Nasoalveolar Molding in Cleft Care—Experience in 40 Patients from a Single Centre in Germany

Nasoalveolar molding (NAM) has gained wide acceptance and evidence in cleft therapy. However, standardized treatment protocols and experiences recorded from European centres are lacking. The results of 40 infants with cleft lip and palate treated with presurgical NAM according to the Grayson technique were analyzed. Standardized parameters of cleft width and nasal symmetry were measured in pre- and posttreatment plaster casts and in digitalized 3-dimensional STL models. Statistical analyses were performed by using Student´s t-test in a per-protocol manner. 27 out of 40 infants completed NAM and were analyzed. In 13 patients NAM was either temporarily interrupted or terminated prematurely due to skin irritations or lack of parental support. These cases were excluded from statistical analysis, resulting in a drop-out rate of 32.5%. Intersegmental alveolar distance (ISAD), intersegmental lip distance (ISLD), nostril height (NH), nostril width (NW) and columella deviation angle (CDA) were significantly changed in unilateral cleft lip and palate (UCLP) (n = 8). In unilateral cleft lip (UCL) (n = 9), only ISLD, NH and CDA were significantly changed. ISAD of the right and left side, ISLD of the right and left side, premaxilla deviation angle, nostril height and columella length were changed significantly in bilateral cleft lip and palate (BCLP) cases (n = 10). NAM is a suitable presurgical treatment modality. A positive effect has been seen in UCLP and BCLP infants, as compared with their birth status.     

On the symmetry of limb deficiencies among children with multiple congenital anomalies

In humans, unpaired organs are placed in a highly ordered pattern along the left-right axis. As indicated by animal studies, a cascade of signaling molecules establish left-right asymmetry in the developing embryo. Some of the same genes are involved also in limb patterning. To provide a better insight into the connection between these processes in humans, we analysed the symmetry of limb deficiencies among infants with multiple congenital anomalies. The study was based on data collected by the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS). Registries of the ICBDMS provided information on infants who, in addition to a limb deficiency, also had at least one major congenital anomaly in other organ systems. We reviewed 815 such cases of which 149 cases (18.3 %) were syndromic and 666 (81.7 %) were nonsyndromic. The comparisons were made within the associated limb deficiencies, considering the information on symmetry, using a comparison group with malformations associated not involved in the index association. Among the non-syndromic cases, the left-right distribution of limb deficiencies did not differ appreciably between limb deficiency subtypes (e.g., preaxial, transverse, longitudinal). The left-right distribution of limb anomalies did not differ among most types of non-limb anomalies, though a predominance of left-sided limb deficiencies was observed in the presence of severe genital defects - odds ratio [OR], 2.6; 95 % CI, 1.1-6.4). Limb deficiencies (LDs) were more often unilateral than bilateral when accompanied by gastroschisis (OR, 0.1) or axial skeletal defects (OR, 0.5). On the contrary, LDs were more often bilateral than unilateral when associated with cleft lip with or without cleft palate (OR, 3.9) or micrognathia (OR, 2.6). Specifically, we found an association between bilateral preaxial deficiencies and cleft lip, bilateral amelia with gastroschisis and urinary tract anomalies, and bilateral transverse deficiencies and gastroschisis and axial skeleton defects. Of 149 syndromic cases, 62 (41.6 %) were diagnosed as trisomy 18. Out of the 30 cases of trisomy 18 with known laterality, 20 cases were bilateral. In the remainder the right and left sides were equally affected. Also, in most cases (74.4 %) only the upper limbs were involved. In conclusion the left-right distribution of limb deficiencies among some non-limb anomalies may suggest a relationship between the development of the limb and the left-right axis of the embryo.     

National estimates and race/ethnic-specific variation of selected birth defects in the United States, 1999-2001

BACKGROUND: In the United States, birth defects affect approximately 3% of all births, are a leading cause of infant mortality, and contribute substantially to childhood morbidity. METHODS: Population-based data from the National Birth Defects Prevention Network were combined to estimate the prevalence of 21 selected defects for 1999-2001, stratified by surveillance system type. National prevalence was estimated for each defect by pooling data from 11 states with active case-finding, and adjusting for the racial/ethnic distribution of US live births. We also assessed racial/ethnic variation of the selected birth defects. RESULTS: National birth defect prevalence estimates ranged from 0.82 per 10,000 live births for truncus arteriosus to 13.65 per 10,000 live births for Down syndrome. Compared with infants of non-Hispanic (NH) white mothers, infants of NH black mothers had a significantly higher birth prevalence of tetralogy of Fallot, lower limb reduction defects, and trisomy 18, and a significantly lower birth prevalence of cleft palate, cleft lip with or without cleft palate, esophageal atresia/tracheoesophageal fistula, gastroschisis, and Down syndrome. Infants of Hispanic mothers, compared with infants of NH white mothers, had a significantly higher birth prevalence of anencephalus, spina bifida, encephalocele, gastroschisis, and Down syndrome, and a significantly lower birth prevalence of tetralogy of Fallot, hypoplastic left heart syndrome, cleft palate without cleft lip, and esophageal atresia/tracheoesophageal fistula. CONCLUSIONS: This study can be used to evaluate individual state surveillance data, and to help plan for public health care and educational needs. It also provides valuable data on racial/ethnic patterns of selected major birth defects.     

Influence of paternal age, smoking, and alcohol consumption on congenital anomalies

The potential effects of paternal exposures on fetal development are of great public and scientific concern, yet few epidemiologic studies have examined this association. Single live births from 1959 to 1966 among 14,685 Kaiser Foundation Health Plan members who participated in the Child Health and Development Studies were analyzed to assess the impact of paternal age, cigarette smoking, and alcohol consumption on the occurrence of birth defects in the offspring. Prevalence odds ratios for anomalies identified by age 5 were analyzed, contrasting exposed to unexposed fathers with adjustment for maternal age, race, education, smoking, and alcohol use. Advanced paternal age was associated with increased risk of preauricular cyst, nasal aplasia, cleft palate, hydrocephalus, pulmonic stenosis, urethral stenosis, and hemangioma. Father's cigarette smoking was more common among children with cleft lip +/- cleft palate, hydrocephalus, ventricular septal defect, and urethral stenosis. Alcohol use by the father was most positively related to the offspring's risk of ventricular septal defect. For both smoking and alcohol use, inverse associations were more common than positive associations. These data generally do not indicate strong or widespread associations between paternal attributes and birth defects. However, because of this study's imprecision, limited ability to isolate defects most likely to be of paternal origin, and the identification of several suggestive associations with age and smoking, further study of this issue would be of value.     

Recurrent cleft lip and palate in siblings of a patient with malabsorption syndrome, probably caused by hypovitaminosis a associated with folic acid and vitamin B(2) deficiencies

We present a woman with metabolic disorders secondary to malabsorption and renal disease who gave birth to a stillborn male fetus with left unilateral cleft lip and palate and a live born infant with left unilateral cleft lip and palate. We discuss potential cofactors that could be implicated in the abnormal embryonic process.     

Characteristics of the hearing loss in unilateral cleft lip and palate-influence on communication

Etiology of otitis media with effusion (OME) is still unclear and often described as multi-factorial. It is very usual finding in cleft palate population. We tested relationship between the hearing level, audiometric frequencies, aging and ear side in unilateral cleft lip and palate 101 children (UCLP) and subgroups of left (UCLP)(L) and right cleft side (UCLP)(R). Group of left ears is prone to higher frequency and more severe hearing disturbances than groups of right ears, with less chance of normalizing hearing level with aging. Characteristics of hearing loss level and its improvement, in UCLP children depend of cleft type, ear side and age group.     

Cancer Risk in Children and Adolescents with Birth Defects: A Population-Based Cohort Study

Objective

Birth defects are an increasing health priority worldwide, and the subject of a major 2010 World Health Assembly Resolution. Excess cancer risk may be an added burden in this vulnerable group of children, but studies to date have provided inconsistent findings. This study assessed the risk for cancer in children and young adolescents with major birth defects.

Methods and Findings

This retrospective, statewide, population-based, cohort study was conducted in three US states (Utah, Arizona, Iowa). A cohort of 44,151 children and young adolescents (0 through 14 years of age) with selected major, non-chromosomal birth defects or chromosomal anomalies was compared to a reference cohort of 147,940 children without birth defects randomly sampled from each state’s births and frequency matched by year of birth. The primary outcome was rate of cancer prior to age 15 years, by type of cancer and type of birth defect. The incidence of cancer was increased 2.9-fold (95% CI, 2.3 to 3.7) in children with birth defects (123 cases of cancer) compared to the reference cohort; the incidence rates were 33.8 and 11.7 per 100,000 person-years, respectively. However, the excess risk varied markedly by type of birth defect. Increased risks were seen in children with microcephaly, cleft palate, and selected eye, cardiac, and renal defects. Cancer risk was not increased with many common birth defects, including hypospadias, cleft lip with or without cleft palate, or hydrocephalus.

Conclusion

Children with some structural, non-chromosomal birth defects, but not others, have a moderately increased risk for childhood cancer. Information on such selective risk can promote more effective clinical evaluation, counseling, and research.     

Functional asymmetry in the face.

The possible existence of one-sided dominance in the face, similar to the phenomena of handedness and footedness, has been investigated by studying smiling pattern, movements of the angles of mouth, winking, platysma contraction, raising and everting the upper lip with dilatation of the nostril, and vertical wrinkling of the forehead, on 300 right-handed and 30 left-handed persons. The conclusions are as follows: 1. The large majority of persons investigated do not use the two sides of face equally. 2. Facial ambilaterality is a rare feature. 3. There is no clear-cut correlation between handedness and the dominant side of the face. 4. The greater percentage (58.66%) of right-handed persons show a left-sided smile and find it more convenient to perform almost all exercises with the left side of the face. A still greater percentage (73.33%) of left-handed persons shows a right-sided smile and a better performance of all exercises with the right side of the face. The contralateral relationship of handedness to the dominant side of the face is significant in the right-handed and more so, in the left-handed persons.     

Maternal age and non‐chromosomal birth defects,Atlanta—1968–2000: Teenager or thirty‐something,who is at risk?

OBJECTIVE: This investigation explored the association between maternal age and non-chromosomal birth defects to assess any increased risk associated with maternal age. METHODS: Birth defect cases were ascertained by the Metropolitan Atlanta Congenital Defects Program (MACDP), denominator information was obtained using birth certificate data. Infants with any chromosomal diagnosis were excluded. Effect estimates were calculated using 5-year maternal age categories with 25-29 years as the referent. Multiple logistic regression was used to adjust for maternal race, parity, infant sex, and birth year. RESULTS: A total of 1,050,616 singleton infants, born after > or = 20 weeks gestation in the five counties of metropolitan Atlanta from 1968 through 2000 who did not have a chromosomal abnormality and whose mother was 14 to 40 years old, were included in the analyses, 32,816 of them were identified with birth defects by the MACDP. Young maternal age (14-19 years) was associated with anencephaly (OR = 1.81, 95% CI = 1.30-2.52), hydrocephaly without neural tube defect (OR = 1.56, 95% CI = 1.23-1.96), all ear defects (OR = 1.28, 95% CI = 1.10-1.49), cleft lip (OR = 1.88, 95% CI = 1.30-2.73), female genital defects (OR = 1.57, 95% CI = 1.12-2.19), hydronephrosis (OR = 1.42, 95% CI = 1.11-1.82), polydactyly (OR = 1.29, 95% CI = 1.09-1.52), omphalocele (OR = 2.08, 95% CI = 1.39-3.12), and gastroschisis (OR = 7.18, 95% CI = 4.39-11.75). Advanced maternal age (35-40 years) was associated with all heart defects (OR = 1.12, 95% CI = 1.03-1.22), tricuspid atresia (OR = 1.24, 95% CI = 1.02-1.50), right outflow tract defects (OR = 1.28, 95% CI = 1.10-1.49), hypospadias 2nd degree or higher (OR = 1.85, 95% CI = 1.33-2.58), male genital defects excluding hypospadias (OR = 1.25, 95% CI = 1.08-1.45) and craniosynostosis (OR = 1.65, 95% CI = 1.18-2.30). CONCLUSIONS: Young and advanced maternal ages are associated with different types of birth defects. Underlying causes for these associations are not clear.     

Unilateral cleft lip repair

The marking of the medial lip segment of the Millard rotation advancement procedure for repair of the unilateral cleft lip has been altered in the uppermost portion by utilizing tissue from the columellar base. Once adequate length has been obtained, cutback is utilized at approximately 90 degrees. With adequate full-thickness release of this medial lip segment and subsequent rotation into the proper position, the C flap is advanced into the donor defect of the columellar base and is also used to lengthen the shortened columella on the cleft side. This results in placement of a scar that will closely simulate the "mirror image" of the noninvolved philtral column. Fifty-seven patients with unilateral cleft lip have been repaired utilizing this technique during the past 14 years. Several of these children have required secondary surgeries because of mucosal irregularities or residual nasal deformities, but none has required additional surgery because of inadequate rotation of the medial lip segment or for correction of any donor-site defect at the base of the columella.     

A comparative study of the skin envelope of the unilateral cleft lip nose subsequent to rotation-advancement and triangular flap lip repairs

The secondary nasal skin envelope asymmetries were studied after unilateral cleft lip repair using the original (obsolete) rotation-advancement (Millard I) and the triangular flap techniques (Bardach's modification). Secondary correction of the nasal deformity was not performed in either group. Our findings indicated that in both groups, vertical asymmetries of the nasal skin envelope were similar. The alar dome on the cleft side was depressed, the columella was shorter on the cleft side, and there was hooding at the nostril apex. The principal difference between the two lip repairs was observed in the horizontal dimension of the nasal skin envelope. The position of the alar base was more normal following the Millard I repair, while the triangular flap repair left the alar base laterally displaced. When considered together with flattening of the cleft alar dome, a horizontal skin-envelope deficiency from middome to lateral alar crease was produced in the Millard I group. More lateral positioning of the alar base after the triangular flap technique minimized this horizontal skin deficiency. The triangular flap technique produced a secondary nasal deformity that looked worse but was easier to correct. The clinical implications of these findings are discussed.     

Transverse relationships of the infraorbital foramina in cleft and noncleft individuals

An evaluation of the location of the infraorbital foramina in a transverse plane was undertaken by direct skull and radiographic measurements in unrepaired cleft palate and age- and sex-matched noncleft individuals. Physioprints were obtained on six dry skulls with left-sided clefts of the primary and secondary palates and on six age- and sex-matched noncleft palate skulls. The left infraorbital foramen was found to be significantly superior in a transverse plane to the right infraorbital foramen in the cleft palate skulls. No significant differences in transverse location of the infraorbital foramina were found in the cleft skull group based on differences in sex or age. Posterior-anterior cephalographs were obtained on 15 left unilateral cleft palate individuals and on age- and sex-matched noncleft palate individuals. The location of the infraorbital foramina in a transverse plane in the posterior-anterior cephalographs was found to be too variable to permit the use of parametric statistical tests. When the data on location of the infraorbital foramina were analyzed by a nonparametric statistical test it was found that the left infraorbital foramen was significantly superior to the right infraorbital foramen in the cleft palate individuals. The more superiorly placed infraorbital foramen on the cleft side was suggestive of a vertical deficiency of the maxilla on the cleft side.     

Regulation of gut and heart left-right asymmetry by context-dependent interactions between xenopus lefty and BMP4 signaling

The Lefty subfamily of TGFbeta signaling molecules has been implicated in early development in mouse, zebrafish, and chick. Here, we show that Xenopus lefty (Xlefty) is expressed both bilaterally in symmetric midline domains and unilaterally in left lateral plate mesoderm and anterior dorsal endoderm. To examine the roles of Xlefty in left-right development, we created a system for scoring gut asymmetry and examined the effects of unilateral Xlefty misexpression on gut development, heart development, and Xnr-1 and XPitx2 expression. In contrast to the unilateral effects of Vg1, Activin, Nodal, or BMPs, targeted expression of Xlefty in either the left or the right side of Xenopus embryos randomized the direction of heart looping, gut coiling, and left-right positioning of the gut and downregulated the asymmetric expression of Xnr-1 and XPitx2. It is currently thought that Lefty proteins act as feedback inhibitors of Nodal signaling. However, this would not explain the effects of right-sided Xlefty misexpression. Here, we show that Xlefty interacts with the signaling pathways of other members of the TGFbeta family during left-right development. Results from coexpression of Xlefty and Vg1 indicate that Xlefty can nullify the effects of Vg1 ectopic expression and that Xlefty is downstream of left-sided Vg1 signaling. Results from coexpression of Xlefty and XBMP4 indicate that XLefty and XBMP4 interact both synergistically and antagonistically in a context-dependent manner. We propose a model in which interactions of Xlefty with multiple members of the TGFbeta family enhance the differences between the right-sided BMP/ALK2/Smad pathway and the left-sided Vg1/anti-BMP/Nodal pathway, leading to left-right morphogenesis of the gut and heart.     

Lip height and lip width after extended Mohler unilateral cleft lip repair

The purpose of this study was to evaluate the symmetry in lip height and lip width after extended Mohler unilateral cleft lip repair, with long-term follow-up monitoring. In the Mohler repair procedure, Millard's C-flap is used to fill the entire defect created by the downward rotation of the medial lip element. Because a lateral advancement flap is not transposed into this defect, Mohler repair is often expected to produce a short lip. In a retrospective study of 120 patients, anthropometric measurements were made on black-and-white photographs. Of those patients, 49 met the study criterion of having a set of photographs taken 13 months or less postoperatively and another set taken at least 2 years postoperatively. The distance from the Cupid's bow peak to a line tangent to the base of the columella (lip height) and the distance from the Cupid's bow peak to the ipsilateral commissure (lip width) were measured with a Vernier caliper. The medial intercanthal distance was also measured, for standardization of all measurements. All values were normalized to the mean intercanthal distance at age 6, as reported by Farkas. Matched-pair test analyses were used to assess the statistical significance of differences in cleft-side versus non-cleft-side measurements for each group, as well as changes with time. No statistically significant difference in cleft side versus non-cleft-side lip height for the two groups or with time was observed (< or =13 months, p = 0.28; >2 years, p = 0.08; change with time, p = 0.69). Statistically significant differences in lip width between the cleft side and the non-cleft side were observed for both time groups. The average difference in lip width at 1 to 13 months was 8.6 percent (p < 0.001). The average difference in lip width at 2 years or more postoperatively was 5.8 percent (p < 0.001). In comparisons of early versus late measurements, it was noted that lip width significantly increased with time (mean, 0.91 mm; p = 0.035). The findings suggest that extended Mohler repair does not produce a short lip. Interestingly, lip width was observed to be significantly smaller on the cleft side in the immediate postoperative period. However, this deficiency was observed to decrease significantly during long-term follow-up monitoring.     

Ambient Air Pollution and Birth Defects in Brisbane,Australia

Background

Birth defects are a major public health concern as they are the leading cause of neonatal and infant mortality. Observational studies have linked environmental pollution to adverse birth outcomes, including congenital anomalies. This study examined potential associations between ambient air pollution and congenital heart defects and cleft lip or palate among births in Brisbane, Australia (1998–2004).

Methods

Ambient air pollution levels were averaged over weeks 3–8 of pregnancy among 150,308 births. Using a case–control design, we used conditional logistic regression and matched cases to 5 controls. Analyses were conducted using all births, and then births where the mother resided within 6 and 12 kilometers of an ambient air quality monitor.

Findings

When analyzing all births there was no indication that ambient air pollution in Brisbane was associated with a higher risk of cardiac defects. Among births where the mother resided within 6 kilometers of an ambient air quality monitor, a 5 ppb increase in O₃ was associated with an increased risk of pulmonary artery and valve defects (OR 2.96, 95% CI: 1.34, 7.52) while a 0.6 ppb increase in SO₂ was associated with an increased risk of aortic artery and valve defects (OR 10.76, 95% CI: 1.50, 179.8). For oral cleft defects among all births, the only adverse association was between SO₂ and cleft lip with or without cleft palate (OR 1.27, 95% CI: 1.01, 1.62). However, various significant inverse associations were also found between air pollutants and birth defects.

Conclusions

This study found mixed results and it is difficult to conclude whether ambient air pollution in Brisbane has an adverse association with the birth defects examined. Studies using more detailed estimates of air pollution exposure are needed.     

Anatomy of the nasal cartilages of the unilateral complete cleft lip nose

The purpose of this study was to disclose the relationship between the anomaly of the cartilaginous framework and the nasal deformity of cleft lip. The noses of six stillborn infants with unilateral complete cleft lip were carefully dissected. The size and weight of the lower lateral cartilages were measured to determine whether there was a significant difference between the normal and involved sides. The position of the nasal cartilages was observed, and the distance between them was measured to determine whether they were normal. The surgical dissection revealed that the lower lateral cartilages from both sides were asymmetrical in three dimensions, indicating the displacement of the lower lateral cartilage on the involved side. There was displacement of the cartilaginous septum and the upper lateral cartilage. The statistical evaluation did not demonstrate a significant difference between weight and size of the two sides. One of the major causative factors of nasal deformity is displacement of the nasal cartilages. There is no hypoplasia of nasal cartilage in newborn infants with cleft lip.     

National rates of birth defects among hospitalized newborns

BACKGROUND: The Healthcare Cost and Utilization Project (HCUP) family of hospital discharge databases offer an unprecedented opportunity to generate national estimates of newborn infants with birth defects. This report estimates national hospital admissions for newborn infants diagnosed with birth defects computed from HCUP and compares them to pooled prevalence figures computed from state birth defect surveillance systems. METHODS: HCUP-derived rates of 36 birth defects from 1997 through 2001 were compared to rates derived from pooled data reported by 26 state-based surveillance systems stratified by inclusion of elective terminations in case definitions. Rate ratios (RRs) were calculated for each birth defect by dividing the rate derived from HCUP by the rate derived from the relevant surveillance systems. RESULTS: HCUP newborn hospitalization rates for birth defects closely approximate pooled birth defect rates for surveillance systems that do not include elective terminations. HCUP rates were not significantly different for 35 of 36 defects. Overall, 20 HCUP rates were within 10% of state rates, 11 more were within 20% of state rates, and only 1 differed by more than 50%. HCUP rates compared most closely to state rates for cardiovascular (VSD RR = 0.98, ASD = 0.96, pulmonary valve atresia and stenosis = 0.92), orofacial (cleft palate RR = 1.10, cleft lip = 1.06), and genitourinary defects (obstructive genitourinary RR = 1.01, bladder exstrophy = 0.97). HCUP rates compared less favorably to rates derived from surveillance systems that included elective terminations. CONCLUSIONS: HCUP data approximate state-based surveillance system data for defects that are easily recognized in the newborn period and infrequently a cause for elective termination. HCUP data can be used to examine the impact of public health efforts on the number of infants born with birth defects as well as the cost and consequences of variations in the hospital management of birth defects.     

Radiographic analysis of the midface of a stillborn infant with a unilateral cleft lip and palate

The midface of a full-term stillborn infant with a right complete unilateral cleft lip and palate was studied with plain-film radiography and tomography, xeroradiography, and computerized axial tomography. Gross skeletal and soft-tissue deficiencies on the cleft side were evident as compared to the noncleft side and involved the entire bony maxillary complex and antrum, the orbit, and the nasal pyramid and intranasal structures. The area on the cleft side was 19 percent less than the noncleft side, and the maximal anteroposterior dimension was 16 percent less. The cleft bony palatal shelf was 12.5 mm wide compared to 20 mm on the noncleft side. The findings demonstrate the deficient and abnormal functional matrix inherent in the cleft condition.