BACKGROUND AND PURPOSE:

• Previous studies have demonstrated
  • An association between smoking and fetal growth restriction
  • An association between smoking and low maternal folic acid levels
• Yusuf et al (JAMA Pediatrics, 2019) sought to determine the efficacy of higher-dose folic acid to prevent reduction in fetal size among smokers

METHODS:

• Randomized clinical trial (RCT)
• Participants
  • Active smokers based on self-report and cotinine biomarker
  • Aged 18-44 years
  • <21 weeks at study entry
• Exposures
  • Higher-dose group: 4 mg of folic acid per day
  • Standard-dose group: 0.8 mg of folic acid per day
• Both study groups received counseling on smoking cessation
• Primary outcomes
  • Infant birth weight
  • Infant status as small of gestational age (SGA): Defined as weights <10^th percentile of birthweight for their GA
  • Fetal growth restriction (FGR): Defined as fetal growth ratio <0.85 (ratio = observed birthweight to expected mean birthweight based on GA)
• Data analysis
  • Estimated relative risk of SGA birth and FGR
  • Estimated mean differences in birth weight
  • Regression models used to account for confounding

RESULTS:

• Intention-to-treat analysis was based on 312 study participants
• Study population
  • Baseline characteristics in both treatment groups were well matched except race
    • 11.1% in high dose vs 21.8% in low dose group were of ‘other’ race (neither white and black)
    • Variable controlled for in analyses
• Mean (SD) birthweight: 3059.0 (640.2) g | Incidence of SGA: 23.7% | Incidence of FGR: 29.2%
• Higher dose folic acid was associated with
  • Increased birthweight: Adjusted mean difference: 140.39g (95% CI, 1.63-279.15)
  • Decreased risk for FGR: RR 0.65 (95% CI, 0.46-0.93)
• For SGA, higher-dose group had a 31% lower risk of small for gestational age, but result was not statistically significant
• There was no elevated risk of adverse effects associated with higher-dose folic acid

CONCLUSION:

• Women who smoked but received higher-dose folic acid supplements had a statistically significant increase in birth weight
• Higher-dose folic acid group were also 35% less likely to have FGR
• The authors suggest that higher doses of folic acid may be a safe and effective way to minimize fetal growth risks for women who continue to smoke during pregnancy

Learn More – Primary Sources:

Comparing Folic Acid Dosage Strengths to Prevent Reduction in Fetal Size Among Pregnant Women Who Smoked Cigarettes

Related ObG Topics:

Does Smoking During Pregnancy Affect the Fetal Immune System?

Reduced Risk of Autism in Offspring Exposed to Folic Acid During Pregnancy

Does Folic Acid Decrease Preeclampsia Rates in Those at Risk?