Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels

Abstract

Background: Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden.

Methods: Systematic reviews and meta-analyses were undertaken of national prevalence, mortality, and kernicterus due to Rh disease and EHB. We applied a compartmental model to estimate neonatal survivors and impairment cases for 2010.

Results: Twenty-four million (18% of 134 million live births ≥ 32 wk gestational age from 184 countries; uncertainty range: 23-26 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800-477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000-131,000), with a 24% risk for death (114,100; uncertainty range: 59,700-172,000), 13% for kernicterus (75,400), and 11% for stillbirths. Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. Kernicterus with Rh disease ranged from 38, 28, 28, and 25/100,000 live births for Eastern Europe/Central Asian, sub-Saharan African, South Asian, and Latin American regions, respectively. More than 83% of survivors with kernicterus had one or more impairments.

Conclusion: Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries.

Figure 1

Schematic representation of the prenatal and neonatal risk factors for Rhesus (Rh) disease and extreme hyperbilirubinemia and their impact on stillbirths, neonatal death due to kernicterus, and long-term impairment of kernicterus during childhood. In view of the complex confluence of biological risk, interaction with other childhood disease, and social–cultural factors, we did not estimate childhood death due to kernicterus. ABE, acute bilirubin encephalophathy.

Figure 2

Schematic representation of the three-compartmental model. This model delineates the serial steps toward input of country-specific parameters, processes, and outputs to estimate prevalence, burden of Rhesus (Rh) disease and extreme hyperbilirubinemia–related mortality, and the number of postneonatal survivors with kernicterus and long-term impairment. A/CBE, acute/chronic bilirubin encephalophathy.

Figure 3

Number of stillbirths (due to Rhesus (Rh) disease; white bars) and neonatal deaths/100,000 live births due to kernicterus (black bars) for all live births in 2010. These data are shown for regional geographic distribution. Regional categorization of countries is consistent with the global burden of diseases (54,55).

Figure 4

Estimated rates of kernicterus (per 100,000 live births). Data are presented and attributed to cause of hyperbilirubinemia due to prematurity by yellow bars; G6PD deficiency by green; hemolytic and idiopathic conditions by blue; and Rhesus (Rh) disease by red. These are shown for regional geographic distribution worldwide using global burden of diseases (GBD) categorization (54,55).

Figure 5

Outcomes for Rhesus (Rh) disease–affected pregnancies and extreme hyperbilirubinemia (without Rh disease). ^aStillbirths due to non-Rh disease have not been estimated or included.

Figure 6

Number of infants with major impairments due to kernicterus as presented for hearing loss (white bars) and athetoid cerebral palsy (black bars). Data shown for all live births in 2010 are shown for regional geographic distribution. Regional categorization of countries is consistent with the global burden of diseases (54,55).