Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02671305 |
| Other study ID # |
152-2014 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 9, 2016 |
| Est. completion date |
September 15, 2023 |
Study information
| Verified date |
June 2024 |
| Source |
University of Florence |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Preterm newborns receiving placental transfusion at birth (a volume of blood coming from the
placenta towards the newborn till the cord is left unclamped) have better neonatal outcomes
(in particular reduction of intraventricular hemorrhage all grade). The placental transfusion
strategies performed in preterm babies at delivery have been delayed cord clamping and cord
milking. Both experimental strategies do not explore the contribution of the start of
breathing on placental transfusion, as performed in a small time frame (30-60 seconds for
delayed clamping and less than 20 sec for cord milking). To assist the newborn bedside near
to the delivering mother, leaving the cord unclamped, would allow to explore the contribution
of breathing,both spontaneously started or assisted by initial steps in stabilization, on
early postnatal adaptation.
The purpose of the present study is to assess the feasibility and effectiveness of delivery
room assistance with the placental circulation intact in comparison to cord milking for
improving outcomes in very preterm newborns.
Description:
At delivery, if the cord is not clamped immediately, a volume of blood coming from the
placenta continues to pass into the newborn: this placental transfusion ranges between 25 and
40 ml/kg body weight, depending on gestational age, timing of cord clamping, position of the
infant at birth, onset of respirations, and administration of uterotonics to the mother.
Recent research studies on animals have indicated a possible physiological role of placental
transfusion in the first minutes of life, during the postnatal transition phase. During fetal
life, oxygenated blood coming from the placenta through the umbilical vein largely reach the
heart left ventricle through the foramen ovale. So, before birth, the placenta guarantees the
left ventricle pre-load, thus maintaining cardiac output towards the aorta and epi-aortic
vessels. At birth, if the cord is clamped immediately, left ventricle suddenly loose the
source of its filling and the left ventricle preload becomes fully dependent on pulmonary
veins return from the lungs. Pulmonary blood flow increases slowly after birth as the newly
born starts breathing, in fact ventilation triggers the fall of pulmonary vascular
resistances. The period between cord clamping and the onset of breathing has been indicated
as "non respiring interval", when the newly born is no more receiving oxygenated blood from
the placenta and not yet from the lungs. During this period, cardiac output is decreased, and
hemodynamic fluctuations associated to reduced cerebral oxygenation have been demonstrated in
animals. Otherwise, if the cord is maintained unclamped, blood coming from the placenta
through the umbilical vein continues to fill left ventricle, while the onset of newborn's
ventilation increases pulmonary blood flow and venous return. Thus, delaying cord clamping
till after the start of breathing would maintain left ventricle pre-load unchanged, as
demonstrated by the absence of hemodynamic fluctuations associated to reduced cerebral
oxygenation in animal studies. These phenomena are probably responsible for the reduced
incidence of intra-ventricular hemorrhage in babies receiving placental transfusion. Recent
meta-analysis in preterm newborns demonstrated that delayed cord clamping is associated to
improvement in cardiovascular stability and reduced need for inotropes, lower incidence of
all grade intra-ventricular hemorrhage and necrotizing enterocolitis, lower oxygen
requirement at 36 week of post-menstrual age, and less need for red blood cell transfusions,
apparently without any severe short-term related morbidities or adverse effects; however,
randomized trials have not yet investigated newly born infants requiring resuscitation.
Placental transfusion in preterm babies may take longer, and may be incomplete if the cord is
clamped within 30 to 90 seconds. This seems logical, as at term, two-thirds of the
feto-placental circulation is in the infant, whilst below 30 weeks gestation, a greater
proportion is in the placenta. Also, the umbilical vein is smaller than at term, and uterine
contraction less efficient. Therefore, preterm babies who start breathing during a prolonged
placental transfusion would probably receive the best benefits in terms of improved outcomes.
Cord milking (pinching the cord close to the mother and running the fingers towards the baby,
usually 3 to 5 times) has been suggested for preterm births as a means to obtain a placental
transfusion more rapidly. This procedure takes less than 20 seconds to be performed thus
allowing a timely resuscitation of the newborn, in a standard setting, if needed. Cord
milking over-rides the infant's physiological control of its own blood volume and blood
pressure, however, and disrupts umbilical blood flow. Cord milking compared to immediate cord
clamping has been recently associated in a systematic review and meta-analysis with some
benefits (less oxygen requirement at 36w of gestation, and less IVH all grades) and no
adverse effects in the immediate postnatal period in preterm infants less than 33 weeks of
gestational age; however, further studies are warranted to assess the effect of cord milking
on neonatal and long-term outcomes.
The hypothesis of the study is that to assist a preterm baby less than 30 weeks gestation
with placental circulation intact allows a better postnatal adaptation and improves outcome
in the neonatal period. For an ethical reason the control group will receive cord milking
instead of immediate cord clamping, based on recently published results favoring cord milking
in preterm babies.
The study has been designed as a two-phases study: phase 1 to assess the feasibility of the
protocol (first 20 patients recruited) and phase 2 to compare the efficacy of delivery room
assistance with placental circulation intact (with cord clamping at 3 minutes of life) versus
cord milking for improving outcome in the neonatal period. To maximise efficiency of the
planned full trial, phase 1 data would remain blind by allocated group and so would
contribute to the sample size of the full trial. Recruitment of phase 1 was started on April
2016 and was completed on April 2017. Phase 1 of the study have reached the targets for
feasibility. Recruitment of phase 2 (remaining 182 patients) is expected to be completed by
the end of December 2018.
