Blood lipids in the puerperium

BOYD;

BLOOD Lli'ID;-\ !X TilE !TI<:lU'E!(II'i\1

stt·ual (~yelc mew;truation results from a <·essation iu tit(' Ht'en•!ion ol' !I:•· eorpns lntrmu, and that it occnt's in the ptw:etH·(• of" ili:.'·h <'s1Till <'nllt<·ui of thr hlood. HEI''ERENCE;-\

Allen, E., Pratt, J.P., and Doi~y. E. A.: ;r. A.M. A. 81): :ill!!, J!l:J;}. Allen, J,,·,: Contrib. to Embryo!. Carnegie Inst. Wash. 19: 1, HJ:J'i. Allen, B.: ~··x allll Internal Secretions, Baltimore, 1932, Williams anrl Wilkins. Allen, E.: Obstetries a lid Gynecology, Vol. III, Chicago, 1933, E
BI..JOOD I..JIPIDS IN THE PUERPEIUUl\I rJwoK :;\L BoYD, M.A., :JLD., C.l\:L, H.ocHEsTER,

x. Y.

(From the Department of Obstetrics and Gynecology, The University of Rochester, School of Medicine and Dentistry)

D

URING the past three years, investigations have bef'n perfornH·d

in the laboratories of this department with a view to rstabliRhin~· the significance of changes in fat metabolism dnring pregnane:~ and of their possible relation to disease in )!ravid women. 'fhe 1vork bPgan with a study of micromethods for the estimatimt of all blood Jipids. 1 'l'hese methods were then applied to the analysis of blond in pregnant women, and it was found that thert' was a marked deva1 ion of the values for plasma lipids at the end of pl'egnaney.~ ( \•r·tain lipids, particularly neutral fat, were incrPaSP.d more than other:-~. 'l'lH' lipid content of the red blood cells waH shown to be mw.hang<~d and henee only minor differences were recorded in whole blooll.

A reason was then sought to explain why the blood plasma of' pn·g· nant women contained more fatty substanceH than normally. It wa~ recognized that the fat content of the fetus begins to increase about the same time that the maternal blood lipid:-; rise in Yalne. llvrH•v it was suggested that the increased concentration of maternal pla.sl!la lipids may act as an increased pressure hea
798

AMERICAN JOUR~AL OF OBSTETRICS AND GYNECOLOGY

human fetus at birth was estimated to absorb from umbilical blood between 40 and 50 gm. of lipids per day, of which 75 per cent was phospholipids. These results suggested that the lipemia of pregnancy may be related to the uptake of lipids by the fetus in utero. It is recognized that this relation need not hold for every species of animals; in several speeies, for example cows, rats, and nlhbits, there is actually a decrease in the blood lipids during pregnancy. Fat metabolism varies appreciably from one type of animal to another. especially between herbivora and carnivora, and the results obtained in one species should not be applied witl10ut reservation to the interpretation of the changes in another species. The lipemia of pregnancy has at various times been proposed as a preparation for lactation, it being suggested that the increased concentration of blood lipids assists the production of milk fat by the mammary glands. This theory obviously applies more especially to the period following parturition and raises the question as to what happens to the lipemia of pregnancy once pregnancy is over. Although often suggested, it has never been satisfactorily proved that the blood lipids in the early puerperium are related to lactation. If there is a relation, then one should be able to demonstrate a difference in the blood lipids between women who lactate normally and those in whom the breasts are dried up for various reasons such as a stillborn infant, etc. 1'his method appeared quite feasible and was adopted in the present investigation to proYe or disprove the point. Apparently the only previous investigation of a similar nature was that of Herrmann and Neumann in 1912. 4 These authors used the semiquantitative methods then available to show that whole blood cholesterol and total lipid decreased during normal lactation but remained elevated when lactation did not oecur. 1\Iore recently, Harding and Downs5 have shown that the "lipoid phosphorus'' of blood plasma declines after delivery less ra.pidly if milk secretion is small. Practieally all those who have reported on blood lipids during pregnancy (for list of referenees see Boyd 2 ) have also ineluded readings during the puerperium but did not contrast the changes in normal lactation with those in a "dry puerperium." In the present investigation all lipid groups present in whole blood, plasma and the red blood eells were separately estimated and compared in puerperae of these two types. The changes in the lipid eomposition of the white blood cells during the puerperium have been reported by Boyd. 6 METHOD

The investigation was performed on twelve patients from the Obstetrical Divisions of the Strong Memorial Hospital. Seven o£ these were primiparas and :five multiparas. In all o£ them pregnancy had been normal and delivery was not accompanied by any untoward event such as excessive bleeding, marked perineal tears, etc. In

BOYD:

BLOOD l;li'IDR I:'\ THE ['I'ERPERIF:\1

nine cases lactation set in with the usual amount of milk iiow while three patients were delivered of stillborn infants or the infant contl day postpartum, again on the third or fourth !lay, an•l finally just l1eforr th!' patient was tlisehargetl on thP tenth to tlwlfth days. A sample of blooll eonsist.etl of :20 to :::; e.e. remove•! from the ann veins in the morning following an all-night, fift<•<•n- to ~ixteen-hour fu~l. BLOOD PlASMA

RED BLOOD CELLS

/,000 2 ~

IJ ..; fOO

....

0 0

...

....a::Cl. .3 t :z

«

..

~

8'00

0:

700 600

I

I I

Vl

gs-ooc~ ...J

.t,t.{)()

[

I

I I

~00

ICJO

/~at667RP~

DAYS

1~5~6~7FP$

POSTPARTUM

Fig. 1.-The concentration of lipids in blood plasma and the red blood cells during the puerperium in a seventeen-year-old primipara, nursing her baby with an abundant flow of milk on the third day postpartum. Curve A. total lipid ; curve B, total fatty acids; Curve C, neutral fat; Curve D, phospholipid; Curv-e E, ester cholesterol: Curve F, free cholesterol.

The sample of blood was eitrated, ii c.c. remove•i for whole blood analysis and the remainder r·entrifuged to sepa1·ate cells and plasma. Values for all lipids were then determined in whole blood, plasma, and the re<1 blood cells, using the Bloor oxhla· tive microtechnic as modified by Boyd.I RESULTS

Comparatively slight variations were encountered in the lipid content of whole blood following delivery. In the nine patients in whom normal lactation occurred there was a fall in the total lipid values during t.he first two weeks of the puerperium,

<'-10()

A~IEJUCA:\i ,J(IIIHJ\AL 0~' oB;-;TETH.](';.; A:'\ll fiY:-.iE<'OLO
tIre fall IJPi ng due l'l' in~i pally to a 1leerpa"o in Ht•ntml fat. Plto~ pltol i pid ~ t•xil i hih•d Yl'I'J little ('.hange whil1~ tho n•Jtmining J,loids, n11nwly i'n•n eltoh·st.l'l'lll and l'itoh·~t<'rol ester,;, :tdtt:tl11· ro~e slightly iu l'nlu••. '.I'll" l'ltttllg'~~ i11 1\ltol" J,J""" tli'"" not. lJe dt•sl.)ribcd in any fur-tlrt·r detail ~iw·n tlrn J'L'Httlts in plaslii:L :11111 t.ltt' n:d IJlood <'l'IIH W<>rn !IIU<'lt lllllt't• di•sni['t in: of 1rll:ll w:rs l:tking ]'Ja,., .. 'i'lt<' li i'id l'lllil'<'lll t di ion oJ' l>loud pl:htll:t II' :IS l'll1l!ld t 11 ,],.,.] i til' <"t·easts were drird up, plasJHa lit•ids fell iu ralue n•n.st.s n•sponded to tn·atluont nnd began (11 :dtrink in ,·olunH'. A typi<·alL·xamph• ita~ L><'<'ll ~t·ll'<'ll'rl fronr <':t('h gruup of <'asrs and presentt•
RrD BLOOD CElLS

I 000

<.i

900

<.)

0 0

'30V

0:

w

a.

I

700

..., t

A~

/

bOO

z 500

I I

/

e.__

/

I "'----./

I

I

~ 300

~

c~

J(}OD~

100

2

~

b 8

DAYS

ma

2 • b B M POSTPARTUM

a

l!'ig. 2.-The ~;oncentration of lipids in blood plasma and the red bluoc! cells during the puerperium in a forty-three-yea.r-o!cl para xi, child stillborn, breasts engorged on the third day postpartum but subsequentlv dried up. Curve A, total lipid; Curve B. total fatty acids ; Curve C, neutral fat: Curve D. phospholipid; Curve E. estet· cholesterol and all values equal to zero throughout: Curve l!', free eholesterol;

The decline in value of plasma lipid::~ during laetation was iu a large part clue to loss of plasma. neutral fat. On the average, the concentration of plasma neutral fat fell from 353 ± 75 mg. per eent at (]elivery to 275 ± 115 mg. per cent at the twelfth day postpartum (the figures given m·e means ± the standard deviation), After neutral fat, the greatest deerease was foun•l in the phospholipids nnd next in the free eholesterol and ester L'.holesterol. Changes in the <'.holeste.rol fraction wen' comparatively slight. ·when normal lactation was prevented by drying up the breasts, the downward trend in the concentration of puerperal plasma lipids was halted, as 1llustratefl in Fig. 2. In the nrst three or fonr days of the puerperium, while the hreastR wer••

BOYD:

BLOOD Lll'lP:-< I'\ Till< I'I'EIU'EHI!'J\1

filling, the plasma lipids fell in ya]ue but

un
tlw

br<.'ast~

l>t•gan to

ll<'<'·l'P:t~··

u1

."iZP tl~t> pla~nm lipid~ rose again until :in ~out~.' <·:t~<·~ tltl'.l' 1\'t'l'l' '"'~'11 higher than '"'

i'nrP dPlin•ry. All four of the plasma lipids, nam,•ly lwntral fat, plw8plwlipid~. r'> ,,,, ··IHn rlw 1:ilm~., of ['laRnta lipi•.ls. < ln t h<·

nt h••1 hand, changes were eneonnten•1l in t lu· lip.id ··ontent or t lw n·d hl,nd \I'Pl'l' apparently imlrpell(ltent of ladatiun. It ln1~ 111'<'11 [11'1'\'iously oltn\1'11" tl1ai tl11· fatty eouqH>sition elf t.lu' l'l',Vthrneyt·,.s is not aiT•.·•·ted i>y pn•guHtl•·y. Folli>l'. itti.( .J,·]iy••ry, in a f,,,,. <.'aseR, the •·on•·••atwtion o[ lipid' ill ti"'"'' ,.,.Jb fell fm :< d:1.' 111 t\\11, l11tt in pra(·ljvally e\'l'J)' ~·a::i~· tht• Yalw·~ rn:'lt' ag':till :tlld ro;.:t• (·on"idPr:il.l,\ :il•m•· ll<• Jlot!•d tltnt till' irt<'l'hl~··d f:1t ~onf(•nt of the rr•l blood I'C'II~ in llll' li:·st '"'''k or tl'll day~ of tit•· jlll<'l'f'l't·illm wns <1ne in most. 1:nsts to :m innt•:t-<11 ill ]'lt"~·!•holipilt;; aud he1' <·lto],•,t•·r•.l :tlth•llt;.!_lt lw<·aRionally, aR in Fig. 2, neutral fat IY:t" rt>~pon~ii>l•• for a lllajor p•n·ti<·ll uf tlt1) inl'rrasl>. 'rhis temporary increase in tlw lipi•l •·ont•·nt of the red l.1luod •Tib dnring tlw ••arly days of the puerperium \Yns not :tffPI't••tl by ,IJ·~·ing up the lm·a~t,, 'imilar results hoing obtained in both groups !If ]JU•'l'fll't·a••. It ma.v thu:.; ],.. ·-on ,·Jnd•·
,.,,11, \\'lticlt

l;wtuiion or llolilactation Wl:ls noted to all'evt only the lipids or pla.sma, it 'nlS consiclt'red that Inrtht•l' infOJ'IUUtiun mig·ht lw <~h­ lai!ll'd by IJOl'1 IHtN appt>Hl'f'tl on the iodine number:-; of tlH' blood t
piif'I'JlPI'iltltl.

'!'he rv~nlts ha\'e ltt•m·e bt>cn reported in detail in 'l':tlJll' L

It ll'ill

)w

not,•d

tli~d

the· 1altH·~ obtained :mtl the trends t'IH:
O<'i'un·•·w·e of normal lactation, similar ehangPs liPing n:•<·.ordtld wht•n thl.' lm·ust~ 111'1'1' dri<'d 11p. The iodine number of the total fatty aeid8 nt' ],]ooll plasnm fell fJ'"'"· 11 nwtm of 8S before labor to 76 in t!H• Jir~t week of the puerperium nnrl dttt'ut~-; tho seeond 1verk began to ri~e again to normal, a Jnl'ttn mlne of 81 !tdftlt days postpmtunt. }dt!tongh tltt> lllt':tllH exhillikd ··oll,p:mtlil't'ly minor dtanges, yet iu HI out of 1~ eases the iodiM numbet· Jo"'' ,Juring tlw puerperium usually after a pn·liminary fall .in the first few dnys follo11·in;.:· d<•lirPr.c Tlt<'RP rf>Hnlts illllkatr tltnt immediat,,ly after ]•artmition bl•"td ph"ill:: ··oJtt:t.iJrium, t.ht• ~ahll'ated fHf:t'.;· 1Wi•ls an' grwlually rephw••d i>y mon• an.•l moJ'P unRaturated fatty JJI·.id~, thus in(·n'aHing tht• yalne of tltP iodin1• llllt
802

AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY

These changes in the iodine number of the total fatty acids were found to be due in part if not chiefly to change~ in the iodine numbrr of the phospholipi!l fatty acids. As shown in Table I, the mean value of the iodine number uf the plasma phospholipid fatty acids before parturition was 119. On the first to third days postpartum, the io(line number of the phospholipi
I.

THE IODINE NUMBERS OF T0'£AL FAT1'Y ACIDS AND PHOSPHOLIPID FATTY ACIDS IX BLOOD PLASMA DURING THE EARLY PUERPERIUM

CASE

3 4

5 6 7

8

9 10 11

12

Mean

2 3 4 5 6 7 8 9

10 11 12 Mean

Lactating Lactating I"actating Lactating Lactating Lactating Lactating Lactating Dried up Dried up Dried up

Lactating Lactating Lactating Lactating Lactating I"actating Lactating Lactating Drie
85 68 i)O

82 78 78

77

98

63 124 81 63 81

80 103 81 57 76 61 86 72

78 7~

71 76

148

H:l

136 121 100 fl6 9~

7.~ 1~0

lOG

102

lHl

158

103 71

69 64

l:l7

81) 62 92 73 G7 89

1ii6 112 94 fl2

93 80

84 82 67 86 84 72 81

135 152 116

Jlij

130 137 ()f)

102

9G

();)

](I()

140 117 128 l:JS

114 1:34

"-----·-----····-

12 eases, reaching a mean value of 89. From tltt>n, in all exeP-pt" 2 cases, the iodine number of the phospholipid fatty acids rose steadily in value, reaching a mean o£ 106 at five to seven days postpartum awl 124 or approximately normall, ~ at the tenth to twelfth days postpartum. These results indicate that the phospholipids of hlood plasma after parturition exchange their fatty acids for fatty acids containing fewer double bonds; by the end o£ the seeoml week of the puerpPrium the composition of plasma phospholipid has returned to normal, in terms of its io1line number. DISCUSSION

The results of this investigation lead to certain further conclusions concerning fat metabolism during pregnancy. It has been shown that when milk is secreted by the breasts after delivery, the concentration of all lipids in blood plasma falbi. The greatest decrease was found to occur in plasma neutral fat; next, in order, phospholipids; and finally the least change occurred in the cholesterol (free and ester) fraction. These changes, which resulted in tlw disappearance of the lipemia of

BOYD:

BLOOD fJif'If)f' IN THE I •TlJ:RPFHJ11M

pregnancy as described by Bo;VL1/ are i1lt~ntical in nature to thos{~ fonlHl by Blnor 7 to characterize the disarnwaraneP of lipemias in diabPte8, ehronie hlt>t>ding, E'tc. 'rhe re1·ml1s. in eonjnuetion with thm;t• of a former paper, 2 lead to tlw eondu~ion that the lipemia of pnJ~.!.'t.:.cc .. .. , .. , !HH1t-y. 111 ItS ITlwg·e, nephrosis, {'ft·. On tllP other hand, it has hl>f'n i->how11 that when milk sc•t·retion i;;: JH'P\'<'111('<1 hr drying· np the btNlsts aftPt' tlt•liwr:·. tlw fw..:til.tg· lt'\'t>l of blood lipids rises rather than falls dming· thE• pUt't']li'l'inm. 'l'hrt>t' possible r<>asons may be H(lvanced to <>:xplain thi><. J:<'ir:-~t. it ma~· lw postnlatP(l that the pmcess of drying· np tlH· bt·ra:o~ts hy limiting Huid~. de .. wnnld also ''dry up the hlnod,'' ;wd antomati<·;d],,- iner·easP thl:' <·onc•nntration of plasma lipids. H this m•rt• so thPn thP ]Wl'tPlltag•• of rPcl <·Pll'> should ahw inereaS<". "\" a nratt<•r of freentagt> of red t·t'lh: in blood dnring th•• puerprrimn. Bnt this increase 1n1s noh•<• in ht:th gTonps of JHH'qwras. i.e., tho;..:t> who llldHtPc1 nonnall~· and tlJ<,st' in whom 1hP brPasts 1\'Pt'P drirrpc•1·as tlw Yahw of plasma lipitlf; ft•ll and rose only llfter a binder was applied to Ore hreasts. 'J'his may log·it~ally aeeonnt fol' a slight inerease in tlte IPwl of plasma lipids t•wn after a fast. the milk fats hPing: gTadually ahsorhP!l har·k again into the matrrnal hloo(l strram. Hy tlw tt>nth cln,;· post.pal'tmn the hr0asts, if dried up ftfter mmallr q11ies<'t'nt, and yd at this tim(·. the plaRma lipids werr fonm1 still hig·it and PWil rising i11 \'alrw. l:''mthermnrP. the- fnll breasts preventrd fr·om .~e<·rPting· milk eonld eontain but a fpw g-rams of fat at tlw most, and it is fiy rrspnnsible for the difference i11 thP nends of plmmw lipid Ya]u(>s bPhn•en these two gTonp~ of pnrrpPraR. In other wm·ds. the body reacts to normal laetation b;~- slwwing· creted in milk or brr·
• •

,

,

•

,

,

1

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•

•

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804

AMERICAN JOURNAL OF OBSTETRIC'S AND GYNEl'OLO
of certain hormonE's or other effects, cannot be statt"d at presrnt. 'rhe results indicate that the effect of drying np the breasts immediately after delivrry is not confined to the breasts a lone bnt i~ reflected by a change in body function generally. Certain fact~ indicate that lactation may not be entirely responsible for the fall in plasma lipid~ after delivery. F'ir~t, a~ nott"d before, the sequence by which lipids disappear from plasma after delivery is analogous to the sequence in the disappearancE' of other lipemias in which lactation obviously takes no part. Second, it has been shown that thE' composition of plasma fatty acids, as intlicatE'd by thPir iodine number, undergoes the same changes following parturition irrespective of the onset of normal lactation. And third, the lipid eontent of the red blood cells increases temporarily in the first weE'k of the puerperium also independently of normal lactation. 'l'hesE' changes are probably rpferable more particularly to thr process by which the lipemia of pregnancy diRappPars rather than to the ehang-es aceompanying the onset of laetation. ~ince both of thE'Re faetors come into play in the first WE'ek of the puerperium, one cannot state that lactation alone is the factor responsible for the dPcline in plasma lipid values. It is probably eorreet to conclude that lactation may assist in bringing the coneentration of blood plasma lipids to normal values. But there is no doubt that the prevention of normal lactation results definitely in a Jipemia. In the lower animah;, lactation may have an effect opposite to the above, i.e., it may cause a lipemia. JJactation pro
BOYD:

BLOOD I,IPIDI:\

1~

THE P1'ERI'Eim::M

tract, etc,, in the puerperium, this remoYal wonhl canl'le a lowering of the concentration of blood lipids. Blood lipids are enntim10usly in cquilibrimn ·with tissue lipids; if lipids al'r remoYed from blood, the Joss is made up by the addition of lipids from the fat depots. It is nnlikel? that any remcrval, excPpt a vrry PXl'f'sHiw om• sneh as ocem,; in thr itwrfaRed metabolic rate of frvers," eonl(l of itsPlf aceount fnr a lo"·ering- of thr- vahH' of blood lipirlfl. It is the factors which intlnr>nce thE' N{uiUbrium betwren blood and tissur lipid:-; that WE' muilt ~Pek to E'xplain thr effect of prE'gnancy al'td of lactation. rrhr data preSPntecl above indicate that in thr puerperium this equilibrinm is altt>rPd in the dirt>ction of a lowering· of the lewl of plasma lipidR, but if normal lactation is prevented, the change is inhibited or reYel'SP(l. SU.MMARY

It has been shown that in the puerperium the blood plasma lipids of women decrease in value, the greatest decrease being in neutral fat, next phospholipid, and lt>ast choleRterol and its ester:;. '\Vhen normal lactation 'vas prevt>nted by drying up the breasts, the decrease in plasma lipid levels was inhibited, stoppt>d, or revPrsed. Evidence waR obtained that the lipemia of prrgnancy tends to di:-.appear in the puerperium independently of thr on:M of lactation. f1 was found that in the early puerperium the pla:;ma fatty acids, especially those in combination with phospholipids, become temporarily more saturated, and thifl occurred whether or uot the patients lactatt•d normally. The red blood cells were also found to exhibit temporary increases in their lipid content in the early puerperium and this like wise resulted independently of the onset of normal laetation. And the sequence of lipid ehanges in the puerperium was shown to he identiea] in nature to the sequenee in the disappearanee of any otlH'r lipemia. This information was taken to indicatP that the lip('mia of pt'Pgnancy disappears after delivrry indepenclPntly of thP omwt of la(~ti:l~ tion. It was suggested that lactation may probably assist the decline to normal in the value of plasma lipids. When the breasts were drif'll up, howrver, bodily function was appaeently altt>rrd, t't>:-mlting· in th•· produetion of a new lipemia. REFERENCES

(1) Boyd, H. M.: J. Bioi. Chern. 101: 323, 1933. (2) Boyd, E. M.: J. Clin. Invest. 13: 347, 1934. (3) Boyd, E. M., a?td Wilson, K. M.: J. Olin. Invest.14: 7, 1\!:33. ~4) He-rrmann, E., and Ne'uirr~ann, J.: Wien. klin. Wchnschr. 25: 1557, 1912. (Gl Hm·ding, V. J., and D·owns, E. C.: J. Blol. Chern. 84: 335, 1929. (6) Boyd, E. ,"\1.• : Surg. Gynec, Obst. 59: 744, 1934. (7) Bloor, W. R.: J. Biol. Chem, 49: 201, 1921. (H) Boyd, E. M: Canadian Med. Assn. J. 1935 (in press). (9) Maynar·d, L.A., Harrison. E. S., and McCay, C. M.: J. Biol. Chern. 92: 623, 1931. (10) Meigs, E. B., Blatherwick, N. R., and Cary, C. A.: J. Biol. Chern. 37: 1, 1919. (11) Schaible, P. J.: .T. Bioi. Chern. 95: 79, 1932. (12) Shope, R. E., and Gou•en, J. W.: J. Exper. Med. 48: 25, 1928. (13) Baumann, E. J., and Holly, 0. M.: Am. J. Physiol. 75: 618, 192>i, 1926. (14) Bacmeister and Havers: Deutsche med. Wrhnsrhr. 40: ilH5, 1914.