The incidence of neonatal sepsis varies among the different geographic areas, the highest being registered in Africa and Asia (23-38/1,000 live births) and the lowest, in countries such as the U.S. and Australia (range, 1.5-3.5 /1,000 live births). In South America and the Caribbean, the incidence of neonatal sepsis ranges between 3.5 and 8.9/1,000 live births , while in Mexico, the reported rates range between 4 and 15.4/1,000 live births . Although the neonatal mortality rate has been documented in our southeastern Mexico region, the incidence of sepsis and its associated factors remain unknown. The present study was carried out with a population cohort of 11,790 births with a sepsis incidence of 4.3/1,000 live births. A total of 514 neonates were found with sepsis, of which 87 cases were confirmed by means of blood culture; this low sensitivity of the blood culture can be due to the logistical problems involved in culturing very small quantities of blood . Despite that blood culture is considered the gold standard in the diagnosis of sepsis, it is a technique with a low sensitivity, because under optimal conditions, only 5-10% of suspected cases of sepsis can be confirmed [2, 17, 18]. In a retrospective study with 21,771 registries (Mclntire, et al.), only 0.3% of cases of sepsis were confirmed by blood culture . On the other hand, Cohen-Wolkowiew, et al., in a multicenter study performed between 1997 and 2007 in which 119,130 premature newborns from Intensive care units (ICU) were included, documented that 69% of these had at least one request for blood culture; however, only 0.4% were confirmed by culture. These authors suggest that the incidence of sepsis can be low in premature newborns because only a small number achieved confirmation . Due to that the majority of neonates with sepsis were premature (68.1%), it is difficult to determine whether the diagnosis of sepsis based on clinical signs can be confused with prematurity at birth, given that the specific pathophysiology of the sepsis in the premature neonate includes alterations of the immature myocardium and immaturity of the immunological and autonomous nervous systems [21, 22].
In our study, the majority of episodes of sepsis (387/514) were documented during the first 3 days of life (early-onset) with a mortality rate of 5.7%; furthermore, the isolation of infecting microorganism was low 2.3% (9 isolations) and Staphylococcus CoNS were the most commonly isolated microorganisms, while for late-onset sepsis we documented a lower incidence (127/514), but a higher lethality (21.3%), Staphylococcus CoNS
Staphylococcus aureus and Candida ssp. were the most frequently isolated microorganisms. Currently in the literature, there is no consensus on temporality and type of sepsis; for example, early-onset sepsis can be defined by a period ranging from birth to 48 h or until 6 days of life; this discrepancy affects the interpretation of the rates reported and renders comparison difficult among the different studies. For example, in a study carried out in Kenya in which early-onset sepsis is considered at ≤3 days of life, the authors documented a mortality of 4% in early-onset and of 10% in late-onset sepsis; the most commonly isolated microorganisms were Klebsiella spp. and Citrobacter spp.. In Panama, the authors reported a mortality of early-onset sepsis of 44% and one of 22% for late-onset sepsis, with Klebsiella spp. and Staphylococcus aureus as the most commonly isolated microorganisms; the authors considered early-onset sepsis as ≤5 days of life . In India, where early-onset sepsis is considered up to ≤6 days of life, the authors found a mortality of 49 vs. 86% in late-onset sepsis; Klebsiella spp. and Pseudomonas spp. were the most frequently isolated microorganisms . Thus, some authors have proposed classifying sepsis as a type of transmission without taking temporality into consideration; therefore, early-onset sepsis occurs by vertical transmission and is mainly caused by Gram-negative bacteria that are acquired before or after delivery, while late-onset sepsis takes place by horizontal transmission and is principally associated with Gram-positive bacteria acquired after delivery; its source can be nosocomial- or community-acquired [12, 26, 27]. Recently, Cooper C, et al. reported that early-onset sepsis is defined within 48 h of births, although definitions in some studies include infection up to 72 h after birth, the health care associated infections rarely occur within this period . In the present work, the most frequently isolated microorganism for early- as well as late-onset sepsis was Staphylococcus CoNS. Although this bacterium tends to be normal flora of the skin, it has been suggested that it can be pathogenic in newborns submitted to invasive medical procedures (i.e., venous catherization, endotracheal intubation, prematurity, and a prolonged hospitalization period) [29–31].
It also has been described that Staphylococcus genus CoNS is associated with inflammatory response evasion [32, 33]; resistance to antibiotics is measured by plasmids  or quorum sensing [35, 36]; it also possesses genetic determinants such as operon-Catabolite activator protein (CAP) and the Gamma-glutamyl peptidase (GGP) gene, which confers greater virulence on the bacterium [37, 38]. However, despite all of these virulence factors, and although the hospital has certification in the quality attention processing of patients; we are unable to discard the possibility of contamination during venopuncture, or the presence of microorganisms in moist environmental near patient sources such as room temperature bubble oxygen humidifiers. Even though we used standard guidelines for neonatal study recommendation definitions, our findings should be interpreted in the context of the quality of retrospective studies [21, 39].
Prior studies have identified risk factors for sepsis such as prematurity, low birth weight, premature membrane rupture, maternal pyrexia, poor intra- and postpartum hygiene, invasive medical procedures, and hospital stay [3, 13, 40, 41]. Likewise, in our study, sepsis-associated factors comprised prematurity, abnormal amniotic liquid, premature membrane rupture, and invasive medical procedures such as mechanical ventilation, O2IF ≥60%, respiratory complication, and surgical procedure, as has been described in previous studies [42, 43] (Table 3). All of these factors are present in early-onset sepsis; notwithstanding this, in late-onset sepsis, we documented additional factors such as postmaturity, multiple-pregnancy product, perinatal asphyxia, and all invasive therapeutic procedures (Table 3). It is noteworthy that in this study, we documented that postmaturity is a late-onset sepsis-associated factor (Relative Risk [RR] 7.7; 95% CI, 1.4-35.7). In this context, Hákansson, et al. reported that post-term infants with >42 weeks of gestational age had a 1.8 times greater risk of developing sepsis and pneumonia ; on the other hand; Cheng, et al. documented that in neonates with >40 gestational weeks, the risk of neonatal damage increases mainly due to meconium aspiration (adjusted Odds ratio [OR], 1.27; 95% CI, 1.17-1.37), which can condition sepsis development . More detailed studies are required that evaluate the specific risk factors for post-term infants.
When we evaluated the clinical factors associated with poor prognosis in 514 neonates with sepsis, we found that prematurity, low birth weight, perinatal asphyxia, and an Apgar score of ≤5, as well as invasive medical procedures, are mortality-associated factors (Table 5). These results are in agreement with previous reports that associate these factors with poor prognosis and death in the neonate with infection [46–49]. Recently, it has been documented that the incidence of pre-term births (at <37 gestational wks) has increased in many countries worldwide and that this represents a public health problem because >70% of pre-term infants are found within the range of 34–36 gestational weeks (late-onset pre-term). This is relevant because the majority of epidemiological descriptions for neonatal sepsis are directed toward or limited to neonates with very low gestational age (<33 wks) or very low birth weight. Pre-term neonates with late-onset sepsis are traditionally treated by clinicians as full-term neonates; however, there is evidence suggesting that pre-term neonates with late-onset sepsis have a substantial increase in the risk for morbi-mortality . Cheng, et al. have reported that neonates with 37 gestational weeks have a greater frequency of a low Apgar of <7 at 5 min of life (adjusted OR, 1.69; 95% CI, 1.59-1.79) and a 5-min Apgar of <4 (adjusted OR, 1.87; 95% CI, 1.63-2.15) with respect to neonates born between 38 and 39 gestational weeks . It has also been described that neonates of <37 weeks have a greater risk of presenting respiratory complications and of consequently requiring mechanical ventilation, which conditions them for greater susceptibility for sepsis [49, 50].
We also acknowledge some limitations of this work. First, this study is of retrospective design, and this might inevitably be complicated by incomplete data due to lost records. Second, diagnoses were provided by different caregivers. Unfortunately, ideal prospective data collection by designated study personnel proves extremely difficult in a developing country with limited resources.