Folate and Clefts of the Lip and Palate—A U.K.-Based Case-Control Study: Part II: Biochemical and Genetic Analysis

2008 ◽  
Vol 45 (4) ◽  
pp. 428-438 ◽  
Author(s):  
J. Little ◽  
M. Gilmour ◽  
P. A. Mossey ◽  
D. FitzPatrick ◽  
A. Cardy ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Mthfr C677t ◽  
Serum Folate ◽  
Inverse Association ◽  
Folic Acid Fortification ◽  
Regression Methods ◽  
The United Kingdom ◽  
Increased Risk ◽  
Log Linear

Objective: To investigate associations between nonsyndromic oral clefts and biochemical measures of folate status and the MTHFR C677T variant in the United Kingdom, where there has been no folic acid fortification program. Method: Dietary details were obtained from the mothers of 112 cases of cleft lip with or without cleft palate (CL±P), 78 cleft palate only (CP) cases, and 248 unaffected infants. Infant and parental MTHFR C677T genotype was determined. Red blood cell (RBC) and serum folate and homocysteine levels were assessed in 12-month postpartum blood samples from a subset of mothers. The data were analyzed by logistic and log-linear regression methods. Results: There was an inverse association between CL±P and maternal MTHFR CT (odds ratio [OR]  =  0.5, 95% confidence interval [CI]  =  0.31–0.95) and TT (OR  =  0.6, 95% CI  =  0.21–1.50) genotypes, with similar risk estimates for CP. There was no clear association with infant MTHFR genotype. Higher levels of maternal postpartum RBC and serum folate were associated with a lower risk for CL±P and an increased risk for CP. Higher levels of serum homocysteine were associated with a slightly increased risk for both CL±P and CP. Conclusion: While the inverse relation between the mother's having the MTHFR C677T variant and both CL±P and CP suggests perturbation of maternal folate metabolism is of etiological importance, contrasting relations between maternal postpartum levels of RBC and serum folate by type of cleft are difficult to explain.

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

2007 ◽  
Vol 44 (3) ◽  
pp. 244-250 ◽  
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.

scholarly journals Maternal Vitamin B12 Status and Risk of Cleft Lip and Cleft Palate Birth Defects in Tamil Nadu State, India

2021 ◽  
Vol 58 (5) ◽  
pp. 567-576
Author(s):  
Ronald G. Munger ◽  
Rajarajeswari Kuppuswamy ◽  
Jyotsna Murthy ◽  
Kalpana Balakrishnan ◽  
Gurusamy Thangavel ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Tamil Nadu ◽  
Cleft Lip ◽  
Maternal Nutrition ◽  
Case Control ◽  
Vitamin B ◽  
Plasma Vitamin ◽  
Maternal Vitamin ◽  
Increased Risk ◽  
Tamil Nadu State

Background and Objective: The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B12 and low folate status are each associated with an increased risk of isolated cleft lip with or without cleft palate (CL±P) in a case–control study in Tamil Nadu state, India. Methods: Case-mothers of CL±P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B12, methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured at that time. Logistic regression analyses estimated associations between nutrient biomarkers and case–control status. Results: Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B12 (OR = 2.48, 95% CI, 1.02-6.01) and high versus low plasma MMA, an indicator of poor B12 status (OR = 3.65 95% CI, 1.21-11.05). Case–control status was not consistently associated with folate or tHcy levels. Low vitamin B12 status, when defined by a combination of both plasma vitamin B12 and MMA levels, had an even stronger association with case-mothers (OR = 6.54, 95% CI, 1.33-32.09). Conclusions: Mothers of CL±P children in southern India were 6.5 times more likely to have poor vitamin B12 status, defined by multiple biomarkers, compared to control-mothers. Further studies in populations with diverse nutritional backgrounds are required to determine whether poor maternal vitamin B12 or folate levels or their interactions are causally related to CL±P.

A Closer Look at Delayed Primary Cleft Surgery and Unrepaired Cleft Lip and/or Palate in 5 UK Cleft Centers

2021 ◽  
pp. 105566562110217
Author(s):  
Sophie Butterworth ◽  
Clare Rivers ◽  
Marnie Fullarton ◽  
Colm Murphy ◽  
Victoria Beale ◽  
...  
Keyword(s):  
United Kingdom ◽  
Cleft Palate ◽  
Cleft Lip ◽  
Medical Problems ◽  
Primary Surgery ◽  
The United Kingdom ◽  
Number Of Patients ◽  
Primary Palate ◽  
Palate Repair ◽  
Cleft Surgery

Background: There may be many reasons for delays to primary cleft surgery. Our aim was to investigate the age of children undergoing primary cleft lip or primary cleft palate repair in 5 cleft centers within the United Kingdom. Identify the reasons for delayed primary cleft lip repair (beyond 6 months) and delayed primary palate repair (beyond 13 months). Identify children who had a cleft lip and/or palate (CL±P) that was intentionally unrepaired and the reasons for this. Methods: A retrospective, multicenter review of patients born with a CL±P between December 1, 2012, and December 31, 2016. Three regional cleft centers, comprising of 5 cleft administrative units in the United Kingdom participated. Results: In all, 1826 patients with CL±P were identified. Of them, 120 patients had delayed lip repair, outside the expected standard of 183 days. And, 178 patients in total had delayed palate repair, outside the expected standard of 396 days. Twenty (1%) patients had an unrepaired cleft palate. Conclusions: This large retrospective review highlights variations between centers regarding the timing of lip and palate surgery and details the reasons stated for delayed primary surgery. A small number of patients with an unrepaired cleft palate were identified. All had complex medical problems or comorbidities listed as a reason for the decision not to operate and 50% had a syndromic diagnosis. The number of patients receiving delayed surgery due to comorbidities, being underweight or prematurity, highlights the importance of the cleft specialist nurse and pediatrician within the cleft multidisciplinary team.

Greater Palatal Cleft Width Predicts an Increased Risk for Unfavorable Outcomes in Cleft Palate Repair

2021 ◽  
pp. 105566562110295
Author(s):  
Åsa C. Okhiria ◽  
Fatemeh Jabbari ◽  
Malin M. Hakelius ◽  
Monica M. Blom Johansson ◽  
Daniel J. Nowinski
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
University Hospital ◽  
Velopharyngeal Insufficiency ◽  
Secondary Surgery ◽  
Increased Risk ◽  
Cleft Palate Repair ◽  
The Impact ◽  
Nasal Emission

Objective: To investigate the impact of cleft width and cleft type on the need for secondary surgery and velopharyngeal competence from a longitudinal perspective. Design: Retrospective, longitudinal study. Setting: A single multidisciplinary craniofacial team at a university hospital. Patients: Consecutive patients with unilateral or bilateral cleft lip and palate and cleft palate only (n = 313) born from 1984 to 2002, treated with 2-stage palatal surgery, were reviewed. A total of 213 patients were included. Main Outcome Measures: The impact of initial cleft width and cleft type on secondary surgery. Assessment of hypernasality, audible nasal emission, and glottal articulation from routine follow-ups from 3 to 16 years of age. The assessments were compared with reassessments of 10% of the recordings. Results: Cleft width, but not cleft type, predicted the need for secondary surgery, either due to palatal dehiscence or velopharyngeal insufficiency. The distribution of cleft width between the scale steps on a 4-point scale for hypernasality and audible nasal emission differed significantly at 5 years of age but not at any other age. Presence of glottal articulation differed significantly at 3 and 5 years of age. No differences between cleft types were seen at any age for any speech variable. Conclusions: Cleft width emerged as a predictor of the need for secondary surgery as well as more deviance in speech variables related to velopharyngeal competence during the preschool years. Cleft type was not related to the need for secondary surgery nor speech outcome at any age.

Interaction between Polymorphisms MTHFR C677T and MTRR A66G and Vitamin Levels in Pregnant Women.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3687-3687
Author(s):  
Elvira M. Guerra-Shinohara ◽  
Patricia R. Barbosa ◽  
Luiz F. Sampaio-Neto ◽  
Rosario D. Hirata ◽  
Mario H. Hirata ◽  
...  
Keyword(s):  
High Risk ◽  
Pregnant Women ◽  
Mthfr C677t ◽  
Serum Levels ◽  
Serum Folate ◽  
P Value ◽  
Methionine Synthase Reductase ◽  
Mtrr A66g ◽  
Increased Risk ◽  
677T Allele

Abstract In the homocysteine metabolic pathway, several key enzymes, including methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), have been implicated in abnormal homocysteine accumulation in the presence of rare alleles. In previous study, we showed that lower maternal Cbl levels were associated with higher tHcy and lower S-adenosylmethionine/S-adenosylhomocysteine ratio in pregnant women and their neonates.The aim of this study is to investigate whether MTHFR and MTRR polymorphisms are involved in the risk for elevated total homocysteine (tHcy) and its interaction with low cobalamin (Cbl) or serum folate (SF) levels. Genotypes for polymorphisms MTHFR C677T and MTRR A66G were determined by PCR-FLRP. The serum levels of Cbl, SF and tHcy were determined in 377 pregnant women (37–42 weeks of gestational age), and cutoff values for Cbl and SF were considered the first quartile (low values). Four models of univariate logistic regression analyses were used (Table 1). Pregnant women with MTHFR 677T allele have high risk for elevated tHcy that is increased when 677T allele is associated with low Cbl. Increased risk for elevated tHcy is also met when MTRR 66G allele and low Cbl levels were associated. Women with low SF and common MTHFR and MTRR alleles have high risk for elevated tHcy, that is increased when in association with 677T allele or with 66G allele. Interaction between MTHFR C677T and MTRR A66G polymorphisms and vitamins levels in pregnant women Dependent variables Comparation levels (N) P value Odd Ratios 95% CI P for trend: (a) P<0.001; (b) P<0.001; (c) P=0.067; (d) P<0.001 tHcy>8.3μmol/L MTHFR 677CC genotype and Cbl> 115.8 pmol/L (ref) (136) a 1.00 MTHFR 677CC genotype and≤Cbl 115.8 pmol/L (45) 0.298 1.57 0.67 – 3.63 MTHFR 677CT and 677TT genotypes and Cbl>115.8 pmol/L (145) 0.015 2.09 1.16 – 3.77 MTHFR 677CT and 677TT genotypes and≤Cbl 115.8 pmol/L (48) 0.001 4.63 2.22 – 9.65 tHcy>8.3μmol/L MTHFR 677CC genotype and SF > 10.9 nmol/L (ref) (148) b 1.00 MTHFR 677CC genotype and≤SF 10.9 nmol/L (33) 0.008 3.20 1.35 – 7.59 MTHFR 677CT and 677TT genotypes and SF > 10.9 nmol/L (133) 0.035 1.95 1.05 – 3.61 MTHFR 677CT and 677TT genotypes and≤SF 10.9 nmol/L (59) 0.001 6.62 3.31 – 13.26 tHcy>8.3μmol/L MTRR 66AA genotype and Cbl> 115.8 pmol/L (ref) (96) c 1.00 MTRR 66AA genotype and ≤Cbl 115.8 pmol/L (23) 0.222 1.90 0.68 – 5.29 MTRR 66AG and 66GG genotypes and Cbl>115.8 pmol/L (183) 0.418 1.29 0.70 – 2.39 MTRR 66AG and 66GG genotypes and ≤Cbl 115.8 pmol/L (69) 0.013 2.46 1.21 – 5.01 tHcy>8.3μmol/L MTRR 66AA genotype and SF > 10.9 nmol/L (ref) (92) d 1.00 MTRR 66AA genotype and ≤SF 10.9 nmol/L (27) 0.006 3.83 1.47 – 9.96 MTRR 66AG and 66GG genotypes and SF > 10.9 nmol/L (186) 0.399 1.34 0.68 – 2.63 MTRR 66AG and 66GG genotypes and≤SF 10.9 nmol/L (65) 0.001 4.78 2.26 – 10.10 In conclusion, the interaction between MTHFR and MTRR polymorphisms and low folate and cobalamin serum levels may explain the increased risk for elevated tHcy found in pregnant women.

scholarly journals MTHFR and MDR1 Gene Polymorphisms in Yakut Patients with Non-Syndromic Orofacial Clefts

2021 ◽  
Vol 11 (4) ◽  
pp. 576-580
Author(s):  
Aleksandra Diakonova ◽  
Nadezhda Pavlova ◽  
Vladislav Alekseev ◽  
Lyubov Mironova ◽  
Khariton Kurtanov ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Gene Polymorphisms ◽  
Cleft Lip ◽  
Significant Risk ◽  
Rflp Analysis ◽  
Recessive Model ◽  
Mthfr Gene ◽  
Homozygous Genotype ◽  
Increased Risk ◽  
The Republic

The aim of our study was to investigate the relationship between the MDR1 and MTHFR gene polymorphisms and non-syndromic cleft lip with or without cleft palate (NSCL/P) in the Yakut population in the Republic of Sakha (Yakutia). Methods and Results: The sample of examined persons consisted of 60 children with NSCL/P. The NSCL/P group was divided into the CLP (cleft lip with cleft palate) subgroup (n=31), CLO (cleft lip only) subgroup (n=14), and CPO (cleft palate only) subgroup (n=15). The comparison group (control) included 174 healthy volunteers who did not have relatives with OFCs. The study of the MDR1 rs1045642 SNP and the MTHFR rs1801133 SNP was performed by PCR and RFLP analysis. Analysis of the frequency distribution of alleles and genotypes depending on the severity of clefts showed that the carriage of the TT homozygous genotype of the MDR1 rs1045642 SNP was associated with significant risk for the development of NSCL/P (OR=2.52, 95% CI: 1.19-5.32, P=0.02). Analysis of the recessive model (TT vs CC + TC) also found a significant risk of NSCL/P with the TT genotype carriage (OR=2.20, 95% CI: 1.06-4.57, P=0.04). Analysis of the over-dominant model (TC vs TT + CC) showed that the heterozygous TC genotype had a protective effect (OR=0.41; 95% CI: 0.22-0.77, P=0.01) on the development of NSCL/P. Subgroup analysis according to NSCL/P subtypes (CLO, CPO and CLP) showed that the MDR1 rs1045642 SNP was significantly associated with a high risk of CPO in three genetic models: heterozygous [(TT vs TC): OR=5.03; 95% CI: 1.55-16.32; P=0.01], recessive [(TT vs CC + TC): OR=3.96; 95% CI: 1.32-11.95; P=0.02], and over-dominant [(TC vs TT + CC): OR=0.23; 95% CI: 0.08-0.66; P=0.01]. Conclusion: A study of two SNPs in the MDR1and MTHFR genes revealed a statistically significant increased risk for NSCL/P in carriers of the TT genotype of the MDR1 rs1045642 SNP.

scholarly journals Dental caries and Dental Anomalies in children with cleft Lip and cleft Palate in Bengaluru city, India

2017 ◽  
Vol 8 (4) ◽  
pp. 304-308 ◽  
Author(s):  
Rahul Gaikwad ◽  
Sachin C Sarode ◽  
Seema Kamble ◽  
Shivalinga S Hiremath ◽  
Ashwini Biradar
Keyword(s):  
Dental Caries ◽  
Cleft Palate ◽  
Oral Hygiene ◽  
Cleft Lip ◽  
Open Bite ◽  
World Health ◽  
Caries Experience ◽  
Dental Anomalies ◽  
Anterior Teeth ◽  
Increased Risk

ABSTRACT Aim The aim of this study was to assess the association of dental caries and dental anomalies among 5- to 15-year-old children with cleft lip and cleft palate. Materials and methods A cross-sectional study was conducted among 500 children with cleft lip and/or cleft palate and 500 children without cleft of the age group 5 to 15 years. The clinical examination was carried out using decayed, missing, and filled teeth (DMFT) by Klein Plamer and Knutson, and dmft by Grubbel and 1997 World Health Organization (WHO) pro forma. Results The results showed a statistically significant increase in the prevalence of dental caries in children with cleft lip and/or cleft palate. The mean DMFT was found to be significantly higher in operated children than in the children who were not operated. Other dental abnormalities included an increased frequency of enamel hypoplasia (p < 0.001), hyperdontia (p < 0.014), anterior, unilateral and bilateral cross-bite (p < 0.001), and open bite (p < 0.001). Conclusion The results of this study show that children with cleft have higher prevalence of dental anomalies than the normal children. With increased occurrence of hypoplasia in children with cleft, reduced access for cleaning upper anterior teeth after surgical repair leads to poor oral hygiene status, leading to increased risk to dental caries. Clinical significance Given the high caries experience among the children with cleft lip and cleft palate, it is necessary to advocate a more rigorous approach to the prevention of dental disease in these high-risk children. They should therefore, be subjected to regular checkups, oral hygiene advice, diet advice, appropriate fluoride supplementation, and, when required, appropriate referral for secondary care. How to cite this article Kamble S, Hiremath SS, Puranik MP, Gaikwad R, Biradar A, Gadbail AR, Sarode SC, Sarode GS, Patil S. Dental Caries and Dental Anomalies in Children with Cleft Lip and Cleft Palate in Bengaluru City, India. World J Dent 2017;8(4):304-308.

Maternal Common Cold or Fever During Pregnancy and the Risk of Orofacial Clefts in the Offspring: A Systematic Review and Meta-analysis

2021 ◽  
pp. 105566562110676
Author(s):  
Fang-ping Shi ◽  
Ying-ying Huang ◽  
Qiao-qun Dai ◽  
Yu-lu Chen ◽  
Hai-yin Jiang ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Common Cold ◽  
Cleft Lip ◽  
Meta Analysis ◽  
Case Control Studies ◽  
Orofacial Clefts ◽  
Random Effects Models ◽  
Relative Risks ◽  
Increased Risk ◽  
The Common

The common cold and/or an associated fever during pregnancy have/has been suspected to harm the developing fetus. We sought possible correlations between a maternal common cold or fever during pregnancy and the risk of orofacial clefts in the offspring. We systematically searched PubMed and Embase using appropriate keywords, and we checked the reference lists of retrieved articles. We used random-effects models to estimate overall relative risks. Incidence of orofacial clefts. We included 13 case-control studies. Modest but statistically significant associations were found between a maternal common cold and cleft lip with or without a cleft palate (CL/CP) (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.66–2.83) and a cleft palate only (CPO) (OR 3.08; 95% CI 1.5–6.34). Furthermore, maternal fever was also associated with an increased risk of CL/CP (OR 1.91, 95% CI 1.3–2.8) and CPO (OR 1.48, 95% CI 0.83–2.63) in the offspring. Further analyses of maternal influenza (alone) yielded similar results. Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal common cold or fever during pregnancy may be associated with a greater risk of CL/CP or CPO in the offspring. Future cohort studies using valid assessments of maternal common cold exposure during pregnancy that consider the severity of fever are needed to clarify the contribution of maternal common cold or fever status to the risk of orofacial clefts in children.

Smoking and Orofacial Clefts: A United Kingdom–Based Case-Control Study

2004 ◽  
Vol 41 (4) ◽  
pp. 381-386 ◽  
Author(s):  
J. Little ◽  
A. Cardy ◽  
M. T. Arslan ◽  
M. Gilmour ◽  
P. A. Mossey ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Cleft Palate ◽  
Odds Ratio ◽  
Maternal Smoking ◽  
Cleft Lip ◽  
Case Control Study ◽  
Case Control ◽  
Orofacial Clefts ◽  
Increased Risk ◽  
Control Study

Objective To investigate the association between smoking and orofacial clefts in the United Kingdom. Design Case-control study in which the mother's exposure to tobacco smoke was assessed by a structured interview. Setting Scotland and the Manchester and Merseyside regions of England. Participants One hundred ninety children born with oral cleft between September 1, 1997, and January 31, 2000, and 248 population controls, matched with the cases on sex, date of birth, and region. Main Outcome Measure Cleft lip with or without cleft palate and cleft palate. Results There was a positive association between maternal smoking during the first trimester of pregnancy and both cleft lip with or without cleft palate (odds ratio 1.9, 95% confidence interval 1.1 to 3.1) and cleft palate (odds ratio 2.3, 95% confidence interval 1.3 to 4.1). There was evidence of a dose-response relationship for both types of cleft. An effect of passive smoking could not be excluded in mothers who did not smoke themselves. Conclusion The small increased risk for cleft lip with or without cleft palate in the offspring of women who smoke during pregnancy observed in this study is in line with previous evidence. In contrast to some previous studies, an increased risk was also apparent for cleft palate. In these U.K. data, there was evidence of a dose-response effect of maternal smoking for both types of cleft. The data were compatible with a modest effect of maternal passive smoking, but the study lacked statistical power to detect or exclude such an effect with confidence. It may be useful to incorporate information on the effects of maternal smoking on oral clefts into public health campaigns on the consequences of maternal smoking.

Stability of Orofacial Clefting Rate in Alberta, 1980–2011

2014 ◽  
Vol 51 (6) ◽  
pp. 113-121 ◽  
Author(s):  
R. Brian Lowry ◽  
Barbara Sibbald ◽  
Tanya Bedard
Keyword(s):  
Folic Acid ◽  
Cleft Palate ◽  
Congenital Anomalies ◽  
Cleft Lip ◽  
Folic Acid Supplementation ◽  
Multiple Sources ◽  
Orofacial Clefts ◽  
Folic Acid Fortification ◽  
Orofacial Clefting ◽  
The Impact

Objective To determine the prevalence and trends of orofacial clefts in Alberta (Canada) over a 33-year period (1980 through 2011) and to determine whether the trends differ for subcategories of orofacial clefts for the period from 1997 through 2011. Design A prevalence study based on the Alberta Congenital Anomalies Surveillance System, which has multiple sources of ascertainment, capability of verification, and an upper age limit of 1 year. Inclusion All live born and stillborn babies and fetal deaths less than 20 weeks' gestation (including terminations of pregnancy) born in Alberta of mothers who reside in Alberta. Results and Conclusions Rates for cleft lip with or without cleft palate and cleft palate only have been very stable over the 33-year period (1980 through 2011). These rates include all clefts (isolated, syndromes, recognizable conditions, chromosomal and multiple congenital anomalies). Ascertainment of fetal deaths less than 20 weeks' gestation began in 1997. There are trends for the 1997 through 2011 cohort with a marginally significant increase for cleft lip with or without cleft palate in the isolated category and a significant decrease for cleft palate, mainly in the associated groups. The impact of folic acid fortification and/or multivitamins/folic acid supplementation reports in the literature have shown no consensus with respect to a change in the prevalence of orofacial clefts. It is unclear whether folic acid fortification has had any impact in Alberta.

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