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  • 8/13/2019 Am J Clin Nutr-1992-Suharno-988-93_Cross-Sectional Study on the Iron and Vitamin a Status of Pregnant

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    988 Am J C /in Nuir 199 2;5 6 :9 88 -93 . P rin te d in U S A . 1 99 2 A m eric an S oc iety fo r C lin ic al N utritio n

    C ross-sec tiona l s tudy on the iro n and v itam in A s ta tu s o fp regnan t w om en in W es t Java Indones ia1 2D joko S uharno , C /ire E it e s t M u/u/a l M argo t HGM Log inan F rouw k je G de W aa rtD arw in K ariad i and Joseph GAJ H au tvas t

    A B S I R A C I A cro ss s ec tio n a l stu d y o f th e p rev a len ce o firon and v itam in A defic iency in norm al p reg nan t w om en inW est Java , In dones ia , w as earned ou t. O fth e 3 1 8 w om en s tud ied ,49 .4% w ere anem ic and , acco rd ing to m ultip le c rite ria , 43 .5%had iron-deficiency an em ia , 2 2 .3 % had iron -defic ien t e ry th ro -po ies is, and 6 .6% h ad iron dep le tio n . S erum retino l v alues re -vea led tha t 2 .5 ofthe pregn an t w om en w ere v itam in A defic ien tand 3 1% had m arg ina l v itam in A sta tus . T he re la tive d ose-re -sp onse test ca rr ied ou t on 4 5 w om en sho w ed tha t 4 (8 .9% ) haddefic ien t v itam in A liv er sto res . A fter gesta tiona l stage , pa rity ,and subd istric t w ere ad ju sted fo r, se rum retino l concen tra tionsw ere s ig n ifican tly po sitiv e ly assoc ia ted P < 0 .0 1) w ith hem o-g lo b in con cen trations , hem atocrit, an d se ru m iron co ncen tra-tions . T he subo p tim al v itam in A sta tus assoc ia ted w ith nu tn i-tiona l-de fic ien cy anem ia sugges ts tha t p regnan t w om en in thearea shou ld be supp lem en ted no t on ly w ith iron b u t a lso w ithv itam in A . T h is p rop osa l shou ld be tested in an in terven tio ns tudy . Am J C /in N u tr l992 ;56 :988-93 .

    K E Y W O R D S V ita m in A . iro n a n em ia p reg n a n cy Indonesia

    In tro d u c t io nH um an defic iency ofv itam in A and n u trition a l anem ia con-

    tinue to be ser io us prob lem s in d ev elo p ing cou n tries 1 , 2) . D efic ien cy o f iro n in th e d ie t is reg ard ed as th e m o st im po rtan tfac to r by fa r in th e e tio logy o fnu tritiona l anem ia. S evera l stud iesin h um ans an d a nim als ha ve sho w n tha t v itam in A d efic ien cyis as soc iated w ith a bn orm ali ties of iron m eta bo lism (3 -7) , a ndtha t supp lem en ta tion w ith v itam in A m ay increase iron s ta tu sas m easured by h em ato log ica l ind ex es (8 - 1 3). In hum an vo l-u n tee rs m ain ta ined on very -low vitam in A in takes fo r 1 -2 y .m o dera te anem ia d ev elop ed , w hich w as ref racto ry to m ed ic ina li ron b ut re spo ns ive to v itam in A (14 ). A s a resu lt o fth is f ind ing ,H odges et a l (5 ) rev iew ed th e resu lts o f s tud ies ca rr ied o u t onn onpregn an t and non lac ta ting w om en in deve lop ing co un triesw h ere the in tak e of iron w as 1 4 m g /d . T hey fou nd a s tron gre la tionsh ip be tw een seru m concen tra tions of v itam in A andb lood co ncen tra tion s of hem oglob in .

    In a sim ilar an aly sis of d ata f rom s tud ies c arr ied out at theln s titu to de N utn ic i#{24 3}n d e C en tro A m er ica y P an am a (IN C A P)in G uatem ala , M ejia et a l (3 ), found a pos itive co rre la tionbe tw een seru m iron and b lood hem oglob in con cen trations inch ild ren w ith adequa te in tak es of v itam in A bu t no t in those

    w ith inad eq ua te in takes. In a s tudy of p resch oo l ch ild ren inG ua tem ala , M ejIa and C hew (9) found tha t ch anges in se rumre tin o l sh ow ed a p ositive correla tion w ith to ta l iro n -b ind ing ca-pa city a nd tra nsfern in satu rat ion a nd a n eg ativ e co rrela tio n w ithserum fern itin a fte r 6 m o of fo rtifica tio n w ith v itam in A . S ig -n ifican t assoc ia tio ns of se ru m re tin o l w ith hem atocn it. se rumiron , se ru m fern itin , an d tran sfem n sa tu ra tion have been reportedb y B lo em e t al 1 1) in a cro ss-sec tio nal s tud y of c h ild re n inN o rth eas t T h aila nd .

    L iver iron sto res have been show n to be increased in v itam inA -de fic ien t ra ts (4 , 6 ), and th is inc rease is as soc iated w ith de-creased concen tra tion s ofiron in se rum (4) and fem ur (6 ). T husit w ould seem like ly tha t decreased u tilization of iron fo r he-m oglob in syn thes is m ay be re la ted to an inab ility to m obilizeiron from hepa tic s to res .

    In p regn an t w om en n u trition a l anem ia is o f ten a se riou s re -frac to ry prob lem . A s fa r as w e are aw are , on ly one s tudy hasbeen carried o u t on the ro le o fv itam in A in n u trition a l anem iain p reg na n t w om en , b u t the re su l ts w e re no t v ery c onc lus ive 1 5 ). W e p resen t th e resu lts o f a cro ss sec tio n a l s tu d y in w h ichw e d ete rm ined the preva lence ofv itam in A and iron defic ien cyin pregn an t w o m e n in th e B o gor d istric t o fW es t Jav a, Indo nes ia .W e also exam ined w heth er the re is an assoc ia tion be tw een v i-ta m in A and iron ind exe s in th is po pulatio n .

    S u b jec ts a n d m eth o d sT he s tu dy w as carried ou t in Sep tem ber and O cto ber 19 89

    and in vo lved the ex am in ation of33 3 c lin ica lly norm al p regnan tw om en ag ed 20 -35 y in th e second or th ird trim este r o f p reg -nancy . in 1 3 v illages in 3 subd is tric ts o f B ogor D is tric t, w h ichis s itu ate d a bou t 70 km sou th ofiakarta in the W est Java Pro v-in ce o f Indo ne sia . M uc h of the d istric t co m p ris es fe rtile lan dtha t is b eing used fo r rice an d o ther c rops , ho rticu ltu re , andp lan ta tions , w hereas the so u thern part (28% ) is a m oun taino usarea . T he av erage e leva tion ofthe w este rn part o f B ogor d istric t

    I F rom the D irec to ra te o f C o m m unity N utrition , M in is try o f H ea lthR I J ak ar ta P usa t In d on esia ; th e C en ter fo r R esea rch a n d D ev e lo p m en tin N utr itio n , M in istry of H e alth , B o gor 1 2 1 16 , Ind on esia ; and the D e-pa rtm ent ofH um an N utr itio n , W ag eninge n A gr icu ltu ral U niversity , 6 700E V W a gen ing en , T he N ether lan ds.

    2 R epr in ts no t ava ilab le .R ece ived N ovem ber 19 , 199 1 .A ccep ted fo r pub lica tion June 1 2 , 19 92 .

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    I RO N A N D V I T A M I N A ST A T U S I N PREG N A N C Y 9 8 9i s 1 50-250 m s. B ogor D i stri ct has an area of 0.3 m i l l i on hectares,and a populati on of 3.5 m i l l i on people. M ore than 70% ofthe pregnant w om en use the M other and C hi l d H eal th Serv i cef or antenatal and nutri ti onal care (16).

    T he w om en in this study cam e f rom the m iddle to l ow er so-ci oeconom ic classes and usual ly m ake use of the com m uni tyheal th serv i ces. T he pregnant w om en w ere requested to com eto the Posyandu (i ntegrated serv i ce post) or to the B alai D esa(com m uni ty center) i n the v i l l age f or exam inati on. T he stage ofgestation and estim ated date of del i very w ere cal culated f romthe f i rst day of thei r l ast peri od and com pared w i th resul ts ofthe obstetri c ex am inati on.

    Ev ery thi rd w om an w as questi oned about f ood consum pti on.socioeconom ic status, and hi story of prev ious pregnancy (dataf rom these questi onnai res are not reported in thi s paper) . Of the124 w om en questi oned. every second w om an w as chosen f or

    the relati ve-dose-response (RD R) test f or m easur ing v i tam in Astores. Subjects requi ri ng m edical attenti on w ere treated or re-f er red el sew here i f necessary .

    T he study w as carri ed out f ol l ow ing the ethi cal standards ofthe M ini stry of H eal th i n I ndonesia.

    ..1 , u h, , o / n n u t , l i F i CI b l o od e o l l e e t i a , iA nthropom etr ic m easurem ents com pri si ng height, w eight, and

    m idupper-arm ci rcum f erence (M U A C) w ere per f orm ed. I nf or-m ati on on age. pari ty , chronic diseases, and interval si nce thelast pregnancy w as recorded by using m other and chi l d heal thcards. V enous blood sam ples of 5 m L w ere taken on the sam eday as the antenatal exam ination, and stored on ice f or transportto the laboratory . H em atocni t and hem oglobin concentrati onw ere m easured and serum w as separated f rom blood by cen-tni f ugation at 2000 x g f or 15 m m at room tem perature onarri val . Sam ples of serum w ere stored separatel y at -20 #{ 176} Cnthe dark f or anal ysi s of f erni t i n, v i tam in A , and i ron; bl ood sam -pI es w ere anal yzed f or f ree ery throcy te protoporphynin. A l lanal yses w ere carri ed out w i thi n 3 m o af ter blood col l ecti on.B ioc /zc mica l a na lys is

    H em oglobin concentrati on w as m easured by the cy anom et-hem oglobin m ethod and hem atocni t by the m icrom ethod (17).M easurem ents of f erri t i n w ere perf orm ed by using the enzym e-l i nk ed im m unosorbent assay (EL I SA ) sandw ich assay as de-scnibed by the m anuf acturer (B oehr inger M annheim G m bHD iagnostica, M annheim , G erm any) . Serum iron and total - i ron-bi nding capaci ty w ere m easured spectrophotom etni cal l y asm odi f i ed by Cook et al 1 7) and transf erni n saturati on w as cal -cul ated by di v i di ng the serum i ron concentrati on by the total -i ron-bi nding capaci ty . Free ery throcy te protoporphy r in w asm easured by f luorom etry accordi ng to O rf anos et al I 8 ). R et inolw as m easured by H PL C (19) . T he RD R test f or v i tam in A w ascarri ed out by using a dose of 4000 I U reti ny l acetate 1 200 j igreti nol ) (20) . T he R D R w as cal culated f rom the absolute ri se i nplasm a reti nol concentrati on betw een 0 and 5 h postdosing,w hi ch w as di v i ded by the concentration reached at 5 h and ex-pressed as a percentage. T hus,

    R D R = 100 X (A 5 A 0 ) / A 5w here A 5 i s the plasm a retinol concentration (j zm ol /L ) at 5 haf ter dosing and A 0 i s the plasm a retinol concentrati on (j zm ol /L in th e fa st in g su b j ec t b e for e d os in g .

    I ron status w as assessed by using m ul ti pl e cri teri a (2 1 . Bythi s approach, i ron-def i ci ency anem ia i s diagnosed in pregnantw om en w hen the hem oglobin concentration i s < 1 10 g/L (22)and at l east tw o of the f ol l ow ing three indexes are abnorm al :serum f erni t i n (< 12 j ig/L ) (21). transf er ri n saturati on (< 16% )(2 1), and f ree ery throcy te protoporphy r in [ > 1 .25 j zm ol /L (700j i g/L ) red blood cel l s] (22). W hen the hem oglobin concentrationi s norm al , but there are abnorm al concentrati ons of at l east tw oof these i ron indexes, i ron status i s categori zed as i ron def i ci ent.I ron depleti on is def i ned by a serum f erri t i n concentrati on < I 2j i g/L w hi l e the rest of the i ron indi ces are norm al (21).

    V i tam in A status w as based on the serum retinol concentra-t io n: m ar gi nal . < 0.70 j im ol /L (20 j i g/dL ): and def i cient, < 0.35j im ol /L (10 j i g/dL ), and on R D R values (def i ci ent w hen theR D R w as > 20% ) (23).Stat ist ical ana l i . se .s

    Stati sti cal anal yses com pri sed single and m ul ti pl e regressionand Stu dent s t test. M ul tip le-regression anal yses w ere carri edout w i th the di f f erent i ron indexes as dependent vari ables andserum reti nol . gestati onal age, par i ty , and subdi str i ct as m dc-pendent vari ables. D um m y vari ables w ere used to representpari ty and subdistr i ct i n the m odels w hereas gestati onal age inw eek s w as incl uded as a conti nuous v ar iable. B ecause the di s-tr i buti on of serum f erri t in and transf erri n saturati on w as skew ed,natural log transf orm ed (I n) values f or these biochem ical v an-ables w ere used in the regression m odel s. A l l data w ere anal yzedw i th the SPSS/P stati sti cal pack age (24).

    Re su l t sA f ter the data w ere ex am ined, those of I 5 w om en w ere not

    anaIzed. O f these, 12 w om en had anem ia characteri sti c ofchroni c i nf ection (25, 26) because they had a hem oglobin con-centration < 1 10 g/L and a serum f enni ti n concentrati on 300j i g/L accom panied by reduced transf erni n saturation and/or el -evated f ree eny throcy te protoporphy rin. D ata f rom the rem aini ngthree w om en w ere inconsi stent: they had abnorm al f ree ery th-rocy te protoporphynin values w hen com pared w i th the rest ofthe population [ > 3.50 j im ol /L (2000 j i g/L ) red blood cel l s] ,w hereas al l other indi ces w ere norm al . T hus, data f rom 318w om en w ere anal yzed.

    T able I show s characteri sti cs and indexes of i ron and retinolstatus. T he av erage grav idi ty of the pregnant w om en w as 3.9 2.3 : SD o fw h ich one o ffiv e p r egnan c ies d id no t r esu lti n a l iv e bi rth.

    V i tam in A status based on serum reti nol concentrati ons w asas f ol l ow s: 8 w om en (2.5% ) w ere categori zed as def i ci ent (< 0.35pm ol /L ), 99 w om en (31.1% ) as m arginal (< 0.70 j im ol /L ), and21 1 (66.4% ) as adequate (> 0.70 j im ol /L ). Of the 62 w om enselected, data w ere obtai ned on the R D R test f rom 45 w om enw ho returned to the ex am inati on centers f or the test. The valuesf ound ranged f rom -27.8% to +41% , w i th a m edian of 1.7% .O n the basi s of an RD R > 20% , f our w om en (8.9% ) had def i cientl i ver reti nol stores, tw o of w hom had m arginal and tw o adequateconcentrati ons of v i tam in A in serum . O f the 4 1 w om en w i than R D R < 20% , 1 5 had m arginal and 26 adequate concentra-ti ons of v i tam in A in serum .

    H em ogl obi n concentrati ons < 1 10 g/L w ere f ound in 157pregnant w om en (49.4% ). A low serum f erni tin concentrati on< 12 j i g/L ) w as observed in 160 w om en (50.3% ), and elevated

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    S I S D (g eo m etric m ean) . n = 3 1 8: 46 w om en w ere un classified .

    9 90 S U H A R N O E T A LT A B L E 1C harac teris tic s and b io ch em ica l indexes of the pregnan t

    Pe r c e nt i l e s

    V alu e 5 th 50 th 95 thA ge (y ) 2 5 .9 4 .4 20 .0 25 .0 35 .0H eigh t (cm ) 14 9 .5 4 .9 141 .1 149 .5 157 .7We i g h t k g ) 5 0 . 2 6 . 5 4 1 . 1 4 9 . 5 6 1 . 2M idupp er-a rm circum ference (cm ) 24 .0 2 .1 21 .0 23 .9 27 .6S ys to lic b lood pressu re (m m H g ) 1 1 2 . 1 9. 6 100 .0 1 10 .0 12 0 .0D iasto lic b lood p ressu re (m m H g) 74 .9 7 . 1 60 .0 80 .0 80 .0G es tation al stage (w k) 26 .2 5 .8 16 .0 28 .0 36 .0He mo g l o b i n g / L) 1 0 9 1 0 9 2 1 1 0 1 2 5H em atocn it (L /L ) 32 .9 2 .8 28 .0 33 .0 37 .3Seru m fern itin ( g /L ) 1 3 .8 I 1 .4 (1 1 .0 ) 4 .2 10 .3 33 .0F re e e ry th ro cy te p ro to po rp hy nin

    (pm ol/L R B C ) 1 .56 0 .44 0 .83 1 .55 2 .30Seru m iron ( jim ol/L ) 10 .1 2 .40 6 .05 10 .2 14 .2T ota l- iron -b ind in g cap ac ity

    (jim ol/L ) 59 .9 1 1 .2 41 .9 59 .6 80 .4Tr a n s f e r r i n s a t u r a t i o n 1 7 . 8 6 . 1 1 6 . 8 ) 9 . 5 1 5 . 9 2 9 . 1S erum re tino l (jim ol/L ) 0 .87 0 .35 (0 .80) 0 .43 0 .80 1 .56R ela tive -d ose-respon se tes t (% ) = 45 2. 5 13 .0 -1 7 .2 1 .7 27 .0

    S S D (geom etric m ean): 11 = 3 1 8. excep t w here o therw ise no ted .

    free e ry th rocy te p ro top orphy rin [> 1 .2 5 jzm ol/L (700 jzg /L )] in tra tion w as assoc ia ted sign if ican tly P < 0 .01) w ith an increase237 w o m en (74 .5% ). Iro n sta tus based on m ultip le c rite ria is o f 4 .30 gIL hem og lob in , 1 .37 L /L hem atocrit, an d 1 I 8 j imol /show n in T ab le 2 . A ccord ing to th is m ethod , 1 43 (45 .0% ) w om en L serum iron and a lm ost s ign ifican tly P = 0 .065 ) w ith a decreasehad iron -defic iency anem ia w hereas 7 1 (22 .3 % ) w om en had de- o f free ery th rocy te p ro topo rphyr in of 0 . 1 32 jzm ol/L red b loodfic ien t e ry th ropo iesis an d 2 1 w om en (6 .6% ) h ad iron d ep letion . ce lls. In the m ultip le -reg ression m o de ls, ges ta tiona l stage had aFo rty -six w om en (1 4 .5 % ) co u ld no t b e c lass ified by th is m etho d : s ig n ifican t nega tive assoc ia tio n w ith hem oglo b in P < 0 .05 ), h e-33 had norm al hem oglob in and seru m fem tin concen tra tions m atocn it P < 0 .0 1 , se rum fenn itin P < 0 .00 1 , a nd t ra ns fe rr inbu t abno rm al free e ry th rocy te p ro top orphy rin n = 32) or ab- satu ration P < 0 .05) .no rm al transfe rrin sa tu ra tion ( = 1 ); I 3 w om en had hem oglob inconcen tra t ions < 1 1 0 gIL b u t on ly on e of the th ree ind exes D iscuss ion(se rum ferritin , transfen n in sa tu ra tion , and free e ry th ro cy te p ro -top orphy n in ) w as abnorm al; one w o m an had a hem oglob in con- A n em ia in pregnan t w om en is a p ub lic hea lth p rob lem par-cen t ra t ion < 1 10 g /L and all o the r in dexes w ere n orm al. ticu lar ly in deve lop ing coun tr ies , and the com m on type is iron -

    M ultip le -reg ress ion ana lysis w as used to ad just fo r e ffec ts o f d ef ic iency an em ia (2 7 , 2 8). S evere anem ia during pregn an cy isgesta tio na l s tag e, pa rity , an d sub d istric t. A f te r ad jus tm en t fo r assoc ia ted w ith an increased risk o fm aten na l and feta l m orb id itythese e ffec ts , se rum re tino l rem ained sign if ican tly p ositive ly as- and m orta lity . E ven m ild anem ia is asso cia ted w ith an in creasedsoc ia ted w ith hem oglo b in , hem ato cn it, an d se ru m iron (T ab le risk ofp rem atu re de live ry , low birth w eigh t, p lacen ta l hypertro -3 ). T hu s an in crease o f 1 jzm ol/L in the se rum re tin o l con cen- p hy , and red uced es tn io l excre tion (29). L ow av a ilab ility o f iron

    T A B L E 2Iron sta tus o f p regnan t w o m en on the bas is o f m ultip le cr ite ria5

    Iron-d eficien t Iron -defic ien tN orm al I ron d ep le tio n ery th ropo ies is anem ian = 37 ) n = 21 ) 11 = 71 ) n = 1 4 3 )

    He mo g l o b i n g / L) 1 2 0 6 1 2 1 4 1 1 5 4 1 0 1 6Serum ferritin (jig /L ) 27 .2 19 .5 ( 22 .9 ) 7 .8 2 .7 (6 .7 ) 10 .4 6 .9 (8 .9 ) 10 .0 5 .2 (8 .9 )F re e e ry th ro cy tep r o t o p o r p h y r i n( jzm o l/L R B C ) 1 .00 0 .20 1 .00 0 .2 0 1 .5 0 0 .29 1 .83 0 .38

    T ransfe rrin sa tu ra tio n (% ) 23 .5 4 .4 ( 2 3 .1 ) 2 5 .1 5 .4 ( 24 .6 ) 17 .9 5 .5 ( 17 .2 ) 13 .8 3 .5 ( 13 .3 )

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    I R ON A N D V I T A M I N A ST A T U S I N PREGN A N C Y 9 9 1T A B L E 3M ul ti pl e-regressi on coef fi cients w ith i ron i ndexes as dependentvariables and serum retinol (pm ol /L ) as the independent vari able5

    [ )ependent v ari abl e I ndependent vari able tH em oglobin (g/L ) 4.30 l .432tH em atocri t (L /L ) 1.37 0.430Serum f i. r i ti n ( g/L ) 0.077 0.097F ree er yt hr ocy te pr oto por phy ri n(m ol /L RB C ) -0.132 0.071T ransf erri n saturation (% ) 0.095 0.057Serum iron ( M m oI /L ) l .18t 0.385tT otal -i ron-bi ndi ng capaci ty

    ( M m o l / L ) 2.10 1.898S SE.t Coeti l ci ent adjusted f or subdi str i ct, pari ty , and gestati onal age.t P < 0 . 0 1 . T ransf orm ed to natural l ogari thm .

    i n the diet, poor i ron absorption, repeated and closel y spacedpregnancies. and prolonged lactati on are com m on f actors i n de-veloping countri es that pl ace a constant drain on the i ron storesof pregnant w om en.

    T he prev alence of nutri t i onal anem ia i s hi ghest (65% ) in SouthA sia (2). I n general , anem ia studies i n pregnant w om en con-ducted in I ndonesia hav e revealed that anem ia in pregnantw om en i s m ainl y due to m alnutr i t i on (nutri t ional anem ia)(30-33). Surv ey s in W est and Central Java and ip B al i byM ar toatm odjo et al i n 1973 (30) show ed that the highest prey -al ence of anem ia (77% ) am ong pregnant w om en w as f ound inthe ri ce-eati ng area of W est Java, com pared w i th the ri ce- andsw eet potato-eati ng area of B al i (56% ) and the ri ce- and cassav a-eating area of Central Jav a (46% ). K usin Ct al (34) observed aprevalence of anem ia of 24.5% in a poor rural com m uni ty i nEast Java. A study by H usaini et al i n 1989 (35) show ed thatthe prevalence of anem ia am ong pregnant w om en w as low esti n Central Jav a (39.7% ), 42.6% in East Java, 54.2% in SouthSum atra, and highest (62.9% ) in the ri ce-eati ng area of SouthK al im antan. I n our study in W est Java the higher prevalencecould possibl y be due to the consum pti on of ri ce as a staplef ood com pared w i th m aize in the area studied by K usin et ali n East Java and w i th ri ce and cassava in the area studied byM artoatm odjo et al i n Central Jav a.

    I n our study 2.5% of the pregnant w om en had v i tam in Aconcentrations < 0.35 j .zm ol /L , w hi ch w as regarded as a def i -ciency . This prevalence is < 5 , w hich is regarded as indicati nga problem of publ i c heal th si gni f i cance (23), but i t should beconsidered that th is cutof f point i s based on that f or chi l dren atri sk of xerophthalm ia (36). B ecause x erophthalm ia i s an ex trem ef orm of v i tam in A def i ci ency . i nter f erence w i th m etabol i sm , f orexam ple w i th that of i ron, probabl y ari ses i n i ndiv iduals bef orethis prevalence i s reached in the populati on. Pregnant w om enare par ti cul arl y prone to i ron def i ciency , and perhaps even m i l dv i tam in A def ici ency interf eres w i th thei r i ron m etabol i sm . I naddi ti on, ex tra v i tam in A i s needed duri ng pregnancy f or grow thand m aintenance of the f etus, f or bui ld i ng v i tam in A reservesin the f etal l i ver, and f or m aternal ti ssue grow th. I n our studyw e f ound that 31% of the pregnant w om en had v i tam in A con-centrati ons that could be regarded as m arginal . The I nternati onalV i tam in A Consul tati ve G roup (I V A C G: 19) has proposed that

    w hen the proporti on of the populati on w i th reti nol val ues < 0.70j im ol /L (20 jzg/dL ) i s > 15% , v i tam in A def i ci ency can be re-garded as a publ i c heal th problem . W hen m easured by the RD Rm ethod, a som ew hat hi gher proporti on of w om en (8.9% ; 4 ofthe 45 w om en studied) w as f ound to have def i cient v i tam in Al iv er stores. T hi s m ethod m ight be usef ul i n disti ngui shing sub-cl i ni cal v i tam in A status f rom other f actors that depress plasm aretinol concentrati ons (37) . O f the I 7 w om en w ho had m arginalserum v i tam in A concentrati ons, 2 had v i tam in A -def i cient l i verstores according to the RD R test. A l though som e w om en show ednegati ve RD R values and the test dose of 4000 lU w as not veryhigh 10 000 I U /d being the m ax im um acceptable supplem en-tation f or pregnant w om en) (38), negati ve RD R tests and f ai lureto show a transient ri se af ter a sm al l test dose are not f ound ini ndi v i dual s know n to hav e depleted l iv er stores (20, 39, 40).Regardless of the m ethod used, the ex tent of v i tam in A def i ci encyf ound in the present study indi cates the ex i stence of a publ i cheal th problem al though i t i s m uch less than that observed in acom parable populati on i n East Java by K usin et al (34), i n w hom23% of pregnant w om en com pared w i th 1 3% of nonpregnantcontrol subjects had serum v i tam in A concentrati ons < 0.35j im o l / L .

    T here are sev eral conf ounding f actors that can inf luence thevari ous resul ts f ound. A nem ia i s not only caused by i ron def i -ci ency but al so by other f actors such as v i tam in B - I 2 def i ci ency ,f o late def i ciency (w hi ch, af ter i ron def i ci ency , i s the m ost corn-m on cause of anem ia in pregnant w om en), i nf ectious di seases,and hem oglobinopathi es. M easuri ng hem oglobin concentrati onsi s usef ul f or screening f or anem ia but, because of i ts l ack ofspeci f i ci ty and the m ark ed overl ap in concentrations betw eennorm al and anem ic indi v i dual s, i ts usef ul ness i s som ew hat I im -ited 1 7) . A n addi tional problem in pregnant w om en i s the con-si derable vari ation i n the increase in plasm a volum e that occursduri ng pregnancy (28). Predi cti ng i ron-def i ciency anem ia by theex istence of tw o or three abnorm al indexes of i ron status (serumf erni t i n, transf erri n saturation, and f ree ery throcy te protopor-phy ri n) i s m ore speci f i c than use of hem oglobin concentrati onsalone (4 1 . By these cri teri a, 45% 143 of 3 1 8) of w om en w i thhem ogl obi n concentrati ons < 1 10 giL had tw o or m ore abnor-m al i ron indexes and w ere classi f ied as being i ron-def ici ent ane-m ic. W hen abnorm al i ron indices w ere f i rst considered, 59% ofthe 1 22 pregnant w om en w i th tw o, and 77% of the 92 w om enw i th three abnorm al i ron indexes had hem oglobin values < I 10g/L . T hi s i ncrease in speci f i ci ty , al bei t w i th som e loss of sensi -t i v i tv , w as al so reported by other authors (2 1 4 1 , 42).

    Prevalence of anem ia i s associated w i th gestati onal stage, w i ththe highest prevalence being f ound in the last tr im ester of preg-nancy (28, 34, 43, 44). I n our study the overal l prevalence ofanem ia (hem ogl obi n < 1 10 g/L ) w as 49.4% and the prevalenceof anem ia of w om en in the thi rd tr im ester of pregnancy w as58.1% (data not show n). I n addi ti on. m ean values of i ron indexes(hem oglobin, hem atocri t, serum f erri t in, serum i ron, and trans-f erri n saturati on) and m ean serum retinol values w ere signi f i -cantl y l ow er and m ean values of f ree ery throcy te protoporphy r inand total - i ron-bi nding capaci ty w ere signi f icantl y hi gher i n thethi rd tr im ester than in the second trim ester. T heref ore, in them ul ti pl e- regression anal ysis ex am ining the ef f ect of serum v i -tam in A on i ron indexes, correcti on w as m ade f or gestationalage in w eeks by appl y i ng regression analy si s.

    I n thi s study , i nf ecti on and inf estati on i n the w om en w erenot i nvesti gated. Thus to decrease the ef f ect of such conf ounding

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    99 2 S U H A R N O E T A Lf c to rs. I 2 w o m en w ere n o t in c lu d ed in th e d ata an aly s is b ecau seo f su sp ec ted in f ec tio n . T h ey h ad lo w co n cen tratio n s o f h em o -g lo b in an d h ig h seru m f ern itin co n cen tratio n s to g e th er w ith re -d u ced tran s f e rn in satu ratio n an d /o r elev ated f ree ery th ro cy tep ro to p o rp h y n in . B o th in f ec tio n an d iro n d e f icien cy are ch arac -te riz ed b y a d ep ress io n in seru m iro n an d tran sf e rn in satu ratio nw h ereas f ree ery th ro cy te p ro to p o rp h y n in is in creased 1 7 , 2 5 ,2 7 ). S eru m f ern itin is o f ten e lev ated in ch ro n ic in f ec tio n s an dd ep ressed in iro n d e f ic ien cy .

    A s in d icated in th e in tro d u c tio n , sev eral s tu d ie s h av e p aidatten tio n to th e p o ss ib le asso c iatio n b e tw een in d ex es o f iro n an dv itam in A statu s . In o u r stu d y seru m re tin o l co n cen tratio n w asasso c iated s ig n if ican tly w ith h em o g lo b in , h em ato crit, an d seru miro n w h en ad ju sted f o r e f f ec ts o f g es tatio n al stag e , p arity , an dsu b d is tn icts . In a co m p arab le cro ss -sec tio n al stu d y carried o u tby B lo em e t al I 1 ) w ith ch ild ren in n o rth eas t T h ailan d , anasso c iatio n b e tw een seru m re tin o l an d h em ato cn it an d seru miro n w as f o u n d . T h ey also f o u n d an asso c iatio n b e tw een seru mre tin o l an d tran s f e rrin satu ratio n , tran s f errin , an d seru m f ern itin ,b u t n o asso c iatio n b e tw een seru m re tin o l an d h em o g lo b in . Inin te rv en tio n stu d ie s earn ed o u t su b seq u en tly , th e o b serv ed e f f ecto f v itam in A su p p lem en tatio n o n iro n in d ex es d ep en d ed o n th etim e e lap sed s in ce th e su p p lem en tatio n w as g iv en . In th e f irsts tu d y , ch ild ren w ith a h em og lo b in co n cen tratio n < 7 .5 jim o l/Lw ere se lec ted . A ran d o m su b sam p le rece iv ed v itam in A cap su le s,w h ereas th e rem ain in g ch ild ren serv ed as co n tro l su b jec ts. T w om on th s af te r su p p lem en tatio n , s ig n if ican t d if f eren ces f o r re tin o l,re tin o l-b in d in g p ro tein , seru m iro n , an d tran sf errin satu ratio nw ere f o u n d b e tw een th e su p p lem en ted an d th e co n tro l g ro u p s 1 1). In a f o llo w in g stu d y th ey f o u n d sig n if ican t d if f e ren ces inre tin o l, retin o l-b in d in g p ro te in , h em o g lo b in , h em ato cn it, se ru miro n , an d tran s f e rrin satu ratio n af te r 2 w k o f su p p lem en tatio n ,w h ich ex c lu d ed seaso n al in f lu en ces 1 2 ). In In d ia, Pan th e t al I 5) h av e sh o w n th at th e d ec lin e in h em o g lo b in o ccu rrin g ato n e o f th e tim e p o in ts stu d ied 2 6 -2 8 w k o f g estatio n ) w as p re-v en ted w h en p reg n an t w o m en w ere g iv en 1 8 0 0 IU v itam in A /d f o r> l2 w k .

    B ecau se th e p resen t c ro ss -sec tio n al s tu d y h as sh o w n a re la-tio n sh ip b e tw een th e m e tab o lism o f v itam in A an d th at o f iro n ,an in te rv en tio n stu d y w ith v itam in A an d iro n su p p lem en tatio nis n o w p lan n ed . G ro u p s w ill rece iv e e ith er iro n , v itam in A , o rb o th an d if th e asso ciatio n o f v itam in A w ith iro n tu rn s o u t tob e cau sal, su p p lem en tatio n o f p reg n an t w o m en w ith v itam in Aw ill ex ert an ev en g reate r im p ac t o n p u b lic h ealth b y s im u lta-n eo u s ly red u c in g n u tritio n al an em ia am o n g p reg n an t w o m enan d p ro v id in g th e ad d itio n al v itam in A req u ired d u rin g p reg -n a n cy . 3

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