Bilateral Vocal Fold Abduction Dysfunction: A Report of Two Neonatal Cases.

Stridor is caused by oscillation of the narrowed upper airway. The most common cause of neonatal stridor is laryngomalacia, followed by vocal fold abduction dysfunction. Herein, we present two neonatal cases of idiopathic dysfunction of vocal fold abduction. A neonate was admitted to the neonatal intensive care unit (NICU) on day 4 of life for inspiratory stridor, intermittent subcostal retraction, and cyanosis. A second neonate was admitted to the NICU on day 7 of life for inspiratory stridor and cyanosis when crying. Neither patient had dysmorphic features or unusual cardiac ultrasonography findings. The diagnosis was confirmed by laryngo-bronchoscopy. Conservative treatment with biphasic positive airway pressure was effective in both cases and symptoms resolved within a few months. Resolution of vocal fold abduction dysfunction was confirmed by repeat endoscopy. Clinical manifestations of vocal fold abduction dysfunction vary widely. Although most cases resolve spontaneously, prolonged tube feeding, or even tracheostomy, is needed in some severe cases. Diagnosis of vocal fold abduction dysfunction requires a laryngo-bronchoscopy study; thus, there may be a large number of undiagnosed patients. Vocal fold abduction dysfunction should be considered in the differential diagnosis for neonatal inspiratory stridor.

Sustained sterile inflammation is related to pulmonary morbidities in premature infants.

OBJECTIVE: Sterile inflammation, initiated by endogenous molecules such as high-mobility group box-1 (HMGB1), has come to be recognized as a critical mechanism in a variety of chronic diseases. To elucidate the involvement of sterile inflammation in neonatal disease, the association between serum HMGB1 levels and the development of bronchopulmonary dysplasia (BPD) was evaluated. STUDY DESIGN: Serum HMGB1 levels were measured in 25 premature infants born before 33 weeks of gestation, excluding any infection cases. Samples were collected at birth, two, and four weeks of age and compared according to BPD status. RESULTS: The serum HMGB1 levels in infants with BPD were maintained up to 4 weeks of age, while those without BPD declined with time. Postnatal cardiopulmonary and nutritional transition was delayed in infants with BPD. CONCLUSION: Sustained elevation of serum HMGB1 levels was associated with the development of BPD, suggesting that prolonged sterile inflammation may contribute to lung injury.

Twin-twin transfusion syndrome with anemia-polycythemia developed during the third trimester of pregnancy.

We present here a rare case of twin-twin transfusion syndrome with anemia-polycythemia developed at 34-35 weeks of gestation.

Statistical Evaluation of the First Year of a Neonatal Intensive Care Unit Established in a Medical School Hospital.

BACKGROUND: There has been significant progress in reducing perinatal mortality in Japan. However, due to changes in social conditions, the total fertility rate and the number of births are decreasing, whereas the number of low birth weight infants is increasing along with the number of newborn babies that require intensive care. Further, although the number of high-level perinatal medical centers has increased, so has that of infants who need long-term hospitalization. Conversely, the number of regular obstetric facilities has decreased, thus resulting in insufficient beds for neonatal care. To fill this gap, we established a neonatal intensive care unit (NICU) at our hospital. This study aimed to evaluate our new type by comparing the data from ours with that from other facilities. METHODS: The other facilities assessed were two high-level NICU facilities and two regular obstetric facilities. Data, including sex, gestational age, birth weight, Apgar scores at 1 and 5 min, delivery method, and presence of breathing disorders, were extracted from medical records. RESULTS: The birth weight and gestational age distributions were significantly different in the institutions, except in one facility without a NICU. The new NICU saw more infants with low birth weight and respiratory disorders than the regular obstetric facilities. CONCLUSION: The comparison of birth weight and gestational age distributions, cases of respiratory disorders, and delivery methods indicate that our new NICU is positioned as an intermediate facility between a high-level NICU and a regular obstetrics facility.

A Novel System for Spinal Muscular Atrophy Screening in Newborns: Japanese Pilot Study.

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by SMN1 gene deletion/mutation. The drug nusinersen modifies SMN2 mRNA splicing, increasing the production of the full-length SMN protein. Recent studies have demonstrated the beneficial effects of nusinersen in patients with SMA, particularly when treated in early infancy. Because nusinersen treatment can alter disease trajectory, there is a strong rationale for newborn screening. In the current study, we validated the accuracy of a new system for detecting SMN1 deletion (Japanese patent application No. 2017-196967, PCT/JP2018/37732) using dried blood spots (DBS) from 50 patients with genetically confirmed SMA and 50 controls. Our system consists of two steps: (1) targeted pre-amplification of SMN genes by direct polymerase chain reaction (PCR) and (2) detection of SMN1 deletion by real-time modified competitive oligonucleotide priming-PCR (mCOP-PCR) using the pre-amplified products. Compared with PCR analysis results of freshly collected blood samples, our system exhibited a sensitivity of 1.00 (95% confidence interval [CI] 0.96-1.00) and a specificity of 1.00 (95% CI 0.96-1.00). We also conducted a prospective SMA screening study using DBS from 4157 Japanese newborns. All DBS tested negative, and there were no screening failures. Our results indicate that the new system can be reliably used in SMA newborn screening.

Urinary ß2-microglobulin and bronchopulmonary dysplasia: Trends in preterm infants.

BACKGROUND: The developmental process of bronchopulmonary dysplasia (BPD) is not identical between very preterm infants born small for gestational age (SGA) and those born appropriate for gestational age (AGA). In this study, we compared the pattern of the inflammatory response in infants of each group, by measuring urinary ß2-microglobulin (Uß2M) as an alternative, concise, and less-invasive biomarker. METHODS: Uß2M and clinical details were examined at birth and at 4 weeks of age in 146 very preterm infants. RESULTS: Of the 57 infants diagnosed with BPD, 18 were SGA, and 39 were AGA. Uß2M at birth was significantly lower in SGA BPD infants than in AGA BPD infants, but it increased with time. The prevalence of chorioamnionitis (CAM) was significantly lower in SGA BPD infants than in AGA BPD infants, while that of pregnancy-induced hypertension was the opposite. CONCLUSIONS: Exposure to prenatal factors other than CAM may sensitize fetal lungs to become vulnerable to postnatal inflammation in very preterm SGA infants with BPD.

Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann, Sotos, and Kabuki syndromes: A nationwide survey in Japan.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

Trisomy 13 and massive fetomaternal hemorrhage.

This is the first case report of trisomy 13 complicated by massive fetomaternal hemorrhage (FMH). A pale male infant weighing 2,950 g was delivered with low Apgar scores by emergency cesarean section due to non-reassuring fetal status. The umbilical arterial pH and hemoglobin level were 6.815 and 6.9 g/dL (normal: 13 - 22 g/dL), respectively. The maternal hemoglobin-F and serum alpha-fetoprotein levels were 6.0% (normal: < 1.0%) and 1,150 ng/mL (4.1 multiple of median), respectively. The neonate was diagnosed as having trisomy 13 by a subsequent chromosome examination. In the placenta, massive intervillous thrombosis was observed microscopically. This placental finding has been reported to be associated with both preeclampsia and massive FMH. In addition, the incidence of preeclampsia in pregnancies complicated by trisomy 13 has been reported to be significantly higher than normal karyotype populations. Therefore, the current finding may support the association between trisomy 13 and the incidence of massive FMH.

Timing of elective cesarean singleton delivery and neonatal respiratory outcomes at a Japanese perinatal center.

The present study examined the relation between the timing of elective cesarean delivery at term and neonatal respiratory outcomes at our institution. From 2005 through 2013, 1,951 elective cesarean singleton deliveries were performed at term. Of the neonates, 141 (7%) had respiratory disorders requiring oxygen supplementation. In comparison to the incidence of respiratory disorders in neonates delivered at full term (39-40 weeks), the incidences in neonates delivered at ≤38+1/7 weeks' and at 41 weeks' gestation were significantly higher. Uncomplicated elective cesarean singleton delivery should be avoided at 38+1 weeks or earlier, and we also pay attention to the respiratory outcomes of neonates delivered by elective cesarean section at 41 weeks' gestation.

Cholelithiasis in a patient with type 2 Gaucher disease.

Gaucher disease is an autosomal recessively inherited lysosomal storage disease in which a deficiency of glucocerebrosidase is associated with the accumulation of glucocerebroside in reticuloendothelial cells. Clinically, 3 types of Gaucher disease have been defined on the basis of the presence or absence of neurological symptoms. The frequency of gallbladder involvement is reportedly greater in patients with type 1 Gaucher disease than in healthy persons. We report a case of recurrent cholelithiasis and liver failure in a patient with type 2 Gaucher disease who showed severe progressive neurological involvement.

Neonatal case of late-onset sepsis involving group B Streptococcus type Ib.

Group B Streptococcus (GBS) is an important pathogen that causes neonatal sepsis and meningitis, which have high mortality and morbidity. Most cases of infection are early onset, with late onset infections being less common. Moreover, many cases of infection are caused by type III GBS, while type Ib GBS infections are rare. We report a case of late-onset infection by type Ib GBS. A female neonate weighing 574 g was delivered at 27 weeks' gestation. An endotracheal tube was inserted shortly after birth because of respiratory distress syndrome, and ampicillin was administered by the age of 3 days. At the age of 54 days after cardiopulmonary adaptation had been achieved, the patient presented with tachycardia following refractory apnea and bradycardia, and her skin became pale. She was suspected of having sepsis, and intensive treatment, including intubation and administration of catecholamines, was started. Despite these measures, the patient died after 5 hours after the onset of sepsis. Type Ib GBS infection may be more frequent in Japanese infants because of the low concentration of IgG antibodies against type Ib in pregnant Japanese women.

Perinatal risk factors for adverse long-term pulmonary outcome in premature infants: comparison of different definitions of bronchopulmonary dysplasia/chronic lung disease.

BACKGROUND: The aim of the study was to determine factors that affect adverse long-term pulmonary outcome in premature infants. METHODS: This retrospective analysis was done using 306 clinical records of preterm singleton neonates at <32 weeks of gestation. Two definitions of adverse pulmonary outcome were used: chronic lung disease (CLD), defined as a need for supplemental oxygen for at least 28 days after birth; and bronchopulmonary dysplasia (BPD), defined as oxygen dependency for at least 28 days after birth plus at 36 weeks postmenstrual age and/or a need for positive-pressure ventilatory support. Selected perinatal variables were compared between these definitions, and factors related to disease development were identified on multivariate analysis. RESULTS: The incidence of CLD and of BPD were 42% and 17%, respectively. Regardless of the definitions, the incidence of patent ductus arteriosus and of neonatal infection were significantly higher in the patients who met the disease criteria, but that of chorioamnionitis and of small for gestational age (SGA) were significantly higher in the patients only when the BPD definition was applied. Multivariate analysis identified SGA as an independent risk factor for the development of BPD after controlling for gestational age. CONCLUSIONS: Among selected perinatal variables, prenatal risk factors, particularly SGA, contributed to prolonged dependency on oxygen and/or positive-pressure ventilatory support, in combination with neonatal risk factors.

Neonatal case of herpes simplex virus encephalitis after delivery from a woman whose genital herpes simplex virus infection had been treated with acyclovir.

A case of herpes simplex virus (HSV) encephalitis in a neonate after delivery from a woman whose genital HSV infection had been treated with acyclovir is reported. The main approach to prevent genital HSV infection in the neonate is interruption of transmission at the time of delivery. Guidelines for prophylactic therapy with acyclovir have been established, but the risk of neonatal infection remains. A fever began to develop in a male neonate delivered vaginally from a 35-year-old woman. Treatment with intravenous acyclovir was started on the basis of a diagnosis of HSV encephalitis, because polymerase chain reaction was positive for HSV in the cerebrospinal fluid. The mother had had a first genital HSV infection during the second trimester, but treatment with injected acyclovir had caused the blisters and erosion to resolve by the time of delivery. Important steps for preventing neonatal HSV infection are the appropriate treatment of mothers with a history of genital HSV infection, the assessment of delivery methods, and the appropriate treatment of neonates.

Intussusception in an extremely premature infant following bacterial sepsis.

Intussusception occurring in premature infants is exceedingly rare and shows substantially different characteristics from that in the typical age group or non-premature neonates. We present a case of intussusception in an extremely premature infant following bacterial sepsis, in which necrotizing enterocolitis was initially suspected. The correct diagnosis was made at 35 days old using abdominal ultrasonography, but the general condition of the infant had deteriorated to the point where surgery could not be performed. The patient died of multiple organ failure, and autopsy revealed ileo-ileal intussusception without a recognizable anatomical leading point. Possible mechanisms for this rare clinical entity are discussed.

Prenatal diagnosis of isolated congenitally corrected transposition of the great arteries.

Congenitally corrected transposition of the great arteries (ccTGA) is a rare cardiac defect characterized by the atria connecting with anatomically discordant ventricles and the ventricles connecting with discordant and transposed great arteries, which allows hemodynamic compensation. Most patients with ccTGA have associated intracardiac anomalies, which could be a diagnostic clue, whereas isolated forms are infrequently diagnosed during the neonatal period and in utero. We describe a fetus that was diagnosed with ccTGA and without additional cardiac anomalies at 25 weeks of gestation. The parallel course of the great arteries discovered during a routine obstetric scan indicated this rare cardiac anomaly. Further detailed examination of the ventricular morphology helped to confirm the diagnosis. Despite hemodynamic compensation, the long-term prognosis of ccTGA is uncertain because of the possible development of arrhythmias or heart failure later in life. Our findings showed that fetal echocardiography can detect prenatal ccTGA.

An infant with congenital nemaline myopathy and hypertrophic cardiomyopathy.

We describe an infant with nemaline myopathy accompanied by hypertrophic cardiomyopathy. The patient required long-term, intermittent positive-pressure ventilation after birth owing to muscle weakness, and cardiac failure developed during infancy. We diagnosed hypertrophic cardiomyopathy with outflow tract obstruction, and treated the heart failure with beta-adrenergic and angiotensin II receptor blockers. We discuss the prognosis of nemaline myopathy combined with hypertrophic cardiomyopathy.