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Increased frequency of severe major anomalies in children conceived by intracytoplasmic sperm injection
I Sanchez-Albisua1, S Borell-Kost, U A Mau-Holzmann
1University Children's Hospital, Department of Medical Genetics, Tübingen, Germany. iciar.sanchez@med.uni-tuebingen.de
Insights
Children born after intracytoplasmic sperm injection (ICSI) show a higher rate of severe congenital anomalies. However, excluding these severe cases, their neurodevelopmental outcomes are similar to spontaneously conceived children.
Area of Science:
- Reproductive Medicine and Developmental Pediatrics
- Assisted Reproductive Technologies
- Neurodevelopmental Outcomes
Background:
- The neurodevelopmental trajectory of children conceived via intracytoplasmic sperm injection (ICSI) remains a subject of ongoing research and debate.
- Existing studies present varied findings regarding the long-term health and developmental status of ICSI-conceived singletons.
- A comprehensive comparison with a control group is essential to clarify potential risks associated with ICSI.
Purpose of the Study:
- To compare the medical and neurodevelopmental outcomes of children born after ICSI with those of a control group.
- To identify any significant differences in the incidence of major congenital anomalies (MaCAs) and developmental assessments.
- To evaluate the potential association between ICSI and imprinting defects.
Main Methods:
- A cohort of 34 singletons born after ICSI underwent physical assessments and developmental testing across motor and language domains.
- Outcomes were compared against 39 case-controlled children conceived spontaneously.
- Karyotyping was performed on a subset of ICSI children; imprinting defect analysis was conducted where indicated.
Main Results:
- Children born after ICSI exhibited a higher frequency of severe major congenital anomalies (MaCAs) compared to controls (4/34 vs. 0/39, p=0.04).
- Specific severe MaCAs included Angelman syndrome, lissencephaly, Hanhart syndrome, and persistent hyperinsulinemic hypoglycemia of infancy.
- Excluding children with severe MaCAs, neurodevelopmental outcomes at four years of age were comparable between ICSI and control groups.
Conclusions:
- A higher incidence of severe congenital anomalies is observed in children born following ICSI.
- The risk of imprinting defects in ICSI-conceived children warrants further investigation.
- When severe anomalies are excluded, ICSI-conceived children demonstrate neurodevelopmental outcomes similar to spontaneously conceived peers.
Abstract:
The neurodevelopmental outcome of children born after intracytoplasmic sperm injection (ICSI) is controversial. We compared the medical and developmental outcome of 34 singletons born after ICSI (20 males, 14 females; mean ages of 18 mo and 40 mo [SD 9 mo]; range 2 y 10 mo-4 y 8 mo) with 39 case control studies (21 males, 18 females; mean ages of 18 mo and 40 mo [SD 4 mo]; range 3 y-4 y 1 mo). Each child was assessed physically and tested in three development domains (fine motor, gross motor, and language). Five children born after ICSI versus two control children (p=0.2) had major congenital anomalies (MaCAs). Four children born after ICSI versus no control children had severe MaCAs (p=0.04). These were defined as having a significant impact on development or causing chronic disease: Angelman syndrome (n=1), lissencephaly (n=1), Hanhart syndrome (n=1), and persistent hyperinsulinemic hypoglycaemia of infancy (n=1). Karyotyping in 23 children born after ICSI revealed no abnormalities. An imprinting defect was found in the child with Angelman syndrome. Results of developmental assessment were in all cases normal at the age of 18 months except for the three children with Angelman and Hanhart syndromes, and lissencephaly. At the second assessment, five more children born after ICSI and four control children showed abnormalities in one or more developmental domains. We conclude that there seems to be a higher frequency of severe major anomalies in children born after ICSI. An increased risk for imprinting defects cannot be excluded. If we exclude children with severe MaCAs, the incidence of an abnormal somatic or neurodevelopmental outcome in the fourth year of life in children born after ICSI is similar to that of spontaneously conceived children.
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