Hypospadias and Vegetarian Diets
by Jack Norris, RD | Last updated: June 2012
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); as of June 2012, this was still the most recent data reported. 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).
As of June 2012, there have been six studies comparing hypospadias cases in boys born to vegetarians versus non-vegetarians. Table 1 lists them.
|Table 1. Rate of hypospadias cases in boys born to vegetarian mothers|
|Study||Type||No. of Boys||Cases||Vegetarians||Vegetarian cases||Rate|
|UK 2000 (2)||Prospective||6296||51||321||7||5.0 (2.1, 11.9)|
|Netherlands 2007 (7)||Case-Control||834||583||17||10||0.6 (0.3, 1.6)|
|Sweden & Denmark 2008 (1)||Case-Control||719||291||22||14||4.6 (1.6, 13)|
|UK 2009 (10)||Case-Control||949||467||168||77||0.85 (0.61, 1.2)|
|India 2011 (11)||Case-Control||200||80||123||52||1.28 (.71, 2.3)|
|USA 2012 (9)||Case-Control||4368||1250||43||10||0.6 (0.3, 1.2)|
The only prospective study (UK, 2000), and the first study to examine the link, found that a vegetarian diet increased the rate of hypospadias by five times and it was fairly statistically significant.
Since 2007, there have been five case-control studies of various sizes. One found a 4.6 times higher risk for vegetarian mothers and the other four found no increased risk.
Two of these studies deserve more weight: The 2000 UK study which found a link between vegetarian diet and hypospadias, and the 2012 USA which did not. The 2000 UK is a prospective study and prospective studies generally hold more weight than do case-control because they involve less risk of mischaracterizing dietary patterns. However, in the case of vegetarians and hypospadias, mischaracterizing dietary patterns in case-control studies is probably not much of an issue because diet recall happened relatively shortly after hypospadias diagnosis. The 2012 USA study was very large, making random chance findings unlikely - in fact, it contained almost 25 times as many cases of hypospadias than did the 2000 UK study. Additionally, these two studies were designed with the purpose of investigating vegetarian diets while the aim of the other studies was broader. Thus, we have the two most important studies with different findings, though reason to put significant weight on the 2012 USA study.
What could be going on here?
A first guess would be that vitamin B12 deficiency among vegans and even some lacto-ovo vegetarians could have increased the risk of hypospadias. And in the interim time between the 2000 UK and 2012 USA studies, there was much education in the vegan community about the need for vitamin B12 explaining why the risk might have disappeared. However, there are many documented cases of vegan infants whose mothers had been deficient in vitamin B12 and to my knowledge none of these boys have been reported to have been born with hypospadias. Additionally, most of the women in these studies have been lacto-ovo vegetarian, not vegan. So it seems like we can rule out vitamin B12 deficiency.
What about other molecules involved in one-carbon metabolism such as folate (or folic acid), choline, and methionine?
As for folic acid, a 2006 meta-analysis (6) found no effects of folic acid supplementation on preventing hypospadias.
There is a bit of evidence that methionine could play a role (12). In a report coming from the National Birth Defects Prevention Study (USA, 2009), women who ate more than 1,870 mg/day of methionine had a 40% reduced risk of having a baby with hypospadias (0.6, 0.4-0.9). Methionine is an essential amino acid, the RDA is well under 1,870 mg/day for most pregnant women, and it could be hard for vegetarians to eat 1,870 mg per day. Without more evidence, it's probably unnecessary to strive for 1,870 mg per day. However, it is a good idea to make sure a pregnant vegan's diet has plenty of methionine. The plant foods highest in methionine can be seen in Table 3 of Protein and are tempeh, peanuts, oatmeal, quinoa, and spaghetti.
Choline, a nutrient that can be on the low end in vegan diets, was investigated in the National Birth Defects Prevention Study (12). They did not find a statistically significant association between high choline intakes and risk of hypospadias (.7, .5-1.1), but it is still a nutrient to consider regarding vegans. Here a links to information on choline of which pregnant vegans should be making sure they are getting enough.
Because there is speculation that pesticides might be a cause of hypospadias, the 2000 UK 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 hypospadias, compared with 0.6% who never bought organically grown vegetables).
While there might be something to the pesticide/organic vegetable link, there doesn't seem to be enough statistical power to draw any conclusions.
Finally, there is soy, a food no discussion on vegetarianism should ever be without! The concern is that the plant estrogens in soy might interfere with the sexual development of boys.
While there was a trend in the 2000 UK prospective study for drinking soy milk versus not (3.7, .87-15.4) and eating soy meats more than once a week versus never (2.95, .90, 9.68), the findings were not statistically significant. In this study, it might have been hard to separate eating soy milk and meats from simply being vegetarian. The authors wrote:
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'.
|Table 2. Hypospadias & Soy (2004)4|
|Soy Protein Intake|
|0 to 20 g/day||1.1 (.5, 2.5)|
|20+ g/day||1.0 (.5, 2.2)|
A 2004 study from the Netherlands (4) also measured soy intake and hypospadias and found no link for maternal soy intake. Results are in Table 2.
Under the worst case scenario, based on the 2000 UK study, a vegetarian mother would have a 4% chance of having a baby with hypospadias. The trend since that first report has been to find no association between a vegetarian diet and hypospadias and that is punctuated by the most recent 2012 USA study with almost 25 times as many cases of hypospadias than the 2000 UK study. This gives reasonable confidence that a vegetarian diet is not a significant risk. Making sure pregnant vegans get enough methionine and choline can help alleviate any potential risks.
1. Akre O, Boyd HA, Ahlgren M, Wilbrand K, Westergaard T, Hjalgrim H, Nordenskjold 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. Strom BL, Schinnar R, Ziegler EE, Barnhart KT, Sammel MD, Macones GA, Stallings VA, Drulis JM, Nelson SE, Hanson SA. Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA. 2001 Aug 15;286(7):807-14. Link
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.
9. Carmichael SL, Ma C, Feldkamp ML, Munger RG, Olney RS, Botto LD, Shaw GM, Correa A. Nutritional factors and hypospadias risks. Paediatr Perinat Epidemiol. 2012 Jul;26(4):353-60. (link)
10. Ormond G, Nieuwenhuijsen MJ, Nelson P, Toledano MB, Iszatt N, Geneletti S, Elliott P. Endocrine disruptors in the workplace, hair spray, folate supplementation, and risk of hypospadias: case-control study. Environ Health Perspect. 2009 Feb;117(2):303-7. (link)
11. Shekharyadav C, Bajpai M, Kumar V, Ahmed RS, Gupta P, Banerjee BD. Polymorphism in CYP1A1, GSTMI, GSTT1 genes and organochlorine pesticides in the etiology of hypospadias. Hum Exp Toxicol. 2011 Oct;30(10):1464-74. Epub 2011 Feb 7. (link)
12. Carmichael SL, Yang W, Correa A, Olney RS, Shaw GM; National Birth Defects Prevention Study. Hypospadias and intake of nutrients related to one-carbon metabolism. J Urol. 2009 Jan;181(1):315-21; discussion 321. (link)
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.
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.
Giordano F, Carbone P, Nori F, Mantovani A, Taruscio D, Figa-Talamanca I. Maternal diet and the risk of hypospadias and cryptorchidism in the offspring. Paediatr Perinat Epidemiol. 2008 May;22(3):249-60. (link)
Giordano F, Abballe A, De Felip E, di Domenico A, Ferro F, Grammatico P, Ingelido AM, Marra V, Marrocco G, Vallasciani S, Figa-Talamanca I. Maternal exposures to endocrine disrupting chemicals and hypospadias in offspring. Birth Defects Res A Clin Mol Teratol. 2010 Apr;88(4):241-50. (link)
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.
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)