Document baZ5dJr9N8eRRNvRZ6pQyQaZ6

(Jr~ f - ' / < I > tKI .-" op . A 'hi c \/--------1:,, ' !'c7<- < I 13 s V? FOR ADMINISTRATIVE USE LIMITED DISTRIBUTION HOT FOR PUBLICATION* PUBLIC HEALTH SERVICE-CDC-Atlanta EPI-76-60-2 July 26, 1976 TO : Director, Center for Disease Control FROM : Cancer and Birth Detects Division Bureau of Epidemiology SUBJECT: Congenital Central Nervous System Malformations, Kanawha County, West Virginia SUMMARY Data available through the Birth Defects Monitoring Program (BDMP) revealed that from 1970 through 1974, Kanawha County, West Virginia-- where 1 of the 40 polyvinyl chloride production plants in the United States is located--had rates of congenital central nervous system defects that were significantly higher than national BDMP rates for those years. In February 1976 an Investigation was undertaken because of the possibility that these higher than expected rates may have been related to parents' occupational or residential exposure to vinyl chloride. The study confirmed that an increase in CNS defect rates had occurred In Kanawha County, and cases clustered primarily in the area cast of the plant; however, no relationship between Infants with malformations and parents' exposure to vinyl chloride could be established. INTRODUCTION . Because of continuing concern regarding the possibility that birth defects cf the central nervous system (CNS) may be caused by parents' occupational or residential exposure to vinyl chloride, CDC's Birth Defects Branch, Cancer, and Birth Defects Division, Bureau of Epidemiology, reviewed 1970-1974 data available through the Birth Defects Monitoring Program (BDMP), a hospital-based system.for monitoring the inci dence of birth defects and otnar newborn conditions noted in infants discharged from approximately 1,200 United States hospitals (JL). Of the 40 polyvinyl chloride (PVC) pro duction plants in the United States (2), 17 are located in counties which have a: least 1 hospital that was participating in the BDMP in 1974 and thus could be included In the review. In 10 of the 17 counties, BDMP data are reported on less than 50% cf the total reported births; therefore, even though higher than normal CNS rates were noted in 2 of these counties, they were not included in this study because of the low percentage of total births they represented. In the 7 counties where the majority of birth3 are reported to the BDMP, 2 had rates of CNS defects in infants born from 1970 through 1974 that were significantly higher than national BDMP rates for these years: Lake County, Ohio (Pair.esvilie), the site of a previous investigation (3), and Kanawha County, West Virginia. The Kanawha County findings (Table 1) ware discussed with William L. Cooke, M.D., Vest Virginia State Epidemiologist, and Peter Infante, D.D.S., Dr.P.H., National Institute GC 003:3' for Occupational Safety a Jic.ilth ('I I OSH) , who agreed witn need for further investigation. On February 10, Larry Edmonds, M.S.P.H., and ,,arol E. Anderson, M.D. , met with Dr. Cooke in Charleston, West Virginia, and began an investigation. Others yho participated in the investigation and in the preparation of this report included Joseph Carney, Director, and Lucas Seas, Statistician, West Virginia State Department of Health, Division of Vital Statistics; Paul Seekford, M.D,, Director, and Edna Smith, R.N., Charlcston-Kanawha County Health Department; and Carl Beard, XI, Director, . Vfest Virginia Air Pollution Control Commission. .' . BACKGROUND The principal centers of population in Kanawha County (1970 population 229,113) are Charleston, South Charleston, Dunbar, St. Albans, and Nitro. All are located along the Kanawha River, which flows from southeast to northwest through the valley's hilly terrain. In 1970 the chemical industry employed 12% of the county's work force. There are 7 v major chemical plants and several smaller ones in the Kanawha River Valley within 10 silles of Charleston. Only 1 of these plants produces PVC. This Diant, which becan production in 1935, uses the solvent, emission, and modified emulsion processes. Vinyl chloride monomer (VCM) is released into the atmosphere as part of the production process. METHODS . "^ i , : i TVo data sources were used in this investigation: 1) BDMP listing of infants born with CMS defects from January 1, 1970, through December 31, 1974, and 2) West Virginia Department of Vital Statistics records (birth and fetal death certificates) on infants b.om with CMS defects from January 1, 1968, through December 31, 1974, Data obtained f.r.om these 2 sources were not entirely comparable (4) , since BDMP data represented 95% Of. all hospital births in Kanawha County without regard to parents' residence, and vital statistics records represented only those infants bom to county residents. The data were examined separately for trends, and then both sets were combined to deter mine all CIS defects incidence for 1970 through 1974. A case was defined as a hospitalconfirmed CMS defect in an infanc born between January 1, 1970, and December 31, 1974, tp parents who were residents of Kanawha County at the time of the infant's birth. We reviewed hospital records to confirm diagnoses, rule out miscoding, and check each "* mother's place of residence. For each confirmed case, we selected 2 controls from vital statistics records. These controls, all with parents who resided in Kanawha County, were the first livebom infants without malformations born immediately before and after an infant with a CMS defect and were matched according to the following criteria: 1) month of birth, 2) race, 3) paternal education (number of years: 0-8, 9-12, and 13 and over), and 4) maternal age within 2 years. With the permission of the attending physicians, we interviewed by telephone the families of affected infants and 1 randomly chosen control. The following information was obtained: 1) history of previous pregnancies, including information about miscarriages, stillbirths, and children with malformations in their family, 2) 5-year residential history before and including the year of birth of the child in question, and 3) 5-year occupational history for both parents, including location of work and exposure to chemicals. Case and control families could not be interviewed blindly, since the families often remarked about either the malformation or the normal development of their child. The Kanawha County Health Department and the MI0SH staff assisted in locating families who had changed residences and/or jobs and those who did not have telephones. 2 GGC -jG3 1 35 RESULTS Except for 1974, Kanawha County rates shown in the BDMP for total CMS, as well as the particular defects anencephaly and hydrocephaly, were higher chan U.S. rates (Table 1). A decline in total CNS defect rates in Kanawha County was noted In both data sets (Tables 1 and 2). In both data sources, the total rates in 1974 were distinctly lower than those in previous years, although the decline was also evident in the 1973 vital records data. Earlier data were available only for 196S and 1969from vital records. In both years, there were fewer cases than there were In 1970. The highest BDM? rates for all defects occurred in 1971. Preliminary BD.M? data obtained for 1975, the year following the study period, showed that total CNS rates were similar to U.S. rates. Table 1 Reported Incidence* of CNS Malformations in Kanawha County^ West Virginia, and the United States Birth Defects Monitoring Program, 1970-1975 Anencenhalv Kanawha Co. ' U.S. 1970 1971 1972 1973 1974 Cases Rate Cases Rate Cases Rate Cases Rate Cases Rate 9.0 6 16.3 6 16.6 2 5.6 5.4 4.9 5.2 4.9 4 9.6 4.4 Spina bifida Kanawha Co. U.S. Hydrocephalus** Kanawha Co. U.S. 12.0 8 21,8 1 7.2 7.9 6.0 4 10.9 2 4.8 4.9 2.8 4 10.5 2 7.4 6.4 1 5.5 4 10.5 0 4.9 4.5 4.8 6.0 0.0 3.8 Other CMS Kanawha Co. U.S. 9.0 1 4.2 2.7 2 3.9 5.5 1 4.4 2.6 0 4.1 0.0 4.2 Total CNS Kanawha Co. 12 35.9 19 ' 51.7 11 30.5 11 28.9 6 14.4 U.S. 21.8 - 22.1 21.6 19.9 18.4 Rates per 10,000 total births Excludes cases with spina bifida Table 2 Incidence* of CNS Malformations Reported through Vital Records**, Kanawha County, West Virginia, Residents, 1968-1974 1968 1969 1970 1971 1972 1973 1974 Cases Rate Cases Rate Cases Rate Cases Rate CA3e9 Rate Ca53 Race Cases JuiCC Anencephaly 5 13.6 3 7.6 . 9 24.1 5 13.2 6 17.3 3 9.0 - 0.0 Spina bifida 6 16.3 3 7.6 3 13.4 4 13.2 2 5.8 - 0.0 1 3.0 Rydrocephalua 2 3.4 2 5.1 2 3.3 3 7.9 5 14.6 2 6.0 - 0.0 Other CNS - 0.0 - 0.0 - 0.0 1 2.7 - 0.0 - 0.0 - 0.0 Total CSS 13 33.4 8 20.3 16 42.8 13 34.4 13 37.9 3 15.0 1 3.0 *P.atee per 10,000 totsl births **Mrth and fecal death certificates. Vest Virginia State Departaenc of Health OGC C'J" Combined race's fori ' .n"ha County for the hospital andV statistics data are given in' Table 3, The rates re high from 1970 through 1972, v i a decline in 1973 and only 1 case reported in 1974, giving a 1974 rate well below expected. -Forty-seven confirmed CNS defect cases were in infants born to residents of Kanawha County at time of the child's birth. Families of 46 of these infants and of their matched controls were located and interviewed. Five infants' parents were not residents of Kanawha County at the time of conception and were excluded from further analysis. All mal formed infants were white, and females predominated (25:16), as usual in anencephaly and spina bifida cases. No seasonal variation was noted in the rates. Of the spe cific defects, anencephaly had the highest rate. Malformation Table 3 Confirmed Cases and Rates* of CNS Malformations, t Kanawha County Residents, 1970-1974 1970--19 74 1970 1971 1972 1973 Cases Rate Cases Rate iCases Rate Cases Rate Cases Rate 19 74 Cases Rate Anencephaly 23 13.0 9 24.1 5 13.2 6 17.5 3 Spina bifida 15 8.5 4 10.7 6 15.9 3 8.7 1 9.0 3.6 1 0.0 3.0 Hydrocephalus Other CNS 7 2 4.0 1.1 1 0.0 3 2.7 1 8.7 3 2.7 8.7 1 0.0 - 3.0 0.0 0.0 0.0 Total CNS 47 26.7 14 37.5 15 39.7 12 34.9 5 15.0 1 3.0 *Per 10,000 total births Age, Education, and Socioeconomic Index - Close case--control matching was achieved for paternal education, maternal age, and Hollingshead Index, an indicator of socioeconomic . etai.ua (table 4). Case ana control groups were also comparable regarding maternal edu cation (12.4 and 12.0 years, respectively). Paternal age was slightly older in the case group (27.3 years) than in the control group (25.8 years), but the difference was not statistically significant. Table 4 Age, Education, and Socioeconomic Index, CNS Defect Cases and Controls, By Malformation Matching Variables Total CNS Anencenhalv Soina Bifida Other CNS Cases Controls Cases Controls Cases Controls Cases Controls Paternal education* 12.6 12.8 12.6 12.2 13.7 14.1 10.9 12.0 Maternal age* 24.3 23.9 24.8 24.4 25.8 25.1 24.3 20.3 Non-matching variables Paternal age* 27.3 25.8 26.8 26.4 29.2 26.5 25.4 22.7 Maternal education* 12.1 12.0 11.9 11.9 12.7 12.5 12.1 11.9 Hollingshead Index Mean score Class *Mean number of years 47.5 IV 45.5 IV 49.3 IV 48.5 IV 4 38.9 III 38.6 III 58.3 IV 49.4 IV Generally, eases onl. ~or ols were similar in the speci'-^; '''feet categories. Among the specific defect categories, parents in the spina bifIda - -.'oup (both case and control) had the highest education and were the oldest; in the "Other CNS" category (mainly hydrocephalus), parents had the least education and were the youngest. Reproductive history - The total number of previous pregnancies of mothers in the case group (4'7) was almost the same as that observed for mothers in the control group (48). Other similarities included live births (cases 78%, controls'77%), fetal deaths (cases 22%, controls 23,%), and other children with congenital anomalies (1 in each group). The fetal death rates among cases and controls were higher than the rate of 16.1% reported by Warburton and Fraser (5). A family history of birth defects was reported by 11 of 41 families in the case group but by only 4 of 41 in the control group. Five "case" parents and no "control" par ents reported a family history of CNS defects. A possible explanation for the differ ence is that parental recall is affected by the birth of a child with a congenital malformation (6). Occupation - Two "case" fathers and 2 "control" fathers were employed in the PVC plant et the time their affected infants were conceived. Fathers of 3 additional controls had worked in the plant on a contract basis for a short time and therefore also had had possible exposures. None of the mothers in either group had ever worked at the PVC plant. One other occupational category is worth noting. In the case group, 2 mothers were employed in dental laboratories when they became pregnant, and 2 fathers had worked in dental laboratories before their infants were conceived. Parents in the case and control groups were asked about the location of their place of work at the time of their infant's conception. Only parents with a permanent v;ork location were counted, thus excluding workers such as truck drivers and salesmen. The homes of housewives and unemployed parents were considered to be their place of employment. On this basis, distance from work place to the PVC plant was calculated. Ko difference was observed between case and control groups for either parent regard ing distance of work place from the FVC plant. Residence - Parents' place of residence at time of their infant's conception was plotted on county maps, and we then calculated distances from the PVC plant. Table 5 presents the mileage from the plant by 1-mile increments up to 15 miles. Using a chi-square test at 1-mile intervals, we found no significant difference between the 2 groups. Matched pairs of cases and controls were also tested by using the matched pair t-test of significance; no differences were noted. Table 5 Residential Distance from PVC Plant,, Cases and Controls, By Malformation Distance from Plant (Miles) Total CNS Cases Controls AnenceDhalv Cases Controls Spina Bifida Cases Controls Other CNS Cases Controls <1 3100 32 <2 '4 4 0 0 3 4 <3 9 10 1 5 5 4 < 4 14 14 4 6 6 5 < 5 17 15 6 7 7 5 < 6 21 16 9 8 8 5 < 7 23 17 9 8 10 6 <8 24 22 10 10 10 9 <9 27 24 12 11 11 9 < 10 30 30 15 13 11 11 < 15 35 34 19 16 12 12 0' 0 10 31 43 43 43 43 43 44 46 40 TOTAL 41 41 21 21 13 13 7 7 5 Although no dlff. i,,, w,.4 . observed in measured distance vil concentric circles, 'within the 3-mih- ' ,t <ln: PVC plant, there were more case lamily residences in the area northe.u.i '/in' lvcr anc* morc control family residences in the area south of the river (l'ii,i.i). Fig! CONGENITAL CNS DEFECTS CASES AND CONTROLS, . CHARLESTON-SOUTH CHARLESTON, WEST VIRGINIA, AREA 1 , Using the PVC plant as the origin, we determined x and y coordinates for parents' residence at time of each infant's conception (case and control groups). Four cumulative groups were defined for both cases and controls based on distance of residence from the PVC plant: <2 miles, <5 miles, <10 miles, and-the total group. Case and control groups were then compared for statistically significant differences in their respectfvt-` cencers of gravity (average position), using multivariate extensions of the Wllcoxon matched-pairs signed-ranks test and the Kruskal-Wallis test (2). .. The matched-pair test was used to test the total group (all case-control pairs). Since in the disi .mee-defined groups case-control pairs were split, these 3 groups were analysed by the (unpaired) Kruskal-Wallis analysis of variance. The only significant difl,,r``nce was for infants in the case and control groups whose families resided within > miles of the plant (p <.02) (Table 6). V Table 6 . ^ ....... Significance Testing of Differences in Centers of Gravity, CMS Defect Cases and Controls Distance from plant______ . X* (2 Degrees of Freedom) . Probability <3 miles <5 miles <To miles All distances 8.72 3.06 1.09 0.91 <.02 >.20 >.30 >.50 The case and control parents who resided within 3 miles of the PVC plant at their child's conception had a higher socioeconomic status than those who resided more than 3 miles from the plant, as reflected by a class III Hollingshead Index; the remaining group had a class IV- The distribution of this group by date of birth was similar to the remaining group. There were 9 infants in the case group: 5 with spina bifida, 2 with congenital hydrocephalus, 1 with microcephaly, and 1 with anenccphaly. In at least 3 cases there was evidence of a familial component to the defect occurrence. One mother gave birth to 2 of the infants: 1 with spina bifida and another with aucnccphaiy. Another case mother reported that her sister had spina bifida, and a third mother had a cousin with a heart defect. Although familial components do not exclude an environmental cause, they do suggest the possibility of genetic causation. There was no difference in previous stillbirths or abortions between case and control parents who lived within 3 miles of the PVC Pi ant or between these parents and those who lived more than 3 miles from the plant. No difference was noted between the mean years of residence of case parents (1.9) and control parents (2.0) who lived within 3 miles of the PVC plant. Environmental Studies - Atmospheric and environmental data related to VCM and ether emissions in Kanawha County are limited. Data on VCM emissions provided by the South Charleston plant at the request of the West Virginia Air Pollution Commission are provided in Table 7. The data included the average amount (pounds per hour) of each year's emissions from 1967 through 1975 and the number of abnormally heavy emissions. On October 1, 1974, after the largest known single emission in the years 1967-1975, measurements were made by plant personnel in the comuni ty, The wind was blowing from the southwest, and the highest atmospheric VCM levels (grab samples) were to the northeast (.1 - .2 ppmv). The wind patterns in Kanawha Valley are variable according to the season of the year, time of day, and place of measurement. Monthly wind measurements also made at the plant indicated that the wind was blowing out of the south and west 42% of the time, and north and east 33% of the time during the months the Infants with CNS defects were conceived. 7 Table 7 Annual Average Vinyl Chloride Monomer Emissions, South Chariest on Plant, West Virginia Year Emissionsi (lbs/hr) Estimated Abnormally He. 1967 1968 1969 1970 1971 1972 1973 1974 1975 240 260 250 260 270 235 265 180 76 28 18 12 5 2 0 *Amounts ranged from 1,000-8,000 pounds, with an estimated average of 2,0C0 Source: Polyvinyl chloride plant, at the request of the West Virginia Air Pollution Commission Should the release of emission coincide with the southwest winds, then one might xpect that more emissions could be blown from the plant to the northeast. The West Virginia Air Pollution Control Commission measured suspended and settleable particulate matter, another indicator of wind direction, at various points within the community (Table 8). The reported levels were greater in the southwest, suggesting a prevailing wind from the northeast, Table 8 . Mean Annual Levels of Suspended and Settleable Particulate Matter, 1965-1975 Year - Geometric Mean Suspended Particulate Matter (nicrogram/cubic meter) 12 Arithmetic Mean Settleable Particulate Matter (tons/souare mile/month) 1 3, 1965 1967 1968 1969 1970 1971 1972 1973 1974 1975 1970-1973 1967-1973 205 171 150 136 102 105 123.2 160 113 131 107 107 93 94 114.5 92.2 133.2 82.3 68.6 47.6 30.0 24.0 18.0 57.7 62.0 68.9 63.6 35.4 35.9 24.0 24.0 15.0 18.5 13.3 38.1 *South Charleston High School (southwest) 2Fcderal Building, Quarricr Street (northeast) 3Uorth Charleston Fire Department (northeast) Source: West Virginia Air Pollution Control Commission 8 OGC 003138 '/ / DISCUSSION V "k The investigation in Kanawha County confirmed that an increase had occurred in total congenital CNS malformation rates in 1970-1974. Rates were highest in 1970-1972 aad dropped in 1973 to below national rates and in 1974 to only 1 confirmed case. Such a decline was not unique to Kanawha County. A similar, though less marked, trend was also present in BDMP data for other parts of the country. Furthermore, preliminary 1975 BDMP data on CNS defects for the county were higher than 1974 data, suggesting that the apparent low incidence for th3t year may reflect the variability of small numbers. As in the Paincsvillc study (3), there were no differences between case and control groups regarding parents' possible occupational exposure to VCM or to other environmental agents at time of their child's conception or for 5 years before conception. On this basis, there was no evidence that the high CNS defect rate for Kanawha County was related to parental occupation in industries producing PVC or other chemicals. - A difference between the locations of residences of the case and control groups vithin a 3-mile radius of the plant was noted. Although approximately the same number from each group resided within the 3-mile area, those in the case group tended to live east of the plant, and those in the control group lived across the river and south of the plant. Such a pattern night be chance distribution, or it could be related in some way to an environmental exposure limited to the part of the city lying east of the plant. Aside from a slightly higher socioeconomic status, there was nothing to distinguish the families of cases and controls from other families who lived within the 3-mile area. Furthermore, there was no difference in the distribution of the types of defects or the years of birth (or conception). Since the investigation was undertaken because of a possible association between the high CNS defect rates observed in Kanawha County and the presence of a PVC plant, we gave particular attention to the pessibili-ty that the cluster may have been caused by increased VCM emissions. To explain the case cluster on the basis of a teratogenic effect of atmospheric \ S. VCM exposure, one would also expect an approximate correlation between a decrease in atmospheric VCM levels and a fall in CNS defect rates. The decrease in CNS rates which occurred in 1973 preceded the decline in measured VCM emissions and lagged considerably behind the overall decrease in particulates noted in the late 1960s. This investigation did not reveal an association between the case clustering within 3 miles of the plant and exposure to VCM or other chemicals. Available data suggest that atmospheric and meteorologic conditions along the Kanawha River are variable. To propose that some wind-born teratogen had settled in a particular location in the community, one would have to postulate also the timing of plant emissions with the appropriate wind direction and other atmospheric conditions. No data are available to reconstruct such circumstances. Furthermore, it must be noted that over 100 compounds other than VCM have been associated with emissions from the plants in the Kanawha Valley area. One Study estimated that 52,457 tons of organic compounds, including VCM, were emitted each year by Charleston chemical plants (8). Some of these compounds have heen identified as toxic to animals and humans; their individual and combined teratogenic potentials arc not known. 9' ji. V Although there was a cluster of CNS defect cases to the east of the PVC plant in Kanawha County, the role of VCM or other compounds in explaining this cluster is Conjectural at present. REFERENCES 1. jCcnter for Disease Control: Congenital Malformations Surveillance, Annual Summary 1974. Atlanta, CDC, 1975 2. Environmental Protection Agency: Scientific and Technical Assessment Report on Vinyl Chloride and Polyvinyl Chloride. Issued June 1975 '3. Edmonds LD, Falk H, Nissim JE: Congenital malformations and vinyl chloride, lancet, 1098, Nov 1975 4. Hay S: Variables in underreporting of clefts on birth certificates. Public Health'Rep 82:935, 1967 5. Warburton D, Fraser C: Spontaneous abortion risks in man: Data from reproductive histories collected in a medical genetics unit. Am J Human Genet 16:1, 1964 Fraser.FC, Warburton D: No association of emotional stress or vitamin supplement during pregnancy to cleft lip or palate in man. Plastic and Recon structive Surgery' 33:395-399 , 1964 7. Puri ML, Sen PK: Nonparametric Methods in Multivariate Analysis. New York, John Wiley, 1971, pp 184-193 '8. Department of Health, Education, and Welfare: Kanawha Valley Air Pollution Study, Washington Government Printing Office, 1970 Larry D. Edmonds, M.S.P.H. Birth Defects Branch Cancer and Birth Defects Division Bureau of Epidemiology \dXJl*ur>7 Carol E. Anderson, M.D. Birth Defects Branch Cancer and Birth Defects Division Bureau of Epidemiology J. 'William FlyntJ, Jr.,\T/.D. Chief, Birth Defects Branch Cancer and Birth Defects Division Bureau of -Epidemiology Clark W. Heath, Jr., M.D., Director Cancer and Birth Defects Division Bureau of Epidemiology DISTRIBUTION Mailing keys 53-1,2,3 William L. Cooke, M.D., State Epidemiologist, State Department of Health, State House, Building 3, 1800 Washington Streec E., Charleston, West Virginia 25305 Joseph Carney ."Director, Department of Vital Statistics, State Department of Health, E-U_ild.i.ri2 3 1800 Washington Street ., Charleston, West Virginia 25305 Page H. Seekford, M.D., Director, Kanawha County-Charleston Health Department, 1426 Kanawha Boulevard E., Charleston, West Virginia 25301 Carl G. Beard, II, Director, West Virginia Air Pollution Control Commission, 1553 Washington Street E., Charleston, West Virginia 25311 P.alph Rhodes, Director, Toxic Substances, Environmental Protection Agency, Region III, Sixth and Walnut Streets, Philadelphia, Pennsylvania 19106 John Finklea, M.D., Director, National Institute for Occupational Safety and Health, . 12420 parklawn Drive, Rockville, Maryland 20852 Bobby F. Craft, Ph.D., Deputy Associate Director for Cincinnati Operations, National Institute for Occupational Safety and Health, U.S. Post Office Building, Room 543, 1014 P.roadway, Cincinnati, Ohio 45202 Peter Infante, D.D.S., Dr.P.H., Biometry Branch, Division of Field Studies and Chemical Investigations, National Institute for Occupational Safety and Health, U.S. Post Office Building, Cincinnati, Ohio 45202 10 v k Robe .re W. Miller, M.D., C.^af, Epidemiology Branch, National .oncer Institute, National Institutes of Health, A-521 Lnndou Building, Bechesda, Maryland 20014 Laurence A. Plumlce, M.D., Medical Science Advisor, Environmental Protection Agency, 401 "M" Street, S.W., Room 905, West Tower (RD 67B), Washington, D.C. 20460 Arnold H. Spellman, Manager, Project Development Group, Information Services, Commission on Professional and Hospital Activities, 1968 Green Road, Ann Arbor, Michigan 48105 Gabriel Stickle, Vice-President for Program, National Foundation-March of Dimes, 1275 Maaaroncck Avenue, White Plains, New York 10605 Daniel G. Seigcl, S.D., Chief, Biostatistics Section, Epidemiology and Biometry Branch, National Institute of Child Health and Human Development, Notional Institutes of Health, Building 31, Room 2A10, Bcthesda, Maryland 20014