This article reviews clefts involving the lip with or without the palate (CLP±P) and isolated clefts of the palate (CP) from genetic and epidemiologic perspectives. Particular attention is given to management strategies to address issues arising in the neonatal period before the deformity is treated. The multidisciplinary team is especially important in tailoring care to the needs of the child. Regional specialist services are recommended during early childhood for infants who have CLP±P or CP.
After completing this article, readers should be able to:
Discuss aberrant orofacial development in cleft lip and palate.
Describe known genetic and environmental contributing factors to the development of nonsyndromic cleft lip and palate.
Discuss how to tailor care of the preterm infant to the presence of an untreated cleft lip or palate deformity.
Delineate the functional impact of cleft lip or palate on feeding, tooth development, and speech and language.
Clefts involving the lip with or without the palate (CLP±P) or isolated clefts of the palate (CP) are two of the most common congenital anomalies to affect the craniofacial region in humans (Fig. 1). The preterm infant who has a facial cleft requires prompt and tailored assessment to receive norms of neonatal care. Risks associated with compromised growth, inadequate nutritional intake, pulmonary aspiration, and interference with parental bonding necessitate careful management, especially before corrective surgery.
CLP±P affects between 1 in 700 and 1 in 1,000 live births. Both genetic and environmental factors have been implicated. CLP±P are usually isolated (80%) but can recur in families (16%) and can be a feature of 150 discrete syndromes. (1) Maternal smoking, alcohol intake, and certain drug regimens may also mediate genetic mechanisms. (2) Although phenotypic similarities can exist, CLP±P and CP are considered distinct conditions because cosegregation is rare within individual families. However, both conditions can be seen in association with craniofacial syndromes or in isolation. (3)(4) The severity of the parental defect does not relate to the incidence in offspring.
CLP±P occurs 50% more frequently in Asian populations than white and twice as commonly in white than African American populations. CLP±P is also sex-related, occurring nearly twice as often in boys than girls. Isolated CP, however, occurs slightly more commonly in girls than boys and equally in all races. (5)
A benchmark population study of Northern European children (6) assessed the relationship of nonsyndromic facial clefts (n=843) with infant growth compared with controls (n=>2,000,000). Isolated CP and CLP±P, but not isolated cleft lip (CL) were associated with reduced body weight and body length. Infants who had bilateral CLP±P were significantly smaller and lighter than those who had unilateral CLP±P. Further, CLP±P was associated with an increased likelihood of prematurity and isolated CP and CLP±P were associated with being small for gestational age, defined as being below the 10th percentile for gestational age on standard growth charting.
Disruption in the normal mechanisms involved during early embryologic development of the face (4)(7)(8)(9)(10) can produce facial clefts. In recent years, much progress has been made in elucidating the molecular mechanisms underlying early facial development, largely using mouse models. (11) These investigations have relied on increasingly sophisticated gene targeting experiments to demonstrate the activity of numerous molecular signaling pathways (Hedgehog, Wnt, transforming growth factor, fibroblast growth factor) during development of the early face and palate and provide a database of loci for investigating the genetic basis of human cleft conditions (Tcof1, Satb2, Msx1, Sox9, Pax9, Tbx1). (11)(12) Genes have been identified that are responsible for mendelian syndromic disorders associated with CLP±P, including van der Woude syndrome (IRF6) (13) and CLP±P-ectodermal dysplasia (PVRL1); (14) syndromic CP, including Treacher Collins syndrome X-linked CP (TBX22); (15) and rare ectodermal dysplasia-type mixed clefting syndromes, such as ectrodactyly–ectodermal dysplasia–cleft syndrome (p63). (16)(17)
Despite the identification of these syndromes, orofacial clefting most commonly occurs in isolation in children who have no other anomalies. Such forms of clefting are complex multifactorial conditions, the product of both genetic and environmental factors that influence embryogenesis and, in particular, facial development at the relevant developmental stage. A number of environmental factors have been implicated in clefting, including exposure to therapeutic agents (phenytoin), alcohol consumption, cigarette smoking, and maternal nutritional status. (18)
Although less is known about the genetic basis of nonsyndromic CLP±P and CP, advances in DNA sequencing techniques have supported progress, particularly for CLP±P (Table 1). It has been estimated that up to 14 interacting loci may be involved in nonsyndromic CLP±P, (19) and single nucleotide polymorphisms in the fibroblast growth factor pathway might account for up to 5% of cases. (20) Mutations in IRF6, the causative gene in van der Woude syndrome, one of the most common causes of syndromic CLP±P, have also been associated with isolated CLP±P. (21) More recently, genome-wide association studies have identified a number of susceptibility loci for nonsyndromic CLP±P on chromosomes: 8q24, (22)(23) 10q25.3, and 17q22. (24) There has been much less success in identifying loci for nonsyndromic CP, although TBX22 has been demonstrated as a causative locus for nonsyndromic CP in several populations. (25)(26) This demonstrates the potential importance of several loci in causing both syndromic and nonsyndromic forms of orofacial clefting. (9)
Robbins and associates (27) suggest that prenatal detection by screening ultrasonography at 20 weeks' gestation may facilitate preparations for the feeding requirements of neonates who have clefts. Unfortunately, their series and a further series from the United Kingdom (28) in the last decade report a CLP±P prenatal diagnosis rate in newborns of only 28% and isolated CP diagnosis rate that is negligible. Further, they report that a diagnosis of CLP±P did not result in birth planning in the regional center or improve overall parental satisfaction with cleft management care.
If a facial cleft is not identified by prenatal screening scan, the CL will be identified in the immediate postnatal period. Intraoral examination (ie, inspection and palpation with finger) (Fig. 2) performed during a routine newborn examination allows identification of CP as well as milder variants such as a bifid uvula or submucosal clefting.
When CP is diagnosed, further systemic examination is indicated because every sixth newborn who has the disorder may have additional malformations, such as congenital heart disease or urinary tract anomalies. (2) Rates of associated anomalies are even higher in newborns who have bilateral clefts.
The diagnosis of CLP±P should prompt referral to the nearest regional specialty center. Assessment by a member of a multidisciplinary specialist team is appropriate once the child is stable and preferably before discharge. Liaison with the specialist team during the perinatal phase is important to prepare both the child and the family for the plan of care and future surgical interventions.
The preterm infant who has a nonsyndromic form of CLP±P or CP requires prompt and tailored assessment to deliver norms of neonatal support. The neonatologist needs to retain a holistic approach to the child, giving priority to ventilation, feeding and nutrition, early diagnosis and treatment of recurrent infections, exclusion of associated anomalies, child-parent bonding, and developmental progress.
Airway and Ventilation
Ventilatory support is usually the priority immediately after delivery. Such support is particularly pertinent because both noninvasive and invasive ventilator support are often indicated in preterm infants. In the term infant, it may be possible to maintain an adequate airway by using the prone position.
Whether the CL is complete or not influences the delivery of nasal continuous airway pressure (CPAP). Incomplete CL does not prohibit effective delivery of CPAP via nasal prongs. Complete CL, however, is likely to contribute to a loss of CPAP and could interfere with stabilization of the infant. Adaptation of standard nasal apparatus with an oronasal resuscitation mask that covers the entire defect (Fig. 3) usually provides a good seal, although a slight increase of dead space can be expected compared with the use of standard nasal CPAP. (29)
Alternatively, to deliver CPAP for unilateral CLP±P, a section of nasopharyngeal tube (30) can be placed into the normally shaped nostril in conjunction with a well-fitting palatal plate (Fig. 4). Air leakage can be minimized by positioning hydrocolloid bandages over the cleft defect. Once a palatal plate is available to separate the nasal and oral cavities, conventional delivery of CPAP via a nasal mask is often possible.
In the early phase, safe and effective feeding, preferably by breastfeeding, becomes a concern. Infants younger than 34 weeks' gestation have variably developed orofacial reflexes that coordinate suck, swallow, and airway control. (31) Enteral nutrition support via a nasogastric or orogastric feeding tube is appropriate for extremely low-birthweight and very low-birthweight infants, regardless of the characteristic of the CLP±P defect. For preterm infants who have no clefts, introduction to oral feeding strategies (eg, non-nutritive sucking) is started after a gestational age of 30 weeks, when the synaptic maturation at the level of the brainstem has occurred.
Incomplete and complete CL generally do not interfere with effective lip seal during breastfeeding because the breast is manipulated to fill the defect. Further, patients who have isolated CP limited to the soft palate are relatively unimpaired and may respond to wider bottle teats, although feeding times maybe prolonged. (32)
Nutritive feeding is difficult in those who have CLP±P or complete CP because loss of negative pressure and effective tongue control of areola and nipple are not present. (33) This contributes to increased infant fatigue, prolonged feeding times, increased burping requirement, and poor weight gain. Practical solutions include the use of squeezable bottles and teats with wide apertures to provide sufficient flow rates or spoon feeding.
A Cochrane review (34) examining the role of various interventions to augment nutritional intake in neonates from birth (with no clear exclusion of preterm births) to 6 months of age found a statistically significant difference in weight at 6 weeks postsurgery in favor of breastfeeding when compared with spoon feeding. A weak but significant difference was found supporting the use of squeezable bottles versus rigid bottles. No significant difference in terms of weight increase, developmental progress, and parental satisfaction was seen between infants fitted with a maxillary plate and those who had no plate.
Parental anxiety may negatively affect the mother-infant bond and lead to further feeding difficulties. Lactation consultants, nurses, and therapists skilled in suck-and-swallow coordination may prove useful in supporting the mother and mitigating against the worst emotional sequelae in this situation. (35)
Palatal plates are custom-made acrylic prostheses that are retained by close adaptation to the intraoral palatal anatomy. Palatal plates may be prescribed by the cleft surgeon soon after birth until definitive palatal repair is undertaken at 8 months. The infant may require transfer to a specialist unit before such an appliance can be fabricated because the technical expertise of a dental prosthodontist may only be available in larger centers. Palatal plates may aid in preventing the development of abnormal suckling behaviors, maxillary segment collapse, superior tongue excursion, oronasal reflux, milk aspiration, and fatigue and inadequate caloric intake from prolonged feeding. In those who do not have clefts, plates may have a role in preventing permanent palatal grooving. (36)
Savion and Huband (37) detail fabrication of the palatal plate. The dental technician must be careful to avoid thermal trauma when using materials that set with an exothermic setting reaction. For the first 48 hours of use, the oral tissues should be monitored for ulcerations. A new appliance should be fabricated approximately every 3 months to keep up with the facial growth.
Evidence of associated maxillofacial abnormalities (Table 1) may contribute to upper airway obstruction. For infants who have Pierre Robin sequence, extreme micrognathia can produce retropulsion of the tongue base coincident with CP. Intubation and mechanical ventilation may be indicated during the neonatal period, although prone positioning is sometimes successful. Such infants may require earlier surgical intervention for stabilization.
Among syndromes associated with CP or CLP±P, van der Woude is the most common multiple malformation syndrome. Additional features in the oral cavity include hypodontia and missing central and lateral incisors, with 80% of affected children demonstrating lower lip pits. Velocardiofacial syndrome (22q11 deletion) is a separate entity from DiGeorge syndrome. Craniofacial problems in affected children include cleft of the secondary palate, velopharyngeal incompetence contributing to delayed speech development in later life, and retruded mandible with chin deficiency. Another syndrome associated with mandibular hypoplasia and clefts of the hard or soft palate and sometimes uvula is Stickler syndrome. As stated previously, all affected children benefit from a multidisciplinary, well-organized approach to treatment plans and long-term management (Table 2).
Timing of Surgery
To improve cosmetic appearance and aid oral feeding, primary repair of the lip is usually undertaken at 3 months of age postterm. Earlier intervention is generally avoided because of perceived risks of immaturity and increased technical difficulty with a smaller operating field. Few data support the optimal timing of lip repair in the preterm infant; such repair depends on the infant's size and condition and the degree of surgical expertise available for a patient of this size. Placement of tympanostomy tubes can be considered at the time of the repair or later, depending on the presence of middle ear effusion.
To maximize chances of achieving normal speech and hearing, correction of the CP is usually scheduled at approximately 8 months postterm. Delay beyond 1 to 2 years of age results in a high incidence of pharyngeal and glottal disarticulations. (38) Avoiding delay in repair is balanced by the concern that operating earlier may limit maxillary growth, although evidence is limited by confounding techniques and measurement strategies. (2) Middle ear pathologies occur less frequently after cleft closure.
Revision of the lip scar can be undertaken when it becomes a cosmetic issue for the child. Operative repair of palatal fistula and placement of tympanostomy tubes is frequently needed in the first 4 years after birth. Adenoidectomy should be avoided whenever possible. Physiologic involution of the adenoid tissue later in adolescence can produce speech hypernasality, which can be treated by a pharyngeal flap procedure. Bone grafting of the canine region of the maxilla is often necessary to facilitate eruption of the canines and is performed at approximately 8 to 9 years of age, when maxillary growth is near completion and before canine eruption.
Care for the preterm infant who has untreated CLP±P deformity must be tailored to the infant's size and clinical state. Multidisciplinary team work, with regular consultations with regional specialists, is critical to meet the various needs that present during early childhood.
American Board of Pediatrics Neonatal-Perinatal Medicine Content Specification
Know the incidence, genetics, evaluation, and management of cleft lip and palate.
Drs Tighe, Petrick, and Cobourne have disclosed no financial relationships relevant to this article. Dr Rabe has disclosed that she has an unrestricted grant from and is a consultant to MBR Optical Systems, Germany. This article does not contain a discussion of an unapproved/investigative use of a commercial product/device.
- Copyright © 2011 by the American Academy of Pediatrics
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