**2. Descriptive epidemiology**

#### **2.1. Prevalence**

The overall prevalence of OFC is estimated to be approximately 1 in 700 live births, accounting for nearly one half of all craniofacial anomalies [1, 2]. As reported by the World Health Organization (WHO), the prevalence at birth of OFC varies worldwide, ranging 3.4–22.9 per 10,000 births for CL/P, and 1.3–25.3 per 10,000 births for CPO [3]. The incidence of CL/P and CPO can vary greatly between studies. The inclusion criteria, case definition, data sources, and selection bias contribute to the varying incidence estimates. Even though there are many different variables regarding the inclusion or exclusion criteria of in studies, the majority report a higher incidence of CL/P compared to CPO.

Prevalence has been found to vary based on ancestry, with the highest incidence rates observed amongst Asian populations (0.82–4.04 per 1000 live births), intermediate rates amongst Caucasians (0.9–2.69 per 1000 live births), and the lowest rates amongst African populations (0.18–1.67 per 1000 live births) [1, 4]. Prevalence has also been found to vary further by subgroup, for example, with one study reporting lower rates of OFC amongst Far East Asians compared to Filipinos [5].

#### **2.2. Gender ratio**

Prevalence of OFC additionally varies according to gender and cleft pattern. Male predominance has been consistently identified in CLP, with a male/female sex ratio of 1.81 (CI 95%: 1.75–1.86). For CP, the opposite has been shown, with a reported sex ratio of 0.93 (CI 95%: 0.89–0.96) [3]; however, this may be due in part to sampling bias, as one Danish study could not find a significant predominance of females in individuals with CP after combining both surgically treated and nonsurgically treated cases [6].

#### **2.3. Laterality**

palate alone (CPO) even though the etiology of each may be unique. Whether or not CL/P and

It is often found in epidemiological studies that CL/P and CPO is considered underneath the umbrella of either "syndromic" or "nonsyndromic." Furthermore, "nonsyndromic" CL/P and CPO cases can be subgrouped into those that are isolated or those that have additional malformations that do not form a recognizable syndrome. Relatively, the etiology of nonsyndromic cases of CL/P and CPO is lesser known compared to those found identified with a syndrome. Due to the poorly characterized etiology of CL/P and CPO, in general, there is still debate for the best method of grouping CL/P and CPO in epidemiological studies, but the most common current classifications are used to help determine associations and thus help

The genetic basis for many syndromic cases of CL/P and CPO are well-described. Evidence for genetic factors underlying nonsyndromic CL/P and CPO has begun to materialize as well. While less well-described, it is also known that epigenetic modifications can play a role in the development of CL/P and CPO. Recently, the association between OFC and cancer has been explored, with evidence suggesting existence of a link between the presence of OFC in

The overall prevalence of OFC is estimated to be approximately 1 in 700 live births, accounting for nearly one half of all craniofacial anomalies [1, 2]. As reported by the World Health Organization (WHO), the prevalence at birth of OFC varies worldwide, ranging 3.4–22.9 per 10,000 births for CL/P, and 1.3–25.3 per 10,000 births for CPO [3]. The incidence of CL/P and CPO can vary greatly between studies. The inclusion criteria, case definition, data sources, and selection bias contribute to the varying incidence estimates. Even though there are many different variables regarding the inclusion or exclusion criteria of in studies, the majority

Prevalence has been found to vary based on ancestry, with the highest incidence rates observed amongst Asian populations (0.82–4.04 per 1000 live births), intermediate rates amongst Caucasians (0.9–2.69 per 1000 live births), and the lowest rates amongst African populations (0.18–1.67 per 1000 live births) [1, 4]. Prevalence has also been found to vary further by subgroup, for example, with one study reporting lower rates of OFC amongst Far East

Prevalence of OFC additionally varies according to gender and cleft pattern. Male predominance has been consistently identified in CLP, with a male/female sex ratio of 1.81 (CI 95%:

CPO have distinct etiology and should be combined in investigations is under debate.

the clinician with their diagnosis and subsequent treatment.

patients and risk of cancer in these patients and/or their families.

report a higher incidence of CL/P compared to CPO.

**2. Descriptive epidemiology**

4 Designing Strategies for Cleft Lip and Palate Care

Asians compared to Filipinos [5].

**2.2. Gender ratio**

**2.1. Prevalence**

OFC may be unilateral or bilateral. According to the International Perinatal Database of Typical Orofacial Clefts (IPDTOC) working group, the proportion of bilateral cases is 10.3% for cleft lip without palate (CL) and 30.2% for cleft lip with palate (CLP). Amongst unilateral cases, 36.9% of CL and 41.1% of CLP occur on the right side, suggesting that unilateral cases of CL/P occur more frequently on the left [7].
