10 Obstetrics O B .GYN. NEWS • July 15, 2005

D RUGS, PREGNANCY, Expert: Repeat Steroids Can A ND L ACTATION Be Justified in Certain Cases Antihyperlipidemic Agents he antihyperlipidemic class of drugs chromosome defect. The remaining two BY SHERRY BOSCHERT teroid group. With weekly corticosteroids, Tcan be subdivided into bile acid se- cases involved unilateral cleft lip and a San Francisco Bureau 33% developed RDS, and 12% had severe questrants, HMG-CoA reductase in- clubfoot, neither of which appear to be RDS, compared with 41% and 20%, re- hibitors, fibric acid derivatives, ezetim- attributable to simvastatin. S AN F RANCISCO — Three random- spectively, in the placebo group. ibe, and niacin. With the possible A 2004 reference described 178 cases ized, controlled trials now show evidence The need for oxygen or mechanical exception of familial hypercholes- of first-trimester exposure to statins re- of beneficial effects from a limited num- ventilation fell less dramatically in the terolemia, there appears to be no ma- ported to the Food and Drug Adminis- ber of repeat courses of prenatal corti- weekly corticosteroids group, compared ternal benefit for treating hyperlipi- tration. Among the 52 cases suitable for costeroids for fetuses at risk of preterm with placebo, but it was not clear whether demia in gestation. Nearly all reported evaluation, there were 20 major malfor- delivery, according to Julian T. Parer, these differences were significant. pregnancy exposures have occurred ac- mations, some thought to be consistent M.D. There were no significant differences cidentally. If treatment is required, only with inhibition of cholesterol biosyn- Those aren’t necessarily the official between groups in the need for intensive bile acid sequestrants are considered thesis. All defects involved a lipophilic conclusions of the studies, however, he care, duration of intensive care, rates of compatible in pregnancy and lactation. statin (atorvastatin, cerivastatin [Baycol], acknowledged at a meeting on antepar- chronic lung disease or severe intraven- Ezetimibe (Zetia) ap- lovastatin, or simvastatin). tum and intra- tricular hemor- pears to be low risk in ges- No defects were reported partum manage- rhage, or maternal tation, but not in lactation. with pravastatin, a hy- ment sponsored by With weekly outcomes. Because most drug-in- drophilic agent with low the University of steroids, 33% Although birth duced adverse effects in tissue penetration that is California, San developed RDS, weights were nursing infants have been not associated with ani- Francisco. compared somewhat lower in reported during the first mal developmental toxic- Two of the three with 41% in the the steroid group, month after birth, delay- ity. Because all statins are studies found no placebo group. the weight differ- ing treatment of a nursing probably excreted into overall benefit ences between mother until after this pe- milk, women taking these from repeat prena- DR. PARER groups resolved by riod appears to be the best drugs should not breast- tal steroids but re- the time of hospital course. feed. ported significantly less respiratory dis- discharge, he said. Average neonatal length Cholesterol is the pre- BY GERALD G. Among fibric acid de- tress and morbidity in babies born at and head circumference did not differ be- cursor of bile acids that BRIGGS, B.PHARM. rivatives, only gemfibrozil younger gestational ages if they got more tween groups. are excreted from the liv- (Lopid) has some human than one course of betamethasone pre- No harmful effects of repeat corticos- er and gallbladder into the intestine to data. The other agent, fenofibrate (Tri- natally. teroids were noted. Of those women aid in the digestion of fat. Bile acid se- Cor), has no human data. The animal The third study showed a benefit from who received repeat courses, 24% re- questrants—cholestyramine (Questran data (developmental toxicity in two an- repeat prenatal steroids, but the investi- ceived at least four courses. The investi- and various other names), colestipol imal species at doses up to 10 times the gators will not draw conclusions about gators declined to present a conclusion (Colestid), and colesevelam (WelChol)— human dose) for each drug suggest there the results until after a 2-year follow-up until they’ve completed 2 years of neu- are anion exchange resins that form in- may be a risk to the human embryo or period, said Dr. Parer, who is professor of rodevelopmental follow-up, he said at soluble complexes with bile acids in the fetus. The safest course is to avoid these ob.gyn. at the university. the meeting. intestine. The complexes are then ex- drugs in pregnancy (both are risk factor Dr. Parer said he has no financial rela- A separate study, which was reported creted in the feces, removing cholesterol C). Although there are no data, the drugs tionships with companies that make cor- at the Society of Maternal and Fetal from the system. are probably excreted into milk, and ticosteroids. Medicine meeting in 2004, randomized Cholestyramine has been used as a women on these agents should not A consensus statement issued in 2000 by 495 women after an initial course of pre- treatment for intrahepatic cholestasis of breast-feed. the National Institutes of Health says that natal corticosteroids to weekly courses pregnancy and as an antidote for some Ezetimibe (risk factor C) selectively repeat courses of corticosteroids should or placebo. types of diarrhea, chlordecone pesticide inhibits the intestinal absorption of cho- not be used routinely due to insufficient The study was stopped prematurely at poisoning, and digitalis toxicity. Because lesterol and related phytosterols. At data from randomized clinical trials. 23% of its expected enrollment due to bile acid sequestrants are not absorbed doses up to 10 times the human dose, Data from these three more recent stud- concerns about birth weights, and no into the systemic circulation, they do the drug is teratogenic in rats but not in ies, however, support the administration of signs of a substantial reduction in over- not represent a direct risk to the embryo rabbits. Human pregnancy exposures more than one course of prenatal corti- all morbidity in the steroid group. or fetus and are considered compatible have not been reported. If therapy dur- costeroids for women who are at at high The investigators concluded that there with pregnancy (all are rated risk factor ing pregnancy is mandated, ezetimibe risk of delivering before 28 weeks, Dr. Par- was no benefit to repeated courses of B) and lactation. However, the resins appears to be a better choice than er said. corticosteroids, but Dr. Parer highlighted also bind fat-soluble vitamins (vitamins statins. There are no data on use during “It is possible to justify repeating at the “much more impressive” results in in- A, D, E, and K) in the gut, and defi- lactation, but the drug is probably ex- least a single course in those patients, fants delivered at less than 32 weeks. ciencies of these vitamins may result. creted into milk. Nursing infants should particularly if given at a 2-week interval,” These babies had significantly less bron- The six HMG-CoA reductase in- be monitored for headache, diarrhea, he said. chopulmonary dysplasia and less need for hibitors (statins) are atorvastatin (Lipi- arthralgia, pharyngitis, sinusitis, and Dr. Parer relayed results of the third, mechanical ventilation or continuous pos- tor), fluvastatin (Lescol), lovastatin other adverse effects observed in adults. and most recent, study that he heard pre- itive airway pressure if they had received (Mevacor, Altocor), pravastatin (Prava- Niacin (nicotinic acid) is converted in sented at a conference in Australia earli- repeat corticosteroids, he noted. Birth chol), rosuvastatin (Crestor), and sim- vivo to niacinamide, the active form of er this year. That study included 982 weights were lower only in infants who vastatin (Zocor). All are contraindicated vitamin B3. But high doses (up to 2,000 pregnant women at risk for preterm de- had been exposed to more than four in pregnancy (risk factor X). Case reports mg/day) used for hyperlipidemia have livery who had received one course of courses of corticosteroids. and surveillance studies have described not been studied in pregnancy. Because prenatal corticosteroids. A third study that randomized 502 healthy outcomes from a number of niacinamide is actively transported to The women were randomized to women to a single course or weekly cours- pregnancies inadvertently exposed in the fetus, producing higher concentra- weekly corticosteroids or placebo; treat- es of corticosteroids also was stopped ear- the first trimester and later. The largest tions in the fetus and newborn than in ment continued until 32 weeks’ gestation ly and reported no benefit from weekly number of cases (187) were reported the mother, niacin is best avoided dur- only if the risk for preterm delivery con- prenatal steroids (JAMA 2001;286:1581- with simvastatin, with 86 cases that ing pregnancy and lactation. tinued. 7). could be evaluated: 74% had normal The study included singletons, twins, That study also reported a significantly outcomes, 15% resulted in spontaneous MR. BRIGGS is a pharmacist clinical and triplets for a total of 1,100 fetuses lower incidence of RDS in babies born be- abortion, 6% of cases demonstrated specialist, Women’s Pavilion, Miller that were a mean of 28 weeks’ gestation fore 28 weeks whose mothers received re- with congenital anomalies, 4% of cases Children’s Hospital, Long Beach, Calif.; at enrollment. The risk factors for peated courses of corticosteroids, Dr. Par- had effects related to prematurity, and clinical professor of pharmacy, University preterm birth were similar between er noted. 1% resulted in fetal death. Three of the of California, San Francisco; and groups. Critics contend that both of these stud- five birth defect cases were not related adjunct professor of pharmacy, Results showed significantly lower rates ies were too small and too short to detect to simvastatin because of the timing of University of Southern California, Los of respiratory distress syndrome (RDS) significant differences in their primary end exposure or the outcome was a known Angeles. and severe RDS in the weekly corticos- point of composite morbidity. ■

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