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Use o The apeu ic Hypo he mia in Sudden Unexpec ed
Pos na al Collapse: A Re ospec i e S udy
Uso de Hipo e mia Induzida no Colapso Súbi o Pós-Na al:
Um Es udo Re ospec i o
Sa a BRITO1, Isabel SAMPAIO2, Alexand a DINIS3, Elisa PROENÇA4, Ana VILAN5, Eunice SOARES1,
Filomena PINTO1, Te esa TOMÉ1, And é M. GRAÇA2,6
Ac a Med Po 2021 34(AOP) ▪ h ps://doi.o g/10.20344/amp.13767
ABSTRACT
In oduc ion: Sudden and unexpec ed pos na al collapse is a a e e en wi h po en ially d ama ic consequences. In e en ion ap-
p oaches a e limi ed, bu hypo he mia has been conside ed a e pos na al collapse. The aim o his s udy was o analyse sudden and
unexpec ed pos na al collapse cases ha unde wen he apeu ic hypo he mia in he i e Po uguese hypo he mia cen es.
Ma e ial and Me hods: In his mul icen e, e ospec i e and desc ip i e s udy, clinical, ul asonog aphy, ampli ude-in eg a ed elec o-
encephalog aphy and b ain magne ic esonance indings o newbo ns wi h pos na al collapse ha unde wen he apeu ic hypo he mia
a e epo ed (2010 - 2018). S a is ical analysis was pe o med by using IBM SPSS S a is ics e sion 21.
Resul s: Twen y- wo cases o sudden and unexpec ed pos na al collapse we e e e ed o he apeu ic hypo he mia (82% ou bo n),
all ≥ 36 weeks, wi h Apga 5´ ≥ 8. Collapse occu ed du ing he i s wo hou s in 73% (all < 24 hou s), 50% du ing skin- o-skin ca e,
55% ela ed o eeding and 23% du ing co-bedding. Mode a e-se e e encephalopa hy and se e e acidosis we e obse ed (median:
Thompson sco e 16, pH 6.90, base de ici 22 mmol/L). Ampli ude-in eg a ed elec oencephalog am was abno mal in 95% and magne ic
esonance imaging showed se e e b ain inju y in 46%. The mo ali y a e was 50%. A possible cause was iden i ied in 27%.
Discussion: The incidence a e o 2.7 sudden cases o pos na al collapse pe 100 000 bi hs, is possibly unde -es ima ed. All in an s
su e ed he collapse in he i s day, mos ly wi hin he i s wo hou s, as epo ed be o e. Possible causes we e iden i ied in less han
a hi d o cases, bu mul iple p edisposing condi ions we e iden i ied, sugges ing ha p e en ion may be possible. Newbo n posi ioning
and skin- o-skin ca e ha e been he mos discussed p ac ices. A signi ican p opo ion o in an s had poo ou comes. Lowe Thompson
sco e, elec oencephalog am ampli ude no maliza ion and no mal magne ic esonance imaging seemed o indica e be e ou comes.
Al hough conclusi e ials on he apeu ic hypo he mia a e pos na al collapse a e no a ailable, i s use has been conside ed indi idu-
ally. No se e e ad e se e ec s di ec ly ela ed o hypo he mia we e egis e ed in his s udy, bu he esul s do no allow d awing mean-
ing ul conclusions.
Conclusion: In ou na ional sample o 22 in an s who su e ed sudden and unexpec ed pos na al collapse and unde wen he apeu ic
hypo he mia, a signi ican p opo ion had poo ou comes. Absolu e conclusions om ou expe ience wi h hypo he mia in pos na al col-
lapse canno be d awn, bu sys ema ic epo ing o cases and long- e m clinical e alua ion would acili a e unde s anding o he eal
bene i s o hypo he mia. As his p ocedu e has no been alida ed wi h clinical ials o his indica ion, i s use should be conside ed on
a case-by-case app oach. The po en ially a oidable na u e o unexpec ed pos na al collapse is e iden om i s associa ion wi h ce ain
beha iou s and isk ac o s. Su eillance p ac ices du ing he i s hou s should be implemen ed, whils he bene i s o b eas eeding
and skin- o-skin ca e should con inue o be widely p omo ed.
Keywo ds: Hypo he mia, Induced; Hypoxia-Ischemia, B ain/ he apy; In an , Newbo n; Kanga oo-Mo he Ca e Me hod
RESUMO
In odução: O colapso pós-na al súbi o inespe ado, apesa de a o, condiciona po enciais consequências d amá icas. As in e enções
e apêu icas são limi adas, mas a hipo e mia induzida em sido conside ada após es es e en os. O obje i o des e es udo oi analisa
os casos de colapso pós-na al súbi o inespe ado subme idos a hipo e mia induzida nos cinco cen os po ugueses que a ealizam.
Ma e ial e Mé odos: Es udo desc i i o e ospe i o mul icên ico dos ecém-nascidos subme idos a hipo e mia induzida após colapso
pós-na al en e 2010 e 2018. Fo am analisadas as a iá eis clínicas, a moni o ização po ele oence alog ama de ampli ude in eg ada
e imagem po ul assonog a ia e a essonância magné ica ce eb al. A análise es a ís ica oi e e uada com apoio do IBM SPSS S a is ics
e sion 21.
Resul ados: Fo am subme idos a hipo e mia e apêu ica po colapso súbi o 22 ecém-nascidos, 82% ou bo n, odos com 36 ou mais
semanas de ges ação e Apga 5´ ≥ 8. A si uação oco eu nas p imei as duas ho as de ida em 73% ( odos com menos de 24 ho as de
ida), 50% no con ac o pele-a-pele, 55% associados à amamen ação e 23% du an e pa ilha de cama. Os ecém-nascidos obse ados
ap esen a am ence alopa ia mode ada a g a e e acidose g a e (mediana: Thompson 16, pH 6,90, dé ice bases 22 mmol/L). En e os
ecém-nascidos, 95% egis a am al e ação no ele oence alog ama e 46% pad ões g a es de essonância ce eb al. A axa de mo a-
lidade oi de 50%. Iden i ica am-se possí eis causas em 27%.
Discussão: Es imou-se uma incidência de 2,7 casos de colapso pós-na al súbi o inespe ado po cada 100 000 nascimen os, um alo
possi elmen e subes imado. O colapso oco eu no p imei o dia em odas as c ianças, a maio ia nas p imei as duas ho as, al como
1. Se iço de Neona ologia. Á ea de Pedia ia Médica. Ma e nidade D . Al edo da Cos a. Cen o Hospi ala Uni e si á io de Lisboa Cen al. Lisboa. Po ugal.
2. Se iço de Neona ologia. Depa amen o de Pedia ia. Hospi al de San a Ma ia. Cen o Hospi ala Uni e si á io Lisboa No e. Lisboa. Po ugal.
3. Unidade de Cuidados In ensi os Pediá icos. Hospi al Pediá ico de Coimb a. Cen o Hospi ala e Uni e si á io de Coimb a. Coimb a. Po ugal.
4. Unidade de Cuidados In ensi os Neona ais. Cen o Hospi ala Uni e si á io do Po o. Po o. Po ugal.
5. Se iço de Neona ologia. Hospi al Pediá ico In eg ado. Cen o Hospi ala Uni e si á io de São João. Po o. Po ugal.
6. Clínica Uni e si á ia de Pedia ia. Faculdade de Medicina. Uni e sidade de Lisboa. Lisboa. Po ugal.
 Au o co esponden e: Sa a B i o. [email p o ec ed]
Recebido: 22 de ma ço de 2020 - Acei e: 28 de se emb o de 2020 - Fi s published: 22 de ab il de 2021
Copy igh © O dem dos Médicos 2021
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desc i o em publicações an e io es. Iden i ica am-se possí eis causas em menos de um e ço dos casos, mas múl iplas condições p e-
disponen es o am e e idas, o que suge e a possibilidade de adoção de medidas p e en i as. O posicionamen o do ecém-nascido e o
con ac o pele-a-pele êm sido as p á icas mais discu idas. Uma p opo ção signi ica i a das c ianças e e uma e olução des a o á el.
Um des echo mais posi i o pa ece e oco ido nos casos em que se e i ica am alo es in e io es na escala de Thompson, no ma-
lização do ele oence alog ama de ampli ude in eg ada e essonância magné ica no mal. Embo a não es ejam disponí eis ensaios
conclusi os sob e a u ilização da hipo e mia e apêu ica após o colapso pós-na al, o seu uso em sido conside ado indi idualmen e.
Nes a e isão não o am obse ados e ei os ad e sos di e amen e elacionados com o p ocedimen o, mas os esul ados não pe mi em
ob e conclusões signi ica i as.
Conclusão: Na nossa amos a nacional de 22 c ianças que so e am colapso súbi o pós-na al e subme idas a hipo e mia e apêu i-
ca, uma p opo ção signi ica i a e e uma e olução des a o á el. A nossa expe iência e a a idade da en idade clínica não pe mi em
delinea conclusões p ecisas sob e a aplicação da hipo e mia induzida no colapso pós-na al súbi o inespe ado, pelo que se conside a
essencial a p e enção. O bene ício des a e apêu ica pode á se cla i icado a a és do egis o sis emá ico dos casos e do seguimen o
a longo p azo das c ianças. Embo a não exis am ensaios clínicos que pe mi am a sua alidação após es es e en os, a hipo e mia
induzida de e se uma opção a conside a indi idualmen e. A associação do colapso pós-na al com de e minados compo amen os e
a o es de isco e idenciam a sua po encial p e enção. De em se implemen adas es a égias de moni o ização nas p imei as ho as
de ida que pe mi am simul aneamen e a con ínua p omoção da amamen ação e do con ac o pele-a-pele.
Pala as-cha e: Hipo e mia Induzida; Hipóxia-Isquemia Ence álica; Mé odo Cangu u; Recém-Nascido
INTRODUCTION
The sudden and unexpec ed pos na al collapse (SUPC) o a p esumably heal hy e m newbo n is a a e e en , as-
socia ed wi h po en ially ca as ophic consequences.1,2 I may ep esen he i s mani es a ion o a congeni al anomaly,
in ec ion o me abolic diso de , bu in mos cases no unde lying condi ion is iden i ied, and i seems o ha e a complex
pa hophysiology, which is s ill poo ly unde s ood.1,3
I is gene ally cha ac e ized by apnoea, hypo onia, pallo , b adyca dia, cyanosis, collapse and ca diac o espi a o y
ailu e.1–5 Despi e inc easing awa eness o SUPC as a clinical en i y, he e is no a consensual de ini ion.3 Guidelines en-
do sed by he B i ish Associa ion o Pe ina al Medicine in 2014 de ined SUPC as “a e m o nea - e m in an who is well
a bi h, assigned o ou ine pos na al ca e and who collapses unexpec edly wi hin he i s se en days o li e, equi ing
esusci a ion wi h in e mi en posi i e p essu e en ila ion and who ei he dies, equi es ongoing in ensi e ca e o de elops
encephalopa hy”.6,7 This de ini ion is inc easingly accep ed ac oss he pe ina al communi y.
The e a e now o e 400 cases desc ibed in he medical li e a u e men ioning a a iable incidence o all-cause SUPC.
Recen popula ion-based s udies es ima e an incidence o 2.6 - 38.0 cases pe 100 000 li e bi hs.1,3,4,8–11 This wide in e al
can be a ibu ed o di e ences in de ini ion and inclusion c i e ia, including ges a ional and pos na al age and se e i y o
he collapse (wi h milde cases being excluded om mos s udies), sugges ing ha his si ua ion is unde epo ed.3,4,6
One- hi d o SUPC cases end o occu in he i s wo hou s a e bi h, ano he hi d be ween wo and 24 hou s and
he las hi d be ween one and se en pos na al days.5,10 Ea lie s udies highligh ed an e en ea lie occu ence, a ying
be ween 55% and 73% wi hin he i s and second pos na al hou s.1,4
Al hough no cause is ound o he majo i y o cases, mul iple p edisposing condi ions ha e been iden i ied, such as co-
bedding, p one posi ion and impai ed ma e nal awa eness, he e o e sugges ing he possibili y o p e en i e s a egies.6
Skin- o-skin con ac (SSC), ecommended o all heal hy e m newbo ns by some au ho i ies (Wo ld Heal h O ganiza-
ion, Ame ican Academy o Pedia ics, Ame ican College o Obs e icians and Gynecologis s, Cen e s o Disease Con ol
and P e en ion, Academy o B eas eeding Medicine, Uni ed Na ions In e na ional Child en’s Eme gency Fund),12,13 has
mul iple bene icial e ec s on in an s and hei amilies.12–16 I con ibu es o imp o ed empe a u e egula ion, allows be e
ca dio- espi a o y s abili y and glycemic con ol, educes in an discom o and p omo es success o b eas eeding.2,11–16
Immedia e SSC also in luences mic obio a coloniza ion o he newbo n16 and, simul aneously, imp o es pa en al bonding
and ma e nal clinical eco e y.2,13–16
Despi e hose ecommenda ions, he p ac ice o SSC a bi h is s ill no globally widesp ead, p obably due o a lack
o knowledge abou i s bene i s, absence o a s anda dized me hod o uni o m p ac ice, occasional un amilia i y wi h he
adequa e assessmen o he mo he -in an dyad and hei sa e posi ioning, and lack o aining on he egula physiologic
moni o ing ha is equi ed and on he measu es o minimize po en ial complica ions.12,14 Acco ding o some e iews, his
in e en ion is no associa ed wi h sho o long- e m nega i e e ec s.13,15 None heless, SUPC has been conside ed an
eme ging complica ion o SSC and b eas eeding, om he i s hou s o he i s days a e bi h13,14 and i s ising incidence
migh be a ibu ed o he g adual implemen a ion o hese p ac ices.
I is, he e o e, necessa y, o iden i y possible isk ac o s a o ing hypoxic e en s and o implemen p e en i e assess-
men ools, which could acili a e com o , knowledge and compe ence in assessing in an s and ensu ing hei sa e y du ing
SSC and b eas eeding.
Al hough SUPC is in equen , i is associa ed wi h high mo ali y a es and long- e m disabili y in mo e han hal o he
su i o s.3,4,6,10,14 Mo eo e , he apeu ic app oaches o p e en such un a ou able ou comes a e limi ed.
Conside ing he sa e y o he apeu ic hypo he mia (TH) and pa hophysiologic simila i y be ween neona al hypoxic-
ischaemic encephalopa hy (HIE) and he hypoxic-ischaemic insul in SUPC, TH has been conside ed in some neona al
in ensi e ca e uni s (NICU) as a he apeu ic app oach.3,17-19 Despi e lack o e idence o andomized con olled ials o
B i o S, e al. Use o he apeu ic hypo he mia in sudden unexpec ed pos na al collapse, Ac a Med Po 2021 34(AOP)
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B i o S, e al. Use o he apeu ic hypo he mia in sudden unexpec ed pos na al collapse, Ac a Med Po 2021 34(AOP)
suppo i s bene i s in SUPC, i s use is being ex ensi ely desc ibed.17,19-24
The aim o his s udy was o e iew all he SUPC cases ha unde wen TH e ospec i ely and assess he ci cum-
s ances o he e en s and hei sho - e m ou comes. Secondly, we aimed o iden i y po en ial p ognos ic indica o s. We
in ended o poin ou possible p e en i e s a egies in he immedia e pos na al pe iod and o asce ain he e en ual ole o
TH in amelio a ing long e m neu ological inju y.
MATERIAL AND METHODS
We pe o med a desc ip i e and mul icen e s udy, including e m and nea - e m newbo ns wi h SUPC needing ad-
anced esusci a ion, who unde wen TH in he i e Po uguese neona al e e al cen es, be ween 2010 and 2018.
We included newbo ns e e ed o he pe ina al cen es in he i s six hou s a e ca dio- espi a o y collapse, who
p esen ed wi h mode a e o se e e encephalopa hy (al e ed le el o consciousness, one, e lexes, o espi a o y d i e) o
se e e me abolic acidosis (pH < 7.00 o base excess < -16 mmol/L), who could po en ially bene i om he apeu ic hypo-
he mia (excep ional indica ion conside ed).
Pa en s we e in o med and consen was ob ained p io o he beginning o cooling, ei he in he w i en o m o e bally,
so as no o delay ea men in case hey we e no immedia ely p esen . In some si ua ions, consen was p ima ily p e-
sumed on he g ounds o u gency in ea men , and e i ied la e on. The e we e no pa en al objec ions o ea men .
Clinical da a we e collec ed e ospec i ely om medical eco ds, conce ning in o ma ion on p egnancy and bi h,
ci cums ances o he e en , labo a o y da a and in es iga ion o exclude a possible unde lying disease wi h in ec ion,
me abolic and ca diac sc eening, con inuous ampli ude-in eg a ed elec oencephalog aphy (aEEG) moni o ing, c anial
ul asound (C-US), b ain magne ic esonance imaging (MRI), clinical e olu ion in he Neona al In ensi e Ca e Uni (NICU)
and neu ological examina ion a discha ge. Su i ing and non-su i ing newbo ns we e compa ed.
Whole-body cooling a co e a ge empe a u e 33.5°C o 72 hou s was used. The whole p ocedu e and clinical, adio-
logical and labo a o y moni o ing we e applied acco ding o he Po uguese Socie y o Neona ology p o ocol o pe ina al
HIE.25
The aEEG moni o ing was pe o med using one o wo-channel sys ems.
Backg ound ac i i y was classi ied using a ol age classi ica ion (Naqeeb e al), as26,27:
1. No mal: uppe ma gin o band o aEEG ac i i y > 10 mV and lowe ma gin > 5 mV;
2. Mode a ely abno mal: uppe ma gin > 10 mV and lowe ma gin < 5 mV;
3. Se e ely abno mal: uppe ma gin < 10 mV and lowe ma gin < 5 mV, possibly accompanied by bu s s o high ol -
age ac i i y (bu s supp ession).
Any o hese h ee g oups could be accompanied by seizu es.26
The aEEG pa e n was addi ionally desc ibed acco ding o Hells om-Wes as e al as27,28:
1. No mal - con inuous no mal ol age/CNV: con inuous ac i i y wi h uppe ma gin > 10 mV and lowe ma gin > 5 mV;
2. No mal - discon inuous no mal ol age/DNV: discon inuous ac i i y wi h uppe ma gin > 10 mV and a iable lowe
ma gin bu < 5 mV;
3. Abno mal - bu s -supp ession/BS: discon inuous ac i i y wi h minimum ampli ude wi hou a iabili y and bu s s wi h
ma gin > 25 mV;
4. Abno mal - low ol age/LV: con inuous backg ound pa e n o e y low ol age ≤ 5 mV;
5. Abno mal - la ace/FT: isoelec ic acing < 5 mV.
Encephalopa hy was classi ied in ag eemen wi h Sa na e al.29 The Thompson encephalopa hy sco e was calcula ed
egula ly du ing he ea men pe iod using he c i e ia speci ied by Thompson e al.30 Hemodynamic dys unc ion was de-
ined o pa ien s who needed luid, asop esso o ino opic suppo . Respi a o y dys unc ion was no men ioned, since
mos pa ien s unde wen mechanical en ila ion in o de o comple e TH. Acu e kidney inju y was de ined as se um c ea i-
nine ≥ 1.5 mg/dL o a ise > 0.3 mg/dL/day.
S a is ical analysis was pe o med by using IBM SPSS S a is ics e sion 21. The χ2 es and he Fishe exac es we e
used o ca ego ical a iables and he Mann-Whi ney U es was used o con inuous a iables. A p alue o < 0.05 was
conside ed s a is ically signi ican .
E hics Commi ee app o al was no speci ically eques ed. The au ho s con i m ha da a we e collec ed e ospec i ely
and anonymously in each medical ins i u ion acco ding o pe sonal da a p i acy ules. In addi ion, we emphasize ha he
s udy was conduc ed in acco dance o he e hical p inciples exp essed in he Decla a ion o Helsinki, he Po uguese law
and Good Clinical P ac ice guidelines.
RESULTS
Du ing he s udy pe iod (2010 - 2018), 22 cases o SUPC we e e e ed o TH (82% o hem we e ou bo n). All o hem
we e e m o nea - e m in an s (median 39 weeks, all o e 36 weeks) and mos had adequa e bi hweigh (median 3100 g;
ange 2335 – 4250 g). No signi ican gende p edominance was no iced ( emale 55%). All newbo ns had an Apga sco e
o e se en a i e minu es a e bi h. They we e bo n o aginal deli e y in 73% (50% non-ins umen al aginal deli e y).
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Mean ma e nal age was 29 ± 7 yea s (median 28.5; ange 17 - 39), 86% we e p imipa ous and adequa e obs e ic su -
eillance was no ed in 91% o he cases. P egnancy was une en ul in 64%, he emainde ha ing isk ac o s such as ges-
a ional diabe es (14%), ges a ional induced hype ension (5%), ma e nal a hy hmia (5%), oe al g ow h es ic ion (5%),
oxoplasma se ological con e sion (5%), ma e nal hypo hy oidism (5%), ma e nal dep essi e diso de (5%) and amily
his o y o sudden dea h (5%). Neona al demog aphic cha ac e is ics, as well as p egnancy and deli e y ci cums ances a e
displayed in Table 1.
Table 2 desc ibes ch onological, clinical and ci cums ances ela ed o sudden unexpec ed pos na al collapse (SUPC)
cases.
Bo h su i ing and non-su i ing newbo ns we e compa ed.
All newbo ns su e ed an unexpec ed collapse needing esusci a ion du ing he i s day o li e, a a median o 98 min-
u es (median 1.6 hou s, ange 0.3 - 23) and 73% occu ed in he i s wo hou s o li e.
All he pa ien s equi ed ad anced li e suppo including in uba ion and posi i e p essu e en ila ion. Ches comp es-
sions we e pe o med in 77% and 68% equi ed d ugs o esusci a ion.
The e en occu ed du ing ea ly SSC wi h mo he / a he in 50% o newbo ns and 23% we e co-bedding wi h he
mo he . The e was a ch onological ela ionship wi h eeding in mo e han hal (14% immedia ely be o e, 18% du ing and
23% immedia ely a e b eas eeding).
The scena io whe e pa ien s we e ound was conside ed unsa e in 59%, due o in an posi ion (lying p one, on mo he ´s
b eas o abdomen wi h ulne able ai way pa ency), mo he ´s anaes hesia o mo he ´s dis ac ibili y.
On admission a he e ia y pe ina al cen e, 91% showed signs o mode a e (32%) o se e e encephalopa hy (59%)
(Table 3). Se e e me abolic acidosis was uni e sally p esen , wi h median alues o 6.9 o pH ( ange 6.7 - 7.17) and 22
mmol/L o base de ici ( ange 6 - 27). Maximum median Thompson sco e was 16 ( ange 5 - 20).
TH was s a ed a a median o six hou s a e bi h ( ange 2 - 32) and a a median o 4.4 hou s a e SUPC ( ange
0.5 - 18) and s ic a ge ed empe a u e managemen was main ained o 72 hou s. Clinical, adiological and labo a o y
moni o ing we e applied acco ding o he Po uguese Socie y o Neona ology p o ocol o pe ina al HIE.25
Ini ial aEEG backg ound ac i i y showed abno mal ampli ude in all excep one pa ien : mode a ely abno mal in 18%
and se e ely abno mal in 77%. As o pa e n classi ica ion, CNV was ound in 5%, DNV in 18%, LV in 32% and BS in 45%.
P og ession wi hin 48 hou s o TH o a no mal aEEG backg ound occu ed in 45% (no mal ol age and sleep-wake
cycling).
Elec ical seizu e ac i i y was eco ded in 55%, while clinically appa en seizu es we e desc ibed in 82% o newbo ns.
C anial ul asonog aphy abno mali ies du ing he i s 72 hou s we e desc ibed in 77% o ou cases and hese indings
included edema and loss o g ay/whi e ma e di e en ia ion (77%) and inc eased echogenici y o basal ganglia and hala-
mus (54%).
Abno mal b ain MRI was iden i ied in 54% o ou cases. Mino abno mali ies we e p esen in 9% and mode a e o se-
e e hypoxic-ischemic inju y in 46% pa ien s. Findings consis ed o combina ions o abno mal signal in ensi y on one o
mo e o sequences (T1, T2, di usion) in ol ing ce eb al co ex, whi e ma e , pos e io limb o in e nal capsule, halamus
and basal ganglia. Two babies (9%) did no pe o m MRI due o ea ly a al ou come and bo h had se e e US abno mali ies.
A sea ch o po en ial causes o SUPC was pe o med o all babies, including in ec ion, me abolic and ca dio ascula
sc eening. No cause was iden i ied in 73% o cases. Some como bidi ies ha could ela e o SUPC o igin we e iden i ied
in six cases (27%): ea ly sepsis (n = 2), hype ophic ca diomyopa hy wi hou le en icle ou low obs uc ion (n = 1), idi-
opa hic pe sis en pulmona y hype ension wi h associa ed a e ial hype ension (n = 1), ype 1 la yngeal cle (n = 1) and
uppe ai way haemo hage (n = 1).
Hal o he pa ien s died, a a median o 12 days a e bi h ( ange 2 - 57). In mos cases, dea h was ela ed wi h he
se e i y o he neu ological inju y, jus i ying li e suppo wi hd awal, a e mul idisciplina y discussion and pa en al pa icipa-
ion.
The ele en su i ing newbo ns we e ans e ed o o he medical uni s o discha ged home a a median o 13.5 days
a e bi h ( ange 6 - 30).
No signi ican complica ions ela ed wi h he TH p ocedu e we e ound, including cen al ne ous sys em haemo hage.
DISCUSSION
This s udy emphasises he ci cums ances and se e i y o SUPC e en s ha occu ed in Po ugal a e implemen a ion
o TH in 2009.18
We ound an incidence o 2.7 cases pe 100 000 bi hs du ing he s udy yea s, which is wi hin he ange o incidence
desc ibed in he li e a u e.1,4,6,10 We only included pa ien s e e ed o TH, so he eal incidence es ima e may lie abo e his
alue, since some pa ien s may ha e no been e e ed o TH, pa icula ly du ing he ea lie yea s a e in oduc ion o TH.
Ou mo ali y a e was 50%, which is simila o he a es indica ed in he li e a u e.6,10 Some epo s es ima e highe su i al
a es (60% - 73%),1,4 mos likely due o accessibili y o ad anced esusci a ion and in ensi e ca e.6,10 Limi a ions on he
epo ing and di e en ial access o non-consensual he apeu ic in e en ions may in luence he eal incidence and modi y
B i o S, e al. Use o he apeu ic hypo he mia in sudden unexpec ed pos na al collapse, Ac a Med Po 2021 34(AOP)
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conclusions ega ding ou comes.1,4,6,8–10 P ecise na ional da a is no known and e o s should be made o acknowledge his
eali y, including he c ea ion o a na ional egis y o his clinical en i y. Awa eness o he possibili y o i s occu ence and
egula aining is also essen ial.
As expec ed and in acco dance o i s in insic de ini ion,3,6,7 mos in an s we e a e m o nea e m, wi h no signi ican
an icipa ed isks and wi h appa en good adap a ion o ex au e ine li e. The e was a end o non-su i o s o ha e been
bo n om p egnancies wi h isk ac o s, e en hough he small numbe o pa ien s p ecludes d awing obus conclusions.
Gende , bi hweigh , ges a ional age and ou bo n s a us we e no associa ed wi h su i al. In addi ion, no signi ican di e -
ence was iden i ied when compa ing su i ing and non-su i ing pa ien s in ela ion o he ex en o esusci a ion immedi-
a ely a e SUPC, he ime o i s occu ence and he ime be ween he e en and ini ia ion o TH.
All in an s su e ed he collapse in he i s day, mos ly (73%) wi hin he i s wo hou s o li e. These esul s a e co -
obo a ed by o he epo s men ioning a es o 33% - 73% o he i s wo hou s.1,3,4,10 No pa ien was ei he e e ed o TH
a e he i s pos na al day o s a ed on TH mo e han six hou s a e he hypoxic insul .
The wo in an s wi h mild encephalopa hy su i ed and he deceased in an s had mode a e o se e e HIE, wi h highe
Thompson sco es (p < 0.005) and mo e in ense me abolic acidosis (p < 0.05). The e we e no ema kable di e ences in
hemodynamic s a us, kidney inju y o labo a o y cy olysis be ween he wo g oups.
Al hough he e is a con inuum showing inc easing isk o encephalopa hy along wi h deepening acidemia,31 i s posi i e
p edic i e alue, sensi i i y and speci ici y in p edic ing b ain inju y is known o be low.32 On he o he side, he p edic i e
alues o he Thompson sco e sys em o neu ological ou comes a one yea a e signi ican , pa icula ly when he highes
alue and main enance o abno mal signs a e combined.30 This sco e consis s o a simple clinical me hod o assessmen
o encephalopa hy in neona es wi h pe ina al asphyxia, including a neu ological examina ion, assessmen o espi a ion
and on anelle ension and aking in o accoun he mos se e e signs and hei pe sis ence.30,33 This me hod is s ongly
ecommended o moni o ing o HIE in an s, and i is ecognized as aluable o iden i y in an s a highe isk o un a ou able
ou comes.33,34
All deceased newbo ns excep one had abno mal c anial US indings. This pa ien had se e e encephalopa hy, se e e
me abolic acidosis a admission (pH 6.88, base de ici 25.9 mEq/L), enal inju y and ca dio ascula ins abili y, supp essed
aEEG and died du ing he second day o li e. Ne e heless, C-US is known o i s low sensi i i y and speci ici y in e m
HIE.35
Pe sis ence o abno mal aEEG a 48 hou s o TH was ema kably mo e common in non-su i o s (p < 0.005), as well
as elec ical seizu e ac i i y (p < 0.05). The incidence o clinical seizu es was iden ical be ween g oups.
The g ea majo i y o newbo ns who died had mode a e o se e e b ain MRI indings, wi h s a is ically signi ican di e -
ences compa ed o su i ing pa ien s.
In HIE, aEEG assessmen consis en ly p edic ed neu ode elopmen al ou comes a he age o one yea , wi h s ong
associa ion wi h he se e i y o abno mali ies and i s p og ession (speci ically, no mal ol age eco e y and sleep-wake
cycling).24,26,32,36 Ce ain MRI inju y pa e ns ha e ele an p ognos ic and diagnos ic alue and no el echniques (such as
di usion weigh ed MRI and p o on spec oscopy) ac as po en p edic o s o neu ological ou comes.37 The e o e, in SUPC
cases, one migh conside an iden ical in e p e a ion abou he p ognos ic alue o aEEG and b ain MRI indings as in he
newbo ns exposed o TH in pe ina al HIE.24,26,32,36–39
Possible causes we e iden i ied in 27% o cases. Repo s on SUPC suppo his inding, desc ibing ha abou 30%
- 50% o in an s who su e SUPC a e subsequen ly ecognised as ha ing an unde lying condi ion.1,5,6 A s a i ied isk as-
sessmen o in ec ion, hypoglycaemia, me abolic diseases, pulmona y hype ension o congeni al anomalies should be
ca ied ou .5,7 A pos -mo em examina ion is ecommended, e en hough mos he dea h causes emain unexplained.6,7
Beyond ae iology, mul iple p edisposing condi ions ha e been iden i ied, sugges ing ha p e en ion may be possible
in mos cases. Implemen a ion o s uc u ed s a egies o minimize he isk o SUPC and imely assessmen o isk ac o s
a e pa amoun .1,2,8,9,31,40
An impo an cons ain o hese goals is ha he p ecise pa hophysiology o SUPC is no comple ely unde s ood. The
iple isk hypo hesis has been conside ed, unde sco ing he in e play be ween in insic and ex insic ac o s du ing a c i i-
cal de elopmen al pe iod: in insic ulne abili y, posi ioning and lack o awa eness.1,3,6,9,10,14,41
As mos SUPC cases occu in p oximi y o bi h, in an s mus ha e an in insic suscep ibili y du ing he complex ex au-
e ine adap a ion, being less ole an o hypoxia, blun ing he a ousal esponse ( he ole o oxy ocin sec e ion, ho monal
changes, b ain imma u i y, au onomic imma u e egula ion wi h dec easing sympa he ic one and high pulmona y ascula
esis ance)5,6,14 and being po en ially exposed o ma e nal d ugs du ing labou (e.g. opioids and magnesium sulpha e).3,14,41
Posi ioning is one o he mos ele an aspec s and includes a combina ion o p one posi ioning, SSC, co-bedding,
b eas eeding and ma e nal habi us.1,6,9,10,14,41
In an s who su e ed om SUPC ha e been ound p one in he mo he ’s b eas , ches o abdomen, swaddled and
held supine by he mo he , a he o g andmo he , lying beside a pa en on he pa en ’s bed o on hei sides in he co .13,14
Lying p one on he b eas o abdomen o la e ally beside he mo he ´s ches a e he mos equen ly desc ibed sce-
na ios.1,4,8,9,41–43 These a e po en ially ‘asphyxia ing’ a i udes, a o ing ai way obs uc ion, hypo en ila ion and su oca ion

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by blocking he nos ils o by pos e io displacemen o he ongue. Addi ionally, ma e nal posi ion o habi us/obesi y may
hinde he newbo n a emp s o elie e obs uc ion.1,6,9,10,14,41
In ela ion o SSC, s udies a e con adic o y.2,6,12,13,15,16,41 Eu opean obse a ional da a demons a ed a ise in SUPC
incidence ollowing he implemen a ion o ou ine SSC.6,41 In con as , a sys ema ic e iew concluded ha his p ac ice does
no ha e appa en ad e se sho o long- e m consequences, bu he included ials had limi ed me hodological quali y.15
Indeed, a ecen la ge s udy showed ha inc easing a es o b eas eeding ini ia i es and skin- o-skin ca e we e, in ac ,
empo ally associa ed wi h dec easing SUPC p e alence in he six days pos bi h.2
In ou sample, co-bedding was iden i ied in 23% and an unsa e scena io, associa ion wi h eeding and occu ence du -
ing SSC we e ound in mo e han hal o he e en s.
Lack o awa eness comp ises he hi d impo an g oup o con ibu o s o he isk: ela i e inexpe ience o mo he ,
sleepiness, a igue, seda ion, dim ligh ing, unsupe ised b eas eeding and in equen obse a ion by a heal hca e p o es-
sional.1,4,6,9,10,14,41,44 Dis ac ion om mobile phone use has also been epo ed.3,9
In acco dance wi h he li e a u e, ou esul s showed a high p e alence o p imipa ous mo he s. Inexpe ience in ca ing,
holding he baby o b eas eeding and li le knowledge on wellness signals, migh pa ially explain his phenomenon.4,6,10,14
Because de elopmen al ulne abili y o he in an canno be modi ied and in insic ac o s may be di icul o iden i y
be o e bi h, i is c i ical ha ex insic condi ions o SUPC a e ully app ecia ed in o de o educe he isk o ha m, while
ensu ing ha bene i s om sa e SSC, b eas eeding and heal hy bonding a e p ese ed.3,6,14
Se e al ecommenda ions ha e eme ged on hese issues. Heal hca e p o essionals should, on an immedia e, ongoing
and con inued basis, obse e he in an s’ b ea hing, ac i i y, colou and one, h oughou he eco e y pe iod in he labou
and deli e y uni .3,11,14 Su eillance o he in an s’ head, neck, nose, and mou h is c i ical o p e en ion o SUPC. In iew
o hese ac s, Luding on-Hoe e al de eloped a newbo n assessmen ool o p e-emp in an de e io a ion, inco po a ing
sa e posi ion equi emen s and including ‘ espi a o y’, ‘ac i i y’, ‘pe usion’ and ‘posi ion’ (RAPP) i ems.14 Yea s la e , ‘ one’
assessmen was added o he a o emen ioned ool, named as RAPPT, which was compa ed o he Apga sco e o acili a e
i s adop ion and o s eng hen i s e ec i eness in p edic ing isk.11 Ano he pos na al su eillance p o ocol was ecom-
mended in an I alian cen e, ensu ing pa ency o he newbo n ai way and con inuous moni o ing o he dyad o e he i s
wo hou s.6,45
F om a p ac ical poin o iew, some au ho s belie e ha hese in e en ions can be ela i ely in usi e, equi e human
and echnical esou ces and may no imp o e sa e y o he in an .6,14,46,47 Ne e heless, ecen publica ions suppo hei
ad an age, when implemen ed on an o ganized basis.3,6,11,14,45
Unob usi e assessmen du ing he momen s o inc eased isk, namely when he mo he o pa ne canno sense he
newbo n wellbeing, has been encou aged as a a ional way o imp o e sa e ca e and i is now ecommended by some
ecognized in e na ional and na ional o ganiza ions.6,14 The impo ance o heal hca e pe sonnel equen ly checking on
he in an ’s condi ion du ing he i s 2 - 3 hou s du ing SSC is emphasized, ensu ing a sa e posi ion and non-occlusion o
nose and mou h.6,16 Some s a emen s s eng hen he ole o he heal hca e p o essional and ad ise elec onical moni o ing
(mul i-pa ame e o pulse oxime y) i no app op ia ely ained pe son can emain in he oom pe manen ly.14,47
When p e en ion ails and he e en ensues, i is essen ial o he clinician o acknowledge po en ial he apeu ic in e -
en ions. In o de o minimize inju y om SUPC, he apeu ic hypo he mia is conside ed in aluable.17,19–23,48
While TH is a s anda d o ca e in e m in an s wi h in apa um HIE, he e is no clea e idence o i s bene i a e SUPC.
The i s ials on hypo he mia excluded in an s wi h pos na al collapse. Mo eo e , i s in equen occu ence, he unce -
ain y abou i s pa hophysiology and lack o knowledge on he mul iplici y o causes, p ecludes he design o a conclusi e
ial.6,18
Addi ionally, he po en ial lack o bene i and e en isk o ha m mus be ecognised, as in he case o in ec ion, pulmo-
na y hype ension, ca diac s uc u al o dys hy hmic diso de s, in ac anial haemo hage and some me abolic condi ions,
which may be ad e sely a ec ed by unc ional changes induced by hypo he mia.6,17,19,20
Despi e hese limi a ions, a ew case epo s on SUPC in an s unde going TH we e published.6,9,17,19–23 I s use is sup-
po ed on physiological mechanisms: app oxima ely 75% o newbo ns wi h no es ablished cause o collapse de elop a
ypical pos -asphyxia encephalopa hy1,48 (e oking pe ina al HIE), p obably subsequen o a sho bu se e e hypoxic insul
om acu e ai way obs uc ion and ca diac a es .1,48 The e o e, he e is a plausible bene i om TH in hese pa ien s, which
should be judiciously conside ed on an indi idual basis. Signed pa en al in o med consen s a ing he po en ial bene i ,
despi e he lack o e idence and al e na i es, should be ob ained in all cases.
Desc ibed sho e m ou comes a e TH a e a iable and long e m da a a e spa se.6,9,17,19–21,23 Inc easing expe ience
and e ol ing in es iga ion emphasize TH as a p omising ool a e SUPC. In ou sample, no se e e ad e se e ec s di ec ly
ela ed o TH we e egis e ed. Rega ding ou comes, we ound su i al a es simila o hose desc ibed in he li e a u e,
al hough long e m neu ode elopmen esul s ha e no been e alua ed o compa ed ye and signi ican conclusions canno
be d awn.
The limi a ions o ou s udy a e i s e ospec i e na u e, he small sample size, he spa se desc ip ion o clinical
examina ion, he lack o knowledge on mo bidi y in he sho and long e m (conce ning neu ode elopmen , mo o sequels
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and senso ial de ici s), and, inally, he absence o da a on ou comes o in an s su e ing SUPC who did no unde go TH.
Inclusion o na ional esul s, he discussion o i al p e en i e s a egies o implemen in na ional ins i u ions and he
conside a ion o a p omising in e en ion in such a se ious condi ion, a e some o he s eng hs o his pape .
Addi ionally, we aim o in ensi y awa eness on SUPC ci cums ances and implica ions, so as o imp o e i s p e en ion
and a ou quali y o ca e o ou newbo ns and hei amilies.
CONCLUSION
In ou na ional sample o 22 in an s who su e ed SUPC and unde wen he apeu ic hypo he mia, a signi ican p opo -
ion had poo ou comes.
Lowe Thompson sco es, aEEG ampli ude no maliza ion and sleep-wake cycling be o e 48 hou s o cooling and no -
mal MRI seemed o be ela ed wi h be e ou comes, bu he educed numbe o pa ien s included does no allow d awing
de ini e conclusions.
Sys ema ic epo ing o SUPC e en s and long- e m ollow-up is impo an . Fu u e esea ch is needed in o de o be e
unde s and he bene i s o TH in his clinical en i y. I s use is s ill conside ed on an indi idual basis, bu ac ual e idence
poin s o i s gene al e icacy and sa e y.
SUPC is a a e bu equen ly a al e en and he e is consensus ega ding i s po en ially a oidable na u e, h ough
be e ecogni ion and a oidance o isk ac o s.
Adequa e educa ion and aining o heal hca e pe sonnel and amilies on accu a e newbo n physiologic assessmen
and sa e posi ioning, along wi h app op ia e su eillance p ac ices du ing he i s hou s o li e should cons i u e a p io i y,
whils he bene i s o b eas eeding and skin- o-skin ca e should con inue o be widely p omo ed.
PROTECTION OF HUMANS AND ANIMALS
The au ho s decla e ha he p ocedu es we e ollowed acco ding o he egula ions es ablished by he Clinical Re-
sea ch and E hics Commi ee and o he Helsinki Decla a ion o he Wo ld Medical Associa ion, upda ed in 2013.
DATA CONFIDENTIALITY
The au ho s decla e ha ing ollowed he p o ocols in use a hei wo king cen e ega ding pa ien s’ da a publica ion.
COMPETING INTERESTS
The au ho s ha e decla ed ha no compe ing in e es s exis .
FUNDING SOURCES
This esea ch ecei ed no speci ic g an om any unding agency in he public, comme cial, o no - o -p o i sec o s.
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B i o S, e al. Use o he apeu ic hypo he mia in sudden unexpec ed pos na al collapse, Ac a Med Po 2021 34(AOP)
Table 1 – Newbo n demog aphic da a and deli e y ci cums ances
Su i o s
(n = 11)
Non-su i o s
(n = 11)
To al
(n = 22) p alue
Ges a ional age, weeks*39
(38 - 40)
39
(38 - 40)
39
(38 - 40) n.s.
Bi hweigh , g ams*3040
(2745 - 3450)
3130
(2665 - 3535)
3100
(2669 - 3471) n.s.
Female, % 54.5 54.5 54.5 n.s.
P egnancy su eillance, % 90.9 90.9 90.9 n.s.
P egnancy diso de s, % 18.2 54.5 36.4 n.s.
Mo he ´s age, yea s*28
(26 - 32)
29
(21 - 38)
28.5
(22.7 - 35.5) n.s.
P imipa i y, % 100 72.7 86.4 n.s.
Ou bo n, % 81.8 81.8 81.8 n.s.
Vaginal deli e y, % 72.7 72.7 72.7 n.s.
Apga 1s min ≥ 8, % 100 81.8 90.1 n.s.
Apga 5 h min ≥ 8, % 100 100 100 n.s.
* Median (In e Qua ile Range)
Table 2 – Sudden unexpec ed collapse ci cums ances
Su i o s
(n = 11)
Non-su i o s
(n = 11)
To al
(n = 22) p alue
Time pos -bi h o SUPC, hou s*1.0
(0.5 - 1.8)
2.0
(1.0 - 4.0)
1.6
(0.95 - 2.6) n.s.
Time pos -SUPC o s a TH, hou s*4.5
(2.0 - 7.6)
4.0
(2.0 - 5.9)
4.4
(2.0 - 6.4) n.s.
Resusci a ion, % n.s.
- In uba ion and PPV 100 100 100
- Ca diac comp essions 72.7 81.8 77.3
- D ugs 63.6 72.7 68.2
Unsa e scena io, % 54.5 63.6 59.1 n.s
Associa ion o eeding, % 63.6 45.5 54.5 -
Place o occu ence, %
- Skin- o-skin con ac 45.4 54.5 11.0
- Co-bedding 18.2 27.3 22.7
- Co 9.1 0.0 4.6
- Unknown 27.3 18.2 22.7 -
PPV: posi i e p essu e en ila ion; SUPC: sudden unexpec ed pos na al collapse; TH: he apeu ic hypo he mia
* Median (In e Qua ile Range)