CYP2C9*3 Increases the Ibuprofen Response of Hemodynamically Significant Patent Ductus Arteriosus in the Infants with Gestational Age of More Than 30 Weeks

Background: Patent Ductus Arteriosus (PDA) is considered one of the most prevalent types of congenital heart disease. The closure of the ductus arteriosus physiologically occurs at the first 48-72 hours after the birth in healthy term infants. Different causes can result in the pathological opening of ductus arteriosus. This study aims to investigate the effect of oral acetaminophen on the closure of PDA in preterm neonates. Methods: The present study is a trial without control. Forty-five preterm neonates with a gestational age of <32 weeks were studied. Acetaminophen was orally administered with a dose of 10mg/kg every 6 hours for three days. Closure of ductus arteriosus was considered as the success of treatment. Data were analyzed using SPSS 15. Data were reported as )frequency-percent) and mean ± SD. To evaluate the normal distribution of data, we used a Kolmogorov-Smirnov test. Statistical significance was defined as P<0.05. Results: The study population consisted of 20 male and 25 female infants with the mean gestational age of 28.95 ± 1.66 weeks. Cesarean-born infants and vaginal-born infants consisted 17.8% and 82.2% of the study population, respectively. The proportion of PDA closure after administration of oralacetaminophen was 82.3%. Conclusion: The current study indicates that oral acetaminophen is highly effective in closing PDA. Considering its trivial side effects, it has the potency to be a convenient option for treating this condition.

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Echocardiography predicts closure of patent ductus arteriosus in response to ibuprofen in infants less than 28week gestational age

Early Human Development ◽

10.1016/j.earlhumdev.2010.06.012 ◽

2010 ◽

Vol 86 (8) ◽

pp. 503-508 ◽

Cited By ~ 14

Author(s):

Christiane Pees ◽

Elisabeth Walch ◽

Michael Obladen ◽

Petra Koehne

Keyword(s):

Patent Ductus Arteriosus ◽

Gestational Age ◽

Ductus Arteriosus ◽

Patent Ductus

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Efficacy of a First Course of Ibuprofen for Patent Ductus Arteriosus Closure in Extremely Preterm Newborns According to Their Gestational Age-Specific Z-Score for Birth Weight

PLoS ONE ◽

10.1371/journal.pone.0124804 ◽

2015 ◽

Vol 10 (4) ◽

pp. e0124804 ◽

Cited By ~ 7

Author(s):

Doriane Madeleneau ◽

Marie-Stephanie Aubelle ◽

Charlotte Pierron ◽

Emmanuel Lopez ◽

Juliana Patkai ◽

...

Keyword(s):

Birth Weight ◽

Patent Ductus Arteriosus ◽

Gestational Age ◽

Ductus Arteriosus ◽

Z Score ◽

Extremely Preterm ◽

Patent Ductus Arteriosus Closure ◽

Preterm Newborns ◽

Patent Ductus

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A High Ductal Flow Velocity Is Associated with Successful Pharmacological Closure of Patent Ductus Arteriosus in Infants 22–27 Weeks Gestational Age

Critical Care Research and Practice ◽

10.1155/2012/715265 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Karl Wilhelm Olsson ◽

Anders Jonzon ◽

Richard Sindelar

Keyword(s):

Patent Ductus Arteriosus ◽

Flow Velocity ◽

Gestational Age ◽

Pharmacological Treatment ◽

Ductus Arteriosus ◽

Newborn Infants ◽

Cyclooxygenase Inhibitors ◽

Antenatal Steroids ◽

Ductal Closure ◽

Patent Ductus

Objective. To identify factors affecting closure of patent ductus arteriosus (PDA) in newborn infants born at 22–27 weeks gestational age (GA) during pharmacological treatment with cyclooxygenase inhibitors.Method. Infants born at 22–27 weeks of GA between January 2006 and December 2009 who had been treated pharmacologically for PDA were identified retrospectively. Medical records were assessed for clinical, ventilatory, and outcome parameters. Echocardiographic examinations during treatment were reviewed.Results. Fifty-six infants were included in the study. Overall success rate of ductal closure with pharmacological treatment was 52%. Infants whose PDA was successfully closed had a higher GA (25+4weeks versus24+3weeks;P=0.047),and a higher pretreatment left to right maximal ductal flow velocity (1.6 m/s versus 1.1 m/s;P=0.023). Correcting for GA, preeclampsia, antenatal steroids, and age at start of treatment, a higher maximal ductal flow velocity was still associated with successful ductal closure (OR 3.04;P=0.049).Conclusion. Maximal ductal flow velocity was independently associated with success of PDA treatment.

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Blood pressure changes during the first 24 hours of life and the association with the persistence of a patent ductus arteriosus and occurrence of intraventricular haemorrhage

PLoS ONE ◽

10.1371/journal.pone.0260377 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0260377

Author(s):

Robert Boldt ◽

Pauliina M. Mäkelä ◽

Lotta Immeli ◽

Reijo Sund ◽

Markus Leskinen ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Patent Ductus Arteriosus ◽

Gestational Age ◽

Odds Ratio ◽

Low Birthweight ◽

Ductus Arteriosus ◽

Intraventricular Haemorrhage ◽

Vlbw Infants ◽

Patent Ductus

Very low birthweight (VLBW) infants are at risk of intraventricular haemorrhage (IVH) and delayed closure of ductus arteriosus. We investigated mean arterially recorded blood pressure (MAP) changes during the first day of life in VLBW infants as potential risk factors for a patent ductus arteriosus (PDA) and IVH. This retrospective cohort study exploring MAP changes during adaption and risk factors for a PDA and IVH comprised 844 VLBW infants admitted to the Helsinki University Children’s Hospital during 2005–2013. For each infant, we investigated 600 time-points of MAP recorded 4–24 hours after birth. Based on blood pressure patterns revealed by a data-driven method, we divided the infants into two groups. Group 1 (n = 327, mean birthweight = 1019 g, mean gestational age = 28 + 1/7 weeks) consisted of infants whose mean MAP was lower at 18–24 hours than at 4–10 hours after birth. Group 2 (n = 517, mean birthweight = 1070 g, mean gestational age = 28 + 5/7 weeks) included infants with a higher mean MAP at 18–24 hours than at 4–10 hours after birth. We used the group assignments, MAP, gestational age at birth, relative size for gestational age, surfactant administration, inotrope usage, invasive ventilation, presence of respiratory distress syndrome or sepsis, fluid intake, and administration of antenatal steroids to predict the occurrence of IVH and use of pharmacological or surgical therapy for a PDA before 42 weeks of gestational age. Infants whose mean MAP is lower at 18–24 hours than at 4–10 hours after birth are more likely to undergo surgical ligation of a PDA (odds ratio = 2.1; CI 1.14–3.89; p = 0.018) and to suffer from IVH (odds ratio = 1.83; CI 1.23–2.72; p = 0.003).

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CYP2C9*2 is associated with indomethacin treatment failure for patent ductus arteriosus

Pharmacogenomics ◽

10.2217/pgs-2019-0079 ◽

2019 ◽

Vol 20 (13) ◽

pp. 939-946

Author(s):

Sydney R Rooney ◽

Elaine L Shelton ◽

Ida Aka ◽

Christian M Shaffer ◽

Ronald I Clyman ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Treatment Failure ◽

Preterm Infants ◽

Gestational Age ◽

Genetic Factors ◽

Ductus Arteriosus ◽

Preterm Neonates ◽

Multicenter Cohort Study ◽

Patent Ductus ◽

Indomethacin Treatment

Aims: To identify clinical andgenetic factors associated with indomethacin treatment failure in preterm neonates with patent ductus arteriosus (PDA). Patients & Methods: This is a multicenter cohort study of 144 preterm infants (22–32 weeks gestational age) at three centers who received at least one treatment course of indomethacin for PDA. Indomethacin failure was defined as requiring subsequent surgical intervention. Results: In multivariate analysis, gestational age (AOR 0.76, 95% CI 0.60–0.96), surfactant use (AOR 9.77, 95% CI 1.15–83.26), and CYP2C9*2 (AOR 3.74; 95% CI 1.34–10.44) were each associated with indomethacin failure. Conclusion: Age, surfactant use, and CYP2C9*2 influence indomethacin treatment outcome in preterm infants with PDA. This combination of clinical and genetic factors may facilitate targeted indomethacin use for PDA.

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Clinical Pharmacology of Ibuprofen and Indomethacin in Preterm Infants with Patent Ductus Arteriosus

Current Pediatric Reviews ◽

10.2174/1573396310666140228235815 ◽

2014 ◽

Vol 10 (3) ◽

pp. 216-237 ◽

Cited By ~ 8

Author(s):

Gian Maria Pacifici

Keyword(s):

Patent Ductus Arteriosus ◽

Serum Creatinine ◽

Prostaglandin E2 ◽

Preterm Infants ◽

Gestational Age ◽

Urine Output ◽

Ductus Arteriosus ◽

Closure Rate ◽

Term Infants ◽

Patent Ductus

Background: Ibuprofen and indomethacin are potent non-selective cyclo-oxygenase inhibitors and inhibit prostaglandin E2 synthesis. The patent ductus arteriosus (PDA) occurs in more than 70% of preterm infants weighing <1500 g. Prostaglandin E2 relaxes smooth muscle, tends to inhibit the closure of PDA, yields vasodilatation of the afferent renal arterioles and maintains glomerular filtration rate (GFR). Ibuprofen and indomethacin inhibiting prostaglandin E2 synthesis close PDA and reduce GFR with consequent decrease of urine output and increase of serum creatinine concentrations. Aims: The aims of this study are to give the definitive estimates of PDA closure rate following ibuprofen or indomethacin treatment and to evaluate the extent of renal side effects following the administration of these drugs to preterm infants. Other aims are to review the metabolism and the pharmacokinetics of ibuprofen and indomethacin in preterm infants with PDA. Methods: The bibliographic search was performed using PubMed and EMBASE databases as search engines, January 2013 was the cutoff point. Results: The %PDA closed by ibuprofen (n=24) and indomethacin (n=24) is 77.7±14.1 and 77.3±11.0, respectively. For ibuprofen, the gestational age of the infants included in the study ranged from 25.0 to 39.0 weeks (mean±SD=29.3±3.1 weeks). The %PDA did not correlate with the gestational age (p=0.2516). For indomethacin, the gestational age of infants included in the study ranged from 25.0 and 39.0 weeks (mean±SD=29.4±2.9 weeks). The %PDA did not correlate with the gestational age (p=0.3742). The treatment with ibuprofen reduces the urine output and increases the serum creatinine concentrations less extensively than indomethacin. The half-life (t1/2) of ibuprofen and indomethacin is lengthened and the clearance is reduced in preterm infants as compared with fullterm infants. Conclusions. Ibuprofen and indomethacin are equally effective in closing PDA. Treatment with ibuprofen decreases the risk of renal failure. Ibuprofen has the most favourable risk/benefit ratio. The rate of metabolism is reduced and t1/2 is lengthened in prematures as compared with term infants.

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Novel strategy to personalise use of ibuprofen for closure of patent ductus arteriosus in preterm neonates

Archives of Disease in Childhood ◽

10.1136/archdischild-2020-321381 ◽

2021 ◽

pp. archdischild-2020-321381

Author(s):

Samira Samiee-Zafarghandy ◽

Tamara van Donge ◽

Gerhard Fusch ◽

Marc Pfister ◽

George Jacob ◽

...

Keyword(s):

Patent Ductus Arteriosus ◽

Gestational Age ◽

Ductus Arteriosus ◽

Plasma Concentrations ◽

Preterm Neonates ◽

Pharmacokinetic Parameters ◽

Therapeutic Drug ◽

Population Pharmacokinetic ◽

Target Exposure ◽

Patent Ductus

ObjectiveExploration of a novel therapeutic drug monitoring (TDM) strategy to personalise use of ibuprofen for closure of patent ductus arteriosus (PDA) in preterm neonates.DesignProspective, single-centre, open-label, pharmacokinetics study in preterm neonates.SettingNeonatal intensive care unit at McMaster Children’s Hospital.PatientsNeonates with a gestational age ≤28+6 weeks treated with oral ibuprofen for closure of a PDA.MethodsPopulation pharmacokinetic parameters, concentration-time profiles and exposure metrics were obtained using pharmacometric modelling and simulation.Main outcome measureAssociation between ibuprofen plasma concentrations measured at various sampling time points on the first day of treatment and attainment of the target exposure over the first 3 days of treatment (AUC0–72h >900 mg·hour/L).ResultsTwenty-three preterm neonates (median birth weight 780 g and gestational age 25.9 weeks) were included, yielding 155 plasma ibuprofen plasma samples. Starting from 8 hours’ postdose on the first day, a strong correlation between ibuprofen concentrations and AUC0–72h was observed. At 8 hours after the first dose, an ibuprofen concentration >20.5 mg/L was associated with a 90% probability of reaching the target exposure.ConclusionWe designed a novel and practical TDM strategy and have shown that the chance of reaching the target exposure (AUC0–72h >900 mg·hour/L) can be predicted with a single sample collection on the first day of treatment. This newly acquired knowledge can be leveraged to personalise ibuprofen dosing regimens and improve the efficacy of ibuprofen use for pharmacological closure of a PDA.

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Diagnosis and Management of Patent Ductus Arteriosus in Newborn: An Update

Dhaka Shishu (Children) Hospital Journal ◽

10.3329/dshj.v36i1.52643 ◽

2021 ◽

Vol 36 (1) ◽

pp. 61-66

Author(s):

Gazi Mohammad Imranul Haque ◽

Probir Kumar Sarkar

Keyword(s):

Patent Ductus Arteriosus ◽

Preterm Infant ◽

Gestational Age ◽

Medical Management ◽

Ductus Arteriosus ◽

Pharmacological Therapy ◽

Fluid Restriction ◽

Term Infants ◽

Fetal Survival ◽

Patent Ductus

Patent ductus arteriosus is one of the common congenital acyanotic heart disease in neonates, especially in preterm. Patent ductus arteriosus (PDA) is a congenital condition, characterized by a persistent connection between the aorta and the pulmonary artery. Patency of Ductus Arteriosus is essential for fetal survival. Patent ductus arteriosus is one of the most common clinical findings and most frequent source of complications in premature infant. After birth, in term infants, the ductus usually closes within the first day of life, starting with functional closure followed by anatomical closure with vascular remodeling. The persistence of the PDA in preterm infant is inversely related to gestational age and birth weight. The incidence of Patent Ductus Arteriosus is 31% in preterm infant weighing 501 to 1500 gm and gestational age 29 weeks. The treatment options available are conservative medical management, pharmacological therapy or surgical ligation. Conservative medical management involves fluid restriction; watchful waiting and ventilator support. DS (Child) H J 2020; 36(1) : 61-66

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