Biventricular function in preterm infants with patent ductus arteriosus ligation: A three-dimensional echocardiographic study.

BACKGROUND: The detailed hemodynamics after patent ductus arteriosus (PDA) ligation in preterm infants remain unknown. We aimed to clarify the effect of surgical ligation on left ventricular (LV) and right ventricular (RV) volume and function. METHODS: Echocardiography was performed in 41 preterm infants (median gestational age: 25 weeks) before and after PDA ligation. Global longitudinal strain was determined using three-dimensional speckle-tracking echocardiography. These values were compared with those in 36 preterm infants without PDA (non-PDA). RESULTS: Preoperatively, the PDA group had greater end-diastolic volume (EDV) and cardiac output (CO) in both ventricles, a higher LV ejection fraction (LVEF) (53% vs 44%) and LV global longitudinal strain, and a lower RVEF (47% vs 52%) than the non-PDA group. At 4-8 h postoperatively, the two groups had a similar LVEDV and RVEDV. However, the PDA group had a lower EF and CO in both ventricles than the non-PDA group. At 24-48 h postoperatively, the RVEF was increased, but the LVEF remained decreased, and LVCO was increased. CONCLUSIONS: PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery. Three-dimensional echocardiography may be beneficial to understand the status of both ventricles. IMPACT: Preterm infants are at high risk of hemodynamic compromise following a sudden change in loading conditions after PDA ligation. Three-dimensional echocardiography enables quantitative and serial evaluation of ventricular function and volume in preterm infants with PDA. PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery.

The cost-effectiveness of maternal and neonatal screening for congenital cytomegalovirus infection in Japan.

Congenital cytomegalovirus infection is the most common congenital infection. Using a decision tree model, cost-effectiveness of maternal screening with subsequent prenatal valacyclovir treatment and newborn screening with neonatal valganciclovir treatment was evaluated. The incremental cost-effectiveness ratio (ICER) was calculated for (1) universal maternal antibody screening with prenatal valacyclovir treatment compared to targeted newborn screening, and (2) universal newborn screening with postnatal valganciclovir treatment compared to targeted newborn screening. We performed a one-way sensitivity analysis. Compared to targeted newborn screening, the ICERs for universal newborn screening and maternal screening were 2 966 296 Japanese Yen (JPY) (21 188 USD) and 1 026 984 JPY (7336 USD), respectively. In all scenarios in the one-way sensitivity analysis, the ICERs of the maternal screening and the universal newborn screening strategies were less than three gross domestic product per capita compared with the targeted newborn screening strategy. Both maternal and universal newborn screening strategies may be cost-effective than a targeted newborn screening program. The potential utility of the maternal screening with valacyclovir treatment strategy, while potentially cost effective in regions with lower baseline seroprevalence rates, requires further study as the modeling was based on limited evidence.

Right to left ventricular volume ratio is associated with mortality in congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality. We performed this study to test the hypothesis that left ventricular (LV) and right ventricular (RV) volumes assessed by three-dimensional echocardiography may be associated with mortality in CDH. METHODS: This study was a single-center retrospective cohort study involving 35 infants with CDH. RV and LV end-diastolic volume (RVEDV and LVEDV, respectively) were measured by three-dimensional echocardiography and were corrected by birth body weight (BBW) on day 1. RVEDV/BBW, LVEDV/BBW, and LVEDV/RVEDV were compared between CDH survivors and non-survivors. Receiver-operating characteristic curve analysis was performed to assess the predictive ability for mortality of the echocardiographic parameters. RESULTS: Comparing CDH non-survivors (n = 6) with survivors (n = 29), respectively, RVEDV/BBW was significantly larger (2.54 ± 0.33 vs 1.86 ± 0.35 ml/kg; P < 0.01), LVEDV/BBW was significantly smaller (0.86 ± 0.21 vs 1.22 ± 0.33 ml/kg; P < 0.001), and LVEDV/RVEDV was significantly lower (0.34 ± 0.06 vs 0.66 ± 0.18; P < 0.001). The area under the curve for LVEDV/RVEDV was the largest (0.98). CONCLUSIONS: Three-dimensional echocardiographic volume imbalance between the RV and LV was remarkable in CDH non-survivors. The LVEDV/RVEDV ratio may be associated with mortality in CDH. IMPACT: Mortality with congenital diaphragmatic hernia (CDH) is high, and evaluating left and right ventricular structures and functions may be helpful in assessing the prognosis. Three-dimensional (3D) echocardiography indicated that the left ventricular end-diastolic volume/right ventricular end-diastolic volume ratio within 24 h after birth was associated with mortality in CDH infants. The usefulness of this ratio should be validated in prospective multicenter studies involving larger numbers of patients.

Predictive value of the Thompson score for short-term adverse outcomes in neonatal encephalopathy.

BACKGROUND: To explore the predictive value of the Thompson score during the first 4 days of life for estimating short-term adverse outcomes in neonatal encephalopathy. METHODS: This observational study evaluated infants with neonatal encephalopathy (≥36 weeks of gestation) registered in a multicenter cohort of cooled infants in Japan. The Thompson score was evaluated at 0-24, 24-48, 48-72, and 72-90 h of age. Adverse outcomes included death, survival with respiratory impairment (requiring tracheostomy), or survival with feeding impairment (requiring gavage feeding) at discharge. RESULTS: Of the 632 infants, 21 (3.3%) died, 59 (9.3%) survived with respiratory impairment, and 113 (17.9%) survived with feeding impairment. The Thompson score throughout the first 4 days accurately predicted death, respiratory impairment, or feeding impairment. The 72-90 h score showed the highest accuracy. A cutoff of ≥15 had a sensitivity of 0.85 and specificity of 0.92 for death or respiratory impairment, while a cutoff of ≥14 had a sensitivity of 0.71 and a specificity of 0.92 for death, respiratory or feeding impairment. CONCLUSION: A high Thompson score during the first 4 days of life, especially at 72-90 h could thus be useful for estimating the need for prolonged life support. IMPACT: The Thompson score on days 1-4 of age was useful in predicting death and respiratory or feeding impairments. The 72-90 h Thompson score showed the highest predictive capability. Owing to the rarity of withdrawal of life-sustaining treatment in Japan, 43% of infants with persistent severe encephalopathy with a Thompson score of ≥15 at 72-90 h of age could regain spontaneous breathing, be extubated, and survive without tracheostomy. Meanwhile, approximately 50% of infants who survived without tracheostomy required gavage feeding. Our results could provide useful information for clinical decision making regarding infants with persistent severe encephalopathy.

Hemostatic rebalance in neonatal intrahepatic cholestasis with citrin deficiency.

BACKGROUND: Neonatal intrahepatic cholestasis with citrin deficiency (NICCD) results in coagulopathy due to decreased levels of vitamin (V)K-dependent clotting factors, similar to biliary atresia (BA). However, the involvement of VK-independent coagulant and anticoagulant factor(s) remains unknown. We examined relationships between coagulant and anticoagulant potential before and after nutritional treatment in NICCD. METHODS: Three cases (aged 12, 21, and 45 days) with NICCD-associated coagulopathy were evaluated with standard coagulation/anticoagulation tests and comprehensive coagulation assays, rotational thromboelastometry, and protein C/protein S (PC/PS) pathway function assay (ThromboPath® ), before and after nutritional treatment. RESULTS: In all cases, activated partial thromboplastin time and prothrombin time were significantly prolonged, which is associated with very low levels of VK-independent fibrinogen and antithrombin. The initiation of nutritional treatment of medium-chain triglycerides oil improved these levels within the normal range, although low levels of other clotting factors were modestly increased. Whole blood- rotational thromboelastometry analysis revealed near-normal coagulation potential, even before treatment, comparable to healthy adults, and supportive of their non-bleeding symptoms. The introduction of nutritional treatment had further improved comprehensive coagulation potential. The global PC/PS-pathway function assay demonstrated the absence of the features of this function associated with the pathogenesis of NICCD. Compared to BA, the plasma levels of fibrinogen and antithrombin in all cases were markedly low, whilst those after treatment improved, especially to similar level of BA. CONCLUSIONS: Neonatal intrahepatic cholestasis with citrin deficiency has the characteristic of rebalancing hemostatic mechanisms associated with coagulant and anticoagulant potential involving low levels of fibrinogen and antithrombin, suggesting a pathophysiological coagulopathy distinct from BA.

Disease burden of congenital cytomegalovirus infection in Japan.

INTRODUCTION: Cytomegalovirus is the most frequently acquired congenital infectious agent that causes malformation in newborns in developed countries. Although there are many discussions worldwide about neonatal screening and treatment, there is scarce information relating to the lifetime economic burden of this disease, which is essential for calculating the cost-effectiveness of any screening and treatment programs. MATERIALS AND METHODS: Economic and lifetime health burdens of congenital cytomegalovirus infection in the Japanese annual birth cohort in 2019 were calculated, using demographic, epidemiologic, health value, and economic indicators. The economic burden was divided into medical and social costs. Sensitivity analysis was performed, using high and low values for some indicators. RESULTS: Our model estimated that the overall cost due to congenital cytomegalovirus infection in 2019 was 27.6 billion JPY. Acute care costs comprised a small portion of the medical costs. Social costs were much higher than medical costs. CONCLUSION: Our study revealed the economic burden of congenital cytomegalovirus infection in Japan, which highlighted the significance of this disease. Our study will be helpful for guiding national strategies in Japan, including neonatal screening and early treatment.

How to recover lost vaccine acceptance? A multi-center survey on HPV vaccine acceptance in Japan.

BACKGROUND: The plummeting acceptance rate of the HPV vaccine in Japan is one of the most disappointing vaccine-related events in recent times. Since 2013, the national HPV vaccine coverage rate fell from more than 70% to less than 1%. This survey investigated parental HPV vaccine acceptance and the factors that influence it. METHODS: A multi-center survey was conducted in eight hospitals in Nara prefecture, Japan, from July 2019 to March 2020. Parents were asked to answer a series of questions in a survey that included information on the HPV vaccine. RESULTS: Among the 1884 parents who answered the questionnaire, 21.8% indicated that they had accepted the HPV vaccine even before reading the information provided in the questionnaire. The overall acceptance rate after everyone had read the information increased to 50.2% (p < 0.001). Among those who still did not accept the vaccine after reading the information (N = 925), 26.7% indicated that they might change their mind if more vaccine safety reports were to appear in the mass media; other potentially influencing factors were direct communication from health care providers (35.1%), a recommendation by government (19.5%), and peer behavior (16.8%). CONCLUSION: The study showed that providing appropriate medical information significantly improves HPV vaccine acceptance. To reverse the loss of HPV vaccine acceptance in Japan, a multi-discipline approach that includes the mass media, health care providers, the government and the general population will be needed.

The efficacy of routine brain MRI for term neonates admitted to neonatal intensive care unit.

OBJECTIVE: The efficacy of routine brain MRI for term infants admitted to a neonatal intensive care unit (NICU) has not been well studied. This study aimed to investigate the types and frequencies of abnormal findings on routine brain MRI and the predictors of abnormality for term infants in an NICU setting. METHODS: We examined the results of routine brain MRI of 239 term infants who were hospitalized in the NICU. Data on the perinatal factors were also collected, and the association with MRI abnormalities was assessed. RESULTS: Of the 239 MRI scans, we found abnormal findings in 52 (21.8%) patients. Intracranial hemorrhage accounted for 74% of the abnormal findings, including subdural, intraparenchymal, cerebellar, and subependymal hemorrhages. Twenty-six percent of these were ischemic lesions, including cerebral infarction, white matter abnormal intensities, and cystic periventricular leukomalacia (PVL). Five (2.1%) MRI scans required detailed examination or were known to be associated with a poor neurological prognosis. No patient needed treatment for the findings. An Apgar score ≤7 points at 5 min was identified as a perinatal factor significantly associated with abnormal MRI findings (adjusted OR = 3.034, 95% CI: 1.107-8.315, p = .031). CONCLUSION: The efficacy of routine brain MRI for term infants admitted to the NICU was limited. Routine brain MRI is not recommended for this population.

The incremental burden of invasive pneumococcal disease associated with a decline in childhood vaccination using a dynamic transmission model in Japan: A secondary impact of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted childhood vaccinations, including pneumococcal conjugate vaccine (PCV). Evaluating the possible impact on the invasive pneumococcal disease (IPD) incidence associated with a decline in childhood pneumococcal vaccination is important to advocate the PCV programs. Using a deterministic, dynamic transmission model, the differential incidence and burden of IPD in children younger than 5 years in Japan were estimated between the rapid vaccination recovery (January 2021) and the delayed vaccination recovery (April 2022) scenarios for the next 10 years. In our model, the IPD incidence was reduced from 11.9/100,000 in 2019 to 6.3/100,000 in 2020, caused by a reduced transmission rate due to the COVID-19 mitigation measures. Assuming a recovery in the transmission rate in 2022 April, the incidence of IPD was estimated to increase with maximal incidence of 12.1 and 13.1/100,000 children under 5 years in the rapid and the delayed vaccination recovery scenarios. The difference in the total IPD incidence between these two scenarios was primarily driven by vaccine serotypes IPD incidence. The difference of incidence was not observed between the two scenarios after 2025. The persistent decline in childhood pneumococcal vaccination rates due to the impact of COVID-19 might lead to an increased IPD incidence and an incremental disease burden.

A model for the incremental burden of invasive Haemophilus influenzae type b due to a decline of childhood vaccination during the COVID-19 outbreak: A dynamic transmission model in Japan.

BACKGROUND: The current coronavirus disease 2019 (COVID-19) outbreak has caused a persistent decline in childhood vaccination coverage, including Haemophilus influenzae type b (Hib) vaccine, in some countries. Our objective was to evaluate the impact of decreased Hib vaccination due to COVID-19 on invasive Hib disease burden in Japan. METHODS: Using a deterministic dynamic transmission model (susceptible-carriage-infection-recovery model), the incidence rates of invasive Hib disease in under 5 year olds in rapid vaccination recovery and persistent vaccination declined scenarios were compared for the next 10 years after 2020. The national Hib vaccination rate after the impact of COVID-19 reduced to 87% and 73% in 2020 from approximately 97% each in 2013-2019 for primary and booster doses. RESULTS: While the persistent decline scenarios revealed an increase in invasive Hib disease incidence to 0.50/100,000 children under 5 years old, the incidence of the rapid recovery scenario slightly increased with a consistent decline of incidence after 2021. The shorter the duration of the decline in vaccination rate was, the smaller the incremental disease burden observed in the model. Compared to the rapid recovery scenario, the permanent decline scenario showed a 296.87 cumulative incremental quality-adjusted life years (QALY) loss for the next 10 years. CONCLUSIONS: The persistent decline of Hib vaccination rate due to COVID-19 causes an incremental disease burden irrespective of the possible decline of Hib transmission rate by COVID-19 mitigation measures. A rapid recovery of vaccination coverage rate can prevent this possible incremental disease burden.

The estimated impact of decreased childhood vaccination due to COVID-19 using a dynamic transmission model of mumps in Japan.

The exact impact of the decline in childhood vaccination coverage during COVID-19 outbreak has not been estimated for any vaccine-preventable diseases. Our objective was to evaluate the impact of decreased mumps vaccination due to COVID-19 on the disease burden of mumps in Japan. Using a previously validated dynamic transmission model of mumps infection in Japan, the incidence rate of mumps over the next 30 y since July 2020 was estimated. The estimated average incidences were 269.1, 302.0, and 455.4/100,000 person-years in rapid recovery, slow recovery, and permanent decline scenarios. Compared with the rapid recovery scenario, the incremental number of mumps cases, total costs, and QALYs loss over the next 30 y were 6.53 million cases, 2.63 billion USD, and 49,246 for the permanent decline scenario, respectively. In conclusion, the persistent decline of mumps vaccination rate as an impact of COVID-19 causes a significant incremental disease burden of mumps, which is consistent irrespective of the possible decline of transmission rate of mumps infection, unless the rapid recovery of coverage rate is achieved. The immediate measures to advocate the vaccination program is essential to mitigate the incremental disease burden in the COVID-19 period.

Acute effect of hydrocortisone for respiratory deterioration in preterm infants: Oxygenation, ventilation, vital signs, and electrolytes.

BACKGROUND: Preterm infants with severe bronchopulmonary dysplasia require rescue therapy with glucocorticoids, and hydrocortisone is increasingly replacing dexamethasone. The standard for rescue therapy is unclear. AIM: To quantify the short-term effects of respiratory rescue hydrocortisone of 4 mg/kg/day for 3 days. STUDY DESIGN: Retrospective single-center study. SUBJECTS: Ventilator-dependent infants born at <28 weeks of gestation with an increased oxygen demand to maintain the target oxygen saturation at 88% to 95% >1 week after birth. OUTCOME MEASURES: Ventilator settings, SpO2/FiO2 ratio, heart rate, and blood parameters within 24 h before and 228 h after starting hydrocortisone. RESULTS: Twenty-five infants (median gestational age, 25.1 weeks) received hydrocortisone at a median age of 16 days. The median pre-therapy SpO2/FiO2 was 297 (interquartile range, 265-320) and began to rise after 12 h of administration, reaching 307 (interquartile range, 278-335). The increase in SpO2/FiO2 peaked from the third day to 3 days after therapy (median range, 341-356). SpO2/FiO2 decreased thereafter and remained unchanged from 6 and 7 days after therapy (median range, 304-314). The pCO2 level (median range, 49-53 mmHg) did not change significantly. The heart rate significantly decreased from -4 to -6 beats/min from the first day to 1 day after therapy. Systolic blood pressure increased by a median of 4 to 8 mmHg after therapy. Blood electrolytes and glucose were similar after therapy. CONCLUSION: Rescue hydrocortisone administration improved oxygenation without particular adverse effects at the stage of respiratory deterioration in preterm infants.