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.

A case of bacteremia and meningitis in a neonate infected with Group B Streptococcus via breastfeeding who survived without neurological sequelae: A case report.

Invasive neonatal infection with Group B Streptococcus (GBS) is a disease of concern that can lead to neurological sequelae. Guidelines for preventing mother-to-child transmission have been introduced to reduce the incidence of early-onset infection, but guidelines for controlling the late-onset form are lacking. Recently, the trans-breastfeeding route of transmission has been highlighted as an example of late-onset infection, but no consensus on how to manage such infections has been reached. In this report, we describe a case of late-onset bacteremia/meningitis in a neonate suspected to have been infected with GBS via breastfeeding. A vaginal culture test of the mother at 35 weeks' gestation was negative for GBS. Since she had symptoms of mastitis, breast milk and nipple cultures were also tested and found to be positive for the strain of GBS identified in the neonate on genetic analysis. Diagnosis of trans-mammary GBS infection is challenging because breastfeeding-related events are difficult to identify. In our case, the diagnosis was based on the mother's history of mastitis, and the patient was treated without escalation to sequelae. When a neonate develops a fever, physicians should consider GBS infection and examine the mother's medical history to facilitate accurate diagnosis, especially if the history includes mastitis. A breast milk culture should be performed if the mother has mastitis, especially in cases of infection in preterm infants and in recurrent cases.

Neonatal Respiratory Morbidity after Late Preterm, Singleton, Cesarean Delivery before Labor by Mothers Who Did Not Receive Antenatal Corticosteroids.

BACKGROUND: Some evidence suggests that administration of antenatal corticosteroids (ACS) reduces neonatal respiratory complications among women at risk for late preterm birth. However, because of concerns regarding long-term outcomes of children, ACS is not recommended in Japan for pregnant women at risk in late preterm. We assessed the risk of neonatal respiratory morbidity after late preterm, singleton, cesarean delivery before labor by mothers who did not receive ACS. METHODS: We retrospectively reviewed and analyzed data on singleton cesarean deliveries of late preterm infants. The prevalence of neonatal respiratory morbidity requiring ventilatory support, such as continuous positive airway pressure or mechanical ventilation, was analyzed in relation to gestational age in late preterm. Respiratory distress syndrome (RDS) in neonates was also evaluated. RESULTS: We analyzed data from 100 late preterm, singleton, cesarean deliveries: 22 neonates were delivered at 34 weeks, 34 at 35 weeks, and 44 at 36 weeks. Respiratory morbidity significantly decreased in relation to gestational age (p < 0.001). Similarly, there was a significant difference in RDS, which was most frequent at 34 weeks (18.2%, p = 0.017). There were no cases of RDS at 36 weeks. CONCLUSION: Late preterm, singleton, cesarean delivery before labor in mothers who did not receive ACS was associated with a need for ventilation, especially for infants born at 34 and 35 weeks. ACS treatment might therefore be beneficial before elective cesarean section for mothers with a risk of preterm delivery before 35 weeks and 6 days.

Inflammation in preterm birth: Novel mechanism of preterm birth associated with innate and acquired immunity.

Preterm birth (PB) is the most-frequent complication occurring during pregnancy, with a significant impact on neonatal morbidity and mortality. Chorioamnionitis (CAM), the neutrophil infiltration into chorioamniotic membranes, is a major cause of PB. However, several cases of PB have also been reported without apparent pathogenic infection or CAM. Such cases are now attributed to "sterile inflammation." The concept of sterile inflammation has already attracted attention in various diseases, like cardiovascular diseases, diabetes, and autoimmune diseases; recently been discussed for obstetric complications such as miscarriage, PB, gestational hypertension, and gestational diabetes. Sterile inflammation is induced by alarmins, such as high-mobility group box 1 (HMGB1), interleukins (IL-33 and IL-1α), and S100 proteins, that are released by cellular damage without apparent pathogenic infection. These antigens are recognized by pattern-recognition receptors, expressed mainly on antigen-presenting cells of decidua, placenta, amnion, and myometrium, which consequently trigger inflammation. In reproduction, these alarmins are associated with the development of various pregnancy complications, including PB. In this review, we have summarized the development of PB related to acute CAM, chronic CAM, and sterile inflammation as well as proposed a new mechanism for PB that involves innate immunity, acquired immunity, and sterile inflammation.

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.

Role of a Fetal Ultrasound Clinic in Promoting Multidisciplinary and Inter-Facility Perinatal Care.

BACKGROUND: With the increasing rate of high-risk pregnancies, there is an increased need for early evaluation of at-risk fetuses. Fetal ultrasound imaging has become a pivotal part of this evaluation. METHODS: To evaluate the role played by a fetal ultrasound clinic in promoting comprehensive perinatal care of patients with high-risk pregnancies, we retrospectively analyzed the indications and findings of fetal scans and the outcomes of the examined fetuses collected over the past 7 years (2014-2020) by our institute, which is reorganized as a perinatal medical center. RESULTS: During the study period, we conducted 345 fetal scans in high-risk pregnancy cases. Of these, 158 cases (46%) were referrals from other institutes. Eighty-nine neonates were admitted to our neonatal intensive care unit (NICU) after being evaluated, of which 10 neonates underwent surgery during their NICU stays. Thirty-nine pregnant women were referred to other tertiary care hospitals mainly due to fetal diagnoses with complex cardiac anomalies. Fourteen cases resulted in intrauterine fetal death or artificial abortion. CONCLUSIONS: Fetal ultrasound clinics have established their role in facilitating sophisticated regional perinatal care via multidisciplinary and inter-facility cooperation for high-risk pregnancy cases. In addition, providing psychological support and counseling for pregnant women whose fetuses are diagnosed with severe congenital anomalies should not be neglected.

Interfacility Neonatal Transport for Convalescent Care: Improving Regionalized Care.

BACKGROUND: Transfer of infants who no longer need intensive or specialized care from tertiary to community hospitals or clinics contributes to efficient bed utilization in neonatal intensive care units (NICUs). METHODS: We retrospectively analyzed the records of all 1,503 infants admitted to our NICU during the 6-year period from April 2013 through March 2019 to evaluate the impact of interfacility neonatal transport for convalescent care. RESULTS: During the study period, our NICU accepted 33 infants from other tertiary NICUs and transferred 103 infants to other hospitals or clinics before their home discharge for convalescent care. Our NICU covered 39% of the total hospital days of infants accepted from other NICUs. Among infants transferred to other facilities, 81% born at our hospital were born to mothers transported to our obstetrics department as imminent high-risk deliveries; 94% of infants born at other hospitals were moved back to the referring facility. CONCLUSIONS: Interfacility neonatal transport for accepting and transferring infants for convalescent care is now an integral part of NICU practice, to bridge gaps between higher-level care facilities and homes. Establishment of well-defined transfer criteria and appropriate allocation of medical and staff resources among relevant facilities are desirable.

Harmful and beneficial effects of inflammatory response on reproduction: sterile and pathogen-associated inflammation.

In reproduction, inflammatory processes play important roles in the development of many pregnancy complications such as preterm labor/birth, recurrent pregnancy loss, recurrent implantation failure, and preeclampsia. Inflammation can be initiated by both microbial and non-microbial causes. Bacterial infection in the feto-maternal interface and uterus can provoke preterm labor/birth, miscarriage, and chronic endometritis. By contrast, inflammation without infection, or 'sterile inflammation,' can also lead to many kinds of complications, such as preterm labor/birth, miscarriage, or preeclampsia. Aberrant inflammation is facilitated by immune cells such as macrophages, dendritic cells, natural killer cells, and invariant natural killer T cells. In addition, cytokines, chemokines, and several kinds of inflammatory mediators are involved. On the other hand, appropriate inflammation is required for a successful offspring during the progression of the entire pregnancy. Herein, we discuss the relation between pregnancy and inflammation with immunological alterations. Understanding the role of inflammation in complications during pregnancy may establish new perspectives of the progress of normal pregnancy as well as treatments during pregnancy complications.

Inappropriate activation of invariant natural killer T cells and antigen-presenting cells with the elevation of HMGB1 in preterm births without acute chorioamnionitis.

PROBLEM: Acute chorioamnionitis (aCAM) associated with microbial infection is a primary cause of preterm birth (PB). However, recent studies have demonstrated that innate immunity and sterile inflammation are causes of PB in the absence of aCAM. Therefore, we analyzed immune cells in the decidua of early to moderate PB without aCAM. METHOD OF STUDY: Deciduas were obtained from patients with PB at a gestational age of 24+0 to 33+6  weeks without aCAM in pathological diagnosis. The patients were divided into two groups as follows: patients with labor and/or rupture of membrane (ROM) (no aCAM with labor and/or ROM: nCAM-w-LR), and patients without labor and/or ROM (no aCAM without labor and/or ROM: nCAM-w/o-LR). The immune cells and high mobility group box 1 (HMGB1) levels in the decidua were analyzed using flow cytometry. Co-culture of CD56+ cells with dendritic cells (DCs) and macrophages obtained from the decidua was also performed in the presence of HMGB1. RESULTS: The nCAM-w-LR group demonstrated an accumulation of iNKT cells, and increased expression of HMGB1, TLR4, receptors for advanced glycation end products, and CD1d on DCs and macrophages. HMGB1 facilitated the proliferation of iNKT cells co-cultured with DCs and macrophages, which was found to be inhibited by heparin. CONCLUSIONS: Inappropriate activation of innate immune cells and increased HMGB1 expression may represent parturition signs in human pregnancy. Therefore, control of these cells and HMGB1 antigenicity may be represent a potential therapeutic target for the prevention of PB.

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.

Comparative evaluation of square and rectangular slot three-point play behavior.

The play between bracket slots and archwires affects tooth movement and the transmission of orthodontic force by multi-bracket appliances. We assessed play by quantifying the play behavior of three-point brackets and comparing the amount of play that occurred with square and rectangular slots, respectively, by using archwires of various sizes. Horizontal play with the square slot was significantly smaller than that with the rectangular slot. These data demonstrate that brackets with square slots can more effectively bring about tooth movement in the labio-lingual direction and control rotational movement with round and square archwires. Since the horizontal and vertical play ratios for the round and square wires within the square slot were approximately 1.0, three-dimensional tooth movement may also be achieved with uniform play in the vertical and horizontal directions.

Resection of Kommerell's diverticulum in an infant with prenatal diagnosis of right aortic arch.

BACKGROUND: A right aortic arch is a congenital vascular anomaly that is present in up to 0.1% of pregnancies. The anomaly observed by fetal ultrasonography was recently reported to indicate vascular and chromosomal abnormalities that may complicate postnatal management. CASE PRESENTATION: We report the successful resection of a Kommerell's diverticulum with left subclavian artery transfer to the left carotid artery in a 5-month-old Japanese boy. The patient was prenatally diagnosed as having a right aortic arch, and a vascular ring was confirmed at 4 months of age with enhanced computed tomography. The pathology of the resected aortic wall revealed severe disruption and fragmentation of elastic fibers associated with a disarray of smooth muscle cells in the tunica media, and cystic medial necrosis with mucoid extracellular matrix deposition. CONCLUSION: These abnormal pathological findings supported the resection of Kommerell's diverticulum at this point of time, and division of the ligamentum arteriosus alone was not recommended. Early intervention in this condition once the diagnosis is made may thus be advocated. The fetal diagnosis of a right aortic arch may provide a clue to the possibility of a vascular ring.

A case of anhidrotic ectodermal dysplasia presenting with pyrexia, atopic eczema, and food allergy.

Anhidrotic ectodermal dysplasia (AED) is a rare hereditary disorder with a triad of sparse hair, dental hypoplasia, and anhidrosis. Here we report a case of AED with food allergy and atopic eczema. The patient was a 11-month-old boy admitted to our hospital with pyrexia for 2 weeks. He presented with a history of dry skin, eczema, and food allergy to egg. On clinical examination, his body temperature was 38.8°C, with dry skin and eczema almost all over the body, sparse eyebrows, and scalp hair. Laboratory investigations and physical examination did not show any evidence of infection. Radioallergosorbent test was positive to egg yolk, egg white, ovomucoid, milk, house dust, and house dust mite. As the child did not sweat despite the high fever, we performed the sweat test which revealed a total lack of sweat glands. Genetic examination revealed a mutation of the EDA gene and he was diagnosed as AED. His pyrexia improved upon cooling with ice and fan. His mother had lost 8 teeth and her sweat test demonstrated low sweating, suggestive of her being a carrier of AED. Atopy and immune deficiencies have been shown to have a higher prevalence in patients with AED. Disruption of the skin barrier in patients with AED make them more prone to allergic diseases such as atopic eczema, bronchial asthma, allergic rhinitis and food allergy. Careful assessment of the familial history is essential to differentiate AED when examining patients with pyrexia of unknown origin and comorbid allergic diseases.

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.

Distribution of invariant natural killer T cells and dendritic cells in late pre-term birth without acute chorioamnionitis.

PROBLEM: Acute chorioamnionitis (aCAM) is an important cause of pre-term birth. However, little is known about the pathogenesis of late pre-term birth without aCAM that was the most common category of pre-term birth. Here we analyze the kinetics of immune cells obtained from the decidua of women with late pre-term births with and without aCAM. METHOD OF STUDY: Deciduas were obtained from women who underwent labor with late pre-term birth without aCAM (PB-n/aCAM) or with aCAM (PB-w/aCAM). The population of DEC-205+ dendritic cells (DCs), macrophages, invariant natural killer T (iNKT) cells, NK cells, CD8+ T cells, and CD4+ T cells were analyzed by flow cytometry. RESULTS: The number of iNKT cells was higher in the decidua obtained from women with PB-n/aCAM than PB-w/aCAM. DEC-205+ DCs obtained from women with PB-n/aCAM preferentially induced iNKT cell proliferation. CONCLUSION: iNKT cell accumulation with DEC-205+ DCs in PB-n/aCAM suggests that iNKT cells contribute to the onset of PB-n/aCAM.

Prenatal Detection of Peters' Plus Syndrome in a Patient with No Known Family History.

Peters' plus syndrome is a rare autosomal recessive condition characterized by a combination of typical ocular defects and other systemic abnormalities. We present a case of this uncommon syndrome that we diagnosed during a fetal ultrasonographical examination. Because the patient exhibited microcephaly and anterior staphyloma of the right eye and because impending rupture was feared, we performed ophthalmectomy during the neonatal period. Fetal ophthalmological anomalies are often detected during ultrasonographic examination targeting other systemic abnormalities, with positive family histories providing important diagnostic clues. This case is, to our knowledge, the first to be reported of prenatally diagnosed Peters' plus syndrome in a patient with no known family history in whom total blindness was prevented with an early referral to specialists.

Effect on clinical work practice of establishing a neonatal intensive care unit at a medical school-affiliated teaching hospital.

OBJECTIVE: The aim of this study was to examine the effects of a newly established neonatal intensive care unit (NICU) on clinical work practice and educational activity at Nippon Medical School Musashikosugi Hospital. METHODS: This retrospective study analyzed the clinical records of all neonates admitted to the NICU from December 2010 through November 2013. Anthropometric data, clinical status, problems, and outcomes of patients and the related obstetrical history were extracted and analyzed. RESULTS: Of the 568 neonatal admissions, about half were related to preterm birth (49%) and low birth weight (55%). Forty-eight percent of patients were born via caesarean delivery. Maternal hypertension, diabetes, and thyroid disease were found in 8%, 5%, and 2% of cases, respectively. Mechanical ventilatory support was provided for 20% of patients. Neonates from multiple pregnancy and with significant congenital anomalies accounted for 17% and 10% of all patients, respectively. Five patients died during hospitalization. In addition training was provided in the NICU for an average of 10 residents and 20 medical students per year. CONCLUSION: Since the NICU was established, closer cooperation beyond the framework of a single department has come to be needed. In addition, NICUs in teaching hospitals are expected to provide opportunities for medical students and residents to observe and participate in multidisciplinary medical care.

Postnatal changes of cytokines in premature infants with or without funisitis.

OBJECTIVE: Fetal inflammatory response syndrome (FIRS), which induces hypercytokinemia, is important for the outcomes of premature infants. It is necessary to focus on the fetal inflammatory environments. METHODS: A total of 37 premature infants (gestational age ≤32 weeks) were divided into three groups: (1) 15 without chorioamnionitis (CAM) and funisitis; C(-)F(-) group, (2) 15 with CAM but without funisitis; C(+)F(-) group and (3) 7 with CAM and funisitis; C(+)F(+) group. Blood interleukin (IL)-1ß, IL-6 and IL-8 levels were measured on day 0 (= in umbilical cord blood), 3, 7, 14, 21 and 28. RESULTS: (1) day 0: Cord blood concentrations of IL-1ß, IL-6 and IL-8 were significantly higher in the C(+)F(+) group than in the C(+)F(-) group and C(-)F(-) group. On the other hand, they were comparable between the C(+)F(-) group and C(-)F(-) group. (2) Days 3-28: elevated cytokines levels in the C(+)F(+) group with funisitis decreased on day 3 and later. CONCLUSIONS: We suggested that hypercytokinemia in the cord blood in premature infants were greatly related with funisitis. Diagnosis of funisitis would be important to find the premature infants who need to be managed their risk of FIRS. In addition, hypercytokinemia disappeared in a few days after birth; therefore, cord blood data analysis of cytokines and/or inflammation-related proteins concentrations is necessary to evaluate the fetal inflammatory environments in premature infants after birth.

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.