Hypospadias and Vegetarian Diets

Hypospadias is a male birth defect in which the opening of the urethra (the tube through which urine passes) is not located at the tip of the penis as it should be. The rate of hypospadias has appeared to be increasing in recent decades and there is speculation that it is due to an abnormal hormone state during pregnancy. As of the early 1990s, the nationwide rate in hypospadias for the USA was about 37 cases per 10,000 births, or 1 in 270 (3). The milder forms of hypospadias, which are by far the largest number of cases (3), are relatively easy to repair. Surgical repair usually results in a penis with normal or near-normal function and appearance and no future problems (8).

There have been three studies examining the link between a maternal vegetarian diet and hypospadias. Two studies found a link (1, 2) and one did not (7).

2000 UK Study

This study found a link between hypospadias and a vegetarian diet, and also for eating legumes. It did not find a statistically significant result for drinking soy milk or eating soy meats. Here are the disease rate ratios:

Apparently, the results for legumes did not hold after the authors adjusted for other variables. My suspicion is that eating more beans was merely a marker for being vegetarian and that legume intake has no bearing on the risk of hypospadias.

Because there is speculation that pesticides might be a cause of hypospadias, the study also examined the purchase of organic vegetables. The authors state:

Unfortunately, only 163 mothers always bought organic vegetables; that none of these mothers had a son with hypospadias is of some interest, but only one case would have been expected. No reduction in risk was evident among those who sometimes bought organic vegetables (0.8% had hypospadiaas, compared with 0.6% who never bought organically grown vegetables).

2007 Netherlands Study

A small 2007 study from the Netherlands, did not find a link between a maternal vegetarian diet and hypospadias (7):

2008 Sweden and Denmark Study

The 2008 study from Sweden and Denmark found that not eating meat or fish, and not eating meat at least weekly, was associated with hypospadias. Eating fish less than once a week, compared to one to two times per week, was also associated, whereas drinking milk was not. Unless noted, the results were adjusted for other variables that affected the hypospadias rate.

The authors surmised that the cause of the hypospadias might be due to increased soy consumption among the vegetarian women, although they didn't actually measure their soy intake.

Soy

The authors of the 2000 study state:

The consumption of soya as a substitute for meat is increasing in the UK, partly as a result of the recent problems with beef and partly from concepts of 'healthy eating'. It is now widely used in the food industry, with the advent of vegetarian-style meals, and it provides the highest concentrations of phytoestrogens (particularly isoflavones) of all edible plant matter. However, the estimated daily exposure to exogenous oestrogens by consumers of soya is minimal compared to, e.g. that from oral contraceptives. Such low levels of exposure would perhaps indicate small risks (or benefits), as the biological activity of phytoestrogens is considered to be low. Nevertheless, extended prolonged exposure may cause phytoestrogens in the body to reach biologically significant levels. The possible effects on humans should not be dismissed until more experimental data are available. MacLusky discussed the more indirect role of phytoestrogens; rather than having a direct oestrogenic effect, they may interact with other factors in the diet and lead to an interference with 'normal oestrogen biosynthesis and action'.

In their study, use of oral contraceptives had no affect on the rate of hypospadias.

I could find only one article that measured soy intake and hypospadias, a 2004 study from the Netherlands (4) that found no link for maternal soy intake:

Vitamin B12 Deficiency?

What else could be causing this increase in hypospadias? Although vitamin B12 is found in dairy products and eggs, lacto-ovo vegetarians often have somewhat deficient B12 levels.

A search of PubMed did not result in any studies on vitamin B12 deficiency and hypospadias. However, folic acid is involved in the vitamin B12 pathway that, when disrupted, can cause genetic defects. Because meat-eaters tend to have adequate B12 levels but are often low in folic acid, I did a search on studies of folic acid and hypospadias and found two.

The most relevant was a 2004 trial in Hungary which found that a high dose folic acid supplement (6,000 mcg per day) reduced hypospadias when supplemented during the first trimester (.68, .55-.86) and during the second trimester .78 (.66-.92). A multivitamin containing less folic acid, as well as B12 and B6, did not reduce hypospadias to a statistically significant degree (.62, .32 - 1.53). Most of these patients probably had adequate B12 and B6 intake.

A 2006 meta-analysis found no effects of folic acid supplementation on preventing hypospadias (.44, .13 - 1.43). The analysis included the 2004 Hungary study, but was not clear on what others it included, if any.

I would consider the two papers on folic acid and hypospadias to provide some, but not much, evidence that vitamin B12 might be involved in causing an increase of hypospadias in vegetarian mothers.

In contrast to the idea that vitamin B12 deficiency is at the root of the problem for vegetarian mothers who have had boys with hypospadias are the many cases of vegan infants of mothers with B12 deficiency, and none of these boys were reported to have been born with hypospadias.

Conclusion

To summarize, two studies found that being vegetarian was significantly linked to an increased risk of hypospadias, one study did not find a link, and two studies did not find a link with soy intake.

For what it's worth, I know many women who have had vegetarian and vegan pregnancies and, as far as I know, none of them had boys born with hypospadias.

References

1. Akre O, Boyd HA, Ahlgren M, Wilbrand K, Westergaard T, Hjalgrim H, Nordenskjöld A, Ekbom A, Melbye M. Maternal and gestational risk factors for hypospadias. Environ Health Perspect. 2008 Aug;116(8):1071-6.
2. North K, Golding J. A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. BJU Int. 2000 Jan;85(1):107-13.
3. Paulozzi Leonard J. International Trends in Rates of Hypospadias and Cryptorchidism. Environmental Health Perspectives 1999 Apr;107(4):297 .
4. Pierik FH, Burdorf A, Deddens JA, Juttmann RE, Weber RF. Maternal and paternal risk factors for cryptorchidism and hypospadias: a case-control study in newborn boys. Environ Health Perspect. 2004 Nov;112(15):1570-6.
5. Czeizel AE. The primary prevention of birth defects: Multivitamins or folic acid? Int J Med Sci. 2004;1(1):50-61. Epub 2004 Mar 20.
6. Goh YI, Bollano E, Einarson TR, Koren G. Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis. J Obstet Gynaecol Can. 2006 Aug;28(8):680-9. Review.
7. Brouwers MM, Feitz WF, Roelofs LA, Kiemeney LA, de Gier RP, Roeleveld N. Risk factors for hypospadias. Eur J Pediatr. 2007 Jul;166(7):671-8. Epub 2006 Nov 14.
8. Hypospadias:Treatments and Drugs. MayoClinic.com. www.mayoclinic.com/health/hypospadias. Accessed November 11. 2008.

Also reviewed in preparing this article:

Botto LD, Mulinare J, Erickson JD. Occurrence of omphalocele in relation to maternal multivitamin use: a population-based study. Pediatrics. 2002 May;109(5):904-8.
Vilela ML, Willingham E, Buckley J, Liu BC, Agras K, Shiroyanagi Y, Baskin LS. Endocrine disruptors and hypospadias: role of genistein and the fungicide vinclozolin. Urology. 2007 Sep;70(3):618-21. (Abstract)