./·

Effect of prenatal multiple micronutrient supplements on maternal weight and skinfold changes: A randomized double-blind clinical trial in Mexico

Usha Rarnakrishnan, Teresa González-Cossío, Lynnette Maríe Neufeld, Juan Rivera, and Reynaldo Martorell

Abstract

Backgrormd. Recen/ trinls of prenatal m11/tivitc1mi11-minernl supplcments have yielded mixed findings for outcomes such (IS birth size, lmt i-he benejits of prenatal multivitmnin-minernl supplements for nulfr.tnal 011t­comes are unknow11.

Objectfre. The nwin objecti1•e ofthis study was to exam­ine the ejfect of prenatnl mu/tiple micronutrient supple­me11ts (MM) com¡mred to iron cm/y (FE) supplenumts 011 changes in maternal weight and body compositian during preg1wncy ami the early postpnrt:um period.

Methods. A mndomized do11ble-/Jli11d clinical triul was conducted in semi-rnral Mexico. Women received either MM or FE supplemenls, 6 cfoys per week from early preg­nancy to delive1y. Anthropometric measiirements were obtained 111 rccruitment, 26 and 37 weeks pregnancy, and 1 mcmth post¡mrtum. V\1innen in both groups were similar at recruitment except tlwt IJOdy-mass index (13MJ) 1wis

greater in the FE group. Results. Mean weight gain during ¡m:gnanq was

signific:mltlr greater ( ~0.6 kg) in the MM group (n = 283) compared to the FE graup (n = 287), bttt not ofter adjuslingfor nwtemnl BMI at recruitment. Ovcrweíght women in tlze MM group gained 0.53 kg between recruit­ment and 1 month postpartHm, whereas those in tire FE group last 0.63 kg; there were na difjérences between

Usha Ramakrishnan and Rcynaldo M.artorcll are affiliated with tlw Dcpartmcnt uf Global Hcalth, Rollins School of Public Health, Emury University, Atlanta, Ga, USA. Teresa Gonz.;\lez-Cossfo, Lynncttc Marie Neufel<l, ami Jmm Rivera <ll'l' affiliatcd with Centro de Investigaciones en Nutricion y Salud, Instituto Nacional de Salud Pública (lNSP), Cucr­navaca, Murcios, Mcxico. Presented at the Annual Meeting of the American Public Health Assocíation, Atlanta, Ga, Octobcr 2001.

Picase dircct qucrics to thc corrcsponding author: Usha R<1makrishnan, Ph.D., Associate Profcssor, Department of Global Hcalth, Rollins School of Public Hcalth at Emory lJni­vcrsity, Atlanta, NE, GA, USA 30322; e-mail: uramakr@sph. cmory.cdu.

1vl<?ntion of the namcs of fínm and <:ommercia! products does not i1nply cndorst'mcnt by thc United Nations University.

experimentnl grcHtflS among non-overweight women (p = .06far inlemctirm).

Co11clusians . Compored to iron supplemrmts, MM rnpplements díd 11ot inc1·ease weigflt gain d11ring preg­nanry after adj11sti11gfor baseline differences in l3Ml lmt may lend to grcnter postpnrtum weight rctention among overweig/11' women.

l<ey words: Wcight gain, prcgnancy, iron, multivita­min-mincral supplements, body composition

lntroduction

Pour maternal nutrition hoth befurc and during p rcg­nancy is an important cause of ¡mor prcgnancy out­cnmes, cspecially in dcvclopíng countrícs ¡ 1, 2]. Weight gain during prcgnancy is widcly uscd as an índicator of thc adcquacy of nutrition during prcgnancy and has bcen associated with ínfant outcomcs such as mortal­ity, prcmaturity, and low birthweight [l, 3]. Studics haw shown that whilc Wl'ight gain in hcalthy popula­tions, SlKh as the United Slales, avcragcs around !2.5 kg, weight gain is only 7 to 8 kg in many devi.:loping count:ríes [ 4]. Severa! intervention trials havc becn conducted to rvaluate the bencfits of increasing fond intakcs during prcgnancy on maternal and infant out­cornes, but the findíngs have varicd cither by thc type nf nutcome cxamined or study sctting 12]. Although improved bírth outcomes such as bigher bírthweight are usually accomp<micd by incrcascd maternal wcight gain and/nr body fat, this has not always bcen the case [5, 6); fmthn documcntation of thc impact uf imprnwd nutrition during prl·gnancy on matt·rnal outrnmes in addition to birth outcunws is necessary.

lmprowd m icronutricnl intak<.:s during pn:gnancy may con tribute to incrcased energy intakcs by iníluenc­ing appetite [ 7]. Although several intcrvention tria!.~ lrnvc hccn conducted using cithcr food supplcmcnts or single nutricn ts such as vitam in A or zinc, few have rxamincd tlw impact of prenatal multivitamin

Food and N11triiio11 Bulleii11, vol. 26, no. 3 @ 2005, The United Natiom University. 273

274

mineral supplcments (MVMS), an approach that is being consíden·d by many ín terna tional agencies as a simpler st.rat.egy t.o imprnve pregnancy outn1mes. 'Two observational studies in thc US havc shown that routine consumption of MVMS supplements was associated with increascd weight gain during preg­nancy ami ímprovcd birth outcomcs (low birthwcight and prctenn ddivcries) even aftcr controlling for dif­fcrcnccs in factors such as access to prenatal carc and bascline nutritiunal status [8, 9]. In une intcrwntion tri<1l, multivitamín supplcrnents rcduccd the incidrncc of prcmaturity and low birthwcight by about 40% comparcd to routinc iron-folatc (FE-folatc) supplc­ments [JO J. and al so improved maternal T-cell counts and weight gaín during pregnancy in H!V-positive asymptomatic wumcn l 1 l j.

The benefit of multiple micronutrient (MM) sup­plements for non-H'lV infectcd womcn, howevcr, is not known. In Nepal [12], MVMS did not improvc birth outcomc·s whcn comparcd to ¡;E-folate suppk­mcnts (rcgarded as a standard of carc), but thc impact un maternal outrnmcs was not reponed. Wc• n:ccntly conductt·d ¡t randomir.ed, duubk-blin.d controllcd tria! in semi-rural Mcxíco to mm pare the cfficacy uf a multiplc micronutrient (MM) supplcmcn.t wmparcd toan iron-only (FE) supplement: during pregnancy in improving maternal ancl infant outcomes. In a previous publication, wc rcportcd that MM supplcmcnts did not improve birth weight or length compared to iron-only supplements f 131. Mean birth weight was 2.981 and 2.977 kg in thc MM and FE groups, rcspcctivcly. The spccific outcomes examined in this paper are wcight gain and changes in maternal an thropomctry both during prcgnancy and at l month postpartum.

Methods

Study settlng and desígn

This study was a collaborative pmject betwccn thc Rol­lins School of Public Health, Emory Univcrsity, Atlanta Ca, USA, and thc Ccntrn de lnvestigaóón en Nutrición y Salud, Instituto Nacional de Salud Pública (INSP), Cucmavaca, Mcxico. Thc study sitc was a semi-rural community, near thc city of Cucrnavaca, in Mordos, Mcxico. We used a randomir.cd doublc-blind dcsign in which thc trcatmcnt group rcccivcd tht~ MM su pplc­ment containing l to l .5 RDA (Rccommendcd Dict.ary Allowancc) of key vit.amins (A, D, E, !31, 131, B_1, 136, Bl2' C, and folie acid) and mincrals (Zn, Mg), and 60 mg of iron. The control group rcceived 60 mg iron, which was thc standard practice of thc Ministry of Health in Mcxico at thc t ime the study was conducted.

Thc study protocol was approved by tht~ Human Investigations Committcc at Emory l.lnivcrsity ancl at INSP, and writtcn informcd conscnt was obtaincd

U. Ramakrishnan et al.

from ali eligible subjccts al rcc.:ruitmcnL. We cx:dudcd womcn whu were morl' 1.han 13 wt·cks prcgnant: at rccruitment or who reponed thc use l>Í micronutr i­cnt supplemcnts (11 == 8). Ali el igible prcgnancics wcrc randomly allocated to cit:hcr the MM or FE group using four color-coded groups ( two per trcatmcnt) assigncd a priori using a computcr-gcncratcd list. Participants werc visitcd at thcir homes six days a week by trained workcrs who administcrcd and rccordcd thc consump­tion of supplcmcnts until dclívcry. Ali study pcrsonncl and invt·stigators WtT(' blindt·d to group assignmcnt, the dctails of which wer(' kept in seakd envdopcs in both institutions and oprncd unly aflcr preliminary dala analysis was complete<l. Additional details of thc supplcmcnt composition and of recruitmt'nl and trcat­ment allocation are provided clsewhere l 13 I.

Data collection

At recruitmcnt, which bcgan in July 1997, ali partici­pants werc providcd with a prrnatal t~xamination tbat indmkd a dctailcd obstctric history, pbysical cxami­nation, anthropometric and dietary assessmcnts, and bloud draw. A.JI cxaminations and assessments wcrr carricd out by thc study physician anda tcam uf lraincd nurses at. t:he study heaclquarters. 1-leight, weight, mid upper arm circumference (MUAC), tricep >l<infold (TSF), and subscapular skinfold (SSF) thickncsscs were mcasurcd severa! time> by workers trained in standard anthrnpometric tcchniqucs [ 141. Ali subjects wcrc askcd to come tu the study hca<lquartcrs for routine prenatal carc visits at 26, 32, and 37 weeks of prcgnancy. An additional cxam was conductcd in cach participant's home al une month puslpartum , during which anthro¡x1mctric m t asmcmc·nts werc lllktn again. Dueto budgetary Jimitat.ions, a mud ific·d pwtornl was implcmcnlcd aftcr Scptcmbcr l , 1999, from which point only weight was measured at the 32- and 37-week prenatal visit>. Sncinccnnomic status (SES) was dctermined using a qucstiun naire that indudcd dctails of education, ctlrnicíty, water and sani ta tion, quality of housing, hnuschold sir.e, nccupatinn, and posscssions such as a tclcvísion set, radio, or bicyclc. An in<kx of cconomic status was dcrivcd frorn these dat<1 using factor analysis [ 15 I.

Data analysis

Thc main outcumc variables wcrc maternal wcight ¡;ain and changcs in MUAC, TSF, and SSF from recruitmenl to 37 wceks pregnancy and frn m rccruitmcnt to l month postpartum. Wc also examincd carly (rccruit­mcn t to 26 wceks prcgnancy) and late wc•ight gain (26 weeks to 37 wecks pregnancy) an d dcfin ed inadequate wcight gain cluring prcgnancy as wcckly wcight gain bt·low 225 g/weck.

Using an int.cn t-to-treat design, ali prcgnancies

Prenatal micronulrient supplcmcntation in Mexlcan women

assigned to trcatment bclwccn July 1 Y97 and Deccmbcr 31 , J 999 were include<l and the effectiveness of ran­dnmization was tested by comparing the two grnups for sclcctcd sociodcmngraphic, hralth, ancl nutrition characteristics of the womcn at recruitment. Com­parisons between thc final samplc with infnrmation 011

maternal wcight gain ami changes in antbropometry and thost' p<ll'ticip<mts lost to follow-up werc abo done for selccted basdinc charnctcristic.s ami for mcasurcs nf compliamx~ (clefinecl as thc pruportion uf supplcments consumed while in the slltdy). Ali comparisons Wl'rc done using Studcnt's /'-tests for normally clistributed variabks and chi-square tests of proportíons for cat­t~gorical variables.

The analysis was restricted to prcgnancies that rcsultcd ín singlcton tcrm livc births and had data avail­able on the outcomes of interest. Following unadjusted comparisons of key outcomes by intcrvention gmup, acljustcd analyscs using multívariatc techniqucs (gen­eral linear modcls) wcrc done to control fór maternal body-mass indcx (BMI) and marital status, both of whkh difüTcd significantly bctwl·cn gruups at rccruit­mcnt. In addition, effcct modification by characterist.ics sckctt~d a priori (maternal overwl·ight at rccrnítment and cconomic status) was testee!. Ovcrwcight was defined using the World 1-Jcalth Organizatíon (WHO) definition nf BMJ ¿ 25 kg/m2 [ 16 J. Ali statistical analy­scs wcrc conductcd using SAS 8.2 (SAS lnstitutc, Cary, NC, USA). Sí ne.e somc women contributrd more than onc pregnancy to the study, repeatcd mcasures analysis (SAS l'ROC MIXED) wcre uscd to compare thc main outcom('.S of intcrcst. Statistical significancc was bascd

275

un thc críleriun of p < .OS for simple gruup diffcrcnces and p < 0. 15 fo r l<:sts of intcractions.

Results

A total of 921 prcgnancics werc identificd and 873 wcn~ assigned to tn·atmcnt---435 to tlH~ mul t.ipk micrnnutricnt group and 438 to thc iron gmup. Dctails uf birth outrnmes and rcasons for luss to folluw-up hm'l' bern describcd dscwhcrt· 113]. Ti·it• comparison of sclected maternal charactcristic:s at rccruitmt·nt (table 1) slwwcd that thc two gruups wcrt· similar for t:he majority of characteristics, including maternal age al recruitment, number of weeks pregnant at entry, pcrccnt primip<1rous, ycars nf schooling, economic status, ancl pl~rccnt anemic. There werc also no diffrr­cnces in reported cnergy and micronutrient intakcs bctwccn intcrvcntion groups at haselinc (rcsults not shown). Howcvn, the proportion of single mothns was higher in thc MM group cnmparcd to thc FE grnup, althuugh a majority ~>f wumen in both groups had a partncr. Additionally, althuugh 1m·an hcight was similar bc:twccn thc groups, wnmt'n in thl~ FE grnup werc significantly hcavicr (p < .05) comparcd to thosc in the MM group as demonstrated by grcater weight, BMI, and skínfold rneasurements; alrnost a third were uverwcight with a highcr proportion in thc FE group (38.71Yc>), compared to thc MM group (.'I0.81Yc>).

Out of thc final sample of 602 prrgnancics that resullcd in singkton tcrm livc births, maternal wcights wcrc availablc at rccruitmrnt and 37 wccks' gc·station

TAI3LE l. Maternal charnctcristics at recruitment for ali womcn assigned to receivc multiple micro­nutrient (MM) or iron only (FE) supplements during pregn;mcy using intent-to-trcat design

Maternal agc (yr) Wcd;s ¡m•gnant (wk) Prímíparnus (%)

Schnoling ( yr )

1 Economic status 1 Jndigcnous ethnicity (%)

Single mother (%)

Ancmi<I (%)

l:kight (cm)

Wdght (kg) j Body-mass indcx (kg/1117.) i MUAC i TSF lhiclmcss

SSF thickncss

Multiplc micronutrients ! lrnn (N=435) i (N==439)

~N-~.·-. __ Mc,;n~~s.~~~~--!L.1 Mc•111_! S~''. __ .-___ .I'~-·-1l34 2:H>9 J: SAH ! 1B 6 23.00 :!: 5.12 .80

431 9.24 J_ 2.51 1!32 9.31 -t. 3.00 .73

431 36.1 432 34.3 .51

396 t1. ll4 ± 3.4 l 402 7.05 :t 3.24 .36

:ws 0.00 ·.•.· 1.fJ:I :1<.>:-\ O.O:'\ + l .06 .27

396 32.:l 402 29. 1 .32

:~95 4.6 402 2.0 .IM

400 13.3 40.' I0.2 .l l\ 432 148.66 i 1.95 439 148.51 :!: 4. 70 .72 433 52.78 :!: 9.67 439 54.15 ± 10.00 ,()4

431 23.!\3 1· 3.94 ·1'.19 24.5:~ t 4.:11 .Ol

433 27.22 ± 3.21 439 27 .82 ± :t69 .01 433 21.6 l :!: 6.S3 439 22.7 1 :1; 7. 11 .02 433 15.62 ± 4.89 439 16.46 ± 5.14 .Ol

M lJAC, mid uppcr arm d rwmf1•r,•nc,:; TSl', t riccps skinfold; SSF, rnbsc<lpular skinfold 11. Mean ± SD unlcss índirnlcd olhcrwisr. 11. Using Slll<knt's 1-icsl for comparison <>f roll'a<>s and chí-sqtHlfl' lcsls for rntcgorirnl l'uiablcs.

·., ,.·

276

for 570 prcgnancics (502 wumcn), and al rccrnit­ment and 1 month postpartum for 577 pregnancies (505 women). Approximately 14% of women con­tributcd more than one pregmmcy to the study. Mean birth weight was 3.1 kg with no group differcnccs. The complete battery of anthrnpometric variables was availablc for a smallcr subsamplc at 37 wccks' gcstation ( 11 '.:: 371) and 1 month postpartum (n == 456), as only wcight was measurcd aftcr Scptembcr 1999. Womcn for wlwm data un wcight gain during prcgnancy wcrc availablc wcrc youngt·1· (p < .05) comparl'd tu thoSl' without availablc data, and the subsamplcs with fu ll anthrupomctry h<td a lowcr hcmoglobin cunccntra­tion (p < .05) compared to tJrnse without these data. J-lowever, there werc no differences in ant.hrnpometric mcasurcmcnts at rccruitment f\¡r ali subsamplcs.

Thc mean values for thc changes in weight and other anthropometric measuremcnts from rccruitment to 37 wccks' gcstation and 1 month postpartum are prcscntcd by intcrvrntion group in table 2. Wcight gain during pregnancy was lowcr than rccommendcd in both gruups [ 4). approximatcly 7-8 kg from rccruitmcnt to 37 wrcks. Although mean weight gain was about 0.6 kg greater for the MM group, thesc difforences were attcn­uatcd to 0.32 kg and ccased to be st:at.istically significan! (p = .24) after adjusting for baseline differences in HMl. The findíngs were similar for d iffercnces in wct~kly wcight gain (270 g/weck). Thc incidcncc oflow wcight gain was lowcr in the MM group (34.1%) comparcd Lo

U. Ra111akrish11an et al.

thc FE group (40.1 %), but thcsc diffcrcnces (odds ratio: 0.75; 95% confidence int.erval [Cf ): 0.54, 1.06) were also attenuated after adjusting for baseline cliffert•nces in BMI (adjustcd odds ratio: 0.89; 9SºA> CI: 0.62, 1.28). Women retaincd about 2 kg from the time of recruit­ment to l mnnth postpartum; although this was grcater for thc MM group (O. 71 kg), thcsc diffcrcnccs wcrc also attcnuated (0.33 kg) and not significantly díffcrcnt aftt'r adjusting for basclinc d iffcrcnccs in BMl. Thcre werc no significant diffcn.:nccs in changcs in MlJAC, TSF, and SSf lwtwct·n 1hc cxµcrimt·n tal groups. Rt·strict­ing thc analysis to womcn who contributcd only one prcgnanc.:y did no t alter thcsc find ings.

The comparison of the pattern of weight gain during pregnancy by int.ervcnli<rn grnup (table 3) also did not n:vcal any signifit:.ant diffcrcnccs aftcr ad.iusting for baseline difkrences. Weight gain from rccruitment to 26 wceks' prt·gnancy was highcr in the MM group comparcd to thc FE group in tcrms of actual wcight gained and ratl~ of wn·kly gain, but thCSl' difkrenccs wcrc attenuated ami not statistically significant aftcr adjusting for basclinc diffcrcnccs in BMI. In contras!, weight gain during late prcgnancy i.c., from 26 wcdcs to 37 wccks of prcgnancy was simil<ir in both groups, suggcsting that thc d iffcrcnccs st:cn in owrall wcight gain beforc adjustment occurred in t:he fi rst half of pregnancy.

Therc wcrc no intcrnctions fur changcs in anLhro­pomC'try and weight during pregnancy ancl from

TABLE 2. Changcs in makrnal anlhropomctry from rccruilmml lo 37 Wl'l'ks' grslation ami \o 1 month post-partum by intt~rvention group r Multipk 111icrnn11tricnts Jron _,

·· ··-···········r ........ -····--··-···-·--···---- ---··-•··• • • ·· • ·· •••••••••"• " "• '' ' "W''" ............... _ ...•... .. ¡ :····-Ñ··-~·: ¡ · ········M;:~;:;;··~_ -:s-~)·-·:··· N 1 Mean ·t SD 1

¡· ·-·· ···· ···· ·r· Hccruitmcnt to 37 wccks' gt!Slation '

6 Wcighl (kg) um11/jus1ecl 283 7.71 ± 3.57 287 7.01\ ± 3.58 11dju.<1t~db 7.57 ± 3.30 7.25 :l: 3.30

6MUAC(cm) 11nadj11sted 180 -0.13 ± 1.32 191 -0.32 ± UI fl<ljust·t!d1' - 0.19 ± 1.18 - 0.25± 1.18

l.lTSF (mm) 1111111(jt1slc<i 180 - 0.98 ± 4.17 191 - 1.04±4. 17 adj11stedb -1.l '.\ ± 3.97 -0.90 :!: 3.97

6 SSF (mm) u111uljusted 180 0.66 ± 3.14 191 0.21 ±3.14 adjmredb 0.54 ± 2.95 0.31 ± 2.96

Rccru itmcnt to 1 mo posl-partum

ti Wcight (kg) 1111111/j11.<tl'd 287 2.38 ± J.52 290 1.67 ± 3.53 111/juswdl> 2.1!\ ± 3.05 U\5 ± 3.05

D. MUAC (cm) 1m11djusted 222 - 0.42 :.\: 1.4 1 B4 - 0.56 ± 1.50 adj11sted¡, - 0.50 :1: 1.3 l - 0.4'7 :1: 1.27

ó TSF (mm) unwlittsted 222 -2.29 :J: 4.47 234 - 2.59± 1.50 arlj11$1crJb - 2.'1 8 ~: 4.17 -2.40 :!: 4.16

t:.. SSF (mm) /lrlllllj11$ll!d J 222 0.39 :!: .3.28 231

l 0.04 ± 3.37

mljustcc/1' 0.28 :t 3.13 0.20 ± J .06

M ll/IC, mid uppcr arm rircmnfcr~n·:~; TSF, trkq 1s skinf11ltl ; SSF, &11bsG1pular skinfo ld íl. lJsing. n~pc<1tcd mt.·r1surc~ c.mul ~1si:; for frnnparisnn nf mea ns. /J. Adjusling for body-nrns5 intkx al n·nuilmcnt.

y"

.04

.24

. !tí

.62

.89

.60

.16

.'14

1

.o2 1 .20 1

.32 1

.70 1

.47

1 .BS

.26

J .76

Pren;ltal micronutrient supplemcntalion in Mexican wornen 277

TABLE 3. Pattcrns of wcight gain dt1ring pregnancy by intt>rvention group

Multipk mkrum1tricnts j lrun (Ne:: 270) . (N º' 281)

1-Recn1l·~~-;;;1·;·t~)·;~>-~~~i·;.-g~-;t·.1tio~-~~~-1~-·· ~ ~c~'._:_l. ~.u ........ . !· . -0<:~.11 ~. s.I?. - l- .J.i'~ ----¡ 6. Wcight (kg) ll/UldjUStec/ 1 4.20 ± 2.69 3.bO l: 2.71 .01 t mliusted" ' 4.05 i 2.37 3.77 ± 2.37 .17 ¡ ¡ Ratc of wdght gain (kg/wk) .[ll 1 23

1 26 - 3 7 wccks' g,•stalion i 6. Wcight (kg)

Weekly weight gain (kg/wk)

f.t, Usi ng n.~pc:alcU n11..·asur<..'.S a1rnlysh; for <.:ornp¡~rison of rll<:an:;. b. i\djusting for body-mass indcx at r<'cnlitnwn1.

rc~crnitmcnt to 1 month post-partum by tcrtilcs of cconomic status. In contrast, therc is evidcncc of dfoct modification by maternal overweight at rccruitmcnt (tables 4 and 5). Comparcd to tht· FE group, ovcr­wcight womi:n in thc MM group tended to gain more wcight (p == .08) and havc smallcr n•ductions in MUAC (p = .05), TSF (p = .3) ami SSF (p = .08) duríng prcg­nancy. There were no differences by treatment group (p > .3) among non-overweight: wnmen (table 4). Simi­lar intcractions by maternal overwcight <it rccruitmcnt (p < .1 for all interactions) were seen in mean changes

TABLE 4. Effcct of prenatal multiplc mícronmricnt (MM) supplcrncnts 011 diangt•s in maternal anthropomctry from rccruilmcnl to 37 wccks' g<~stalion slratificd by maternal overweight ar recruitmcnt"

Multiplc mícrnnutrients lrun

-----.. -· :~~~1~~.;~~ª~~~.l~.:.i.;\~~~'?..1/1.~ .. , A Wcight (kg) ! l i I

Normal 192 ! 8.4!:! :t 3.34 177 i 8.22 :!: 3 .. 34 .320 ! Owrweight 91 ! 6.12 :t :u1 11O1 5.27 :1: .'l.36

,1 i 6.MUAC[cm) 1

Normal ! 23 i O. 13 J 1.22 t 1 7 ! 0.18 !; 1.18 . 1031 Ovcrwcight 57 -0.68 t 1.21

ATSF (mm)

Normal

Ovcrweight

L\ SSF (mm)

Normal Oven'/(~ight

123 ,- 0.41 ± 3.99

57 l-2.22 :!: 3.99 ; 1

123 il l. lo J 3.00 57 - 0.29 :!: 3.00

74 -1.ll ± 0.94

¡ 17 0.16 t 3.99 .135

741- 2.95 :l.: :~.9S !

1 1

11 71 1.10 ~t23.0l .1•19 1 74 -l.2'1 ·- 3.02 J

MUAC, mid uppn arrn drc11111fcrrnc<'; TSF, trkq>s skinfold; SSF, st1hsc;1pt1lar skínfokl r1. Norma!: body-mass ín<kx < 25 k~lmi ; owrwdght.: boclr·mass

índcx ~ 25 kg/mZ. /J. Using rq1,·atcd nwaslll\'S analysi.1.

.73

.90

.79

.96

in wcight and body composition from rccruitmcnt to l month postpartum (table 5). Ovcrwcíght womcn rctaincd more weight (0.53 kg) in thc MM group comparcd to tbc FE group, who lo~t 0.63 kg (p < .01), in contrast to 11011-overwl·ight women, who rct<lÍncd about 3 kg in buth gruups (p "" .7). Thc rcductions in MUAC, TSF, <lnd SSF thíckncss from rccruitmcnt to 1 month post:partum among overweight women were less in the MM group when compared to the FE grnup (p "' .06, p :;:: .12, and p "' .07, respectivcly), with no diffcrences by treatment grnup among non-owrweight women (p > .25). lt shnuld alsn be noted that thesc

TABLE S. Effoct of prenatal multipk micron utrícnt (MM) suppkmcnts nn changcs in maternal anthropomdry írom rco-uitment to 1 month postpMtum stratificd by maternal ovcrwcight at rccrnitmcnt"

Multipk micrun11 tricnts lrnn

N f~kan :l: SD N ·¡ Mean + SD pb 1~ Wdghl [kg) r· I - .. . .... :.:.· ·.. . 1

Normal 195 3.24±3.IC> 178¡

1

3.11± 3.15 .0621

Ovcnwight 92 0.53:!:3.17 112 - 0.6J±:u 1 1

t. MUAC (cm) 1 1

Norma! 155 - 0.12 ± l .36 145 i 0.01 ± 1.35 .030 '

Ovcrwcight 67 --1.12 ± l.36 89 ¡-1.53 ± l.34

6. TSF (mm)

Normal 122 -1.54 ± 4.21 145 -1.08 ± 4.20 .07 1

Ovcrwcight 67 -3.99±4.21 89 - 5.05 ±4. 19

¡ A ssr (mm) 1

1

Normal 155 0.91 ±3.13 H 5 . 1.10± 3.12 .0751 Ovcrwl'ight, 67 !-0.76±3.l2j 89!-l.6l\:U. l lj ;

MUAC, mid upp(T arm circumlá('nrc; TSF, triccps skiníold; S~F. rn bscapu lar skinf(1ld 11. Nor111al: bodl'·111ass ínckx < 25 k~/m2 ; ow rwdghl: bodv· 111ass

indcx <: 25 kgim~. . ' ' h. Usin1~ rq1,'i1kd nwastm's <llrnlysis.

278

intcraaiuns rcmaincd significant (p < .05 for changcs from recruilment to 1-month postpartum) when restricted l:o the sample of women who contributed only one prcgnancy.

Discussion

Thc abscncc of an cffcct of the intervcntion on mater­nal wcight gain an<l changcs in anthropumctry during prcgnancy as wcll as frum rccruitment to 1-munth poslpartum folluwing a<ljustments for baselíne <liffor­cnces in BMI are consist:rnt with our carlier findings of no improv(•ments in birth size [ 13 ]. T hese results are not affected by ina<lequate sample size for most of the outcomcs. Powcr calculations indicatc that our study sample had at least 80% power to detect a difference of0.6 kg between thc two groups for both weight gain during pn:gnancy and changrs from rccruitmcnt to l month postpartum, assuming a two-tailcd tt~st and significanct! leve! of .05 [ 17]. Similar cakulations also rcvcakd that Wl' had at kast 80% powcr to dctcct a differencc of 0.5 cm and l mm for changt·s in MUAC and skinfold thickncss during prcgnancy (n == .~7 l) and from rccruitmcnt to J nwnth postpartum (11 :: 456) except for changes in TSF during prt•gnancy (power ::: 0.64 and 0.74 for a two- and one-tailed test. respec­tivcly). lt should be nutcd that thc ab\!vc di ffcrcnccs rcprcscn t small to medium cffcct sizcs (0.2-0.35 SO). The obscrved changes in body compositinn werc also small and thc mean valucs in buth trcatmcnt groups fdl within thc normal distribution ()f valucs for Cau­casian womcn of comparable agc mcasurcd in thc first ancl scwnd National Hcalth and Ex1mlination Survcys (NHANES) in the Unitcd Statt!s [18].

Furthcrmon', therc appcars to b(! no sdcction bias tha t may cxplain thcsc fin<lin gs. Bascline anthro­pometric measurements wcrc similar in t:h e final samples when compared tu the original sample of ali prcgnancics rccruitcd in thc trial. The wmparison of basclinc characteristics by intcrvention group in thr final subsamples (data not shown) was also similar to thosc prcscntrd for the original samplc ( table 1). Finally, although wc had to cxcludc prctcrm births (11 '~ 43) as thcy preduded mcasun~mcnts at 37 wceks, wc found similar findings whcn wc cxamincd wcight gain during carly prcgnancy for thc largcr samplc (11 = 664) ami includcd prctcrm birlhs in thc analysis of outcomcs frnm rccruilmcnl to 1-month poslpartum (data not shown).

lt is also important lo note that: thc lack of effect occurred in thc cuntcxl of lowcr-than-rccommrndcd weight gains (mean = 12 kg) and cannot be attributed to a ceiling effect 14). Although there is less informatinn on clrnngcs in body composition [ 19 J, ovcrall wcight gain in this study is similar to thosc reportcd in popula­tions from dcvclnping countrics [l , 4·, 20, 21 ]. Rcccnt

U. Ramakrishnan el al.

findings from a longitudinal pruspcct.ivc stu<ly in Gua­temala using similar prolocols show mean wt;ight gain during prcgnancy of apprnximatdy 7 kg 122].

Although scvcrnl observational studics and food sup­plcmentatinn trials havc cxamined maternal outcomes surh as weight gain during pregnancy [2, 23], there is vcry little information as tll thc role of micronutricnts. Villamor t'\ al. l l l] reported that avt'ral~l' wcight gain (306 g/wcck) was significantly highcr during thc th ird trimcstt'r in tht· group uf HIV-pusitiw wumcn who rt·ceivcd prenatal m ul tivitamins cumpatTd t:o thuse who rcccived thc placebo. Thesc samc researchers also rcportcd t:hat thc risk of low wcight gain ( < 100 g/wk) was also signilicantly lowt'r (-'.~0%) in the intervention gruup l l J J, whích is cnnsistent wi th t:hei r previously rcpnrtcd rcsults uf rcductions in thc incidcncc of low birth weight l 10]. Howcvc.r, the relevancc of thcse findings to 11011-HJV infectcd populations is unclear. Among studics conduncd in non-H IV infcctcd popu­lations, a prospcctivc study of young African-Am<'rirnn womrn by SdH1ll et al. [8] found that thc proportion of wumcn with inadcquatc wcight gain (28.7%) was significantly hight•r among women who did not rcport wnsuming prenatal MVMS cumparcd to thosl' whu did (22%). Similarly, in an carlier supplcmcntation tria! from Chile l 24 l. women who consumed a fortified milk supplement had significantly highcr weight gain ( 12.3 kg) cumparcd tu tl11isl' whu reccivcd thc unfortified suppkment (l J.5 kg). lmproved birth outcomes were reportcd in both these studies.

Thc changc in wright from rccruitmcnt tu l month postpartum is consistcnt with studies in wdl-nourishcd populations showing that postpartum wcight rctcn­tit>ll rangcs from nunc to 2 kg pcr prcgnancy [25]. This is in contrast to overall wcight loss, i.c., "maternal deplct ion syndrome" common in populations with modera te to se vi: re chronic cncrgy dcficic111:y (26, 27], Pregnancy-related weight rt'tt·ntion is of increasi ng C«>ncern in populations such as thc Uniled Stalt'S, whcre overwcight and obt'sity are signi ficant public hcalth problcms. Rt'cent data from the National Nutri ­tion Surwy in Mexico alsn indicale that overweight and obcsity are cmcrging public hcalth prnblcms tlrnt nccd to be addrcsscd along with undcrnutrition [28]. Therefon', our flnding that ovcrwcight womcn whu rclcivcd MM rctaincd more wcight. comparcd to those whl> rcn·iwd only iron may be or concern. It is impurtant to note that tlll'Sl'. womcn gaifl(•d only about 6 kg during prcgnant:y, with li ttlc ur no wcight rctc:n­tion poslpartum. Thesc weight gains art: comparable to the recommendations for nvcrwcight womcn in the Unitcd Statcs l 4 I and it would thcrcfore be import<lnt to determine if thc observed dífferences are transicnt or not. Ongoing follow-up studics of these women will pmvidc valuablc information. Similarly, although tlw diffcrenccs in MUAC and SSF mrasurcmrnts sug­gcst that t:hcrc may be incrcased rctcntion of body fat

. ' . . .

Prenatal micronutrient supplcmcntatlon in Mcxican womcn

storcs in t.hc MM group, Lhcrc wcrc dccrcases in MlJAC and SSF in owrweight women in both supplement grnups. !t. should also be noted that. ou r findings were nnt affcctcd by tite cxdusion of prcterm births, as wc had similar findings. Although fow intervention trials have cxamined chungcs in maternal body composi­tion, obscrvational studics primarily from thc Unitcd Statcs havc shown that higher gcstational wcight gain, African-Amcrican racc, youngcr age and low socio­cwnomic status haVl' bccn positivcly a~so<.:iatl·d with incrc:ast•d prcgnancy-rdatt·d wcight rl'tcnt ion l 25). whercas prcpregnancy BMI was ncgativcly associated with uvcrall wcight gain 14] as wcll as fat gain during pregnancy 129).

In summary, our findings indicate that rnmparecl to iron suppkmcnts, MM supplcmcnt:s do not affcct weight gain during pregnancy, but may lead to greater postpartum weight retention and smaller decreases in MUAC and skinfold thickncss among ovcrwcight

References

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279

womcn. lt slwuld, howcvcr, be noted that: whilc fJ valucs < .15 or even < .20 are rccommended for tests of interactions, sume may cal! for more stringen L criteria, i.c., p < .05, and tlrnt thcre is a necd to confirm thcse findings. Furthcr work that examines whether these differenccs are explaincd by changt~s in d ietary intakcs during prcgnancy will abll be uscful in un<.krstanding potrntial m('chanisms, as well in (ktcrmining if thcn· are othcr bcncfits such as improvcd quality of brcast milk in tcrms uf micronutricnt contc.:nt. and infant growth and dcvcloµmt·nt.

Acknowledgments

This study was supportcd by funds from thc Tlmu;hcr Research Fund, UNICEF, New York, Conacyt and lNSP, Mcxicn.

rcra G, Kapiga S, Willctt W, Huntcr DJ. llandornized tria) of cffccts of vitamin supplc1m•nts on prcgnancy outcomcs and T cdl counts in HIV-1-infc.ctt•d womcn in 'fanzania. Lancct 1998;351: 1477-82.

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