Assessing the adherence and acceptability to iron and folic acid compared with multiple micronutrient supplements during pregnancy: a cluster-randomized noninferiority trial in Cambodia.

BACKGROUND

The Cambodian Ministry of Health is exploring transitioning from iron and folic acid (IFA) to multiple micronutrient supplements (MMS) during pregnancy and is seeking rigorous evidence to inform this policy change.

OBJECTIVE

We aimed to assess the adherence and acceptability of MMS compared with IFA supplementation during pregnancy.

METHODS

We conducted an open-label cluster-randomized noninferiority trial across 48 health centers in Cambodia. A total of 1546 healthy pregnant individuals (18-45 y) were recruited at their first antenatal care (ANC) visit (<14 weeks of gestation) and randomized to 1 of 3 arms at the health center level: 1) IFA for 90 d (IFA-90, n = 515), the current standard of care; 2) MMS for 180 d via 1 180-tablet bottle (MMS-180, n = 516); or 3) MMS for 180 d via 2 90-tablet bottles (MMS-90, n = 515). Our primary outcome was the noninferiority of adherence rates of MMS-180 compared with IFA-90, assessed by tablet counts and compared against a predefined noninferiority margin of -15%. Mixed-effects linear regression models were used to estimate the mean difference (95% confidence interval [95% CI]) in adherence rates. Our secondary outcomes included the mean difference in ANC attendance between the MMS groups and the acceptability of MMS across 6 domains.

RESULTS

Overall, 88% of participants completed the trial, with high mean adherence rates across arms (91% for IFA-90, 95% for MMS-180, and 95% for MMS-90). The adjusted mean (95% CI) difference in adherence rates between MMS-180 and IFA-90 groups was 3.9% (1.7, 6.2). The adjusted mean (95% CI) difference in ANC visits for MMS-180 and MMS-90 groups was 0.0 (-0.1, 0.2) visits. The acceptability of MMS was positive (90%-100% "agreement" across 6 domains).

CONCLUSIONS

Both IFA and MMS were highly acceptable, yet adherence to MMS was superior to IFA. These findings support the transition from IFA to MMS in Cambodia. This trial was registered at Clinicaltrials.gov as NCT05867836.