Fewer infants with isolated cleft palate who had primary Surgery to close it at age 6 months had insufficient closure between their velum and pharyngeal walls later in childhood than infants who had surgery at 12 months, the TOPS clinical trial found.

Among 558 infants in Europe and South America, 8.9% in the 6-month surgery group versus 15% in the 12-month surgery group had insufficient Velopharyngeal function at age 5 (risk ratio 0.59, 95% CI 0.36-0.99, P=0.04), reported Carrol Gamble, PhD, of the University of Liverpool in England, and colleagues in the New England Journal of Medicine.

A greater percentage of the 6-month group had canonical babbling at age 1, but no clear differences were seen in other secondary outcomes. Postoperative complications were similar and few in both groups.

Even after palatal surgery, about 30% of children have symptoms of Velopharyngeal Insufficiency, leading to hypernasality, audible nasal emission, and inadequate intra-oral pressure to produce pressure consonants, Gamble and co-authors noted.

“Although analyses of large cohorts have suggested an association between later repair and poorer speech outcomes during childhood, there have been repeated calls for a definitive randomized, controlled trial to assess whether this association exists,” they wrote.

However, the TOPS findings should be interpreted in the context of the overall trial design, noted Raymond Tse, MD, of the University of Washington in Seattle, and Oksana Jackson, MD, of the University of Pennsylvania in Philadelphia, in an accompanying editorial.

In some cases, speech was evaluated after additional surgery was performed, they pointed out. Secondary surgery to treat velopharyngeal insufficiency occurred more in the 6-month group than in the 12-month group, which meant it was “unclear whether the better primary-outcome response was due to the initial timing of primary surgery or due to the increased occurrence of secondary surgery to treat velopharyngeal insufficiency,” they wrote.

“In addition, without standardization of the timing of secondary surgery, the trial is susceptible to treatment biases,” the editorialists observed.

The researchers randomized 281 and 277 infants into the 6-month and 12-month groups. All had isolated cleft palate and were medically fit for surgery at 6 months. Infants with severe developmental delay, syndromic cleft palate, congenital sensorineural hearing loss, structural middle-ear anomalies, or whose anatomy was considered unsuitable for one-stage closure with the surgical technique used were excluded.

Infants came from 23 centers in Europe and South America specializing in cleft lip and palate repairs from September 2010 to July 2015. Surgeons used the Sommerlad technique, and received in-person, written, and video training for it.

Velopharyngeal insufficiency was defined as a velopharyngeal composite score of 4 or higher on a scale of 0-6, with higher scores indicating greater severity.

Speech and language therapists assessed velopharyngeal insufficiency using a sum of scores from three components of single-word recordings: hypernasality, non-oral errors, and symptoms of velopharyngeal insufficiency. Using case report forms, speech recordings (audio and video), photographs, and impressions, they assessed secondary outcomes at 1, 3, and 5 years. These included velopharyngeal function, canonical babbling, articulation, postoperative complications, hearing level, middle ear function, dentofacial development, and growth.

In the 6- and 12-month groups, participants were, respectively, 40.9% and 40.7% male, 91.8% and 87.2% white. Overall, participants had more soft and hard palate clefts than soft palate clefts alone.

Gamble and colleagues reported that at 1 year, hearing sensitivity and middle-ear function appeared worse in the 12-month group, but these differences were not seen at 3 and 5 years. Growth at 1 year was no different between the groups. At 5 years, maxillary arch constriction appeared greater in the 6-month group, but this finding was not considered clinically meaningful. Three adverse events occurred in the 6-month group and one in the 12-month group, all had resolved at follow-up.

More children in the 6-month group required a secondary surgery for velopharyngeal insufficiency (9.7% vs 5.9%), but more children in the 12-month group needed a secondary surgery for fistula, Gamble and co-authors noted.

Speech was evaluated at age 5 without regard for additional interventions like speech therapy or secondary surgery for velopharyngeal insufficiency, the researchers acknowledged. Additional limitations included possible variations in surgical technique and the language-dependence of speech quality. The study also was underpowered to detect differences in safety between the two groups.