Fortbildung Frauenklinik Perinatalzentrum Luzern Die Sicht ... · Intakte Einlingsgravidität,...

23
Die Sicht des Neonatologen Dr. med. Matteo Fontana Leitender Arzt Neonatologie 4. Luzerner Perinatal-Forum Wie früh ist zu früh?

Transcript of Fortbildung Frauenklinik Perinatalzentrum Luzern Die Sicht ... · Intakte Einlingsgravidität,...

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Die Sicht des NeonatologenDr. med. Matteo Fontana

Leitender Arzt Neonatologie

Fortbildung Frauenklinik Perinatalzentrum Luzern

Donnerstag, 19. April 2018 14.30-17.45 Uhr Hörsaal Spitalzentrum, 3. OG Luzerner Kantonsspital

4. Luzerner Perinatal-Forum

Zielpublikum: Geburtshelfer, Hebammen, Pädiater, Kinderchirurgen, Neonatologen und Ge-netiker

Wie früh ist zu früh?

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Der FallJetziges Leiden:

Notfallmässige Zuweisung bei frühem vorzeitigem Blasensprung in der 17 5/7 SSW.

US: Intakte Einlingsgravidität, I.BEL, reduziertes Bewegungsmuster, Anhydramnion.

Persönliche Anamnese: 35-jährige GI / wPISt. n. Insemination Vor einer Woche (frühes 2. Screening): ungünstige fetale Lage bei II.dorsoposterioren BEL, sonst unauffällig.

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Dilemma

Schwangerschaftsabbruch aus

(sozial-)medizinischer Indikation

Weiterführung der Schwangerschaft

Frühgeburt

Spätabort

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Festgelegtes Procedere Stationäre Aufnahme zur Überwachung

regelmässige Abnahme der Infektparameter

Die Patientin wurde über das abwartende Prozedere informiert

“Ebenfalls kurz erläutert wurde die Geburt mit einer eventuellen Nachkürettage” “Eine psychologische Betreuung lehnt die Patientin aktuell ab”

Verlaufskontrolle mit 18 5/7

“erneut ausführliches Gespräch mit dem Paar über die ernste Situation und die unklare Prognose. Möchten aktuell alles für das Kind machen”

Verlaufskontrolle mit 19 0/7

“ausführliches Gespräch über Konsequenzen eines frühen vorzeitigen Blasensprungs”

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Suche und Analyse

Kinder aufgenommen auf unsere NeoIPSnach prolongiertem frühem vorzeitigem Blasensprung

von mindestens 6 Wochenin der Jahren 2011-2018

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AFI: Amniotic Fluid Index

Bauch der Schwangeren in 4 Quadranten aufgeteilt

In jedem Quadrant wird das grösste FW-Depot gemessen

Die Summer der 4 Messungen in cm ist der AFI

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Vorgeburtliche AnamnesePaul14 6/7

Noel15 4/7

Leandro17 5/7

Mario22 4/7

Jarno25 4/7

SSW bei Geburt 28 0/7 35 6/7 30 4/7 30 3/7 34 0/7

Latenz (Wochen) 13 1/7 20 2/7 12 6/7 7 6/7 8 3/7

SSW bei LRI Abschluss 23 5/7 25 1/7 23 6/7 + 30 2/7 24 1/7 25 5/7

Geburtsmodus sek. Sectio (BEL) SG SG Notfallsektio

(vorz. Plazentalösung) SG

Geburtsgewicht 995g (P25-50)

2615 g (P25-50)

1430g (P25-50)

1270g (P25)

2190g (P25-50)

NS-pH 7.43 7.33 7.23 7.42 (ven) 7.37

APGAR 4/6/8 7/7/7 4/6/6 1/4/5 3/4/5

Surfactant 22’ 25’ 15’ 12’ 38’0

5

10

14 16 18 20 22 24 26 28 30 32 34 36SSW

AFI

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Vorgeburtliche Anamnese + GeburtPaul14 6/7

Noel15 4/7

Leandro17 5/7

Mario22 4/7

Jarno25 4/7

SSW bei Geburt 28 0/7 35 6/7 30 4/7 30 3/7 34 0/7

Latenz (Wochen) 13 1/7 20 2/7 12 6/7 7 6/7 8 3/7

SSW bei LRI Abschluss 23 5/7 25 1/7 23 6/7 + 30 2/7 24 1/7 25 5/7

Geburtsmodus sek. Sectio (BEL) SG SG Notfallsektio

(vorz. Plazentalösung) SG

Geburtsgewicht 995g (P25-50)

2615 g (P25-50)

1430g (P25-50)

1270g (P25)

2190g (P25-50)

NS-pH 7.43 7.33 7.23 7.42 (ven) 7.37

APGAR 4/6/8 7/7/7 4/6/6 1/4/5 3/4/5

Surfactant 22’ 25’ 15’ 12’ 38’

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Verlauf AtemunterstützungPaul14 6/7

Noel15 4/7

Leandro17 5/7

Mario22 4/7

Jarno25 4/7

SSW bei Geburt 28 0/7 35 6/7 30 4/7 30 3/7 34 0/7

Surfactant Ja Ja Ja Ja Ja (2x)

Beatmung 13 Tage 5 Tage 6 Tage 3 Tage 3 Tage

NIV 56 Tage 3 Tage 40 Tage 45 Tage -

O2-Bedarf (d) 68 Tage 4 Tage 43 Tage 2 Tage 9 Tage

NO 8 Tage 2 Tage 2 Tage 1 Tag 6 Tage

Oxygenation Index 11 n.m. 26.2 26.9 33.6

höchster MAP (HFO) 12 12 15 12 16

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0

5

10

14 16 18 20 22 24 26 28 30 32 34 36

Welches Bild passt zu welchem Kind

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Dry lung McIntosch beschrieb 4 Kinder mit:

Prolongiertem BlasensprungSchwerem Atemnotsyndrom (wie gesehen bei Lungenhypoplasie)Hohen benötigten BeatmungsdrückenUnerwarteter “dramatischer” Verbesserung innerhalb von 2 Tagen

McIntosh N. Dry lung syndrome after oligohydramnios. Arch Dis Child. 1988 Feb;63(2):190-3.

Losa M, Kind C. Dry lung syndrome: complete airway collapse mimicking pulmonary hypoplasia? Eur J Pediatr. 1998 Nov;157(11):935-8.

Die Kollegen in Sankt-Gallen haben folgende Kriterien vorgeschlagen (alle zu erfüllen): Frühgeburtlichkeit mit VBS > 4 TageSchweres Atemnotsyndrom welches hohe Beatmungsdrücke benötigt hatDramatische Verbesserung der Atemunterstützung innerhalb von 24-36hAusschluss von anderen Pathologien wie hyaline Membrankrankheit oder Sepsis

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Medikamenten-BedarfPaul14 6/7

Noel15 4/7

Leandro17 5/7

Mario22 4/7

Jarno25 4/7

SSW bei Geburt 28 0/7 35 6/7 30 4/7 30 3/7 34 0/7

Surfactant Ja Ja Ja Ja Ja (2x)

NO 8 Tage 2 Tage 2 Tage 1 Tag 6 Tage

Hydrocortison (pulmonale Indikation)

33 Tage - - - -

Diuretika Ja - Ja - -

Montelukast Ja - - - -

Katecholaminen DobutaminMilrinone Noradrenalin Dobutamin

NoradrenalinDobutamin

Noradrenalin -

Hydrocortison (BD - Indikation)

- - Ja Ja Ja

Antibiotika (Strepto B)

8 Tage(+)

4 Tage(+)

6 Tage(+)

2 Tage(neg)

8 Tage(neg)

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0

5

10

14 16 18 20 22 24 26 28 30 32 34 36

Welche Kinder haben eine Hirnblutung gehabt

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0

5

10

14 16 18 20 22 24 26 28 30 32 34 36

Welches Kinder hat eine Hüftluxation gehabt

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OutcomesPaul14 6/7

Noel15 4/7

Leandro17 5/7

Mario22 4/7

Jarno25 4/7

SSW bei Geburt 28 0/7 35 6/7 30 4/7 30 3/7 34 0/7

PNX - Ja - - Ja (bds)

BPD Ja(mittelschwer) - Ja

(mittelschwer) - -

SUS ICH gr. II li iO iO iO ICH gr. I

Orthopädisch - ArthrogryposisHüftluxation - - -

ROP Keine - Keine Keine -

Hosp-Dauer 101 Tage 19 Tage 68 Tage 59 Tage 40 Tage

Korr. Alter bei Entlassung 40 3/7 38 4/7 40 2/7 38 6/7 39 5/7

Neuro EQ 80% Normal Normal Normal Normal

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AmnioninfusionCochrane Database Syst Rev. 2014 Mar 30;(3):CD000942. doi: 10.1002/14651858.CD000942.pub3. Amnioinfusion for third trimester preterm premature rupture of membranes. Hofmeyr GJ et al

Authors’ conclusions: These results are encouraging but… therefore further evidence is required before amnioinfusion for PPROM can be recommended for routine clinical practice.

BMC Pregnancy Childbirth. 2014 Apr 4;14:128. doi: 10.1186/1471-2393-14-128. Midtrimester preterm prelabour rupture of membranes (PPROM): expectant management or amnioinfusion for improving perinatal outcomes (PPROMEXIL - III trial). van Teeffelen AS et al

Oligohydramnion nach VBS in der 16-24. SSW, dauernd < 21 Tage. Randomisierung. Um eine Mortalitätsreduktion von 70 auf 35% durch Amnioninfusion, werden 56 Patientinnen benötigt.

Does amnioinfusion improve perinatal outcome in midtrimester rupture of membranes?: A randomized controlled trial (PPROMEXIL - III trial). van Kempen LE et al

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Linehan LA et al. (Dempsey E)

Neonatal and maternal outcomes following midtrimester preterm premature rupture of the membranes: a retrospective cohort study.

BMC Pregnancy Childbirth. 2016 Jan 29;16:25. doi: 10.1186/s12884-016-0813-3.

Methode: retrospektive deskriptive Kohortenstudie PROM 14 0/7 und 23 6/7

Zwischen April 2007 und Juni 2012In Cork, Ireland (University Maternity Hospital:

8500 Geburten / Jahr => 44500 Geburten in der Studienzeit

Resultate: 42 Fälle (0.1%)

Mittlere Gestationsalter bei PPROM: 18. SSW bei Geburt: 20 5/7 Mittlere Latenz: 13 Tage32 Kinder (77%) sind in utero oder intrapartum verstorben

10 Lebendgeburten (23%), 9 Kinder sind aufgenommen worden1 Kind hat bis zur Entlassung nach Hause überlebt

PPROM 17 3/7, Geburt 29 4/7 , GG 930gEntlassung in der korr. 45. SSW, BPD, mit 4 Jahren zeigt eine normale Entwicklung

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van Teeffelen A et al.

The Relation between Duration of Ruptured Membranes and Perinatal Outcome in Patients with Midtrimester Prelabor Rupture of Membranes.

Am J Perinatol. 2015 Oct;32(12):1112-8. doi: 10.1055/s-0035-1548539. Epub 2015 May 13.

Resultate: Überlebensraten

Methode: retrospektive deskriptive Beobachtungsstudie PROM < 26 0/7

Geburt ab 22 0/7 nach mindestens 24h nach Blasensprung (ohne: kongenitale Anomalien, Zwillingen)In Holland von Januar 1999 bis Dezember 2007 (insgesamt 1.5 Mio Kinder geboren)

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Methode: retrospektive deskriptive Beobachtungsstudie PROM < 26 0/7

Geburt ab 22 0/7 nach mindestens 24h nach Blasensprung (ohne: kongenitale Anomalien, Zwillingen)In Holland von Januar 1999 bis Dezember 2007 (insgesamt 1.5 Mio Kinder geboren)

van Teeffelen A et al.

The Relation between Duration of Ruptured Membranes and Perinatal Outcome in Patients with Midtrimester Prelabor Rupture of Membranes.

Am J Perinatol. 2015 Oct;32(12):1112-8. doi: 10.1055/s-0035-1548539. Epub 2015 May 13.

Resultate: Überlebensraten ohne schwere Morbidität (IVH, BPD, HMK, Sepsis, 5’-APGAR <7)

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Internationale StudienvergleichAuthor Publikations-

JahrStudien-

JahreSSW

bei VBS Zwillinge N Überlebens- Rate

Azria 2012 2003-2007 15-25 Nein 57 63

Deutsch 2010 2000-2007 18-24 Ja 105 27

Homer 2012 1998-2008 15-26 Nein 30 70

Manuck 2009 2001-2007 14-24 Nein 159 59

Margato 2012 1996-2008 14-24 Ja 32 34

Van der Hejden 2013 1994-2009 13-24 Ja 198 34

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Methode: gepaarte KohortenstudieAlle Kinder geboren < 32. SSW

Studiengruppe: VBS < 24. SSW, VBS > 1 Woche lang. Kontrollgruppe (pro Fall 2-3 Indexpatienten): kein VBS

Erfassung Juli 2004 - October 2007

J Perinatol. 2010 Oct;30(10):645-9. doi: 10.1038/jp.2010.11. Epub 2010 Mar 11.

Rupture of membranes before the age of viability and birth after the age of viability: comparison of outcomes in a matched cohort study.

Soylu H1, Jefferies A, Diambomba Y, Windrim R, Shah PS.

keine Differenz zwischen PPROM < 20. SSW (n=12) und > 20. SSW (n=17) (P = 0.42)

Resultate:

antenatal steroids, with a higher proportion of infants in thePPROM group receiving a complete course compared with thematched cohort. As expected, the duration of rupture ofmembranes (ROM) and GA at ROM were different between groups(Table 1). Results of other neonatal outcomes are reported inTable 2. There was significantly increased risk of mortality orsevere morbidities among cases (69 vs 47%; P¼ 0.02, unadjustedOR 2.5, 95% CI 1.0, 6.1). Logistic regression analyses confirmedPPROM at a previable age to be significantly associated withcomposite primary outcome (adjusted OR 4.0, 95% CI 1.2, 13.6).Univariate subgroup analysis revealed no significant differencein composite adverse outcome between groups of infants whohad PPROM before 20 weeks (n¼ 12) compared with those whohad PPROM after 20 weeks (n¼ 17) (58 vs 76%; P¼ 0.42).Reported causes of death among cases (n¼ 7) were pulmonaryhypoplasia in three, candida sepsis in one, bacterial sepsis in one,severe IVH in one and extreme prematurity in one infant.

Oligohydramnios or anhydramnios was present in 17 (63%)cases. For all cases, a course of prophylactic antibiotics, usually5 days of erythromycin, was used at the time of PPROM in keepingwith hospital policy. There was no difference in the risk ofcomposite outcome among those who had oligo- or anhydramnioscompared with those who did not have oligo- or anhydramnios.(65 vs 70%). Among the five patients who had anhydramnios,composite outcome was present in four, two patients died, three

had severe IVH/periventricular leukomalacia, three had severe ROPand one developed CLD at 36 weeks.

Discussion

Counseling women who present with PPROM at previable GA ischallenging. Many of these women will go into spontaneous labor,or will need to be delivered at a previable GA due to maternalhealth risks. Furthermore, in our local experience, a very poorprognosis for the fetus/neonate is often presented to the patient andtermination of pregnancy is frequently recommended. However,in the subset of women who experience PPROM at a previable GAand choose to continue their pregnancy to reach a viable GA, wereport a 76% survival to discharge from NICU for their preterminfants born at <32 weeks. In fact, our study may underestimatesurvival as we restricted our analysis to those infants who wereborn between 24 and 32 weeks GA. This cohort of preterm infantsborn following very early PPROM experienced higher rates ofcombined adverse outcomes including death or severe neurologicalinjury, severe ROP or CLD than matched preterm infants. Weacknowledge that our data are from a select group of infants whosurvived early PPROM and not a population-based cohort ofmothers who had ruptured and were serially followed up to assessthe outcomes.

Lindner et al.,12 in a retrospective matched cohort study of19 infants, reported that PPROM before 20 weeks was associatedwith higher risk of mortality, CLD and air leak when comparedwith infants not exposed to PPROM. However, the differences were

Table 1 Baseline characteristics

Characteristics Cases

(n¼ 29)

Controls

(n¼ 74)

P

GA (mean±s.d.) week 27±2 27±2 0.62

BW (mean±s.d.) g 1048 ±379 1007±344 0.61

Male, n (%) 20 (69) 46 (62) 0.79

IUGR, n (%) 0 (0) 4 (5) 0.20

Cesarean birth, n (%) 12 (41) 42 (57) 0.12

Median Apgar 1 min (range) 4 (2–5) 5 (3–8) 0.19

Median Apgar 5 min (range) 7 (5–9) 8 (7–9) 0.07

CRIB score (mean±s.d.) 7±4 4±4 <0.01*

TRIPS score (mean±s.d.) 31±14 20±10 <0.01*

Complete course of antenatal steroid, n (%) 28 (93) 48 (65) 0.015*

Chorioamnionitis, n (%) 9 (31) 6 (8) <0.01*

Duration of rupture of membranes (days)

Mean+s.d. 45+30 2+1 <0.01

Median (range) 39 (8–103) 1 (1–7) <0.01

GA at rupture of membranes (weeks)

Mean+s.d. 21±2 27±2 <0.01

Median (range) 22 (15–23) 27 (23–31) <0.01

Abbreviations: BW, body weight; CRIB, Clinical Risk Index for Babies; GA, gestational age;IUGR, intrauterine growth restriction; TRIPS, Transport Risk Index of PhysiologicStability.*P<0.05.

Table 2 Secondary outcomes and components of primary outcomes

Outcome Cases

(n¼ 29)

Matched cohort

(n¼ 74)

P

Respiratory distress syndrome, n (%) 28 (97) 62 (84) 0.08

Air leak, n (%) 5 (17) 5 (4) 0.02*

Persistent pulmonary hypertension, n (%) 6 (21) 0 (0) <0.001*

Sepsis, n (%) 4 (14) 17 (23) 0.30

Retinopathy of prematurity >stage 2, n (%) 5 (17) 11 (15) 0.77

Grade 3 or 4 IVH or PVL, n (%) 7 (24) 11 (15) 0.27

Chronic lung disease at 36 weeks, n (%) 10 (34) 23 (31) 0.94

Mortality, n (%) 7 (24) 10 (13) 0.19

Composite adverse outcome among

survivors, n/N (%)

13/22 (59) 25/64 (39) 0.14

Duration of artificial ventilation

(mean±s.d.) days

15±18 18±22 0.52

Duration of respiratory support

(mean±s.d.) days

39±31 39±33 0.98

Duration of intravenous access

(mean±s.d.) days

17±15 23±19 0.13

Length of stay (mean±s.d.) days 54±43 55±41 0.86

Abbreviations: IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia.*P<0.05.

PPROM before age of viability and neonatal outcomesH Soylu et al

647

Journal of Perinatology

antenatal steroids, with a higher proportion of infants in thePPROM group receiving a complete course compared with thematched cohort. As expected, the duration of rupture ofmembranes (ROM) and GA at ROM were different between groups(Table 1). Results of other neonatal outcomes are reported inTable 2. There was significantly increased risk of mortality orsevere morbidities among cases (69 vs 47%; P¼ 0.02, unadjustedOR 2.5, 95% CI 1.0, 6.1). Logistic regression analyses confirmedPPROM at a previable age to be significantly associated withcomposite primary outcome (adjusted OR 4.0, 95% CI 1.2, 13.6).Univariate subgroup analysis revealed no significant differencein composite adverse outcome between groups of infants whohad PPROM before 20 weeks (n¼ 12) compared with those whohad PPROM after 20 weeks (n¼ 17) (58 vs 76%; P¼ 0.42).Reported causes of death among cases (n¼ 7) were pulmonaryhypoplasia in three, candida sepsis in one, bacterial sepsis in one,severe IVH in one and extreme prematurity in one infant.

Oligohydramnios or anhydramnios was present in 17 (63%)cases. For all cases, a course of prophylactic antibiotics, usually5 days of erythromycin, was used at the time of PPROM in keepingwith hospital policy. There was no difference in the risk ofcomposite outcome among those who had oligo- or anhydramnioscompared with those who did not have oligo- or anhydramnios.(65 vs 70%). Among the five patients who had anhydramnios,composite outcome was present in four, two patients died, three

had severe IVH/periventricular leukomalacia, three had severe ROPand one developed CLD at 36 weeks.

Discussion

Counseling women who present with PPROM at previable GA ischallenging. Many of these women will go into spontaneous labor,or will need to be delivered at a previable GA due to maternalhealth risks. Furthermore, in our local experience, a very poorprognosis for the fetus/neonate is often presented to the patient andtermination of pregnancy is frequently recommended. However,in the subset of women who experience PPROM at a previable GAand choose to continue their pregnancy to reach a viable GA, wereport a 76% survival to discharge from NICU for their preterminfants born at <32 weeks. In fact, our study may underestimatesurvival as we restricted our analysis to those infants who wereborn between 24 and 32 weeks GA. This cohort of preterm infantsborn following very early PPROM experienced higher rates ofcombined adverse outcomes including death or severe neurologicalinjury, severe ROP or CLD than matched preterm infants. Weacknowledge that our data are from a select group of infants whosurvived early PPROM and not a population-based cohort ofmothers who had ruptured and were serially followed up to assessthe outcomes.

Lindner et al.,12 in a retrospective matched cohort study of19 infants, reported that PPROM before 20 weeks was associatedwith higher risk of mortality, CLD and air leak when comparedwith infants not exposed to PPROM. However, the differences were

Table 1 Baseline characteristics

Characteristics Cases

(n¼ 29)

Controls

(n¼ 74)

P

GA (mean±s.d.) week 27±2 27±2 0.62

BW (mean±s.d.) g 1048 ±379 1007±344 0.61

Male, n (%) 20 (69) 46 (62) 0.79

IUGR, n (%) 0 (0) 4 (5) 0.20

Cesarean birth, n (%) 12 (41) 42 (57) 0.12

Median Apgar 1 min (range) 4 (2–5) 5 (3–8) 0.19

Median Apgar 5 min (range) 7 (5–9) 8 (7–9) 0.07

CRIB score (mean±s.d.) 7±4 4±4 <0.01*

TRIPS score (mean±s.d.) 31±14 20±10 <0.01*

Complete course of antenatal steroid, n (%) 28 (93) 48 (65) 0.015*

Chorioamnionitis, n (%) 9 (31) 6 (8) <0.01*

Duration of rupture of membranes (days)

Mean+s.d. 45+30 2+1 <0.01

Median (range) 39 (8–103) 1 (1–7) <0.01

GA at rupture of membranes (weeks)

Mean+s.d. 21±2 27±2 <0.01

Median (range) 22 (15–23) 27 (23–31) <0.01

Abbreviations: BW, body weight; CRIB, Clinical Risk Index for Babies; GA, gestational age;IUGR, intrauterine growth restriction; TRIPS, Transport Risk Index of PhysiologicStability.*P<0.05.

Table 2 Secondary outcomes and components of primary outcomes

Outcome Cases

(n¼ 29)

Matched cohort

(n¼ 74)

P

Respiratory distress syndrome, n (%) 28 (97) 62 (84) 0.08

Air leak, n (%) 5 (17) 5 (4) 0.02*

Persistent pulmonary hypertension, n (%) 6 (21) 0 (0) <0.001*

Sepsis, n (%) 4 (14) 17 (23) 0.30

Retinopathy of prematurity >stage 2, n (%) 5 (17) 11 (15) 0.77

Grade 3 or 4 IVH or PVL, n (%) 7 (24) 11 (15) 0.27

Chronic lung disease at 36 weeks, n (%) 10 (34) 23 (31) 0.94

Mortality, n (%) 7 (24) 10 (13) 0.19

Composite adverse outcome among

survivors, n/N (%)

13/22 (59) 25/64 (39) 0.14

Duration of artificial ventilation

(mean±s.d.) days

15±18 18±22 0.52

Duration of respiratory support

(mean±s.d.) days

39±31 39±33 0.98

Duration of intravenous access

(mean±s.d.) days

17±15 23±19 0.13

Length of stay (mean±s.d.) days 54±43 55±41 0.86

Abbreviations: IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia.*P<0.05.

PPROM before age of viability and neonatal outcomesH Soylu et al

647

Journal of Perinatology

antenatal steroids, with a higher proportion of infants in thePPROM group receiving a complete course compared with thematched cohort. As expected, the duration of rupture ofmembranes (ROM) and GA at ROM were different between groups(Table 1). Results of other neonatal outcomes are reported inTable 2. There was significantly increased risk of mortality orsevere morbidities among cases (69 vs 47%; P¼ 0.02, unadjustedOR 2.5, 95% CI 1.0, 6.1). Logistic regression analyses confirmedPPROM at a previable age to be significantly associated withcomposite primary outcome (adjusted OR 4.0, 95% CI 1.2, 13.6).Univariate subgroup analysis revealed no significant differencein composite adverse outcome between groups of infants whohad PPROM before 20 weeks (n¼ 12) compared with those whohad PPROM after 20 weeks (n¼ 17) (58 vs 76%; P¼ 0.42).Reported causes of death among cases (n¼ 7) were pulmonaryhypoplasia in three, candida sepsis in one, bacterial sepsis in one,severe IVH in one and extreme prematurity in one infant.

Oligohydramnios or anhydramnios was present in 17 (63%)cases. For all cases, a course of prophylactic antibiotics, usually5 days of erythromycin, was used at the time of PPROM in keepingwith hospital policy. There was no difference in the risk ofcomposite outcome among those who had oligo- or anhydramnioscompared with those who did not have oligo- or anhydramnios.(65 vs 70%). Among the five patients who had anhydramnios,composite outcome was present in four, two patients died, three

had severe IVH/periventricular leukomalacia, three had severe ROPand one developed CLD at 36 weeks.

Discussion

Counseling women who present with PPROM at previable GA ischallenging. Many of these women will go into spontaneous labor,or will need to be delivered at a previable GA due to maternalhealth risks. Furthermore, in our local experience, a very poorprognosis for the fetus/neonate is often presented to the patient andtermination of pregnancy is frequently recommended. However,in the subset of women who experience PPROM at a previable GAand choose to continue their pregnancy to reach a viable GA, wereport a 76% survival to discharge from NICU for their preterminfants born at <32 weeks. In fact, our study may underestimatesurvival as we restricted our analysis to those infants who wereborn between 24 and 32 weeks GA. This cohort of preterm infantsborn following very early PPROM experienced higher rates ofcombined adverse outcomes including death or severe neurologicalinjury, severe ROP or CLD than matched preterm infants. Weacknowledge that our data are from a select group of infants whosurvived early PPROM and not a population-based cohort ofmothers who had ruptured and were serially followed up to assessthe outcomes.

Lindner et al.,12 in a retrospective matched cohort study of19 infants, reported that PPROM before 20 weeks was associatedwith higher risk of mortality, CLD and air leak when comparedwith infants not exposed to PPROM. However, the differences were

Table 1 Baseline characteristics

Characteristics Cases

(n¼ 29)

Controls

(n¼ 74)

P

GA (mean±s.d.) week 27±2 27±2 0.62

BW (mean±s.d.) g 1048 ±379 1007±344 0.61

Male, n (%) 20 (69) 46 (62) 0.79

IUGR, n (%) 0 (0) 4 (5) 0.20

Cesarean birth, n (%) 12 (41) 42 (57) 0.12

Median Apgar 1 min (range) 4 (2–5) 5 (3–8) 0.19

Median Apgar 5 min (range) 7 (5–9) 8 (7–9) 0.07

CRIB score (mean±s.d.) 7±4 4±4 <0.01*

TRIPS score (mean±s.d.) 31±14 20±10 <0.01*

Complete course of antenatal steroid, n (%) 28 (93) 48 (65) 0.015*

Chorioamnionitis, n (%) 9 (31) 6 (8) <0.01*

Duration of rupture of membranes (days)

Mean+s.d. 45+30 2+1 <0.01

Median (range) 39 (8–103) 1 (1–7) <0.01

GA at rupture of membranes (weeks)

Mean+s.d. 21±2 27±2 <0.01

Median (range) 22 (15–23) 27 (23–31) <0.01

Abbreviations: BW, body weight; CRIB, Clinical Risk Index for Babies; GA, gestational age;IUGR, intrauterine growth restriction; TRIPS, Transport Risk Index of PhysiologicStability.*P<0.05.

Table 2 Secondary outcomes and components of primary outcomes

Outcome Cases

(n¼ 29)

Matched cohort

(n¼ 74)

P

Respiratory distress syndrome, n (%) 28 (97) 62 (84) 0.08

Air leak, n (%) 5 (17) 5 (4) 0.02*

Persistent pulmonary hypertension, n (%) 6 (21) 0 (0) <0.001*

Sepsis, n (%) 4 (14) 17 (23) 0.30

Retinopathy of prematurity >stage 2, n (%) 5 (17) 11 (15) 0.77

Grade 3 or 4 IVH or PVL, n (%) 7 (24) 11 (15) 0.27

Chronic lung disease at 36 weeks, n (%) 10 (34) 23 (31) 0.94

Mortality, n (%) 7 (24) 10 (13) 0.19

Composite adverse outcome among

survivors, n/N (%)

13/22 (59) 25/64 (39) 0.14

Duration of artificial ventilation

(mean±s.d.) days

15±18 18±22 0.52

Duration of respiratory support

(mean±s.d.) days

39±31 39±33 0.98

Duration of intravenous access

(mean±s.d.) days

17±15 23±19 0.13

Length of stay (mean±s.d.) days 54±43 55±41 0.86

Abbreviations: IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia.*P<0.05.

PPROM before age of viability and neonatal outcomesH Soylu et al

647

Journal of Perinatology

antenatal steroids, with a higher proportion of infants in thePPROM group receiving a complete course compared with thematched cohort. As expected, the duration of rupture ofmembranes (ROM) and GA at ROM were different between groups(Table 1). Results of other neonatal outcomes are reported inTable 2. There was significantly increased risk of mortality orsevere morbidities among cases (69 vs 47%; P¼ 0.02, unadjustedOR 2.5, 95% CI 1.0, 6.1). Logistic regression analyses confirmedPPROM at a previable age to be significantly associated withcomposite primary outcome (adjusted OR 4.0, 95% CI 1.2, 13.6).Univariate subgroup analysis revealed no significant differencein composite adverse outcome between groups of infants whohad PPROM before 20 weeks (n¼ 12) compared with those whohad PPROM after 20 weeks (n¼ 17) (58 vs 76%; P¼ 0.42).Reported causes of death among cases (n¼ 7) were pulmonaryhypoplasia in three, candida sepsis in one, bacterial sepsis in one,severe IVH in one and extreme prematurity in one infant.

Oligohydramnios or anhydramnios was present in 17 (63%)cases. For all cases, a course of prophylactic antibiotics, usually5 days of erythromycin, was used at the time of PPROM in keepingwith hospital policy. There was no difference in the risk ofcomposite outcome among those who had oligo- or anhydramnioscompared with those who did not have oligo- or anhydramnios.(65 vs 70%). Among the five patients who had anhydramnios,composite outcome was present in four, two patients died, three

had severe IVH/periventricular leukomalacia, three had severe ROPand one developed CLD at 36 weeks.

Discussion

Counseling women who present with PPROM at previable GA ischallenging. Many of these women will go into spontaneous labor,or will need to be delivered at a previable GA due to maternalhealth risks. Furthermore, in our local experience, a very poorprognosis for the fetus/neonate is often presented to the patient andtermination of pregnancy is frequently recommended. However,in the subset of women who experience PPROM at a previable GAand choose to continue their pregnancy to reach a viable GA, wereport a 76% survival to discharge from NICU for their preterminfants born at <32 weeks. In fact, our study may underestimatesurvival as we restricted our analysis to those infants who wereborn between 24 and 32 weeks GA. This cohort of preterm infantsborn following very early PPROM experienced higher rates ofcombined adverse outcomes including death or severe neurologicalinjury, severe ROP or CLD than matched preterm infants. Weacknowledge that our data are from a select group of infants whosurvived early PPROM and not a population-based cohort ofmothers who had ruptured and were serially followed up to assessthe outcomes.

Lindner et al.,12 in a retrospective matched cohort study of19 infants, reported that PPROM before 20 weeks was associatedwith higher risk of mortality, CLD and air leak when comparedwith infants not exposed to PPROM. However, the differences were

Table 1 Baseline characteristics

Characteristics Cases

(n¼ 29)

Controls

(n¼ 74)

P

GA (mean±s.d.) week 27±2 27±2 0.62

BW (mean±s.d.) g 1048 ±379 1007±344 0.61

Male, n (%) 20 (69) 46 (62) 0.79

IUGR, n (%) 0 (0) 4 (5) 0.20

Cesarean birth, n (%) 12 (41) 42 (57) 0.12

Median Apgar 1 min (range) 4 (2–5) 5 (3–8) 0.19

Median Apgar 5 min (range) 7 (5–9) 8 (7–9) 0.07

CRIB score (mean±s.d.) 7±4 4±4 <0.01*

TRIPS score (mean±s.d.) 31±14 20±10 <0.01*

Complete course of antenatal steroid, n (%) 28 (93) 48 (65) 0.015*

Chorioamnionitis, n (%) 9 (31) 6 (8) <0.01*

Duration of rupture of membranes (days)

Mean+s.d. 45+30 2+1 <0.01

Median (range) 39 (8–103) 1 (1–7) <0.01

GA at rupture of membranes (weeks)

Mean+s.d. 21±2 27±2 <0.01

Median (range) 22 (15–23) 27 (23–31) <0.01

Abbreviations: BW, body weight; CRIB, Clinical Risk Index for Babies; GA, gestational age;IUGR, intrauterine growth restriction; TRIPS, Transport Risk Index of PhysiologicStability.*P<0.05.

Table 2 Secondary outcomes and components of primary outcomes

Outcome Cases

(n¼ 29)

Matched cohort

(n¼ 74)

P

Respiratory distress syndrome, n (%) 28 (97) 62 (84) 0.08

Air leak, n (%) 5 (17) 5 (4) 0.02*

Persistent pulmonary hypertension, n (%) 6 (21) 0 (0) <0.001*

Sepsis, n (%) 4 (14) 17 (23) 0.30

Retinopathy of prematurity >stage 2, n (%) 5 (17) 11 (15) 0.77

Grade 3 or 4 IVH or PVL, n (%) 7 (24) 11 (15) 0.27

Chronic lung disease at 36 weeks, n (%) 10 (34) 23 (31) 0.94

Mortality, n (%) 7 (24) 10 (13) 0.19

Composite adverse outcome among

survivors, n/N (%)

13/22 (59) 25/64 (39) 0.14

Duration of artificial ventilation

(mean±s.d.) days

15±18 18±22 0.52

Duration of respiratory support

(mean±s.d.) days

39±31 39±33 0.98

Duration of intravenous access

(mean±s.d.) days

17±15 23±19 0.13

Length of stay (mean±s.d.) days 54±43 55±41 0.86

Abbreviations: IVH, intraventricular hemorrhage; PVL, periventricular leukomalacia.*P<0.05.

PPROM before age of viability and neonatal outcomesH Soylu et al

647

Journal of Perinatology

Page 22: Fortbildung Frauenklinik Perinatalzentrum Luzern Die Sicht ... · Intakte Einlingsgravidität, I.BEL, reduziertes Bewegungsmuster, Anhydramnion. Persönliche Anamnese: 35-jährige

TAKE HOME MESSAGEWeiterführung einer Schwangerschaft bei frühem vorzeitigem Blasensprung (bei fehlenden Infektzeichen) ist sicher ein begehbarer Weg.

Es ist zu erwarten, dass die Kinder in den ersten Lebenstage grosse Unterstützung benötigen können

Mortalitäts- und Morbiditätsrate sind nicht signifikant erhöht in Vergleich zu gleichaltrigen Kindern.

Page 23: Fortbildung Frauenklinik Perinatalzentrum Luzern Die Sicht ... · Intakte Einlingsgravidität, I.BEL, reduziertes Bewegungsmuster, Anhydramnion. Persönliche Anamnese: 35-jährige

Vielen Dank geht an :

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