TABLE 5. Effect of Serum Bilirubin Levels on Neurologic or Behavioral Outcomes in All Infants
| Author, Year |
Subjects, N (Control) |
Peak Bilirubin Level (Range), mg/dL |
Outcomes |
Confounders or Biases |
Quality |
|
| Vohr et al53 (1989) |
23* (27) |
14.3 ± 2.8 (10–20) |
On day 1 to 2: BNBAS. Jaundiced infants had significantly lower BNBAS scores in every behavioral item except autonomic stability. Significant correlations were found in increased levels of TSB with decreased scores on the individual BNBAS items. After controlling for PhotoRx by partial correlations, most correlations remained significant except for state regulation and autonomic stability. |
PhotoRx |
A |
| Vohr et al52 (1990) |
|
|
|
|
| Hyman et al50 (1969) |
405 |
 15 |
At 4 years of age: CNS abnormalities. No significant difference in incidence of CNS abnormalities among infants exposed to different levels of bilirubin <20 mg/dL. However, with TSB >20 mg/dL, the incidence of CNS abnormalities increased sharply. |
BET; streptomycin Rx; BW; selection bias |
B |
| Valaes et al51 (1980) |
44 (445) |
47% (16–20) |
At 61–81 months of age: visual-motor integration test. Degree of jaundice was found not to be associated with neurologic scores. |
Prematurity; BET; phenobarbital |
B |
|
29% (20–25) |
|
|
|
24% (>25) |
|
|
|
| Yilmaz et al56 (2001) |
87 |
11% (23–20) 49% (20–23.9) 39% (24) |
At 10–72 months: neurologic examination. Subjects with maximum TSB <20 mg/dL did not show any neurologic abnormalities, whereas 9.3% of the subjects with TSB 20–23.9 mg/dL (N = 43) had only disconjugate gaze and 17.6% of the subjects with TSB 24 mg/dL had neurologic manifestations. |
PhotoRx; BET; duration of jaundice |
C |
| Agrawal et al46 (1998) |
30|| (25) |
22.4 ± 2.7 |
At 1 year of age: DDST. Neurologic development was normal in all infants with TSB levels of 15–20 mg/dL, in 89% of infants with TSB levels of 21–25 mg/dL, and in 67% infants with TSB >25 mg/dL. |
PhotoRx; BET; lost to follow-up |
C |
| Wolf et al55 (1997) |
45¶ at 4 months |
28.5 ± 6.3 |
At 4 months of age: infant motor screening (IMS). Linear correlation showed an association of maximum TSB and test rating at 4 months (r = .32, P <.05) and test scores at 4 months (r = .44, P < .03). The mean TSB level in the normal IMS group was 27.3 ± 5.3 mg/dL; in the suspect and abnormal IMS group, the mean TSB levels were 28 ± 4 and 33.7 ± 10.3 mg/dL, respectively. These differences were not significant (P = .06). |
PhotoRx; BET; prematurity; illness |
C |
| Wolf et al54 (1999) |
35 at 1 year |
|
At 1 year of age: Bayley (BSID-PDI). Eight (23%) term infants, with a mean TSB level of 33.4 mg/dL, had abnormal and suspect BSID and clinical diagnosis. Twenty-seven (77%) term infants, with a mean TSB level of 26.5 mg/dL, scored normal on the BSID. "The correlation between the Bayley raw scores at 10 months and TSB concentration was 0.59 (P < .001)" |
|
|
| Chen et al47 (1995) |
72 (22) |
39% (10–15) |
At 1 year of age: DDST and neurologic examination. None (0%) of the infants with TSB levels of 10–20 mg/dL showed any abnormality in the DDST and neurologic examination. Among infants with TSB >20 mg/dL, 4 (22%) were abnormal in gross motor and fine motor skills on DDST. |
PhotoRx; BET |
C |
|
32% (15–20) |
|
|
|
|
29% (>20) |
|
|
| Grunebaum et al48 (1991) |
46 |
12.06 ± 2.6 |
At age 31.1 ± 16.6 months: growth, neurologic examination, and DDST. Growth and neurologic examinations were normal in all infants. Two (4%) had abnormal DDST, but all had normal DDST repeated 1 month later. |
PhotoRx; lost to follow-up |
C |
| Holmes et al49 (1968) |
63 (17)# |
6.4–24 (46% 6.4–12.5; 54% 15–24) |
At 4 years, 7 months to 7 years, 8 months: neurologic examination, motor development (Oseretsky test), and audiometric examinations. In normal term babies, mild-to-moderate hyperbilirubinemia is not associated with findings on the Oseretsky motor development test. All had normal hearing, including a subset with streptomycin Rx. |
Age; BET; streptomycin Rx |
C |
|
BNBAS indicates Brazelton Neonatal Behavioral Assessment Scale; PhotoRx, phototherapy; CNS, central nervous system; DDST, Denver Developmental Screening Test; BSID, Bayley's Scales of Infant Development; PDI, Psychomotor Development Index; Rx, prescription.
* Sixty percent ABO incompatibility (56% of controls had ABO incompatibility as well).
Including 10% preterm infants and some hemolytic diseases.
Twenty-nine percent ABO incompatibility, 2% glucose-6-phosphate dehydrogenase deficiency, and 69% unknown cause of jaundice.
Forty-four percent ABO incompatibility, 16% Rh incompatibility, and 40% nonhemolytic jaundice.
|| Approximately one fourth (26.7%) had ABO incompatibility, and 63.3% had idiopathic hyperbilirubinemia.
¶ Forty-three percent term + 57% preterm (mean GA 36.6±3.5 weeks). Forty-four percent low birth weight, 16% ABO incompatibility, 16% sepsis, and 6% congenital syphilis.
# All causes of jaundice were included in the study.
