Clin. Cardiol. 2,246-256 (1979) 0 G. Witzstrock Publishing House Inc.

Original Contributions

Fetal Cardiovascular System as Influenced by Maternal Smoking I. ASMUSSEN, M . D.

Department of Ultrastructural Research, University of Copenhagen, Copenhagen, Denmark

Summary: Primary prevention of atherosclerosis should be initiated early in life, preferably in childhood. Nevertheless, it tends to be forgotten that a child has existed for nine months before birth, and that the newborn child might already have been exposed to agents capable of causing vessel damage. Studies of the umbilical artery, umbilical vein, and vessels of the placental villi (2, 3, 4, 5, 6) revealed that, in this portion of the fetal cardiovascular system, severe damage to the vessel wall is associated with maternal tobacco smoking during pregnancy. These alterations within the fetal cardiovascular system were never found in the children of non-smoking mothers. If similar changes occur in the other vessels of the newborn child, which it seems reasonable to expect, they might give rise to sequelae later in life. It should therefore strongly be advocated that pregnant women abandon tobacco smoking. Keywords: smoking, atherogenesis, pregnancy, umbilical artery, umbilical vein, placenta

Address for reprints: Inger Asmussen, M. D. Dept. of Ultrastructural Research University Institute of Pathology University of Copenhagen Frederik V's Vej 1 1 DK-2100 Copenhagen, Denmark Received: January 18, 1979 Accepted with revision: April 30, 1979

Methods Patients Pregnant women admitted to the Department of Obstetrics YA at Rigshospitalet, Copenhagen were selected for the study. All patients were examined by the same investigator, and each subject completed a questionnaire on smoking habits before and during pregnancy. Twentyeight patients took part in the study, fifteen non-smokers and 13 heavy smokers. Non-smokers were defined as women who had never smoked, neither before nor during pregnancy. All heavy smokers were inhaling cigarette smokers, and one of them smoked as many as 6 0 cigarettes per day. Women suffering from hypertension, diabetes, and other diseases, those who were given medical treatment, and those with Rh negative blood types, were excluded from the study. The patients chosen for the study were clinically normal both before and during pregnancy: the results of laboratory investigations, including urinary analyses for sugar, protein and estriol, were normal. Thus, the only difference between the two experimental groups was in smoking habits. The clinical data for these women and the newborn children are presented in Table I. All the patients had normal pregnancies and delivered healthy babies at full term. All the children were mature and no malformations were found. The average weight of children born to smokers was 3,370 g whilst that of children born to non-smokers was 3,695 g, a difference of 325 g. A corresponding difference of 123 g was found in the weights of the placentas. Neonatal icterus was found in five cases, four of which were in the control group. Ten of the 13 children born to smokers were female.

I. Asmussen: Early Atherosclerotic Lesions in Man

247

Table I Clinical data mother's weight cigarettes/ day 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 10 10 10 15 15 20 20 20 20 20 25 30 60

child's

(kg)

birth weight (9)

child's length (cm)

65 56 76 55 53 64 54 48 64 50 55 45 55 52 60 60 55 51 75 50 60 92 75 63 52 50 60 69

3760 2830 3850 4150 3455 3285 3900 3340 3850 3900 4000 3300 3800 3900 4100 3550 3150 3450 3745 3550 3125 3500 2650 3400 3343 3120 3980 3250

52 50 50 54 50 53 54 50 50 52 55 51 50 52 53 50 52 52 52 50 51 51 51 50 51 51 54 50

mother's

before

age (years)

pregnancy

32 30 22 29 21 28 26 26 32 25 34 18 23 36 24 32 22 17 21 29 26 28 21 23 19 20 30 31

Tissue Biopsies and Preparation for Microscopy Within ten minutes after the delivery of the placenta, biopsies were taken from the umbilical artery, the umbilical vein, and the placenta. The placental biopsy was taken from a macroscopically normal part of the fetal surface of the placenta and cut into 1 mm3 blocks for immersion fixation in glutaraldehyde. Perfusion fixation of the umbilical artery and vein was performed at low pressure, using a soft plastic catheter. Initial perfusion with Ringer's solution was followed by perfusion with 4.5% cold purified glutaraldehyde buffered to pH 7.4 with 0.2 M phosphate buffer. Thereafter, the vessels were dissected out, cut into 1 mm3 blocks, and placed in the same glutaraldehyde for 1-2 h. Postfixation was performed in 1% buffered osmium tetroxide (pH 7.4) for 1 h at 4" C. Tissue blocks were dehydrated in ethanol, cleared in propylene oxide, and embedded in Epon 812 or Araldite. Ultrathin sections were cut on glass knives with an LKB Ultrotome 111, mounted on uncoated copper grids, and contrasted with magnesium

APP sex

score

F F

10/10 9/10 10/10 9/10 9/10 10/10 10/10 10/10 10/10 10/10 9/10 10/10 10/10 3/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 10/10 8/10 10/10 10/10 10/10 10/10 10/10

M M F F

M F

M M F

M M M M M

M F F F F F F

F M F F

F

icterus

placenta weight

k days

(g)

to term

620 840 840 1100 870 650 600 730 7 10 750 950 530 750 950 850

+2 -7 10 -1 28 +21 +8 40? +5 -2 +6 0 14 -2 10 +8 -21 -3 +2 15 +8 -4 18 - 10 -6 0 -11 0

630 780 680 900 570 665 440 660 750 450 780 6 10

+ + +

+ +

+ +

duration of labor (h)

< 12