Study: Maternal Folate Levels Predict Heart Health of Newborns
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Congenital (meaning present at birth) heart disease (CHD) is a term used to describe several different conditions that affect the heart. These heart abnormalities occur during the development of the baby’s heart during pregnancy, before the baby is born. CHD is estimated to affect 1 in 120 babies born in the United States1, making them the most common birth defect that occurs.
See also: CDC information on CHD
During gestation, specific developmental processes must take place in order for the heart to form correctly. Often, CHD occurs as a result of one of these crucial steps not happening at the right time.
Types of congenital heart disease
Without going into too much detail that would exceed the scope of this post, CHD can be classified into several different categories, namely:
- Defects that cause too much blood to pass through the lungs
- Defects that cause too little blood to pass through the lungs
- Defects that cause too little blood to travel to the body
Many of these defects can be detected during pregnancy during the routine ultrasound exam, while others may be diagnosed shortly after birth. Most forms of congenital heart disease have no known cause. Recently, cardiac gene regulators, cardiac-specific genes, and certain signaling pathways that are involved in early cardiac development have been extensively studied in both human and animal experiments, but leave much to be desired2… until now.
Ground-breaking research: Maternal folate levels predict CHD
It is well known that folate is a crucial nutrient required for embryonic development and that maternal folate supplementation is required to protect against neural tube defects. Previous studies have shown that when measuring homocysteine, vitamin B12, and folate concentrations in women with and without CHD-affected fetuses, women with CHD-affected pregnancies had higher plasma homocysteine concentrations than women with unaffected pregnancies. 3,4,5 What does homocysteine have to do with folate? Well, high homocysteine concentrations may be caused by lower folate and vitamin B6 levels and are often used as a marker for increased risk of vascular complications.6
Folate metabolism
MTHFR (methylenetetrahydrofolate reductase) is the enzyme produced by the MTHFR gene that is required for metabolizing folate and breaking down homocysteine.
Up to 60 % of the U.S. population have an MTHFR genetic enzyme variant that often goes unnoticed by the individual. If two copies of the MTHFR variant are present, the ability to convert folic acid into its useable form is challenging.
Two main MTHFR gene variants are currently being studied: C677T and A1298C.
Measurement of Red blood cell (RBC) folate in mothers was key.
Red blood cell (RBC) folate reflects the long-term folate status of the individual and is the gold-standard measure recommended by the World Health Organization (WHO).7 Importantly, no prior studies have measured this biomarker in the critical time window before or close to the time when fetal heart development occurs to quantify whether maternal folate levels and offspring CHD are linked.
The Study & The Role of MTHFR
A nested case-control and mendelian randomization study published in the Annals of Internal Medicine looked at 197 mothers of offspring with CHD and 788 mothers of offspring without CHD from 29 maternity institutions in 12 districts of Greater Shanghai, China.8
Researchers measured RBC folate levels either before conception (approximately 6 months before) or during early pregnancy (approximately 3 months after conception), and offspring were monitored for CHD using ultrasound during the second trimester, by neonatal screening at birth, and through routine childcare examinations.
Mothers were also assessed for the MTHFR C677T genetic variant, which is a variant that is associated with folate metabolism that causes a 10% to 35% reduction in plasma folate levels.
Based on the primary analysis using the MTHFR-C677T variant as the instrument variable, the case patients had lower median maternal RBC folate concentrations than control participants, which was expected.
Also, higher maternal folate levels were associated with a lower risk for CHD and concluded by providing strong evidence of the preventive effect of folic acid supplementation around the time of conception on CHD prevention. The authors propose that RBC folate levels higher than those currently recommended for neural tube defect prevention should be considered for CHD prevention.
It is largely unknown, but the results from this study have caused the authors to speculate the following8: A reduction in folate may affect the neural crest cells, which are a group of cells in the fetus that develop into several tissues. These cells have a demand for folate, particularly during the first 12 weeks after conception.
Evidence suggests that these neural crest cells have been traced and documented in several other parts of the developing heart, including the inlet of the heart and the aortic arch. Limiting folate transport to embryonic tissues through nutritional folate deficiency or genetic alternations may thus result in the development of CHD.
The pre-conceptional use of folic acid has not increased, despite its importance before and during pregnancy.
You would think that by now, with all the research that has been conducted, women would be more aware of the importance of folic acid during pregnancy. Alarmingly, this does not seem to be the case.
The authors of the ground-breaking research that I discussed earlier conducted a cross-sectional study to determine whether the recommended dosage of folic acid was being taken before pregnancy.9 They found that only 42.6% of women took the recommended 400 mcg of folic acid daily before pregnancy. What was more worrying was that the RBC folate levels of women preparing for pregnancy were, on average, 490 nmol/L, which was 90.1% below the 906-nmol/L cut-off.
The Bottom line
This study has provided convincing evidence on the importance of taking folic acid prior to conception, not only to prevent neural tube defects but to also prevent congenital heart defects. It would also be helpful to know your MTHFR status before you decide to conceive so that you can discuss the optimal dosage of folic acid you should be taking with your health care practitioner. This will ensure a healthy pregnancy for yourself and your baby.
