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I Smoking and Pregnancy Maternal Smoking I. Low Birth Weight Infants II. Neonatal and Perinatal Mortality III. Spontaneous Abortioa IV. Congenital Malformations V. Stillbirths VI. Sudden Infant Death Syndrome

( . C Low Birth Weight Infants Claims have been made that smoking in pregnancy leads to adverse effects, particularly that infants of smokers are more likely to have lower birth weight (LBW)f infants. Other claims have been made that smoking during pregnancy causes intrauterine growth retardation spontaneous abortion, premature birth, stillbirths, congenital malformations and an increase in neonatal and perinatal mortality rates. Some of those who make such claims have also stated that "passive smoking" in the presence of a pregnant woman will cause these same effects. While many studies exist in the literature with regard to the smoking, pregnant woman, the literature contains few articles on the potential effect of "passive smoking" on the fetus and newborn. Low Birth Weight Support for this claim consists of statistical studies which cannot prove a causal role. In fact, the evidence suggests that smokinT and nonsmoking womenhave many differences inlifestyle which shouldbe taken into account along with data on alcohol and drug consumption, diet, air pollutionexposure, maternal size, maternal health, race, occupation, and socio-economic status. For example, women who smoke have been found to change jobs more frequently, drink more coffee and alcohol and have a higher twinning rate than nonsmokers.2 The late Dr. Jacob Yerushalmy, a bio-statistician, wrote that much of the data "almost clinch the argument against causation": This conclusion follows from the finding that women who eventually became smokers, produced a large proportion of low birth weight infants even before they started to smoke . . . ."3 I In 1974 Johnstone and Inglis reported that sisters of women who produced low birth~weight babies also tend to p produce lighter weight babies. They reported, "This tendency C..W is independent of social class, maternal size, or smoking ~ habits. 4 V CJ Some who claim that smoking causes intrauterine N growth~retardation also claim that the child remains deficient in physical and intellectual capacities for several years into childhood. Hardy and Mellits, however, studied these parameters in seven-year-old children of mothers who smoked 10 or more cigarettes a day during their pregnancies. They did not findsignificant differences between the children of smoke~rs andnonsmokers.5

The indecisive scientific evidence mthe relationship between~maternal smoking and LBW indicates smoking has not been proven to affect fetal development. .

R E F E R E N C E S 1. James, W. H. "Smoking and Pregnancy," Nature 246: 235, November 23, 1973. 2. Yerushalmy, J. "Infants with Low Birth Weights Born Before Their Mothers Started to Smoke Cigarettes," Amer. J. Obstet. Gynec. 112(2) 282-283, January 15, 1972. 3. Congressional Record - Senate 119 (part III), 3856, February 7, 1973. 4. Johnstone, F. and L. Inglis "Familial Trends in Low Birth Weight," BMJ 3, 659-661, 1974. 5. Hardy, J. B. and E. D. Mellits "Does Maternal Smoking During Pregnancy Have a Long-Term Effect on~the Child?" The Lancet, 1332-1336, December 23, 1972. l r

M1' Neonatal and Perinatal Mortality In a National Academy of Sciences publication, Siegel and Morris report "...[S]moking is not significantly associated with excess fetal or neonatal mortality or the incidence of con enital malformation."1 The Ontario Perinatal Mortality S6udy,2 Yerushalmy,3 O'Lane,4 Underwood5 and Rantakallio also found no increased mortality for infants of smoking mothers. In fact, Yerushalmy reported in 1972 that Smoking mothers have a higher incidence of low- birth-weight infants but infants of smoking mothers do not suffer higher perinatal mortality rates than those of nonsmokers. The low-birth-weight infants of smoking mothers have considerably lower perinatal mortality rates than low-birth-weight infants of nonsmoking mothers.7 Dr. Yerushalmy also noted that the "...[N]eo- natal mortality rate and the risk of congenital anomalies of low-birth-weight infants were considerably lower for smoking .than for nonsmoking mothers." Further, among premature births the neonatal mortality rates were only half as high if the mother smoked during pregnancy. Comstock, et al.8 found a higher mortality risk for children of smokers only when~the father was poorly educated'. In fact, the authors make the statement, it .[F]or children whose fathers had more than a grade school education, the neonatal mortality was slightly lower if the mother had smoked." Another surprising finding was that there was an increase in neonatal mortality among children whose mothers did not smoke until after the pregnancy. And finally, there was no association between the amount and duration of smoking during pregnancy on mortality.

(' R E~~ F E~ R E N C~ E S, 1. Siegel, E., and M. Morris. "The Epidemiology of Human Reproductive Casualties with Emphasis on the Role of Nutrition," Chapter 2 In Maternal Nutrition andithe Course of Pregnancy, Nationial Academy of Sciences, Washington, D. C., 5-40, 1970. 2.. Ontario Perinatal Mortality Study Committee, Second Report of the Perinatal Mortality Study in Ten University Teaching Hospitals, Ontario Department of Health, Ontario, Canada, 1967. 3. Yerushalmy, J. "The Relationship of Parents' Cigarette Smoking to Outcome of Pregnancy - Implications as to the Problem of Inferring Causation from Observed Associations," American Journal of Epidemiology 93(6), 443-456, June, 1971. 4. O'Lane, J. M. "Some Fetal Effects of Maternal Cigarette Smoking," Obstet. Gynec. 22, 181, 1963. 5. Underwood~, P., et al. "Parental Smoking Empirically Related to Pregnancy Outcome," Obstet. Gynec. 29(1), 1-8, January, 1967. 6. Rantakallio, P. "Groups at Risk in Low Birth Weight Infants and Perinatal Mortality," Acta. Paed. Scand. (Supplement) 193:1-71, 1969. 7. Yerushalmy, J. "Infants with Low Birth Weight Born Before Their Mother Started to Smoke Cigarettes," American Journal of Obstetrics and Gynecology 112(2) 282-283, January 15, 1972. 8. Comstock, G. W. et al. "Parental Smoking and Perinatal Mortality," Americ~Journal of Obstetrics and Gynecology 98(5), 708-718, 1967.

( C C C Spontaneous Abortion The significance of studies which find a relationship between smoking inipregnancy and spontaneous abortion is impossible to assess since no accounting has been made for all factors which may influence the rate of abortion. One way to study abortion is to karotype specimens for chromosomal anomalies after spontaneous abortion has occurred. Alberman et al., after karotyping 992 specimens, concluded that maternal smoking history did not have any significant effect on the frequency of chromosome abnormalities.1 Underwood et al. also reported that there was not a significant increase in abortion~rate among smokers.2 Kavoussi found an increased rate among pregnant industrial workers, regardless of smoking~.3 McKean,4 in a letter to the editor of the New England Journal of Medicine remarked that if a patient "were uptight About a floundering pregnancy" and~thus, were smoking as a result of tension, "...[T]his circumstance might distort the picture just enough to make it appear that smoking is an etiologic agent of spontaneous abortion, when it in fact may merely be a more prevalent behavioral characteristic in a troubled~pregnancy." McKean notes that "companion behavioral consumptions" (such~as the use of alcohol, etc.) must be controlled for before one can speculate as to the cause of abortion. Even then, says McKean~, "Almost surely it is a special mix of genetic, behavioral and biologic insult that brings about the spontaneous abortion." Unless gestation~time at abortion is recorded in studies, and unless all cases are reported~ [many occur at home and go unreported) "...[I]t is," according,to Scottish! obstetrician B. B. K. Pirani, "not possible to come to any definite conclusions about the association~between~cigarette smoking and the rate of spontaneous abortion."5 -6-

C C R E' F E: R E N C E S 1. Alberman, E., et al. "Maternal Factors Associated With Fetal Chromosomal Anomalies in~Spontaneous Abortions," Br. J. Obstet. Gynaecol. 83(8) 621-627, 1976. 2. Underwood, P. B., et al. "The Relationship of Smoking to the Outcome of Pregnancy," Amer. J. Obstet. Gynec. 91, 270, 1965. 3. Kavoussi, N. "The Effect of Industrialization on Spontaneous Abortion in Iran," J. Occup. Med. 19(6): 419-423, 1977. 4. McKean, H. E. Letter to the Editor, "Smoking and Abortion," N.E.J.M. 298(2) 113, 1978. 5. Pirani, B. B. K. "Smoking During Pregnancy," Obstetric and Gynecological Survey 33 (1) , 1-13, 1978. \

( Congenital Malformations If tobacco smoke were a genetic mutagen, one could expect consistent findings with regard to the incidepce of congenital malformations in children of smoking mothers. However, there is conflicting evidence, and most studies do not take into account the other factors which may be involved. Underwood et al.1 found no significant difference in the occurrence of major fetal abnormalities in nonsmokers and smokers, nor was any pattern of particular type of abnormality established. Several other studies which conclude that smoking in pregnancy did n2t affect con3 enital malformations are those of Siegel and Morris; Yerushalmy; Reckzeh, et al.4 and the Ontario Perinatal Mortality Study.5 Yerushalmy also found that the incidence of congenital heart disease did not differ between the childrenof nonsmoking and smoking mothers. Chung,and~Myrianthopoulos found that children of smoking mothers appeared to have a lower risk of malformation.6 The Lancet notes that "Viruses that cross the placental barrier early in pregnancy may give rise to con- genital cardiac and other malformations. ..."'~ Sinzinger, et al.8 compared the fetuses of smokers and nonsmokers inorder to see whether the fetuses differed in cardiovascular malformations such as lipid~deposits. No differences were observed. Tobacco smoke, then does not appear to act as a genetic mutagen. After Damon set out to establish that maternal smoking had a mutagenic effect on the fetus, he reported a failure to confirm his hypothesis.9 O ~ ~ C11 ~ W ~ CD

{ 1. 2. 3. 4. 5. f 6. 7. 8. 9. R E F E R E N C E S Underwood, P. B., et al. "The Relationship of Smoking to the Outcome of Pregnancy," American Journal of Obstetrics and Gynecology 91, 270, 1965. Siegel, E. P., and M. Morris. "The Epidemiology of Human Reproductive Casualties with~Emphasis on the Role of Nutrition," Chapter 2 in Maternal Nutrition and the Course of Pregnancy, National Academy of Sciences, Washington, D.C., 5-40, 1970. Yerushalmy, J. "Congenital Heart Disease and Maternal Smoking, .Habits," Nature 242: 262, March 23, 1973. Reckzeh, G., et al. "Testing of Cigarette Smoke Inhalation for Teratogenicity in Rats," Toxicology 4, 289-295, 1975. Ontario Perinatal Mortality Study Committee, Second Report of the Perinatal Mortality Study in Ten University Teaching Hospitals, Ontario Department of Health, Ontario, Canada, 1967. Chung, C. S. an&N. C. Myrianthopoulos. "Factors Affecting Risks of Congenital Malformations: Analysis of Epidemiologic Factors in Congenital Malformations: Report from the Collaborative Perinatal Project," Birth Defects 11(10): 1-19, 1-22, 7.975. "Viruses and Heart-Disease," The Lancet 991-992, October 26, 1974. Sinzinger, H., et al. "Does Atherosclerosis Begin~in Fetal Life?" An. Anat. 25(65), 437-442, 1976. Damony A., et al. "Tobacco Smoke as a Possible Mutagen: Parental Smoking and Sex of Children," American Journal of Epidemiology 83, 530, 1966.

C ( c I Stillbirths Many of the studies which report on stillbirths as well as low birth weight, perinatal mortality, etc. do not standardize the population for age, parity, sex of the infant, social class, race and other more subtle factors. Unfortunately, this fact makes if difficult to judge the role of possible causative factors. From the following study, one can find examples of potential causative agents perhaps working in concert to affect the fetus. Comstock et al. reported that maternal ' smoking did not account for st-illbirths, but that they are more common if the father is poorly educated.l The stillbirth rates were similar for nonsmokers, maternal smokers, and couples where both partners smoked. This study, from the Johns Hopkins University School of Hygiene and Public Health, also reported that the risk of stillbirths was higher for parents who attended church infrequently or if the home lacked sanitary facilities. Underwood, et al. also found no increase in stillbirths .for smoking mothers.2 Knutzen and Davey found that "the interrelationship of maternal height, maternal weight and weight gain is important"3 with respect to stillbirths and perinatal mortality rate. Few studies have been published in recent years which discuss the role of tobacco in stillbirths. Because of the high probability that the cause is multi-factorial, much more research ys needed before any one agent can be proven harmful.

1 R E F E R E N C E S 1. Comstock, G. W., et al. "Parental Smoking and Perinatal Mortality," American Journal of Obstetrics and Gynecology 98(5), 708-718, 1967. 2. Underwood, P. D., et al., "The Relationship of Smoking to the Outcome of Pregnancy,"' American Journal of Obstetrics and Gynecology 91, 270, 1965. 3. Knutzen, V. K. and D. A. Davey. "The Relationship Between Maternal Height and Weight at Booking and Perinatal Mortality," South African Medical Journal 51(19) 672-675, 1977. ~

SUDDEN I.`7FAONT DEATIi SY2JDRO?iE C A review of the literature on sudden infant death syndrome shows that the cause is not known. While a few nonsmokers may believe "passive smoking" causes S.I.D.S, ". .[R]ecent studies have revealed clear differences, existing from birth, between S.I.D.S. victims and survivors of the first six months."1-5 The following factors have been proposed as risk factors for S.I.D.S.: 1. Young mother.6 2. Late birth order.:6 3. Mother's blood group 0, B, or AB.6,7 4. Mother had urinary tract infection~in pregnancy.6 5. Premature birth (lower gestational ag,e).6,9 6. Bottle fed.6 7. Medical attention;received.6 8. Brainstem abnormality.8 9. Parents are smokers.l0 10. Defect in the regulation of alveolar ventilation.11 11. Botulism.12 12. Low socio-economic statuls.7 13. Maternal influenza infections.7 14. Anemic mother.7 15. Protracted second state of labor.7 16. Postnatal clinic appointment unkept.7 17. Drug use by the mother.l4 O 18. Non-Caucasian race.15 W kl 0;~b 19. Male sex.15 ~ 20. Hypothalmic dysfunction. w 16

1 C C More research is badly needed before any conclusions can~be made about the cause of S.I.D.S. Those who would blame smoking parents have "come full circle to the state of the art prior to 1950."l7 Because many S.I.D.S. parents are not smokers, it is necessary to assess other possible causes before judging that parental smoking or any other factor may be or is the only factor involved. ~

C R E F E' R E 11 C E S 1. 2. 3. 4. 5. 6. 7. ~ 8. 9. C Lipsitt, L. P. In Psychology: From Research to Practice (Edited by H. L. Pick and H. W. Stevenson). New York, 1978 Lipsitt, L. P. In Infants Born~at Risk (Ed'ited'by T. M. Field~, A. M. Sostek, S. Goldberg, and H. H. Shuman). New York, 1978. Valdes-Dapena, M.A.D.H.E.W., Publication No. (HSA)l, 78-5255, 1978. Naeye, R. L. and Drage, J. Pediat. Res., 1975:9, 298 (Abstract). Naeye, R. L., et al. Am. J. Dis. Child, 130, 1207, 1976. "Preventing Sudden Infant Death," Science News, Vol. 112, 167, September 10, 1977. Protestos, C. Di., et al. "Obstetric and Perinatal Histories of Children who Died Unexpectedly," Arch. Dis. Child 48(0): 835-841, 1973. Gunby, Phil. "Brainstem Abnormality May Characterize S.I.D.S. Victims," JArIA, Vol. 240, No. 20, 2138, 2144, November 10, 1978. "Unexpected Infant Death," The Lancet, 692, September 23, 1978. 10. Bergman, A. B., et al. "Relationship of Passive Cigarette- Smoking to Sudden Infant Death Syndrome," Pediatrics 58(5): 665-668, 1976. 11. Shannon, Daniel C., et al., "Abnormal Regulation of Ventila- tion in Infants at Risk for Sudden-Infant-Death Syndrome," N.E.J.r4., Vol. 297, No. 14, 747-750, October 6, 1977. 12. Pottgen, Paul, Ph.D., and~L. H. Hillegass. "Botulism and Sudden Infant Death Syndrome," JAM, Vol. 238, No. 15, 1629, October 10, 1977. 13. Protestos, C. D., et al., Supra. -_ O W ~ ~ En W ~ ~,

14. Oleske, J. M., et al., "Experiences with 118 Infants Born to Narcotic-Using Mothers: Does a Lowered Serum,lonized Calcium Level Contribute to the Symptoms of Withdrawal?" Clinical Pediatrics 16(5)~:418-423, 1977. 15. Bergman, A. B., et al., Supra. 16. Goodkin, Franklin. "Hypothalamic Implications of Crib Death," The Lancet, 997, November 4, 1978. 17. Waite, Charles L., Letter to the Honorable Sidney Goldmann, Hearings of the New Jersey Public Health Council, Trenton, New Jersey, October 27, 1977. l