Cleft lip and palate in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin: a morphological in vivo study

It is well-known that TCDD (2,3,7,8, tetrachloridedibenzo-p-dioxin) induces cleft palates (CPs) in pregnant C57BL mice. However, it is unclear if TCDD is a possible teratogen for cleft lip. We examined maxillofacial malformations including cleft lip in three animal strains: A/J mice, C57BL/6J mice and ICR mice. The A/J mouse develops cleft lip and palate spontaneously at a 5-10% rate. TCDD was administered in olive oil on gestation day (GD) 12.5 with gastric tubes at 10 microg/kg, 20 microg/kg, or 40 microg/kg to examine the dose-response, and on a single day from GD 8.5-14.5 to examine the timing effects of TCDD administration on lip and palate formation. Furthermore, the palatal shelf movements during GD 8.5-14.5 were observed with a stereoscopic microscope. All embryos had cleft palates when the TCDD was administered just before palatogenesis (GD11.5-GD12.5). With respect to the TCDD effects, there were large differences among the strains. In the A/J mice, the difference between a lethal dose and a dose that could induce a cleft palate was close. Cleft lips were not induced, even when the TCDD was given just before labiogenesis. Morphologically, both palatal shelves contacted perfectly along their lengths, but separated and formed cleft palates. In conclusion, TCDD is a strong inducer of cleft palates, and interferes with the fusion phase of the secondary palate, but has no effect on the lip.     

Morphological and immunohistochemical studies on cleft palates induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice

Morphological and immunohistological examinations were performed to reveal the mechanisms of cleft palate induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). ICR strain mice 8-10 weeks of age were used in the study. TCDD was administered in olive oil on gestation day (GD) 12.5 with gastric tubes at 40 microg/kg. From GD 13.5 to 16.5, palates were examined by scanning electron microscopy (SEM), hematoxyline-eosin (HE) staining, and immunohistochemical staining of FGFR1/2, TGF-beta3, MSX1 and LHX8. In the control group, both of the palatal shelves began elevating on GD 14.0 and finished within 6 h. After the elevation, all of the shelves had completely fused with each other on GD 14.5. In the TCDD-treated group, palatal shelves elevated 1 day later than in the control group. However, all palates had elevated by GD 15.0. After the elevation, the shelves contacted each other and fused; however, they were separated on GD16.0. HE staining showed that medial edge epithelium (MEE) was thinner in the TCDD group than in the control group. MEE observed under a high magnification (x2500) exhibited filopodia-like filaments and the cells were bulged in the control group. In contrast, in the TCDD group, no filaments were observed and the cells were flat with unclear boundaries. Immunohistologically, there were no characteristic findings except for FGFR1. FGFR1 was not expressed in the TCDD group after the fusion phase (GD 14.5). TCDD induces many morphological and molecular changes to MEE cells and causes cleft palates.     

Analysis of Palatogenesis in the Mouse with Exencephaly Induced by Cadmium Chloride

ABSTRACT It has been revealed that exencephalic mouse embryos were resistant to cleft palate induction when they were exposed to several teratogens known as cleft palate inducing agents. In the present study, palatogenesis in exencephalic mouse embryos, which were not exposed to cleft palate inducing teratogens, was observed. A single dose of 6 mg CdCl₂/kg body weight was intraperitoneally injected into pregnant Jcl:ICR mice at day 7.5 of gestation (plug day = day 0). Embryos were dissected from uterus at day 13.5 to 15.5, and the secondary palate was observed with a dissecting microscope or a scanning electron microscope (SEM). Of live embryos, 71.5% had exencephaly. Palatal shelves of exencephalic embryos were elevated earlier than non-exencephalic embryos, and there seem to be two modes of palatal fusion in exencephalic embryos. (1) "Parallel-shape." The anterior part of shelves were elevated at day 13.5. Distance between the opposite medial edges of both shelves decreased at the posterior part, and this closing proceeded to the anterior part, where the shelves began to fuse. (2) "V-shape." The posterior part of palatal shelves became closer at day 14.0 or day 14.25. The medial edge of both shelves began to fuse at this part, and this fusion proceeded anteriorly. The anterior parts of the shelves were elevated, and the medial edge of the anterior shelves was fused independently. It is suggested that these alterations of palatogenesis in exencephalic embryos are related to inhibitive mechanism(s) against cleft palate induction. Key words : palate, neural tube defects, skull, mice, cadmium     

Palatal Slit and Cleft Palate in Rats Treated with a Glucocorticoid 1. Teratogenicity of Dexamethasone

The sensitive period and the dose-response characteristics for dexametha-sone-induced cleft palate and palatal slit in rats were examined. Pregnant rats were injected subcutaneously with dexamethasone in a single dose of 2–6 mg/kg on one day between day 8 and 16 of the gestational period or once each day for two successive days (days 14 and 15 of gestation). All animals were euthanized on day 20 of gestation and the palatal condition of their fetuses was inspected after fixation under a dissecting microscope. The sensitive stage of palatal slit and cleft palate induction was determined and the dose-response relationship was analyzed by the log-probit transformation method.
No maternal lethality was elicited in any of the treatment groups. High frequencies of palatal slit and cleft palate were induced when dexamethasone was administered as a single dose on any individual day from day 12 to day 14 of gestation. Omphalocele and general edema were also found to be significantly more frequent in the high-dose group treated on days 12–14 of gestation. All groups treated showed a reduction in fetal body weight. The response data for palatal slit and cleft palate after administration of dexamethasone fitted to similar linear regression slopes, suggesting a similarity in the underlying mechanisms for palatal slit and cleft palate induction in rats. ED50 values were 3.48 mg/kg for palatal slit and 6.64 mg/kg for cleft palate. These findings indicate that dexamethasone treatment is effective in inducing palatal slit and cleft palate in rats, as well as in mice. Key words: glucocorticoid, dexamethasone, palatal slit, cleft palate, sensitive stage, doseresponse, rats     

Critical periods for the teratogenicity of immune-suppressant Leflunomide in mice

Leflunomide has inhibitory effects on dihydroorotate-dehydrogenase activity and protein tyrosine kinase activity. In the present study, a single dose of 50 mg/kg Leflunomide was administered to pregnant mice on one of gestation days (GD)6–11. Characteristic external malformations were craniofacial defects following dosing on GD7, cleft palate on GD9, cleft palate and limb and tail deformities on GD10, and limb deformities on GD11. Skeletal examination revealed cervical to caudal vertebral malformations after treatment on GD7, GD8, GD9 or GD10. In the viscera, cardiovascular deformities were observed in the GD7 and GD9 Leflunomide-treated groups. These results demonstrate that multiple malformations were seen in various organs and most of the malformations observed appeared to be developmental stage-specific responses to Leflunomide treatment.     

Organ culture of the fetal mouse palate for screening the developmental toxicity of chemicals: a validation study

Using in vitro organ culture of the fetal mouse palate in a chemically defined serumless medium, the toxicity of 24 chemical compounds was investigated. Explanted palates of day-12.5 mouse fetuses were exposed for 72 h in vitro to various concentrations of each chemical, and the fusion rate and growth parameters were compared between the experimental group and respective controls. The average rate of palate fusion was 84% in vehicle controls. For compounds that are teratogenic in experimental animals in vivo, the fusion rates of palatal shelves decreased as the concentration of the test chemicals increased, showing a dose-dependent relationship. Palate fusion was inhibited by 11 of the 15 in vivo teratogens, and the predictability of in vivo developmental toxicity in this culture system was 73%. Cyclophosphamide itself did not inhibit the growth and fusion of explanted palates, but supplementation of hepatic S-9 fraction and cofactors for a monooxygenase system converted it to a toxic substance, as was shown in other in vitro systems. The 50% inhibitory concentration (IC50) value calculated based on the fusion rate was also found to be a useful parameter for evaluating the developmental toxicity of drugs. The teratogenic risk in the human fetus could be assessed by comparing the minimal toxic concentrations of the test compound on cultured palates with the maximal plasma level in pregnant women under therapeutic conditions and with the plasma concentrations when its minimal teratogenic dose is given to pregnant mice. This organ culture system of the fetal palate should be useful for screening the developmental toxicity of drugs and other environmental agents, and its value should increase when it is used in combination with other battery test systems.     

Congenital anomalies induced by triamcinolone acetonide in murine embryos.

INTRODUCTION: We have studied the morphogenesis of anorectal malformations in mice using retinoids. Several investigators have reported an interaction between glucocorticoids and retinoids. It was supposed that glucocorticoids had some effects on the morphogenesis of murine embryos similar to retinoids. Therefore, we investigated alterations in the morphogenesis of murine embryos after triamcinolone acetonide (TAC) administration. MATERIAL AND METHODS: TAC was administered in a single dose (15 mg/kg or 30 mg/kg body weight) to pregnant ICR-SLC mice on embryonic day 7 (E7), 8, 9, and 10. They were sacrificed on E18, and fetuses were examined for internal and external malformations. Randomly chosen fetuses were embedded in paraffin for immunohistochemical staining of the glucocorticoid receptor (GR). RESULTS: The groups given 15 mg/kg TAC had one peak in the incidence of cleft palate on E9 (100 %) and the groups given 30 mg/kg TAC showed a biphasic pattern in the incidence of cleft palate on E7 and E10. No other anomalies were found. GR expression was marked in the subepithelial layer of palatal processes in the treated specimens. CONCLUSION: The group given 15 mg/kg TAC on E9 provided a good model of cleft palate in ICR-SLC mice, and cleft palate was probably induced by various factors including disturbance of the bone morphogenetic protein (BMP) signaling pathway, shown by GR overexpression.     

Tissue uptake of EGF receptor antisense oligonucleotides in organ culture of fetal mouse palates and their effects on in vitro palatogenesis

ABSTRACT To investigate the incorporation of oligonucleotides (ODNs) into the tissues of cultured fetal mouse palates and their effects on in vitro palatogenesis, we cultured day-12.5 fetal mouse palates in a chemically defined serumless medium supplemented with either antisense or sense ODNs to epidermal growth factor receptor (EGF-r). The EGF-r ODNs were found to be incorporated into the palatal tissue and remained detectable for at least 72 hr. Immunohistochemical and immunoblot analyses revealed that the treatment with 5μM EGF-r antisense ODN suppressed the production of EGF-r protein. No pathological change was observed in the explanted palates when they were treated with 5 μM EGF-r antisense or sense ODNs, but the treatment with 10 or 20 μM ODN caused pyknotic changes in the palatal epithelium, probably due to the ODN toxicity. The present results indicate that under optimal conditions, antisense ODNs to EGF-r can be incorporated into fetal organs cultured in vitro and specifically inhibit the production of EGF-r protein. Since the suppression of the production of EGF-r protein did not prevent the palate fusion, EGF and/or EGF-r alone may not play a critical role in palatogenesis, as suggested by previous studies. The antisense ODN technique could be of potential use for analyzing the roles of specific molecules in normal and abnormal morphogenesis.     

Delay in the Development of the Secondary Palate in Ay/a Mouse Embryos

The effects of the A^y gene on the normal development were investigated by using a inbred strain of C57BL/6 (a/a) and its congenic strain of C57BL/6-A^y (A^y/a) mice. Three mating groups (female× male), i. e., group I, a/a × a/a; group II, a/a × A^y/a; and group III, A^y/a × a/a, were set, and the rating of normal development was compared among the groups on gestation days 13, 14, 15 or 16 with special attention to the secondary palate. On day 13, the palates were wide-open and the palatal shelves were vertical in all embryos in all groups. In group I, both shelves became horizontal in 63.3% of the embryos on day 14. The incidences of embryos having completely closed palates were 95.8% and 100% on days 15 and 16, respectively. In group II, in which half of the embryos were expected to carry the A^y gene, the frequencies of shelf horizontalization on day 14 (31.1%) and of the complete closure on day 15 (74.3%) were significantly lowered as compared with those in group I, although the external morphological rating was comparable. On day 16, however, the palatal closure was completed in almost all embryos. In group III, in which maternal mice as well as half of their embryos carried the A^y gene, the external morphological rating was delayed as compared with that in either group I or II, and the frequencies of shelf horizontalization on day 14 and of the complete closure on day 15 were as low as 10.9% and 39.6%, respectively. The palatal closure was not yet completed in 15.3% of the embryos on day 16. These results indicate that the A^y gene causes a delay in shelf horizontalization and closure of the secondary palate of mouse embryos as compared with the a gene.     

Susceptibility of Day-12.5 and Day-13.5 Fetal Mouse Palates Cultured in Vitro to 5-Fluorouracil and Hydroxyurea

Abstract The maxillary regions of day-12.5 and day-13.5 ICR mouse fetuses were cultivated in a chemically-defined serumless medium by a suspension culture technique to examine the toxic effects of 5-fluorouracil (5-FU) and hydroxyurea (HU) on cultured palates and to compare the sensitivity of fetal mouse palates at different stages of development. The palates of day-12.5 and day-13.5 fetal mice were explanted and exposed in vitro for 72 hr to 0.1–50 μg 5-FU/ml or to 5–76 μg HU/ml. 5-FU inhibited the growth and fusion of day-12.5 palatal shelves in vitro dependently on its concentrations. Day-13.5 palates were significantly less sensitive to 5-FU than day-12.5 palates, and the minimal toxic concentrations (MTCs) of 5-FU were 0.1 and 10 μg/ml for day-12.5 and day-13.5 fetal palates, respectively. HU inhibited the in vitro growth and fusion of day-12.5 fetal palatal shelves in a concentration dependent manner, but only slightly suppressed the growth of day-13.5 fetal palates. The MTCs of HU were 19 and 76 μg/ml for day-12.5 and day-13.5 fetal palates, respectively. Therefore, day-12.5 fetal mouse palates (at stage-1 or earlier stages of palatogenesis) seemed significantly more susceptible to these teratogenic chemicals than day-13.5 fetal palates (at stages 2–3 of palatogenesis). The palates of day-12.5 ICR fetal mice may be more suitable than day-13.5 palates for in vitro teratogen screening and for the study of mechanisms of normal and abnormal palatogenesis.     

Variations in Palatal Rugae in Near Term Fetuses from Untreated Jcl:ICR Mice

ABSTRACT The oral surface of the mouse palate has eight or nine pairs of transverse ridges, or rugae. Abnormalities in the pattern of palatal rugae have been reported in mutant mice and mice exposed to teratogens in utero. The purpose of this study was to describe control data of ruga variations for proper definition of "anomalous" ruga patterns. Jc1:ICR mice on gestation day 18 were killed, and the fetuses were fixed in Bouin's solution. Fetal palates were examined under a dissecting microscope. In total, 251 fetuses from 19 dams were observed. Among these fetuses 88% had one or more variations in the palatal rugae. Common variations were supernumerary anterior to the fourth ruga, division, and lateral bifurcation, and these were regarded as variations in the "normal" range. Variations rare in fetuses from untreated dams were shortness, fusion, cross, and supernumerary posterior to the fifth ruga, and these should be defined as "anomalous" ruga patterns in teratology experiments. Key words: mouse, palate, rugae, developmental toxicity test     

Roles of retinoic acid signaling in normal and abnormal development of the palate and tongue

Palatogenesis involves various developmental events such as growth, elevation, elongation and fusion of opposing palatal shelves. Extrinsic factors such as mouth opening and subsequent tongue withdrawal are also needed for the horizontal elevation of palate shelves. Failure of any of these steps can lead to cleft palate, one of the most common birth defects in humans. It has been shown that retinoic acid (RA) plays important roles during palate development, but excess RA causes cleft palate in fetuses of both rodents and humans. Thus, the coordinated regulation of retinoid metabolism is essential for normal palatogenesis. The endogenous RA level is determined by the balance of RA‐synthesizing (retinaldehyde dehydrogenases: RALDHs ) and RA‐degrading enzymes ( CYP26s ). Cyp26b1 is a key player in normal palatogenesis. In this review, we discuss recent progress in the study of the pathogenesis of RA‐induced cleft palate, with special reference to the regulation of endogenous RA levels by RA‐degrading enzymes.     

In Vitro Developmental Toxicity of Aspirin and Its Major Metabolites on Cultured Fetal Mouse Palates

Palatal primordia of day-12.5 ICR mouse fetuses were cultured in a chemically-defined serumless medium by a suspension culture technique, and the developmental toxicity of aspirin and its metabolites on in vitro palatogenesis was studied. Explanted fetal palates were exposed in vitro for 72 hr to 0.5-2 mM aspirin (ASP), 0.25-2 mM salicylic acid (SA), 0.5-2 mM salicyluric acid (SUA), 1–2 mM 2,3-dihydroxybenzoic acid (3DHB), or 1–2 mM 2,5-dihydroxybenzoic acid (5DHB). After 72 hr culture, ASP at 2 mM and SA at 0.25 mM inhibited the growth and fusion of palatal shelves, and SUA at 1 mM prevented palatal fusion. On the other hand, 3DHB and 5DHB did not exert any significant toxic effects on cultured palates at concentrations up to 2 mM. Judging from the 50% inhibitory concentration (IC₅₀), SA (IC₅₀= 0.9 mM) was the most toxic of the 5 compounds tested, with a decreasing order of ASP (IC₅₀= 1.5 mM), SUA (IC₅₀= 1.6 mM), and DHBs (IC₅₀= over 2 mM for both 3DHB and 5DHB). With respect to developmental toxicity, cultured fetal mouse palates showed the susceptibility to aspirin and its metabolites which is intermediate between the susceptibility of rat embryos in vivo and that of postimplantation rat embryos cultured in vitro. The significance of fetal organ culture for evaluating developmental toxicity of chemicals is also discussed.     

Higher risk of orofacial clefts in children born to mothers with angina pectoris: A population‐based case‐control study

Previously an unexpected association of maternal angina pectoris (MAP) during pregnancy with a higher risk of orofacial clefts in their children was found. There were three objectives of this study: (i) to evaluate the validity of MAP‐diagnoses in the previous study and the recent history of mothers with MAP in a follow‐up study; (ii) to estimate the prevalence of other congenital abnormalities in the offspring of mothers with MAP; and (iii) to analyze the possible effect of confounders for the risk of orofacial clefts. The large dataset of population‐based Hungarian Case‐Control Surveillance System of Congenital Abnormalities, 1980–1996 was evaluated including 22 843 cases with congenital abnormalities and 38 151 controls without any defect. Twenty‐two cases (0.10%) and 12 controls (0.03%) were born to mothers with medically recorded MAP (odds ratio [OR] with 95% confidence interval [CI]: 3.7, 1.8–7.3). Of 22 cases, six had isolated cleft lip ± palate (OR with 95% CI: 13.3, 4.9–35.9) and two were affected with isolated cleft palate (OR with 95% CI: 10.5, 2.3–47.6). The diagnosis of MAP was confirmed in seven women visited at home in 2009–2010, two had recent myocardial infarction and five were smokers. There was no higher risk for other congenital abnormalities. In conclusion the higher risk of orofacial clefts was confirmed in the children of mothers with MAP and smoking may trigger the genetic predisposition of both MAP and orofacial clefts. However, the number of cases was limited and therefore further studies are needed to confirm or reject this theoretically and practically important observation.     

Molecular contribution to cleft palate production in cleft lip mice

Cleft palate following cleft lip may include a developmental disorder during palatogenesis. CL/Fr mice fetuses, which develop cleft lip and palate spontaneously, have less capability for in vivo cell proliferation in palatal mesenchyme compared with CL/Fr normal fetuses. In order to know the changes of signaling molecules contributing to cleft palate morphogenesis following cleft lip, the mRNA expression profiles were compared in palatal shelves oriented vertically (before elevation) in CL/Fr fetuses with or without cleft lip. The changes in mRNA profile of cleft palate morphogenesis were presented in a microarray analysis, and genes were restricted to lists contributing to cleft palate development in CL/Fr fetuses with cleft lip. Four candidate genes (Ywhab, Nek2, Tacc1 and Frk) were linked in a gene network that associates with cell proliferation (cell cycle, MAPK, Wnt and Tgf beta pathways). Quantitative real‐time RT‐PCR highlighted the candidate genes that significantly changed in CL/Fr fetuses with cleft lip (Ywhab, Nek2 and Tacc1). The results of these molecular contributions will provide useful information for a better understanding of palatogenesis in cleft palate following cleft lip. Our data indicated the genetic contribution to cleft palate morphogenesis following cleft lip.     

Comparison of low‐dose and high‐dose cosyntropin stimulation testing in children

Background: There is no consensus among pediatric endocrinologists in using low‐dose (LD) versus high‐dose (HD) cosyntropin to test for secondary/tertiary adrenal insufficiency. This paper compares LD and HD cosyntropin stimulation testing in children for evaluation of hypothalamic‐pituitary‐adrenal axis (HPAA) and suggests a new peak cortisol cut‐off value for LD stimulation testing to avoid false positivity. Methods: Data of 36 children receiving LD (1 µg) and HD (249 µg) cosyntropin consecutively during growth hormone (GH) stimulation testing were analyzed in two groups. Group A were patients who passed GH stimulation testing and were not on oral, inhaled or intranasal steroids (intact hypothalamic‐pituitary axis, n= 19). Group B were patients who failed GH stimulation testing and/or were on oral, inhaled or intranasal steroids (impaired hypothalamic‐pituitary axis, n= 17). Results: In group A, the mean peak cortisol response in LD cosyntropin was 18.5 ± 2.4 µg/dL and that for the HD cosyntropin was 24.8 ± 3.1 µg/dL (r: 0.76, P≤ 0.05). In group B, the mean peak cortisol response in LD cosyntropin was 15.7 ± 6.1 µg/dL and that for HD cosyntropin was 21.7 ± 7.9 µg/dL (r: 0.98, P≤ 0.05). When a standard cut‐off of 18 µg/dL was used, 37% of the patients with intact HPAA failed LD cosyntropin testing, but a cut‐off of 14 µg/dL eliminated false positive results. Conclusions: LD cosyntropin stimulation testing results should be interpreted cautiously when used alone to prevent unnecessary long‐term treatment. Using a lower cut‐off for LD (≥14 µg/dL) seems to avoid false positive results and still detects most cases of impaired HPAA.     

Delayed detection of cleft palate: an audit of newborn examination

Aims

To identify prevalence of delayed detection of cleft palate, and associated factors that could lead to improved identification at neonatal clinical examination.

Methods

Audit of hospital notes, parental questionnaire incorporating open ended questions, and telephone questionnaire of junior doctors in the referring hospitals incorporating fixed choice questions.

Results

Of 344 cleft palate patients without cleft lip or submucous cleft palate, the day the cleft was detected was recorded in 92%. Delayed detection, after the first day, was 28% overall, distributed as 37% with isolated cleft palate and 23% with syndromic cleft palate. Narrow V shaped clefts were more likely to be delayed in detection compared with broad U shaped clefts, as were soft palate clefts compared with hard palate clefts. Five with isolated cleft palates were not detected until after the first year. Babies born at home were unlikely to be detected on day 1. Symptoms were significantly increased in the delayed detection group for feeding problems and nasal regurgitation. A telephone questionnaire of trainee paediatricians in referring units revealed that digital examination was more commonly practised than visual inspection, and few recalled receiving specific instruction on examination of the palate.

Conclusion

Delayed detection of cleft palate was not uncommon, and the features of those more likely to be missed suggested digital examination was related. Trainee doctors and midwives should be instructed to inspect visually using a light and tongue depressor, then digitally if submucous cleft palate is suspected.     

Delayed detection of cleft palate: an audit of newborn examination.

AIMS: To identify prevalence of delayed detection of cleft palate, and associated factors that could lead to improved identification at neonatal clinical examination. METHODS: Audit of hospital notes, parental questionnaire incorporating open ended questions, and telephone questionnaire of junior doctors in the referring hospitals incorporating fixed choice questions. RESULTS: Of 344 cleft palate patients without cleft lip or submucous cleft palate, the day the cleft was detected was recorded in 92%. Delayed detection, after the first day, was 28% overall, distributed as 37% with isolated cleft palate and 23% with syndromic cleft palate. Narrow V shaped clefts were more likely to be delayed in detection compared with broad U shaped clefts, as were soft palate clefts compared with hard palate clefts. Five with isolated cleft palates were not detected until after the first year. Babies born at home were unlikely to be detected on day 1. Symptoms were significantly increased in the delayed detection group for feeding problems and nasal regurgitation. A telephone questionnaire of trainee paediatricians in referring units revealed that digital examination was more commonly practised than visual inspection, and few recalled receiving specific instruction on examination of the palate. CONCLUSION: Delayed detection of cleft palate was not uncommon, and the features of those more likely to be missed suggested digital examination was related. Trainee doctors and midwives should be instructed to inspect visually using a light and tongue depressor, then digitally if submucous cleft palate is suspected.     

Deformation of the palate in preterm infants

AIM—To investigate the effect of gestation, postmenstrual age, and orotracheal intubation on palate morphology.
METHODS—A prospective study was made of 76 newborn infants of 25 to 41 weeks'' gestation. Palate dimensions were measured on plaster models produced from serial palatal impressions. Palate size relative to that of the mouth was assessed using a ratio of palate depth to palate width (Palatal Index).
RESULTS—Palate depth and width were related to postmenstrual age and gestation. Palatal Index ranged from 0.15 to 0.57, indicating a wide variation in palate shape, but gestation and postmenstrual age had no effect. Prolonged intubation had a small effect, equivalent to an increase in palatal depth of less than 2 mm at 32 weeks'' postmenstrual age. The effect was transient.
CONCLUSION—Prolonged orotracheal intubation (>10 days) leads to a small and temporary increase in palatal depth. However, this is unlikely to account for palatal grooving, which is probably caused by an overgrowth of the lateral palatine ridges.