Journal of Cleft Lip Palate and Craniofacial Anomalies

: 2023  |  Volume : 10  |  Issue : 1  |  Page : 26--30

Prenatal management in clefts

Harsha Vardhan1, Manju Lata Verma2,  
1 Department of Plastic Surgery, King George's Medical University, Lucknow, Uttar Pradesh, India
2 Department of Obstetric and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh, India

Correspondence Address:
Dr. Harsha Vardhan
Department of Plastic Surgery, King George's Medical University, Lucknow - 226 003, Uttar Pradesh


Cleft lip and palate is one of the most common craniofacial anomaly. The management of this entity has led to the development of the field of craniofacial surgery. Improvement in understanding of clefts and refinement in surgical techniques have improved the life of children with clefts. However, like with all congenital anomalies, the impulse is to look earlier. Fetal management of cleft lip and palate is an attractive avenue. In this paper we explore this less travelled road, to see the advances in the field of detection of cleft lip and palate in the fetus, and to see the current state of fetal surgery for cleft lip and palate.

How to cite this article:
Vardhan H, Verma ML. Prenatal management in clefts.J Cleft Lip Palate Craniofac Anomal 2023;10:26-30

How to cite this URL:
Vardhan H, Verma ML. Prenatal management in clefts. J Cleft Lip Palate Craniofac Anomal [serial online] 2023 [cited 2023 Jun 6 ];10:26-30
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The birth of a child is a landmark event, met with much anticipation and celebrated with much pomp. This practice is seen all over the world and even in different species. The child is considered auspicious, bringing joy to the house and converting a couple into a family. However, this celebration can be marred by the birth of a baby born with deformities. Cleft lip and palate are the most common craniofacial anomaly. The correction of this craniofacial anomaly has been attempted for ages, with newer techniques and a better understanding of biology opening new avenues of management. The early management of cleft is one such avenue that has opened. The improvements in antenatal detection techniques and the possibility of in utero interventions allow the management of these deformities to start even before the child has born. In this article, we shed light on the status of the management of the fetal cleft lip and palate. A review of literature was done initially, in PubMed and Google Scholar, using the keywords “Fetal” AND “Cleft lip” OR “Cleft Palate.” Search was then expanded by scanning the references from the included articles.


With the advancement in imaging modalities, it has become possible to diagnose cleft lip and palate antenatally. The standard antenatal ultrasound scan can be used to diagnose cleft lip and palate.[1] The Targeted Imaging for Fetal Anomalies scan is done in the second trimester to specifically evaluate the fetal anomalies at around 20 weeks of gestation. The usual two-dimensional (2D) scans can be used to detect the fetal clefts. These 2D scans observe the surface of the face and create an image of the face. The lip defects can be visualized on these images. Ultrasonography has evolved with the advent of three-dimensional (3D) scans that are better at picking up craniofacial anomalies.[2] These take multiplanar images, which are then processed to create and image of the face. This makes it a better tool for evaluation.

There are various signs of cleft lip and palate. Discontinuity of t[he orbicularis in the lip is an obvious sign of the cleft [Figure 1], [Figure 2]. A gap in the maxillary tooth-bearing segment shows the presence of a cleft alveolus, given the name of “maxillary gap sign [Figure 3], [Figure 4].”[3] The bilateral cleft lip and palate show a protruding premaxilla [Figure 4], which is distinctly visible. The coronal views of the face can show the cleft clearly. A normal uvula can be seen (equal sign) and is absent in the clefting of the palate [Figure 5], [Figure 6], [Figure 7]. Other software exist that assists in the same as the OmniView algorithm[4] and the 3D geometrical analysis.[5]{Figure 1}{Figure 2}{Figure 3}{Figure 4}{Figure 5}{Figure 6}{Figure 7}

Magnetic resonance imaging (MRI) is another modality that has been shown to be useful in the antenatal diagnosis of cleft lip and palate. Comparing the efficacy of ultrasound and MRI, it is seen that although 3D Ultrasound (USG) is as good as MRI for detecting cleft lip. Isolated cleft palate is difficult to detect by USG, with some Smarius et al. reporting detection rates ranging from 0% to 1.4%.[6] MRI has a clear advantage in this. MRI also helped detect other associated anomalies better and was found to be more useful in cases of multiple pregnancies.[7] The presence of the tongue within the cleft is suggestive of the Pierre Robin sequence.[8]

Although classically detected during the second trimester, the advancements in ultrasonography allow the deformity to be detected earlier. The first trimester ultrasound done at 11–14 weeks of gestation can be reliably used to detect cleft lip.[9],[10]

 Associated Anomalies

Cleft lip and palate, by itself, is not a life-threatening condition requiring the termination of pregnancy. The affected child is expected to survive and lead a fruitful life. However, it may be associated with other anomalies. In all instances, a deeper search for other anomalies needs to be done. This can be done by a systemic USG or an MRI, or it may require chromosomal analysis. An earlier detection of the anomaly is particularly useful in these instances as it allows time for the termination of pregnancy, which may be difficult if the ultrasound is done in the second trimester.

Gillham et al.[11] found that the associated anomalies were present in 9.8% of unilateral cleft lip and palate, 25% of bilateral cleft lip and palate, and 100% of midline clefts. They suggested that if rare craniofacial clefts are present, karyotyping is always performed. Maarse et al.[12] suggested that for isolated cleft lip, no further fetal evaluation was required. In cleft lip and palate, karyotyping was suggested. Midline cleft always required further assessment. If associated anomalies are detected, further evaluation may be done using karyotyping, multiplex ligation-dependent probe amplification, comparative genomic hybridization array, gene target sequencing, and exome sequencing.[13]


Nyberg et al.[14] classified fetal clefts into:

Cleft lip aloneUnilateral cleft lip and palateBilateral cleft lip and palateMidline cleft lip and palateFacial defects associated with the amniotic band.


The antenatal behavior affects the fetal morphology. In addition to the usual suspects of teratogenicity, children affected with neonatal abstinence syndrome have been shown to be associated with isolated cleft palate.[15] Neonatal abstinence syndrome is seen in children, whose mothers consumed opioids during pregnancy. This opioid crosses the placental barrier and reaches the child. After delivery, the child undergoes withdrawal symptoms due to cessation in the delivery of the opioid. This causes cleft palate by reducing the mobility of the fetus. The neck of the fetus remains flexed, thus not allowing the mandible to grow, resulting in a Pierre Robin-like sequence. Anabasine, a drug derived from Nicotiana glauca, which reduced fetal mobility in a similar way, is used to create cleft palates in animal models to study fetal surgery. Furthermore, research is targeted at the dopamine receptor pathways, implicated in fetal motility disorders and their management.[16]


It is known that the type of healing seen in fetal life is scarless healing. At some point of intrauterine life, this scarless healing is converted into the traditional healing by scar formation. It is an attractive prospect to utilize this property for repair of defects in utero. Theoretically, this would result in lesser scarring that seen in cases where the surgery is performed later in life.[17]

The field of fetal surgery was pioneered by Dr. Micheal Harrison from California, who performed an open surgery after exteriorizing the fetus. This required opening of the uterus to bring the baby out and repairing the problem. This had risks of premature labor, and there was a considerable risk of fetal loss. Hence, these surgeries were reserved for deformities in the presence of which normal continuation of life is not possible. His contribution was in the field of congenital diaphragmatic hernia. Other indications include congenital hydronephrosis due to lower urinary tract obstruction, congenital hydrocephalus, and meningomyelocele.[18] With the advent of fetoscopes and the progress in laser surgery, fetal surgery has become relatively safer.[19] The chances of fetal loss are still high. The results in twin-to-twin transfusion syndrome are encouraging.

The fetal surgery has been performed mostly in experimental animals. The usual animals used are goats and lambs. Midgestational sheep is perhaps the most frequently used animal for cleft surgery. Monkeys make better models, but ethical concerns prevent their use for fetal surgery readily.[20] Cleft can be created surgically of medically. Medically, they are made by administering anabasine. Surgically created clefts required another intervention for its creation. These clefts are then repaired either through exteriorization or endoscopically. There is a considerable risk for fetal mortality. The mechanisms postulated are direct trauma to the myometrium or the fetal membranes and premature prelabor rupture of the membrane with a decrease in uterine blood flow. Stelnicki et al.[21] compared the long-term effects of cleft surgery performed antenatally and postnatally, in an ovine model. They performed a straight-line repair and found a greater scarring, poorer cosmesis, and higher maxillary hypoplasia in postnatally repaired clefts. The presence of staples has been shown to lead to a poorer prognosis, and resorbable staples were suggested.

Fetal surgery for humans has been reported rarely. The first case was performed by Dr. Oritz Monasterio in 1997. Since then, a few reports exist. Fetal surgery, with all its risks, is currently considered unjustifiable in cleft lip and palate.[22] In general, the interest in fetal surgery has reduced from the peaks of the early 2000s, with the limitations of fetal surgery coming to the fore.

 Psychological Effect of Fetal Diagnosis

The diagnosis of cleft lip is a traumatic one for the parents. However, if this information is provided antenatally, the parents have a chance to process the information. They can understand the nature of the deformity, to educate themselves about it and, in general, be prepared to receive the child. Knowing that the deformity is treatable reassures the parent.[23],[24] In a survey-based analysis, Matthews[25] assessed the attitude of craniofacial surgeons toward prenatal counseling. It was found that most of the parents sought prenatal counseling for information. Abortion is an important aspect of this discussion, but it is infrequently sought. Prenatal counseling has not been shown to increase the rates of pregnancy.[26] The prenatal management of clefts is essentially multidisciplinary with the involvement of obstetrician, pediatrician, psychiatrist, plastic surgeon, and most importantly, the parents.[27]


The technological advances have opened new fields in the management of age-old ailments. The antenatal fetal cleft management is one such avenue. At present, the implications are diagnostic, but in the future may allow the antenatal correction of cleft anomalies.


The authors thank Dr. P. K. Srivastava Consultant Radiologist, Yashdeep Scan Centre, Lucknow, for providing the photographs included in this article.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Liu Y, Freitas Rda S, Magriples U, Persing JA, Shin JH. Fetal diagnosis of cleft lip: Natural history and outcomes. J Craniofac Surg 2008;19:1195-8.
2Lee W, Kirk JS, Shaheen KW, Romero R, Hodges AN, Comstock CH. Fetal cleft lip and palate detection by three-dimensional ultrasonography. Ultrasound Obstet Gynecol 2000;16:314-20.
3Lachmann R, Schilling U, Brückmann D, Weichert A, Brückmann A. Isolated cleft lip and palate: Maxillary gap sign and Palatino-maxillary diameter at 11-13 weeks. Fetal Diagn Ther 2018;44:241-6.
4Tonni G, Lituania M. OmniView algorithm: A novel 3-dimensional sonographic technique in the study of the fetal hard and soft palates. J Ultrasound Med 2012;31:313-8.
5Vezzetti E, Marcolin F. Geometrical descriptors for human face morphological analysis and recognition. Robot Autonom Syst 2012;60:928-39.
6Smarius B, Loozen C, Manten W, Bekker M, Pistorius L, Breugem C. Accurate diagnosis of prenatal cleft lip/palate by understanding the embryology. World J Methodol 2017;7:93-100.
7Tian M, Xiao L, Jian N, Wei X, Liu S, Zhao H, et al. Accurate diagnosis of fetal cleft lip/palate by typical signs of magnetic resonance imaging. Prenat Diagn 2019;39:883-9.
8Resnick CM, Kooiman TD, Calabrese CE, Zurakowski D, Padwa BL, Koudstaal MJ, et al. An algorithm for predicting Robin sequence from fetal MRI. Prenat Diagn 2018;38:357-64.
9Martinez-Ten P, Adiego B, Illescas T, Bermejo C, Wong AE, Sepulveda W. First-trimester diagnosis of cleft lip and palate using three-dimensional ultrasound. Ultrasound Obstet Gynecol 2012;40:40-6.
10Gullino E, Serra M, Ansaldi C, Massobrio M, Pagliano M. Bilateral cleft lip and palate diagnosed sonographically at 11 weeks of pregnancy. J Clin Ultrasound 2006;34:398-401.
11Gillham JC, Anand S, Bullen PJ. Antenatal detection of cleft lip with or without cleft palate: Incidence of associated chromosomal and structural anomalies. Ultrasound Obstet Gynecol 2009;34:410-5.
12Maarse W, Bergé SJ, Pistorius L, van Barneveld T, Kon M, Breugem C, et al. Diagnostic accuracy of transabdominal ultrasound in detecting prenatal cleft lip and palate: A systematic review. Ultrasound Obstet Gynecol 2010;35:495-502.
13Brito LA, Meira JG, Kobayashi GS, Passos-Bueno MR. Genetics and management of the patient with orofacial cleft. Plast Surg Int 2012;2012:782821.
14Nyberg DA, Sickler GK, Hegge FN, Kramer DJ, Kropp RJ. Fetal cleft lip with and without cleft palate: US classification and correlation with outcome. Radiology 1995;195:677-84.
15Danis DO 3rd, Bachrach K, Piraquive J, Marston AP, Levi JR. Cleft lip and palate in newborns diagnosed with neonatal abstinence syndrome. Otolaryngol Head Neck Surg 2021;164:199-205.
16Weinzweig J, Panter KE, Patel J, Smith DM, Spangenberger A, Freeman MB. The fetal cleft palate: V. Elucidation of the mechanism of palatal clefting in the congenital caprine model. Plast Reconstr Surg 2008;121:1328-34.
17Ozturk S, Karagoz H, Zor F, Inangil G, Kara K. Fetal cleft lip/palate surgery: End of a dream? Fetal Pediatr Pathol 2016;35:277-81.
18Evans LL, Harrison MR. Modern fetal surgery-a historical review of the happenings that shaped modern fetal surgery and its practices. Transl Pediatr 2021;10:1401-17.
19Oberg KC, Robles AE, Ducsay C, Childers B, Rasi CR, Gates DL, et al. Endoscopic excision and repair of simulated bilateral cleft lips in fetal lambs. Plast Reconstr Surg 1998;102:1-9.
20Papadopulos NA, Papadopoulos MA, Kovacs L, Zeilhofer HF, Henke J, Boettcher P, et al. Foetal surgery and cleft lip and palate: Current status and new perspectives. Br J Plast Surg 2005;58:593-607.
21Stelnicki EJ, Lee S, Hoffman W, Lopoo J, Foster R, Harrison MR, et al. A long-term, controlled-outcome analysis of in utero versus neonatal cleft lip repair using an ovine model. Plast Reconstr Surg 1999;104:607-15.
22Harrison MR. Unborn: Historical perspective of the fetus as a patient. Pharos Alpha Omega Alpha Honor Med Soc 1982;45:19-24.
23Davalbhakta A, Hall PN. The impact of antenatal diagnosis on the effectiveness and timing of counselling for cleft lip and palate. Br J Plast Surg 2000;53:298-301.
24Sreejith VP, Arun V, Devarajan AP, Gopinath A, Sunil M. Psychological effect of prenatal diagnosis of cleft lip and palate: A systematic review. Contemp Clin Dent 2018;9:304-8.
25Matthews MS. Beyond easy answers: The plastic surgeon and prenatal diagnosis. Cleft Palate Craniofac J 2002;39:179-82.
26Nusbaum R, Grubs RE, Losee JE, Weidman C, Ford MD, Marazita ML. A qualitative description of receiving a diagnosis of clefting in the prenatal or postnatal period. J Genet Couns 2008;17:336-50.
27Han HH, Choi EJ, Kim JM, Shin JC, Rhie JW. The importance of multidisciplinary management during prenatal care for cleft lip and palate. Arch Plast Surg 2016;43:153-9.