Book Review: Mortality and Maldevelopment Part II: The Saga of Neural Tube Defects By Harold Kalter Springer , 2009 £108.00 (Hardback) , 268 pages ISBN 978-1-4020-9605-1

This book is like a good detective novel, building up the evidence in a methodical and painstaking way to reach its denouement. The ‘saga’ is of the epidemiology and etiology of neural tube defects (NTDs) and their variable frequency around the world in a range of populations and the various theories of causation which might explain the enormous variability. Thus, the incidence on the Celtic fringes of Britain, with rates reaching nearly one percent of pregnancies for anencephaly and spina bifida, is contrasted to areas such as Western Canada, with rates of one-tenth seen elsewhere.

We discover that there is a drift from high prevalence to low not only from Northern Ireland to the southeast of England, but also from the North American Atlantic seaboard to the Pacific Coast. This difference is not entirely explicable by the colonization of North America by Scots-Irish, for how then could the differences between the high prevalence in New Zealand and the low prevalence seen in Australia, from similar original populations, be explained? By a minute examination of the evidence we come to the conclusion that the etiology must have both a genetic and environmental root. There is a sex difference: females are more often affected than males, particularly in relation to anencephaly but with no relationship to maternal age. However, the crux of the story is in relation to the current theory of folate deficiency placed alongside a long-term trend of a steady decline in incidence of NTDs over the last 50 years in all high-risk populations.

The final conclusion, found in the last few chapters, is that there is no satisfactory explanation! There was a spectacular rise in the incidence of NTDs from 1900 to the 1950s and then a fall down to levels today similar to the turn of the 20th century, despite the introduction of periconceptual vitamins. The real message of this book is that over the last 100 years our ability to do effective epidemiological and intervention studies has not improved, as evidenced by the recent studies on vitamin supplementation in the last chapter.

This is a fascinating and very detailed account of our inability to get to the root cause of one of our more common types of congenital malformations despite 100 years of research. Paediatricians, paediatric neurologists, and surgeons may find it helpful to dip in to this book for data on the pattern in their own area and get an overview of the research on folate supplementation. Epidemiologists will find it helpful to illustrate the difficulties in researching causality.