune system and skin barrier of undernourished neonates especially of those who born with low birth weight might make them vulnerable to environmental acquired infections.²⁹ However, we did not have data on birth weights of the participants of this study.

In this study, seasonality (winter season) was found to influence the development of LONS. In an Indian study, Bang et al found that umbilical infections, bacterial skin infections, conjunctivitis, and upper respiratory symptoms of neonates were increased in the winter.³⁹ Becker et al and Burkart et al also observed that neonatal death due to respiratory diseases peaked in the winter in rural areas.^40,41 In the cool season, inadequate thermal protections along with increased congestion of people inside house, indoor air pollution from fire, decreased bathing, and washing of clothes are common in low socioeconomic condition and in rural areas like Matlab.³⁹ Although we do not have all these data, we can speculate our patient population often had an exposure to these risks and might have an impact on our observation.

Our finding that the offspring of less educated mothers were in higher risk of developing LONS was in line with the observation of a Brazilian study by Victoria et al where they found that infants of mothers with less or no education were prone to develop sepsis.⁴² Gebremedhin et al also had somewhat similar findings.⁴³ Lack of appropriate maternal care, which is related to maternal illiteracy, might be responsible for the babies’ acquiring serious infections in the late neonatal period.⁴²

Primiparity was found to be associated with EONS in a Brazilian study by Vaciloto et al,⁴⁴ but no study directly explored the relationship between primiparity and LONS. Schrag et al concluded that some special characteristics of primiparous women (age <20 years, prolonged labor, prolonged rupture of membranes, and low infant birth weight) made their neonates vulnerable to adverse outcomes like sepsis,⁴⁵ which might explain the relation found in the current study between LONS and primiparity.

In this study, home delivery was one of the important determinants of community-acquired LONS. We can speculate that contaminated floor and unhygienic practice in the delivery room, unsterile cord care, and scarcity of skilled birth attendants might contribute to the development of sepsis in home deliveries as observed in previous studies.^29,39

Our observation of association of the babies from food-insecure households with LONS is understandable. Household food insecurity prevailing in poor socioeconomic conditions along with lack of maternal education may lead to maternal malnutrition and consequently may result in low birth weight infants.⁴⁶ These babies may again face that food insecurity and become malnourished and susceptible to LONS.

Among the LONS cases, the duration of hospital stay was higher compared with the control group, which imposed a significant financial burden to the rural community. Besides, adverse outcomes (referral to higher center, death) were also higher among the cases in comparison to the controls. These findings were consistent with the observations of Stoll et al in a study in the United States.²⁵

In this study, median age of the babies with LONS was 13 days, which was aligned with the findings of Vergnano et al,¹¹ Boghossian et al,¹⁴ and Hammoud et al,¹⁷ who found that the peak incidence of LONS occurred between the 10th and the 22nd day. No difference in sex distribution was observed between the cases and the controls. Ng et al had a similar finding in a study of LONS.⁴⁷

Although this study is important due to its unique nature for being the first study done in low-resource setting exploring the influence of sociodemographic and other factors on the development of community-acquired LONS, its findings should be interpreted in light of several limitations. The first limitation was the retrospective nature of our study, which confined our sample size, and did not allow for the systematic collection of data with stringent quality control. Since the study was done on admitted neonates, the results might not be generalized to all neonates in the catchment community. Although controls were taken from admitted neonates who had minor illnesses as evident by the absence of deaths, they merely represented healthy community controls. Moreover, as we did not have access to antenatal data, it was not possible for us to adjust certain maternal characteristics (ie, antenatal checkup, maternal disease, etc). The lack of laboratory evidence and the subjectivity in the assessment of the clinical signs of sepsis in neonates was another limitation.

To conclude, in our study, LONS posed a considerable economic and social burden to the families and the community considering that neonates with LONS had a longer hospital stay, higher number of referrals, and most importantly, higher case fatality compared with those without LONS. Our study revealed that undernutrition, winter season, mother’s schooling <10 years, primiparity, home delivery, and household food insecurity were the independent determinants of community-acquired LONS. Further studies with larger sample size are required to consolidate our observation on the relationship between community-driven factors and LONS especially in resource-limited settings.

Footnotes

Acknowledgements

The authors would like to express their sincere thanks to all the staff members of the “Neonatal Ward” of Matlab Hospital including physicians, nurses, clinical attendants, feeding team, and cleaners for their invaluable support in patient care. The authors also offer their sincere gratitude to Dr Syed Imran Ahmed for his moral and intellectual support.

Author Contributions

KNS, SMTH, MAK, TA, and MJC conceived and designed the study; KNS, SMTH, and MJC collected, merged, and cleaned the data; SMTH, KNS, and MJC analyzed the data; MAK and TA gave technical support and conceptual advice; KNS, SMTH, MAK, and TA wrote the manuscript; MJC finally approved the manuscript. All authors read and approved the final manuscript.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by core donors that provide unrestricted support to icddr,b for its operations and research. Current donors providing unrestricted support include Governments of Australia, Bangladesh, Canada, Sweden, and the United Kingdom. The authors gratefully acknowledge these donors for their support and commitment to icddr,b’s research efforts.

ORCID iDs

Kazi Nazmus Saqeeb

S. M. Tafsir Hasan

References

Wynn

Wong

Shanley

Bizzarro

Saiman

Polin

RA.

Time for a neonatal-specific consensus definition for sepsis. Pediatr Crit Care Med. 2014;15:523-528.

Goldstein

Giroir

Randolph

; International Consensus Conference on Pediatric Sepsis. International Pediatric Sepsis Consensus Conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6:2-8.

Verma

Berwal

Nagaraj

Swami

Jivaji

Narayan

Neonatal sepsis: epidemiology, clinical spectrum, recent antimicrobial agents and their antibiotic susceptibility pattern. Int J Contemp Pediatrics. 2017;2:176-180.

Black

Cousens

Johnson

et al ; Child Health Epidemiology Reference Group of WHO and UNICEF. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet. 2010;375:1969-1987.

Lawn

Cousens

Zupan

; Lancet Neonatal Survival Steering Team. 4 million neonatal deaths: when? Where? Why? Lancet. 2005;365:891-900.

Shane

Stoll

BJ.

Neonatal sepsis: progress towards improved outcomes. J Infect. 2014;68(suppl 1):S24-S32.

Qazi

Stoll

BJ.

Neonatal sepsis: a major global public health challenge. Pediatr Infect Dis J. 2009;28(1 suppl):S1-S2.

Shah

Padbury

JF.

Neonatal sepsis: an old problem with new insights. Virulence. 2014;5:170-178.

UNICEF. Committing to Child Survival: A Promise Renewed—Progress Report 2015. New York, NY: UNICEF; 2015.

10.

Leal

Álvarez-Nemegyei

Velázquez

et al . Risk factors and prognosis for neonatal sepsis in southeastern Mexico: analysis of a four-year historic cohort follow-up. BMC Pregnancy Childbirth. 2012;12:48.

11.

Vergnano

Menson

Kennea

et al . Neonatal infections in England: the NeonIN surveillance network. Arch Dis Child Fetal Neonatal Ed. 2011;96:F9-F14.

12.

Camacho-Gonzalez

Spearman

Stoll

BJ.

Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am. 2013;60:367-389.

13.

Polin RA; Committee on Fetus and Newborn. Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics. 2012;129:1006-1015.

14.

Boghossian

Page

Bell

et al ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births. J Pediatr. 2013;162:1120-1124.e1.

15.

Dong

Speer

CP.

Late-onset neonatal sepsis: recent developments. Arch Dis Child Fetal Neonatal Ed. 2015;100:F257-F263.

16.

Bulkowstein

Ben-Shimol

Givon-Lavi

Melamed

Shany

Greenberg

Comparison of early onset sepsis and community-acquired late onset sepsis in infants less than 3 months of age. BMC Pediatr. 2016;16:82.

17.

Hammoud

Al-Taiar

Thalib

Al-Sweih

Pathan

Isaacs

Incidence, aetiology and resistance of late-onset neonatal sepsis: a five-year prospective study. J Paediatr Child Health. 2012;48:604-609.

18.

Tsai

Hsu

Chu

et al . Incidence, clinical characteristics and risk factors for adverse outcome in neonates with late-onset sepsis. Pediatr Infect Dis J. 2014;33:e7-e13.

19.

Bizzarro

Raskind

Baltimore

Gallagher

PG.

Seventy-five years of neonatal sepsis at Yale: 1928-2003. Pediatrics. 2005;116:595-602.

20.

Shim

Kim

et al . Trends in epidemiology of neonatal sepsis in a tertiary center in Korea: a 26-year longitudinal analysis, 1980-2005. J Korean Med Sci. 2011;26:284-289.

21.

Al-Taiar

Hammoud

Cuiqing

et al . Neonatal infections in China, Malaysia, Hong Kong and Thailand. Arch Dis Child Fetal Neonatal Ed. 2013;98:F249-F255.

22.

Ahmed

Chowdhury

Hoque

Darmstadt

GL.

Clinical and bacteriological profile of neonatal septicemia in a tertiary level pediatric hospital in Bangladesh. Indian Pediatr. 2002;39:1034-1039.

23.

Chowdhury

Thompson

Ali

Alam

Yunus

Streatfield

PK.

Causes of neonatal deaths in a rural subdistrict of Bangladesh: implications for intervention. J Health Popul Nutr. 2010;28:375-382.

24.

Hammoud

Al-Taiar

Al-Abdi

et al . Late-onset neonatal sepsis in Arab states in the Gulf region: two-year prospective study. Int J Infect Dis. 2017;55:125-130.

25.

Stoll

Hansen

Fanaroff

et al . Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics. 2002;110(2 pt 1):285-291.

26.

Isaacs

Barfield

Clothier

et al . Late-onset infections of infants in neonatal units. J Paediatr Child Health. 1996;32:158-161.

27.

Resende

Peppe

ALG

dos Reis

Abdallah

VOS

Ribas

Filho

PPG

. Late onset sepsis in newborn babies: epidemiology and effect of a bundle to prevent central line associated bloodstream infections in the neonatal intensive care unit. Braz J Infect Dis. 2015;19:52-57.

28.

Waters

Jawad

Ahmad

et al . Aetiology of community-acquired neonatal sepsis in low and middle income countries. J Glob Health. 2011;1:154-170.

29.

Zaidi

Thaver

Ali

Khan

TA.

Pathogens associated with sepsis in newborns and young infants in developing countries. Pediatr Infect Dis J. 2009;28(1 suppl):S10-S18.

30.

Darmstadt

Saha

Choi

et al ; Bangladesh Projahnmo-2 (Mirzapur) Study Group. Population-based incidence and etiology of community-acquired neonatal bacteremia in Mirzapur, Bangladesh: an observational study. J Infect Dis. 2009;200:906-915.

31.

Giannoni

Agyeman

Stocker

et al ; Swiss Pediatric Sepsis Study. Neonatal sepsis of early onset, and hospital-acquired and community-acquired late onset: a prospective population-based cohort study. J Pediatr. 2018;201:106-114.e4.

32.

Bhuiya

Mahmood

Rana

Wahed

Ahmed

Chowdhury

AMR

. A multidimensional approach to measure poverty in rural Bangladesh. J Health Popul Nutr. 2007;25:134-145.

33.

icddr

, Health and Demographic Surveillance System—Matlab. Vol 48. Household Socio-Economic Census 2014. Dhaka, Bangladesh: icddr, b; 2016.

34.

icddr

Health and Demographic Surveillance System–Matlab. Vol 49. Registration of Health and Demographic Events 2014. Scientific Report No. 133. Dhaka, Bangladesh: icddr,b; 2016.

35.

World Health Organization. Pocket Book of Hospital Care for Children. 2nd ed. Geneva, Switzerland: World Health Organization; 2013:52,54.

36.

Banglapedia, National Encyclopeda of Bangladesh. Season. http://en.banglapedia.org/index.php?title=Season. Accessed October 21, 2016.

37.

Hosmer

Jr Lemeshow

Sturdivant

RX.

Applied Logistic Regression. 3rd ed. Hoboken, NJ: John Wiley; 2013.

38.

Miller-Keane, O’Toole

. Miller-Keane Encyclopedia and Dictionary of Medicine Nursing, and Allied Health. 7th ed. Philadelphia, PA: Saunders; 2003. https://medical-dictionary.thefreedictionary.com/primipara

39.

Bang

Reddy

Baitule

Deshmukh

Bang

RA.

The incidence of morbidities in a cohort of neonates in rural Gadchiroli, India: seasonal and temporal variation and a hypothesis about prevention. J Perinatol. 2005;25(suppl 1):S18-S28.

40.

Becker

Weng

Seasonal patterns of deaths in Matlab, Bangladesh. Int J Epidemiol. 1998;27:814-823.

41.

Burkart

Khan

Krämer

Breitner

Schneider

Endlicher

WR.

Seasonal variations of all-cause and cause-specific mortality by age, gender, and socioeconomic condition in urban and rural areas of Bangladesh. Int J Equity Health. 2011;10:32.

42.

Victoria

Huttly

Barros

Lombardi

Vaughan

JP.

Maternal education in relation to early and late child health outcomes: findings from a Brazilian cohort study. Soc Sci Med. 1992;34:899-905.

43.

Gebremedhin

Berhe

Gebrekirstos

Risk factors for neonatal sepsis in public hospitals of Mekelle City, North Ethiopia, 2015: unmatched case control study. PLoS One. 2016;11:e0154798.

44.

Vaciloto

Richtmann

de Paula Fiod Costa

Kusano

EJU

de Almeida

Amaro

ER.

A survey of the incidence of neonatal sepsis by group B Streptococcus during a decade in a Brazilian maternity hospital. Braz J Infect Dis. 2002;6:55-62.

45.

Schrag

Cutland

Zell

et al . Risk factors for neonatal sepsis and perinatal death among infants enrolled in the prevention of perinatal sepsis trial, Soweto, South Africa. Pediatr Infect Dis J. 2012;31:821-826.

46.

Beasley

Amir

LH.

Infant feeding, poverty and human development. Int Breastfeed J. 2007;2:14.

47.

Cheng

Chui

et al . Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 1997;77:F221-F227.