COVID-19 vaccine and non-syndromic orofacial clefts in five arab countries. A case-control study.

OBJECTIVES: Risk factors for non-syndromic orofacial cleft (NSOFCs) include genetic profile and environmental exposure to medication and illnesses during pregnancy. We assessed the association between the COVID-19 vaccination and the incidence of NSOFC across five Middle Eastern countries. MATERIALS AND METHODS: This multi-country, hospital-based, case-control study included infants with NSOFCs whose first 3 intrauterine months coincided with the time when pregnant women were allowed to receive COVID-19 vaccination in the countries participating in the study. Newborns with NSOFCs were examined for cleft type and their parents were interviewed for maternal exposures and COVID-19 vaccination. Controls were newborns matched to cases in gender and setting. RESULTS: The study recruited 977 (348 children with NSOFCs and 629 controls). Maternal use of nicotine (Adjusted Odds Ratio (AOR): 2.437; P = 0.044) and family history of NSOFC (AOR: 11.059; P < 0.001) increased significantly the AOR of having a child with NSOFC. On the other hand, COVID-19 vaccine administration to pregnant mothers have significantly decreased the AOR of having a child with NSOFC (AOR: 0.337; P = 0.006). CONCLUSION: This study suggests that COVID-19 vaccination is not related to NSOFC and might protect against having a child affected with such a congenital anomaly. CLINICAL RELEVANCE: The finding of this study is important for healthcare providers for considering COVID-19 vaccination for pregnant woman. Clear communication and education about the potential risks and benefits would be crucial for informed decision-making. The study's results would directly impact pregnant individuals, as they would need accurate information to make informed decisions about their health and the health of their infants.

Maternal Exposure to Stress During Covid-19 and Non-Syndromic Orofacial Clefts: A Cohort Retrospective Study.

OBJECTIVE: The coronavirus (COVID-19) pandemic presents an opportunity to study stress's effect on the development of non-syndromic orofacial clefts (NSOFCs). This study was aimed at assessing maternal stress exposure during the pregestational to first trimester pregnancy periods and the development of NSOFCs during a year of the COVID-19 pandemic. DESIGN: Cohort study of infants with NSOFCs and controls matched based on recruitment site and age. SETTING: Government hospitals in Saudi Arabia between November 2020 and November 2021. MAIN OUTCOME MEASURES: Data collection included NSOFC clinical examination and maternal stress exposure assessment using the Modified Life Events Questionnaire, the Fear of COVID-19 Scale, and a focus on the lack of pregnancy planning and a threatened miscarriage. RESULTS: Of the 557 infants recruited, 191 had NSOFCs. Logistic regression analysis with adjusted odds ratios (AORs) that removed the effects of confounders showed that any of the seven stressful life events (AOR:3.78, P < .001) and the family histories of relatives with NSOFCs (AOR:9.73, P < .001) increased the AOR for NSOFC development. In contrast, maternal folic acid (AOR:0.56, P.010), threatened miscarriage (AOR:0.17, P = .001), fear of COVID-19 (AOR:0.83, P = .038), and suspected COVID-19 infection (AOR:0.43, P = .008) decreased the AOR for NSOFC development. CONCLUSION: Along with an established risk associated with family history of birth defects, stressful life events may be a risk factor for NSOFC development. Beyond folic acid's known benefit, it may be that higher maternal health concerns contribute to increased protective health behaviors during pregnancy. Ongoing research is needed to specify the maternal risk factors for NSOFC.

Incidence of non-syndromic orofacial cleft during the COVID-19 pandemic in Saudi Arabia.

OBJECTIVES: This is the first national study to investigate the incidence of non-syndromic oro-facial clefts (NSOFC) and Pierre-Robin-Sequence in Saudi Arabia over the Covid-19 pandemic period. METHODS: All maternity hospitals (30-hospitals) in the major regions and cities of Saudi from November 2020-to-2021 were included in the study. Patients were evaluated for cleft phenotype using the LASHAL-classification system. The incidence of NSOFC in Saudi Arabia was calculated by comparing the number of NSOFCs cases born out of all live births during the study period at the included hospitals. Clinical examination was performed and information was gathered using a validated data collection form. RESULTS: In one year, 140,380 live-infants were born at the selected hospitals. Of these, 177 were diagnosed with NSOFC giving an incidence of 1.26/1,000 live-births in Saudi Arabia and the highest incidence in Medina city (2.46/1000 live-births). The incidence of cleft lip-and-palate (0.67/1000 live-births) was higher than that of cleft-palate (0.37/1000 live-births) and cleft-lip (0.22/1000 live-births). Pierre-Robin Sequence incidence was (0.04/1000 live-births). There were 21(12.1) or 23(13.2%) of NSOFC's mothers exposed or vaccinated with Covid-19, respectively. CONCLUSION: The national incidence of NSOFC in Saudi Arabia was 1.26/1000 live births with variation between phenotypes and regions in the country. In addition, to reporting Covid-19 infection prevalence and vaccine exposure among NSOFC's mothers, this study represents the first of its type to evaluate NSOFC prevalence in Saudi Arabia on a national level.

COVID-19 related risk factors and their association with non-syndromic orofacial clefts in five Arab countries: a case-control study.

BACKGROUND: The environmental etiology of non-syndromic orofacial clefts (NSOFCs) is still under research. The aim of this case-control study is to assess COVID-19 associated factors that may be related to the risk of NSOFC in five Arab countries. These factors include COVID-19 infection, COVID-19 symptoms, family member or friends infected with COVID-19, stress, smoking, socioeconomic status and fear of COVID-19. METHODS: The study took place in governmental hospitals in five Arab countries from November 2020 to November 2021. Controls are matched in the month of delivery and site of recruitment. A clinical examination was carried out using LASHAL classification. Maternal exposure to medication, illnesses, supplementation, COVID-19 infection during their pregestation and 1st trimester periods were evaluated using a validated questionnaire. Maternal exposure to stress was assessed using the Life Events scale, fear of covid-19 scale, family member or friend affected with covid-19 infection, pregnancy planning and threatened abortion. RESULTS: The study recruited 1135 infants (386 NSOFC and 749 controls). Living in urban areas, maternal exposure to medications 3-months pregestation, maternal exposure to any of the prenatal life events and maternal fear of COVID-19 significantly increased the risk of having a child with NSOFC. On the other hand, mothers exposed to supplementation 3-months pregestation, mothers suspected of having COVID-19 infection, family members or friends testing positive with COVID-19 significantly decreased the risk of having a child with NSOFC. CONCLUSIONS: This study suggests that NSOFC may be associated with maternal exposure to lifetime stress and COVID-19 fear in particular, with no direct effect of the COVID-19 infection itself. This highlights the importance of providing psychological support for expecting mothers during stressful events that affect populations such as the COVID-19 pandemic, in addition to the usual antenatal care.

Molecular Screening of VAX1 Gene Polymorphisms Uncovered the Genetic Heterogeneity of Nonsyndromic Orofacial Cleft Among Saudi Arabian Patients.

OBJECTIVE: Nonsyndromic orofacial cleft (NSOFC) including cleft lip with or without cleft palate (CL±P) and cleft palate (CP) are multifactorial developmental disorders with both genetic and environmental etiological factors. In this study we investigated the association between CL±P and CP, and two polymorphisms previously determined using genome-wide association studies, as well as the association between consanguinity and CL±P and CP. METHODS: DNA was extracted from saliva specimens from 171 triads consisting of affected individuals and their parents, as well as 189 control triads (matched for age, gender, and location) that were recruited from 11 referral hospitals in Saudi Arabia. Two polymorphisms, rs4752028 and rs7078160, located in the VAX1 gene were genotyped using real-time polymerase chain reaction. A transmission disequilibrium test was carried out using the Family-Based Association Test and PLINK (genetic tool-set) to measure the parent-of-origin effect. RESULTS: Significant differences were found between affected individuals and the control group. In the case of the rs4752028 risk allele in cleft, the phenotypes were: CL±P (fathers: odds ratio [OR] 2.16 [95% CI 1.38-3.4]; mothers: OR 2.39 [95% CI 1.53-3.71]; and infants: OR 2.77 [95% CI 1.77-4.34]) and CP (fathers: OR 2.24 [95% CI 1.15-4.36] and infants: OR 2.43 [95% CI 1.25-4.7]). For CL±P and the rs7078160 risk allele, the phenotypes were: (fathers: OR 1.7 [95% CI 1.05-2.86]; mothers: OR 2.43 [95% CI 1.49-3.97]; and infants: OR 2.34 [95% CI 1.44-3.81]). In terms of consanguinity, we found significant association between consanguinity and the rs4752028 polymorphism minor allele among CL±P compared with controls (p = 0.001). CONCLUSION: This is the first study to find a relationship between these two loci on 10q25 (rs4752028 and rs7078160) and NSOFC in a population with high levels of consanguinity.

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.