The Effect of Intermittent Antenatal Iron Supplementation on Maternal and Infant Outcomes in Rural Viet Nam: A Cluster Randomised Trial

Cluster randomized controlled trial conducted in Ha Nam Province, Viet Nam. 1,258 pregnant women (<16 weeks gestation), aged 16+, from 104 rural communes; inclusion: residence in trial communes and registration with a commune health station; exclusion: high-risk pregnancy or severe anemia; communes randomized to three arms: daily IFA, twice weekly IFA, and twice weekly MMN; follow-up through birth and 6 months postpartum; outcomes included birth weight, maternal Hb and ferritin at 32 weeks, and infant cognitive development at 6 months (BSID III).

Daily IFA: 60 mg elemental iron + 0.4 mg folic acid per tablet; 1 tablet daily (7 tablets/week); from enrolment until 3 months postpartum. Twice weekly IFA: 60 mg elemental iron + 1.5 mg folic acid per capsule; 2 capsules per week; from enrolment until 3 months postpartum. Twice weekly MMN: 60 mg elemental iron + 1.5 mg folic acid plus UNIMMAP micronutrients per capsule; 2 capsules per week; from enrolment until 3 months postpartum.

Primary outcome (birth weight) showed no clinically important difference between twice weekly IFA or MMN and daily IFA. Twice weekly IFA vs daily IFA: MD 28 g; 95% CI 222 to 78. Twice weekly MMN vs daily IFA: MD 236.8 g; 95% CI 282 to 8.2. At 32 weeks, ferritin was lower in twice weekly groups vs daily IFA (GM ratios 0.73 and 0.62 respectively) with no Hb difference. At 6 months, cognitive development higher in infants of twice weekly IFA recipients versus daily IFA (MD 1.89; 95% CI 0.23 to 3.56); no robust difference for MMN. Head circumference smaller in twice weekly IFA vs daily IFA (MD -0.70 cm; 95% CI -1.26 to -0.14). Adherence higher in twice weekly IFA (96%) than daily IFA (91%), and lower in MMN (85%). Authors conclude intermittent regimens did not affect birth weight and may improve adherence; a cognitive benefit with twice weekly IFA requires further study and should be interpreted with caution.

Potential type I error due to multiple outcomes; some outcomes had low prevalence and the trial may be underpowered for those outcomes; higher loss to follow-up for birth weight in the daily IFA arm; head circumference measured in only 47% of infants; blinding was not possible for the daily arm, introducing potential bias; generalizability may be limited to similar rural settings in Viet Nam; cognitive outcomes at 6 months require cautious interpretation and longer follow-up.