The effect of short-term preoperative nutritional intervention for cleft surgery eligibility

**Background:** Children with orofacial clefts (OFC) are highly susceptible to malnutrition, with prevalence rates of 30–50% globally. Malnutrition increases the risk of wound healing complications and infections, making patients ineligible for surgery even when free surgical care is available. Ready-to-use therapeutic foods (RUTF) have proven effective for treating malnutrition in low- and middle-income countries (LMICs), but their effectiveness as a preoperative intervention for children with OFC had not been studied. This study assessed whether short-term RUTF supplementation could transition malnourished children with OFC who were initially ineligible for surgery into surgical candidates.

**Methods:** This prospective cohort study followed malnourished pediatric patients with OFC enrolled in a nutrition program across six countries (Ghana, Honduras, Madagascar, Malawi, Nicaragua, and Venezuela) from June 2017 to January 2020. Patients aged 6 months to 19 years with OFC and malnutrition (z-score ≤ -1) were included. Malnutrition severity was stratified as mild (z-score -1 to >-2), moderate (-2 to >-3), or severe (≤ -3). Patients received RUTF sachets (each containing ~500 kcal, 12.5 g protein, 29 g fat, 47 g carbohydrates plus micronutrients) with dosing determined by pediatricians based on weight, malnutrition severity, and follow-up feasibility. Families were advised to return every two weeks. The primary outcome was achieving adequate nutritional status (z-score ≥ -1); secondary outcome was receiving surgery. Weight-for-length z-score (WLZ) was used for children 0–23 months, weight-for-height z-score (WHZ) for 24–59 months, and BMI-for-age for children 2–20 years. Statistical significance was set at p < 0.05.

**Key Results:** Of 677 patients enrolled, 556 were included in analysis (mean baseline age 37 months, range 6–225 months). At baseline, 28.2% (n=157) had severe malnutrition, 21.0% (n=117) moderate, and 50.7% (n=282) mild malnutrition. The most common cleft type was cleft lip and palate (47.4%), followed by cleft lip only (37.7%), and cleft palate only (13.5%). A total of 324 patients (58.3%) returned for at least one follow-up visit. Of those, 207 (63.7%) achieved optimal nutritional status (z-score ≥ -1). Among those who recovered, 70.0% (n=145) had initially mild malnutrition, 14.5% (n=30) moderate, and 15.5% (n=32) severe. The mean time to achieve surgical eligibility was 6 weeks (range 1–103 weeks). By the second visit, the mean z-score increased from -2.5 (moderate) to -1.7 (mild) (p < 0.001). At the first follow-up, patients gained an average of 7.8% of initial body weight, with a strong positive correlation between number of visits and weight gain (r=0.89). By the 6th visit, the mean z-score for 44 returning patients reached the normal range (z > -1). Significant country-level differences were observed in both baseline malnutrition severity and improvement rates (p < 0.001). Madagascar showed significant improvement from -2.4 to -0.34 by the 2nd visit (p < 0.001), while Nicaragua improved from -1.7 to -1.0 (p=0.003), and Ghana from -2.7 to -1.9 (p=0.023). A total of 195 surgeries were confirmed. The average cost per patient was approximately $25 USD.

**Clinical Implications:** This study provides the first evidence that short-term preoperative RUTF supplementation is highly effective in treating malnutrition and enabling surgical eligibility in children with OFC in LMICs. The finding that over 60% of returning patients achieved surgical candidacy in an average of 6 weeks at low cost (~$25 per patient) has significant programmatic implications. The high proportion of mild malnutrition cases (50.7%) suggests many patients require only brief, low-intensity intervention. The partnership model between a non-governmental organization (Operation Smile), private sector (Birdsong Peanuts, MANA Nutrition), and local communities proved feasible across six countries on three continents. Key limitations include high loss to follow-up (41.7% did not return), lack of a control group, potential leakage of RUTF to other family members, and the COVID-19 pandemic halting surgical programs during approximately one-third of the study period. Despite these limitations, the findings support implementing large-scale, cost-effective preoperative nutrition programs to reduce disparities in surgical access for children with unrepaired clefts.