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Observations on pyridoxine metabolism in pregnancy
OBSERVATIONS EDWIN (From
the
Departments
ON PYRIDOXINE
METABOLISM
IN
PREGNANCY
R. ZARTMAN, M.D., ALLAN C. BARNES, M.D., AND DOROTHY J. HICKS, M.D., CLEVELAND, OHIO of Obstetrics and Western
and
Gynecology,
Reserve
University,
Ohio State Cleveland)
University,
Columbus,
ESPITE the rather frequent employment of pyridoxine in obstetrics and gynecology, chiefly in the treatment of the vomiting of pregnancy,l-* there remains no immediate way of measuring a relative deficiency of the vitamin and no direct chemical test for B, is available. The evidence for the therapeutic application of pyridoxine has, of necessity, been indirect and empirical, and open to dispute.5-c Indirect measurements of deficiencies of this vitamin can be made, however, by observing its effect, on the metabolism of tryptophan.7-8 When tryptophan, one of the essential amino acids, is taken orally by a B,-deficient animal, the abnormal metabolit,e, xanthurenic acicl, is excreted in the urine. This also occurs in the human subject,g and is immediately correcbed by the administration of pyridoxine. Employing this test, Sprince and co-workerslO and Wachstein and Qudaitis8p I1 report evidences of a relative deficiency of vitamin B, in pregnancy. The present brief report is concerned with this test as an index of the pyridoxine status of the normal pregnant patient. Ten grams of tryptophan* was administered orally at night, and beginning two hours later a 10 hour specimen of urine collected. Prom the time of taking the tryptophan to the conclusion of the test, no other food or fluids were consumed. The xanthurenic acid excreted was determined calorimetrically, using the technique of Rosen, Lowy, and Sprince,12 as modified by Wachstein and Gudaitis8 and expressing the result in milligrams of xanthurenic acid excreted per total 10 hour period. Using this technique, recovery experiments of measured amounts of pure xanthurenic acidt added to urine showed statistically reliable results with an average recovery of 107.2 per cent. A total of 48 patients were studied, the individual tests being grouped to provide controls both between the pregnant ancl the nonpregnant, and between the pregnant patient.s who received pyridoxine and those who received placebos or other H fractions.
D
Results A. XA Eswetion After I’ryptophan in Nornlal Men tend Womn.In 12 normal subjects, 9 women and 3 men, between the ages of 23 and 45 years of age, the excretion of XA after tryptophan administration varied *Obtained from R. A. Peterman. tobtained from Foundation. Raritan, respectively.
Merck
& Co.,
Inc.,
Rahway.
New
Sharpe & Dohme, Inc., West Point, N. J., through the courtesy of Dr. 645
Jersey,
through
the
courtesy
of Dr.
Pa., and from the Ortho Research L. E. Amow and Dr. Fred Rosen.
646
ZARTMAN,
13ARNES,
AND
HICKS
Am. J. Obst. & Gynei.. September, I’);-
\.clrious Ntagcs of’ Gestation- --‘1%~ test was performed on 114 women who were less than 48 hours post palturn or were at various gestational periods. None of these women had any evidence of toxemia or any other recognized organic abnormalities. About half of the women in this group were living in a home for unmarried preguant woIlleIl. With one exception, the XA excretion values in this group r~il~lge~l from 116 to 741. mg. per 10 hour overnight urine sample. The overall average was 251 mg. The single value below this range (26 mg.) occurred it) a w0111ai1 at, 25 weeks of gestation who was the only patient in the group who was receiving a vitamin supplement. This was in the form of a m&i\,itanlin capsule and contained 0.2 mg. of pyridoxine, taken one each day. C. The Exccj.etiotL of X-.,1 in Normul Pregnunt Women in I’arioUs fi%yes oj. PregrLamy Who Received Pyrido.x;inc Prior to Tryptophan.--This group was comprised of 8 individuals, 4 of whom had delivered less than 48 hours prior to beginning the t,est. Four of them had had a previous S.A determination. Each one was given 50 mg. of pyridoxine orally. In half of the group the pyridoxine was given 7 hours, and in the other half 1’0 hours, Ijefore the administ,ration of tryptophan. All pa,tients showed a reduction in the values of XA equivalent to those obtained in normal nonpregnant women and normal men. The over-all average of this group was 23 mg. This reduction in XA excretion was even more rapid than in the experiments of Wachstein and Guda.itis,” \vho gave a. greater amount of pyridoxine over a longer period of time to t,h& subjects. Alt.hough the series is small, these results together with those of Wachstein and Gudaitis demonstrate quite clearly the depressing effect on YA excretion of small amount,s of pyridoxine. Apparently neither the stage of pregnancy nor the previous level of XA excretion influences the effect of the pyridoxine. D. The E:zcretion of X4. iv& iVo~~~o,l Pregrmnt Ll/‘of~le,~ Who Beceived Aspirin Prior to Trylptophan.-This group wa.s composed of 9 individuals, and served as a control fot the group who received pyridoxine. Three of these women had had XA determinations 3 weeks earlier. All 9 of them received 4,800 mg.. of aspirin over :I 36 hour period prior to being given tryptophan. This series showed more variation than was expect,ed. Two of the patients who had both tests showed a.n appreciable rise in XA excretion over a 3 week interval. The third patient showed a 32 per cent deerease in XA excretion following aspirin administration, although the value obtained (236 mg.) was still in the range found to be characteristic of pregnancy. Wachstein and Gudaitisll have noticed that pregnant women without. abnormality may show appreciable differences in XA excretion when tested at various times in pregnancy. Of the 6 who had had no pre-aspirin testing, the XA deterrninations in 3 showed values consistent with those of normal pregnancy (164, 273, and 590 mg.) . The remaining 3 patients showed XA values of 48, 60, and 64 mg. These are considerably lower t,han our previous results in pregnant women would indicate that they should have been, but were still higher than those obtained in normal nonpregnant women and normal men. Tf these results are representative, it can be conclucked that aspirin will not depress XA excretion as much or as consistently as pyridoxine. The over-all average for this group was 233 mg., with a range of 48 to 590 mg. (Table I).
PYRIDOXINE
Volume Number 703
TABLE
I.
XA
THE
EXCRETION
METABOLISM IN
IN
NORMAL PREGNANT TO TRYPTOPHAN
PREGNANCY WOMEN
WHO
NAME
I
AGE
E. U. R. E. L. R.
20 15
Ei A: J: J. U. T.
2 19 17
il. s.
E
URINE VOLUMEIN loHOURS (ML.) 420 950 400 325 795 567 485 642 120
XA* IN loHOURS (M'J.1 347 132 239
ii: 32 ii 38 38
R.T.
C. G. *The iThese
WEEKS PREGNANT
determination of XA three samples were
includes done
the interfering 3 weeks after
the
substances. original
RECEIVED
ASPIRIN
PRIOR
EXCRETION AFTER RECEIVING ASPIRIN BEFORETRYPTOPHAN
EXCRETIONAFTER TRYPTOPHAN URINE VOLUMEIN loHOURS (ML.) 227 824 230
647
XA" IN lo HOT7RS (MG.)
236t 250t 411t 60 48 164 273 590 64
test.
E. The Excretion of XA in Normal Pregnant Women in Various Stages of Pregnancy Who Received Nicotinic Acid Prior to Tryptophan.In an attempt to determine whether or not pyridoxine is the specific vitamin which will depress XA excretion, five patients received 200 mg. of nicotinic acid in the 24 hour period prior to taking tryptophan. The average XA excretion of this group was 221 mg., with a range from 78.3 to 452.3 mg. Nicotinic acid, in other words, does not share with pyridoxine the ability to lower the xanthurenic acid excretion as dramatically. F. The Excretion of XA in the Newborn.The possibility that the pregnant woman does not have a deficiency of pyridoxine, but that the placenta “traps” it in the fetal side as it traps vitamin F-l6 cannot be excluded. Accordingly, an attempt was made to determine the xanthurenic acid level in the urine of newborn children, both with and without the feeding of tryptophan. Such a study would be of value only to the extent that the finding of a neonatal deficiency would rule out the possibility of a one-way transfer across the placenta favoring the fetus and lowering the maternal reserves of pyridoxine. The tryptophan was put into solution with the addition of a small amount of sodium hydroxide, and 1 Gm. was fed by stomach tube. The urine was collected over the next 12 hours for XA determination. The difficulties in obtaining complete specimens of urine render the studies less than quantitative, but of the 5 babies (out of 17 studied) with complete retention of the feedings and accurate urine collections, the xanthurenic acid excretion ranged between zero and 97 mg. per 24 hours. In none of these cases could a deficiency be demonstrated in the baby which would correspond to the deficiency seen in the pregnant woman. None of the mothers was receiving a pyridoxine supplement.
Comment It is quite evident from the foregoing that marked increases in XA can be detected, after tryptophan intake, in the urine of normal pregnant women as early as the second trimester of pregnancy. OtherslO have shown even more marked elevations in the XA values of pre-eclamptic, eclamptic, and certain pregnant patients with concurrent diseases. Sprince and associatesl” noted high values in several “normal” pregnant women who later went on to develop signs of eclamptogenic toxemia. The follow-up on our patients with
the higher values has riot revealed any’ signs of tosetnia of prt?g:‘li;ttic~ to cliitfb. \Ywchstein and (+utlaitis” statcvl that 10 01 their 2-C l)tvguatif wometi si ttdivrl ClllP to two days after tle1ivc~r.v htltl shontt sigtts of tosririia ilt Utte titrrv 01. atlcithet~. The :tvvt’>tgt* XA \ttlttrb itt this tc)scaniic. ~IYIU/I W:~S :111 tjrg. I)t’r Z-4 houtx, while it WIS 191 ttig. iti 1-11~notttosctniv groul). (hir grouy, of 1101’111i11 I>l’cgIMllt WOlllPll iii the Ii& trimester of ~)t’~~Ilill~~‘~ hilt1 \-;llLlCbS 01’ 280 Itip. 01’ SA per JO hours. III view of the witlr I’iltlgf’ itt S;Z escretiott itt 110th yt~c~ul~s tr11tl itr our OWII set-irs. plus the I*t~lttti~(~l> studied hy Wachst~eitt ant1 (:utlaitis. stttttll uutnher of patients so far stutlir(l, it is itnpossihlr at this titttc lo VOIIvlutlr that XA esvretiott dlects 01’ indicates thr prrsence of toxemia. b’urthermo~‘c, the complete sl)rcificity of the t.rttvtiotl for tlrticicttcic~s or ~(~l:tti\.(~ (I(,fivipttcirs of vitnmitt I:,;. whilr highly I)t~oltitltl~. is not I)t*o\.;tI,Ie ft*otn thvsts diltil illOl1~~. ilittle is knowtt itl:out the actual rcquiretuents of this xdtantin lty the hu111atl ItotIy. l%ett less is kttown of the tquit*emrttt tlut*ing ~n~g~ancy. T’ilier and his co-workers’” did not feel that the K,; status was an intltortant factor ill F’rom ii stutlp of cliets, llolts01i’~ l’outttl the maintenance of nornral pregnancy. eviclences of a lack of Itoth nicotittic ttcitl ant1 p~ridosin~~. Since clinical trtnuifrstations of vitamin l:,; deficiency van 1~ pr~ttlucetl only under the most extretttc esperirnental conditions, it seettts uulikely thitt [IJ’egmlilcy itself wouItI leatl to such a deficiency in its early weeks. The nrwl~orn ltwI~- does not sevtt~ f o sha.1.r this maternal “ deficiency ’ ’ and the possibility thnt the pla(zetltit ‘itt~a~)~” vit,amin I:,; as it traps vitamin (’ 0111-hr fctd sitlr (xitttll(jt he rs~lutle~1.
Summary
and Conclusions
The administration of tryptophwtt lends to the excretion of sattthurettic* acid in urine in the presence of a deficiency of yitatttin B,;. This procetlure has heett ;tltplietl 10 pytlgtt:tttt ;1nt1 nonpregnant patients ; to subjects receiving supplements of pyriclositie ant1 aul),jects receiving placehas. The results indicate it relative deficiency of I:,; iti l)tTgnitttey. partirnlarly detttonstrahle in the Inst. tr*itnrster autl the imtrtccliaf e postpartum period. SO deficiettcy c~ultl Iw tletno~tstratctl in the n~mal newborn infant, :I Ithough the data are not conclusirc.
References 1. Willis,
R. S., TTinn, W. \V., Slorris, J. OBST. & GYNEC. 44: 265, 1943.
A.
T.,
Newson,
A.
I\.,
and
3. Weinstein, R. H., Mitchell, G. .J., ant1 Sustendal, G. F.: AM. 383, 1943. 3. IVei&ein, H. B., Woltl, z., &Iitrhd, (;. tl., n~ld 81lSt?lllld, G. v.: 47: 389, 1944. 4. Aill)ernagel,
\V.
bl.,
and
Burt,
0.
P.:
Ohio
hl.
.l. 39:
1113,
Tilaasey, J.
\\-.
OBST..
LiFX.
EL:
AN.
81 GYNW.
46:
J. OBST.
pi GYNE(‘.
OBST.
& G~ssc’.
l!M.
AM. J. OBRT. $ GPNEC. 51: 82, 1946. 5. Hesseltine, H. C.: Anr. ti. Rilhernagel, W. M., Burt, 0. P., and Hesseltine, H. C.: (Correspondence) 62: 173, 1946. 7. Lepovsky, S., Roboz, E., and Haag-Smit, A. J.: J. Biol. Chem. 149: S. Wachstein, M., and Gudaitis, A.: ilm. J. Clin. Path. 22: 652, 1952.
.I.
195, 1943.
Volume Numbcr
70 3
PYRIDOXINE
METABOLISM
IN
PREGNANCY
649
9. Greenberg, L. D., Boh, D. F., McGrath, H., and Rinehart, J. F.: Arch. Biochem. 21: 237, 1949. 1.0. Sprince, H., Lowy, R. S., Folsome, C. E., and Behrman, J.: AM. J. OBST. & GYNEC. 62: 84, 1951. 1.1. Wachstein, M., and Gudaitis, A.: (a) J. Lab. & Clin. Med. 40: 550, 1952. (b) J. Lab. & Clin. Med. 42: 98, 1953. 12. Rosen, F., Lowy, R. S., and Sprince, A.: Proc. Sot. Exper. Biol. & Med. 77: 339, 1951. 13. Vilter, C. F., Morgan, D., and Spies, T. D.: Surg., Gynec. & Obst. 83: 561, 1946. 14. Hobson, W.: J. Hyg. 46: 198, 1948. 15. Barnes, A. C.: AY. J. OBST. & GYNEC. 5, 3: 645, 1947. 16. Holzaepfel, J. H., and Barnes, A. C.: AI a. J. OBST. & GYNEC. 53: 864, 1947.
the
Departments
ON PYRIDOXINE
METABOLISM
IN
PREGNANCY
R. ZARTMAN, M.D., ALLAN C. BARNES, M.D., AND DOROTHY J. HICKS, M.D., CLEVELAND, OHIO of Obstetrics and Western
and
Gynecology,
Reserve
University,
Ohio State Cleveland)
University,
Columbus,
ESPITE the rather frequent employment of pyridoxine in obstetrics and gynecology, chiefly in the treatment of the vomiting of pregnancy,l-* there remains no immediate way of measuring a relative deficiency of the vitamin and no direct chemical test for B, is available. The evidence for the therapeutic application of pyridoxine has, of necessity, been indirect and empirical, and open to dispute.5-c Indirect measurements of deficiencies of this vitamin can be made, however, by observing its effect, on the metabolism of tryptophan.7-8 When tryptophan, one of the essential amino acids, is taken orally by a B,-deficient animal, the abnormal metabolit,e, xanthurenic acicl, is excreted in the urine. This also occurs in the human subject,g and is immediately correcbed by the administration of pyridoxine. Employing this test, Sprince and co-workerslO and Wachstein and Qudaitis8p I1 report evidences of a relative deficiency of vitamin B, in pregnancy. The present brief report is concerned with this test as an index of the pyridoxine status of the normal pregnant patient. Ten grams of tryptophan* was administered orally at night, and beginning two hours later a 10 hour specimen of urine collected. Prom the time of taking the tryptophan to the conclusion of the test, no other food or fluids were consumed. The xanthurenic acid excreted was determined calorimetrically, using the technique of Rosen, Lowy, and Sprince,12 as modified by Wachstein and Gudaitis8 and expressing the result in milligrams of xanthurenic acid excreted per total 10 hour period. Using this technique, recovery experiments of measured amounts of pure xanthurenic acidt added to urine showed statistically reliable results with an average recovery of 107.2 per cent. A total of 48 patients were studied, the individual tests being grouped to provide controls both between the pregnant ancl the nonpregnant, and between the pregnant patient.s who received pyridoxine and those who received placebos or other H fractions.
D
Results A. XA Eswetion After I’ryptophan in Nornlal Men tend Womn.In 12 normal subjects, 9 women and 3 men, between the ages of 23 and 45 years of age, the excretion of XA after tryptophan administration varied *Obtained from R. A. Peterman. tobtained from Foundation. Raritan, respectively.
Merck
& Co.,
Inc.,
Rahway.
New
Sharpe & Dohme, Inc., West Point, N. J., through the courtesy of Dr. 645
Jersey,
through
the
courtesy
of Dr.
Pa., and from the Ortho Research L. E. Amow and Dr. Fred Rosen.
646
ZARTMAN,
13ARNES,
AND
HICKS
Am. J. Obst. & Gynei.. September, I’);-
\.clrious Ntagcs of’ Gestation- --‘1%~ test was performed on 114 women who were less than 48 hours post palturn or were at various gestational periods. None of these women had any evidence of toxemia or any other recognized organic abnormalities. About half of the women in this group were living in a home for unmarried preguant woIlleIl. With one exception, the XA excretion values in this group r~il~lge~l from 116 to 741. mg. per 10 hour overnight urine sample. The overall average was 251 mg. The single value below this range (26 mg.) occurred it) a w0111ai1 at, 25 weeks of gestation who was the only patient in the group who was receiving a vitamin supplement. This was in the form of a m&i\,itanlin capsule and contained 0.2 mg. of pyridoxine, taken one each day. C. The Exccj.etiotL of X-.,1 in Normul Pregnunt Women in I’arioUs fi%yes oj. PregrLamy Who Received Pyrido.x;inc Prior to Tryptophan.--This group was comprised of 8 individuals, 4 of whom had delivered less than 48 hours prior to beginning the t,est. Four of them had had a previous S.A determination. Each one was given 50 mg. of pyridoxine orally. In half of the group the pyridoxine was given 7 hours, and in the other half 1’0 hours, Ijefore the administ,ration of tryptophan. All pa,tients showed a reduction in the values of XA equivalent to those obtained in normal nonpregnant women and normal men. The over-all average of this group was 23 mg. This reduction in XA excretion was even more rapid than in the experiments of Wachstein and Guda.itis,” \vho gave a. greater amount of pyridoxine over a longer period of time to t,h& subjects. Alt.hough the series is small, these results together with those of Wachstein and Gudaitis demonstrate quite clearly the depressing effect on YA excretion of small amount,s of pyridoxine. Apparently neither the stage of pregnancy nor the previous level of XA excretion influences the effect of the pyridoxine. D. The E:zcretion of X4. iv& iVo~~~o,l Pregrmnt Ll/‘of~le,~ Who Beceived Aspirin Prior to Trylptophan.-This group wa.s composed of 9 individuals, and served as a control fot the group who received pyridoxine. Three of these women had had XA determinations 3 weeks earlier. All 9 of them received 4,800 mg.. of aspirin over :I 36 hour period prior to being given tryptophan. This series showed more variation than was expect,ed. Two of the patients who had both tests showed a.n appreciable rise in XA excretion over a 3 week interval. The third patient showed a 32 per cent deerease in XA excretion following aspirin administration, although the value obtained (236 mg.) was still in the range found to be characteristic of pregnancy. Wachstein and Gudaitisll have noticed that pregnant women without. abnormality may show appreciable differences in XA excretion when tested at various times in pregnancy. Of the 6 who had had no pre-aspirin testing, the XA deterrninations in 3 showed values consistent with those of normal pregnancy (164, 273, and 590 mg.) . The remaining 3 patients showed XA values of 48, 60, and 64 mg. These are considerably lower t,han our previous results in pregnant women would indicate that they should have been, but were still higher than those obtained in normal nonpregnant women and normal men. Tf these results are representative, it can be conclucked that aspirin will not depress XA excretion as much or as consistently as pyridoxine. The over-all average for this group was 233 mg., with a range of 48 to 590 mg. (Table I).
PYRIDOXINE
Volume Number 703
TABLE
I.
XA
THE
EXCRETION
METABOLISM IN
IN
NORMAL PREGNANT TO TRYPTOPHAN
PREGNANCY WOMEN
WHO
NAME
I
AGE
E. U. R. E. L. R.
20 15
Ei A: J: J. U. T.
2 19 17
il. s.
E
URINE VOLUMEIN loHOURS (ML.) 420 950 400 325 795 567 485 642 120
XA* IN loHOURS (M'J.1 347 132 239
ii: 32 ii 38 38
R.T.
C. G. *The iThese
WEEKS PREGNANT
determination of XA three samples were
includes done
the interfering 3 weeks after
the
substances. original
RECEIVED
ASPIRIN
PRIOR
EXCRETION AFTER RECEIVING ASPIRIN BEFORETRYPTOPHAN
EXCRETIONAFTER TRYPTOPHAN URINE VOLUMEIN loHOURS (ML.) 227 824 230
647
XA" IN lo HOT7RS (MG.)
236t 250t 411t 60 48 164 273 590 64
test.
E. The Excretion of XA in Normal Pregnant Women in Various Stages of Pregnancy Who Received Nicotinic Acid Prior to Tryptophan.In an attempt to determine whether or not pyridoxine is the specific vitamin which will depress XA excretion, five patients received 200 mg. of nicotinic acid in the 24 hour period prior to taking tryptophan. The average XA excretion of this group was 221 mg., with a range from 78.3 to 452.3 mg. Nicotinic acid, in other words, does not share with pyridoxine the ability to lower the xanthurenic acid excretion as dramatically. F. The Excretion of XA in the Newborn.The possibility that the pregnant woman does not have a deficiency of pyridoxine, but that the placenta “traps” it in the fetal side as it traps vitamin F-l6 cannot be excluded. Accordingly, an attempt was made to determine the xanthurenic acid level in the urine of newborn children, both with and without the feeding of tryptophan. Such a study would be of value only to the extent that the finding of a neonatal deficiency would rule out the possibility of a one-way transfer across the placenta favoring the fetus and lowering the maternal reserves of pyridoxine. The tryptophan was put into solution with the addition of a small amount of sodium hydroxide, and 1 Gm. was fed by stomach tube. The urine was collected over the next 12 hours for XA determination. The difficulties in obtaining complete specimens of urine render the studies less than quantitative, but of the 5 babies (out of 17 studied) with complete retention of the feedings and accurate urine collections, the xanthurenic acid excretion ranged between zero and 97 mg. per 24 hours. In none of these cases could a deficiency be demonstrated in the baby which would correspond to the deficiency seen in the pregnant woman. None of the mothers was receiving a pyridoxine supplement.
Comment It is quite evident from the foregoing that marked increases in XA can be detected, after tryptophan intake, in the urine of normal pregnant women as early as the second trimester of pregnancy. OtherslO have shown even more marked elevations in the XA values of pre-eclamptic, eclamptic, and certain pregnant patients with concurrent diseases. Sprince and associatesl” noted high values in several “normal” pregnant women who later went on to develop signs of eclamptogenic toxemia. The follow-up on our patients with
the higher values has riot revealed any’ signs of tosetnia of prt?g:‘li;ttic~ to cliitfb. \Ywchstein and (+utlaitis” statcvl that 10 01 their 2-C l)tvguatif wometi si ttdivrl ClllP to two days after tle1ivc~r.v htltl shontt sigtts of tosririia ilt Utte titrrv 01. atlcithet~. The :tvvt’>tgt* XA \ttlttrb itt this tc)scaniic. ~IYIU/I W:~S :111 tjrg. I)t’r Z-4 houtx, while it WIS 191 ttig. iti 1-11~notttosctniv groul). (hir grouy, of 1101’111i11 I>l’cgIMllt WOlllPll iii the Ii& trimester of ~)t’~~Ilill~~‘~ hilt1 \-;llLlCbS 01’ 280 Itip. 01’ SA per JO hours. III view of the witlr I’iltlgf’ itt S;Z escretiott itt 110th yt~c~ul~s tr11tl itr our OWII set-irs. plus the I*t~lttti~(~l> studied hy Wachst~eitt ant1 (:utlaitis. stttttll uutnher of patients so far stutlir(l, it is itnpossihlr at this titttc lo VOIIvlutlr that XA esvretiott dlects 01’ indicates thr prrsence of toxemia. b’urthermo~‘c, the complete sl)rcificity of the t.rttvtiotl for tlrticicttcic~s or ~(~l:tti\.(~ (I(,fivipttcirs of vitnmitt I:,;. whilr highly I)t~oltitltl~. is not I)t*o\.;tI,Ie ft*otn thvsts diltil illOl1~~. ilittle is knowtt itl:out the actual rcquiretuents of this xdtantin lty the hu111atl ItotIy. l%ett less is kttown of the tquit*emrttt tlut*ing ~n~g~ancy. T’ilier and his co-workers’” did not feel that the K,; status was an intltortant factor ill F’rom ii stutlp of cliets, llolts01i’~ l’outttl the maintenance of nornral pregnancy. eviclences of a lack of Itoth nicotittic ttcitl ant1 p~ridosin~~. Since clinical trtnuifrstations of vitamin l:,; deficiency van 1~ pr~ttlucetl only under the most extretttc esperirnental conditions, it seettts uulikely thitt [IJ’egmlilcy itself wouItI leatl to such a deficiency in its early weeks. The nrwl~orn ltwI~- does not sevtt~ f o sha.1.r this maternal “ deficiency ’ ’ and the possibility thnt the pla(zetltit ‘itt~a~)~” vit,amin I:,; as it traps vitamin (’ 0111-hr fctd sitlr (xitttll(jt he rs~lutle~1.
Summary
and Conclusions
The administration of tryptophwtt lends to the excretion of sattthurettic* acid in urine in the presence of a deficiency of yitatttin B,;. This procetlure has heett ;tltplietl 10 pytlgtt:tttt ;1nt1 nonpregnant patients ; to subjects receiving supplements of pyriclositie ant1 aul),jects receiving placehas. The results indicate it relative deficiency of I:,; iti l)tTgnitttey. partirnlarly detttonstrahle in the Inst. tr*itnrster autl the imtrtccliaf e postpartum period. SO deficiettcy c~ultl Iw tletno~tstratctl in the n~mal newborn infant, :I Ithough the data are not conclusirc.
References 1. Willis,
R. S., TTinn, W. \V., Slorris, J. OBST. & GYNEC. 44: 265, 1943.
A.
T.,
Newson,
A.
I\.,
and
3. Weinstein, R. H., Mitchell, G. .J., ant1 Sustendal, G. F.: AM. 383, 1943. 3. IVei&ein, H. B., Woltl, z., &Iitrhd, (;. tl., n~ld 81lSt?lllld, G. v.: 47: 389, 1944. 4. Aill)ernagel,
\V.
bl.,
and
Burt,
0.
P.:
Ohio
hl.
.l. 39:
1113,
Tilaasey, J.
\\-.
OBST..
LiFX.
EL:
AN.
81 GYNW.
46:
J. OBST.
pi GYNE(‘.
OBST.
& G~ssc’.
l!M.
AM. J. OBRT. $ GPNEC. 51: 82, 1946. 5. Hesseltine, H. C.: Anr. ti. Rilhernagel, W. M., Burt, 0. P., and Hesseltine, H. C.: (Correspondence) 62: 173, 1946. 7. Lepovsky, S., Roboz, E., and Haag-Smit, A. J.: J. Biol. Chem. 149: S. Wachstein, M., and Gudaitis, A.: ilm. J. Clin. Path. 22: 652, 1952.
.I.
195, 1943.
Volume Numbcr
70 3
PYRIDOXINE
METABOLISM
IN
PREGNANCY
649
9. Greenberg, L. D., Boh, D. F., McGrath, H., and Rinehart, J. F.: Arch. Biochem. 21: 237, 1949. 1.0. Sprince, H., Lowy, R. S., Folsome, C. E., and Behrman, J.: AM. J. OBST. & GYNEC. 62: 84, 1951. 1.1. Wachstein, M., and Gudaitis, A.: (a) J. Lab. & Clin. Med. 40: 550, 1952. (b) J. Lab. & Clin. Med. 42: 98, 1953. 12. Rosen, F., Lowy, R. S., and Sprince, A.: Proc. Sot. Exper. Biol. & Med. 77: 339, 1951. 13. Vilter, C. F., Morgan, D., and Spies, T. D.: Surg., Gynec. & Obst. 83: 561, 1946. 14. Hobson, W.: J. Hyg. 46: 198, 1948. 15. Barnes, A. C.: AY. J. OBST. & GYNEC. 5, 3: 645, 1947. 16. Holzaepfel, J. H., and Barnes, A. C.: AI a. J. OBST. & GYNEC. 53: 864, 1947.