Factors associated with deaths from early and late-onset sepsis in a neonatal intensive care unit

INTRODUCTION

Healthcare-Associated Infections (HAIs) are problems that have had an impact on healthcare in Neonatal Intensive Care Units (NICUs), jeopardizing the maintenance of life.¹

Among the HAIs, neonatal sepsis is one of the main preventable causes of death that are still relevant in Brazil, being an important parameter for evaluating the quality of neonatal care.² Sepses are classified into early-onset and late-onset: early-onset sepses affect the newborn up to 48 hours of life, come from the mother with risk factors of infection, and can occur during passage through the birth canal, by chorioamnionitis or hematogenous dissemination; late-onset sepses are those that occur after 48 hours of the newborn's life, resulting from contamination by microorganisms from the hospital environment,¹ through the hands of professionals or contaminated invasive objects and devices.³

Late-onset sepsis affects around three million neonates⁴ and causes around 750.000 deaths a year worldwide,⁵ resulting in longer hospital stays and increased care-related costs.

National data made available on the Mortality Information System (Sistema de Informação de Mortalidade - SIM) by DATASUS (2024) showed that in Brazil, in 2022, 1.118 deaths from bacterial septicemia of newborns between zero and six days old and 1.028 between seven and 27 days old were reported. In Ceará, in the same year, 84 deaths were reported, 50 between zero and six days old, and 34 between seven and 27 days old.⁶

Given the epidemiological relevance and severity of neonatal deaths from early and late-onset sepsis, it becomes necessary to quantify them. In addition, the institution that hosted the study is a tertiary referral maternity hospital with the mission of providing excellent care for women and newborns, along with theoretical and practical teaching for technical, undergraduate and medical and multiprofessional residency students, as well as research, linked to the Federal University of Ceará, and it is the largest public maternity hospital in Ceará - Brazil. It is therefore necessary to investigate this issue so that the institution studied has indicators that make it easier to evaluate care practices, identify opportunities for improvement and, as a result, fulfill its mission with excellence.⁷

In view of the above, the objective was to analyze the factors associated with deaths from early and late-onset sepsis in a neonatal intensive care unit in a reference maternity hospital in Ceará, Brazil.

OBJECTIVE

To analyze the factors associated with early and late-onset sepsis deaths in a neonatal intensive care unit in a reference maternity hospital in Ceará, Brazil.

METHOD

This is a quantitative, descriptive, documentary study. The survey was carried out in the NICU of a maternity hospital of reference for tertiary care for women and newborns linked to the Federal University of Ceará, in Fortaleza, Ceará, Brazil.

The sample was consecutive and time-based, consisting of newborns who died of sepsis in the NICU of the institution in which the study was carried out between 2019 and 2021, totaling 119 participants.

The inclusion criteria involved participants who had hospital investigation forms for infant death, a model provided by the Ministry of Health (MH), filled out by the institution's Hospital Commission for the Prevention of Maternal, Infant and Fetal Death, as well as infection monitoring forms in the NICU filled out by the Hospital Infection Control Service (Serviço de Controle de Infecção Hospitalar - SCIH). Exclusion criteria involved newborns with incomplete forms. Data were collected by consulting these forms and recorded on the data collection form.

The data were entered and stored in a Microsoft Excel® spreadsheet, version 2016. Simple frequencies and percentages were calculated for each variable. Statistical tests were not applied because the survey did not involve two groups of participants, with and without deaths, in order to compare variables between the two groups.

The data were collected after approval by the MEAC Research Ethics Committee, according to opinion 5.471.900. Ethical aspects were respected in accordance with CNS Resolution 466/12.

RESULTS

Table 1 shows the characterization of participants who died from neonatal and post-neonatal sepsis in under one-year-olds, according to maternal and neonatal variables.

With regard to maternal variables, it was found that the majority of mothers were adults (77-64,8%), high-risk multigravidae (71-59,6%), and the route of delivery was mostly caesarean section.

Among the most prevalent maternal factors related to neonatal and post-neonatal death from sepsis in under one-yeaolds were hypertension/eclampsia and Urinary Tract Infection (UTI), which affected 49 (41,1%) and 43 (36,1%) mothers, respectively.

The weight of most participants was lower than 1.000 grams both at birth (72–60,5%) and on the day of death (60–50,4%). Gestational ages were under 30 weeks (78–65,5%).

It was found that the most prevalent chronological age on the day of death was in the neonatal period in children under 28 days old (78–65,6%). When identifying the sex of the newborns, the majority were found to be male (65–54,6%).

The most prevalent APGAR scores in the first minute of life were lower than seven (83-69,8%), being higher than seven (89–74,8%) in the fifth minute.

Table 1. Characterization of participants with an outcome of death from neonatal and post-neonatal sepsis in under one-year-olds according to maternal and neonatal variables. Fortaleza (CE), Brazil, 2023.

MATERNAL VARIABLES
Maternal age (years)*	N	%
Adolescent (10 – 19)	10	8,4
Young adult (20 – 24)	32	26,8
Adult (25 and over)	77	64,8
Type of delivery*
Caesarean	77	64,7
Vaginal	32	35,3
Pregnancies*
Primigravida (first pregnancy)	37	31,1
Multigravida (second and fourth pregnancies)	71	59,7
Large multigravida (five or more pregnancies)	11	9,2
Maternal risk factors related to the death*
Arterial hypertension/Eclampsia	49	41,1
Urinary tract infection	43	36,1
Bulkhead rupture of ovular membranes/premature amniorrhexis	26	21,8
Preterm labor/Inhibition of preterm labor	19	15,9
NEONATAL VARIABLES
Weight at birth (grams)*	N	%
<750	45	37,8
750–999	27	22,7
1000–1499	20	16,8
1500–2499	16	13,5
≥2500	11	9,2
Weight on the day of death (grams)*
<750	38	31,9
750–999	22	18,5
1000–1499	20	16,8
1500–2499	20	16,8
≥2500	19	16,0
Gestational age*
Less than 30 weeks	78	65,5
30–34 weeks	22	18,5
35–36 weeks	8	6,7
37–41 weeks	11	9,3
Chronological age on the day of death (days)*
<24 hours	8	6,7
1-7	36	30,3
8-2	34	28,6
28-364	41	34,4
Sex of the newborn*
Male	64	54,6
Female	54	45,4
APGAR score in the 1st minute of life*
0-3	46	38,7
4-6	37	31,1
7-10	35	29,4
No score	1	0,8
APGAR score in the 5th minute of life *
0-3	6	5,1
4-6	23	19,3
7-10	89	74,8
No score	1	0,8
Days lived from diagnosis to death (days)*
0-2	50	42,0
3-7	27	22,7
8-14	10	8,4
15-21	10	8,4
22-30	5	4,2
≥31	17	14,3
* N is equal to 119 participants. †The N value used to calculate the percentage of each variable stratification, individually, was 119 newborns, as some participants presented more than one maternal risk factor related to the death.

As for the procedures performed in the delivery room and NICU, Table 2 shows that endotracheal intubation and Central Venous Catheter (CVC) insertion were most prevalent, 91-76,5% and 201 CVC, respectively. The number of CVC inserted exceeded the number of participants studied due to some having used more than one CVC during hospitalization. As for the problems presented by the participants at birth, extreme prematurity was identified (94–79,0%).

Table 2. Characterization of participants with an outcome of death from neonatal and post-neonatal sepsis in under one-year-olds according to problems presented at birth and procedures in the delivery room. Fortaleza (CE), Brazil, 2023.

VARIABLES
Immediate newborn care procedures	N†	%
Endotracheal intubation	91	76,5
Airway suction	77	64,7
Oxygen under mask/manual resuscitation	77	64,7
Umbilical venous catheterization	24	20,2
Orogastric tube passage	12	10,1
Intravenous medication	7	5,9
Oxygen inhalation	1	0,8
Procedure used during NICU hospitalization
Central venous catheter	201‡	-
Parenteral nutrition	110	92,4
Mechanical ventilation	106	89,1
Intravenous medication	104	87,4
Intubation	88	73,9
Orogastric tube	70	58,8
CPAP*	23	19,3
Helmet for oxygen	21	7,6
Inhalation oxygen therapy	2	1,7
Problems presented by newborns at birth
Extreme prematurity	94	79,0
Hyaline membrane disease	88	73,9
Newborn with suspected infection	52	43,7
Asphyxia/fetal distress	29	24,4
Congenital malformation	17	14,3
Meconium aspiration syndrome	2	1,7
Transient tachypnea in the newborn	2	1,7
*Continuous Positive Airway Pressure.  †The N value used to calculate the percentage of each variable stratification, individually, was 119 newborns, as some participants underwent more than one immediate care procedure and during hospitalization, as well as being affected by more than one disease diagnosis. ‡The percentage was not calculated because several newborns used more than one central venous catheter.

Table 3 shows the distribution of participants in terms of the use of antibiotics and their respective classes, the results of blood culture and the causes associated with the death.

Most of the newborns were given empirical antibiotic therapy, i.e., before the diagnosis of sepsis was confirmed (78–65,6%), the most commonly used classes of antibiotics being aminoglycosides (50–42,0%) and glycopeptides (44–37,0%). Among the blood culture results, the negative ones were the most prevalent (86–72,3%). The most frequent causes of death were prematurity (75-63,0%), septic shock (57-47,9%) and sepsis (38-31,9%).

Table 3. Characterization of participants with an outcome of death from neonatal and post-neonatal sepsis in under one-year-olds according to empirical use of antibiotics and classes of antibiotics used, blood culture results and causes associated with the death. Fortaleza (CE), Brazil, 2023.

VARIABLES
Empirical use of antibiotics	N*	%
Yes	78	65,6
No	41	34,4
Classes of antibiotics used to treat sepsis	N†	%
Aminoglycosides (gentamicin, amikacin)	50	42,0
Glycopeptides (vancomycin, teicoplanin)	44	37,0
Fourth-generation cephalosporin (cefepime)	39	32,8
Betalactams (ampicillin)	26	21,8
Carbapenems (meropenem)	22	18,5
Betalactams (oxacillin)	19	16,0
Nitroimidazole (metronidazole)	16	13,4
Quinolones (ciprofloxacin)	9	7,6
Antifungal (amphotericin)	8	6,7
Ecnocandin (micafungin)	6	5,0
Lincosamide (clindamycin)	3	2,5
Oxazolidinone (linezolid)	2	1,7
Cationic polypeptide (polymyxin)	2	1,7
Result of blood culture
Negative	86	72,3
Gram-positive bacteria	26	21,8
Gram-negative anaerobe	4	3,2
Gram-positive anaerobe	2	1,7
Gram-negative bacteria	1	0,8
Fungus	0	0
Causes associated with the death
Premature birth	75	63,0
Septic shock	57	47,9
Sepsis	38	31,9
Renal insufficiency	24	20,2
Necrotizing enterocolitis	23	19,3
Late-onset sepsis	17	14,3
Early-onset sepsis	11	9,2
Neonatal and post-neonatal infection	11	9,2
Surgical infection	5	4,2
Urinary tract infection	2	1,7
Others	4	3,4
*N is equal to 119 participants. †The N used to calculate the percentage of each variable stratification was 119 newborns, as some participants used more than one class of antibiotics, had more than one blood culture result, and presented more than one cause associated with the death.

DISCUSSION

 It has been shown that neonatal and postnatal deaths from sepsis in under one-year-olds are associated with various maternal risk factors, such as caesarean section; maternal age over 25; pregnancy complications, such as maternal UTI, premature or prolonged rupture of ovarian membranes and pre-eclampsia/eclampsia; and neonatal complications, such as premature labor, low birth weight and low gestational age.

As for the association between the type of delivery and neonatal mortality, a descriptive and retrospective study in a NICU found that the incidence was higher in newborns delivered by caesarean section (112-62,92%).⁸

It should be emphasized that a caesarean section is recommended in cases of placenta previa, placenta accreta, meconium and fetal distress, and that the greater prevalence of caesarean section leads to a greater possibility of complications for the newborn in terms of respiratory dysfunction, prematurity and admission to the NICU, leading to an increase in neonatal mortality.⁹ The institution under study is peculiar in that, as it provides care for high-risk pregnant women and newborns, it has higher than expected rates of caesarean sections, since such patients often need to undergo a caesarean section to resolve a high-risk pregnancy.

With regard to maternal factors related to neonatal death, the perinatal outcome of death in premature birth is more associated with hypertensive mothers,¹⁰ pathology that can result in the need for early termination of pregnancy to preserve maternal life, causing premature birth and all the unfavorable outcomes that come with prematurity.

Low birth weight and UTI are also frequently associated with neonatal sepsis and death.¹¹ A meta-analysis aimed at evaluating the association between neonatal sepsis, gestational UTI and intrapartum fever found that newborns had a 3,55 times greater risk of developing neonatal sepsis.¹²

Given the importance of maternal UTI in the incidence of neonatal death, there is a need to improve primary care measures for pregnant women as an effective strategy for the prevention and early treatment of UTI, mitigating the vertical transmission of microorganisms that result in antepartum rupture of ovarian membranes, preventing premature birth and neonatal death from sepsis.

With regard to parity and neonatal and post-neonatal sepsis in under one-year-olds, this study found that multiparity is more frequently associated with death. This finding prompts further research to elucidate the relationship between these two variables so that preventive measures can be adopted for this population.

Multidisciplinary educational actions with pregnant women during prenatal care involving encouragement of normal childbirth, skin-to-skin contact and breastfeeding, providing information on risky gestational situations such as preventive measures, control and treatment of maternal UTI, preterm labor, control of arterial hypertension and gestational diabetes favor the prevention of preterm birth, of vertical transmission of infection and, consequently, of neonatal and post-neonatal death due to sepsis in under one-year-olds.

A literature review aimed at evaluating risk factors for neonatal sepsis showed that in 9 out of 15 studies, low birth weight was a risk factor for neonatal sepsis, with level of evidence 2B in five studies, and 3B in three.¹³

A study that investigated risk factors for HAI in newborns highlighted prematurity; low birth weight (between 751 and 1.500 grams); the clinical conditions at birth; decreased neonatal immune defense; the need for invasive procedures, such as blood collection, tracheal intubation, mechanical ventilation, use of a Central Venous Catheter (CVC), vesical probing, chest drainage; hospitalization for longer than eight days; use of H₂ blockers; gastrointestinal tract disease or surgical treatment; and use of parenteral nutrition.¹⁴

When verifying the effects of maternal and neonatal risk factors on the development of neonatal sepsis, it was found that prematurity, resuscitation at birth, and a low APGAR score are significant risk factors for the onset of sepsis,¹⁵ and the presence of congenital malformation, preterm birth, and low birth weight were associated with a higher chance of perinatal death, indicating the importance of adequate prenatal care to promote the reduction of fatal outcomes.¹⁶

Prematurity of newborns of under 26 weeks is the most important risk factor responsible for the higher incidence of early-onset neonatal sepsis.¹³

In this study, the chronological age on the day of neonatal death due to sepsis was predominant in newborns (from zero to 27 days old). Studies have shown a reduction in infant mortality in recent decades; however, neonatal deaths and deaths in under one-year-olds are still a public health problem,¹⁷ since they mostly affect underweight individuals. Moreover, the higher the maternal schooling, the lower the incidence.¹⁸

Further research is needed to highlight the challenges that still exist in preventing infant mortality, identifying opportunities to improve care during pregnancy, childbirth and puerperium, with a view to making progress in reducing mortality in under one-year-olds in the neonatal and post-neonatal periods.

Factors related to the NICU environment, such as average length of hospital stay, time and use of invasive devices (for instance, CVC, invasive mechanical ventilation, and parenteral nutrition) for more than 10 days,¹⁵  are aggravated by the immune immaturity of the newborn and, consequently, associated with neonatal deaths from sepsis.¹⁹

As for respiratory distress, it was found to be the most frequent diagnosis associated with death from neonatal sepsis, since its high prevalence can lead to a similar rate of orotracheal intubation.²⁰

The mechanism associated with the higher risk of sepsis due to the use of CVC occurs because the CVC is a gateway for contamination of the bloodstream during insertion and use of the intravenous device, favoring the occurrence of PBI, of an increase in hospitalization time, and a higher risk of sepsis and death.²¹

Pneumonia associated with mechanical ventilation, PBI associated with CVC, and UTI related to vesical probe delay are preventable hospital infections as they are linked to hospital care during the insertion and use of invasive devices that when inserted and used with good practices connected to aseptic technique will keep neonates free from contamination. The development and use of care bundles for the insertion, maintenance and removal of these devices are fundamental to preventing these infections.

The use of institutional policies based on indicators of NICU infections, deaths, adherence to good care practices for infection prevention, and wide disclosure of these indicators to the care team, as well as continuing education for the care team can be effective tools for preventing hospital infections and deaths in the NICU.

In this study, the majority of blood cultures isolated gram-positive bacteria. A study shows that, in terms of the classes of microorganisms that cause neonatal sepsis, gram-positive bacteria are extremely important pathogens in the hospital environment.²²

Gram-negative bacteria are associated with death from neonatal sepsis, followed by the coagulase-negative Staphylococus.¹³ Gram-negative bacilli contain endotoxin that causes a systemic and severe inflammatory process, making this type of bacteria more virulent than the gram-positive ones.²³

Based on the greater virulence of gram-negative bacteria, there is an urgent need to epidemiologically identify the bacterial flora of institutions that care for newborns and to adopt strategic measures to control the increased incidence of these microorganisms in order to mitigate the contamination of neonates with this pathogen, reducing the risk of death.

In the routine of the institution where this study was carried out, there are systematic practices to control overcrowding; adequate hospital hygiene practices in the NICU; training in hand hygiene, as well as evaluating adherence rates to this practice; rational use of antimicrobials; use of an exclusive intravenous route for parenteral nutrition infusion; disinfection of intravascular devices immediately before use, among other good practices for insertion and use of CVC; reduction of the antimicrobial spectrum; and implementation of monotherapy guided by the result of the antibiogram in order to reduce the possibilities of causing selection of more virulent microorganisms and bacterial resistance.

Amikacin and gentamicin were among the most commonly used drugs in this study. The choice of oxacillin and amikacin for empirical use is recommended due to the low induction of resistance and high sensitivity of gram-negative rods when compared to other antimicrobials, as well as the wide availability and low cost of these pharmaceutical drugs. The cautious use of aminoglycosides and vancomycin, due to the risk of nephrotoxicity and ototoxicity, should be considered in higher-risk newborns.²⁴

Prolonged use of broad-spectrum antimicrobials has been indicated as a risk factor for necrotizing enterocolitis, bronchopulmonary dysplasia and invasive candidiasis, which can worsen the clinical condition and lead to neonatal death from sepsis.²⁵

The finding considered most relevant by the authors of this study concerns the causes associated with neonatal and post-neonatal death in under one-year-olds shown on the institution's death notification forms.

These forms were found not to differentiate between the causes of death from sepsis, whether early-onset, late-onset, with an infectious focus or PBI associated with CVC (without an infectious focus), which makes it difficult to identify the origin of contamination of newborns, whether associated with maternal factors (early-onset sepsis), hospital care (late-onset sepsis with an infectious focus), or PBI associated with CVC (infection associated with CVC insertion and use).

The benefit of identifying the origin of sepsis is that effective prevention and treatment measures can be taken in different ways for each case. In the case of early-onset sepsis (of maternal origin), opportunities for improvement would be assertive if implemented in the care of pregnant women and their fetuses during prenatal care, rather than in the hospital environment, as is the case with late-onset sepsis. Actions to prevent and effectively treat maternal conditions, such as maternal infectious diseases, maternal UTIs, premature rupture of membranes and chorioamnionitis, should be reviewed and updated.

With regard to the newborn, the approach involves drawing up and widely disclosing protocols with a view to institutional standardization of procedures for managing the risk of early neonatal infection, such as collecting blood samples within 2 hours of life; starting empirical antibiotic therapy (ampicillin and gentamicin); doing a complete blood count; C-reactive protein at 12 hours of life; establishing a rational use of antibiotics, not escalating the antibiotic to a broader spectrum without the proper indication; assessing antibiotic suspension based on clinical and laboratory criteria; collecting cerebrospinal fluid from newborns weighing less than 1.500 grams.²⁶

In cases of late-onset sepsis, preventive and curative measures will have to be applied in the hospital environment. Thus, measures to prevent PBI associated with CVC, necrotizing enterocolitis, meningitis, fungal infection, UTI, among others, as well as standardized therapeutic management of these infections are fundamental to mitigate the hematogenous dissemination of microorganisms and consequent occurrence of late-onset sepsis, consequently reducing neonatal and post-neonatal deaths in under one-year-olds due to this condition.

Another opportunity for improvement was identified when filling in the notification forms for neonatal deaths. It was found that in the recording of causes associated with death, such as septic shock, sepsis, neonatal infection, such causes can occur in both early-onset and late-onset sepsis, as evidenced by the number of deaths recorded in this study, where 11 (9.2%) had causes associated with early-onset sepsis, and 17 (14.3%) with late-onset sepsis.

Based on the premise that sepsis is classified into two categories, either early-onset (maternal origin) or late-onset (hospital origin), only 28 (23.5%) participants had the origin of the sepsis that caused the death identified. Thus, the indicators of causes associated with neonatal and post-neonatal death in under one-year-olds limit the power of comparing the institution's data to others with a similar profile. Furthermore, the targets of prevention measures for neonatal and post-neonatal sepsis in under one-year-olds are restricted, as it is not known whether the origin of sepsis is in hospital care or not, making it difficult to assess the quality-of-care indicators at the institution under study.

According to the Brazilian list of causes of preventable deaths in under five-year-olds, "due to causes reducible by adequate care for the newborn", it can be seen that infections specific to the perinatal period, including code P36 - bacterial septicemia of the newborn, do not provide stratification according to the origin of the septicemia: whether early-onset, late-onset with an infectious focus, or without an infectious focus (PBI associated with CVC).⁶

The International Classification of Diseases 11 (ICD-11), version 2022, has been translated and revised by the countries that committed to using it for reporting on mortality and morbidity in 2022, a commitment signed during the World Health Assembly in May 2019.²⁷

The ICD guides reimbursement decisions by public and private health managers at all spheres who monitor progress in global health and decide on the allocation of health resources. ICD-11 also provides data on safety in health care, identifying and reducing unnecessary events that can harm health, such as unhealthy work practices in hospitals.²⁷

In ICD-11, 11^th revision, in the "ICD-11 for mortality and morbidity statistics" section, item 01, "certain infectious or parasitic diseases"; in the "sepsis" item, the classification is "sepsis of the fetus or newborn". In the description, the text highlights the causes of sepsis associated with resistant microorganisms, infectious agents, bacteria, viruses, fungi, parasites and other pathogens, circulatory, renal and pulmonary failure; however, it does not mention the origin of these microorganisms, whether in-hospital or out-of-hospital.²⁸

Therefore, this study describes the nomenclature used to identify the causes of deaths from neonatal and post-neonatal sepsis in under one-year-olds, with a view to resolving this information gap and promoting assertive actions to allocate resources to mother and child health care, to evaluate care practices, and to adopt measures that foster improvements in the quality of NICU care and the prevention of death from sepsis in this age group.

The limitations of this study include the failure to assess factors associated with early-onset neonatal, late-onset neonatal and post-neonatal sepsis in under one-year-olds, with and without the outcome of death from these causes, making it impossible to apply statistical tests to compare these groups.

CONCLUSION

Death from neonatal and post-neonatal sepsis in under one-year-olds was found to be multifactorial and can occur in a cascade effect. Maternal risk factors for neonatal infection can result in premature birth, which in turn requires invasive therapies to promote life, prolonging hospitalization and exposing the newborn to hospital microbiota that are often quite virulent, increasing the risk of neonatal and post-neonatal sepsis in the under one-year-olds. Due to the immune and physiological fragility of the newborn, these events can lead to death.

Based on the maternal and neonatal factors associated with the occurrence of deaths from sepsis presented above, there is a need to intensify sepsis prevention measures that should be initiated from the gestational period, with emphasis on UTI and on controlling gestational hypertension. The collected data, therefore, made it possible to find out the indicators of death from neonatal and post-neonatal sepsis in under one-year-olds in the NICU, besides providing a comparison with other services with the same care profile.

These data suggest the possibility of evaluating the multi-professional care provided in the NICU of the institution where the study was carried out, and in the prenatal care offered by the health care network where the patients admitted to the institution come from, followed by a team discussion about current care practices. Hence, there are opportunities to draw up and implement in-hospital and out-of-hospital action plans with recruitment from the local, state and national spheres of health care for pregnant women and newborns, with a view to improving the care provided, founded on evidence-based practice to promote patient safety, with a positive impact on preventing sepsis and deaths from this cause.

The need for adjustments to sepsis death registers at local, national and/or international levels, identifying the origin of the sepsis, is emphasized, with the aim of improving the guidelines for filling out death certificates for infectious causes, so as to help identify the source of the contamination that generated the sepsis, whether in-hospital or out-of-hospital, in order to better direct the attention of managers and the allocation of public financial and assistance resources at the appropriate level of health care (primary, secondary or tertiary), with a view to preventing deaths from early-onset or late-onset sepsis in patients admitted to the neonatal intensive care unit.

CONTRIBUTIONS

The authors contributed equally to the conception of the article, data collection, organization, design, research and writing of the study. Furthermore, all the authors of this study have approved the final version of the manuscript and take public responsibility for its content.

CONFLICTS OF INTERESTS

Nothing to report.

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Corresponding author

Lívia Karoline Torres Brito

E-mail: livia3418@gmail.com