Prolonged jaundice is a commonly evaluated condition. The aim of this study was to assess the risk factors of jaundice in healthy infants at one month of age. This prospective cohort study enrolled 509 healthy infants from 2013 to 2018. Those with gestational age (GA) less than 35 weeks, birth weight less than 2000 grams, and illness were not enrolled. Jaundice was defined as a transcutaneous bilirubin value ≥5 mg/dL at 25–45 days of age. Umbilical cord blood samples were obtained to examine seven common gene variants. The incidence of prolonged jaundice was 32.2%. Prolonged jaundice was more common in infants with exclusive breastfeeding (p < 0.001), GA 35~37 w (p = 0.001), stool passage >4 times/d (p < 0.001), previous phototherapy (p < 0.001), and gene variant of G to A at nt 211 of UGT1A1 (p = 0.004). A multivariate logistic regression analysis demonstrated the greatest risk for prolonged jaundice was exclusive breastfeeding (OR = 2.818, 95% CI = 1.851–4.292), followed by previous phototherapy (OR = 2.593, 95% CI = 1.716–3.919), GA 35~37 w (OR = 2.468, 95% CI = 1.350–4.512), and G to A at nt 211 of UGT1A1 (OR = 1.645, 95% CI = 1.070–2.528). In conclusion, infants with exclusive breastfeeding, GA 35~37 w, previous phototherapy, or G to A at nt 211 of UGT1A1 are at greater risk of prolonged jaundice. Healthcare professionals should consider these risk factors in their assessment of prolonged jaundice.
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