A Selected Review of the Mortality Rates of Neonatal Intensive Care Units

Introduction Newborn babies in need of critical medical attention are normally admitted to the neonatal intensive care unit (NICU). These infants tend to be preterm, have low birth weight, and/or have serious medical conditions. Neonatal survival varies, but progress in perinatal and neonatal care has notably diminished mortality rates. In this selected review, we examine and compare the NICU mortality rates and etiologies of death in different countries. Methods A literature search was conducted in Ovid MEDLINE, OLDMEDLINE, EMBASE Classic, and EMBASE. The primary endpoint was the mortality rates in NICUs. Secondary endpoints included the reasons for death and the correlation between infant age and mortality outcome. For the main analysis, we examined all infants admitted to NICUs. Subgroup analyses included extremely low birth weight infants (based on the authors’ own definition), very low birth weight infants, very preterm infants, preterm infants, preterm infants with a birth weight of ≤1,500 g, and by developed and developing countries. Results The literature search yielded 1,865 articles, of which 20 were included. The total mortality rates greatly varied among countries. Infants in developed and developing countries had similar ages at death, ranging from 4 to 20 days and 1 to 28.9 days, respectively. The mortality rates ranged from 4 to 46% in developed countries and 0.2 to 64.4% in developing countries. Conclusion The mortality rates of NICUs vary between nations but remain high in both developing and developed countries.


Materials and Methods
A literature search was conducted in Ovid MEDLINE and OLDMEDLINE (1946 to June Week 1, 2015) and EMBASE Classic and EMBASE  Week 24). The key search terms were "neonatal intensive care units" and "mortality" (see Figures 1 and 2). Titles and abstracts were screened to identify if studies were relevant for full-text screening, after which full-texts were included if they met the pre-specified inclusion criteria.

Data extraction and endpoints
The primary endpoint was the in-hospital mortality rate, which was defined as the number of deceased individuals divided by the sample size. Secondary endpoints included the reasons for death and the correlation between infant age and mortality outcome.
For the main analysis, we examined all infants admitted to NICUs. Based on the authors' own definition, the subgroup analyses were extremely low birth weight infants, very low birth weight infants, very preterm infants, preterm infants, and preterm infants with a birth weight of ≤1,500 g. We also grouped studies based on whether they came from developed or developing countries as classified by the United Nations (19).
Two articles (21,26) studied the mean age of infants with extremely low birth weights. Keir et al. (21) found that the mean GA of the deceased infants was 24.4 ± 1.4 weeks in Australia, while Tagare et al. (26) noted that the mean GA of the late infants was 27.2 weeks in India (

Mortality rates in Overall in-hospital Deaths
Two studies reported on all in-hospital deaths at a NICU, for which both trials defined the in-hospital mortality as all inpatient deaths during the study period (23,28). However, each study calculated the in-hospital mortality rate differently;  (23). Prematurity and its complications was a common cause of death; in Israel, 76% (182/239) of late infants died from these circumstances (28)

Mortality rates in Very Preterm infants (<32 weeks ga)
Two studies reported the mortality outcomes for very preterm infants (24,29). Zhou et al. (24) examined the age at death, noting that 49% (28/58) of deceased infants died in the late neonatal period (7-28 days). The overall in-hospital mortality rates were noted to be 8% in China between October 2010 and September 2011 (24), and 18.8% in Italy in 2005 (29) ( Table 6).

Mortality rates in Preterm infants (<37 weeks ga)
One study reported the mortality outcomes for preterm infants (31). The overall in-hospital mortality rate was 20.6% in Nepal between 2007 and 2009 (31) (

Discussion
The age at death for all infants admitted to NICUs globally ranged from 1 to 12 days (20,22,25,(33)(34)(35)(36)(37). Similarly, deaths in the NICU tended to occur on the first and sixteenth days of life in Israel and Canada, respectively (23,28). By contrast, very preterm (24) and preterm infants with birth weight of ≤1,500 g (27) were the infants with the oldest age at death. Zhou et al. (24) reported that approximately half [49% (28/58)] of late very preterm infants died in the late neonatal period (7-28 days). Navaei et al. (27) found that the average age at death for preterm infants with birth weight of ≤1,500 g was 28.9 days. It is surprising that very preterm infants had a longer life span than all NICU patients. The delayed mortality in premature infants suggests that a greater percentage of preterm neonates are surviving the immediate conditions of prematurity, only to contract lethal complications later (23). This may be due to the substantial improvements in supportive efforts for these high-risk patients in the first week(s) of life (23). However, it is unclear whether this increased survival for very preterm infants and preterm infants with birth weight of ≤1,500 g is attributable to improved medical care or lengthened suffering prior to death (23). Consistent with the findings above, studies analyzing the outcomes of all infants admitted to NICUs (20,22,25,(33)(34)(35)(36)(37) and all in-hospital deaths (23,28) reported the lowest mortality rates. The mortality rates were 0.2% in Israel (28) and 7.6% in Canada (23), while it ranged from 3.1 to 29% globally (20,22,25,(33)(34)(35)(36)(37). The mortality rates for the other articles, in ascending order, are as follows: very low birth weight infants .8%] (30,32,39), very preterm infants [8][9][10][11][12][13][14][15][16][17][18].8%] (24,29), preterm infants (20.6%) (31), and extremely low birth weight infants [34-6%] (21,26,27,38). Among all included analyses, the overall mortality rates for all infants admitted to NICUs and all in-hospital deaths are the lowest, as the study samples include both higher and lower-risk neonates. Conversely, infants who were born premature and with very low birth weight had more severe issues, putting them at a very high risk for death.
The mortality rate of NICUs varies but remains high in both developing and developed countries. Prematurity is a very common etiology of death, as very low birth weight infants (32), infants who died in hospital (23,28), and preterm infants with very low birth weight (27) were all prematurely born. This could be attributable to the large number of preterm births; in fact, in 2005, the World Health Organization estimated that 12.9 million births of all births (9.6%) in the world were preterm (40).
The findings of this selected review are important for NICUs. Through examining the etiologies of death in different countries, further insight is provided, allowing care providers, policymakers, and researchers to address improvements on areas that will most benefit patients (23). Also, by comparing and contrasting various mortality rates and the age of infants at death, it provides NICUs with many different comparators.
The limitations of our study were that all information was taken from study cohorts. Another weakness was the heterogeneity in the definitions of medical terms (e.g., extremely low birth weight).