Risk factors for gastroschisis
Authors: Pierpaolo Mastroiacovo
Journal: BMJ (2008)

Gastroschisis is a small abdominal fissure lateral to an intact umbilical cord, generally to the right. The bowel herniates throughout the fissure and is not covered by membrane. Unlike most other birth defects, reported rates of gastroschisis have increased over the past 25 years from 0.1-1.0 per 10 000 births to 3.0-5.0 per 10 000 births in many developed and developing countries, with the notable exception of Italy, where rates have remained stable at under 1.0 per 10 000.1 2 3 In the linked research paper, Feldkamp and colleagues assess whether genitourinary infections increased the risk for gastroschisis in participants in the national birth defects prevention study (NBDPS).4

Research on risk factors has previously been hampered by the relative rarity of the defect and by unclear case definition. For example, the ICD-9 (international classification of diseases, 9th revision) coding system combined omphalocele and gastroschisis under a single code (756.7). Moreover, the pathogenesis and the embryological period during which the defect develops are still unclear. The debate about whether gastroschisis is a disruption occurring after the formation of the abdominal wall or a primary malformation of the folding process of the abdominal wall has recently reopened.5

Nevertheless, one consistent risk factor has been shown in all epidemiological studies, young maternal age. For example, one European study found that compared with mothers aged 25-29, the relative risk was 7.0 (95% confidence interval 5.6 to 8.7) for mothers under 20 and 2.4 (2.0 to 3.0) for mothers aged 20-24 years.3 The correlation with young maternal age suggests that environmental factors are involved.

In their case-control study, Feldkamp and colleagues assess the association between gastroschisis and genitourinary infection from one month before conception through to the end of the first trimester.4 Diagnosis was by expert review of all cases in live born infants, stillbirths, and terminations of pregnancy. The study uses a computer assisted telephone interview in English or Spanish as part of an ongoing population based study funded by the Centers for Disease Control and Prevention, which includes 10 state run surveillance systems of birth defects in the United States. A genitourinary infection was self reported by 16.2% of women with affected infants (n=505) and 8.7% of mothers of healthy live born infants (n=4924). The resulting odds ratio—adjusted for maternal age, body mass index before conception, smoking, and Hispanic ethnicity (a specific genetic background and suggestive of a low socioeconomic status)—was 1.5 (1.1 to 1.9).

The study is important not only because it highlights genitourinary infection as a new risk factor for gastroschisis, but also because the risk factors used in the logistic model to compute adjusted odds ratios were found to be important in previous studies.6 For example, a recent large population based case-control study in the United Kingdom found significant adjusted odds ratios for the use of aspirin (20.4), use of vasoconstrictive recreational drugs (ecstasy, amphetamine, and cocaine) (3.3), history of gynaecological infection (2.6), use of any recreational drug (2.2), low body mass index (2.0), unmarried status (1.8), and cigarette smoking (1.7).7 If the associations are causal, the highest population attributable risk is for cigarette smoking (28%); this information is useful for promoting preventive action.

Other case-control studies have indicated that having at least two children, each from a different father, is a further risk factor.8 Moreover, an increased risk of gastroschisis has been reported in women who smoke cigarettes or marijuana (26.5, 7.9 to 89.4) and women with a low body mass index.9 An interaction between smoking and gene polymorphisms (ICAM-1 gly241arg, NOS3 glu298asp, NPPA T22238C) has also been suggested.10

The overall pattern of findings from all of these studies suggests that the risk for having an infant with gastroschisis is highest in young women, mainly teenagers, with one or more of the following characteristics—have low socioeconomic status, smoke cigarettes, eat too little, drink alcohol, use illicit drugs, have early and unprotected sexual intercourse, and have genitourinary infection.

These risk factors—perhaps in combination with genetic susceptibility—may explain the link between low maternal age and increased frequency of the defect in many countries. But to explain the threefold to fivefold increase seen in many countries in the past few decades, several risk factors—which may be under ascertained and under reported—must strongly interact.

The study by Feldkamp and colleagues is from a large and growing dataset, and it provides an opportunity to evaluate the interacting web of risk factors suggested so far.4 Moreover, it is interesting that 43% of mothers with affected infants reported a Chlamydia trachomatis infection because this infection has many common risk factors with gastroschisis, plus it can be screened for and treated.11 Ascertaining a history of C trachomatis infection should be considered in future studies.

In the meantime, preventive actions to reduce the frequency of gastroschisis worldwide must be seriously considered and urgently implemented. Global reproductive health counselling, which involves several preventive actions tailored to the needs of adolescents and young women, should be advocated as the best approach to deal with the complex biomedical and sociocultural set of risk factors.12