Edited by: Frederick Robert Carrick, Carrick Institute, USA
Reviewed by: Jugesh Chhatwal, Christian Medical College & Hospital, India; Susan Elizabeth Esposito, Life University, USA; Linda Mullin Elkins, Life University, USA
Specialty section: This article was submitted to Child Health and Human Development, a section of the journal Frontiers in Public Health
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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.
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.
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.
The mortality rates of NICUs vary between nations but remain high in both developing and developed countries.
Newborn babies in need of critical medical attention are normally admitted to the neonatal intensive care unit (NICU) (
Neonatal survival varies with the quality of medical care (
Progress in perinatal and neonatal care has notably diminished mortality and has improved the health of premature infants admitted to NICUs (
A literature search was conducted in Ovid MEDLINE and OLDMEDLINE (1946 to June Week 1, 2015) and EMBASE Classic and EMBASE (1947–2015 Week 24). The key search terms were “neonatal intensive care units” and “mortality” (see Figures
Articles were selected for full-text screening if the title or abstract mentioned mortality in addition to either “neonatal intensive care unit” and/or “NICU.” Another requirement was that there had to be a numerical mortality outcome following admittance to the NICU. Articles that did not have mortality rate statistics were excluded. Only English language studies were included. Duplicates of articles found in each database, as well as non-original research and small (i.e., <5 patients) studies, were excluded.
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 (
The literature search yielded 1,865 articles, with 285 from MEDLINE and 1,580 from EMBASE. Of those, 40 articles were identified for full-text review as specified by the inclusion criteria; 20 of the 40 articles were rejected after full-text review. Some of the reasons for exclusion were the absence of numerical mortality rates, lack/absence of relevant information regarding NICU mortality, and repeat data. Of the 20 remaining articles (
Author | Country | Year(s) | Methods | Age of infants | Mortality outcome | Reasons for death |
---|---|---|---|---|---|---|
Feng et al. ( |
Australia | 1995–2006 | Data for 24,131 infants admitted to 10 NICUs | GA of <24 weeks ( |
Overall mortality rate: 9.2% (2,224/24,131) |
Overall leading causes of death: congenital abnormalities ( |
Keir et al. ( |
Australia | 2005–2010 | Data for 36 extremely low birth weight infants (≤500 g), including 26 NICU patients, born at a tertiary hospital | GA of ≥22 weeks |
46% (12/26) | NEC ( |
Sankaran et al. ( |
Canada | January 8, 1996–October 31, 1997 | Data for 19,265 infants admitted to 17 tertiary-level NICUs. | Age at death: 2 ( |
Overall mortality rate: 4% (795/19 265) |
Outborn status ( |
Simpson et al. ( |
Canada | 1997, 2002, 2007 | Data for 156 in-hospital deaths (53 in 1997, 50 in 2002, 53 in 2007) at a tertiary-level NICU | 2007: GA of 23–27 ( |
Average annual mortality rate between 1988 and 2007: 7.6% | 2007: gastrointestinal ( |
Zhou et al. ( |
China | October 2010–September 2011 | Data for 729 very preterm infants admitted to a tertiary NICU | GA of <32 weeks |
Overall mortality rate: 8% (58/729) |
Not listed |
Manktelow et al. ( |
England | 2008–2010 | Data for 2,995 white singleton infants admitted to NICUs in the East Midlands and Yorkshire regions of England | GA of 23 ( |
8.1% (244/2,995) | Not listed |
Tagare et al. ( |
India | December 1, 2006–April 30, 2008 | Data for 87 extremely low birth weight infants admitted to a level III NICU | Mean GA of deceased infants: 27.2 weeks (range: 26.6–27.8) | 45.9% (40/87) | Pulmonary hemorrhage ( |
Navaei et al. ( |
Iran | January 2005–March 2006 | Data for 194 preterm infants with birth weight of ≤1,500 g who were admitted to two NICUs | GA of 24–27 ( |
64.4% (125/194) | Prematurity, low birth weight |
Eventov-Friedman et al. ( |
Israel | 2000–2009 | Data for the in-hospital deaths at two tertiary-level NICUs | Age at death: 69 (29%) of the 239 infants died on the first day of life, 31 (13%) dying at up to 48 h of life, 55 (23%) died between days 3 and 7, 53 (22%) died between days 8 and 30, 33 (14%) died after 30 days of life | 0.2% (239/96 643) | Overall leading cause of death: prematurity and its complications ( |
Corchia et al. ( |
Italy | 2005 | Data for 4,014 very preterm infants admitted to 105 tertiary-level NICUs | GA of ≤23 ( |
18.8% (755/4,014) | Not listed |
Shim et al. ( |
Korea | 2009 | Data for 2,584 very low birth weight infants admitted to NICUs in 76 hospitals | Not listed | Mortality rate for infants with birth weight of <750 g: 44.8% |
Not listed |
Shrestha et al. ( |
Nepal | 2007–2009 | Data for 150 preterm infants admitted to a level III NICU | Mean GA: 30.0 ± 0.37 weeks | Total mortality rate: 20.6% (31/150) |
HMD ( |
Battin et al. ( |
New Zealand | 1959–2009 | Data for very low birth weight (≤1,500 g) infants born at a single tertiary neonatal unit | Not listed | Mortality rate of infants with birth weight of 501–1,000 g in 2009: 30% |
2008: prematurity and early cardiorespiratory problems (predominantly RDS) (33%), infection (29%), congenital anomalies (12%), NEC (12%) |
Ekwochi et al. ( |
Nigeria | June 2012–May 2013 | Data for 261 infants admitted to a special care baby unit | Mean age at death: 4.44 days | 14.2% (37/261) | Severe form of perinatal asphyxia ( |
Costa et al. ( |
Portugal | 2004–2008 | Data for 1,938 infants admitted to a NICU | Median GA: 34 weeks |
5.7% (110/1,938) | Congenital malformations, including cardiac anomalies ( |
Parappil et al. ( |
Qatar | 2002–2006 | Data for 597 infants admitted to a tertiary-level NICU | GA of 28–32 weeks | Total mortality rate: 6.5% (39/597) |
Lethal congenital and chromosomal anomalies ( |
Pepler et al. ( |
South Africa | 2007–2008 | Data for 1,578 infants born in 2007 and 2,376 infants born in 2008 admitted to 15 NICUs in private hospitals | Median GA in 2008: 35.9 weeks (range: 23–42.3 weeks) | 2007: 3.1% (49/1,578) |
Not listed |
Musooko et al. ( |
Uganda | February 1–March 31, 2013 | Data for 635 infants, including 341 infants with severe perinatal morbidity, admitted to a NICU | GA of ≥28 weeks |
Overall mortality rate for all NICU patients in 2012: 26–29% |
Not listed |
Alleman et al. ( |
United States of America | 2006–2009 | Data for 5,418 extremely low birth weight (401–1,000 g) infants born at 16 Neonatal Research Network centers | GA of 22–28 weeks | Median mortality of all infants in the 16 centers: 34% (~1,842/5,418) (range: 11–53%) |
Not listed |
Lake et al. ( |
United States of America | 2007–2008 | Data for 72,235 very low birth weight (501–1,500 g) infants born at 558 Vermont Oxford Network hospital NICUs | Mean GA: 28.2 weeks ( |
12.9% (9,278/71,936) | Not listed |
Eight studies reported the mortality outcomes for all admissions to the NICU (
Author | Country | Year(s) | Methods | Age of Infants | Mortality Outcome | Reasons for Death |
---|---|---|---|---|---|---|
Feng et al. ( |
Australia | 1995–2006 | Data for 24,131 infants admitted to 10 NICUs | GA of <24 weeks ( |
Overall mortality rate: 9.2% (2,224/24,131) |
Overall leading causes of death: congenital abnormalities ( |
Sankaran et al. ( |
Canada | January 8, 1996–October 31, 1997 | Data for 19,265 infants admitted to 17 tertiary-level NICUs | Age at death: 2 ( |
Overall mortality rate: 4% (795/19,265) |
Outborn status ( |
Manktelow et al. ( |
England | 2008–2010 | Data for 2,995 white singleton infants admitted to NICUs in the East Midlands and Yorkshire regions of England | GA of 23 ( |
8.1% (244/2,995) | Not listed |
Ekwochi et al. ( |
Nigeria | June 2012–May 2013 | Data for 261 infants admitted to a special care baby unit | Mean age at death: 4.44 days | 14.2% (37/261) | Severe form of perinatal asphyxia ( |
Costa et al. ( |
Portugal | 2004–2008 | Data for 1,938 infants admitted to a NICU | Median GA: 34 weeks |
5.7% (110/1,938) | Congenital malformations, including cardiac anomalies ( |
Parappil et al. ( |
Qatar | 2002–2006 | Data for 597 infants admitted to a tertiary-level NICU | GA of 28–32 weeks | Total mortality rate: 6.5% (39/597) |
Lethal congenital and chromosomal anomalies ( |
Pepler et al. ( |
South Africa | 2007–2008 | Data for 1,578 infants born in 2007 and 2,376 infants born in 2008 admitted to 15 NICUs in private hospitals | Median GA in 2008: 35.9 weeks (range: 23–42.3 weeks) | 2007: 3.1% (49/1,578) |
Not listed |
Musooko et al. ( |
Uganda | February 1–March 31, 2013 | Data for 635 infants, including 341 infants with severe perinatal morbidity, admitted to a NICU | GA of ≥28 weeks |
Overall mortality rate for all NICU patients in 2012: 26–29% |
Not listed |
The total mortality rates varied between countries. The overall in-hospital mortality rates were reported to be 3.1 and 3.8% in South Africa in 2007 and 2008, respectively (
Five publications (
Severe forms of perinatal asphyxia and neonatal sepsis were among the primary reasons for death in Nigeria [asphyxia = 8% (3/37); sepsis = 4% (1/37)] (
Three studies reported the mortality outcomes for extremely low birth weight infants (
Two articles (
Author | Country | Year(s) | Methods | Age of infants | Mortality outcome | Reasons for death |
---|---|---|---|---|---|---|
Keir et al. ( |
Australia | 2005–2010 | Data for 36 extremely low birth weight infants (≤500 g), including 26 NICU patients, born at a tertiary hospital | GA of ≥22 weeks |
46% (12/26) | NEC ( |
Tagare et al. ( |
India | December 1, 2006–April 30, 2008 | Data for 87 extremely low birth weight infants admitted to a level III NICU | Mean GA of deceased infants: 27.2 weeks (range: 26.6–27.8) | 45.9% (40/87) | Pulmonary hemorrhage ( |
Alleman et al. ( |
United States of America | 2006–2009 | Data for 5,418 extremely low birth weight (401–1,000 g) infants born at 16 Neonatal Research Network centers | GA of 22–28 weeks | Median mortality of all infants in the 16 centers: 34% (~1,842/5,418) (range: 11–53%) |
Not listed |
Two publications (
Three studies reported the mortality outcomes for very low birth weight infants (
Author | Country | Year(s) | Methods | Age of infants | Mortality outcome | Reasons for death |
---|---|---|---|---|---|---|
Shim et al. ( |
Korea | 2009 | Data for 2,584 very low birth weight infants admitted to NICUs in 76 hospitals | Not listed | Mortality rate for infants with birth weight of <750 g: 44.8% |
Not listed |
Battin et al. ( |
New Zealand | 1959–2009 | Data for very low birth weight (≤1,500 g) infants born at a single tertiary neonatal unit | Not listed | Mortality rate of infants with birth weight of 501–1,000 g in 2009: 30% |
2008: prematurity and early cardiorespiratory problems (predominantly RDS) (33%), infection (29%), congenital anomalies (12%), NEC (12%) |
Lake et al. ( |
United States of America | 2007–2008 | Data for 72,235 very low birth weight (501–1,500 g) infants born at 558 Vermont Oxford Network hospital NICUs | Mean GA: 28.2 weeks ( |
12.9% (9,278/71,936) | Not listed |
Battin et al. (
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 (
Author | Country | Year(s) | Methods | Age of infants | Mortality outcome | Reasons for death |
---|---|---|---|---|---|---|
Simpson et al. ( |
Canada | 1997, 2002, 2007 | Data for 156 in-hospital deaths (53 in 1997, 50 in 2002, 53 in 2007) at a tertiary-level NICU | 2007: GA of 23–27 ( |
Average annual mortality rate between 1988 and 2007: 7.6% | 2007: gastrointestinal ( |
Eventov-Friedman et al. ( |
Israel | 2000–2009 | Data for the in-hospital deaths at two tertiary-level NICUs | Age at death: 69 (29%) of the 239 infants died on the first day of life, 31 (13%) dying at up to 48 h of life, 55 (23%) died between days 3 and 7, 53 (22%) died between days 8 and 30, 33 (14%) died after 30 days of life | 0.2% (239/96 643) | Overall leading cause of death: prematurity and its complications ( |
Two studies reported the mortality outcomes for very preterm infants (
Author | Country | Year(s) | Methods | Age of infants | Mortality outcome | Reasons for death |
---|---|---|---|---|---|---|
Zhou et al. ( |
China | October 2010–September 2011 | Data for 729 very preterm infants admitted to a tertiary NICU | GA of <32 weeks |
Overall mortality rate: 8% (58/729) |
Not listed |
Corchia et al. ( |
Italy | 2005 | Data for 4,014 very preterm infants admitted to 105 tertiary-level NICUs | GA of ≤23 ( |
18.8% (755/4,014) | Not listed |
One study reported the mortality outcomes for preterm infants (
Author | Country | Year(s) | Methods | Age of infants | Mortality outcome | Reasons for death |
---|---|---|---|---|---|---|
Shrestha et al. ( |
Nepal | 2007–2009 | Data for 150 preterm infants admitted to a level III NICU | Mean GA: 30.0 ± 0.37 weeks | Total mortality rate: 20.6% (31/150) |
HMD ( |
Of the 20 articles included in this selected review (
Infants in developed and developing countries had similar ages at death, ranging from 4 to 20 days (
Author | Country | Year(s) | Methods | Age of infants | Mortality outcome | Reasons for death |
---|---|---|---|---|---|---|
Feng et al. ( |
Australia | 1995–2006 | Data for 24,131 infants admitted to 10 NICUs | GA <24 weeks ( |
Overall mortality rate: 9.2% (2,224/24,131) |
Overall leading causes of death: congenital abnormalities ( |
Keir et al. ( |
Australia | 2005–2010 | Data for 36 extremely low birth weight infants (≤500 g), including 26 NICU patients, born at a tertiary hospital | GA of ≥22 weeks |
46% (12/26) | NEC ( |
Sankaran et al. ( |
Canada | January 8, 1996–October 31, 1997 | Data for 19,265 infants admitted to 17 tertiary-level NICUs | Age at death: 2 ( |
Overall mortality rate: 4% (795/19,265) |
Outborn status ( |
Simpson et al. ( |
Canada | 1997, 2002, 2007 | Data for 156 in-hospital deaths (53 in 1997, 50 in 2002, 53 in 2007) at a tertiary-level NICU | 2007: GA of 23–27 ( |
Average annual mortality rate between 1988 and 2007: 7.6% | 2007: gastrointestinal ( |
Manktelow et al. ( |
England | 2008–2010 | Data for 2,995 white singleton infants admitted to NICUs in the East Midlands and Yorkshire regions of England | GA of 23 ( |
8.1% (244/2,995) | Not listed |
Corchia et al. ( |
Italy | 2005 | Data for 4,014 very preterm infants admitted to 105 tertiary-level NICUs | GA of ≤ 23 ( |
18.8% (755/4,014) | Not listed |
Battin et al. ( |
New Zealand | 1959–2009 | Data for very low birth weight (≤1,500 g) infants born at a single tertiary neonatal unit | Not listed | Mortality rate of infants with birth weight of 501–1,000 g in 2009: 30% |
2008: prematurity and early cardiorespiratory problems (predominantly RDS) (33%), infection (29%), congenital anomalies (12%), NEC (12%) |
Costa et al. ( |
Portugal | 2004–2008 | Data for 1,938 infants admitted to a NICU | Median GA: 34 weeks |
5.7% (110/1,938) | Congenital malformations, including cardiac anomalies ( |
Alleman et al. ( |
United States of America | 2006–2009 | Data for 5,418 extremely low birth weight (401–1,000 g) infants born at 16 Neonatal Research Network centers | GA of 22–28 weeks | Median mortality of all infants in the 16 centers: 34% (~1,842/5,418) (range: 11–53%)Median mortality of infants <25 weeks GA in the 16 centers: 63% (range: 28–90%) |
Not listed |
Lake et al. ( |
United States of America | 2007–2008 | Data for 72,235 very low birth weight (501–1,500 g) infants born at 558 Vermont Oxford Network hospital NICUs | Mean GA: 28.2 weeks ( |
12.9% (9,278/71,936) | Not listed |
Author | Country | Year(s) | Methods | Age of infants | Mortality outcome | Reasons for death |
---|---|---|---|---|---|---|
Zhou et al. ( |
China | October 2010–September 2011 | Data for 729 very preterm infants admitted to a tertiary NICU | GA of <32 weeks |
Overall mortality rate: 8% (58/729) |
Not listed |
Tagare et al. ( |
India | December 1, 2006–April 30, 2008 | Data for 87 extremely low birth weight infants admitted to a level III NICU. | Mean GA of deceased infants: 27.2 weeks (range: 26.6–27.8) | 45.9% (40/87) | Pulmonary hemorrhage ( |
Navaei et al. ( |
Iran | January 2005–March 2006 | Data for 194 preterm infants with birth weight of ≤1,500 g who were admitted to 2 NICUs | GA of 24–27 ( |
64.4% (125/194) | Prematurity, low birth weight |
Eventov-Friedman et al. ( |
Israel | 2000–2009 | Data for the in-hospital deaths at two tertiary-level NICUs | Age at death: 69 (29%) of the 239 infants died on the first day of life, 31 (13%) dying at up to 48 h of life, 55 (23%) died between days 3 and 7, 53 (22%) died between days 8 and 30, 33 (14%) died after 30 days of life | 0.2% (239/96,643) | Overall leading cause of death: prematurity and its complications ( |
Shim et al. ( |
Korea | 2009 | Data for 2,584 very low birth weight infants admitted to NICUs in 76 hospitals | Not listed | Mortality rate for infants with birth weight of < 750 g: 44.8% |
Not listed |
Shrestha et al. ( |
Nepal | 2007–2009 | Data for 150 preterm infants admitted to a level III NICU | Mean GA: 30.0 ± 0.37 weeks | Total mortality rate: 20.6% (31/150) |
HMD ( |
Ekwochi et al. ( |
Nigeria | June 2012–May 2013 | Data for 261 infants admitted to a special care baby unit | Mean age at death: 4.44 days | 14.2% (37/261) | Severe form of perinatal asphyxia ( |
Parappil et al. ( |
Qatar | 2002–2006 | Data for 597 infants admitted to a tertiary-level NICU | GA of 28–32 weeks | Total mortality rate: 6.5% (39/597) |
Lethal congenital and chromosomal anomalies ( |
Pepler et al. ( |
South Africa | 2007–2008 | Data for 1,578 infants born in 2007 and 2,376 infants born in 2008 admitted to 15 NICUs in private hospitals | Median GA in 2008: 35.9 weeks (range: 23–42.3 weeks) | 2007: 3.1% (49/1,578) |
Not listed |
Musooko et al. ( |
Uganda | February 1–March 31, 2013 | Data for 635 infants, including 341 infants with severe perinatal morbidity, admitted to a NICU | GA of ≥28 weeks |
Overall mortality rate for all NICU patients in 2012: 26–29% |
Not listed |
The age at death for all infants admitted to NICUs globally ranged from 1 to 12 days (
Consistent with the findings above, studies analyzing the outcomes of all infants admitted to NICUs (
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 (
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 (
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).
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.