The Effect of Heavy Metals and Trace Elements in the Meconium on Preterm Delivery of Unknown Etiology

Transcription

1 ORİJİNAL ARAŞTIRMA The Effect of Heavy Metals and Trace Elements in the Meconium on Preterm Delivery of Unknown Etiology Gamze ÖZSOY, MD, Msc, a Gülcan TÜRKER, MD, Assoc.Prof., b Semra ÖZDEMİR, MD, Assoc.Prof., c Ayşe Sevim GÖKALP, MD, Prof. a,b Ümit Bora BARUTÇU, MD, Prof. c a Department of Pediatrics, b Division of Neonatology, Kocaeli University Faculty of Medicine, Kocaeli c Department of Biophysics, İstanbul University Cerrahpaşa Faculty of Medicine, İstanbul Ge liş Ta ri hi/re ce i ved: Ka bul Ta ri hi/ac cep ted: Ya zış ma Ad re si/cor res pon den ce: Gülcan TÜRKER, MD, Assoc.Prof. Kocaeli University Faculty of Medicine, Division of Neonatology, Kocaeli, TÜRKİYE/TURKEY gulcanturker@kocaeli.edu.tr doi: /medsci Cop yright 2012 by Tür ki ye Kli nik le ri ABS TRACT Ob jec ti ve: Pre ma tu rity is an im por tant eti o lo gic fac tor for pe ri na tal mor ta lity and mor bi dity. In our co untry, pre term births and comp li ca ti ons of pre ma tu rity ac co unt for 26% of pe ri na tal mor ta lity. The re are many ma ter nal, fe tal or pla cen tal, ge ne tic and en vi ron men tal etio lo gic fac tors that ca u se pre ma tu rity. The re ha ve be en no stu di es to show an as so ci a ti on bet we - en pre term de li very of unk nown eti o logy and ex po su re to he avy me tals and tra ce ele ments at to xic le vels in me co ni um. The pur po se of this study is to me a su re the le vels of he avy me tals (le - ad, cad mi um) and tra ce ele ments (zinc, iron, cop per) in me co ni um samp les and to un ders tand the - ir as so ci a ti ons with pre term de li very of unk nown eti o logy. Ma te ri al and Met hods: The le vels of he avy me tals and tra ce ele ments in the me co ni ums of 810 term or pre term in fants with known and unk nown eti o logy for be ing pre term we re me a su red with a fla me ato mic ab sorp ti on spec trop - ho to me ter. Re sults: Le ad and cad mi um we re de tec ted in all me co ni um samp les. He avy me tal and tra ce ele ment le vels in me co ni um we re sig ni fi cantly hig her in pre terms of unk nown and known eti o logy for be ing pre term com pa red to term in fants (for all p<0.0001). Le ad le vels in me co ni um we re sig ni fi cantly hig her in pre term of unk nown eti o logy com pa red to pre term of known eti o - logy in post hoc analy sis with Bon fer ro ni cor rec ted Mann Whit ney U test. Conc lu si on: The se results may sug gest that le ad le vels in me co ni um samp les are hig her in pre term new borns es pe ci ally with unk nown eti o logy com pa red to term new borns. The re fo re, we sug gest that pre term de li very of unk nown eti o logy may be dec re a sed by dec re a sing air pol lu ti on. Key Words: Cad mi um; le ad; me co ni um ÖZET Amaç: Pre ma tü ri te pe ri na tal mor ta li te ve mor bi di te için önem li bir risk fak tö rü dür. Ül ke miz - de er ken do ğum lar ve pre ma tü ri te nin komp li kas yon la rı pe ri na tal mor ta li te nin %26 sın dan so rum - lu dur. Pre ma tü ri te ye ne den olan çok sa yı da ma ter nal, fö tal ve ya pla sen tal, ge ne tik ve çev re sel etiyolojik fak tör var dır. Etiyoloji si bi lin me yen er ken do ğum la me kon yum da ki tok sik dü zey ler de ağır me tal le re ve eser ele met le re ma ru zi yet ara sın da ki ilis ki yi gös te ren hiç bir ça lıs ma yok tur. Bu ça - lıs ma nın ama cı me kon yum ör nek le rin de ağır me tal (kur sun, kad mi yum) ve eser ele ment (çin ko, de - mir, ba kır) dü zey le ri ni ölç mek ve etiyoloji si bi lin me yen er ken do ğum la iliş ki le ri ni an la mak tır. Ge reç ve Yön tem ler: Etiyoloji si bi li nen ve bi lin me yen 810 term ve ya pre term be be ğin me kon yum - la rın da ki ağır me tal ler ve eser ele ment ler alev li ato mik ab sorb si yon spek tro fo to met re si ile öl çül dü. Bul gu lar: Tüm me kon yum ör nek le rin de kur sun ve kad mi yum sap tan dı. Me kon yum da ki ağır me - tal ve eser ele ment dü zey le ri etiyoloji si bi li nen ve bi lin me yen pre term ler de term be bek le re gö re be - lir gin ola rak yük sek ti (tü mü için p<0,0001). Tu key tes tiy le post-hoc ana liz de sa de ce me kon yum da ki kur sun dü zey le ri etiyoloji si bi lin me yen pre term ler de etiyoloji si bi li nen pre term le re gö re be lir gin ola rak yük sek ti. So nuç: Bu so nuç lar me kon yum ör nek le rin de ki kur sun dü zey le ri nin pre term ye ni - do ğan lar da özel lik le ne de ni bi lin me yen pre term do ğum lar da term ye ni do ğan la ra gö re da ha yük sek ol du ğu nu dü sün dü re bi lir. Bu yüz den ha va kir li li ği azal tı la rak ne de ni bel li ol ma yan pre ma tu re do - ğum la rın azal tı la bi le ce ği dü şü nü le bi li riz. Anah tar Ke li me ler: Kad mi yum; kur şun; me kon yum Turkiye Klinikleri J Med Sci 2012;32(4): Turkiye Klinikleri J Med Sci 2012;32(4) 925

2 Özsoy ve ark. re ma tu rity is an im por tant eti o lo gic fac tor for pe ri na tal mor ta lity and mor bi dity. 1 In our co - untry, pre term births and comp li ca ti ons of pre ma tu rity ac co unt for 26% of pe ri na tal mor ta lity. 2 The re are many ma ter nal, fe tal or pla cen tal, ge ne tic and en vi ron men tal eti o lo gic fac tors that ca u se prema tu rity. In re cent ye ars, one of the most fre qu ently dis cus sed eti o lo gic fac tors for pre ma tu rity is en vi - ron men tal pol lu ti on. Many stu di es sug gest that en viron men tal pol lu ti on, es pe ci ally air pol lu ti on, is clo sely re la ted to pre ma tu rity. 3-8 Two furt her stu di es sug gest an as so ci a ti on bet we en pre ma tu rity and mater nal blo od le ad or me co ni um mer cury con tents. 9,10 Nut ri ti o nal ele ments and to xic subs tan ces are trans por ted from mot her to fe tus vi a blo od cir cu - la ti on, and ex ces si ve le vels of to xins and cer ta in to - xic me tals harm the fe tus. The le vels of tra ce ele ments and to xic me tals in fe tal blo od may not ref lect the deg re e of fe tal ex po su re to to xic me tals or ac tu al deg re es of ex cess or de fi ci ency of tra ce ele ments. Many subs tan ces pro ces sed by the fe tus accu mu la te in the fe tal in tes ti ne, thus me co ni um analy sis may al so be used to as sess le vels of fe tal expo su re to to xic me tals and mi ne ral con tent It has be en sug ges ted that, in dry me co ni um, con centra ti ons of tra ce ele ments hig her than 100 μg/g (0.01%) can in di ca te to xi city. 12 Rep la cing tra ce ele ment de fi ci en ci es or de to xif ying af ter to xic me tal ex po su re po se sig ni fi cant chal len ges for the ne o na - to lo gist in the first few we eks of an in fant s li fe. 15 Ko ca e li is lo ca ted in Wes tern Ana to li a and it is an in dus tri al city that con ta ins 17% of all firms and fac to ri es in Tur key. Tur key s lar gest ship yard and lar gest ti re fac tory are in Ko ca e li. In ad di ti on, the - re are nu me ro us in dus tri al fac to ri es, inc lu ding pet ro le um, plas tic, rub ber, dye, che mistry, far ming, drugs, iron, ste el, cop per, au to mo bi le spa re parts, cab le, glass, li me and ce ra mic fac to ri es. The se fo - un da ti ons are sta ti o ned along si de the high way bet we en Eu ro pe and Asi a. Mo re o ver, the high way, au to bahn, and ra il ro ad con nec ting Eu ro pe and Asi - a are lo ca ted in this city. In this study, the le vels of to xic me tals (le ad, cad mi um) and tra ce ele ments (zinc, iron and copper) of pre term and term new borns we re me a su - red in me co ni um samp les. MA TE RI AL AND MET HODS Neonatoloji The study was ap pro ved by the Ko ca e li Uni ver sity, Fa culty of Me di ci ne Et hics Com mit te e (Et hic Com mit te e num ber is 108/15/20). Term and prema tu re in fants who we re born at Ko ca e li Uni ver - sity Hos pi tal and/or hos pi ta li zed in the new born in ten si ve ca re unit bet we en No vem ber 2006 and Feb ru ary 2009 we re inc lu ded in the study gro up. In fants who se me co ni um samp les co uld not be ta - ken be ca u se of (1) early disc har ge (es pe ci ally in nor mal spon ta ne o us va gi nal birth), (2) lack of pa - ren tal per mis si on, (3) in suf fi ci ent me co ni um (espe ci ally in pre ma tu re in fants), and in fants with con ge ni tal ab nor ma li ti es we re exc lu ded. An appro val form was sig ned by the pa rents. Risk factors for pre ma tu rity (fe tal dis tress, mul tip le ges ta ti ons, pla cen tal di se a ses, ute ri ne ab nor ma li - ti es cer vi cal in suf fi ci ency, pre ec lamp si a/ec lamp si - a, ma ter nal di se a ses, drug and ci ga ret te use du ring preg nancy, in fec ti on, clo se de li very, pre ma tu re rup tu re of mem bra nes, polyh ydram ni os and oli - gohy dram ni os) we re in ves ti ga ted in the form comp le ted for each in fant. Ge ne ral in fant cha rac - te ris tics, inc lu ding gen der, ges ta ti o nal age, type of birth and me co ni um col lec ti on ti me as well as demog rap hic fe a tu res of pa rents (age, edu ca ti on and so ci al in su ran ce sta tus, oc cu pa ti on, in co me, number of pe op le li ving to get her in the sa me ho u se) we re re cor ded. The in fants we re di vi ded in to thre e gro ups: 1- Pre term de li very of unk nown eti o logy, 2- Pre term de li very of known eti o logy, 3- Term de li very. Last mens tru al pe ri od and the new Bal lard sco - re we re used to de ter mi ne the ges ta ti o nal age. Whi le eva lu a ting the risk fac tors for pre ma tu rity, all pla cen tal di se a ses (pla cen ta pre vi a, etc.), ute ri ne ano ma li es and cer vi cal in suf fi ci ency we re iden ti fi - ed as gy ne co lo gi cal di se a ses in the sta tis tics. Me - di cal re cords of mot hers we re used for the di ag no sis of gyne co lo gi cal di se a ses, pre ec lamp si a/ec lamp si a, polyh ydram ni os, and oli gohy dram ni os. Uri nary tract in fec ti on and va gi ni tis his tory was ob ta i ned from the mot her for di ag no sis of ma ter nal in fec ti Turkiye Klinikleri J Med Sci 2012;32(4)

3 Neonatology on. In ad di ti on, acu te pha se re ac tants (whi te cell co unt and le vels of C-re ac ti ve pro te in) and the any an ti bi o tic the rapy ta ken we re re cor ded from the mot hers fi les. If the in ter val bet we en this ges ta ti - on and the pri or ges ta ti on was less than two ye ars, clo se de li ver y was as su med. Me co ni um col lec ti on ti me was re cor ded. The me co ni um was usu ally col lec ted in the first or se - cond post na tal days for term in fants whi le it was col lec ted la ter for pre term in fants. The la test me coni um col lec ti on ti me was the sixth post na tal day of a 24-we ek ges ta ti o nal age in fant. Edu ca ti on le vels of the pa rents we re ca te go ri - zed in six gro ups: (1) il li te ra te, (2) li te ra te, (3) primary scho ol, (4) se con dary scho ol, (5) high scho ol, and (6) uni ver sity. So ci al in su ran ce of pa rents we - re re cor ded as fol lows: (1) no se cu rity, (2) he alth se cu rity for the po or, cal led gre en car d in Tur - key, (3) so ci al in su ran ce ins ti tu ti on, a kind of he - alth se cu rity for pri va te firms and wor kers, (4) pen si on fund, he alth se cu rity for go vern ment emp lo ye es, (5) so ci al in su ran ce for ar ti sans and the self-emp lo yed, and (6) pri va te in su ran ce. Pa rent oc cu pa ti ons we re re cor ded ba sed on the ir sta te ments. Ma ter nal oc cu pa ti ons we re gro u - ped as fol lows: stay-at-ho me mom, of fi cer or wor - ker. Pa ter nal and ma ter nal oc cu pa ti ons we re clas si fi ed ac cor ding to the ir ex po su re le vels to to xic me tals as fol lows: low-risk (go vern ment emp lo ye - e, te ac her, far mer, co ok, doc tor, etc.), me di um-risk (cons truc ti on wor ker, fac tory wor ker, en gi ne er, etc.), high-risk (dri ver, wor ker in au to mo ti ve industry or tur nery, whi te was her, pa in ter, fur nis her, etc.) and very high-risk (me tal wor ker, prin ter, che mist, scrap de a ler, etc.). In 2007, the Tur kish Sta tis ti cal Ins ti tu te dec - la red the monthly po verty le vel for a fa mily of fo - ur to be 619 new Tur kish li ras. In this study, pa ren tal eco no mi cal sta tus was clas si fi ed in to two ca te go ri es: low in co me le vel (fe wer than 155 new Tur kish li ras monthly in di vi du al in co me) and midd le or high in co me le vel. Pa rents we re gro u ped ac cor ding to so ci o e co - no mic sta tus by Bar ratt sco re (The Bar ratt Simp li - fi ed Me a su re of So ci al Sta tus). Tab les in the Bar ratt Özsoy et al. sco re we re used. The sum of the ave ra ged edu ca ti - on le vel po ints and oc cu pa ti on po ints of the pa rents we re ac cep ted as the Bar ratt sco re. ME CO NI UM ANALY SIS Me co ni um samp les, which we re ta ken with wo o - den pi pe from di a per, we re put in the non-me tal cups, qu ickly fro zen and kept at -20ºC. Me co ni um le vels of Pb, Cd, Zn, Cu, and Fe we re de ter mi ned in a fla me ato mic ab sorp ti on spec trop ho to me ter (Shimad zu AA- 680) at the bi oph ysics la bo ra tory of Cer rah pa sa Me di cal Fa culty. Me a su re ments we re ba sed on a com pa ri son with ex ter nal stan dards. The stan dards we re freshly pre pa red from stan dard stock me tal so lu ti ons (Tit ri sol mg/l, Merck) im me di a tely pri or to analy sis, and we re used for ini ti al ca lib ra ti on for each subs tan ce. The - se so lu ti ons we re al so used as in ter nal qu a lity standards. Hol low Cat ho de Lamp and Back gro und Cor rec ti on (with De u te ri um Lamp) mo des we re selec ted for ele ment analy ses. Each re sult was correc ted for the ap prop ri a te re a gent used and mat rix blanks. For the ac cu racy of tra ce ele ment con cen - tra ti ons, each samp le was me a su red twi ce for each ele ment analy sis and dif fe ren ces of <5% bet we en two me a su re ments we re ac cep ted. The re sult for each subs tan ce was ex pres sed as na nog rams per gram of dry me co ni um ηg/g). 18 De i o ni zed wa ter was used to cle an the cham ber and as a ze ro con trol for each analy sis. The stock stan dard me tal so lu ti - ons for every me tal (Merck, 1,000 mg/l) we re used for po si ti ve con trols and tes ted for every 25 samp - les, to en su re me a su re ment re li a bi lity. Mi ni mum de tec tab le li mits for Pb, Cd, Zn, Cu, and Fe we re 0.045, 0.009, 0.037, and μg/ml, res pec - ti vely. The re co very of tra ce ele ments (Zn, Fe and Cu) spi ked in me co ni um ran ged bet we en 94.1% ( %) and % and the per cent va ri an - ce ran ged aro und 2.6% ( %) The re co - very of he avy me tals (Pb and Cd) spi ked in me co ni um ran ged bet we en 100% and 102%. The in ter-as say-co ef fi ci ent of va ri a bi lity ran ged bet we - en 0.34% and 8.9%; the in tra-as say co ef fi ci ent of va ri a bi lity ran ged bet we en 0.44% and 8.44% The pre ci si on, as re la ti ve stan dard de vi a ti on (RSD), was bet we en 3.9% and 6.7% for Cd. 22 Turkiye Klinikleri J Med Sci 2012;32(4) 927

4 Özsoy ve ark. The va lu es of me tal le vels in me co ni um; we re di vi ded by birth we ight in or der to stan dar di ze the me tal le vels and we re ex pres sed as (ηg/g/kg). STA TIS TI CAL ANALY SIS Sta tis ti cal analy sis was per for med with the SPSS- 13 prog ram. Con ti nu o us va ri ab les we re gi ven as me di an (mi ni mum-ma xi mum) and me an + standard de vi a ti on; ca te go ri cal va ri ab les we re de fi ned as per cen ta ges. Con ti nu o us va ri ab les we re com pa - red by Krus kal-wal lis analy sis be ca u se the da ta we re not nor mally dis tri bu ted. Chi-squ a re test was used for the ca te go ri cal va ri ab les among thre e gro - ups. Post-hoc analy sis with Bon fer ro ni cor rec ted Mann-Whit ney U test was used for con ti nu o us va - ri ab les of thre e gro ups. RE SULTS GE NE RAL CHA RAC TE RIS TICS AND DE MOG RAP HIC CHA RAC TE RIS TICS The pre term de li very of unk nown eti o logy and known eti o logy gro ups and the term birth gro up had sta tis ti cally si mi lar gen der dis tri bu ti ons. Medi an (min-max) va lu es of ges ta ti o nal we eks in the pre term and term gro ups we re 34 (24-36) and 38 (37-41) we eks, res pec ti vely. When pre na tal risk fac tors we re com pa red bet we en the two gro ups, the ra te of mul tip le ges ta ti ons, pla cen ta pre vi a, pre - ec lamp si a, ma ter nal in fec ti on, pre ma tu re rup tu re of mem bra nes, and oli gohy dram ni os we re hig her in the pre term gro up (Tab le 1). The ra te of Ce sa re - an sec ti on was hig her in the pre term gro up than in the term gro up. First and fifth mi nu te Ap gar sco res we re sig ni fi cantly lo wer in the pre term gro ups (Tab le 1). Two gro ups had sta tis ti cally si mi lar pa r- ent ages (Tab le 1). Bar ratt sco res as so ci a ted with soci o e co no mic sta tus we re fo und to be sig ni fi cantly lo wer in the pre term gro up (Tab le 1). TO XIC ME TAL AND TRA CE ELE MENT LE VELS IN ME CO NI UM The to xic me tals le ad and cad mi um we re de tec ted in all me co ni um samp les. Zinc, iron and cop per le - vels in me co ni um samp les we re hig her than 100 μg/g in 809 (99.9%), 590 (72.8%) and 408 (50.4%) in fants, res pec ti vely. The me tal le vels of both pre - term gro ups we re sig ni fi cantly hig her than the me - tal le vels of the term in fants (for all p<0.001). In Post-Hoc analy sis with Bon fer ro ni cor rec ted Mann Whit ney U test, only le ad le vels in pre term de li ve - ri es of unk nown eti o logy we re hig her than in pre - term de li ve ri es of known eti o logy (p <0.0001). The ot her he avy me tal and tra ce ele ment le vels in pre - term de li ve ri es of unk nown eti o logy we re not signi fi cantly hig her than in pre term de li ve ri es of known eti o logy (for all p >0.05) (Tab le 2). Cor ra la ti on of the me tal le vels with gen der of in fants was not sta tis ti cally sig ni fi cant (p>0.05). DIS CUS SI ON Neonatoloji The to xic me tals le ad and cad mi um we re de tec ted in all me co ni um samp les. Tra ce ele ment le vels we - re de tec ted at to xic le vels in most of the samp les. Mul tip le ges ta ti on ra te, pla cen ta pre vi a, pre ec - lamp si a, ma ter nal in fec ti on, pre ma tu re rup tu re of the mem bra nes, and oli gohy dram ni os we re fo und to be hig her in the pre term de li very of unk nown eti o logy gro up, in ac cor dan ce with pre vi o us stu di - es. 1,22,23 Ot her pre na tal risk fac tors (ute ri ne ano m- aly, cer vi cal in suf fi ci ency, ma ter nal chro nic di se a ses, ma ter nal smo king) we re in sig ni fi cant. The re a son for this may be du e to a de fi ci ency in the ir num bers. Most ad mis si ons to the uni ver sity hos pi tal are risky preg nan ci es. This fac tor co uld exp la in the incre a sed ra te of Ce sa re an sec ti on in this study. So ci o e co no mic sta tus is as so ci a ted with prema tu rity. 1,24-27 The fol lo wing fin dings in this study show that so ci o e co no mic sta tus is al so clo sely asso ci a ted with pre ma tu rity as Bar ratt sco res we re lo - wer in the pre ma tu re gro ups. Me an va lu es of to xic me tal and tra ce ele ment le vels in me co ni um we re fo und to be hig her in this study com pa red to ot her stu di es. 10,15-17 It is no te - worthy that le ad le vels in me co ni um that we re detec ted by Li et al. in Gu i yu, an elec tro nic was te recy cling town in Chi na, we re re mar kably lo wer than in our study and pre vi o us re ports. 10,27 The re ha ve be en few stu di es in ves ti ga ting to - xic me tal and tra ce ele ment le vels in me co ni um. In the se stu di es, the re we re dif fe ren ces in me a su re Turkiye Klinikleri J Med Sci 2012;32(4)

5 Neonatology Özsoy et al. TABLE 1: General characteristics of study groups. Preterm delivery of Preterm deliver of unknown etiology n=131 known etiology n= 176 Term n=503 p Gestational age (week) < Sex F/M 52/79 93/83 266/ Number of hospitalization <0.001 Multiple gestations <0.001 Fetal distress >0.005 Placenta previa <0.001 Uterine anomalies >0.005 Cervical insufficiency Preeclampsia <0.001 Maternal chronic disease >0.05 Maternal smoking >0.005 Maternal infection <0.001 Close delivery Premature rupture of membranes <0.001 Polyhydramnios >0.005 Oligohydramnios Cesarean section Apgar (1. minute)* 8 (2-9) 8 (0-9) 8 (3-10) <0.001 Apgar (5. minute)* 10 (0-10) 10(0-10) 10 (4-10) <0.001 Birth weight (grams)* 2180 ( ) 2000 ( ) 3170 ( ) <0.001 Maternal age (years)* 28 (19-43) 27 (18-42) 28 (17-43) >0.005 Paternal age (years)* 31(22-46) 31(19-58) 31(18-61) >0.005 Barratt score* Maternal occupation score Paternal occupation score Chi square test, * median (min-max) Kruskall-Wallis test was used. TABLE 2: Meconium toxic metal and trace element levels in the preterm and term infants. Preterm delivery of Preterm delivery of unknown etiology known etiology Term p a P b Lead 14.5 ( ) 15.5 ( ) 10.2 ( ) <0.001 < Cadmium 1.08 ( ) 1.31 ( ) 0.78 ( ) <0.001 <0.05 Zinc 88.4 ( ) 98.3 ( ) 60.6( ) <0.001 <0.05 Iron 50.8 ( ) 59.6 ( ) 34.8 ( ) <0.001 <0.05 Copper 44.8 ( ) 51.6 ( ) 31.4( ) <0.001 <0.05 Values are median (min-max), metal levels are (ng/g/kg). P a values are comparisons between term and preterm groups (Kruskal-Wallis H test was used). P b values are comparisons between preterm delivery of unknown etiology and preterm delivery of known etiology (Post-Hoc analysis with Bonferroni corrected Mann Whitney U test was used). Turkiye Klinikleri J Med Sci 2012;32(4) 929

6 Özsoy ve ark. ment met hods, such as using va ri o us units for me t- als and dif fe rent ato mic ab sorp ti on spec trop ho to - me ters (ex cept fla me). As ex pec ted, in fants body sur fa ce are a was dis tri bu ted in a wi de in ter val in a study gro up that con sis ted of term and pre ma tu re in fants. Ex po su re ti me to to xic me tals in ute ro is lon ger in term infants. Be ca u se of the se re a sons, units of me tal le v- els in this study we re rep re sen ted as ng/g/kg in or der to stan dar di ze me tal le vels. When pre vi o us re ports we re exa mi ned, it was de ter mi ned that the re we re only two stu di es abo - ut to xic me tals and pre ma tu rity By con trast, the re ha ve be en a lar ge num ber of stu di es sho wing an as so ci a ti on bet we en air pol lu ti on and pre ma tu - rity. 3,6,27-31 Os tre a et al. se arc hed for to xic me tals (le- ad, cad mi um, mer cury and ar se nic) and pes ti ci des in 426 me co ni um samp les from fi ve hos pi tals. 10 Arse nic was not de tec ted in any samp le. Mer cury, le - ad and cad mi um we re de tec ted in 83.9%, 26.5% and 8.5% of me co ni um samp les, res pec ti vely. The pre ma tu rity ra te was hig her in the mer cury-po si ti - ve gro up (p<0.05). It may be that the re a son that no re la ti on was de tec ted bet we en pre ma tu rity and le ad and cad mi um le vels in this study is du e to an in suf fi ci ent po si ti ve samp le num ber. Jel lif fe-paw - lows ki et al. me a su red preg nancy blo od le ad le vels in 262 wo men. 9 They com pa red wo men with ma - xi mum preg nancy blo od le ad le vels 10 mg/dl and tho se with lo wer le vels, and fo und a thre e fold incre a sed risk for pre term de li very (ad jus ted OR= 3.2, 95% CI ) in the hig her ma xi mum preg nancy blo od le ad le vels gro up. The risk for pre term de li - very in in fants who had to xic me tals and tra ce ele ments de tec ted in the ir me co ni um samp les was in cre a sed one fold in our study. Des pi te be ing from a sing le hos pi tal, our samp le co unt was tho ught to be suf fi ci ent for de mons - tra ting an as so ci a ti on bet we en pre ma tu rity and to xic me tals and tra ce ele ments. He avy me tal le v- els (le ad and cad mi um) and to xic le vels of tra ce ele ments (zinc, iron and cop per) in me co ni um samp les we re hig her in both pre term gro ups compa red to the term gro up (p<0.001). In Post-Hoc analy sis, le ad in me co ni um samp les was sig ni fi - cantly hig her in pre term de li ve ri es of unk nown eti o logy com pa red to pre term de li ve ri es of known eti o logy. Re sults of the se analy ses may sug gest that in-ute ro ex po su re of le ad may ca u se pre term de li - very of unk nown eti o logy. In one study, Ko ca e li Uni ver sity Pub lic He alth De part ment sho wed that to xic me tals and tra ce ele ments, es pe ci ally iron, spre ad un con trol led to the air and wa ter from facto ri es in all re gi ons of Ko ca e li. 31 The risk of to xic me tal and tra ce ele ment ex po su re is very high in Ko ca e li and its pe rip hery, as exp la i ned in the results of this and our pre vi o us stu di es. 32 The analysis in this study sho wed that in cre a sed le vels of le ad in me co ni um samp les we re as so ci a ted es pe ci ally with pre term de li ve ri es of unk nown eti o logy and may af fect ges ta ti o nal age at the fe tal sta ge. The re - fo re, we sug gest that pre term de li ve ri es of unk - nown eti o logy may be dec re a sed by dec re a sing air pol lu ti on. Furt her mo re, the re sults of this study may po ten ti ally ser ve to in ves ti ga te the as so ci a ti - on bet we en ne u ro de ve lop men tal de lay and al te ra - ti on in the mi ne ral com po si ti on of me co ni um. It is con ce i vab le that analy sis of me co ni um may be used as no nin va si ve ap pro ach to furt her cla rify unans - we red qu es ti ons re gar ding the ef fect of en vi ron - men tal pol lu ti on to fe tus. CONC LU SI ON Neonatoloji The re sults in this study may sug gest that le ad le v- els in me co ni um samp les are hig her in pre term new borns, es pe ci ally with unk nown eti o logy, than term new borns. The re fo re, we sug gest that pre term de li ve ri es of unk nown eti o logy may be dec re a sed by dec re a sing air pol lu ti on. 930 Turkiye Klinikleri J Med Sci 2012;32(4)

7 Neonatology Özsoy et al. 1. Gol den berg RL, Cul ha ne JF, Iams JD, Ro me - ro R. Epi de mi o logy and ca u ses of pre term birth. Lan cet 2008;371(9606): Er dem G. Pe ri na tal mor ta lity in Tur key. Pa e - di atr Pe ri nat Epi de mi ol 2003;17(1): Xu X, Ding H, Wang X. Acu te ef fects of to tal sus pen ded par tic les and sul fur di o xi des on pre term de li very: a com mu nity-ba sed co hort study. Arch En vi ron He alth 1995;50(6): Bo bak M. Out do or air pol lu ti on, low birth we - ight, and pre ma tu rity. En vi ron He alth Pers pect 2000;108(2): Pe re i ra LA, Lo o mis D, Con ce ição GM, Bra ga AL, Ar cas RM, Kis hi HS, et al. As so ci a ti on bet we en air pol lu ti on and in tra u te ri ne mor ta lity in São Pa u lo, Bra zil. En vi ron He alth Pers pect 1998;106(6): Ritz B, Yu F, Cha pa G, Fru in S. Ef fect of air pol lu ti on on pre term birth among chil dren born in So ut hern Ca li for ni a bet we en 1989 and Epi de mi o logy 2000;11(5): Lin MC, Chi u HF, Yu HS, Tsa i SS, Cheng BH, Wu TN, et al. In cre a sed risk of pre term de li - very in are as with air pol lu ti on from a pet ro le - um re fi nery plant in Ta i wan. J To xi col En vi ron He alth A 2001;64(8): Schwartz J. Air pol lu ti on and chil dren's he alth. Pe di at rics 2004;113(4Suppl): Jel lif fe-paw lows ki LL, Mi les SQ, Co urt ney JG, Ma ter na B, Charl ton V. Ef fect of mag ni tu de and ti ming of ma ter nal preg nancy blo od le ad (Pb) le vels on birth out co mes. J Pe ri na tol 2006;26(3): Os tre a EM, Mo ra les V, Ngo umg na E, Pres cil - la R, Tan E, Her nan dez E, et al. Pre va len ce of fe tal ex po su re to en vi ron men tal to xins as deter mi ned by me co ni um analy sis. Ne u ro to xi co - logy 2002;23(3): Har ri es JT. Me co ni um in he alth and di se a se. Br Med Bull 1978;34(1): Ernst JA, Ne al PR. Mi ne rals and tra ce ele - ments. In: Po lin RA, Fox WW, eds. Fe tal and REFERENCES Ne o na tal Physi o logy. 2 nd ed. Phi la delp hi a: WB Sa un ders; p Kuh nert BR, Kuh nert PM, La zeb nik N, Er hard P. The re la ti ons hip bet we en pla cen tal cad mi - um, zinc, and cop per. J Am Coll Nutr 1993;12 (1): Fri el JK, Matt hew JD, An drews WL, Skin ner CT. Tra ce ele ments in me co ni um from pre - term and full-term in fants. Bi ol Ne o na te 1989;55(4-5): Ha ram-mo u ra bet S, Har per RG, Wap nir RA. Mi ne ral com po si ti on of me co ni um: ef fect of pre ma tu rity. J Am Coll Nutr 1998;17(4): De roc hes A, Jo u a nel P, Mot ta C, Vi al lard JL, Ga ler ne D, Ba u don J, et al. [The mi ne ral compo si ti on of me co ni um in the hu man spe ci es]. J Gyn Obst Bi ol Repr 1974;3(3): González de Di os J, Mo ya Be na vent M, Cortés Cas tell E. [Qu an ti fi ca ti on of fe cal excre ti on of tra ce ele ments in new borns as expres si on of fe tal in tes ti nal sec re ti on]. An Esp Pe di atr 1996;45(3): Even son MA. Me a su re ment of cop per in bi o - lo gi cal samp les by fla me or elec trot her mal ato mic ab sorp ti on spec tro metry. Met hods Enz ymol 1988;158: Bryś M, Naw roc ka AD, Mi e koś E, Zydek C, Fok siński M, Ba rec ki A, et al. Zinc and cad mi - um analy ses in hu man pros ta te ne op lasm. Bi - ol Tra ce Elem Res 1997;59(1-3): Chu ji an C, Sho u yang Y, Shun yi B, Rong L. Zinc me ta bo lism and re qu i re ment in Chi ne se presc ho ol chil dren con su ming dif fe rent di ets. J Nutr 1998;128(12): Tay lor A, Branch S, Halls D, Pat ri ar ca M, Whi - te M. Ato mic spec tro metry up da te. Cli ni cal and bi o lo gi cal ma te ri als, fo ods and be ve ra ges. J Anal At Spec trom 2004;19: Slat tery M, Mor ri son J. Pre term de li very. Lan - cet 2002;360(9344): Ma co nes GA. Pre ma tu rity: ca u ses and preven ti on. In: Ta e usch H, Bal lard R, Gle a son C, Avery ME, eds. Avery s Di se a ses of the Newborn. 8 th ed. Phi la delp hi a, USA: El se vi ers Sa - un ders; p Ze ka A, Melly SJ, Schwartz J. The ef fects of so ci o e co no mic sta tus and in di ces of physi cal en vi ron ment on re du ced birth we ight and pre - term births in Eas tern Mas sac hu setts. En vi ron He alth 2008;7: Wen SW, Smith G, Yang Q, Wal ker M. Epi de - mi o logy of pre term birth and ne o na tal out co - me. Se min Fe tal Ne o na tal Med 2004;9(6): Smith LK, Dra per ES, Mank te low BN, Dor ling JS, Fi eld DJ. So ci o e co no mic ine qu a li ti es in very pre term birth ra tes. Arch Dis Child Fe tal Ne o na tal Ed 2007;92(1):F Li Y, Xu X, Wu K, Chen G, Li u J, Chen S, et al. Mo ni to ring of le ad lo ad and its ef fect on ne o - na tal be ha vi o ral ne u ro lo gi cal as sess ment sco - res in Gu i yu, an elec tro nic was te recy cling town in Chi na. J En vi ron Mo nit 2008;10(10): Ritz B, Yu F, Cha pa G, Fru in S. Ef fect of air pol lu ti on on pre term birth among chil dren born in So ut hern Ca li for ni a bet we en 1989 and Epi de mi o logy 2000;11(5): Bo bak M, Le on DA. Air pol lu ti on and in fant mor ta lity in the Czech Re pub lic, Lan - cet 1992;340(8826): Wil helm M, Ritz B. Re si den ti al pro xi mity to traf fic and ad ver se birth out co mes in Los An ge les Co unty, Ca li for ni a, En vi ron He alth Pers pect 2003;111(2): Er do gan MS, Ya vuz C, Cag la yan C, Eti ler N, Ham za og lu O. An analy sis of the en vi ron - men tal thre ats po sed by in dustry in Ko ca e li, Tur key. Ma nag En vi ron Qu al Int J 2005;16 (1): Tur ker G, Er gen K, Ka ra koç Y, Ari soy AE, Ba - rut cu UB. Con cen tra ti ons of to xic me tals and tra ce ele ments in the me co ni um of new borns from an in dus tri al city. Bi ol Ne o na te 2006;89 (4): Turkiye Klinikleri J Med Sci 2012;32(4) 931