Second-generation effects pregnancy

Even more disconcerting than the second-generation effects in women exposed to diethylstilbestrol during pregnancy is the possibility of third-generation effects. There is no certainty regarding these, but worrying cases have been reported at intervals over the last thirty years or more (SED-14,1449). 

The adverse effects of the statins are mostly limited to slight increases in liver and muscle cnzym cs in the blood. Hypersensitivity reactions are very rare. There is no evidence of tumor-inducing effects. Second-generation effects are suspected, and statins should not be used during pregnancy. 

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). 

There is no evidence that piperazine has any second-generation effects it has been nsed extensively in pregnancy withont nntoward incidents, bnt as a precantion WHO advises against administration in the first trimester. 

The current difficulty in many reports of second-generation complications is to determine whether the mother actually took diethylstilbestrol during her pregnancy. In a case of a very large clear-cell carcinoma of the cervix in a teenager with no known history of maternal use of diethylstilbestrol, in view of the dates it was likely to have been non-drug-related, but the possibility of third-generation effects must also be borne in mind (13). 

Diethylstilbestrol was used extensively in pregnancies between 1940 and about 1975, in the belief that it could protect threatened pregnancies and counter the risk of spontaneous abortion. Toward the end of that period, increasingly clear evidence emerged that diethylstilbestrol could have an adverse effect on the second generation that... 

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