Fetal Reversed Constrictive Effect of Indomethacin and Postnatal Delayed Closure of the Ductus Arteriosus following Administration of Transplacental Magnesium Sulfate in Rats

Toyoshima, Katsuaki; Momma, Kazuo; Nakanishi, Toshio

doi:10.1159/000208794

Cited by 7 publications

(5 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previously demonstrated in a 2009 animal study, hypermagnesemia induced by transplacental magnesium sulfate attenuated the fetal ductus-constricting effects of indomethacin and delayed postnatal ductal closure in rats [5]. This phenomenon has also been reported in extremely preterm neonates in which antenatal magnesium sulfate treatment has been associated with a greater frequency of DA patency and reduced clinical responsiveness of the DA to indomethacin therapy [6,7].…”

Section: Discussionsupporting

confidence: 64%

“…We defined DA constriction as a PI ≤1.94 [3], and quantified DA constriction as severe (PI ≤1.0) or mild-to-moderate constriction (PI > 1.0 and ≤1.94) (Figure 1). We used the PI to determine the severity of DA constriction, as it remains constant despite changes in gestational age [3] and is relatively angle independent [5].…”

Section: Fetal Hemodynamic Datamentioning

confidence: 99%

See 1 more Smart Citation

Indomethacin Dosing and Constriction of the Ductus Arteriosus During Open Fetal Surgery for Myelomeningocele Repair

Howley¹,

Chatterjee

Patel

et al. 2018

Fetal Diagn Ther

View full text Add to dashboard Cite

Introduction: The use of perioperative tocolytic agents in fetal surgery is imperative to prevent preterm labor. Indomethacin, a well-known tocolytic agent, can cause ductus arteriosus (DA) constriction. We sought to determine whether a relationship exists between preoperative indomethacin dosing and fetal DA constriction. Materials and Methods: This is an IRB-approved, single-center retrospective observational case series of 42 pregnant mothers who underwent open fetal myelomeningocele repair. Preoperatively, mothers received either 1 (QD) or 2 (BID) indomethacin doses. Maternal anesthetic drug exposures and fetal cardiac dysfunction measures were collected from surgical and anesthesia records and intraoperative fetal echocardiography. Pulsatility Index was used to calculate DA constriction severity. Comparative testing between groups was performed using t- and chi-square testing. Results: DA constriction was observed in all fetuses receiving BID indomethacin and in 71.4% of those receiving QD dosing (p = 0.0002). Severe DA constriction was observed only in the BID group (35.7%). QD indomethacin group received more intraoperative magnesium sulfate (p < 0.0001). Minimal fetal cardiac dysfunction (9.5%) and bradycardia (9.5%) were observed in all groups independent of indomethacin dosing. Conclusions: DA constriction was the most frequent and severe in the BID indomethacin group. QD indomethacin and greater magnesium sulfate dosing was associated with reduced DA constriction.

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Fetal Hemodynamic Datamentioning

confidence: 99%

Indomethacin Dosing and Constriction of the Ductus Arteriosus During Open Fetal Surgery for Myelomeningocele Repair

Howley¹,

Chatterjee

Patel

et al. 2018

Fetal Diagn Ther

View full text Add to dashboard Cite

show abstract

“…Some studies reported dilation of foetal ductus arteriosus following maternal administration of phosphodiesterase 3 or 5 inhibitor, and magnesium sulphate in rats. [14][15][16] These agents dilated constrictive ductus arteriosus by indomethacin in foetal rats, suggesting the potential usefulness of maternal administration of these agents for the treatment of idiopathic or secondary foetal ductal narrowing. Patients having right ventricular outflow tract obstruction with foetal ductal narrowing may need maternal administration of these agents for the treatment and prophylaxis of constrictive ductus arteriosus.…”

Section: Discussionmentioning

confidence: 99%

High incidence of ductal closure or narrowing at birth in patients with right ventricular outflow tract obstruction with normal orientation of the ductus arteriosus

et al. 2018

View full text Add to dashboard Cite

BackgroundDuctal patency is mandatory to manage patients with ductal-dependent pulmonary circulation. The aim of this study is to elucidate the morphological and haemodynamic features of ductus arteriosus with right ventricular outflow tract obstruction, and investigate the appropriate perinatal management.Patients and methodsPatients with prenatal diagnosis of right ventricular outflow tract obstruction at our institution between 2010 and 2015 were included in the study. Reverse orientation of the ductus arteriosus is defined as an inferior angle of <90° at the aortic junction, and normal orientation of the ductus arteriosus as an angle of >90°. We retrospectively reviewed the shape and flow pattern of ductus arteriosus and the clinical characteristics of the cases.ResultsA total of 39 patients were enrolled. The shape was divided into normal orientation (n=15) and reverse orientation (n=24) of the ductus arteriosus. There was no significant difference in the type of oxygen saturation at birth and age at shunt operation between both the groups. However, the median narrowest diameter of ductus arteriosus in the normal orientation group was significantly smaller than that in the reverse orientation group (2.0 [1.0–5.4] versus 3.0 [1.3–4.4] mm, p<0.05). In two patients of the normal orientation group, ductus arteriosus had closed at birth, and one of whom died because of severe cyanosis.ConclusionsNormal orientation pattern might have high incidence of an early narrowing or closure of ductus arteriosus at birth. The critical patients need careful evaluation by repeated foetal echocardiography and further maternal interventions.

show abstract

“…Mg 2+ , a natural calcium channel blocker, administered antenatally as MgSO 4 , results in a dose-dependent delayed DA closure and a higher incidence of PDA. [130][131][132][133][134] This effect seems to be short, since the responsiveness to postnatal INDO prophylaxis is reduced while the symptomatic treatment in a later phase is not influenced. 132 The only report on antenatal use of a calcium channel blocker, nifedipine, did not find a higher prevalence of PDA.…”

Section: The Effect Of Ante-or Postnatal Exposure To Various Medicatimentioning

confidence: 99%

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

Hundscheid¹,

Broek

Lee³

et al. 2019

Pediatr Res

View full text Add to dashboard Cite

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.

show abstract

Fetal Reversed Constrictive Effect of Indomethacin and Postnatal Delayed Closure of the Ductus Arteriosus following Administration of Transplacental Magnesium Sulfate in Rats

Cited by 7 publications

References 37 publications

Indomethacin Dosing and Constriction of the Ductus Arteriosus During Open Fetal Surgery for Myelomeningocele Repair

Indomethacin Dosing and Constriction of the Ductus Arteriosus During Open Fetal Surgery for Myelomeningocele Repair

High incidence of ductal closure or narrowing at birth in patients with right ventricular outflow tract obstruction with normal orientation of the ductus arteriosus

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

Contact Info

Product

Resources

About