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Chapter 59: Special Aspects of Perinatal & Pediatric Pharmacology

Sean P. Elliott; Gideon Koren

INTRODUCTION

The effects of drugs on the fetus and newborn infant are based on the general principles set forth in Chapters 1–4 of this book. However, the physiologic contexts in which these pharmacologic principles operate are different in pregnant women and in rapidly maturing infants. At present, the unique pharmacokinetic factors operative in these patients are beginning to be understood, whereas information regarding pharmacodynamic differences (eg, receptor characteristics and responses) is still grossly incomplete.

DRUG THERAPY IN PREGNANCY

Pharmacokinetics

Most drugs taken by pregnant women can cross the placenta and expose the developing embryo and fetus to their pharmacologic and teratogenic effects. However, most drugs, despite entering the fetal compartment, do not endanger the fetus when used in recommended doses. Table 59–1 lists teratogenic drugs in humans. Critical factors affecting placental drug transfer and drug effects on the fetus include the following: (1) the physicochemical properties of the drug; (2) the rate at which the drug crosses the placenta and the amount of drug reaching the fetus; (3) the duration of exposure to the drug; (4) distribution characteristics in different fetal tissues; (5) the stage of placental and fetal development at the time of exposure to the drug; and (6) the effects of drugs used in combination.

TABLE 59–1Drugs with significant teratogenic or other adverse effects on the fetus.
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TABLE 59–1 Drugs with significant teratogenic or other adverse effects on the fetus.
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Drug Trimester Effect
ACE inhibitors All, especially second and third Renal damage, hypocalvaria
Aminopterin First Multiple major anomalies
Amphetamines All Suspected abnormal developmental patterns, decreased school performance
Androgens Second and third Masculinization of female fetus
Antidepressants, tricyclic Third Neonatal withdrawal symptoms have been reported in a few cases with clomipramine, desipramine, and imipramine.
Barbiturates All Chronic use can lead to neonatal dependence
Busulfan All Various major malformations
Carbamazepine First Neural tube defects
Chlorpropamide All Prolonged symptomatic neonatal hypoglycemia
Clomipramine Third Neonatal lethargy, hypotonia, cyanosis, hypothermia
Cocaine All Increased risk of spontaneous abortion, abruptio placentae, and premature labor; neonatal cerebral infarction, increased risk for attention deficit hyperactivity disorder
Cyclophosphamide First Various major malformations
Cytarabine First, second Various major malformations
Diazepam All Chronic use may lead to neonatal dependence
Dydrogesterone First   Hypospadias, cardiovascular malformations, spina bifida
Diethylstilbestrol All Vaginal adenosis, clear cell vaginal adenocarcinoma
Ethanol All Risk of fetal alcohol spectrum disorder
Etretinate All High risk of major congenital malformations
Heroin All Chronic use leads to neonatal abstinence syndrome.
Iodide All Congenital goiter, hypothyroidism
Isotretinoin All High risk of CNS, face, ear, and other malformations
Lithium First, third Ebstein anomaly and other cardiac malformations, neonatal toxicity after third trimester exposure
Methadone All Chronic use may lead to neonatal abstinence syndrome.
Methotrexate First Multiple major malformations
Misoprostol First Möbius sequence
Mycophenolate mofetil First Major malformations of the face, limbs, and other organs
Organic solvents

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