Stabilisation of preterm infants with intact umbilical cord · Stabilisation of preterm infants...

Stabilisation of preterm infants with

intact umbilical cord

Ronny Knol

47th Annual Conference BVK

Brussels, March 21st 2019

Introduction

Modified from Rudolph AM. Congenital diseases of the heart. Chicago: Year Book Publishers; 1974, p. 1-48; and from Freed MD. Fetal

and transitional circulation. In: Fyler DC, editor. Nadas’ pediatric cardiology. Philadelphia: Mosby-Year Book; 1992. p. 57-61.

Introduction

Introduction

Delayed Cord Clamping in preterm infants:

More haemoglobin

Less hypotension

Less IVH

Less NEC

Fogarty et al. Am J Obstet Gynecol 2018

Introduction

Van Vonderen et al. Neonatology 2014

Bhatt et al. J Physiol feb 2013

Introduction

Clamp Vent

Introduction

Bhatt et al. J Physiol feb 2013

Blank et al. ADC FN 2017

Duley et al. ADC FNN 2017

Duley et al. ADC FNN 2017

Katheria et al. J Pediatr 2016

Winter et al. Am J Perinatol 2016

Aeration, breathing and then clamping Physiological based cord clamping

Physiological based cord clamping

Illustrations by Sophie Cramer, 2018

Physiological based cord clamping

Cord Clamping:

Spontaneous breathing with CPAP

Heart rate > 100 bpm

SpO2 > 90%

FiO2 < 0.4

Aeration, Breathing, Clamping

1. Feasibility study, single-center

2. Effectiveness study, 2 centers, non-inferiority

Randomised

3. (Inter)national multi-center randomised clinical trial

ABC1 study, feasibility

Brouwer et al. ADC FN 2018

Perinatal outcomes

All infants (n=37)

PBCC 33 (89.2)

Cord clamping time, min 4:23 [3:00 – 5:11]

Apgar score 1 min 7 [5 – 8]

Apgar score 5 min 8 [8 – 9]

Umbilical cord – pH 7.25 ± 0.10

Respiratory support at delivery

CPAP

PPV

Intubation

35 (94.6)

35 (94.6)

11 (29.7)

0

Maternal blood loss, ml 300 [200 – 475]

Temperature at admission, °C 36.0 ± 0.70

Hemoglobin < 24 h, mmol/l 11.18 ± 1.73

Aeration, Breathing, Clamping

1. Feasibility study, single-center

2. Effectiveness study, 2 centers, non-inferiority

Randomised

3. (Inter)national multi-center randomised clinical trial

Brouwer et al. ADC FN 2018

37 preterm infants

ABC2 study

• Randomised clinical trial, non-inferiority design

P: Preterm infants 24 - 31+6 weeks GA

I: Physiological Based Cord Clamping (PBCC)

C: Standard care (Time Based Cord Clamping, TBCC)

O: Time to stabilisation

• Definition of ‘stabilisation’:

Spontaneous breathing with CPAP, HR > 100/min, SpO2 > 90%, FiO2 < 40%.

Infant baseline characteristics

PBCC (n=19)

Control (n=17)

Gestational age, weeks 29.0 ± 1.8 29.2 ± 2.3

Birthweight, grams 1183 ± 270 1306 ± 437

Twins, infants 5 (26.3) 3 (17.6)

Antenatal steroids 19 (100%)

17 (100%)

Caesarean Section 9 (47.4) 9 (52.9)

PE/HELLP 3 (15.8) 2 (11.8)

Premature contractions 14 (73.7) 12 (70.6)

ABC2 study, results

Primary outcomes (intention-to-treat)

PBCC (n=19)

Control (n=17)

P value

Time to stabilisation (from birth)

5:54 ± 2:27 7:07 ± 2:54 0.18

Time to cord clamping

5:33 ± 2:24 1:02 ± 0:30 0.00

ABC2 study, results

Safety parameters (intention-to-treat)

PBCC (n=17)

Control (n=16)

P value

Postoperative infection (after CS) 0/9 0/8

Maternal blood loss, mL 300 [200-700] 450 [263-537] 0.557

PPH, >1000 mL 2 (11.8) 2 (12.5)

PBCC (n=19)

Control (n=17)

Infant temperature at admission 36.5 ± 0.9 36.7 ± 0.6 0.58

Infant temperature < 36.0 4 (23.5) 1 (5.9) 0.19

ABC2 study, results

Aeration, Breathing, Clamping

1. Feasibility study, single-center

2. Effectiveness study, 2 centers, non-inferiority

Randomised

3. (Inter)national multi-center randomised clinical trial

Brouwer et al. ADC FN 2018

37 preterm infants

36 preterm infants

Physiological based cord clamping

Cord Clamping:

Heart rate > 100 bpm

SpO2 > 85%

FiO2 < 0.4

Trial of CPAP before clamping

ABC3 study

• Multicenter randomised clinical trial (2 x 330 infants)

P: Preterm infants ≤ 29+6 weeks GA

I: Physiological Based Cord Clamping (PBCC)

C: Standard care (Time Based Cord Clamping, TBCC)

O: Survival without major cerebral injury (IVH≥2, PVL≥2, venous infarction) and/or

necrotizing enterocolitis (NEC≥2).

TAKE HOME

Stabilisation of preterm infants with intact umbilical cord may result in a

more stable cardiopulmonary transition.

Stabilisation of preterm infants with intact umbilical cord is feasible and

at least as effective as standard stabilisation.

Timing of cord clamping should be based on transitional physiology:

Physiological Based Cord Clamping

Need for more physiological and clinical data…

Aeration, Breathing, Clamping

Leiden University Medical Center:

Arjan te Pas

Frans Klumper

Thomas van den Akker

Emma Brouwer

Romy Berkhout

Enrico Lopriore

Amsterdam University Medical Center:

Anton van Kaam

Netherlands Neonatal Research Network (NNRN):

Wes Onland

Debbie Nuytemans

Erasmus Medical Center, Rotterdam:

Ronny Knol

Philip DeKoninck

Marijn Vermeulen

Nanda van Vliet

Irwin Reiss

Monash University, Melbourne, Australia:

Stuart Hooper

Graeme Polglase

r.knol@erasmusmc.nl