Low folic acid levels during pregnancy increase the risk of adverse pregnancy outcomes, according to a recent study published in Tzu Chi Medical Journal.
Takeaways
- Low levels of folic acid during pregnancy are associated with an increased risk of adverse pregnancy outcomes, including first- and second-trimester miscarriages, preterm delivery, and fetal growth restriction.
- Folic acid plays crucial roles in vital biochemical processes, red blood cell formulation, and brain function. During pregnancy, it is especially important for embryonic formation and neural tube closure.
- The study was conducted as a hospital-based observational study involving pregnant women in the first or early second trimester with spontaneous conceptions. Exclusion criteria were multifetal pregnancy, assisted reproductive technology conception, chronic hypertension, pregestational diabetes, and thrombophilia.
- Plasma folic acid levels were measured during the booking visit, with a cutoff of 8.6 ng/mL. Participants were divided into two groups based on folic acid levels: those below 8.6 ng/mL and those equal to or above 8.6 ng/mL.
- Results indicated a higher incidence of adverse pregnancy outcomes among patients with folic acid levels below 8.6 ng/mL, including increased risk of miscarriages and preterm delivery. The study suggests further research to determine the optimal dose and duration of folic acid supplementation during pregnancy.
Folic acid is responsible for vital biochemical processes, red blood cell formulation, and brain function. During pregnancy, folic acid supports embryonic formation and neural tube closure. However, maternal plasma folate concentration decreases during pregnancy to approximately 50% of non-pregnant levels.
Data has indicated an association between folate deficiency and increased spontaneous abortion, stillbirth, and recurrent pregnancy loss risks. However, this data is limited by small sample sizes and other cofounding risk factors in participants. Findings for other risks such as preeclampsia also remain uncertain, indicating a need for more robust data.
To evaluate the association between folic acid levels and adverse pregnancy levels, investigators conducted a hospital-based observational study. Participants included pregnant women in the first or early second trimester with spontaneous conceptions.
Exclusion criteria included multifetal pregnancy, conception with assisted reproductive technology, chronic hypertension, pregestational diabetes, and thrombophilia. Data obtained included baseline demographic characteristics, dietary habits, and clinical evaluation.
An automated chemiluminescence assay was used to measure plasma folic acid levels during the booking visit, with a cutoff of 8.6 ng/mL. Patients were placed into 2 groups, one with folic acid values below 8.6 ng/mL and one with values above 8.6 ng/mL.
Outcomes included first- and second-trimester miscarriage, anemia, gestational hypertension, preeclampsia, gestational diabetes mellitus, placental abruption, hypothyroidism, and intrauterine fetal growth restriction (FGR). Data on intrauterine fetal demise and fetal neural tube defects was also obtained.
There were 308 patients included in the final analysis, 78.57% with folic acid levels above 8.6 ng/mL and 21.43% with levels equal to or below 8.6 ng/mL. There were no significant differences in folic acid levels observed across age groups and gravidity categories, but vitamin B12 deficiency was associated with reduced folic acid levels, with a relative risk (RR) of 1.33.
First- and second-trimester miscarriages were reported in 7.57% of women with folic acid levels below 8.6 ng/mL vs 2.06% in women with levels equal to or above 8.6 ng/mL. A RR of 2.48 was reported, indicating a 2.48-fold increased risk among women with levels below 8.6 ng/mL.
Anemia was reported in 18.8% of women with folic acid levels equal to or above 8.6 ng/mL and 25.4% with levels below 8.6 ng/mL. The RR was not significantly different for anemia. Overall, significant differences were not observed for the incidence of gestational hypertension, anemia, gestational diabetes, and preeclampsia.
Preterm delivery was reported in 16.94% of the folic acid levels below 8.6 ng/mL group vs 7.53% of the levels above 8.6 ng/mL group. FGR was reported in 27.11% and 13.38% of these groups, respectively. However, low Apgar score at 5 minutes did not significantly differ between the 2 groups.
These results indicated increased risk of adverse pregnancy outcomes among patients with folic acid levels below 8.6 ng/mL. Investigators recommended further studies to determine the optimal dose and duration of folic acid supplementation during pregnancy.
Reference
Dey M, Dhume P, Sharma SK, et al. Folic acid: The key to a healthy pregnancy - A prospective study on fetomaternal outcome. Tzu Chi Med J. 2023;36(1):98-102. doi:10.4103/tcmj.tcmj_110_23
