Small for Gestational Age Infants Are at Higher Risk for Direct Hyperbilirubinemia During the First Week of Life

Background: Infants who are small for gestational age (SGA) have increased incidence of metabolic abnormalities and liver dysfunction compared to infants who are appropriate for gestational age (AGA). This may increase the risk of direct hyperbilirubinemia in this population. There is a paucity of data on the levels of direct bilirubin (DB) immediately after birth in SGA infants. This study aims to compare the levels of DB and the incidence of cholestasis during the first week of life between SGA and non-SGA infants.

Methods: This is a case-control study of all infants admitted to the Neonatal Intensive Care Unit between May 2006 and September 2019. Demographic data, relevant clinical information, total and direct bilirubin levels were extracted from the medical records and compared between SGA and non-SGA infants. Cholestasis was defined as a direct bilirubin level ≥1 mg/dl with an associated total bilirubin of ≤5 mg/dl or a direct bilirubin level >20% of the corresponding total bilirubin >5 mg/dl. The course and the causes of cholestasis were determined and compared between the two groups.

Results: A total of 7767 infants were admitted to the NICU during the study period. Data on 6499 infants (83.8%) was available for analysis. Of the 6499 infants, 937 (14.4%) were SGA and 5662 (85.6%) were non-SGA. Maternal history of hypertensive disorders, drug abuse and smoking were significantly higher in the SGA group (Table 1). The median DB levels on days 1, 2, 3, 5 and 7 of life were significantly higher in the SGA group. The incidence of elevated DB of ≥1 mg/dl within the first 3 and 7 days of life was higher in the SGA group. Similarly, significantly more infants in the SGA group had DB level of ≥2 mg/dl during the first 7 days of life and the incidence of cholestasis was higher in the SGA group. Hypoxic ischemic encephalopathy was the most commonly diagnosed reason for cholestasis, and diagnosed significantly more in the non-SGA group (Table 2). Diagnosed and treatable etiologies in both groups included biliary atresia, congenital cytomegalovirus, and possible gestational alloimmune liver disease (GALD). SGA infants were significantly more likely to not have an identified cause of their cholestasis, and almost all of them resolved spontaneously in few days.

Conclusion: Cholestasis is more common in SGA infants compared to non-SGA infants during the first week of life. SGA infants were significantly more likely to have an unidentified cause of cholestasis which resolve on its own. While screening for DB may identify treatable causes of cholestasis in SGA and non-SGA infants, SGA infants with mild cholestasis can be observed for spontaneous resolution before initiating an extensive work-up for the etiology of cholestasis.