Imprinting diseases and IVF: Danish National IVF cohort study

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Abstract
BACKGROUND: The aim of this study was to compare the frequency of imprinting diseases in children born after IVF with the incidence in naturally conceived children. METHODS: All singleton children born in Denmark from January 1, 1995 through December 31, 2001 were stratified into children born without and after IVF, and were followed from birth until the end of 2002 in the National Register of Patients and the Central Register of Psychiatric Diseases, which include all discharge diagnoses from somatic and psychiatric hospitals/clinics, respectively. Included in the study were malignancies, mental, behavioural and neurological diseases, congenital syndromes, and developmental disturbances. Only diagnosis codes potentially relevant for imprinting diseases were included. RESULTS: During the 7-year study period, 442 349 singleton non-IVF and 6052 IVF children were born. Mean follow-up time was 4.5 and 4.1 years for the two groups, respectively, corresponding to 2 million and 25 000 follow-up years. In the IVF/non-IVF cohort, we detected 0/72 children with cancer, 47/3766 with mental diseases, 72/3654 neurological diseases, 4/287 congenital syndromes and 96/6727 developmental disturbances, in a total of 219/14 506 clinical outcomes. The number of children with specific imprinting diseases in the non-IVF group was 54: 44 kidney cancers, five retinoblastoma, three Prader–Willi syndrome and two Russel–Silver syndrome. Anticipating the same occurrence in IVF children, the total expected number was calculated to be 0.74. The observed number in the IVF group was 0. We found a significantly increased risk of cerebral palsy in the IVF group, with a rate ratio (RR) (IVF:non-IVF) of 1.8 [95% confidence interval (CI) 1.2–2.8; P<0.01], and of sleeping disturbances, with an RR 2.0 (95% CI 1.2–3.3). The incidence rate of childhood cancers, mental diseases, congenital syndromes and developmental disturbances was equal in the two groups. CONCLUSIONS: We found no indication of an increased risk of imprinting diseases after IVF, but an 80% increased risk of cerebral palsy. We observed equal frequencies of childhood cancers, mental diseases, congenital syndromes and developmental disturbances in the two groups. Danish register data do not support reports of an increased risk of imprinting diseases after IVF.