A claim you hear on longevity podcasts

Does folic acid before pregnancy prevent neural tube defects?

The claim checked: Folic acid before pregnancy lowers the risk of neural tube defects Hear it at 17:31

What do the studies say?

Strong consensus for

Nine of ten studies found that folic acid lowers the risk of neural tube defects. These are birth defects of the spine and brain. The studies tested folic acid before and early in pregnancy, and they include the Cochrane reviews of trials. A pooled analysis put the risk at 0.38 times that of women who took none. One California study came after flour was fortified. It found pills added only a small benefit on top.

Computed from 10 studies that test this point, each judged by two readers, in full. 10 more studies are waiting for a full read and do not count yet.

What was said on the podcast?

“there's good evidence that folic acid deficiency increases the risk of having a neural tube defect in the baby”
Kathryn Gray, a guest on The Drive · 410 ‒ The biology of pregnancy: physiologic adaptation, childbirth, and long-term maternal health · 17:31 on YouTube
Episode check Insulin does the most for the newborn, the episode says. Ten studies split on it. 5 claims checked against 69 studies · 24 chapters not checked yet See the whole episode →
The point checked Strong consensus for

Taking folic acid before conception and in early pregnancy lowers the risk of neural tube defects in the baby

Agree 9

pooled analysis · 2015 · landmark

“Folic acid, alone or in combination with vitamins and minerals, prevents NTDs, but does not have a clear effect on other birth defects.”

Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst Rev
Who: Women who became pregnant or were 12 or fewer weeks pregnant, with (2033) or without (5358) a history of an NTD-affected pregnancy, in randomised or quasi-randomised trials in nine high-income and one low-middle-income country
PMID 26662928

pooled analysis · 2010

“A meta-analysis of these four studies produced an estimated risk ratio for the effect of folic acid supplementation on the incidence of NTDs of 0.38 (95% CI: 0.29–0.51; Figure 2 b).”

Folic acid to reduce neonatal mortality from neural tube disorders. Int J Epidemiol
Who: Pregnancies/neonates exposed to periconceptional folic acid supplementation or food fortification vs none (RCTs, cohort, and before-and-after population studies)
PMID 20348114

pooled analysis · 2010

“Folic acid, alone or in combination with vitamins and minerals, prevents NTDs but does not have a clear effect on other birth defects.”

Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev
Who: women planning pregnancy in randomised or quasi-randomised trials: 1949 with a prior NTD-affected pregnancy and 4156 with no history of NTDs
PMID 20927767

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other primary study · 2014

“Our results indicate that risk of neural tube defects is substantially attenuated in populations with higher red blood cell folate concentrations.”

Population red blood cell folate concentrations for prevention of neural tube defects: Bayesian model. BMJ
Who: Chinese women in the Community Intervention Project (1993-95) encouraged to take 400 ug/day folic acid when planning pregnancy, with red blood cell folate modeled from Folic Acid Dosing Trial participants
PMID 25073783

other primary study · 2015

“The first study, a nested case-control study conducted in an Irish population, found higher RBC folate concentrations in early pregnancy to be associated with a lower NTD risk ( 7 ).”

Optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects: World Health Organization guidelines. MMWR Morb Mortal Wkly Rep
Who: Women of reproductive age; evidence from an Irish nested case-control study and two Chinese population-based cohorts, plus US NHANES 2007-2012 data
PMID 25905896

other primary study · 2004

“The total annual rate of NTDs fell by 78% after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35, p < 0.0001).”

A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects. BMC Pregnancy Childbirth
Who: Newfoundland and Labrador population births (live births, stillbirths, terminations for NTD) 1976-2001; plus random samples of non-pregnant women aged 19-44 and seniors 65+ for diet and blood folate
PMID 15450123

other primary study · 2018

“Ensuring 400 μg/d intake of folic acid prior to pregnancy has the potential to increase the number of babies born without an NTD.”

Modeling the impact of folic acid fortification and supplementation on red blood cell folate concentrations and predicted neural tube defect risk in the United States: have we reached optimal prevention? Am J Clin Nutr
Who: nonpregnant US women aged 12-49 in NHANES 2007-2012 with RBC folate, supplement and dietary recall data
PMID 29767673

other primary study · 2004

“There was a significant reduction in the total (birth+fetal) prevalence of these cases after the folic acid supplementation in the first month of gestation.”

The primary prevention of birth defects: Multivitamins or folic acid? Int J Med Sci
Who: Hungarian women in a periconceptional RCT and a two-cohort controlled trial of a folic acid-containing multivitamin, plus a population-based case-control dataset (HCCSCA, 1980-1996) of malformed offspring and matched controls
PMID 15912190

other primary study · 2016

“Our study demonstrates that an estimated threefold greater reduction in the prevalence of NTDs would have been achieved if fortification of flour with folic acid had been adopted.”

Prevention of neural tube defects in the UK: a missed opportunity. Arch Dis Child
Who: Pregnancies (live births, late fetal deaths >20 weeks and terminations) with a neural tube defect recorded by eight regional congenital anomaly registers in England and Wales, 1991-2012
PMID 26681697

Partly agree 1

other primary study · 2010

“This study of California births, conceived after folic acid fortification of the food supply, found that periconceptional intake of folic acid-containing supplements was only modestly if at all protective against NTDs.”

Periconceptional nutrient intakes and risks of neural tube defects in California. Birth Defects Res A Clin Mol Teratol
Who: Mothers of fetuses and live born infants with spina bifida or anencephaly and of nonmalformed live born controls in Los Angeles, San Francisco and Santa Clara counties, California, deliveries 1999-2003 (after folic acid fortification); majority Hispanic
PMID 20740594

Disagree 0

None.

What else was said but not tested?

  • By the time a pregnancy is recognized it is too late to raise folate levels
  • Most people eating a balanced diet with fortified foods have adequate folate

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