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

Mette Julsgaard; Jantien W. Wieringa; Simon M.D. Baunwall; Bo M. Bibby; Gertjan J.A. Driessen; Linda Kievit; Jacob B. Brodersen; Anja Poulsen; Jens Kjeldsen; Mette M. Hansen; Hai Q. Tang; Christina L. Balmer; Henning Glerup; Jakob B. Seidelin; Kent V. Haderslev; Lise Svenningsen; Signe Wildt; Mie A. Juel; Anders Neumann; Jens Fuglsang; Tine Jess; Anne Mette Haase; Christian L. Hvas; Jens Kelsen; C. Janneke van der Woude; NEXUS Collaborator Group; Uffe Lund Lystbæk

doi:10.1016/j.cgh.2024.01.008

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

Mette Julsgaard^*, Jantien W. Wieringa, Simon M.D. Baunwall, Bo M. Bibby, Gertjan J.A. Driessen, Linda Kievit, Jacob B. Brodersen, Anja Poulsen, Jens Kjeldsen, Mette M. Hansen, Hai Q. Tang, Christina L. Balmer, Henning Glerup, Jakob B. Seidelin, Kent V. Haderslev, Lise Svenningsen, Signe Wildt, Mie A. Juel, Anders Neumann, Jens FuglsangTine Jess, Anne Mette Haase, Christian L. Hvas, Jens Kelsen, C. Janneke van der Woude, NEXUS Collaborator Group, Uffe Lund Lystbæk

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	134-143
Number of pages	10
Journal	Clinical Gastroenterology and Hepatology
Volume	23
Issue number	1
DOIs	https://doi.org/10.1016/j.cgh.2024.01.008
Publication status	Published - Jan 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s)

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Julsgaard, M., Wieringa, J. W., Baunwall, S. M. D., Bibby, B. M., Driessen, G. J. A., Kievit, L., Brodersen, J. B., Poulsen, A., Kjeldsen, J., Hansen, M. M., Tang, H. Q., Balmer, C. L., Glerup, H., Seidelin, J. B., Haderslev, K. V., Svenningsen, L., Wildt, S., Juel, M. A., Neumann, A., ... Lystbæk, U. L. (2025). Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy. Clinical Gastroenterology and Hepatology, 23(1), 134-143. https://doi.org/10.1016/j.cgh.2024.01.008

@article{bd848fd705c84e139a1c09e16586c9dd,

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

abstract = "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.",

author = "Mette Julsgaard and Wieringa, {Jantien W.} and Baunwall, {Simon M.D.} and Bibby, {Bo M.} and Driessen, {Gertjan J.A.} and Linda Kievit and Brodersen, {Jacob B.} and Anja Poulsen and Jens Kjeldsen and Hansen, {Mette M.} and Tang, {Hai Q.} and Balmer, {Christina L.} and Henning Glerup and Seidelin, {Jakob B.} and Haderslev, {Kent V.} and Lise Svenningsen and Signe Wildt and Juel, {Mie A.} and Anders Neumann and Jens Fuglsang and Tine Jess and Haase, {Anne Mette} and Hvas, {Christian L.} and Jens Kelsen and {Janneke van der Woude}, C. and {NEXUS Collaborator Group} and Julie Korgaard and Thea Vestergaard and Lystb{\ae}k, {Uffe Lund} and Anne Berg and Mikkelsen, {Anette Tyrsted} and Holm, {Anne Marie} and Hansen, {Annebirthe Bo} and Ole Mathiesen and Jensen, {Jette Kr{\"u}ger} and Lone Neumann and Jane Boris and Marianne Lemming and Marianne Rahbek and S{\o}resen, {Heidi Gram} and Storkholm, {Marie H{\o}jriis} and Jeanette Ziska and Vestergaard, {Else Marie} and {B{\o}ggild Ipsen}, {Sidsel Elisabeth} and J{\o}rgen Gram and Gunhild Brixen and Westergaard, {Hanne Brix} and Friis-Hansen, {Lennart Jan} and Olsen, {Bettina Friis} and Heidi Fischer and Bjerrum, {Poul Jannik}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

month = jan,

doi = "10.1016/j.cgh.2024.01.008",

language = "English",

volume = "23",

pages = "134--143",

journal = "Clinical Gastroenterology and Hepatology",

issn = "1542-3565",

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Julsgaard, M, Wieringa, JW, Baunwall, SMD, Bibby, BM, Driessen, GJA, Kievit, L, Brodersen, JB, Poulsen, A, Kjeldsen, J, Hansen, MM, Tang, HQ, Balmer, CL, Glerup, H, Seidelin, JB, Haderslev, KV, Svenningsen, L, Wildt, S, Juel, MA, Neumann, A, Fuglsang, J, Jess, T, Haase, AM, Hvas, CL, Kelsen, J, Janneke van der Woude, C, NEXUS Collaborator Group & Lystbæk, UL 2025, 'Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy', Clinical Gastroenterology and Hepatology, vol. 23, no. 1, pp. 134-143. https://doi.org/10.1016/j.cgh.2024.01.008

TY - JOUR

T1 - Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy

AU - Julsgaard, Mette

AU - Wieringa, Jantien W.

AU - Baunwall, Simon M.D.

AU - Bibby, Bo M.

AU - Driessen, Gertjan J.A.

AU - Kievit, Linda

AU - Brodersen, Jacob B.

AU - Poulsen, Anja

AU - Kjeldsen, Jens

AU - Hansen, Mette M.

AU - Tang, Hai Q.

AU - Balmer, Christina L.

AU - Glerup, Henning

AU - Seidelin, Jakob B.

AU - Haderslev, Kent V.

AU - Svenningsen, Lise

AU - Wildt, Signe

AU - Juel, Mie A.

AU - Neumann, Anders

AU - Fuglsang, Jens

AU - Jess, Tine

AU - Haase, Anne Mette

AU - Hvas, Christian L.

AU - Kelsen, Jens

AU - Janneke van der Woude, C.

AU - NEXUS Collaborator Group

AU - Korgaard, Julie

AU - Vestergaard, Thea

AU - Lystbæk, Uffe Lund

AU - Berg, Anne

AU - Mikkelsen, Anette Tyrsted

AU - Holm, Anne Marie

AU - Hansen, Annebirthe Bo

AU - Mathiesen, Ole

AU - Jensen, Jette Krüger

AU - Neumann, Lone

AU - Boris, Jane

AU - Lemming, Marianne

AU - Rahbek, Marianne

AU - Søresen, Heidi Gram

AU - Storkholm, Marie Højriis

AU - Ziska, Jeanette

AU - Vestergaard, Else Marie

AU - Bøggild Ipsen, Sidsel Elisabeth

AU - Gram, Jørgen

AU - Brixen, Gunhild

AU - Westergaard, Hanne Brix

AU - Friis-Hansen, Lennart Jan

AU - Olsen, Bettina Friis

AU - Fischer, Heidi

AU - Bjerrum, Poul Jannik

PY - 2025/1

Y1 - 2025/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85186093313&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2024.01.008

DO - 10.1016/j.cgh.2024.01.008

M3 - Article

C2 - 38278191

AN - SCOPUS:85186093313

SN - 1542-3565

VL - 23

SP - 134

EP - 143

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

IS - 1

ER -

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

Abstract

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