The Maternal Mediterranean Diet during Pregnancy and Risk of Spina Bifida in the Offspring

Environment and Reproductive Health

The maternal placenta was long believed to protect the developing embryo from environmental hazards. However, it has become evident that viruses, drugs, alcohol use, tobacco smoke, and nutritional imbalance can reach the embryo and foetus and are related to suboptimal pregnancy outcome and health later in life1. The role of nutrition is particularly important because this exposure is modifiable and has a large public health potential2.

The Maternal Diet and Risk of Spina Bifida Offspring

In the past, many epidemiological studies have focused upon single nutrients, such as the B-vitamin folic acid with regard to risk of neural tube defects and other malformations3. Lately, dietary pattern analysis has emerged as a new method of assessing overall behaviour in food consumption4. We were interested whether the periconceptional maternal diet is also associated with the risk of spina bifida in the offspring5. In a case–control trial study in the Netherlands, dietary patterns in 50 mothers of children with spina bifida and 81 control mothers were analyzed (1999–2001). Maternal food intakes were obtained by food frequency questionnaires at the standardised study moment of 14 months after the birth of the index child. Principal component factor analysis and reduced rank regression were used to identify the most prevalent patterns in food consumption in this study population4, 6. Dietary patterns were validated with the maternal biomarkers folate, vitamin B12 and homocysteine of the homocysteine pathway.

The Mediterranean Diet

The Mediterranean dietary pattern was most prevalent among study participants and was characterised by high intakes of fruit, vegetables, vegetable oil, fish, legumes and cereals, moderate alcohol intake, and low intakes of potatoes and sweets. These healthy foods and drinks have traditionally been consumed by people living in countries near the Mediterranean Sea7. In our study we observed that the Mediterranean dietary pattern was associated with higher folate and vitamin B12 and lower homocysteine concentrations. The intake of alcohol consisted mainly of wine and was restricted to 1-2 glasses per week on average. An important finding was that we also found that the risk to give birth to a child with spina bifida was reduced by 70% in women with high adherence to a Mediterranean diet.

Nutrition, Epigenetics, and Spina Bifida

The associations between the Mediterranean diet, biomarkers of the homocysteine pathway and spina bifida risk are in line with our previous data and that of others3. It is known that in Southern European countries the Mediterranean diet is more often used, compared with Northern European countries. Moreover, in this population the blood concentrations of homocysteine are also slightly lower and of folate higher. The homocysteine pathway plays an important role during periods of rapid cell division and growth, such as embryogenesis. Recent understanding from animal and epidemiological studies shows that nutritional stimuli can influence genetic expression through DNA methylation8. This mechanism requires methyl groups derived from the human diet (e.g. folate, choline, and methionine of the homocysteine pathway) to establish appropriate gene activating and silencing patterns during embryonic and fetal development9. Thus, it seems plausible that the Mediterranean diet provides a natural rich source of methyl groups and may affect underlying epigenetic mechanisms. Understanding how the Mediterranean diet modifies biological processes may raise new possibilities for primary prevention measures in (pre)pregnancy to avoid Birth defects in offspring, especially spina bifida.

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