Heba J. Sabbagh

Passive smoking in the etiology of non-syndromic orofacial clefts: a systematic review and meta-analysis.

Background Studies have found a consistent positive association between maternal smoking and non-syndromic orofacial clefts (NSOFC). However, no comprehensive assessment of the association between NSOFC and passive smoking has been undertaken. This systematic review and meta-analysis explores the relationship between maternal passive smoking and NSOFC, and compares the associations between passive and active smoking. Methods and Findings Search strategy, inclusion / exclusion criteria, and data extraction from studies reporting maternal passive smoking and NSOFC was implemented without language restrictions. Risks of bias in the identified studies were assessed and this information was used in sensitivity analyses to explain heterogeneity. Meta-analysis and meta-regression of the extracted data were performed. Eggers test was used to test for small study effects. Fourteen eligible articles were identified. Maternal passive smoking exposure was associated with a twofold increase in risk of NSOFC (odds ratio: 2.11, 95% confidence interval: 1.54–2.89); this was apparent for both cleft lip with and without palate (OR: 2.05, 95% CI: 1.27–3.3) and cleft palate (OR: 2.11, 95% CI: 1.23–3.62). There was substantial heterogeneity between studies. In the studies that provided data enabling crude and adjusted odd ratios to be compared, adjustment for potential confounders attenuated the magnitude of association to about a 1.5-fold increase in risk. Conclusion Overall, maternal passive smoking exposure results in a 1.5 fold increase in risk of NSOFC, similar to the magnitude of risk reported for active smoking, but there is marked heterogeneity between studies. This heterogeneity is not explained by differences in the distribution of cleft types, adjustment for covariates, broad geographic region, or study bias/quality. This thorough meta-analysis provides further evidence to minimize exposure to environmental tobacco smoke in policy making fora and in health promotion initiatives.

Prevalence of orofacial clefts in Saudi Arabia and neighboring countries: A systematic review

UNLABELLED Cleft lip and/or palate are among the most common birth defects in the world. The prevalence of these conditions varies considerably across geographic areas and ethnic groups. OBJECTIVE The aim of this study was to carry out a systematic review and appraisal of the literature on the prevalence of cleft lip and/or palate in Saudi Arabia and comparable Middle Eastern countries. MATERIALS AND METHODS All published articles on orofacial clefts (OFC) in Saudi Arabia and its bordering countries in the Middle East with similar and comparable population characteristics were reviewed in July 2010. RESULTS After reviewing the articles, only eight matched the inclusion criteria. Three studies were carried out in two regions in Saudi Arabia (Riyadh and Al-Qaseem). The other five studies were set in Dubai, Oman, and Jordan. The prevalence of cleft lip and/or palate reported in these studies varied greatly from 0.3 to 2.4 per 1000 live births. The birth prevalence of orofacial clefts in males was reported to be higher than in females. The isolated cleft palate prevalence was reported to be higher in females in most of the studies. CONCLUSION The eightfold variation in the prevalence of orofacial clefts between highest and lowest prevalence is likely to be due, at least in part, to problems with ascertainment, but there may also be underlying genetic or environmental factors that require further investigation.

Environmental Risk Factors in the Etiology of Nonsyndromic Orofacial Clefts in the Western Region of Saudi Arabia

Objectives Nonsyndromic orofacial cleft (NSOFC) etiology is multifactorial and heterogeneous. This study aimed to identify environmental risk factors related to NSOFC in the Western Region of Saudi Arabia. Methods A case-control study carried out in seven hospitals in two main cities (Jeddah and Maddina) over 2 years on parents of 112 infants with NSOFC (infants were also examined) and 138 infant controls, matched for age (≤18 months), gender, and location, completed a questionnaire on 3-month pregestation and first trimester events. Results There was significantly increased NSOFC risk with twin pregnancies (P = .01, odds ratio [OR] = 9.5, 95% confidence interval [CI]: 1.15 to 78.4), maternal antibiotic use (P = .021, OR = 2.71, 95% CI: 1.11 to 6.62), antiemetic medication (P = .005, OR = 2.85, 95% CI: 1.3 to 6), severe morning sickness (P = .006, OR = 3.6, 95% CI: 1.34 to 9.65), illness (P = .009, OR = 2.19, 95% CI: 1.17 to 4.08), common cold/flu (P = .003, OR = 3.32, 95% CI: 1.48 to 7.58), Jorak smoking (P = .004, OR = 14.07, 95% CI: 1.55 to 128.1), and passive smoking (P = .05, OR = 2.05, 95% CI: 1.05 to 4.01). Reduced NSOFC risk was found with calcium supplementation (P = .02, OR = 0.32, 95% CI: 0.11 to 0.88), incense use (P = .03, OR = 0.58, 95% CI: 0.34 to 0.98), and maternal drinking water, with Zamzam water (which contains a high concentration of minerals) showing a significant protective effect compared with tap water (P = .01, 95% CI: 0.06 to 0.6) and bottled water (P = .02, 95% CI: 0.03 to 0.57). Conclusion Twin births, maternal antibiotic use, antiemetic medication, severe morning sickness, common cold/flu, Jorak smoking, and passive smoking were associated with infants born with NSOFC. Calcium supplementation, incense use, and Zamzam water reduced the risk of NSOFC, raising the possibility of community preventive programs.

Parental Consanguinity and Nonsyndromic Orofacial Clefts in Children: A Systematic Review and Meta-Analyses

Objective To assess whether individuals born to consanguineous parents had a higher frequency of nonsyndromic orofacial clefts compared with those with no parental consanguinity. Design A prespecified plan for a search strategy, inclusion/exclusion criteria, and data extraction from studies reporting consanguinity in relation to nonsyndromic orofacial clefts (NSOFC) was carried out. Papers reporting observational studies with control populations were included, without language restrictions, and these reports were assessed for quality. Sensitivity analyses using subgroups, homogeneity evaluation, and assessment of publication bias were carried out, and meta-analyses of extracted data were performed. Results Sixteen studies fulfilled the selection criteria and were included in the metaanalyses. There were statistically significant relationships between consanguinity and NSOFC for all 16 studies combined (P = .0003), with odds ratio (OR) = 1.83 and 95% confidence interval (CI) = (1.31, 2.54); 10 case-control studies (P = .006), with OR = 2.06 and 95% CI = (1.23, 3.46); six cross-sectional studies (P = .03), with OR = 1.34 and 95% CI = (1.02, 1.76); first cousins consanguineous marriages (P = .04), with OR = 1.40 and 95% CI = (1.01, 1.93); cleft palate alone (P = .01), with OR = 1.89 and 95% CI = (1.14, 3.13); and cleft lip with or without cleft palate cases (P = .002), with OR = 1.56 and 95% CI = (1.18, 2.07). Conclusion Although there was a high level of study heterogeneity, the evidence is consistent in suggesting that consanguinity is a risk factor for NSOFC, with an overall OR of 1.83 (95% CI, 1.31 to 2.54), implying that there was almost twice the risk of a child with NSOFC being born if there was parental consanguinity.

Birth prevalence of non-syndromic orofacial clefts in Saudi Arabia and the effects of parental consanguinity

Objectives: To describe the characteristics and prevalence of non-syndromic orofacial clefting (NSOFC) and assess the effects of parental consanguinity on NSOFC phenotypes in the 3 main cities of Saudi Arabia. Methods: All infants (114,035) born at 3 referral centers in Riyadh, and 6 hospitals in Jeddah and Madinah between January 2010 and December 2011 were screened. The NSOFC cases (n=133) were identified and data was collected through clinical examination and records, and information on consanguinity through parent interviews. The diagnosis was confirmed by reviewing medical records and contacting the infants’ pediatricians. Control infants (n=233) matched for gender and born in the same hospitals during the same period, were selected. Results: The prevalence of NSOFC was 1.07/1000 births in Riyadh, and 1.17/1000 births overall; cleft lip (CL) was 0.47/1000 births, cleft lip and palate (CLP) was 0.42/1000 births, and cleft palate (CP) was 0.28/1000 births. Cleft palate was significantly associated with consanguinity (p=0.047, odds ratio: 2.5, 95% confidence interval: 1 to 6.46), particularly for first cousin marriages. Conclusion: The birth prevalence of NSOFC in Riyadh alone, and in the 3 main cities of Saudi Arabia were marginally lower than the mean global prevalence. While birth prevalence for CLP was comparable to global figures, the CL:CLP ratio was high, and only CP was significantly associated with consanguinity.

Consequences of early extraction of compromised first permanent molar: a systematic review

BackgroundThe aim of this study was to systematically review the literature to determine the sequelae of early extraction of compromised first permanent molars (FPMs) with regard to the skeletal and dental development of 5- to 15-year-old children. Meta-analysis was conducted when applicable.MethodsOur research protocol included a search strategy, inclusion/exclusion criteria, and a data extraction plan. The search engines used were PubMed, Scopus, and Science Direct. Study selection was performed independently by three reviewers. Articles published from 1960 to 2017 were reviewed based on inclusion and exclusion criteria. Meta-analysis was performed to compare space closure between upper and lower arches.ResultsEleven studies fulfilled the inclusion criteria. The consequences were decrease in post extraction space, accelerated development and eruption of second permanents molars (SPMs) and third molars, a decrease in caries and/or fillings on the proximal surfaces of adjacent teeth, lingual tipping and retrusion of incisors, and counter clockwise rotation of the occlusal plane.ConclusionThere were several consequences of early extraction of FPMs, which were related to skeletal and dental development. Our systematic review suggests that comprehensive evaluation of the compromised FPMs should be performed before planning an extraction. The ideal time for FPM extraction is when the SPM is at the early bifurcation stage in order to achieve complete closure of the extraction space by the SPM. Benefits should be weighed over the risks to decrease the risk of unfavorable outcomes as much as possible. However, due to the limited evidence on the outcomes and variables that influence them, high-quality prospective studies are needed.

Interferon Regulatory Factor 6 (IRF6) and Gene – Environment Interactions in Non-Syndromic Orofacial Cleft Cases in Saudi Arabia-A Case Control Study

The association between interferon regulatory factor 6 (IRF6) and nonsyndromic orofacial cleft (NSOFC) is affected by ethnicity. Also, gene-environment interactions (GEI) may play an important role in its etiology.Objectives: This case-control study investigated whether IRF6 gene variants were associated with NSOFC in Saudi Arabian population and whether the gene was affected by maternal environmental exposures.Methods: We extracted DNA from saliva samples obtained from 171 infant–parent triad cases and 189 matched controls (age, gender, and location) from January 2010–December 2011; this study included a total of 11 referral hospitals in Saudi Arabia. IRF6 (rs2013162, rs2235375, and rs2235371) polymorphisms were genotyped using restriction-digestion polymerase chain reaction. Data on environmental exposures, for GEI analyses, were collected through questionnaire-led interviews with parents.Results: We found statistically significant over transmission of the common IRF6 rs2013162 allele among cleft lip with or without palate CL(P) cases. No associations were found for either of the other two IRF6 SNPs. Maternal exposure to antipyretics, folic acid, fever, antibiotics, illnesses, common cold/flu, paternal water pipe smoking, stress, x-rays, and/or chemicals could significantly interact with the maternal IRF6 (rs2013162 and rs2235375) gene variants, affecting the likelihood of having an offspring with NSOFC.Conclusion: The common allele at IRF6 rs2013162 was significantly over transmitted among CL(P) cases. This study provides hypotheses for future investigations into genetic and environmental factors and their interaction in the etiology of NSOFC.