Pulmonary hypertension with bronchopulmonary dysplasia: Aichi cohort study.

BACKGROUND: The incidence of pulmonary hypertension (PH) associated with bronchopulmonary dysplasia (BPD) has not been investigated in regional cohorts. The aim of this study was to clarify the incidence of PH associated with BPD in all very low birthweight infants (VLBWIs) born during the study period in Aichi Prefecture, Japan. METHODS: We conducted a retrospective observational cohort study of all VLBWIs born in Aichi Prefecture. The inclusion criteria were VLB, birth between 1 January 2015 and 31 December 2015, and admission to any neonatal intensive care unit in Aichi Prefecture. BPD28d and BPD36w were defined as the need for supplemental oxygen or any respiratory support at 28 days of age or 36 weeks of postmenstrual age (PMA). The primary outcome was the incidence of PH after 36 weeks' PMA (PH36w) in VLBWIs with BPD28d and BPD36w. The secondary outcomes were the clinical factors related to PH36w in BPD36w patients. Mann-Whitney U-test and Fisher's exact test were used for univariate analysis. Differences were considered statistically significant at P < 0.05. Risk ratio (RR) and 95% confidence interval (CI) were also evaluated. RESULTS: A total of 441 patients were analyzed. A total of 217 and 131 patients met the definition of BPD28d and BPD36w, respectively. Nine patients were diagnosed with PH36w (4.2% and 6.9% of the BPD28d and BPD36w patients, respectively). The presence of oligohydramnios (RR, 2.71; 95% CI: 1.55-4.73, P = 0.014) and sepsis (RR, 3.62; 95% CI: 1.51-8.63, P = 0.025) was significant in the PH36w patients. CONCLUSIONS: The incidence of PH36w was 4.2% and 6.9% in the BPD28d and BPD36w patients, respectively. Oligohydramnios and sepsis were significantly associated with PH36w in VLBWIs.

Peripheral nerves are involved in hypomyelinating leukodystrophy-3 caused by a homozygous AIMP1 variant.

INTRODUCTION: Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the multi-tRNA synthetase complex that catalyzes the ligation of amino acids to their correct tRNAs. Bi-allelic truncating variants in the AIMP1 gene have been associated with hypomyelinating leukodystrophy-3 (HLD3; MIM 260600), which is characterized by hypomyelination, microcephaly, seizures and decreased life expectancy. Although peripheral nerve involvement has been assumed for HLD3, no compelling evidence is available to date. CASE REPORT: The case was a first-born Filipino male. He showed profound developmental delay, failure to thrive, and spasticity in his limbs. At three months of age he developed refractory epilepsy. Serial magnetic resonance imaging (MRIs) showed profound myelination delay and progressive cerebral atrophy. He showed abnormal nerve conduction studies. Genetic testing revealed a homozygous pathogenic variant in the AIMP1 gene (NM_004757.3: c.115C > T: p.Gln39*). The parents were heterozygous for the same variant. CONCLUSION: Here, we report a patient with a homozygous nonsense AIMP1 variant showing peripheral neuropathy as well as HLD3. Our case suggests that AIMP1 plays a pivotal role in the peripheral nerve as well as the central nervous system.

Multicenter study for brain/body hypothermia for hypoxic-ischemic encephalopathy: Changes in HMGB-1.

BACKGROUND: We measured changes in the blood level of high-mobility group box-1 (HMGB-1) at 24 h intervals in neonates treated with brain/body hypothermia (body hypothermia therapy: BHT) for hypoxic-ischemic encephalopathy (HIE), to evaluate the usefulness of HMGB-1 level for determining outcomes. METHODS: We studied 15 neonates with HIE who underwent BHT (BHT (+) group) and six neonates with HIE who did not (BHT (-) group). We recorded HMGB-1 changes at 24 h intervals, creatinine phosphokinase, and the resistance index of the anterior cerebral artery. Magnetic resonance imaging (MRI) was used to determine short-term outcome. RESULT: Baseline HMGB-1 was significantly higher in the BHT (+) group than in the BHT (-) group. Thereafter, HMGB-1 in the BHT (+) group significantly decreased at 24 h intervals, reaching the reference range by 2 days of age. In the BHT (+) group, when patients were classified into clinically significant neurological disorder due to HIE (+) and (-) according to MRI, the neurological disorder (+) group had higher mean HMGB-1. CONCLUSIONS: In HIE, HMGB-1 differs according to the presence of BHT, suggesting that HMGB-1 measurement soon after birth might be useful for determining BHT necessity and short-term outcome.

Prognostic factors of hydrops fetalis with pleural effusion.

BACKGROUND: Hydrops fetalis (HF) has a low survival rate, particularly in the case of preterm birth. In addition, the severity index of HF has not been fully investigated yet. The aim of this study was to clarify the prognostic factors of HF with pleural effusion. METHODS: All live-born HF patients with pleural effusion, except for chromosomal abnormality or complex congenital heart disease, born from 2009 to 2013 in Aichi Prefecture in Japan were included. Prenatal, perinatal, and postnatal information was obtained from the medical records and was retrospectively analyzed. RESULTS: Forty-one HF patients with pleural effusion were included, and 28 patients (68%) survived. On multivariate logistic stepwise analysis, gestational birth week (OR, 0.71; 95% CI: 0.52-0.96, P = 0.027) and standard deviation (SD) score of the birthweight (OR, 1.74; 95% CI: 1.01-2.99, P = 0.045) were significant factors for postnatal death. All patients with both ≥32 gestational weeks and <3.0 birthweight SD score survived. CONCLUSIONS: Combined with the gestational weeks data, birthweight SD score may be useful to estimate the prognosis of HF with pleural effusion.

Late-onset circulatory dysfunction of premature infants and late-onset periventricular leukomalacia.

BACKGROUND: The sudden appearance of hypotension and oliguria without obvious cause following stable circulation and respiration in preterm infants is frequent in Japan. Such episodes are referred to as late-onset circulatory dysfunction of premature infants (LCD). Volume expanders and inotropic agents are often ineffective against this condition, whereas i.v. steroids are significantly effective. A major problem is that cystic periventricular leukomalacia (PVL) often develops a few weeks after an episode. The aim of the present study was to clarify the risk factors, including LCD, related to cystic PVL. METHODS: A case-control study was performed for preterm infants who were delivered at <33 weeks of gestation and admitted to seven neonatal intensive care units in Japan. Cystic PVL infants were stratified into early-onset PVL diagnosed within 28 days of age and late-onset PVL diagnosed after more than 28 days of age. The reported and new risk factors for PVL, for each group of PVL infants, and for all PVL infants, were compared with controls. RESULTS: Thirty-two infants were diagnosed with cystic PVL (17 early-onset and 15 late-onset). All PVL infants significantly differed from controls on Apgar score, number of abortions and pregnancies, intraventricular hemorrhage, and LCD. LCD was diagnosed in 28.1% of both PVL groups compared with 6.3% of controls (P = 0.02). Multivariate analysis demonstrated significant association between late-onset PVL and LCD. CONCLUSION: LCD was significantly associated with cystic PVL, especially late-onset PVL. Elucidating the cause of LCD might reduce the incidence of PVL and improve the neurological prognosis of preterm infants.

Periventricular leukomalacia with late-onset circulatory dysfunction of premature infants: correlation with severity of magnetic resonance imaging findings and neurological outcomes.

The incidence of late-onset circulatory dysfunction (LCD) of premature infants, which is characterized by sudden hypotension and oliguria, has recently increased in Japan. This condition suddenly occurs after several days of age without obvious causes in preterm infants with stable respiration and circulation. Intravenous steroids frequently improve the hypotension. The main problem with LCD is the subsequent and frequent onset of periventricular leukomalacia (PVL), and neurological development appears to be worse in PVL patients with LCD than those without LCD. The aim of this study was to determine whether the severity of magnetic resonance imaging (MRI) findings and neurological outcomes differ between infants who developed PVL after LCD and those who developed PVL without LCD. We retrospectively studied preterm infants who were delivered at less than 33 weeks of gestation between the years 2000 and 2003. During the study period, 10 and 26 infants developed PVL with and without LCD, respectively. The incidence of severe or moderate MRI findings was significantly higher in PVL patients with LCD (100%) than those without LCD (50%; p < 0.05). The incidence of severe cerebral palsy was 88% in PVL infants with LCD and 43% in PVL infants without LCD (p < 0.05). Moreover, the incidence of visual disorders was significantly higher in PVL infants with LCD (63%) than those without LCD (9%; p < 0.01). In conclusion, neurological outcomes are worse in preterm infants who develop PVL with LCD than those without LCD, which is well correlated to the severity judged by MRI findings.

ACTH(1-24) down-regulates expression of ciliary neurotrophic factor mRNA in cultured rat astrocyte.

We examined the effects on astrocytes of ACTH, which is used to treat West syndrome. We stimulated cultured rat astrocytes with ACTH(1-24), corticotropin-releasing factor, and dexamethasone, and examined changes in neurotrophic factor mRNAs by reverse transcription-PCR. Down-regulation of ciliary neurotrophic factor mRNA expression was observed by stimulation with ACTH(1-24), but the expression of nerve growth factor, brain-derived neurotrophic factor, and nerotrophin-3 mRNAs was unaffected. Northern blot analysis revealed that the decrease in ciliary neurotrophic factor mRNA occurred 4 h after stimulation with more than 10 nM of ACTH(1-24). Up-regulation of nerotrophin-3 mRNA expression was found after stimulation with 1 mM dexamethasone. These results suggest that ACTH(1-24) administrated in West syndrome may influence the expression of neurotrophic factors in astrocytes in vivo.