Abstract
Children born after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) have been reported to have a higher risk of cerebral palsy (CP), perhaps due to the higher frequency of preterm birth, multiple births or vanishing embryo in the pregnancies. However, it has been suggested that the underlying infertility may be part of the pathway. In this study, we examined whether untreated subfecundity (measured by time to pregnancy) or infertility treatment was associated with an increased risk of CP in the offspring. Using the Danish National Birth Cohort (1997-2003), we compared children born after 0-2 months of waiting time to pregnancy (n = 35 848) with those born after a time to pregnancy of 3-5 months (n = 15 361), 6-12 months (n = 11 528) and >12 months (n = 7387), as well as those born after IVF/ICSI (n = 3617), ovulation induction with or without intrauterine insemination (n = 3000), and unplanned pregnancies (n = 13 462). CP cases were identified through the Danish CP Register. In total, 165 (0.18%) children were diagnosed with CP in the entire cohort. We found no significant association between time to pregnancy and the risk of CP in children conceived spontaneously. Children born after IVF/ICSI had an increased risk of CP, even after adjustment for preterm birth and multiplicity (hazard ratio 2.30, 95% confidence interval 1.12-4.73). Subfecundity per se did not appear to be associated with the risk of CP in children, whereas being born after IVF/ICSI conferred an increased risk.
MeSH Terms
Cerebral Palsy/epidemiology,etiology
Child
Child, Preschool
Denmark/epidemiology
Female
Fertilization in Vitro/adverse effects
Humans
Infertility/etiology
Pregnancy
Registries
Reproductive Techniques, Assisted/adverse effects
Sperm Injections, Intracytoplasmic/adverse effects
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Zhu Jin Liang
The Danish Epidemiology Science Centre, Department of Epidemiology, School of Public Health, University of Aarhus, Aarhus C, Denmark.
[email protected]
Hvidtjørn Dorte
Basso Olga
Obel Carsten
Thorsen Poul
Uldall Peter
Olsen Jørn
References (22)
22 references, click to expand
-
Does low participation in cohort studies induce bias?
Epidemiology. 2006 Jul;17(4):413-8
PMID: 16755269
-
Morbidity in a Danish national cohort of 472 IVF/ICSI twins, 1132 non-IVF/ICSI twins and 634 IVF/ICSI singletons: health-related and social implications for the children and their families.
Hum Reprod. 2003 Jun;18(6):1234-43
PMID: 12773452
-
Cerebral palsy and assisted reproductive technologies: a case-control study.
Dev Med Child Neurol. 2010 Jul;52(7):e161-6
PMID: 20015250
-
Health of children born as a result of in vitro fertilization.
Pediatrics. 2006 Nov;118(5):1819-27
PMID: 17079550
-
A report: the definition and classification of cerebral palsy April 2006.
Dev Med Child Neurol Suppl. 2007 Feb;109:8-14
PMID: 17370477
-
Validation of a cerebral palsy register.
J Clin Epidemiol. 1997 Sep;50(9):1017-23
PMID: 9363036
-
The Danish National Birth Cohort--its background, structure and aim.
Scand J Public Health. 2001 Dec;29(4):300-7
PMID: 11775787
-
Hospital care utilization of infants born after IVF.
Hum Reprod. 2002 Apr;17(4):929-32
PMID: 11925384
-
Consequences of vanishing twins in IVF/ICSI pregnancies.
Hum Reprod. 2005 Oct;20(10):2821-9
PMID: 15979998
-
Multiplicity and early gestational age contribute to an increased risk of cerebral palsy from assisted conception: a population-based cohort study.
Hum Reprod. 2010 Aug;25(8):2115-23
PMID: 20554642
-
Cerebral palsy among children born after in vitro fertilization: the role of preterm delivery--a population-based, cohort study.
Pediatrics. 2006 Aug;118(2):475-82
PMID: 16882798
-
Neurological sequelae in twins born after assisted conception: controlled national cohort study.
BMJ. 2004 Aug 7;329(7461):311
PMID: 15256418
-
Imprinting diseases and IVF: Danish National IVF cohort study.
Hum Reprod. 2005 Apr;20(4):950-4
PMID: 15665017
-
Diagnosis, treatment, and prevention of cerebral palsy.
Clin Obstet Gynecol. 2008 Dec;51(4):816-28
PMID: 18981805
-
Cerebral palsy, autism spectrum disorders, and developmental delay in children born after assisted conception: a systematic review and meta-analysis.
Arch Pediatr Adolesc Med. 2009 Jan;163(1):72-83
PMID: 19124707
-
Validation of self-reported data on assisted conception in The Danish National Birth Cohort.
Hum Reprod. 2009 Sep;24(9):2332-40
PMID: 19454590
-
Prevalence and characteristics of children with cerebral palsy in Europe.
Dev Med Child Neurol. 2002 Sep;44(9):633-40
PMID: 12227618
-
Neurological sequelae in children born after in-vitro fertilisation: a population-based study.
Lancet. 2002 Feb 9;359(9305):461-5
PMID: 11853790
-
Validity of self-reported time to pregnancy.
Epidemiology. 2009 Jan;20(1):56-9
PMID: 19057382
-
In vitro fertilization in Sweden: child morbidity including cancer risk.
Fertil Steril. 2005 Sep;84(3):605-10
PMID: 16169392
-
The Danish Cerebral Palsy Registry. A registry on a specific impairment.
Dan Med Bull. 2001 Aug;48(3):161-3
PMID: 11556266
-
Vanishing twin: a possible cause of cerebral impairment.
Twin Res Hum Genet. 2007 Feb;10(1):202-9
PMID: 17539381