Smolich Joseph J, Kenna Kelly R
Heart Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.
J Physiol. 2025 Feb;603(4):949-970. doi: 10.1113/JP287817. Epub 2025 Jan 12.
Although the corticosteroid betamethasone is routinely administered to accelerate lung and cardiovascular maturation in the preterm fetus prior to birth, and use of delayed cord clamping (DCC) is recommended at birth by professional bodies, it is unknown whether antenatal betamethasone alters perinatal pulmonary or systemic arterial blood flow accompaniments of DCC. To address this issue, preterm fetal lambs [gestation 127 (1) days, term = 147 days] with (n = 10) or without (n = 10) antenatal betamethasone treatment were acutely instrumented under general anaesthesia with flow probes to obtain left (LV) and right ventricular (RV) outputs, major central arterial blood flows and shunt flow across both the ductus arteriosus and foramen ovale (FO). After delivery, lambs underwent initial ventilation for 2 min prior to DCC. During initial ventilation and after DCC, betamethasone (1) augmented rises in pulmonary arterial blood flow, with this greater increase supported during initial ventilation by enhanced pulmonary distribution of a higher RV output that was largely underpinned by newly emergent and substantial left-to-right (L → R) shunting across the FO, and after DCC, by an added contribution from more pronounced L → R ductal shunting; (2) increased a redistribution of LV output away from the upper body region, accompanied by lowering of upper body blood flow and O delivery; and (3) accentuated a progressive systemic-to-pulmonary arterial shift in the distribution of the combined LV and RV output that occurred in conjunction with more pronounced perinatal L → R shunting. These findings suggest that antenatal betamethasone substantially alters arterial blood flow effects of initial ventilation and DCC in the preterm birth transition. KEY POINTS: Betamethasone is given to increase fetal lung and cardiovascular maturation prior to preterm birth, while delayed cord clamping (DCC) is recommended at birth. Whether antenatal betamethasone alters perinatal arterial blood flow responses to DCC is unknown. Anaesthetized preterm fetal lambs with or without betamethasone pretreatment were instrumented with central arterial flow probes and, at birth, underwent ∼2 min of ventilation before DCC. Betamethasone augmented perinatal rises in pulmonary arterial blood flow, related to enhanced pulmonary distribution during initial ventilation of a higher right ventricular output largely underpinned by left-to-right (L → R) shunting across the foramen ovale, with an added contribution from more pronounced L → R ductal shunting after DCC. Betamethasone increased a redistribution of left ventricular output away from the upper body region, with lowering of upper body blood flow and O delivery. Betamethasone accentuated a systemic-to-pulmonary arterial shift in the distribution of combined ventricular output occurring with greater perinatal L → R shunting.
尽管在早产前常规给予皮质类固醇倍他米松以加速早产胎儿的肺和心血管成熟，并且专业机构建议在出生时采用延迟脐带结扎（DCC），但尚不清楚产前倍他米松是否会改变DCC时的围产期肺或全身动脉血流情况。为了解决这个问题，对妊娠127（1）天（足月为147天）的早产羔羊进行研究，其中10只接受产前倍他米松治疗，10只未接受治疗，在全身麻醉下通过血流探头进行急性监测，以获取左心室（LV）和右心室（RV）输出量、主要中心动脉血流量以及动脉导管和卵圆孔（FO）处的分流流量。分娩后，羔羊在进行DCC前先进行2分钟的初始通气。在初始通气期间和DCC后，倍他米松：（1）增强了肺动脉血流量的增加，在初始通气期间，这种更大的增加是由更高的RV输出量在肺内更广泛的分布所支持，这主要是由新出现的、大量的通过FO的左向右（L→R）分流所致，而在DCC后，则是由更明显的L→R动脉导管分流的额外作用所致；（2）增加了LV输出量从上半身区域的重新分配，伴随着上半身血流量和氧输送的降低；（3）加剧了LV和RV联合输出量分布中从全身动脉到肺动脉的逐渐转变，这与围产期更明显的L→R分流同时发生。这些发现表明，产前倍他米松在早产过渡过程中显著改变了初始通气和DCC的动脉血流效应。要点：在早产前给予倍他米松以增加胎儿肺和心血管成熟，而出生时建议采用延迟脐带结扎（DCC）。产前倍他米松是否会改变围产期对DCC的动脉血流反应尚不清楚。对有或没有倍他米松预处理的麻醉早产羔羊用中心动脉血流探头进行监测，出生时在DCC前进行约2分钟的通气。倍他米松增强了围产期肺动脉血流量的增加，这与初始通气期间更高的右心室输出量在肺内更广泛的分布有关，这主要是由通过卵圆孔的左向右（L→R）分流所致，DCC后更明显的L→R动脉导管分流起到了额外作用。倍他米松增加了左心室输出量从上半身区域的重新分配，导致上半身血流量和氧输送降低。倍他米松加剧了联合心室输出量分布中从全身动脉到肺动脉的转变，同时伴有围产期更明显的L→R分流。
