Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs

Abstract

Delayed cord clamping improves circulatory stability in preterm infants at birth, but the underlying physiology is unclear. We investigated the effects of umbilical cord clamping, before and after ventilation onset, on cardiovascular function at birth. Prenatal surgery was performed on lambs (123 days) to implant catheters into the pulmonary and carotid arteries and probes to measure pulmonary (PBF), carotid (CaBF) and ductus arteriosus blood flows. Lambs were delivered at 126 ± 1 days and: (1) the umbilical cord was clamped at delivery and ventilation was delayed for about 2 min (Clamp 1st; n = 6), and (2) umbilical cord clamping was delayed for 3-4 min, until after ventilation was established (Vent 1st; n = 6). All lambs were subsequently ventilated for 30 min. In Clamp 1st lambs, cord clamping rapidly (within four heartbeats), but transiently, increased pulmonary and carotid arterial pressures (by ∼30%) and CaBF (from 30.2 ± 5.6 to 40.1 ± 4.6 ml min(-1) kg(-1)), which then decreased again within 30-60 s. Following ventilation onset, these parameters rapidly increased again. In Clamp 1st lambs, cord clamping reduced heart rate (by ∼40%) and right ventricular output (RVO; from 114.6 ± 14.4 to 38.8 ± 9.7 ml min(-1) kg(-1)), which were restored by ventilation. In Vent 1st lambs, cord clamping reduced RVO from 153.5 ± 3.8 to 119.2 ± 10.6 ml min(-1) kg(-1), did not affect heart rates and resulted in stable blood flows and pressures during transition. Delaying cord clamping for 3-4 min until after ventilation is established improves cardiovascular function by increasing pulmonary blood flow before the cord is clamped. As a result, cardiac output remains stable, leading to a smoother cardiovascular transition throughout the early newborn period.

Figure 1. Recordings in unventilated and ventilated lambs before and after umbilical cord occlusion

Carotid arterial pressure (P_CA), pulmonary arterial pressure (P_PA), pulmonary blood flow (PBF), blood flow through the ductus arteriosus (DABF) and carotid arterial blood flow (CaBF) in unventilated (left) and ventilated (right) lambs before and after umbilical cord occlusion (indicated by dotted line).

Figure 2. Parameter changes in ventilated and unventilated lambs before and after umbilical cord occlusion

A–F, changes in mean (±SEM) carotid arterial blood pressure (A), heart rate (B), carotid arterial blood flow (C), pulmonary blood flow (D), ductus arteriosus (DA) blood flow (E) and right ventricular output (F) in ventilated (open circles) and unventilated lambs (filled circles) before and after umbilical cord occlusion (indicated by dotted line).

Figure 3. Parameter changes in ventilated and unventilated lambs for the first 10 heart beats after umbilical cord occlusion

A–F, changes in mean (±SEM) carotid arterial blood pressure (A), pulmonary arterial pressure (B), carotid arterial blood flow (C), minimum carotid arterial blood flow (D), pulmonary blood flow (E) and ductus arteriosus (DA) blood flow (F) in ventilated (open circles) and unventilated lambs (filled circles) for the first 10 heart beats after umbilical cord occlusion (indicated by dotted line). ‘0’ represents the heart beat immediately before cord clamping.

Figure 4. Parameter changes in response to ventilation onset

A–F, changes in mean (±SEM) carotid arterial blood pressure (A), heart rate (B), carotid arterial blood flow (C), pulmonary blood flow (D), ductus arteriosus (DA) blood flow (E) and right ventricular output (F) in response to ventilation onset (indicated by dotted line). Lambs either had an open, intact umbilical cord (open circles) or had a clamped umbilical cord (filled circles).

Figure 5. Time course of changes in Vent 1st and Clamp 1st lambs

A–F, time course for changes in mean (±SEM) carotid arterial blood pressure (A), heart rate (B), carotid arterial blood flow (C), pulmonary blood flow (D), ductus arteriosus (DA) blood flow (E) and right ventricular output (F) from birth in Vent 1st (open circles) and Clamp 1st lambs (filled circles). The left dotted line (at time 0) indicates the time of cord clamping in Clamp 1st lambs and the time of ventilation onset in Vent 1st lambs. The right dotted line indicates the time of ventilation onset in Clamp 1st lambs and the time of cord clamping in Vent 1st lambs.

Figure 6. Time course of changes in for the first 30 min after birth in Vent 1st and Clamp 1st lambs

A–D, time course for changes in mean (±SEM) carotid arterial blood flow (A), pulmonary blood flow (B), ductus arteriosus (DA) blood flow (C) and right ventricular output (D) for the first 30 min after birth in Vent 1st (open circles) and Clamp 1st lambs (filled circles).