Maternal Drug Use and Infant Cleft Lip/Palate with Special Reference to Corticoids

Objective To study the association between maternal drug use in early pregnancy and orofacial cleft in the infant. Design Register analysis based on prospectively collected information. Patients All delivered women in Sweden July 1, 1995, through December 31, 2001. Main outcome measure Presence of orofacial cleft in infant. Results Prospective information on maternal drug use during the first trimester, as reported in early pregnancy, was studied in 1142 infants with orofacial clefts, isolated or with other malformations, excluding chromosome anomalies. Any drug use was not associated with clefts (odds ratio [OR] = 0.98, 95% confidence interval [95% CI] = 0.85 to 1.13), with isolated clefts (OR = 0.92) with isolated median cleft palate (OR = 1.03, 95% CI = 0.79 to 1.36) or with isolated cleft lip with or without cleft palate (OR = 0.86, 95% CI = 0.71 to 1.05). Reported use of multivitamins, folic acid, or B12 was not associated with a decrease in orofacial cleft risk (OR = 1.00, 95% CI = 0.63 to 1.52). ORs above 2 were seen for some drugs: sulfasalazine, naproxen, and anticonvulsants, but only a few exposed cases occurred. An association between glucocorticoid use and infant cleft was indicated and seemed to be strongest for median cleft palate. Conclusion Maternal drug use seems to play only a small role for the origin of orofacial clefts, at least in Sweden.

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Prevention of Orofacial Clefts: Does Pregnancy Planning Have a Role?

The Cleft Palate-Craniofacial Journal ◽

10.1597/06-002 ◽

2007 ◽

Vol 44 (3) ◽

pp. 244-250 ◽

Cited By ~ 19

Author(s):

Peter A. Mossey ◽

Janet A. Davies ◽

Julian Little

Keyword(s):

Cleft Palate ◽

Cleft Lip ◽

Unplanned Pregnancy ◽

First Trimester ◽

Inverse Association ◽

Orofacial Cleft ◽

Orofacial Clefts ◽

Pregnancy Planning ◽

The United Kingdom ◽

First Trimester Of Pregnancy

Objective: To investigate the association between pregnancy planning and orofacial clefts in the United Kingdom. Design: Case–control study. Setting: Scotland and the Manchester and Merseyside regions of England. Participants: One hundred and ninety-one children born with nonsyndromic orofacial cleft, 1997 to 2000, and 247 controls. Main outcome measure: Cleft lip with and without cleft palate, and cleft palate. Results: There was an inverse association between planning for pregnancy and orofacial cleft in the offspring (odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.33–0.79). An unplanned pregnancy together with smoking in the first trimester of pregnancy resulted in almost treble the risk of a child with an orofacial cleft when compared with those who planned their pregnancy and did not smoke (OR = 2.92, CI = 1.50–5.65). Conclusions: Planned pregnancies were associated with a lower risk of orofacial clefts. Isolation of the elements of pregnancy planning implicated in these results is difficult. Current preconception advice needs to reach a wider audience; however, for maximum impact, efforts are needed to reduce the numbers of unplanned pregnancies.

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Incidence of Orofacial Clefts in Kumasi, Ghana

ISRN Plastic Surgery ◽

10.5402/2013/280903 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

P. Agbenorku ◽

M. Yore ◽

K. A. Danso ◽

C. Turpin

Keyword(s):

Cleft Palate ◽

Congenital Anomalies ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

Orofacial Clefts ◽

Female Ratio ◽

Live Births ◽

Male Female Ratio ◽

Cleft Lip Palate ◽

History Of

Background. Cleft lip and cleft palate are among the most common orofacial congenital anomalies. This study is to establish Orofacial Clefts Database for Kumasi, Ghana, with a view to extend it to other cities in future to obtain a national orofacial anomaly database. Methods. A descriptive prospective survey was carried out at eleven selected health facilities in Kumasi. Results. The total number of live births recorded was 27,449. Orofacial anomalies recorded were 36, giving an incidence of 1.31/1000 live births or 1 in 763 live births. The mean maternal age of cleft lip/palate babies was 29.85 years (range 18–40 years). The male : female ratio for the orofacial anomalies babies was 1.3 : 1; the male : female ratio was 0.5 : 1 in the cleft lip group, 1.3 : 1 in the cleft lip and palate group, and 4 : 1 in the cleft palate group. The majority of clefts were unilateral (69.4%, n=25), with females (n=14) outnumbering males (n=11). A family history of cleft was recorded with five babies (13.9%). Associated congenital anomalies were recorded in seven (19.4%) cleft lips and/or palates. Conclusion. The incidence of 1 in 763 live births found in this study indicates that cleft lip/palate is a common congenital anomaly in Kumasi.

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Prevalence and Characteristics of Non-Syndromic Orofacial Clefts and the Influence of Consanguinity

Journal of Clinical Pediatric Dentistry ◽

10.17796/jcpd.38.3.bm4m2158v17p2535 ◽

2014 ◽

Vol 38 (3) ◽

pp. 241-246 ◽

Cited By ~ 2

Author(s):

NM Alamoudi ◽

H J Sabbagh ◽

NPT Innes ◽

D El Derwi ◽

AZ Hanno ◽

...

Keyword(s):

Saudi Arabia ◽

Cleft Palate ◽

Cleft Lip ◽

Orofacial Cleft ◽

Prospective Surveillance ◽

Orofacial Clefts ◽

Birth Prevalence ◽

Live Births ◽

Jeddah City ◽

The Relationship

The Objective of this study was to identify the prevalence and describe the characteristics of non-syndromic orofacial cleft (NSOFC) in Jeddah, Saudi Arabia and examine the influence of consanguinity. Study Design: Six hospitals were selected to represent Jeddah's five municipal districts. New born infants with NSOFC born between 1st of January 2010 to 31st of December 2011 were clinically examined and their number compared to the total number of infants born in these hospitals to calculate the prevalence of NSOFC types and sub-phenotypes. Referred Infants were included for the purpose of studying NSOFC characteristics and their relationship to consanguinity. Information on NSOFC infants was gathered through parents’ interviews, infants’ files and patient examinations. Results: Prospective surveillance of births resulted in identifying 37 NSOFC infants born between 1st of January 2010 to 31st of December 2011 giving a birth prevalence of 0.80/1000 living births. The total infants seen, including referred cases, were 79 children. Consanguinity among parents of cleft palate (CP) cases was statistically higher than that among cleft lip with or without cleft palate (CL/P) patients (P=0.039). Although there appears to be a trend in the relationship between consanguinity and severity of CL/P sub-phenotype, it was not statistically significant (P= 0.248). Conclusions: Birth prevalence of NSOFC in Jeddah City was 0.8/1000 live births with CL/P: 0.68/1000 and CP: 0.13/1000. Both figures were low compared to the global birth prevalence (NSOFC: 1.25/1000, CL/P: 0.94/1000 and CP: 0.31/1000 live births). Consanguineous parents were statistically higher among CP cases than among other NSOFC phenotypes.

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Diagnosis of cleft lip-palate during nuchal translucency screening – case report and review of the literature

Case Reports in Perinatal Medicine ◽

10.1515/crpm-2011-0002 ◽

2012 ◽

Vol 1 (1-2) ◽

Author(s):

Ashwin R. Jadhav ◽

Ana Monteagudo ◽

Rosalba Santos ◽

Ilan Timor

Keyword(s):

Cleft Palate ◽

Cleft Lip ◽

Cleft Lip And Palate ◽

First Trimester ◽

Nuchal Translucency ◽

3D Ultrasound ◽

Ultrasound Screening ◽

Aneuploidy Screening ◽

Detection Rates ◽

Cleft Lip Palate

AbstractOrofacial clefts are the most common group of craniofacial anomalies. The detection rate of cleft lip during the mid-trimester, using two-dimensional (2D) ultrasound screening, has improved over the last three decades. However, the detection rates of defects involving the hard palate or isolated cleft palate have remained poor. Over the last decade, many investigators have studied the use of 3D ultrasound to improve the detection rates of these defects. With the increasing use and acceptance of first-trimester aneuploidy screening in the US, there is growing interest in performing first-trimester fetal anatomy surveys. Reports of first-trimester diagnosis of cleft lip and palate are rare, and this aspect of prenatal sonographic diagnosis remains underexplored. We report a case of unilateral cleft lip and cleft palate diagnosed during a routine first-trimester screening at 12 weeks’ gestation and review the pertinent literature on first-trimester diagnosis of cleft lip/palate.

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Maternal Smoking during Early Pregnancy, GSTP1 and EPHX1 Variants, and Risk of Isolated Orofacial Clefts

The Cleft Palate-Craniofacial Journal ◽

10.1597/06-011.1 ◽

2007 ◽

Vol 44 (4) ◽

pp. 366-373 ◽

Cited By ~ 15

Author(s):

Dorian Ramirez ◽

Edward J. Lammer ◽

David M. Iovannisci ◽

Cecile Laurent ◽

Richard H. Finnell ◽

...

Keyword(s):

Cleft Palate ◽

Maternal Smoking ◽

Cleft Lip ◽

Detoxification Enzymes ◽

Glutathione S Transferase ◽

Orofacial Clefts ◽

Functional Polymorphisms ◽

Increased Risk ◽

Cleft Lip Palate ◽

Isolated Cleft Palate

Objective: To examine the interactions between four fetal xenobiotic metabolizing gene polymorphisms, maternal cigarette smoking, and risk for oral cleft defects. Design and Participants: California population–based case-control study of 431 infants born with isolated orofacial clefts and 299 nonmalformed controls. Main Outcome Measures: Infants were genotyped for functional polymorphisms of the detoxification enzymes microsomal epoxide hydrolase-1 (EPHX1 T→C [Tyr113His], and A→G [His139Arg]), and glutathione-S transferase Pi-1 (GSTP1 A→G [Ile105Val] and C→T [Ala114Val]), and risks for cleft outcomes were measured for gene only and gene-maternal smoking effects. Results: Although smoking was associated with an increased risk for isolated cleft lip ± palate, we found no independent associations of genotypes of EPHX1-codon 113 or GSTP1-codon 105 polymorphisms for either isolated cleft lip ± palate or isolated cleft palate. The heterozygote genotype for the EPHX1-codon 139 polymorphism was associated with an increased risk of isolated cleft palate (odds ratio = 1.6 [95% confidence interval, 1.0 to 2.6]). Infant EPHX1 and GTSP1 polymorphic variants did not appreciably alter the risks for clefts associated with maternal smoking, nor were any EPHX1 combined genotype-specific risks found. Infant genotypes of the GSTP1-codon 105 polymorphism, combined with glutathione-S-transferase-μ-1 null genotypes, did not appreciably alter the risk of orofacial clefts. Conclusions: Our results suggest that genetic variation of the detoxification enzymes EPHX1 and GSTP1 did not increase the risks of orofacial clefting, nor do they influence the risks associated with maternal smoking.

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First trimester exposure to ambient gaseous air pollutants and risk of orofacial clefts: a case–control study in Changsha, China

BMC Oral Health ◽

10.1186/s12903-021-01876-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wen Jiang ◽

Wanqin Xie ◽

Bin Ni ◽

Haiyan Zhou ◽

Zhiyu Liu ◽

...

Keyword(s):

Particulate Matter ◽

Cleft Palate ◽

Air Pollutants ◽

Cleft Lip ◽

Case Control Study ◽

First Trimester ◽

Case Control ◽

Orofacial Clefts ◽

First Trimester Of Pregnancy ◽

Control Study

Abstract Background A growing body of studies have investigated the association between air pollution exposure during early pregnancy and the risk of orofacial clefts, but these studies put more emphasis on particulate matter and reported inconsistent results, while research on the independent effects of gaseous air pollutants on orofacial clefts has been quite inadequate, especially in China. Methods A case–control study was conducted in Changsha, China from 2015 to 2018. A total of 446 cases and 4460 controls were included in the study. Daily concentrations of CO, NO2, SO2, O3, PM2.5 and PM10 during the first trimester of pregnancy were assigned to each subject using the nearest monitoring station method. Multivariate logistic regression models were applied to evaluate the associations of monthly average exposure to gaseous air pollutants with orofacial clefts and its subtypes before and after adjusting for particulate matter. Variance inflation factors (VIFs) were used to determine if the effects of gaseous air pollutants could be independent of particulate matter. Results Increase in CO, NO2 and SO2 significantly increased the risk of cleft lip with or without cleft palate (CL/P) in all months during the first trimester of pregnancy, with aORs ranging from 1.39 to 1.48, from 1.35 to 1.61 and from 1.22 to 1.35, respectively. The risk of cleft palate only (CPO) increased with increasing NO2 exposure levels in the first trimester of pregnancy, with aORs ranging from 1.60 to 1.66. These effects sustained and even exacerbated after adjusting for particulate matter. No significant effect of O3 was observed. Conclusions Our study suggested that maternal exposure to CO, NO2, and SO2 during the first trimester of pregnancy might contribute to the development of orofacial clefts, and the associations were potentially independent of particulate matter.

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Infant TGF-Alpha Genotype, Orofacial Clefts, and Maternal Periconceptional Multivitamin Use

The Cleft Palate-Craniofacial Journal ◽

10.1597/1545-1569_1998_035_0366_itagoc_2.3.co_2 ◽

1998 ◽

Vol 35 (4) ◽

pp. 366-370 ◽

Cited By ~ 17

Author(s):

Gary M. Shaw ◽

Cathy R. Wasserman ◽

Jeffrey C. Murray ◽

Edward J. Lammer

Keyword(s):

Cigarette Smoking ◽

Cleft Palate ◽

Cleft Lip ◽

Transforming Growth Factor ◽

Strong Association ◽

Preliminary Evidence ◽

Serum Folate ◽

Orofacial Cleft ◽

Orofacial Clefts ◽

Multivitamin Use

Objective We previously demonstrated a strong association between periconceptional maternal cigarette smoking, infant transforming growth factor–alpha (TGFa) genotype, and risk of orofacial clefts. Because serum folate may be decreased by cigarette smoking and because maternal periconceptional use of multivitamins containing folic acid has been associated with a reduced risk of clefting, we explored whether a potential relation existed between infant TGFa genotype, maternal multivitamin use, and risk of orofacial cleft phenotypes. Design Data were derived from a population-based case–control study of fetuses and live-born infants among a cohort of 1987 to 1989 California births (n = 548,844). Information concerning periconceptional multivitamin use was obtained via telephone interviews with mothers of 731 (84.7% of eligible) orofacial cleft case infants, and of 734 (78.2%) nonmalformed control infants. DNA was obtained from newborn screening bloodspots and genotyped for the Taq1 polymorphism of TGFa. Among infants of interviewed mothers, genotypes were available for 571 (78.1%) case infants and 640 (87.2%) control infants. Setting The study encompassed all hospitals in selected California counties. Main Outcome Measure The main outcome measures were the risks of specific cleft phenotypes among infants with uncommon TGFa genotypes and whose mothers did not use multivitamins periconceptionally. Results Compared with infants homozygous for the common TGFa genotype and whose mothers used multivitamins, increased clefting risks were observed for infants with the A2 genotype (homozygous or heterozygous) and whose mothers did not use multivitamins. Risk estimates were 3.0 (1.4–6.6 [95% confidence interval]) for isolated cleft lip with or without cleft palate (CLP), 2.4 (0.69–11.6) for multiple CLP, 2.6 (0.97–7.7) for isolated cleft palate (CP), 4.2 (1.3–16.2) for multiple CP, and 8.1 (2.6–27.7) for “known-syndrome” clefts. Clefting risks for infants with the A2 genotype and whose mothers used multivitamins were substantially smaller, as were the risks for infants with the A1 genotype whose mothers did not use multivitamins. Conclusion These data provide preliminary evidence for a gene–nutrient interaction in risk of clefting.

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Maternal multivitamin intake and orofacial clefts in offspring: Japan Environment and Children's Study (JECS) cohort study

BMJ Open ◽

10.1136/bmjopen-2019-035817 ◽

2020 ◽

Vol 10 (3) ◽

pp. e035817

Author(s):

Satomi Yoshida ◽

Masato Takeuchi ◽

Chihiro Kawakami ◽

Koji Kawakami ◽

Shuichi Ito

Keyword(s):

Cohort Study ◽

Cleft Lip ◽

Maternal Nutrition ◽

Cleft Lip And Palate ◽

Multinomial Logistic Regression ◽

First Trimester ◽

Secondary Outcome ◽

Orofacial Cleft ◽

Orofacial Clefts ◽

Multivitamin Supplementation

ObjectivesOrofacial clefts are common birth defects with a lack of strong evidence regarding their association with maternal nutrition. We aimed to determine whether a relationship exists between maternal nutrient or multivitamin intake and orofacial clefts.DesignThis is a prospective, population-based nationwide cohort study.SettingThe study was conducted in 15 regional centres, consisting of local administrative units and study areas.ParticipantsA total of 98 787 eligible mother–child pairs of the Japan Environment and Children’s Study were included.InterventionExposures were maternal nutrition and the use of supplemental multivitamins in mothers.Primary and secondary outcome measuresOutcomes were the occurrence of any orofacial cleft at birth. Multinomial logistic regression analyses were used to evaluate the association between maternal multivitamin intake and the incidence of orofacial clefts.ResultsOf the 98 787 children, 69 (0.07%) were diagnosed with cleft lip alone, 113 (0.11%) were diagnosed with cleft lip and palate, and 52 (0.05%) were diagnosed with cleft palate within 1 month after birth. Regarding the total orofacial cleft outcome, statistically significant point estimates of relative risk ratios (RR) were determined for multivitamin intake before pregnancy (RR=1.71; 95% CI 1.06 to 2.77) and during the first trimester (RR=2.00; 95% CI 1.18 to 3.37), but the association was not significant for multivitamin intake after the first trimester (RR=1.34; 95% CI 0.59 to 3.01). Maternal micronutrient intake via food was not associated with the incidence of orofacial clefts in offspring.ConclusionsIntake of multivitamin supplements shortly before conception or during the first trimester of pregnancy was found to be associated with an increased incidence of orofacial clefts at birth. Pregnant women and those intending to become pregnant should be advised of the potential risks of multivitamin supplementation.

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