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


METHODS
Controlled, national register based, cohort study.


METHODS
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.


METHODS
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.


METHODS
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) nu 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.
Pinborg
Anja
A
Fertility Clinic, University of Copenhagen, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. apinborg@rh.dk
Loft
Anne
A
Schmidt
Lone
L
Greisen
Gorm
G
Rasmussen
Steen
S
Andersen
Anders Nyboe
AN
D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004200:Diseases in Twins / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000453:epidemiology / Q000209:etiology*; D011247:Pregnancy; D011272:Pregnancy, Multiple; D015995:Prevalence; D012307:Risk Factors; D014427:Twins