Blood lipids in pregnancy

SCHWARZ

ET

AL.

:

BLOOD

LIPIDS

IN

PREGNANCY

203

Thoqsm, D. L., md CoZQ, J. B.: Ibid. 31: 1113, 1934. (100) Black, P. P., Collip, J. B., and Thomsolz, D. L.: J. Physiol. 82: 385, 1934. (101) CoZZip, J. B., ad AmGwm, E. M.: Lancet 1: 76, 1934. (102) Bachmti, C., Collip, J. B., and Selye, H.: Proc. Sot. Exper. Biol. & Med. 32: 544, 1934. (103) Black, P. T.: J. Physiol. 84: 15, 1935. (104) Young, F. G.: Biochem. J. 32: 656, 1935. (105) (a) CoZZip, J. B.: Ann. Int. Med. 8: 10, 1934. (b) Collip, J. B.: Ibid. 9: 150, 1935. (106) (a) Nm, P., Schmeckebier, X. X., and L,oeb, L.: Endocrinoloq 19: 329, 1935. (b) Du.Shane, G. P., Levine, Ff. T., Pfeiffer, G. A., and Wits&, E.: Proc. Roe. Exper. Biol. & Med. 33: 339, 1935. (c) T~ombl~, C. H.: Endocrinology 20: 311, 1936. (11) Owner, S. C. : Proc. Sot. Exper. Biol. & Med. 34: 392, 1936. (107) Collip, J. B., Selye, H., and. Thomson, D. I,.: Biological Reviews. In press. (108) Collip, J. B.: Canad. M. A. J. 36: 199, 1937. (109) Parkes, 8. s., and z0thnas, I. r.: J. Physiol. 88: 305, 1936. (110) COZli& J. B.: (lanatl. Jf. A. J. 42: 2, 19-W.

BLOOD LIPIDS OTTO

(From

H.

SCHWARZ,

the Washington Gynecology,

IN PREGNANCY*

M.D., S. D.

SOUL,E,

ST.

I,OUIS,

University tha St. Louis

MD.,

AND

BERNICE,

DUNIE,

A.B.,

110.

School of Bledicine, Mntcrnity Hoq~itnl

Department and Barnes

of Obstetrics Hospital)

F

and

AT metabolism in the adult, male or female, has presented some interesting problems. Leathes and Rape? in their monograph, “The Fats, “’ discuss the synthesis of fat in animals. It is very difficult to demonstrate the formation of fat from protein. Direct evidence of a transformation of carbohydrate into fat has not been obtained in any organ. Also, the carbohydrates differ so greatly from the fats in chemical characteristics and composition that it is unlikely that the processesof transformation of carbohydrate into fa.t would be demonstrated easily esperiment.allp. l+‘urthermorc, with the understanding of the processesof digestion, absorption, and int,ermcdiate metabolism, the problems of lipid synthesis from protein and carbohydrate lose much of their practical interest. The developing product, of conception presents a distinct lipid problem. The growing fetus has a definite lipid requirement for essential cell growth. This question of fat synthesis in the fetus or fat transportion across the plaeent.al barrier is a problem of magnitude comparable to that which confronted observers who solved the problems involved in fat metabolism in the adult. It is interesting to review the facts that, t,he fetus begins to store fat at, about the same stage of gestation that the Langhans layer of cells begins to disappear from the placenta, and at about, the same time that the blood lipids are beginning to show a general increase in concentration in the maternal circulation. With t.he advent of a rllicrotrc~hniqne” for determination of blood lipids, a steadily increasing literature has developed. Unt51 recently the studies in this phase of biologic chemistry which have been concaerned with pregnancy hare not been sustained. No *Presented Crynmologists

at the Annual and Ab&minal

Meeting Surgeons.

of

the American Hot Springs,

Va.,

Association September

of

Obstetricians, 7 to 9. 1939.

effort has been made on thcb pat? ot’ one observer to carry the probl~ll1 through in tile same pwt,iclnt f1*o111onst>t of pregnarlcd>-, throngh labor an<1 the pnerperinm. ‘I’rrlly, esc*rl lent observations have been malle of lipids through pregnancy. for indiridual mcnibc~~s 01’ tile pwllp IMailed studies are ;1\->~il;~bl(~for intlividual patients at term, in labor, Bo~cl~~ presents a most, Pomplete picture and during the puerperiuin. of the lipemia of pregnant.>- wt ternI. We have not l’ouutl pllblished any complete lipitl stntlies 011the fame indivitlual from the early weeks Of pregnanc*y tllYougl1 ~estiltioll. Numerous observers have demonstrated the so-called lipcmia of pregnancy and Bloor and later Boyd hare discussed the similarity of this Iipemia t.o cha.ngcs in blood lipids associated with rarions constitutional disease conditions. Tt. is not within thr province* c)f this present discussion to go into t,he origin of’ tile lipemia of pregnancy. Rather, we should like to present our findings ;IS a preliminary study of blood lipids during normal pregnancy. From various clues wc hare obtained in this study we expect to carry this work further. possibly adding somcthinz to the question of how the fetus gels its lipids. Nost

of the literaturft ~cm~~~ni nj: lipitls in pregnancy ha* to tlo with c*holesterol Hermann and Neumann4 reported an increase of blood cholesterol esters during pregnancy. Blemons antl Curtis: reported an absence of cholesterol esters in fetal blood when no :tnesth+?&c ww employed and concluded t,hat the placenta was impermeable to this fraction of blood lipid. Slemons and Standers showed that the large quant,ity of fat in maternal ljlood was not associated with a corresponding change in the circulation of the fetus and further conc*luded that the placenta was impermeable to fat and lipid. Gardner and Gainsborough? reported that free cholesterol increases during pregnancyto the thirtieth week with a decrease in ester cholesterol to almnt the same time. Tn their series, there occurs then, a rerersal of curve so tllat at parturit,ion approximately a normal relationship exists again. Kaufmann and Miihlbock* do not note this fluctuation but report little variation from thr second month of gestation to term. Plass and Tompkins9 reported tot.:ll ant? lipid phosphorus much higher in maternal than fetal 7,lnod serum; they also note that sex and Ijirthweight have no influence on blood phosphorus. These observers feel that fats and lipids are probably synthesized in the fetal organxim. Miihlbockln concludes that from the fourth month to term therta is a progressive increase in iodine-qomhining power which is similar to the hrperlipemia of pregnancy. indicating an increase in unsaturation uf the fatty acids during pregnancy. Boyda has shown that the ~(1 l)lood cells show no marked I-ariation in lipid composition during pregnanr-y. The significant changes in lipid concentrations of the blood are noted in the bloorl plasma or serum. I3oyd demonstrated that the total lipids of blood plasma during pregnancy are increased on the arerage to one-half as high again as in the nonpregnant. All of the component lipids are increased, the greatest increase being in neutral fat. Phospholipid, free and ester cholesterol are each higher than their pregestational value. The normal ratios between phospholipid, ester and free cholesterol are but slightly altered. Phospholipid and free cholesterol are each increased about 25 per cent; ester cholesterol only about 9 per cent higher. The iodin? numbers of total and phospholipid fatty acids are similar in pregnancy to those of the nongravid female.

studies.

Comparisons of mean values may or may not wa,rrant valid deductions. With the use OS standard deviation formulas, sound conclusions may he drawn. Our information is presented in two forms. The graphs demonstrate the trend of concentration of the various lipid constituents through gestation and in the pnerperium. It will be noted that

SCHWARZ

ET

AL.

:

BLOOD

LIPIDS

IN

PREGNANCY

205

the normal variations in concentration of lipids are great. With such a range of normal, the curve of progressive change throughout a whole pregnancy is of more importance than relationship of the patient’s particular findings to an average. The group of tables presents the detailed findings of each paGent throughout her particular pregnancy. Significant points of history are added. It is from these tables that subsequent items of importance may be found. The human subject is selected for this study because of the variable response of experimental animals, and the constant doubt as to the ~'ABLE I NUXBER

35617

I.

B~,OOD SERUM DURATIOX

-

-

Total lipid Neutral fat Total fatty acid Total cholesterol Elster cholesterol Free cholesterol I 69 Phospholipid 102 Pl. F. A. I, No. 103 T. F. A 1: No. Total fatty acid to 1 1.71 Phospholqud Phospholipid to 1 1.33 Total cholesterol f Ester cholesterol to 1 Total cholesterol ( - 0.73 Negro,

24 WK. 7ti5

=

WK.

639

176 462 210 147 63

142 367 193 135 55 215

112 2.65

2.43

1.35

1.x

1.71

0.74

0.77

1.08

1.40

1.11

0.69

0.71

0.72

0.70

22(i

4

.779

453 239 171 IiS 186 117 10.5

210 385 194 135 60 14.5

PERlENTAGE I NC'REASE

POST I '.4RTUM

DELIVERY

29 780 170 447 238 173 65 256 108 99

639

-

IN PRIWXAWT

OF P6 1E( :NAN(

18 WK.

12 WK. 481 123 290 127 93 24

LIPIDS

=

2%i

77 105 81 88 8Ci

100 75

1 1:: 107

t1.7n -

L

-

19 yr., gravida i, estimated date of eonflnement Aug. 17, 1939, delivered Aug. 3, 1939, weight gain 27 pounds from eleventh meek. R.B.C. 3,370,000, Hb. 75 per cent. Urine negative. Labor 11lA; hours. Seminarcosis: DilaudidHyoscine. Baby: 2,480 gm., breast fed. Anesthesia: 15 C.C. of CHCJ, 50 cc. of ether. TABLE

II.

BLOOD

SERUM

LIPIDS

IS

PREGNANCY ZXZZ

NUMBER

"1747

Total lipid Neutral fat Total fatty acids Total cholesterol Ester cholesterol Free cholesterol Phosoholinid Pl. F. A. AIz No. T. F. A. 1” No. Total fatty acid Phospholipid Phospholipid Total cholesterol Ester cholesterol Total cholesterol Patient,

DURATIOK

20 WK. 672

-

OF PREGNAK;CY

33 WK.

-

IELIVERY

POST PARTUM

107

577 210 142 68 189 96 90

40 WK. 1006 309 623 “68 197 71 297 99 93

1.74

3.00

2.09

1.83

1.87

1.12

0.90

1.10

1.21

1.13

0.67

0.73

0.69

0.69

155 390 200 140

60 224

0.70 _

911

249 551 247 172 75 300 100 101

.-

791 210 472 224 156 68 253

--

PERC'ENTAGB I! TCREASE

50 100 60 35 40 25 34

ii estimated white, 27 years, gravida date of confinement June 5, 1939, delivered June 10. 1939. wei :t gain 22 uounds from twentieth week. R.B.C. 4,370,000, Hb. 80’per cent. g:‘rice negat&e. Labor 51h hours. Seminarcosis: Seconal-Hyoscine. Baby : 3,720 gm., breast fed. Anesthesia: 4 C.C. of CHCl, for delivery.

..\TItl 19 WK. -Sll) 237 488 252 180 72

P NITMBER

14 WK.

22373

lipid Neutral fat Total fatty acids Tot,al cholesterol Ester cholesterol Free cholesterol PhospholirJid Ph~o&o;$do fatty

766

Total

Total fatty acid I, No. Total fatty acid Phospholipid Phospholipid Total cholesterol Ester cholesterol Tot.al rholesterol Negro,

152 436 '234 173 til "64 104

i (

35

30 WK.

WK. 99% 337 @>,o -a

878 218 523 245 177 68 297 SO

25% 180 73 302 92

368 679 248 176 72 318 1'1

99

9%

2.08

2.13

3 .l'

1.21

1.19

1.28

a.71

1%

35368

n ie - :hTIO 18 WK. Y---

WK.

Total linid Neutral’fat Total fat,ty acids Total cholesterol Ester cholesterol Free cholesterol Phospholipid Pl. F. A. I, No. T. F. A. I, No. Total fatty acitl Phospholipid Phospholipid Total cholesterol Ester cholesterol Total cholesterol

0.72 0.71 0.71 ~da .tr 0 f confinement

-

OF

__

WK.

21 761 245

205 385 "20 356 64

459 230 159 71 180 66 100

106

Aug. 22, 1939, defourteenth week. R.B.C. Labor 22% hours. Semigm., breast fed. Anesthesia:

from

=

w -

059

540 122 .?lli 154 1 Od 48 194 79 105

37 742 5:: s 4 20 20

-

18 yews, gravida. i, estimated livered Aug. Iti, 1939, weight gain 18 pounds 3,600,000, Hb. 60 per cent. Urine negative. Baby: 3,890 narcosis : Seconal-Hyosc.ine. 15 c.e. of CHCl,, X8 C.C. of etller.

NT’MBER

-xi-

1.76

0.71

PERCENTAGE [A-CREBSE

DELIVERY

1 .G

=

Patient,

_-

GNAN

100

117

1

-

PI

FNAb :(‘I -%30 WK. WK. -‘i88 873

219 476

PREMATURE DELIVERY

233 5% 245 182 63 275 114 109

216 147 70 255 6% 104

ZZ

PERPOST CENTAGE P ARTUM [ I [NCREAGE _-_

1103

66(i

335 tia7 232 %Ol

121

81 353 94 95

371

?I1 151 60 334

I.62

1.86

1.90

1.94

158

l.%i

1.18

1.1%

1.25

1.10

0.71

0.71

0.68

-

0.70

-

0.74

0.68

-

104 174 117 88 90 70 81

white, 22 years, gravida i, estimated date of confinement Aug. :21, 1939, delivered July 10, 1939. Premature twins. Labor 10 hours and 55 minutes. Weight gain 20 pounds from twelfth week. Urine negative. R’.B.C. 3 ,780,00~, Hb. 80 per cent. Seminarcosis: Seconal, Morphia, Hyoscine. Babies: 1,650 gm., 1,820 gm., no hrca$t. Aner;thesin: 6 t?.c. of CHCI,,, 80 c..c. of ether. -

SCHWARX

ET

AI,.

:

BLOOD

LIPIDS

IN

PREGNAN(‘Y

207

The women in this series were selected without special regard for age, color, parity, or habitus. They were all patients in the out-patient department . Their habitual diet was not supervised beyond the usual dietary instructions given all prenatal cases. Blood was drawn between 2:OO and 3 :00 P.M., during usual clinic hours. The patients were not requested to refrain from food. Man and Gildea” have not found any relation between variations in serum lipids and changes in body weight, food intake, hemoconcentration, t,he menstrual period or season of the Boydl* notes that in normal man a consistent and significant pear. TABLE

NUMBER

BI,OOD

V.

SERI'M

LIPIDS

IS I-'REGNAN(Y

DI-RATloP; - OF PREGNAN(‘Y23 28 38 WK. -- WK. WK. _. 904 1 123 1170 265 259 298 543 654 ti92 332 342 270 202 240 253 68 92 89 372 361 111 107 107 110 99

31075

Total Neutral Total Total Ester

lipid fat fatty acids cholesterol cholesterol Free cholesterol Phospholipid PI. F. A. I, No. T. F. A. I, No. Total fatty acid Phonpholipid Phospholipid Total cholesterol Ester cholesterol Total cholesterol

1

1.58

1.75

1.91

1.38

1.12

1.05

-i42 WK. ,W" -ir 451 793 291 206 85 343

POST 'ARTCM

IELIVERY

1305 384 805 34” 243 99 417 100 88

1148 329 702 311 226 85 357

PERCENTAGE NCREASE 5% 137 58 42 47 62 30

0.72 0.74 0 . 7”- 0.74 I L Patient, white, 20 years, gravida ii, estimated date of confinement July 17, 1939, delivered Aug. 9, 1939, weight gain 26 pounds from eighteenth week. R.B.C. 4,520,000, Hb. 80 per cent. Urine negative. Labor 4 hours and 35 minutes. Seminarcosis : Seconal-Hyoscine. No anesthesia. Baby : 3,540 gm., breast fed. TABLE

NUXBER

IN PREGNANCY

.-

206 435 177 126 51 232 89 106

WK. 821 262 513 276 161 55 235 84 98

1.87

2.18

2.11

1.85

1.82

1.87

1.31

1.09

1.18

1.14

1.49

1.16

1 0.71

0.74

0.69

0.72

699

Patient,

LIPIDS

OF PREGNANCY 27 31 34 WK. WK. WK. 894 940 920 297 241 222 565 561 540 225 266 270 156 194 198 69 72 72 267 303 296 90 93 96 99 102 99

lipid Neutral fat Total fatty acid Total cholesterol Ester cholesterol Free cholesterol PhosuholiDid Pl. $. A.‘I, No. T. F. A. I? No. Total fatty acid Phospholipid Phospholipid Total cholesterol Ester cholesterol Total cholesterol

/

SERUM

DITRATION

18 WK.

1

BLOOD

-

25943

Total

VI.

23

I

0.73

.-

-

38 WK. 940 246 567 2tio 197 63 302 96 97

DEPOST [VERJ !F 'ARTUM 908

272 566 229 166 63 296 107 95

513 84 281 168 124 45 180

IN:REASE, AZ?.-

34 44 30 56 57 41 31

1.91

0.75

white, 24 years, gravida ii, estimated date of ’ con ement June 17, 1939, delivered June 17, 1939, weight gain 24 pounds fr ‘om eighteenth week. Urine negative. Labor 5ya hours. Seminarcosis: None. Baby: 4,080 gm., breast fed. Anesthesia: 7 C.C. of CHCI, for delivery.

f

z b 4 c g

Total lipid Neutral fat Total fatty acid Total cholesterol Ester cholesterol Free cholesterol I’hospholipid PI. F. A. I, No. T. P. A. I? No. Total fatt,y acid Phospholipid Phospholipid Total cholesterol Ester cholesterol Total cholesterol Patient,

-

i

I a

L

270 Ii02 :I::,” 242 $0

267 710 363 2741 sx:

297 709 3.55 264 91/

4OS / :17’7 ( !I:! / /

j

943

246 “46 662 I 554 365 286 209 268 100 ii 27” 374 101

2.04 1.12

1.72 Il.iRi

1.06 0.74

I.111

j

! I I / ! 1

0.95 0.73

0.73 --

-

white, 18 years, grarida ii, estimated date of confinement Aug. 1, 1939, from eleventh week. R.B.C. delivered Aug. 5, 1939, weight gain 29 pounds 4,‘750,000, Hb. 85 per cent. Urine: Trace of sugar last month. Seminarcosis: Seconal-Morphia-Hyoscinr. Baby: 3,170 gm., breast fed. Labor 13lh hours. Anesthesia: CHCl, ii c.c., ether 45 C.C.

post-prandial lipemia is not producecl until the amount of ingested fat reaches 200 gm. The method used in these analyses is that described by Boydl” with several minor changes of our own. This technique is the most recently published modification of Bloor ‘9. I4 micromethod of lipid determinations. Iodine numbers were calculated as suggested by Yasudal” and complemented by Boyd.‘” RESULTS Graphs 1 to 4, inclusive, demonstrate the variations of the individual members of the blood serum lipids throughout pregnancy from the first sample through the puerperium. On these graphs are charted the findings of each patient for each constituent lipid. All serum lipids show a steady increase in value from the first observation to term. The increment of all these serum lipids is essentially a gradual one. Even with neutral fat, which is stored late in gestation, there is no abrupt rise in the latter months of pregnancy. Tables I to VII, inclusive, give a composite picture for each patient. Here again we note a great variation in values for the same serum lipid among the various subjects. The pereentage increase for total lipids varied from 34 to 122 per cent; of neut.ral fat, from 44 to 172 per cent; of total fatty acids, from 30 to 117 per cent; of total cholesterol, from 8 to 136 per cent; of ester cholesterol, from 4 to 150 pel cent; of free cholesterol, from 20 to 113 per cent; of phospholipid, from 20 to 160 per cent. Neutral fat values showed the greatest percentage increase at term, compared to the first calculations in early pregnancy in six of seven sets of calculations. These findings are essentially in accord with variations in the various lipid values in normal, nonpregnant individuals.

SCHWARZ

ET

AL’.

:

BLOOD

LIPIDS

IN

PREGNANCY

209

Boy&7 records normal plasma neutral fat values of from none to 773 mg. per cent; phospholipid of 21 to 510 mg. per cent; free cholesterol of 5 to 136 mg. per cent. Thus the important information is the curve of value of the various lipids for each subject rather than the individual value of a lipid fraction.

In

Graph

1.

Graph

2.

some instances the delivery specimen demonstrated a decreased value over last previous calculation. No apparent relation can be attributed to gain in weight, hemoglobin concentration, duration of labor, seminarcosis, or anesthesia. Nautral fat in 6 of 7 sets of determinations showed the greatest percentage increase in value.

the

Graph

3.

Graph

4.

SCHWARB

ET

AL’.

:

BLOOD

LIPIDS

IN

PREGNANCY

211

There is a rise in phospholipid similar in percentage to that of cholesterol. The phospholipid : total cholesterol ratio is of special interest because of the antagonistic behavior of these two elements as observed in several biologic processes. No consistent change in this ratio is noted with the progress of pregnancy. Phospholipid fatty acid iodine numbers and total fatty acid iodine numbers, indices to the degree of unsaturation of these respective factors, show some variations. These changes are not within any range as to warrant a conclusion as to any degree of change in saturation of the fatty acids. The ratio of total fatty acids: phospholipid has been considered to be of general importance in lipid metabolism because of the relation between these two factors during fat absorption. DISCUSSION

The results discussed at this time are in the nature of a preliminary report. The changes in blood serum lipid concentration from early pregnancy to term are reported. Findings in fetal cord blood serum and in the puerperium will be recorded at a subsequent time. The close organic relationship of certain members of the lipid group to substances which are of great significance in obstetrics and gynecology is recognized. The organic structure of cholesterol is closely related to that of the estrogens, progesterone, and ergosterol. Phospholipid and cholesterol balance is one to warrant close consideration. The antagonism of these two lipids is extremely interesting and may play an important role in obstetrics. The hydrophilic and hydrophobic properties of these two substances have not been considered extensively by the clinician (Sinclair**). Boydl’ notes that human plasma contains about the same amount of fatty substances as it doesof inorga,nic salts and much more lipid than of water-soluble organic compounds such as the nitrogenous derivatives, and glucose. The lipids of plasma are exceeded only by the albumins and

globulins in amount present and are about equal in concentration to that of fibrinogen. The relation of this relatively large concentration of lipids to colloidal osmotic pressure of plasma and to the genesis of edema warrants further study. CONCLUSIONS

Blood serum lipids were studied at frequent intervals in a series of normal women from early pregnancy through parturition and in the puerperium. A lipemia is noted in pregnancy. It is characterized by a most marked increase in neutral fat and a lesser increment in cholesterol fractions and phospholipid. The rise in lipid content is gradual through gestation. No significant changes in unsaturation of the phospholipid fatty acids or total fatty acids were noted. The ester cholesterol : total cholesterol ratio remains remarkably constant throughout pregnancy. The phospholipid: total cholesterol ratio exhibited was quite variable but no constant change was noted. No apparent relation of weight gain, weight of the baby, hemoconcentration, seminarcosis, or anesthesia was noted.

212

AMERICAN

JOTTRNAI.

A decrease in all lipid stantly, at delivery.

OF

0138'1'E:l?K1~'S

clcments

AND

(:Y1;EC'OLOGY

\vas noted freyucntly,

A subsequent report will discuss blood serum lipids in the pucrperium.

fetal cord blood serum

hul.

1101, m-

lipids

and

REFERENCES (1) Leathes, J. B., and Rape,, H. S.: Monographs in Biochemistry: The Fats, New York, 1925, Longmans, Green & Co. (2) Blool; W. R.: J. Biol. Chem. 77: J. Clin. Investigation 13: 347, 1934. (4) Hermann, 531, 1928. (3) Boy& E. M.: E., and Neumann, J. : Biol. Ztschr. 43: 47, 1912. (5) Slemons, J. M., and Cwtis, C. S.: AK J. OBST. & GYNEC. 75: 569, 1917. (6) Slemons, 6. M., and Stander, H. J.: Johns Hopkins Hosp. Bull. 34: 7, 1923. (7) Gardner, J. A., and Gainsborough, H.: Lancet 1: 603, 1929. (8) Kuufman~n, C., and Miihlboclc, 0.: Ztschr. f. d. ges. exper. Med. 89: 200, 1933. (9) Plass, E. D., and Tompkins, H.: J. Biol. Chem. 56: 309, 1923. (10) Miihlbock, 0.: Monatschr. f. Geburtsh. u. Gynlk. 106: 53, 1937. (11) J. Biol. Chem. 119: 769, 1937. (12) Bcyd, E. Y.: Ma?l, E. B., and Gildea, E. P.: Ibid. 110: 61, 1935. (13) Idem : Am. J. Clin. Path. 8: 77, 1938. (14) Bloor, W. R.: J. Biol. Chem. 82: 273, 1929. (15) Y~su&I, M.: Ibid. 94: 401, 1931. (16) Bcyd, E. M,: Ibid. 101: 323, 1933. (17) Idem: Canad. J. Research 15: 1, 1937. (18) Sinclair, R. G.: Physiol. Rev. 14: 351, 1931. DISCUSSION DR. E. D. PLASS, IOWA CITY, Iowa.-At our last meeting one of the blood lipids, cholesterol, was introduced by Drs. Colvin and Bartholomew into their discusTheir findings indicated that the sion of the etiology of the toxemias of pregnancy. whole blood of toxemic patients had a higher concentration of total cholesterol than that of normal women at corresponding periods of gestation. They then postulated a cholesterol vascular change as predisposing to the placental infarction, which they believe to be of etiologic significance. On the other hand, the paper which we have just heard deals only with the changes in the various determinable fat fractions of the blood serum during the course of normal pregnancy. Each of the women studied showed gradual increases in the several lipid constituents up to the time of delivery, even though there was no consistent and significant alteration in the degree of unsaturation of either the phospholipid fatty acids or the total fatty acids. The significance of this lipemia is not clear, but it must be viewed as part of the normal metabolic response to pregnancy. The liver plays a dominant role in fat metabolism, and the question naturally arises as to whether the detected alterations in the serum lipids during normal preg nancy are consistent with hepatic malfunction, which has long been postulated but never clearly proved. Data concerning the variations in human liver disease unassociated with jaundice are conflicting, but a recent and still unpublished study by Levine indicates that there is a decrease in the unsaturation of the various fatty acids and in both the total and the esterified cholesterol. On the basis of these findings it seems reasonable to conclude that the fat metabolizing ability of the liver is not diminished by pregnancy. Such negative evidence Serves to strengthen the belief that deficient hepatic function is not a conspicuous part of the metabolic changes incident to gestation, and that the importance attached to this organ as a possible cause of cerain of the complications of pregnancy was unjustified. DR. JAMES R. BLOSS, HUNTINGTON, W. VA.-I wish to report two additional patients who have shown positive Wassermanns and were also posit,ively hypoendocrine. These two, together with three previously reported, became negative immediately upon the change of the lochia. ,411 five of the babies of these patients were negative, both from the cord and from blood taken from their heels. I cannot explain this phenomenon other than by some change in the blood cholesterols of these hypoendocrine patients.

CARTER ET AL,.: DR. JAMES E. DAVIS, has been made upon the lipoid

AXN

VULVOVAGINAL

ARBOR,

MIcH.-May

213

MYCOSES

I ask Dr. Soule if any check

level and the gonadotropie levels in the patients he has studied1 In pregnancy there is normally an increase of nnabolic activity, and there is a very great difference in the constitutional reaction of different individuals to pregnancy. The lipoids and the cholesterols are increased, and generally the gonadotropic level is also increased. In thyroid hypofunction and pituitary hyperfunction, the blood lipoids are changed. DR. SOULE (closing).-Basal metabolisms were run on two of these eight patients and were normal. There is a great possibility that there is some such relationship between the gonadotropic hormones and lipids. There is also a close relationship of certain members of the lipid group organically. Cholesterol and progesterone, estrin and ergosterol, are all closely related structurally. Phospholipids and cholesterol balances also require close observation. The hydrophilic and hydrophobic properties of these substances have not been studied enough by the clinician. The relation of this relatively large concentration of lipids to colloidal osmotic pressure of plasma and to the tendemy to edema is another problem which warrants further study.

VULVOVAGINAL WITH

THE RELATION

MYCOSES

IN PREGNANCY”

OF SYMPTOMS TO GENERA AND SPECIES OF FUNGI

BAYARD CARTER, M.D., CLAUDIUS P. JONES, R. A. Ross, M.D., WALTER L. THOMAS, M.D., DURHAM,N. C. (From

the

Department

of

Obstetrics and Gynecology, Medicine and Duke Hospital)

Duke

University

AND

School

of

P

REGNANCY as a predisposing factor in the occurrence of yeastlike fungi in the vagina and on the vulva is becoming generally well recognized. Carter and Jonesls in 1937 studied the vaginal flora of 114 apparently normal pregnant patients and of 100 apparently normal gynecologic patients. Yeastlike fungi were isolated from 32 per cent of the 114 pregnant patients and from 14 per cent of the 100 gynecologic patients. Much of the confusion regarding mycotic vulvovaginitis is due to the inability to identify the genera and species of yeastlike fungi isolated from the vagina and vulva. Lack of systematic methods of study and classification and the fact that yeastlike fungi are frequently isolated from apparently normal vulvas and vaginas have added to the existing confusion. Jones and MartinI and Martin, Jones, Yao, and LeeI published a method of classifying yeastlike fungi isolated from the vagina. This method of classification was based upon the study of 68 freshly isolated vaginal strains. All of the strains were classified as belonging to the genus Cryptococcus or to 1 of 5 species of Monidia,i including a new and previously undescribed species, Monilia stellatoidea. -“Presented at the Annual Meeting of the American Association of Obstetricians, Gynecologists and Abdominal Surgeons, Hot Springs, Va., September 7 to 9, 1939. Aided by grants from the John and Mary R. Markle Foundation and the Research Council, Duke University. tThe generic name Monilia is not the correct name for the mycelial forming, nonascosporogenous yeastlike fungi. It has been used in this paper in preference to any of the several generic names that have been applied to this group. Recent papers by Langeron and Guerra, Didders and Ladder. and Ciferri and Redaelli show a tendency to adopt a single generic name for these fungi and it is hoped that some agreement may be reached and terms universally adoPted.