Prediction of Therapeutic Response to Cyclooxygenase Inhibitors in Preterm Infants with Patent Ductus Arteriosus

Hu, Yang; Jin, Hongfang; Jiang, Yi; Du, Junbao

doi:10.1007/s00246-018-1831-x

Cited by 11 publications

(11 citation statements)

References 31 publications

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“…Although these parameters are regarded as good markers for the severity and natural course of PDA 15,20,24 , studies of the echocardiographic parameters that predict drug response rate are scarce. In a small study of preterm infants <28 weeks of gestation, the baseline ductal diameter did not differ between responders and non-responders to the first ibuprofen course 25 . By contrast, in a study of relatively mature preterm infants (gestational age <35 weeks), an index of PDA diameter squared/birth weight >9 mm 2 /kg was reported to predict failure of treatment with indomethacin 26 .…”

Section: Discussionmentioning

confidence: 81%

Plasma B-type natriuretic peptide cannot predict treatment response to ibuprofen in preterm infants with patent ductus arteriosus

Lee

Jung

et al. 2020

Sci Rep

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Plasma B-type natriuretic peptide (BNP) is a useful marker for diagnosis of hemodynamically significant pDA (hspDA) and serial Bnp measurement is also valuable for monitoring treatment response. this retrospective study was performed to evaluate whether plasma Bnp level can predict treatment response to ibuprofen in preterm infants born at <30 weeks of gestation with hsPDA. Plasma BNP was measured before (baseline) and 12 to 24 h after (post-treatment) completion of the first (IBU1) and second (IBU2) course of ibuprofen. We compared the BNP levels of responders (closed or insignificant PDA) with those of non-responders (hspDA requiring further pharmacologic or surgical closure) to each course of ibuprofen. The treatment response rates for IBU1 (n = 92) and IBU2 (n = 19) were 74% and 26%, respectively. In IBU1, non-responders had lower gestational age and birth weight than responders (both, P = 0.004), while in IBU2, non-responders had lower birth weight (P = 0.014) and platelet counts (P = 0.005) than responders; however, baseline BNP levels did not differ significantly between responders and non-responders in either IBU1 (median 1,434 vs. 1,750 pg/mL) or IBU2 (415 vs. 596 pg/mL). Post-treatment BNP was a useful marker for monitoring treatment efficacy of IBU1 and IBU2 for hsPDA with a cutoff value of 331 pg/mL (P < 0.001) and 423 pg/mL(P < 0.010), respectively. We did not identify a cutoff baseline BNP level that could predict treatment response to ibuprofen in preterm infants with hspDA.

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Section: Discussionmentioning

confidence: 81%

Plasma B-type natriuretic peptide cannot predict treatment response to ibuprofen in preterm infants with patent ductus arteriosus

Lee

Jung

et al. 2020

Sci Rep

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“…It is secreted from the ventricles in response to increased cardiac stress and increases intracellular cGMP, inducing vasodilation. In PDA, the volume of left-to-right shunting is associated with the BNP level and higher levels predict a hemodynamically significant PDA and a poor response to indomethacinin preterm infants ( 63 , 64 ). Bradykinin induces ductal constriction through BK-1 receptors ( 29 ).…”

Section: Functional Closurementioning

confidence: 99%

“…At the same time, they will be responsive to prosglandins, and be susceptible to re-opening in case of prostaglandin surge as it happens in sepsis or necrotizing enterocolitis. In contrast, preterm ductus produces NO after birth, due to the growth of new vasa vasorum that synthesize NO ( 63 ). Therefore, the ductus becomes more dependent on vasodilators other than prostaglandins after the first few weeks.…”

Section: Anatomic Closure and Remodelingmentioning

confidence: 99%

Molecular and Mechanical Mechanisms Regulating Ductus Arteriosus Closure in Preterm Infants

Ovalı

2020

Front. Pediatr.

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Failure of ductus arteriosus closure after preterm birth is associated with significant morbidities. Ductal closure requires and is regulated by a complex interplay of molecular and mechanical mechanisms with underlying genetic factors. In utero patency of the ductus is maintained by low oxygen tension, high levels of prostaglandins, nitric oxide and carbon monoxide. After birth, ductal closure occurs first by functional closure, followed by anatomical remodeling. High oxygen tension and decreased prostaglandin levels mediated by numerous factors including potassium channels, endothelin-1, isoprostanes lead to the contraction of the ductus. Bradykinin and corticosteroids also induce ductal constriction by attenuating the sensitivity of the ductus to PGE2. Smooth muscle cells of the ductus can sense oxygen through a mitochondrial network by the role of Rho-kinase pathway which ends up with increased intracellular calcium levels and contraction of myosin light chains. Anatomical closure of the ductus is also complex with various mechanisms such as migration and proliferation of smooth muscle cells, extracellular matrix production, endothelial cell proliferation which mediate cushion formation with the interaction of blood cells. Regulation of vessel walls is affected by retinoic acid, TGF-β1, notch signaling, hyaluronan, fibronectin, chondroitin sulfate, elastin, and vascular endothelial cell growth factor (VEGF). Formation of the platelet plug facilitates luminal remodeling by the obstruction of the constricted ductal lumen. Vasa vasorum are more pronounced in the term ductus but are less active in the preterm ductus. More than 100 genes are effective in the prostaglandin pathway or in vascular smooth muscle development and structure may affect the patency of ductus. Hemodynamic changes after birth including fluid load and flow characteristics as well as shear forces within the ductus also stimulate closure. Current pharmacological treatment for the closure of a patent ductus is based on the blockage of the prostaglandin pathway mainly through COX or POX inhibition, albeit with some limitations and side effects. Further research for new agents aiming ductal closure should focus on a clear understanding of vascular biology of the ductus.

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“…127 In PDA, the volume of left-to-right shunting is associated with NP level. 128 Higher baseline levels before INDO treatment predict a poor response. 114,128 The NP mediated increase in cGMP actually neutralizes INDO mediated reduction in cAMP, shifting the balance to vasodilation.…”

Section: Patent Da In the Preterm Infantmentioning

confidence: 99%

“…128 Higher baseline levels before INDO treatment predict a poor response. 114,128 The NP mediated increase in cGMP actually neutralizes INDO mediated reduction in cAMP, shifting the balance to vasodilation. These findings suggest that NP is not only a marker of cardiac failure, but could also play a role in DA tone and therapeutic failure.…”

Section: Patent Da In the Preterm Infantmentioning

confidence: 99%

Understanding the pathobiology in patent ductus arteriosus in prematurity—beyond prostaglandins and oxygen

Hundscheid¹,

Broek

Lee³

et al. 2019

Pediatr Res

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The ductus arteriosus (DA) is probably the most intriguing vessel in postnatal hemodynamic transition. DA patency in utero is an active state, in which prostaglandin E 2 (PGE 2) and nitric monoxide (NO), play an important role. Since the DA gets programmed for postnatal closure as gestation advances, in preterm infants the DA frequently remains patent (PDA). PGE 2 exposure programs functional postnatal closure by inducing gene expression of ion channels and phosphodiesterases and anatomical closure by inducing intimal thickening. Postnatally, oxygen inhibits potassium and activates calcium channels, which ultimately leads to a rise in intracellular calcium concentration consequently inducing phosphorylation of the myosin light chain and thereby vasoconstriction of the DA. Since ion channel expression is lower in preterm infants, oxygen induced functional vasoconstriction is attenuated in comparison with full term newborns. Furthermore, the preterm DA is more sensitive to both PGE 2 and NO compared to the term DA pushing the balance toward less constriction. In this review we explain the physiology of DA patency in utero and subsequent postnatal functional closure. We will focus on the pathobiology of PDA in preterm infants and the (un)intended effect of antenatal exposure to medication on both fetal and neonatal DA vascular tone.

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Prediction of Therapeutic Response to Cyclooxygenase Inhibitors in Preterm Infants with Patent Ductus Arteriosus

Cited by 11 publications

References 31 publications

Plasma B-type natriuretic peptide cannot predict treatment response to ibuprofen in preterm infants with patent ductus arteriosus

Plasma B-type natriuretic peptide cannot predict treatment response to ibuprofen in preterm infants with patent ductus arteriosus

Molecular and Mechanical Mechanisms Regulating Ductus Arteriosus Closure in Preterm Infants

Understanding the pathobiology in patent ductus arteriosus in prematurity—beyond prostaglandins and oxygen

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