Congenital anomalies

A serious adverse event (experience) or reaction is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. 

Developmental Effects. Evidence from human studies on congenital anomalies as an end point (Emhart et al. 1985, 1986 McMichael et al. 1986 Needleman et al. 1984) indicate no association between prenatal exposure to low levels of lead and the occurrence of major congenital anomalies. This conclusion is further supported by developmental toxicity studies conducted in rats and mice these studies provide no evidence that lead compounds (acetate or nitrate) are teratogenic when exposure is by natural routes (i.e., inhalation, oral, dermal). Intravenous or intraperitoneal injection of lead compounds (acetate, chloride, or nitrate) into pregnant rats, mice, or hamsters, however, has produced malformations in several studies reviewed by EPA (1986a). 

Developmental Toxicity. Three human studies that described congenital malformations as an end point allow no definitive conclusion to be drawn regarding an association between prenatal lead exposure and the occurrence of congenital anomalies (Emhart et al. 1985, 1986 McMichael et al. 1986 ... 

Needleman HL, Rabinowitz M, Leviton A, et al. 1984. The relationship between prenatal exposure to lead and congenital anomalies. JAMA 251 2956-2959. 

Our discussion has not included the dozens of congenital anomalies (abnormalities) which involve the heart and the great vessels and which have been regarded as pathological. It is suggestive that, although many individuals who are afflicted with such anomalies die in infancy or early youth, some live to beyond seventy and then may die of some other disease. It is difficult to draw the borderline between what is anomalous and what is not. 

Shimizu N, Aoyama H, Hojo H, et al Prenatal developmental toxicity studies of 1,1,1-trichloro-2,2-bis(4-methoxyphenyl)ethane (methoxychlor) in rats and rabbits. Congenital Anomalies 41(4) 329-337, 2001... 

Ten Berg K, Hoogeboom AJ, Wesby-van Swaaij E, et al Maternal occupational methyl ethyl ketone exposure and multiple congenital anomalies. Teratology 65(6) 326, 2002... 

Reports, primarily from Brazil, of congenital anomalies and fetal death subsequent to use of misoprostol alone, as an abortifacient, have been received. 

Pregnancy Fetal death and/or congenital anomalies have occurred do not use in women of childbearing potential unless benefits outweigh possible risks. Pregnant women with psoriasis or RA should not receive methotrexate (see Contraindications). 

Primary sclerosing cholangitis, congenital anomalies of the pancreaticobiliary tree, and parasitic infections are also associated with bile duct cancer. 

Any cancers and congenital anomalies or birth defects should also be regarded as serious. 

Rosenkrantz JG, Lynch FP, Frost WW (1970) Congenital anomalies in the pig teratogenic... 

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). 

Avoidance of routine prophylaxis with antiparkinsonian agents, including benztropine, diphenhydramine, and amantadine, all of which have been associated with congenital anomalies. Calcium supplementation may be a useful alternative (10), and propranolol or atenolol may be used for akathisia if cardiovascular status is stable (7). 

Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies a HuGE review. Am JEpidemiol 2000 151 862-877. 

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