Prevalence and Incidence of Cleft Lip and/or Palate in Europe: A Scoping Review and Meta-Analysis

Abstract

Objective

This study synthesized and described the prevalence and incidence of cleft lip and/or palate (CL/P) reported by different studies in Europe.

Design

A scoping review was designed according to the Joanna Briggs Institute methodology and an advanced search was conducted using MedLine, Science Direct, and Semantic Scholar without time or language restrictions. Two reviewers extracted data from the articles included.

Participants

The extracted data included specific details on the type of orofacial cleft, the European regions (Northern Europe, Western Europe, Eastern Europe, and Southern Europe).

Main Outcome Measure(s)

A meta-analysis was conducted with the data reported for the incidence and prevalence of CL/P.

Results

A total of 66 studies were obtained reporting from 29 European countries. According to what was obtained from the meta-analysis, a prevalence of cleft lip and palate (CLP) of 0.7/1000 95% CI: (0.6–0.7) births is reported in Europe, followed by cleft palate (CP) and cleft lip (CL) with 0.5/1000 95% CI: (0.4–0.5) and 0.3/1000 95% CI: (0.3–0.4), respectively. A total prevalence of CL/P in Europe is estimated at 1.1/1000 95% CI: (1.0–1.2) between 1950 and 2014. The incidence of CLP is reported to be 0.7/1000 95% CI: (0.6 to 0.8) followed by CP and CL with 0.5/1000 95% CI: (0.5–0.6) and 0.4/1000 95% CI: (0.3–0.4), respectively. The total incidence of CL/P in Europe is estimated at 1.6/1000 95% CI: (1.5–1.7) between 1948 and 2018.

Conclusion

This review provides a description of the status of the prevalence and incidence of CL/P in Europe and its regions, and can be considered as a guide for the development of promotion and prevention programs.

Keywords

prevalence incidence cleft lip cleft palate Europe.

Introduction

Cleft lip and/or palate (CL/P) is considered one of the most frequent congenital orofacial clefts with an approximate prevalence of 1 in every 700 live births. However, estimates may vary depending on geographic location, group ethnicity, and socioeconomic level.¹ Literature shows that the risk of CL/P is greater when the mother is exposed to factors, such as tobacco use, use of medications during pregnancy, alcohol use, contaminated water consumption, exposure to chemicals, and folic acid deficiency. Furthermore, other factors, such as the mother's advanced age or a greater number of pregnancies, also have a negative influence.²

Children with CL/P may have speech, nutrition, and hearing disorders as well as alterations in their general, mental, and social growth and development. Therefore, early and timely treatment and special care is essential for their rehabilitation.³ CL/P's impact on healthcare services necessitates epidemiological monitoring of its behavior among the population through epidemiological incidence and prevalence indices in order to plan ways to meet the treatment needs of these individuals.⁴

Many reports have been published on the prevalence/incidence of CL/P in different regions. However, these studies do not consider all European countries and their regions and, in many cases, the sample sizes or the lack of information about the inclusion criteria hinders data analysis and application. Indiscriminate use of the terms “incidence” and “prevalence,” lack of standardization in reports that fail to describe whether the estimates are reported based on 1000 or 10,000 individuals, and some study results lacking clarification of whether they are estimated at an institutional, national, local, or regional level results in high heterogeneity of study results, which makes it difficult to analyze data, monitor the event adequately and synthesize information to obtain more precise estimates on the frequency of the disease.⁵

In 2022, Nader et al. reported a total prevalence of CL/P of 0.45/1000 live births as a result of a meta-analysis based on estimates from 55 studies. However, their analysis did not involve all European regions or countries.⁶ Other studies, such as the one carried out by IPTDOC WORKING GROUP-2011, report data regarding the prevalence of CL/P in different regions worldwide. Few studies cover recent information from European countries based on observational studies.⁷ These registries may have limitations in providing accurate information on the epidemiology of CL/P in all European regions, even though there are international registries, such as EUROCAT and ICBDSR, which collect hospital and population data from different countries.⁸

This research is aimed at conducting a scoping review of the literature and a meta-analysis that allows for synthesizing, updating, and describing the incidence and prevalence of CL/P in Europe and its regions based on the evidence currently available in the literature as a complementary tool to the current population records of CL/P.

Methods

A scoping review was designed according to the Joanna Briggs Institute methodology.⁹ The search strategy was aimed at locating published studies that reported epidemiological data on the prevalence, incidence, or frequencies of cleft lip (CL), cleft palate (CP), cleft lip and palate (CLP), or cleft lip and/or palate (CL/P) in European countries. Advanced searches were performed using MEDLINE (via PubMed), Science Direct (via Elsevier), and Semantic Scholar. The terms used during the search included: Prevalence OR Incidence + Europe* + Cleft lip OR Cleft palate. No time restrictions (publication, study development) were considered in this review for the inclusion of studies and all relevant studies were included without language restrictions.

After a pilot test, one reviewer independently evaluated the studies obtained through the search strategy, and studies were initially screened and preselected by title and abstract according to their suitability for inclusion. A full-text evaluation of the shortlisted group of articles was then conducted to make sure they reflected the objectives of this review.

Two independent reviewers extracted data from the articles included with a data extraction tool developed by them. The extracted data included specific details about participants, such as cleft type, context, European region, study methods, and relevant epidemiological findings.

Data regarding the incidence and prevalence of CL/P were taken from the included articles. For articles that did not report these CL/P indicators but did report the total number of cases and births according to the period evaluated, the prevalence and incidence were obtained individually using the formula (x = number of cases/total of births × 1000). Finally, the results were described as frequency distribution for articles that did not provide incidence and/or prevalence of CL/P or total number of births but did report the number of cases of CL/P for each sex.

A narrative approach was used when reporting the results of the studies and conducting a thematic analysis of the findings. Results were structured sequentially according to the indicator, as they were reported: prevalence, incidence, or frequency distribution in patients with CL/P. Considering this, prevalence and incidence rates were reported according to the country's geographic location (Northern, Western, Eastern, And Southern Europe). Mean estimates of CL, CP, CLP, and CL/P ratios were pooled by European regions for meta-analysis using the Stata software package, version 14, with the metaprop and metacommands. In addition, I² was estimated to evaluate the proportion of variance due to heterogeneity.

For the assessment of publication bias, funnel plots were generated and Egger's test was applied using RStudio with the metafor and meta packages. The funnel plots, generated using the meta package, provided a visual assessment of the symmetry of the studies included in each subgroup. Egger's test, applied with the metafor package, quantified the asymmetry and evaluated the potential presence of publication bias in the data.

Results

A total of 494 articles were obtained through the advanced search. Out of these, 100 were selected during the screening process and, 66 full-text publications that reported some epidemiological indicator associated with CL, CP, CLP, or CL/P in Europe were included for the scoping review. The study selection process is presented in Supplementary Figure S1.

The evidence collected includes 29 countries: 5 reports from Germany,^7,10–13 3 from Austria,^7,12,13 2 from Belgium,^7,12 4 from Croatia,^7,12–14 9 from Denmark^{7,12,13,15–20} 4 from Slovakia,^7,21–23 1 from Slovenia,²⁴ 5 from Spain,^{7,12,13,25,26} 1 from Estonia,²⁷ 4 from Finland,^7,28–30 6 from France,^{7,12,13,31–33} 5 from Hungary,^7,34–37 4 from Ireland,^4,12,38,39 1 from Iceland,⁴⁰ 5 from Italy,^{7,12,13,41,42} 1 from Lithuania,¹³ 2 from Malta,^7,12 6 from Norway,^42–48 9 from the Netherlands,^{7,12,13,49–54} 4 from Poland,^7,55–57 2 from Portugal,^7,12 1 from the United Kingdom England, Wales, and Ireland,⁵⁸ 5 from Scotland,^12,58–61 5 from England,^{12,13,62–64} 4 from the Czech Republic,^7,65–67 4 from Sweden,^68–71 3 from Switzerland,^7,12,13 1 from Russia,⁷ 2 from Ukraine,^7,13 and 2 from unspecified regions of Europe.^6,72 Two studies reported data for the Europe without discriminating by country (Table 1).

Table 1.

Number of Reports Included in the Scoping Review, According to Europe's Area and Type of Indicator.

Europa zone	Number of reports	Incidence	Prevalence	Frequency distribution
Northern Europe	23	9	10	4
Eastern Europe	15	5	8	2
Western Europe	22	9	14	2
South Europe	12	2	6	1
NS	2	0	2	0
Total	74	25	40	9

NS: not specified.

A total of 32 publications that analyzed prevalence were considered as cross-sectional studies and another 25 cohort studies reported indicators of CL/P incidence. Furthermore, 9 cross-sectional studies evaluating the sex frequency distribution of CL/P were included. The indices for each of the European regions are reported below.

Epidemiological Indicators of CL/P in European Regions

Northern Europe

A total of 10 prevalence and 9 incidence reports on CL/P were found in the literature search for Northern Europe. The highest CP prevalence in Northern Europe was reported in Denmark with 1.47/1000 live births,¹⁵ followed by Scotland and Ireland with 0.81/1000 total births⁵⁹ and 0.78/1000 live births,⁴ respectively. No CP prevalence estimates were found for Finland. The highest CL prevalence was also found in Denmark with 0.63/1000 total live births,⁷ followed by England with 0.42/1000 total births.⁶² The highest CLP estimate was reported in Denmark with 1.48/1000 live births,^16,17 followed by England with 1.14/1000 total births,¹³ and Lithuania with 1.05/1000 total births.¹³ The country that reported the highest estimate of CL/P was Denmark with 2.43/1000 live births,¹⁵ followed by Scotland and Ireland with 1.56/1000 total births⁵⁹ and 1.45/1000 live births,⁴ respectively (Table 2).

Table 2.

Prevalence Estimates of CL, CP, CLP, and CL/P According to Country and European Region.

Country/Region	Evaluation period	Total cases	Total births	Sex M/F	Total CP/1000	Total CL/1000	Total CLP/1000	Total CL/P/1000	ref
NORTH EUROPE
Denmark: DK, FO and GL	DK: 1950–1987 FO Y GL: 1950–1999	DK: 5137 FO: 96 GL:104	LB: DK: 2707.942 LB: FO: 39,364 LB: GL: 59,037	NR	DK: 0.5 FO: 1.47 GL: 1.11	NR	DK: 1.4 FO: 0.96 GL: 0.64	DK: 1.9 FO: 2.43 GL: 1.75	¹⁵
Denmark	1981–2002	3.094	LB: 1.319.426	NR	0.86	NR	1.48	2.34	¹⁶
Denmark: Funen	1980–2014	398	TB: 182.907	NR	0.69	NR	1.48	2.17	¹⁷
Denmark: Odense	1980–2000	169	TB:111.954	NR	NR	NR	NR	1.5	¹²
Denmark: Odense	1996–1998	13	TB: 8.788	NR	0.68	NR	0.8	1.48	¹³
Denmark: Odense	2001–2003	26	TB: 15.768	NR	NR	0.63	1.01	1.64	⁷
Denmark	1996–2008	1232	LB: 832.636	NR	0.43	0.37	0.68	1.48	²⁰
Finland	2004	54	TB: 57.945	NR	NR	0.36	0.57	0.93	⁷
Ireland: N-IE	1981–2000	741	LB: 511.693	NR	0.78	0.23	0.44	1.45	⁴
Ireland: Galway, Dublin	G: 1981–1999 D: 1980–2000	G: 37 D: 377	TB: G: 54.509 TB: 441.774	NR	NR	NR	NR	G: 0.68 D: 0.85	¹²
Lithuania	1996–1998	124	TB: 94.469	NR	0.25	NR	1.05	1.3	¹³
Scotland: GLG	1974–1985	247	TB:158.668	135/85	0.81	0.21	0.54	1.56	⁵⁹
Scotland: GLG	1980–2000	236	TB: 253.316	NR	NR	NR	NR	0.93	¹²
England: LIV	1960–1982	456	TB: 325.727	NR	0.47	0.42	0.51	1.4	⁶²
England: NTY	1991–2000	475	TB: 471.189	NR	NR	NR	NR	1	¹²
England: OXF, WSX	1996–1998	OXF: 16 WSX: 63	TB: OXF: 13.136 TB: WSX: 65.559	NR	OXF: 0077 WSX: 0.23	NR	OXF: 1.14 WSX: 0.73	OXF: 1.22 WSX: 0.96	¹³
WESTERN EUROPE
Germany	2002–2004	34	TB: 37.634	NR	NR	NR	NR	0.9/1.000	¹⁰
Germany	1987–1989	309	TB: 171.182	NR	NR	NR	NR	1.80/ 1.000	¹¹
Germany: ST, Mainz	ST: 1987–2000 Mainz: 1990–2000	ST: 244 Mainz: 37	TB: ST: 161.687 TB: Mainz: 40.582	NR	NR	NR	NR	ST: 1.5 Mainz:0.9	¹²
Germany: Leipzig, Mainz	1996–1998	Leipzig: 4 Mainz: 23	TB: Leipzig: 8.745 TB: Mainz: 9.535	NR	Leipzig: 0.11 Mainz: 0.52	NR	Leipzig: 0.34 Mainz: 1.89	Leipzig: 0.45 Mainz: 2.41	¹³
Germany: Mainz	2001–2002	15	TB: 6.290	NR	NR	0.79	1.56	2.35	⁷
Germany: Saxony Anhalt	2001–2005	127	TB: 87.458	NR	NR	0.38	1.07	1.45	⁷
Austria: Styria	1985–2000	256	TB: 203.607	NR	NR	NR	NR	1.26	¹²
Austria: Styria	1996–1998	16	TB: 29.026	NR	0.27	NR	0.27	0.54	¹³
Austria: Styria	2001	11	TB: 10.050	NR	NR	0.20	0.90	1.1	⁷
Belgium: Hainaut-Namur	1980–2000	253	TB: 227.163	NR	NR	NR	NR	1.1	¹²
Belgium: Antwerp	2001–2003	62	TB: 52.868	NR	NR	0.45	0.72	1.17	⁷
Belgium: Hainaut	2001–2003	29	TB: 36.461	NR	NR	0.38	0.41	0.79	⁷
France: Bas-Rhin	1995–2006	321	TB: 153.644	NR	0.76	NR	1.33	2.09	³¹
Paris France	1982	192	TB: 126.087	NR	0.56	NR	0.96	1.52	³²
France: Strasbourg, Paris	1996–1998	Strasbourg:37 Paris:38	TB: Strasbourg:33.155 TB: Paris:27.550	NR	Strasbourg:0.21 Paris:0.47	NR	Strasbourg:0.90 Paris:0.91	Strasbourg:1.11 Paris:1.38	¹³
France: Paris, Strasbourg	Paris:1981–2000 Strasbourg:1982–2000	Paris:620 Strasbourg:285	TB: Paris:737.764 TB:Strasbourg:253.988	NR	NR	NR	NR	Paris:0.84 Strasbourg:1.12	¹²
France: Strasbourg	2001	14	TB: 13.860	NR	NR	0.58	0.43	1.01	⁷
Paris France	2002–2003	83	TB: 77.000	NR	NR	0.32	0.57	0.89	⁷
France	2001–2004	279	TB: 425.304	NR	NR	0.22	0.43	0.65	⁷
Norway	1986–1992	523	TB: 347.419	316/207	0.49	0.51	0.49	1.49	⁴³
Norway	1967–2010	2890	TB: 2.449.218	NR	NR	1.18	NR	1.18	⁴⁷
Norway	1968–1997	2.694	LB: 1.845.357	NR	NR	0.61	0.85	1.46	⁴⁸
Netherlands	2008–2012	330	NR	200/123	NR	NR	NR	1.5	⁴⁹
Netherlands: North, R-NL	1997–2007	Norte: 456 R-NL:3118	LB: Norte: 213.209, LB: R-NL: 1.938.999	NR	Norte: 0.67 R-NL: 0.53	NR	Norte: 1.47 R-NL: 1.08	Norte: 2.14 R-NL: 1.61	⁵⁰
Netherlands	1997–2006	3308	LB: 1.970.872	NR	0.55	NR	1.13	1.68	⁵¹
Netherlands: North, South	1996–1998	Norte: 61 Sur: 31	TB: Norte: 34,085 TB: Sur: 47.895	NR	Norte: 0.47 Sur: 0.25	NR	Norte:1.32 Sur: 0.40	Norte:1.79 Sur: 0.65	¹³
Netherlands	1981–2000	465	TB: 308.565	NR	NR	NR	NR	1.51	¹²
Netherlands: R-NL, North	1997–2007	R-NL: 3.574 Norte: 454	LB: R-NL: 2.152.208 LB: Norte: 213.209	NR	R-NL: 0.54 Norte: 0.67	NR	R-NL:1.12 Norte: 1.46	R-NL:1.66 Norte: 2.13	⁵²
Netherlands: North	2001–2003	89	TB: 60.924	NR	NR	0.57	0.89	1.46	⁷
Switzerland: Vaud	1989–2000	85	TB: 92.107	NR	NR	NR	NR	0.92	¹²
Switzerland: Vaud	2001–2003	22	TB: 20.942	NR	NR	0.43	0.62	1.05	⁷
Switzerland: Lausanne	1996–1998	37	TB: 18.907	NR	1.11	NR	0.85	1.96	¹³
SOUTH EUROPE
Croatia: Zagreb	1983–2000	100	TB: 109.07	NR	NR	NR	NR	0.92	¹²
Croatia: Zagreb	1996–1998	17	TB: 10.718	NR	0.37	NR	1.21	1.58	¹³
Croatia	2001–2003	11	TB: 16.739	NR	NR	0.24	0.42	0.66	⁷
Spain: Asturias	1990–2004	145	TB:103.452	NR	0.63	0.38	0.40	1.41	²⁵
Spain: Asturias	2001–2003	14	TB: 20.911	NR	NR	0.24	0.43	0.67	⁷
Spain: Basque Countries	2001–2003	29	TB: 55.188	NR	NR	0.16	0.36	0.52	⁷
Spain: AS, PV, B	AS:1990–2000 PV:1990–2000 B:1992–2000	AS:63 PV109 B:68	TB: AS:75.616 TB: PV:178.583 TB: B:111.903	NR	NR	NR	NR	AS:0.83 PV:0.61 B:0.6	¹²
Spain: El Valles, B, PV	1996–1998	El Valles:10 B:17 Pv:24	TB: El Valles:5.737 TB: B:1.357 TB: Pv:32.429	NR	El Valles:0.17 B:0.26 Pv:0	NR	El Valles:1.57 B:0.62 Pv:0.74	El Valles1.74 B:0.88 Pv:0.74	¹³
Italy: North	1978–1986	200	TB: 150.168	NR	0.58	NR	0.74	1.32	⁴¹
Italy: North-East, ER, T, C	Norte-Este:1981–2000 Emilia Romagna:1981–2000 Tuscany:1980–2000 Campania:1996–2000	Norte-Este:754 Emilia Romagna:318 Tuscany:234 Campania:137	TB: Norte-Este: 949.396 TB: Emilia Romagna:470.128 TB: Tuscany:333.768 TB: Campania:196.081	NR	NR	NR	NR	Norte-Este:0.79 Emilia Romagna:0.68 Tuscany:0.70 Campania:0.70	¹²
Italy: Emilia Romagna	2001–2003	48	TB: 81.642	NR	NR	0.15	0.44	0.59	⁷
Italy: Campania	2001–2003	79	TB: 172.300	NR	NR	0.19	0.27	0.46	⁷
Italy: Tuscany	2001–2003	48	TB: 80.505	NR	NR	0.20	0.40	0.60	⁷
Italy: North and ER	1981–1989	766	TB: 561.539	NR	0.54	NR	0.82	1.36	⁴²
Italy: North and East	2002–2004	105	TB: 174.857	NR	NR	0.39	0.21	0.6	⁷
Italy: S, T, N-IT	1996–1998	S:29 T:49 N-IT:115	TB: S:25.339 TB: T:67.120 TB: N-IT:111.719	NR	S:0.35 T:0.25 N-IT:0.30	NR	S:0.79 T:0.48 N-IT:0.73	S:1.14 T:0.73 N-IT:1.03	¹³
Italia: East Sicily	2001–2002	25	TB: 33.022	NR	NR	0.21	0.54	0.75	⁷
Malta	1986–2000	54	TB: 75.626	NR	NR	NR	NR	0.71	¹²
Malta	2001–2003	8	TB: 11.629	NR	NR	0.43	0.26	0.69	⁷
Portugal: South	2001–2002	24	TB: 37.163	NR	NR	0.16	0.48	0.64	⁷
Portugal: South	1990–2000	73	TB: 131.998	NR	NR	NR	NR	0.55	¹²
EASTERN EUROPE
Slovakia: West, Bratislava	1985–2000	Oeste: 151 Bratislava: 69	LB: Oeste: 110.046, LB: Bratislava: 37.828	89–62/40–29	Oeste: 0.46 Bratislava: 0.89	Oeste: 0.31 Bratislava: 0.47	Oeste: 0.58 Bratislava: 0.37	Oeste: 1.35 Bratislava: 1.73	²¹
Slovakia	2001–2005	261	TB: 258.112	NR	NR	0.29	0.72	1.01	⁷
Hungary	1980	809	NR	NR	NR	0.36	0.67	1.03	³⁴
Hungary	1973–1982	2319	LB: 1.667.166	NR	0.38	0.36	0.65	1.39	³⁵
Hungary	2001–2004	307	TB: 385.714	NR	NR	0.29	0.51	0.8	⁷
Poland	2001–2003	641	TB: 724.742	NR	NR	0.32	0.57	0.89	⁷
Poland: Lodz	1981–2010	389	LB: 222.053	194/193	0.72	0.36	0.67	1.75	⁵⁵
Poland: Lodz	2001–2010	70	LB: 60.109	32/38	0.51	0.18	0.47	1.16	⁵⁶
Czech Republic: Bohemia	1964–2000	5619	LB: 3.080.891	1.582.625/ 1.498.266	0.65	0.44	0.72	1.81	⁶⁵
Czech Republic	2000–2003	141	TB: 191.349	NR	NR	0.34	0.39	0.73	⁷
Russia: Moscow	2002–2004	116	TB: 161.595	NR	NR	0.25	0.47	0.72	⁷
Ukraine	2001–2004	87	TB: 101.510	NR	NR	0.42	0.43	0.85	⁷
Ukraine: South	1996–1998	27	TB: 44.761	NR	0	NR	0.6	0.6	¹³

LB: life births, TB: total births, NR: no reporter, DK: Denmark, FO: Faroe Islands, GL: Greenland, N-IE: North Ireland, G: Galway, D: Dublin, GLG: Glasgow, LIV: Liverpool, NTY: North Thames, OXF: Oxford, WSX: West Sussex, ST: Saxony Anhalt, NL: Rest of the Netherlands, AS: Asturias, PV: Basque Country, B: Barcelona, ER: Emilia Romagna, T: Tuscany, C : Campania, S: Sicily, N-IT: Northern Italy.

According to the results of our meta-analysis, the estimated CL prevalence reported for Northern Europe was 0.3/1000 total births 95% CI (0.2–0.5) between 1960 and 2008 (Supplementary Figure S2). For CP, it was 0.6/1000 births 95% CI (0.4–0.8) between 1950 and 2014 (Supplementary Figure S3). For CLP, it was 0.8/1000 births 95% CI (0.6–0.10) between 1950 and 2014 (Supplementary Figure S4), and for CL/P it was 1.4/1000 births 95% CI (1.2–1.6) between 1950 and 2014 (Supplementary Figure S5).

According to the incidence data reported in Northern Europe, the country with the highest incidence of CP is Finland with 0.97/1000 live births,²⁹ followed by England with 0.7/1000 live births,⁶⁴ and Scotland with 0.64/1000 total births.⁶⁰ For CL, Denmark reported the highest incidence with 0.63/1000 live births,¹⁸ followed by Scotland and Finland with 0.35/1000 total births⁶⁰ and 0.22/1000 total births,²⁸ respectively. The highest estimate for CLP was observed in England with 1.12/1000 live births,⁶⁴ followed by Scotland with 0.85/1000 live births,⁵⁸ and Finland with 0.77/1000 live births.²⁹ For CL/P, Denmark reported the highest estimate with 1.89/1000 live births,¹⁸ followed by England with 1.82/1000 live births,⁶⁴ and Finland with 1.74/1000 live births²⁹ (Table 3).

Table 3.

Estimates of Incidence of CL, CP, CLP, and CL/P According to Country and European Region.

Country/region	Evaluation period	Total cases	Total births	Sex M/F	Total CP/1000	Total CL/1000	Total CLP/1000	Total CL/P/1000	Ref
NORTHERN EUROPE
Denmark: Copenhagen And Arhus	1976–1981	678	LB: 359.027	411/267	0.52	0.63	0.74	CO Y AR: 1.89	¹⁸
Finland	1967–1971	793	TB: 463.723	NR	0.87	0.22	0.46	1.71	²⁸
Finland	1948–1975	3928	LB: 2.258.850	NR	0.97	NR	0.77	1.74	²⁹
Ireland: North	1980–1990	398	NR	NR	NR	NR	NR	1.28	³⁹
Ireland: West	1980–1996	96	LB: 92.318	51/53	0.4	0043	0.59	1.03	³⁸
UK: EWNI, SCT	2000–2018	EWNI: 20.049 SCT: 1.720	LB: EWNI: 13.225.737 LB: SCT: 1.038.843	NR	NR	NR	EWNI: 0.77 SCT: 0.85	EWNI: 1.51 SCT: 1.65	⁵⁸
Scotland: LOTH	1971–1990	502	TB: 356.773	291/211	0.64	0.35	0.42	1.41	⁶⁰
England	1993–1997	30	TB: 23.577	NR	0.42	0.17	0.68	1.27	⁶³
England	1973–1982	930	LB: NR	517/413	0.7	NR	1.12	1.82	⁶⁴
WESTERN EUROPE
Iceland	1956–1962	64	TB: 32.979	38/26	0.6	0.48	0.85	1.93	⁴⁰
France: North and East	1979–1987	207	TB: 118.265	113/94	0.77	0.39	0.59	1.75	³³
Norway	1967–1974	1073	LB: 516.657	633/440	0.65	0.66	0.76	2.07	⁴⁴
Norway: Hordaland	1993–2012	989	NR	581/407	NR	NR	NR	1.9	⁴⁵
Norway: Oslo	1954–1975	1555	LB: 1.401.343	885/670	0.43	0.3	0.37	1.1	⁴⁶
Netherlands: North	1981–1988	168	LB: 73.879	NR	0.65	NR	1.62	2.27	⁵³
Sweden Stockholm	1991–1995	251	LB: 122.148	157/94	0.74	0.61	0.67	2.02	⁶⁸
Sweden: North, South, Center	1958–1970	436	TB: North 93.239 TB: South: 44.109 TB: Center:16.120	NR	North: 0.74 South: 0.36 Center:0.47	NR	North: 1.1 South: 1.34 Center: 1.17	North: 1.84 South: 1.7 Center: 1.64	⁶⁹
Sweden Stockholm	1975–1992	616	NR	367/249	NR	NR	NR	1.7	⁷⁰
SOUTH EUROPE
Croatia	1988–1998	903	LB: 525.298	509/394	0.65	0.29	0.75	1.69	¹⁴
Slovenia	1973–1993	920	LB: 590.249	NR	0.6	0.38	0.54	1.52	²⁴
EASTERN EUROPE
Slovakia: East	1996–2013	477	LB: 347.715	286/207	0.39	0.34	0.64	1.37	²²
Slovakia	1985–2000	1849	LB: 1.147.236	1008/841	0.53	0.42	0.65	1.60	²³
Hungary: Hungary, Budapest	1962–1967	Hungría: 697 Budapest: 129	TB: Hungría: 714.091 TB: Budapest: NR	NR	Hungría:0.27 Budapest:0.38	Hungría:0.23 Budapest:0.48	Hungría: 0.46 Budapest:0.69	Hungría: 0.96 Budapest:1.55	³⁶
Czech Republic	1994–2008	2417	LB: 1.471.789	1422/995	0.68	0.39	0.57	1.64	⁶⁶
Czech Republic	1964–1982	3315	LB: 1.831.036	1903/1412	0.6	0.43	0.76	1.79	⁶⁷

LB: life births, TB: total births, NR: no reporter, EWNI: (England, Wales, North Ireland), SCT: Scotland.

The results of the meta-analysis show an incidence of CL of 0.3/1000 births 95% CI (0.1–0.4) between 1967 and 1997 for Northern Europe (Supplementary Figure S6). For CP, it was 0.6/1000 births 95% CI (0.4–0.7) between 1948 and 1997 (Supplementary Figure S7). For CLP, it was 0.7/1000 births 95% CI (0.5–0.9) between 1948 and 2018 (Supplementary Figure S8), and for CL/P it was 1.5/1000 births 95% CI (1.3–1.7) between 1948 and 2018 (Supplementary Figure S9).

Eastern Europe

The literature search for Eastern Europe identified 8 prevalence reports and 5 incidence reports. The highest prevalence of CP in Eastern Europe was found in Slovakia with 0.89/1000 live births,²¹ followed by Poland and the Czech Republic with 0.72/1000 live births⁵⁵ and 0.65/1000 live births,⁶⁵ respectively. The highest CL estimate was reported in Slovakia with 0.47/1000 live births,²¹ followed by Czech Republic with 0.44/1000 live births,⁶⁵ and Ukraine with 0.42/1000 total births.⁷ For CLP, the highest value was reported in Slovakia and Czech Republic with 0.72/1000 live births,^7,65 followed by Poland with 0.67/1000 live births,⁵⁵ and Ukraine with 0.6/1000 total births.¹³ The Czech Republic reported the highest estimate of CL/P with 1.81/1000 live births,⁶⁵ followed by Poland with 1.75/1000 live births,⁵⁵ and Slovakia with 1.73/1000 live births²¹ (Table 2).

Our meta-analysis showed a CL prevalence of 0.3/1000 births 95% CI (0.2–0.4) between 1964 and 2005 for Eastern Europe (Supplementary Figure S2). For CP, an estimate of 0.6/1000 births 95% CI (0.3–0.8) between 1964 and 2010 was found (Supplementary Figure S3). For CLP, it was 0.5/1000 births 95% CI (0.4–0.7) between 1964 and 2010 (Supplementary Figure S4), and for CL/P, it was 1.1/1000 births 95% CI (0.9–1.3) between 1964 and 2010 (Supplementary Figure S5).

The country that showed the highest incidence value for CP in Eastern Europe was Czech Republic with 0.68/1000 live births,⁶⁶ followed by Slovakia and Hungary with 0.53/1000 live births²³ and 0.38/1000 total births,³⁶ respectively. For CL, the highest estimate was reported in Hungary with 0.48/1000 total births,³⁶ followed by Czech Republic with 0.43/1000 live births,⁶⁷ and Slovakia with 0.42/1000 live births.²³ For CLP, the highest incidence was reported in the Czech Republic with 0.76/1000 live births,⁶⁷ followed by Hungary with 0.69/1000 total births,³⁶ and Slovakia with 0.65/1000 live births.²³ The country with the highest estimate of CL/P was the Czech Republic with 1.79/1000 live births,⁶⁷ followed by Slovakia and Hungary with 1.60/1000 live births²³ and 1.55/1000 total births,³⁶ respectively (Table 3).

The results of our meta-analysis show an incidence of CL of 0.3/1000 births 95% CI (0.2–0.5) between 1962 and 2013 for Eastern Europe (Supplementary Figure S6). For CP, it was 0.4/1000 births 95% CI (0.3–0.6) between 1962 and 2013 (Supplementary Figure S7). For CLP, an estimate of 0.6/1000 95% CI (0.5–0.8) between 1962 and 2013 was found (Supplementary Figure S8) and, for CL/P, it was 1.5/1000 births 95% CI (1.2–1.7) between 1962 and 2013 (Supplementary Figure S9).

Western Europe

The literature reported 14 prevalence and 9 incidence reports for Western Europe.

The highest prevalence of CP in Western Europe was reported in Switzerland with 1.11/1000 total births,¹³ followed by France with 0.76/1000 total births,³¹ and the Netherlands with 0.67/1000 live births.⁵⁰ For CL, the highest rate was found in Norway with 1.18/1000 total births,⁴⁷ followed by Germany and France with 0.79/1000 and 0.58/1000 total births,⁷ respectively. The highest estimate of CLP was reported in Germany with 1.89/1000 total births,¹³ followed by the Netherlands with 1.47/1000 live births.⁵⁰ The country with the highest estimate of CL/P was Germany with 2.41/1000 total births,¹³ followed by the Netherlands with 2.14/1000 live births⁵⁰ and France with 2.09/1000 total births³¹ (Table 2).

The results of our meta-analysis show a prevalence of CL of 0.4/1000 births 95% CI (0.3–0.6) between 1967 and 2010 for Western Europe (Supplementary Figure S2). For CP, it was 0.5/1000 births 95% CI (0.3–0.6) between 1982 and 2007 (Supplementary Figure S3). For CLP, it was 0.8/1000 births 95% CI (0.7–1.0) between 1982 and 2007 (Supplementary Figure S4), and for CL/P it was 1.3/1000 births 95% CI (1.1–1.4) between 1967 and 2012 (Supplementary Figure S5).

The highest incidence of CP in Western Europe was observed in France with 0.77/1000 total births,³³ followed by Sweden with 0.74/1000 total births^68,69 and Norway together with Netherlands with 0.65/1000 live births.^44,53 For CL, the highest estimate was reported in Norway with 0.66/1000 live births,⁴⁴ followed by Sweden with 0.61/1000 live births,⁶⁸ and Iceland with 0.48/1000 total births.⁴⁰ The country with the highest incidence of CLP was the Netherlands with 1.62/1000 live births,⁵³ followed by Sweden with 1.34/1000 total births,⁶⁹ and Iceland with 0.85/1000 total births.⁴⁰ The Netherlands reported the highest estimate of CL/P with 2.27/1000 live births,⁵³ followed by Norway with 2.07/1000 live births,⁴⁴ and Sweden with 2.02/1000 live births⁶⁸ (Table 3).

The results of our meta-analysis show an incidence of CL of 0.5/1000 births 95% CI (0.3–0.6) between 1954 and 1995 for Western Europe (Supplementary Figure S6). For CP, it was 0.6/1000 births 95% CI (0.4–0.7) between 1954 and 1995 (Supplementary Figure S7). For CLP, it was 0.9/1000 births 95% CI (0.6–1.1) between 1954 and 1995 (Supplementary Figure S8), and for CL/P, it was 1.8/1000 births 95% CI (1.5–2.0) between 1954 and 2012 (Supplementary Figure S9).

Southern Europe

A total of 6 prevalence and 2 incidence reports were found for Southern Europe. The highest CP prevalence rate was found in Spain with 0.63/1000 total births,²⁵ followed by Italy and Croatia with 0.58/1000 total births⁴² and 0.37/1000 total births,¹³ respectively. For CL, the highest estimate was reported in Malta with 0.43/1000 total births,⁷ followed by Italy with 0.39/1000 total births⁷ and Spain with 0.38/1000 total births.²⁵ The highest prevalence rate for CLP was reported in Spain with 1.57/1000 total births,¹³ followed by Croatia with 1.21/1000 total births,¹³ and Italy with 0.82/1000 total births.⁴² For CL/P, the highest estimate was found in Spain with 1.74/1000 live births,¹³ followed by Croatia and Malta with 1.58/1000 total births¹³ and 0.71/1000 total births,¹² respectively (Table 2).

According to the meta-analysis results, the prevalence showed an estimate of CL of 0.2/1000 births 95% CI (0.1–0.3) between 1990 and 2004 for Southern Europe (Supplementary Figure S3). For CP, it was 0.4/1000 births 95% CI (0.2–0.5) between 1978 and 2004 (Supplementary Figure S3). For CLP, it was 0.5/1000 births 95% CI (0.4–0.6) between 1978 and 2004 (Supplementary Figure S4) and, for CL/P, it was 0.8/1000 births 95% CI (0.7–0.9) between 1978 and 2004 (Supplementary Figure S5).

The country with the highest incidence of CP for Southern Europe is Croatia with 0.65/1000 live births,¹⁴ followed by Slovenia with 0.60/1000 live births.²⁴ For CL, the highest estimate was found in Slovenia with 0.38/1000 live births,²⁴ followed by Croatia with 0.29/1000 live births.¹⁴ For CLP, the highest estimate was seen in Croatia with 0.75/1000 live births,¹⁴ followed by Slovenia with 0.54/1000 live births,²⁴ and for CL/P the highest incidence rate was reported in Croatia with 1.69/1000 live births,¹⁴ followed by Slovenia with 1.52/1000 live births²⁴ (Table 3).

The results of our meta-analysis show an incidence of CL of 0.3/1000 births 95% CI (0.1–0.6) between 1973 and 1998 for Southern Europe (Supplementary Figure S6). For CP, it was 0.6/1000 births 95% CI (0.3–1.0) between 1973 and 1998 (Supplementary Figure S7). For CLP, it was 0.6/1000 births 95% CI (0.3–1.0) between 1973 and 1998 (Supplementary Figure S8) and, for CL/P, it was 1.6/1000 births 95% CI (1.1–2.1) between 1973 and 1998 (Supplementary Figure S9).

Europe

Two studies conducted in 2011 by Loane et al. in 2011⁵ and Boyd et al.,⁶⁹ analyzing the 1999–2008 and 2004–2008 periods, respectively, report a total prevalence of CL/P of 1.45 per 1000 births in Europe. However, these two studies do not report which European countries these prevalence rates belong to, nor the total number of births, which is why they were analyzed separately from the geographical regions of Europe

According to the results of our meta-analysis, CL prevalence was 0.3/1000 births 95% CI (0.3–0.4) between 1960 and 2010 for all of Europe (Supplementary Figure S2). For CP, it was 0.5/1000 births 95% CI (0.4–0.5) between 1950 and 2014 (Supplementary Figure S3). For CLP, it was 0.7/1000 births 95% CI (0.6–0.7) between 1950 and 2014 (Supplementary Figure S4), and for CL/P, it was 1.1/1000 births 95% CI (1.0–1.2) between 1950 and 2014 (Supplementary Figure S5).

The results of our meta-analysis showed an incidence of CL of 0.4/1000 births 95% CI (0.3–0.4) between 1954 and 2013 for all of Europe (Supplementary Figure S6). For CP, it was 0.5/1000 births 95% CI (0.5–0.6) between 1948 and 2013 (Supplementary Figure S7). For CLP, it was 0.7/1000 births 95% CI (0.6–0.8) between 1948 and 2018 (Supplementary Figure S8), for CL/P, it was 1.6/1000 births 95% CI (1.5–1.7) between 1948 and 2018 (Supplementary Figure S9).

Geographic distribution of the pooled incidence and prevalence of lip and/or palate in Europe per 1000 inhabitants are presented in Figures 1 and 2.

Figure 1.

Geographic distribution of the pooled prevalence and prevalence of lip and/or palate in Europe per 1000 inhabitants.

Figure 2.

Geographic distribution of the pooled incidente and prevalence of lip and/or palate in Europe per 1000 inhabitants.

The funnel plots presented in the supplementary file (Figure S10) show significant asymmetry across all subgroups of analyzed conditions (CL, CP, CL/P, OFC) in both prevalence and incidence, according to Egger's test results (p < 0.0001). Bias estimates were highest in the prevalence and incidence of CL (160.43, SE = 4.28; 167.20, SE = 6.37) and CP (126.21, SE = 3.18; 101.96, SE = 1.38), and lowest in OFC (84.41, SE = 0.32; 80.96, SE = 0.11).

Frequency Distribution

We found 9 different studies that report total cases of CL/P according to the type of condition. In Northern, Southern, Eastern, and Western Europe, there is a greater number of CLP cases, followed by CP and CL, except for the studies carried out in Finland and Poland during 1998 to 2011 and 1981 to 2015, respectively, which report a greater number of CP cases, followed by CLP. Several studies in Scotland, Denmark, Sweden, the Netherlands, and Hungary did not determine the number of CL and/or CP cases. Furthermore, most reports present a greater number of cases in men than in women, and only one study carried out in Finland during 1998 to 2011 reported a greater number of cases in women than in men (Table 4).

Table 4.

Estimates of CL/P Frequency Distribution by Country and European Region.

Country/region	Evaluation period	Total cases	Total births	Sex M/F	CP	CL	CLP	CL/P	REF
NORTHERN EUROPE
Estonia: Tartu	1970–1980	583	NR	333/250	228	111	244	583	²⁷
Finland: Oulu	1998–2011	214	NR	95/119	147	27	40	214	³⁰
Scotland: Glasgow	1999–2008	459	NR	–	223	–	236	459	⁶¹
Denmark	1941–1968	1895	NR	1284/611	–	678	1217	1895	¹⁹
WESTERN EUROPE
Sweden	1965–1974	1313	NR	–	378	–	935	1313	⁷¹
Netherlands	2006–2016	2065	NR	1311/778	613	–	1452	2065	⁵⁴
EUROPA DEL SUR
Spain: Seville	2009–2010	123	NR	75/48	18	9	96	123	²⁶
EASTERN EUROPE
Poland: Lodz	1981–2015	434	NR	218/216	181	96	156	434	⁵⁷
Hungary: Budapest	1962–1967	1899	NR	–	–	222	1677	1899	³⁷

NR: no report.

Discussion

Our scoping review collected the information available in the main academic literature databases regarding the prevalence and incidence of CL/P in the different regions of Europe. The analysis integrated epidemiological prevalence and incidence rates from 29 countries without time restriction, and the total estimate of CL/P could be determined in the vast majority. The number of prevalence studies reported in different European regions was higher than the number of incidence studies. Estimates varied depending on the period and region evaluated. For example, when a longer period and a larger area were evaluated, more reliable and precise data could be obtained regarding the situation of a country or region.

Although there is a similarity in the prevalence of CL between European regions, the data obtained from the meta-analysis of proportions suggest that the Western region has the highest estimate of 0.4/1000 births, followed by the North and East regions of 0.3/1000 births and, to a lesser extent, the South regions of 0.2/1000 births. According to our meta-analysis, studies of LC incidence in Western Europe present the highest rate with 0.5/1000 total births, except for the Northern, Southern, and Eastern regions, which report equal but lower estimates, with 0.3/1000 total births.

The prevalence of CP suggests higher estimates in the Northern and Eastern regions with 0.6/1000 total births, whereas the Southern region has the lowest rate with 0.4/1000 total births, reporting the lowest number of studies with only 3 countries. Only 2 incidence and 6 prevalence studies were found in the Southern region, reporting the lowest number of epidemiological records at present, despite describing CP incidence estimates between regions. Our meta-analysis suggests that the two indicators evaluated for CLP vary depending on the European region analyzed. For example, the higher prevalence of CLP in the North and West (0.8/1000 total births), followed by the Southern and Eastern regions (0.5/1000 total births), may suggest patterns that may be related to risk factors specific to each region.

The results of our review suggest a total prevalence estimate of 1.1/1000 and an incidence of 0.9/1000 in Europe, which is higher than that reported by the IPTDOC GROUP in 2011 in the regions of Europe (0. 81/1000). Furthermore, this scoping review reports information regarding the number of CL/P cases, distribution by sex (male or female), and other phenotypic subgroups taken into account in the study —specifically CL, CP, CLP, and CL/P.⁷ It also provides relevant information for public health care and decision-making in each subregion. Our findings can be complementary to the information held in European registries such as EUROCAT (European Network of Population Registries for the Epidemiological Surveillance of Congenital Anomalies).^5,69

The scoping review, however, showed an indiscriminate use of the epidemiological terms “incidence” and “prevalence” for CL/P, and this high level of heterogeneity limits comparison between the different indicators. Although some authors argue that the number of births with malformations is seen and best described as a degree of prevalence due to their prenatal development—that is, long before birth, other authors suggest that this corresponds to a new event.⁸

Information records, integration of data, and evidence of craniofacial malformations should be promoted in healthcare worldwide. Estimates of prevalence and incidence of congenital malformations, including CL/P, provide information about the behavior of the disease in different populations. This allows for the impact and value of interventions to be assessed, in the same way they support the planning of the resources necessary for prevention and care. It has been reported that 30% to 40% of infant mortality in Europe is due to congenital malformations, which is why new strategies are required for adequate prevention or treatment of this group of diseases that involve constant epidemiological monitoring and standardization of concepts.^70,73

Efforts were made to control heterogeneity in clinical aspects by stratifying meta-analyses according to cleft type, population characteristics such as geographic location, and methodological aspects, including study design and indicators used (prevalence, incidence). However, the statistical analysis results displayed significant heterogeneity in some cases, as shown in the forest plot graphs (Supplementary File: Figures S2–S9), which may constitute a limitation of the study.

This heterogeneity may stem from factors such as differences in the time periods analyzed across studies, varying risk factors, population characteristics, or country-specific local differences, including the approach or implementation of the information systems from which reported data are derived. These factors may result in under- or overestimation of cases. Nonetheless, the heterogeneity's impact in certain grouped results appears minimal, as reflected by the precision of the confidence intervals, supporting the consistency of the results.

Additionally, the publication bias analysis showed significant asymmetry across all condition subgroups (CL, CP, CLP, OFC) evaluated in both prevalence and incidence, according to Egger's test (p < 0.0001). The highest bias estimates were observed in the CL and CP analyses, while OFC showed the lowest. These results suggest the presence of publication bias, which could influence the accuracy of overall estimates. However, when considering region-specific analyses, results remained consistent, indicating that although publication bias is a limitation, it does not substantially compromise the overall interpretation of the findings.

This research was limited to the databases MEDLINE (via PubMed), Science Direct (via Elsevier), and Semantic Scholar and, therefore, it may not cover all studies, especially those published in local non-indexed journals. Most studies reported only the prevalence and incidence rate of some phenotypic subgroup of CL/P, and a few others provide complete information on estimates of all subgroups, despite the extensive search of literature on CL/P epidemiology in Europe. This limits the possibility of establishing an ideal report of all types of CL/P on the European continent. Furthermore, the results of the meta-analysis may be influenced by incomplete reporting of the different phenotypic subgroups, in addition to the lack of precision of the authors in the description of the data.

Conclusion

This scoping review provides a broad overview of the status of the prevalence and incidence of CL/P in Europe and its different regions. The values of the epidemiological indices described in this study should be considered with caution and can be used as a guide for the development of programs for promoting, preventing, and treating individuals with CL/P, as well as the comparison of data with local, national, and global mean values.

Supplemental Material

sj-docx-1-cpc-10.1177_10556656241304210 - Supplemental material for Prevalence and Incidence of Cleft Lip and/or Palate in Europe: A Scoping Review and Meta-Analysis

Supplemental material, sj-docx-1-cpc-10.1177_10556656241304210 for Prevalence and Incidence of Cleft Lip and/or Palate in Europe: A Scoping Review and Meta-Analysis by Andrés Cornelis Pérez-Hettinga, María Clara González-Carrera, Erick Alexander Duque-García, Ingrid Isabel Mora-Diaz, Herney Alonso Rengifo-Reina and David Díaz-Báez in The Cleft Palate Craniofacial Journal

Footnotes

Acknowledgments

The authors thank to Universidad El Bosque, for their contribution to facilitate the present investigation.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethics Approval

Since the current study is an integrative study of secondary sources, involving no primary data collection from human subjects, approval from the institutional ethics committee was not required. The data analyzed were obtained from publicly available and previously published studies.

Funding

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

ORCID iDs

María Clara González-Carrera

Ingrid Isabel Mora-Diaz

Herney Alonso Rengifo-Reina

Supplemental Material

Supplemental material for this article is available online.

References

Mossey

Modell

. Epidemiology of oral clefts 2012: an international perspective. Front Oral Biol. 2012;16:1-18. doi:https://doi.org/10.1159/000337464

Watkins

Meyer

Strauss

Aylsworth

. Classification, epidemiology, and genetics of orofacial clefts. Clin Plast Surg. 2014;41(2):149-163. doi:https://doi.org/10.1016/j.cps.2013.12.003

Sandy

Davies

Humphries

Ireland

Wren

. Cleft lip and palate: care configuration, national registration, and research strategies. J World Fed Orthod. 2020;9(3):S40-S44. doi:https://doi.org/10.1016/j.ejwf.2020.09.003

Gregg

Leonard

Hayden

Howard

Coyle

. Birth prevalence of cleft lip and palate in Northern Ireland (1981 to 2000). Cleft Palate Craniofac J. 2008;45(2):141-147. doi:https://doi.org/10.1597/06-045.1

Loane

Dolk

Kelly

, et al. EUROCAT statistical monitoring: identification and investigation of ten-year trends of congenital anomalies in Europe. Birth Defects Res A Clin Mol Teratol. 2011;91(1S):S31-S43. doi:https://doi.org/10.1002/bdra.20778

Salari

Darvishi

Heydari

, et al. Global prevalence of cleft palate, cleft lip, and cleft palate and lip: a systematic review and meta-analysis. J Stomatol Oral Maxillofac Surg. 2022;123(2):110-120. doi:https://doi.org/10.1016/j.jormas.2021.05.008

IPDTOC Working Group. Prevalence at birth of cleft lip with or without cleft palate: data from the International Perinatal Database of Typical Oral Clefts (IPDTOC). Cleft Palate Craniofac J. 2011;48(1):66-81. doi:https://doi.org/10.1016/s0266-4356(96)90242-9

Derijcke

Eerens

Carels

. The incidence of oral clefts: a review. Br J Oral Maxillofac Surg. 1996;34(6):488-494. doi:https://doi.org/10.1016/s0266-4356(96)90242-9

Peters

Godfrey

McInerney

, et al. Joanna Briggs Institute Reviewers’ manual 2015: methodology for JBI scoping reviews. Joanna Briggs Institute. 2015;1:6-24.

10.

Olbertz

Voigt

Straube

, et al. Congenital malformations: a systematic cohort study from Mecklenburg-Western Pomerania (Germany). Z Geburtshilfe Neonatol. 2010;214(6):243-248. doi:https://doi.org/10.1055/s-0030-1267187

11.

Rösch

Steinbicker

Röse

. Häufigkeit oraler Spaltbildungen in der Region Magdeburg. Mund Kiefer GesichtsChir. 1998;2(1):5-10. doi:https://doi.org/10.1007/s100060050019

12.

Calzolari

Pierini

Astolfi

, et al. Associated anomalies in multi-malformed infants with cleft lip and palate: an epidemiologic study of nearly 6 million births in 23 EUROCAT registries. Am J Med Genet A. 2007;143(6):528-537. doi:https://doi.org/10.1002/ajmg.a.31447

13.

Clementi

Tenconi

Bianchi

, et al. Evaluation of prenatal diagnosis of cleft lip with or without cleft palate and cleft palate by ultrasound: experience from 20 European registries. Prenat Diagn. 2000;20(11):870-875. doi: https://doi.org/10.1002/1097-0223(200011)20:113.3.CO;2-A

14.

Magdalenić-Meštrović

Bagatin

. An epidemiological study of orofacial clefts in Croatia 1988–1998. J Craniomaxillofac Surg. 2005;33(2):85-90. doi:https://doi.org/10.1016/j.jcms.2005.01.002

15.

Jakobsen

Mølsted

Christensen

. Occurrence of cleft lip and palate in the Faroe Islands and Greenland from 1950 to 1999. Cleft Palate Craniofac J. 2003;40(4):426-430. doi:https://doi.org/10.1597/1545-1569_2003_040_0426_ooclap_2.0.co_2

16.

Pedersen

Almind Pedersen

Hvas Mortensen

Nybo Andersen

Christensen

. Ethnic variation in oral cleft occurrence in Denmark 1981–2002. Cleft Palate Craniofac J. 2014;51(6):677-685. doi:https://doi.org/10.1597/13-140

17.

Paaske

Garne

. Epidemiology of orofacial clefts in a Danish county over 35 years–before and after implementation of a prenatal screening programme for congenital anomalies. Eur J Med Genet. 2018;61(9):489-492. doi:https://doi.org/10.1016/j.ejmg.2018.05.016

18.

Jensen

Kreiborg

Dahl

Fogh-Andersen

. Cleft lip and palate in Denmark, 1976-1981: epidemiology, variability, and early somatic development. Cleft Palate J. 1988;25(3):258-269.

19.

Melnick

Bixler

Fogh-Andersen

Conneally

Elston

. Cleft lip±cleft palate: an overview of the literature and an analysis of Danish cases born between 1941 and 1968. Am J Med Genet. 1980;6(1):83-97. doi:https://doi.org/10.1002/ajmg.1320060108

20.

Fedeles

Jr Ziak

Krizko

, et al. Prevalence of cleft lip and palate in western Slovakia in the years 2001-2007. Bratisl Lek Listy. 2012;113(2):117-119. doi:https://doi.org/10.4149/bll_2012_027

21.

Pacáková

Zábavníková

MikIosová

Kukel'ova

Dankovcik

. Epidemiological study of orofacial clefts among population of eastern Slovakia during the period 1996-2013. Cent Eur J Public Health. 2016;24(2):128-132. doi:https://doi.org/10.21101/cejph.a4131

22.

Macháčová

Bánsky

Špaleková

Guzanin

Sabovčík

Slobodník

. Incidence of orofacial clefts in the Slovak Republic. Cent Eur J Public Health. 2006;14(3):122-125. doi:https://doi.org/10.21101/cejph.a3387

23.

Koželj

. Epidemiology of orofacial clefts in Slovenia, 1973–1993: comparison of the incidence in six European countries. J Craniomaxillofac Surg. 1996;24(6):378-382. doi:https://doi.org/10.1016/s1010-5182(96)80040-0

24.

Galán

. The epidemiology of cleft lip and palate over the period 1990-2004 in Asturias. An Pediatr (Barc). 2009;73(3):132-137. doi:https://doi.org/10.1016/j.anpedi.2009.07.013

25.

Yáñez-Vico

Iglesias-Linares

Gómez-Mendo

, et al. A descriptive epidemiologic study of cleft lip and palate in Spain. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114(5Suppl):S1-S4. doi:https://doi.org/10.1016/j.tripleo.2011.07.046

26.

Jagomagi

Soots

Saag

. Epidemiologic factors causing cleft lip and palate and their regularities of occurrence in Estonia. Stomatologija. 2010;12(4):105-108.

27.

Saxén

. Epidemiology of cleft lip and palate. An attempt to rule out chance correlations. J Epidemiol Community Health. 1975;29(2):103-110.

28.

Rintala

Stegars

. Increasing incidence of clefts in Finland: reliability of hospital records and central register of congenital malformations. Scand J Plast Reconstr Surg. 1982;16(1):35-40. doi:https://doi.org/10.3109/02844318209006568

29.

Lithovius

Ylikontiola

Harila

Sándor

. A descriptive epidemiology study of cleft lip and palate in Northern Finland. Acta Odontol Scand. 2014;72(5):372-375. doi:https://doi.org/10.3109/00016357.2013.840737

30.

Doray

Badila-Timbolschi

Schaefer

, et al. Epidemiology of orofacial clefts (1995-2006) in France (congenital malformations of Alsace registry). Arch Pediatr. 2012;19(10):1021-1029. doi:https://doi.org/10.1016/j.arcped.2012.07.002

31.

Bonaiti

Briard

Feingold

, et al. An epidemiological and genetic study of facial clefting in France. I. Epidemiology and frequency in relatives. J Med Genet. 1982;19(1):8-15. doi:https://doi.org/10.1136/jmg.19.1.8

32.

Stoll

Alembik

Dott

Roth

. Epidemiological and genetic study in 207 cases of oral clefts in Alsace, north-eastern France. J Med Genet. 1991;28(5):325-329. doi:https://doi.org/10.1136/jmg.28.5.325

33.

Czeizel

Hirschberg

. Orofacial clefts in Hungary. Folia Phoniatr Logop. 1997;49(3-4):111-116. doi:https://doi.org/10.1159/000266446

34.

Sárközi

Wyszynski

Czeizel

. Oral clefts with associated anomalies: findings in the Hungarian congenital abnormality registry. BMC Oral Health. 2005;5(4):1-6. doi:https://doi.org/10.1186/1472-6831-5-4

35.

Czeizel

Tusnady

. An epidemiologic study of cleft lip with or without cleft palate and posterior cleft palate in Hungary. Hum Hered. 1971;21(1):17-38. doi:https://doi.org/10.1159/000152380

36.

Czeizel

Tusnady

. A family study on cleft lip with or without cleft palate and posterior cleft palate in Hungary. Hum Hered. 1972;22(5-6):405-416. doi:https://doi.org/10.1159/000152518

37.

Hewson

McNamara

. Cleft lip and/or palate in the West of Ireland, 1980–1996. Spec Care Dentist. 2000;20(4):143-146. doi:https://doi.org/10.1111/j.1754-4505.2000.tb01151.x

38.

Gregg

Boyd

Richardson

. The incidence of cleft lip and palate in Northern Ireland from 1980–1990. Br J Orthod. 1994;21(4):387-392. doi:https://doi.org/10.1179/bjo.21.4.387

39.

Moller

Dunbar

. Cleft lip and cleft palate in Iceland. Alabama J Med Sci. 1966;3(4):370-372.

40.

Calzolari

Milan

Cavazzuti

, et al. Epidemiological and genetic study of 200 cases of oral cleft in the Emilia Romagna region of northern Italy. Teratology. 1988;38(6):559-564. doi:https://doi.org/10.1002/tera.1420380603

41.

Milan

Astolfi

Volpato

, et al. 766 Cases of oral cleft in Italy: data from Emilia Romagna (IMER) and Northeast Italy (NEI) registers. Eur J Epidemiol. 1994;10:317-324. doi:https://doi.org/10.1007/BF01719356

42.

Gjerdevik

Lie

Haaland

ØA

, et al. Isolated oral clefts and school grades: population-based cohort study from Norway. BMJ Open. 2021;11(10):1-7. doi:https://doi.org/10.1136/bmjopen-2020-046944

43.

Âbyholm

. Cleft lip and palate in Norway: I. Registration, incidence, and early mortality of infants with CLP. Scand J Plast Reconstr Surg. 1978;12(1):29-34. doi:https://doi.org/10.3109/02844317809010477

44.

Sæle

Østhus

Ådalen

, et al. Pattern of clefts and dental anomalies in six-year-old children: a retrospective observational study in western Norway. Acta Odontol Scand. 2017;75(2):100-105. doi:https://doi.org/10.1080/00016357.2016.1260770

45.

Âbyholm

. Cleft lip and palate in a Norwegian population: II. A numerical study of 1555 CLP-patients admitted for surgical treatment 1954–75. Scand J Plast Reconstr Surg. 1978;12(1):35-43. doi:https://doi.org/10.3109/02844317809010478

46.

Fleurke-Rozema

Van de Kamp

Bakker

, et al. Prevalence, diagnosis, and outcome of cleft lip with or without cleft palate in The Netherlands. Ultrasound Obstet Gynecol. 2016;48(4):458-463. doi:https://doi.org/10.1002/uog.15834

47.

Rozendaal

Mohangoo

Ongkosuwito

, et al. Regional variation in prevalence of oral cleft live births in The Netherlands 1997–2007: time-trend analysis of data from three Dutch registries. Am J Med Genet A. 2012;158(1):66-74. doi:https://doi.org/10.1002/ajmg.a.34343

48.

Rozendaal

Luijsterburg

Ongkosuwito

, et al. Decreasing prevalence of oral cleft live births in The Netherlands, 1997–2006. Arch Dis Child Fetal Neonatal Ed. 2011;96(3):212-216. doi:https://doi.org/10.1136/adc.2010.193599

49.

Rozendaal

Mohangoo

Luijsterburg

, et al. Prevalentie van schisis in Nederland en Noord-Nederland in 1997-2007: trendanalyse van gegevens uit drie Nederlandse registraties. Tijdschr Kindergeneeskd. 2011;79:16-25. doi:https://doi.org/10.1007/s12456-011-0003-1

50.

Cornel

Spreen

Meijer

, et al. Some epidemiological data on oral clefts in the northern Netherlands, 1981–1988. J Craniomaxillofac Surg. 1992;20(4):147-152. doi:https://doi.org/10.1016/s1010-5182(05)80389-0

51.

Pool

der Lek

de Jong

, et al. Embryologically based classification specifies gender differences in the prevalence of orofacial cleft subphenotypes. Cleft Palate Craniofac J. 2021;58(1):54-60. doi:https://doi.org/10.1177/1055665620935363

52.

Antoszewski

Fijałkowska

. Prevalence of cleft lip and/or palate in children from Lódz between years 1981–2010. Congenit Anom. 2016;56(2):60-64. doi:https://doi.org/10.1111/cga.12133

53.

Antoszewski

Fijałkowska

. The prevalence of cleft lip and/or palate in children from Łódź in years 2001-2010. Pol J Surg. 2013;85(6):329-332. doi:https://doi.org/10.2478/pjs-2013-0049

54.

Antoszewski

Fijałkowska

. Distribution of lip and/or palate clefts types among children from Lodz during years 1981-2015. Pol J Surg. 2018;90(3):1-6. doi:https://doi.org/10.5604/01.3001.0011.8162

55.

Fell

Russell

Medina

, et al. The impact of changing cigarette smoking habits and smoke-free legislation on orofacial cleft incidence in the United Kingdom: evidence from two time-series studies. PLoS One. 2021;16(11):e0259820. doi:https://doi.org/10.1371/journal.pone.0259820

56.

Womersley

Stone

. Epidemiology of facial clefts. Arch Dis Child. 1987;62(7):717-720. doi:https://doi.org/10.1136/adc.62.7.717

57.

Bellis

Wohlgemuth

. The incidence of cleft lip and palate deformities in the south-east of Scotland (1971-1990). Br J Orthod. 1999;26(2):121-125. doi:https://doi.org/10.1093/ortho/26.2.121

58.

Paterson

Sher

Wylie

, et al. Cleft lip/palate: incidence of prenatal diagnosis in Glasgow, Scotland, and comparison with other centers in the United Kingdom. Cleft Palate Craniofac J. 2011;48(5):608-613. doi:https://doi.org/10.1597/09-238

59.

Owens

Jones

Harris

. Epidemiology of facial clefting. Arch Dis Child. 1985;60(6):521-524. doi:https://doi.org/10.1136/adc.60.6.521

60.

Bister

Set

Cash

, et al. Incidence of facial clefts in Cambridge, United Kingdom. Eur J Orthod. 2011;33(4):372-376. doi:https://doi.org/10.1093/ejo/cjq117

61.

Coupland

. Seasonality, incidence, and sex distribution of cleft lip and palate births in trent region, 1973-1982. Cleft Palate J. 1988;25(1):33-37.

62.

Peterka

Likovsky

Panczak

Peterkova

. Long-term significant seasonal differences in the numbers of new-borns with an orofacial cleft in the Czech Republic–a retrospective study. BMC Pregnancy Childbirth. 2018;18(1):1-1. doi:https://doi.org/10.1186/s12884-018-1981-0

63.

Urbanova

Kotova

Vankova

. The incidence of cleft lip and palate in the Czech Republic in 1994-2008. Bratisl Lek Listy. 2013;114(8):474-479. doi:https://doi.org/10.4149/bll_2013_099

64.

Tolarova

. A study of the incidence, sex-ratio, laterality and clinical severity in 3,660 probands with facial clefts in Czechoslovakia. Acta Chir Plast. 1987;29(2):77-87.

65.

Hagberg

Larson

Milerad

. Incidence of cleft lip and palate and risks of additional malformations. Cleft Palate Craniofac J. 1998;35(1):40-45. doi:https://doi.org/10.1597/1545-1569_1998_035_0040_ioclap_2.3.co_2

66.

Beckman

Myrberg

. The incidence of cleft lip and palate in Northern Sweden. Hum Hered. 1972;22(5-6):417-422. doi:https://doi.org/10.1159/000152519

67.

Milerad

Larson

Hagberg

Ideberg

. Associated malformations in infants with cleft lip and palate: a prospective, population-based study. Pediatrics. 1997;100(2):180-186. doi:https://doi.org/10.1542/peds.100.2.180

68.

Sandahl

. Seasonal incidence of cleft lips and cleft palates in Sweden, 1965–1974. Scand J Plast Reconstr Surg. 1977;11(1):39-43. doi:https://doi.org/10.3109/02844317709025495

69.

Boyd

Haeusler

Barisic

, et al. The EUROCAT network—organization and processes. Birth Defects Res A Clin Mol Teratol. 2011;91(S1):2-15. doi:https://doi.org/10.1002/bdra.20780

70.

Rosano

Botto

Botting

Mastroiacovo

. Infant mortality and congenital anomalies from 1950 to 1994: an international perspective. J Epidemiol Community Health. 2000;54(9):660-666. doi:https://doi.org/10.1136/jech.54.9.660

71.

Berg

Lie

Sivertsen

Haaland

ØA

. Parental age and the risk of isolated cleft lip: a registry-based study. Ann Epidemiol. 2015;25(12):942-947. doi:https://doi.org/10.1016/j.annepidem.2015.05.003

72.

Harville

Wilcox

Lie

Vindenes

Åbyholm

. Cleft lip and palate versus cleft lip only: are they distinct defects? Am J Epidemiol. 2005;162(5):448-453. doi:https://doi.org/10.1093/aje/kwi214

73.

Hviid

Mølgaard-Nielsen

. Corticosteroid use during pregnancy and risk of orofacial clefts. CMAJ. 2011;183(7):796-804. doi:https://doi.org/10.1503/cmaj.101063

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

2.04 MB