Original article
Risk Factors for Severe Hyperbilirubinemia among Infants with Borderline Bilirubin Levels: A Nested Case-Control Study

https://doi.org/10.1016/j.jpeds.2008.01.028Get rights and content

Objective

To estimate the effect of phototherapy and other predictors on the risk of total serum bilirubin (TSB) ≥ 25 mg/dL in infants with a TSB of 17 to 22.9 mg/dL at age ≥ 48 hours.

Study design

From a cohort of 285295 infants ≥ 34 weeks gestation and ≥ 2000 g born between 1995 and 2004 in northern California Kaiser hospitals, we identified 17986 with a TSB of 17 to 22.9 mg/dL at age ≥ 48 hours. All infants exhibiting a TSB ≥ 25 mg/dL were selected as cases for the study. Four randomly selected controls were matched to each case based on the difference between their qualifying TSB and the American Academy of Pediatrics' phototherapy threshold.

Results

A total of 62 cases were identified (0.4%). Six of these (10%) received inpatient phototherapy within 8 hours, along with 101 controls (41%) (adjusted odds ratio [AOR] 0.15; 95% confidence interval [CI] 0.06 to 0.40). Cases more often had lower gestational age (AOR 3.24; 95% CI 1.24 to 8.47 for 38 to 39 weeks and AOR = 3.70; 95% CI 0.61 to 22.4 for 34 to 37 weeks compared with ≥ 40-week infants), bruising, (AOR 2.52; 95% CI 1.16 to 5.50), exclusive breast-feeding (AOR 2.09; 95% CI 1.05 to 4.03), and TSB increase of ≥ 6 mg/dL/day (AOR 2.39; 95% CI 1.18 to 4.85).

Conclusions

Phototherapy was 85% effective in preventing TSB ≥ 25 mg/dL. The strongest predictors of TSB ≥ 25 mg/dL were gestational age, bruising, family history, and rapid rise in TSB.

Section snippets

Study Design

This nested case-control study began with a cohort of 285 295 infants born in northern California Kaiser Permanente Medical Care Program (KPMCP) hospitals between January 1, 1995 and December 30, 2004, who were at least 34 weeks gestational age and weighed ≥ 2000 g at birth. The KPMCP has information systems built around a common medical record number, permitting linkage across multiple laboratory and neonatal databases.2, 15, 16, 17

Subjects

The Figure illustrates the sample selection. We identified 17

Results

There were 17,986 infants with a TSB between 17 and 22.9 mg/dL at age ≥ 48 hours. Of this group, 62 infants reached a TSB ≥ 25 mg/dL. For 1859 infants, their last TSB was also their highest TSB measured, suggesting incomplete follow-up. The maximum TSB levels of these 1859 infants were drawn at a mean age of 4.5 days, and 92% were < 20 mg/dL.

Table I summarizes characteristics of the study cohort. The cases and controls did not differ significantly by sex, race, birth weight, or duration of

Discussion

Our study illustrates what factors physicians should take into account when making difficult treatment decisions in infants with TSB between 17 and 22.9 mg/dL at 48 hours or longer after birth. At study entry, 97% of the infants had a TSB level above the 2004 AAP threshold for phototherapy; however, only 35% of all infants received inpatient phototherapy. This underscores the substantial variation in treating these infants and the need for an evidence-based approach to treating neonatal

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  • Cited by (0)

    Supported by by National Institute of Child Health and Human Development grant RO1 HD047557 and a grant from the Glaser Pediatric Research Network (M.K.)

    No reprints are available from the authors.

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