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Causal Hypothesis for Some Congenital Anomalies

Published online by Cambridge University Press:  21 February 2012

Peter O. D. Pharoah*
Affiliation:
FSID Unit of Perinatal and Paediatric Epidemiology, Department of Public Health, University of Liverpool, Liverpool, United Kingdom. [email protected]
*
*Address for correspondence: Emeritus Professor POD Pharoah, FSID Unit of Perinatal and Paediatric Epidemiology, Department of Public Health, University of Liverpool, Liverpool L69 3GB, UK.

Abstract

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Congenital anomalies are a major cause of fetal and neonatal death and of childhood morbidity. Chromosomal and other genetic abnormalities, environmental teratogens and some nutritional deficiencies account for some congenital anomalies but the majority are of unknown etiology. The hypothesis is here proposed that a significant proportion of congenital anomalies and cerebral palsy of unknown etiology are attributable to a monozygotic multiple conception with monochorionic placentation and that these anomalies, even in singletons, may be explained by early, unrecognized or unrecorded loss of one conceptus in a monochorionic monozygotic conception. The pathological mechanism is hemodynamic instability with episodes of acute feto–fetal transfusion that produce ischemic organ impairment in either or both twins. The resultant clinical abnormality will depend on range of severity (fetal death, infant death, congenital anomaly, normal infant), site or combination of sites (which organ[s] present[s] with the congenital anomaly) and timing (early, middle or late in gestation as shown by variation in brain pathology that is observed).

Type
Articles
Copyright
Copyright © Cambridge University Press 2005