Effect of maternal oxytocin on umbilical venous and arterial blood flows during physiological-based cord clamping in preterm lambs

Abstract

Background: Delayed umbilical cord clamping (UCC) after birth is thought to cause placental to infant blood transfusion, but the mechanisms are unknown. It has been suggested that uterine contractions force blood out of the placenta and into the infant during delayed cord clamping. We have investigated the effect of uterine contractions, induced by maternal oxytocin administration, on umbilical artery (UA) and venous (UV) blood flows before and after ventilation onset to determine whether uterine contractions cause placental transfusion in preterm lambs.

Methods and findings: At ~128 days of gestation, UA and UV blood flows, pulmonary arterial blood flow (PBF) and carotid arterial (CA) pressures and blood flows were measured in three groups of fetal sheep during delayed UCC; maternal oxytocin following mifepristone, mifepristone alone, and saline controls. Each successive uterine contraction significantly (p<0.05) decreased UV (26.2±6.0 to 14.1±4.5 mL.min-1.kg-1) and UA (41.2±6.3 to 20.7 ± 4.0 mL.min-1.kg-1) flows and increased CA pressure and flow (47.1±3.4 to 52.8±3.5 mmHg and 29.4±2.6 to 37.3±3.4 mL.min-1.kg-1). These flows and pressures were partially restored between contractions, but did not return to pre-oxytocin administration levels. Ventilation onset during DCC increased the effects of uterine contractions on UA and UV flows, with retrograde UA flow (away from the placenta) commonly occurring during diastole.

Conclusions: We found no evidence that amplification of uterine contractions with oxytocin increase placental transfusion during DCC. Instead they decreased both UA and UV flow and caused a net loss of blood from the lamb. Uterine contractions did, however, have significant cardiovascular effects and reduced systemic and cerebral oxygenation.

Fig 1. Physiological recordings of blood flows in the left pulmonary artery (PA), carotid artery, umbilical vein (UV) and umbilical artery (UA) before and immediately after oxytocin administration (iv) to the ewe in a newborn lamb prior to UCC and before ventilation onset.

Note that during the contraction, UV flow decreases to 0, UA flow decreases and reverses during diastole (indicated by diastolic flows below zero) and CA flow increases.

Fig 2

Changes in (A) mean (± SEM) umbilical arterial (UA) blood flow, (B) venous (UV) blood flow (C) arterial oxygen saturation (SaO₂) and (D) cerebral tissue oxygenation (SctO₂) levels in RU486 plus saline treated lambs (open cycles) and RU486 plus oxytocin treated lambs (closed squares). Samples were collected during the first 5 minutes after oxytocin/saline administration and before ventilation onset (A & B) and for 5 minutes after ventilation onset (indicated by shaded area; C & D). Data from saline-infused control animals (no RU486) have been omitted for clarity.

Fig 3. Blood flow in the umbilical vein (UV) and umbilical artery (UA) measured immediately before (black bar) and during (grey bar) consecutive uterine contractions and before (BV) and after (AV) ventilation onset.

UV and UA blood flows measured during each contraction were significantly lower than flows measured immediately prior to the contraction (p<0.0001).

Fig 4. Diastolic blood flow in the umbilical artery (UA) measured immediately before (black bar) and during (grey bar) consecutive uterine contractions and before (BV) and after (AV) ventilation onset.

Flows that have a value below zero indicate retrograde flow in the UA. Blood flows measured during each contraction were significantly lower than flows measured immediately prior to the contraction (p<0.0001).

Fig 5. Physiological recordings of mean blood flows in the umbilical vein (UV), umbilical artery (UA) and the arithmetic derivation of UV-UA flow in a newborn lamb during consecutive uterine contractions.

A value for UV-UA flow that is below zero indicates a net loss of blood flow from the lamb into the placenta. Note that during the contraction, both UV and UA flow decrease to near zero, but that the reduction in UV flow is significantly delayed compared to the UA flow. As a result, much of the reduction in UV flow occurs while the UA flow is recovering, resulting in a net loss of blood from the lamb. However, with the onset of the next contraction, because the reduction in UV flow is delayed, there is a net flow of blood from the placenta to the lamb.

Fig 6. Mean carotid arterial (CA) pressures measured immediately before (black bar) and during (grey bar) consecutive uterine contractions and before (BV) and after ventilation (AV) onset.

Arterial pressures measured during each contraction were significantly higher than pressures measured immediately prior to the contraction (p<0.0002).

Fig 7

Mean blood flows in the umbilical vein (UV; open circles) and umbilical artery (UA; closed squares) measured immediately before (A) and during (B) consecutive uterine contractions before and after ventilation onset. Both UV and UA flow significantly decreased with increasing contraction number during (p<0.0001 and p = 0.015, respectively) between (p = 0.0001 and p = 0.001, respectively) contractions (C) The percentage reduction in UV flow during a uterine contraction was significantly greater (p<0.0001) after ventilation onset (grey bar) compared to before ventilation onset (black bar).