This was a randomized, parallel-arm clinical trial with a 1:1 allocation ratio, conducted within a superiority trial framework. The study protocol was registered in the PACTR (Pan African Clinical Trial Register) under the identification number PACTR202310506519010. Ethical approval and written informed consent were obtained from the patients’ guardians.

The infants enrolled in the current study were selected according to the following criteria: (1) infants between 1 week and 3 months of age; (2) non-syndromic with no other medical conditions; and (3) complete UCLP.

Infants with syndromic CLP, incomplete UCLP, or bilateral CLP were excluded from the study. The research was carried out at a private maxillo-facial center, Innovinity Medical Hub, located in Heliopolis, Cairo, Egypt. This facility served as the sole center for PSIO treatment, follow-ups, and data collection. To exclude any cleft-associated syndromes, all infants underwent evaluation by a genetics specialist. This evaluation included a comprehensive review of family and medical histories along with a detailed clinical examination. During the examination, anomalies in the eyes, ears, skin tags, and both upper and lower limbs were assessed. Sixteen infants with complete UCLP were recruited and subsequently randomized for the study.

After the diagnosis and selection of eligible infants, written consent was obtained from the parents or caregivers to approve participation in the study and initiation of the treatment. Infants were then randomized to receive either a modified Grayson NAM appliance with a nasal stent or elastic-taped Dyna-Cleft with an external nasal elevator.

In the NAM group, the infant was securely held upside down in the parent/caregiver’s lap to facilitate the impression-taking of the maxillary arch. This was done using a custom-made tray of appropriate size, loaded with heavy-body rubber putty and a light-body rubber as a washout (Zetaplus System, Zhermack). Before taking the impression, a piece of gauze soaked in glycerin was placed in the cleft gap and secured with dental floss. Care was taken to ensure that all impression material was completely removed from the oral cavity once set, to prevent any blockage of the airways. The impressions were then cast in dental stone to create a master cast, on which the NAM plate was constructed using clear self-cure acrylic. The nasal stent component, included from the outset, was made from stainless steel wire (0.036-inch width) with an acrylic bulb at the end. Alongside the NAM plate and nasal stent, a dental conditioner was applied to the acrylic plate, and adhesive tape was used to approximate the lips and alveolar segments and to secure the plate in place. Patients were scheduled for weekly follow-ups, during which the NAM plate was modified by selectively grinding the acrylic in areas where movement was desired and adding a soft liner in the opposite areas. Adjustments to the position of the nasal stent were made at each visit to maintain the correct positioning and desired pressure.

In the DynaCleft group, the elastic adhesive DynaCleft tape was applied directly over the cleft area to bring the lips and alveolar segments closer together. An external nasal elevator was placed on the nostril of the affected side and secured with adhesive tape on the forehead. The tension from the elastic adhesive tape was maintained by progressively shortening the ends, and the nasal elevator was adjusted regularly to ensure it remained in the correct position. Infants in both groups attended weekly follow-up appointments for adjustments. The study lasted for at least 2 months, culminating in a surgical lip repair at 3 months of age. This procedure was performed by an experienced oral and maxillo-facial surgeon using the Delaire technique, which notably avoids the blind dissection of the alar cartilage [15]. The surgery took place in a specialized maxillo-facial hospital, not at the center.

The newly proposed core outcome set for anthropometric evaluations for PSIO in UCLP [14] served as the primary outcome of this study. Nine anthropometric measures were employed to assess the effectiveness of PSIO using extraoral measures targeting the nasolabial soft tissue esthetics. The measures are as follows: (1) Columella height: the vertical distance between the junction point of the columella to the philtrum and the superior medial point of the nostril apertures; (2) Nasal tip projection: the vertical distance between the nasal apex and the junction point of the columella with the philtrum; (3) Projection alar length: the vertical distance between the nasal apex and the alar grooves; (4) Width of the nostril: the horizontal distance between the inner lateral and medial borders of the nostril aperture; (5) Nasal basal width: the horizontal distance between the junction point of the columella to the philtrum and the point of the labial insertion of the nasal ala; (6) Angle of the columella: the angle formed from the tip of the columella to the junction point of the columella with the philtrum and the bisector of the reference line. The angle measurement is done on the affected nostril; (7) Cleft lip segment: it represents the cleft gap length presented by the distance between the medial point of the greater lip segment to the more medial point of the lesser lip segment; (8) Height of the noncleft lip: distance between the midpoint of the junction of the columella with the philtrum to the junction of the ridge and external cupid’s bow inside the noncleft lip; and (9) Height of the cleft lip: distance between the midpoint of the junction of the columella with the philtrum to the junction of the ridge and external cupid’s bow inside the cleft lip.

The extraoral measurements were taken in centimeters on both the affected (cleft) and unaffected (noncleft) sides, with the exception of the nasal tip projection and the cleft lip segment. These measurements are depicted in Fig. 1. Data were collected at baseline (T0) and after PISO treatment (T1) using standardized high-resolution images captured with a Canon EOS 2000D camera. The software tool imagemeasurement.online was utilized for these measurements. Each image included a ruler for photo calibration and standardization purposes. During the sessions, infants were seated on the lap of a parent or caregiver, and both frontal and basal extraoral views were captured at baseline and post-treatment.

In addition to the primary measures, the symmetry ratio was calculated as the ratio of the affected side to the non-affected side before and after PISO treatment. Improved symmetry is indicated by a ratio value approaching one [16]. Two blinded researchers conducted all the measurements. To ensure interobserver and intra-observer agreement, these measurements were repeated after 1 week by the same researchers.

The sample size was calculated based on a previous study [17] that assessed cleft lip height following PSIO treatment. The independent t-test was used, assuming a 5% level of statistical significance, 80% power, and an effect size of 1.95. Initially, the total sample size required was 12 infants. To accommodate a potential 25% dropout rate, this number was increased to 16. Consequently, with an allocation ratio of 1:1, each group consisted of eight infants. The sample size calculation was performed using G*Power software version 3.1.9.7 [18].

Sequence generation was performed using a computer-generated random number from the random.org website, maintaining a 1:1 allocation ratio [19]. Allocation sequence concealment was achieved through the use of opaque sealed envelopes, sequentially numbered and containing a folded paper with the name of the intervention. Implementation was conducted by a researcher who was blinded to the intervention, enrolling patients irreversibly into each group based on the contents of the envelope.

The current study employed a single-blind design. Outcome assessors were blinded, as they evaluated images that did not reveal the PSIO appliance being used. Due to the nature of the intervention, it was not possible to blind the operators or the parents of the patients.

The level of statistical significance was set at 5%. Statistical analysis was conducted using R and R Studio software [20,21]. Data were organized, manipulated, and summarized with the “tidyverse” R package [22]. Continuous data were presented as mean and standard deviation. The normality of the data distribution was assessed using the Shapiro-Wilk test function from the “rstatix” R package [23]. For intergroup comparisons at T1, the independent t-test was utilized. In contrast, the paired t-test was employed for intragroup comparisons between T0 and T1, as well as for the symmetry ratio intragroup comparison. These analyses were performed using the t-test function from the “rstatix” R package, with the “paired” argument set to true when necessary [23]. Effect sizes and their 95% confidence intervals were calculated using Cohen’s d effect size with the Hedge’s bias correction for small sample sizes. This was done using the Cohen’s d effect size function from the “rstatix” R package, again setting the “paired” argument to “true” for paired samples [23]. Results were tabulated using the “knitr” and “kableExtra” R packages [24,25]. Interclass correlation coefficients, which assess intra-observer and inter-observer reliability, were calculated using the intraclass correlation function from the “psych” R package [26]. Higher values (i.e., closer to 1) indicate greater reliability.

Interclass correlation coefficients were calculated to assess both intra-observer and inter-observer reliability. The reliability values for intra-observer measurements ranged from 0.76 to 0.87, while inter-observer measurements ranged from 0.79 to 0.89, indicating good reliability in all assessments.

Tables 2 and 3 present the measurement values for each group before and after PSIO treatment. Approximately half of the measurements (on both cleft and noncleft sides) demonstrated statistically significant improvement at T1 compared to baseline values, while the remaining measurements showed nonsignificant improvement.

Table 4 presents a comparison between the two groups at T1 (after PSIO treatment). The projection alar length (on both sides), the angle of the columella, and the nasal tip projection were statistically significantly greater in the DynaCleft group than in the NAM group.

Table 5 presents the symmetry ratios for each group by calculating the ratio of the affected side (cleft side) to the non-affected side (noncleft side) before and after treatment. While symmetry improved in both groups, significant enhancement was observed in only three measures.