Periconceptional folic acid associated with an increased risk of oral clefts relative to non-folate related malformations in the Northern Netherlands: a population based case-control study.

Periconceptional folic acid has been associated with a reduced risk of neural tube defects, but findings on its effect in oral clefts are largely inconclusive. This case-control study assesses the effects of periconceptional folic acid on cleft risk, using complementary data from the Dutch Oral Cleft Registry and a population-based birth defects registry (Eurocat) of children and foetuses born in the Northern Netherlands between 1997 and 2009. Cases were live-born infants with non-syndromic clefts (n = 367) and controls were infants or foetuses with chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We analyzed type/timing/duration of supplement use related to traditional cleft categories as well as to their timing (early/late embryonic periods) and underlying embryological processes (fusion/differentiation defects). Consistent supplement use during the aetiologically relevant period (weeks 0-12 postconception) was associated with an increased risk of clefts (adjusted odds ratio 1.72, 95% confidence interval 1.19-2.49), especially of cleft lip/alveolus (3.16, 1.69-5.91). Further analysis systematically showed twofold to threefold increased risks for late differentiation defects-mainly clefts of the lip/alveolus-with no significant associations for early/late fusion defects. Effects were attributable to folic acid and not to other multivitamin components, and inclusion of partial use (not covering the complete aetiologically relevant period) generally weakened associations. In conclusion, this study presents several lines of evidence indicating that periconceptional folic acid in the Northern Netherlands is associated with an increased risk of clefts, in particular of cleft lip/alveolus. This association is strengthened by the specificity, consistency, systematic pattern, and duration of exposure-response relationship of our findings, underlining the need to evaluate public health strategies regarding folic acid and to further investigate potential adverse effects.

Measuring speech sound development: an item response model approach.

RESEARCH AIM: The primary aim of our study is to investigate if there is an ordering in the speech sound development of children aged 3-6, similar to the ordering in general language development. METHOD: The speech sound development of 1035 children was tested with a revised version of Logo-Articulation Assessment. The data were analyzed with the Mokken Scale Program (MSP) in order to construct scales with satisfactory scalability (H-coefficient) and sufficient reliability (rho). RESULTS: The majority of children over 4.3 years of age turned out to have mastered most speech sounds. An ordering was only found in the youngest age group (3.8-4.3 years of age), for the sounds of /r/ in initial and final position and /s/ in initial position. This resulted in a set of scales. The scales developed for /r/ (in initial and final position) and /s/ were moderately scalable (H>0.43) and reliable (rho>0.83), and independent of gender. Moreover, we found variation in the judgment of speech sound development, which may perhaps have been due to where exactly the examiner was positioned during the assessment procedure: in front of the child, or sitting beside the child. CONCLUSIONS: We could not detect an ordering for all speech sounds. We only found an ordering for /r/ in initial and final position and /s/ in initial position. In the Mokken analysis we conducted, these scales turned out to be moderately strong and reliable. Our research also underlines that speech sound development is judged not only in an auditory sense, but judgment also depends on the visual interpretation of the listener.

Limited evidence for the effect of presurgical nasoalveolar molding in unilateral cleft on nasal symmetry: a call for unified research.

BACKGROUND: In the past two decades, presurgical nasoalveolar molding has been applied increasingly in the care of patients with a cleft to improve nasal symmetry and facilitate closure of the lip and secondary rhinoplasty. Many cleft centers do not apply presurgical molding, because its effect is disputed. This review aims to quantify the effect of nasal symmetry in the long term. METHODS: A systematic review of the literature with the intention of performing a meta-analysis was performed. The search terms "cleft" AND ("molding" OR "moulding") were used in three databases. Twelve studies met the following inclusion criteria: (1) participants were humans with nonsyndromic unilateral cleft; (2) data concerning the effect of nasoalveolar molding on symmetry of the nose are reported or can be deduced; (3) article was written in English, German, or Dutch. RESULTS: The heterogeneity of the study designs, outcome variables, outcome variable expressions, follow-up periods, and inadequate data reporting made it impossible to calculate effect sizes and to perform a meta-analysis. All studies had a low Grading of Recommendations Assessment, Development and Evaluation level. Five studies reported exclusively positive effects on nasal symmetry, six studies reported mixed effects, and one study reported exclusively no effects. CONCLUSIONS: Results of studies of nasoalveolar molding are inconsistent regarding changes in nasal symmetry; however, there is a trend toward a positive effect. Studies concerning nasoalveolar molding in unilateral cleft lip, jaw, and palate are heterogeneous and lack adequate reporting. Recommendations for future research were provided to construct a consensus about the effect of nasoalveolar molding. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Nasal growth and maturation age in adolescents: a systematic review.

OBJECTIVE: To define the end of the nasofacial growth spurt in order to schedule rhinoseptoplasty in patients with cleft without disturbing nasofacial growth. DATA SOURCES: We searched the PubMed and Cochrane bibliographic databases from inception through December 31, 2007, using the primary indexing term facial growth with the confining search terms growth AND (face OR nose) AND (cephalometry OR anthropometry). The reference lists of the retrieved articles were searched for missed relevant studies. Articles written in English, German, or Dutch were included in the review. STUDY SELECTION: Studies of white adolescents without genetic disorders or malformations whose growth patterns had been followed up from at least 12 years of age until 18 years of age, with intervals between relevant measurements not longer than 2 years, were selected for this review. DATA EXTRACTION: A reviewer performed data extraction by obtaining raw study data from the selected studies or by requesting them from the authors. DATA SYNTHESIS: Growth velocity curves were fit to different relevant measures for nasofacial growth. The end of the nasofacial growth spurt was defined as the age at which these growth velocity curves have their steepest descending slope. This definition yielded an average age of 13.1 years for adolescent girls and 14.7 years for adolescent boys. Because no information could be found for the spread in age of nasal growth spurt of individuals, 2 SDs of the age distribution for body height growth velocity were added. This resulted in 98% of white adolescent girls being nasally mature at the age of 15.8 years and 98% of white adolescent boys being nasally mature at the age of 16.9 years. CONCLUSION: Rhinoseptoplasty can safely be performed after the age of 16 years in girls and 17 years in boys.

The ordering of milestones in language development for children from 1 to 6 years of age.

PURPOSE: To scale language milestones in a group of 527 children to provide an instrument for screening language development. Procedure The questionnaire regarding these milestones was completed by parental report. It was evaluated whether the scaled milestones satisfied the assumptions of the Mokken item response model. RESULTS: The scalability of the final scale of 14 milestones was strong (H = .95), its reliability was high (rho = .96), and it satisfied the assumptions of the Mokken model. CONCLUSIONS: A single, unidimensional scale of diverse milestones was developed. It taps lexical, syntactic, and phonological skills, as well as both receptive and expressive language skills, and is well suited for mapping progress in language ability.

Does the interaction between maternal folate intake and the methylenetetrahydrofolate reductase polymorphisms affect the risk of cleft lip with or without cleft palate?

Periconceptional folic acid supplementation may reduce the risk of cleft lip with or without cleft palate (CL(P)). Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene reduce availability of 5-methyltetrahydrofolate, the predominant circulating form of folate. To determine the effect of MTHFR C677T and MTHFR A1298C genotypes and haplotypes on CL(P) risk and the interaction with maternal periconceptional dietary folate and folic acid supplement intake, the authors conducted a case-control triad study in the Netherlands (1998-2000) among 179 CL(P) and 204 control families. Infant and parental MTHFR C677T and MTHFR A1298C genotypes and haplotypes were not associated with CL(P) risk in the case-control and transmission disequilibrium test analyses. Mothers carrying the MTHFR 677TT genotype and who either did not use folic acid supplements periconceptionally or had a low dietary folate intake, or both, had an increased risk of delivering a CL(P) child (odds ratio (OR) = 5.9, 95% confidence interval (CI): 1.1, 30.9; OR = 2.8, 95% CI: 0.7, 10.5; OR = 10.0, 95% CI: 1.3, 79.1, respectively). No supplement use, low dietary folate intake, and maternal MTHFR 1298CC genotype increased the risk of CL(P) offspring almost sevenfold (OR = 6.5, 95% CI: 1.4, 30.2). Thus, the detrimental effect of low periconceptional folate intake on the risk of giving birth to a CL(P) child was more pronounced in mothers with the MTHFR 677TT or MTHFR 1298CC genotype.

Short-term and long-term results of speech improvement after surgery for velopharyngeal insufficiency with pharyngeal flaps in patients younger and older than 6 years old: 10-year experience.

Velopharyngeal insufficiency (VPI) is a well-known cause for hypernasality. To overcome this problem, the authors use a static surgical technique: a cranially or caudally based flap. In 93 patients, the results of this technique on speech (hypernasality, nasal air escape, articulation) and velopharyngeal function were evaluated over a period of at least 1 year. In 53 patients, pharyngoplasty flaps were based caudally. In 40 patients, pharyngoplasty flaps were based cranially. The patients were age 2.5 to 24.5 years, with a mean of 5.5 years (SD: 4 years and 2 months). Improvement was found in almost all patients. The patients who underwent surgery when they were younger than age 6 significantly improved better then the patients who were treated when they were older than age 6. There were no differences in outcome between cranially based and caudally based flaps. There were also no differences between patients with plain VPI and patients with VPI (e.g., Pierre Robin sequence and Shprintzen).

A 10-year review of perioperative complications in pharyngeal flap surgery.

A 10-year retrospective study was undertaken to investigate perioperative complications in pharyngeal flap surgery in one institution using inferiorly and superiorly based flaps. In this fashion the current practice of surgical technique based on local findings and perioperative care, through regular monitoring by experienced nurses on the ward, was evaluated for adequacy. The charts of 275 patients who had 287 pharyngeal flap procedures were studied. Demographics, type and duration of operation, associated procedures, surgeon, anesthetist, duration of hospital stay, associated medical conditions, and perioperative complications such as bleeding, respiratory insufficiency, or flap dehiscence were evaluated. In this series a total complication rate of 6 percent was found, with 2.4 percent early (<6 weeks) and 3.8 percent late (>6 weeks) complications. Only two patients (0.7 percent) had postoperative bleeding requiring reoperation, and one patient (0.3 percent) needed reintubation. The most frequent complication was flap dehiscence in nine patients (3.1 percent), which occurred early in three and late in six. Pharyngeal flap surgery can be performed safely with very few complications provided the correct experience and infrastructure are present. Careful surgery, in conjunction with adequate anesthesia and postoperative monitoring, makes these procedures safe and rewarding.