Occurrence Of Orofacial Clefts Research Articles

Orofacial Cleft and Its Association with Consanguineous Marriage and Other Risk Factors: A Case-control Study from a Tertiary Care Hospital in Jammu Province.

Orofacial cleft is among the most common craniofacial malformations. It presents a complex and multifactorial etiology that involves genetic and environmental factors. One of the etiological factors is consanguinity (marriage between blood relatives). Multiple environmental risk factors, such as advanced maternal age, parity, maternal smoking, radiation, alcohol consumption, diabetes mellitus, and maternal use of drugs (i.e., anticonvulsants), folic acid deficiency, etc., have also been linked to the development of cleft lip and/or palate (CL/P). There is a dearth of literature reporting the occurrence of cleft due to consanguinity and other risk factors. The aim of this study is to describe the orofacial cleft demographics and to determine the influence of parental consanguinity and other associated risk factors on the occurrence of orofacial clefts (OFC) at a tertiary healthcare hospital in Jammu Province. This was a hospital-based case-control study. In the present study, data collection was specifically done regarding demographic features, history of consanguinity, degree of consanguinity, and other associated maternal risk factors in both the cleft and control groups. This study elucidates a significant association between parental consanguinity, degree of consanguinity, and other associated risk factors (i.e., maternal age ≥30 years, birth order ≥3, maternal smoking, alcohol consumption, and lack of folic acid consumption) with the occurrence of OFC. Prevention is better than cure. Awareness programs and appropriate counseling should be conducted to educate the community about the risk factors and the anticipated genetic consequences of consanguinity to prevent the development of cleft anomalies in such populations. Gupta A, Kaul B, Gulbar S, et al. Orofacial Cleft and Its Association with Consanguineous Marriage and Other Risk Factors: A Case-control Study from a Tertiary Care Hospital in Jammu Province. Int J Clin Pediatr Dent 2024;17(11):1258-1264.

Elementomics of 32 elements in cord serum depicts the risk of orofacial clefts: A case-control study in Shanxi, China

Maternal exposure to various metallic and non-metallic elements has been linked to the occurrence of orofacial clefts (OFCs), yet there remains a dearth of comprehensive research on the potential ramifications of simultaneous exposure to multiple elements. In this study, we investigated the individual and combined effects of element exposure on OFCs in a cohort of 168 pregnant women (49 cases and 119 controls) in the Shanxi province of northern China from 2010 to 2015. Cord serum samples were obtained from all participants to analyze the levels of 32 elements using inductively coupled plasma-mass spectrometry. The study examined the independent correlation between element concentrations and OFCs using two machine screening models, Boruta and Least Absolute Shrinkage and Selection Operator. Bayesian kernel machine regression (BKMR) was utilized to determine the combined effects of key exposure elements on OFCs and to clarify the interaction between exposed elements through the generalized additive model (GAM). The screening models identified lead (Pb), tin (Sn), iron (Fe), and cesium (Cs) as the most significant risk factors for OFC development in offspring. In the BKMR model, the probability of OFCs increased with higher overall levels of these risk elements, with Pb emerging as the primary contributor to the combined effect of the mixture. The findings of the GAM indicated that the combined exposure to Pb and Sn had a synergistic effect on the risk of developing OFCs. Analysis of elemental exposure in umbilical cord serum suggested that Pb exposure may have detrimental effects on OFC development in offspring, which may be further intensified by a synergistic interaction between Sn and Pb in the occurrence of OFCs.

Association between gestational exposure and risk of orofacial clefts: a systematic review and meta-analysis

BackgroundThe occurrence of orofacial Clefts (OFCs) is a congenital disease caused by many factors. According to recent studies, air pollution has a strong correlation with the occurrence of OFCs. However, there are still some controversies about the current research results, and there is no relevant research to review the latest results in recent years.ObjectiveIn this paper, the authors conducted a systematic review and meta-analysis to explore the correlation between ambient air pollution and the occurrence of neonatal OFCs deformity.MethodsWe searched Pubmed, Web of science, and Embase databases from the establishment of the database to May 2023. We included observational studies on the relationship between prenatal exposure to fine particulate matter 2.5 (PM2.5), fine particulate matter 10 (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO) and the risk of cleft lip (CL), cleft palate (CP), cleft lip with or without palate (CL/P). the Newcastle-Ottawa quality assessment scale (NOS) was used to evaluate the quality of the literature. Funnel plot and Egger’s regression were used to verify the publication bias. Random effect model or fixed effect model was used to estimate the combined relative risk (RR) and 95% confidence interval (95%CI).ResultsA total of eleven studies were included in this study, including four cohort studies and seven case-control studies, including 22,453 cases of OFCs. Ten studies had low risk of bias and only one study had high risk of bias. Three studies reported that PM2.5 was positively correlated with CL and CP, with a combined RR and 95%CI of 1.287(1.174,1.411) and 1.267 (1.105,1.454). Two studies reported a positive correlation between O3 and CL, with a combined RR and 95%CI of 1.132(1.047,1.225). Two studies reported a positive correlation between PM10 and CL, with a combined RR and 95%CI of 1.108 (1.017,1.206). No association was found between SO2, CO, NO2 exposure during pregnancy and the risk of OFCs.ConclusionThe results of this study showed that there was a significant statistical correlation between exposure to PM10, PM2.5, O3 and the risk of OFCs in the second month of pregnancy. Exposure assessment, research methods and mechanisms need to be further explored.

P07-003-23 The Occurrence of Oro-Facial Clefts in Ghana, a National Priority for Policy Action

P07-003-23 The Occurrence of Oro-Facial Clefts in Ghana, a National Priority for Policy Action

Alterations in DNA Methylation in Orofacial Clefts.

Orofacial clefts are among the most common craniofacial anomalies with multifactorial etiologies, including genetics and environments. DNA methylation, one of the most acknowledged mechanisms of epigenetics, is involved in the development of orofacial clefts. DNA methylation has been examined in patients with non-syndromic cleft lip with cleft palate (nsCL/P) from multiple specimens, including blood, saliva, lip, and palate, as well as experimental studies in mice. The results can be reported in two different trends: hypomethylation and hypermethylation. Both hypomethylation and hypermethylation can potentially increase the risk of nsCL/P depending on the types of specimens and the specific regions on each gene and chromosome. This is the most up-to-date review, intending to summarize evidence of the alterations of DNA methylation in association with the occurrence of orofacial clefts. To make things straightforward to understand, we have systematically categorized the data into four main groups: human blood, human tissues, animal models, and the factors associated with DNA methylation. With this review, we are moving closer to the core of DNA methylation associated with nsCL/P development; we hope this is the initial step to find a genetic tool for early detection and prevention of the occurrence of nsCL/P.

Alkali and alkaline earth elements in maternal serum and occurrence of orofacial clefts in offspring

Alkali elements (AEs) and alkaline earth elements (AEEs) play critical roles in numerous physiological and pathological processes. However, the effects of maternal exposure to AEs and AEEs on the risk for fetal orofacial clefts (OFCs) remain unclear. We explored the associations between levels of eight AEs and AEEs in maternal serum during pregnancy and occurrence of fetal OFCs. Concentrations of four AEs and four AEEs in maternal serum of 130 OFC cases and 260 non-malformed controls were assessed. Multilevel mixed-effects logistic regression and bayesian kernel machine regression (BKMR) were performed to evaluate the single and combined effects, respectively, of exposure to AEs and AEEs on OFC risk. When individual elements were analyzed separately as categorical variables, the odds of OFCs increased by 2.08-fold (1.10–3.93) and 2.35-fold (1.24–4.45) for sodium and by 1.98-fold (1.04–3.77) and 1.92-fold (1.21–3.61) for strontium but decreased by 0.54-fold (0.29–0.98) and 0.42-fold (0.22–0.78) for potassium in the second and third tertiles, respectively, with the lowest tertile concentration being used as the referent. When all eight elements were considered as a mixture, potassium and calcium showed protective effects, whereas sodium and strontium increased odds of OFCs in the BKMR model. No joint effect on OFC risk was observed when the eight elements were considered as a mixture. Taken together, higher levels of sodium and strontium in maternal serum were associated with an increased odds of fetal OFCs, whereas higher levels of potassium in maternal serum were associated with a decreased odds of OFCs.

Higher concentration of selenium in placental tissues is associated with reduced risk for orofacial clefts

Growing evidence suggests that essential trace element imbalance during pregnancy may contribute to fetal malformations, but the role of essential trace elements in the occurrence of orofacial clefts (OFCs) is unknown. We aimed to examine the association between concentrations of zinc (Zn), manganese (Mn), selenium (Se), cobalt (Co), molybdenum (Mo), and nickel (Ni) in placental tissues and the risk for OFCs in offspring in a rural population in northern China with a high prevalence of OFCs. The case-control study subjects were 103 OFC infants and 206 non-malformed infants. The concentrations of selected trace elements in placental tissues were determined using inductively coupled plasma-mass spectrometry. Sociodemographic information was collected from the mothers through face-to-face interviews using a structured questionnaire. The risk for OFCs in association with higher concentrations of the trace elements was estimated using the odds ratio (OR) with its 95% confidence interval (95% CI). The placental median concentrations of Se and Ni were significantly lower, but those of Mo were significantly higher in OFC cases than in controls (all P<0.05). A Se concentration above the median of all subjects was associated with a 58% reduced risk for OFCs (adjusted OR 0.42, 95% CI 0.23, 0.77) after adjusting for potential confounding factors. The risk for OFCs decreased with increases in placental Se concentrations, with adjusted ORs of 0.45 (95% CI 0.22, 0.92) for the second tertile and 0.22 (95% CI 0.10, 0.49) for the top tertile of Se concentration, with the lowest tertile concentration as the referent (Ptrend<0.001). No association was observed between placental Zn, Mn, Co, Mo, or Ni concentration and risk for OFC. The concentration of Se in placental tissues was dose-dependently associated with decreased risk for OFCs in offspring. This finding suggests that maternal Se intake during pregnancy may protect against OFCs in offspring.

Seasonal Variation of Orofacial Clefts.

Orofacial clefts represent the most common craniofacial malformation diagnosed at birth and may be divided into isolated cleft lip (CL), cleft lip and palate (CL/P), or isolated cleft palate (CP). The causes of orofacial clefts have long been understood to be multifactorial; however, research into the genetic and environmental factors underpinning these disorders in African populations is scant. Seasonal variation in the occurrence of orofacial clefts was investigated. Seasonal variation is defined as differences due to periodic, temporal, and external influences, namely the particular time or season of the year. The study design is a retrospective record review and sampled patients presenting to the Cleft Clinic at Charlotte Maxeke Johannesburg Academic Hospital during the time period October 2000 to October 2015. Ethical approval was obtained. Information recorded included patient demographics (date of birth and gender), diagnosis and laterality of the cleft. This study includes 512 infants. This study shows seasonal variation in the incidence of orofacial clefts limited to patients with both a CL/P. There was no significant seasonal variation observed in isolated CL or CP and laterality of the cleft. Significant seasonal variation was observed only in those born in winter versus summer, with more children born with a CL/P in winter months. Seasonal (or temporal) variation indicates a distinct environmental influence on the formation of orofacial clefts in utero, more specifically in pregnancies with the first trimester during spring. Several reasons have been advanced and include sunlight exposure and vitamin D levels, weight gain, and maternal obesity. More study is required to further elucidate these reasons.

The relationship between maternal corticosteroid use and orofacial clefts-a meta-analysis

The aim was to evaluate the relationship between maternal corticosteroid use during first trimester of pregnancy and risk of orofacial clefts (OC). The overall findings showed a certain association between maternal corticosteroid use and occurrence of OC, compared with non-users (OR=1.16 [95% CI: 1.01–1.33]). When study type was considered this association was significant only for case-control studies (OR=1.22 [95% CI: 1.02–1.47]), and not for cohort studies (OR=1.09 [95% CI: 0.88–1.34]) when there are many confounders (dose, route of application, disease etc.) and biases (re-call, loss-to follow-up etc.) that still need to be considered. A subgroup analysis based on the type of OC gave an overall OR of 1.41 (95% CI: 1.14–1.74) in the case-control studies for cleft lip with or without palate (CL/P) and 1.09 (95% CI: 0.80–1.48) for cleft palate only (CPO), when comparing maternal corticosteroid users with non-users. However, for cohort studies, the overall OR for CL/P is 1.06 (95% CI: 0.82–1.37) and 1.20 (95% CI: 0.83–1.75) for CPO. The absolute risk of facial cleft after prenatal exposure to corticosteroids, if any, is small.

Epidemiological Study of Orofacial Clefts among Population of Eastern Slovakia during the Period 1996-2013.

Over the past 18 years, according to data from the Clinic of Plastic and Reconstructive Surgery, L. Pasteur University Hospital, there have been 493 cases of orofacial clefts (OC) reported in the area of Eastern Slovakia. The aim of this study was to map the occurrence of orofacial clefts reported in the area of Eastern Slovakia during the years 1996-2013. Also, we compared the occurrence of different types of clefts between the groups in relation to gender and ethnicity. The statistical analysis shows relationship between variables of location and gender and gender differences in the occurrence of various types of clefts. Moreover, in comparison with another study which analyzed the years 1985-2000 (1.29/10(3) live births), there was an increase in the incidence (1.42/10(3) live births) of OC in Eastern Slovakia. Our findings seem contradictive to similar studies which discuss ethnic differences in relation to OC. We recognize the relatively high occurrence of OC in Eastern Slovakia, and we link this phenomenon to several extrinsic factors, in particular socioeconomic status and embryotoxic factors.

Maternal alcohol consumption during pregnancy and the risk of orofacial clefts in infants: a systematic review and meta-analysis.

The teratogenic effects of maternal alcohol consumption during pregnancy include anomalies of craniofacial structures derived from the cranial neural crest cells. The presence of specific craniofacial anomalies contributes to the diagnosis of fetal alcohol spectrum disorders. Cleft lip and palate [orofacial clefts (OFCs)], also derived from the cranial neural crest cells, are common congenital anomalies, but their relationship with prenatal alcohol consumption is unknown. To evaluate the association between maternal consumption of alcohol during pregnancy and the occurrence of OFCs in infants, we conducted a systematic review and meta-analyses of published studies. We examined the associations between any alcohol consumption, binge level drinking, and heavy and moderate levels of consumption vs. no or low levels of consumption. After screening 737 publications, we identified 33 studies (23 case-control and 10 cohort studies). There was considerable heterogeneity in individual study design, quality measures and study results. Findings from random effects meta-analyses suggest no relationship between prenatal alcohol consumption and the occurrence of OFCs {pooled odds ratios for any alcohol intake and binge level drinking respectively: cleft lip with or without cleft palate 1.00 [95% confidence interval (CI) 0.86, 1.16] from 18,349 participants in 13 studies, 1.04 [95% CI 0.87, 1.24] [8763 individuals, 4 studies]; cleft palate only 1.05 [95% CI 0.92, 1.21] [21,459 individuals, 17 studies], 0.94 [95% CI 0.74, 1.21] [7730 participants, 4 studies]}. While we found no association between alcohol consumption during pregnancy and OFCs in infants, the influence of study design, particularly in relation to alcohol exposure measurement and OFC ascertainment cannot be ignored.

Consanguinity and occurrence of cleft lip/palate: A hospital‐based registry study in Riyadh

This paper focuses on the influence of consanguinity on the occurrence of orofacial clefts. All patients with orofacial clefts registered at King Faisal Specialist Hospital and Research Center, Riyadh since June 1999 until December 2009 were included in this study. Patients were classified in two distinct groups: cleft lip with or without cleft palate (CL ± P) and isolated cleft palate (CP). Chi-squared test was used to test independence of variables. Intracluster correlation coefficient was estimated to assess the degree of concordance between siblings. Among 1,171 total patients, CL ± P was found to be more common (64.0%). Males were more likely to be affected with CL ± P (M:F = 1.5:1) and females were more likely to be affected with CP (M:F = 0.9:1; P < 0.0001). About a third of patients had a family history of clefts; family history was more likely to be positive for patients with CL ± P than for patients with CP (33.6% vs. 22.0%; P < 0.0001). Consanguineous relationships were seen in 56.8% of our patients' parents. Family history was more likely to be positive for patients whose parents were consanguineous than those who were non-consanguineous (34.2% vs. 25.8%; P = 0.003), both for the CL ± P and CP groups. Recurrence among siblings did not differ between those born to consanguineous versus non-consanguineous parents. Recurrence of clefts in offspring was higher among parents affected by cleft compared to those who were not affected (51.4% vs. 11.4%; P < 0.0001), both for CL ± P and CP groups. Education about anticipated genetic consequences of consanguinity is important for populations with a high degree of consanguinity.

Maternal dietary B vitamin intake, other than folate, and the association with orofacial cleft in the offspring.

Periconceptional folic acid supplementation is suggested to prevent orofacial clefts (OFCs). Other B vitamins however may be beneficial as well. To investigate the maternal periconceptional dietary intake of thiamine, riboflavin, niacin, pyridoxine and cobalamin in association with the occurrence of OFC. Two hundred and six mothers of a child with nonsyndromic OFC and 203 control mothers filled out a general questionnaire and a food frequency questionnaire around 14 months postpartum as a proxy for periconceptional intake. After exclusion of known pregnant and lactating mothers, those who reported to have altered their diet compared to the periconceptional period, and mothers with incidental folic acid supplement use periconceptionally, data of 182 OFC mothers and 173 controls were analysed. After logarithmic transformation, geometric means (P5-P95) were calculated and compared between the groups. After subsequent adjustment for energy, quintiles of dietary B vitamin intake were created. The periconceptional intake of thiamine, niacin and pyridoxine was significantly lower in mothers of an OFC child. A trend towards risk reduction for OFC with increasing dietary intake was demonstrated for thiamine (p = 0.04) and pyridoxine (p = 0.03). Risk reductions were only demonstrated in women using folic acid supplements periconceptionally. Supplement users tended to consume a diet richer in B vitamins. Periconceptional intake of thiamine, niacin and pyridoxine seems to contribute to the prevention of OFC.

Orofacial clefts in the newborn and environmental and occupational parental exposures: a case-control study in Rio de Janeiro, Brazil

OBJECTIVES: to evaluate risk factors involving environmental and occupational parental exposures associated with occurrence of orofacial clefts in a group of Brazilian children. METHODS: a secondary base case-control study was conducted with 274 cases of cleft lip with or without cleft palate (CL±P) and cleft palate only, with 548 controls (1:2). The authors analyzed residential proximity to industrial areas, exposure to commercial insecticides, agricultural pesticides, and vector control spraying, as well as various occupational exposures. The results were obtained by conditional regression analysis. RESULTS: proximity to industrial installations as a risk factor (OR = 3,32; 95%CI: 2,18-5,05) for all orofacial clefts, as well as the combined use of household insecticides and urban vector control pesticide spraying (OR = 5,73; 95%CI: 2,51-11,28). A group of maternal occupations heavily associated with orofacial clefts was domestic services (OR = 2,89; 95%CI: 1,76-4,86). CONCLUSIONS: solvents are frequently associated with CL ± P and that they are contained in numerous industrial products and household cleaning products, the results pertaining to occupational exposure become plausible. Other associations such as the routine use of domestic insecticides require further specific research for confirmation of the hypothesis.