Why Is It So Difficult to Study Obstetric Complications and Schizophrenia?

Statistical Power

The effect sizes for the relationship between obstetric risk factors and later schizophrenia are generally small, with odds ratios of less than 2. This is the sort of effect size reported for the relationship between passive smoking and lung cancer or the risk of breast cancer among users of the oral contraceptive pill. Such small effects are usually controversial and are some way from indicating strong causality. One may be dealing with proxy effects for some other lifestyle or socioeconomic factors or interactive effects with as-yet-unknown genetic or epigenetic factors. The study of individual obstetric risk factors for schizophrenia could be conceptualized as the search for rare risk factors for a rare disease and is therefore truly suitable neither for the classic cohort design nor for case-control designs. The power of even the largest population-based studies to detect odds ratios of 1.5 was less than 70% . Methods such as the "nested" case-control design are useful, but, even so, the lack of independence of individual obstetric complications (discussed earlier) and possible interactive effects further erode statistical power. Some studies have tried to overcome low statistical power by examining only one exposure on the basis of a prior hypothesis. This has proved a relatively fruitful endeavor, showing significant effects for the putative risk-increasing mechanism of hypoxic and ischemic damage, but each set of researchers has used different combinations of exposures, hindering replication and comparison or pooling of the results between studies.

Definition of Obstetric Complications

No one realized initially just how common the broadly defined Lewis-Murray obstetric complications are in the general population—about 25%–30% of births involve at least one Lewis-Murray complication. So many discrete exposures are wrapped up in the term "obstetric complication" that it is essentially meaningless to consider them as one risk factor. Before beginning to judge whether any association should be interpreted as causal, researchers must consider many distinct associations in terms of chance, bias, or confounding. If the field is to progress, advances are needed not only in population-based methods but also in sharpening the definitions of the exposures under scrutiny. A broad definition of obstetric complications should no longer be used as it will not improve our understanding of the field any further. More careful definition of exposures, such as prenatal measurement of maternal antibodies, and more extensive use of quantitative measures, including birth weight or head circumference, are likely to show larger and more consistent effects.

Information on the Prenatal Period

Birth records tend to include detailed information about the delivery and neonatal period, but information about the prenatal period is less reliable. Details about the course of the pregnancy are often recorded at the time of admission to the labor ward. Major pregnancy complications, such as preeclampsia, are usually mentioned, but there may be no record of problems such as prenatal stress or there may be insufficient detail about timing of infection or bleeding.