怀孕期间使用抗菌药物的相关风险

November 2, 2009 — Many antibiotics used during pregnancy, except for sulfonamides and nitrofurantoins, are not associated with many birth defects, according to the results of a population-based, multisite, case-control study reported in the November issue of Archives of Pediatric & Adolescent Medicine.

"Antimicrobials, and antibacterial drugs in particular, are among the most commonly used medications during pregnancy because treatment of infections is critical to the health of a mother and her fetus," write Krista S. Crider, PhD, from the US Centers for Disease Control and Prevention in Atlanta, Georgia, and colleagues. "Although it appears that some classes of antibiotics have been used relatively safely during pregnancy, to our knowledge there have been no large-scale studies addressing safety or risk for many classes of antibacterial drugs."

The goal of the study was to characterize the association between use of antibacterial medications during the critical developmental stages in early pregnancy (from 1 month before pregnancy through the third month of pregnancy) and selected birth defects.

The National Birth Defects Prevention Study is an ongoing population-based, case-control study of birth defects in the United States. Case patients were 13,155 women who had pregnancies affected by 1 of more than 30 eligible major birth defects that were detected via birth defect surveillance programs in 10 states. Control subjects were 4941 women randomly selected from the same geographic regions.

The exposure of interest was reported maternal use of antibiotics during the period from 1 month before pregnancy through the end of the first trimester, and the primary study endpoints were odds ratios (ORs) describing the association between use of a specific antibiotic and selected birth defects, after adjustment for potential confounders.

During pregnancy, the reported use of antibiotics increased, peaking during the third month. Antibacterial use at one time during the period from 3 months before pregnancy to the end of pregnancy was reported by 29.4% of case mothers and 29.7% of control subjects.

Birth defects associated with sulfonamide use were anencephaly (adjusted OR ,3.4; 95% confidence interval [CI], 1.3 - 8.8), hypoplastic left heart syndrome (adjusted OR, 3.2; 95% CI, 1.3 - 7.6), coarctation of the aorta (adjusted OR, 2.7; 95% CI, 1.3 - 5.6), choanal atresia (adjusted OR, 8.0; 95% CI, 2.7 - 23.5), transverse limb deficiency (adjusted OR, 2.5; 95% CI, 1.0 - 5.9), and diaphragmatic hernia (adjusted OR, 2.4; 95% CI, 1.1 - 5.4).

Birth defects associated with nitrofurantoins were anophthalmia or microphthalmos (adjusted OR, 3.7; 95% CI, 1.1 - 12.2), hypoplastic left heart syndrome (adjusted OR, 4.2; 95% CI, 1.9 - 9.1), atrial septal defects (adjusted OR, 1.9; 95% CI, 1.1 - 3.4), and cleft lip with cleft palate (adjusted OR, 2.1; 95% CI, 1.2 - 3.9). Among other antibiotics, erythromycins were associated with 2 defects, and penicillins, cephalosporins, and quinolones were each associated with 1 defect.

"Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects," the study authors write. "Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny."

Limitations of this study include retrospective design with inability to determine causal relationships, possible selection bias, and difficulty determining whether a defect is linked to a particular antibiotic or to the underlying infection.

"Determining the causes of birth defects is problematic," the authors write. "A single defect can have multiple causes, or multiple seemingly unrelated defects may have a common cause. This study could not determine the safety of drugs during pregnancy, but the lack of widespread increased risk associated with many classes of antibacterials used during pregnancy should be reassuring."
http://www.medscape.com/viewarticle/711665

在怀孕期间使用的抗菌药物研究比较少，存在不可预测的风险。

孕妇使用青霉素类、头孢菌素类和红霉素，没有相关的出生缺陷的报告，FDA妊娠期分类B，孕妇使用时应权衡利弊！
磺胺类药物及呋喃妥因与一些出生缺陷有关，可是呋喃妥因的FDA妊娠期分类为B、SMZ/TMP的FDA妊娠期分类为C。呋喃妥因药品说明书中，妊娠晚期禁用、新生儿禁用、哺乳妇女暂停哺乳！SMZ/TMP药品说明书中，孕妇哺乳妇女禁用！