Antibiotic (Penicillin)
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: Compatible
PREGNANCY SUMMARY
Penicillin G is used routinely for maternal infections during pregnancy. Reproduction studies in mice, rats, and rabbits revealed no evidence of impaired fertility or fetal harm (1). The antibiotic is considered low risk in pregnancy.
FETAL RISK SUMMARY
Several investigators have documented the rapid passage of penicillin G into the fetal circulation and amniotic fluid (2–6). Therapeutic levels are reached in both sites except for the amniotic fluid during the 1st trimester (6). At term, maternal serum and amniotic fluid concentrations are equal 60–90 minutes after IV administration (3). Continuous IV infusions (10,000 U/hr) produce equal concentrations of penicillin G at 20 hours in maternal serum, cord serum, and amniotic fluid (3).
The early use of penicillin G was linked to increased uterine activity and abortion (7–11). It is not known whether this was related to impurities in the drug or to penicillin itself. No reports of this effect have appeared since a report published in 1950 (11). An anaphylactic reaction in a pregnant patient reportedly led to the death of her fetus in utero (12).
Only one reference has linked the use of penicillin G with congenital abnormalities (13). An examination of hospital records indicated that in three of four cases the administration of penicillin G had been followed by the birth of a malformed baby. A retrospective review of additional patients exposed to antibiotics in the 1st trimester indicated an increase in congenital defects. Unfortunately, the authors did not analyze their data for each antibiotic, so no causal relationship to penicillin G could be shown (13,14).
In another case, a patient was treated in early pregnancy with high doses of penicillin G procaine IV,* cortisone, and sodium salicylate (15). A cyclopic male was delivered at term but died 5 minutes later. The defect was attributed to salicylates, cortisone, or maternal viremia. In a controlled study, 110 patients received one to three antibiotics during the 1st trimester for a total of 589 weeks (16). Penicillin G was given for a total of 107 weeks. The incidence of birth defects was no different from that in a nontreated control group. (*Penicillin G procaine should not be given IV. Presumably, the drug was either given IM or the procaine form was not used. Attempts to clarify this with the authors have been unsuccessful.)
The Collaborative Perinatal Project monitored 50,282 mother–child pairs, 3546 of whom had 1st trimester exposure to penicillin derivatives (17, pp. 297–313). For use anytime during pregnancy, 7171 exposures were recorded (17, p. 435). In neither group was evidence found to suggest a relationship to large categories of major or minor malformations or to individual defects. From these data, it is unlikely that penicillin G is teratogenic.
BREASTFEEDING SUMMARY
Penicillin G is excreted into breast milk in low concentrations. Milk:plasma ratios following IM doses of 100,000 U in 11 patients varied between 0.02 and 0.13 (18). The maximum concentration measured in milk was 0.6 U/mL after this dose. Although no adverse effects were reported, three potential problems exist for the nursing infant: modification of bowel flora, direct effects on the infant (e.g., allergic response), and interference with the interpretation of culture results if a fever workup is required.
References
1.Product information. Pfizerpen. Pfizer, 2000.
2.Herrel W, Nichols D, Heilman D. Penicillin. Its usefulness, limitations, diffusion and detection, with analysis of 150 cases in which it was employed. JAMA 1944;125:1003–11.
3.Woltz J, Zintel H. The transmission of penicillin to amniotic fluid and fetal blood in the human. Am J Obstet Gynecol 1945;50:338–40.
4.Hutter A, Parks J. The transmission of penicillin through the placenta. A preliminary report. Am J Obstet Gynecol 1945;49:663–5.
5.Woltz J, Wiley M. The transmission of penicillin to the previable fetus. JAMA 1946;131:969–70.
6.Wasz-Hockert O, Nummi S, Vuopala S, Jarvinen P. Transplacental passage of azidocillin, ampicillin and penicillin G during early and late pregnancy. Acta Paediatr Scand (Suppl) 1970;206:109–10.
7.Lentz J, Ingraham N Jr, Beerman H, Stokes J. Penicillin in the prevention and treatment of congenital syphilis. JAMA 1944;126:408–13.
8.Leavitt H. Clinical action of penicillin on the uterus. J Vener Dis Inf 1945;26:150–3.
9.McLachlan A, Brown D. The effects of penicillin administration on menstrual and other sexual functions. Br J Vener Dis 1947;23:1–10.
10.Mazingarbe A. Le pencilline possede-t-elle une action abortive? Gynecol Obstet 1946;45:487.
11.Perin L, Sissmann R, Detre F, Chertier A. La pencilline a-t-elle une action abortive? Bull Soc Fr Dermatol 1950;57:534–8.
12.Kosim H. Intrauterine fetal death as a result of anaphylactic reaction to penicillin in a pregnant woman. Dapim Refuiim 1959;18:136–7.
13.Carter M, Wilson F. Antibiotics and congenital malformations. Lancet 1963;1:1267–8.
14.Carter M, Wilson F. Antibiotics in early pregnancy and congenital malformations. Dev Med Child Neurol 1965;7:353–9.
15.Khudr G, Olding L. Cyclopia. Am J Dis Child 1973;125:120–2.
16.Ravid R, Toaff R. On the possible teratogenicity of antibiotic drugs administered during pregnancy-a prospective study. In Klingberg M, Abramovici A, Chemki J, eds. Drugs and Fetal Development. New York, NY: Plenum Press, 1972:505–10.
17.Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977.
18.Greene H, Burkhart B, Hobby G. Excretion of penicillin in human milk following parturition. Am J Obstet Gynecol 1946;51:732–3.