Higher periconception folate level may lower congenital heart disease risk in offspring
Click Here to Manage Email Alerts
Researchers in China determined that higher maternal periconception red blood cell folate concentration was associated with reduced risk for congenital heart disease in offspring.
“Our prospective nested case-control study found that higher periconception maternal red blood cell folate was significantly associated with a lower risk for offspring congenital heart disease,” Hongyan Chen, PhD, of the department of clinical epidemiology and clinical trial unit at the Children's Hospital of Fudan University, National Children’s Medical Center, and Shanghai Key Laboratory of Birth Defects in Shanghai, and colleagues wrote in the Annals of Internal Medicine. “When comparing women whose red blood cell folate levels were below the threshold of clinical sufficiency (906 nmol/L), we saw a significant decline of 39% fewer congenital heart disease cases among women whose red blood cell folate levels were above this threshold. Of note, the association showed an approximate threshold effect in that the reduction in congenital heart disease risk seemed to flatten out at red blood cell folate levels approaching 1,360 nmol/L (600 ng/mL).”
Current guideline recommendations
In 2015, WHO issued its guideline on optimal serum and red blood cell folate concentrations, the “gold-standard” biomarker of folate exposure, in women of reproductive age for prevention of neural tube defects, with the following recommendations:
- At the population level, red blood cell folate should be above 400 ng/mL (906 nmol/L) in women of reproductive age.
- This threshold can be used as an indicator of folate insufficiency in women of reproductive age; however, low folate concentrations cannot explain all cases of neural tube defects and this threshold cannot predict the individual risk.
- No specific threshold is recommended for the prevention of neural tube defects in women of reproductive age at the population level.
- Microbiological assay is recommended as the most reliable choice to obtain comparable results for red blood cell folate across countries, according to the guideline.
Folic acid supplementation is guideline-recommended in women of reproductive age for the prevention of neural tube defects by WHO and the U.S. Preventive Services Task Force.
To better understand the relationship between red blood cell folate and subsequent risk for congenital heart disease in offspring, researchers evaluated 197 mothers with offspring with congenital heart disease and 788 matched controls without offspring with congenital heart disease from 29 maternity centers in Shanghai.
Maternal red blood cell folate was measured during the periconception period of pregnancy and researchers then estimated the likelihood of congenital heart disease using conditional logistic regression after adjustment for covariates.
Folate concentration and congenital heart disease
“No prior studies have measured this biomarker in the critical time window before or close to fetal heart development to quantify the association between maternal folate and offspring congenital heart disease,” the researchers wrote.
Mothers with offspring with congenital heart disease had lower median red blood cell folate compared with matched controls (714 vs. 788 nmol/L), according to the study.
Researchers reported that periconception red blood cell folate level was inversely associated with offspring likelihood of developing congenital heart disease, with an approximately 7% lower risk per 100 nmol/L increase in folate concentration (adjusted OR per 100 nmol/L = 0.93; 95% CI, 0.89-0.99).
In addition, mothers with periconception red blood cell folate of 906 nmol/L or more, compared with those with less than 906 nmol/L, were less likely to have offspring with CHD (adjusted OR = 0.61; 95% CI, 0.4-0.93).
Moreover, for every 100 nmol/L increase in red blood cell folate concentration, researchers observed reduction in offspring risk for congenital heart disease (OR = 0.75; CI, 0.61-0.92).
“Our prospective nested case-control analysis ... provides direct evidence that higher maternal red blood cell folate is associated with reduced risk for offspring congenital heart disease,” the researchers wrote. “We propose that target red blood cell folate levels higher than those currently recommended for neural tube defect prevention be considered for primary congenital heart disease prevention. Further studies across different populations or ethnicities would be useful to support the extrapolation of our findings outside of the considered contexts.”
References:
- Bibbins-Domingo K, et al. JAMA. 2017;doi:10.1001/jama.2016.19438.
- Optimal Serum and Red Blood Cell Folate Concentrations in Women of Reproductive Age for Prevention of Neural Tube Defects: World Health Organization Guidelines. www.cdc.gov/mmwr/preview/mmwrhtml/mm6415a5.htm. Published April 24, 2015. Accessed Aug. 23, 2022.
- WHO I Guideline: Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects. apps.who.int/iris/bitstream/handle/10665/161988/9789241549042_eng.pdf. Published in 2015. Accessed August 23, 2022.
Collapse
Read more about
Click Here to Manage Email Alerts