P676 Unveiling the impact on in utero exposure to biologic treatments for inflammatory bowel disease (IBD) on children's psychomotor development: Insights from the DUMBO registry of GETECCU
Authors: Palomino Pérez L M , Velasco Rodríguez-Belvís M , Brenes Ruiz Y , Leo-Carnerero E , Calviño Suarez C , Rivero M , Calvo M , Arroyo M T , Fernández-Clotet A , Pérez-Martínez I , Masedo González Á , Hernández V , Ruiz-Cerulla A , López Serrano P , Vega P , Rodríguez-Lago I , Vicente Lidón R , De Jorge M Á , Guerra I , Arias García L , Molina Arriero G , Hervías Cruz D , Busquets D , Gutiérrez Casbas A , Van Domselaar M , Valldosera Gomis G , Vázquez Morón J M , Piqueras Cano M , Lucendo A J , Martín Arranz M D , Ramírez de la Piscina P , Martínez Tirado M D P , Robles Alonso V , Marín Pedrosa S , Camargo Camero R , Armesto Gonzalez E , García-Salido A , Muñoz Codoceo R , Gisbert J P , Chaparro M ,   *Authors share senior authorship
Published: January 2024

Abstract

Background
Understanding the impact of in utero exposure to biologic medications in children is crucial to providing recommendations during pregnancy. The effect of biologics, particularly non-anti-TNF ones, on children's psychomotor development, has been inadequately studied.
Our aim was to evaluate the impact of the exposure of biologics in utero on the psychomotor development of children during the first year of life.

Methods
Data from children born to IBD patients included in the DUMBO registry with complete Age and Stages Questionnaire (AQS-3) available up to 12 months of age were analysed. DUMBO is a prospective, observational, and multicentre registry endorsed by GETECCU, which enrols pregnant women with IBD throughout 5 years in 70 centres in Spain. Study protocol is summarized in figure 1a. Normal psychomotor development was defined by ASQ-3 scores above the lower limit of normality (referral zone) in all domains (communication, gross motor, fine motor, problem-solving, personal-social). Serious adverse events (SAE) were defined in accordance with the ICH Topic E 2 A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting by European Medicines Agency. Variables associated with the risk of having impaired psychomotor development, including exposure to biologics in utero, were evaluated.

Results
352 children born to 343 mothers were included (9 pair of twins) (tables 1a, 1b and 1c). 134 children (38%) had been exposed to biologics in utero; from them, 50 (37%) had been exposed to adalimumab, 44 (32%) to infliximab, 3 (2.2%) to certolizumab, 1 (0.7%) to golimumab, 28 (20%) to ustekinumab, and 10 (7.5%) to vedolizumab. 8% of the mothers were smokers during pregnancy; no other toxic consumption (alcohol or drugs) was recorded. The ASQ-3 results across different domains are presented in figure 1b, and the impact of the different factors associated with the neurodevelopment in these children is summarised in table 1d. In the multivariate analysis, to have been born to a mother with CD (vs. UC) was associated with higher likelihood (OR=2, 95%CI=1.1-3.9), while to be premature was associated with lower likelihood (OR=0.3, 95%CI=0.1-0.6) of having ASQ-3 scores above the limit of normality in all domains at 12 months of age. Other variables, including the exposure to biologics in utero, had no impact on the AQS-3 scores at month 12.

Conclusion
In the multicenter, prospective DUMBO registry, the exposure to biologics for the treatment of IBD in utero (including anti-TNF and non-anti-TNF agents) did not impair the psychomotor development of the children. Our findings support the safety of these drugs and reinforce the recommendation to continue them during pregnancy.