Alliance for the Improvement of Maternity Services (AIMS)

Return to Home Page

OBSTETRIC DRUGS: THEIR EFFECTS ON MOTHER AND INFANT

Most women assume that the drugs offered them by their obstetricians during pregnancy, labor, birth and lactation have been approved by the U.S. Food and Drug Administration as safe for use under those condition. The fact is, there is no maternally administered drug that has been proven safe for the fetus. Nor is there any law or regulation that prohibits a physician from prescribing or administered to a childbearing woman a drug that has never been approved by the FDA as safe for such use.

INHERENT RISKS OF OBSTETRIC RELATED DRUGS

Seldom are pregnant women advised by their obstetricians that an unborn baby's central nervous system is rapidly forming throughout the latter months of pregnancy, childbirth and the first two years of life, and during that time the central nervous system is susceptible to permanent damage from drugs prescribed for or administered to the pregnant woman.

Changes in the placenta as pregnancy advances heighten the transfer to the fetal circulation of all drugs used in obstetric analgesia and anesthesia. As the time of birth grows near the fetal brain is relatively large and the cerebral blood flow is high in comparison to the adult brain. In addition, the myelin content of the brain, the fat-like substance which protects the nerve fibers of the brain, is low when compared to the adult. The baby's brain and central nervous system, therefore, are relatively more vulnerable to drugs administered to or taken by the mother during the perinatal period and during lactation.

Gestational age, previous and concomitant exposure to other drugs, relative hypoxia and various pathological conditions can affect how a drug given to the mother will affect her unborn or newborn infant. The brain and heart of an about-to-be-born or newly born infant is vessel-rich. Hypoxemia (low levels of oxygen of the blood) and a resulting build up of lactic acid in the fetal blood during labor and birth can increase the uptake by the fetal brain and heart of drugs given to the mother.

Several studies have shown that drugs administered to the mother alter fetal brain function. Whether this dysfunction has implications for the child's future central nervous system development has not been the subject of a well-controlled scientific investigation. But many respected scientists are beginning to express their concern that drugs administered with the very best of intentions to the pregnant woman near or at term may limit the exposed offspring's ability to achieve his or her full potential in life.

Mothers-to-be are sometimes cautioned by their obstetrician or anesthesiologist that experiencing pain during labor can decrease the oxygen supply to the fetus. This may make the physician feel more noble but, in fact, No research has shown this to be true in the human fetus.

Drugs trapped in the infant's brain at birth have the potential to affect adversely the rapidly developing nerve circuity of the brain and central nervous system by altering the following brain processes:

1. The rate at which the nerve cells in the brain mature

2. The process by which the brain cells develop individual characteristics and capacity to carry out specific functions

3. The process by which the brain cells are guided into their proper place within the brain and central nervous system.

4. The interconnection of the branch-like nerve fibers as the circuitry of the brain is formed, and

5. The forming of the insulating sheath of myelin (fat-like substance) around the nerve fibers which helps to assure that the nerve impulses - the messages to and from the brain - will travel their normal route at the normal rate of speed.

Dr. Joseph Altman, neurobiologist, University of Indiana, pointed out at a Washington Conference on the Precursor of Learning Disability that the development of the human brain appears to be programmed so that certain cells and nerve fibers must develop in synchrony, in order to make appropriate connections within the central nervous system. He expressed concern that drug-induced alterations of the chemical components within the brain may interfere with the growth of the cells and nerve fibers, causing subtle or substantial misconnections within the developing brain.

To better understand this hypothesis, picture a technician preparing to connect hundreds of wires. The ends of each wire are color-coded, to serve as a guide as to which wire should be connected with another. A chemical is spilled over the wires, removing the color. To meet his schedule the technician must continue to connect the wires, unable to be sure which wire to connect to another.The job is finished on schedule, the system functions, but functions imperfectly.

Any alteration in the development of the intricately complex nerve circuitry of the brain has the potential for permanently altering the way the brain processes and responds to information. How much an individual fetus or newborn infant will be affected by a drug administered to the mother during pregnancy, childbirth or lactation is unpredictable. Genetic susceptibility, which affects the final outcome, varies greatly, even among siblings. Well-controlled experiments in animals, for example, often produce varying results in the test animals, even among litter mates.

Most physicians and pharmaceutical manufacturers are quick to say that there is no drug on the market that is without risk. None of the drugs or chemicals used as medications or food additives, or in shampoo, hair coloring, underarm deodorants and skin treatments, and the like, have been subjected to a well-controlled scientific investigation to determine what effect the drug or chemical has on the fetus.

That doesn't mean that all of these drugs and chemicals are harmful. It just means that we do not know if there are any adverse effects on the fetus and newborn.

FDA STATUS OF DRUGS

The United States Food and Drug Administration (FDA) never approves a drug for general or "universal" use, but only for specific indications and conditions. Only if the words "pregnancy", "obstetrics", "labor", "delivery", or "lactation" appear in the "INDICATIONS" section of the drug's package insert, (the FDA-approved information leaflet included in each carton of an approved drug) has the FDA approved the use of the drug for those conditions. If the conditions described above are discussed elsewhere in the package insert but are not specifically noted in the "INDICATIONS" section, the drug has not been approved by the FDA for such uses.

If the package insert makes no mention that the use of the drug is contraindicated in pregnancy, labor, delivery, or lactation one cannot assume that the drug is safe to be used at those times.The FDA, in general, does not require drug manufacturers to list contraindications to the use of a drug in the package insert.

FDA APPROVED DRUGS IN OBSTETRICS

Two drugs approved by the FDA for use during pregnancy, are a combination of doxcylamine and pyridoxine (Bendectin) and ritodrine (Yutopar). Once prescribed as a remedy for morning sickness, Bendectin was taken off the market in 1983 because of the high cost of defending the company against law suits. Several lawsuits have been brought against the manufacturer of Bendectin by parents who contend that their children's birth defects resulted from prenatal exposure to the drug. Currently the litigation is lumbering through the courts with both sides claiming victories. No one knows how many cases have been settled out of court, since in most such cases the plaintiffs must swear to secrecy in order to receive the settlement.

The only other drug specifically approved by the FDA for use during pregnancy is ritodrine (Yutapar), a neurotransmitter prescribed or administered to pregnant women in order to halt preterm labor.Another drug, terbutaline, is also administered for the same purpose. However, the drug has not been approved by the FDA for that use.

Until fairly recently some tranquilizers, such as diazepam (Valium), were frequently administered to women during labor to alleviate their anxiety. Because of their adverse effects on the newborn infant the FDA no longer approves these drugs for such use. But as mentioned earlier, lack of FDA approval does not mean that your doctor is prohibited from prescribing a tranquilizer for you during labor.

ANALGESICS

The most frequently used drug in labor is a narcotic-like analgesic called meperidine, Demerol (Pethidine in the UK). The use of meperidine has largely replaced the use of morphine during labor. This drug is frequently offered to the laboring woman by the obstetrician, nurse or midwife, accompanied by the standard remark, "This will help to take the edge off the contractions."

Meperidine does not eradicate pain, but for many women it makes the discomfort or pain of the contractions more tolerable. Other women find that meperidine causes them to lose control of their labor.

Meperidine is usually administered by injection either intramuscularly (IM) or intravenously (IV) in doses of 50 mg repeated every four hours, if the health care provider so desires and the mother agrees. As with most pain relieving drugs, meperidine can slow maternal respiration and circulation.When a narcotized mother breathes more slowly than normal and her blood flows more slowly than normal through her lung tissue there is always the likelihood that the fetus will receive less than a normal supply of oxygen.

In a well-controlled investigation by John Morrison, an obstetrician at the University of Mississippi, one of every 10 infants of mothers who received only 50 mg of meperidine during labor required resuscitation at birth. For this within 1 to 3 hours before delivery required resuscitation at birth.Unfortunately, it is difficult to insure that the baby will be born at a time when the effect of meperidine is minimal. For this reason midwives often administer the drug in smaller doses. such as 25 mg or 12 mg (or none at all) in order to insure that the mother will feel in control of her labor and the baby will be ready to breathe on his own immediately after birth. After repeated administrations of the drug, even in smaller doses, meperidine and its metabolite normeperidine tend to accumulate in the fetal circulation.

Meperidine is not without side effects, such as: sweating, dizziness, headache, nausea, vomiting, slowing of gastric function, agitation, tremor, uncoordinated muscle movement, transient hallucinations and disorientation, and visual disturbance.

The more serious hazards of meperidine for the mother are respiratory depression, respiratory arrest, circulatory depression, shock, cardiac arrest, coma and death. A less well known fact about meperidine is that the drug can cause an increase in cerebral spinal fluid pressure. The implications of this effect on mother, fetus and newborn infant, however, have not been investigated.

We have no way of knowing how frequently these adverse effects occur under normal clinical conditions because the law does not require physicians or midwives to report adverse drug reactions to the FDA, even if the patient dies.

The FDA has allowed the manufacturers of meperidine to provide in the drug's package insert only a minimum of information in regard to the drug's adverse effects on the fetus and newborn infant. The insert acknowledges that the drug crosses the placenta and can depress the respiratory and the psychophysiologic functions of the newborn infant and can increase the likelihood that the newborn infant may require resuscitation. The insert does not make clear that meperidine given to the mother during labor can slow the fetal heart and impede the normal transfer of oxygen from the mother's circulation to that of her fetus.

Severe or prolonged oxygen depletion has been shown to cause the fetal brain to swell. Whether an increase in cerebral spinal fluid pressure in the presense of fetal hypoxia, ruptured membranes and/or forceps extraction increases the likelihood of permanent brain dysfunction has yet to be investigated.

There is some concern that the severely narcotized newborn infant may be more prone to aspirate (inhale its gastric fluids) because the drug has blunted or paralyzed his protective gag reflex.

Other narcotic-like drugs approved by the FDA for use in labor are nalbuphine (Nubain), butorphanol (Stadol) and alphaprodine (Nisentil). Other drugs, namely hydromorphone (Dilaudid), fentanyl citrate (Sublimaze), and codeine, are also used in labor, but the FDA has not approved them for such use. Like meperidine, the delayed or long-term effects of drugs given during labor on the exposed fetus have not been adequately investigated. The little research that has been done on Nubain has shown the drug to concentrate more in the fetal circulation than in the mother's. Butorphanol is forty times more powerful than meperidine and must be administered with extreme care to avoid an overdose.

Hydroxyzine (Vistaril) is an antianxiety, antinausea drug sometimes administered to women during labor. The potentiating action of hydroxyzine must be considered when the drug is used in conjunction with other drugs which depress the central nervous system.

NARCOTIC ANTAGONIST

Naloxone (Narcan) has been approved by the FDA for use in infants narcotized by drugs administered to the mother, but the FDA has not approved the use of naloxone during labor. In most cases the sluggish, drugged infant becomes alert after receiving naloxone. However, once the short-acting naloxone has worn off, those infants given naloxone show no improvement over those infants who did not receive the drug. The infant receiving naloxone must be carefully and continuously observed because if the naloxone wears off before the effects of the meperidine have dissipated the baby could be jeopardy.

Naloxone should not be administered to a depressed infant unless the infant is narcotized. If the newborn infant is hypoxic for reasons other than being narcotized naloxone can actually deepen the hypoxic state of the infant.

ANTIEMETICS

Meperidine is often administered in conjunction with a drug called promethazine (Phenergan) or in a combination called Mepergan. Promethazine relieves the nausea and vomiting caused by the administration of meperidine or other powerful pain relievers. Promethazine is thought to potentiate the effects of meperidine, allowing less of the latter drug to be used. The drug is not without risk, however. Research has shown that promethazine can markedly impair platelet aggregation in the fetus and newborn, a condition that can cause bleeding within the brain of the fetus and newborn without a similar effect in the mother.

ANTACIDS

Nausea and vomiting are common maternal side effects of the powerful pain relieving drugs administered during labor. In an attempt to minimize the possibility of chemical pneumonia, which can occur if the heavily drugged or anesthetized mother vomits and aspirates the fluids or food from her stomach, women have been given various antacids during labor to reduce the acidity of the stomach's contents. This is done in the belief that, should the mother regurgitate in response to anesthesia, she is less likely to suffer chemical pneumonia. Antacids may improve the odds of a safe outcome but they can not be relied upon to prevent maternal mortality from aspiration. If aspiration occurs following the administration of an antacid, particles in the antacid itself can cause substantial maternal morbidity.

Although the FDA has not approved the drug for such use, a systemic antacid, sodium citrate and citric acid (Bicitra), is frequently administered to women during labor. The drug does cross the placenta and enter the fetus and its delayed, long term effects on the exposed offspring have not been investigated. As with other antacids, the drug has not been approved by the FDA for use in obstetric care.

REGIONAL ANESTHESIA:

Drugs most commonly used in regional anesthesia to block pain impulses are bupivacaine (Marcaine, Sensorcaine), lidocaine (Xylocaine), mepivacaine (Carbocaine) and chloroprocaine (Nesacaine). Depending on the area to be anesthetized, they are administered as an epidural, spinal, caudal, saddle, or pudendal block, or as a local infiltration for episiotomy repair. The once popular paracervical block has been abandoned in most obstetric services because of its adverse effects on the fetus.

Epidural, spinal and caudal anesthesia numb the woman from above her navel to her toes. All regional anesthetics reach the fetal circulation and, consequently, the fetal brain within seconds or minutes of administration to the mother.

Each of these drugs has its own inherent risks. Because a health care provider is not required to report an adverse drug effect to the FDA, there is no way of knowing the exact incidence of such effects. Perhaps the text of the package insert of bupivacaine is the best example of potential problems. The package insert reads in part:

"Local anesthetics rapidly cross the placenta, and when used for epidural, caudal or pudendal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity.The incidence and degree of toxicity depend upon the procedure performed, the type and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus and neonate involve alteration of the central nervous system, peripheral vascular tone, and cardiac function......"

"Neurologic effects following epidural or caudal anesthesia may include spinal block of varying magnitude (including high or total spinal block); hypotension secondary to spinal block; urinary retention; fecal and urinary incontinence; loss of perineal sensation and sexual function; persistent anesthesia; paresthesia, weakness, paralysis of the lower extremities, and loss of sphincter control, all of which may have slow, incomplete or no recovery; headache; backache; septic meningitis; meningismus; slowing of labor; increased incidence of forceps delivery; cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid."

Wide experience with the use of epidural blocks also indicates that epidural block (injection into the space between the spinal column and the dural membrane enveloping the spinal cord) is associated with significantly longer labors, more use of oxytocin ("pit drip"), rotational forceps deliveries and markedly more postpartum bladder catheterization. It is well accepted that an episiotomy is almost unavoidable if regional anesthesia is in effect during delivery because the epidural block causes the mother to lose her ability to bear down effectively, unduly prolonging the expulsion of the baby. Picture

SPINAL HEADACHE

The severe headache that some mothers experience for days, weeks, even months, after having an epidural or spinal block is more likely to be due to the leakage of cerebral spinal fluid from the injection site than from the anesthetic itself.While a blood patch can be administered to stop the leakage, there is no guarantee that it will be successful in quelling the headache.

The package insert for regional anesthetics provide little information as to the effect of the drugs on the immediate neurologic development of the exposed offspring and none on the delayed, long term effects. Deborah Rosenblatt and her colleagues at St. Mary's Hospital in London found correlations between epidural anesthesia in childbirth and certain neurologic effects in the exposed offspring that persisted throughout a six week testing period. More recent research by Sepkoski et. al. supports the findings of Rosenblatt et. al. Research by Thorp and colleagues has shown a 10 fold increase in the rate od cesarean section where first time mothers have an epidural block during labor

Most obstetricians quietly agree that epidural block also increases the rate of cesarean section. An epidural block causes the pelvic musculature to become flaccid or limp. Therefore, the "trough" of pelvic muscles which normally rotates the baby into the proper position to move efficiently through the birth process dysfunctions.

PUDENDAL BLOCK

Mothers who experience a drug free birth often comment that, one of the most rewarding sensations of giving birth is the feeling of power as they ease their babies out into the world. Yet, well meaning obstetricians frequently take away this gratifying moment by administering a pudendal block to numb the mother's perineum just as she is about to give birth. A pudendal block is performed by injecting an anesthetic drug through the vagina into the pudendal nerve on either side of the vagina. The irony of this misguided kindness is that it can indirectly cause the mother's perineum to rupture. Why? Because the pudendal block blunts or obliterates the burning sensation which normally occurs as the baby's head distends the mother's perineum. This warning sensation, when intact, warns the mother to bear down with just enough force to ease her baby out but not enough to rupture her perineum.

The anesthetic used in a pudendal block reaches the infant's circulation in seconds or minutes and has the potential for having the same neurological effect on the fetus as an epidural injection of the same drug. Since a pudendal block is relatively short lived, an additional anesthetic is usually administered to numb the perineum if sutures are required to repair an episiotomy or a rupture in the perineum.

GENERAL ANESTHESIA

General anesthesia is seldom used for vaginal birth today in the United States. It is used, however, for cesarean section if a rapid delivery is needed or if the mother is bleeding. It may also be used if there is a need or desire to provide absence of sensation and consciousness. Typically, for general anesthesia an induction anesthetic such as thiopental (Pentothal) is given by injection, rapidly followed by an injection of succinylcholine (Anectine). A few seconds later the mother drifts into unconsciousness, and pressure is applied to the cricoid cartilage, just below the larynx, to prevent aspiration while a laryngoscope is inserted into the mother's trachea. An endotracheal tube is inserted through the laryngoscope, and the cuff of the endotracheal tube is inflated to seal any space in the mother's trachea that the tube does not fill. The anesthetist or anesthesiologist listens to the mother's lungs with a stethoscope to be certain the endotracheal tube is in her airway and not in her esophagus.Once the seal is assured anesthesia is maintained with nitrous oxide and oxygen. A low concentration of a volatile agent such as halothane (Fluothane) is also given to provide amnesia. The endotracheal tube must not be removed until the mother is able to follow commands.

As with any type of anesthesia, general anesthesia must be given skillfully. Although women are often told not to eat if they think they may be in labor, there is no documented case of aspiration in a woman who was properly anesthetized, whether or not she ate.

The combination of nitrous oxide and oxygen can also be given by mask as analgesia, but it is seldom used in the United States.

Sedatives and hypnotics such as barbiturates (Seconal, Luminal, Nembutal), chloral hydrate, and flurazepam (Dalmane) may sometimes be used in early labor, but the FDA has not approved their use in pregnancy or labor. These drugs may cause respiratory depression in the newborn.

Whether or not exposure to analgesic drugs during labor and birth contributes to the high rate of subtle difficulties in learning and behavior in children has yet to be adequately investigated.

UTERINE STIMULANTS

Oxytocin (Pitocin, Syntocinon) is a powerful synthetic hormone administered to women in order to initiate and/or to stimulate labor. The drug is frequently the physician's preferred method of stimulating contractions and speeding up labor, even though it is well known that helping the mother to walk, stand or sit during labor reduces the discomfort of contraction and facilitates the normal progress of labor in the majority of women. Oxytocin is frequently necessary when epidural block alters the normal progress of labor.

The FDA has approved the use of oxytocin in labor and delivery when medically indicated. Prostaglandin gel is also administered in some hospitals as a uterine stimulant or cervical "softener", but the FDA has not approved prostaglandin for such use.

The use of oxytocin in obstetrics, even if necessary, is not without risk. If the mother's membranes have ruptured the augmentation of contractions can adversely affect the fetal brain by increasing compression of the fetal skull, increasing intracranial pressure, increasing the possibility of tears in the cerebral membranes, and by inhibiting the normal transfer of oxygen from the mother's circulatory system to the fetal brain. During a normal contraction the maternal blood vessels which carry oxygenated blood through the uterine wall to the placenta are constricted. During these periods of diminished blood flow the oxygen in the mother's blood, which stores up in the placenta's intervillous space between contractions maintains the fetal brain with a relatively constant supply of oxygen. Uterine stimulants which foreshorten these oxygen-replenishing intervals, by making the contractions too long, too strong, or too close together, increase the likelihood that brain cells will die. The situation is somewhat analogous to holding an infant under the surface of the water, allowing the infant to come to the surface to gasp for air, but not to breathe.

British scientific investigators have noted that the use of oxytocin to induce labor increases the incidence of jaundice in the newborn. Whether the frequent use of oxytocin in the United States to stimulate labor contributes to the high incidence of jaundice in the newborn period has yet to be investigated.

All of us would like to be able to provide the laboring woman with a magic remedy that would take away her pain, leave her with all her senses intact, and would be free of harm to her and her baby. Such a drug is not yet at hand. For now, each mother (and father as well) must be given the facts and allowed to make their own decision as to what is right for them and their baby.

©2000 DORIS B. HAIRE

Back to Home Page