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Università degli Studi di Parma | Facoltà di Medicina e ChirurgiaClinica Ginecologica ed OstetricaDirettore: Prof. Alberto Bacchi Modena
Stillbirth & SIUDProf. Giovanni PIANTELLI | Dott.ssa Ilaria IODURI
Giornata Regionale SIDS, SIUD & ALTE
LA SPEZIA_27 NOVEMBRE 2010
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STILLBIRTHWHO
DATI SOTTOSTIMATIDATI SOTTOSTIMATI
% STILLBIRTH
INDICATORE DELLA QUALITA’ DELLE CURE OFFERTE ALLA POPOLAZIONE GRAVIDA
1995: 4,3 MILIONI
2000: 3,3 MILIONI
2004: 3 MILIONI
Giovanni Piantelli | Stillbirth & SIUD
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NATIMORTALITANATIMORTALITA ’’: MEFMEFnati morti / totale nati (vivi + morti) x 1000
**MORTALITA**MORTALITA ’’ PERINATALE:PERINATALE:nati morti + morti primi 7 gg / totale nati (vivi + morti) x 1000
MORTALITAMORTALITA ’’ NEONATALE:NEONATALE:morti primi 28 gg / nati vivi x 1000
** World Health Organization: Stillbirths = Mortalità perinatale
Giovanni Piantelli | Stillbirth & SIUD
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Percentuali di MEF dal 1967 al 2007 rispetto ai due aspetti della definizione (peso fetale/settimana gestazionale)
- solo il 4% delle MEF con peso >500gr avvengono < 22sett
- solo il 19% delle MEF dopo la 22^ sett. presentano un peso <500gr
Giovanni Piantelli | Stillbirth & SIUD
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Perinatal and post-neonatal mortality in England and Wales 1993����2002
Maternal and Child Health Consortium: CESDI 8th Annual Report 2004
Giovanni Piantelli | Stillbirth & SIUD
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ANTEPARTUM
6.3 / 1000
INTRAPARTUM
0.7 / 1000
MEFMEF
7 casi su 1000 nati
Am J of Obstet & Gyn (2005) 192, 1475-7
A review of intrapartum fetal deaths, 1982 to 2002Fiona Mattatall, MD, *Collen M. O’Connell, PhD, Thomas F. Baskett, MB
121.659 nati: 835 MEF
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7 CASI SU 1000 nati
2,5‰ (36%)
< 28 SETTIMANE
4,5‰ (64%)
> 28 SETTIMANE
Giovanni Piantelli | Stillbirth & SIUD
Am J of Obstet & Gyn (2005) 192, 1475-7
A review of intrapartum fetal deaths, 1982 to 2002Fiona Mattatall, MD, *Collen M. O’Connell, PhD, Thomas F. Baskett, MB
121.659 nati: 835 MEF
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SPIEGABILESPIEGABILE
STILLBIRTHSTILLBIRTHGiustificata dall’esame autopticodel feto e degli annessi; dall’esame istologicodel cordone ombelicale, della placenta, delle membrane e del feto “midollo allungato” e/o attraverso lo studio dei disordini metabolici.
MEFINSPIEGABILE : INSPIEGABILE : SIUDSIUDSSuddenudden II ntrauterine ntrauterine UUnexplainednexplainedDDeatheath
Morte endouterina prima del parto di un feto con età gestazionale >/ = di 22 settimane complete o con un peso di almeno 500 grammi, che sia inaspettata in base alla storia clinica della paziente e della gravidanza, e per la quale l’ autopsia del feto insieme con l’esame macroscopico e istologico del cordone ombelicale, della placenta e delle membrane, non sia in grado di dimostrare la causa di morte.
Giovanni Piantelli | Stillbirth & SIUD
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FATTORI DI RISCHIO PER LA MEFFATTORI DI RISCHIO PER LA MEF
� Età materna
� Fumo
� Nulliparità
� Etnia
� Bassi fattori socio-economici
� Sovrappeso e Obesità
� IUGR
� Complicanze in gravidanze precedenti
� Gravidanze multiple
� Età gestazionale avanzata, soprattutto oltre il termine
3.7> 40
1.935 - 39
1.330 - 34
1.0< 30
OREtà materna
Smith G.C.S., Min.Gin. 2005; 57:397-410
Rasmussen S. Early Human Development. 2003; 71: 39-52
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Razza Bianca
Razza Nera
Antepartum 3.4 / 1000
Intrapartum 0.5 / 1000
Antepartum 5.6 / 1000
Intrapartum 1.1 / 1000
M
E
F
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Donne con pregressa MEF
OR 4.7
di avere nuova MEF (22.7 / 1000)
Nelle pazienti di razza nera OR 2.6, in più, per ricorrenza MEF rispetto alle donne di razza bianca
Obstet Gynecol 2006; 107:391-7
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L’obesità materna ( BMI > 30 ) aumenta di 3 volte il rischio di MEF
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OR 2.07 obesità vs normale
MEF
OR 1.47 sovrappeso vs normale
9 studi pubblicati tra il 2000 e il 2006
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PREVALENZA SIUD vs MEF %
1954 � 2004
15RE.CO.DE (Gardosi J., BMJ 2005;331:1113-1117)
66WIGGLESWORTH (Lancet 1980)
67ABERDEEN (Baird and Thomson, J of Ob & Gyn British
Empire 1954)
%CLASSIFICAZIONE
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PREVALENZA SIUD vs MEF %
Giovanni Piantelli | Stillbirth & SIUD
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13FROEN JF (Arch dis child fetal neonatal ed, 2002)
25FROEN JF, GARDOSI J (Acta Ob & Gyn Scandinavica2004)
27MONTREAL ( Ob & Gyn 2000)
9SCANDINAVIAN ( Acta Ob & Gyn Scandinavica 1995)
22WHITFIELD’S STUDY (BJOG 1986)
12SCANDINAVIAN ( BJOG 1983)
%TRIALS
PREVALENZA SIUD (%)
1983 ���� 2006
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ReCoDe: Relevant Condition at DeathGiovanni Piantelli | Stillbirth & SIUD
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!!
Giovanni Piantelli | Stillbirth & SIUD
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Giovanni Piantelli | Stillbirth & SIUD
Rischio MEF � settimana di gestazione SGA, AGA & LGA
Australian-New Zeland Obstetric Gynaecol 2007; 47: 302-6
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Anamnesi ostetrica: parto pretermine + IUGR
= ↑ rischio MEF
ORCondizione
5.0Pregresso parto pretermine
<32 con feto IUGR
3.4Pregresso parto pretermine >32 <36 sett con feto IUGR
2.1Pregressa parto con IUGR
nato a termine
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CAUSEInfezioni 24 %
Insufficienza placentare / IUGR 22%
Distacco di placenta 19 %
Patologie materne 12 %
Malformazioni fetali 10 %
Patologie del cordone 9 %
SIUD 10 %MEF SPIEGATA 90 %
188 MEF
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All’aumentare dell’epoca gestazionale, vi è un aumento della SIUD
Giovanni Piantelli | Stillbirth & SIUD
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Rasmussen S. Early Human Development (2003); 71: 39-52
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Late fetal death: EG > 25Settimane o feto > 1000gr
MEF5 – 12 casi su 1000 SIUD
50-80 % delle MEF
Giovanni Piantelli | Stillbirth & SIUD
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Gravidanze gemellari (15.748)
Late fetal death > 28 sett.
12.8 / 1000Giovanni Piantelli | Stillbirth & SIUD
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PLoS Medicine, (2005), vol.2; issue 6: 521, 527.
High risk of unespected late fetal death in monochorionic twins despite intensive ultrasound surveillance: a cohort study
O. Barigye, L. Pasquini, P. Galea, H. Chambers, L. Chappel, Nicholas M.Fisk
GravidanzeGravidanze GemellariGemellari MonocorialiMonocorialinon complicatenon complicate
ΤΤ
TT-- signsign
GravidanzeGravidanze GemellariGemellari MonocorialiMonocorialinon complicatenon complicate
ΤΤ
TT-- signsign
No TTTS, No IUGR, LA regolare, Doppler regolare
(ecografie ogni 2 sett.)
Late fetal death > 32 sett.
43 / 1000
17 TTTS
26 SIUD
( Diagnosi autoptica )
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Late fetal death > 32 sett.
26 / 1000
GravidanzeGravidanze GemellariGemellari MonocorialiMonocoriali
Complicate e non complicateNelle gravidanze
gemellari monocoriali
biamniotiche èconsigliato
l’espletamento del parto con taglio
cesareo a 36 settimane gest.
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Br J Obstet Gynaecol. 1997 Oct;104(10):1203-7. Links
The hidden mortality of monochorionic twin pregnancies.Sebire NJ, Snijders RJ, Hughes K, Sepulveda W, Nicolaides KH
12 % di MEF tra 14 e 24 settimane
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Gravidanze Gemellari Monocoriali
12.5-25% IUGR selettivo
25 % va incontro a MEF
Il gemello con crescita regolare, dopo la morte del gemello IUGR, va incontro a MEF o irreversibile danno d’organo in più
del 26% casi
Seminars in Fetal & Neonatal Medicine 2007;12:439-449
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TRANSLUCENZA NUCALE & MEF
…Il capo…la nuca piatta è ricoperta da cute lassa, color giallo sporco e priva di elasticità apparendo sovrabbondante rispetto al corpo…..“Collo di gatto”
Langdon Down (1866) Observations on an ethnic classification ofLangdon Down (1866) Observations on an ethnic classification of idiotsidiots
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TRANSLUCENZA NUCALE & MEFTRANSLUCENZA NUCALE & MEF
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Cardiac defects in chromosomally normalfetuses
•• N = 6,907N = 6,907•• GA 12 (11GA 12 (11--13) wks13) wks•• CRL 62 (45CRL 62 (45--84) mm84) mm•• FetalFetalechocardiographyechocardiography
1212--15 wks15 wks1616--22 wks22 wks
Atzei et al 2004
0
50
100
150
200
>M<95th >95th>95th-3.4 3.5-4.4 4.5-5.4 5.5-6.4 >6.5
Nuchal translucency thickness (mm)
Pre
vale
nce
(per
100
0)
164
98
65
3218
9
2,062 2,361 649 199 102 122
<Med 1,412
4
Prevalenza: 8-12/1000
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Congenital defects & death
0
10
20
30
40
50
60
CNSRes
pirat
ory
Mus
culos
kelet
alGen
itour
inary
GIT /
Facial
Chrom
osom
alOth
ers
Neonatal death
Cardia
c
Childhood death
%Cause of death
50%
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PAPPPAPP--A & MEFA & MEF
PAPP-A: Pregnancy Associated Plasma Protein A
� proteina prodotta dal sinciziotrofoblasto ( IGF: Insuline like Growth Factor)
� I° trimestre di gravidanza (dosata a 12 settimane)
PAPP-A < 5°P
Disfunzione placentare
preeclampsia
2.5 OR
IUGR
2.5 OR
MEF
4 OR
Smith G.C., JAMA. 2004 Nov 10;292:2249-54
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msAFP & MEFmsAFP & MEF
msAFP: maternal serum Alpha-FetoProtein
� prodotta da sacco vitellino e poi da fegato fetale > intestino fetale > urine fetali > LA > placenta > membrane amniotiche > sangue materno
� misurata tra 15 e 19 settimane di gravidanza
msAFP > 3 MoM
11 OR di MEF
Smith G.C.S., JAMA 2004; 292:2249
Gordon C.S., New England J of Medicine 2004; 351: 978:86
6.7 OR preeclampsia
9.7 OR IUGR
Chitayat D.Am J Ob Gyn 2002;87:758-763
Giovanni Piantelli | Stillbirth & SIUD Low PAPP-A & High msAFP: MEF OR 36.7
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TROMBOFILIA & MEF
Trombofilia congenitaTrombofilia congenita IpercoagulabilitIpercoagulabilit àà gest.gest.
Trombosi Vasi PlacentariTrombosi Vasi Placentari
Insufficienza uteroInsufficienza utero--placentareplacentare
� Aborto ricorrente
� Preeclampsia
� IUGR
� Distacco di placenta
AJOG 2004; 191: 412-24
Trombophilia and pregnancy complications
Jody L. Kujovich, MD
MEF MEF
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TROMBOFILIA & MEFTROMBOFILIA & MEF
DISORDINI TROMBOFILICI FETAL LOSS (OR)*
FATTORE V LEIDEN 2 – 5
RESISTENZA PROTEINA C ATTIVATA 3 - 4
MUTAZIONE GENE PROTROMBINA 2 - 9
DEFICIENZA ANTITROMBINA III 2 - 5
DEFICIENZA PROTEINA C 2 – 3
DEFICIENZA PROTEINA S 3 – 40
OMOZIGOSI MTHFR C677T 0.4 - 3
IPEROMOCISTEINEMIA 3 - 7
DISORDINI MULTIPLI 5 - 14
* Sia precoce che tardiva
Jody L. KujovichTrombophilia and pregnancy complications AJOG 2004; 191: 412-24.
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TROMBOFILIA & MEF
Disordini Disordini Trombofilici Trombofilici
MultipliMultipli
Disordine Disordine Trombofilico Trombofilico
SingoloSingolo4 OR4 OR
14 OR14 OR
Rischio di
LATE FETAL LOSS
Jody L. KujovichTrombophilia and pregnancy complications AJOG 2004; 191: 412-24.
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SINDROME DI SJOGREN & MEFSINDROME DI SJOGREN & MEF
Gravidanza + Anticorpi S.
Sjogren (Ro-SSA/La-SSB)
BLOCCO ATRIO -VENTRICOLARE completo
nel 2 - 5 % dei feti
ECOCARDIO FETALE tra 16-32 settimane
PR Index (QT all’ECG)
> 0,15 sec (vn 0.12+/-0.02 sec)
BAV I°grado
Andrew H.Van Bergen, MD, Bettina, Cuneo, Davis, MA Prospective echocardiographic evalutation of AV conduction in fetus with maternal Sjogren’s antibodies. AJOG 2004; 191: 1014-8 P Bujon 2007
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SINDROME DA ANTIFOSFOLIPIDI (APL) & MEFSINDROME DA ANTIFOSFOLIPIDI (APL) & MEF
Sindrome da APL:� Anticorpi Anticardiolipina
� Lupus Anticoagulant
� in anamnesi trombosi a-v
� poliabortività
Trombosi Vasi PlacentariTrombosi Vasi Placentari
Insufficienza uteroInsufficienza utero--placentareplacentare
IUGR, oligoidramnios, IUGR, oligoidramnios, alterazioni cardiachealterazioni cardiache
c
Ipossia fetaleIpossia fetalec
c
MEF: OR 6MEF: OR 6--2020
Clinical Ob & Gyn 2001; 44: 11-19
Mechanism of pregnancy Loss in Antiphospholipid Syndrome
Azzudin, Gharavi, Nigel Harris
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LESLES
neonatale con / senza
BAV
1 %
MEF
20 %Parto Pretermine
25 / 50 %
IUGR
30 %
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MEFMEF
Not-yet-diagnosedLES group
Already-diagnosedLES group
OR
9.89
OR
3.85
LES
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INFEZIONI & MEF
BATTERI� Escherichia Coli
� Streptococco gr. B
� Ureaplasma Urealyticum
� Listeria monocytogenes
� Mycoplasma hominis
� Bacterioides
� Treponema pallidum
VIRUS� Parvovirus
� Coxackievirus
� Citomegalovirus
MALARIA
PROTOZOI� Toxoplasma gondii
� Leptospirosis
Infection and Stillbirth. Seminars in Fetal & Neonatal Medicine. 2009;14:182-189
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INFEZIONI & MEF
Paesi sviluppati
10 – 20 %
% di MEF dovute a infezioni% di MEF dovute a infezioni
Paesi in via di sviluppo
40 - 70 %
MEF attraverso infezione MEF attraverso infezione maternomaterno--fetalefetale diretta (via ascendente, diretta (via ascendente, ematogena), danno placentare, ematogena), danno placentare, corionamniotitecorionamniotite
Moyo S.R., Stillbirths and intrauterine infection, histologic chorioamnionitis and micobiological findings. Int J Gyn Ob. 1996; 54: 115-123
Robert L., The infectious origins of stillbirth. AJOG - 2003
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IL NOSTRO PROTOCOLLO DI
ESAMI PER LE
GRAVIDANZE A
RISCHIO,
ATTUALE O
ANAMNESTICO
Giovanni Piantelli | Stillbirth & SIUD
Dipartimento Materno InfantileUNITA’ OPERATIVA OSTETRICIA E GINECOLOGIA
Direttore: Prof A. Bacchi Modena
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Etiology and prevention of stillbirth AJOG 2005; 193:1923-35
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CUORE FETALE
SISTEMA IMMUNITARIO
SNC: NUCLEI
PONTO
MESENCEFALICI FATTORI TROMBOFILICI
DISTACCO DI PLACENTA
INSUFFICIENZA PLACENTARE
IPERTENSIONE GESTAZIONALE
IUGR
IPOSSIA
ACIDOSI
?
Sistema di conduzione miocardio
MEF - SIUD
PLACENTA
INFEZIONI
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Università degli Studi di Parma | Facoltà di Medicina e ChirurgiaClinica Ginecologica ed OstetricaDirettore: Prof. Alberto Bacchi Modena
Stillbirth & SIUDProf. Giovanni PIANTELLI
Grazie…