Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990

Abstract

Background: Intrapartum hypoxic events ("birth asphyxia") may result in stillbirth, neonatal or postneonatal mortality, and impairment. Systematic morbidity estimates for the burden of impairment outcomes are currently limited. Neonatal encephalopathy (NE) following an intrapartum hypoxic event is a strong predictor of long-term impairment.

Methods: Linear regression modeling was conducted on data identified through systematic reviews to estimate NE incidence and time trends for 184 countries. Meta-analyses were undertaken to estimate the risk of NE by sex of the newborn, neonatal case fatality rate, and impairment risk. A compartmental model estimated postneonatal survivors of NE, depending on access to care, and then the proportion of survivors with impairment. Separate modeling for the Global Burden of Disease 2010 (GBD2010) study estimated disability adjusted life years (DALYs), years of life with disability (YLDs), and years of life lost (YLLs) attributed to intrapartum-related events.

Results: In 2010, 1.15 million babies (uncertainty range: 0.89-1.60 million; 8.5 cases per 1,000 live births) were estimated to have developed NE associated with intrapartum events, with 96% born in low- and middle-income countries, as compared with 1.60 million in 1990 (11.7 cases per 1,000 live births). An estimated 287,000 (181,000-440,000) neonates with NE died in 2010; 233,000 (163,000-342,000) survived with moderate or severe neurodevelopmental impairment; and 181,000 (82,000-319,000) had mild impairment. In GBD2010, intrapartum-related conditions comprised 50.2 million DALYs (2.4% of total) and 6.1 million YLDs.

Conclusion: Intrapartum-related conditions are a large global burden, mostly due to high mortality in low-income countries. Universal coverage of obstetric care and neonatal resuscitation would prevent most of these deaths and disabilities. Rates of impairment are highest in middle-income countries where neonatal intensive care was more recently introduced, but quality may be poor. In settings without neonatal intensive care, the impairment rate is low due to high mortality, which is relevant for the scale-up of basic neonatal resuscitation.

Figure 1

Global burden of disease schematic for intrapartum-related events “birth asphyxia.” See Table 4 for clinical definitions pertaining to intrapartum-related events.

Figure 2

Compartmental model: parameters required and methods for estimation of the global burden of impairment related to intrapartum-related events and neonatal encephalopathy.

Figure 3

Modeling estimates of the incidence of intrapartum-related neonatal encephalopathy (NE): predicted values compared to observed values for study data inputs. See Supplementary Information online for details of the study data inputs.

Figure 4

Estimated incident cases of neonatal encephalopathy by region by the sex of the baby in 2010. White, male; black, female.

Figure 5

Estimated time trends in incident neonatal encephalopathy cases by region 1990–2010. Diamond, East, Southeast Asia and Pacific; square, South Asia; triangle, Eastern Europe/Central Asia; X, high income; asterisk, Latin American and Caribbean; circle, North Africa and Middle East; vertical bar, sub-Saharan Africa.

Figure 6

Meta-analysis of 29 studies (1,482 neonatal encephalopathy (NE) survivors) reporting moderate/severe impairment for infants with NE in countries with neonatal mortality rate <5 per 1,000 (level 1). Study name = country and median year of study. Citations: Australia (1989) (115), Australia (1995) (67), Australia (1996) (116), Canada (1993) (31), France (2000) (117,118), Ireland (2004) (118), Italy (1998) (119), Italy (2001) (120), Italy (2004) (58), Italy (2005) (121), Multi-country (2001) (122), Multi-country (2004) (105), Multi-country (2004) (107), Netherlands (1995) (123), Netherlands (1998) (124), Netherlands (2001) (125), New Zealand (1998) (126), New Zealand (1998) (127), Singapore (1994) (128), Sweden (1985) (59), Sweden (1988) (53), Switzerland (1981) (129), Switzerland (1994) (130), United Kingdom (1994) (51), United Kingdom (1997) (131), United Kingdom (2004) (106), United States (1997) (132), United States (1999) (133), United States (2002) (134).

Figure 7

Meta-analysis of 16 studies (858 neonatal encephalopathy (NE) survivors) reporting moderate/severe impairment for infants with neonatal encephalopathy from countries with neonatal mortality rate ≥5 per 1,000 (level 2–3). Study name = country and median year of study. Citations: Australia (1986) (135), Canada (1980) (136), Canada (1980) (62), Canada (1985) (19), China (2004) (137), China (2005) (138), China (2009) (139), China–Hong Kong (1986) (140), India (after 1990) (141), Ireland (1983) (142), Italy (1988) (143), Nepal (1995) (68), Serbia (1994) (144), South Africa (1997) (17), Tanzania (2002) (145), Turkey (1995) (146).

Figure 8

Meta-analysis of eight studies (384 neonatal encephalopathy (NE) survivors) reporting mild cognitive impairment for infants with NE for countries with neonatal mortality rate <5 per 1,000 (level 1). Study name = country and median year of study. Citations: Italy (2005) (121), Netherlands (1995) (123), New Zealand (1998) (126), Sweden (1985) (59), United Kingdom (1997) (131), United Kingdom (2004) (106), United States (1999) (133), United States (2002) (134).

Figure 9

Meta-analysis of nine studies (533 neonatal encephalopathy (NE) survivors) reporting mild cognitive impairment for infants with neonatal encephalopathy for countries with neonatal mortality rate ≥5 per 1,000 (level 2–3). Australia (1986) (135), Canada (1980) (62), Canada (1985) (19), China (2004) (137), China–Hong Kong (1986) (140), India (after 1990) (141), Nepal (1995) (68), Serbia (1994) (144), South Africa (1997) (17).

Figure 10

Regional burden of intrapartum-related stillbirths, neonatal deaths, and neonatal encephalopathy outcomes for babies affected by intrapartum-related events in 2010.

Figure 11

Summary of deaths and disability outcomes that are intrapartum related based on 125 million births worldwide in 2010. Sources: intrapartum stillbirth estimate (8), neonatal deaths (6). Neonatal encephalopathy (NE) cases, mortality, and impairment outcomes are derived from the estimation process described in this article.