Pas, A.B. de
Citation
Pas, A. B. de. (2009, March 5). Spontaneous breathing and respiratory support of preterm infants at birth. Retrieved from
https://hdl.handle.net/1887/13595
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
Downloaded from: https://hdl.handle.net/1887/13595
Note: To cite this publication please use the final published version (if applicable).
A randomized controlled trial of
delivery room respiratory management in very preterm infants
Arjan B. te Pas, Frans J. Walther
9^k^h^dcd[CZdcVidad\n!9ZeVgibZcid[EZY^Vig^Xh!AZ^YZcJc^kZgh^inBZY^XVa8ZciZg!AZ^YZc!
i]ZCZi]ZgaVcYh
Pediatrics 2007;120:322-9
Abstract
Background.>c^i^VakZci^aVi^dchigViZ\nbVneaVnVc^bedgiVcigdaZ^ci]ZYZkZadebZcid[
WgdcX]dejabdcVgnYnheaVh^V7E9^ckZgnegZiZgb^c[Vcih#:VgancVhVaXdci^cjdjhedh^i^kZ
V^glVnegZhhjgZ8E6E^hVcVXXZeiZYVeegdVX]!WjigVcYdb^hZYXa^c^XVaig^VahVgZaVX`^c\#
DjgV^blVhidYZiZgb^cZl]Zi]ZgZVgancVhVa8E6E!egZXZYZYWnVhjhiV^cZY^cÅVi^dc!^h
bdgZZ[[ZXi^kZVcYaZhh^c_jg^djh^ckZgnegZiZgb^c[Vcihi]VcXdckZci^dcVa^ciZgkZci^dc#
Methods. Ild ]jcYgZY VcY hZkZc kZgn egZiZgb ^c[Vcih lZgZ gVcYdban Vhh^\cZY ^c i]Z
YZa^kZgngddbidZ^i]ZgVhjhiV^cZY^cÅVi^dci]gdj\]VcVhde]Vgnc\ZVaijWZ[daadlZYWn
ZVgancVhVa8E6EZVgan[jcXi^dcVagZh^YjVaXVeVX^in^ciZgkZci^dcdggZeZViZYbVcjVa^cÅV"
i^dchl^i]VhZa["^cÅVi^c\WV\VcYbVh`[daadlZYWncVhVa8E6E!^[cZXZhhVgn!V[iZgVgg^kVaVi
i]ZcZdcViVa^ciZch^kZXVgZjc^i#Eg^bVgndjiXdbZbZVhjgZlVh^cijWVi^dc1,']djghd[V\Z
VcYWgdcX]dejabdcVgnYnheaVh^VVi(+lZZ`hlVhjhZYVhhZXdcYVgndjiXdbZ#I]^hig^Va^h
gZ\^hiZgZYVhi]ZZVgan[jcXi^dcVagZh^YjVaXVeVX^in^ciZgkZci^dcig^Va>HG8IC&',*,,')#
Results. >c i]Z ZVgan [jcXi^dcVa gZh^YjVa XVeVX^in ^ciZgkZci^dc \gdje [ZlZg ^c[Vcih lZgZ
^cijWViZY1,']djghd[V\ZDG%#*,.*8>%#('"%#.-dggZXZ^kZYbdgZi]Vc&YdhZd[
hjg[VXiVciDG%#(..*8>%#&-"%#--VcYi]ZVkZgV\ZYjgVi^dcd[kZci^aVidgnhjeedgilVh
aZhhbZY^VcYVnh>FG/'#,%#*"&%kh)#(%#*"'%0E2%#%&#>c[Vcih^ci]ZZVgan[jcXi^dcVa
gZh^YjVaXVeVX^in^ciZgkZci^dc\gdjeYZkZadeZYaZhh7E9DG%#)&.*8>%#&-"%#.+#
Conclusion.6hjhiV^cZY^cÅVi^dc[daadlZYWnZVgancVhVa8E6E!YZa^kZgZYi]gdj\]VcVhd"
e]Vgnc\ZVaijWZ!^hVbdgZZ[ÄX^ZcihigViZ\ni]VcgZeZViZYbVcjVa^cÅVi^dchl^i]VhZa["
^cÅVi^c\WV\VcYbVh`[daadlZYWncVhVa8E6EdcVYb^hh^dcidi]ZC>8J#
Introduction
I]Z eVi]d\ZcZh^h d[ WgdcX]dejabdcVgn YnheaVh^V 7E9 dg X]gdc^X ajc\ Y^hZVhZ ^c kZgn
egZiZgb^c[Vcih^hbjai^[VXidg^Va!WjikZci^aVidg"^cYjXZYajc\^c_jgneaVnhVbV_dgXdcig^W"
ji^c\ gdaZ &# KVg^djh cZl kZci^aVi^dc higViZ\^Zh ]VkZ WZZc ^cigdYjXZY! Wji i]^h ]Vh cdi
gZYjXZY i]Z ^cX^YZcXZ d[ 7E9 '# :Vgan gZhe^gVidgn bVcV\ZbZci! ^#Z# kZci^aVidgn hjeedgi
[gdbW^gi]Yjg^c\i]ZÄghiYVnhd[a^[Z!bVn^cÅjZcXZejabdcVgndjiXdbZ!Wji!YjZidaVX`
d[YViV!i]ZgZ^hcdXdchZchjhdci]ZZVgangZhe^gVidgnbVcV\ZbZcid[egZiZgb^c[Vcih(#
GZigdheZXi^kZXd]dgiVcYZmeZg^bZciVahijY^Zhhj\\Zhii]Vii]Z^c^i^VakZci^aVi^dchigViZ\n
bVneaVnVc^bedgiVcigdaZ^ci]ZYZkZadebZcid[7E9)".#I]ZbdhiZ[[ZXi^kZVcYaZVhi
^c_jg^djh lVn id gZXgj^i i]Z ajc\ ^c egZiZgb ^c[Vcih Vi W^gi] bVn WZ V XdbW^cVi^dc d[ V
hjhiV^cZY^cÅVi^dcVcYZVgancVhVaXdci^cjdjhedh^i^kZV^glVnegZhhjgZ8E6E#I]^hViiZbei
idVkd^Y^cijWVi^dcVcYbZX]Vc^XVakZci^aVi^dc!bVngZYjXZajc\^c_jgnVcY7E9^cegZiZgb
^c[VcihVhhj\\ZhiZY^cVgZigdheZXi^kZhijYnWnA^cYcZgZiVa&%#6ig^Vad[ZVgancVhVa8E6E
ViW^gi]hZZbh_jhi^ÄZY^c^c[VcihVig^h`d[gZhe^gVidgnY^higZhhhncYgdbZG9H!egdk^Y^c\
ZVganhjg[VXiVcigZhXjZ^h\^kZc^[gZfj^gZY&&0&'#LZeZg[dgbZYVgVcYdb^oZYXdcigdaaZY
ig^VaVcYXdbeVgZYi]ZigVY^i^dcVagZhe^gVidgnVeegdVX]l^i]VcZlbZi]dYi]ViXdbW^cZY
V cjbWZg d[ iZX]c^fjZh! l]^X] i]ZdgZi^XVaan XdjaY ^begdkZ i]Z gZhe^gVidgn djiXdbZ d[
egZiZgb^c[Vcih#LZ]nedi]Zh^oZYi]ViVhjhiV^cZY^cÅVi^dc[daadlZYWnZVgancVhVa8E6E!
jh^c\VegZhhjgZ"a^b^iZYbZX]Vc^XVaYZk^XZ!^hVbdgZZ[[ZXi^kZVcYaZhh^c_jg^djhbVcV\Z"
bZcihigViZ\n^cegZiZgb^c[Vcihi]VcXdckZci^dcVa^ciZgkZci^dc#
Patients and Methods
I]Z a^b^ih d[ k^VW^a^in ^c i]Z CZi]ZgaVcYh VgZ hZi Vi '* lZZ`h¼ \ZhiVi^dc# 6aa kZgn egZiZgb
^c[Vcih1((lZZ`h¼\ZhiVi^dc!Wdgc^ci]ZAZ^YZcJc^kZgh^inBZY^XVa8ZciZglZgZZa^\^WaZ
[dg i]^h hijYn ^[ i]Zn lZgZ [gZZ [gdb `cdlc bV_dg Xdc\Zc^iVa VcdbVa^Zh# I]Z hijYn lVh
VeegdkZYWni]Z:i]^XhGZk^Zl8dbb^iiZZd[i]Z]dhe^iVa#EVi^ZcihlZgZ^cXajYZYWZ[dgZ
W^gi]VcY^c[dgbZYXdchZcilVhdWiV^cZY[gdbi]Z^c[Vci¼heVgZcihdgaZ\Va\jVgY^Vc#7Z[dgZ
W^gi] eVi^Zcih lZgZ Vhh^\cZY gVcYdban id ZVgan [jcXi^dcVa gZh^YjVa XVeVX^in ^ciZgkZci^dc
:;JG8>dgXdckZci^dcVa^ciZgkZci^dcWnjh^c\hZVaZYZckZadeZh#7adX`ZYgVcYdb^oVi^dc
VcYhigVi^ÄXVi^dc[dgZVX]lZZ`d[\ZhiVi^dcVaV\ZlZgZjhZYidZchjgZigZVibZciWVaVcXZ
WZilZZci]ZildVgbh#
EFURCI-approach
6[iZgdgde]Vgnc\ZVaVcYcVhVahjXi^dc^c\i^bZ2%"(%hZXdcYh!VcY^[WgZVi]^c\lVh^chj["
ÄX^Zci^#Z#cdh^\chd[hedciVcZdjhWgZVi]^c\dghedciVcZdjhWgZVi]^c\egZhZci!Wjih^\ch
d[eddgV^g"ZcignhZkZgZgZigVXi^dch!cVhVaÅVg^c\!VegZhhjgZa^b^iZY'%Xb='D^cÅVi^dc
lVh hjhiV^cZY [dg &% hZXdcYh! jh^c\ V cVhde]Vgnc\ZVa ijWZ VcY V I"e^ZXZ kZci^aVidg
CZdej[[>c[VciGZhjhX^iVidg!;^h]ZgVcYEVn`Za!CZlOZVaVcYi^bZ2(%")*hZXdcYh#I]^h
I"e^ZXZkZci^aVidg^hVegZhhjgZ"a^b^iZYbZX]Vc^XVaYZk^XZl]^X]hjeea^ZhVXdch^hiZcieZV`
^che^gVidgnegZhhjgZVcYedh^i^kZZcY"Zme^gVidgnegZhhjgZE::EVcY^hXVeVWaZd[YZa^kZg"
^c\VhjhiV^cZY^cÅVi^dc&("&+#JhZd[VhjhiV^cZY^cÅVi^dcgZYjXZhi]ZcZZY[dg]^\]Zg
^c^i^Va V^glVn egZhhjgZh# Id Vkd^Y aZV`V\Z! V cVhde]Vgnc\ZVa ijWZ lVh jhZY Vh ^ciZg[VXZ
&,# CVhde]Vgnc\ZVa ijWZh l^i] V Y^VbZiZg d[ '#*")#% bb lZgZ jhZY! VXXdgY^c\ id \Zh"
iVi^dcVaV\Z$W^gi]lZ^\]i#I]ZaZc\i]d[i]ZijWZlVhXjiYdlcid+Xb#I]Zbdji]VcY
di]Zgcdhig^alZgZ]ZaYXadhZYbVcjVaanYjg^c\i]Z^cÅVi^dc#I]^hegdXZYjgZlVhgZeZViZY
i^bZ2*%"+*hZXdcYhl^i]Vc^cXgZVhZYeZV`^che^gVidgnegZhhjgZ'*Xb='D^[WgZVi]^c\
gZbV^cZY^chj[ÄX^ZciVcY$dgi]Z]ZVgigViZlVh1&%%WZVieZgb^cjiZVcY$dgi]Z^c[Vci
lVh XnVcdi^X# 6[iZg i]Z ^c^i^Va ^cÅVi^dc! ZVgan cVhVa 8E6E Vi * id + Xb ='D lVh hiVgiZY# >[
WgZVi]^c\lVhhj[ÄX^Zci!i]ZeVi^ZcilVhdWhZgkZY^ci]ZYZa^kZgngddbWZ[dgZigVchedgiV"
i^dc id i]Z C>8J# >[ i]ZgZ lVh ^begdkZbZci ]ZVgi gViZ 3&%% WZVih eZg b^cjiZ VcY e^c`
Xdadjg!WjiVecZVdg^chj[ÄX^ZciWgZVi]^c\!^ciZgb^iiZcikZci^aVi^dcl^i]VeZV`^che^gVidgn
egZhhjgZd['%id'*Xb='DVcYVgViZd[+%eZgb^cjiZlVhYZa^kZgZYi]gdj\]i]ZcVhd"
e]Vgnc\ZVaijWZ[dghZkZgVab^cjiZhjci^ai]Z^c[Vci^begdkZY]ZVgigViZ3&%%WZViheZg
b^cjiZ!e^c`XdadjgVcYhedciVcZdjhWgZVi]^c\#:cYdigVX]ZVa^cijWVi^dcVcYbZX]Vc^XVa
kZci^aVi^dclVh^c^i^ViZY^[i]Z]ZVgigViZY^Ycdi^cXgZVhZVWdkZ&%%WZViheZgb^cjiZ!i]Z
^c[VcigZbV^cZYXnVcdhZY!WgZVi]^c\lVhVWhZci!dgbVg`ZYYnhecdZVdXXjggZYi^bZ2.%
hZXdcYh"*b^cjiZh#EVi^ZcihlZgZigVch[ZggZYidi]ZC>8Jl^i]ZVgancVhVa8E6Edg>ciZgb^i"
iZciEdh^i^kZEgZhhjgZKZci^aVi^dc#
Conventional intervention group
>ci]^h\gdjeVhZa["^cÅVi^c\WV\VcYbVh`l^i]VWj^ai"^cegZhhjgZa^b^iVi^dc6bWj7VWnG
GZhjhX^iVidgh!6bWj!7VaaZgje!9ZcbVg`VcYVcdmn\ZcgZhZgkd^glZgZjhZYV[iZgW^gi]#6
bVcdbZiZglVhViiVX]ZYidbdc^idgi]ZegZhhjgZh\^kZc#I]ZbVh`VcYWV\YZa^kZg^cXdc"
h^hiZciE>EVcYb^c^bVaE::EVcYVgZjcVWaZidYZa^kZgVhjhiV^cZY^cÅVi^dc&)0&-0&.#L^i]
i]^hVeegdVX]V]^\]Zg^c^i^VaegZhhjgZ^hjhZYiddeZci]Zajc\VcYZVgancVhVa8E6ElVhdcan
\^kZcdcVgg^kVa^ci]ZC>8J^[cZZYZY#BVh`VcYWV\kZci^aVi^dclVhVYb^c^hiZgZYYjg^c\
(%hZXdcYh^[WgZVi]^c\lVh^chj[ÄX^ZciV[iZgdgde]Vgnc\ZVaVcYcVhVahjXi^dc^c\i^bZ2
(%"+%hZXdcYh#>c^i^Va^cÅVi^dcegZhhjgZhd[(%")%Xb='DlZgZjhZY!V[iZgi]VicdibdgZ
i]Vc'%Xb='DlVhVaadlZY(#>[WgZVi]^c\gZbV^cZY^chj[ÄX^Zci!dgi]Z]ZVgigViZlVh
1&%%WZViheZgb^cjiZ!dgi]Z^c[VcigZbV^cZYXnVcdi^X!dg^cÅVi^dclVhcdiedhh^WaZ!ZcYd"
igVX]ZVa ^cijWVi^dc VcY bZX]Vc^XVa kZci^aVi^dc lZgZ eZg[dgbZY i^bZ 2 +%".% hZXdcYh#
>[ WV\ VcY bVh` gZhjhX^iVi^dc lVh hjXXZhh[ja VcY WgZVi]^c\ lVh hj[ÄX^Zci hedciVcZdjh
WgZVi]^c\!cdgbVaX]ZhibdkZbZcih!cdXnVcdh^h!]ZVgigViZ3&%%WZViheZgb^cjiZ!i]Z
^c[VcilVhdWhZgkZY^ci]ZYZa^kZgngddbVcYigVch[ZggZYidi]ZC>8J#Cdc^cijWViZY^c[Vcih
lZgZigVch[ZggZYl^i]dmn\Zcbdc^idgZYWnbZVhjg^c\dmn\ZchVijgVi^dc#
In both groups
DcZ]jcYgZYeZgXZcidmn\ZclVh^c^i^VaanjhZYVcYlZVcZYYdlcVhfj^X`anVhedhh^WaZ
YZeZcY^c\ dc i]Z ^c[Vcih¼ gZhedchZ! Xdadjg VcY ]ZVgi gViZ# EjahZ dm^bZign lVh hiVgiZY
^bbZY^ViZanV[iZggZhjhX^iVi^dc#>[cdgZhe^gVidgnhjeedgi^ci]ZYZa^kZgngddblVhcZZYZY!
i]Z^c[VcilVhdWhZgkZYVcYigVch[ZggZYidi]ZC>8J#CVhVa8E6ElVhhiVgiZY^[i]ZgZlZgZ
h^\chd[gZhe^gVidgnY^higZhhdgi]Z;^D'lVh3%#(#>c[VcihdcZVgancVhVa8E6ElZgZeaVXZY
dcVc>c[Vci;adl9Zk^XZ:B:Ig^XdbZY!7g^\]idc!J@dg>c[VciHiVgkZci^aVidg>c[gVhdc"
^Xh>cX#!HVc9^Z\d!86!JH6l^i]=jYhdcegdc\h=jYhdc"G8>!IZbZXjaV!8Va^[dgc^V!JH6#
I]ZaZkZad[egZhhjgZlVhi^igViZY[gdb*id-Xb='DVXXdgY^c\idi]ZYZ\gZZd[gZhe^gVidgn
Y^higZhh!VhhZhhZYWndWhZgk^c\X]ZhigZigVXi^dch!Z[[dgid[WgZVi]^c\!X]ZhigVY^d\gVe]!VcY
dmn\ZcgZfj^gZbZciEVD'3*%bb=\!l]^aZe=3,#'%VcYEV8D'1+%bb=\#
8V[[Z^cZdgi]Zde]naa^cZlZgZ\^kZcVhhddcVhedhh^WaZV[iZgW^gi]id^c[Vcih1(%lZZ`h
d[ \ZhiVi^dc VcY ^c bdgZ bVijgZ ^c[Vcih ^[ i]Zn ]VY VecZV# 6giZg^Va VcY igVchXjiVcZdjh
eVgi^Va egZhhjgZh d[ dmn\Zc VcY XVgWdc Y^dm^YZ VcY dmn\Zc hVijgVi^dc lZgZ bdc^idgZY#
G9HlVhYZÄcZY^ci]ZegZhZcXZd[Xa^c^XVa[ZVijgZhcZZYd[hjeeaZbZciVadmn\Zc!hiZgcVa
gZigVXi^dc!^ciZgXdhiVaVcYhjWXdhiVagZXZhh^dc!\gjci^c\VcYiVX]necZVVcYgVY^dad\^XVa
ÄcY^c\d[eddgajc\ZmeVch^dc#8]ZhiM"gVnhlZgZjhZYidVhhZhhi]ZhZkZg^ind[G9HVcY
ajc\ZmeVch^dc#8]ZhiM"gVnhlZgZgZk^ZlZYWnVgVY^dad\^hiVcYi]ZgZVY^c\lVhgZXdgYZY
^ci]ZYViVWVhZ#I]ZgVY^dad\^hiY^YcdieVgi^X^eViZ^ci]^hig^Va!dcani]ZjhjVaXa^c^XVa^c[dg"
bVi^dclVh\^kZc!VcY]Z$h]ZlVhcdiVlVgZd[i]ZigZVibZciVhh^\cbZci#>cijWVi^dcVcY
bZX]Vc^XVa kZci^aVi^dc lZgZ ^c^i^ViZY Z^i]Zg l]Zc i]Z VgiZg^Va dmn\Zc hVijgVi^dc kVajZh
lZgZ1--dgEVD'≤*%bb=\l]^aZgZXZ^k^c\;^D'≥%#)%XdggZhedcY^c\l^i]Vc6VED' gVi^d1%#''!dgi]ZEV8D'lVh3+%bb=\!l^i]Ve=1,#'%!dgi]ZgZlZgZbdgZi]Vc)
VecdZ^XZe^hdYZh^cdcZ]djgdgi]Z^c[VcicZZYZY3'Ze^hdYZhd[WV\\^c\eZg]djg#I]ZhZ
Xg^iZg^VlZgZV\gZZYdcWneVgi^X^eVi^c\Xa^c^X^VchWZ[dgZi]ZhijYnhiVgiZYVcYlZgZVeea^ZY
g^\dgdjhan# I]Z YZX^h^dc lVh bVYZ Wn Xa^c^X^Vch di]Zg i]Vc i]Z ^ckZhi^\Vidgh# L]ZcZkZg
dcZd[i]Z^ckZhi^\VidghlVhhjeZgk^h^c\i]ZC>8J!dcZd[i]Z^gXdaaZV\jZh[ZaadlhbVYZ
i]ZYZX^h^dcid^cijWViZdgcdi^ci]Z^c[Vcih^cXajYZY^ci]ZhijYn#Hjg[VXiVci8jgdhjg[!
8]^Zh^!>iVanlVh\^kZcVi&']djg^ciZgkVahl]ZcdcbZX]Vc^XVakZci^aVi^dcl^i]VbZVc
V^glVnegZhhjgZm;^D'gVi^d3'#6aa^c[Vcih^cijWViZY^ci]ZYZa^kZgngddbgZXZ^kZYhjg[VX"
iVcih]dgianV[iZgVgg^kVa^ci]ZC>8J!^[gZfj^gZY#6aa^c[Vcih^cijWViZYaViZgdc^ci]ZC>8J
gZXZ^kZYhjg[VXiVcih]dgianV[iZg^cijWVi^dc^[gZfj^gZY#>c[VcihlZgZZmijWViZYVhhddcVh
i]Z;^D'lVhaZhhi]Vc%#(VcYi]ZbZVcV^glVnegZhhjgZ1,Xb='D#>bbZY^ViZanV[iZgZmij"
WVi^dccVhVa8E6ElVhhiVgiZY#CVhVa8E6ElVhY^hXdci^cjZYl]Zci]ZcZdcViZgZbV^cZY
hiVWaZl^i]VXVe^aaVgnE8D'1+%bb=\!dmn\ZchVijgVi^dc3.'l^i]djihjeeaZbZciVgn
D'# L]Zc iV`Zc d[[ cVhVa 8E6E! ^c[Vcih lZgZ \^kZc hjeeaZbZciVa dmn\Zc jh^c\ adl Ådl
cVhVaXVccjaVZ^[hVijgVi^dc1.'#>[dmn\ZcgZfj^gZbZcihZmXZZYZY(%Z[[ZXi^kZ;^D'
'%!cVhVa8E6ElVhgZhiVgiZY#
I]Z eg^bVgn djiXdbZ bZVhjgZ lVh i]Z eZgXZciV\Z d[ ^c[Vcih ^cijWViZY l^i]^c ,' ]djgh
d[V\Z#HZXdcYVgndjiXdbZbZVhjgZhlZgZ^cijWVi^dc^ci]ZYZa^kZgngddb!i]ZcZZY[dg
bZX]Vc^XVa kZci^aVi^dc VcY hjg[VXiVci igZVibZci! YZVi] Yjg^c\ VYb^hh^dc dg 7E9 WVhZY
dc i]Z CVi^dcVa >chi^ijiZ d[ 8]^aY =ZVai] VcY =jbVc 9ZkZadebZci C>8=9 YZÄc^i^dc
'&!^cigVkZcig^XjaVg]Zbdgg]V\Z>K=!eZg^kZcig^XjaVgaZjXdbVaVX^VEKA!gZi^cdeVi]nd[
egZbVijg^inGDE!eZgh^hiZciYjXijhVgiZg^dhjhE96!VcYcZXgdi^o^c\ZciZgdXda^i^hC:8#
6aa^c[Vcih]VYXZgZWgVajaigVhdjcYhYdcZViaZVhii]gZZi^bZh^ci]ZÄghilZZ`VcYlZZ`an
i]ZgZV[iZg#
9ViVVgZgZedgiZYVhbZVchVcYH9hdgVhbZY^VchVcY^ciZgfjVgi^aZgVc\Z>FG^[Veegdeg^"
ViZ#HVbeaZh^oZVcVanh^hh]dlZYi]ViidYZiZXiVgZYjXi^dc^c^cijWVi^dcVcYbZX]Vc^XVa
kZci^aVi^dc[gdb+%id)%!l^i]VedlZgd[-%VcYVcVZggdgd[*ildiV^aZYiZhi!.,
^c[VcihlZgZgZfj^gZY[dgZVX]Vgbd[i]ZhijYn#6hdjgXZciZgVYb^ihVWdji'%%Za^\^WaZ
cZlWdgcheZgnZVgVcYlZZmeZXiZY'%d[i]ZeVgZcihidgZ[jhZXdchZci!i]ZYjgVi^dc
d[ i]Z hijYn lVh Zhi^bViZY Vi & nZVg VcY ( bdci]h# 6aa VcVanhZh lZgZ eZg[dgbZY dc Vc
^ciZci^dc"id"igZVi eg^cX^eaZ# I]Z WVhZa^cZ X]VgVXiZg^hi^Xh VcY djiXdbZ eVgVbZiZgh ^c i]Z
' igZVibZci \gdjeh lZgZ XdbeVgZY jh^c\ HijYZci¼h i iZhi [dg eVgVbZig^X VcY i]Z BVcc"
L]^icZnJiZhi[dgcdc"eVgVbZig^XXdbeVg^hdch[dgXdci^cjdjhkVg^VWaZh!VcYi]ZC'iZhi
[dgXViZ\dg^XVakVg^VWaZh#GZedgiZYEkVajZhVgZild"h^YZY!VcYE1#%*lVhXdch^YZgZYhiV"
i^hi^XVaanh^\c^ÄXVci#I]ZegZhZciZYdYYhgVi^dDGl^i]i]ZXdggZhedcY^c\.*XdcÄYZcXZ
^ciZgkVa^hVcVeegdm^bVi^dcidi]ZgZaVi^kZg^h`#
I]^hhijYnlVhVeegdkZYWni]ZAZ^YZcJc^kZgh^inBZY^XVa8ZciZg:i]^XhGZk^Zl8dbb^iiZZ#
Results
6idiVad['&,^cWdgckZgnegZiZgb^c[Vcih\ZhiVi^dcVaV\Z/'*"('lZZ`hlZgZVYb^iiZY
idi]ZC>8JWZilZZc6eg^a&!'%%*VcY?jan&'!'%%+#;^kZ^c[VcihlZgZZmXajYZYWZXVjhZ
d[hZkZgZXVgY^VXdggZhe^gVidgnVcdbVa^ZhdghncYgdbZh^cXdbeVi^WaZl^i]hjgk^kVa#;^kZ
lZgZcdi^cXajYZYWZXVjhZi]Z^geVgZcihY^YcdiXdchZciVciZcViVaan#I]ZZVgangZhe^gVidgn
bVcV\ZbZcid[i]Z'%,^c[Vcih^hh]dlc^c;^\&#I]ZYZbd\gVe]^XX]VgVXiZg^hi^Xhd[Wdi]
\gdjehVgZegZhZciZY^cIVWaZ&#
;ZlZg^c[Vcih^ci]Z:;JG8>\gdjelZgZ^cijWViZYl^i]^c,']djghd[V\Z(-$&%)(,kh#
*'$&%(*&0E2#%)0DG%#*,.*8>%#('"%#.-#>ci]Z:;JG8>\gdje,(,%d[&%)^c[Vcih
cZZYZYVegdadc\ZY^cÅVi^dc!))+%d[,(^c[VcihXdjaYWZhiVW^a^oZYV[iZg^cÅVi^dcd[
'%Xb='D!'.)%d[,(cZZYZYVhZXdcY^cÅVi^dcd['*Xb='D!VcY&-d[i]ZhZ'.+'
^c[VcihVahdcZZYZY^cijWVi^dc#CVhVa^ciZgb^iiZciedh^i^kZegZhhjgZkZci^aVi^dcdei^dcVa
V[iZghjhiV^cZY^cÅVi^dc^cXVhZd[VWhZci$^chj[ÄX^ZciWgZVi]^c\!lVhjhZY^c&*&)d[
&%)^c[Vcih#6abdhiVaad[i]ZhZ^c[Vcih&(d[&*]VYidWZ^cijWViZY^ci]ZYZa^kZgngddb#
HZXdcYVgndjiXdbZhVgZh]dlc^cIVWaZ'#I]ZYjgVi^dcd[kZci^aVidgnhjeedgi^cXajY^c\
cVhVa8E6ElVhh]dgiZg^ci]Z:;JG8>\gdjeXdbeVgZYidi]ZXdckZci^dcVa\gdjebZY^Vc
207very
preterm
neonates
included
Conventional103 EFURCI104
37
intubation 66M+B
37
none
18
intubation
73
neopuff+ENCPAP 31
none
16
none
21
NCPAP
21
NCPAP 8
none
1 3 1 10 Total52
17
none 14
NCPAP
0 5 15 Total38
DR
management
NICU
management
Intubation<
72hours
Figure 1#:VgangZhe^gVidgnbVcV\ZbZcid[i]Zildig^Va\gdjeh#
Table 1#9Zbd\gVe]^XX]VgVXiZg^hi^Xh#
8]dg^dVbc^dc^i^h/bViZgcVa[ZkZgl^i]ViaZVhidcZd[i]Z[daadl^c\hnbeidbh/aZjXdXnidh^h!iZcYZgcZhhd[
i]ZjiZgjh![ZiVaiVX]nXVgY^V![dja"hbZaa^c\Vbc^di^XÅj^Y0VciZcViVahiZgd^Yh/VcncjbWZgd[YdhZhd[hiZgd^Yh
[dg^cYjXi^dcd[[ZiVaajc\bVijgVi^dc0EEGDB2egZiZgbegZbVijgZgjeijgZd[i]ZbZbWgVcZh0>J<G2^cigV
jiZg^cZ\gdli]gZiVgYVi^dc#
Characteristic EFURCI
C2&%)
Conventional C2&%(
7^gi]lZ^\]i!\gVbh!bZVcH9 &(&&)%( &'.%(.'
<ZhiVi^dcVaV\Z!lZZ`h!bZVcH9 '.#)&#. '.#*&#.
BVaZ\ZcYZg!c *+*) *,**
JbW^a^XVaVgiZg^Vae=!bZVcH9 ,#'*%#%. ,#'*%#&%
EgZcViVahiZgd^Yh!c -*-' -(-&
8]dg^dVbc^dc^i^h!c &'&' --
EEGDB!c '&'% '-',
EgZ"ZXaVbeh^V!c '('' '+'*
;ZiVaY^higZhh!c '('' &*&*
>J<G!c &+&* &.&-
8VZhVgZVchZXi^dc!c )-)+ (-(,
*b^c6e\VghXdgZ!bZY^Vc>FG .-". -,".
H^c\aZidch!c (+(* ),)+
YVnh>FG/'#,%#*"&%kh)#(%#*"'%0E2#%&#>ci]ZhjW\gdjed[^c[VcihkZci^aViZYl^i]^c
,' ]djgh d[ V\Z! idiVa i^bZ d[ kZci^aVidgn hjeedgi ^cXajY^c\ cVhVa 8E6E lVh aZhh ^c i]Z
:;JG8>i]Vc^ci]ZXdckZci^dcVa\gdjebZY^VcYVnh>FG/&%)"&.#*kh&**#+"(+#(0E2
#%)#I]ZÄghie=!EV8D'VcY;^D'jedcVgg^kVa^ci]ZC>8JVcYbVm^bjbd[;^D'jhZYlZgZ
h^b^aVg^cWdi]\gdjehe=,#'(£%#&^cWdi]\gdjeh0EV8D'+#.£&#)kh+#-£&#+`EV0;^D'
%#('£%#&,kh#%#('£%#&.0bVm^bjb;^D'jhZY%#)£%#'*kh#%#(+£%#&.#I]Z^cX^YZcXZd[
G9HlVhaZhh^ci]Z:;JG8>"\gdjeXdbeVgZYidi]ZXdckZci^dcVa\gdje(.(-d[&%)
kh#*+*)d[&%(0E2#%&*0DG%#*%.*8>%#'."%#--#I]Z^cX^YZcXZd[ecZjbdi]dgVXZh
lVhcdih^\c^ÄXVciY^[[ZgZciWZilZZci]Z\gdjeh&&d[&%)kh#,,d[&%(0E2#%,0DG
%#&(.*8>%#%'"&#&%#
Edhi"]dXVcVanh^hd[\ZhiVi^dcVaV\ZhjW\gdjeh;^\'h]dlZYi]Vii]Z\gZViZhiZ[[ZXilVh
Vi '-"(% lZZ`h¼ \ZhiVi^dc ^cijWVi^dc 1 ,' ]djgh/ &+ (' d[ *% kh ', *. d[ ),0 E 2
#%&0DG%#((.*8>%#&)"%#,+#>ci]ZhjW\gdje1'-lZZ`h¼\ZhiVi^dc![ZlZg^c[VcihlZgZ
^cijWViZY^ci]ZYZa^kZgngddb-)%d['%kZghjh&*,.d[&.0E2#%'0DG%#&-8>%#%)"
%#,)!Wjii]ZgZlVhcdh^\c^ÄXVciY^[[ZgZcXZ^c^cijWVi^dc1,']djgh&(+*d['%kh&*
,.d[&.0cdih^\c^ÄXVci#
Table 2#HZXdcYVgndjiXdbZh/7E92WgdcX]dejabdcVgnYnheaVh^V0E962eViZciYjXijhVgiZg^dhjh0C:8
2 cZXigdi^o^c\ ZciZgdXda^i^h0 GDE 2 gZi^cdeVi]n d[ egZbVijg^in0 >K= 2 ^cigVkZcig^XjaVg ]Zbdgg]V\Z0 EKA 2
eZg^kZcig^XjaVgaZjXdbVaVX^V#
Secondary outcomes EFURCI
N = 104
Conventional N = 103
Univariate anaysis (P)
Odds Ratio (95% CI)
>cijWVi^dcYZa^kZgngddb!c &-&, (,(+ %#%%' %#(,%#'%"%#,%
IdiVaeZg^dYd[bZX]Vc^XVakZc"
i^aVi^dcd[^cijWViZY^c[Vcih1,'
]djghd[V\Z!YVnh!bZY^Vc>FG
'#*&"-#(
C2(-
)#*'"&&#*
C2*'
%#'
IdiVaeZg^dYd[C8E6Ed[idiVa
\gdje!YVnh!bZY^Vc>FG
'%#("- '%"&& %#%)
Hjg[VXiVciYdhZh!bZVcH9 %#)%#- %#+&#% %#(
Hjg[VXiVci3&YdhZ!c &%$&%)&% ''$&%('& %#%' %#(.%#&-"%#--
BdgiVa^in!c '' )) %#)
7E9idiVa!c '''' ()() %#%*
7E9bdYZgViZ"hZkZgZ!c .. &.&. %#%) %#)&8>%#&-"%#.+
E96cZZY^c\igZVibZci!c '&'% &+&+ %#)
C:8≥hiV\Z'!c %% && %#*
GDE3\gVYZ(!c %% && %#*
>K=\gVYZ( )!c ,, (( %#(
8nhi^XEKA!c '' ** %#)
2eZgXZciV\Zd[hjgk^kdgh
Discussion
I]^h gVcYdb^oZY XdcigdaaZY ig^Va h]dlh i]Vi kZgn egZiZgb ^c[Vcih cZZY aZhh ^cijWVi^dc!
bZX]Vc^XVa kZci^aVi^dc! YVnh dc cVhVa 8E6E VcY ]VY aZhh G9H! V^g aZV`h VcY bdYZgViZ"
id"hZkZgZ 7E9 l]Zc V egdadc\ZY ^cÅVi^dc i]gdj\] V cVhde]Vgnc\ZVa ijWZ! ^bbZY^ViZan
[daadlZY Wn cVhVa 8E6E :;JG8>! ^h jhZY ^chiZVY d[ WV\ VcY bVh` kZci^aVi^dc VcY cVhVa
8E6E dc VYb^hh^dc id i]Z C>8J# IgZVibZci l^i] hjg[VXiVci lVh cdi Y^[[ZgZci Wji [ZlZg
^c[VcihgZXZ^kZYbdgZi]VcdcZYdhZ^ci]Z:;JG8>\gdje#I]ZhZYViVhj\\Zhii]Vii]^hajc\
gZXgj^ibZcibVcZjkZghjhiV^cZY^cÅVi^dc[daadlZYWncVhVa8E6E^hVbdgZZ[[ZXi^kZbVc"
V\ZbZcihigViZ\n[dgkZci^aVi^dcd[kZgnegZiZgb^c[Vcih^ci]ZYZa^kZgngddb#
I]^h ^h i]Z Äghi gVcYdb^oZY XdcigdaaZY ig^Va ^c l]^X] i]Z :;JG8> kZci^aVi^dc higViZ\n ^h
XdbeVgZYl^i]WV\VcYbVh`kZci^aVi^dcVYk^hZYWn^ciZgcVi^dcVacZdcViVagZhjhX^iVi^dc
\j^YZa^cZh (# Djg gZhjaih VgZ Xdch^hiZci l^i] i]Z ÄcY^c\h ^c i]Z gZigdheZXi^kZ gZedgi d[
A^cYcZgZiVa#!l]dXdbeVgZYi]ZhVbZajc\gZXgj^ibZcibVcdZjkgZVcYZVgancVhVa8E6E^c
0 5 10 15 20 25 30
DR < 72 hours DR <72 hours DR < 72 hours
conv conv
conv
40%
79%
65%
79%
16%
37%
32%
60%
6%
13%
16%
16%
< 28 weeks 28-30 weeks >30 weeks
number of patients
Figure 2#CjbWZgd[^c[Vcih^cijWViZY^cYZa^kZgngddbVcY1,']djgheadiiZYV\V^chihjW\gdjeh\ZhiV"
i^dcVaV\Z!:;JG8>khXdckZci^dcVa#
L]^iZ2:;JG8>0WaVX`2XdckZci^dcVa#
&..+l^i]ZaZXi^kZ^cijWVi^dcVh]^hidg^XVaXdcigda^c&..)&%#I]Z^ghijYn\gdjeXdch^hiZY
d[hbVaaZg^c[VcihbZVc\ZhiVi^dcVaV\Z'+#.lZZ`hVcYW^gi]lZ^\]i,(.\gVbh^ci]Z^ciZg"
kZci^dc\gdje!Wjii]Z^g^cijWVi^dcgViZ^ci]ZYZa^kZgngddbYZXgZVhZY[gdb-)id)%
E 1 #%%& VcY , lZgZ cZkZg ^cijWViZY ^c i]Z &..) \gdje XdbeVgZY l^i] '* ^c &..+
E1#%&#I]ZgViZd[bdYZgViZ"id"hZkZgZ7E9gViZYZXgZVhZY[gdb('id&'E1%#%*
&%#8dch^hiZcil^i]djggZhjaih!cd]Vgb[jaZ[[ZXihd[i]Z^gcZlVeegdVX]lZgZ[djcY0[dg
ZmVbeaZ!cd^cXgZVhZYgViZhd[>K=dgecZjbdi]dgVm#
Djgig^Vah]dlZYi]Vii]Z:;JG8>VeegdVX]VaadlhbdgZ^c[VcihidWgZVi]ZYjg^c\i]ZÄghi
YVnh l^i] ZVgan cVhVa 8E6E VadcZ# :Vgan cVhVa 8E6E VcY hZaZXi^kZ hjg[VXiVci igZVibZci ^h
VcVXXZeiZYVaiZgcVi^kZ!VcYgZigdheZXi^kZhijY^Zh]VkZh]dlcaZhhbdgW^Y^inl]ZcZVgan
cVhVa8E6E^hjhZY^ci]ZYZa^kZgngddbidVkd^Y^cijWVi^dc!ZkZc^[8E6E[V^ahaViZgdcVcY
^cijWVi^dc[daadlh&0)0''"')#BdgZegdheZXi^kZig^VahVgZjcYZglVn!Wjii]ZgZ^hXjggZcian
^chj[ÄX^Zci^c[dgbVi^dcidZkVajViZi]ZZ[[ZXi^kZcZhhd[egde]naVXi^X2ZVgancVhVa8E6E^c
kZgnegZiZgb^c[Vcih'*#;^cZgZiVa#[djcY!^cV[ZVh^W^a^inhijYnVbdc\^c[Vcih1'-lZZ`h¼
\ZhiVi^dcgZXZ^k^c\8E6E$E::Edgcdi^ci]ZYZa^kZgngddb!cdY^[[ZgZcXZh^c^cijWVi^dcgViZ
dghjg[VXiVcijhZ'+#
6c^bVahijY^Zh]VkZh]dlci]ViVc^cÅVbbVidgnegdXZhhXVcWZ^c^i^ViZYl^i]i]ZÄghiaVg\Z
bVcjVa WgZVi]h Yjg^c\ gZhjhX^iVi^dc VcY bVn jai^bViZan aZVY id 7E9 *".# KZgn egZiZgb
^c[VcihbVncdiWZVWaZid\ZcZgViZ]^\]Zcdj\]^che^gVidgnegZhhjgZhidVX]^ZkZZ[[ZXi^kZ
ajc\ZmeVch^dcVcYi]ZgZ[dgZcZZYgZhe^gVidgnhjeedgi',0'-#6egdadc\ZY^cÅVi^dci^bZ!
jhZY^[hedciVcZdjhWgZVi]^c\^h^cVYZfjViZ!bVn]Zaei]ZegZiZgb^c[VciiddkZgXdbZi]Z
adc\i^bZXdchiVcid[Va^fj^Y"ÄaaZYajc\VcYegZkZcii]ZjhZd[ediZci^VaanYVc\Zgdjh!]^\]
^che^gVidgnegZhhjgZh'.0(%#
I]Z WZcZÄX^Va Z[[ZXih d[ V hjhiV^cZY ^cÅVi^dc lZgZ cdi XdcÄgbZY ^c gZXZci gVcYdb^oZY
XdcigdaaZY ig^Vah (&0('# A^cYcZg Zi Va# XdbeVgZY V &* hZXdcYh ^cÅVi^dc id ^ciZgb^iiZci
bVcYVidgnkZci^aVi^dc^c^c[Vcih1'.lZZ`h¼\ZhiVi^dc#8dch^hiZcil^i]djgÄcY^c\hi]ZgZ
lVh cd Y^[[ZgZcXZ gZ\VgY^c\ i]Z ^cijWVi^dc gViZ 1 ,' ]djgh ^c i]^h \gdje d[ ^c[Vcih (&#
=Vga^c\ Zi Va# jhZY V Y^[[ZgZci bZi]dY Wn XdbeVg^c\ V hjhiV^cZY ^cÅVi^dc d[ * hZXdcYh
l^i] V XdckZci^dcVa ^cÅVi^dc d[ ' hZXdcYh ('# 7di] hijY^Zh aVX`ZY edlZg WZXVjhZ d[
hbVaa hVbeaZ h^oZh# Id bV^ciV^c Vc VYZfjViZ ajc\ kdajbZ V[iZg ^cÅVi^dc VcY id egZkZci
ViZaZXigVjbV! Veea^XVi^dc d[ E::E$8E6E ^h cZXZhhVgn (("(*# HiVgi^c\ i^bZ d[ ZVgan cVhVa
8E6E ^h ^bedgiVci! WZXVjhZ V cdcXdbea^Vci! hjg[VXiVci"YZÄX^Zci ajc\ ]Vh V iZcYZcXn id
XdaaVehZVcYajc\kdajbZ^hcdibV^ciV^cZY^[8E6E$E::E^hcdi\^kZc^bbZY^ViZanid`ZZe
i]Zajc\deZc#HZa["^cÅVi^c\WV\hbVnYZa^kZg^chj[ÄX^ZcidgZmXZhh^kZan]^\]eZV`^che^"
gVidgnegZhhjgZVcYb^c^bVaE::E!aZVY^c\idkdajigVjbVVcYViZaZXigVjbV!ZkZcl]ZcV
bVcdbZiZg^h^cXdgedgViZY&)0&-0&.#6egZhhjgZ"a^b^iZYbZX]Vc^XVaYZk^XZl^i]VI"e^ZXZ
YZa^kZghbdgZXdch^hiZcieZV`^che^gVidgnegZhhjgZVcYE::EVcY^hWZiiZgVWaZidYZa^kZg
VhjhiV^cZY^cÅVi^dcXdbeVgZYidVhZa["^cÅVi^c\WV\&("&+#6cdi]ZgVYkVciV\Z^hi]Vi^i
^hZVhnidjhZVcYi]ZgZWn^cXgZVhZhi]ZX]VcXZd[Z[[ZXi^kZkZci^aVi^dc!ZkZc^ci]Z]VcYh
d[^cZmeZg^ZcXZYe]nh^X^Vch&)#>i^hY^[ÄXjaiidYZa^kZgE::El^i]V[VXZbVh`Vhi]ZhZVa
XVc WgZV` kZgn ZVh^an &*0(+# Id Vkd^Y i]^h E::E aZV`V\Z! V cVhde]Vgnc\ZVa ijWZ ^h jhZY
Vh^ciZg[VXZ#9ViV^ha^b^iZY!WjiVgVcYdb^oZYig^Vah]dlZYh^\c^ÄXVciaZhh^cijWVi^dch^c
cZdcViZhl^i]bdYZgViZVhe]nm^V&,#6cdi]ZgVYkVciV\Zd[jh^c\VcVhde]Vgnc\ZVaijWZ
Vh^ciZg[VXZ^hi]Vi8E6E$E::EXVcWZXdci^cjZYkZgnZVh^anVcYY^gZXianV[iZggZhjhX^iVi^dc#
I]ZgZlVhVh^\c^ÄXVciYZXgZVhZd[G9H^ci]Z:;JG8>\gdje#6edhh^WaZZmeaVcVi^dc[dgi]^h
^hi]Vii]Z:;JG8>^ciZgkZci^dclVhZ[[ZXi^kZ^cegZhZgk^c\hjg[VXiVci#9jg^c\^c^i^VaVhhZhh"
bZcid[VkZgnegZiZgb^c[Vci^ci]ZYZa^kZgngddb^i^hY^[ÄXjaiidY^[[ZgZci^ViZWZilZZcgZhe^"
gVidgnY^higZhhYjZidigVch^i^dcVaegdWaZbhdgG9HVcYVig^Vad[ZVgancVhVa8E6Eegdk^YZh
i^bZidhdakZi]^hegdWaZb#>ci]ZXdckZci^dcVa\gdje!hdbZegZiZgbcZdcViZhl]dlZgZ
^cijWViZY VcY kZci^aViZY ^c i]Z YZa^kZgn gddb bVn ]VkZ ]VY igVch^i^dcVa egdWaZbh! Wji
YZkZadeZYG9HhZXdcYVgnidajc\^c_jgn#
HdbZkZgnegZiZgb^c[Vcih[V^aZYZVgancVhVa8E6EaViZgdc!ZheZX^Vaan^c[Vcih1'-lZZ`h¼
\ZhiVi^dc l^i] G9H# I]Z bVm^bjb aZkZa d[ 8E6E jhZY lVh - Xb ='D VcY V ]^\]Zg aZkZa
d[ 8E6E dg V gZXgj^ibZci bVcdZjkgZ Yjg^c\ 8E6E b^\]i ]VkZ gZYjXZY aViZg igZVibZci
[V^ajgZ#6cdi]ZgZmeaVcVi^dc[dgZVgancVhVa8E6E[V^ajgZbVn]VkZWZZci]Zadli]gZh]daY
[dg^cijWVi^dcVcYhjg[VXiVciigZVibZciVidjg^chi^iji^dc;^D'3)%dgEV8D'3-#%`EV#
I]^hadli]gZh]daYlVhX]dhZcidegZkZcii]ZY^hVYkVciV\ZdjhVcYYZaZiZg^djhZ[[ZXihd[
VaViZgZhXjZl^i]hjg[VXiVciigZVibZci;^D'≥%#+^c^c[Vcihl]dVgZfj^X`anYZiZg^dgVi^c\
WZXVjhZ d[ G9H &&0(,# Egde]naVXi^X dg ZVgan hjg[VXiVci igZVibZci d[ cZdcViZh gZfj^g^c\
bZX]Vc^XVa kZci^aVi^dc ^h bdgZ Z[[ZXi^kZ i]Vc aViZ gZhXjZ igZVibZci (-0(.! Wji ]Vh i]Z
ediZci^Va Y^hVYkVciV\Z i]Vi hdbZ egZiZgb cZdcViZh VgZ igZViZY l]d VgZ hjg[VXiVci hj["
ÄX^ZciVcYl^aacdiYZkZadeG9H#
I]ZgZVgZa^b^iVi^dchd[i]^hgVcYdb^oZYXdcigdaaZYig^Va#IdgZVX]i]ZbdhiZ[[ZXi^kZVeea^"
XVi^dc d[ Vc deZc ajc\ higViZ\n! lZ XdbW^cZY hZkZgVa iZX]c^fjZh bZX]Vc^XVa egZhhjgZ"
a^b^iZYYZk^XZ!egdadc\ZY^cÅVi^dc!cVhde]Vgnc\ZVaijWZVh^ciZg[VXZVcYY^gZXicVhVa8E6E
^ci]ZYZa^kZgngddb#I]^hbV`Zh^i^bedhh^WaZidYZiZgb^cZl]^X][VXidgXdcig^WjiZhbdhi
idi]ZÄcVagZhjai#>ci]ZXdckZci^dcVabZi]dYV]^\]ZgegZhhjgZ^hjhZY^c^i^VaaniddeZci]Z
ajc\#6ai]dj\]i]^hiZX]c^fjZ^h^cV\gZZbZcil^i]i]Z^ciZgcVi^dcVa\j^YZa^cZh!i]^hXdjaY
]VkZXdcig^WjiZYidi]ZeddgZgdjiXdbZ#7^VhZh^ci]ZbVcV\ZbZciXdjaY]VkZdXXjggZY
Vh i]Z hijYn lVh cdi Wa^cYZY VcY i]Z hiV[[ eZg[dgb^c\ i]Z hijYn Vahd idd` XVgZ d[ i]Z
^c[VcihaViZgdc#=dlZkZg!i]ZYZX^h^dcid^cijWViZlVhbVYZWnXa^c^X^Vchdi]Zgi]Vci]Z
^ckZhi^\Vidgh#L]ZcZkZgdcZd[i]Z^ckZhi^\VidghlVhhjeZgk^h^c\!dcZd[i]Z^gXdaaZV\jZh
[ZaadlbVYZi]ZYZX^h^dcid^cijWViZdgcdi^ci]Z^c[Vcih^cXajYZY^ci]ZhijYn#LZig^ZY
idb^c^b^oZi]ZhZW^VhZhWnbV^ciV^c^c\hig^XiXg^iZg^VVcYYZÄc^i^dchYjg^c\i]Zig^Va#I]^h
ig^ValVheZg[dgbZY^cVh^c\aZXZciZgl^i]ZmeZg^ZcXZYcZdcVidad\^hih!igV^cZY^ci]ZiZX]"
c^fjZhd[:;JG8>!VcY^i^hedhh^WaZi]Vidi]Zghb^\]icdi\Zii]ZhVbZgZhjaih#
A^b^ihd[k^VW^a^in^ci]ZCZi]ZgaVcYhVgZhZiVi'*lZZ`h¼\ZhiVi^dc!hdi]ZgZhjaihd[i]^hhijYn
XVccdiWZVeea^ZYid^c[Vcih1'*lZZ`h¼\ZhiVi^dc#LZYZiZXiZYa^iiaZZ[[ZXid[i]Z:;JG8>"
VeegdVX]^c^c[Vcih1'-lZZ`h¼\ZhiVi^dc!Wjii]^hig^ValVhcdiYZh^\cZYVcYedlZgZYid
YZiZXiVY^[[ZgZcXZ^ci]^hhjW\gdje#L]Zi]Zgi]Z:;JG8>VeegdVX]^hbdgZZ[ÄX^ZciVcY
aZhh^c_jg^djhVbdc\i]ZbdhikjacZgVWaZegZiZgb^c[Vcih!i]Vi^h!i]dhZl^i]V\ZhiVi^dcVa
V\Zd['(id',lZZ`h!cZZYh[jgi]ZgZkVajVi^dc#
>cXdcXajh^dc!i]^hgVcYdb^oZYXdcigdaaZYig^VaXdbeVg^c\ildkZci^aVidgnVeegdVX]Zh]Vh
h]dlci]Vii]ZXdbW^cVi^dcd[VhjhiV^cZY^cÅVi^dcWgZVi]VcYZVgancVhVa8E6Ehjeea^ZY
WnVbZX]Vc^XVaegZhhjgZ"a^b^iZYYZk^XZVcYVcVhde]Vgnc\ZVaijWZVh^ciZg[VXZ^hVbdgZ
Z[ÄX^Zci higViZ\n i]Vc gZeZViZY bVcjVa ^cÅVi^dch l^i] V hZa["^cÅVi^c\ WV\ VcY bVh` [dg
i]ZZVgangZhe^gVidgnbVcV\ZbZcid[kZgnegZiZgb^c[Vcih^ci]ZYZa^kZgngddb#:VgancVhVa
8E6E Vahd Wjnh i^bZ id Y^[[ZgZci^ViZ WZilZZc G9H VcY igVch^i^dc egdWaZbh VcY gZYjXZh
i]Z cjbWZg d[ egZiZgb ^c[Vcih ^cijWViZY jccZXZhhVg^an# BdgZ ^ckZhi^\Vi^dc ^h cZZYZY id
YZiZgb^cZl]^X]eVgid[i]Z:;JG8>VeegdVX]Xdcig^WjiZYi]Zbdhi#6ai]dj\]i]^hig^Va]Vh
h]dlci]Z^bedgiVcXZd[ZVgangZhe^gVidgnbVcV\ZbZci[dgejabdcVgndjiXdbZ7E9^c
egZiZgb^c[Vcih!bdgZgVcYdb^oZYig^Vah!ZheZX^Vaan^c^c[Vcih1'-lZZ`hd[\ZhiVi^dc!VgZ
cZZYZYidYZkZadeVcdei^bVahigViZ\n[dgZmigZbZanegZiZgb^c[Vcih#
Acknowledgement
LZi]Vc`Egd[#8da^c?#BdgaZn[dg]^hXg^i^XVagZk^Zld[i]^hbVcjhXg^ei#
References
&# KVcBVgiZgA?!6aagZY:C!EV\VcdBZiVa#9dXa^c^XVabVg`Zghd[WVgdigVjbVVcYdmn\Zcidm^X^inZmeaV^c
^ciZg]dhe^iVakVg^Vi^dc^cgViZhd[X]gdc^Xajc\Y^hZVhZ4I]ZCZdcVidad\n8dbb^iiZZ[dgi]Z9ZkZade"
bZciVaCZildg`#EZY^Vig^Xh'%%%0&%*+/&&.)"&'%&#
'# <gZZcdj\]6#JeYViZdcbdYVa^i^Zhd[bZX]Vc^XVakZci^aVidgh#6gX]9^h8]^aY;ZiVaCZdcViVa:Y'%%'0
-,&/;(";+#
(# I]Z>ciZgcVi^dcVaA^V^hdc8dbb^iiZZdcGZhjhX^iVi^dc>A8DGXdchZchjhdchX^ZcXZl^i]igZVibZcigZX"
dbbZcYVi^dch[dgeZY^Vig^XVcYcZdcViVaeVi^Zcih/cZdcViVagZhjhX^iVi^dc#EZY^Vig^Xh'%%+0&&,*/Z.,-"
Z.--#
)# 6an=!BVhhVgd6C!EViZa@ZiVa#>h^ihV[Zgid^cijWViZegZbVijgZ^c[Vcih^ci]ZYZa^kZgngddb4EZY^Vig^Xh
'%%*0&&*+/&++%"&++*#
*# 7_dg`ajcYA?!>c\^bVghhdc?!8jghiZYiIZiVa#BVcjVakZci^aVi^dcl^i]V[ZlaVg\ZWgZVi]hViW^gi]Xdbegd"
b^hZhi]Zi]ZgVeZji^XZ[[ZXid[hjWhZfjZcihjg[VXiVcigZeaVXZbZci^c^bbVijgZaVbWh#EZY^VigGZh&..,0
)'(/()-"(**#
+# 7_dg`ajcY A?! >c\^bVghhdc ?! 8jghiZYi I Zi Va gZXgj^ibZci Vi W^gi] YdZh cdi ^begdkZ ajc\ [jcXi^dc ^c
^bbVijgZaVbWhgZXZ^k^c\hjg[VXiVci#6XiV6cVZhi]Zh^daHXVcY'%%&0)*-/.-+"..(#
,# >c\^bVghhdc?!7_dg`ajcYA?!8jghiZYiIZiVa#>cXdbeaZiZegdiZXi^dcWnegde]naVXi^Xhjg[VXiVciV\V^chii]Z
VYkZghZZ[[ZXihd[aVg\Zajc\^cÅVi^dchViW^gi]^c^bbVijgZaVbWh#>ciZch^kZ8VgZBZY'%%)0(%,/&))+"
&)*(#
-# >`Z\Vb^B!@VaaVejgH!B^X]cV?ZiVa#Ajc\^c_jgnVcYhjg[VXiVcibZiVWda^hbV[iZg]neZgkZci^aVi^dcd[
egZbVijgZaVbWh#EZY^VigGZh'%%%0),(/(.-")%)#
.# LVYV@!?dWZ6=!>`Z\Vb^B#I^YVakdajbZZ[[ZXihdchjg[VXiVciigZVibZcigZhedchZhl^i]i]Z^c^i^Vi^dc
d[kZci^aVi^dc^cegZiZgbaVbWh#?6eeaE]nh^da&..,0-()/&%*)"&%+&#
&%# A^cYcZgL!KdhhWZX`H!=jbbaZg=ZiVa#9Za^kZgngddbbVcV\ZbZcid[ZmigZbZanadlW^gi]lZ^\]i
^c[Vcih/hedciVcZdjhWgZVi]^c\dg^cijWVi^dc4EZY^Vig^Xh&...0&%(*Ei&/.+&".+,#
&&# KZgYZg=!6aWZgihZcE!:WWZhZc;ZiVa#CVhVaXdci^cjdjhedh^i^kZV^glVnegZhhjgZVcYZVganhjg[VXiVci
i]ZgVen[dggZhe^gVidgnY^higZhhhncYgdbZ^ccZlWdgchd[aZhhi]Vc(%lZZ`h¼\ZhiVi^dc#EZY^Vig^Xh&...0
&%('/:')#
&'# L^ciZgbVg`E!IdahV?;!KVcBZaaZ<ZiVa#Adc\"iZgbdjiXdbZd[egZiZgb^c[VcihigZViZYl^i]cVhVaXdc"
i^cjdjhedh^i^kZV^glVnegZhhjgZ#:jg?EZY^Vig'%%+0&++*/),("-(
&(# ;^cZgCC!G^X]L!8gV[i6ZiVa#8dbeVg^hdcd[bZi]dYhd[WV\VcYbVh`kZci^aVi^dc[dgcZdcViVagZhjhX^"
iVi^dc#GZhjhX^iVi^dc'%%&0).(/'.."(%*#
&)# =jhhZnH<!GnVc86!Bjge]n7E#8dbeVg^hdcd[i]gZZbVcjVakZci^aVi^dcYZk^XZhjh^c\Vc^cijWViZY
bVccZfj^c#6gX]9^h8]^aY;ZiVaCZdcViVa:Y'%%)0-.+/;).%";).(#
&*# D¼9dccZaa8E!9Vk^hE<!AVjGZiVa#CZdcViVagZhjhX^iVi^dc'/6cZkVajVi^dcd[bVcjVakZci^aVi^dcYZk^XZh
VcY[VXZbVh`h#6gX]9^h8]^aY;ZiVaCZdcViVa:Y'%%*0.%*/;(.'";(.+##
&+# 7ZccZiiH!;^cZgCC!G^X]LZiVa#6XdbeVg^hdcd[i]gZZcZdcViVagZhjhX^iVi^dcYZk^XZh#GZhjhX^iVi^dc
'%%*0+,&/&&("&&-#
&,# 8VeVhhdA!8VeVhhd6!GV^bdcY^;ZiVa#6gVcYdb^oZYig^VaXdbeVg^c\dmn\ZcYZa^kZgndc^ciZgb^iiZci
edh^i^kZegZhhjgZl^i]cVhVaXVccjaVZkZghjh[VX^VabVh`^ccZdcViVaeg^bVgngZhjhX^iVi^dc#6XiVEVZY^Vig
'%%*0.)'/&.,"'%%#
&-# @V^cOC!7ZgYZ87!7Zc_Vb^cE@ZiVa#EZg[dgbVcXZd[eZY^Vig^XgZhjhX^iVi^dcWV\hVhhZhhZYl^i]Vc^c[Vci
ajc\h^bjaVidg#6cZhi]6cVa\&..(0,,'/'+&"'+)#
&.# ;^cZg CC! 7Vgg^c\idc @?! 6a ;VYaZn ; Zi Va# A^b^iVi^dch d[ hZa["^cÅVi^c\ gZhjhX^iVidgh# EZY^Vig^Xh &.-+0
,,(/)&,")'%#
'%# LVah] B! :c\aZ L! AVeidd` 6 Zi Va# Dmn\Zc YZa^kZgn i]gdj\] cVhVa XVccjaVZ id egZiZgb ^c[Vcih/ XVc
egVXi^XZWZ^begdkZY4EZY^Vig^Xh'%%*0&&+)/-*,"-+&#
'&# ?dWZ6=!7VcXVaVg^:#7gdcX]dejabdcVgnYnheaVh^V#6b?GZhe^g8g^i8VgZBZY'%%&0&+(,/&,'("&,'.#
''# 6an=!BVhhVgd6C!:aBd]VcYZh66#8VcYZa^kZgngddbbVcV\ZbZci^beVXii]ZaZc\i]d[]dhe^iVahiVn
^cegZbVijgZ^c[Vcih4?EZg^cVida'%%+0'+&%/*.("*.+#
'(# 6kZgnB:!IddaZnL=!@ZaaZg?7ZiVa#>hX]gdc^Xajc\Y^hZVhZ^cadlW^gi]lZ^\]i^c[VcihegZkZciVWaZ46
hjgkZnd[Z^\]iXZciZgh#EZY^Vig^Xh&.-,0,.&/'+"(%#
')# 6bbVg^6!Hjg^B!B^a^hVka_Zk^XKZiVa#KVg^VWaZh6hhdX^ViZYl^i]i]Z:Vgan;V^ajgZd[CVhVa8E6E^cKZgn
Adl7^gi]LZ^\]i>c[Vcih#?EZY^Vig'%%*0&),(/()&"(),#
'*# HjWgVbVc^VbE!=ZcYZghdc"HbVgi9?!9Vk^hE<#Egde]naVXi^XcVhVaXdci^cjdjhedh^i^kZV^glVnhegZhhjgZ
[dgegZkZci^c\bdgW^Y^inVcYbdgiVa^in^ckZgnegZiZgb^c[Vcih#8dX]gVcZ9ViVWVhZHnhiGZk'%%%0'/
89%%&')(#
'+# ;^cZgCC!8VgadL6!9jVgVHZiVa#9Za^kZgngddbXdci^cjdjhedh^i^kZV^glVnegZhhjgZ$edh^i^kZZcY"Zme^"
gVidgnegZhhjgZ^cZmigZbZanadlW^gi]lZ^\]i^c[Vcih/V[ZVh^W^a^inig^Va#EZY^Vig^Xh'%%)0&&)(/+*&"+*,#
',# <Zg]VgYiI!7VcXVaVg^:#8]ZhilVaaXdbea^VcXZ^c[jaa"iZgbVcYegZbVijgZ^c[Vcih#6XiVEVZY^VigHXVcY
&.-%0+.(/(*."(+)#
'-# =ZaYi<E!BX>agdnB7#9ncVb^Xhd[X]ZhilVaa^cegZiZgb^c[Vcih#?6eeaE]nh^da&.-,0+'&/&,%"&,)#
'.# KnVh =! B^acZg 69! =de`^c >: Zi Va# E]nh^dad\^X gZhedchZh id egdadc\ZY VcY hadl"g^hZ ^cÅVi^dc ^c i]Z
gZhjhX^iVi^dcd[i]ZVhe]nm^ViZYcZlWdgc^c[Vci#?EZY^Vig&.-&0..)/+(*"+(.#
(%# =^gYB;!<gZZcdj\]6!<Vbhj=G#>cÅVi^c\egZhhjgZh[dgZ[[ZXi^kZgZhjhX^iVi^dcd[egZiZgb^c[Vcih#:Vgan
=jb9Zk&..&0'+&/+.",'#
(&# A^cYcZgL!=d\Za?!Ed]aVcYi;#HjhiV^cZYegZhhjgZ"XdcigdaaZY^cÅVi^dcdg^ciZgb^iiZcibVcYVidgnkZc"
i^aVi^dc ^c egZiZgb ^c[Vcih ^c i]Z YZa^kZgn gddb4 6 gVcYdb^oZY! XdcigdaaZY ig^Va dc ^c^i^Va gZhe^gVidgn
hjeedgik^VcVhde]Vgnc\ZVaijWZ#6XiVEVZY^Vig#'%%*0.)(/(%(".#
('# =Vga^c\ 6:! 7ZgZh[dgY BL! K^cXZ <H Zi Va# 9dZh hjhiV^cZY ajc\ ^cÅVi^dc Vi gZhjhX^iVi^dc gZYjXZ ajc\
^c_jgn^ci]ZegZiZgb^c[Vci46gX]9^h8]^aY;ZiVaCZdcViVa:Y'%%*0.%*/;)%+";)&%#
((# 8aVg`G=#Hjeedgid[\VhZmX]Vc\Z^ci]ZYZa^kZgngddbVcYWZndcY/]dlYdlZVkd^Y]jgi^c\i]ZWVWn
lZhZZ`idhVkZ48a^cEZg^cVida&...0'+(/++."+-&#
()# >`Z\Vb^ B! GZWZaad 8B! ?dWZ 6=# Hjg[VXiVci ^c]^W^i^dc Wn eaVhbV/ \ZhiVi^dcVa V\Z VcY hjg[VXiVci
igZVibZciZ[[ZXih^cegZiZgbaVbWh#?6eeaE]nh^da&..+0-&+/'*&,"'*''#
(*# Jeidc 8?! B^acZg 69# :cYdigVX]ZVa gZhjhX^iVi^dc d[ cZdcViZh jh^c\ V gZWgZVi]^c\ WV\#6gX] 9^h 8]^aY
&..&0++/(.")'#
(+# B^acZg 69! KnVh =! =de`^c >:# :[ÄXVXn d[ [VXZbVh` gZhjhX^iVi^dc Vi W^gi]# 7g BZY ? 8a^cGZh :Y &.-)0
'-.+)*-/&*+("&*+*#
(,# 7Zk^aVXfjV <! =Vaa^YVn =! EVgb^\^Vc^ H Zi Va# GVcYdb^oZY bjai^XZcigZ ig^Va d[ igZVibZci l^i] edgX^cZ
cVijgVa hjg[VXiVci [dg bdYZgViZan hZkZgZ cZdcViVa gZhe^gVidgn Y^higZhh hncYgdbZ# I]Z 8daaVWdgVi^kZ
:jgdeZVcBjai^XZcigZHijYn<gdje#?EZg^cViBZY&..(0'&*/('."()%#
(-# HdaaG;!BdgaZn8?#Egde]naVXi^XkZghjhhZaZXi^kZjhZd[hjg[VXiVci^cegZkZci^c\bdgW^Y^inVcYbdgiVa^in
^cegZiZgb^c[Vcih#8dX]gVcZ9ViVWVhZHnhiGZk'%%&0'/89%%%*&%#
(.# Ndhi 88! Hdaa G;# :Vgan kZghjh YZaVnZY hZaZXi^kZ hjg[VXiVci igZVibZci [dg cZdcViVa gZhe^gVidgn Y^higZhh
hncYgdbZ#8dX]gVcZ9ViVWVhZHnhiGZk'%%%0'/89%%&)*+#