Volume 156 Number 5

cerebral vascular resistance from the prenatal to the netmatal period. Despite this, resistance change indexes of flow remain constant.

In summary, this preliminary report describes the use of perinatal continuous-wave intracranial Doppler indexes. We hope that this initiates further noninvasive study of blood flow to the brain during labor and de­livery. We have seen cerebral vascular resistance change during labor with flow shifting from diastole to systole, but during the normal labor process indexes of blood flow to the brain appear unaltered. Further study is necessary to test whether this procedure can detect pathologic changes in cerebral perfusion.

REFERENCES

1. MacDonald HM, Mulligan JC, Allen A, Taylor PM. Neo­natal asphyxia I. Relationship of obstetric and neonatal complications to neonatal mortality in 38,405 consecutive deliveries. J Pediatr 1980;96:898.

2. Brown AW Jr, Schwartz JR. Central nervous system dis­turbances. In: Behrman RE, ed. Neonatal perinatal med­icine. St. Louis: The CV Mosby Company, 1983:385.

3. Oliver TK, DemisJA, Bates GD. Serial blood gas tensions and acid base balance during the first hour of life in hu­man infants. Acta Pediatr 1961 ;50:346.

Perinatal intracranial Doppler flow indexes

4. Volpe JJ. Neurology of the newborn. Philadelphia: WB Saunders Co, 1981: 180.

5. Creasy RK, Resnik R. Maternal fetal medicine-principle and practice. Philadelphia: WB Saunders Co, 1984:419.

6. Hansen NB, Stonestreet BS, Rosenkrantz TS, Oh W. Val­idation of Doppler measurements of anterior/cerebral ar­tery blood flow velocity: correlation with brain blood flow in piglets. Pediatrics 1983;72:526.

7. Bada HS, Hajjar W, Chua C, Sumner DS. Noninvasive diagnosis of neonatal asphyxia and intraveritricular hem­orrhage by Doppler ultrasound.-J Pediatr 1979;95:775.

8. Pourcelot L. Applications cliniques de l'examen Doppler transcutane. In: Peronneau, editor: velocimetre ulttaso­nore Doppler. Paris: INSERM, 1975:213.

9. Zar JH. Biostatistical analysis. Englewood Cliffs, NJ: Pren-tice-Hall Inc, 1974:185. .

10. Perlman JM, McMenanin JB, Volpe JJ. Fluctuating ce­rebral blood flow velocity in respiratory distress syn­drome: relation to the development of intraventricular hemorrhage. N Engl .I Med 1983;309:204.

11. Bishop EN. Ultrasonic fetal monitoring. Clih Obstet Gy­necol 1968; II: 1154.

12. Schulman H, Fleischer A, Stern W, Farmakides G, Ja­gani H, Blattner P. Umbilical velocity wave ratios in hu­man pregnancy. AM .I OBSTET GV;\JECOL 1984; 148:985.

13. Erskine RLA, Ritchie Jwk. Umbilical blood flow char­acteristics in normal and growth retarded fetuses. Br .I Obstet Gynaecol 1985;92:605.

14. Campbell S, Griffin DR, Pearce .1M, et al. New Doppler technique for assessing uteroplacental blood flow. Lancet 1983; 1:675.

Maternal alcohol ingestion and the incidence of respiratory distress syndrome

Semyon Ioffe, D.Sc., and Victor Chernick, M.D.

WinniPeg, Manitoba, Canada

The risk of respiratory distress syndrome in infants born to mothers with varying quantities of alcohol intake during pregnancy was assessed. In infants <37 weeks' gestation, there was a decreasing incidence of respiratory distress syndrome with increasing maternal alcohol consumption (p < 0.02). In addition, in infants <37 weeks' gestation, maternal alcohol ingestion was associated with a decreased risk of respiratory distress syndrome even when adjusted for other factors such as smoking, gestational age, birth weight, Apgar score, and sex of the infant. It is suggested that maternal alcohol ingestion enhances the maturation of the fetal lung. (AM J OSSTET GYNECOL 1987;156:1231-5.)

Key words: Respiratory distress syndrome; hyaline membrane disease; alcohol ingestion during pregnancy; effect of alcohol in offspring

From the Perinatal Physiology Laboratory, Department of Pediatrics, University of Manitoba.

Supported by the Medical Research Council of Canada, the Children's Hospital of Winnipeg Research Foundation, Inc., and Health and tv elfare Canada.

Received for publication April 21 , 1986; revised December 10, 1986; accepted December 24, 1986.

Reprint requests: S. loffe, D.Sc., Perinatal Physiology, 770 Ban­natyne Ave., Winnipeg, Manitoba, Canada R3E OW3.

Ingestion of alcohol has been shown to influence the function of the adult lung. Specifically, reduced ciliary activity, pulmonary macrophage function, and uptake of phosphoiipid precursors have been reported.'-' The influence of alcohol on the fetus has been extensively studied since the first description of fetal alcohol syn­drome by Lemoine et aV in 1968. Such infants have

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1232 loffe and Chernick May 1987 Am J Obstet Gyneco1

Table I. Relationship between alcohol consumption and incidence of R.DS

Alcohol intake Absolute alcohol group consumption

Abstainers ° Occasional <0,5 oz per occasion Social 0.5-1.0 oz per occasion Binge >2.5 oz per occasion Alcoholic

low birth weight, reduced head circumference, and characteristic electroencephalographic changes and phenotype.5

.7 The effect of chronic alcohol exposure

on fetal lung development and the development of re­spiratory distress syndrome (RDS) has not been system­atically studied. During a study of the electroenceph­alograms of infants born to mothers with varying amounts of alcohol ingestion during pregnancy we noted apparent small numbers of infants with RDS born to alcoholic mothers. We therefore assessed the effect of varying amounts of alcohol intake on the in­cidence of RDS.

Subjects and methods

As part of a larger study of the effect of maternal alcohol ingestion on maturation demonstrated by the electroencephalogram, we administered a standardized questionnaire to 840 pregnant women at the time of admission to the labor floor. 7 Information included his­tory of alcohol ingestion throughout pregnancy and history of smoking or drug abuse. Mothers with a his­tory of drug abuse were excluded from the study. The remaining 531 subjects were grouped into five cate­gories in relation to their alcohol intake during preg­nancy as previously describedB

: (1) abstainers; (2) oc­casional drinkers «0.5 ounce of alcohol per occasion, once a month or less); (3) social drinkers (0.5 to 1 ounce alcohol per occasion, more than once a month); (4) binge drinkers (>2.5 ounces of alcohol per episode, at least twice a month); (5) frankly alcoholic drinkers (women known to be alcoholic who continued to drink during pregnancy).

The infants' gestational ages were all measured by the scoring method of Dubowitz et al. 9 Data on the clinical course of each infant were analyzed and the presence or absence of RDS noted. RDS was defined on the basis of respiratory distress, chest roentgeno­gram, and blood gas criteria.

Comparison of the incidence of RDS between groups of infants at various gestational ages was done with X2 analyses. In addition a multivariate analysis with the use of a logistic regression model and maximum like-

Incidence of RDS

28 to 36 Weeks' 37 to 42 Weeks' gestation (N = 134) gestation (N = 397)

% I n % I n

44,8 58 4,5 133 38.1 21 6.4 110 26.7 15 4.7 43 16.7 12 8.8 57 21.4 28 7.4 54

lihood estimation was performed. This technique pro­duces an odds ratio (relative risk) for factors that may affect the incidence of RDS. The factors tested were maternal alcohol intake, smoking history, gestational age, birth weight, Apgar score, and sex of the infant. 1O

Results

Of the 531 infants included in this study, 134 had a gestational age between 28 and 36 weeks, and 397 had a gestational age between 37 and 42 weeks (Table I). In infants between 28 and 36 weeks' gestation the in­cidence of RDS in infants of abstainers was significantly greater than in infants of frankly alcoholic mothers (X2 = 4.42, P < 0.05). Assuming equal intervals of al­cohol intake among the five groups there was a signif­icant decrease in the incidence of RDS with increasing alcohol intake in the preterm infant when other factors were not taken into account (X2 = 6.42, P < 0.02).

Variables other than alcohol that could influence the incidence of RDS in infants of 28 to 36 weeks' gestation were analyzed further and are presented in Table II. There was no difference in mean weight at 34 weeks' gestation or 1- and 5-minute Apgar scores between the groups. Male infants had a greater chance than female infants of developing RDS (p < 0.03). There was no association between the incidence of small for gesta­tional age infants and RDS (p > 0.05). The incidence of smoking increased with increasing alcohol con­sumption.

Analyses of the incidence of RDS in infants born between 37 and 42 weeks' gestation did not reveal a significant relationship with alcohol consumption. However, there was a trend toward an increased inci­dence in infants whose mothers were binge drinkers or frankly alcoholic. The effects of other variables on the incidence of RDS in this gestational age group were analyzed further (Table IiI). The infant's body weight (adjusted to 39 weeks' gestation) was significantly de~ creased in binge drinkers and alcoholic mothers but there was no association between body weight and the incidence of RDS. Other fattors such as Apgar score, incidence of small for gestational age infants, or sex

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Maternal alcohol ingestion and RDS 1233

Table II. Data from infants of 28 to 36 weeks' gestation for each alcohol intake group*

Apgar score Sex

Alcohol intake No. of Body weightt

I Incidence of small Incidence of

Male I Female for gestational smoking group infants (gm) 1 min 5 min (%) (%) age infants (%) (%)

Abstainers Occasional Social Binge Alcoholic

28 15 14 12 22

1941 ± 584 1810 ± 483 2086 ± 757 2151 ± 444 2087 ± 477

7.3 ± 2.8 5.6 ± 2.1 6.2 ± 2.3 7.0 ± 2.2 6.4 ± 2.8

7.6 ± 1.7 8.3 ± 1.0 8.2 ± 2.0 8.9 ± 0.8 8.3 ± 1.6

53 73 43 42 63

47 27 57 58 36

14 33 36 50 36

46 60 57 83 86

*Total number of infants is less than in Table I since not all of the data were available for each infant. t Adjusted to 34 weeks' gestation.

Table III. Data from infants of 37 to 42 weeks' gestation for each alcohol intake group*

Apgar score Sex

Alcohol intake

I

Incidence of small Incidence of No. of Body weightt Male I Female for gestational smoking

group infants (gm) 1 min 5 min (%) (%) age infants (%) (%)

Abstainers 83 3418 ± 668 7.6 ± 2.1 9.1 ± 1.2 51 49 7 27 Occasional 79 3314 ± 678 7.9 ± 1.4 9.1 ± 1.1 52 48 10 51 Social 37 3330 ± 484 8.1 ± 1.2 9.2 ± 0.8 41 59 3 70 Binge 46 3074 ± 562* 6.8 ± 2.6 9.Q ± 1.0 50 50 15 89 Alcoholic 32 2898 ± 681§ 6.4 ± 2.3 8.8 ± 1.2 47 53 25 72

*Total number of infants is different from that in Table I since not all of the data were available for each infant. t Adjusted to 39 weeks' of gestation.

*p < 0.05. §p < 0.01.

ratio were not significantly different between the dif­ferent alcohol intake groups. The incidence of smoking increased with increasing alcohol consumption.

Factors that might affect the incidence of RDS in the different alcohol intake groups were analyzed further with unadjusted and adjusted logistic odds ratios (Ta­ble IV). The younger gestational age group had a 10.6-fold greater chance than the older gestational age group of developing RDS. However, this odds ratio dropped to 7.06 when adjusted for alcohol intake and other factors. Similarly infants with Apgar scores of 0 to 4 had RDS 7.4 times more often than infants with scores between 8 and 10. Infants of abstainers and oc­casional drinkers had 2.05 times the risk of RDS when compared with that of the other alcohol intake groups. Infants with a birth weight <2000 gm had 4.23 times the risk of RDS when compared with that of heavier infants. Male infants had 2.5 times the risk ofRDS when compared with that of female infants.

Further comparison between infants of abstainers and those of occasional drinkers (grouped together) (group 1) versus those of the social, binge, and frankly alcoholic drinkers grouped together (group 2) is shown in Table V. In the younger gestational age group, in­fants in group 1 had a 1.29 times greater risk of RDS than infants in group 2 and this ratio was even greater

at 5.86. in the older gestational age group. These ratios were significantly> 1.0 (p = 0.0384). Although an in­creasing Apgar score in infants in group 1 was asso­ciated with a decreased risk of RDS, the risk was always greater (1.83- to 5.83-fold) than in infants in group 2. Thus, for an Apgar score of 0 to 4, infants in group 1 had 5.83 times the risk of RDS conferred to infants in group 2. Heavier infants (>2.5 kg) in group 1 had a greater risk of RDS (3.17) than those in group 2. The relative risk of RDS of infants in group 1 decreased from 3.14 to 1.65 if the mothers smoked during preg­nancy.

Comment Alcohol is known to reduce ciliary activity and mac­

rophage function in the lung. 1.3 The influence of al­

cohol on surfactant in the adult lung is complex. Phos­pholipid precursor uptake has been shown to be re­duced in the lungs of adult rats exposed to alcohol.' However, another study has shown that the concentra­tion of saturated phosphatidylcholine in lung lavage fluid of adult rats exposed to alcohol was significantly increased while tissue pools of saturated phosphati­dylcholine were not affected. 11 A preliminary report indicated that alcohol-exposed fetal rabbit lungs have an accelerated maturation such that lung distensibility

1234 loffe and Chernick May 198 Am J Obstet Gynecc

Table IV. Analysis of factors influencing development of RDS

Unadjusted odds Factor ratio

Gestational age 28-36 wk 10.60 37-42 wk 1.00

1 min Apgar score 0-4 10.70 5-7 3.50 8-10 1.00

Alcohol level Abstainers and occasional 2.40 Social, binge, and alcoholic 1.00

Birth weight -=2000 gm 7.23 >2000 gm 1.00

Sex Female 0.87 Male 1.00

Table V. Factor-adjusted logistic odds ratio ofRDS

Cofactor

Gestational age 28-36 wk 37-42 wk

1 min Apgar score 0-4 5-7 8-10

Birth weight -=2500 gm >2500 gm

Smoking Yes No

Group 1* versus group 2t

x· = 4.29; P = 0.0384 1.29 5.86 x· = 4.126; p = 0.03 5.83 2.22 1.83 x· = 6.143; P = 0.0132 1.6 3.17 x· = 27.605; p = 0.0001 1.65 3.14

*Group 1 = abstainers and occasional drinkers. tGroup 2 = social, binge, and alcoholic drinkers.

and residual volume and lecithin/sphingomyelin ratios are increased. 12

One study has reported that acute alcohol adminis­tration to mothers in premature labour decreases the incidence ofRDS;13 However, to our knowledge no data exist regarding the influence of various quantities of chronic maternal alcohol consumption on the incidence of RDS. The present study, however, indicates a re­duced incidence of RDS in preterm offspring of moth­ers who are binge drinkers or frankly alcoholic. Since alcohol is known to influence fetal growth it was im­portant to group infarits according to an objective as­sessment bf gestational age rather than by birth weight or by gestational age calculated ftom dates.

There was. a statistically significant decrease in inci­dence of RDS in preterm infants with increasing daily alcohol intake (Table I). These findings might be ex­plained on the basis of accelerated maturation of the fetal lung, particularly the surfactant system.

Factor-adjusted logistic 95% Confidence limit odds ratio

5.1-22.4 7.06 1.00

7.40 4.4-26.7 1.4-8.6 2.72

1.00

1.2-4.6 2.05 1.00

3.6-14.7 4.23 1.00

0.45-1.7 0.40 1.00

The use of odds ratios was necessary in order to adjust for variables such as gestational age, sex, Apgar score, and birth weight, which can influence the risk of RDS. in addition, smoking has been shown to reduce the incidence of RDS. H Alcohol intake did not affect birth weights of babies before 36 weeks' gestation (ad­justed to 34 weeks' gestation) but did significantly af­fect birth weights of more. mature infants (Tables II and III). We did not find an association between RDS and the incidence of small for gestational age babies, which suggests that any association between RDS and birth weight must be related to the etfects of alcohol per se. This suggestion is supported by the finding that the odds of having a birth weight >2.5 kg and RDS was more than threefold greater in infants in group 1 (abstainers plus occasional drinkers) than in infants in group 2 (social, binge, and alcohoiic drinkers) and this odds ratio fell to 1.6 for smaller babies.

We also found that smoking reduced the incidence of RDS in group 1 infants (odds ratios of 1.65 versus 3; 14). Similar to what has been reported previously, our finding was that female infants had less RDS than male infants and that the incidence of RDS increased with low gestational age.

In summary, chronic alcohol ingestion during preg­nancy decreases the incidence of RDS in infants <37 weeks' gestation even after adjustment for confounding factors such as smoking history or sex of the infant. This observation suggests that chronic maternal alcohol ingestion enhances the maturation of the fetal lung.

We gratefully acknowledge the expert computer analysis by Mr. Chris McLennan.

REFERENCES 1. Green GM. Pulmonary clearance of infectious agents.

Ann Rev Med 1968;19:315. 2. Green GM, Kass EM. The influence of bacterial species

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on pulmonary resistance to infection in mice su~jected to hypoxia, cold stress, and ethanolic intoxication. Br J Exp Pathol 1965;46:360.

3. Guarneri JJ, Laurenzi GA. Effect of ethanol on phos­pholipid metabolism by rat lung. Am J Physiol 1975; 229:1316.

4. Wagner M, Heinemann HD. Effect of ethanol on phos­pholipid metabolism by rat lung. Am J Physiol 1975; 229:1316.

5. Lemoine P, Harousseau M, Borteqru JP, Minuit JC. Les enfants de parents alcooliques: anomalies observees a pro­pos de 127 cos (Fetal alcohol syndrome; children of al­coholic parents: anomalies observed in 127 cases). Quest Med 1968;21:476.

6. Jones KL, Smith DW. Recognition of fetal alcohol syn­drome in early infancy. Lancet 1973;2:999.

7. Chernick V, Childiaeva R, Ioffe S. Effects of maternal alcohol intake and smoking on neonatal electroencepha­logram and anthropometric measurements. AM J OBSTET GVNECOL 1983;146:41.

8. Havlicek V, Childiaeva R. Sleep EEG in newborns of

Maternal alcohol ingestion and RDS

mothers using alcohol. In: Fetal alcohol syndrome. Hu­man studies. Boca Raton, Florida: CRC Press, 1982, vol 2:149.

9. Dubowitz MS, Dubowitz V, Goldberg C. Clinical assess­ment of gestational age in the newborn infant. J Pediatr 1970;77:1.

10. Brislow NW, Day NE. Statistical methods in cancer. vol 1. The analysis of case control studies. IARC Sci Publ 1980;20:347.

11. Liau DF, Hashim SA, Purson RN III, Ryan SF. Alcohol induced lipid changes in the lung. J Lipid Res 1981; 22:680.

12. Menon L, Vadapalli M, Kumar A, Scarpelli EM. Fetal ethanol: dextran infusion and fetal pulmonary matura­tion. Pediatrics 1984;274:27.

13. Barrada MI, Virnig NL, Edwards LE, Makanson EY. Ma­ternal intravenous ethanol in prevention of respiratory distress syndrome. AM J OBSTET GVNECOL 1977;129:25.

14. Curet LB, Rao AV, Zachman RD, et al. Maternal smoking and respiratory distress syndrome. AM J OBSTET GVNECOL 1983;147:446.

Preterm premature rupture of the membranes: A risk factor for the development of abruptio placentae

Anthony M. Vintzileos, M.D., Winston A. Campbell, M.D., David J. Nochimson, M.D., and Paul J. Weinbaum, M.D.

Farmington, Connecticut

A retrospective study of 298 patients with preterm premature rupture of the membranes managed expectantly during a 3-year period investigated the association between preterm premature rupture of the membranes and abruptio placentae. Expectant management was associated with the development of abruptio placentae in 19 of these 298 patients (6.3%). The prevalence of abruptio placentae in the entire population during the same 3-year period was 2.7%, whereas in patients without preterm premature rupture of the membranes it was 2%. None of the patients developed clinical or laboratory evidence of disseminated intravascular coagulation and no infection (maternal or neonatal) was noted among the patients who had abruptio placentae. Patients with preterm premature rupture of the membranes and severe oligohydramnios (largest pocket <1 cm) seem to be at particular risk for developing this complication. These data suggest that abruptio placentae should be considered as one of the possible risks of expectant management in preterm premature rupture of the membranes. (AM J OBSTET GVNECOL

1987;156:1235-8.)

Key words: Pre term premature rupture of the membranes, abruptio placentae

Preterm premature rupture of the membranes is one of the most common and challenging problems in peri­natal medicine. Because immediate delivery of the fetus

From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Connecticut Health Center.

carries a significant risk of hyaline membrane disease, expectant management has been advocated by previous investigators.1-4 Expectant management is known to be associated with an increased risk of maternal/neonatal infection and cord prolapse, but these risks are rela­tively small compared with those of severe respiratory distress syndrome. [.4

Received for publication October 15, 1986; accepted December 31, 1986.

Reprint requests: Anthony M. Vintzileos, M.D., Division of Maternal­Fetal Medicine, Department of Obstetrics and Gynecology, the Uni­versity of Connecticut Health Center, 263 Farmington Ave., Far­mington, CT 06032.

Nelson et al." recently reported an increased risk (4%) for the development of abruptio placentae during the course of expectant management of patients with pro­longed preterm premature rupture of the membranes. Stimulated by this report, we studied retrospectively all

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