Abstract
Background
As surges in circulating norepinephrine and epinephrine have chronotropic, pressor, and inotropic effects, we tested the hypothesis that blunted rises in these catecholamines during preterm birth accompanied hemodynamic stability observed after early ventilation and delayed cord clamping (DCC), with findings compared to immediate cord clamping (ICC) and a non-asphyxial cord clamp-to-ventilation interval.
Methods
Anesthetized preterm fetal lambs were instrumented with arterial micromanometers to obtain pressure and the maximal rate of pressure rise (dP/dtmax) as a surrogate of ventricular contractility and an aortic catheter to obtain blood samples for catecholamine assay. Fetuses were delivered and mechanically ventilated before cord clamping ∼1.5 min later (DCC, n = 9) or subjected to ICC with ventilation started ∼40 s later (n = 8).
Results
Perinatal hemodynamics were stable after DCC, with greater fluctuations evident following birth after ICC (P ≤ 0.05). With DCC, circulating norepinephrine and epinephrine were unchanged after early ventilation but rose following cord clamping (P ≤ 0.01), with concentrations below the threshold for hemodynamic effects. Norepinephrine was higher in the ICC group after cord clamping and immediately after ventilation (P < 0.025), but catecholamine levels were otherwise similar between groups.
Conclusion
Hemodynamic stability at birth after DCC is accompanied by sub-threshold rises in circulating norepinephrine and epinephrine and thus blunted sympathoadrenal activation.
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Acknowledgements
We thank Magdy Sourial, Amy Tilley, Sara White, Aaron Mocciaro, Rebecca Sutton, Dr. Nikita Gupta, and Dr. Ramona Krauss for technical assistance with experimental studies. This work was supported by Project Grant 1105137 from the National Health and Medical Research Council of Australia (NHMRC) and the Victorian Government’s Operational Infrastructure Support Program. J.P.M. was supported by a co-funded NHMRC Career Development Fellowship and National Heart Foundation Future Leader Fellowship and G.W.L. by an NHMRC Research Fellowship.
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J.J.S.: (1) substantial contributions to study conception and design and data acquisition, analysis and interpretation, (2) drafted and critically revised article for important intellectual content, (3) gave final approval of the published version. K.R.K. and S.E.P.: (1) substantial contributions to data acquisition and analysis, (2) revised article critically for important intellectual content, (3) gave final approval of the published version. J.P.M.: (1) substantial contributions to data interpretation, (2) revised article critically for important intellectual content, (3) gave final approval of the published version. G.W.L.: (1) substantial contributions to study conception and data interpretation, (2) revised article critically for important intellectual content, (3) gave final approval of published version.
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G.W.L.’s laboratory receives/has received research funding from Medtronic, Abbott Pharmaceuticals, Servier Australia, and Allergan. G.W.L. has acted as a consultant for Medtronic and has received honoraria or travel support for presentations from Pfizer, Wyeth Pharmaceuticals, Servier, and Medtronic. J.P.M. is a consultant for the Brain Protection Company. These companies provided no input into this study. The other authors declare no competing interests.
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Smolich, J.J., Kenna, K.R., Mynard, J.P. et al. Blunted sympathoadrenal activation accompanies hemodynamic stability after early ventilation and delayed cord clamping at birth in preterm lambs. Pediatr Res 86, 478–484 (2019). https://doi.org/10.1038/s41390-019-0448-y
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DOI: https://doi.org/10.1038/s41390-019-0448-y
