Evaluation of deep gray matter for early brain development using quantitative susceptibility mapping.

OBJECTIVES: To evaluate susceptibility values associated with iron accumulation in the deep gray matter during postnatal development and to compare magnetic susceptibility between patients with normal and delayed development. METHODS: Patients with postmenstrual age (PMA) ≤ 1000 days underwent MR scans between August 2015 and April 2020 at our hospital. Quantitative susceptibility mapping (QSM) was performed, and magnetic susceptibility was measured using three-dimensional volumes of interest (VOIs) for the caudate nucleus (CN), globus pallidus (GP), putamen (PT), and ventrolateral thalamic nucleus (VL). Cross-sectional analysis was performed for 99 patients with normal development and 39 patients with delayed development. Longitudinal analysis was also performed to interpret changes over time in 13 patients with normal development. Correlations between magnetic susceptibility in VOIs and PMA or chronological age (CA) were assessed. RESULTS: Susceptibility values for CN, GP, PT, and VL showed positive moderate correlations with both PMA (ρ = 0.45, 0.69, 0.62, and 0.33, respectively) and CA (ρ = 0.53, 0.69, 0.66, and 0.39, respectively). The slope of the correlation between susceptibility values and age was highest in the GP among the four gray matter areas. Susceptibility values for the CN, GP, PT, and VL were higher with normal development than with delayed development at early postnatal age, although a significant difference was only observed for the CN. Susceptibility values also increased with age in the longitudinal analysis. CONCLUSIONS: Magnetic susceptibility values in deep gray matter increased with age ≤ 1000 days. The normal development group showed higher susceptibility values than the delayed development group at early postnatal age (PMA ≤ 285 days). KEY POINTS: • Magnetic susceptibilities in deep gray matter nuclei increased with age (postmenstrual age ≤ 1000 days) in a large number of pediatric patients. • The normal development group showed higher susceptibility values than the delayed development group in the basal ganglia and ventrolateral thalamic nucleus at early postnatal age (PMA ≤ 285 days).

The prognosis of neonatal respiratory status within three years after birth in chronic abruption-oligohydramnios sequence.

AIM: Chronic abruption-oligohydramnios sequence (CAOS), which is characterized by vaginal bleeding and oligohydramnios, adversely affects the lungs of fetuses due to bloody amniotic fluid and oligohydramnios. The criteria for termination of pregnancy remain controversial. This study aimed to examine respiratory function in infants within 3 years after birth and risk factors for respiratory prognosis, and to clarify the management of CAOS. METHODS: This study is a case series of patients with CAOS managed at our institution between 2010 and 2020. The clinical data of the patients and their infants within 3 years after birth were reviewed. The amniotic fluid volume was measured using the maximum vertical pocket (MVP). RESULTS: Six of 17 neonates (35.3%) used inhaled nitric oxide (iNO) to improve oxygenation. Women with longer periods of MVP <1 cm delivered more neonates using iNO; however, periods of MVP <2 cm were not associated with iNO use. Almost half of the infants required home oxygen therapy when discharged, regardless of amniotic fluid volume. At 18 months corrected age, only one child needed respiratory support, and the others discontinued. Two neonates, both born at 23 weeks of gestational age, died within 1 month after birth because of extremely preterm birth. CONCLUSIONS: The amniotic fluid volume could predict the use of iNO in neonates, but it did not affect the child's respiratory function after the newborn period. Almost all children born to women with CAOS can improve their respiratory function as they grow up.

The status of chronic lung disease diagnosis in Japan: Secondary publication.

BACKGROUND: In Japan, the definition and classification of neonatal chronic lung disease (CLD) used for its diagnosis are a combination of those used in Japan and abroad. METHODS: To clarify the current state of CLD diagnosis, a questionnaire survey was conducted. RESULTS: Half of the patients of the medical centers included in the study were diagnosed with CLD in real time, while the other half were diagnosed after discharge. In addition, in approximately 70% of the facilities, diagnosis was made after discussions various among medical teams. In approximately 80% of the centers, the chest radiography used for CLD diagnosis were evaluated by multiple doctors. Furthermore, some centers used chest X-rays that were taken at approximately 28 days of age for CLD diagnosis, whereas at other facilities, diagnosis was made regardless of time at which the chest radiography were obtained. Only a small number of centers have established criteria for determining the necessity of oxygen at the corrected age of 36 weeks, and the target saturation of peripheral oxygen levels also tend to vary for each facility. Whether the conditions wherein the patient receives respiratory support for apnea or respiratory tract diseases should be considered as CLD also differed among the facilities. CONCLUSIONS: It is necessary to reassess the definition and classification of CLD in Japan to accurately evaluate and improve the quality of respiratory management based on the long-term prognosis.

Comparison of two methods measuring serum alkaline phosphatase in neonates.

BACKGROUND: Serum alkaline phosphatase (ALP) is a useful bone turnover marker to diagnose metabolic bone disease in preterm infants. In Japan, serum ALP levels were generally measured using the Japan Society of Clinical Chemistry (JSCC) method. It is problematic that ALP levels measured using the JSCC method tend to be higher in people with blood types B and O regardless of the disease. For international standardization, since 2020, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) method has been used as a reference method for ALP measurement instead of the JSCC method. However, no report has investigated the correlation between these two methods in neonates. We therefore aimed to compare the JSCC and IFCC methods and demonstrate a conversion formula in neonates. METHODS: In this retrospective study, we used a total of 402 samples in 49 preterm and 38 term infants. Serum ALP levels were measured using the JSCC and IFCC methods. RESULTS: Alkaline phosphatase measured using the JSCC method strongly correlated with that measured using the IFCC method in all blood types in preterm and term infants (P < 0.01 for all). CONCLUSIONS: We found that the serum ALP levels measured using the IFCC method could be calculated as 0.34 times the ALP levels measured using the JSCC method in preterm and term infants with any blood type: ALP levels (IFCC method) = 0.34 × ALP levels (JSCC method).

Signal Intensity and Volume of Pituitary and Thyroid Glands in Preterm and Term Infants.

BACKGROUND: Hypothalamic-pituitary-thyroid (HPT) maturation has not been extensively evaluated using neonatal MRI, even though both structures are visualized on MRI. HYPOTHESIS: That signal intensity and volume of pituitary and thyroid (T) glands on MRI in neonates may be interrelated. STUDY TYPE: Retrospective. SUBJECTS: In all, 102 participants. FIELD STRENGTH/SEQUENCE: 3.0T, T1 -weighted pointwise encoding time reduction with radial acquisition (PETRA). ASSESSMENT: The volume of interest of the anterior pituitary (AP), posterior pituitary (PP), and T on MRI were defined on T1 -PETRA by two radiologists, and volumes of AP (AP_vol) and thyroid (T_vol) were calculated. Gestational age (GA), chronological age (CA), GA+CA, birth weight (BW), and thyroid function were recorded. Mean and maximum signal intensities of AP, PP, and T were normalized using signals from the pons and spinal cord as follows: signal ratio of anterior pituitary/pons (AP/pons), signal ratio of posterior pituitary/pons (PP/pons), and signal ratio of thyroid/cord (T/cord) T/cord, respectively. STATISTICAL TESTS: Correlations between signal intensity and volume measures and GA, CA, GA+CA, and BW were assessed using Pearson's correlation coefficient or Spearman's rank correlation coefficient. Thyroid function analysis and Tmean /cord, Tmax /cord, and T_vol were evaluated using the Steel-Dwass test. RESULTS: APmean /pons correlated positively with GA (ρ = 0.62, P < 0.001) and BW (ρ = 0.74, P < 0.001), and negatively with CA (ρ = -0.86, P < 0.001) and GA+CA (ρ = -0.46, P < 0.001). PPmean /pons correlated positively with GA (ρ = 0.49, P < 0.001) and BW (ρ = 0.63, P < 0.001), and negatively with CA (ρ = -0.70, P < 0.001) and GA+CA (r = -0.38, P < 0.001). Tmean /cord correlated positively with GA (ρ = 0.48, P < 0.001) and BW (ρ = 0.55, P < 0.001), and negatively with CA (ρ = -0.59, P < 0.001) and GA+CA (ρ = -0.22, P = 0.03). AP_vol correlated positively with GA (ρ = 0.68, P < 0.001) and BW (ρ = 0.73, P < 0.001), and negatively with CA (ρ = -0.72, P < 0.001). T_vol correlated positively with GA (ρ = 0.50, P < 0.001) and BW (ρ = 0.61, P < 0.001), and negatively with CA (ρ = -0.54, P < 0.001). APmean /pons correlated positively with Tmean /cord (ρ = 0.61, P < 0.001). DATA CONCLUSION: Signal and volume of pituitary and thyroid glands correlated positively with GA and BW, and negatively with CA in neonates. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 5.

Clinical features of very-low-birthweight infants with congenital heart disease.

BACKGROUND: Few studies have investigated the developmental prognosis of very-low-birthweight (VLBW) infants with congenital heart diseases (CHDs). This study aimed to determine the mortality and morbidity, including the developmental prognosis, of VLBW infants with CHD. METHODS: This single-center, retrospective cohort study included VLBW infants admitted to the neonatal intensive care unit from January 2006 to December 2011. Perinatal records were reviewed for CHD diagnosis, treatment details, comorbidities, mortality, and long-term neurodevelopmental outcomes. The characteristics and neurological developmental quotients at around the age of 3 years were compared among the following three groups of VLBW infants with CHDs: biventricular circulation without intervention (without surgery), biventricular circulation with intervention (catheter intervention or one-stage surgery), and single-ventricular circulation (Fontan-type multiple-stage surgery). RESULTS: Among a total of 449 VLBW infants admitted during this period, 45 (10.0%) infants had CHDs, including 25 infants with congenital abnormalities (chromosomal abnormalities and/or multiple anomalies). All 13 infants who died before discharge had congenital abnormalities. The incidence rates of comorbidities were not higher in VLBW infants with CHDs than in those without CHDs. The developmental quotients of the no-surgery, catheter intervention or one-stage surgery, and Fontan-type multiple-stage surgery groups were 87.2 ± 10.9, 91.3 ± 4.7, and 63.7 ± 8.6, respectively. CONCLUSIONS: The neurological development at around the age of 3 years in VLBW infants with biventricular circulation was in the borderline-to-normal range; however, that in infants with single-ventricular circulation was poor. Further studies are needed to comprehend the neurological development of VLBW infants with CHDs better.

Antenatal Glucocorticoids Reduce the Incidence of Refractory Hypotension in Low Birthweight Infants during the Early Neonatal Period, but Do Not Affect It beyond This Time.

OBJECTIVE: This study aimed to clarify the effect of antenatal glucocorticoids (AGs) on the incidence of refractory hypotension (RH) in very low birthweight (VLBW) infants after the first week of life. STUDY DESIGN: We included VLBW infants born at a gestational age of <30 weeks and divided them into three groups: the complete group (born within 7 days of completing a single course [two doses] of AGs), the incomplete group (born without complete course), and the late delivery group (born at ≥8 days after a single course). We compared the incidence and period of onset of RH among the three groups. RESULTS: A total of 115 infants were enrolled. The incidence of RH in the first week of life was significantly lower in the complete group than in the other groups. However, there was no significant difference in the incidence of RH after the first week of life among the groups. CONCLUSION: AGs contribute to circulatory stabilization during the first week of life, but this effect does not last after 1 or 2 weeks of administration. In infants who receive AGs, physicians should consider that the risk of RH after the first week of life is not low.

Antenatal corticosteroids for threatened labour facilitate thyroid maturation among preterm neonates.

OBJECTIVE: To examine the effect of antenatal corticosteroids (ANS) on the maturation of thyroid function in the preterm infants. CONTEXT: ANS reduce mortality and morbidities in preterm neonates. Organ maturation by the glucocorticoids is the key, at least in part. However, the effect of ANS on thyroid is controversial. PATIENTS: A study group of 99 very low birthweight neonates (<34 weeks' gestational age) with the exception of those born more than 7 days after ANS administration were divided into a complete group (n = 49) whose mothers completed two doses of betamethasone and who were born more than 24 hours after the completion of ANS administration, and an incomplete group (n = 50) who were not exposed to any ANS or were born within 24 hours after the completion of ANS administration. Serum-free thyroxine and thyroid-stimulating hormone (TSH) levels were measured, and thyrotropin-releasing hormone (TRH) stimulation tests were performed at about 2 weeks of age. RESULTS: The incidence of hyperthyrotropinaemia (TSH > 15 mIU/L) in the complete group was significantly lower than in the incomplete group (6% vs 22%, P = .023). Exaggerated responses to TRH tests were more frequent in the incomplete group (17% vs 44%; P = .053). TSH30 was significantly lower in the complete group, (P = .046). Multivariate logistic regression analysis showed that the incidence of hyperthyrotropinaemia was associated with complete ANS administration (adjusted odds ratios 0.39). CONCLUSIONS: ANS administration might facilitate thyroid maturation in preterm neonates.

Reliability of real-time continuous glucose monitoring in infants.

BACKGROUND: Neonatal hypoglycemia is a common and treatable risk factor for neurological impairment. Real-time continuous glucose monitoring (RT-CGM) can show glucose concentration in real time. Using an RT-CGM alarm, physicians can be alerted and intervene in hypoglycemia. No reports, however, have evaluated the reliability of RT-CGM at low glucose levels in infants. This study therefore investigated the difference between blood glucose (BG) and RT-CGM sensor data at low glucose levels and assessed the optimum method of using a hypoglycemic alarm in infants. METHODS: We enrolled infants whose glycemic management was difficult. We calculated the mean absolute difference (MAD) and mean absolute relative difference (MARD) between BG and RT-CGM sensor data. We compared the MAD and MARD between the low BG fluctuation and high BG fluctuation groups. RESULTS: We used RT-CGM for 12 patients (29 times) and investigated 448 pairs of BG and RT-CGM sensor data. The MAD between these pairs was 9.3 ± 8.9 mg/dL, and the MARD was 11.5%. The MAD at low glucose was 7.7 ± 6.0 mg/dL, and the MARD was 16.2%. The MAD and MARD were 6.8 ± 5.4 mg/dL and 7.8% in the low fluctuation group and 10.1 ± 9.5 mg/dL and 12.7% in the high fluctuation group, respectively. CONCLUSIONS: The difference between BG and RT-CGM sensor data changes with the degree of fluctuation in BG. When physicians set the hypoglycemic alarm, consideration of this difference and a change in the alarm setting according to the degree of fluctuation in BG may be useful.

Association between cord blood cystatin C levels and early mortality of neonates with congenital abnormalities of the kidney and urinary tract: a single-center, retrospective cohort study.

BACKGROUND: Some fetuses with congenital abnormalities of the kidney and urinary tract (CAKUT) have severe renal dysfunction during the prenatal period that can result in oligohydramnios, pulmonary hypoplasia, and death following birth. We hypothesized that cord blood cystatin C (CysC) levels are elevated in neonates who have life-threatening pulmonary hypoplasia and oligohydramnios due to severe renal dysfunction. In this study we compared cord blood CysC levels between a non-survivor group with CAKUT and a survivor group. METHODS: This was a single-center, retrospective cohort study conducted between January 2007 and December 2015. Eighty-seven neonates who were prenatally diagnosed with CAKUT were included in the study. Cord blood CysC and creatinine levels were compared between the survivor and non-survivor groups at discharge from hospital. RESULTS: Of the 87 neonates enrolled in the study, 67 survived and 21 died before discharge. Median cord blood CysC levels were higher in the non-survivor group than in the survivor group (4.28 vs. 1.96 mg/L, respectively; p < 0.001). Cord blood creatinine levels were not significantly different between the two groups. In patients with oligohydramnios (n = 28), cord blood CysC levels were significantly higher in the non-survivor group than in the survivor group (4.28 vs. 2.23 mg/L, respectively; p = 0.002). CONCLUSIONS: In this study population, cord blood CysC levels were significantly higher in the non-survivor group with CAKUT than in the survivor group. These results suggest that cord blood CysC levels may be a good marker of the severity of renal dysfunction at birth.

Proactive Diagnosis and Tailor-Made Treatment of Patent Ductus Arteriosus in Very Preterm Infants with Routine Echocardiography in Japan: A post hoc Analysis of the PLASE Study.

INTRODUCTION: A feature of the management of extremely preterm infants in Japan is proactive circulatory management using early routine echocardiography performed by neonatologists. METHODS: This study was a post hoc analysis of the Patent ductus arteriosus and Left Atrial Size Evaluation in preterm infants (PLASE) study, which is a prospective cohort study including preterm infants admitted to 34 tertiary neonatal intensive care units in Japan between October 2015 and December 2016. We described the details of the treatment strategy of patent ductus arteriosus (PDA) based on early routine echocardiography. RESULTS: In total, 613 preterm infants were included into the analysis. Twenty percent of infants with prophylactic indomethacin were switched to therapeutic cyclooxygenase inhibitor (COX-I) before the completion of the full prophylactic indomethacin course. Therapeutic COX-I was mostly administered based on echocardiographic findings before PDA became symptomatic or hemodynamically significant. Therapeutic COX-I was frequently discontinued after one or two doses before the full course (three doses) was completed. The proportion of infants requiring additional treatment (additional therapeutic COX-I course or surgical PDA closure) after discontinued COX-I courses (<3 doses) compared to infants after completed 3 doses course was significantly lower (after the first therapeutic COX-I course 46% vs. 68%, p < 0.001) or without a significant difference (after the second or third course). CONCLUSIONS: The clinical management of PDA in Japan featured (1) COX-I administration based on echocardiographic findings before symptomatic or hemodynamically significant PDA appeared and (2) frequent discontinuation of therapeutic COX-I before completing the standard three doses course.

Severe Bronchopulmonary Dysplasia Adversely Affects Brain Growth in Preterm Infants.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) is associated with neurodevelopmental outcomes of preterm infants, but its effect on brain growth in preterm infants after the neonatal period is unknown. This study aimed to evaluate the effect of severe BPD on brain growth of preterm infants from term to 18 months of corrected age (CA). METHODS: Sixty-three preterm infants (42 with severe BPD and 21 without severe BPD) who underwent magnetic resonance imaging at term equivalent age (TEA) and 18 months of CA were studied by using the Infant Brain Extraction and Analysis Toolbox (iBEAT). We measured segmented brain volumes and compared brain volume and brain growth velocity between the severe BPD group and the non-severe BPD group. RESULTS: There was no significant difference in brain volumes at TEA between the groups. However, the brain volumes of the total brain and cerebral white matter in the severe BPD group were significantly smaller than those in the non-severe BPD group at 18 months of CA. The brain growth velocities from TEA to 18 months of CA in the total brain, cerebral cortex, and cerebral white matter in the severe BPD group were lower than those in the non-severe BPD group. CONCLUSION: Brain growth in preterm infants with severe BPD from TEA age to 18 months of CA is less than that in preterm infants without severe BPD.

Potential treatment option of rivaroxaban for breastfeeding women: A case series.

The use of direct oral anticoagulants (DOACs) in breastfeeding women is currently challenging due to limited safety data for breastfeeding infants, and there have been no previous studies on the drug concentration in breastfeeding infants. We treated 2 patients (one case was twin pregnancy) with venous thromboembolisms in breastfeeding women administered rivaroxaban at our institution. Blood samples from the mothers and breastmilk samples were collected at time 0 and 2 h after the rivaroxaban administration, breastfeeding was conducted 2 h after the rivaroxaban administration, and blood samples from the infants were collected 2 h after breastfeeding (4 h after maternal rivaroxaban administration). The milk-to-plasma (M:P) ratios were 0.27 in Case 1 and 0.32 in Case 2. The estimated relative infant dose (RID) was 0.82 % in Case 1 Children 1 and 2, and 1.27 % in Case 2. The rivaroxaban concentration in the infant plasma was below the lower limit of quantification in all infants. In addition, even in the high-exposure case simulation based on 5 days of breastfeeding in Case 2, the infant plasma concentration level was below the lower limit of quantification. At 3 months of follow-up, breastfeeding was continued, and all infants grew and developed without any health problems including bleeding events. The current case series showed that there were no pharmacokinetic or clinical concerns for breastfeeding women or breastfed infants, and provides support for rivaroxaban as a safe treatment option for these patients.

Variations in medical practice of retinopathy of prematurity among 8 Asian countries from an international survey.

Advances in perinatal care have led to the increased survival of preterm infants with subsequent neonatal morbidities, such as retinopathy of prematurity (ROP). This study aims to compare the differences of neonatal healthcare systems, resources, and clinical practice concerning ROP in Asia with review of current literature. An on-line survey at the institutional level was sent to the directors of 336 neonatal intensive care units (NICU) in 8 collaborating national neonatal networks through the Asian Neonatal Network Collaboration (AsianNeo). ROP screening was performed in infants born at < 34 weeks in Indonesia and Japan. In South Korea, Malaysia, and Taiwan, most screened for ROP in infants born at < 32 weeks. In all networks, majority of NICUs conducted ROP screening to infants with birth weight < 1500 g. In most NICU's in-hospital ophthalmologists performed indirect ophthalmoscopy and some were supplemented with digital imaging. Both laser photocoagulation and anti-vascular endothelial growth factor injection are performed for treatment and, vitreous surgeries are conducted less frequently in all countries. Despite limited information collected by the survey, this first study to compare ROP practices implemented in eight Asian countries through AsianNeo will enable an understanding of the differences and facilitate quality improvement by sharing better practices.

Electrocardiogram shows reliable heart rates much earlier than pulse oximetry during neonatal resuscitation.

BACKGROUND: The aim of this study was to determine the usefulness of the three-lead electrocardiogram (ECG) during neonatal resuscitation. METHODS: Both pulse oximetry (PO) and ECG were applied immediately after delivery to measure heart rate (HR). We reviewed video recordings of the respective monitors, and checked the time at which each monitor started to display reliable rate values. RESULTS: In 20 deliveries, ECG showed HR much earlier than PO (median 38 s vs 122 s after delivery). ECG displayed reliable HR throughout resuscitation. We were able to confirm the effectiveness of the initial respiratory support from the elevation in HR. CONCLUSIONS: ECG was a safe and reliable method for showing HR, and was used to determine the initiation and the effectiveness of resuscitation in the delivery room.

Clinical Features of Neurodevelopmental Outcomes in Children with Preterm Severe Fetal Growth Restriction: A Retrospective Observational Study.

Introduction: Fetal growth restriction (FGR) is a clinical condition wherein a fetus fails to achieve the expected growth potential. Although FGR is the leading cause of perinatal morbidity and mortality, there is a lack of knowledge about the long-term developmental outcomes of children who had FGR in Japan. Here, we sought to clarify the features of neurodevelopmental outcomes in preterm-born children with severe FGR (sFGR) and identify associated clinical factors. Methods: The clinical data of 26 preterm sFGR cases and 26 preterm appropriate for gestational age (AGA) cases with a similar gestational age distribution were reviewed retrospectively. Developmental quotient (DQ) scores assessed during the 1- and 2-year corrected ages using the Kyoto Scale of Psychological Development were analyzed. Results: sFGR was diagnosed at 26 (18-34) weeks of gestation, and the gestational age at delivery was 31 (25-36) weeks. The overall DQ scores of children in the sFGR group were significantly lower than those in the AGA group (80 vs. 90.5, P = 0.0127). Of the three areas that comprise the DQ (Postural-Motor, Cognitive-Adaptive, and Language-Social), the sFGR group only showed significantly lower DQ scores (72.5 vs. 88, P = 0.0255) in the Language-Social area. Both fetal body weight and fetal body weight Z score at birth significantly correlated with the DQ scores (r = 0.4912, P = 0.0108, and r = 0.5621, P = 0.0028), whereas neither the duration of fetal growth arrest nor the gestational age at birth correlated with the DQ scores (r = 0.3598, P = 0.0842, and r = 0.3522, P = 0.0776). Conclusions: Our results indicate that preterm-born children with sFGR have greater neurodevelopmental impairment than preterm-born children without FGR, specifically in terms of the DQ scores for the Language-Social area. It is imperative to encourage continuous long-term follow-up and appropriate interventions after birth.

Effect of doxapram on the electrical activity of the diaphragm waveform pattern of preterm infants.

OBJECTIVE: This study aimed to evaluate the change in the waveform pattern of the electrical activity of the diaphragm (Edi) following the administration of doxapram in extremely preterm infants ventilated with neurally adjusted ventilatory assist (NAVA). STUDY DESIGN: We conducted this retrospective cohort study in our neonatal intensive care unit between November 2019 and September 2021. The study participants were extremely preterm infants under the gestational age of 28 weeks who were ventilated with NAVA and administered doxapram. We collected the data of the Edi waveform pattern and calculated the proportion. To analyze the change in the proportion of the Edi waveform pattern, we compared the proportion of the data for 1 h before and after doxapram administration. RESULTS: Ten extremely preterm infants were included. Almost all the patients' respiratory condition improved after doxapram administration. The ventilatory parameters-Edi peak, Edi minimum, peak inspiratory pressure, time in backup ventilation, and number of switches to backup ventilation-did not change significantly. However, the proportion of phasic pattern significantly increased (before: 46% vs. after: 72%; p < 0.05), whereas the central apnea pattern significantly decreased after doxapram administration (before: 31% vs. after: 8.3%; p < 0.05). The proportion of irregular low-voltage patterns tended to decrease, albeit with no significant changes. CONCLUSION: Our results indicated that the proportion of Edi waveform patterns changed following doxapram administration. Edi waveform pattern analysis could be a sensitive indicator of effect with other intervention for respiratory conditions.

Ductus diameter and left pulmonary artery end-diastolic velocity at 3 days of age predict the future need for surgical closure of patent ductus arteriosus in preterm infants: A post-hoc analysis of a prospective multicenter study.

BACKGROUND: There is inconsistent evidence suggesting the clinical relevance of the early detection of future needs of preterm patent ductus arteriosus (PDA) surgery. We tested the hypothesis that echocardiographic indices at 3 days of age predict the future need for PDA surgery. METHODS: We analyzed a database including the clinical and echocardiographic data of 710 preterm infants with gestational ages between 23 and 29 weeks in 34 Japanese neonatal intensive care units, and prospectively collected data over 14 months. The predictive or discriminative ability of each echocardiographic index at 3 days of age for future PDA surgical closure was evaluated using multivariable logistic regression analyses with adjustment for gestational age, sex, and small-for-gestational-age status, according to the areas under the receiver-operating characteristic curves (AUCs) of the models. RESULTS: A total of 688 eligible patients (median gestational age: 26 weeks, body weight at birth: 843 g) were analyzed, of whom 77 (11%) underwent PDA surgery (median age: 21 days) after full consideration of clinical conditions. The AUC of PDA diameter (PDAd) was the largest, followed by that of the left pulmonary artery end-diastolic velocity (LPAedv). Compared with the ratio of left atrial-to-aorta diameter (AUC 0.76), PDAd (AUC 0.84, p < 0.001) and LPAedv (AUC 0.82, p = 0.003) were significantly better predictors of future PDA surgery. CONCLUSION: Echocardiographic indices at 3 days of age, especially PDAd and LPAedv, may predict the future need for surgical closure of PDA in preterm infants.