Trends in cleft palate incidence in the era of obstetric sonography and early detection

Abstract

Background

The effect of improvement in prenatal identification of cleft lip or palate (CL/P) on termination of pregnancy (TOP) worldwide is scarcely reported. Our aim was to assess changes in the prevalence of cleft palate attributed to the high access and availability of prenatal advanced screening and pregnancy termination in Israel.

Methods

A retrospective study was conducted on CL/P patients which were treated in our institute and born between January 2000 and December 2018. Clinical and demographic data were extracted from medical records. Data on TOP were collected based on accessible information from the Ministry of Health. Cleft palate severity was evaluated using the Veau Classification.

Results

The study was conducted on 258 patients. Higher incidence of Veau II and III was evident throughout the examined period (2000–2018). However, when evaluating the incidence per year, we found that the incidence of severe cases (Veau III and IV) decreased every year showing a major decline of 60% in the last decade, whereas mild cases (Veau type I and II) demonstrated a marked increase of 90%. Regarding the incidence of abortions in Israel, a decrease of 30% was observed in the last two decades, meanwhile a substantial increase was detected in the rate of abortions related to physical malformations of the fetus. Additionally, the number of late terminations due to physical malformations significantly increased in the last decade.

Conclusions

Significant decrease was observed in the incidence of severe cleft palate cases in the last decade. Concurrently, we found a substantial increase in percentage of abortions performed due to physical malformations. We suggest that these changes might be attributed to the accessibility of advanced prenatal screening and pregnancy termination in Israel under the social healthcare system.

Keywords:

• Cleft lip and palate
• termination of pregnancy
• obstetric sonography

Background

Cleft lip with or without cleft palate (CL/P) is the most common congenital craniofacial malformation, with a prevalence of approximately one in 700 live births worldwide [1,2]. Its development (CL/P) is associated with environmental and genetic factors [1–3].

Many different classification systems of varying complexity have been proposed for cleft lip and palate. Veau’s classification [4], is a widely used example of a simplified system which categorizes defects into four morphological classes. Group I: Soft palate; Group II: Hard and soft palate; Group III: soft palate extending through the alveolus, usually including the lip; Group IV: complete bilateral clefts [4].

Prenatal detection of cleft lip and palate can be achieved using a transabdominal ultrasound (US) examination [5,6]. In Israel, this examination is routinely offered to pregnant women during the second trimester, at gestational weeks 19–25 [7]. It should be mentioned that in Israel a high number of obstetric sonography scans are routinely performed during pregnancy, typically five examinations in parallel with other screening and complementary tests in order to rule out as many congenital and syndromic malformations as possible [7]. Each country supports different protocols regarding ultrasound screening in pregnancy, some of which do not include screening for facial clefts [8].

An accurate prenatal diagnosis of lip and palate anomaly is crucial for determining effective long-term treatment planning, prediction of prognosis, and proper parental counseling [9]. During the last decade, several new methods were established including the use of 3D transabdominal ultrasound, prenatal magnetic resonance imaging (MRI) and the use of the “equal sign” [10–12]. These led to an increase in antenatal diagnosis of facial clefts.

Limited data exist on termination of pregnancy on account of prenatal identification of cleft lip or palate. Our aim was to investigate the current status of cleft palate prevalence and evaluate changes in severity of cases (Veau III and IV) treated in our institute over the last two decades, in light of the significant progress of prenatal ultrasound screening and the public access to medical services, pregnancy screening and abortion in Israel.

Methods

Data collection

This is a retrospective cohort medical record review of consecutive pediatric patients with cleft palate, with or without cleft lip, syndromic or with isolated clefts, who were treated at the Department of Oral and Maxillofacial Surgery, Rambam Health Care Center from January 2000 to December 2018. Clinical and demographic data were extracted for review and analysis using medical records obtained from the Database Registry. Data on abortions in Israel were extracted using available and accessible data from the Ministry of Health on applications and induced abortions [7,13].

Statistics

Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY, USA). Numerical variables were compared using the independent samples t-test. p-Value for all results exhibiting difference stated as significant was <.05.

Ethical approval

The study was approved by the Rambam Independent Review Board (IRB approval number RMB-D-0265-21).

Results

Demographic and medical background

258 patients were diagnosed or treated in our institute from 1 January 2000 until 31 December 2018. 116 patients exhibited solitary cleft palate, while 142 patients exhibited both cleft lip and palate. Most of the patients with cleft lip and palate had unilateral CL/P (173 patients), with the left side being the prevalent one, similar to the literature. Additionally, approximately one third of the patients (85) exhibited bilateral cleft lip and palate. Demographic distribution showed 63% males and 37% females. The majority of patients with CL/P were non syndromic (200 patients). Of the 58 syndromic patients referred to us, Pierre Robin sequence was the most prevalent (23 patients), followed by ectodermal dysplasia (3 patients) and DiGeorge syndrome (2 patients).

Changes in the cleft distribution over the last two decades based on the Veau classification

To classify the CL/P patients we used the Veau classification. While examining the incidence of CL/P during the entire period (1 January 2000–31 December 2018), we found that Veau class II and III were the most common (29 and ∼32%, respectively) whereas Veau class I and IV were less prevalent (19 and ∼20%, respectively, Figure 1(A)). Next, we examined the prevalence of each Veau class at different time periods. We found a shift in the ratio of prevalence when looking on different severity of CL/P during the last two decades. Figure 1(B) exhibits that between the years 2010 and 2018, the number of patients with Veau Class III or IV (higher severity) decreased, compared to the time period of 2000–2009. The number of patients with Veau Class III decreased from 61 to 21 patients (p <10⁻⁵) and the number of patients with Veau Class IV from 33 to 17 (p = .04). On the other hand, we found that a significantly higher number of patients were diagnosed with Veau Classes I or II (solitary cleft palate) between the years 2010 and 2018 compared to the 2000–2009. The number of patients with Veau Class I increased from 15 to 36 patients (p = .01) and the number of patients with Veau Class II from 29 to 47 patients (p = .04). Furthermore, throughout all the examined period the pattern is maintained and there is a constant decrease every year in observed Veau Classes III and IV cases, while an increase in Veau Classes I and II is evident (Figure 1(C)).

Figure 1. VEAU Classification of CL/P in patients diagnosed and treated in our institute. (A) Bar graph of all patients by Veau class throughout the period of study. (B) Bar graph of the change of CL/P Veau class diagnosis between the last two decades. (C) Bar graph demonstrating number of patients (Y axis) with VEAU class I & II (blue bar) or III & IV (red bar) in correlation with their year of birth.

Trends of abortion in Israel during recent decades

A decrease in the number of abortions has been observed in Israel over the last two decades, showing a decrease of 30% in the rate of abortions per 1,000 women of childbearing age.

A decrease has also been observed in the absolute number of abortions (Figure 2(A,B)). However, the rate of abortions performed due to fetal malformations has significantly increased, accounting for almost 20% of abortions performed in Israel between the years 2014 and 2018 with a constant increase over the years (Figure 2(C,D)). Furthermore, the number of late terminations of pregnancy due to fetal malformations has increased from an average of 197 abortions per year in 2000–2009 to 259 in 2010–2018 (p = .01) (Figure 2(E)). The percentage of late abortions performed due to fetal malformations increased from 1.1% (n = 175) in 2000 to 1.7% (n = 301) in 2018, an increase of ∼55%.

Figure 2. Change in number of approved abortions in Israel since 2000. (A) Abortions per 1,000 women of childbearing age. (B) Number of abortions per year. (C, D) Percentage of terminations of pregnancy (TOP) by indication. (E) Number of late TOP due to physical malformation of the fetus.

Discussion

Cleft lip and palate are common congenital malformations occurring in approximately one out of 700 live births. Since the use of obstetric sonography has become the standard of care, prenatal diagnosis of oral clefts is increasing. By week 14 of gestation, the facial contour of the developing fetus is virtually complete [14]. Therefore, detection of this anomaly should be attempted as early as the late first trimester/early second trimester of pregnancy. It is important to remember CL/P may be associated with other fetal malformations in 7–13% of cases, as a manifestation of one of many syndromes [14–16].

As for parental, social, and ethical consequences of prenatal detection of oral clefts, high controversy exists [17]. Prenatal detection of CL/P has several advantages. First, parents can better prepare psychologically for the anomaly, and this early diagnosis provides an opportunity to educate parents regarding both the treatment and the management of possible feeding problems. On the other hand, disadvantages of prenatal diagnosis include the chance of a false positive diagnosis, which may be up to 5% in some reports, leading to subsequent emotional stress [11]. Additionally, there are concerns regarding the potentially increasing number of pregnancy terminations in cases of fetuses with an isolated non syndromic cleft [18]. Since nonsyndromic oral clefts are nonlethal birth defects, which have an excellent functional and esthetic prognosis with appropriate treatment, the use of prenatal diagnosis raises important ethical issues, in terms of pregnancy termination [19,20].

Solid data on CL/P as a reason for termination of pregnancy worldwide is limited. Also, the perception that early detection of CL/P is a significant factor in the decision to perform termination of pregnancy is controversial. An epidemiological study regarding the incidence of CL/P among both Bedouin and Jewish populations in Israel between 1996 and 2006, in the demographic region of the Negev, found a significant decrease in the occurrence of CL/P live births among the Bedouin population. In this study the authors suggest that the change may be attributed to increased access to prenatal care [21]. In Northern Israel, a group of obstetricians and gynecologists from our hospital presented their 10 years' experience of 24,000 scans detecting 15 cases of cleft lip, of which 14 (93%) pregnancies were subsequently terminated [18]. Additionally, other studies in Israel and around the world suggest high numbers of pregnancy terminations are due to the detection of CL/P [9,14,18,22,23]. Furthermore, recently published data suggest that the overall decrease in occurrence of cleft lip worldwide may be attributed to the availability of prenatal screening and elective pregnancy termination [24]. On the other hand, evidence from the Netherlands suggests that although routine screening for physical congenital anomalies was introduced by legislation in 2007, termination of pregnancy in cases of CL/P remains limited [25,26]. However, it should be noted that prenatal screening in the Netherlands has traditionally been less prevalent compared to other countries [27]. Moreover, other studies suggest that prenatal diagnosis enables counseling and a sense of preparedness for the majority of affected families, and only rarely results in termination for isolated clefts [28].

Our results show that relatively fewer abortions are performed in Israel compared to most Western countries. In 2010, the abortion rate in Israel was 10.7 per 1,000 women, compared with 14.2 in the UK, 19.6 in the US and 20.8 in Sweden [29]. However, the rate of abortions performed due to fetal malformations has significantly increased, leading to a constantly elevating relative portion attributed to these abortions performed in Israel, resulting in almost 20% of total abortions. In comparison, only 2% of abortions performed in England in 2017 were performed for this reason [29].

Advances in ultrasound technology have given rise to ethical dilemmas due to early detection of birth defects. In the past early detection of cleft palate was less common. Our study recognized a new trend in the abortion pattern of children with cleft lip and palate in the last decade in Israel. While an increase in birth of patients with less severe clefts is observed, a decrease in births of patients with severe clefts is evident. Additionally, we see that while abortion rate in Israel has decreased over the years, the rate of abortions performed due to fetal malformations such as cleft lip or palate has increased. Furthermore, the number of late terminations due to fetal malformations has also significantly increased over the last decade. One of the obstacles in collecting and analyzing the data was to firmly correlate the increased rate of abortions performed due to fetal malformations exclusively with cleft lip or palate. However, based on previous reports in Israel, and according to the changes we have shown in the frequency of severe CL/P in our institution, we suggest that these changes may be attributed to the accessibility of advanced prenatal screening and pregnancy termination in Israel under the social healthcare system. The records of the terminations of pregnancy from the Ministry of Health do not distinguish between the various classes of cleft palate and the fate of the pregnancy. Prenatal characterization of CL/P severity can be inaccurate and a revision of the type of detected clefting has been reported to occur in 30% of the cases by one study [30]. With advancing technology such as 3D sonography or referral to MRI it is possible that the accuracy has increased, and more severe cases are terminated.

Nowadays parents have access to health information freely available on the internet. Physicians are more careful in dispensing information and taking part in the decision on abortion. Social media create a judgmental environment which leads to a desire for a “picture-perfect life” and “beautiful people”. The future aim of cleft surgery is providing information and support on raising a child with cleft lip and palate in light of advances in medical technology and treatment.

Conclusions

CLP are common malformations, treated surgically with good outcomes. However, a substantial increase in percentage of abortions performed due to physical malformations has been observed in Israel, some of which are cleft palate fetuses whose abortion has been increasing in the past years, while numbers of pregnancy terminations from other causes has remained constant or decreased during the same timeframe. Interestingly, we show the incidence of severe cases that have presented at our institute (Veau III and IV) decreased every year whereas mild cases (Veau type I and II) demonstrated a marked increase. We attribute this shift to the increase in quality and quantity of standard prenatal screening. We believe a protocol for parental education by a craniofacial team in collaboration with obstetricians should be established early following detection of the anomaly, thus making sure all future aspects, treatment options and outcomes are fully understood.

Ethical approval

All guidelines in the Declaration of Helsinki were followed during the preparation of this work. All authors have contributed to the work in accordance with ICMJE guidelines for authorship and have approved the submitted version of the work.

Acknowledgment

The authors received no financial support for the research, authorship, and/or publication of this article.

Disclosure statement

No potential conflict of interest was reported by the author(s).