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

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