Oral cleft

In rare instances (0.5% to 2% of pregnancies), NVP progresses to hyperemesis gravidarum.9 Treatment may require the use of enteral or parenteral nutrition if weight loss is present. A corticosteroid such as methylprednisolone may be considered. Methylprednisolone is associated with oral clefts in the fetus when used during the first trimester therefore, corticosteroids should be reserved as a last resort and should be avoided during the first 10 weeks of gestation.9,11... 

The target organs of chloroform toxicity in humans and animals are the central nervous system, liver, and kidneys. There is a great deal of similarity between chloroform-induced effects following inhalation and oral exposure. No studies were located regarding reproductive effects in humans after exposure to chloroform alone however, Bove et al. (1995) studied the effects of drinking-water consumption on birth outcomes and found that exposure to TTHM at levels >0.1 ppm resulted in reduced birth weight and size as well as an increased risk of oral cleft, central nervous system, and neural tube defects. Since the authors... 

Administration of APDs can require the use of concomitant agents to help control EPS. Two studies suggest a possible association between benztropine exposure and major malformations (Heinonen et ah, 1977 Briggs et ah, 1998). One of these studies also suggests a link between first-trimester exposure to trihexyphenidyl and minor malformations (Heinonen et ah, 1977). Conflicting reports exist about the teratogenic risk of diphenhydramine. One study supports an association between diphenhydramine use in the first trimester and oral clefts (Saxen, 1974), while other studies do not report an increased risk for major congenital anomalies (Heinonen et ah, 1977 Aselton et ah, 1985). 

Benzodiazepines (BZDs) are commonly prescribed in the psychiatric practice to treat anxiety, insomnia, and unpleasant side effects associated with other psychotropic agents. While early case-control studies found that maternal BZD exposure increased the risk of cleft lip and cleft palate, a recent meta-analysis (Dolovich et ah, 1998) examining pooled data from cohort studies published between 1966 and 1998 found no association between antenatal BZD exposure and oral cleft or other major malformations. However, when examining case-control studies published during this period, the authors did find a small, but significant, odds ratio of... 

II. 39, p = 0.01) suggesting an association between oral clefts and first trimester BZD use. However, other statistical analyses cast doubt on the validity of these marginally significant results (Dolovich et ah, 1998 Cates 1999). 

Cates, C. (1999) Benzodiazepine use in pregnancy and major malformations or oral clefts pooled results are sensitive to zero transformation used. BM] 319 918-9. 

Dolovich, L., Addis, A., Vaillancourt, J.M.R., Power, J.D.B., Koren, G., and Einarson, T.R. (1998) Benzodiazepine use in pregnancy and malformations ot oral clefts meta-analysis of cohott and case-control studies. BMJ 317 839—843. 

American Psychiatric Association Benzodiazepine Dependence, Toxicity, and Abuse A Task Force Report of the American Psychiatric Association. Washington, DC, American Psychiatric Association, 1990 Cohn JB, Wilcox CS Low-sedation potential of buspirone compared with alprazolam and lorazepam in the treatment of anxious patients a double-blind study. J Clin Psychiatry 47 409 12, 1986 Dolovich LR, Addis A, Vaillancourt JM, et al Benzodiazepine use in pregnancy and major malformations or oral cleft meta-analysis of cohort and case-control studies. BMJ 317 839-843, 1998 Goldberg HL, Finnerty RJ The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry 136 1184—1187, 1979 Kupfer DJ, Reynolds CF 111 Management of insomnia. N Engl J Med 336 341-346, 1997... 

The experience of pregnancy itself is often anxiety provoking, and symptoms sufficient to warrant drug therapy are common in this group ( 16). Although this discussion primarily focuses on the benzodiazepines (BZDs), antidepressants and buspirone may also be used for women of childbearing age with certain anxiety-related disorders. Perhaps the best-documented adverse effect of the BZDs is a neonatal withdrawal syndrome, which has been reported to occur with several of the agents (e.g., diazepam, alprazolam, and triazolam). In addition, there is a weak positive relationship between diazepam exposure and oral clefts ( 17). 

Laumon B, Martin JL, Collet P, Bertucat I, Vemey MP, Robert E (1996) Exposure to organic solvents during pregnancy and oral clefts a case-control study. Reprod Toxicol, 10(1) 15-19 [published erratum appears in Reprod Toxicol 1996,10(3) vi],... 

Lorente C, Cordier S, Bergeret A, De Walle HE, Goujard J, Ayme S, Knill-Jones R, Calzolari E, Bianchi F (2000) Maternal occupational risk factors for oral clefts. Occupational Exposure and Congenital Malformation Working Group. Scand J Work Environ Health, 26 137-145. 

Diazepam All Chronic use may lead to neonatal dependence and increase risk for oral cleft... 

Hwang SJ, Beaty TH, Panny SR, Street NA, Joseph JM, Gordon S, McIntosh I, Francomano CA (1995) Association study of transforming growth factor alpha (TGF alpha) Taql polymerase and oral clefts Indication of gene-environment interaction in a population-based sample of infants with birth defects. Am J Epidemiol, 141(7) 629-636. 

First-trimester exposure appears to confer a small but definite increased risk (from a baseline of 0.06% up to 0.7%) of oral cleft in infants (27). However, second-generation effects are infrequent and usually reversible (28), although some doubt remains about the extent of developmental delay in children who have been exposed in utero (27). A review has emphasized that concerns about second-generation effects are mainly theoretical, and has concluded that some agents (for example chlor-diazepoxide) are probably safe during pregnancy and lactation and that others (for example alprazolam) are best avoided (29). 

Benzodiazepines readily pass from the mother to fetus through the placenta (117). There may be a risk of congenital malformations, particularly oral cleft, if a pregnant woman takes a benzodiazepine during the first trimester, but the data are inconsistent across drugs (alprazolam having the most clearly defined risk), and any overall effect is probably small (27,28). The risk of benzodiazepine-induced birth defects thus remains uncertain (118), despite two cases of fetal-alcohol syndrome reported after benzodiazepine exposure alone (119). 

Rosenberg L, Mitchell A A, Parsells JL, Pashayan H, Louik C, Shapiro S. Lack of relation of oral clefts to diazepam use during pregnancy. N Engl J Med 1983 309(21) 1282-5. 

In pregnant women who reported for prenatal care between 1959 and 1966 there was an excess of oral clefts in the offspring of mothers who had taken amphetamines in the first 56 days from their last menstrual period, but this was considered to be either a chance finding or one element in a multifactorial situation (SED-9, 9). 

Martinez-Frias ML, Rodriguez-Pinilla E, Bermejo E, Blanco M. Prenatal exposure to penicillamine and oral clefts case report. Am J Med Genet 1998 76(3) 274-5. 

There is an association of phenobarbital with oral clefts and cardiac malformations (10). This is also the case for methylphenobarbital (10). 

An early review of newer case reports and placebo-controlled trials involving several hundred patients did not show an increase in fetal abnormalities (176). However, the relative risks of cardiovascular defects and oral clefts in infants whose mothers were exposed to dihydrofolate reductase inhibitors, such as trimethoprim, during the second or third month after the last menstrual period, compared with infants whose mothers had no such exposure, are 3.4 (95% Cl = 1.8, 6.4) and 2.6 (1.1, 6.1) respectively (177). Multivitamin supplements containing folic acid reduced the adverse effects of dihydrofolate reductase inhibitors. There have been two reports of severe spinal malformations in the fetuses of HIV-positive women treated with combination antiretroviral therapy and co-trimoxazole (178). 

A. A. Mitchell, L. Rosenberg, S. Shapiro, D. Slone. Birth Defects Related to Bendectin Use in Pregnancy. I. Oral Clefts and Cardiac Defects. Journal of the American Medical Association. Vol 245, pgs. 2311-2314,1981. 

Developmental Effects. Studies examining the association between drinking water contamination and birth outcome in humans suggest that there may be an association between birth defects, especially oral cleft defects, and tetrachloroethylene contamination (Bove et al. 1995 Lagakos et al. 1986). These studies are confoiuided by more than one contaminant, and the Lagakos et al. (1986) study combined birth defects in the analysis in a manner that has questionable biological relevance. 

Extraordinary genomics assay for congenital maxillofacial deformities (Sdlya K et al Orvosi Hetilap Budapest 2015 156 1483-1490. doi 10.1556/650.2015. 30240). No increased incidence of malignant tumors in 8093 patients with oral clefts (Bille C et al Am J Epidemiol 2005 161 1047-1055). 

Holmberg et al. cc R CNS, oral clefts, musculoskeletal, cardiac defects... 

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