pain and stress in the human fetus
DESCRIPTION
Pain and stress in the human fetusTRANSCRIPT
Article Lead Author Smith Richard Date 2000 Article Pain and stress in the human fetus
NOTE when there are multiple columns on a page add column reference to page reference
1 Pain felt at
a If the article specifically asserts unborn children feel pain at what postshy
fertilization age
b Page 162 Left Column Second Paragraph Neonates also have behavioral
responses to pain for example by facial expression or by crying
2 Nociceptors
a Ifthe article states nociceptors are present at what post-fertilization age
b Page
3 Thalamus link
a If the article states nerves link nociceptors to the thalamus at what postshy
fertilization age
b Page
4 Subcortical plate link
a If the article states nerves link to the subcortical plate at what post-fertilization
age
b Page 161 Right Column First Paragraph However between 20 and 26 weeks
the subplate zone of the cortex contains an abundant mixture of cholinergic
thalamo-cortical and corticocortical waiting neurons
S Noxious stimuli reaction
a Does the article refer to reaction to noxious stimuli At what post-fertilization
age
b Page
6 Stress hormones
a Does the article refer to increase in stress hormones with noxious stimuli At
w hat post-fertilization age
b Page 162 Left Column First Paragraph However studies showed that
neonates even when preterm mounted a sizeable stress response to cardiac
surgery
Page 162 Right Column Third Paragraph piercing the fetal abdomen to
access the IHV for transfusion is associated with substantial rises in these
hormones from as early as 18 weeks gestation
7 Long-term effects
a Does the article describe long term harmful effects from exposure to noxious
stimuli
b Page
8 Fetal anesthesia
a Does the article refer to use of fetal anesthesia and its effect At what postshy
fertilization age
b Page
9 Cortex
a Does the article relate to the asserted need for cortical involvement to
experience pain How
b Page
ELSEVlER
OBSHTRICS amp GYNf OLOGY
~~ltL1f flnwf o~ Ck t (frt1)~ lnJ
R~-nd Ytit 0 middotI~ L(nl) Itl IfIlt
Pain and stress in the human fetusg
Richard p Smith R Oitau V (Hover Nicholas M fisk fNIOnitl r1 (tr ar_tI maS Fdd j [rudt1J ( CWflt Itti F~f CdT -btMltwl (I ~fIfr llfJJ ( rM(af~
(tftJitlttJJ 4 1to~ $~1Jr1Ul t1 jJ JU~)~ t )rr ttJ (~ttmr J VIfJ - lfoltlJtu l C fII4mJt NJ t muJron 1) orr l ~
AIrt
ImmiddotmiddotlVt diagThllC rut thJ~lJJtic CCihli~ Ucent irnmiddotloingl) ilf-l ic w lhc- fcl u h i ~ nul ~n it the fCh - (Cd~ ~l lin lurU~ gtlih p(tgtCdllr W I tJl ((1U ~ (flucuH ~OV1 btornlO1UlLlJnd InU ~)t) ~hUJ1j(C n l~S4Jn~ow t~- hc~ tnttn lX--20 middotd~~ ~ru1Wl
gtI~ may h Q too~t 1m eulCldvellgtjmUlhlimllilt ri ClIl r1ltJji Olgt (cia) ~I) uan1 IInOTol NIi tlgtlt ~i ptlI~ r1 JlntIIgt() ltla fI~t in d Plaquo ltdurlt~ fClll l lll1llJvm~ Ieu~ dlllknloe Th~ opli(J1al lt1mI lt1lt 011lt1 MIle of ndtniniltI W0I1 ronn0 tlttmlneJ lt OOO ~c S culte T~ (If Ail r~h ~t(ltI
1 Introduction
Tile 1= nbili y lli ltli~gn(lSe and treal Itllt reUl in uRNI
r~Qhe-d flOo eetltlIIetll in ill - ~ie pnx-WUf~S io mltfermiddot su[[uio(ral palhrh ~ivlonad inl6gthlli1 ukuu ill illallillyen Tbtgte pl(_middotllu~ r~l(ing (ltltlin ttllla -OUIlltl-lilJ(d
nudr~ upirlliO) Uuou-lI lt I (JflC1l feLl sOXXet) lIIt ill IQding 10 he tlbvil)Ul qllt~iQn 11~ l~ felus f~el pain
The ~0t1(ep1 II iflt- I ~ ts i~ amiddotpatient in ilaquo ow~ risht hlb lcod 0 illOtllS5 iultmS1 in lhe iuhjeel of 1111 p~ill _ A j llgtlitiClllion rnr providing reUl anuJgeltld 8M o~hlti
11lt lIti~1 POt only Icru~o( a tlIDtlll obIi~alion to Ir~v-~nl uiTeril~ 001 alllU hcc~le paii~ aN I~~ may affect ~at i vQ and have kjjl-~ ~ulXfemiddotelopnl~lItal Mgt4uclle
1middotltt-cr Ih evideuct e rf Ihi_ is limited lIrgl l ~
t)clilU~ R~emh in hunHtti (tJu- js Itmr by laquoIlucal ltOltIstlllUTts 111 ~t(l due 1( probl~nlt iSelining 1Ii(ul101) oUhltlIDt lite utes
2 F~lalllJl ilt
111 b llel ohj~cli mcasurerntnl of pain- il I uhj~l i C epcrien~ TI~ (elmiddot is unahle 11 Iell 11 imiddotf il
Rcn I~ be J~~1I 1 hYfrtf f Ohtclll( lt t tt)~~ I i3 Jlltf
h1Yj~ c Ul4~ P t1lkci at Inuh F llI fh iiJUCI rod n wIll II) Ih T l11J 1 U(-IO-101 I 1~)uV 1 f1((tfUniorJ hh Cht lhmiddot~tt bull lHd It~l flt tI l r(IInrnI lin
( QfTnrWIil)C JUU- Tt middot +J 1(1k ~ 1 1H)
Iampt middotll~I( 11
r r bullbullbull ~fu middot r r ~~uh~ I k I( 1lt rl Smill bullbull
II ~ t ~ll (I _ 1 111 11
Ill rr I i I ~ I II tI 1111 J ~
rul~ puin W ohlr e ickn~ fn PetJgtltd to deltitie at what g(~tutin it i likdmiddot) h~1 the t((u ~lt 10 fed (gtlill Senor inlltn~linn (f lilt Sil ~ fhlJn)lliIl (lIUl ~middotti()n hctyttfl
lil~ jiphCT~ ijnd piud (lTd h~~e hegl bf S welth lIlt ( thr~ ~()(Ilg into tho spine ltu a ul HI (el lllt ltbrat
ltm~ ~rl form ~t Ini Maltt ilh dilrt r~lilIilt1 inlt nelru~s Ilb ~tia n htltlltJd ~ ~ qa(ling a bull hmiddotUI Ir ~k aru1 clnlirruillpound ng (tfler birth Pain lillres p~s thf)uSIt lite IlYAlillHiS en muk I lhe CN-X Th~ tinlinl~ of ~Scent tJtuUll)-lti1 CUIu(lin~ l md al itt dcciltJing when Ihe ret~ tiN b(t)mes C1bl-e or leltling (Xli llti is lItI u a or C)flgtitef-dIle c(Jntmel1l ~~pd (Jotsi- nini(~ l~chniI~ Ii sbo11 th~ Hrgr_middotI L1[ Jlyener~nt lilgtre inln lite )(il~1 ptalt netweto 26-middot111(1 11 ~b olle~atitll1 rIj which loa middotitd un~ 10 dude the few i irnapgtlc
f r~elin~ piill prior to 26 ee~ i ~1 H we ~lwecn 20 ami 26 middoteeL Ilttlt ubplate t(M r One lt()main an abondanl milllIC of middothotiner~i dIfIl-ctlrucal and ()nirti(1 iting flluroOC and Ihere art Ironsefll lell middotn3plti it bel-een Ib~ ubplal and m1ical pll~ nfutIli- f- f wh r~lIe~ of lin h onidtf(d 10 require CHIlU( ~I~en Ille nlftelt ltIld peolhery hough Ihi rtt~pl i(ll middotuld fender animal- IJclJn it (ne Itch a n~prL1e in(~ar)bk ot fJtr(t~idl ~ pall It I 11()t kn l~n at whlll 1Ic 110l in the otaUtn il11l h fW lt3tL-coienl
(Ihl) 1Il~k conlC(ltlI11 to Igtennult nt multiple L(nnL~~ middot
lilIh the f(ttl rna) blt-nw plhk )f fedil)~ plin (nJ It
Hla~ ~J ~~(ihbulljl Jther tha n MIJlkn l(aumiddot i ll I Iu ~urtlltJry
pritn Id 1 I t~~k li w felll- lt1(lt tH hnc ttmiddot rlefJrH~lnalll
Uli l~~t t pth ) rb-c to fed p~i ~ -~~n ] ~nd ~() ~c L 1 hII J llhmiddotLc)fti~f 1 ~ onnl~ lIrm tfl fpftH mg ami ~ I t(~l
Unfiled Notes Page I
1(1 Iote-i I~ fihl ht le n~middot l ~ Ioj1) c o no ~llln l( htt l (li n
ilUd the la1 eltlIde bull he IIlGtlt IfNltltI a( it ere
illClahl~ ltgtf (einv pain HIlncf ludi ~b() ed II 11Cltuamp lt7~ 11 hl prolcrm fll(UllIed a ileahlc Ift
r0lnet u cardia 11~ry 1-11 willt rilaquo in 1ln 1l~nc nor(dntrldinc (Uld corti)I Some [ hc lt IJ~~~ ~re reducd hy o(i bullid PMIamp~~ 141 In one f1llldl~d Mud) opin u~ihe~b It (~lltlilut ~ilb it rmuIil(l it peri lltW~I I C mq rtalil ru Si[ll~e tlep ~ ofeualglj ia dunng nto111i1 tl)liy b ~ ltcnr~ th ~tJlltdifttl o( care
Nt(lu~ (e fo hwe beh~i(UJral ~PO~ 10 pail (or e~aR)plo by focitllpr~nor by cryIgt1 1lK r-~ II hrelll~inlt by facial Klio ~~ dpoudlns Ql (~ sleep lIle s~ 11 the llcuate Illgc~tiilg lhill the belI(lu r~1 ~(IlU I of pnin ~rrnt lgtel1alUrll eXfrc~itlftmiddot C~~Jl befole the IlPflOfIlJUily rrgt( leamrlt1 repoll~ (clJr tnt
Becau~ of th~ otw iou difticlIlic- ill swdyillg (eldl betlavlour ltlCfi~middotalim lr the bgtJl()lltabfll)-p1lUfI~r)-adrenal RI L (0 SI~~ replt1Il1lte j hl$ been pto(gt)~ I ~urt(gtt iniIkal(Jrof fdl1 pain Thi h~ Ilmfitiiltl IIRraquo i1~pomes db 1101 I ltetiJ Idly iillflly ~in ( I ) iuntpl~dUfinpound ne~hel aqd st~ $fltI~ d) 11111 inolv~ Ihe c(rta HQ~er~ lhe conee i Ill liilllllypltgtIheSl iob in lbe absetlct tlf d ile r~ponse the (elus I ulllile ly 10 CI)(fRlrielllte (lin Also llllt (1lt1ld ~ue 11111 stress rpontgt is ll1~ rcle~Itlt in fIll
of imm~llIll and lnSlaquorm ~lucl~hetblf or 1101 0-shyci tetl wilh in in Ih~ retu
Sludi I IuiJmm~ iU~ liruilltltl by (tie n rOTan elhil1lI ymiddot llllble lJIod1 namdy tho fdu~middot ulltk1oII dinimiddot all~ middotirtdiealed pro~dore~ for ililgflOo( k- Of UlClapeutk
Cltgtrd ---shy
tC~l~)fh i t~ JC utlictI fc(u(~ (HKk rgting I1HI~Hucuta r
hllltd INtblllSion ht II 11gtlt collecli llin of lterial bllt _lmrk JI tlgt 1gtC~lInirll 111 ltnd ( I~ pn~cdlJrc Inmiddotmiddot ltJure at Iht rOCf1(1 oor inSLrtin 0gt( I hid j
inne~I~ltI 0 be otllflrcd ilh IlIn(j al lhe inlfmiddot hCf)bulltti( 111 (fUV- whidl illv~ ron Srt ing rhe fetal (rulll (Flg I 10 O1f unil~ the ~ilc or ~[fNllJCh h bltgtltcll IClhnic lil actt depcrlllcnl m rCla l nd rlacem~1 PitiOll ilh h If ugt~ oJ dPpfI~im [ ~ ~Ol r Ihe time While the IHV ~lrroJmiddoth may I e k cr ri oCltl01(1lilJI n ltIII fI cord l am lQn~ltle ad al1cNl1 paltlll the Plt1 aplwKh i~ ldinit~l1y e cr
1 lumui IlrsPfHtW
A~li~lin 01 Ih JiIltIl hH)(illr~lamomiddotpihJil4rl OOleflal ~xi~ can t-lt iJecod h~ ltIe~~ufin)sect ~t(e~ hurmltlOmiddot1o lllt--il J~
l(llreruthnlt c(lisvl and 1middotlod1lhiu Siudying tllple nblqillltlt1 III kl blood (r~Ifim allo cOnpiIJiwll nr kvel of Ill h(rntuw t(OIe l(a~fin tinlmedi8Iel) ~l~f ae 1( Ift~ lollll dflll ~tlltlJ i tlahlilh_d bull (Ill 1(v~L al Ihe (nd 1 Irlflsfusi4l11 (illS bel~gtre Ihe notJle i~ 111(middot bull bull (1) Afur Ir-tnffusion at Ih PCI (her i lillie ch~nge in felMI 1lt1f((It~line conN or Ilmiddotendorpitin I7SI middot
HI)middotet JIgt inu~rr~d ilt ISgt2 pjerciIt~ tht felal ~blto shymen [0 acces~ lh~ tHY fur r~nfusion ~ ~SlSltlmiddoti at~d with u lanlial f~~ In ttl~e hOfJl)()ne~ rrom a early ~ 13 wltiltk fO~lil)rl Til median i1cr~~e ill fl~l1dlImiddotphin Icd~ a~ 90 in ol1i~d l Iemiddotd WIIS 183c~ lfPltJ III norkl1e)atine I~~h ~ Ii P] 5hlll1er flI(~IIIt [ucn a5 ~Id MUttpitni) Wih(lut trau rlLiJCJmiddotl ero nnl a~~xialcd with ti~ in cOllij(1 fUI I~middotcndtgtfpJjIJ IlIlt then- as bull MIImiddot d j1)
(lie tll bull 1(C f~pl(j llltrrHdnII~line uSlonse
TIle ietult ro L(C ~o laliltJu ha Ii l1ar~oh[l Capil to r~tJj~ribu(~ 1( lHOl)Q Aomiddot in repltltl-C III tr~r [c prUIttl
mo~ jul Orts Kn 1lt IgtrJin and mnltarllum a rh~
S1ltt 01 tHV n=JHng
[In fileci Nnt ~ P~P
PiJ~ - l411nut) nm il~ nmiddotpU~ l~ih1iraquo_ [i c-f k rqitm -j ~J r~ 11QiIl ~ ItU l r-~ftnii411t lllt ftC i
peIse I ot1~r oriMlt It ~~ lUt- ~Jdtie - uW I~ ~trUlitj~ [91 Nullerouolt explt-nrnenta lJJdic h~v middot ) 1shy
firIt1CiJ ltIe fe~IlJI~ IlO elt~ lyp elllia -r mlI I Iwe nl1rrn8~ 1121 and fttllkeltl 411ltrill hrfltld n)W I L~J Similargt- Dowler slud I hUIII klu t ilh inwwler ill growtIl =triOI10II (IUOR I h fnund dlaquorMSc1 r~L I ind i~Q ill cerehr~ 1 I H I and adrenul (l51 bkl)d 10
chgte) lOcj()fn lt (FVW Cllnmiddot i IcentRI witll 11 HailI iltlrI ~tld il1m~5e(1 ltldie~ in FVW ftolll ~imiddoti~Jt~ al o~~ hQlh ~ud1 he renal 11 61 nmood If7 1 aAd (ullntIIMY Itlll ntctic ~-oiJ~enl w III middotWOIOslrk ikn ~Io$norfl (erllrILiOmd our gtlltl(l h itIlwn lI middotfaU of
l-l5 slllildar~ dO[1IIv UI mjdtl~ C~rellrll itMIr pllsshy(iIi indl oI( lli ilh lliis re(JI hruill~I1 jng f~(lLcent ~~ ~~III rrw()h- t1l~ Irai) II- iN llgt( IJie felilI1noll~ (rom ead~ liS 16 wtels_ TIe lUcc~niiJtl fo( thi ~ nol
~kaf bm COlllplilible with m increnM III L(reht-al 1_ Tllcentrt ~Iw an wrt i II retial and remora I ancr) re~i shy
lanc~ ind an rroedurc~ iihl1l vinllr~ngress i(n (lr the feM ulld ~imililrl y (II1I~lie ilh fewl llrltln paring imanllri11 in 1lt1lIrilliunl TIcsc Odg are Ilt)( setl)
afterr pn_des HI Ill PCL n redhtnhuljul1 in bU_ltgtlt1 f1m may tllt ~UI~-ltJ hy Ih ~UlathIk sytem lr 1gt lgtther undcent~l1lliIcent lI)~anit-_
There is inc~a5i() eiMItI( Ihat ~acl)- p~inrul or sire ) eertl~ CiII n-itis n ittltli idual III l1t~ r~ill or sires Evince from irerlllal Iudies indk~le- Ilql A trsshd perina OJ I ~ en~ cm kn~ kg~ I-fn elfeltll on hiPfXW m1pal dc elupmcm ott tI~~ ~hil i()UL In roJt~ which ttt bum al
It Ia c ~(uII-e 1t in bullkIfI1~nt to rhe Il~ l1unlltln fClu earl y pllslnoU1l hJ11dJiS ~LL all i(l~TOe in 1WOCltfltuid R-p tnr lknsrl in 11 bullbullipIocarnp and ifdonlt mod-
MCAPI
~ltTn tj~ IS] ~id M( 1) lt to Hf U=-ti f ktu TrWn no ~iwmmiddot1lD(
iIcafiou in hehlwjltoutl l Ir~ res(Jltlns rfiJI middot Ratlt Ifl d perinmaUy ~ ~et e more c(t(l icuitcT(1Ht Jnd ~h~t iol sh1Alr return IltY basal levels in ~trerlJl illlalin 1201
Tht primill~ lUlmh~ ~l beell u~ltd tltgt ) the efe~h uf slrcs h6nJlon~ lntl ~f~ o Aumini s-fralKw of dt ~ arrlCI1w middot (me tO pr~anl thesu mon~e~S in lhelal1e~ Ihird of pregllMlC~ al ~ tHlt 1mHac to Ihat uu ill humans i axim~Il iU clcgoeri hM lIe$ in II~ f~lal hif1lgtcam middot rjl~ fl ll iJlllSlre h a 2middotwlaquok ~lwd 1 1 e use1oli~ ACf H i~ 3K)CiaIW with illjlaired 111(l(Or lt(llrdiiarlol llud tlW d~
1 iCily reducat allenl( 11 iUld gfnlcr irritatiility P21middot poDlre I~ -I=~ in the lallcr lhiro of (XCllnncyis 1--
tud 111 hiShu ~~- 0( AcrH and ooi~ol in Ille ~eqMI wh~n ~rrS~od nJj _((ure 10 ire in utm
ellec iill l) dUrilfl lit Iil third nf preglY ~tI shylialclti 1m tower nre or alte and IIltUmmOll maturshyilv ilfler birth 1~41
bull 11 huma n~ 1lM(1 inlIlllCiinn ithlU analgesia Il been ~fmwn 10 tncnttsc ubse(lUIH llaln hchoriollr (mea shy~u~d lttjtIjtl fnlrl1 vileo(Jpe by M indpe~ltknl (lh~er ~ kllli)Ving middotcinalion 4~ -6 Olonths I(ermiddotwltcn C()lDpd d 10 llncir~lIlIlcilt1 olrols [25 _Tlth SUSS ilial bull stQgle SUl~ flil eVCflt centarly ill ir~_ nn 11tlt n~ou~ ~ stem i till (teVflo-pfuamp Can innuilIc lltUCIgtLkyklpcIll1If and m y hJje
~ lifllllli eft- on ~I~ Plt)~~_ Fl1hern1Urc gtrwpeIdshyli~ ~jQ1tlenl with Ilxal u~I~tic cr~alll 1I1t~nua1edlbe ~PO~ 10 acn~ljlln Iamp iog tta nclg~ltia cn~lt~r tilt tn~c t uf Sire (n neurodegtelopmlll I ~ I
[n re51OOse 10 vlIltcinaliltn in illfau~y we h3 found Ihl blbielt )m hy jI IJlne ntgt ddivcr) have a gre~lu ric tr
salhlry Nl1igtnl and cl)- for Ig~r Ihm lhe hOnl oormally whHc thn~ born h) el~ctiC Cae~ut an orlou hl1t J
rnatll n( oJ cry I Ihan he n(Jrm1 group l2til Whcthltf fIl itl ~Ire~~ til Ul~nl h~ (nl-ICnn impliodion
l ItOt kuon~ illttl ~ttldle) are hWLlc-U by the tlbknl nted ( 0
cl)nfifl( 11l~~ie rcdure to lh (J gtC ligtl hieb thcti i
Unfiled Notes Page 3
b Page
8 Fetal anesthesia
a Does the article refer to use of fetal anesthesia and its effect At what postshy
fertilization age
b Page
9 Cortex
a Does the article relate to the asserted need for cortical involvement to
experience pain How
b Page
ELSEVlER
OBSHTRICS amp GYNf OLOGY
~~ltL1f flnwf o~ Ck t (frt1)~ lnJ
R~-nd Ytit 0 middotI~ L(nl) Itl IfIlt
Pain and stress in the human fetusg
Richard p Smith R Oitau V (Hover Nicholas M fisk fNIOnitl r1 (tr ar_tI maS Fdd j [rudt1J ( CWflt Itti F~f CdT -btMltwl (I ~fIfr llfJJ ( rM(af~
(tftJitlttJJ 4 1to~ $~1Jr1Ul t1 jJ JU~)~ t )rr ttJ (~ttmr J VIfJ - lfoltlJtu l C fII4mJt NJ t muJron 1) orr l ~
AIrt
ImmiddotmiddotlVt diagThllC rut thJ~lJJtic CCihli~ Ucent irnmiddotloingl) ilf-l ic w lhc- fcl u h i ~ nul ~n it the fCh - (Cd~ ~l lin lurU~ gtlih p(tgtCdllr W I tJl ((1U ~ (flucuH ~OV1 btornlO1UlLlJnd InU ~)t) ~hUJ1j(C n l~S4Jn~ow t~- hc~ tnttn lX--20 middotd~~ ~ru1Wl
gtI~ may h Q too~t 1m eulCldvellgtjmUlhlimllilt ri ClIl r1ltJji Olgt (cia) ~I) uan1 IInOTol NIi tlgtlt ~i ptlI~ r1 JlntIIgt() ltla fI~t in d Plaquo ltdurlt~ fClll l lll1llJvm~ Ieu~ dlllknloe Th~ opli(J1al lt1mI lt1lt 011lt1 MIle of ndtniniltI W0I1 ronn0 tlttmlneJ lt OOO ~c S culte T~ (If Ail r~h ~t(ltI
1 Introduction
Tile 1= nbili y lli ltli~gn(lSe and treal Itllt reUl in uRNI
r~Qhe-d flOo eetltlIIetll in ill - ~ie pnx-WUf~S io mltfermiddot su[[uio(ral palhrh ~ivlonad inl6gthlli1 ukuu ill illallillyen Tbtgte pl(_middotllu~ r~l(ing (ltltlin ttllla -OUIlltl-lilJ(d
nudr~ upirlliO) Uuou-lI lt I (JflC1l feLl sOXXet) lIIt ill IQding 10 he tlbvil)Ul qllt~iQn 11~ l~ felus f~el pain
The ~0t1(ep1 II iflt- I ~ ts i~ amiddotpatient in ilaquo ow~ risht hlb lcod 0 illOtllS5 iultmS1 in lhe iuhjeel of 1111 p~ill _ A j llgtlitiClllion rnr providing reUl anuJgeltld 8M o~hlti
11lt lIti~1 POt only Icru~o( a tlIDtlll obIi~alion to Ir~v-~nl uiTeril~ 001 alllU hcc~le paii~ aN I~~ may affect ~at i vQ and have kjjl-~ ~ulXfemiddotelopnl~lItal Mgt4uclle
1middotltt-cr Ih evideuct e rf Ihi_ is limited lIrgl l ~
t)clilU~ R~emh in hunHtti (tJu- js Itmr by laquoIlucal ltOltIstlllUTts 111 ~t(l due 1( probl~nlt iSelining 1Ii(ul101) oUhltlIDt lite utes
2 F~lalllJl ilt
111 b llel ohj~cli mcasurerntnl of pain- il I uhj~l i C epcrien~ TI~ (elmiddot is unahle 11 Iell 11 imiddotf il
Rcn I~ be J~~1I 1 hYfrtf f Ohtclll( lt t tt)~~ I i3 Jlltf
h1Yj~ c Ul4~ P t1lkci at Inuh F llI fh iiJUCI rod n wIll II) Ih T l11J 1 U(-IO-101 I 1~)uV 1 f1((tfUniorJ hh Cht lhmiddot~tt bull lHd It~l flt tI l r(IInrnI lin
( QfTnrWIil)C JUU- Tt middot +J 1(1k ~ 1 1H)
Iampt middotll~I( 11
r r bullbullbull ~fu middot r r ~~uh~ I k I( 1lt rl Smill bullbull
II ~ t ~ll (I _ 1 111 11
Ill rr I i I ~ I II tI 1111 J ~
rul~ puin W ohlr e ickn~ fn PetJgtltd to deltitie at what g(~tutin it i likdmiddot) h~1 the t((u ~lt 10 fed (gtlill Senor inlltn~linn (f lilt Sil ~ fhlJn)lliIl (lIUl ~middotti()n hctyttfl
lil~ jiphCT~ ijnd piud (lTd h~~e hegl bf S welth lIlt ( thr~ ~()(Ilg into tho spine ltu a ul HI (el lllt ltbrat
ltm~ ~rl form ~t Ini Maltt ilh dilrt r~lilIilt1 inlt nelru~s Ilb ~tia n htltlltJd ~ ~ qa(ling a bull hmiddotUI Ir ~k aru1 clnlirruillpound ng (tfler birth Pain lillres p~s thf)uSIt lite IlYAlillHiS en muk I lhe CN-X Th~ tinlinl~ of ~Scent tJtuUll)-lti1 CUIu(lin~ l md al itt dcciltJing when Ihe ret~ tiN b(t)mes C1bl-e or leltling (Xli llti is lItI u a or C)flgtitef-dIle c(Jntmel1l ~~pd (Jotsi- nini(~ l~chniI~ Ii sbo11 th~ Hrgr_middotI L1[ Jlyener~nt lilgtre inln lite )(il~1 ptalt netweto 26-middot111(1 11 ~b olle~atitll1 rIj which loa middotitd un~ 10 dude the few i irnapgtlc
f r~elin~ piill prior to 26 ee~ i ~1 H we ~lwecn 20 ami 26 middoteeL Ilttlt ubplate t(M r One lt()main an abondanl milllIC of middothotiner~i dIfIl-ctlrucal and ()nirti(1 iting flluroOC and Ihere art Ironsefll lell middotn3plti it bel-een Ib~ ubplal and m1ical pll~ nfutIli- f- f wh r~lIe~ of lin h onidtf(d 10 require CHIlU( ~I~en Ille nlftelt ltIld peolhery hough Ihi rtt~pl i(ll middotuld fender animal- IJclJn it (ne Itch a n~prL1e in(~ar)bk ot fJtr(t~idl ~ pall It I 11()t kn l~n at whlll 1Ic 110l in the otaUtn il11l h fW lt3tL-coienl
(Ihl) 1Il~k conlC(ltlI11 to Igtennult nt multiple L(nnL~~ middot
lilIh the f(ttl rna) blt-nw plhk )f fedil)~ plin (nJ It
Hla~ ~J ~~(ihbulljl Jther tha n MIJlkn l(aumiddot i ll I Iu ~urtlltJry
pritn Id 1 I t~~k li w felll- lt1(lt tH hnc ttmiddot rlefJrH~lnalll
Uli l~~t t pth ) rb-c to fed p~i ~ -~~n ] ~nd ~() ~c L 1 hII J llhmiddotLc)fti~f 1 ~ onnl~ lIrm tfl fpftH mg ami ~ I t(~l
Unfiled Notes Page I
1(1 Iote-i I~ fihl ht le n~middot l ~ Ioj1) c o no ~llln l( htt l (li n
ilUd the la1 eltlIde bull he IIlGtlt IfNltltI a( it ere
illClahl~ ltgtf (einv pain HIlncf ludi ~b() ed II 11Cltuamp lt7~ 11 hl prolcrm fll(UllIed a ileahlc Ift
r0lnet u cardia 11~ry 1-11 willt rilaquo in 1ln 1l~nc nor(dntrldinc (Uld corti)I Some [ hc lt IJ~~~ ~re reducd hy o(i bullid PMIamp~~ 141 In one f1llldl~d Mud) opin u~ihe~b It (~lltlilut ~ilb it rmuIil(l it peri lltW~I I C mq rtalil ru Si[ll~e tlep ~ ofeualglj ia dunng nto111i1 tl)liy b ~ ltcnr~ th ~tJlltdifttl o( care
Nt(lu~ (e fo hwe beh~i(UJral ~PO~ 10 pail (or e~aR)plo by focitllpr~nor by cryIgt1 1lK r-~ II hrelll~inlt by facial Klio ~~ dpoudlns Ql (~ sleep lIle s~ 11 the llcuate Illgc~tiilg lhill the belI(lu r~1 ~(IlU I of pnin ~rrnt lgtel1alUrll eXfrc~itlftmiddot C~~Jl befole the IlPflOfIlJUily rrgt( leamrlt1 repoll~ (clJr tnt
Becau~ of th~ otw iou difticlIlic- ill swdyillg (eldl betlavlour ltlCfi~middotalim lr the bgtJl()lltabfll)-p1lUfI~r)-adrenal RI L (0 SI~~ replt1Il1lte j hl$ been pto(gt)~ I ~urt(gtt iniIkal(Jrof fdl1 pain Thi h~ Ilmfitiiltl IIRraquo i1~pomes db 1101 I ltetiJ Idly iillflly ~in ( I ) iuntpl~dUfinpound ne~hel aqd st~ $fltI~ d) 11111 inolv~ Ihe c(rta HQ~er~ lhe conee i Ill liilllllypltgtIheSl iob in lbe absetlct tlf d ile r~ponse the (elus I ulllile ly 10 CI)(fRlrielllte (lin Also llllt (1lt1ld ~ue 11111 stress rpontgt is ll1~ rcle~Itlt in fIll
of imm~llIll and lnSlaquorm ~lucl~hetblf or 1101 0-shyci tetl wilh in in Ih~ retu
Sludi I IuiJmm~ iU~ liruilltltl by (tie n rOTan elhil1lI ymiddot llllble lJIod1 namdy tho fdu~middot ulltk1oII dinimiddot all~ middotirtdiealed pro~dore~ for ililgflOo( k- Of UlClapeutk
Cltgtrd ---shy
tC~l~)fh i t~ JC utlictI fc(u(~ (HKk rgting I1HI~Hucuta r
hllltd INtblllSion ht II 11gtlt collecli llin of lterial bllt _lmrk JI tlgt 1gtC~lInirll 111 ltnd ( I~ pn~cdlJrc Inmiddotmiddot ltJure at Iht rOCf1(1 oor inSLrtin 0gt( I hid j
inne~I~ltI 0 be otllflrcd ilh IlIn(j al lhe inlfmiddot hCf)bulltti( 111 (fUV- whidl illv~ ron Srt ing rhe fetal (rulll (Flg I 10 O1f unil~ the ~ilc or ~[fNllJCh h bltgtltcll IClhnic lil actt depcrlllcnl m rCla l nd rlacem~1 PitiOll ilh h If ugt~ oJ dPpfI~im [ ~ ~Ol r Ihe time While the IHV ~lrroJmiddoth may I e k cr ri oCltl01(1lilJI n ltIII fI cord l am lQn~ltle ad al1cNl1 paltlll the Plt1 aplwKh i~ ldinit~l1y e cr
1 lumui IlrsPfHtW
A~li~lin 01 Ih JiIltIl hH)(illr~lamomiddotpihJil4rl OOleflal ~xi~ can t-lt iJecod h~ ltIe~~ufin)sect ~t(e~ hurmltlOmiddot1o lllt--il J~
l(llreruthnlt c(lisvl and 1middotlod1lhiu Siudying tllple nblqillltlt1 III kl blood (r~Ifim allo cOnpiIJiwll nr kvel of Ill h(rntuw t(OIe l(a~fin tinlmedi8Iel) ~l~f ae 1( Ift~ lollll dflll ~tlltlJ i tlahlilh_d bull (Ill 1(v~L al Ihe (nd 1 Irlflsfusi4l11 (illS bel~gtre Ihe notJle i~ 111(middot bull bull (1) Afur Ir-tnffusion at Ih PCI (her i lillie ch~nge in felMI 1lt1f((It~line conN or Ilmiddotendorpitin I7SI middot
HI)middotet JIgt inu~rr~d ilt ISgt2 pjerciIt~ tht felal ~blto shymen [0 acces~ lh~ tHY fur r~nfusion ~ ~SlSltlmiddoti at~d with u lanlial f~~ In ttl~e hOfJl)()ne~ rrom a early ~ 13 wltiltk fO~lil)rl Til median i1cr~~e ill fl~l1dlImiddotphin Icd~ a~ 90 in ol1i~d l Iemiddotd WIIS 183c~ lfPltJ III norkl1e)atine I~~h ~ Ii P] 5hlll1er flI(~IIIt [ucn a5 ~Id MUttpitni) Wih(lut trau rlLiJCJmiddotl ero nnl a~~xialcd with ti~ in cOllij(1 fUI I~middotcndtgtfpJjIJ IlIlt then- as bull MIImiddot d j1)
(lie tll bull 1(C f~pl(j llltrrHdnII~line uSlonse
TIle ietult ro L(C ~o laliltJu ha Ii l1ar~oh[l Capil to r~tJj~ribu(~ 1( lHOl)Q Aomiddot in repltltl-C III tr~r [c prUIttl
mo~ jul Orts Kn 1lt IgtrJin and mnltarllum a rh~
S1ltt 01 tHV n=JHng
[In fileci Nnt ~ P~P
PiJ~ - l411nut) nm il~ nmiddotpU~ l~ih1iraquo_ [i c-f k rqitm -j ~J r~ 11QiIl ~ ItU l r-~ftnii411t lllt ftC i
peIse I ot1~r oriMlt It ~~ lUt- ~Jdtie - uW I~ ~trUlitj~ [91 Nullerouolt explt-nrnenta lJJdic h~v middot ) 1shy
firIt1CiJ ltIe fe~IlJI~ IlO elt~ lyp elllia -r mlI I Iwe nl1rrn8~ 1121 and fttllkeltl 411ltrill hrfltld n)W I L~J Similargt- Dowler slud I hUIII klu t ilh inwwler ill growtIl =triOI10II (IUOR I h fnund dlaquorMSc1 r~L I ind i~Q ill cerehr~ 1 I H I and adrenul (l51 bkl)d 10
chgte) lOcj()fn lt (FVW Cllnmiddot i IcentRI witll 11 HailI iltlrI ~tld il1m~5e(1 ltldie~ in FVW ftolll ~imiddoti~Jt~ al o~~ hQlh ~ud1 he renal 11 61 nmood If7 1 aAd (ullntIIMY Itlll ntctic ~-oiJ~enl w III middotWOIOslrk ikn ~Io$norfl (erllrILiOmd our gtlltl(l h itIlwn lI middotfaU of
l-l5 slllildar~ dO[1IIv UI mjdtl~ C~rellrll itMIr pllsshy(iIi indl oI( lli ilh lliis re(JI hruill~I1 jng f~(lLcent ~~ ~~III rrw()h- t1l~ Irai) II- iN llgt( IJie felilI1noll~ (rom ead~ liS 16 wtels_ TIe lUcc~niiJtl fo( thi ~ nol
~kaf bm COlllplilible with m increnM III L(reht-al 1_ Tllcentrt ~Iw an wrt i II retial and remora I ancr) re~i shy
lanc~ ind an rroedurc~ iihl1l vinllr~ngress i(n (lr the feM ulld ~imililrl y (II1I~lie ilh fewl llrltln paring imanllri11 in 1lt1lIrilliunl TIcsc Odg are Ilt)( setl)
afterr pn_des HI Ill PCL n redhtnhuljul1 in bU_ltgtlt1 f1m may tllt ~UI~-ltJ hy Ih ~UlathIk sytem lr 1gt lgtther undcent~l1lliIcent lI)~anit-_
There is inc~a5i() eiMItI( Ihat ~acl)- p~inrul or sire ) eertl~ CiII n-itis n ittltli idual III l1t~ r~ill or sires Evince from irerlllal Iudies indk~le- Ilql A trsshd perina OJ I ~ en~ cm kn~ kg~ I-fn elfeltll on hiPfXW m1pal dc elupmcm ott tI~~ ~hil i()UL In roJt~ which ttt bum al
It Ia c ~(uII-e 1t in bullkIfI1~nt to rhe Il~ l1unlltln fClu earl y pllslnoU1l hJ11dJiS ~LL all i(l~TOe in 1WOCltfltuid R-p tnr lknsrl in 11 bullbullipIocarnp and ifdonlt mod-
MCAPI
~ltTn tj~ IS] ~id M( 1) lt to Hf U=-ti f ktu TrWn no ~iwmmiddot1lD(
iIcafiou in hehlwjltoutl l Ir~ res(Jltlns rfiJI middot Ratlt Ifl d perinmaUy ~ ~et e more c(t(l icuitcT(1Ht Jnd ~h~t iol sh1Alr return IltY basal levels in ~trerlJl illlalin 1201
Tht primill~ lUlmh~ ~l beell u~ltd tltgt ) the efe~h uf slrcs h6nJlon~ lntl ~f~ o Aumini s-fralKw of dt ~ arrlCI1w middot (me tO pr~anl thesu mon~e~S in lhelal1e~ Ihird of pregllMlC~ al ~ tHlt 1mHac to Ihat uu ill humans i axim~Il iU clcgoeri hM lIe$ in II~ f~lal hif1lgtcam middot rjl~ fl ll iJlllSlre h a 2middotwlaquok ~lwd 1 1 e use1oli~ ACf H i~ 3K)CiaIW with illjlaired 111(l(Or lt(llrdiiarlol llud tlW d~
1 iCily reducat allenl( 11 iUld gfnlcr irritatiility P21middot poDlre I~ -I=~ in the lallcr lhiro of (XCllnncyis 1--
tud 111 hiShu ~~- 0( AcrH and ooi~ol in Ille ~eqMI wh~n ~rrS~od nJj _((ure 10 ire in utm
ellec iill l) dUrilfl lit Iil third nf preglY ~tI shylialclti 1m tower nre or alte and IIltUmmOll maturshyilv ilfler birth 1~41
bull 11 huma n~ 1lM(1 inlIlllCiinn ithlU analgesia Il been ~fmwn 10 tncnttsc ubse(lUIH llaln hchoriollr (mea shy~u~d lttjtIjtl fnlrl1 vileo(Jpe by M indpe~ltknl (lh~er ~ kllli)Ving middotcinalion 4~ -6 Olonths I(ermiddotwltcn C()lDpd d 10 llncir~lIlIlcilt1 olrols [25 _Tlth SUSS ilial bull stQgle SUl~ flil eVCflt centarly ill ir~_ nn 11tlt n~ou~ ~ stem i till (teVflo-pfuamp Can innuilIc lltUCIgtLkyklpcIll1If and m y hJje
~ lifllllli eft- on ~I~ Plt)~~_ Fl1hern1Urc gtrwpeIdshyli~ ~jQ1tlenl with Ilxal u~I~tic cr~alll 1I1t~nua1edlbe ~PO~ 10 acn~ljlln Iamp iog tta nclg~ltia cn~lt~r tilt tn~c t uf Sire (n neurodegtelopmlll I ~ I
[n re51OOse 10 vlIltcinaliltn in illfau~y we h3 found Ihl blbielt )m hy jI IJlne ntgt ddivcr) have a gre~lu ric tr
salhlry Nl1igtnl and cl)- for Ig~r Ihm lhe hOnl oormally whHc thn~ born h) el~ctiC Cae~ut an orlou hl1t J
rnatll n( oJ cry I Ihan he n(Jrm1 group l2til Whcthltf fIl itl ~Ire~~ til Ul~nl h~ (nl-ICnn impliodion
l ItOt kuon~ illttl ~ttldle) are hWLlc-U by the tlbknl nted ( 0
cl)nfifl( 11l~~ie rcdure to lh (J gtC ligtl hieb thcti i
Unfiled Notes Page 3
ELSEVlER
OBSHTRICS amp GYNf OLOGY
~~ltL1f flnwf o~ Ck t (frt1)~ lnJ
R~-nd Ytit 0 middotI~ L(nl) Itl IfIlt
Pain and stress in the human fetusg
Richard p Smith R Oitau V (Hover Nicholas M fisk fNIOnitl r1 (tr ar_tI maS Fdd j [rudt1J ( CWflt Itti F~f CdT -btMltwl (I ~fIfr llfJJ ( rM(af~
(tftJitlttJJ 4 1to~ $~1Jr1Ul t1 jJ JU~)~ t )rr ttJ (~ttmr J VIfJ - lfoltlJtu l C fII4mJt NJ t muJron 1) orr l ~
AIrt
ImmiddotmiddotlVt diagThllC rut thJ~lJJtic CCihli~ Ucent irnmiddotloingl) ilf-l ic w lhc- fcl u h i ~ nul ~n it the fCh - (Cd~ ~l lin lurU~ gtlih p(tgtCdllr W I tJl ((1U ~ (flucuH ~OV1 btornlO1UlLlJnd InU ~)t) ~hUJ1j(C n l~S4Jn~ow t~- hc~ tnttn lX--20 middotd~~ ~ru1Wl
gtI~ may h Q too~t 1m eulCldvellgtjmUlhlimllilt ri ClIl r1ltJji Olgt (cia) ~I) uan1 IInOTol NIi tlgtlt ~i ptlI~ r1 JlntIIgt() ltla fI~t in d Plaquo ltdurlt~ fClll l lll1llJvm~ Ieu~ dlllknloe Th~ opli(J1al lt1mI lt1lt 011lt1 MIle of ndtniniltI W0I1 ronn0 tlttmlneJ lt OOO ~c S culte T~ (If Ail r~h ~t(ltI
1 Introduction
Tile 1= nbili y lli ltli~gn(lSe and treal Itllt reUl in uRNI
r~Qhe-d flOo eetltlIIetll in ill - ~ie pnx-WUf~S io mltfermiddot su[[uio(ral palhrh ~ivlonad inl6gthlli1 ukuu ill illallillyen Tbtgte pl(_middotllu~ r~l(ing (ltltlin ttllla -OUIlltl-lilJ(d
nudr~ upirlliO) Uuou-lI lt I (JflC1l feLl sOXXet) lIIt ill IQding 10 he tlbvil)Ul qllt~iQn 11~ l~ felus f~el pain
The ~0t1(ep1 II iflt- I ~ ts i~ amiddotpatient in ilaquo ow~ risht hlb lcod 0 illOtllS5 iultmS1 in lhe iuhjeel of 1111 p~ill _ A j llgtlitiClllion rnr providing reUl anuJgeltld 8M o~hlti
11lt lIti~1 POt only Icru~o( a tlIDtlll obIi~alion to Ir~v-~nl uiTeril~ 001 alllU hcc~le paii~ aN I~~ may affect ~at i vQ and have kjjl-~ ~ulXfemiddotelopnl~lItal Mgt4uclle
1middotltt-cr Ih evideuct e rf Ihi_ is limited lIrgl l ~
t)clilU~ R~emh in hunHtti (tJu- js Itmr by laquoIlucal ltOltIstlllUTts 111 ~t(l due 1( probl~nlt iSelining 1Ii(ul101) oUhltlIDt lite utes
2 F~lalllJl ilt
111 b llel ohj~cli mcasurerntnl of pain- il I uhj~l i C epcrien~ TI~ (elmiddot is unahle 11 Iell 11 imiddotf il
Rcn I~ be J~~1I 1 hYfrtf f Ohtclll( lt t tt)~~ I i3 Jlltf
h1Yj~ c Ul4~ P t1lkci at Inuh F llI fh iiJUCI rod n wIll II) Ih T l11J 1 U(-IO-101 I 1~)uV 1 f1((tfUniorJ hh Cht lhmiddot~tt bull lHd It~l flt tI l r(IInrnI lin
( QfTnrWIil)C JUU- Tt middot +J 1(1k ~ 1 1H)
Iampt middotll~I( 11
r r bullbullbull ~fu middot r r ~~uh~ I k I( 1lt rl Smill bullbull
II ~ t ~ll (I _ 1 111 11
Ill rr I i I ~ I II tI 1111 J ~
rul~ puin W ohlr e ickn~ fn PetJgtltd to deltitie at what g(~tutin it i likdmiddot) h~1 the t((u ~lt 10 fed (gtlill Senor inlltn~linn (f lilt Sil ~ fhlJn)lliIl (lIUl ~middotti()n hctyttfl
lil~ jiphCT~ ijnd piud (lTd h~~e hegl bf S welth lIlt ( thr~ ~()(Ilg into tho spine ltu a ul HI (el lllt ltbrat
ltm~ ~rl form ~t Ini Maltt ilh dilrt r~lilIilt1 inlt nelru~s Ilb ~tia n htltlltJd ~ ~ qa(ling a bull hmiddotUI Ir ~k aru1 clnlirruillpound ng (tfler birth Pain lillres p~s thf)uSIt lite IlYAlillHiS en muk I lhe CN-X Th~ tinlinl~ of ~Scent tJtuUll)-lti1 CUIu(lin~ l md al itt dcciltJing when Ihe ret~ tiN b(t)mes C1bl-e or leltling (Xli llti is lItI u a or C)flgtitef-dIle c(Jntmel1l ~~pd (Jotsi- nini(~ l~chniI~ Ii sbo11 th~ Hrgr_middotI L1[ Jlyener~nt lilgtre inln lite )(il~1 ptalt netweto 26-middot111(1 11 ~b olle~atitll1 rIj which loa middotitd un~ 10 dude the few i irnapgtlc
f r~elin~ piill prior to 26 ee~ i ~1 H we ~lwecn 20 ami 26 middoteeL Ilttlt ubplate t(M r One lt()main an abondanl milllIC of middothotiner~i dIfIl-ctlrucal and ()nirti(1 iting flluroOC and Ihere art Ironsefll lell middotn3plti it bel-een Ib~ ubplal and m1ical pll~ nfutIli- f- f wh r~lIe~ of lin h onidtf(d 10 require CHIlU( ~I~en Ille nlftelt ltIld peolhery hough Ihi rtt~pl i(ll middotuld fender animal- IJclJn it (ne Itch a n~prL1e in(~ar)bk ot fJtr(t~idl ~ pall It I 11()t kn l~n at whlll 1Ic 110l in the otaUtn il11l h fW lt3tL-coienl
(Ihl) 1Il~k conlC(ltlI11 to Igtennult nt multiple L(nnL~~ middot
lilIh the f(ttl rna) blt-nw plhk )f fedil)~ plin (nJ It
Hla~ ~J ~~(ihbulljl Jther tha n MIJlkn l(aumiddot i ll I Iu ~urtlltJry
pritn Id 1 I t~~k li w felll- lt1(lt tH hnc ttmiddot rlefJrH~lnalll
Uli l~~t t pth ) rb-c to fed p~i ~ -~~n ] ~nd ~() ~c L 1 hII J llhmiddotLc)fti~f 1 ~ onnl~ lIrm tfl fpftH mg ami ~ I t(~l
Unfiled Notes Page I
1(1 Iote-i I~ fihl ht le n~middot l ~ Ioj1) c o no ~llln l( htt l (li n
ilUd the la1 eltlIde bull he IIlGtlt IfNltltI a( it ere
illClahl~ ltgtf (einv pain HIlncf ludi ~b() ed II 11Cltuamp lt7~ 11 hl prolcrm fll(UllIed a ileahlc Ift
r0lnet u cardia 11~ry 1-11 willt rilaquo in 1ln 1l~nc nor(dntrldinc (Uld corti)I Some [ hc lt IJ~~~ ~re reducd hy o(i bullid PMIamp~~ 141 In one f1llldl~d Mud) opin u~ihe~b It (~lltlilut ~ilb it rmuIil(l it peri lltW~I I C mq rtalil ru Si[ll~e tlep ~ ofeualglj ia dunng nto111i1 tl)liy b ~ ltcnr~ th ~tJlltdifttl o( care
Nt(lu~ (e fo hwe beh~i(UJral ~PO~ 10 pail (or e~aR)plo by focitllpr~nor by cryIgt1 1lK r-~ II hrelll~inlt by facial Klio ~~ dpoudlns Ql (~ sleep lIle s~ 11 the llcuate Illgc~tiilg lhill the belI(lu r~1 ~(IlU I of pnin ~rrnt lgtel1alUrll eXfrc~itlftmiddot C~~Jl befole the IlPflOfIlJUily rrgt( leamrlt1 repoll~ (clJr tnt
Becau~ of th~ otw iou difticlIlic- ill swdyillg (eldl betlavlour ltlCfi~middotalim lr the bgtJl()lltabfll)-p1lUfI~r)-adrenal RI L (0 SI~~ replt1Il1lte j hl$ been pto(gt)~ I ~urt(gtt iniIkal(Jrof fdl1 pain Thi h~ Ilmfitiiltl IIRraquo i1~pomes db 1101 I ltetiJ Idly iillflly ~in ( I ) iuntpl~dUfinpound ne~hel aqd st~ $fltI~ d) 11111 inolv~ Ihe c(rta HQ~er~ lhe conee i Ill liilllllypltgtIheSl iob in lbe absetlct tlf d ile r~ponse the (elus I ulllile ly 10 CI)(fRlrielllte (lin Also llllt (1lt1ld ~ue 11111 stress rpontgt is ll1~ rcle~Itlt in fIll
of imm~llIll and lnSlaquorm ~lucl~hetblf or 1101 0-shyci tetl wilh in in Ih~ retu
Sludi I IuiJmm~ iU~ liruilltltl by (tie n rOTan elhil1lI ymiddot llllble lJIod1 namdy tho fdu~middot ulltk1oII dinimiddot all~ middotirtdiealed pro~dore~ for ililgflOo( k- Of UlClapeutk
Cltgtrd ---shy
tC~l~)fh i t~ JC utlictI fc(u(~ (HKk rgting I1HI~Hucuta r
hllltd INtblllSion ht II 11gtlt collecli llin of lterial bllt _lmrk JI tlgt 1gtC~lInirll 111 ltnd ( I~ pn~cdlJrc Inmiddotmiddot ltJure at Iht rOCf1(1 oor inSLrtin 0gt( I hid j
inne~I~ltI 0 be otllflrcd ilh IlIn(j al lhe inlfmiddot hCf)bulltti( 111 (fUV- whidl illv~ ron Srt ing rhe fetal (rulll (Flg I 10 O1f unil~ the ~ilc or ~[fNllJCh h bltgtltcll IClhnic lil actt depcrlllcnl m rCla l nd rlacem~1 PitiOll ilh h If ugt~ oJ dPpfI~im [ ~ ~Ol r Ihe time While the IHV ~lrroJmiddoth may I e k cr ri oCltl01(1lilJI n ltIII fI cord l am lQn~ltle ad al1cNl1 paltlll the Plt1 aplwKh i~ ldinit~l1y e cr
1 lumui IlrsPfHtW
A~li~lin 01 Ih JiIltIl hH)(illr~lamomiddotpihJil4rl OOleflal ~xi~ can t-lt iJecod h~ ltIe~~ufin)sect ~t(e~ hurmltlOmiddot1o lllt--il J~
l(llreruthnlt c(lisvl and 1middotlod1lhiu Siudying tllple nblqillltlt1 III kl blood (r~Ifim allo cOnpiIJiwll nr kvel of Ill h(rntuw t(OIe l(a~fin tinlmedi8Iel) ~l~f ae 1( Ift~ lollll dflll ~tlltlJ i tlahlilh_d bull (Ill 1(v~L al Ihe (nd 1 Irlflsfusi4l11 (illS bel~gtre Ihe notJle i~ 111(middot bull bull (1) Afur Ir-tnffusion at Ih PCI (her i lillie ch~nge in felMI 1lt1f((It~line conN or Ilmiddotendorpitin I7SI middot
HI)middotet JIgt inu~rr~d ilt ISgt2 pjerciIt~ tht felal ~blto shymen [0 acces~ lh~ tHY fur r~nfusion ~ ~SlSltlmiddoti at~d with u lanlial f~~ In ttl~e hOfJl)()ne~ rrom a early ~ 13 wltiltk fO~lil)rl Til median i1cr~~e ill fl~l1dlImiddotphin Icd~ a~ 90 in ol1i~d l Iemiddotd WIIS 183c~ lfPltJ III norkl1e)atine I~~h ~ Ii P] 5hlll1er flI(~IIIt [ucn a5 ~Id MUttpitni) Wih(lut trau rlLiJCJmiddotl ero nnl a~~xialcd with ti~ in cOllij(1 fUI I~middotcndtgtfpJjIJ IlIlt then- as bull MIImiddot d j1)
(lie tll bull 1(C f~pl(j llltrrHdnII~line uSlonse
TIle ietult ro L(C ~o laliltJu ha Ii l1ar~oh[l Capil to r~tJj~ribu(~ 1( lHOl)Q Aomiddot in repltltl-C III tr~r [c prUIttl
mo~ jul Orts Kn 1lt IgtrJin and mnltarllum a rh~
S1ltt 01 tHV n=JHng
[In fileci Nnt ~ P~P
PiJ~ - l411nut) nm il~ nmiddotpU~ l~ih1iraquo_ [i c-f k rqitm -j ~J r~ 11QiIl ~ ItU l r-~ftnii411t lllt ftC i
peIse I ot1~r oriMlt It ~~ lUt- ~Jdtie - uW I~ ~trUlitj~ [91 Nullerouolt explt-nrnenta lJJdic h~v middot ) 1shy
firIt1CiJ ltIe fe~IlJI~ IlO elt~ lyp elllia -r mlI I Iwe nl1rrn8~ 1121 and fttllkeltl 411ltrill hrfltld n)W I L~J Similargt- Dowler slud I hUIII klu t ilh inwwler ill growtIl =triOI10II (IUOR I h fnund dlaquorMSc1 r~L I ind i~Q ill cerehr~ 1 I H I and adrenul (l51 bkl)d 10
chgte) lOcj()fn lt (FVW Cllnmiddot i IcentRI witll 11 HailI iltlrI ~tld il1m~5e(1 ltldie~ in FVW ftolll ~imiddoti~Jt~ al o~~ hQlh ~ud1 he renal 11 61 nmood If7 1 aAd (ullntIIMY Itlll ntctic ~-oiJ~enl w III middotWOIOslrk ikn ~Io$norfl (erllrILiOmd our gtlltl(l h itIlwn lI middotfaU of
l-l5 slllildar~ dO[1IIv UI mjdtl~ C~rellrll itMIr pllsshy(iIi indl oI( lli ilh lliis re(JI hruill~I1 jng f~(lLcent ~~ ~~III rrw()h- t1l~ Irai) II- iN llgt( IJie felilI1noll~ (rom ead~ liS 16 wtels_ TIe lUcc~niiJtl fo( thi ~ nol
~kaf bm COlllplilible with m increnM III L(reht-al 1_ Tllcentrt ~Iw an wrt i II retial and remora I ancr) re~i shy
lanc~ ind an rroedurc~ iihl1l vinllr~ngress i(n (lr the feM ulld ~imililrl y (II1I~lie ilh fewl llrltln paring imanllri11 in 1lt1lIrilliunl TIcsc Odg are Ilt)( setl)
afterr pn_des HI Ill PCL n redhtnhuljul1 in bU_ltgtlt1 f1m may tllt ~UI~-ltJ hy Ih ~UlathIk sytem lr 1gt lgtther undcent~l1lliIcent lI)~anit-_
There is inc~a5i() eiMItI( Ihat ~acl)- p~inrul or sire ) eertl~ CiII n-itis n ittltli idual III l1t~ r~ill or sires Evince from irerlllal Iudies indk~le- Ilql A trsshd perina OJ I ~ en~ cm kn~ kg~ I-fn elfeltll on hiPfXW m1pal dc elupmcm ott tI~~ ~hil i()UL In roJt~ which ttt bum al
It Ia c ~(uII-e 1t in bullkIfI1~nt to rhe Il~ l1unlltln fClu earl y pllslnoU1l hJ11dJiS ~LL all i(l~TOe in 1WOCltfltuid R-p tnr lknsrl in 11 bullbullipIocarnp and ifdonlt mod-
MCAPI
~ltTn tj~ IS] ~id M( 1) lt to Hf U=-ti f ktu TrWn no ~iwmmiddot1lD(
iIcafiou in hehlwjltoutl l Ir~ res(Jltlns rfiJI middot Ratlt Ifl d perinmaUy ~ ~et e more c(t(l icuitcT(1Ht Jnd ~h~t iol sh1Alr return IltY basal levels in ~trerlJl illlalin 1201
Tht primill~ lUlmh~ ~l beell u~ltd tltgt ) the efe~h uf slrcs h6nJlon~ lntl ~f~ o Aumini s-fralKw of dt ~ arrlCI1w middot (me tO pr~anl thesu mon~e~S in lhelal1e~ Ihird of pregllMlC~ al ~ tHlt 1mHac to Ihat uu ill humans i axim~Il iU clcgoeri hM lIe$ in II~ f~lal hif1lgtcam middot rjl~ fl ll iJlllSlre h a 2middotwlaquok ~lwd 1 1 e use1oli~ ACf H i~ 3K)CiaIW with illjlaired 111(l(Or lt(llrdiiarlol llud tlW d~
1 iCily reducat allenl( 11 iUld gfnlcr irritatiility P21middot poDlre I~ -I=~ in the lallcr lhiro of (XCllnncyis 1--
tud 111 hiShu ~~- 0( AcrH and ooi~ol in Ille ~eqMI wh~n ~rrS~od nJj _((ure 10 ire in utm
ellec iill l) dUrilfl lit Iil third nf preglY ~tI shylialclti 1m tower nre or alte and IIltUmmOll maturshyilv ilfler birth 1~41
bull 11 huma n~ 1lM(1 inlIlllCiinn ithlU analgesia Il been ~fmwn 10 tncnttsc ubse(lUIH llaln hchoriollr (mea shy~u~d lttjtIjtl fnlrl1 vileo(Jpe by M indpe~ltknl (lh~er ~ kllli)Ving middotcinalion 4~ -6 Olonths I(ermiddotwltcn C()lDpd d 10 llncir~lIlIlcilt1 olrols [25 _Tlth SUSS ilial bull stQgle SUl~ flil eVCflt centarly ill ir~_ nn 11tlt n~ou~ ~ stem i till (teVflo-pfuamp Can innuilIc lltUCIgtLkyklpcIll1If and m y hJje
~ lifllllli eft- on ~I~ Plt)~~_ Fl1hern1Urc gtrwpeIdshyli~ ~jQ1tlenl with Ilxal u~I~tic cr~alll 1I1t~nua1edlbe ~PO~ 10 acn~ljlln Iamp iog tta nclg~ltia cn~lt~r tilt tn~c t uf Sire (n neurodegtelopmlll I ~ I
[n re51OOse 10 vlIltcinaliltn in illfau~y we h3 found Ihl blbielt )m hy jI IJlne ntgt ddivcr) have a gre~lu ric tr
salhlry Nl1igtnl and cl)- for Ig~r Ihm lhe hOnl oormally whHc thn~ born h) el~ctiC Cae~ut an orlou hl1t J
rnatll n( oJ cry I Ihan he n(Jrm1 group l2til Whcthltf fIl itl ~Ire~~ til Ul~nl h~ (nl-ICnn impliodion
l ItOt kuon~ illttl ~ttldle) are hWLlc-U by the tlbknl nted ( 0
cl)nfifl( 11l~~ie rcdure to lh (J gtC ligtl hieb thcti i
Unfiled Notes Page 3
1(1 Iote-i I~ fihl ht le n~middot l ~ Ioj1) c o no ~llln l( htt l (li n
ilUd the la1 eltlIde bull he IIlGtlt IfNltltI a( it ere
illClahl~ ltgtf (einv pain HIlncf ludi ~b() ed II 11Cltuamp lt7~ 11 hl prolcrm fll(UllIed a ileahlc Ift
r0lnet u cardia 11~ry 1-11 willt rilaquo in 1ln 1l~nc nor(dntrldinc (Uld corti)I Some [ hc lt IJ~~~ ~re reducd hy o(i bullid PMIamp~~ 141 In one f1llldl~d Mud) opin u~ihe~b It (~lltlilut ~ilb it rmuIil(l it peri lltW~I I C mq rtalil ru Si[ll~e tlep ~ ofeualglj ia dunng nto111i1 tl)liy b ~ ltcnr~ th ~tJlltdifttl o( care
Nt(lu~ (e fo hwe beh~i(UJral ~PO~ 10 pail (or e~aR)plo by focitllpr~nor by cryIgt1 1lK r-~ II hrelll~inlt by facial Klio ~~ dpoudlns Ql (~ sleep lIle s~ 11 the llcuate Illgc~tiilg lhill the belI(lu r~1 ~(IlU I of pnin ~rrnt lgtel1alUrll eXfrc~itlftmiddot C~~Jl befole the IlPflOfIlJUily rrgt( leamrlt1 repoll~ (clJr tnt
Becau~ of th~ otw iou difticlIlic- ill swdyillg (eldl betlavlour ltlCfi~middotalim lr the bgtJl()lltabfll)-p1lUfI~r)-adrenal RI L (0 SI~~ replt1Il1lte j hl$ been pto(gt)~ I ~urt(gtt iniIkal(Jrof fdl1 pain Thi h~ Ilmfitiiltl IIRraquo i1~pomes db 1101 I ltetiJ Idly iillflly ~in ( I ) iuntpl~dUfinpound ne~hel aqd st~ $fltI~ d) 11111 inolv~ Ihe c(rta HQ~er~ lhe conee i Ill liilllllypltgtIheSl iob in lbe absetlct tlf d ile r~ponse the (elus I ulllile ly 10 CI)(fRlrielllte (lin Also llllt (1lt1ld ~ue 11111 stress rpontgt is ll1~ rcle~Itlt in fIll
of imm~llIll and lnSlaquorm ~lucl~hetblf or 1101 0-shyci tetl wilh in in Ih~ retu
Sludi I IuiJmm~ iU~ liruilltltl by (tie n rOTan elhil1lI ymiddot llllble lJIod1 namdy tho fdu~middot ulltk1oII dinimiddot all~ middotirtdiealed pro~dore~ for ililgflOo( k- Of UlClapeutk
Cltgtrd ---shy
tC~l~)fh i t~ JC utlictI fc(u(~ (HKk rgting I1HI~Hucuta r
hllltd INtblllSion ht II 11gtlt collecli llin of lterial bllt _lmrk JI tlgt 1gtC~lInirll 111 ltnd ( I~ pn~cdlJrc Inmiddotmiddot ltJure at Iht rOCf1(1 oor inSLrtin 0gt( I hid j
inne~I~ltI 0 be otllflrcd ilh IlIn(j al lhe inlfmiddot hCf)bulltti( 111 (fUV- whidl illv~ ron Srt ing rhe fetal (rulll (Flg I 10 O1f unil~ the ~ilc or ~[fNllJCh h bltgtltcll IClhnic lil actt depcrlllcnl m rCla l nd rlacem~1 PitiOll ilh h If ugt~ oJ dPpfI~im [ ~ ~Ol r Ihe time While the IHV ~lrroJmiddoth may I e k cr ri oCltl01(1lilJI n ltIII fI cord l am lQn~ltle ad al1cNl1 paltlll the Plt1 aplwKh i~ ldinit~l1y e cr
1 lumui IlrsPfHtW
A~li~lin 01 Ih JiIltIl hH)(illr~lamomiddotpihJil4rl OOleflal ~xi~ can t-lt iJecod h~ ltIe~~ufin)sect ~t(e~ hurmltlOmiddot1o lllt--il J~
l(llreruthnlt c(lisvl and 1middotlod1lhiu Siudying tllple nblqillltlt1 III kl blood (r~Ifim allo cOnpiIJiwll nr kvel of Ill h(rntuw t(OIe l(a~fin tinlmedi8Iel) ~l~f ae 1( Ift~ lollll dflll ~tlltlJ i tlahlilh_d bull (Ill 1(v~L al Ihe (nd 1 Irlflsfusi4l11 (illS bel~gtre Ihe notJle i~ 111(middot bull bull (1) Afur Ir-tnffusion at Ih PCI (her i lillie ch~nge in felMI 1lt1f((It~line conN or Ilmiddotendorpitin I7SI middot
HI)middotet JIgt inu~rr~d ilt ISgt2 pjerciIt~ tht felal ~blto shymen [0 acces~ lh~ tHY fur r~nfusion ~ ~SlSltlmiddoti at~d with u lanlial f~~ In ttl~e hOfJl)()ne~ rrom a early ~ 13 wltiltk fO~lil)rl Til median i1cr~~e ill fl~l1dlImiddotphin Icd~ a~ 90 in ol1i~d l Iemiddotd WIIS 183c~ lfPltJ III norkl1e)atine I~~h ~ Ii P] 5hlll1er flI(~IIIt [ucn a5 ~Id MUttpitni) Wih(lut trau rlLiJCJmiddotl ero nnl a~~xialcd with ti~ in cOllij(1 fUI I~middotcndtgtfpJjIJ IlIlt then- as bull MIImiddot d j1)
(lie tll bull 1(C f~pl(j llltrrHdnII~line uSlonse
TIle ietult ro L(C ~o laliltJu ha Ii l1ar~oh[l Capil to r~tJj~ribu(~ 1( lHOl)Q Aomiddot in repltltl-C III tr~r [c prUIttl
mo~ jul Orts Kn 1lt IgtrJin and mnltarllum a rh~
S1ltt 01 tHV n=JHng
[In fileci Nnt ~ P~P
PiJ~ - l411nut) nm il~ nmiddotpU~ l~ih1iraquo_ [i c-f k rqitm -j ~J r~ 11QiIl ~ ItU l r-~ftnii411t lllt ftC i
peIse I ot1~r oriMlt It ~~ lUt- ~Jdtie - uW I~ ~trUlitj~ [91 Nullerouolt explt-nrnenta lJJdic h~v middot ) 1shy
firIt1CiJ ltIe fe~IlJI~ IlO elt~ lyp elllia -r mlI I Iwe nl1rrn8~ 1121 and fttllkeltl 411ltrill hrfltld n)W I L~J Similargt- Dowler slud I hUIII klu t ilh inwwler ill growtIl =triOI10II (IUOR I h fnund dlaquorMSc1 r~L I ind i~Q ill cerehr~ 1 I H I and adrenul (l51 bkl)d 10
chgte) lOcj()fn lt (FVW Cllnmiddot i IcentRI witll 11 HailI iltlrI ~tld il1m~5e(1 ltldie~ in FVW ftolll ~imiddoti~Jt~ al o~~ hQlh ~ud1 he renal 11 61 nmood If7 1 aAd (ullntIIMY Itlll ntctic ~-oiJ~enl w III middotWOIOslrk ikn ~Io$norfl (erllrILiOmd our gtlltl(l h itIlwn lI middotfaU of
l-l5 slllildar~ dO[1IIv UI mjdtl~ C~rellrll itMIr pllsshy(iIi indl oI( lli ilh lliis re(JI hruill~I1 jng f~(lLcent ~~ ~~III rrw()h- t1l~ Irai) II- iN llgt( IJie felilI1noll~ (rom ead~ liS 16 wtels_ TIe lUcc~niiJtl fo( thi ~ nol
~kaf bm COlllplilible with m increnM III L(reht-al 1_ Tllcentrt ~Iw an wrt i II retial and remora I ancr) re~i shy
lanc~ ind an rroedurc~ iihl1l vinllr~ngress i(n (lr the feM ulld ~imililrl y (II1I~lie ilh fewl llrltln paring imanllri11 in 1lt1lIrilliunl TIcsc Odg are Ilt)( setl)
afterr pn_des HI Ill PCL n redhtnhuljul1 in bU_ltgtlt1 f1m may tllt ~UI~-ltJ hy Ih ~UlathIk sytem lr 1gt lgtther undcent~l1lliIcent lI)~anit-_
There is inc~a5i() eiMItI( Ihat ~acl)- p~inrul or sire ) eertl~ CiII n-itis n ittltli idual III l1t~ r~ill or sires Evince from irerlllal Iudies indk~le- Ilql A trsshd perina OJ I ~ en~ cm kn~ kg~ I-fn elfeltll on hiPfXW m1pal dc elupmcm ott tI~~ ~hil i()UL In roJt~ which ttt bum al
It Ia c ~(uII-e 1t in bullkIfI1~nt to rhe Il~ l1unlltln fClu earl y pllslnoU1l hJ11dJiS ~LL all i(l~TOe in 1WOCltfltuid R-p tnr lknsrl in 11 bullbullipIocarnp and ifdonlt mod-
MCAPI
~ltTn tj~ IS] ~id M( 1) lt to Hf U=-ti f ktu TrWn no ~iwmmiddot1lD(
iIcafiou in hehlwjltoutl l Ir~ res(Jltlns rfiJI middot Ratlt Ifl d perinmaUy ~ ~et e more c(t(l icuitcT(1Ht Jnd ~h~t iol sh1Alr return IltY basal levels in ~trerlJl illlalin 1201
Tht primill~ lUlmh~ ~l beell u~ltd tltgt ) the efe~h uf slrcs h6nJlon~ lntl ~f~ o Aumini s-fralKw of dt ~ arrlCI1w middot (me tO pr~anl thesu mon~e~S in lhelal1e~ Ihird of pregllMlC~ al ~ tHlt 1mHac to Ihat uu ill humans i axim~Il iU clcgoeri hM lIe$ in II~ f~lal hif1lgtcam middot rjl~ fl ll iJlllSlre h a 2middotwlaquok ~lwd 1 1 e use1oli~ ACf H i~ 3K)CiaIW with illjlaired 111(l(Or lt(llrdiiarlol llud tlW d~
1 iCily reducat allenl( 11 iUld gfnlcr irritatiility P21middot poDlre I~ -I=~ in the lallcr lhiro of (XCllnncyis 1--
tud 111 hiShu ~~- 0( AcrH and ooi~ol in Ille ~eqMI wh~n ~rrS~od nJj _((ure 10 ire in utm
ellec iill l) dUrilfl lit Iil third nf preglY ~tI shylialclti 1m tower nre or alte and IIltUmmOll maturshyilv ilfler birth 1~41
bull 11 huma n~ 1lM(1 inlIlllCiinn ithlU analgesia Il been ~fmwn 10 tncnttsc ubse(lUIH llaln hchoriollr (mea shy~u~d lttjtIjtl fnlrl1 vileo(Jpe by M indpe~ltknl (lh~er ~ kllli)Ving middotcinalion 4~ -6 Olonths I(ermiddotwltcn C()lDpd d 10 llncir~lIlIlcilt1 olrols [25 _Tlth SUSS ilial bull stQgle SUl~ flil eVCflt centarly ill ir~_ nn 11tlt n~ou~ ~ stem i till (teVflo-pfuamp Can innuilIc lltUCIgtLkyklpcIll1If and m y hJje
~ lifllllli eft- on ~I~ Plt)~~_ Fl1hern1Urc gtrwpeIdshyli~ ~jQ1tlenl with Ilxal u~I~tic cr~alll 1I1t~nua1edlbe ~PO~ 10 acn~ljlln Iamp iog tta nclg~ltia cn~lt~r tilt tn~c t uf Sire (n neurodegtelopmlll I ~ I
[n re51OOse 10 vlIltcinaliltn in illfau~y we h3 found Ihl blbielt )m hy jI IJlne ntgt ddivcr) have a gre~lu ric tr
salhlry Nl1igtnl and cl)- for Ig~r Ihm lhe hOnl oormally whHc thn~ born h) el~ctiC Cae~ut an orlou hl1t J
rnatll n( oJ cry I Ihan he n(Jrm1 group l2til Whcthltf fIl itl ~Ire~~ til Ul~nl h~ (nl-ICnn impliodion
l ItOt kuon~ illttl ~ttldle) are hWLlc-U by the tlbknl nted ( 0
cl)nfifl( 11l~~ie rcdure to lh (J gtC ligtl hieb thcti i
Unfiled Notes Page 3
PiJ~ - l411nut) nm il~ nmiddotpU~ l~ih1iraquo_ [i c-f k rqitm -j ~J r~ 11QiIl ~ ItU l r-~ftnii411t lllt ftC i
peIse I ot1~r oriMlt It ~~ lUt- ~Jdtie - uW I~ ~trUlitj~ [91 Nullerouolt explt-nrnenta lJJdic h~v middot ) 1shy
firIt1CiJ ltIe fe~IlJI~ IlO elt~ lyp elllia -r mlI I Iwe nl1rrn8~ 1121 and fttllkeltl 411ltrill hrfltld n)W I L~J Similargt- Dowler slud I hUIII klu t ilh inwwler ill growtIl =triOI10II (IUOR I h fnund dlaquorMSc1 r~L I ind i~Q ill cerehr~ 1 I H I and adrenul (l51 bkl)d 10
chgte) lOcj()fn lt (FVW Cllnmiddot i IcentRI witll 11 HailI iltlrI ~tld il1m~5e(1 ltldie~ in FVW ftolll ~imiddoti~Jt~ al o~~ hQlh ~ud1 he renal 11 61 nmood If7 1 aAd (ullntIIMY Itlll ntctic ~-oiJ~enl w III middotWOIOslrk ikn ~Io$norfl (erllrILiOmd our gtlltl(l h itIlwn lI middotfaU of
l-l5 slllildar~ dO[1IIv UI mjdtl~ C~rellrll itMIr pllsshy(iIi indl oI( lli ilh lliis re(JI hruill~I1 jng f~(lLcent ~~ ~~III rrw()h- t1l~ Irai) II- iN llgt( IJie felilI1noll~ (rom ead~ liS 16 wtels_ TIe lUcc~niiJtl fo( thi ~ nol
~kaf bm COlllplilible with m increnM III L(reht-al 1_ Tllcentrt ~Iw an wrt i II retial and remora I ancr) re~i shy
lanc~ ind an rroedurc~ iihl1l vinllr~ngress i(n (lr the feM ulld ~imililrl y (II1I~lie ilh fewl llrltln paring imanllri11 in 1lt1lIrilliunl TIcsc Odg are Ilt)( setl)
afterr pn_des HI Ill PCL n redhtnhuljul1 in bU_ltgtlt1 f1m may tllt ~UI~-ltJ hy Ih ~UlathIk sytem lr 1gt lgtther undcent~l1lliIcent lI)~anit-_
There is inc~a5i() eiMItI( Ihat ~acl)- p~inrul or sire ) eertl~ CiII n-itis n ittltli idual III l1t~ r~ill or sires Evince from irerlllal Iudies indk~le- Ilql A trsshd perina OJ I ~ en~ cm kn~ kg~ I-fn elfeltll on hiPfXW m1pal dc elupmcm ott tI~~ ~hil i()UL In roJt~ which ttt bum al
It Ia c ~(uII-e 1t in bullkIfI1~nt to rhe Il~ l1unlltln fClu earl y pllslnoU1l hJ11dJiS ~LL all i(l~TOe in 1WOCltfltuid R-p tnr lknsrl in 11 bullbullipIocarnp and ifdonlt mod-
MCAPI
~ltTn tj~ IS] ~id M( 1) lt to Hf U=-ti f ktu TrWn no ~iwmmiddot1lD(
iIcafiou in hehlwjltoutl l Ir~ res(Jltlns rfiJI middot Ratlt Ifl d perinmaUy ~ ~et e more c(t(l icuitcT(1Ht Jnd ~h~t iol sh1Alr return IltY basal levels in ~trerlJl illlalin 1201
Tht primill~ lUlmh~ ~l beell u~ltd tltgt ) the efe~h uf slrcs h6nJlon~ lntl ~f~ o Aumini s-fralKw of dt ~ arrlCI1w middot (me tO pr~anl thesu mon~e~S in lhelal1e~ Ihird of pregllMlC~ al ~ tHlt 1mHac to Ihat uu ill humans i axim~Il iU clcgoeri hM lIe$ in II~ f~lal hif1lgtcam middot rjl~ fl ll iJlllSlre h a 2middotwlaquok ~lwd 1 1 e use1oli~ ACf H i~ 3K)CiaIW with illjlaired 111(l(Or lt(llrdiiarlol llud tlW d~
1 iCily reducat allenl( 11 iUld gfnlcr irritatiility P21middot poDlre I~ -I=~ in the lallcr lhiro of (XCllnncyis 1--
tud 111 hiShu ~~- 0( AcrH and ooi~ol in Ille ~eqMI wh~n ~rrS~od nJj _((ure 10 ire in utm
ellec iill l) dUrilfl lit Iil third nf preglY ~tI shylialclti 1m tower nre or alte and IIltUmmOll maturshyilv ilfler birth 1~41
bull 11 huma n~ 1lM(1 inlIlllCiinn ithlU analgesia Il been ~fmwn 10 tncnttsc ubse(lUIH llaln hchoriollr (mea shy~u~d lttjtIjtl fnlrl1 vileo(Jpe by M indpe~ltknl (lh~er ~ kllli)Ving middotcinalion 4~ -6 Olonths I(ermiddotwltcn C()lDpd d 10 llncir~lIlIlcilt1 olrols [25 _Tlth SUSS ilial bull stQgle SUl~ flil eVCflt centarly ill ir~_ nn 11tlt n~ou~ ~ stem i till (teVflo-pfuamp Can innuilIc lltUCIgtLkyklpcIll1If and m y hJje
~ lifllllli eft- on ~I~ Plt)~~_ Fl1hern1Urc gtrwpeIdshyli~ ~jQ1tlenl with Ilxal u~I~tic cr~alll 1I1t~nua1edlbe ~PO~ 10 acn~ljlln Iamp iog tta nclg~ltia cn~lt~r tilt tn~c t uf Sire (n neurodegtelopmlll I ~ I
[n re51OOse 10 vlIltcinaliltn in illfau~y we h3 found Ihl blbielt )m hy jI IJlne ntgt ddivcr) have a gre~lu ric tr
salhlry Nl1igtnl and cl)- for Ig~r Ihm lhe hOnl oormally whHc thn~ born h) el~ctiC Cae~ut an orlou hl1t J
rnatll n( oJ cry I Ihan he n(Jrm1 group l2til Whcthltf fIl itl ~Ire~~ til Ul~nl h~ (nl-ICnn impliodion
l ItOt kuon~ illttl ~ttldle) are hWLlc-U by the tlbknl nted ( 0
cl)nfifl( 11l~~ie rcdure to lh (J gtC ligtl hieb thcti i
Unfiled Notes Page 3