ML20133C747
| ML20133C747 | |
| Person / Time | |
|---|---|
| Site: | Three Mile Island  |
| Issue date: | 03/29/1981 |
| From: | Tokuhata G PENNSYLVANIA, COMMONWEALTH OF |
| To: | |
| Shared Package | |
| ML20132B167 | List: |
| References | |
| FOIA-85-285 NUDOCS 8507200561 | |
| Download: ML20133C747 (8) | |
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, PREGNANCY OUTCOME AROUND THREE MILE ISLAND'
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h George K. Tokuhata, Dr.P.H., Ph.D.
- Director
{ Division of Epidemiological Research Bureau of Epidemiology and Diessee Prevention
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I Pennsylvania Department of Health Professor of Epidemiology and Biostatistics (Adjunct) ,
Graduate School of Public Health 9
University of Pittsburgh P.O. Box 90 Harrisburg, PA 17106 9
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PREGNANCY OUTCOME AROUND THREE MILE ISLAND __
Subsequent to the March 28,1979 nuclear accident at the Three Mile Island, the Pennsyl-
- vania Department ~
of Health initiated a comprehensive epidemiological investigation of possible health effects of the accident upon local population. Durmg the 10 day period of crisis, it was not possible to ascertain accurate information regarding radioactive emissions from the damaged nuclear reacter into the environment. However, the presence of rather thffuse and growing psychological disturbance in the area was apparent.
Within a short period of days following the accident, we'were able to conceptualize and de-velop a multidisciplinary plan for a variety of researds studies speci5cally designed to assess the impact of the TMI accident. ' Studies conceived during this critical period mostly reflected the existing epi-demiological knowledge regarding biological effects of low level ionizing radiation and severe emo-tional stress.
I was designated by the Governor of Pennsylvania to coordinate and manage all health re-lated research activities relative to TMI. At the same time, a special Advisory Panel was commissioned l by the Secretary of Health to oversee and guide all TMI related studies adciinistered by the Depart-ment of Health.
One of the most important studies developed shortly after the accident was to evaluate pos-sible impact of the accident upon pregnancy outcome in the vicinity of the damaged nuclear reactor.
j We knew that both ionizing radiation and emotional stress can affect human reproductive process and l pregnancy outcome. We also recognized the fact that the embryo and the fetus are highly sensitive to l
such environmental insults, depending upon their severity, j Before describing the methodology and study design in detail,let me review briefly the cur-I rent state of epidemiology of pregnancy outcome, particularly in relation to radiation and stress.
Radiation and Pregnancy Outcome:
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Much information is now available regarding the effects of ionizing radiation on the embryo ,
and fetus. Most of the more reliable data are derived from animal experiment; however, certain l
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f experimental findings may be applicable to the humans, at least in a qualitative sense, while raaa==idag inherent limitations or difficulties in such cross-species inferences.
The most eniMe=_at damage from exposure to ionizing radiation results from the direct interac-tion of the stream of ions produced by radiation with the nucleus of the irradiated cells. The cell
! may be killed, the radiation mar produce no damage, or such d==7 may be repaired. There is another type of damage which is probably the most significant one, i.e., the damaged cell sur-vives and reproduces a clone of abnormal cells which may result in ===1t=nancies or congenital anomahes.
I Possible effects of radiation on pregnancy outcome are (a) intrauterine and extrauterine growth retardation, (b) embryonic, fetal or neonatal death, and (c) gross congenital malforma-tions. The tissue (organ) most readily and consistently affected by radiation is the central nervous system.
Laboratory and clinical studies by and large support the contention that doses of radiation less than 10 rada do not contribute to intrauterine or extrauterine growth retardation or to gross con-I genital malformations #l. Distribution of the absorbed dose from X rays or gamma rays extem-ally exposed is considered to be rather uniform in the developing embryo or fetus; thus, a child '
i with multiple radiation induced malformations is also likely to have intrauterine growth retarda-tion and some CNS abnormalities.
- To determine the effect of radiation upon pregnancy outcome, one must consider (a) the ab-sorbed dose, (b) the dose rate (acute or chronic; continuous or intermittent), (c) the stage of gestation at which the exposure occurred, (d) the age of the mother when conceived, and (e) the health condition of the mother, in general. If the dose rate is reduced significantly, the damaged cell may recover from it in time. The pre. implanted stage of the embryo is the most sensitive to lethal effects of radiation. Embryos destroyed at this stage of pregnancy may never be recog-i mzed or recorded. However, preplantation irradiation has no apparent relationship to teratogene-sis. Radiation has its greatest effectiveness in producing congenital malformations during the
! organogenesis period. In humans, this corresponds to the 14th 49th day of gestationI #l.
The peak incidence of gross malformations occurs when the fetus is irradiated during the early l organogenesis period, although cellular, tissue and organ hypoplasia, including growth retarda-i tion can be produced by radiation throughout organogenesis, and fetal and neonatal periods, if i the dose is high enough. These are usually limited to CNS abnormalities and other organs, which continue to differentiate throughout gestation. Thus, cerebral hypoplasia, microcephaly, cere.
bellar hypoplasia, and testicular atrophy can be produced by "high" doses at specific stages of ges-tation.
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A number of studies suggest that " low" levels of radiation with less than 10 rads of acute or chronic exposure may produce some pathologic effects in the embryoW,(#1,(#1, N, but these minor effects may be subtle and thus difficult to detect. For this reason, the National Council on Radiation Protection and Measurements has established the maximum permissible dose (MPD) to the fetus from occupational exposure of the expectant mother well below the known teratogenie
, dose. The neonatal death rate is highest in the survivmg embryos irradiated durmg the early organogenesis period.
i Radioactive isotopes =Iraini*-red internally to the pregnant woman have a variable distribution in the embryo and fetus dependmg upon (a) the stage of gestation, (b) whether the radioactive material crosses the placenta, and (c) the biochemical affinities of the type of radiation emitted 1
(alpha, beta, or gamma). Thus, the evaluation of the reiztive risk is much more complex and dif-ficult for radiations absorbed from internally =Immistered radioactive mtterials than for radia-tion delivered from external X rays or gamma ray sources.
I It is generally assumed that embryonic germ cells are susceptible to the mutagenic effects of radi-ation throughout gestation. However, there is some uncertainty as to whether " low" doses be-low 10 R or low dose rates can produce significant cytogenetic defects. There has been no con-vincing evidence that cytogenetic (chromosome) abnormalities as such caused by radiation in utero have caused any significant increase in the incidence of clinical diseases.
There is no doubt that "high" doses of radiation can be carcinogenic. However, whether or not
" low" doses, such as below 2 rads, can induce leukemia and/or other malignant tumors in the humans has been debated by some epidemiologists and radiation biologists. It appears improb-able that radioactive fallout as reported in the past or natural background radiation as such, sig-niScantly attects the incidence of congenital malformations, growth retardation or fetal deaths.
The exact nature and extent of damages caused by low" doses of radiation upon humans'are still unknown. However, if the cell nucleus is damaged by radiation and some genetic materials (DNA) are lost or impaired, one may not conclude that the risk is zero. It is logical to as'sume then, that there is no threshold in radiation effect which may increase more or less with the in.
i crease or accumulation of exposure. However, the problem we are facmg today is that anomalies caused by such " low" doses of radiation, if any, may not be detectable with the existing method of epidemiologic inquiry.
It is also important to recognize that not all persons run the same risk of developing a malignancy or other abnormalities from a given radiation exposure. These variations depend upon individual genetic-constitutional makeups, as well as different individual experiences and environmental ex-posures.
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Stress and Pregnancy Outcome:
Stress or psychoemotional disturbance is considered by many researchers as a precursor to dis-ease. There are a number of studies in humans which have found an association between prenatal I anxiety / stress and gestational, perinatal and developmental pathology. While some of these stud-les seem to have methodological flaws, several have found a sigmficant relationship to either complications of pregnancy /7) (#1, or to infant growth and development
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Nucholls, in particular, studied the effect of " social support" upon pregnancy outcome l' #1. Wo-men with a high number of " psychological assets" had one third the pregnancy and perinatal complication rate of women whose " psychological assets" were low.
Newtonf' #1 in a retrospective study of postpartum women showed that pregnancies terminat-ing in premature labor were more likely to have beert stressful. In terms of the average number of life events per pregnancy, it was clear that the more premature the onset of labor, the higher the level of psychological stress was likely to be. The groups were matched for age, gravidity, and par-ity. The results of the study were independent of socioeconomic levels.
The findings of the studies cited above suggest a number of practihal and scientific questions to be addressed within the context of TMI Health Effect Research Program. The first, and most ob-vious question, is whether or not the local population, including pregnant women, as a whole ex-pe-ienced any detectable stress effects. Previous studies of stress and pregnancy complications have found relationships which are either relatively weakt :21 or restricted to subgroup of the oversl! study population.
A second question concems factors which render individual women, particularly vulnerable to stress effects. As reviewed earlier, stress may be associated with morbidity only in the absence of supportive interpersonal relations. This observation is in accord with other studies of stress and illness /' > >, as well as with Burchfield'sf2 41 argument that a maladaptive response to stress'is atypical, and likely to occur only when adequate coping resources are unavailable.
An assessment of the role of social support, as well as other possible mediating factors, would contribute to the study of stress as a scientific concept and provide information as to which seg.
ments of the pregnant population might be at risk for stress induced morbidity.
While specific mechanism of stress-induced morbidity is not yet fully understood, there may be
! several different explanations with respect to pregnancy outcome; e.g., stress anxiety induced changes (a) in maternal behavior, such as increased smoking, drmkmg or medication during preg-nancy, (b) in obstetric practice, such as increased prescription of analgesics and psychotropic drugs or use of special procedures, (c) in maternal. infant bonding and child. rearing practices, and (d) in the hypothalamic-adrenocortical mechanisms I '#i.
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A careful designed retrospective cohort study of Pregnancy Outcome wasinitiated in August, 1979 following four months of preparation. This study covered all pregnant women residing within a ,
ten mile radius of the TMI, who gave births during a one year period from March 28, 1979 through March 27,1980. This study cohort consistmg of approximately 4,000 deliveries will be compared with l
a control cohort of another 4,000 deliveries during a one year period immediately following the study cohort in the same geographic area. The study cohort will also be compared with similar data collected in the same general,aren during the immediately preceding four year period. This design will make it possible to compare pregnancy outcome measures among three cohorts, one study group and before-and-after control groups.
Measures of adverse pregnancy outcome being investigated are: fetal deaths (stillbirths with and without abortions of 16-week or more gestation) an expressed per 1,000 deliveries, neonatal deaths (deaths within 28 days postpartum) as expressed per 1,000 live births, hebdomadal deaths (deaths within seven days postpartum) as expressed per 1,000 live births, permatal deaths (combined measure of fetal and neonatal deaths) as expressed per 1,000 deliveries, prematurity (gestation less than 37 weeks) as expressed in percent, immaturity (birth weight less than 2,500 grams) as expressed in percent, congenital malformations (one or more defects observed at birth) as expressed in percent, and low Apgar score (less than seven at one minute of delivery) as expressed in percent.
As indicated earlier, the main objective of the present investigation is to determine if the TMI nuclear accident has had a measurable effect on pregnancy outcome. However, there are numer-ous factors other than radiation and stress that are known or suspected to influence the course of preg-nancy and fetal outcome. In order to delineate the effect of the TMI accident, other known influences must be taken into account. This necessitated ascertamment of the appropriate data on a large number of variables pertaining to the pregnant women themselves and the surrounding complex environment to which they have been exposed. -
The maternal factors considered in this study include: sociodemogmphic chameteristics, such as race, age, education, occupation, employment, marital status, religion and residence; behaui-oral attributes such as smoking, drmking, and birth control practice; and medical-obstetric histories, such as diabetes, hypertension, thyroid disease, obesity, previous abortions nuscarnages, previous fetal deaths, prematurity / immaturity, congenital malformations, and gravidity /index birth order.
The provider factors that were taken into account are: medical specialty of the attending physician.(obstetrician; general family practitioner; osteopath; etc.); type ofpractice (solo vs. group);
and prenatal care (initiation of medical care, frequency of visits, special procedures or tests done, in-structions given, medications administered, X-ray exposures, etc.).
Maternal stress durmg the index pregnancy is being measured by overt personal statements of " anxiety fear" as experienced by individual women during the crisis, as well as by actual stress-cop-ing patterns, such as takmg tranquilizers and sleeping pills. Maternal radiation exposure during the 10-
! day crisis following the nuclear accident is being estimated by the Department of Radiation Health of l
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the University of Pittsburgh Graduate School of Public Health. For this purpose, all available and reli-able radiation source data compiled by various agencies are being reviewed carefully, consolidated and computer analyzed on the digitized electronic maps with respect to distance and direction of each pregnant woman from the Three Mile Island. Also, added to this body of data is detailed data relative to indivulual whereabouts during the 10. day period so that more accurate radiation exposure can be estimated. Eventually, two series of dose estunates on an individual basis will be established, namely, maximum possible dose and most likely dose.
These radiation dose estimates, together with the measures of psychological stress will be re-lated to each of the eight pregnancy outcome measures, while holding constant influences of all other factors considered in the study. The impact of the TMI nuclear accident will be assessed in terms of both radiation and stress combined, as well as each factor considered independently.
Since the level of radiation exposure is considered to be very low and thus no major radia-tion effect upon pregnancy outcome is expected. On the other hand, it is possible that some measur.
able radiation effects might be detected if the originally " reported" radiation dose data were signif!- ,
cantly underestunated. Our ability to detect relatively small differences in the incidence of adverse consequences attributable to the nuclear accident will heavily depend. upon how well we can control (take into account) the influences of all the other factors, some of which are known to be much more important than low level radiation and/or psychological stress being investigated.
The Three Mile Island nuclear accident has caused an extensive social-political unrest world-wide. At the same time, the accident has presented social scientists and biomedicalinvestigators a unique opportunity to evaluate its impact upon local population. Probably the most important con-cern is that of safety and health effects of this unprecedented event.
From the currently available epidemiological knowledge, no signi5 cant physical health ef-fects are expected from the low level radiation reported to have been released from the damaged TMI
! nuclear facility. However, in the absence of absolute certainty as to the exact ar.tount of radioactive contamination of the local environment and the population, particularly during the early period fol-lowing the accident, carefully designed epidemiological studies, such as this, are justified in an attempt to evaluate possible health effects of the accident. Additional support for this view is the fact that some substantial psychological impacts have been indicated among certain segments of the local popu-lation.
It is not known, at this time, how long such psychological disturbance will continue, partic-ularly in view of the time-consuming decontamination process, to what extent psychosomatic symp-toms " reported" earlier % among local residents within a 15 mile radius are true, and what signifi-cant physical manifestations may actually ensue over an extended period of years. A careful evalua-tion of pregnancy outcome, both immediate and long-term, in the surrounding communities should
! be pursued and documented oecause of the known high sensitivity of the fetus to ionizing radiation and severe emotional stress of the pregnant women.
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REFERENCES J
- 1. Brent, R. L and Gorson, R. O.: Radiation Exposure in Pregnancy. Current Problems in Radiology, Vol II, No. 5,1972.
- 2. Brent, R. L: Effects ofIonising Radiation on Gmwth and Development. Contributions to Epidemi.
ology and Biostatistics, Vol I,1979.
- 3. Meyer, M., Diamond, E. and Metz. T.: Sex Ratio of Children Born to Mothers Who Had Been Exposed to X rays in Utem. Johns Hopkins M.J. 123: 123, 1968.
- 4. Segall A., MacMahon, B., and %=nie=n, M.: Congenital Malformations and Background Radiation in Northern New England. J. Chron. Dis. 17:915, 1964.
- 5. Tabuchi, A.: FetalDisorders Due to Ionising Radiation, Hiroshima J. M.Sc. 13:125, 1964.
- 6. Kinlen, L. J. and Acheson, E. D.: Diagnostic Irradiation, Congenital Malformations and Spontaneous Abortions, Brit. J. Radiot. 41:648,1968.
- 7. Nuckolls, K. B.: Psychological Assets, Life Crisis and the Prognosis of Pregnancy. American J. Epid.
95:431, 1972.
- 8. Mormhima, H. O.: The Influence of Maternal Psychological Stress on the Fetus. Amer. J. Obs. and Gyn.131:286,1978.
- 9. Barlow, S. M.: Delay of Postnatal Growth and Development of Offspring Produced by Maternal Re.
straint Stress During Pregnancy in the Rat. Teratology 18:211,1978.
- 10. Nuckolls, K. B.: op. cit.
- 11. Newton, R. W.: Psychosocial Stress in Pregnancy and Its Relation to the Onset of Premature Labor.
Brit. Med. J. 2:411, 1979.
- 12. Gossuch, R. L and Kay, M. K.: Abnormalities in Pregnancy as a Function of Anxiety and Life Stress.
Psychosomatic Med. 36:352,1974. ,
- 13. Berkman, L F. and Syme, S. L: Social Networks, Host Resistance, and Mor;ality. American J. Epid.
109:186, 1979.
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- 14. Burchfield, S. R.: The Stress Response A New Perspective. Psychosomatic Med. 41:661, 1979.
- 15. Smith, D. J,: Modification of Prenatal Stress Effacts in Rats by Adrenalectomy, Dexamethasone, and Chlorpromsxine. Physiology and Behavior 15:461,1975.
- 16. Houts, P. S., Miller, R. W., Tokuhata, G. K., and Ham, K. S.: Health-Related BehavioralImpact of the
- Three Mile Island Nuclear Incidence. Report submitted to the TMI Advisory Panel on Health Research Studies, Pennsylvania Department of Health. Part L April,1980.
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