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Neurological sequelae in twins born after assisted conception: controlled national cohort study

BMJ 2004; 329 doi: https://doi.org/10.1136/bmj.38156.715694.3A (Published 05 August 2004) Cite this as: BMJ 2004;329:311
  1. Anja Pinborg (apinborg{at}rh.dk), research fellow1,
  2. Anne Loft, consultant1,
  3. Lone Schmidt, associate professor2,
  4. Gorm Greisen, professor3,
  5. Steen Rasmussen, senior consultant4,
  6. Anders Nyboe Andersen, professor1
  1. 1 Fertility Clinic, University of Copenhagen, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
  2. 2 Institute of Public Health, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark
  3. 3 Department of Neonatology, University of Copenhagen, Rigshospitalet
  4. 4 National Board of Health, Health Statistics, Islandsbrygge 67, DK-2300 Copenhagen, Denmark
  1. Correspondence to: A Pinborg
  • Accepted 3 June 2004

Abstract

Objective To compare neurological sequelae in twins born after assisted conception with singletons after assisted conception and naturally conceived twins and to assess neurological sequelae in children conceived after in vitro fertilisation (IVF) compared with intracytoplasmic sperm injection (ICSI).

Design Controlled, national register based, cohort study.

Participants Twins (n = 3393) and singletons (n = 5130) conceived by using assisted reproductive technologies and naturally conceived twins (n = 10 239) born in Denmark between 1995 and 2000. The children's age at time of follow up was 2-7 years.

Data sources Children were identified by cross linkage of the national medical birth registry and the national registry for in vitro fertilisation. Neurological and psychiatric diagnoses were retrieved from the national patients' registry and the Danish psychiatric central registry.

Main outcome measures Neurological sequelae, defined as cerebral palsy, mental retardation, severe mental developmental disturbances, and retarded psychomotor development. Further we made separate analyses on the specific cerebral palsy diagnosis.

Results The crude prevalence rates per 1000 of neurological sequelae in twins and singletons after assisted conception and in naturally conceived twins were 8.8, 8.2, and 9.6, and of cerebral palsy 3.2, 2.5, and 4.0, respectively. In twins after assisted conception compared with control twins, the odds ratios of neurological sequelae and specifically of cerebral palsy, adjusted for child sex and year of birth, were 0.9 (95% confidence interval 0.6 to 1.4) and 0.8 (0.4 to 1.6), respectively. The corresponding odds ratios for twins after assisted conception compared with singletons after assisted conception were 1.1 (0.7 to 1.7) for neurological sequelae and 1.3 (0.6 to 2.9) for cerebral palsy. The odds ratio of neurological sequelae in children conceived by ICSI was 0.9 (0.5 to 1.7) ν children conceived by IVF.

Conclusions Twins from assisted conception have a similar risk of neurological sequelae as their naturally conceived peers and singletons from assisted conception. Children born after ICSI have the same risk of neurological sequelae as children born after IVF.

Footnotes

  • We thank Lone Mortensen, Health Statistics, Danish National Board of Health.

  • Contributors AL contributed to study design, interpretation of results, and reviewing the manuscript. LS participated in interpretation of results and reviewing the manuscript. GG supervised planning of classification of outcome and reviewing the manuscript. SR undertook the data retrieval. ANA contributed to study planning, interpretation of results, and reviewing the manuscript. AP was involved in study design, analyses of results, and writing the report. ANA is the guarantor.

  • Funding Danish Medical Research Council; Danish Hospital Foundation for Medical Research; Region of Copenhagen, the Faroe Islands and Greenland; and the Research Foundation of Queen Louise's Paediatric Hospital.

  • Competing interests None declared.

  • Ethical approval The trial was approved by the local research ethics committee and the Danish Data Protection Agency. A specific authorisation from the Danish Data Protection Agency was obtained to data retrieval from the Danish Psychiatric Central Registry.

  • Accepted 3 June 2004
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