Clinical presentation and transmission of postnatal cytomegalovirus infection in preterm infants.

Background: Preterm infants are at greater risk of developing postnatal cytomegalovirus (CMV) infection with serious symptoms. Breast milk is the main route of CMV transmission in populations with a high seroprevalence. Objectives: This study aimed to investigate the clinical presentation and transmission of postnatal CMV (pCMV) infection via breast milk in preterm infants under the specific setting of our neonatal intensive care unit (NICU). Methods: The medical records of 147 preterm infants were reviewed retrospectively, and their clinical characteristics and outcomes were analyzed. Breast milk and infant urine samples were collected every two weeks until discharge, and the kinetics of CMV loads were evaluated using a polymerase chain reaction assay. Results: Seventeen infants (11.6%) were diagnosed with pCMV infection during the study period. In comparison between the pCMV and control groups, the mean birth weight was significantly lower in the pCMV group than in the control group (1084.1 ± 404.8 g vs. 1362.5 ± 553.8 g, P = 0.047). Four (23.5%) patients had leukocytopenia, six (35.3%) had neutropenia, three (17.6%) had thrombocytopenia, and two (11.8%) had hyperbilirubinemia in the pCMV group. Five patients were treated with antiviral agents, and their CMV load in the urine decreased after treatment. CMV loads peaked at 3-5 weeks in breast milk, whereas they peaked at 8-12 weeks of postnatal age in infants' urine. A comparison between the median CMV load in breast milk from the pCMV and control groups revealed a significant difference (P = 0.043). Conclusion: Most preterm infants with pCMV infection present a favorable clinical course and outcomes. A high CMV viral load in breast milk is associated with transmission. Further studies are warranted to prevent transmission and severe pCMV infections in preterm infants.

Impact of the definition of bronchopulmonary dysplasia on neurodevelopmental outcomes.

Understanding the short and long-term pulmonary and neurologic outcomes of neonates with bronchopulmonary dysplasia (BPD) is important in neonatal care for low-birth-weight infants. Different criteria for BPD may have different associations with long-term outcomes. Currently, two criteria for diagnosing BPD have been proposed by the NIH (2001) and NRN (2019) for preterm infants at a postmenstrual age (PMA) of 36 weeks. We investigated which BPD definition best predicts long-term outcomes. Korean nationwide data for preterm infants born between 24+0 and < 32+0 weeks gestation from January 2013 to December 2015 were collected. For long-term outcomes, severity based on the NRN criteria was significantly related to neurodevelopmental impairment (NDI) in a univariate analysis after other risk factors were controlled. For the admission rate for respiratory disorder, grade 3 BPD of the NRN criteria had the highest specificity (96%), negative predictive value (86%), and accuracy (83%). For predicting NDI at the 18-24 month follow-up, grade 3 BPD of the NRN criteria had the best specificity (98%), positive (64%) and negative (79%) predictive values, and accuracy (78%) while NIH severe BPD had the highest sensitivity (60%). The NRN definition was more strongly associated with poor 2-year developmental outcomes. BPD diagnosed by NRN definitions might better identify infants at high risk for NDI.

Early pulmonary hypertension is a risk factor for bronchopulmonary dysplasia-associated late pulmonary hypertension in extremely preterm infants.

This study evaluated whether early pulmonary hypertension (PH) in extremely preterm infants (EPIs) at 22-27 weeks of gestation detected clinically with echocardiography at 4-7 postnatal days (PND) is a risk factor for death before 36 weeks post-menstrual age (PMA) or late PH in moderate or severe (m/s) bronchopulmonary dysplasia (BPD) (BPD-PH). We analyzed risk factors for death before 36 weeks PMA or BPD-PH. Among 247 EPIs enrolled, 74 (30.0%) had early PH. Twenty-one (28.4%) infants with early PH and 18 (10.4%) without early PH died before 36 weeks PMA; 14 (18.9%) infants with early PH and 9 (5.2%) without early PH had BPD-PH at 36-38 weeks PMA. Multivariate analysis revealed that early PH (adjusted odds ratio, 6.55; 95% confidence interval, 3.10-13.82, P < 0.05), clinical chorioamnionitis (2.50; 1.18-5.31), intraventricular hemorrhage (grade 3-4) (3.43; 1.26-9.37), and late sepsis (6.76; 3.20-14.28) independently increased the risk of development of death before 36 weeks PMA or BPD-PH. Subgroup analysis among m/s BPD patients revealed that early PH (4.50; 1.61-12.58) and prolonged invasive ventilator care (> 28 days) (4.91; 1.02-23.68) increased the risk for late PH independently. In conclusion, EPIs with early PH at 4-7 PND should be monitored for BPD-associated late PH development.

Risk factors that affect the degree of bronchopulmonary dysplasia: Comparison by severity in the same gestational age.

OBJECTIVE: To investigate the risk factors for BPD severity by gestational age (GA) and identify a way to reduce the incidence of moderate-to-severe BPD. STUDY DESIGN: This was a retrospective cohort study of very-low-birth-weight-infants (VLBWIs) delivered at 24 to 28 weeks GA from Korean Neonatal Network registry between 2013 and 2016. BPD was defined using the National Institutes of Health criteria. Study populations were divided by GA and subdivided into no/mild BPD and moderate/severe BPD. The initial statuses of all infants, including those who died before BPD diagnosis and the maternal and neonatal factors of the live infants were compared. Statistical methods included descriptive statistics, comparative tests, and logistic regression. RESULTS: Of 3,976 infants, 3,717 were included (24weeks, n = 456; 25 weeks, n = 650, 26 weeks, n = 742; 27 weeks, n = 836; 28 weeks, n = 1,033). The overall mortality rate was 18% and the rates by GA were 43%, 29%, 11%, and 6% in the 24-, 25-, 26-, 27-, 28-GA groups, respectively. Small for GA (SGA), treated patent ductus arteriosus (PDA), hypotension, and late-onset sepsis were significant risk factors for developing moderate/severe BPD in the 25 to 28-week GA groups in the multivariate analyses. However, for infants born at 24 weeks GA, there were no significant risk factors apart from initial resuscitation. CONCLUSIONS: Effective initial resuscitation was the most important factor for infants delivered at 24 weeks GA determining the severity of BPD. For infants delivered between 25 and 28 weeks, judicious care of SGA infants, aggressive treatment for PDA and hypotension, and intense efforts to decrease the sepsis rate are needed to reduce the development of moderate-to-severe BPD.

The Impact of Surgical Intervention on Neurodevelopmental Outcomes in Very Low Birth Weight Infants: a Nationwide Cohort Study in Korea.

BACKGROUND: To investigate the incidence of surgical intervention in very low birth weight (VLBW) infants and the impact of surgery on neurodevelopmental outcomes at corrected ages (CAs) of 18-24 months, using data from the Korean Neonatal Network (KNN). METHODS: Data from 7,885 VLBW infants who were born and registered with the KNN between 2013 to 2016 were analyzed in this study. The incidences of various surgical interventions and related morbidities were analyzed. Long-term neurodevelopmental outcomes at CAs of 18-24 months were compared between infants (born during 2013 to 2015, n = 3,777) with and without surgery. RESULTS: A total of 1,509 out of 7,885 (19.1%) infants received surgical interventions during neonatal intensive care unit (NICU) hospitalization. Surgical ligation of patent ductus arteriosus (n = 840) was most frequently performed, followed by laser therapy for retinopathy of prematurity and laparotomy due to intestinal perforation. Infants who underwent surgery had higher mortality rates and greater neurodevelopmental impairment than infants who did not undergo surgery (P value < 0.01, both). On multivariate analysis, single or multiple surgeries increased the risk of neurodevelopmental impairment compared to no surgery with adjusted odds ratios (ORs) of 1.6 with 95% confidence interval (CI) of 1.1-2.6 and 2.3 with 95% CI of 1.1-4.9. CONCLUSION: Approximately one fifth of VLBW infants underwent one or more surgical interventions during NICU hospitalization. The impact of surgical intervention on long-term neurodevelopmental outcomes was sustained over a follow-up of CA 18-24 months. Infants with multiple surgeries had an increased risk of neurodevelopmental impairment compared to infants with single surgeries or no surgeries after adjustment for possible confounders.

Continuous Renal Replacement Therapy in Preterm Infants.

PURPOSE: Despite the increasing use of continuous renal replacement therapy (CRRT) in the neonatal intensive care unit (NICU), few studies have investigated its use in preterm infants. This study evaluated the prognosis of preterm infants after CRRT and identified risk factors of mortality after CRRT. MATERIALS AND METHODS: A retrospective review was performed in 33 preterm infants who underwent CRRT at the NICU of Samsung Medical Center between 2008 and 2017. Data of the demographic characteristics, predisposing morbidity, cardiopulmonary function, and CRRT were collected and compared between surviving and non-surviving preterm infants treated with CRRT. Univariable and multivariable analyses were performed to identify factors affecting mortality. RESULTS: Compared with the survivors, the non-survivors showed younger gestational age (29.3 vs. 33.6 weeks), lower birth weight (1359 vs. 2174 g), and lower Apgar scores at 1 minute (4.4 vs. 6.6) and 5 minutes (6.5 vs. 8.6). At the initiation of CRRT, the non-survivors showed a higher incidence of inotropic use (93% vs. 40%, p=0.017) and fluid overload (16.8% vs. 4.0%, p=0.031). Multivariable analysis revealed that fluid overload >10% at CRRT initiation was the primary determinant of mortality after CRRT in premature infants, with an adjusted odds ratio of 14.6 and a 95% confidence interval of 1.10-211.29. CONCLUSION: Our data suggest that the degree of immaturity, cardiopulmonary instability, and fluid overload affect the prognosis of preterm infants after CRRT. Preventing fluid overload and earlier initiation of CRRT may improve treatment outcomes.

Different degrees of maternal Ureaplasma colonization and its correlation with bronchopulmonary dysplasia in <32 weeks' preterm infants.

BACKGROUND: Ureaplasma spp. is a known risk factor for bronchopulmonary dysplasia (BPD). However, little is known about the effect of different degrees of maternal Ureaplasma colonization and their adverse outcomes. Hence, the aim of this study was to determine the effects of different degrees of maternal Ureaplasma colonization on BPD. METHODS: A retrospective cohort study of preterm infants delivered at <32 weeks' gestational age (GA) was performed. The infants were divided according to maternal Ureaplasma status as follows: high-colonization (≥104 CCU/ml, UUH), low-colonization (<104 CCU/ml, UUL), and noncolonization (controls). Subgroup analysis according to neonatal respiratory Ureaplasma (n-UU) was also performed to evaluate vertical transmission. RESULTS: In total, 245 infants were included in this study (UUH = 105, UUL = 47, controls = 93). The rates of preterm labor and histological chorioamnionitis were significantly different. The rate of BPD was significantly high in UUH (P = 0.044). The transmission rate of n-UU colonization was 36% in UUH and 32% in UUL (P = 0.609). The rate of BPD was 78% in n-UU (+) of UUH but 43% in n-UU (-) of UUL (P = 0.027). CONCLUSIONS: High-degree colonization of maternal Ureaplasma was associated with preterm labor, histological chorioamnionitis, and neonatal BPD. The incidence of BPD was significantly higher in Ureaplasma-colonized infants born to women with high-degree colonization.