ANALYSIS OF PAHO COLLABORATIVE STUDIES OF NUTRITIONAL ANEMIAS IN LATIN AMERICA AND TIE CARIBBEAN' Ref: RD 8/14. 9 June 1969

Transcription

1 Pan American Health Organizatin ADVSORY COMMTTEE ON MEDCAL RESEARCH Eighth Meetini Wnahin3-nn DC.. 9-1; Jurip 19q9q.. C2LS1 s ALAVV~ BALA_ tem 11.4 f the A,2n~ : De - s As s_ a ANALYSS OF PAHO COLLABORATVE STUDES OF NUTRTONAL ANEMAS N LATN AMERCA AND TE CARBBEAN' Ref: RD 8/14 9 June 1969 PAN AMERCAN HEALTH ORGANZATON Pan American Sanitary Bureau, Reginal Office f the WORLD HEALTH ORGANZATON Washingtn, D.C.

2 ANALYSS OF PAHO COLLABORATVE STUDES OF NUTRTONAL ANEMA N LATN AMERCA AND THE CARBBEAN During the past several years, cllabrative studies have been perfrmed under the jint directin f WHO and PAHO in varius cuntries f Latin America and the Caribbean t determine the incidence f latent and manifest nutritinal anemia. The present reprt deals with the statistical analysis f this data. A prtin f the material included in the present reprt was initially evaluated in preparatin fr a meeting spnsred by PAHO in Caracas, Venezuela, in August, During the past year, it has becme apparent that a cmparatively large number f errrs ccurred in transferring the data t a medium suitable fr cmputer analysis. These errrs were the result f insufficient time t verify the data after transfer. n additin values fr many f the parameters were nt available fr the 132 cases included in that reprt. n preparatin fr the present reprt, the riginal data was returned t the investigatrs fr review. As a result, rughly tw-thirds f these cases have been crrected r mdified with respect t ne r mre measurements. n additin the ttal size f the survey has gradually enlarged t a current ttal f 185 cases n which the present analysis was perfrmed. SURVEY MATERAL Rughly tw-thirds f the cases included in this reprt (142) were

3 Page 2 btained during the secnd and third trimester f pregnancy. The remaining cases which will be referred t here as 'cntrls', were btained in nn-pregnant female and male subjects which ttaled 485 and 313 respectively. The fllwing is a brief résumé f the type f ppulatin sampled in each series: Caracas, Venezuela (altitude: 3 ft.). The subjects in the pregnancy grup and bth cntrl grups were frm the city f Caracas and belnged t the same lw sci-ecnmic class. All pregnant females attended a charity Maternity. Sa Paul, Brazil (altitude: 25 ft.). The pregnant females were wives f hard labrers living within the city f Sa Paul. The standard f living fr these families was cnsidered t be 'reasnable' and the ppulatin might be classified as lw-middle. The limited number f samples in bth cntrl grups were btained in healthy medical and high schl students. Guatemala City, Guatemala (altitude: 5-7 ft.). The survey was made in bth urban and rural ppulatins living in the city f Guatemala and surrunding area. The urban and rural subjects were nt kept separate in the present analysis. An average altitude f 6 ft. abve sea level was assumed. The sci-ecnmic status f the subjects has nt been stated; the three surveys were presumably btained

4 Page 3 in cmparable ppulatins. Mexic City, Mexic (altitude: ft.). Three separate surveys in pregnant females are referred t in the descriptin f the results as A, B and C. Pregnancy 'A' series and the data fr bth nnpregnant female and male cntrls was btained in a rural ppulatin living in a small twn 8 miles frm Mexic City (Humantla, State f Tlaxcala, altitude 84 ft.). The sci-ecnmic status f these subjects is described as 'very pr.' The remaining tw series in pregnant females were btained in subjects living in Mexic City (altitude 74 ft.). The standard f living in 'B' series was lwer than in 'C' but apparently smewhat better than the rural ppulatin f series 'A'. Typically, the families in 'B' series were unable t pay scial security and had an average mnthly incme f US $7 (range $24 - $16). The families in the 'C' series have been classified as upper-lw and lw-medium and are distinguished frm the 'B' series in their ability t pay scial security and thereby attend a maternity hspital supprted by the Scial Security Agency. The incme f these families ranged frm $1- $2 per mnth. Frm the ethnic standpint, subjects in all series can be cnsidered as "mestizs". Medellin, Clmbia (altitude: 48 ft.). The sci-ecnmic status was rughly cmparable t Mexic 'C' series in that all families

5 Page 4 were able t pay fr scial securíty. The sci-ecnmic status is classified as 'lw-middle' and the ethnic backgrund f the ppulatin was a mixture f white, Negr and ndian with mre prevalence f white than ther races. Lima, Peru (sea level). N descriptin f the ppulatins surveyed is available at this time. The samples were presumably btained in subjects living within the city f Lima. Crrientes, Argentina (sea level). The survey was perfrmed in an urban ppulatin classified as 'lw' with respect t sci-ecnmic status. The ethnic backgrund f the subjects was exclusively white. METHODS OF ANALYSS The analysis was perfrmed n all cases in which a hemglbin determinatin was available. The cases were cded accrding t the cuntry and study grup. The number assigned teach case by the investigatrs during the riginal survey was retained fr identificatin purpses. The fllwing measurements were then recrded fr each case when available: hemglbin, hematcrit, reticulcyte cunt, serum irn, ttal irn-binding capacity, serum flate, serum vitamin B 12, serum albumin, and average lbe cunt f plymrphnuclear leukcytes. n additin, the time f gestatin was entered fr all samples in pregnancy. Values fr the mean crpuscular hemglbin cncentratin and transferrin saturatin were calculated by the cmputer frm the parameters listed abve.

6 Page 5 Missing values were encuntered fr certain measurements in all surveys. All missing values were cded with the result that measurements in which a value f was actually btained were mitted frm the analysis. This resulted in the exclusin f a limited number f serum vitamin B12 measurements in the Caracas series fr which n micrbilgical grwth had been bserved. An ccasinal reticulcyte cunt may have been mitted fr a similar reasn. Altitude crrectins. n rder t cmpare ppulatins living at varying altitudes, a crrectin was applied t all hemglbin values recrded in the tables. Althugh there is sme evidence in the literature that the hemglbin level is lgarithmically related t altitude ver the range f - 14,9 ft. abve sea level, a linear relatinship was assumed ver the mre limited range f - 8,4 ft. which ccurred with the present data. A factr f.2 g per 1 ft. altitude was emplyed which resulted in the fllwing ttal crrectin t hemglbin in the varius series: Venezuela,.6 g; Brazil,.5 g; Guatemala, 1.2 g; Mexic, 1.68 g and 1.47 g; Clmbia,.95 g. N crrectins were applied t data received frm Peru r Argentina. The calculatin f mean crpuscular hemglbin cncentratin was f curse made befre applying any f the abve crrectins. Criteria fr anemia and nutritinal deficiency. Guidelines established by the 1968 WHO Scientific Grup n Nutritinal Anemia were used

7 Page 6 and are summarized as fllws: Hemglbin adult females, pregnant adult females, nn-pregnant adult males rn Deficiency (a) serum irn (b) transferrin irn Flate Deficiency Vitamin B 1 2 Deficiency - Hb < 11 g/1 ml - Hb < 12 g/1 ml - Hb < 13 g/1 ml - <5 tg/1 ml - <15% < 3 ng/ml - <8 pg/ml Exclusin f data. Certain data was nt suitable fr all types f statistical analysis. Fr determinatins f the accumulative frequency distributin and in calculating crrelatin cefficients, surveys e cntaining less than 3 bservatins were mitted. The secnd type f mmisin ccurred when determining the incidence f anemia r deficiencies f irn flate r vitamin B 12. The need t characterize nrmality r abnrmality with respect t these parameters made it necessary t exclude any cases which did nt have values fr ne f the fllwing: hemglbin, serum irn, TBC, serum flate and serum vitamin B12. RESULTS The results f the analysis have been extensively recrded in the 25 tables appended t the reprt. The bjective here was t include

8 Page 7 sufficient infrmatin t allw individual interpretatins. Data summarized n all but the last fur tables is descriptive in nature and will be cmmented n nly briefly. The results f frmal statistical analysis utlined in the last fur tables will be described in greater detail. n Table, the sampling time f the varius pregnancy surveys is classified accrding t secnd r third trimester. Subjects frm Venezuela, Brazil, Guatemala and Mexic 'B' and 'C' series were btained exclusively during the third trimester. Rughly nethird f the cases frm Clmbia and Peru and a smewhat smaller prtin frm Mexic 'A' series and Argentina were btained during the secnd trimester. Althugh the prtcl fr the cllabrative study specified nly third trimester samples, it was decided t include all f the submitted pregnancy data in the reprt. Because f the failure t demnstrate a crrelatin between sampling time and hemglbin level in any f the series, it was decided nt t apply any systematic crrectin fr the sampling time in gestatin. n Table - X inclusive, the individual measurements are summarized fr each series as the mean, standard deviatin and number f cases. Values have als been given in these tables fr the percentiles rthe values fr the particular measurements belw which lie 1%, 5% (the median) and 9% f the ppulatin. The type f infrmatin given by

9 Page 8 these percentile values might best be shwn by example. n the pregnancy series fr Brazil and Guatemala, nearly identical values have been btained fr the 5 and 9 percentile f the hemglbin level. The value fr the 1 percentile is rughly 2 1/2 g lwer in the case f the Guatemala series hwever indicating an unusual number f lw values. This is reflected in the disparity between the mean and median hemglbin level fr Guatemala (which indicates significant negative skewing f the frequency distributin) A mre detailed descriptin f the frequency distributin fr six f the mre imprtant measurements is given in Tables inclusive. These tables list the percentage f cases with values eaual t r less than the level f the measurement given at the head f each clumn. The number f cases frm which these distributins were determined is identical with the numbers listed in Tables - X fr the crrespnding measurement. The term 'cmpsite' in these and the remaining tables were calculated frm the individual survey means weighted accrding t the number f bservatins. The incidence f anemia has' been given in Table XV where a distinctin has been made between anemia withut assciated deficiency, with a single deficiency (either irn, flate r vitamin B 12 ) and with tw r mre simultaneus deficiencies. rn deficiency was defined fr the purpses f this table in terms f the serum irn level rather than the transferrin saturatin. Attentin is drawn t the high incidence f 25.5% in the pregnancy data fr 'unexplained' r islated anemia which ccurred O

10 Page 9 mre frequenctly than anemia assciated with ne r mre deficiencies. The implicatin here is that the value f 11 g hemglbin n which anemia in pregnancy was defined may be inapprpriately high. Similar cmments apply t the female cntrls. One additinal pint f interest in this table is the unusually high frequency f anemia assciated with multiple deficiency in pregnancy series frm Venezuela and Argentina (14.6 and 1. 2 % respectively). The incidence f irn deficiency has been summarized in Table XV accrding t the serum irn level and in Table XX accrding t the transferrin saturatin. The use f the latter definitin results in a mre than tw-fld higher prevalence f irn deficiency with the difference mst apparent in the pregnancy series. An interesting difference in the tw tables is seen in tha pregnancy data where the incidence f islated irn deficiency with and withut anemia is given. The use f the serum irn level rather than transferrin saturatin reduces the incidence f irn deficiency withut anemia by a factr f 4 whereas the prevalence f irn deficiency with anemia is different by a factr f nly 2. This same pattern is seen in female cntrls and perhaps suggests that the serum irn level is a mre valid defining parameter than the transferrin saturatin. A similar frmat has been used t list the prevalence f flate and vitamin B12 deficiency in Tables XX and XX. n the case f flate, the

11 Page 1 cmpsite value fr ttal prevalence f flate deficiency is surprisingly similar fr all three study grups ( %). t is discncerting t lw find that flate levels were rarely assciated with anemia, itneither female r male cntrls. n the fllwing table vitamin B12 deficiency is cnspicuusly absent in cntrl subjects and,in pregnancy surveys, it was mre ften assciated with nrmal than a subnrmal hemglbin value. Sme dubt as t the validity f serum vitamin B12 measurements r their interlabratry standardizatin is raised by the relative immunity t abnrmal vitamin B12 levels in the Mexic data and the inrdinately high frequency in the Brazil series where the ccurrence f ther deficiencies r f anemia was unusual. t remains t evaluate the validity f the parameters n which we define anemia r a specific nutritinal deficiency. f a particular measurement is t be valid as an index f -nutritinal anemia, then sme relatinship must be demnstrated between this measurement and the level f hemglbin. This premise was the basis fr statistical analyses which are summarized in the remaining tables. n the first apprach summarized were calculated in Tables XX and XX, crrelatin cefficients/in each survey fr all pssible cmbinatins f the survey measurements. Sme f tha mre interesting crrelatins frm the ttal f mre than 16 values which were examined, are expressed in this table as the prbability (%) that the value culd have been bserved by chance alne. Thus the lwer the

12 Page 11 each value, the clser the assciatin between/pair f measurements, values f less than 5 usually being taken as statistically significant. A negative sign preceding the value indicates a reciprcal relatinship (as X increases, Y decreases), i.e., a negative crrelatin cefficient. Many f the crrelatins shwn in Table XX have been included as a matter f interest and the mst imprtant nes are given in the first 5 clumns. The mst impressive finding was the highly significant crrelatin between hemglbin and serum irn in all but the female cntrl grup frm Clmbia and the male cntrl grup frm Venezuela. Anther impressive finding was the clse relatinship between the serum albumin and hemglbin level in all but three f the series in which the serum albumin was measured. n cntrast with these relatinships, a significant relatinship between hemglbin and serum flate was seen in nly three f the pregnancy series and in the female cntrls frm Mexic. Even in these series, the degree f crrelatin was nt impressive. Fr hemglbin and serum vitamin B12, nly ne f the series (Brazil, pregnancy grup) shwed a significant relatinship. Of the remaining relatinships the crrelatin between serum irn and MCHC was statistically significant in the majrity f series and particularly in the pregnancy subjects. Neither flic acid r serum vitamin B12 were related t the MCHC. Other significant crrelatins were spradic althugh it is interesting t nte that the serum albumin

13 Page 12 was nt infrequently related t the serum irn, TBC, serum flate r serum vitamin B 1 2. A final pint f nte is the crrelatin between the serum flate and mean lbe cunt in the three pregnancy series in which this latter measurement was perfrmed. n Table XX, crrelatin cefficients have been expressed in the same manner fr the mre imprtant measurements and the sampling time in the pregnancy surveys. t is f interest that with increasing gestatin time, the rise in TBC was mre apparent than the fall in serum irn level. Only in Mexic 'A' series was sme relatinship bserved between the hemglbin level and gestatin time. Finally bth the serum flate and serum vitamin B12 level shwed a fall with increasing gestatin althugh it shuld be nted that fr Guatemala, the serum flate underwent significant rise rather than fall ; the same bservatin applies t serum vitamin B12 levels frm Brazil. The secnd apprach t assessing the validity f the defining parameters is summarized in Table XXV. n each series, subjects were divided int thse with and withut a deficiency(in ne f the three nutrients) and the difference in mean hemglbin between these tw grups was tested by the familiar Students t. are listed fr tha number f deficient subjects, Fr each nutrient, values difference in mean hemglbin(between the deficient and nrmal grup) and finally the prbability that tha t value fr significance f this difference in means

14 Page 13 expressed as a percent. The interpretatin f the significance prbability is identical with that described fr crrelatin analysis in that the greater the difference in mean hemglbin, the lwer the percentage prbability and the mre significant the result. n using the serum irn level t define irn deficiency, the number f deficient subjects was frequently t small. Values in bradcets under irn deficiency give the result btained when the transferrin saturatin was used rather than the serum irn level. Tha data summarized in Table XXV established a clear difference in hemglbin level between nrmal and irn deficient subjects with single exceptin f samples btained in pregnancy frm Brazil. Equally impressive was the lack f this difference in the case f flate r vitamin B12 levels. n the case f serum flate, three series shwed a between significant difference in hemglbin levels nrmal and flate deficient grups (pregnant subjects frm Argentina, female cntrls frm Venezuela and male cntrls frm Mexic) but in tw f these cases, the hemglbin level was fund t be significantly higher in the deficient subjects as cmpared with nrmals!!

15 Page 14 SUMMARY AND CONCLUSONS 1. The prevalence f anemia and deficiency f nutrients which might accunt fr it have been examined accrding t criteria established by the WHO Scientific Grup n Nutritinal Anemia, in 185 subjects frm seven cuntries in Latin America and the Caribbean. 2. rn deficiency has been identified as a cmmn and imprtant cause f nutritinal anemia in bth pregnant and nn-pregnant females f the lw sci-ecnmic ppulatins surveyed. While in n deficiency anemia culd nt be identfied with certainty in the male ppulatin, the significant crrelatins bserved between serum irn and hemglbin in mst series suggest that at least bdy irn depletin if nt anemia exists als in males. 3. Ten per cent f pregnant females and bth female and male cntrls had flate deficiency by the criteria emplyed. The significance f this in relatin t nutritinal anemia, hwever, requires further clarificatin. While sme marginal evidence was btained that flate deplitin may ccur in late pregnancy, in nne f the study grups culd flate deficiency anemia be identified and in bth cntrl grups, flate deficiency and anemia appeared t be mutually exclusive.

16 Page Subnrmal levels in serum vitamin B 1 2 were encuntered nly in third trimester pregnancy. Evidence that these were in any way related t nutritinal anemia hwever, was cnspicuusly absent. t is cncluded that either ur present methds are wrthless fr detecting significant depletin in bdy B 1 2 r that such a depletin des nt arise n a nutritinal basis in the ppulatins studied. 5. The serum albumin has emerged as a useful index f verall nutritinal status. The usefulness f this parameters might be further enhanced in prevalence surveys by instituting a prgram f interlabratry standardizatin. 6. The cncept f third trimester sampling in prevalence surveys needs t be re-examined. N clear evidence was btained in the present analysis that subnrmal levels f the deficiency parameters in pregnancy represented anything mre than a cmplex physilgic change which characterizes the gestatin perid. While mre meaningful infrmatin might be btained by revising the criteria f deficiency in pregnancy, a mre rewarding apprach t sampling may be the mre handicapped segments f a ppulatin(such as infants r elderly subjects where the cnsequences f nutritinal anemia may be mre serius. 7. The limitatins f defining anemia accrding t a single hemglbin level will nt be re-stated here. Fr thse wh feel mre secure with such criteria, validity might be enhanced by reducing the level in bth pregnant and nn-pregnant females and increasing it fr male subjects.

17 l ( E< 4( (OD C a) U'O O.D LO a) a m C ( w CO w E-- c E-' ' -%4 CO lk ) 'A 3 r U) v~~~u c "~~l D a) CO a CO L cm N N O v v v CM m 'A V ',D O m C9 C*, (O C m L' co U)P'P ro az m :Z a - Er w w F m :2 E- u.> -14. CD 1 LO OD 1 (. C'J cm co - :i Z < $ E-' C P4 C> U) CS CM A V a (1 D CS] V O mj LO O el] 1-.( 1- CS i i- cr) CV~c CD C C 4c 4-' cl >i z 5 b~ r-l : w N m- c a,< w 5 ~ < < O z - C at E

18 TABLE. HEMOGLOBN LEVEL COUNTRY NO. OF CASES MEAN SD 1% PERCENTLES 5%* 9% ( g 1 ml WB ) PREGNANCY BRAZL MEXCO (A) MEXCO (B) MEXCO (C) COLOMBA ARGENTNA COMPOSTE** FEMALE CONTROLS BRAZL MEXCO COLOMBA ARGENTNA e COMPOSTE MALE CONTROLS BRAZL G UATEMALA MEXCO COMPOSTE * Median. **The average value fr all cuntries has been calculated by weighting with the number f bservatins in each series.

19 TABLE MEAN CORPUSCULAR HEMOGLOBN CONCENTRATON COUNTRY NO. OF CASES MEAN SD PREGNANCY ( g 1 PERCENTLES 1% 5% 99 D1 ml WB ) 1 BRAZL GUATE MALA MEXCO (A) MEXCO (B) MEXCO (C) COLOMBA ARGENTNA COMPOSTE FEMALE CONTROLS BRAZL MEXCO COLOMBA ARGENTNA COMPOSTE MALE CONTROLS BRAZL MEXCO COMPOSTE

20 TABLE V SERUM RON. COUNTRY NO. OF CASES MEAN SD 1% PERCENTLES 5% 9% ( 1 ml PREGNANCY BRAZL MEXCO (A) MEXCO (B) MEXCO (C) COLOMBA ARGENTNA COMPOSTE FEMALE CONTROLS BRAZL MEXCO COLOMBA ARGENTNA COMPOSTE MALE CONTROLS BRAZL MEXCO COM POSTE

21 TABLE V TOTAL RON-BNDNG CAPACTY COUNTRY NO. OF CASES MEAN SD PERCENTLES 1% 5% 9% ( pg Fe 1 ml PREGNANCY BRAZL MEXCO (A) MEXCO (B) MEXCO (C) COLOMBA ARGENTNA COMPOSTE FEMALE CONTROLS BRAZL MEXCO COLOMBA ARGENTNA COMPOSTE MALE CONTROLS BRAZL MEXCO COMPOSTE

22 TABLE V TRANSFERRN SATURATON COU NTRY NO. OF CASES MEAN SD PERCENTLES 1% 5% 9% PREGNANCY BRAZL MEXCO (A) MEXCO (B) MEXCO (C) COLOMBA ARGENTNA COMPOSTE FEMALE CONTROLS BRAZL MEXCO COLOMBA ARGE NTNA COM POSTE MALE CONTROLS BRAZL MEXCO COMPOSTE

23 TABLE V SERUM FOLATE PERCENTLES COUNTRY NO. OF CASES MEAN SD ERCENTLES 1% 5% 9% PREGNANCY ( ng ml ) BRAZL MEXCO (A) MEXCO (B) MEXCO (C) COLOMBA ARGENTNA COMPOSTE FEMALE CONTROLS BRAZL MEXCO COLOMBA ARGENTNA COMPOSTE MALE CONTROLS BRAZL MEXCO COMPOSTE

24 TABLE V SERUM VTAMN B12 COUNTRY NO. OF CASES MEAN SD 1% PERCENTLES 5% 9% ( pg ml ) PREGNANCY BRAZL MEXCO (A) MEXCO (B) MEXCO (C) ARGE NT NA COM POSTE l FEMALE CONTROLS BRAZL MEXCO COM POSTE MALE CONTROLS BRAZL MEXCO COM POSTE e

25 TABLE X SERUM ALBUMN COUNTRY NO. OF CASES MEAN SD 1% PERCENTLES 5% 9% ( g 1 ml ) PREGNANCY BRAZL MEXCO (A) MEXCO (B) MEXCO (C) COLOMBA ARGENTNA COMPOSTE FEMALE CONTROLS BRAZL MEXCO COLOMBA ARGENTNA COMPOSTE MALE CONTROLS BRAZL MEXCO COMPOSTE

26 TABLE X. MEAN LOBE COUNT* COUNTRY NO. OF CASES MEAN SD PERCENTLES 1% 5% 9% PREGNANCY BRAZL COLOMBA COMPOSTE FEMALE CONTROLS COLOMBA COMPOSTE MALE CONTROLS * Average number f lbes in plymrphnuclear leukcytes n peripheral bld smear.

27 TABLE X ACCUMULATVE FREQUENCY DSTRBUTON OF HEMOGLOBN LEVELS Cuntry Prprtin (%) f Cases with the Fllwing Hemglbin Levels (g/1 ml WB) Pregnancy Z9 1 1 z12 l Venezuela Brazil Guatemala Mexic (A) Mexic (B) Mexic (C) Clmbia Peru Argentina Cmpsite* Female Cntrls 21 z z Venezuela Guatemala Mexic Clmbia Peru Cmpsite Male Cntrls 11 _12 _13 _14 d15 16 Venezuela Guatemala Mexic Peru Cmpsite * The previus values weighted accrding t the number f bservatins in each series.

28 TABLE X ACCUMULATVE FREQUENCY DSTRBUTON OF SERUM RON Cuntry Prprtin (%) f Cases with the Fllwing Serum rn (Gg/1 ml) Z Z4 z5 <6 Pregnancy Venezuela Brazil Guatemala Mexic (A) Mexic (B) Mexic (C) Clmbia Peru Argentina Cmpsite Female Cntrls Venezuela Guatemala Mexic Clmbia Peru Cmpsite Male Cntrls Venezuela Guatemala Mexic Peru Cmpsite e

29 TABLE X ACCUMULATVE FREQUENCY DSTRBUTON OF TOTAL RON-BNDNG CAPACTY Cuntry Prprtin (%) f Cases with the Fllwing Ttal rn-binding Capacity (jig Fe/1 ml) >65 >6 >55 >5 >45 >4 Pregnancy Venezuela Brazil Guatemala Mexic (A) Mexic (B) Mexic (C) Clmbia Peru Argentina Cmpsite Female Cntrls Venezuela 7, 31. Guatemala Mexic Clmbia Peru Cmpsite Male Cntrls Venezuela 9.1 Guatemala Mexic 5.6 Peru Cmpsite

30 TABLE XV ACCUMULATVE FREQUENCY DSTRBUTON OF TRANSFERRN SATURATON Cuntry Prprtin (%O) f Cases with the Fllwing Transferrin Saturatin Z7.5 Z Z Z2 Pregnancy Venezuela Brazil Guatemala Mexic (A) Mexic (B) Mexic (C) Clmbia Peru Argentina Cmpsite Female Cntrls Venezuela Guatemala Mexic Clmbia Peru Cmpsite Male Cntrls Venezuela Guatemala Mexic Peru Cmpsite e

31 TABLE XV ACCUMULATVE FREQUENCY DSTRBUTON OF SERUM FOLATE Cuntry Prprtin (%) f Cases with the Fllwing Serum Flate (ng / m ) c1 z2 z3 z4 z5 <6 Pregnancy Venezuela Brazil Guatemala Mexic (A) Mexic (B) Mexic (C) Clmbia Peru Argentina Cmpsite Female Cntrls Venezuela Guatemala Mexic Clmbia Peru Cmpsite Male Cntrls Venezuela Guatemala Mexic Peru Cmpsite

32 TABLE XV ACCUMULATVE FREQUENCY DSTRBUTON OF SERUM VTAMN B 12 Cuntry Prprtin (%) f Cases with the Fllwing Serum Vitamin B17 ( pg / ml ) 54 8 < R Pregnancy Venezuela Brazil Guatemala Mexic (A) Mexic (B) Mexic (C) Peru Argentina Cmpsite Female Cntrls Venezuela Guatemala Mexic Peru Cmpsite Male Cntrls Venezuela Guatemala Mexic Peru Cmpsite

33 TABLE XV NCDENCE OF ANEMA* Cuntry Pregnancy N. f Subj ects With slated Deficiency ( % With Multiple Deficiency f N Deficiency Cases Ttal Venezuela Brazil Guatemala Mexic (A) Mexic (B) Mexic (C) Peru Argentina Cmpsite Female Cntrls Venezuela Guatemala Mexic Peru Cmpsite Male Cntrls Venezuela Guatemala Mexic Peru Cm psite * Anemia defined as a hemglbin value f less than 11. in pregnancy, 12. in nnpregnant females, and 13. in male subjects.

34 TABLE XV NCDENCE OF RON DEFCENCY* COUNTRY NO. OF SUBJECTS SOLATED Withut With Anemia Anemia MULTPLE TOTAL f Ttal Cases ) PREGNANCY BRAZL MEXCO (A) MEXCO (B) MEXCO (C) ARGENTNA COMPOSTE ' FEMALE CONTROLS MEXCO COMPOSTE MALE CONTROLS MEXCO COMPOSTE * rn deficiency defined as a serum irn less than 5 pg per 1 ml..

35 - TABLE XX NCDENCE OF RON DEFCENCY* COUNTRY NO. OF SUBJECTS SOLATED Withut With Anemia Anemia MULTPLE# TOTAL ( % f Cases ) PREGNANCY BRAZL MEXCO (A) M EXCO (B) MEXCO (C) ARGENTNA COMPOSTE FEMALE CONTROLS MEXCO COMPOSTE MALE CONTROLS MEXCO COMPOSTE * rn deficiency is # rn deficiency in defined as a transferrin saturatin f less than 15%. additin t either flate r vitamin B 12 deficiency.

36 TABLE XX NCDENCE OF FOLATE DEFCENCY* COUNTRY NO. OF SUBJECTS SOLATED Withut With Anemia Anemia MULTPLE TOTAL ( f Ttal Cases ) PREGNANCY BRAZL MEXCO (A) MEXCO (B) MEXCO (C) ARGENTNA COMPOSTE FEMALE CONTROLS MEXCO COMPOSTE MALE CONTROLS MEXCO COMPOSTE * Flate deficiency defined as a serum flate value f less than 3 ng/ml.

37 TABLE XX NCDENCE OF VTAMN B12 DEFCENCY* COUNTRY NO. OF SOLA TED MULTPLE TOTAL Withut With Anemia Anemia ( % f Ttal Cases PREGNANCY BRAZL MEXCO (A) MEXCO (B) 12 MEXCO (C) ARGENTNA COMPOSTE FEMALE CONTROLS MEXCO COMPOSTE MALE CONTROLS MEXCO COMPOSTE * Vitamin B12 deficiency defined as a serum vitamin B12 less than 8 pg/ml.

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