Human chorionic somatomammotropin in normal adolescent primiparous pregnancy

Human chorionic somatomammotropin normal adolescent primiparous

in

pregnancy

I. Effect of smoking

RUSSELL

J.

DOROTHY JAY LYNN

MOSER, R.

W.

HOLLINGSWORTH,

CARLSON,

M.D.

B.S.

LAMOTTE,

Lexington,

PH.D.

PH.D.

Kentucky

Human chorionic somatomammotropin (HCS) measurements were made on a well-defined normal smoking and nonsmoking population comprising 136 primiparous teenagers ranging in age from 12 to 18 years. The smoking population was divided into the following groups: deep and shallow inhalers, long and short puffers, high and low tar, and high and low nicotine. Shallow inhaling and low nicotine exposure patients were found to have a later age at mcnarche as compared to the nonsmokers (13.2 vs. 12.3 years), and the mean baby weight of the mothers who smoked was slightly less (61 Cm.) than that of nonsmoking mothers. Over all, smokers had significantly lower HCS values throughout pregnancy than nonsmokers. Quantitative analysis of the smoking data by trimester revealed that in the second trimester both high and low smoking exposure groups had lower average HCS values than nonsmokers. In the third trimester, patients with the lowest smoking exposures had the lowest HCS values and the heavier smokers had slightly higher mean values than nonsmokers. These preliminary data suggest that HCS production may be more sensitive to low tar and nicotine exposure with possible tolerance or even stimulation occurring in larger doses.

1 T H A s B E E N agreed1-13 and disputed I47 ” that smoking causes mothers to have smaller babies. Since one of every four adult females indulges in varying degrees of smokFrom the Department College of Medicine, Kentucky.

ing,16 this is a relationship which should be investigated. Following the Surgeon General’s report of 1964,17 information has been garnered only on easily measured parameters i.e., birth weight, placental weight) and ( previous reports have not focused on possible hormonal effects of nicotine exposure in pregnancy. Similarly, there has been no presentation of quantitative data of nicotine and tar exposure in normal pregnancy. Previous studies in nonpregnant patients have documented the effect of smoking and nicotine on release of antidiuretic hormone, 18-21 oxytocin,22 plasma fibrinogenz3 adrenocortical secretion,24l 25 catecholamines,z6, H growth hormone, and insulin.2al 2g These were acute experiments in individuals in whom smoking behavior was not quantitated.

of Pediatrics, University of

This work was supported by Grant 25019 from the University of Kentucky Tobacco and Health Institute and Grant S3183 from the Kentucky Department of Maternal and Child Health. Received Revised Accepted

for publication April May

April

1, 1974.

30, 1974. 6, 1974.

Reprint requests: Dr. Russell J. Moser, Department of Pediatrics, University of Kentucky College of Medicine, Lexington, Kentucky 40506.

1080

Volume Number

120 8

HCS

Table I. Characteristics

of smoking

and nonsmoking

Chafacteristics Age at menarche (yr.) Age at conception (yr.) Height (in. ) Prepregnancy weight (lb.) Weight gain during pregnancy Placental weight (Gm.) Baby weight (Gm.) Baby length (cni.) Baby head circumference (cm.)

Table II. Smoking

parameters

deviation

Material

and

P 0.i 7 0.30 0.91 O?l Ki7 0.59 0.34 0.63 o.T!4

teenage

cigarette

ume (ml.)

rette

per

(min.)

8.38 4.57 1.0 23.0

22.80 14.95 4.61 73.95

1.65 0.50 0.93 3.24

37.93 14.99 12.57 87.41

3.06 1.84 0.20 6.50

Normal study population. The total patient population was comprised of 252 young women admitted consecutively to the University of Kentucky Young Mothers Program for adolescents between the ages of 12 and 18 who were pregnant for the first time. In this report baseline data are presented on 136 normal pregnancies according to the criteria of Spellacy and associate?’

Total smoking time per ciga-

smoking

Average @4[

methods

mothers

12.3 15.7 62.2 119.0 26.3 639.8 3,183.0 49.3 34.4

pregnant

Recently, Blake and Sawyer30 have reported the interesting observation that in lactating rats the rapid suckling-induced release of pituitary prolactin into circulating blood is inhibited by a subcutaneous injection of nicotine. This action presumably results from direct hypothalamic stimulation of prolactininhibiting factor (PIF) . The present studies were undertaken to determine whether smoking might have an effect on the production of the placental growth hormone, human chorionic somatomammotropin (HCS) . HCS levels are reported in normal smoking and nonsmoking primiparous adolescents.

1081

12.7 15.9 62.0 124.5 25.9 626.5 3,122.0 49.5 34.2

Average puff duration (sec.)

per

!

Nonsmokers (N = 65)

Average interval between Puffs (sec.)

No. of Puffs

Mean Standard Minimum Maximum

adolescent

pregnancy.

Smokers (N = 71)

(lb.)

of normal

in adolescent

Avera.9 cigarettes

population

I

’

day

Daily tar (mg.)

Daily nicotine (mg.)

Average butt length (mm.)

10.40 8.86 1 .oo 33.3

152.53 136.21 9.22 577.13

10.65 9.20 0.63 36.49

35.94 5.05 26.11 50.70

Reported no. of cigarettes smoked 12.75 10.85 2.00 50.00

(i.e., normal blood pressure, no detectable diabetes mellitus, delivery of apparently normal infants weighing 2,500 to 4,000 grams who survived, and no twins). There were 76 black and 60 white patients from families with incomes ranging from $1,000 to $16,000 per year (mean, $3,941 per year). There were 100 urban and 36 rural patients. Data collection and description. All patients studied signed a consent form describing the research procedures and were interviewed in the Obstetrics Clinic by a welltrained interviewer using the smoking history interview schedule.16 After the interview, patients who smoked cigarettes were asked to smoke one cigarette on the smoking characterization equipment.3” Each smoker was then given a week’s supply of the brand of her choice and instructed to return the butts of the cigarettes she smoked to the Tobacco and Health Laboratory for analysis.‘” Smoking characteristics listed in Table I were derived from smoking history interview schedules, as were “reported number of cigarettes smoked” listed in Table II. The smok-

1082

Moser

December

et al. Am.

LONG

PUFFERS

(9) I

DEEP SHORT SHALLOW LOW

IP=.46 JP=.47

NICOTINE(20) INHALER SMOKERS PUFFERS INHALERS

(45) (71)

1 P=.O9 IP=.O3

(521

I P=.OO5

(16)

NICOTINE

(23)

LOW TAR

(211

15, 1974 Gynecol.

1 P=.51

NONSMOKERS (65) HIGH TAR (22) HIGH

J. Obstet.

I P=.O4 1 P=.OO4

J III

P=.OO~

’

I

I

I

I

I

5

6

7 HCS(yg/ml

6

9

IO

I

Fig. 1. Mean HCS values during normal pregnancy in smokers and nonsmokers. ing characterization equipment provided data for items 1 through 5 and butt analyses supplied data for items 6 through 9 in Table II. The questionnaire was completed by 71 smokers and 65 nonsmokers. Smoking characterization was obtained on 61 smokers and butt analysis was completed for 43 smokers. Human chorionic somatomammotropin (HCS) was measured throughout pregnancy by radioimmunoassay, as previously described by Moser and Hollingsworth.33 During the 136 normal pregnancies, 203 HCS measurements \vere made on the 65 nonsmokers; 208 values were obtained on the 7 1 smokers. Smoking classifications. Patients who had never smoked were classified as nonsmokers. Patients who smoked during pregnancy were classified as smokers. Patients who did not smoke during pregnancy but had smoked previously were eliminated from this study. Statistical analysis of interview data of smoking characteristics was condensed from continuous (or multiple-response) measurements to dichotomous classifications (i.e., depth of inhalation, measured by the patient’s choice of one of four responses to a question on the questionnaire, was condensed to deep [if the response was the “deepest” of the four] and shallow [any of the other three responses] inhalation.) The continuous measurements on nicotine and tar were condensed to two classes each, chosen to split the data roughly in half in each characteristic: low (<125 mg.) and high (2 125 mg.) average daily tar, and low ( < 10 mg.) and average daily nicotine. high (210 mg.)

Average puff duration was split at 2.2 seconds, a value used previously by Griffith and associates.3’ Statistical methods. Comparisons of characteristics of smoking and nonsmoking patients (see Tables I and II) were evaluated with standard t statistics for comparisons of means. P values (probabilities of a t statistic larger .than the one observed if, in fact, the two populations had equal means) were computed for each comparison. Very few HCS determinations were obtained during the first trimester as these adolescent women first presented to the clinic at a mean pregnancy time of 25 weeks. For total HCS data, an average HCS value was computed for each patient. In trimester analysis of HCS values, an average was computed for each patient for each trimester. These averages were treated as individual observations and unweighted by number of determinations in computations of t statistics and P values. Statistical computations were performed on the IBM 360-65 computer at the University of Kentucky Computing Center with the Statistical Package for Social Sciences.3’

Results In this relatively young obstetric patient group, the average smoking time among the smokers was 2.3 years, with a range from one week to nine years. Table I compares nine characteristics of the teenage smoking and nonsmoking women in our normal pregnancy group. In none of these categories do smokers, as a total group,

Volume Number

120 8

HCS

LONG

PUFFERS

NONSMOKERS

INHALERS

(241 (391

PIJFFeRS

(341 (13) (181

LOW TAR

(17)

I I

I

Fig. 2. Mean HCS values during

PUFFERS

(61)

HIGH

(20)

TAR

1 2 HCS(pg/ml)

I 4

I 3

I 5

second trimester in smokers and nonsmokers.

(8)

NONSMOHERS NICOTINE

(18) ^

L/ Fig. 3. Mean

1083

13)

SH ALLOW INHALERS LOW NICOTINE

HIGH

I

(33)

SMOKERS SHORT

LONG

pregnancy.

HIGH TAR (I31 NICOTINE 02)

HIGH DEEP

in adolescent

5

HCS values during

6

third

differ significantly from nonsmokers. Both groups had first menstrual periods at a mean age of 12 years and a mean pregnancy age of 16 years. Both groups had a mean height of 62 inches, and comparable body weights. Weight gain during pregnancy was slightly less in the smokers. Placental and baby weights were slightly less in smokers but the difference was not statistically significant. Baby head circumference and length were almost identical in the two groups. When the Table I characteristics of smokers were subdivided as deep and shallow inhalers, an interesting observation was noted. Menarche occurred later ( 13.2 years) in shallow inhalers than in nonsmokers ( 12.3 years, P= 0.03). Similarly, the low nicotine group had a mean age of menarche at 13.0 years as compared with 12.3 years for nonsmokers (p = 0.05). Table II quantitates the smoking patterns of the normal pregnant smoking population. On the average, the group took eight puffs

7 HCS ( jJg/mlj

trimester

8

9

--

IO

in smokers and nonsmokers.

per cigarette, had a puff volume of 38 ml., held it within their mouth, throat, and lungs for 1.7 seconds, averaged 23 seconds between exhaling and next cigarette draw, had a total single cigarette smoking time of 3.1 minutes, and smoked 10.4 cigarettes per day. Analysis of the butt data revealed that smokers smoked a mean of 12.8 cigarettes per day. The average daily tar intake was 153 mg. daily, average nicotine intake was 11 mg., and the average butt length was 36 mm. Fig. 1 depicts mean HCS values during normal pregnancy in the smokers and nonsmokers. Though the smoking categories are not independent, it is striking that among smokers, only long puffers had higher HCS values than did nonsmokers, but even this difference was not statistically significant (P = 0.51). In each smoking category, the lower exposure categories had lower average HCS values than the higher exposure groups. Patients with higher levels of exposure had average HCS levels similar to those of non-

1084

Moser

et al.

smokers. Differences between long and short puffers, low and high nicotine, and low high tar groups were large (P 5 0.01)) whereas the difference between deep and shallow inhalers was not. Figs. 2 and 3 show average HCS levels for the second and third trimesters of pregnancy. In the second trimester, both high and low exposure groups had lower average HCS values than nonsmokers. In the third trimester, observations on 62 smokers revealed that three lower exposure groups (shallow inhalers, low nicotine, and low tar) all had lower HCS values than nonsmokers (P 5 0.1). High exposure groups (long puffers, deep inhalers, high nicotine, high tar) had slightly higher average HCS values than nonsmokers, though none of these groups differed significantly from nonsmokers. There were too few HCS measurements in the first trimester for meaningful analysis. Comment Numerous studies have reported the intriguing observation that mothers who smoke have smaller babies.le3 Mulcahy and Knaggs” reported a significantly lower birth weight and a higher proportion of neonatal deaths, stillborn infants, and abortions among smokers. In a later study of 100 mothers of term infants, Mulcahy and associatesT found no difference in maternal weight, gross disease, or weight difference in the placentas of the smoking and nonsmoking mothers. Anderson and Turnbull noted that in healthy, young primigravidas the proportion of patients delivered before the end of the thirty-ninth week was significantly greater for smokers than nonsmokers, and Herriot and associates’ reported smaller birth weights even when age, parity, height, and social class are taken into account. Yerushalmy14, lB has published several interesting and provocative articles on the relationship of parents’ cigarette smoking to outcome of pregnancy. On interviewing a heterogenous group of nearly 10,000 white and more than 3,000 black women early in pregnancy, he confirmed the higher incidence of low-birth-weight infants among smoking

December Am. J. Obstet.

1.5, 1974 Gynecol.

mothers. He did not find an increase in neonatal mortality rate or increased risk of congenital anomalies. He was impressed that his nonsmokers lived at a slower and more moderate pace, and that smokers had an earlier age of menarche. In order to study the role of cigarette smoke and two of its constituents, tar and nicotine, on intrauterine growth we have attempted to collect data on a well-defined population of teenagers from the same socioeconomic background having their first babies. It seemed critical, particularly in view of Yerushalmy’s findings, that an attempt be made for the first time to report quantitative smoking data in relation to pregnancy outcome. Since the pertinent question has been raised that the mother who produces a low-birth-weight infant may be different in other variables than smoking, it seemed essential to first examine “normal pregnancies” with the Spellacy criteria and report “abnormal pregnancies” in a separate communication. In contrast to Yerushalmy; we did not find a difference between the total group of smokers and nonsmokers for age at menarche, conception for the first time, prepregnancy weight, height, or weight gain during pregnancy. However, when quantitative data were examined, shallow inhaling patients and the low nicotine group had a later age at menarche. In smokers, placental weights were slightly lower (13.3 Gm.) and mean baby weights were less (61 Cm.) ; but these differences were not statistically significant. This teenage smoking population had characteristics associated with the new smoker. Compared with hospitalized, nonpregnant women patients35 (average age, 26 years; 2 to 5 years of smoking time; average height, 64 inches; average weight, 120 pounds), these young mothers had 2 lesser number of puffs, a shorter interval between puffs, lower puff duration, smaller puff volume, and shorter total smoking time. As compared with hospitalized, older patients,lG teenage mothers had significantly less daily tar and nicotine exposure and reportedly smoked a lesser number of ciga-

v1>1ume Number

120 8

rettes. The average length of the cigarette butts was not significantly different. In 1961, Ito and Higash?” described a placental growth hormone which was later tailed human placental Iactogen (HPL) by Josimovich and MacLaren.37 Subsequent studies have shown that human placental lactogen is produced exclusively by the placenta with no contribution from either the fetal or maternal pituitary glands. The hormone has now been renamed human chorionic somatomammotropin (HCS) . The combined effects of placental growth hormone are anabolic and diabetogenic. A relationship between the levels of HCS in maternal blood and weight of placenta has been reported “*. 3R and disputed.40 In quantitating the effect of smoking on HCS production, it appears that lower doses of smoke and nicotine exposure have the most marked effect on lowering HCS levels. The data obtained during the third trimester are of particular interest as they reflect complete studies on 62 smokers. All lower exposure groups had lower mean WCS values than nonsmokers. All but one of this group (short puffers) had significantly lower levels of HCS. These differences could not be shown in the heaviest smokers, who actually had slightly higher mean HCS levels. None of this group had HCS levels that were

REFERENCES

1. Simpson, W. J.: AM. J. OBSTET. GYNECOL. 73: SOS, 1957: 2. Lowe, C. R.: Br. Med. J. 2: 673, 1959. 3. Frazier, T. M., Davis, G. H., Goldstein, H., and Goldbere. I. D.: AM. 1. OBSTET. GYNECDL. 81: 988:‘1961. ” 4. Herriot, A., Billewicz, W. Z., and Hytten, F. E.: Lancet 1: 771, 1962. 5. Ravenholt, R. T., and Levinski, M. J.: Lancet 1: 961, 1965. 6. Mulcahy, R., and Knaggs, J. F.: AM. J. OBSTET. GYNECOL. 101: 844, 1968. 7. Mulcahy, R., Murphy, J., and Martin, F.: AM. J. OBSTET. GYNECOL. 106: 703, 1970. 8. Underwood, I’., Hester, L. L., Jr., Lafitte, T., and Greeg, K. V.: Communications to the American College of Obstetrics and Gynecologists, Washington, D. C., 1963. 9. Anderson, A. B. M., and Turnbull, A. C.: AM. J. OBSTET. GYNECOL. 105: 1207, 1969.

HCS

in adolescent

pregnancy.

I

1085

statistically different from nonsmokers.These findings are at present unexplained but suggest the interesting possibility that small amounts of nicotine may have effects on HCS synthesis and. release that are not apparent with heavier exposure. There seemsto be well-documented evidence that nicotine may act on a variety of neuroendocrine centers and that in some instances “adaptation” may occur~I”. 20,32, L’5,30 In normal pregnancy, neither the mechanisms of placental growth nor those of fetal growth are fully understood. It seems quite possible that an exogenous drug such as nicotine might effect hormonal release in a dose-related fashion. This study was a preliminary attempt to relate HCS production to quantitative smoke exposure in normal pregnancy. To determine the effects of smoking and pregnancy more precisely, it will be important to examine quantitative data from large numbers of pregnant women of all ages. In addition, it may be important to quantitate the smdking habits of their husbands and consorts. We wish to thank Mrs. Helen Black, of the Tobacco and Health Medical Program, Department of Medicine, University of Kentucky Medical Center, for conductingthe smokinginterviews and obtaining

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in Reference

ANI)

agreed

Blake, C. A., and Sawyer, C. H.: Science 177: 619, 1972. Spellacy, W. N., Teoh, E. S., Buhi, W. C., Birk, S. A., and McCreary, S. A.: AX J. OBSTET. GYNECOL. 109: 588, 1971. Griffith, R. B., Benner, J. F., and Reinhardt, B.: Proceedings of the University of Kentucky Tobacco and Health Research Institute, Lexington, January 1972. Moser, R. J., and Hollingsworth, D. R.: Clin. Chem. 19: 602, 1973. National Opinion Research Center, University of Chicago: Subprogram T-test, April 1972 version. Griffith, R. B.: Unpublished data. Ito, Y., and Higashi, K.: Endocrinol. Jap. 8: 279, 1961. Josimovich, J. B., and MacLaren, J. A.: Endocrinology 71: 209, 1962. Sciarra, J. J., Sherwood, L. M., Varma,.A. A., and Lundberg, W. B.: AM. J. OBSTET. GYNECOL. 101: 413, 1968. Saxena, B. N., Emerson, K., and Selenkow, H. A.: N. Engl. J. Med. 281: 225, 1969. Spellacy, W. N., Carlson, K. L., and Birk, S. A.: AM. J. OBSTET. GYNECOL. 96: 1164, 1966.

Style

to add the article title to references in the AMERICAN References will now conform to the style of the Cumulated Index Medicus, viz., name of author, title of article, name of periodical, volume, page, and year. Authors are always encouraged to limit references to sixteen for the following journal sections: Obstetrics, Gynecology, and Fetus, Placenta, and Newborn. JOURNAL

and

D.:

GYNECOLOGY.

15, 1974 Gynecol.