Risk and prognostic factors for diarrheal
disease in Brazilian infants:
a special case-control design application
Fatores de risco e prognósticos para diarréia
entre crianças brasileiras: uma aplicação especial
do delineamento de casos e controles
1 Dep artam en to d e M ed icin a Socia l, Fa cu ld a d e d e M ed icin a , Un iv ersid a d e Fed era l d o Rio Gra n d e d o Su l. Ru a Ra m iro Ba rcelos 2600, sa la 415, Port o Alegre, RS 90035- 003, Bra sil. scfu ch s@z a z .com .b r 2 Dep artam en to d e Med icin a Socia l, Fa cu ld a d e d e M ed icin a , Un iv ersid a d e Fed era l d e Pelot a s. C. P. 464, Pelot a s, RS 96001, Bra sil.
Sa n d ra Cost a Fu ch s 1 Cesa r Gom es Vict ora 2
Abstract Th e a im of t h is st u d y w a s t o ex a m in e t h e effect of d em ogra p h ic, socioecon om ic, en v i-ron m en t al, m at ern al rep rod u ct ive, d iet ary, an d n u t rit ion al variables on d iarrh ea risk an d p rog-n o si s u si rog-n g a h i era rch i ca l f ra m ew o rk . A ca se- co rog-n t ro l st u d y o f ch i ld rerog-n a ged 0- 23 m o rog-n t h s i rog-n Grea t er M et rop olit a n Port o Alegre w a s con d u ct ed d u rin g t h e p ea k sea son for d ia rrh ea in 1987-1988. Th ree grou p s w ere in v est iga t ed , w it h 192 ch ild ren ea ch . Th e first grou p in clu d ed h osp it a l-iz ed ch ild ren w it h a n ep isod e of a cu t e d ia rrh ea com p lica t ed by m od era t e t o sev ere d eh yd ra t ion . Th e secon d grou p in clu d ed ch ild ren w it h a cu t e m ild d ia rrh ea w it h ou t sign s of d eh yd ra t ion w h o w ere i d en t i fi ed i n t h e sa m e n ei gh b orh ood a s h osp i t a li z ed ca ses. T h e t h i rd grou p con si st ed of con t rols w it h ou t d ia rrh ea . M ot h ers w ere in t erv iew ed by t ra in ed in t erv iew ers u sin g a st a n d a rd -iz ed q u est ion n a ire. Da t a a n a lysis in clu d ed a h iera rch ica l a p p roa ch t o con t rol for con fou n d in g, u sin g con d it ion a l logist ic regression . Com p a rison of t h e t h ree grou p s a im ed t o id en t ify risk fa t ors for d ia rrh ea com p lica t ed b y d eh yd ra t ion , p rogn ost ic fa ct ors for d eh yd ra t ion , a n d risk fa c-t ors for m ild d ia rrh ea . Low b irc-t h w eigh c-t , sc-t u n c-t in g, a n d la ck or b rea sc-t feed in g a cc-t ed sim u lc-t a n e-ou sly as risk an d p rogn ost ic fact ors for d iarrh ea.
Key words Diarrh ea; Ch ild Healt h ; Risk Fact ors; Case-Con t rol St u d ies; Ep id em iology
Resumo O ob jet iv o d est e est u d o foi ex a m in a r o efeit o d e v a riá v eis d em ográ fica s, sócio- econ ô-m ica s, a ô-m bien t a is, rep rod u t iva s ô-m a t ern a s, d iet ét ica s e n u t ricion a is sobre o risco e o p rogn óst ico d e d ia rréia u sa n d o a n á lise h iera rq u iz a d a . Um est u d o d e ca so- con t role in clu in d o cria n ça s en t re 0- 23 m eses d e id a d e, resid en t es n a á rea m et rop olit a n a d e Port o Alegre, foi rea liz a d o d u ra n t e os m eses d e v erã o d e 1987- 88. In v est iga ra m - se t rês gru p os d e 192 cria n ça s, in clu in d o a s h osp it a li-z a d a s com u m ep i sód i o a gu d o d e d i a rréi a e d esi d ra t a çã o m od era d a a gra v e; a s cri a n ça s com d i a rréi a a gu d a lev e e sem d esi d ra t a çã o, i d en t i f i ca d a s n a v i z i n h a n ça d o s ca so s, a ssi m co m o crian ças sem d iarréia. En t rev ist as p ad ron iz ad as foram realiz ad as p or en t rev ist ad oras t rein ad as. Ut iliz ou - se a n á lise h iera rq u iz a d a n o con t role d e fa t ores d e con fu sã o. Ca lcu la ra m - se ra z ões d e od d s e in t erv a los d e con fia n ça d e 95% a t ra v és d e regressã o logíst ica con d icion a l. O em p a relh a -m en t o d e d iferen t es co-m b in a ções d e ca sos e con t roles p er-m it iu in v et iga r fa t ores d e risco p a ra d iarréia grave, fat ores p rogn óst icos e fat ores d e risco p ara d iarréia leve. Baix o p eso d e n ascim en -t o, d éfici-t a l-t u ra - id a d e e a u sên cia d e a lei-t a m en -t o m a -t ern o fora m sim u l-t a n ea m en -t e fa -t ores d e risco e p rogn óst ico p ara d iarréia.
Introduction
D ia r r h e a l d ise a se s a re st ill a sso c ia t e d wit h a h igh m o r t a lit y ra t e a m o n g ch ild re n (Mu rra y & Lo p e z, 1997), ca u sin g a n e stim a te d 1.5 m illio n d e a t h s in t h e ye a r 2000 ( Vic t o ra e t a l., 2000). Dia r r h e a is a wo r ld wid e p ro b le m , b u t t h e im -p lica tio n s o f d ia rrh ea l d isea ses a re -p a rticu la rly evid en t in d evelop in g cou n tries.
Alth ou gh ora l reh yd ra tion th era p y h a s b een a va ila b le fo r a p p roxim a tely th irty yea rs a n d its u se h a s c o n t r ib u t e d t o a m a jo r d e c lin e in t h e d ia r r h e a l m o r t a lit y ra t e ( Vic t o ra e t a l., 2000), d ia r r h e a l m o r b id it y is st ill a m a jo r p ro b le m a m o n g u n d e r- five s, m o st ly in t h e fir st ye a r o f life. Pooled d a ta p u b lish ed in 1992 from 22 lon -git u d in a l st u d ie s c o n d u c t e d in 12 c o u n t r ie s sh owe d t h a t in fa n t s a ge d 6- 11 m o n t h s h a d a m e d ia n in cid e n ce o f five e p iso d e s o f d ia rr h e a p er yea r (Bern et a l., 1992). Severa l rep orts h a ve id en tified so cio eco n o m ic, en viro n m en ta l, m a -tern a l, n u tritio n a l, a n d o th er ch a ra cteristics a s risk fa ctors for d ia rrh ea l m orb id ity or m orta lity (Awasth i et al., 1996; Clem en s et al., 1999; Mirza e t a l., 1997). Pove r t y, low p a re n t a l sc h o o lin g, p oor sa n ita tion , la ck of wa ter su p p ly, crowd in g, e a r ly c h ild b ir t h , sh o r t b ir t h in t e r va ls, la c k o f b rea stfeed in g, a n d m a ln u tritio n a re fa cto rs a s-so c ia t e d wit h d ia r r h e a (Awa st h i e t a l., 1996; Bra t t a c h a r ya e t a l., 1995; Howie e t a l., 1990; Mirza et a l., 1997; Ra isler et a l., 1999; Sca ria ti et a l., 1997).
Mo st st u d ie s h a ve u se d c ro ss- se c t io n a l o r c o h o r t d e sign s a s o p p o se d t o a c a se - c o n t ro l m e t h o d o lo gy. We fo u n d n o ca se co n t ro l st u d -ie s d e sign e d t o sim u lt a n e o u sly c o m p a re r isk a n d p ro gn o st ic fa c t o r s fo r d e h yd ra t in g d ia r -r h e a , u sin g d a t a f-ro m t h e sa m e p o p u la t io n . Id en tifica tio n o f fa cto rs rela ted sim u lta n eo u sly t o t h e r isk o f a cq u ir in g d ia r r h e a a n d it s p ro g-n o sis wo u ld b e p a rticu la rly releva g-n t, p o teg-n tia lly b o lsterin g th e effect o f a p a rticu la r in terven t io n . We t h e re fo re e xa m in e d t h e e ffe ct s o f so cio e co n o m ic, e n viro n m e n t a l, m a t e rn a l re p ro -d u c t ive, -d ie t a r y, a n -d n u t r it io n a l va r ia b le s o n t h e r isk a n d p ro gn o sis o f d ia rr h e a , u sin g d a t a from a 1987-1988 ca se-con trol stu d y.
Participants and methods
Design
Th is wa s a ca se - co n t ro l st u d y in clu d in g t h re e gro u p s: d e h yd ra tin g d ia rrh e a ca se s, m ild d ia r-rh ea ca ses, a n d n on -d ia rr-rh ea con trols.
Study definitions
De h yd ra t in g d ia rr h e a ca se s in clu d e d ch ild re n a ge d 0 23 m o n t h s re sid in g in Gre a t e r Me t ro -p o lit a n Po rt o Ale gre, so u t h e rn Bra zil, e n ro lle d fro m D e c e m b e r 1987 t o Ma rc h 1988 fro m t h e city’s two la rgest p ed ia tric h o sp ita ls. Deh yd ra t-in g d ia rrh ea wa s d eft-in ed a s a n ep isod e of a cu te d ia r r h e a (le ss t h a n e igh t d a ys d u ra t io n ) a n d p re se n c e o f a p e r sist e n t skin fo ld p lu s a t le a st on e of th e followin g sign s: su n ken fon ta n el, d ry m o u t h a n d t o n gu e, su n ke n e ye s, re d u ce d u r n a r y o u t p u t , we a k p u lse, d rowsin e ss, o r ir r i-t a b ilii-t y. D ia gn o sis o f d ia r r h e a wa s b a se d o n t h re e o r m o re lo o se o r wa t e r y b owe l m ove -m en ts with in 24 h ou rs for ch ild ren old er th a n 3 m o n t h s o r a cco rd in g t o t h e m o t h e r’s re p o r t o f m o re fre q u e n t a n d p o o r ly fo r m e d st o o ls (a s co m p a re d to n o rm a l) fo r yo u n ge r ch ild re n . All ch ild re n m e e t in g t h e se cr it e r ia we re e n ro lle d fro m t h e la rge st p e d ia t r ic h o sp it a l, a n d a sys-t e m a sys-t ic ra n d o m sa m p le o f e ligib le c h ild re n fro m t h e se co n d h o sp it a l wa s in clu d e d . Ca se s o f m ild d ia rrh e a we re d e fin e d a s ch ild re n with d ia rrh ea in th e seven d a ys p reced in g th e in ter-vie w a n d wit h o u t sign s o f d e h yd ra t io n . Th e y we re in d ivid u a lly m a t ch e d t o t h e se ve re d ia r -r h e a c a se s b y a ge (0- 11, 12- 23 m o n t h s) a n d n eigh b o rh o o d . Wh en a h o sp ita l ca se wa s id en -t ifie d , a n in -t e r vie we r visi-t e d -t h is ch ild ’s h o m e t o in t e r vie w t h e m o t h e r. St a r t in g a t t h is sit e, t h e in t e r vie we r u se d a st a n d a rd p ro c e d u re t o m ove a ro u n d th e n e igh b o rh o o d , visitin g e ve r y h o u se u n t il a c h ild wit h m ild d ia r r h e a wa s id en tified .
No n d ia rrh e a co n t ro ls we re ch ild re n id e n -t ifie d in -t h e sa m e n e igh b o r h o o d a n d fro m -t h e sa m e a ge b ra cke t a s d e h yd ra tin g d ia rrh e a ca se s, wh o h a d n o t p rse sse n tse d d ia rrh se a in th se p rse -ced in g seven d a ys.
Figu re 1 sh ows t h e fra m e wo rk fo r e n ro ll-m en t o f ca ses a n d co n tro ls. Risk fa cto rs fo r d eh yd ra t in g d ia rr eh e a we re in ve st iga t e d b y co m p a rin g ca ses o f d eh yd ra tin g d ia rrh ea a n d n o n -d ia rrh e a co n tro ls. Pro gn o stic fa cto rs fo r -d e h y-d ra tion were esta b lish ey-d by com p a rin g ca ses of d e h yd ra t in g a n d m ild d ia r r h e a . Fin a lly, r isk fa c t o r s fo r m ild d ia r r h e a we re a sc e r t a in e d b y co m p a rin g ca ses o f m ild d ia rrh ea with n o n -d i-a rrh ei-a con trols.
Study variables and data collection
ris-t ics we re a sse sse d ris-t h ro u gh o b se r va ris-t io n b y six t ra in e d in t e r vie we r s. Th e va r ia b le s p re se n t e d in t h is p a p e r in clu d e d ch ild re n’s a ge (0-1, 2-3, 4-5, 6-8, 9-11, 12-17, o r 18-23 m o n t h s), fa m ily in c o m e (m e a su re d a s “t im e s t h e p re va ilin g m in im u m wa ge”; ≤3.6 o r > 3.6), fa t h e r’s p re s-e n cs-e in h o u ss-e h o ld a n d sch o o lin g (a b ss-e n t a n d illit e ra t e o r 1 o r m o re ye a r s o f sc h o o lin g), m oth er’s sch oolin g (in yea rs, ≤8 or > 8), typ e of h ou sin g (m a son ry con stru ction versu s sh a cks), wa t e r su p p ly (in d o o r r u n n in g wa t e r, o u t d o o r r u n n in g wa t e r o n p ro p e r t y, o u t d o o r r u n n in g wa t e r in n e igh b o r h o o d , p u b lic we ll, o r r ive r ), flu sh t o ile t (ye s o r n o ), n u m b e r o f u n d e r-five s livin g in t h e h o u se (1- 2 o r 3- 6), h o m e cle a n li-n e ss (n d e x b a se d o li-n o b se r va tio li-n o f a va ila b ili-t y o f so a p fo r wa sh in g h a n d s a n d ili-t owe ls fo r d r yin g, fo o d sc ra p s in u n c ove re d p a n s, p a n s ke p t cove re d o n t h e st ove, p re se n ce a n d n u m -b e r o f flie s in t h e kit ch e n o r livin g ro o m , fe ce s or stan d in g water in th e yard , p resen ce of p ets), m a t e rn a l a ge (≤20 ye a rs o ld ve rsu s > 20), t win b irt h (ye s o r n o ), b irt h o rd e r (1-2, 3, > 3), b irt h weigh t (rep o rted b y th e m o th er o r reco rd ed o n t h e b ir t h c e r t ific a t e, c a t e go r ize d a s < 2,500, 2,500-2,999, ≥3,000g), h e igh t fo ra ge, we igh t -fo r- h e igh t , a n d we igh t - -fo r- a ge (a ll t h re e in z-sco re s ca te go rize d a s, ≤2, 1 to 1,9, > 1), p re -viou s h osp ita liza tion for a n y rea son (yes or n o), t yp e o f m ilk c o n su m e d (b re a st , b re a st + n o n -b re a st, n o n --b re a st), a n d cu rre n t -b re a stfe e d in g sta tu s (still b re a stfe e d in g, if b re a stm ilk co n sti-t u sti-t e d a n y p o r sti-t io n o f sti-t h e c h ild ’s d ie sti-t ; ssti-t o p p e d b re a st fe e d in g; n e ve r b re a st fe d ). Sin ce b re a st -fe e d in g m a y h a ve b e e n in t e rr u p t e d a s a re su lt o f t h e d ia r r h e a , c h ild re n we a n e d d u r in g t h e ep iso d e were cla ssified a s still b rea stfed .
Sample size and strategies for data analysis
Th e sam p le size was calcu lated to d etect an od d s ra tio of a t lea st 1.5, with 80% p ower a n d 5% sig-n ifica sig-n ce le ve l (t wo -t a ile d ) fo r a p re va le sig-n ce o f e xp o su re a m o n g co n tro ls ra n gin g fro m 20% to 65%. In d ep en d en t va ria b les were gro u p ed in to d iffe re n t h ie ra rch ica l le ve ls o f d e t e r m in a t io n , ra n gin g fro m d ista l d e te rm in a n ts su ch so cio e c o n o m ic c h a ra c t e r ist ic s, in c lu d in g e n viro n m e n t a l, m a t e r n a l re p ro d u c t ive, a n d d e m o -gra p h ic fa cto rs, a n d lea d in g to p roxim a l d eter-m in a n ts su ch a s n u tritio n (a n th ro p o eter-m etry a n d d iet). We in clu d ed va ria b les a t ea ch level b a sed o n t h e st re n gt h o f a sso c ia t io n in t h e c r u d e a n a lyses (a p level < 0.1 wa s req u ired ).
On e regressio n eq u a tio n wa s fitted fo r ea ch h iera rch ica l level, a lso in clu d in g va ria b les from h igh e r le ve ls o f d e t e r m in a t io n ( Vic t o ra e t a l., 1997). We con d u cted sep arate an alyses for each
ca se-co n tro l co m b in a tio n th ro u gh co n d itio n a l lo gist ic re gre ssio n u sin g t h e Egre t st a t ist ic a l p a cka ge (Breslow & Da y, 1980).
Results
All b u t eigh t ch ild ren o u t o f 200 id en tified with d eh yd ra tin g d ia rrh ea were stu d ied . Seven ch ild re n wit h m ilild ild ia r r h e a c o u lild n o t b e in t e r -viewed a n d were rep la ced by th eir n ext-n ea rest e ligib le n e igh b o r. All e ligib le ch ild re n wit h o u t d ia r r h e a a gre e d t o p a r t ic ip a t e. Ta b le 1 sh ows th e d istrib u tion of ta rget va ria b les a ccord in g to t h e d ia rrh e a o u t co m e s. Mo st o f t h e ch a ra ct e r-istics o f ch ild ren with m ild d ia rrh ea sh owed a n in t e rm e d ia t e d ist rib u t io n b e t we e n t h o se fro m d e h yd ra t in g d ia rr h e a ca se s a n d n o n - d ia rr h e a con trols.
Ta b le 2 sh ows t h a t a ge wa s c lo se ly re la t e d t o a ll d ia r r h e a o u t c o m e s, b u t t h e gro u p s a t h igh e st r isk va r ie d . Ch ild re n in t h e fir st t wo m o n th s o f life were p ro tected fro m d evelo p in g d ia r r h e a , b u t o n c e t h e y a c q u ire d t h e d ise a se, th ey were a t a b ou t 23 tim es th e risk of d eh yd ra -t io n a s c o m p a re d -t o -t h o se in -t h e 9- 11 m o n -t h a ge b ra cke t . In fa n t s a ge d t wo t o t h re e m o n t h s h a d se ve n t im e s t h e like lih o o d o f d e ve lo p in g d e h yd ra t in g d ia rr h e a a s co m p a re d t o t h o se 9-11 m on th s old . Du e to m a tch in g, ch ild ren a ged 12- 23 m o n t h s h a d t o b e a n a lyze d se p a ra t e ly fro m t h o se u n d e r 12 m o n t h s. In t h e se c o n d ye a r o f life a n in c re a s e d r is k o f d e h yd r a t in g d ia r r h e a a p p e a re d in c h ild re n a ge d 12 t o 17 m o n th s. Ou r d a ta a n a lysis d id n o t in d ica te a n y
Children with dehydrating diarrhea
v Children with mild diarrhea
v
Prognostic factors for diarrhea Figure 1
Framework for studying risk and prognostic factors for diarrheal diseases.
Healthy children
Risk factors for mild diarrhea
Risk factors for dehydrating diarrhea
gen d er-rela ted d ifferen ces in risk or p rogn ostic fa ctors for d ia rrh ea .
Low so c io e c o n o m ic st a t u s wa s o n e d e t e r -m in a n t o f d e h yd ra t in g d ia r r h e a , a lt h o u gh t h e re wa s n o sign ifica n t a sso cia t io n wit h m ild d ia rrh ea ( Ta b le 3). Low fa m ily in co m e d o u b led th e risk o f d eh yd ra tin g d ia rrh ea , in d ep en d en t-ly o f t h e fa t h e r’s p re se n ce in t h e h o u se h o ld o r ed u ca tion a l level or th e m oth er’s skin color. Pa -t e r n a l sch o o lin g wa s -t h e m a in so cio e co n o m ic risk a n d p rogn ostic fa ctor for d eh yd ra tin g d ia rr h e a , wh ile m a t e rr n a l e d u c a t io n h a d n o in d e -p e n d e n t e ffe ct . Mixe d skin co lo r cla ssifica t io n of m oth ers, a lth ou gh a d ju sted for oth er socioeco n o m ic va ria b le s, wa s a sso cia t e d wit h a t wo fo ld in cre a se in t h e r isk a n d in a p o o r p ro gn o sis fo r d eh yd ra tio n . Ch ild ren o f wo rkin g m o th -e r s w-e r-e l-e ss lik-e ly t o h a v-e a p o o r p ro gn o sis th a n ch ild ren o f n o n -wo rkin g m o th ers.
Ta b le 4 sh ows th a t livin g in th e sa m e h ou se-h o ld witse-h tse-h re e to six o tse-h e r u n d e r-five s o r la ck o f h o m e c le a n lin e ss (in t h e kit c h e n , livin g room , a n d ya rd ) in crea sed th e risk of d eh yd ra t-in g d ia rrh e a , st-in ce b o th va ria b le s we re a sso ci-a t e d wit h t h e r isk o f m ild d ici-a r r h e ci-a ci-a s we ll ci-a s wit h a p o o r p ro gn o sis. La c k o f a re fr ige ra t o r wa s a sso cia t e d wit h a t wo -fo ld in cre a se in t h e risk of d evelop in g m ild d ia rrh ea .
Ch ild re n o f m o t h e r s u n d e r 20 ye a r s o f a ge h a d a p p roxim a tely fo u r tim es th e risk o f d eh y-d ra tion , sin ce th is exp osu re wa s in y-d ep en y-d en tly a sso c ia t e d wit h r isk a n d p ro gn o sis fo r d e h yd ra tin g yd ia rrh e a ( Ta b le 5). Am o n g th e re m a in in g m atern al rep rod u ctive ch aracteristics, h igh -er b irth o rd -er wa s a sso cia ted with a p o o r p ro gn o sis, wh ile t wign sh ip wa s a sso c ia t e d wit h ign -crea sed risk of d eh yd ra tin g d ia rrh ea .
Ta b le 6 sh ows t h e st re n gt h o f in d e p e n d e n t a sso cia t io n s b e t we e n n u t r it io n a l st a t u s/ fe e d in g p ra ctices a n d d ia rrh ea o u tco m es. Mo st n u -tritio n a l va ria b les were sign ifica n tly a sso cia ted with b o th th e risk o f d e h yd ra tin g d ia rrh e a a n d a p o o r p ro gn o sis, b u t n o t wit h r isk o f m ild d i-a rrh ei-a . Low b irth -weigh t ch ild ren were i-a t i-a sign ific a sign t ly h igh e r r isk o f d e ve lo p isign g d e h yd ra -t io n a s c o m p a re d -t o n o r m a l- we igh -t c h ild re n . Po o r n u tritio n a l sta tu s a s m e a su re d b y h e igh t-fo r- a ge re su lt e d in a 4.5- t-fo ld in c re a se in t h e risk of d eh yd ratin g d iarrh ea. Poor feed in g p ra c-tice s a cco u n te d fo r b o th a n in cre a se d risk a n d a wo rse p ro gn o sis. Du rin g th e first two yea rs o f life, in terru p tin g b rea stfeed in g ju st p rio r to th e o n se t o f t h e e p iso d e re su lt e d in a 6 fo ld in -crea se in th e risk of d evelop in g d eh yd ra tin g d i-a rrh ei-a .
Table 1
Distribution of variables for healthy children and according to diarrhea outcomes.
Variables Dehydrating Mild Healthy
diarrhea diarrhea children
% (n = 192) % (n = 192) % (n = 192)
Age (months)
0-1 16 4 14
2-3 23 15 9
4-5 17 11 13
6-8 20 28 24
9-11 9 29 25
12-17 9 7 5
18-23 5 6 9
Gender
Male 53 52 51
Female 47 48 49
Family income (times minimum wage)
≥3,6 19 24 29
< 3,6 81 76 71
Father’s presence and schooling (years)
≥1 61 82 83
absent or 0 39 18 17
Maternal schooling (years)
≥8 11 15 18
< 8 89 85 82
Mother’s skin color
White 53 68 66
Black 20 18 17
Mixed 27 14 16
Maternal work
No 59 53 62
Yes 41 47 38
Type of housing
Masonry 54 66 72
Shack 46 34 28
Water supply
Indoor running water 52 58 68
Outdoor running water (on property) 31 28 20 Outdoor running (public) 11 10 9
Well or river 6 4 2
Use of refrigerator
Yes 42 49 59
No 58 51 41
Number of under-fives in household
1-2 77 86 89
3-6 23 14 11
Home cleanliness
Yes 21 37 45
No 79 63 55
Discussion
Ta b le 7 su m m a r ize s b o t h r isk a n d p ro gn o st ic fa cto rs. Fa cto rs th a t in crea sed th e risk o f d eh y-d ra t in g y-d ia r r h e a we re a sso c ia t e y-d wit h a p o o r p rogn osis for a given ep isod e of d ia rrh ea ra th er th a n in crea sin g th e risk o f m ild d ia rrh ea . In so -fa r a s th e stu d y wa s a b le to a scerta in , socioeco-n o m ic va ria b les d id socioeco-n o t d istisocioeco-n gu ish ch ild resocioeco-n a t risk of d evelop in g m ild d ia rrh ea .
Ch ild re n in low- in c o m e a re a s o ft e n h a ve sim ila r exp o su res, su ch a s low p a ren ta l ed u ca -t io n . Th e n e igh b o r h o o d - m a -t c h e d d e sign d id n o t a llow t h e id e n t ifica t io n o f t h e se va r ia b le s a s risk fa cto rs fo r d evelo p in g m ild d ia rrh ea . Al-th o u gh co n d itio n a l lo gistic regressio n wa s p er-form ed a n d th e a n a lyses were b a sed on d iscor-d a n t p a irs, overm a tch in g m a y still h a ve a ffected th e p recision of od d s ra tios estim a tes (Roth -m a n &a-mp; Green la n d , 1998).
Ch ild re n we re m a t c h e d in t wo b ro a d a ge c a t e go r ie s t o t h e d e h yd ra t in g d ia r r h e a c a se s. Howe ve r, sin ce th e re we re re sid u a l d iffe re n ce s a n d a n a lyse s we re co n d u ct e d wit h in sm a ll in -ter va ls, a ge wa s b o th a risk a n d p ro gn o stic fa c-t o r fo r d e h yd ra c-t in g d ia r r h e a . Ch ild re n u n d e r t wo m o n t h s we re la rge ly p ro t e ct e d fro m m ild d ia rrh ea , b u t th ey were a lso a t in crea sed risk of d e h yd ra t io n , sin c e t h e p ro gn o sis o f d ia r r h e a im p rove d sh a rp ly with a ge. Fu rth e rm o re, ch il-d ren a geil-d two to th ree m on th s were eq u a lly ex-p o sed to a h igh risk a n d ex-p o o r ex-p ro gn o sis fo r d e-h yd ra tin g d ia rre-h e a . Te-h e se a sso cia tio n s m a y b e lin ked to feed in g p ra ctices, p a rticu la rly th e in -terru p tion of b rea stfeed in g.
Th e effects o f ea ch so cio eco n o m ic risk fa c-t o r we re a d ju sc-t e d fo r c-t h o se o f a ll o c-t h e r su c h va ria b les. Both very low h ou seh old in com e a n d low p a t e r n a l e d u ca t io n we re in d e p e n d e n t d e -t e r m in a n -t s o f d e h yd ra -t in g d ia rr h e a . Al-t h o u gh m o st stu d ie s d e te cte d m a te rn a l sch o o lin g a s a r isk fa c t o r fo r c h ild h o o d d ia r r h e a (Hu ssa in & Sm it h , 1999; Yo o n e t a l., 1996), o u r st u d y d id n o t d etect a n a sso cia tio n with m o th er’s ed u ca -tio n . Th is m a y b e exp la in ed by th e in clu sio n o f p a te rn a l sch o o lin g in th e sa m e m o d e l, a tte n u -a t in g t h e e ffe c t o f t h e fo r m e r (D e s-a i &-amp; Alv-a , 1998) a n d su gge st in g t h a t t h e e ffe ct o f m a t e rn a l e d u ca t io rn is rn o t irn d e p e rn d e rn t o f so cio e co n o m ic le ve l (Da rge n tMo lin a e t a l., 1994). Ma -t e r n a l wo rk h a d a p a ra d oxica l e ffe c-t . Ch ild re n o f wo rkin g m o t h e r s t e n d e d t o b e a t in cre a se d risk o f m ild d ia rrh ea (a lth o u gh sta tistica lly n o t q u it e sign ifica n t ) (Hu ssa in & Sm it h , 1999) b u t a t th e sa m e tim e h a d a b etter p rogn osis. Ma ter-n a l wo rk m a y ke e p wo m e ter-n o u t sid e t h e h o m e wit h o u t sim u lt a n e o u sly e n su r in g a d e q u a t e ch ild ca re (La m o n ta gn e et a l., 1998; Reed et a l.,
1996). Howe ver, o n ce th eir ch ild ren h a d d evel-op ed d iarrh ea, workin g m oth ers rein forced th eir care an d were th u s ab le to p reven t d eh yd ration .
Alth ou gh several en viron m en tal factors were sign ifica n tly a sso cia ted with d ia rrh ea l m o rb id -ity a cco rd in g to b iva ria te a n a lysis, a fter a d ju stin g for con fou n d stin g on ly th e la ck of a refrigera -t o r in -t h e h o u se h o ld re m a in e d a s a r isk fa c-t o r fo r m ild d ia r r h e a (Hu ssa in & Sm it h , 1999). Fa m ilie s livin g in t h is c it y se ld o m u se d o p e n we lls o r r ive r s a s t h e ir so u rce o f d r in kin g a n d cookin g water. Accord in gly, th e od d s ratios were a p p ro xim a t e ly e q u a l t o t h re e b u t t h e c o n fid en ce in terva ls were wifid e fid u e to th e low p reva -len ce of exp osu re. Ch ild ren of fa m ilies wh o h a d o u t d o o r r u n n in g wa t e r h a d a t wo - fo ld r isk o f d eh yd ratin g d iarrh ea as com p ared to th ose with
Table 1 (continued from previous page)
Variables Dehydrating Mild Healthy
diarrhea diarrhea children
% (n = 192) % (n = 192) % (n = 192)
Maternal age (years)
≥20 76 80 88
< 20 24 20 12
Birth order
1-2 41 52 54
3 22 20 13
> 3 37 28 33
Twin
No 94 97 99
Yes 6 3 1
Birth weight (grams)
> 3,000 54 67 73
2,999–2,500 22 22 18
< 2,500 24 11 9
Height-for-age (z score)
> -1 30 59 64
-1 to -1.9 37 27 25
≤-2 33 14 11
Weight-for-age (z score)
> -1 46 63 73
-1 to -1.9 29 26 20
≤-2 25 11 7
Type of milk consumed
Breast 8 15 23
Breast + non-breast 17 23 23
Non-breast 75 62 54
Breastfeeding history
Still breastfeeding 25 38 46
Stopped breastfeeding 70 59 50
Table 2
Association between demographic variables and diarrhea outcomes.
Variables Dehydrating diarrhea Prognosis of diarrhea Mild diarrhea
Crude odds ratio (95% CI) Crude odds ratio (95% CI) Crude odds ratio (95% CI)
Age (months)
0-1 2.6 (1.3-5.5) 23.1 (6.9-77.8) 0.2 (0.1-0.6) 2-3 7.1 (3.0-16.5) 7.1 (2.9-17.4) 1.2 (0.6-2.5) 4-5 3.5 (1.6-7.5) 6.8 (2.7-17.3) 0.9 (0.4-1.7) 6-8 2.4 (1.2-4.8) 3.2 (1.4-7.4) 0.9 (0.5-1.5)
9-11 1.0 1.0 1.0
p level* < 0.001 < 0.001 0.05
12-17 3.7 (1.0-13.1) 0.8 (0.3-2.5) 0.9 (0.6-1.3)
18-23 1.0 1.0 1.0
p level* 0.03 0.80 0.60
Gender
Male 1.0 1.0 1.0
Female 0.9 (0.6-1.4) 0.9 (0.6-1.5) 0.9 (0.6-1.3)
p level* 0.70 0.90 0.60
* p level assessed by likelihood ratio test.
Table 3
Association between socioeconomic variables and diarrhea outcomes.
Variables Dehydrating diarrhea Prognosis of diarrhea Mild diarrhea
Adjusted odds ratio1 Adjusted odds ratio2 Adjusted odds ratio3
(95% CI) (95% CI) (95% CI)
Family income (times minimum wage)
≥3.6 1.0 1.0 1.0
< 3.6 1.8 (1.0-3.1) 1.2 (0.6-2.1) 1.4 (0.9-2.2)
p level* 0.04 0.60 0.15
Father’s presence and schooling (years)
≥1 1.0 1.0 1.0
absent or 0 2.7 (1.6-4.8) 2.7 (1.6-4.6) 0.9 (0.5-1.7)
p level* < 0.001 < 0.001 0.90
Maternal schooling (years)
≥8 1.0 1.0 1.0
< 8 1.5 (0.8-2.7) 1.4 (0.7-2.8) 1.5 (0.8-2.6)
p level* 0.20 0.30 0.20
Mother’s skin color
White 1.0 1.0 1.0
Black 1.7 (0.9-3.1) 1.4 (0.8-2.5) 0.9 (0.5-1.6) Mixed 2.2 (1.2-4.1) 2.3 (1.2-4.2) 1.1 (0.7-1.9)
p level* 0.02 0.03 0.90
Maternal work
No 1.0 1.0 1.0
Yes 1.1 (0.7-1.7) 0.6 (0.3-0.9) 1.4 (0.9-2.1)
p level* 0.80 0.02 0.09
* p level assessed by likelihood ratio test. Odds ratios were adjusted for:
Table 4
Association between environmental variables and diarrhea outcomes.
Variables Dehydrating diarrhea Prognosis of diarrhea Mild diarrhea
Adjusted odds ratio1 Adjusted odds ratio2 Adjusted odds ratio3
(95% CI) (95% CI) (95% CI)
Type of housing
Masonry 1.0 1.0 1.0
Shack 2.3 (1.1-5.0) 1.1 (0.6-1.9) 1.0 (0.6-1.7)
p level* 0.03 0.80 1.00
Water supply
Indoor running water 1.0 1.0 1.0
Outdoor running water (on property) 2.1 (1.1-4.3) 0.9 (0.5-1.6) 1.5 (0.9-2.7) Outdoor running (public) 1.0 (0.4-2.6) 1.0 (0.4-2.5) 0.8 (0.3-2.1) Well or river 3.0 (0.7-12.5) 1.8 (0.5-6.0) 3.3 (0.9-12.9)
p level* 0.08 0.70 0.09
Use of refrigerator
Yes 1.0 1.0 1.0
No 1.1 (0.6-2.2) 0.7 (0.4-1.2) 1.8 (1.2-2.9)
p level* 0.70 0.16 0.009
Number of under-fives in household
1-2 1.0 1.0 1.0
3-6 2.4 (1.0-5.6) 1.9 (1.0-3.6) 1.5 (0.8-2.9)
p level* 0.03 0.05 0.20
Home cleanliness
Yes 1.0 1.0 1.0
No 2.9 (1.5-5.6) 2.0 (1.2-3.4) 0.9 (0.6-1.4)
p level* < 0.001 0.007 0.60
* p level assessed by likelihood ratio test.
Odds ratios were adjusted for variables described in Table 2 plus: 1number of under-fives, type of housing, water supply, home cleanliness; 2number of under-fives, home cleanliness;
3use of refrigerator, water supply.
Table 5
Association between maternal reproductive variables and diarrhea outcomes.
Variables Dehydrating diarrhea Prognosis of diarrhea Mild diarrhea
Adjusted odds ratio1 Adjusted odds ratio2 Adjusted odds ratio3
(95% CI) (95% CI) (95% CI)
Maternal age (years)
≥20 1.0 1.0 1.0
< 20 3.8 (1.6-8.9) 2.4 (1.2-4.6) 1.6 (0.9-3.0)
p level* < 0.001 0.01 0.10
Birth order
1-2 1.0 1.0 1.0
3 2.1 (0.9-4.8) 1.8 (0.9-3.3) 1.7 (0.9-3.1)
> 3 1.2 (0.5-2.4) 2.3 (1.2-4.5) 0.8 (0.5-1.4)
p level* 0.20 0.03 0.08
Twin
No 1.0 1.0 1.0
Yes 11.6 (0.9-143) 1.4 (0.4-5.3) 2.0 (0.4-9.2)
p level* 0.03 0.60 0.40
* p level assessed by likelihood ratio test.
Odds ratios were adjusted for variables described in Table 3 plus: 1twin, maternal age;
in d oor ru n n in g water. Fam ilies ten d ed to u se th e sa m e sin k fo r wa sh in g h a n d s, d ia p e rs, clo th e s, a n d kit ch e n u t e n sils. In a d d it io n , t h e n u m b e r o f u n d e r- five s in t h e h o m e a n d h o m e cle a n li-n e ss we re a sso cia t e d wit h t h e se ve r it y b u t li-n o t wit h t h e in c id e n c e o f d ia r r h e a (Go r t e r e t a l., 1998; Va sq u e z e t a l., 1999).On e m igh t e xp e c t en viron m en ta l fa ctors to b e p rim a rily a ssocia t-e d wit h in c id t-e n c t-e a n d ra t h t-e r t h a n st-e vt-e r it y o f d ia r r h e a . Howe ve r, c h ild re n in su b - st a n d a rd e n viro n m e n t s m a y h a ve b e e n su b je c t e d t o gre a te r m icro b ia l lo a d s a n d th e re fo re p re se n t-ed m ore severe d isea se (a l-Ma zrou et a l., 1995).
Ch ild ren of teen a ge m oth ers were a t grea ter risk of d eh yd ration , su ggestin g th at th ese m oth -e rs w-e r-e l-e ss p r-e p a r-e d t o d -e a l wit h t h -e d is-e a s-e (a l- Ma zro u e t a l., 1995). H igh b ir t h o rd e r wa s a sso cia te d with in cre a se d se ve rity o f d ia rrh e a , a n d t win s we re a t gre a t e r r isk o f d e h yd ra t in g d ia rrh ea , in d ep en d en tly o f m a tern a l a ge.
Low b irth weigh t, la ck of b rea stfeed in g, a n d m a ln u t r it io n h a ve b e e n a sso c ia t e d wit h d
is-ea se b u rd en a n d in cris-ea sed m o rta lity (D’So u za , 1997; Hu ssa in & Sm it h , 1999).Pa r t icu la r ly fo r d ia rrh ea l d isea ses, m o st stu d ies h a ve a n a lyzed risk an d p rogn ostic factors with ou t p rop er con -t ro l fo r p o -t e n -t ia l co n fo u n d in g va r ia b le s (Da r-gen t-Molin a et a l., 1994; Teka et a l., 1996).
Ad ju st m e n t fo r c o n fo u n d in g va r ia b le s is n e ce ssa r y b e ca u se h igh e r so cio e co n o m ic st a -t u s is kn own -t o b e a sso cia -t e d b o -t h wi-t h lowe r ra t e s o f d ia r r h e a a n d b re a st fe e d in g p ra c t ic e s d u rin g in fa n cy. Even ch ild ren selected from th e sa m e n e igh b o r h o o d h a d d iffe re n t e xp o su re levels, a s sh own in th is stu d y fo r severity o f th e d ia rrh e a l e p iso d e. La ck o f b re a st fe e d in g h a d a gre a t e r e ffe c t o n r isk o f d e h yd ra t io n t h a n o n p ro gn o sis o f d ia rrh e a , b u t u n like o th e r stu d ie s it wa s n o t a sso cia ted with m ild d ia rrh ea . Sin ce m ixed -fed an d wean ed in fan ts con su m e greater a m o u n t s o f su p p le m e n t a l liq u id s, t h e p ro t e c-tive effect o f b rea stm ilk wa s sh own by co m p a r-in g to ta l b rea stfed with n o n -b rea stfed ch ild ren (Ra isle r e t a l., 1999). Du e t o t h e sm a ll n u m b e r
Table 6
Association between nutritional variables and diarrhea outcomes.
Variables Dehydrating diarrhea Prognosis of diarrhea Mild diarrhea
Adjusted odds ratio1 Adjusted odds ratio2 Adjusted odds ratio3
(95% CI) (95% CI) (95% CI)
Birth weight (grams)4
> 3,000 1.0 1.0 1.0
2,999–2,500 2.4 (1.2-4.9) 1.3 (0.7-2.3) 1.0 (0.6-1.7) < 2,500 3.6 (1.5-8.8) 3.2 (1.6-6.3) 0.9 (0.5-1.8)
p level* 0.002 0.002 0.90
Height-for-age (z score)
> -1 1.0 1.0 1.0
-1 to -1.9 1.4 (0.6-3.4) 2.5 (1.2-5.1) 0.9 (0.5-1.5) ≤-2 4.5 (1.3-15.5) 4.2 (1.8-9.9) 1.5 (0.8-3.0)
p level* 0.04 < 0.001 0.30
Weight-for-age (z score)
> -1 1.0 1.0 1.0
-1 to -1.9 1.5 (0.5-4.2) 1.7 (0.9-3.1) 1.3 (0.7-2.3) ≤-2 1.9 (0.2-16.9) 2.2 (0.9-5.0) 1.5 (0.7-3.4)
p level* 0.70 0.09 0.50
Type of milk consumed
Breast 1.0 1.0 1.0
Breast + non-breast 1.5 (0.4-5.1) 0.8 (0.3-2.5) 1.2 (0.6-2.3) Non-breast 6.0 (1.9-14.6) 2.3 (0.9-5.9) 1.2 (0.7-2.2)
p level* < 0.001 0.03 0.80
Breastfeeding history
Still breastfeeding 1.0 1.0 1.0
Stopped breastfeeding 6.4 (2.3-17.3) 2.5 (1.2-5.0) 1.1 (0.7-1.7) Never breastfed 0.7 (0.1-3.7) 3.8 (0.5-31.0) 0.5 (0.2-1.8)
p level* < 0.001 0.02 0.50
* p level assessed by likelihood ratio test.
Odds ratios were adjusted for variables described in Table 4 plus:
1birth weight, age of the children, weight-for-age, type of milk, previous hospitalization; 2birth weight, age of the children, height-for-age, type of milk;
Table 7
Summary of p values for findings on risk and prognostic factors for diarrhea outcomes.
Variables Dehydrating diarrhea Prognosis of diarrhea Mild diarrhea
Age (first year of life) < 0.001 < 0.001 0.05
Age (second year of life) 0.03 0.80 0.60
Gender 0.70 0.90 0.60
Family income 0.04 0.60 0.15
Father’s presence and schooling < 0.001 < 0.001 0.90
Maternal schooling 0.20 0.30 0.20
Mother’s skin color 0.02 0.03 0.90
Maternal work 0.80 0.02 0.09
Type of housing 0.03 0.80 1.00
Water supply 0.08 0.70 0.09
Use of refrigerator 0.70 0.16 0.009
Number of under-fives in household 0.03 0.05 0.20
Home cleanliness < 0.001 0.007 0.60
Maternal age < 0.001 0.01 0.10
Birth order 0.20 0.03 0.08
Twin 0.030 0.60 0.40
Birth weight 0.002 0.002 0.90
Height-for-age 0.04 < 0.001 0.30
Weight-for-age 0.70 0.09 0.50
Type of milk consumed < 0.001 0.03 0.80
Breastfeeding history < 0.001 0.02 0.50
o f ch ild re n in so m e ca t e go r ie s, co n fid e n ce in -terva ls were wid e a n d in clu d ed u n ity (p rogn os-tic fa ctor).
Th is st u d y d isc u sse d t h e a p p lic a t io n o f a ca se-co n tro l d esign to a d d ress a n issu e u su a lly exa m in ed by coh ort stu d ies. In a coh ort stu d y a gro u p o f h e a lt h y c h ild re n n e e d s t o b e id e n t i-fied an d followed u p for a certain p eriod of tim e t o d e t e c t d ia r r h e a l e p iso d e s. Alt h o u gh m o st c h ild re n h a ve se lf- lim it in g d ia r r h e a , a fe w p ro gre ss to d e h yd ra tio n . At th is p o in t it wo u ld b e t h e o re t ic a lly p o ssib le t o a sse ss t h e t h re e o u tco m e s: risk fa cto rs fo r m ild d ia rrh e a , p ro g-n o sis o f t h e d ia rrh e a l e p iso d e, a g-n d risk fa ct o rs fo r d e h yd ra t in g d ia rrh e a . Howe ve r, sin ce a d i-a rrh ei-a l ep iso d e m i-a n d i-a tes th e u se o f o ri-a l reh y-d ra t io n t h e ra p y, su c h a n a p p ro a c h wo u ly-d b e eth ica lly u n fea sib le. Secon d , d eh yd ra tion com -p lica t e s le ss t h a n 5% o f a ll d ia rrh e a l e -p iso d e s, a n d a la rge n u m b e r o f ch ild re n wo u ld h a ve t o b e fo llowe d u p in o rd e r t o o b t a in a su ffic ie n t sa m p le. A ca se - co n t ro l d e sign ove rca m e b o t h th e p o ten tia l eth ica l issu e (sin ce ch ild ren were selected a fter th e ou tcom e occu rred ) a n d logis-tic p ro b lem s rela ted to th e sa m p le size.
Som e ad d ition al m eth od ological issu es n eed t o b e h igh ligh t e d . Id e a lly, c a se s a n d c o n t ro ls wo u ld c o m e fro m t h e sa m e p o p u la t io n in o r
-d er to m a ke va li-d co m p a riso n s a b o u t exp o su re co n d it io n s. To a ssu re t h e va lid it y o f t h is ca se -con trol stu d y, com m u n ity -con trols were select-e d fro m t h select-e sa m select-e n select-e igh b o r h o o d a s t h select-e c a sselect-e s treated in th e referen ce h osp itals. Th ese con trols we re e xp e cte d to h a ve b e e n id e n tifie d a s ca se s if th ey h a d d evelo p ed d eh yd ra tin g d ia rrh ea .
However, in d ivid u a l m a tch in g led to p oten t ia l sim ila rit ie s re ga rd in g e xp o su re. Fo r e xa m -p le, m a t c h in g c o n t ro ls t o c a se s a c c o rd in g t o a ge wa s p a rticu la rly releva n t to a llow th e id en -tifica tion of b rea stfeed in g sta tu s a n d oth er a ge-d e p e n ge-d e n t e xp o su re s. Alth o u gh th is a p p ro a ch is a d va n t a ge o u s, ove r m a t ch in g co u ld b e a p o -t e n -t ia l p ro b le m sin c e c a se a n d c o n -t ro ls we re like ly t o sh a re t h e sa m e e n viro n m e n t a l co n d i-tio n s, th e re fo re le a d in g so m e e xp o su re s to n o t b e id en tified a s risk or p rogn ostic fa ctors.
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Su b m itted on 22 Decem b er 2000
Fin a l version resu b m itted on 10 Sep tem b er 2001 Ap p roved on 28 Decem b er 2001
