Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy

Background: Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life. Methods: Pregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time points. Nonlinear regression analysis was applied to estimate clearance. Results: In 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant-mother ustekinumab ratio was 2.18 (95% confidence interval, 1.69–2.81). Mean time to infant clearance was 6.7 months (95% confidence interval, 6.1–7.3 months). One in 4 infants at 6 months had an extremely low median concentration of 0.015 μg/mL (range 0.005–0.12 μg/mL). No variation in median ustekinumab concentration was noted between infants with (2.8 [range 0.4–6.9] μg/mL) and without (3.1 [range 0.7–11.0] μg/mL) infections during the first year of life (P = .41). Conclusions: No adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk.