Ductus Arteriosus, Patent ; drug therapy ; Humans ; Indomethacin ; therapeutic use ; Infant, Extremely Low Birth Weight ; Infant, Newborn

Acetaminophen ; therapeutic use ; Ductus Arteriosus, Patent ; drug therapy ; Humans ; Infant ; Infant, Newborn ; Infant, Premature

Ductus Arteriosus, Patent ; drug therapy ; Humans ; Infant, Newborn ; Infant, Premature ; Natriuretic Peptide, Brain ; therapeutic use ; Peptide Fragments ; therapeutic use

Ductus Arteriosus ; surgery ; Ductus Arteriosus, Patent ; drug therapy ; therapy ; Humans ; Ibuprofen ; administration & dosage ; therapeutic use ; Indomethacin ; administration & dosage ; therapeutic use ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases ; drug therapy ; surgery ; therapy ; Ligation ; methods ; Treatment Outcome

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

Neonates have large inter-individual variability in pharmacokinetic parameters of many drugs due to developmental differences. The aim of this study was to investigate the factors affecting the pharmacokinetic parameters of drugs, which are commonly used in critically ill neonates. Factors that reflect physiologic maturation such as gestational age, postnatal age, postconceptional age, birth weight, and current body weight were correlated with pharmacokinetic parameters in neonates, especially preterm infants. Comorbidity characteristics affecting pharmacokinetics in critically ill neonates were perinatal asphyxia, hypoxic ischemic encephalopathy, patent ductus arteriosus (PDA), and renal dysfunction. Administration of indomethacin or ibuprofen in neonates with PDA was associated with the reduced clearance of renally excreted drugs such as vancomycin and amikacin. Therapeutic hypothermia and extracoporeal membrane oxygenation were influencing factors on pharmacokinetic parameters in critically ill neonates. Dosing adjustment and careful monitoring according to the factors affecting pharmacokinetic variability is required for safe and effective pharmacotherapy in neonatal intensive care unit.
Amikacin ; Asphyxia ; Birth Weight ; Body Weight ; Comorbidity ; Critical Illness* ; Drug Therapy ; Ductus Arteriosus, Patent ; Gestational Age ; Humans ; Hypothermia, Induced ; Hypoxia-Ischemia, Brain ; Ibuprofen ; Indomethacin ; Infant, Newborn* ; Infant, Premature ; Intensive Care, Neonatal ; Membranes ; Oxygen ; Pharmacokinetics ; Vancomycin

OBJECTIVETo study therapeutic effect and safety of early administration of oral ibuprofen in very low birth weight infants (VLBWIs) with patent ductus arteriosus (PDA).

METHODSA total of 64 symptomatic VLBWIs (within 24 hours after birth) with PDA confirmed by bedside Color Doppler ultrasound were randomly divided into two groups: treatment and control (n=32 each). The treatment group was orally administered ibuprofen within 24 hours after birth at 10 mg/kg, followed 24 hours later by a second dose of 5 mg/kg and 48 hours later by a third dose of 5 mg/kg. The control group was treated with placebo (normal saline) at 1 mL/kg, followed 24 hours later by a second dose of 0.5 mL/kg and 48 hours later by a third dose of 0.5 mL/kg. The therapeutic efficacies and adverse effects in both groups were observed.

RESULTSThe treatment group showed a significantly higher closure rate of ductus arterious than the control group after one course of treatment (84% vs 41%; P<0.01). The incidence rates of periventricular leukomalacia and bronchopulmonary dysplasia were significantly lower in the treatment group than in the control group (P<0.05). The duration of mechanical ventilation and mean hospitalization time were significantly shorter in the treatment group than in the control group (P<0.05). There were no significant differences in the incidence rates of intraventricular hemorrhage, early pulmonary hemorrhage and necrotizing enterocolitis between the two groups (P>0.05). No obvious adverse effects were observed in both groups.

CONCLUSIONSEarly administration of oral ibuprofen for treatment of PDA in VLBWIs can decrease the incidence rates of some early complications and shorten hospitalization time, but causes no significant adverse effects.

Administration, Oral ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; Ductus Arteriosus, Patent ; drug therapy ; Female ; Humans ; Ibuprofen ; administration & dosage ; adverse effects ; Infant, Newborn ; Infant, Very Low Birth Weight ; Length of Stay ; Male

Angiocardiography ; Anti-Infective Agents ; therapeutic use ; Aorta ; abnormalities ; surgery ; Bronchopneumonia ; diagnosis ; drug therapy ; Cardiac Surgical Procedures ; methods ; Ductus Arteriosus, Patent ; diagnosis ; surgery ; Female ; Heart Defects, Congenital ; diagnosis ; surgery ; Humans ; Infant ; Pulmonary Artery ; abnormalities ; surgery ; Tomography, Spiral Computed

OBJECTIVEIntravenous indomethacin is the conventional treatment for patent ductus arteriosus (PDA) in preterm infants; however its use is associated with various side effects such as oliguria, gastrointestinal bleeding and reduction of cerebral perfusion. Intravenous ibuprofen has recently been used to treat PDA in preterm infants without reducing cerebral blood flow or affecting intestinal or renal hemodynamics. Intravenous forms of indomethacin and ibuprofen are not available in Iran. This study aimed to examine and compare the efficacy and safety of oral ibuprofen and oral indomethacin for the treatment of PDA in preterm infants.

METHODSThirty-six infants (gestational age less than 34 weeks) who had echocardiographically confirmed PDA were enrolled in this study. The patients were randomly administered with three oral doses of either indomethacin (0.2 mg/kg, at an interval of 24 hrs) or ibuprofen (a first dose of 10 mg/kg, followed at an interval of 24 hrs by two doses of 5 mg/kg each) (n=18 each group). The rate of ductal closure, side effects, complications, and the infants' clinical course were recorded.

RESULTSThe ductus was closed in all of 18 patients (100%) in the ibuprofen group and in 15 (83.3%) patients in the indomethacin group (P > 0.05). There were no significant differences in the levels of serum blood urea nitrogen and creatinine between the two groups before and after treatment. Necrotizing enterocolitis (NEC) occurred in 3 patients in the indomethacin group and none in the ibuprofen group (P < 0.05). The survival rate at 1 month after treatment was 94% (17/18) in both groups. One infant in the ibuprofen group died from sepsis and one in the indomethacin group died as a result of NEC.

CONCLUSIONSOral ibuprofen is as effective as oral indomethacin for the treatment of PDA in preterm infants. Oral ibuprofen therapy is associated with a lower incidence of NEC.

Administration, Oral ; Ductus Arteriosus, Patent ; drug therapy ; Enterocolitis, Necrotizing ; epidemiology ; Humans ; Ibuprofen ; administration & dosage ; adverse effects ; therapeutic use ; Indomethacin ; administration & dosage ; adverse effects ; therapeutic use ; Infant, Newborn ; Infant, Premature