Study setting

This research will take place at the NICU which is a 307-bed tertiary-level referral unit of the West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China. This study will be performed during the period from October 20, 2023, to October 20, 2025.

Eligibility criteria

Inclusion criteria

1.

Diagnosis as preterm, with a birth weight of less than 2500 g, and gestational age ranging from 29+0 to 34+6 weeks.

2.

Stability of vital signs.

3.

Absence of major congenital anomalies, such as congenital heart disease, or congenital digestive tract malformations.

4.

Requirement non-invasive ventilation support, including the use of a high-flow nasal cannula.

5.

Enrollment within the first 72 h of life.

Exclusion criteria

1.

Requirement of mechanical ventilation.

2.

Severe asphyxia.

3.

Prior enrollment in other studies.

4.

Diagnosis of necrotizing enterocolitis (NEC).

5.

Diagnosis of periventricular leukomalacia (PVL).

6.

Diagnosis of intracranial hemorrhage grade III or higher.

7.

Need for reinitiation of non-invasive ventilation support after the start of the OMIs.

There are termination criteria and they are as follows: (1) Occurrence of severe adverse events and complications during the trial. (2) Withdrawal of consent by the parents of the subject. Patients who enter the trial but fail to complete it due to any reason will be considered dropout cases. This includes cases where the doctor determines that the subject has withdrawn from the trial, as well as cases where the subject withdraws on their own, regardless of the timing or reason for withdrawal. All data on the infants will still be recorded.

Who will take informed consent?

The coordinating center will aid in obtaining consent for the research team to approach individuals who may qualify for participation. An eligible status will be determined by a research nurse, and she will also provide information about the study and ensure that signed informed consent is obtained.

Additional consent provisions for collection and use of participant data and biological specimens

N/A: There will be no collection of biological specimens as part of this trial.

InterventionsExplanation for the choice of comparators

The studies demonstrate that oral motor intervention conducted after discontinuing non-invasive ventilation for 48 h is effective [18, 19].

Intervention description

The specific intervention plan is shown in Table 1.

Table 1 Oral stimulation program [7] Early OMIs group

On the basis of routine care, we will implement an oral motor intervention program developed by American researcher Fucile, adapted for the Chinese context made by the domestic expert, Lv et al. [7, 15]. The program includes oral stimulation, which involves stimulation of the lips, cheeks, gums, and tongue, along with non-nutritive sucking. The intervention will start once the infant begins to receive milk and exhibits stable vital signs. It will be conducted once a day, for 15 min at a time, and will continue until the infant reaches full oral feeding and maintains it for 48 h without the need for tube feeding. The timing of each intervention is set for 15–30 min before any feeding session, within the hour of 8:00–18:00. All interventions will be performed by charge nurses who have received uniform training. If the infant experiences changes in their condition such as decreased oxygen saturation, bradycardia, or asphyxia, the intervention will be stopped.

Late OMIs group

The interventions for OMIs will be initiated 48 h following the discontinuation of nasal continuous positive airway pressure. The early OMIs group and the late OMIs are the same in every aspect, with the sole distinction being the difference in the start time.

Criteria for discontinuing or modifying allocated interventions

Modifying the allocation intervention is expected to be unlikely. Nevertheless, parents have the option to remove their preterm infant from the study at any time for any reason.

Strategies to improve adherence to interventions

Every possible endeavor will be undertaken to maintain the authenticity of the intervention. Before the study begins, individuals participating in the research will receive standardized training in accordance with the research manual. Only after passing the assessment will they be allowed to join the study. Any divergence from the protocol will be meticulously recorded, with an intervention fidelity checklist being completed by the research nurse at the conclusion of the procedure.

Relevant concomitant care permitted or prohibited during the trial

To ensure the accuracy and comparability of trial results, during the study, other unrelated oral motor rehabilitation treatments will be prohibited.

Provisions for post-trial care

Patients and their families will receive free consultation and follow-up during and after the research.

Outcomes Primary outcome

Transition time is defined as the number of days needed to progress from the initiation of feeding to the establishment of full oral feeding. In this study, full oral feeding is defined as achieving a feeding volume of 120 ml/(kg/day) without the necessity for tube feeding for at least 48 h [20]. The corrected gestational age (PMA) will be recorded both at the initiation of oral feeding and upon the achievement of full oral feeding.

Secondary outcomes

Feeding performance

This includes feeding efficiency, defined as the average milk intake per minute, and feeding effectiveness, which is the milk intake orally within the first 5 min divided by the ordered milk volume. Feeding performance will be observed at two distinct time points: the day on which full oral feeding is achieved and the day of discharge. Nursing staff who are not involved in the study will record the volume of oral intake and the duration of feeding, from which they will calculate both the feeding efficiency and effectiveness.

Oral motor function

The neonatal oral-motor assessment scale (NOMAS) will be used to evaluate the oral motor function of the study subjects. This scale evaluates the jaw and tongue function of newborns across three dimensions: normal sucking, disorganized sucking, and sucking disorders. Evaluations will be performed at baseline, weekly, upon achievement of full oral feeding, and at the time of discharge. The assessment is scheduled to take place daily between 9 a.m. and 10 a.m. During each assessment, the evaluator will also be required to record a 2-min assessment video for documentation and further analysis purposes.

Weight gain

Weight gain speed will be calculated as follows: [weight gain rate (g/kg /day)] = [1000 × ln(discharge weight/birth weight)]/(age at discharge  − age at return to birth weight).

Length of hospital stay

The length of hospital stay will be determined by recording the admission and discharge dates for each infant, allowing for calculation of the total duration of hospitalization.

Height and head circumference

Height and head circumference will be recorded both at admission and discharge.

Follow-up

The feeding performance, height, weight, head circumference will be evaluated at the corrected ages of 6 and 12 months and neurodevelopmental outcomes will be evaluated at the corrected ages of 18 to 22 months.

Safety indicators

Safety indicators in this study encompass the rate of adverse events occurring during the intervention period. Adverse events are defined as incidents related to this study that are unplanned, unexpected, or typically undesirable such as emesis, aspiration, oxygen desaturation, bradycardia, and other non-routine nursing incidents that may compromise child safety or elicit nursing complaints. Additionally, these incidents may also encompass asphyxiation, tachycardia, tachypnea, bradypnea, apnea, and oral infections.

Participant timeline

The timeline is presented in Table 2.

Sample size

The sample size was calculated using the online calculator available at http://powerandsamplesize.com/, based on the primary outcome measure of transition time—the duration time from the initiation of feeding to achieving full oral feeding. A two-sample independent means comparison method was applied for this calculation. The sample size calculation accounts are based on a type I error probability of 5% and a statistical power of 80%. According to our pilot study (n = 26), the mean transition times for the two groups were found to be μ1 = 11.36 days for the early OMIs group, μ2 = 13.40 days for the late OMIs group, with a σ = 4.99 days. The two groups were allocated in a 1:1 ratio; the initial calculation indicated a need for 126 participants per group. To account for potential dropouts or exclusions, the sample size was augmented by 10%, resulting in a total of 280 participants, or 140 participants per group.

Recruitment

Recruitment is currently in progress. We estimate an average enrollment of 12 participants per month based on the anticipated number of preterm admitted to the NICU and recruitment rates observed in our previous pilot studies. The research team will maintain daily checks of the electronic medical record system and communicate with the clinical team to identify infants who potentially meet the eligibility criteria, along with their parents. The research nurse will approach the eligible infants' parents, provide them with information, and obtain their consent.