Uterus transplantation; first data on neurologic, neuropsychiatric, and physical examination follow-up of children up to 6 years of age

Abstract

Study question: What are the outcomes regarding cognition, development, physical, and psychiatric status of children born after uterus transplantation (UTx) up to 6 years after birth?

Summary answer: The long-term and very long-term outcomes of children born after UTx indicate normal cognitive, neuropsychiatric, and physical development.

What is known already: Previous cohort studies of children born after UTx and followed up to 2-3 years indicate normal neurodevelopment and occasional cases of minor malformations.

Study design, size, duration: A prospective cohort study was performed on 11 offspring after UTx. All children (7 boys, 4 girls) were examined at age 2.5 years and eight children (5 boys, 3 girls) were examined at age 6 years.

Participants/materials, setting, methods: The cognitive evaluations, Bayley-III test and WPPSI-IV, were performed at age 2.5 years (n = 11) and age 6 years (n = 8), respectively. Parental questionnaires pertaining to neurodevelopmental and behavioural problems, including the Strengths and Difficulties questionnaire (SDQ) and the ESSENCE-Q, were administered. All children (age 2.5 years: n = 11; age: 6 years: n = 8) underwent physical examinations.

Main results and the role of chance: Cognitive skills showed results within the normal range at both age 2.5 years and age 6 years. According to the SDQ, emotional problems were the most common symptoms, affecting two children at age 2.5 years and two children at age 6 years. Three children scored above the cut off on the ESSENCE-Q at age 2.5 years, and one child continued to score 'high' at age 6 years. At the first examination, three children had asthma, and speech problems were observed in five children. Among those who were also assessed at age 6 years, these problems had abated. At age 6 years, one child was considered hyperactive, and another child exhibited vocal tics. Developmental and behavioural deviations were observed almost exclusively in the boys.

Limitations, reasons for caution: Limitations of the study include the small sample size, and the lack of a comparison group. The small sample does not offer enough statistical power, and no firm conclusions can therefore be drawn based on the reported deviances.

Wider implications of the findings: The long-term and very long-term outcomes of children born after UTx indicated normal cognitive development. A minority had minor physical and developmental problems, including asthma and speech problems at age 2.5 years, but most of these symptoms subsided by age 6 years. Boys seemed to be over-represented regarding developmental and behavioural deviations. The small sample size limits the ability to generalize the findings to all children born after UTx.

Study funding/competing interest(s): The study was supported by The Swedish research council (Grant/Award Numbers: Dnr 2023-02035 (H.H.), 2024-03487 (M.B.)), the Swedish state under the agreement between the Swedish Government and the country councils, the ALF-agreement, grant/Award-Numbers: ALFGBG-1005108 (H.H.), ALFGBG-965535 (M.B.), Jane and Dan Olsson Foundation for Science (2020-09 (M.B.)), and Knut and Alice Wallenberg Foundation (2017.0363 (M.B.)). There are no conflicts of interest for any of the authors.

Trial registration number: NCT01844362, NCT02987023.

Keywords: cognition; long-term follow-up; neurodevelopment; offspring; uterus transplantation.