Prevenzione e management del parto pretermine Dr Paolo Cavoretto MD PhD Centro di diagnosi prenatale Unità operativa Ostetricia e Ginecologia Ospedale San Raffaele, Milano Direttore Prof Massimo Candiani [email protected]Scientific Institute San Raffaele Convegno La Nascita Prematura ,17 Novembre 2014
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Prevenzione e management del parto pretermine · l’iponutrizione 4. Evitare brevi intervalli intergestazionali (6 mesi) Provvedimenti relativi allo stile di vita ed alla nutrizione
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Significant reduction in PTD with some “side effects”
Reality: Screening and antibiotic treatment of the +ve group may be beneficial
Screening at 21-26 wks, n=16,317; Screen +ve 6.6%
Metronidazole & Erythromycin vs placebo (10d)
Andrews 2003
fFN +ve: RCT, n=703
Delivery <37 wks Delivery <32 wks
1.17 (0.80-1.70) 1.94 (0.83-4.52)
OR 95% CI
Control
1.0 0.5 5 0.2 0.1 10 2
Antibiotics
Asymptomatic patients: Prevention of preterm birth
Screening by Cervicovaginal fFN & Antibiotic Rx of the +ve group
Fetal Fibronectin (fFN): Produced by fetal membranes Adhesive of membranes to decidua
Screening at 24 wks: Delivery <34 wks: DR 53%, FPR 10%
LR+ve 4, LR-ve 0.8
Meta Analysis: Honest 2002; Leitich 2003 Insufficient data to suggest its routine use: Berghella 2008
• High risk for preterm delivery (n=900) • Screening by fFN at 24 & 27 wks • Delivery <30 wks: Metronidazole 21%
Placebo 11% Shennan 2006
F FN
Membrane
Decidua
Scientific Institute San Raffaele
Reality: Screening and antibiotic treatment of the +ve group is not beneficial
Asymptomatic patients: Prevention of preterm delivery
BACTERIAL VAGINOSIS: 13 RCTs, n=5,300
Delivery <37 wks
(n=5,300)
Delivery <34 wks
(n=851)
Delivery <32 wks
(n=3,565)
PPROM (n=2,578)
Control
1.0 0.5 5 0.2 0.1 10 2
0.87 (0.74-
1.03)
1.22 (0.67-
2.19)
1.14 (0.76-
1.74)
0.88 (0.59-
1.17)
OR 95% CI
Antibiotics
Cochrane Database of Systematic Reviews 2005
Screening: Bacterial vaginosis
Scientific Institute San Raffaele
Reality: Screening and antibiotic treatment of the +ve group is not beneficial
Birth
s (
%)
Gestation (wks)
24 28 32 36 40 42
Singleton
Twin
Triplet
0
25
50
75
100
0 10 20 30 40 50 60 70
Cervical length (mm) R
isk o
f d
eliv
ery
<33
wks (
%)
Twins
1163
Triplets
43
Skentou et al 2000; To et al 2001; 2005
Multiple pregnancy: Cervical length at 22-24 wks
Asymptomatic patients: Prediction of spontaneous preterm delivery
Scientific Institute San Raffaele
Reality: multiple pregnancy is a major risk factor for premature birth
Scientific Institute San Raffaele
Management del parto prematuro
Solo 15% partoriscono entro 7 giorni
ORACLE II: Kenyon et al, Lancet 2001; 357: 981-90
Difficile distinguere tra vero e falso travaglio
I tocolitici ritardano il parto di 2-7 giorni Ma non riducono la mortalità perinatale
Gli steroidi riducono la mortalita e la morbilità perinatale (RDS, IVH)
Cicli ripetuti potrebbero aumentare la mortalita e ridurre la crescita fetale Banks BA et al. AJOG 1999;181:709-17, French NP. AJOG 1999;180:114-21
Ospedalizzazione
Tocolitici + Steroidi + Solfato di magnesio
Gestione del parto
0
10
20
30
40
50
60
70
Cervical length (mm)
26-30 >30 1-5 6-10 11-15 16-20 21-25
80 Delivery within 7 days (%)
(%)
Singletons
Twins
0 24 48 72 96 120 144 168
Time from presentation (hrs)
0
10
20
30
40
50
60
70
80
90
100 %
No delivery (%)
Cx >25 mm
N=21
Cervical sonography in threatened preterm labor at 24-34 wks
Cx <25 mm
N=65
Cervical length (mm)
Deli
ve
ry w
ith
in 7
da
ys
(%
)
0
10
20
30
40
50
60
70
80
90
100
n=
11
0-3
n=16
4-7
n=21
8-11
n=37
12-15
n=46
16-19
n=81
20-23
n=271
>23
Tsoi et al 2003; Fuchs et al 2003
Scientific Institute San Raffaele
N=510; Delivery within 7 days: 8%; 0.7% if Cx >15mm & 50% in Cx<15mm
Reality: cervical lenght predicts delivery in thretened preterm labour
Scientific Institute San Raffaele
Hobel et al 1994; Crowther et al 1989, 1990, 1991; Dodd & Crowther 2005, Madennan et al 1990; Hartikainen-Sorri et al
1990; Saunders et al 1985.
Del <37 wks (n=1266)
Singletons
Del <37 wks (n=706)
Delivery <34 wks (n=417)
Twins
Del <37 wks (n=19)
Del <34 wks (n=26)
Triplets
1.0 0.5 5 0.2 0.1 10 2 Bed rest Control
Bed rest : 8 RCTs, n=1,998
Guinn et al 1997; Helfgott et al 1994.
Hydration: 2 RCTs, n=228
Del <37 wks (n=228)
Del <34 wks (n=118)
Del <32 wks (n=110)
1.0 0.5 5 0.2 0.1 10 2 Hydration Control
Management del parto prematuro
Reality: bed rest and hydration are not beneficial
Profilassi con steroidi e magnesio solfato @ 23-34 wks
Scientific Institute San Raffaele
Profilassi RDS con steroidi Neuroprotezione con magnesio solfato
Neonatal death 0.69 (0.58-0.81)* Respiratory distress syndrome 0.66 (0.59-0.73)* Cerebroventricular haemorrage 0.54 (0.43-0.69)* Nectotizing enterocolitis 0.46 (0.29-0.74)* NICU admissions 0.80 (0.65-0.99)* Early systemic infections 0.56 (0.38-0.85)*
Risk Ratio (95%CI)
Roberts D 2006
Systematic review 21 trials; N=3885 woman with 4269 infants @24-34 weeks RCTs - antenatal corticosteroid administration (betamethasone, dexamethasone, or hydrocortisone) with placebo or with no treatment given to women with a singleton or multiple pregnancy, expected to deliver preterm as a result of either spontaneous preterm labour, preterm prelabour rupture of the membranes or elective preterm delivery.
Significant reduction in neonatal mortality and morbility with a single course 12 mgx2 days
Significant reduction ofcerebral palsy with a prenatal course of 4-6 g (1-2 g/h)
Crowther, 2003; Marret, 2007; Rouse 2008; Australian
National Health and Medical Research Council, 2010
Review 3 trials; N=4184 woman @24-33 weeks RCTs – magnesium sulphate administration with placebo or with no treatment given to women with a singleton or multiple pregnancy, expected to deliver preterm as a result of either spontaneous preterm labour, preterm prelabour rupture of the membranes or elective preterm delivery.
Tocolytics vs placebo (11 RCTs)
Threatened preterm labour: prevention of delivery
Betamimetics
MgSO4
Indomethacin
Atosiban
GTN
0.44 (0.34-0.64)
0.52 (0.26-1.05)
0.12 (0.05-0.32)
0.67 (0.47-0.95)
0.33 (0.08-1.15)
95% CI
1.0 0.5 5 0.2 0.1 10 2
Treatment Control
Betamimetics
MgSO4
Indomethacin
Atosiban
Delivery < 48hrs
Delivery < 7 days
0.65 (0.50-0.83)
1.54 (0.85-2.82)
0.07 (0.02-0.27)
0.59 (0.41-0.84)
No significant difference in:
• Preterm delivery
• Perinatal death
• Neonatal sepsis
• RDS, NEC, PDA
Significant increase in maternal:
• Palpitations, tremor, headaches
• Nausea, vomiting, dyspnea
• Hyperglycemia, hypokalemia
• Chorioamnionitis, endomitritis
Prolong pregnancy by 2-7 days
Scientific Institute San Raffaele
Contraindications to tocolisis:
• IUD, Lethal fetal anomaly
• Non-reassuring fetal status
• Severe PET, haemorrage, infection
• Significant maternal disease
Tocolitici utili nella fase acuta per permettere somministrazione di steroidi .
Mancano evidenze di utilità dopo risoluzione dell’episodio acuto