Anesthesia Exposure During Pregnancy

Links to Learning Disabilities, ADD and Behavior Disorders

The following is one chapter from a 1997 Graduate Student Project conducted at the
University of South Florida.  The project involved locating published peer reviewed medical journal articles which have shown environmental and chemical exposure factors can cause learning disabilities, hyperactivity and other disorders by damaging the delicate brain growth period in the unborn child during pregnancy.

Author: Richard W. Pressinger (M.Ed.)
Project Supervisor: Kofi Marfo (Ph.D.)
email correspondence: research@chem-tox.com
Web Site Home Page: www.chem-tox.com/pregnancy/learning_disabilities.htm

Links to Learning Disabilities, ADD and Behavior Disorders

Anesthesia Topics
Select topic or scroll through page below

introduction anesthesia Anesthesia Introduction & Animal Background Studies
anesthesia prevalence How Common are Anesthesia  Exposures While Pregnant
anesthesia alertness decrements Irritability and Decreased Alertness from Anesthesia
Anesthesia Lowers IQ I.Q. Scores Lower for Babies Exposed to Anesthesia
Anesthesia Damages DNA DNA Damage Caused by Anesthesia


Anesthesia: Potential for Permanent Neurological Effects

The level of pain experienced by the mother during childbirth is one of the primary concerns for the physician. However, as shown in the peer reviewed journals below, there is evidence showing the potential for anesthesia to cause not only temporary harm, but also permanent neurological harm as well. This can be observed in the form of in increase in irritability as well as future reductions in IQ (referenced below). Therefore, it is the responsibility of the physician to inform mothers of this potential so decisions can be made accordingly.

Anesthesia effects are not limited to only childbirth, local anesthetics are administered in dentistry being shown to rapidly cross the placenta. The common local anesthetic lidocaine has been shown to take longer to clear the fetal circulation than in an adult. The half life for lidocaine in nonpregnant rats is similar to that for nonpregnant humans, about 2 hours in each. The primary metabolite of lidocaine, glycinexylidide, is thought to be centrally active and has a half life of about 10 hours.

Doctors Bowman and Smith have suggested that drugs which alter central neurotransmitters when administered to the adult may produce irreversible changes in development of neurotransmitter systems when administered during a sensitive period in development (5).

In a statement by anesthesia researcher, Dr. Albert R. Hollenbeck,
(see reference at end of introduction),

"If their hypothesis is correct, administration of local anesthetics such as lidocaine during a sensitive period in gestation should be capable of producing enduring changes in offspring behavior, since they are available to the fetal Central Nervous System, and since they may have effects upon the central nervous system."

Background on Animal Anesthesia Studies

Other studies of general inhalation anesthetics have been reported to cause a wide variety of toxic effects that generates serious concern regarding potential long lasting effects upon the developing baby. For example, decreases in DNA content in the bronchial cells of dogs has been reported after exposure to the common inhalation anesthetic enflurane (Anesthetist 28:120-124, 1979). Abnormal cell division was induced by enflurane in mammalian and chicken embryo cells (Environmental Research 12:366-370, 1976). Problems in sperm production in mice have also been found to occur after exposure to enflurane (Anesthesiology 54:53-56, 1981).


How Common are Anesthetic Exposures During Pregnancy?

JOURNAL: Child Psychiatry and Human Development, 16(2):126-134, 1985

In a study originally designed to examine factors in pregnancy that might relate to cerebral palsy and other forms of damage to the central nervous system, researchers also gathered information on anesthesia exposure. Information on 50,282 mother-child pairs was collected. Subsequent analyses showed an overall prenatal exposure rate to local anesthetics to be 11.34% and a first trimester exposure rate of 5.28% More recent findings reported by Blair et al., found in contrast to the first study, more than 20% of normal pregnancies received local anesthetic agents during pregnancy (does not include delivery exposures which are, of course, much higher figures), however,  the sample size in the Blair study was notably smaller, leaving open the possibility of sample selection bias.

In an attempt to shed more light on these discrepancies, a 1982 research project was conducted by Dr. Albert Hollenbeck and colleagues at George Mason University which analyzed 229 low risk mothers of healthy full term deliveries (64% of the mothers were black, 34% white) to determine the full extent of anesthetic exposure during pregnancy.

The results of their findings showed 47% of the mothers (108 women) had visited a dentist during pregnancy and 23% (52 women) received some form of medication during the visit, usually local anesthesia by injection. In a review of the mothers’ dental records, lidocaine was the most frequently used anesthetic, followed by mepivacaine and nitrous oxide.

When analyzing the outcomes of the "anesthetic exposed" and "not exposed" infants, the researchers found mothers exposed to anesthetics during the nine months of pregnancy had babies that weighed 279 grams less at birth. Also of interest, the researchers found that mothers exposed to anesthetics who also engaged in indoor house painting, had even lower birthweight infants, indoor latex paints contain the chemicals vinyl acetate and ethylene glycol, and at that time in early 1980’s, indoor wall paints also contained a mercury fungicide which was banned in the early 1990’s after reports to the EPA of neurological problems in children after paint exposure.

In conclusion, the researchers stated,

The present findings, in conjunction with the Blair et al. results, are suggestive that prenatal exposure to anesthetic agents may affect physiological mechanisms which have behavioral consequences.... Low birth weight could be an indication of disruption in these metabolic processes (the metabolic process of carbohydrate uptake and protein synthesis). Previous human observations and considerable animal data suggest that early trimester anesthetic exposure may result in neonatal behavioral changes."

Dr. Albert R. Hollenbeck, Ph.D. Robert F. Smith, Ph.D. Eleana S Edens, B.S.
George Mason University, Columbia Hospital for Women
Georgetown University Medical School


Local Anesthesia During Childbirth
Babies More Irritable & Less Alert

JOURNAL: Science 186: 634-635 (1974)

Abstract Quote:

"Administration of local-regional anesthesia during normal deliveries was correlated significantly with newborn behaviors as evaluated by the Brazelton neonatal assessment scale. Three days after birth, infants whose mothers received local-regional anesthesia were more irritable and motorically less mature than those infants whose mothers were not medicated."

Babies who were the most alert, the least irritable, and those who had the most mature motor skills were found to be the ones who were not exposed to local-regional anesthesia during childbirth, according to research at the National Institute of Child Health and Human Development in Bethesda, Maryland. The research was designed to study the possible effects of local-regional anesthetics on behavior characteristics of infants 3 days of age. Doctors tested 60 first-born, healthy infants between 48 and 72 hours of age. The children were born to white middle-class women who had received normal antenatal care and had medically uneventful pregnancies and deliveries. The most frequently administered analgesic agent was Demerol (meperidine) in conjunction with the preanesthetics Phenergan (promethazine hydrochloride) or Vistaril (hydroxyzine pamoate); morphine was given to two women. No women in the study received general anesthesia. Anesthetic solutions used were lidocaine, tetracaine, mepivacaine, and bupivicaine. Of the 52 women who received anesthesia, 42 were given spinal (saddle block) anesthesia, The routes of administration for the other women were pudendal (four), paracervical (one), epidural (two), both epidural and saddle block (two), and both pudendal and saddle block (one). Eight women received no anesthesia.

Infants were evaluated by the Brazelton Neonatal Assessment Scale which tested the following behaviors:

  1. Alertness: the infant’s responsive to visual and auditory, animate and inanimate stimuli
  2. Irritability: the frequency and conditions of state changes and irritable behaviors
  3. Motor maturity: the arcs and smoothness of the baby’s movements, tremulousness, and frequency of startling.

Specific scores on the Brazelton newborn scale showed a 50% poorer score on irritability measures for the "anesthesia exposed" group than the "no-anesthesia" group (20.2 versus 13.5). Motor maturity scores were also found to be 25% lower for the anesthesia exposed babies (21.1 versus 15.1).

According to the research physicians,

"Administration of local-regional anesthesia is correlated significantly with decreased motor maturity and greater irritability. Jerky movements in small arcs, startles and tremulous motions, and frequent state changes and crying were more common in babies of mothers who received anesthesia. Analgesia usage is significantly related to lower scores on motor maturity.... It is known that anesthetic agents cross the placenta and enter fetal circulation,. There is no evidence, however, that these drugs are present in infants later than 1 day after birth. Mepivacaine (a common local anesthetic) was detected in infants’ blood as late as 24 hours after birth, and lidocaine, as late as 8 hours after birth.....Whatever the interpretation, it appears that anesthesia administration during childbirth is significantly related to the functioning of the newborn child. Local-regional anesthetics although known to produce severe physiologic reactions in high doses, continue to be considered a safe choice in standard obstetric procedures. Our data raise questions about the assumption that routine usage of these anesthetic agents is inconsequential, even for the normal, healthy infant."

Drs. Kay Standley, A. Bradley Soule III, Stuart A. Copans and Michael S. Duchowny
Social and Behavioral Sciences Branch,
National Institute of Child Health and Human Dev., Bethesda, MD


IQ Scores Lower in 4 Year Old Children
Exposed to Anesthetics During Pregnancy

JOURNAL: Child Psychiatry and Human Development, 17(1), Fall 1986

 

Abstract Quote:

"This brief report provides the four year follow-up on infants prenatally exposed to anesthetics. Fourteen of 39 infants examined at birth were available for intelligence testing at age four. Results indicate that Peabody Picture Vocabulary IQ scores are correlated with visual preference testing at birth in infants exposed to prenatal anesthetics. The mean IQ’s of these infants also differed from mean IQ’s of unexposed infants at four years. These preliminary data are suggestive of prenatal anesthetic effects that are persistent and that early infant visual screening may be predictive of later IQ."

This anesthetic exposure study measured IQ scores in 4 year old children who were exposed to anesthetic compounds during pregnancy, excluding anesthetics given at birth. Three standardized intelligence measures were given to each child by a trained tester who was not aware of the child’s exposure history, (1) the Peabody Picture Vocabulary Test (PPVT); (2) the vocabulary portion of the Weschler Preschool Primary Scales of Intelligence; and (3) the picture vocabulary portion of the Stanford-Binet Intelligence Test.

Of the three tests given, there were no significant differences found between the anesthesia exposed and non-exposed children on the vocabulary portion of the Weschler and the picture vocabulary portion of the Stanford-Binet tests. However, differences were detected between groups on the Peabody Picture Vocabulary Test. In fact, over one standard deviation separated the means of the anesthesia exposed group and the unexposed group. IQ scores on the PPVT averaged 91 for the anesthetic exposed children and 108 for the unexposed children. These differences can be seen in the graph at top right.

The one weakness of the study is the small number of children (14 total) used in the evaluation. Eight were male and six were female. However, the researchers concluded their report by stating,

"While the few subjects available at four years cloud definitive conclusions about prenatal drug exposure, the significant findings speak to the potential strength of drug effects on human behavior. These preliminary results again clearly suggest the need for a well-controlled extensive human study of prenatal anesthetic exposure."

Dr. Albert Hollenbeck, Ph.D. Leslie A. Grout, B.S., Dr. Robert F. Smith, Ph.D.
George Mason University
Columbia Hospital for Women and Georgetown University Medical School


DNA Damage & Common Anesthesia "Enflurane"

JOURNAL: Environmental Research, 59:476-484 (1992)

Damage to the DNA molecule within the cells (the DNA molecule holds our 100,000 genes) has been found to occur after exposure to the common inhalation anesthetic compound enflurane. Researchers at the Department of Physiological Chemistry, University of Mainz, Germany, found that exposure to enflurane at levels of 0.2% volume resulted in DNA damage to the immune systems of test animals, The damage was comparable to damage after X-radiation levels of 0.1 Gy.

The researchers stated in conclusion,  

"DNA single-strand breaks are common phenomena and indicate genotoxic effects even before DNA repair begins. The detection of DNA single-strand breaks is an instantaneous indication of genotoxicity. However, DNA repair is not always perfect and because of these deficits in DNA repair mechanisms, one can draw conclusions from the presence of DNA single-strand breaks about the rate of possible irreversible DNA damage. For patients with genetic defects in DNA repair, i.e., in patients with xeroderma pigmentosum, anesthesia with enflurane may induce irreversible DNA damage. Determination of DNA damage in cultured cells of these patients before anesthesia is particularly important in evaluating potential side effects of anesthesia especially of repeated anesthesia."

The authors also stated that enflurane also affects mechanisms of mitosis (cell division) and synthesis of nucleic acids (the actual making of genes and DNA). This potential would, therefore, also generate concern for possible harm to the rapid neurological development of the growing embryo and fetus.

Drs. Manfred Reitz, Kunti DasGupta, Ludwig Brandt
Department of Physiological Chemistry and Clinics for Anesthesiology
University of Mainz, Germany

For information on other environmental circumstances
shown to damage brain growth during pregnancy - visit

chem-tox.com/pregnancy/learning_disabilities


Additional References  
Developmental Child Neurology 26 or 28:476-, 1984