Etiology of neonatal cholestasis after emerging molecular diagnostics

In the pediatric group, most cholestatic patients had disease onset at 0-3 months of age, and more and more are found to have specific genetic defects after failing to obtain a definite diagnosis by routine evaluation. To investigate the etiological diagnosis for the newborns with cholestasis during the neonatal period after emerging molecular tests comprehensively.

We conducted a retrospective study to evaluate clinical characteristics, etiologies and outcomes in infants with neonatal cholestasis after emerging molecular diagnostics from January 1st to December 31st, 2019 in Children's Hospital of Fudan University.

There were 160 cases of neonatal cholestasis with mean gestational age (GA) 32.6±4.8 weeks and birth weight (BW) 1,880±991 g, composing 3.4% of total neonatal admissions in 2019. Overall 97.5% (n=156) patients had a definite diagnosis, including 9 obtaining a genetic diagnosis after adding molecular test in routine evaluation, which made the diagnosis rate for cholestasis increased by 5.6%. The most common etiology of cholestasis in the neonatal period was parenteral nutrition-associated cholestasis (PNAC) 48.8% (n=78), followed by cardiovascular and circulatory disorders 18.1%, biliary anatomic obstruction 12.5%, infection 8.7% and genetic disorders 5.6%. PNAC and biliary anatomic obstruction were the most common etiology of cholestasis for preterm and term infants respectively. The mortality rate is 2.5% (n=4) and 91.9% (n=147) patients totally recovery or improve in follow-up.

The causes of cholestasis in neonates are complicated, molecular diagnostics can improve the etiological diagnosis for newborns with cholestasis. But still, quite amount of causes are remediable and transient during the neonatal period, gene test may help to rule out genetic causes and enhance confidence in judging prognosis.