Population-based case-control study of teratogenic potential of corticosteroids. Maternal corticosteroid use and orofacial clefts. Risk of intrauterine growth retardation, malformations and other birth outcomes in children after topical use of corticosteroid in pregnancy. The cosmetic use of skin-lightening products during pregnancy in Dakar, Senegal: a common and potentially hazardous practice. First trimester exposure to corticosteroids and oral clefts. Maternal drug use and infant cleft lip/palate with special reference to corticoids.
The teratogenic potential of oral and topical corticosteroid treatment during pregnancy was evaluated in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1994. Corticosteroid tablet pregnancy exposure was 1.55% among 20,830 malformed cases and 1.41% among 35,727 healthy control births (P = 0.2). Corticosteroid ointment pregnancy exposure was 0.35% among malformed and 0.33% among control births (P = 0.7). The absolute risk of oral and ointment corticosteroid treatment was low in pregnancy and particularly in the second and third months of gestation, i.e., in the critical period for major congenital abnormalities. The adjusted odds ratio and the analysis of case-control pairs did not show any association between the rate of different congenital abnormalities and the corticosteroid treatment in the second and third months of gestation. Thus, treatments with corticosteroids in pregnancy do not appear to noticeably increase the risk of congenital abnormalities in humans. The purpose of this study was to examine whether maternal corticosteroid use during pregnancy is associated with delivering an infant with an orofacial cleft.
                This study included data on deliveries from the National Birth Defects Prevention Study, which is a population-based case-control study. Exposures were assessed by telephone interviews for mothers of 1141 cases with cleft lip +/- cleft palate (CLP), 628 with cleft palate (CP), and 4143 controls.
                Mothers of 33 infants with CLP (2.9%), mothers of 6 infants with CP (1.0%), and 72 control subjects (1.7%) reported corticosteroid use from 4 weeks before through 12 weeks after conception. The crude odds ratio for "any" vs "no" use was 1.7 (95% CI, 1.1-2.6) for CLP and 0.5 (0.2-1.3) for CP. When analyzed by route of administration and medication components, odds ratios for CLP tended to be elevated, and odds ratios for CP tended to be close to 1.
                Our results suggest a moderately increased risk of CLP among women who use corticosteroids during early pregnancy. Topical corticosteroids are frequently used drugs, but little is known of the exposure during pregnancy and birth outcome.
                In a population-based follow-up study restricted to primigravida women, we examined the risk of low birth weight, malformations and other birth outcomes following pregnancy upon exposure to topical corticosteroids. We compared the offspring of 363 women exposed to topical corticosteroids during pregnancy with 9263 controls, who received no prescriptions at all.
                The prevalence of malformations was 2.9% among 170 infants exposed during the first trimester and 3.6% among the controls. Adjusted odds ratios for low birth weight, malformations and preterm delivery among women receiving weak/medium strong corticosteroids were 0.7 (95% CI 0.17-2.85), 0.93 (95% CI 0.23-3.80) and 1.04 (95% CI 0.56-1.92), respectively, and adjusted odds ratios for strong/very strong corticosteroids were 1.23 (95% CI 0.45-3.37), 0.56 (95% CI 0.14-2.28) and 0.99 (95% CI 0.54-1.84), respectively.
                The study showed no increased risk of low birth weight, malformations or preterm delivery in the offspring of women exposed to topical corticosteroid during pregnancy. Many women of childbearing age from sub-Saharan Africa use topical skin lighteners, some of which present a risk of toxic systemic effects. The goals of this study were to evaluate, in this environment, the frequency of this practice during pregnancy, as well as eventual consequences on pregnancy. Ninety-nine women from 6 to 9 months pregnant were randomly selected among those attending a standard maternal centre in Dakar for a prenatal visit. Investigations consisted of questions about the use of skin lighteners, a standard clinical examination, follow-up until delivery and a morning blood sample for plasma cortisol levels. Sixty-eight of the 99 selected women used skin lighteners during their current pregnancy, the main active ingredients being hydroquinone and highly potent steroids (used by 64 and 28 women, respectively). No difference in the main outcomes of pregnancy were found between skin-lightener users and the others; however, women using highly potent steroids, when compared with those who did not, had a statistically significant lower plasma cortisol level and a smaller placenta, and presented a higher rate of low-birth-weight infants. Skin lightening is a common practice during pregnancy in Dakar, and the use of steroids may result in consequences in the mother and her child. The possible association between oral cleft in the newborn and maternal exposure to corticoids during pregnancy is still controversial. The aim of this study was to test this association by a case-control analysis using the large multicentric MADRE database.
                The MADRE database is a collection of information on malformed infants with a history of maternal first-trimester drug exposure. Nine malformation registries participate in the data collection. Cases were defined as infants presenting with a cleft palate or cleft lip, and exposure was defined by the use of corticosteroids during the first trimester of pregnancy.
                After 12 years of data collection, the database includes data on 11,150 malformed infants. A slight association is observed between exposure to corticoids for systemic use and the occurrence of cleft lip with or without cleft palate (OR, 2.59; 95% CI, 1.18-5.67).
                If the observed association is real, an interpretation is suggested, based on a likely interaction between corticosteroids and environmental dioxins. It is indeed possible that human fetuses may become sensitive to the teratogenic effect of corticosteroids when they are exposed in utero to environmental pesticides as well.
                Copyright 2003 Wiley-Liss, Inc. To study the association between maternal drug use in early pregnancy and orofacial cleft in the infant.
                Register analysis based on prospectively collected information.Patients: All delivered women in Sweden July 1, 1995, through December 31, 2001.
                Presence of orofacial cleft in infant.
                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 B(12) 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.
                Maternal drug use seems to play only a small role for the origin of orofacial clefts, at least in Sweden.
Currently limited and inconclusive data are unable to detect an association between topical corticosteroids and congenital abnormality, preterm delivery, or stillbirth. The current evidence shows no statistically significant difference between pregnant women who use and those who do not use topical corticosteroids. However, there does appear to be an association of very potent topical corticosteroids with low birthweight. Cohort studies with comprehensive outcome measures, assessment of effects of corticosteroid potency and dose, application methods, and reasons for giving them, and a very large sample size are needed.