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Non-Narcotic Analgesics

Use in Pregnancy and Fetal and Perinatal Effects

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Summary

Aspirin and related non-narcotic analgesics such as paracetamol (acetaminophen) are present in almost every ‘Western’ household and are so commonly used that the public often does not think of them as drugs. Although the toxic effects of overdoses are well recognised by the medical and related professions, the potential adverse effects of repetitive dosing, within the commonly recommended therapeutic range, are not. This is particularly true during pregnancy, where the relative overall general safety of the agents is overshadowed by the possible subtle but potentially pervasive effects on the fetus. Marketing publicity, particularly about recently introduced related agents, has at times failed to take into account these less obvious, but nevertheless potentially lethal, side effects. It is now likely that aspirin and/or paracetamol are used during pregnancy by most women and that the earlier figures are underestimates.

Although animal studies have shown significant effects of non-steroidal anti-inflammatory agents (NSAIDs) on the fetal circulation, particularly on the developing pulmonary circulation, the data on human pregnancy are less convincing. Nevertheless, the possible association of these drugs with prolonged gestation, and an increased incidence of the syndrome of persistent pulmonary hypertension of the newborn and of intracranial haemorrhage, demand that prudence be exercised when using these drugs during pregnancy. At the very least, more conclusive evidence is necessary that fetal and neonatal complications are not increased.

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References

  • Ahmed, T. and Oliver, W., Jr.: Does slow-reacting substance of anaphylaxis mediate hypoxic pulmonary vasoconstriction? American Review of Respiratory Disease 127: 566–571 (1983).

    PubMed  CAS  Google Scholar 

  • Aiken, J.W.: Aspirin and indomethacin prolong parturition in rats: Evidence that prostaglandins contribute to expulsion of foetus. Nature 240: 21–25 (1972).

    PubMed  CAS  Google Scholar 

  • Anderson, G.G.; Cidlowski, J.A.; Absher, P.M.; Hewitt, J.R. and Douglas, W.H.J.: The effect of dexamethasone and prostaglandin F on production and release of surfactant in Type II alveolar cells. Prostaglandins 16: 923–929 (1978).

    PubMed  CAS  Google Scholar 

  • Anderson, P.O.: Drugs and breast feeding — a review. Drug Intelligence and Clinical Pharmacy 11: 208–223 (1977).

    CAS  Google Scholar 

  • Anderson, R.J.; Bed, T.; McDonald, K.M. and Schrier, R.W.: Evidence for an in vivo antagonism between vasopressin and prostaglandin in the mammalian kidney. Journal of Clinical Investigation 56: 420–426 (1975).

    PubMed  CAS  Google Scholar 

  • Arcilla, R.A.; Thilenius, O.G. and Ranniger, K.: Congestive heart failure from suspected ductal closure in utero. Journal of Pediatrics 75: 74–78 (1969).

    PubMed  CAS  Google Scholar 

  • Berlin, C.M., Jr.: Pharmacologic considerations of drug use in the lactating mother. Obstetrics and Gynecology 58: 17S–23S (1981).

    PubMed  Google Scholar 

  • Berman, W., Jr.; Goodlin, R.C.; Heymann, M.A. and Rudolph, A.M.: Effects of pharmacologic agents on umbilical blood flow in fetal lambs in utero. Biology of the Neonate 33: 225–235 (1978).

    PubMed  CAS  Google Scholar 

  • Bleyer, W.A. and Breckenridge, R.T.: Studies on the detection of adverse drug reactions in the newborn. II. The effects of prenatal aspirin on newborn hemostasis. Journal of the American Medical Association 213: 2049–2053 (1970).

    PubMed  CAS  Google Scholar 

  • Boddy, K. and Dawes, G.S.: Fetal breathing. British Medical Bulletin 31: 3–7 (1975).

    PubMed  CAS  Google Scholar 

  • Bustos, R.; Ballejo, G.; Giussi, G.; Rosas, R. and Isa, J.C.: Inhibition of fetal lung maturation by indomethacin in pregnant rabbits. Journal of Perinatal Medicine 6: 240–245 (1978).

    PubMed  CAS  Google Scholar 

  • Cantor, B.; Tyler, T.; Nelson, R.M. and Stein, G.H.: Oligohydramnios and transient neonatal anuria: A possible association with the maternal use of prostaglandin synthetase inhibitors. Journal of Reproductive Medicine 24: 220–223 (1980).

    PubMed  CAS  Google Scholar 

  • Cassin, S.: Humoral factors affecting pulmonary blood flow in the fetus and newborn infant; in Peckham and Heymann (Eds) Cardiovascular Sequelae of Asphyxia in the Newborn, pp. 10–18 (Ross Laboratories, Columbus, Ohio 1982).

    Google Scholar 

  • Cassin, S.; Tyler, T.L. and Wallis, R.: The effects of prostaglandin E1 on fetal pulmonary vascular resistance (38588). Proceedings of the Society for Experimental Biology and Medicine 148: 584–587 (1975).

    PubMed  CAS  Google Scholar 

  • Cassin, S.; Tod, M.; Philips, J.; Frisinger, J.; Jordan, J. and Gibbs, C.: Effects of prostaglandin D2 in perinatal circulation. American Journal of Physiology 240: H755–H760 (1981a).

    PubMed  CAS  Google Scholar 

  • Cassin, S.; Winikor, I.; Tod, M.; Philips, J.; Frisinger, S.; Jordan, J. and Gibbs, C.: Effects of prostacyclin on the fetal pulmonary circulation. Pediatric Pharmacology 1: 197–207 (1981b).

    PubMed  CAS  Google Scholar 

  • Challis, R.G. and Patrick, J.E.: The production of prostaglandins and thromboxanes in the feto-placental unit and their effects on the developing fetus. Seminars in Perinatology 4: 23–33 (1980).

    PubMed  CAS  Google Scholar 

  • Challis, J.R.G.; Osathanondh, R.; Ryan, K.J. and Tulchinsky, D.: Maternal and fetal plasma prostaglandin levels at vaginal delivery and caesarean section. Prostaglandins 6: 281–288 (1974).

    PubMed  CAS  Google Scholar 

  • Chester, R.; Dukes, M.; Slater, S.R. and Walpole, A.L.: Delay of parturition in the rat by anti-inflammatory agents which inhibit the biosynthesis of prostaglandins. Nature 240: 37 (1972).

    PubMed  CAS  Google Scholar 

  • Clyman, R.I.: Ontogeny of the ductus arteriosus response to prostaglandins and inhibitors of their synthesis. Seminars in Perinatology 4: 115–124 (1980).

    PubMed  CAS  Google Scholar 

  • Clyman, R.I. and Heymann, M.A.: Pharmacology of the ductus arteriosus. Pediatric Clinics of North America 28: 77–93 (1981).

    PubMed  CAS  Google Scholar 

  • Coceani, F. and Olley, P.M.: Role of prostaglandins, prostacyclin, and thromboxanes in the control of prenatal patency and postnatal closure of the ductus arteriosus. Seminars in Perinatology 4: 109–113 (1980).

    PubMed  CAS  Google Scholar 

  • Collins, E.: Maternal and fetal effects of acetaminophen and salicylates in pregnancy. Obstetrics and Gynecology 58: 57S–62S (1981).

    PubMed  CAS  Google Scholar 

  • Collins, E. and Turner, G.: Maternal effects of regular salicylate ingestion in pregnancy. Lancet 2: 335–338 (1975).

    PubMed  CAS  Google Scholar 

  • Corby, D.G.: Aspirin in pregnancy: Maternal and fetal effects. Pediatrics 62S: 930–937 (1978).

    Google Scholar 

  • Corby, D.G.: Editorial comment. Obstetrics and Gynecology 58: 737–740 (1981).

    Google Scholar 

  • Corby, D.G. and Schulman, I.: The effects of antenatal drug administration on aggregation of platelets of newborn infants. Journal of Pediatrics 79: 307–313 (1971).

    PubMed  CAS  Google Scholar 

  • Csaba, I.F.; Sulyok, E. and Ertl, T.: Relationship of maternal treatment with indomethacin to persistence of fetal circulation syndrome. Journal of Pediatrics 92: 484–488 (1978).

    PubMed  CAS  Google Scholar 

  • Dawes, G.L.; Fox, H.E.; Leduc, B.M.; Liggins, G.C. and Richards, R.T.: Respiratory movements. A review. American Journal of Obstetrics and Gynecology 131: 315–338 (1972).

    Google Scholar 

  • Doering, P.L. and Stewart, R.B.: The extent and character of drug consumption during pregnancy. Journal of the American Medical Association 239: 843–846 (1978).

    PubMed  CAS  Google Scholar 

  • Erickson, S.H. and Oppenheim, G.L.: Aspirin in breast milk. Journal of Family Practice 8: 189–190 (1979).

    PubMed  CAS  Google Scholar 

  • Eriksson, M.: Salicylate-induced foetal damage late in pregnancy: an experimental study in mice. Acta Paediatrica Scandinavica, Supplement 211: 1–24 (1971).

    Google Scholar 

  • Feldman, S.; Chen, S.L.; Pickering, L.K.; Cleary, T.G.; Ericsson, C.D. and Hulse, M.: Salicylate absorption from a bismuth subsalicylate antidiarrheal preparation (Pepto-Bismol). Clinical Pharmacology and Therapeutics 29: 788–792 (1981).

    PubMed  CAS  Google Scholar 

  • Findlay, J.W.A.; DeAngelis, R.L.; Kearney, M.F.; Welch, R.M. and Findlay, J.M.: Analgesic drugs in breast milk and plasma. Clinical Pharmacology and Therapeutics 29: 625–633 (1981).

    PubMed  CAS  Google Scholar 

  • Finnigan, D.; Burry, A.F. and Smith, I.D.B.: Analgesic consumption in an antenatal clinic surgery. Medical Journal of Australia 1: 761–762 (1974).

    PubMed  CAS  Google Scholar 

  • Flower, R.J. and Vane, J.R.: Inhibition of prostaglandin biosynthesis. Biochemical Pharmacology 23: 1439–1450 (1974).

    PubMed  CAS  Google Scholar 

  • Garrettson, L.K.; Procknal, J.A. and Levy, G.: Fetal acquisition and neonatal elimination of a large amount of salicylate. Study of a neonate whose mother regularly took therapeutic doses of aspirin during pregnancy. Clinical Pharmacology and Therapeutics 17: 98–103 (1975).

    PubMed  CAS  Google Scholar 

  • Grella, P. and Zanor, P.: Premature labor and indomethacin. Prostaglandins 16: 1007–1017 (1978).

    PubMed  CAS  Google Scholar 

  • Harker, L.C.; Kirkpatrick, S.E.; Fricdman, W.F. and Bloor, C.M.: Effects of indomethacin on fetal rat lungs: A possible cause of persistent fetal circulation. Pediatric Research 15: 147–151 (1981).

    PubMed  CAS  Google Scholar 

  • Harrison, K.; Thomas, I. and Smith, I.: Analgesic use during pregnancy. Medical Journal of Australia 2: 161 (1978).

    PubMed  CAS  Google Scholar 

  • Haslam, R.R.; Ekert, H. and Gillam, G.L.: Hemorrhage in a neonate possibly due to maternal ingestion of salicylate. Journal of Pediatrics 84: 556–557 (1974).

    PubMed  CAS  Google Scholar 

  • Haworth, S.G. and Reid, L.: Persistent fetal circulation: Newly recognized structural features. Journal of Pediatrics 88: 614–620 (1976).

    PubMed  CAS  Google Scholar 

  • Heinonen, O.P.; Slone, D. and Shapiro, S.: Analgesic and antipyretic drugs; in Birth Defects and Drugs in Pregnancy, pp. 286–295 (Publishing Sciences Group Inc., Littleton, Mass. 1977).

    Google Scholar 

  • Heymann, M.A. and Rudolph, A.M.: Effects of acetylsalicylic acid on the ductus arteriosus and circulation of fetal lambs in utero. Circulation Research 38: 418–422 (1976).

    PubMed  CAS  Google Scholar 

  • Hill, R.M.; Craig, J.P.; Chaney, M.D.; Tennyson, L.M. and McCulley, L.B.: Utilization of over-the-counter drugs during pregnancy. Clinical Obstetrics and Gynecology 20: 381–394 (1977).

    PubMed  CAS  Google Scholar 

  • Hislop, A. and Reid, L.: Intra-pulmonary arterial development during fetal life — branching pattern and structure. Journal of Anatomy 113: 35–48 (1972).

    PubMed  CAS  Google Scholar 

  • Itskovitz, J.; Abramovici, H. and Brandes, J.M.: Oligohydramnios, meconium and perinatal death concurrent with indomethacin treatment in human pregnancy. Journal of Reproductive Medicine 24: 137–140 (1980).

    PubMed  CAS  Google Scholar 

  • Jamali, F.; Tarn, Y.K. and Stevens, R.D.: Naproxen excretion in breast milk and its uptake by suckling infant (Abstract). Drug Intelligence and Clinical Pharmacy 16: 475 (1982).

    Google Scholar 

  • Kalter, M.: Nonteratogenicity of indomethacin in mice. Teratology 7: A–19 (1973).

    Google Scholar 

  • Keirse, M.J.N.C.; Flint, A.P.F. and Turnbull, A.C.: F prostaglandins in amniotic fluid during pregnancy and labour. Journal of Obstetrics and Gynaecology of the British Commonwealth 81: 131–135 (1974).

    PubMed  CAS  Google Scholar 

  • Kitterman, J.A.; Liggins, G.C.; Clements, J.A. and Tooley, W.H.: Stimulation of breathing movements in fetal lambs by inhibitors of prostaglandin synthesis. Journal of Developmental Physiology 1: 453–458 (1979).

    PubMed  CAS  Google Scholar 

  • Kohler, H.G.: Intrauterine cardiac failure associated with premature closure of the ductus arteriosus. Archives of Diseases in Childhood 42: 335 (1967).

    Google Scholar 

  • Kumor, K.M.; White, R.D.; Blake, D.A. and Niebyl, J.R.: Indomethacin as a treatment for premature labor. Neonatal outcome. Pediatric Research 13: 370–375 (1979).

    Google Scholar 

  • Larsson, K.S.; Boström, H. and Ericson, B.: Salicylate-induced malformations in mouse embryos. Acta Paediatrica Scandinavica 52: 36–40 (1963).

    CAS  Google Scholar 

  • Leffler, C.W. and Hessler, J.R.: Pulmonary and systemic vascular effects of exogenous prostaglandin I2 in fetal lambs. European Journal of Pharmacology 54: 37–42 (1979).

    PubMed  CAS  Google Scholar 

  • Leffler, C.W.; Tyler, T.L. and Cassin, S.: Effect of indomethacin on pulmonary vascular response to ventilation of fetal goats. American Journal of Physiology 234: H346–H351 (1978).

    PubMed  CAS  Google Scholar 

  • Leffler, C.W.; Hessler, J.R. and Terragno, N.A.: Ventilation-induced release of prostaglandin-like material from fetal lungs. American Journal of Physiology 238: H282–H286 (1980).

    PubMed  CAS  Google Scholar 

  • Leffler, C.W.; Hessler, J.R. and Green, R.S.: Mechanism of stimulation of pulmonary prostaglandin synthesis at birth. Prostaglandins 28: 877–887 (1984a).

    PubMed  CAS  Google Scholar 

  • Leffler, C.W.; Hessler, J.R. and Green, R.S.: The onset of breathing at birth stimulates pulmonary vascular prostacyclin synthesis. Pediatric Research 18: 938–942 (1984b).

    PubMed  CAS  Google Scholar 

  • Levin, D.L.: Rudolph, A.M.; Heymann, M.A. and Phibbs, R.H.: Morphological development of the pulmonary vascular bed in fetal lambs. Circulation 53: 144–151 (1976).

    PubMed  CAS  Google Scholar 

  • Levin, D.L.; Fixier, D.E.; Morriss, F.C and Tyson, J.: Morphologic analysis of the pulmonary vascular bed in infants exposed in utero to prostaglandin synthetase inhibitors. Journal of Pediatrics 92: 478–483 (1978a).

    PubMed  CAS  Google Scholar 

  • Levin, D.L.; Hyman, A.I.; Heymann, M.A. and Rudolph, A.M.: Fetal hypertension and the development of increased pulmonary vascular smooth muscle: A possible mechanism for persistent pulmonary hypertension of the newborn infant. Journal of Pediatrics 92: 265–269 (1978b).

    PubMed  CAS  Google Scholar 

  • Levin, D.L.; Mills, L.J.; Parkey, M.; Garriott, J. and Campbell, W.: Constriction of the fetal ductus arteriosus after administration of indomethacin to the pregnant ewe. Journal of Pediatrics 94: 647–650 (1979a).

    PubMed  CAS  Google Scholar 

  • Levin, D.L.; Mills, L.J.; Weinberg, A.G.; Parkey, M. and Mayhew, E.: Hemodynamic, pulmonary vascular, and myocardial abnormalities secondary to pharmacologic constriction of the fetal ductus arteriosus: A possible mechanism for persistent pulmonary hypertension and transient tricuspid insufficiency in the newborn infant. Circulation 60: 360–364 (1979b).

    PubMed  CAS  Google Scholar 

  • Levy, G.: Pharmacokinetics of fetal and neonatal exposure to drugs. Obstetrics and Gynecology 58: 9S–16S (1981).

    PubMed  CAS  Google Scholar 

  • Levy, G. and Garrettson, L.K.: Kinetics of salicylate elimination by newborn infants of mothers who ingested aspirin before delivery. Pediatrics 53: 201–210 (1974).

    PubMed  CAS  Google Scholar 

  • Levy, G.; Garrettson, L.K. and Soda, D.M.: Evidence of placental transfer of acetaminophen. Pediatrics 55: 895 (1975a).

    PubMed  CAS  Google Scholar 

  • Levy, G.; Procknal, J.A. and Garrettson, L.K.: Distribution of salicylate between neonatal and maternal serum at diffusion equilibrium. Clinical Pharmacology and Therapeutics 18: 210–214 (1975b).

    PubMed  CAS  Google Scholar 

  • Lewis, R.B. and Schulman, J.D.: Influence of acetylsalicylic acid, an inhibitor of prostaglandin synthesis, on the duration of human gestation and labour. Lancet 2: 1159–1161 (1973).

    PubMed  CAS  Google Scholar 

  • Lewis, A.B.; Freed, M.D.; Heymann, M.A.; Roehl, S.L. and Chen Kensey, R.: Side effects of therapy with prostaglandin E1 in infants with critical congenital heart disease. Circulation 64: 893–898 (1981).

    PubMed  CAS  Google Scholar 

  • Louis, T.M.; Challis, J.R.G.; Robinson, J.S. and Thorburn, G.D.: Rapid increase of foetal corticosteroids after prostaglandin E2. Nature 264: 797–799 (1976).

    PubMed  CAS  Google Scholar 

  • Lynd, P.A.; Andreasen, A.C. and Wyatt, R.J.: Intrauterine salicylate intoxication in a newborn. Clinical Pediatrics 15: 912–913 (1976).

    PubMed  CAS  Google Scholar 

  • Manchester, D.; Margolis, H.S. and Sheldon, R.E.: Possible association between maternal indomethacin therapy and primary pulmonary hypertension of the newborn. American Journal of Obstetrics and Gynecology 126: 467–469 (1976).

    PubMed  CAS  Google Scholar 

  • McLaughlin, M.K.; Brennan, S.C. and Chez, R.A.: Effects of indomethacin on sheep uteroplacental circulations and sensitivity to angiotensin II. American Journal of Obstetrics and Gynecology 132: 430–435 (1978).

    PubMed  CAS  Google Scholar 

  • McNiel, J.R.: The possible teratogenic effect of salicylates on the developing fetus: Brief summaries of eight suggestive cases. Clinical Pediatrics 12: 347–350 (1973).

    PubMed  CAS  Google Scholar 

  • Millard, R.W; Baig, H. and Vatner, S.F.: Prostaglandin control of the renal circulation in response to hypoxemia in the fetal lamb in utero. Circulation Research 45: 172–179 (1979).

    PubMed  CAS  Google Scholar 

  • Mitchell, M.D.; Flint, A.P.; Bibby, J.; Brunt, J.; Arnold, J.M.; Anderson, A.B.M. and Turnbull, A.C.: Plasma concentrations of prostaglandins during late human pregnancy: Influence of normal and preterm labor. Journal of Clinical Endocrinology and Metabolism 46: 947–951 (1978).

    PubMed  CAS  Google Scholar 

  • Morganroth, M.L.; Reeves, J.T.; Murphy, R.C. and Voelkel, N.F.: Leukotriene synthesis and receptor blockers block hypoxic pulmonary vasoconstriction. Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology 56: 1340–1346 (1984).

    CAS  Google Scholar 

  • Murphy, J.D.; Rabinovitch, M.; Goldstein, J.D. and Reid, L.M.: The structural basis of persistent pulmonary hypertension of the newborn infant. Journal of Pediatrics 98: 962–967 (1981).

    PubMed  CAS  Google Scholar 

  • Nelson, M.M. and Forfar, J.O.: Associations between drugs administered during pregnancy and congenital abnormalities of the fetus. British Medical Journal 1: 523–527 (1971).

    PubMed  CAS  Google Scholar 

  • Niebyl, J.R.; Blake, D.A.; White, R.D.; Kumor, K.M.; Dubin, N.H.; Robinson, J.C. and Egner, P.G.: The inhibition of premature labor with indomethacin. American Journal of Obstetrics and Gynecology 136: 1014–1019 (1980).

    PubMed  CAS  Google Scholar 

  • Novy, M.J.: Effects of indomethacin on labor, fetal oxygenation, and fetal development in rhesus monkeys; in Coceani and Olley (Eds) Advances in Prostaglandin and Thromboxane Research (Vol 4), pp. 285–300 (Raven Press, New York 1978).

    Google Scholar 

  • Novy, M.J. and Liggins, G.C.: Role of prostaglandins, prostacyclin, and thromboxanes in the physiologic control of the uterus and in parturition. Seminars in Perinatology 4: 45–66 (1980).

    PubMed  CAS  Google Scholar 

  • Novy, M.J.; Cook, M.J. and Manaugh, L.: Indomethacin block of normal onset of parturition in primates. American Journal of Obstetrics and Gynecology 118: 412–416 (1974a).

    PubMed  CAS  Google Scholar 

  • Novy, M.J.; Piasecki, G. and Jackson, B.T.: Effect of prostaglandins E2 and F on umbilical blood flow and fetal hemodynamics. Prostaglandins 5: 543–555 (1974b).

    PubMed  CAS  Google Scholar 

  • Palmisano, P.A. and Cassady, G.: Salicylate exposure in the perinate. Journal of the American Medical Association 209: 556–558 (1969).

    PubMed  CAS  Google Scholar 

  • Parks, B.R.; Jordan, R.L.; Rawson, J.E. and Douglas, B.H.: Indomethacin: Studies of absorption and placental transfer. American Journal of Obstetrics and Gynecology 129: 464–465 (1977).

    PubMed  CAS  Google Scholar 

  • Perkin, R.M.; Levin, D.L. and Clark, R.: Serum salicylate levels and right-to-left ductal shunts in newborn infants with persistent pulmonary hypertension. Journal of Pediatrics 96: 721–726 (1980).

    PubMed  CAS  Google Scholar 

  • Persaud, T.V.N. and Moore, K.L.: Inhibitors of prostaglandin synthesis and fetal development. Lancet 1: 93 (1974).

    PubMed  CAS  Google Scholar 

  • Philipps, A.F.; Matty, P.J.; Porte, P.J. and Raye, J.R.: Inhibition of glucose-induced insulin secretion by indomethacin and sodium salicylate in the fetal lamb. American Journal of Obstetrics and Gynecology 148: 481–487 (1984).

    PubMed  CAS  Google Scholar 

  • Pickering, L.K.; Feldman, S.; Ericsson, C.D. and Cleary, T.G.: Absorption of salicylate and bismuth from a bismuth subsalicylate containing compound (Pepto-Bismol). Journal of Pediatrics 99: 654–656 (1981).

    PubMed  CAS  Google Scholar 

  • Reid, L.: The pulmonary circulation: Remodelling in growth and disease. American Review of Respiratory Disease 119: 531–546 (1979).

    PubMed  CAS  Google Scholar 

  • Reid, L.: The development of the pulmonary circulation; in Peckham and Heymann (Eds) Cardiovascular Sequelae of Asphyxia in the Newborn, pp. 2–10 (Ross Laboratories, Columbus, Ohio 1982).

    Google Scholar 

  • Richards, I.D.G.: Congenital malformations and environmental influences in pregnancy. British Journal of Preventive and Social Medicine 23: 218–225 (1969).

    PubMed  CAS  Google Scholar 

  • Richardson, B.; Natale, R. and Patrick, J.E.: Human fetal breathing activity during electively induced labor at term. American Journal of Obstetrics and Gynecology 133: 247–255 (1979).

    PubMed  CAS  Google Scholar 

  • Robertson, R.T.; Allen, H.L. and Bokelman, D.L.: Aspirin: Teratogenic evaluation in the dog. Teratology 20: 313–317 (1979).

    PubMed  CAS  Google Scholar 

  • Rollins, D.E.; Von Bahr, C.; Glaumann, H.; Moldens, P. and Rane, H.: Acetaminophen: potentially toxic metabolite formed by human fetal and adult liver microsomes and isolated fetal liver cells. Science 205: 1414–1416 (1979).

    PubMed  CAS  Google Scholar 

  • Rubaltelli, F.F.; Chiozza, M.L.; Zanardo, V. and Cantarutti, F.: Effect on neonate of maternal treatment with indomethacin. Journal of Pediatrics 94: 161–172 (1979).

    PubMed  CAS  Google Scholar 

  • Rumack, C.M.; Guggenheim, M.A.; Rumack, B.H.; Peterson, R.G.; Johnson, M.L. and Braithwaite, W.R.: Neonatal intracranial hemorrhage and maternal use of aspirin. Obstetrics and Gynecology 58: 52S–56S (1981).

    PubMed  CAS  Google Scholar 

  • Saxen, I.: Associations between oral clefts and drugs taken during pregnancy. International Journal of Epidemiology 4: 37–44 (1975).

    PubMed  CAS  Google Scholar 

  • Schreiber, M.D.; Heymann, M.A. and Soifer, S.J.: Leukotriene inhibition prevents and reverses hypoxic pulmonary vasoconstriction in newborn lambs. Pediatric Research 19: 437–441 (1985).

    PubMed  CAS  Google Scholar 

  • Schwartz, A.; Brook, I.; Insler, V.; Kohen, F.; Zor, U. and Lindner, H.R.: Effect of flufenamic acid on uterine contractions and plasma levels of 15-keto-13, 14-hydroprostaglandin F2 alpha in preterm labor. Gynecologic and Obstetric Investigation 9: 139–149 (1978).

    PubMed  CAS  Google Scholar 

  • Shapiro, S.; Monson, R.R.; Kaufman, D.W.; Siskind, V.; Heinonen, O.P. and Slone, D.: Perinatal mortality and birth-weight in relation to aspirin taken during pregnancy. Lancet 1: 1375–1376 (1976).

    PubMed  CAS  Google Scholar 

  • Sharpe, G.L.; Thalme, B. and Larsson, K.S.: Studies on closure of the ductus arteriosus: XI. Ductal closure in utero by a prostaglandin synthetase inhibitor. Prostaglandins 8: 363–368 (1974).

    PubMed  CAS  Google Scholar 

  • Sharpe, G.L.; Larsson, K.S. and Thalme, B.: Studies on closure of the ductus arteriosus: XII. In utero effect of indomethacin and sodium salicylate in rats and rabbits. Prostaglandins 9: 585–596 (1975).

    PubMed  CAS  Google Scholar 

  • Simberg, N.: Maternal aspirin administration inhibits pulmonary arachidonic acid metabolism in fetal rabbits. Prostaglandins Leukotrienes and Medicine 13: 323–333 (1984).

    CAS  Google Scholar 

  • Slone, D.; Siskind, V.; Heinonen, O.P.; Monson, R.R.; Kaufman, D.W. and Shapiro, S.: Aspirin and congenital malformations. Lancet 1: 1373–1375 (1976).

    PubMed  CAS  Google Scholar 

  • Soifer, S.J.; Morin, F.C., III and Heymann, M.A.: Prostaglandin D2 reverses induced pulmonary hypertension in the newborn lamb. Journal of Pediatrics 100: 458–463 (1982).

    PubMed  CAS  Google Scholar 

  • Soifer, S.J.; Loitz, R.D.; Roman, C. and Heymann, M.A.: Leukotriene end organ antagonists increase pulmonary blood flow in fetal lambs. American Journal of Physiology (In Press).

  • Soller, R.W. and Stander, H.: Maternal drug exposure and perinatal intracranial hemorrhage. Obstetrics and Gynecology 58: 735–737 (1981).

    PubMed  CAS  Google Scholar 

  • TambyRaja, R.L.; Salmon, J.A.; Karim, S.M.M. and Ratnam, S.S.: F prostaglandin levels in amniotic fluid in premature labour. Prostaglandins 13: 339–348 (1977).

    PubMed  CAS  Google Scholar 

  • Townsend, R.J.; Benedetti, T.; Erickson, S.; Gillespie, W.R. and Albert, K.S.: A study to evaluate the passage of ibuprofen into breast milk (Abstract). Drug Intelligence and Clinical Pharmacy 16: 482–483 (1982).

    Google Scholar 

  • Tuchmann-Duplessis, H.; Hiss, D.; Mottot, G. and Rosner, I.: Effects of prenatal administration of acetylsalicylic acid in rats. Toxicology 3: 207–211 (1975).

    PubMed  CAS  Google Scholar 

  • Turner, G. and Collins, E.: Fetal effects of regular salicylate ingestion in pregnancy. Lancet 2: 338–339 (1975).

    PubMed  CAS  Google Scholar 

  • Tuvemo, T.: Action of prostaglandins and blockers of prostaglandin synthesis on the isolated human umbilical artery; in Coceani and Olley (Eds) Advances in Prostaglandin and Thromboxane Research (Vol 4), pp. 271–274 (Raven Press, New York 1978).

    Google Scholar 

  • Tuvemo, T. and Strandberg, K.: Effects and interactions of oxygen and prostaglandins on the tone of the isolated human umbilical artery. Uppsala Journal of Medical Sciences 80: 131–134 (1975).

    CAS  Google Scholar 

  • Tyler, T.L.; Leffler, C.W. and Cassin, S.: Effects of prostaglandin precursors, prostaglandins, and prostaglandin metabolites on pulmonary circulation in perinatal goats. Chest 71S: 271S–273S (1977).

    Google Scholar 

  • Van Kets, H.; Thiery, M.; Derom, R.; Van Egmond, H. and Baele, G.: Perinatal hazards of chronic antenatal tocolysis with indomethacin. Prostaglandins 18: 893–907 (1979).

    PubMed  Google Scholar 

  • Vane, J.R.: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature (New Biology) 231: 234–235 (1971).

    Google Scholar 

  • Vane, J.R. and Williams, K.I.: Prostaglandin production contributes to the contractions of the rat isolated uterus. British Journal of Pharmacology 45: 146 (1972).

    Google Scholar 

  • Walker, D.W. and Mitchell, M.D.: Prostaglandins in urine of foetal lambs. Nature 271: 161–162 (1978).

    PubMed  CAS  Google Scholar 

  • Wang, L.H.; Rudolph, A.M. and Benet, L.Z.: Pharmacokinetic studies of the disposition of acetaminophen in the sheep maternal-placental-fetal unit. Submitted for publication.

  • Warkany, J. and Takacs, E.: Experimental production of congenital malformations in rats by salicylate poisoning. American Journal of Pathology 35: 315–331 (1959).

    PubMed  CAS  Google Scholar 

  • Weibert, R.T.; Townsend, R.J.; Kaiser, D.G. and Naylor, A.J.: Lack of ibuprofen secretion into human milk. Clinical Pharmacology 1: 457–458 (1982).

    CAS  Google Scholar 

  • Weiss, H.J.: Platelet physiology and abnormalities of platelet function. New England Journal of Medicine 293: 531–541, 580–588 (1975).

    PubMed  CAS  Google Scholar 

  • Wilkinson, A.R.: Naproxen levels in preterm infants after maternal treatment. Lancet 2: 591–592 (1980).

    PubMed  CAS  Google Scholar 

  • Wilkinson, A.R.; Aynsley-Green, A. and Mitchell, M.D.: Persistent pulmonary hypertension and abnormal PGE levels in preterm infants after maternal treatment with naproxen. Archives of Disease in Childhood 54: 942–945 (1979).

    PubMed  CAS  Google Scholar 

  • Wilson, J.G.; Ritter, E.J.; Scott, W.J. and Fradkin, R.: Comparative distribution and embryotoxicity of acetylsalicylic acid in pregnant rats and rhesus monkeys. Toxicology and Applied Pharmacology 41: 67–78 (1977).

    PubMed  CAS  Google Scholar 

  • Wilson, J.T.; Brown, R.D.; Cherek, D.R.; Dailey, J.W.; Human, B.; Jobe, P.C.; Manno, B.R.; Manno, J.E.; Redetzki, H.M. and Stewart, J.J.: Drug excretion in human breast milk: Principles, pharmacokinetics and projected consequences. Clinical Pharmacokinetics 5: 1–66 (1980).

    PubMed  CAS  Google Scholar 

  • Wiqvist, N.: The use of inhibitors of prostaglandin synthesis in obstetrics; in Kierse; Anderson and Bennebroek Gravenhorst (Eds) Human Parturition, pp. 189–200 (Martinus Nijhoff, The Hague 1979).

    Google Scholar 

  • Wiqvist, N.: Preterm labour: other drug possibilities including drugs not to use; in Elder and Hendricks (Eds) Butterworths International Medical Reviews Obstetrics and Gynecology 1: Preterm Labour, pp. 148–175 (Butterworths, London 1981).

    Google Scholar 

  • Wiqvist, N.; Lundstrom, V. and Green, K.: Premature labour and indomethacin. Prostaglandins 10: 515–526 (1975).

    Google Scholar 

  • Yabek, S.M. and Avner, B.P.: Effects of prostaglandin E1 and indomethacin on fetal and neonatal lamb mesenteric artery responses to norepinephrine. Prostaglandins 17: 227–233 (1979).

    PubMed  CAS  Google Scholar 

  • Zuckerman, H. and Harpag-Kerpel, S.: Prostaglandins and their inhibitors in premature labour; in Karim (Ed.) Practical Applications of Prostaglandins and their Synthesis Inhibitors, pp. 411–435 (University Park Press, Baltimore 1979).

    Google Scholar 

  • Zuckerman, H.; Reiss, U. and Rubinstein, I.: Inhibition of human premature labor by indomethacin. Obstetrics and Gynecology 44: 787–792 (1974).

    PubMed  CAS  Google Scholar 

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Heymann, M.A. Non-Narcotic Analgesics. Drugs 32 (Suppl 4), 164–176 (1986). https://doi.org/10.2165/00003495-198600324-00012

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