Document wDd2Y2J0kNx7YzpYprrvR5QqV

p5, SoiUe4s. thOecstio1tu9j7r1y ns' of vein size and :ure technique preministration in this )f George Buckaloo, Lowry Pei is grate- JS fcmndynamie alteraof pentobarbital so>s. Amer J Physiol Jinodynamic changes im pentobarbital an>1 210;817-820, 1966 II: Redistribution of odium pentobarbital ey. Amer J Physiol WK, McCannnoml pental on peripheral sioujgy 22,523-528, fleet of certain een. on the small blood rabbit. Aneshiem- ; NM, Chambers RD; `gents and relaxant* s JjLjSandison Cirri; 3^B:98-112, 1956 `^PRovenstine EA; esthesia on behavior bed. Anesthexiov.- ff. Martz RC, et ah ol on subcutaneous Appl Pharmacol 14; C, Nicoll PA: Neural sel response to hem* ietized bat. Amer I D70 1 Anesthesia. Phils* it, 1963, p 280 ct of barbiturates on lanad Anaesth Soc J mechanism of shock of barbiturates, mudrugs, with observj* treatment. Amer ] of temperature contractile activity xde. Bibl Anat 9; ct of induction f ral haemodynamic'* 215, 1967 it effect on muscle 1 sodium in the c.il. --664, 1963 Anesthesia, Pregnancy, and Miscarriage: A Study of Operating Room Nurses and Anesthetists Ellis N. Cohen, M.O.* J. Weldon Bellville, A4.D.,* Byron W. Brown, Jr., Ph.D.f A survey was undertaken to evaluate the posjjllc relationship between spontaneous mfccar* f;je and exposure to die operating room. The dJjy was carried out by personal interview ofJ17 c,gating room and _92 general duty nurses. , Reu](s indicate tliat during the years 1960-1970, i).1 per cent of pregnancies in operating room uses ended in spontaneous miscarriage, comp.rii with only 8.8 per cent in the control group, A similar pattern was observed in a second Study SO anesthetists and 81 physicians practicing in i/mlties other than anesthesia. During the six* .j period 19G5-1970, the anesthetists evidenced f ;3",8 per cent spontaneous miscarriage rate, com* fc pared with 10.3 per cent in the control group. ' Miscarriages occurred earlier in both operating ' twm nurses and anesthetists compared with their ! t.Jrol groups (eighth versus tenth week). These , (..alts suggest a fetal lethality, possibly due to , anesthetic gases, although the studies do not j i-jirainate any specific anesthetic agent, nor is a t.JiC-dlcet relationship established. (Key words: Wiila anesthetic gases; Spontaneous miscarriages; l.l.l lethality.) creased spontaneous miscarriage rate and to an Increase in the incidence Of fetal anomaliesd3"13- TBe present study was directed towards this significant question. Method Two groups of women working in the op erating room were surveyed through a ques tionnaire designed to elicit information about numbers of pregnancies, miscarriages,! contra ceptive techniques, birth defects, etc. The first study was conducted by means of per sonal interviews of 159 married operating robm and general duty nurses between the ages of 25 and 50 years, employed in three large general hospitals in Northern California. The key questions were purposefully buried within a long detailed questionnaire, so that) the nurses were unaware of the major purpose ' of the study. This precaution was necessary) to try to avoid prejudice in response, as Wellj as to avoid any undue personal concern on thej --\ part of those being interviewed. Nurses in-/ Tn demonstration that inliaiation anesthet-1 terviewed were selected at random, although vht pnrodnuoce tweruatogenic responses in- both ' an eflort was made to interview all duty per iso and mammalian species 1"s has raised sonnel Working on a given nursing station or f;'wn as to their effects in an estimated l floor. Questions were carefully phrased and " ,600 women in the United States who an- 1 asked in a fixed format. All interviews were !`--ly undergo surgery and anesthesia during/1 carried out by two observers, one a nurse, the t iiUon.. 1 Recently it has been recognized other a psychologist. second group of women is also exposed The second group of 131 women included <-e effects of inhalation anesthetics. These gg physicians, aged 25-50 years, whose spe- nurses and anesthetists who work daily <i operating rooms contaminated with trace ':r-cvLitiations of anesthetics.11,13 Several prek-n.iry reports suggest that such continued '""gride exposure may be related to an^in- cialty practice was limited to anesthesia. An other group of 81 physicians in specialties other than anesthesia served as controls. After completion of a mail questionnaire by the participants, they were instructed to open a hofessor of Anesthesia. 'Jtessor of Commnuity and Preventive Medif (BiostatisWcs). t C: . ^I0m the Departments of Anesthesia, i an<l Preventive Medicine, Stanford 1 ;i ruin- Sohool of Medicine, Stanford, CalifoTi' i`t * a- Accepted for publication April 9, ' V.-.^PPorted by National Institutes of Health, * "Oject No. CM-12527. sealed envelope which explained the purpose of the study. Additional comments were so licited, but the participants were requested not to alter their original responses. All data were entered into an IBM 300-50 t Spontaneous loss of conceptus up to the twentieth week of pregnancy. 343 ,r ,i . -tt- ' >}7\ 11 * i m,i ij p;y. r i ASI 000018503 344 COHEX, BELLVILLE, AXO BROWN V Jj, No 4, f>, ^ Ur.,thWoy y jj, .V* 4, Ot Table 1. Obstetrical Information fur 179 Operating Room and General IJtitv Nurses during the Years 1960-1970* opItiTooHitnifie Nurses GDenuetryal Nurses Number in group f>7 02 Mean age (years) 30.0 Years iu ihe operating room (mean) 3.0 0 Number of ; 30 34 I'racliftng contra- ecpf ion i\ 4.i per cent m per c<*nt Number of living rhilihon 20 31 Xuinb(*r of inis- rarriagos Miscarriages''' pregnancu^ ___ _____ ______ 10 1 20.7 percent I --- - -- , --_ >1 ,3.0 per cent - - - -- * All nurses were married and were between the ages ot 2.1 and lit rears. 'l- Mini, 2. Med leal and (iv hernlugic 11 Mi u u- nf Opetaiing 1 bmm and t leneral lnu\ AurM`- l ...... lUlJg 1 < M'TUT ti If i *t iftt Drift' Nnrcs | N ur-v- Kegular periods I ivsincnorrlica llypothvmidi'in Nausea during pregnancy Toxemia Smoke 1 )nnk Ilegular exercise Miscarriage by nurse's mother Week of miscarriage | 7S per cent , S7 per cent I :M per cent 29 [au cent 1 12 per cent S per cent ,'!7 per rent 20 per cent 0 per cent j 2 per cent 30 jjer cent , 30 per cent 7 4 per cent 1 70 per cent 77 per cent I 09 per cent 04 per cent. | 79 per cent 8.3 j I Od) Taupe 3. Comparative Pediatric Histories of Children from Operating Room and General Duty Nursing Groups Month sat Month walked Month talked Heart disease Operation OMlflrpJ) of Oporafint: Room Nurses 7.9 11.3 13.4 8 per cent 10 per cent Children of Genera! Duty Nurses 6.1 11.7 14.1 3 per cent 6 per cent Tabi.f. 4. Obstetrical Information for |:ji Anesthetists and Other Phyniriaiu Practicing during -1970* 1 | Anesthetists 1 OhVyns.K,,1i^ Number in group 50 SI Menu age (yearn l | 39.fi 30.8 Year- iu 1 ho op<*r ititig : room tin<*:in' o.G 0 Number of prmunnoh ; 37 7S IVarfifinfr eon Ira (option 1 00 per cent 0(J iK?r ipt, i Number of living riiiMirn 23 52 Numhot *f tni-i- ! run i.ui'f'- 1n 0 Migran proRtumrit*-1 37.3 percent 10.3 perfra * All pliV'ieians were married and Were helm*; the ages of 2.7 to 711 years. Tun i 7. Medical and Gynecologic Historic,nf Anestheti-i,' and General Physicians Xfie^thetulu (Irr.rr^i PMciw liegulu pet i.ids 1 K sineiioirhea 1 lypol liyroidism Nausea during pregnane Toxemia W eek of miscarriage ] ,S2 per cent 91 per i-ei i IS per cent 11 per ce- 1 12 per cent 13 per re: 74 per cent 54 per cei | 4 per cent .) pmti : 7.7 9.5 health, .smoking I he most strikir in the sj die operating ap.r per cent ol page, compared general duty tv nstically sigrifli exact test. Of mi ses had inor non practiced}, miscarriage rate !i\ mg children j two groups dur Since it prove exactness the J mg room expt nancies, any ex Ittiing the five assigned the tv During the fix cioup averaged ,dax merit in tht The medial' >1 the two gr table 2). Of the opera tine 'xith their implantation "1 the pregnarn xteek of gestato `ainpajed with 'mrsex. \'r, obx ''hie tor thir t computer for storage, retrieval and sGliriu evaluation. For the purpose of analysis, c signment to the operating room group in- l cated any exposure to the operating nvr within the past five years in the case ol i'1, nurses, and within six years for the ph'1 cians. Only data relevant to these time p riods were considered. Findings and Comments Selected information obtained from the c, j eratiiig room and general duty nurses relate t to the immediate past five-year period, 1** 1970, is presented in table 1. The mean M of the operating room nurses was siig!,'| higher (3.4 years), but otherwise the ,l| groups were comparable in terms of Some que *`l'le phvsici U't children "inamed did n.liie 3). ' I'k' sieal peril ''aIked), mer defer '"''re deteetei "'l: is not uiit would bf h'mnces, if p, I)ata cleri bi-veyed bv r ' P(` cent a *' hible 4. I AS I . ,'t 000018504 V 35, NoAn4c,stOluscitolirga!,j VttToct 1971 ANESTHESIA, PREGNANCY, AND MISCARRIAGE 345 ,1 Information for 131 f Other Physicians ing 1963-1970* health, smoking, drinking, exercise habits, etc. The most striking dillercnce was the large inicase in the spontaneous miscarriage rate in (|)g operaling room nurses. In this group, Anesthetists General ; $.7 per"cent of pregnancies ended in misearPhysiciaoj n.ige, compared with only 8.8 per cent in the .0 81 " ' ,'cneral duty nurses. This difference is sta- 9.6 36.8 ihtically significant (P -- 0,045) by Fisher's 5.0 0 7 58 0 per cent 69 per cent '3 52 1 6 7.8 per cent 10.3 per cent aact test. Of interest, the opeiuling room i.uiscs had more pregnancies (less contracep:ion practiced). Thus, despite their increased miscarriage rate, the same average numbers of aving children per muse were produced in the luo groups during the five-year study peiiod. Since it proved impossible to determine with ivictness the duration of effect of an updat ing room exposure upon subsequent preg- nicies, any exposure to the operating rooms narrieti and were betwen ihning the five-year study period aibitiarils' resigned the nuise to the expeiimental group. Dining the five-year peiiod, muses in this r?ynecoluftic Histories uf .<onci`fil Physicians ^^^Hnthetiiits General I'hysiciiitu 82 per cent 91 perceni 18 per cent, 14 per ecu! ! 12 per cent 15 perron; 54 per cent 54 per ctnit 4 per cent o per ctMii 7.5 9.5 retrieval and statistic.!1 sump averaged 77s pei cent time full-time cmlament in the opei.iting rooms. The medical and gvnecologic backgrounds "f the two groups id muses weie similar ,table 2). Of inteiest, a high pciccntage ol the operating room muses esp'eiienecd nausea 'Itli their pregnant a s. suggest.ng atleipiate implantation. On the milage, time nt less 1 the pregnanes' minimi timing the eighth "ret of gestation in tin updating loom gnmp. 1 '.'mpared with tilt' tenth sseek in the contiol 'uiscs. Noohsimis hcirditniv lat tins lesp.mI'lo for this diilei cnee \s ere apjiaient, .tutl 'mihir miscaniage i.ites wore obtained Im withers of the nurses m the two gmups. lorpose of analysis, a'- Some questions svere designed to elicit pos- iting room group in1'1' 1110 physical differences, betsveen the suts iv- ) the operating roy'1' ears in the case of tin1 ls children of (lie two groups, but the data btained did not establish aiiv such differences c years for the pl'fe' I "'Me 3). Thus, no difloiences in lesels of vant to these time p1- "deal performance i month sat up, or month "`Iked), mental acuity (month talked), con- Comments ' n`tul defects (heait disease, surgery, etc.) ye detected among the groups. This find- btained from the 1'" 1 duty nurses relate" 'e year period, I9W'' lei. The mean nurses was slig'1'1' > is not unexpected, since a much huger surl> "ould be necessaiv to establish such difrfnces, if present. ^Jta derived from tile two physician groups ^etecl by mail questionnaire (response rate : otherwise the t" in terms of gen* ,, ccnt after two mailings) aic presented 5Je4. In these studies, the phcsician an Table 6. Comparative Pediatric Histories of Children from Anesthetist and General Physician Croups Children of AnegthetLaU Children of General Physicians Month sat Month walketl Month talked Congenital anomalies 5.3 10.3 15.2 2.0 per cent o.G 12.1 16.8 4.2 per cent esthetist gioup had a 37.8 per cent spontane ous miscarriage rate, compared with 10.3 per cent for the control physicians (P = 0.0035 by Fisher's exact test) (table 4), Except for this finding and that of extensive exposure to the operating room during the six-year peiiod, the two groups appeared comparable (tables 5 and 6), Ol pai titular interest was the observation that loss ol the Ictus aceiaged almost two weeks earlier in the anesthetist group. The dose similaritc of these data to those obtained in the nurses is appaient. Again, no differ ent os between pei fonnanees of the survicing ehihlien piotlueed 1>\ the two gmups ol phyMt laiis were found t table 6). Discussion lla ie e.m be little dmiht that the spontane ous miscaniage iatr is signilicantly higher ill both updating loom muses and anesthetists compared with their control gmups. How es er, the precise eliologic factors involved are difficult to define. It is possible that the slightly greatei ages in the experimental groups compared with their controls (34.3 vs. 30 9 years for the muses, anti 39.6 vs. 36.8 years lor the physicians) might have influenced the mtes of spontaneous miscarriage observed. On the other hand, an analysis of age incidence of abortion in 26,f91 piegnancies indicates that only minor variations in miscarriage rates arc usual at these age levels,16 No other differ ences between the control and study groups were appaient except the extended periods of time spent by the latter in the operating rooms. The data suggest that there is a significant difference between the spontaneous miscarriage 5 During the period 1965-1970, the phvsieians in this group averaged 3,6 years' work in the op erating room. l P ll !l IflUIJJILfJil AS I 000018505 f ! 4" fej l, ia c 1' 1)1 h r 11 346 COHEN. BELLViLLE, AND BROWN V JS, Xa 4, Oct 13,'t rates in the two groups, and that this may be related to something in the operating room environment, possibly the trace concentrations of as'-rihctic-gases present. A somewhat higher miscarriage rate in the physician anes thetist group rs. the operating room nurse group may rcSect tlie former's exposure to the higher gas concentrations adjacent to the an esthesia machine.11 Teratogenicity of the volatile anesthetics in the experimentshimimal has been wellestablished, although in most studies the anesthetic agents were presided in high concentrations and during short periods of exposure.1-s The suggestion that results of the present study re flect a fetal lethality of the anesthetics is sup ported by an earlier mean time of miscarriage in both operating room groups (two weeks earlier than controls). This is a common ef fect of teratogenic drugs. The similarity of the spontaneous miscarriage rates in the moth ers of the operating room nurses and the gen eral duty nurses helps to rule out the likeli hood of a hereditary tendency toward more spontaneous miscarriages in this experimental group. Since a number of measurable physio logic effects, e.gT headache, nausea, enzyme induction, have been shown to result from prolonged "exposure to trace conccritrations df certainTncstfceScs,11 it seems 'reasonable to consider a possible relationship between the., increase in spontaneous miscarriage rate and other physiologically influencing .(toxicologic) factors. One must remember, however, that factors unmeasured by the present study may also have contributed to the results observed. It is possible, for example, that periods of un usual high stress in the operating room, spe cial sprays and solvents used in the operating room" (antiseptic- solutions, propellants, adhe sive Solutions, etc:),"as welTariotherlinkupwn factorsTriay be incriminated. It is even pos sible that biases fn selection of study subjects or in study methods could have caused the differences reported, though great efforts were made to minimize bias. The similarity of the results of the two separate studies is reassuring. To confirm whether the trend revealed by these surveys is real, a number of additional studies are indicated. Cytogenetic examina tion of the abortuses of operating room per sonnel would help define genetic damage and contribute to our understanding of fetal ]-. thality.18 SecoDd, expansion of the presr-t study to include an annual survey would prr. mit us to evaluate the effects of adrrjua;, scavenging precautions upon the rates of spe-. tancous miscarriage. If, over a period rr years, following llie Institution of dean air fa the operating room, the miscarriage rate wer_ reduced to tliat of the control group, we would be more confident of a relationship to the trace anesthetic concentrations formerly pres ent in the operating room. Third, we believe that a large-scale survey may be radicated. Tins would look at the questioned whether there is an alteration in the male-female in fant ratio among wives of anesthesiologists, as well as among yvomery working^ in the operat ing room. Furthermore, a large survey cce'd provide valuable information about the inch dencc of congenital deformities among oilspring of operating room personnel. Finally, it has been shown that certain primates arc satisfactory models for studying the terato genicity and fetal lethality effects of drugs.1 Studies with rhesus monkeys or babooes c posed to chrome concentrations of the irdi vidual anesthetics, or anesthetics in combirntion, would help determine which anesthetic may be implicated in this syndrome. Our earlier study of pollution of the op crating room by anesthetic gases "indicated that trace concentrations oFTialothane v/crc present in the operating roonTatmosphere rri were "measurable in the exhaled air of b, anesthetists and nurses.17 Since jconceriiri tions ot nitrous o'xide. ether, and presume! y other anesthetic agents, are also present in (li; operating room atmosphere, one cannot a.v ciate the observed increase in spontaneous y. carriage rate with any particular nneriHk agent. In the preliminary report by Vaism i; et al. TM the only anesthetics used were nilro'1' oxide and diethyTether. thus, until mn' C. or~disprove.n. all volatile agents presrnt injb. operating room must remain suspect? ' Of practical importance is the recent der' onstration that contamination of the .GpuflV room by anesthetic gases could be rerlundj ' approximately 10-lO^per cerrt (or Icls) '' tliat- previouslypresent throughjho use 1 scavenging svstems. Total elimination ol ^, waste gases is, of course, the goal, nd s?)'1'' ASI 000018506 I itHthtslology \ V 35. No 4, Oct 1971 ANESTHESIA, PREGNANCY, AND MISCARRIAGE 347 be attainable. In the meantime, we recom ent >er- iate on- of r in -'ere >uld llie ireslievc itcd. illler i ins, as ierat* jould inei- mend that all possible corrective measures be initiated as rapidly as possible. In addition to installing adequate scavenging devices, it would seem prudent to restrict the assignment of nurses or doctors planning pregnancy to those operating rooms where volatile anes thetics either are not being used or have been itinoved. Although absolute indications for such pre cautions are not available at the present time, they are reasonable measures and readily un dertaken. On the other side, there remains the likelihood that trace anesthetic concentra tions do produce fetal lethality in chronically exposed female personnel. Under such cir cumstances, we choose not to be complacent, and our institution is proceeding towards rapid elimination of this potential hazard. C offnally, Addendum s are ei ato* ugs.1* li:> ex- indi- Subsequent to the completion of this study-, a report by Askrog and Harvald has indicated simihr findings. (Teratogen effekt af inhalationsaaestetika, Nordisk Medicin 16:498-500, 1970.) lliis survey included 754 persons in 80 anesthena services in Denmark, and indicated that spon nbina- taneous abortion and perinatal death occurred in j .`pproximately 10 per cent of pregnancies prior to W e op- ! I employment. Following employment in the anes1 ihesia service, this percentage rose to 21 per cent. Additionally, more female infants were horn to licaled >. were re and ,f both .centra- personnel working in the operating room, and es pecially to the wives of "male anesthetists. This oula suggest"that chronic exposure to anesthetics induces male-lethality-. We did not observe this in our study, although male lethality with drugs dut are embryotoxic has been reported mnably t in the >t assn>us misesthetic r^Tlre authors gratefully acknowledge the help of In. Lynne Bellville and Mrs. Sylvia Cohen in rwiducting personal interviews with the nursing Mrs- Marie Hu was responsible for comi ruler programming. v'aisni-ia . nitron-1 proven t in tl' References h Anderson NB: The teratogenicity of cyclopro pane in the chicken. Akksthesiouicy 29: , 113-122, 1968 rink BR, Shepard TH. Blandau HJ: Terato- nt den*iperatint lucrd less' >' Kenic activity of nitrous oxide. Nature 214, , 140-148, 10G7 t5?rii f'ln^ HR: The teratogenicity of alothane in the rat. Anesthesiology 29: - 1167-1173, 1968 ector GHM, Eastwood DW; The effects of a atmosphere of nitrous oxide and oxygen n the incubating chick. Anesthtsiolocy 2a:109, 1964 5, Smith BE, Caub ML, Moya F: Teratogenic effects of anesthetic agents; Nitrous oxide. Anesth Analg 44:726-732, 1965 6. Smith BE, Gaub ML, Lehrer SB: Teratogenic effects of diethyl ether in the chick embryo, Toxicity of Anesthetics. Edited by BR Fink. Baltimore, Williams and Wilkins Co., 1968, pp 269-278 7. Snegireff SL, Cox JR, Eastwood DW: The effect of nitrous oxide, cyclopropane, or halothane on neural tube mitotic index, weight, mortality and gross anomaly rate in the developing chick embryo. Toxicity of Anesthetics. Edited by BR Fink. Balti more, Williams and Wilkins Co., 1968, pp 279-293 8. Smith BE, Gaub ML, Moya F: Investigations into the teratogenic effects of anesthetic agents; The fluorinated agents. Anesthesi ology 26:260-261, 1965 9. Shnider SM, Wester GM: Maternal and fetal hazards of surgery during pregnancy. Amer ) Obstet Gynec 92:891-900, 1965 10. Mellin GW: The fetal life study of the Columbia-Presbyterian Medical Center. A pro spective epidemiological study of prenatal influences on fetal development and sur vival, Research Methodology and Needs in Perinatal Studies. Edited by SS Chipman. Springfield, 111., Charles C Thomas, 1966, pp 88-117 11. Linde HW. Bruce DL: Occupational exposure of anesthetists to halothane, nitrous oxide, and radiation. Anesthesiology 30:363368, 1969 12. Haiku B, Ehmer-Samuel H, Thomason M: Measurements of halothane in the atmo sphere of an operating theatre and in ex pired air and blood of the personnel during ioiitinc anesthetic work. Acta Anaesth Seand 14:17-26, 1970 13. Vaisman AI: Working conditions in surgery and their effect on the health of anesthesi ologists. Eksp Khir Anest 3:44, 1967 14. Askrog VF: Teratogenic effects of volatile an esthetics. Abstract, Third European Anes thesiology Conference, Prague, 1970, no. 13/01 15. Leucz L, Nemes C5, Berta L: Fsychische Belastungen und Morbiditiit der Aniisthetisten. Abstract, Third European Anesthesi ology Conference. Prague, 1970, no. 63/02 16. Javert CJ: Spontaneous and Habitual Abor tion. New York, McGraw-Hill Book Co., Inc., 1957, p 209 17. Whitcher CE, Cohen EN, Trudell JR: Chronic exposure to anesthetic gases in the operating room. Anesthesioi,ocy 35:348-353, 1971 18. Carr DH: Chromosome studies in spontaneous abortions. Obstet Gynec 26:308-326, 1965 19. Wilson JG, Gavan JA: Congenital malforma tions in nonhuman primates: Spontaneous and experiineut.illv induced. Anat Hec 158: 99-105, 1967 1{<1 i 1 ywi3jijAS I 000018507 1098 /M CdX TttF I ANCH, N(1VFM|11R 29 1975 ANl NLFPHAI I S AND SPINA Hint), IN OHIO SrAIF A Nil IN` PAlNIMni f IIOM IIAF, OHIO * Per 10 000 total white births. the discrimination of vector of means can be tested for signifi cance. A high discrimination between the malformation group and its mntd'cd controls appeared within the first 10 of the 24 variables (see accompanying figure). Even with 8 variables a significant discrimination of both groups at 1*7 level was found. The discrimination of both groups was also possible without the two factors "abonions/stillbirths in mothers family" and "hours of daily work". So, even in a sample with factors each not discriminating significantly between both groups, the linear discriminancc analysis makes it possible to discriminate between the malfor mation group and the matched controls. This might mean that the malformations in our sample can be explained as caused bv the combination of many minor factors (extrinsic and intrin sic). IrvMMut fur Humangenctik, Khntkuni dcr Johann Wolfgang, (Jocthc- \ 'mvcrsitat, Frankfurt am Main, federal Republic of Germany. J. Kl FINFliRFCIII K.-1I. Dmifnhakdt CONGENITAL MALFORMATIONS AND VINYL CHLORIDE Sir,---In March, 1975, a significantly increased rate of ceniral-nervous-system (c.n.s.) malformations was reported in 3 Ohio communities where polyvinyl chloride (r.v .c.) polymeris ation plants are located;1 the increase was not uniform and appeared more prominent in the Painesville area. There are two p.v.c. plants in Painesville, one of which began operation in 1949 and the other in 1967. The birth-defect rates were computed from birth-certificate data for 1970-73 and were compared with similar data for the entire State of Ohio. This study suggested a relationship between the higher rates of c.n.s. malformations and the increased risk of exposure to vinyl chloride in these communities. lly analysing data collected through the Center for Disease Control's hospital-based birth defects monitoring programme (n.n.M.p.),-1 we examined this relationship. Two hospitals parti cipating in the b.d.m.p. are located in cities with polymerisa tion plants: one is in Pennsylvania, the other in Painesville, Ohio. c.N.s.-malformation rates for white infants born in these two hospitals in 1970-74 were compared with the rates for wliitc infants in each State. No increase was seen in the Pennsjlvania hospital, but an increase, primarily in ancncephaly and spina bifida, was noted in the Painesville hospital for the toTaTfimeT970-74 (see table). The b n.M.r. hospital data for Painesville were compared with birth-certificate data from the Ohio department of health and 1 additional case not included in the b.d.m p. report wa, added, bringing the total to 15. 30 controls, the first normal white infant born before and after each case, were selected from the hospital birth registry. Medical records for cases and controls were reviewed to confirm the diagnosis and to obtain, among other data, the parents' occupation and residence at the time of the infant's birth. In addition, parents of 14 of the affected children were interviewed about previous occupations and residences. The study revealed that none of the interviewed parents of affected infants had ever worked at either of the two P.v.c.-polymerisation plants in Painesville (1 set of parents could not be located, but records show that they did not work at these plants at the time of their infant's birth); 2 of the fathers of controls lied worked at one of the plants at the time of their infants' births. None of the parents in either group lived within 2 miles of the two plants. The chi-square test of significance was used in comparing the distances from residence and work place of mothers and fathers to the p.v.c.. plants for cases and controls. Comparisons were made at distances of 1 to 10 miles, in 1-mile increments. A significantly larger proportion of control mothers than case mothers wwked (TnchTding housewives) wjthih"a_I0:m'ite_fa(rftJS" oTthe p.v.c. ptantraf the T557? confidence level. This is probably a chance Occurrence among multiple comparisons. Vinyl chloride is a known carcinogen,1 and concern has arisen over its possible teratogenic effects. This concern stem, from recent studies which have shown (a) an increase in muta genicity in bacterial assay systems34 5and (b) increased breakage in chromosomes of p.v.c.-polymerisation workers.1 I he Ohio Department of Health study1 is the only report that has sug gested that vinyl chloride causes birth defects in man. Although the follow-up study reported here confirmed a modefatOtncreaseTn c.n.s. malformations in Painesville, Oiuo, no association was found with vmybctfloffiJe exposure. Cancer and Birth Defects Division, Bureau of Epidemiology, Outer for Disease Control, Atlanta, Georgia 30333, U.S.A. Larry D. Edmonds, Hfnry Falk Jack E. Nissim LATE COMPLICATIONS OF TUBAL LIGATION Sir,--Unlike Mr Darwish and Dr Saafan (Nov. 15, p. 975), we are uncertain as to the xtiology of the late sequels of female sterilisation, which they refer to as menstrual irrepu larity, but in our study it will be noted we looked specifically at menorrhagia and dysmenorrheea. It seems unlikely that a P' }chosomatic cause could be present when two different ted 1. Infante, P. in Proceedings of the Conference cm Occupational Carcinogenesis at the New York Academy of Science, 25 March, 1975. New York (in the press). 2. Center for Disease Control. Congenital Malformations Surveillance Annual Summary 3974. Atlanta, 1975. ! 3. Center for Disease Control. Morbidity and Mortalitv Weekly Repori, I 9, 1974, p, 49. 4. Kannug, U. Johansson, A., Ramel, C. Wdchmeister, C. A, Atnf'to. 1974,3, 194. 5. Puttes-Cravioto, F., Lambert, 0., Undstcn, J, Lancet, 1975, i, 459. , AS I 000018508