Relationship between the serum creatinine concentrations of preterm neonates within 24 h of birth and their mothers before delivery.

BACKGROUND: Neonatal serum creatinine (n-sCr) concentrations during the first few days of life have been reported to correlate with the maternal serum Cr (m-sCr) concentrations. We aimed to derive a regression equation to describe the relationship between n-sCr within 24 h of birth in preterm neonates and m-sCr before delivery, and to perform multiple regression analysis to identify factors related to n-sCr and the difference between n-sCr and m-sCr. METHODS: We recruited preterm neonates who were treated at the University of the Ryukyus Hospital between March 2012 and October 2022. Patients with underlying diseases or conditions that might affect hemodynamics were excluded, as were patients whose n-sCr and m-sCr were not measured in pairs. A total of 278 cases were included in the analysis. RESULTS: The median (interquartile range) gestational age, birth weight, n-sCr, and m-sCr were 33.9 weeks (32.0-35.1 weeks), 1901 g (1579-2284 g), 0.55 mg/dL (0.48-0.64 mg/dL), and 0.47 mg/dL (0.42-0.57 mg/dL), respectively. The regression equation derived was n-sCr = 0.092 + 0.970 × m-sCr (R2 = 0.768, p < 0.001). The multiple regression analysis showed that m-sCr was the most potent influencer of n-sCr, and the ratio of placental weight to birth weight (PW/BW ratio) was the most potent influencer of the difference between n-sCr and m-sCr. CONCLUSIONS: We have obtained an approximate equation of n-sCr = 0.1 + m-sCr for preterm neonates. In addition, the high PW/BW ration may reduce the difference between n-sCr and m-sCr.

Early parenteral nutrition in neonates with congenital diaphragmatic hernia.

BACKGROUND: The ideal nutritive strategy for a neonate with congenital diaphragmatic hernia (CDH) has not been elucidated. The purpose of this study was to investigate the efficacy of early parenteral nutrition (PN) in CDH neonates. METHODS: Thirty-five CDH neonates admitted to a single hospital from January 2005 to December 2014 were retrospectively reviewed. For the first 4 years of the study period, neonates received non-early PN (n-EPN) (2005-2008, amino acids [AA] <1.0 g/kg/day, no lipids administered). After the transitional period (TP) (2009-2011, AA 1.0-2.5 g/kg/day, lipid 1.0 g/kg/day), early PN (EPN) (2011-2014, AA ≥3.0 g/kg/day, lipid 1.0 g/kg/day) was performed. We investigated the clinical effect of PN for growth-associated clinical variables and the outcomes. RESULTS: The first day of AA administration was late in the n-EPN period (6.0 ± 4.6, 0.0 ± 0.8, 0.1 ± 0.3 ; n-EPN, TP, EPN: in order). The final day of PN (11.0 ± 3.7, 9.2 ± 4.0, 12.4 ± 3.9) and the first day of enteral feeding (4.5 ± 1.9, 4.3 ± 1.4, 4.5 ± 3.2), the first day of full milk feeding (100 mL/kg/day) (10.8 ± 5.4, 9.2 ± 2.3, 11.5 ± 3.5) were statistically equal in every period. The date and body weight at discharge showed no significant differences among the three groups, but the weight-gain rate from birth to discharge was higher in the EPN group than in the n-EPN group (P = 0.023). The rate of inhaled nitric oxide (NO) gas administration and the duration of ventilation showed no significant differences among the three groups. Severe PN-associated liver disease was not noted during the observation period. CONCLUSIONS: Early PN for CDH neonates promotes weight gain in the neonatal intensive-care unit. The long-term efficacy and safety of EPN for CDH neonates should be elucidated by additional studies.

Evaluation of brain development and damage using magnetic resonance imaging of congenital diaphragmatic hernia survivors: An analysis using the global brain abnormality score.

BACKGROUND: The short-term prognosis of central nervous system in congenital diaphragmatic hernia (CDH) survivors has been determined by magnetic resonance imaging (MRI), but its relationship with acute management is unclear. We aimed to investigate the association between the intubation period and the Global Brain Abnormality Score (GBAS) in CDH survivors using brain MRI. METHODS: Fifty-seven patients with CDH who were hospitalized at a single NICU between January 2004 and December 2019 were retrospectively reviewed. After excluding 5 patients who died shortly after birth and two who could not be weaned from the ventilator, the acute management of the 50 remaining patients was investigated. We also investigated the relationship between the GBAS and intubation period in 25 patients who underwent brain MRI at discharge. RESULTS: The long-intubation group (intubation ≥12 days) had lower Apgar scores and fetal lung-thoracic ratios, and longer time to radical surgery, and parenteral nutrition and tube feeding periods. Nitric oxide inhalation, liver prolapse, patch closure, and extracorporeal membrane oxygenation were independent risk factors for long-intubation. Eighty-four percent of CDH survivors had some imaging abnormalities, including developmental and signaling abnormalities. In the long-intubation group, the body of the corpus callosum was thin and the cerebral hemispheric space was widened, and GBAS deterioration was significantly related to the intubation period. CONCLUSION: Brain MRI abnormalities were found in 84% of CDH survivors. Prolonged intubation is associated with worsening of the GBAS. Thus, the duration of intubation may be a surrogate outcome for the neurological prognosis of CDH survivors.

Additional findings of tibial dysplasia in a male with orofaciodigital syndrome type XVI.

We describe the case of a male patient with orofaciodigital (OFD) syndrome type XVI with a homozygous variant of TMEM107 (p.Phe106del) and the additional findings of tibial dysplasia, which is a pivotal finding of OFD syndrome type IV. His family history included two fetuses with anencephaly with or without cleft lip/palate and polydactyly with no genetic information. Careful attention should be given to the interpretation of this rare pattern.

A Neonatal Case of Mild Encephalopathy/Encephalitis with a Reversible Splenial Lesion.

The neurological symptoms of pediatric mild encephalopathy/encephalitis with a reversible splenial lesion (MERS) are mild and have a good prognosis. However, some aspects of neonatal MERS are unclear due to a lack of clinical knowledge. We present a neonatal case of MERS with features of poor activity and prolonged poor oxygenation after birth without asphyxia. He was diagnosed with MERS by brain magnetic resonance imaging (MRI) on day10, because the diffusion restriction of the splenium of the corpus callosum (SCC) seen on diffusion-weighted MRI on day 5 was attenuating. He was discharged due to good progress on day 26, but growth issues and developmental delay were observed in the follow up from 1-10 months. In rare neonatal cases, many aspects of the clinical course and prognosis are thus unclear. MERS should be considered in newborns who show unexplained non-neural or other encephalopathic symptoms.

Early weight changes after birth and serum high-molecular-weight adiponectin level in preterm infants.

BACKGROUND: Extra-uterine growth retardation (EUGR) is associated with an increased risk for cardiometabolic diseases later in life. The aim of the present study was to examine the relationship between early weight change after birth in preterm infants and adiponectin (adn) multimeric complexes. METHODS: Subjects included 28 preterm infants born between weeks 24 and 33 of gestation. Serum adn multimeric complexes and the anthropometric parameters were measured in preterm infants at birth and at corrected term. RESULTS: Bodyweight (BW) decreased during the first week of life, with birthweight restored at approximately 19 days after birth. Nineteen of the subjects had EUGR at corrected term. Total (T)-adn, high-molecular-weight (H)-adn, and the ratio of H-adn to T-adn (H/T-adn) were significantly elevated at corrected term than at birth. Postmenstrual age, birthweight, birth length and lowest BW after birth were positively correlated with H-adn and H/T-adn. Weight reduction after birth was negatively correlated with H-adn. Age to restore birthweight was negatively correlated with T-adn, H-adn and H/T-adn. Stepwise multiple regression analysis indicated age to restore birthweight as the major predictor of T-adn and H-adn. DISCUSSION: Early weight changes after birth may alter serum adn level in preterm infants at corrected term. The appropriate nutritional support in the early postnatal period could reduce the prevalence of EUGR and the future risk for cardiometabolic diseases.

Critical respiratory failure in pregnancy complicated with COVID-19: A case report.

The case is presented of a 29-year-old primiparous woman who was COVID-19-positive at 34 weeks of gestation and who developed severe acute respiratory distress syndrome. After a four-day history of fever and mild dyspnea, she was referred to hospital. Ciclesonide, dexamethasone, heparin sodium, and sulbactam/ampicillin were initiated, followed by remdesivir and tocilizumab. On the fourth day after admission (at 34 weeks 5 days of gestation), respiratory failure required ventilator management. An emergency cesarean section was performed and a 2565-g male infant was delivered with an Apgar score of 8/8 and negative COVID-19 status. However, on the following day the patient's respiratory condition deteriorated and mechanical ventilation was initiated. Subsequently, her respiratory condition quickly improved and mechanical ventilation was terminated 4 days after intubation. She was discharged 12 days after cesarean delivery. Our case provides additional evidence that raises concerns regarding the unfavorable maternal consequences of COVID-19 infection during pregnancy.

Evaluation of neonatal withdrawal syndrome in neonates delivered by women taking psychotropic or anticonvulsant drugs: A retrospective chart review of the effects of multiple medications and breastfeeding.

OBJECTIVES: Neonates delivered by women who were taking psychotropic or anticonvulsant drugs during pregnancy are at increased risk of developing neonatal withdrawal syndrome. We investigated the incidence of neonatal withdrawal symptoms and the effects of multiple maternal medications and breastfeeding on neonatal withdrawal symptoms. STUDY DESIGN: This study examined the overall incidence of neonatal withdrawal symptoms in neonates delivered from 2004 to 2016 by women who were taking oral antipsychotics, antidepressants, anxiolytics, sedatives, or anticonvulsant drugs during pregnancy. Moreover, we compared the incidence of neonatal symptoms between mothers taking single drugs and multiple drugs, and between breastfed and formula-fed neonates. We scored the neonates according to the neonatal withdrawal syndrome checklist created by Isobe et al., which is widely used in Japan. RESULTS: We examined 131 mothers and their 134 neonates. Withdrawal symptoms were found in 54.5 % of neonates. Symptoms were found in 32.4 % of neonates delivered by mothers taking single drugs and 62.9 % of neonates delivered by mothers taking two or more drugs (p = 0.0019). One or more withdrawal symptoms developed in 46.4 % of breastfed neonates and 66.1 % of formula-fed neonates (p = 0.034). Five infants had a score of 8 or more points on the withdrawal checklist, which is an indication to consider treatment with pharmacotherapy. All five of these neonates were mainly formula-fed, and their mothers were taking two or more drugs. CONCLUSIONS: The incidence of withdrawal symptoms was high in neonates delivered by women taking psychotropic or anticonvulsant drugs; however, there were few serious cases. The risk increased when a mother was taking multiple drugs. Breastfeeding appeared to protect against withdrawal symptoms.

The ratio of high-molecular weight adiponectin and total adiponectin differs in preterm and term infants.

Adiponectin consists of three subspecies (high-, middle- and low-molecular weight adiponectin). Among these, high-molecular weight adiponectin (H-adn) is suggested to be an active form of this protein. To assess the relationship between H-adn and postnatal growth in preterm infants (PIs), serum H-adn and total adiponectin (T-adn) were measured in 46 PIs at birth and at corrected term, and 26 term infants (TI) at birth. T-adn and H-adn concentrations, and the ratio of H-adn to T-adn (H/T-adn) were significantly greater in TI and PI at corrected term than in PI at birth (p < 0.001). T-adn and H-adn concentrations in PI at corrected term were similar to those in TI, but H/T-adn in PI at corrected term was less than that in TI (p < 0.02). Stepwise multiple regression analysis revealed that the factors contributing to H/T-adn and serum concentrations of T- and H-adn in PI at corrected term were different from those in TI. These data suggest that quality of early postnatal growth in PIs is different from that in normally developed TI. Postnatal growth accompanying adipose tissue similar to TI may be important for PI to prevent future development of cardiovascular disease.

A Case of Intrathoracic Gastric Duplication Cyst Detected on Prenatal Ultrasound Examination.

A 37-year-old (G4P3) woman was referred to our hospital at 32 weeks of gestation for the evaluation of a fetus with an intrathoracic cystic lesion. Ultrasonography and magnetic resonance imaging revealed that a fetal cystic lesion without a mucosal layer was located in the posterior mediastinum. These findings were consistent with a bronchogenic cyst. At 38 3/7 weeks of gestation, an elective cesarean section was performed because of her previous cesarean section. A female neonate without any external anomalies, weighing 2,442 g, with Apgar scores of 8 and 9, and requiring no resuscitation was born. Four weeks after delivery, the neonate was admitted because of respiratory distress due to mass effect. At right lateral thoracotomy, a 105 × 65 mm of solitary smooth-walled cyst containing serosanguineous fluid was found in the posterior mediastinum, which was excised completely. Histologic examination revealed the diagnosis of the mediastinal gastric duplication cyst. The neonate made an uneventful recovery. Accurate diagnosis is not necessary, but detection and continuous observation are logical. Although gastric duplication, particularly intrathoracic, is a rare pathology, it should be considered in the differential diagnosis of any intrathoracic cyst.

A new mutation found in newborn screening for Fabry disease evaluated by plasma globotriaosylsphingosine levels.

A pilot study of newborn screening for Fabry disease was performed in Okinawa, Japan. A total of 2,443 neonates were screened using dried blood spot samples over 7 years starting in 2007. Of 13 neonates determined to have low α-galactosidase A (GLA) activity, one boy had a new missense mutation, p.G144D of the GLA gene. This mutation was considered to be a late-onset type, as evaluated based on plasma globotriaosylsphingosine levels and family history.

Fetal Thoracoamniotic Shunting in a Case of Congenital Pulmonary Airway Malformations with Hydrops Fetalis.

Aim We report a case of congenital pulmonary airway malformation (CPAM) with hydrops in which the fetus underwent thoracoamniotic shunting. Case Report A 40-year-old (G1P1) woman was diagnosed with a macrocystic CPAM. Thoracoamniotic shunting was performed at 19 weeks of gestation but not well drained and was successfully performed again at 23 weeks. However, the CPAM volume ratio, abdominal circumference, and amniotic fluid index started increasing from 28 weeks and hydrops worsened. The insufficient shunting and the fetal cardiac failure had to be considered. At 32 weeks, a male infant with general edema and massive ascites was born weighing 3,362 g (+4.79 SD) with Apgar scores of 2 and 4. The infant was intubated and high-frequency oscillation and nitric oxide therapies were instituted. The resection of CPAM was performed on day 2. Nasal continuous positive airway pressure was instituted on day 16. The infant was discharged and prescribed with home oxygen therapy (HOT) on day 65. The infant was able to leave the HOT at 30 months and is currently 34 months of age in good condition. Conclusion Fetal thoracoamniotic shunting may be life-saving in CPAM complicated by hydrops and that this treatment might be sufficient to cure the child.

Serum C-reactive protein and its relation to cardiovascular risk factors and adipocytokines in Japanese children.

BACKGROUND: C-Reactive protein (CRP) is an independent risk factor for atherosclerotic coronary heart diseases (ACHD) in adults. To help prevent ACHD, it may be useful to understand risk factors during childhood. OBJECTIVE: The objective of this study was to investigate serum CRP and its relation to other risk factors for ACHD and adipocytokines (adiponectin, IL-6, and TNF-alpha) in Japanese children. METHODS: CRP, conventional risk factors for ACHD, and adipocytokines were determined in 568 children (340 boys and 228 girls, aged 7-10 yr). Serum concentrations of adipocytokines were measured by sandwich ELISA. RESULTS: Children with high CRP concentrations (highest tertile) had higher body mass index (BMI) sd scores, insulin, insulin resistance, uric acid, and adipocytokines and had more atherogenic lipoprotein profiles than other children. However, after being corrected by BMI sd, only high-density lipoprotein cholesterol, apolipoprotein A-I, IL-6, and TNF-alpha for boys and high-density lipoprotein cholesterol, apolipoprotein B, uric acid, IL-6, and TNF-alpha for girls were significantly correlated with CRP. IL-6 was the strongest predictive variable for CRP and accounted for 26.2 and 27.7% of the variability in serum concentrations of CRP in boys and girls, respectively. Serum concentrations of IL-6 were partly dependent on BMI sd and TNF-alpha in both boys and girls. CONCLUSION: Although serum concentrations of CRP are partly regulated by adipocytokines and conventional risk factors for ACHD, high CRP levels were associated with atherogenic profiles of cardiovascular risk factors in children. Our findings suggest that it may be important to control body weight to prevent an increase in serum CRP in children.

No clinical correlation between bilirubin levels and severity of retinopathy of prematurity.

PURPOSE: To evaluate the hypothesis that bilirubin has a protective effect against the development of severe retinopathy of prematurity (ROP). METHODS: An assessment of 76 infants born at 24 and 25 weeks' gestation and admitted to the level III neonatal intensive care unit at Saitama Children's Medical Center was made. Indirect ophthalmoscopy fundus examinations were performed on all infants to identify the degree and progression to threshold ROP. We analyzed the daily bilirubin levels and grouped the patients according to the severity of ROP based on the infant's worst ROP examination. The first group was comprised of infants with less than stage 3 ROP and infants with stage 3 ROP. The second group was infants with less than prethreshold ROP or prethreshold ROP, and infants with threshold ROP. Next, we divided the infants into 3 groups: less than prethreshold ROP, prethreshold ROP, and threshold ROP. The daily changes in serum bilirubin concentrations during the first 14 days of life were determined for each infant. Three groups (less than prethreshold ROP, prethreshold ROP, and threshold ROP) were comparable as to their basic data, clinical characteristics, and treatments. RESULTS: ROP was found in 76 infants. There were no statistical differences in the clinical characteristics and treatments, excluding the duration of phototherapy, among the 3 groups. During the first 14 days of age, there were no significant differences in the daily mean bilirubin concentrations according to the groups separated by severity of ROP. CONCLUSION: These results indicate that there is no distinct protective effect of bilirubin on the development of severe ROP.

Highly temperature-sensitive liposomes based on a thermosensitive block copolymer for tumor-specific chemotherapy.

Recently, we showed that incorporation of poly[2-(2-ethoxy)ethoxyethyl vinyl ether (EOEOVE)], which exhibits a lower critical solution temperature around 40 degrees C, provides temperature-sensitive properties to stable liposomes. In this study, we applied this thermosensitive polymer for preparation of temperature-sensitive liposomes for tumor-specific chemotherapy with doxorubicin (DOX). We prepared liposomes consisting of PEG-lipid, egg yolk phosphatidylcholine, cholesterol and copoly(EOEOVE-block-octadecyl vinyl ether), which was synthesized as poly(EOEOVE) having anchors for fixation onto liposome membrane. The copolymer-incorporated liposomes were stable and retained DOX in their inside below physiological temperatures. However, they exhibited a significant release of encapsulated DOX above 40 degrees C and released DOX almost completely within 1 min at 45 degrees C. The copolymer-modified liposomes exhibited a long circulating property and biodistribution similar to that of PEG-modified liposomes. The copolymer-modified liposomes loaded with DOX were injected intravenously into tumor-bearing mice. Tumor growth was strongly suppressed when the tumor site was heated to 45 degrees C for 10 min at 6-12 h after injection. However, injection of the liposomes exhibited only slight tumor-suppressive effects as long as mild heating was not applied to the target site. The highly temperature-sensitive properties of the copolymer-incorporated liposomes might contribute to establishment of tumor-selective and effective chemotherapy.

Birthweight and risk factors for cardiovascular diseases in Japanese schoolchildren.

BACKGROUND: Low birthweight (LBW) is associated with an increased risk for atherosclerotic coronary heart disease (ACHD) later in life. However, little information is currently available on the relationship between birthweight (BW) and risk factors for ACHD in children. METHODS: The relationship between BW and risk factors for ACHD was evaluated in 330 Japanese children (187 boys and 143 girls) aged between 7 and 12 years, who underwent screening for lifestyle-related diseases in Okinawa, Japan. Routine chemical methods were used to determine the serum concentrations of lipids, apolipoproteins, uric acid and glucose. Serum insulin and adiponectin were measured by sandwich enzyme-linked immunosorbent assay. RESULTS: BW was significantly correlated with serum concentrations of adiponectin (r= 0.163, P= 0.003) and uric acid (r=-0.166. P= 0.003), but not with insulin, lipids or apolipoproteins. These correlations were still significant even after adjusting for age, gender and body mass index (BMI) percentile (BW and adiponectin, r= 0.239, P= 0.000; BW and uric acid, r=-0.247, P= 0.000). In addition, BW was correlated with high-density lipoprotein-cholesterol (HDL-C) only after adjusting for age, gender and BMI percentile (r= 0.117, P= 0.034). In a stepwise multiple regression analysis, BW was a significant predictive variable for adiponectin and uric acid. However, weight velocity (weight gain/year) was a stronger predictive variable than BW for both adiponectin and uric acid. BW was not a significant predictive variable for HDL-C. Adiponectin was the strongest predictive variable for HDL-C. CONCLUSION: BW is related to serum concentrations of adiponectin and uric acid. However, weight velocity was a stronger determinant of serum adiponectin and uric acid levels than BW in Japanese schoolchildren. Thus, it may be important to control weight gain to prevent the development of ACHD in children, especially in children with LBW.

A case of congenital high airway obstruction syndrome managed by ex utero intrapartum treatment: case report and review of the literature.

Congenital high airway obstruction syndrome (CHAOS) has been reported to be fatal. Ten cases of CHAOS that underwent ex utero intrapartum treatment (EXIT) procedure to secure the fetal airway have been reported. A 36-year-old woman (gravida 3, para 2) was referred to our hospital at 22 weeks of gestation. Sonography revealed large echogenic lungs, flattened diaphragm, and marked hydrops. Magnetic resonance imaging confirmed the diagnosis of CHAOS. Polyhydramnios and fetal skin edema were improved and the fetal ascitic fluid was regressed gradually. At 36 weeks of gestation, an EXIT procedure was undertaken. Fetal laryngoscopy and bronchoscopy showed complete laryngeal obstruction, and a tracheostomy was performed immediately. The infant was discharged from hospital at 6 weeks of age. Thereafter, he developed well both physically and mentally. A laryngoplasty was performed at 20 months of age using silicon sheet as a patent airway. The child has a tracheostomy, is able to phonate but does not speak, and is awaiting decannulation. Use of the EXIT procedure in CHAOS cases offers the potential for salvage and excellent long-term outcome of these fetuses that otherwise would not survive. However, management of the airway, particularly with regard to long-term reconstruction in children with CHAOS, remains challenging.

Temperature sensitization of liposomes by use of thermosensitive block copolymers synthesized by living cationic polymerization: effect of copolymer chain length.

We prepared block copolymers of (2-ethoxy)ethoxyethyl vinyl ether (EOEOVE) and octadecyl vinyl ether (ODVE) with the number average molecular weights of 6900, 9300, and 16 700 by living cationic polymerization. The poly(EOEOVE) block acts as a temperature-sensitive moiety, and the poly(ODVE) block acts as an anchor moiety. We also investigated the effect of chain length of the copolymer poly(EOEOVE) block on the ability to sensitize liposomes. The copolymers underwent a coil-globule transition at approximately 36 degrees C in the presence of a membrane of egg yolk phosphatidylcholine (EYPC), detected using differential scanning calorimetry (DSC). Liposomes encapsulating calcein, a water-soluble fluorescent dye, were prepared from mixtures of dioleoylphosphatidylethanolamine, EYPC, and the copolymers. While the copolymer-modified liposomes released little calcein below 30 degrees C, release was enhanced above 35 degrees C, indicating that dehydrated copolymer chains destabilized the liposome membrane. In addition, copolymers with a longer poly(EOEOVE) block induced a more drastic enhancement of contents release in a narrow temperature region near the transition temperature of the poly(EOEOVE) block. As a result, the copolymer with an average molecular weight of 16 700 generated highly sensitive liposomes that produced rapid and dramatic release of the contents in response to temperature.

A 7-year-old boy with mycoplasmal infection requiring extracorporeal membrane oxygenation.

UNLABELLED: A 7-year-old boy with Down syndrome developed severe acute respiratory distress syndrome after a respiratory infection with Mycoplasma pneumoniae with an unusually high agglutination titre (1:10240). Initially, mechanical ventilation and nitric oxide inhalation were used, but these did not improve the alveolar-arterial oxygen gradient. Extracorporeal membrane oxygenation for 152 h improved the lung condition. CONCLUSION: our case suggests that Mycoplasma pneumoniae should be considered as an aetiological agent in acute respiratory distress syndrome. Extracorporeal membrane oxygenation might have a valuable role in the management.