Micronutrients in fetal growth and development Harry J McArdle and Cheryl J Ashworth Division of Nutrition, Pregnancy and Development, Rowert Research Insinite, Aberdeen, UK The roles that the different vitamins and minerals playin fexal growth and development are reviewed, primarily with respect to growth and ditferentiatn In humans: But a& appropriate, data provided from animal and cellar stucies 1e ato considered, Pregnancy is a period of rapid growth and cell differentiation, both for the mother and che fetus she carries, Consequently, itis a period when both ace very susceptibie zo alceracions in dietary supply especially of rnuceients which are.marginalnunder normal circumstances, Inappco- peiate-putrition lade not only to an increased risk of death in utero, but aiso co alterations in birth weight and functional changes in the neonatal organs. These changes can. have fae Féaching consequences. For example, babies who are smal ar birth are at an increased risk of cardio vascular disease and diabetes as adults’, while animals who arc born to ine deficient mothers have a compromised immune system’, The vaderlying mechanisms relate co nutrition eflecs on gene expression in the fetus. There is an argument, therefore, for supplementation in the dict, in order to avoid the consequences of deficiency during pregnancy. Supplementation with one specific micronutrient is not straightforward, however, since there are many interactions berween them, summarised below. Further, ocher dietary components are also important. For example, phytate inbibic calcium and other meral absorption and the n~ Siar6 ratio in Fatry acids aters fat-soluble vitamin absorption. Up until now, excess inrake has been an uncomumon problem, Howeven with the increasing practice of forcifying foods, especially in developing countries, che possibly of micronutrient coxicity has increased Micronutrient deficiencies have such varied effects because of the : diverse roles they play. During the process of cell growth, DNA is trans- Comontcets: cribed to RNA, which is then eeanslaced to proteins, which provide the Bent mar enzymes and structures of the cell At every stage in the process, micro ame syorients ace essential, either as signals fretnoie acid, for exantple}, ot ] tig ecanun, structural (zinc in transcription factors) or eatalyic (e.g. copper) eleracns, stecees Aen ek ve Different organs develop at different times in pregnancy. This Bives rise (0, Sr ca aed HE AB HED ‘PThe ath come 188Vitamins pie This os critical 1 tartitication WeKAAMATAKLTAIGATHE RL KL AIEAETTe TT TIAA AH HHH Ooes are yur usrients, meludiny vitamins A, E snd C. of sovokers are le smokers, Anciosidaae eutrients ace Believed co aetend duced lny tebacce smoke, Tihe use of these ether would mean that less ace available to peti sil Many human problems associated wih ro-arnbute sa. paeticular vitamia as isolation, Pustl bay tical min datictenc rin deticienes 6 studies report supplements on pregnancy outwome, tor ex muluwstamia use ts associated with a revinced cisk of cone omaa infants’, although ie is nag clear which vitamin is the eltective agent. It is, cherefore, important so refer 19 controlled animat studies to lindersiand dhe consequences al specie visamia def presmancy ant che fecal onan systers pein Fatsoluble vitamins vitamin 4 Retna ae el fa a the maincenanue of eitlerentiated ep « compourd of Biologically active revineids nll, the active element of viseal pexment lopment and Vis the par sldehyde ioe « sllulae messenger which modulates sf che world, veamnia 3 incakes retinol or its precagvor Barone, fsck of nae priate dictars choiges, The Werld Feat Ox iy of fonds cieh in 51% oF pee ni night Dlindaesy, Vitamin & det associated we rennet that vitsmia & deficiency leads te placental seal maHformations, However, many oF ter. Recent stshave Shuwen eeduccions i asungesl liver and N80 pas ducuig late pregnancy ta die survival, by hour 50" and che eclacise heare', Oniy in the ease of faatal hie. Day 20 feral lu dueing prognaney is saectated wth birth defaets 0 | evra! srest, Roghman and colleagues! repoctad t tof wnarmin A per day (RDA = 2670 Iiday) was 1 baby in 57, Incetese> | wy nether fesceganicnts aoe sciiin rows Ags been ober nung species eazosed high dongs ot eaneoten i mia D iin aedison so the factors assostned : described above, Lack oF exposure fo sn f individuns to vitamin D dehsioncy, Materaal secant pies Javed #0 peanatal exiwn- fk hoemone levels at dhe, suggesting thae wie 18 maternal calcium hemenscasis. fry 9 study compl ne bore and wines bom berween Januacy a t lower Sore cxlcin am than babies buen herwves sc that che vitarmin D stacus ott im status of her offspring, sacaees babies, Nas March ad a high: These daca sans tu pactucition atfees the & ‘amin E The reem viemin Eis used as a pamarily tweopherols, syuthesised by planes whic! angioxidsats pratsutiny cells against damaue induced by addition te diecaew ineake, ether taccors can exther faflavin, copper, zine andor ia E requicoments! i i designation foi a Sea separasnae women, no relationship was found herween sex sanventraions a¢ 18) and 3D weeks rion and birch Apgar score of infa be associated with pre-eclampsia and 2 produces in causes vasoconeriction and Pomsequens peegdaney’ induced RYpertension™ ulation oF hid pen lama oom OOO OOOH KAEHTHHOHERHH RH REHRERENECLUE U Eee pony Vitamin & Develo roreie. wich #8 imports pe the use ot a drugs ducing psy a sian ceffeccs of detiemcy sce ction i Guth and hone minartisation, First wimester cies result in masillonassl bypeplasia in the neanate eit plications sshile infants. born 12 n sufter Irom abnnemalides of embryo te feflosted 1 Subseguest Gcial and unhodoasie is sth sia Woter soluble vitamins B vitomine ‘unin BI thay rntakss that ate well below the eee may atfecs she vicamis Hisberes Ie ip alser at ess escent and aay inluen 1s deticiey dy dhnstiag uf Nemethshase he neuralenion-stase ex BV of nent cube a mtomse rode! sunsesee sar adminiscration of #0 bea cenvgle therageutic opsion™ ial ctfects a folate nee not confined co events it earl Marginal levels of maternal folase theoughaut iar growth and cepticn ile mothe The beScan besoanetaced Lack ot marcraal eign IHL? dus 2 fetal nervous spseeni™™ Howeve be posenacsl ademinisericion of sieavacn B12 rensive studies to examine Minerats Miners set important snes (Ca and Fe, 09 ee associated wie det nt or the placenta of anediee much, iinporsane Scare on physiol sof defi re in the west 3 amd in come ren ssed risk of maternal hseraserbaye, ceonvequences for aa angemie cements ef the at nee fy sociated with 1 blood loss has more idee Woolt!" tas al Asse Ikon det cand esi. turn a ont mothers have mereasad eacly aduithood: pugs be inczcased blood pressure by Armaeraia 19 deticienes®, However, chis ma F studies renewed hy Walki t ‘ copoer oy di ae have (ee setrcreney 12 uayasl. This does, of enure, Dur aboue 75% af chese shen serined 26 sere: al vesorption wie a skin, veuronal and fiaic aowormakeees, T the alterations pre not af More recent! ed after psychological aging level ysite atow nalierable changes: pos naney causes 2 disor defwieney copper diticiency ducing pes : his manitiat as mosevlae weakness and acasia tal i, e40, CARNE BS coversed postanaealy Ir hus heen soagested thar the peobleins Ghar arise daring development fated vonatal copper jek excessive pid and geaein dna oraridaaon age ane aoticeabls IeeeTryO i BU gm, They found ehat Ca Zn Ca dlefiviene mein, that thse incidence of abnwneraiiy in thes addition of the sed this effet (reviewed! 46 Keen ef a2) “Howeess, other peable rth copper deficiency capaor be ignored, For exainple. detiiencies in collagen ancl oss finking, die ta dal in Issyl awidase actisity, ead 16 problems mng development and with sortie clasticity, These in cue fead co re dilficaltes, such as persistent respieatory disteess sendrome, and €0 an inereaved risk sf neve aneucysen in early than 300 ervey and results it a wide specteam of first symprom 1s loss of nes. Con Zine is a cenetab are ot a sequently mpaternal dec eng 8 2 505teaine Seleniuin Zane delicieney iy teratoyente ad even alarainat changes can ease mult deficiency ducing peexnaney in vifspritg, which does not jeaey ais causes complications of inbont APROR: csusmmarised an Jameson’) corm dslivery which may be related 10 Deeterm proba tnd a mesesed eek OF Pe va fecenr reviews, Caulticld and callesgues!? ie ako human studies whiek show sypalementation increash Teugth ceereasing eis nf PROM and decreases 0 bh Aw hypothesis linking ine isms sath, toratagenics dhas zeconrly been advanced by Keen and colleagues, Auy ‘cue plsinat zine can eevee ia periods of organogenesis. & hich has important implications tor stra se sclenritce) several ezareyens which act sewoaal sine detieieney. BE this oases i uae amount of free eireulating harmane, and Brossels, where che le and lave defined the limes and importance @t lading in gelation to ihent OF goutre labout 10% nf purients!* in one scudss but ) sm anochect. lodine deficiencies are especially common is oping councries and there ate. as described tether below, Indications char fc jg asencigned wich 22 ner fn both humans and animals, fash selenium status of the of sey thar of the mosher =") Seleniam abanepcien in che de {eenguscuuavatasseveceuasanerereccacenagceslabour conse es segnly may be d selenium stars, there Was an increase in. blood. Preunaney of abour 25% f¢lutathione pee. Oe), se chere is licte yeope Toe cogulatten at gut Wesel ud sathivne problems ih the Tes, However, secent data suugest shar endemic eretinism may result trom combined selenium aad yedine deficienes, tather than iodine deme (see Arthur er a0" for a tovent review Interactions between micronutrients vitamin A ond zine sa, The data ace equivncs Trudies bave been on sppette ancl ts hamans zine problee - liver eiechons, tor esample, Ac Vitanun A and iron are several studies in non-pregnant animals showing an sion berween vitamins A stacus and iron merabolisas, Whetbee the syetian is Emporeane during gregnacey 1s put so clearly established Vitamin A apd copper Ceculoplasnin plasma ate inctes rages that i sets at she pest~tanseeipional Hower. aie sis here vitae A. Data from au [aboratory | Ashizocth CI Antipas aod Mec\rdle H), tmpabliched data) hace suggested char retinol sigee? ceruloplasmin tonically. The signtieance of eis prehmaacy ins to be establishSas sauces fron and cine Copeer and iron Sine wanlies bare are given togechcr if solution, 4a conteast, shen iohibision is nor so appasent. The studies’ reselts J choc there is ol te probable litle physiologically sigaitieane interaction ac culls anid asines, vine aq atfect irom metabolism, Steration of aine and peonein praduccion. ‘per Ueticiensy resus in aecamulacion of ison in sanemia, The anazaa is wot cased by 2 de sos enzemies, bue gather by 3 heap, Whechor this plays 0 role 19 pregnaney eslts n copper dec sn specitic snsues 16%. ron overlnad case in eoppet levels in the hver ~ pasaly By dawn regulanion nf Coinsnon apeake parks’. Key points for clinical practice With the exception of folic acid, there i a dearth of sctenaie evidence deseribing beneficial effects of microauseiene supplements on prexeance ‘outcome in humans. Deficiencies of micronoteienes and ainceals ma more prevalent than previously thous eticiencies, irom and viraanit & for example, siiances au zine shotld be considered. If ron suepiementatinn 1 giver ratcroamtriene supglementation shoukt be considered, Fu mast be gail as to the stage Using pregnancy when the su) given, The “ericieal windows’ of development mean thae if supplements are fiven at an inappropriate cme, Chey wl be ineffective and may even be harmful, Clearly, sore research is nanded ro clarify these windows and eractions, Spat trom the swell kown coppen seleniom addivinnal 1b Syier DIP “ls CF ie Zine ond Wha canna ROT Ce hhh m ann nnn nnn nnHoey 1, Deane 43 Rove prelate | Dawe sa 8 5 ROME Rennes Maloy Mh ‘Rica Rhates th, Weer AP in eel Nest Se T997,125.21 > Seat 80) Viren 9 and pumas se Aare C. 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