Zelda Greene, Colm Pf O'Donnell, Margaret Walshe

Preterm infants (< 37 weeks' post-menstrual age (PMA)) are often delayed in attaining oral feeding. Normal oral feeding is suggested as an important outcome for the timing of discharge from the hospital and can be an early indicator of neuromotor integrity and developmental outcomes. A range of oral stimulation interventions may help infants to develop sucking and oromotor co-ordination, promoting earlier oral feeding and earlier hospital discharge. This is an update of our 2016 review. To determine the effectiveness of oral stimulation interventions for attainment of oral feeding in preterm infants born before 37 weeks' PMA. Searches were run in March 2022 of the following databases: CENTRAL via CRS Web; MEDLINE and Embase via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. Searches were limited by date 2016 (the date of the search for the original review) forward. Note: Due to circumstances beyond our control (COVID and staffing shortages at the editorial base of Cochrane Neonatal), publication of this review, planned for mid 2021, was delayed. Thus, although searches were conducted in 2022 and results screened, potentially relevant studies found after September 2020 have been placed in the section, Awaiting Classification, and not incorporated into our analysis. Randomised and quasi-randomised controlled trials comparing a defined oral stimulation intervention with no intervention, standard care, sham treatment or non-oral intervention (e.g. body stroking protocols or gavage adjustment protocols) in preterm infants and reporting at least one of the specified outcomes. Following the updated search, two review authors screened the titles and abstracts of studies and full-text copies when needed to identify trials for inclusion in the review. The primary outcomes of interest were time (days) to exclusive oral feeding, time (days) spent in NICU, total hospital stay (days), and duration (days) of parenteral nutrition. All review and support authors contributed to independent extraction of data and analysed assigned studies for risk of bias across the five domains of bias using the Cochrane Risk of Bias assessment tool. The GRADE system was used to rate the certainty of the evidence. Studies were divided into two groups for comparison: intervention versus standard care and intervention versus other non-oral or sham intervention. We performed meta-analysis using a fixed-effect model. We included 28 RCTs (1831 participants). Most trials had methodological weaknesses, particularly in relation to allocation concealment and masking of study personnel. Oral stimulation compared with standard care Following meta-analysis, it is uncertain whether oral stimulation reduces the time to transition to oral feeding compared with standard care (mean difference (MD) -4.07 days, 95% confidence interval (CI) -4.81 to -3.32 days, 6 studies, 292 infants; I2 =85%, very low-certainty evidence due to serious risk of bias and inconsistency). Time (days) spent in the neonatal intensive care unit (NICU) was not reported. It is uncertain whether oral stimulation reduces the duration of hospitalisation (MD -4.33, 95% CI -5.97 to -2.68 days, 5 studies, 249 infants; i2 =68%, very low-certainty evidence due to serious risk of bias and inconsistency). Duration (days) of parenteral nutrition was not reported. Oral stimulation compared with non-oral intervention Following meta-analysis, it is uncertain whether oral stimulation reduces the time to transition to exclusive oral feeding compared with a non-oral intervention (MD -7.17, 95% CI -8.04 to -6.29 days, 10 studies, 574 infants; I2 =80%, very low-certainty evidence due to serious risk of bias, inconsistency and precision). Time (days) spent in the NICU was not reported. Oral stimulation may reduce the duration of hospitalisation (MD -6.15, 95% CI -8.63 to -3.66 days, 10 studies, 591 infants; I2 =0%, low-certainty evidence due to serious risk of bias). Oral stimulation may have little or no effect on the duration (days) of parenteral nutrition exposure (MD -2.85, 95% CI -6.13 to 0.42, 3 studies, 268 infants; very low-certainty evidence due to serious risk of bias, inconsistency and imprecision). There remains uncertainty about the effects of oral stimulation (versus either standard care or a non-oral intervention) on transition times to oral feeding, duration of intensive care stay, hospital stay, or exposure to parenteral nutrition for preterm infants. Although we identified 28 eligible trials in this review, only 18 provided data for meta-analyses. Methodological weaknesses, particularly in relation to allocation concealment and masking of study personnel and caregivers, inconsistency between trials in effect size estimates (heterogeneity), and imprecision of pooled estimates were the main reasons for assessing the evidence as low or very low certainty. More well-designed trials of oral stimulation interventions for preterm infants are warranted. Such trials should attempt to mask caregivers to treatment when possible, paying particular attention to blinding of outcome assessors. There are currently 32 ongoing trials. Outcome measures that reflect improvements in oral motor skill development as well as longer term outcome measures beyond six months of age need to be defined and used by researchers to capture the full impact of these interventions.