# Presentation: 457265

## Efficacy of strategies for predicting hyperbilirubinemiaNEMC Evidence Report

- Stanley Ip, MD
- Division of General Pediatrics and Adolescent Medicine
- The Floating Hospital for Children
- Tufts-New England Medical Center

## Strategies evaluated

- Cord Bilirubin (4 studies, n=1105)
- Early Serum Bilirubin (4 studies, n=3105)
- End-tidal Carbon Monoxide Concentration (2 studies, n=1421)
- Predischarge Risk Index (1 study, 73 cases, 423 controls)
- Predischarge Risk Zone, determined by hour-specific bilirubin percentile (1 study, n=2840)

## Subjects from 12 studies

- U.S., China, Denmark, India ,Israel, Japan, Spain
- N: 51 to 2840
- Term only,  term and preterm
- Breast feeding: 4% to 90%
- No Rh, but some included ABO incompatibility
- Some received phototherapy

## Definitions of Hyperbilirubinemia

- TSB >11.7 mg/dl, >15 mg/dl, >17 mg/dl,
-     >25 mg/dl
- TSB >16 mg/dl at 36 hours
- TSB >10 mg/dl at day 2, >14 mg/dl at day 3
-     >17 mg/dl at day 4 and 5
- TSB ≥ 95%tile
- Clinical jaundice (6.4 mg/dl to 19.3 mg/dl)

## Cord Bilirubin

| Study |  | Sensitivity | Specificity |
| --- | --- | --- | --- |
| Carbonell, 2001 
(n=585) | ≥2.2 mg/dl predicts TSB ≥17 mg/dl day 3 to day 4 | 22% | 95% |
| Knudsen, 1992 
(n=132) | ≥ 2.05 mg/dl predicts TSB > 11.7 mg/dl
 | 71% | 68% |
| Risemberg, 1977 
(n=91, ABO) | >4 mg/dl predicts TSB >16 mg/dl at 36h | 92% | 100% |

## Test Performance of Cord Bilirubin Levels Adapted from Knudsen, 1992

- 1.46mg/dl

- 1.75mg/dl

- 2.05mg/dl

- 2.34mg/dl

## Early Serum Bilirubin level

- Awasthi, 1998 (n=274)
-     TSB (18/24) > 3.99 mg/dl predicts TSB>15 mg/dl; sensitivity 69%, specificity 66%
- Carbonell, 2001 (n=1563)
-     TSB(24) ≥ 6 mg/dl predicts TSB > 17 mg/dl; sensitivity 100%, specificity 45.7%
-     TSB (48) ≥ 9 mg/dl predicts TSB > 17 mg/dl; sensitivity 100%, specificity 64.3%
- Seidman, 1999 (n=1177)
-     TSB (24) > 5 mg/dl is associated with 36.5 O.R. of  TSB(day2) >10, (day3) >14, (days 4&5) >17

## Factors associated with JaundiceMultiple Logistic Analysis by Seidman, 1999

- Day 1 TSB (per 1 mg/dl)	3.1 (O.R)
- ∆ in TSB from day 1 to2	2.4
- Maternal blood type O		2.9
- Maternal age (per year)	1.1
- Full breastfeeding		0.4
- Day 1 TSB > 5mg/dl		36.5

## Variables associated with TSB ≥ 25 mg/dlMultiple Logistic Analysis by Newman, 2000

- Early jaundice		   7.3 (O.R.)
- FH of jaundice	    	   6.0
- Exclusive Breastfeed      5.7
- Bruising			   4.0
- Asian Race                      3.5
- Cephalohematoma	   3.3
- Maternal age ≥25	   3.1
- Lower gestational age      0.6/week

## ROC of Predischarge Risk IndexSource: Newman TB, 2000

- ROC of Predischarge Risk IndexSource: Newman TB, 2000

- RI=7

- RI=10

- RI=15

- RI=20

- RI=7

- RI=10

- RI=15

- RI=20

## End-tidal Carbon Monoxide Concentration

-    Okuyama, 2001 (N=51)
-    ETCOc > 1.8 ppm at 42 hours predicts
-    TSB > 15 mg/dl
-    sensitivity 86%, specificity 80%,
-    PPV 40%, NPV 97%

## 	    Predischarge Risk Zone

- 			Bhutani, 1999
- Infants who fulfilled inclusion criteria = 13,003
- Study subjects with at least 2 TSB’s
-    (pre and post discharge) = 2840

## Distribution of TSB values at selected study epochal periods Bhutani, 1999

## Hour Specific TSBBhutani, 1999

## Predischarge Risk ZoneBhutani, 1999

## Slide 16

## Predischarge Risk Zone

- ≥75%tile predischarge zone predicts to subsequent ≥95%tile;
-    sensitivity 90.5%, specificity 84.7%,
-    PPV 21.6%, NPV 99.5%

## Racial distribution of study population

| Race | Bhutani, 1999 | NVS (prelim), 2001 |
| --- | --- | --- |
| African-American | 41% | 15% |
| Asian | 4% | 5% |
| Hispanic | 4% | 21% |
| White | 43% | 58% |
| Other | 8% | 1% |

## ROC Curves Comparing ETCOc, STB Alone, and Combined ETCOc and STB at 30±6 hrsStevenson, 2001

## Stevenson, 2001

| 
Study sites | 
 Study size | TSB ≥ 95%tile 
(from Bhutani,1999) |
| --- | --- | --- |
| Cleveland | 353 | 20     (5.7%) |
| Hong Kong 1 | 303 | 25     (8.3%) |
| Stanford | 194 | 19     (9.8%) |
| Hong Kong 2 | 167 |  9     (5.4%) |
| Jerusalem 1 | 119 |  9      (7.6%) |
| Providence | 116 | 10     (8.6%) |
| Philadelphia | 50 |     8      (16.0%) |
| Jerusalem 2 | 37 |    8      (21.6%) |
| Kobe | 31 |   12      (38.7%) |
| Total | 1370 | 120      (8.8%) |

## Summary

- Not possible to directly compare the accuracy of various strategies
- Higher TSB at an early age is associated with hyperbilirubinemia
- Hour-specific nomogram method appears promising (AUC 0.93) but further validation is needed