Women who take fluoxetine during pregnancy do not have an increased risk of spontaneous pregnancy loss or major fetal anomalies, but women who take fluoxetine in the third trimester are at increased risk for perinatal complications.

Topical tretinoin (Retin-A) is used to treat acne and photodamaged skin. Its teratogenic potential is of concern due to its similarity to isotretinoin (Accutane), a recognized human teratogen. Through the California Teratogen Information Service and Clinical Research Program, between 1983 and 2003, 106 pregnant women with first-trimester exposure to topical tretinoin were prospectively ascertained and followed. Birth outcomes, including pregnancy loss, major structural defects, and pre- and postnatal growth were compared to 389 similarly and prospectively ascertained women with no topical tretinoin exposure during pregnancy. Because a distinct pattern of malformation had already been described for isotretinoin, we also compared exposed (n = 62) and unexposed (n = 191) infants on the prevalence of a specific subset of minor malformations selected to represent the spectrum of defects comprising the retinoic acid embyopathy. There were no significant differences between groups in the proportion of pregnancies ending in spontaneous abortion (6.6% in exposed vs. 8.5% in unexposed; P = 0.53), or infants with major structural defects (2.2% in exposed vs. 1.2% in unexposed; P = 0.62). In addition, the groups were similar in birth weight, length and head circumference, and there were no significant differences between groups in length of gestation. Furthermore, the prevalence of one or more retinoic acid-specific minor malformations did not differ significantly between groups (12.9% in exposed vs. 9.9% in unexposed; P = 0.51). First-trimester topical tretinoin exposure in this study was not associated with an increased risk of any adverse pregnancy outcome evaluated. Specifically, there was no indication that topical tretinoin is associated with an increased risk for minor malformations that are consistent with the retinoic acid embryopathy. Although it is impossible to exclude the possibility that some women/infants may be uniquely susceptible to topical tretinoin exposure, this study provides further reassurance for women who are inadvertently exposed early in pregnancy.

These data do not suggest that women who breastfeed while taking fluoxetine are likely to note unusual behavior in their infants that they consider related to use of the medication. However, although there was no excess of infants in the fluoxetine group with postnatal weight measurements >2 standard deviations below the mean, these data indicate that breastfeeding while taking fluoxetine is associated with reduced growth that may be of clinical importance in situations in which infant weight gain is already of concern.

Although maternal fever has been implicated as a human teratogen in several studies, no prospective study has adequately addressed the full spectrum of birth outcomes following such exposure in pregnancy. The purpose of this study was to determine whether or not maternal fever is associated with an increased risk for structural malformations, prematurity, growth retardation, or pregnancy loss. Using a prospective cohort study design, we ascertained women who had called the California Teratogen Information Service and Clinical Research Program between 1979-1996 with questions regarding fever in a current pregnancy. Of these women, 115 who reported a fever of at least 38.9 degrees C lasting for at least 24 h (high fever group) and 147 women who reported a fever of either less than 38.9 degrees C or lasting less than 24 h (low fever group) were enrolled in the cohort. An additional 298 pregnant women who reported having no fever at any time in pregnancy were enrolled in a control group. All pregnancies were followed in a similar fashion, and outcomes were compared among the three groups. The combined prevalence of all major structural malformations was increased, but not significantly so, in the offspring of women who had a high fever in the first trimester of pregnancy compared to those with a lower fever or to controls (relative risk 1.80 for high fever group compared to controls; 95% confidence interval, 0.54, 6.03; relative risk 1.21 for low fever group compared to controls; 95% confidence interval, 0.36, 4.03). However, 2/34 or 5.9% of women who had a high fever during the critical period for neural tube closure carried fetuses with anencephaly compared to none in the low fever group or controls. Specific minor defects were found more frequently in the high fever group compared to controls and were consistent with the pattern of defects previously reported in a retrospective case series. In addition, stillbirth occurred more frequently in the high fever group compared to controls (2.6% vs. 0%). These data support the conclusion that high maternal fever early in pregnancy is a human teratogen. Women who experience fevers of 38.9 degrees C or higher for extended periods of time in the first month of pregnancy should be considered at increased risk for neural tube defects and should be provided appropriate counseling.

More than half of the callers to the TIS were not compliant with recommendations regarding periconceptional folic acid supplementation. This represents an opportunity for TIS specialists and physicians to intervene in a current pregnancy to encourage maintenance of supplement use in the subsequent interpregnancy interval.