Efficacy of parent-child interaction therapy for children born premature.

BACKGROUND: Premature children are known to be at a high risk of developing behavioral problems. This study examined the effectiveness of parent-child interaction therapy (PCIT) in reducing behavioral problems in young children born premature. METHODS: The study included 18 child-parent pairs with children born at less than 35 weeks of gestation (range: 23-34 weeks, median: 31.0 weeks) and aged 27-52 months (median: 38.0 months). They were assigned to either the PCIT group (n = 7) or the non-PCIT group (n = 11) based on maternal desire for treatment. The study was designed to examine the effects of PCIT. Specifically, the Eyberg Child Behavior Inventory (ECBI) intensity score, ECBI problem score, and Parenting Stress Index Short Form (PSI-SF) scores were compared before treatment and after 6 months. RESULTS: In the PCIT group, the mean ECBI intensity score was 135.7 (SD = 13.5; T-score = 64) at baseline and 90.1 (SD = 15.5; T-score = 46) at post-assessment, the mean ECBI problem score was 9.8 (SD = 1.9; T-score = 54) at baseline and 4.4 (SD = 3.1; T-score = 44) at post-assessment, the mean PSI-SF total score was 60.1 (SD = 4.8; 95%tile) at baseline and 49.6 (SD = 5.6; 85%tile) at post-assessment, showing a significant improvement (ECBI intensity scores: p < 0.001, d = 2.03; ECBI problem scores: p < 0.001, d = 1.94; PSI-SF total scores: p = 0.004, d = 0.86). On the other hand, none of the scores showed significant change in the non-PCIT group. CONCLUSIONS: The PCIT can be considered as a potential treatment option for behavioral problems in young children born premature.

First evaluation of Eyberg Child Behavior Inventory for foster children in Japan.

BACKGROUND: Behavioral problems of foster children are an important issue for the maintenance of the foster care system, but they have not been adequately studied in Japan. We used the Eyberg Child Behavior Inventory (ECBI) to investigate behavioral problems among foster children and to examine associated factors. METHODS: Twenty-nine foster children and their foster parents and 479 non-foster children and parents were recruited for the foster and control groups, respectively. Both groups underwent statistical comparative analyses using data from their ECBI assessments. The ECBI has two scales: the Intensity Scale quantifies the severity of child behavioral problems, and the Problem Scale captures the caregiver's perceived difficulties handling each behavior. We conducted a retrospective investigation of the background of the foster parent-child pairs to explore potential causal relationships with behavioral problems. RESULTS: The mean intensity score for the foster group was significantly higher than that for the control group (p = 0.001). The mean problem scores for the foster group and the control group were not significantly different (p = 0.79). In the foster group, the retrospective investigation revealed two children with neurological or neurodevelopmental disorders, 17 with histories of abuse, and 10 with other issues. CONCLUSION: Intensity scores showed severe behavioral problems among foster children, perhaps caused by neurological disorders, abuse, parental mental health, or economic hardship. Problem scores showed no significant differences between groups. It can therefore be posited that foster parents might exhibit a more lenient parenting style when dealing with children who have a history of abuse by their biological parents.

Prognostic factors, psychomotor development and life of trisomy 13 patients.

BACKGROUND: Infants with trisomy 13 have a very high mortality rate. However, aggressive interventions for their complications, can improve their prognosis and may, thereby, increase the number of long-term survivors with trisomy 13. To date, there is no study on the psychomotor developmental progress of patients with trisomy 13. We conducted this survey to clarify the prognostic factors, living circumstances, and developmental status of infants the trisomy 13. METHODS: Patients with trisomy 13 who were admitted to the Department of Pediatrics, Jichi Medical University Hospital were enrolled. Their clinical data were investigated retrospectively using clinical records. RESULTS: Nine patients with trisomy 13 were enrolled and divided into the early death (died at <1 year) and long-term survival (survived for >1 year) groups. All the early death group patients had severe congenital heart disease. Heart failure at under 1 year of age was associated with early death. All the long-term survival group patients underwent operations (e.g. tracheostomy or gastrostomy) and all used home nursing and/or a social care service. Three patients used home mechanical ventilation. None of the patients was able to stand alone or speak intelligible words. Two patients without severe brain anomalies were able to roll over, sit up, and smile by 3 years of age. CONCLUSIONS: Long-term survivors with trisomy 13 require extensive nursing and medical care. It is important to provide medical and welfare services to reduce the burden on families. In patients without severe brain anomalies, psychomotor development may be expected. However, no clear developmental prognostic factors were found.

A Retrospective Cohort Study on Mortality and Neurodevelopmental Outcomes of Preterm Very Low Birth Weight Infants Born to Mothers with Hypertensive Disorders of Pregnancy.

OBJECTIVE: We examined the effects of maternal hypertensive disorders of pregnancy (HDP) on the mortality and neurodevelopmental outcomes in preterm very low birth weight (VLBW) infants (BW ≤1,500 g) based on their intrauterine growth status and gestational age (GA). STUDY DESIGN: We included singleton VLBW infants born at <32 weeks' gestation registered in the Neonatal Research Network Japan database. The composite outcomes including death, cerebral palsy (CP), and developmental delay (DD) at 3 years of age were retrospectively compared among three groups: appropriate for GA (AGA) infants of mothers with and without HDP (H-AGA and N-AGA) and small for GA (SGA) infants of mothers with HDP (H-SGA). The adjusted odds ratios (AOR) and 95% confidence intervals (CI) stratified by the groups of every two gestational weeks were calculated after adjusting for the center, year of birth, sex, maternal age, maternal diabetes, antenatal steroid use, clinical chorioamnionitis, premature rupture of membranes, non-life-threatening congenital anomalies, and GA. RESULTS: Of 19,323 eligible infants, outcomes were evaluated in 10,192 infants: 683 were H-AGA, 1,719 were H-SGA, and 7,790 were N-AGA. Between H-AGA and N-AGA, no significant difference was observed in the risk for death, CP, or DD in any GA groups. H-AGA had a lower risk for death, CP, or DD than H-SGA in the 24 to 25 weeks group (AOR: 0.434, 95% CI: 0.202-0.930). The odds for death, CP, or DD of H-SGA against N-AGA were found to be higher in the 24 to 25 weeks (AOR: 2.558, 95% CI: 1.558-3.272) and 26 to 27 weeks (AOR: 1.898, 95% CI: 1.427-2.526) groups, but lower in the 30 to 31 weeks group (AOR: 0.518, 95% CI: 0.335-0.800). CONCLUSION: There was a lack of follow-up data; however, the outcomes of liveborn preterm VLBW infants of mothers with HDP depended on their intrauterine growth status and GA at birth. KEY POINTS: · The effects of HDP on preterm low birth weight infants need to be further examined.. · The outcomes were not different between AGA infants with and without maternal HDP.. · The outcomes of SGA infants with maternal HDP were dependent on their GA..

Effect of the Physicochemical Properties of Liquid Paraffin on the Phase State and Rheological Properties of Lecithin Reverse Wormlike Micelles.

Lecithin reverse wormlike micelles (LRWs) have been studied recently for dermal application dosage use but the effects of the physicochemical properties of oils on the formation and rheological properties of LRWs have not been investigated. We studied the effect of oil on the formation of LRWs using 5 types of liquid paraffin (LP) with kinematic viscosities ranging from 4.00 to 88.0 mm2/s. Partial phase diagrams of lecithin/water/LP systems indicated that LPs with low molecular weights could form LRWs with only a small amount of water, but LPs with high molecular weights could not form LRWs, regardless of the water concentration. The solubility of lecithin in LPs was higher for low molecular weight LPs, thus possibly affecting the formation of LRWs. The zero-shear viscosity and relaxation time of LRWs initially increased with increasing water concentration, and then decreased. The water concentration providing the maximum value was dependent on the molecular weight of the LP, whereas the maximum amount and length of the LRWs were independent of the water concentration. Our results indicate that the molecular weight of LP affects the ease of formation and the viscoelasticity of LRWs.

A Case of Infantile Mitochondrial Cardiomyopathy Treated with a Combination of Low-Dose Propranolol and Cibenzoline for Left Ventricular Outflow Tract Stenosis.

Hypertrophic cardiomyopathy is a common cardiac complication in mitochondrial disorders, and the morbidity rate in neonatal cases is up to 40%. The mortality rate within 3 months for neonatal-onset mitochondrial cardiomyopathy is known to be high because there is currently no established treatment.We report the case of a male infant with neonatal-onset mitochondrial disorder presenting lactic acidosis and hypertrophic cardiomyopathy. Genetic analysis of the patient revealed recurrent m.13513G>A, p.Asp393Asn in mitochondrially encoded NADH dehydrogenase 5 gene (MT-ND5). Low-dose propranolol was initially administered for cardiomyopathy; however, he developed hypertrophic obstructive cardiomyopathy (HOCM) at 3 months of age. To reduce the risk of hypoglycemia associated with high-dose propranolol, cibenzoline, a class Ia antiarrhythmic drug, was added at a dose of 2.5 mg/kg/day and increased weekly to 7.5 mg/kg/day with monitoring of the blood concentration of cibenzoline. Left ventricular outflow tract stenosis (LVOTS) dramatically improved from 5.4 to 1.3 m/second in LVOTS peak velocity after 6 weeks, without notable adverse effects. The plasma N-terminal pro-brain natriuretic peptide level decreased from 65,854 to 10,044 pg/mL. Furthermore, myocardial hypertrophy also improved, as the left ventricular mass index decreased from 173.1 to 108.9 g/m2 after 3 months of the treatment.The administration of cibenzoline, in conjunction with low-dose propranolol, may serve an effective treatment for HOCM in infantile patients with mitochondrial disorders.

Vaginal Ureaplasma species increase chorioamnionitis in very preterm infants with preterm premature rupture of the membranes at < 28 weeks of gestation.

Our aim was to investigate the association between vaginal Ureaplasma species (spp.) and the subsequent occurrence of chorioamnionitis (CAM), perinatal death, neonatal morbidity, and long-term neurodevelopmental impairments (NDIs) at 3 years of age. We analyzed 55 pregnant women with singleton pregnancy who had preterm premature rupture of the membranes (pPROM) at < 28+0 weeks of gestation, and delivered between 22+0 and 31+6 weeks at our tertiary hospital in 2007-2016. NDIs were defined as either cerebral palsy or developmental delay evaluated at 1.5 and/or 3 years old. The presence of Ureaplasma spp. and Mycoplasma hominis were evaluated using urea-arginine broth and Mycoplasma PPLO Agar. The presence of Ureaplasma spp. in the vagina was positive in 41%. Vaginal Ureaplasma spp. was a significant risk factor for CAM; however, it was not significantly associated with the occurrence of perinatal death, pulmonary hypoplasia, respiratory distress syndrome, transient tachypnea of the newborn, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia defined as oxygen required and occasional ventilatory assistance required at week 36 as modified (BPD36), or NDIs. The crude odds ratio (95% confidence interval) of Ureaplasma spp. for the occurrence of CAM was 9.5 (1.10-82) (p = 0.041). In very preterm birth infants with pPROM, CAM, BPD36, and NDIs occurred in 78, 60, and 36%, respectively. Vaginal Ureaplasma spp. was a significant risk factor for CAM in very preterm birth infants with pPROM. The incidences of BPD36 and NDIs in such infants were very high, nearing 3/5 and 1/3, respectively.

An 18-Year Follow-up Survey of Dioxin Levels in Human Milk in Japan.

BACKGROUND: Globally, few published studies have tracked the temporal trend of dioxin levels in the human body since 2000. This study describes the annual trend of dioxin levels in human breast milk in Japanese mothers from 1998 through 2015. METHODS: An observational study was conducted from 1998 through 2015. Participants were 1,194 healthy mothers following their first delivery who were recruited annually in Japan. Breast milk samples obtained from participants were analyzed using gas chromatography and mass spectrometry for dioxins, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs). RESULTS: Mean age was 29.5 years, and 53% of participants were 20-25 years old. A declining trend in total dioxin levels was found, from a peak of 20.8 pg toxic equivalence (TEQ)/g fat in 1998 to 7.2 pg TEQ/g fat in 2014. Data from the last 5 years of the study indicated a plateau at minimal levels. In contrast, an increasing trend was found in the mean age of participants during the last 5 years. Although significantly higher dioxin levels were observed in samples from older participants, an upward trend in dioxin levels was not observed, indicating that dietary and environmental exposure to dioxins had greatly diminished in recent years. CONCLUSIONS: Dioxin levels in human breast milk may be approaching a minimum in recent years in Japan. The findings may contribute to global reference levels for environmental pollution of dioxins, which remains a problem for many developing countries.

Constitutively high-level expression of TGFß isoforms in cord blood and its relationship to perinatal findings.

BACKGROUND: The clinical significance of TGFß isoforms in cord blood is not well understood. METHODS: We obtained cord blood samples from 37 term infants and 85 preterm infants who were born in several clinical settings. The serum levels of 3 TGFß isoforms and of the other 17 cytokines in cord blood were investigated using cytometric bead array technology. RESULTS: Very high levels of TGFß1 and TGFß2 isoforms compared to the level of other cytokines were found; mean levels were 44,180 and 1871pg/mL, respectively. The levels of all 3 isoforms of TGFß were significantly correlated with birth weight, and the levels of TGFß1 and TGFß3 were correlated with gestational age. The levels of TGFß1 and ß2 isoforms were strongly correlated with each other, but not with levels of other cytokines. The levels of TGFß1 and TGFß2 were significantly higher in male infants and significantly lower in infants with fetal growth restriction. The prevalence of chronic lung disease was related to a low level of TGFß1, and that of patent ductus arteriosus was related to a high level of TGFß1 in preterm infants. CONCLUSIONS: TGFß1 and TGFß2 appeared to play a significant role in physiological and pathological conditions in the fetus. TGFß isoform levels appear to be regulated independently of those of other cytokines and do not appear to be influenced by inflammation in the fetal period. The role of TGFß3 in cord blood and the postnatal chronological changes of the TGFß isoforms should be investigated in the future.

The Effects of Antenatal Corticosteroids on Short- and Long-Term Outcomes in Small-for-Gestational-Age Infants.

AIM: To evaluate the effect of antenatal corticosteroids (ANS) on short- and long-term outcomes in small-for-gestational age (SGA) infants. METHODS: A retrospective database analysis was performed. A total of 1,931 single infants (birth weight <1,500 g) born at a gestational age between 22 weeks and 33 weeks 6 days who were determined to be SGA registered in the Neonatal Research Network Database in Japan between 2003 and 2007 were evaluated for short-term outcome and long-term outcome. RESULTS: ANS was administered to a total of 719 infants (37%) in the short-term outcome evaluation group and 344 infants (36%) in the long-term outcome evaluation group. There were no significant differences between the ANS group and the no-ANS group for primary short-term outcome (adjusted odds ratio (OR) 0.73; 95% confidence interval (CI) 0.45-1.20; P-value 0.22) or primary long-term outcome (adjusted OR 0.69; 95% CI 0.40-1.17; P-value 0.17). CONCLUSIONS: Our results show that ANS does not affect short- or long-term outcome in SGA infants when the birth weight is less than 1500 g. This study strongly suggests that administration of ANS resulted in few benefits for preterm FGR fetuses.

Gut hormones of preterm infants with abdominal symptoms and hypothyroxinemia.

BACKGROUND: The pathogenesis of abdominal symptoms in premature infants with hypothyroxinemia is not understood; therefore, we investigated changes in gut hormones before and after levothyroxine sodium (T4-Na) supplementation in preterm infants with abdominal symptoms and hypothyroxinemia. METHODS: In eight preterm study subjects and 14 gestational age-matched controls, fasting serum concentration of leptin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide, insulin, amylin and ghrelin was measured using a bead array system. RESULTS: Serum GLP-1, GIP and PYY in the subjects before T4-Na supplementation were lower than in controls at age 2 weeks. After improvement of abdominal symptoms and free thyroxine, serum levels of the three gut hormones in the subjects were increased and were not different from those in the control patients. CONCLUSIONS: In preterm infants with abdominal symptoms, serum GLP-1, GIP and PYY might be related to thyroid function.

Cytokine profile in two siblings with neonatal lupus erythematosus.

We studied the cytokine profile of two siblings with neonatal lupus erythematosus (NLE) born to a mother positive for serum anti-Ro and -La antibodies, who did not receive any medication during the two pregnancies. The first sibling was found to have complete atrioventricular block in utero and became severely ill after birth. He fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis on day 2. The second sibling did not have any fetal symptoms. He was generally stable after birth, but with typical skin rash. Laboratory data suggested that they both had hypercytokinemia during the neonatal period, requiring corticosteroid treatment. Interleukin (IL)-6, interferon-γ, IL-8 and monocyte chemotactic protein-1 were elevated in both cases, while IL-12, IL-13 and IL-17 were elevated only in the second sibling. Comparison of the cytokine profiles suggests the potential roles of different cytokines in the onset and clinical manifestations of NLE.

Long-term outcomes of antenatal corticosteroids treatment in very preterm infants after chorioamnionitis.

PURPOSE: To evaluate the effect of antenatal corticosteroids (AC) therapy on short- and long-term outcomes among very low birth weight preterm infants after histologic chorioamnionitis (HCA). METHODS: We performed a retrospective analysis of 5240 single very low birth weight (VLBW) infants born at 22 + 0 and 33 + 6 weeks of gestation between 2003 and 2007, who registered to the Neonatal Research Network Japan. The effects of AC therapy on mortality, neurodevelopmental outcomes at 3 years of age and neonatal morbidities were analyzed in the groups with or without HCA using logistic regression analysis. RESULTS: In the study subjects, 840 were with HCA, 2734 were without HCA, and 1666 were excluded without data for HCA. AC therapy was significantly associated with decreasing mortality before 3 years of age; [0.52 (0.32-0.86)], [odds ratio (95 % confidence intervals]. There were no differences between the two groups regarding neurodevelopmental outcomes, including cerebral palsy [0.90 (0.41-1.99)], development quotient <70 [0.93 (0.48-1.81)], visual impairment [0.46 (0.04-5.18)], and severe hearing impairment [4.00 (0.30-53.4)] in the group with HCA as well as without HCA. Regarding neonatal morbidities, AC therapy was associated with a lower incidence of respiratory distress syndrome [0.67 (0.50-0.91)], sepsis [0.62 (0.41-0.94)], late-onset adrenal insufficiency [0.62 (0.39-0.98)] and an increased incidence of chronic lung disease [1.62 (1.18-2.24)] in the group with HCA. In the group without HCA, AC therapy was associated with decreasing respiratory distress syndrome [0.60 (0.43-0.84)] and increasing chronic lung disease [1.34 (1.11-1.62)]. CONCLUSION: AC therapy is significantly associated with reduced mortality before 3 years of age in VLBW infants with HCA, but not with neurodevelopmental outcomes, which was same as the results found in infants without HCA. AC therapy is recommended for women with suspected chorioamnionitis, as well as those without chorioamnionitis.

Acute quadruple extremity compartment syndrome due to angio-oedema after polypharmacy overdose including olmesartan medoxomil, telmisartan and vildagliptin.

This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema.

Impact of comprehensive quality improvement program on outcomes in very-low-birth-weight infants: A cluster-randomized controlled trial in Japan.

BACKGROUND: Differences in outcomes among neonatal intensive care units (NICUs) in Japan have been noted, prompting the need for quality improvement. AIM: To assess a comprehensive quality improvement program on outcomes in very-low-birth-weight (VLBW) infants. STUDY DESIGN: A cluster-randomized clinical trial. SUBJECTS: Forty hospitals and VLBW infants born in 2012-2014 and admitted to those hospitals were study subjects. OUTCOME MEASURES: The intervention group (IG) received a comprehensive quality improvement program involving clinical practice guidelines, educational outreach visits, workshops, opinion leader training, audits, and feedback. The control group (CG) was provided only with the guidelines. The primary outcome was survival without neurological impairment at three years of age. RESULTS: IG consisted of 19 hospitals and 1735 infants, while CG included 21 hospitals and 1700 infants. There were no significant differences in gestational weeks, 29.1(26.9-31.3) vs. 29.1(26.7-31.1) or birth weights (g), 1054(789-1298) vs. 1084(810-1309) between the two groups. Both groups showed survival rates without neurological impairment of 67.2 % (1166) and 66.9 % (1137), respectively, without a significant difference. There was no significant difference in mortalities at NICU discharge between the groups, with rates of 4.0 % (70) and 4.2 % (72) respectively. Several clinically relevant improvements were observed in IG, including reduced rates of sepsis, adrenal insufficiency, transfusion for anemia, and a shorter interval to achieve full enteral feeding. However, these did not lead to improvements in the primary outcome. CONCLUSION: The comprehensive quality improvement program to Japanese NICUs did not result in a significant improvement in survival without neurological impairment in VLBW infants.

Do neonates conceived after assisted reproductive technology require neonatal surgery more frequently? A 5-year single-center experience.

AIM: Assisted reproductive technology (ART) has increased the incidences of multiple gestations and low birth weights, which frequently warrant pediatric surgery. ART may have also increased the rate of birth defects. In this study, we aimed to determine whether infants conceived after ART required neonatal surgery more frequently compared with naturally conceived infants. MATERIAL AND METHODS: Our study population comprised 1891 infants (160 ART (+) and 1731 ART (-)) who were admitted to our neonatal intensive care unit during a 5-year period (January 2006-December 2010); of these, 198 infants (9 ART (+) and 189 ART (-)), with diseases requiring surgery, were referred to pediatric surgeons (consultation cases). We examined the following: (i) factors potentially increasing the requirement for surgery; (ii) frequency of birth defects; and (iii) maternal factors that may increase the need for surgery. RESULTS: A significantly higher incidence of multiple gestation and low birth weight was observed in the ART (+) group than the ART (-) group. However, ART did not yield a higher rate of surgery and birth defects: overall, the rate of surgery was 4% (7/160) in the ART (+) group and 8% (143/1731) in the ART (-) group. Of 198 consultation cases, the percentage of infants actually requiring surgery was approximately the same in the ART (+) group (7/9 [78%]) and the ART (-) group (143/189 [76%]). CONCLUSION: Infants conceived after ART comprised a small proportion of neonatal surgery cases, and did not require surgery more frequently.

Neonatal respiratory support related to lung function abnormalities in school-age children with bronchopulmonary dysplasia.

OBJECTIVE: To elucidate the relationship between abnormal lung function (LF) at school age and neonatal respiratory support in very low birth weight children with bronchopulmonary dysplasia (BPD). STUDY DESIGN: We retrospectively examined 78 BPD children whose LF was evaluated at 8-9 years. LF abnormalities were defined by reduced values of spirometric parameters. Adjusted odds ratios (aORs) for abnormal LF by the type and postmenstrual age (PMA) of respiratory support were calculated using logistic regression analysis after controlling perinatal factors. RESULTS: Overall, 24 (31%) patients had LF abnormalities. Antenatal steroid use was associated with a decreased risk of abnormal LF [aOR, 0.31; 95% CI, 0.09-0.92]. Requiring positive-pressure support at 37 weeks' PMA correlated with abnormal LF [aOR, 4.58; 95% CI, 1.15-21.90]; whereas only low-flow oxygen at any PMA did not. CONCLUSION: Requiring positive-pressure support at 37 weeks' PMA could be an indicator of abnormal LF at school age.

Fatal thrombotic microangiopathy with rhabdomyolysis as an initial symptom after the first dose of mRNA-1273 vaccine: A case report.

We report a case of a Japanese man with severe rhabdomyolysis and multiple thrombosis of arterioles after the first dose of mRNA-1273 vaccine. He developed rapidly progressive rhabdomyolysis and infarctions of multiple organs. Antiplatelet factor 4 antibody test was negative. Despite the intensive supportive care, including aggressive fluid administration, hemodialysis, administration of anticoagulants, high-dose steroid, and eculizumab, the patient ultimately died of multiple organ failure. Autopsy revealed multiple thrombosis in the arterioles and organ necrosis. Low serum complements and C3 deposition in the renal glomeruli detected by immunofluorescence suggested a possible immune-mediated mechanism. To our knowledge, this is the first case report of rhabdomyolysis and multiple thrombosis of the arterioles as an adverse event following COVID-19 vaccination.

Neonatal correlates of adverse outcomes in very low-birthweight infants in the NICU Network.

BACKGROUND: The aim of the present study was to explore the relationships among neonatal morbidity, interventions and death or adverse neurodevelopmental outcomes in very low-birthweight (VLBW) infants. METHODS: Subjects were infants with birthweight ≤ 1500 g who were cared for in the tertiary neonatal intensive care units in Japan. Multiple logistic regression analysis was performed to examine the odds ratios (OR) and 95% confidence intervals (CI) of neonatal factors for death or cerebral palsy (CP) and death or developmental delay (developmental quotient <70 or delay judged by physicians) at 3 years of age after adjusting for biological and prenatal variables. RESULTS: Of the 3104 subjects, 257 died and 1826 were evaluated at 3 years of age. Cystic periventricular leukomalacia (PVL; OR, 23.9; 95%CI: 11.0-51.7), gastrointestinal perforation (OR, 8.5; 95%CI: 2.8-25.4), intraventricular hemorrhage (IVH) grade 3 or 4 (OR, 3.1; 95%CI: 1.3-7.2) and sepsis (OR, 2.6; 95%CI: 1.4-4.8) were neonatal factors significantly associated with an increased risk of death or CP. Significant correlates with death or developmental delay were cystic PVL (OR, 7.9; 95%CI: 3.7-16.8), gastrointestinal perforation (OR, 6.3; 95%CI: 1.9-20.8), sepsis (OR, 2.8; 95%CI: 1.6-4.8), IVH grade 3 or 4 (OR, 2.6; 95%CI: 1.2-5.7), chronic lung disease at 36 weeks of corrected gestational age (OR, 1.6; 95%CI: 1.1-2.4) and treatment for retinopathy of prematurity (ROP; OR, 1.5; 95%CI: 1.0-2.3). CONCLUSION: Cystic PVL, gastrointestinal perforation, IVH and sepsis correlated with both death or CP and death or developmental delay in VLBW infants. Chronic lung disease at 36 weeks and treatment for ROP were associated with death or developmental delay, but not with death or CP.