OBJECTIVES: To investigate the risk factors and prognosis of hypotension within 72 hours after birth in extremely preterm infants. METHODS: A retrospective analysis was conducted on clinical data of extremely preterm infants admitted to the Children's Hospital of Zhejiang University School of Medicine from January 2019 to April 2022. Based on the presence of hypotension within 72 hours after birth, the eligible infants were divided into a hypotension group (41 cases) and a normotension group (82 cases). The clinical characteristics, echocardiographic parameters within 72 hours after birth, and early complications were compared between the two groups. Multivariate logistic regression analysis was used to explore the risk factors for hypotension within 72 hours after birth, and receiver operating characteristic curve analysis was performed to evaluate the predictive value of relevant indicators for the occurrence of hypotension within 72 hours after birth in the preterm infants. RESULTS: The proportion of infants who required medication or surgical closure of patent ductus arteriosus (PDA), the proportions of infants with intraventricular hemorrhage ≥ grade III and severe pulmonary hemorrhage, and the mortality rate within 7 days in the hypotension group were significantly higher than those in the normotension group (P<0.05). Multivariate logistic regression analysis showed that lower birth weight, larger PDA diameter, and hemodynamically significant PDA were risk factors for the occurrence of hypotension within 72 hours after birth in extremely preterm infants (P<0.05). The receiver operating characteristic curve analysis showed that the combination of birth weight, PDA diameter, and hemodynamically significant PDA had an area under the curve of 0.873 (95%CI: 0.802-0.944, P<0.05) for predicting hypotension within 72 hours after birth, with a sensitivity of 73.2% and specificity of 91.5%. CONCLUSIONS Hypotension within 72 hours after birth is closely related to birth weight and PDA, and increases the risk of early severe complications and mortality in extremely preterm infants.
Child ; Infant, Newborn ; Humans ; Infant, Extremely Premature ; Birth Weight ; Retrospective Studies ; Ductus Arteriosus, Patent/surgery* ; Cerebral Hemorrhage ; Prognosis ; Hypotension/etiology* ; Risk Factors

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*

Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8∶2 by computer, and non-parametric test or χ² test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.
Infant ; Male ; Infant, Newborn ; Humans ; Pregnancy ; Female ; Bronchopulmonary Dysplasia/epidemiology* ; Infant, Premature ; Hypertension, Pulmonary/epidemiology* ; Retrospective Studies ; Nomograms ; Ductus Arteriosus, Patent/epidemiology* ; Pneumonia, Ventilator-Associated/complications* ; Cesarean Section/adverse effects* ; Gestational Age ; Risk Factors ; Sepsis

Objective: To summarize the outcomes of different types of pulmonary atresia in neonates treated by ductus arteriosus stenting. Methods: This study was a retrospective cohort study. A total of 19 neonates who had pulmonary atresia treated by ductus arteriosus stenting in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from April 2014 to June 2021 were included. They were divided into the intact ventricular septum (PA-IVS) group and the ventricular septal defect (PA-VSD) group. Ductus arteriosus stents were implanted by different approaches. These children were followed up regularly at the 1, 3, 6, and 12 months after the surgery and annually since then to evaluate the outcome. Independent sample t-test was used for the statistical analysis. Results: There were 12 children in PA-IVS group and 7 in PA-VSD group. All of them were full term in fants. The gestational age of the PA-IVS group and the PA-VSD group was (38.8±1.1) and (37.7±1.8) weeks, the birth weights were (3.2±0.4) and (3.4±1.1) kg, and the age at operation was (10±9) and (12±7) days, respectively, without significant difference (all P>0.05). Among the 12 children with PA-IVS, 9 had stents successfully implanted through the femoral artery and 3 through the femoral vein. Of the 7 children with PA-VSD, 2 had the stents successfully implanted via the femoral artery and 2 failed, and the remaining 3 had stents successfully implanted via the left carotid artery. There was no postoperative thromboembolism, arteriovenous fistula, pseudoaneurysm or other vascular complications. Five children with PA-VSD who had successful operations were followed up at 6 months of age. They all had the operation for pulmonary atresia, repair of the ventricular septal defect, removal of arterial duct stents, and ligation of the arterial duct. All children survived without any stent displacement or stenosis and biventricular circulation was achieved during the follow-up. Conclusions: Ductus arteriosous stenting can be the first-stage treatment for children with PA-IVS and PA-VSD. In addition to the traditional femoral vein and femoral artery approach, the carotid artery can be used as a route for stent placement.
Child ; Infant, Newborn ; Humans ; Infant ; Pulmonary Atresia/surgery* ; Ductus Arteriosus ; Retrospective Studies ; China ; Heart Defects, Congenital ; Ductus Arteriosus, Patent/surgery* ; Heart Septal Defects, Ventricular ; Stents

OBJECTIVES: To investigate the clinical characteristics and risk factors for early-onset necrotizing enterocolitis (NEC) in preterm infants with very/extremely low birth weight (VLBW/ELBW). METHODS: A retrospective analysis was performed on the medical data of 194 VLBW/ELBW preterm infants with NEC who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021. These infants were divided into early-onset group (onset in the first two weeks of life; n=62) and late-onset group (onset two weeks after birth; n=132) based on their onset time. The two groups were compared in terms of perinatal conditions, clinical characteristics, laboratory examination results, and clinical outcomes. Sixty-two non-NEC infants with similar gestational age and birth weight who were hospitalized at the same period as these NEC preterm infants were selected as the control group. The risk factors for the development of early-onset NEC were identified using multivariate logistic regression analysis. RESULTS: Compared with the late-onset group, the early-onset group had significantly higher proportions of infants with 1-minute Apgar score ≤3, stage III NEC, surgical intervention, grade ≥3 intraventricular hemorrhage, apnea, and fever or hypothermia (P<0.05). The multivariate logistic regression analysis showed that feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, and hemodynamically significant patent ductus arteriosus were independent risk factors for the development of early-onset NEC in VLBW/ELBW preterm infants (P<0.05). CONCLUSIONS VLBW/ELBW preterm infants with early-onset NEC have more severe conditions compared with those with late-onset NEC. Neonates with feeding intolerance, blood culture-positive early-onset sepsis, severe anemia, or hemodynamically significant patent ductus arteriosus have a higher risk of early-onset NEC.
Child ; Infant ; Female ; Pregnancy ; Infant, Newborn ; Humans ; Infant, Premature ; Infant, Extremely Low Birth Weight ; Ductus Arteriosus, Patent ; Enterocolitis, Necrotizing/etiology* ; Retrospective Studies ; Infant, Newborn, Diseases ; Infant, Premature, Diseases/etiology* ; Risk Factors

OBJECTIVES: To study the value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight (VLBW) infants. METHODS: A retrospective analysis was performed for 51 VLBW infants who were admitted from March 2020 to June 2021, with an age of ≤3 days and a length of hospital stay of ≥14 days. According to the diameter of patent ductus arteriosus (PDA) on days 14 and 28 after birth, the infants were divided into three groups: large PDA group (PDA diameter ≥2 mm), small PDA group (PDA diameter <2 mm), and PDA closure group (PDA diameter =0 mm). The echocardiographic parameters measured at 72 hours after birth were compared among the three groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of the echocardiographic parameters in predicting persistent patency of the ductus arteriosus (PDA≥2 mm) at the ages of 14 and 28 days. RESULTS: On day 14 after birth, there were 17 infants in the large PDA group, 11 in the small PDA group, and 23 in the PDA closure group. On day 28 after birth, there were 14 infants in the large PDA group, 9 in the small PDA group, and 26 in the PDA closure group. There were significant differences in gestational age, birth weight, rate of pulmonary surfactant use, and incidence rate of hypotension among the three groups (P<0.05). PDA diameter, end-diastolic velocity of the left pulmonary artery, left ventricular output, and left ventricular output/superior vena cava flow ratio measured at 72 hours after birth were associated with persistent patency of the ductus arteriosus at the ages of 14 and 28 days (P<0.05), and the ratio of the left atrium to aorta diameter was associated with persistent patency of the ductus arteriosus at the age of 28 days (P<0.05). The ROC curve analysis showed that the area under the curve that the PDA diameter measured at 72 hours after birth predicting the persistent patency of the ductus arteriosus at the ages of 14 and 28 days was the largest (0.841 and 0.927 respectively), followed by end-diastolic velocity of the left pulmonary artery, with the area under the curve of 0.793 and 0.833 respectively. CONCLUSIONS The indicators obtained by beside echocardiography at 72 hours after birth, especially PDA diameter and end-diastolic velocity of the left pulmonary artery, can predict persistent patency of the ductus arteriosus at the ages of 14 and 28 days in VLBW infants, which provides a basis for the implementation of early targeted treatment strategy for PDA.
Ductus Arteriosus, Patent/diagnostic imaging* ; Echocardiography ; Humans ; Infant ; Infant, Newborn ; Infant, Very Low Birth Weight ; Retrospective Studies ; Vena Cava, Superior

OBJECTIVES: To study the effect of timing of surgical ligation of patent ductus arteriosus (PDA) on the prognosis of very low birth weight infants (VLBWI). METHODS: The medical data of VLBWI who underwent transthoracic ligation for PDA from June 2018 to May 2021 were reviewed retrospectively. The infants were divided into early ligation group (≤21 days of age) and late ligation group (>21 days of age) based on the age of ligation. The two groups were compared in terms of perioperative clinical features, complications, and mortality. The risk factors for early surgical ligation were analyzed. RESULTS: A total of 72 VLBWI were enrolled, with 19 infants (26%) in the early ligation group and 53 infants (74%) in the late ligation group. There were significant differences in birth weight, gestational age, weight at operation, days of age at operation, rates of preoperative invasive and noninvasive mechanical ventilation, incidence rate of pulmonary hemorrhage, incidence rate of hypotension, preoperative PDA internal diameter (mm/kg), intraoperative PDA external diameter (mm/kg), incidence rate of post-ligation cardiac syndrome, and duration of postoperative invasive mechanical ventilation between the two groups (P<0.05). A binary logistic regression analysis showed that pulmonary hemorrhage was an indication of early surgical ligation of PDA (P<0.05). There were no significant differences in the incidence rates of post-operative complications and the mortality rate between the early ligation and late ligation groups. CONCLUSIONS Early surgical ligation may be performed for VLBWI who are experiencing pulmonary hemorrhage and hemodynamically significant PDA confirmed by cardiac ultrasound after birth. However, post-ligation cardiac syndrome should attract enough attention. In addition, early surgical ligation of PDA does not increase the risk of surgery-related and long-term complications or death, indicating that it is a safe and feasible treatment option.
Ductus Arteriosus, Patent/surgery* ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Very Low Birth Weight ; Ligation ; Retrospective Studies

OBJECTIVES: To systematically evaluate the risk factors for necrotizing enterocolitis (NEC) in preterm infants. METHODS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data were searched for case-control studies and cohort studies on the risk factors for NEC in preterm infants published up to December 2021. RevMan 5.3 software was used to perform the Meta analysis. RESULTS: A total of 38 studies were included (28 case-control studies and 10 cohort studies). The Meta analysis showed that maternal gestational diabetes (OR=2.96, P<0.001), intrahepatic cholestasis during pregnancy (OR=2.53, P<0.001), preeclampsia (OR=1.73, P=0.020), history of neonatal asphyxia (OR=2.13, P<0.001), low gestational age (OR=1.23, P=0.010), sepsis (OR=5.32, P<0.001), patent ductus arteriosus (OR=1.57, P=0.001), congenital heart disease (OR=3.78, P<0.001), mechanical ventilation (OR=2.23, P=0.020), history of antibiotic use (OR=1.07, P<0.001), use of vasopressors (OR=2.34, P=0.040), and fasting (OR=1.08, P<0.001) were risk factors for NEC in preterm infants, while cesarean section (OR=0.73, P=0.004), use of pulmonary surfactant (OR=0.43, P=0.008), and breastfeeding (OR=0.24, P=0.020) were protective factors against NEC. CONCLUSIONS Maternal gestational diabetes, intrahepatic cholestasis during pregnancy, preeclampsia, low gestational age, fasting, sepsis, patent ductus arteriosus, congenital heart disease, and histories of asphyxia, mechanical ventilation, antibiotic use, and use of vasopressors may increase the risk of NEC in preterm infants, while cesarean section, use of pulmonary surfactant, and breastfeeding may decrease the risk of NEC in preterm infants.
Anti-Bacterial Agents ; Asphyxia ; Cesarean Section ; Cholestasis, Intrahepatic ; Diabetes, Gestational ; Ductus Arteriosus, Patent ; Enterocolitis, Necrotizing ; Female ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Infant, Premature ; Pre-Eclampsia ; Pregnancy ; Pulmonary Surfactants ; Risk Factors ; Sepsis

OBJECTIVES: To investigate the risk factors for moderate/severe bronchopulmonary dysplasia (BPD) in preterm infants with a gestational age of <32 weeks. METHODS: A retrospective analysis was performed on the medical data of preterm infants with a gestational age of <32 weeks and a length of hospital stay of ≥28 days who were admitted to the neonatal intensive care unit (NICU) of 17 institutions of Jiangsu Neonatal Perinatal Cooperation Network from January 1, 2019 to December 31, 2020 and were diagnosed with BPD. The preterm infants were grouped according to gestational age and severity of BPD. A multivariate logistic regression analysis was used to investigate the risk factors for moderate/severe BPD in various gestational age groups. RESULTS: During the two-year period, a total of 2 603 preterm infants with a gestational age of <32 weeks were admitted to the NICU of the 17 institutions, among whom 961 were diagnosed with BPD, and the incidence rates of BPD and moderate/severe BPD were 36.92% (961/2 603) and 8.64% (225/2 603), respectively. The incidence rate of moderate/severe BPD was 56.5% (26/46) in preterm infants with a gestational age of 24⁺⁰-25⁺⁶ weeks, 31.0% (66/213) in those with a gestational age of 26⁺⁰-27⁺⁶ weeks, 16.9% (75/445) in those with a gestational age of 28⁺⁰-29⁺⁶ weeks, and 22.6% (58/257) in those with a gestational age of 30⁺⁰-31⁺⁶ weeks. The multivariate logistic regression analysis showed that there were different risk factors for moderate/severe BPD in preterm infants with different gestational ages: patent ductus arteriosus requiring treatment as risk factors in preterm infants with a gestational age of 24⁺⁰-25⁺⁶ weeks; premature rupture of membranes ≥18 hours, positive pressure ventilation for resuscitation, clinical sepsis, and duration of mechanical ventilation ≥14 days as risk factors in preterm infants with a gestational age of 26⁺⁰-27⁺⁶ weeks; duration of mechanical ventilation ≥14 days, neonatal pneumonia, and patent ductus arteriosus requiring treatment as risk factors in preterm infants with a gestational age of 28⁺⁰-29⁺⁶ weeks; positive pressure ventilation for resuscitation, neonatal pneumonia, and anemia of prematurity as risk factors in preterm infants with a gestational age of 30⁺⁰-31⁺⁶ weeks (P<0.05). CONCLUSIONS The development of moderate/severe BPD is multifactorial in preterm infants with a gestational age of <32 weeks, and there are different risk factors in different gestational age groups. Targeted preventive measures for preterm infants of different gestational ages may be useful to reduce the severity of BPD.
Infant ; Pregnancy ; Female ; Infant, Newborn ; Humans ; Bronchopulmonary Dysplasia/etiology* ; Gestational Age ; Infant, Premature ; Ductus Arteriosus, Patent ; Retrospective Studies ; Risk Factors ; Pneumonia/complications*

Background. Indomethacin has been the gold standard for the closure of patent ductus arteriosus (PDA). Still, the availability of the intravenous (IV) form has been a big issue precluding its use in the Philippines. IV ketorolac is another non-steroidal anti-inflammatory drug (NSAID) that is cheaper and more available in our country and used for post-cardiac surgery pain management among neonates.

Objectives. To compare the efficacy of ketorolac versus indomethacin in the closure of patent ductus arteriosus among preterm infants.

Methods. We conducted a randomized controlled, double-blind, crossover design, non-inferiority trial on the use of iindomethacin versus ketorolac among preterm infants with PDA. We enrolled preterm infants at 5-12 days postnatal life, diagnosed with PDA by echocardiography at the Philippine General Hospital (PGH). We excluded infants with upper gastrointestinal bleeding, renal failure, birthweight < 500 grams, septic shock, and lethal anomalies. Patients were randomly allocated between two treatment groups (indomethacin versus ketorolac). The primary outcome measure was PDA closure measured after the treatment course. Adverse events like oliguria and bleeding were recorded.

Results. A total of 27 preterm infants were randomly assigned to the indomethacin (0.2 mg/kg/dose) and ketorolac (0.6 mg/kg/dose) group. Ketorolac has a 60% success rate for PDA closure (9/15) compared to indomethacin 41.67% (5/12) (p=0.154). No renal insufficiency and bleeding diathesis were noted. Five patients died in the study, four in the group initially allocated in ketorolac and one in indomethacin. Causes of death were late-onset sepsis, bronchopulmonary dysplasia, and congenital adrenal hyperplasia.

Conclusion. The success rate of PDA closure between IV ketorolac and IV indomethacin was not significantly different. There was neither oliguria nor bleeding observed in both groups.