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Hum. Reprod. Advance Access originally published online on December 5, 2008
Human Reproduction 2009 24(3):726-731; doi:10.1093/humrep/den436
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
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Congenital anomalies in multiple births after early loss of a conceptus

P.O.D. Pharoah1,3, S.V. Glinianaia2 and J. Rankin2

1 Department of Public Health, University of Liverpool, Liverpool L69 3GB, UK 2 Institute of Health and Society, Newcastle University, Newcastle upon Tyne NE2 4HH, UK

3 Correspondence address. Pharoah POD Department of Public Health, University of Liverpool, Liverpool L69 3GB, UK. Tel: +44 151 794 5577; Fax: +44 151 794 5272; E-mail: p.o.d.pharoah{at}liv.ac.uk

Background: Congenital anomalies are more common in twins than singletons but in the majority, aetiology is not known. Our aim was to test the hypothesis that survivors of an early loss in a multiple conception, compared with all singletons, are at increased risk of congenital anomaly.

Methods: Data were abstracted from the UK population-based Northern Multiple Pregnancy Register and Northern Congenital Abnormality Survey, 1998–2004.

Results: Among 3311 twin conceptions, both conceptuses were lost at <16 weeks gestation in 67, and one conceptus in 142 conceptions. Of the 142 singleton survivors, two died in infancy, two were terminated for a congenital anomaly and 11 of 138 had a congenital anomaly (prevalence 915.5 per 10 000 births). There were 197 congenital anomalies among 5948 registered twin births (331.2 per 10 000). The relative risk (RR) of congenital anomalies in a singleton with early loss of a conceptus and twins was 2.40 [95% confidence interval (CI): 1.34–4.29]. There were 4265 infants with a congenital anomaly among the 206 914 singletons [206.1 per 10 000 births: RR twin:singleton 1.61 (95% CI 1.40–1.89)].

Conclusions: A highly significant increase in the risk of congenital anomaly in survivors from a multiple conception following early loss of a conceptus supports the hypothesis that many congenital anomalies are associated with monozygotic multiple conceptions.

Key words: multiple pregnancies/twins/congenital anomalies/early fetal loss

Submitted on August 19, 2008; resubmitted on November 3, 2008; accepted on November 11, 2008.


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