A prospective cohort study of newborns born to mothers with serum Toxoplasma gondii immunoglobulin M positivity during pregnancy.

INTRODUCTION: The aims were to investigate the clinical characteristics of Toxoplasma gondii (T. gondii) immunoglobulin (Ig) M-positive mothers and to clarify the incidences of serum T. gondii IgM or blood T. gondii DNA positivity in newborns born to the mothers and the actual congenital T. gondii infection. METHODS: Mothers with T. gondii IgM positivity and newborns born to the mothers from 2013 to 2020 were prospectively investigated. Serum T. gondii IgG and IgM were measured by enzyme-linked immunosorbent assay. Blood T. gondii DNA was detected by semi-nested polymerase chain reaction. Congenital T. gondii infection was diagnosed based on clinical characteristic manifestations with serum T. gondii IgG positivity at any age or T. gondii IgG positivity after 12 months of age. RESULTS: Among 71 T. gondii IgM-positive mothers, including one with triplets, 41% had low T. gondii IgG avidity index and 73% received maternal therapy. Among 73 newborns who were examined for serum T. gondii IgG and IgM at birth, none had clinical manifestations, and one (1.4%) had T. gondii IgM positivity. Among 32 newborns who were examined for blood T. gondii DNA at birth, two (6.3%) were positive. All patients with serum T. gondii IgM or blood T. gondii DNA positivity showed T. gondii IgG negativity within 12 months of age. CONCLUSIONS: A few newborns born to T. gondii IgM-positive mothers were suspected of having congenital T. gondii infection based on serum T. gondii IgM or blood T. gondii DNA testing at birth. However, none developed congenital T. gondii infection.

Successful Treatment of Hyperbilirubinemia by Monitoring Serum Unbound Bilirubin in an Extremely Preterm Infant with Bacterial Infection.

BACKGROUND: Bacterial infections and some antibiotics show displacer effects on bilirubin-albumin binding and increase unbound bilirubin (UB) but not total bilirubin (TB) in serum. METHODS: A case study was conducted to show a successful treatment of hyperbilirubinemia by monitoring UB. RESULTS: In an extremely preterm infant with bloodstream bacterial infection caused by methicillin-resistant coagulase-negative staphylococci, 2 days after high-dose ampicillin and regular-dose amikacin were initiated, UB markedly increased, but TB did not. After vancomycin was substituted, UB decreased immediately with phototherapy and intravenous albumin infusion. CONCLUSIONS: When using antibiotics, the clinicians should be mindful regarding the displacer effect on bilirubin-albumin binding.

Awareness and knowledge of congenital cytomegalovirus infection among pregnant women and the general public: a web-based survey in Japan.

BACKGROUND: The best approach to reduce congenital cytomegalovirus infection (cCMVi) is to practice behaviors that reduce cytomegalovirus (CMV) transmission during pregnancy. Expanding awareness and knowledge of CMV is expected to result in increased practice of preventative behaviors. To this end, it is necessary to understand current awareness and knowledge of CMV. METHODS: This web-based cross-sectional survey assessed the awareness and knowledge of cCMVi among pregnant women and the general public in Japan. Participants aged 20-45 years (pregnant and non-pregnant women, and men) were identified from a consumer panel. Study outcomes (all participants) included awareness of cCMVi and other congenital conditions. Among those aware of cCMVi, outcomes included knowledge of CMV transmission routes, long-term outcomes of cCMVi, and behaviors to prevent CMV transmission during pregnancy. Outcomes limited to pregnant women included the practice of preventative behaviors and opinion on how easy it is to implement these behaviors. The data of the pregnant group (pregnant at the time of the survey) were compared with those of the general group (non-pregnant women and men). RESULTS: There were 535 participants in the pregnant group and 571 in the general group. Awareness of cCMVi was generally low (pregnant, 16.1%; general, 10.2%). Pregnant participants were significantly more aware of most congenital conditions than those in the general group, including cCMVi (P = 0.004). Knowledge about CMV/cCMVi was limited; there were no significant differences between the two groups for 24 of the 26 knowledge questions. A small proportion (one third or less) of pregnant women practiced behaviors to prevent the transmission of CMV, though most (73.3-95.3%) pregnant women who were aware of cCMVi considered such behaviors easy to implement. CONCLUSIONS: Awareness and knowledge of CMV/cCMVi is low among pregnant women in Japan; the level of knowledge is similar to that among the general public. This needs to be improved. Most pregnant women considered behaviors to prevent CMV transmission easy to perform, which indicates that effectively educating pregnant women regarding the long-term outcomes of cCMVi, CMV transmission routes, and preventative behaviors will contribute to a reduced incidence of cCMVi. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000041260 .

Unexplained Late-Onset Hemolytic Jaundice Preceded by High Fetal Hemoglobin Level in an Extremely Low Birth Weight Infant.

BACKGROUND: Preterm infants sometimes have transient late-onset hemolytic jaundice; however, the etiology has yet to be determined. CASE PRESENTATION: In our case, fetal hemoglobin (HbF) level increased significantly to 100% at 23 days of age. Levels of methemoglobin and carboxyhemoglobin also increased to 2.9% and 3.5%, respectively, following the elevated HbF level. At 26 days, hemolytic jaundice developed. No abnormality of red blood cell membranes and enzyme activities was found. CONCLUSIONS: The etiology of late-onset hemolytic jaundice in preterm infants may associate with an impaired switching from HbF to adult hemoglobin (HbA) or reverse switching from HbA to HbF.

Heart-rate evaluation using fetal ultrasonic Doppler during neonatal resuscitation.

BACKGROUND: The objective of the present study was to verify the speed and accuracy of fetal ultrasonic Doppler (fetal Doppler) in measuring heart rate of newborns at rest, including preterm, low-birthweight infants, and its efficacy during neonatal resuscitation, including cases of neonatal asphyxia. METHODS: A three-lead electrocardiogram and fetal Doppler were used to measure resting heart rates in 100 newborns, including 48 preterm, low-birthweight infants, at 0 to 72 h after birth. Times to display heart rate were compared between electrocardiogram and fetal Doppler by the Bland-Altman analysis and Wilcoxon signed-rank test. The time required for the fetal Doppler to measure heart rate during neonatal resuscitation was also assessed. RESULTS: In 100 newborns, the mean error of the resting heart rate in 1,293 measurement points was 0.07 beats/min. To display the heart rate, the fetal Doppler required a median time of 5 s, and electrocardiogram required a median time of 10 s (P < 0.001). During neonatal resuscitation, the heart rate was measured within 10 s in 18 of 21 cases (86%) and displayed with a median time of 5 s; this was measured in all neonatal asphyxia cases (9/9, 100%). CONCLUSIONS: Fetal Doppler can measure heart rate in newborns accurately and rapidly and is useful for evaluating heart rate not only at rest but also during neonatal resuscitation, especially in asphyxia.

Fetal Sinus Bradycardia Is Associated with Congenital Hypothyroidism: An Infant with Ectopic Thyroid Tissue.

Hypothyroidism is rarely included in the differential diagnosis for fetal sinus bradycardia. We report an infant with congenital hypothyroidism caused by ectopic thyroid tissue, who showed antenatal bradycardia. The baseline fetal heart rate was 100-110 bpm at 30 weeks of gestation, and fetal echocardiography revealed sinus bradycardia but no cardiac anomalies. Maternal thyroid function was normal (thyroid-stimulating hormone [TSH] 2.03 µIU/ml, free T3 2.65 pg/ml, and free T4 0.99 ng/dl) when measured at 31 weeks of gestation. Her serum anti SS-A and SS-B antibodies, anti-thyroglobulin, and microsomal antibodies were negative. A male infant without cardiac anomalies was delivered at 35 weeks and 4 days of gestation and admitted for prematurity and respiratory distress syndrome. The infant's heart rate was 70-110 bpm (normal: 120-160 bpm) on admission. On 8 days of age, thyroid function tests revealed that the infant had severe hypothyroidism (TSH 903.3 µIU/ml, free T3 1.05 pg/ml, and free T4 0.26 ng/dl). The prolonged jaundice assumed to be due to hypothyroidism. Oral levothyroxine sodium hydrate (10 µg/kg/day) was immediately started on day 8. After the treatment, the heart rate was gradually increased to 130-140 bpm as the infant's thyroid function was improved (TSH 79.8 µIU/ml, free T3 2.95 pg/dl, and free T4 1.66 ng/dl on day 22). The infant was diagnosed ectopic thyroid tissue because of the high thyroglobulin level (85.9 µg/l). In conclusion, congenital hypothyroidism should be included in the differential diagnosis in cases of fetal bradycardia without cardiac anomalies or maternal autoimmune diseases.

Metabolomic profiles of preterm small-for-gestational age infants.

We aimed to characterize the metabolomic profiles in preterm small-for-gestational age (SGA) infants using cord blood. We conducted a gestational age (GA)-matched case-control study that included 30 preterm infants who were categorized into two groups: SGA infants, with a birth weight (BW) < 10th percentile for GA (n = 15) and non-SGA infants, with BW ≥ 10th percentile for GA (n = 15). SGA infants with chromosomal or genetic abnormalities were excluded. At birth, the umbilicus was double-clamped, and the cord blood was sampled from the umbilical vein. Metabolomic analyses were performed using capillary electrophoresis time-of-flight mass spectrometry. The median GA at birth was not significantly different between the two groups [SGA, 32 (26-36) weeks; non-SGA, 32 (25-35) weeks; p = 0.661)]. Of the 255 metabolites analyzed, 19 (7.5%) showed significant differences between SGA and non-SGA infants. There were significant reductions in the carnosine, hypotaurine, and S-methylcysteine levels in SGA infants as compared to non-SGA infants (p < 0.05). Carnosine was correlated with gestational age, BMI before pregnancy, body weight gain during pregnancy (p = 0.002, p = 0.023, and p = 0.020, respectively). In conclusion, preterm SGA infants have low levels of cord blood antioxidative- and antiglycation-related metabolites, making them vulnerable to oxidative stress.

Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection in Japan 2023: Executive Summary.

Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in developed countries. Although a standard therapy has not yet been established, evidence for the management of cCMV infection has been accumulating. The first edition of the "Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection" was published in Japan in 2023. This summary outlines the clinical questions (CQs) in the guidelines, with reference to the Japanese Medical Information Distribution Service Manual. Overall, 20 CQs with statements regarding prenatal risk assessment, prevention and management at diagnosis (CQs 1-1-1-3), diagnosis (CQs 2-1-2-6), treatment (CQs 3-1-3-7) and follow-up requirements (CQs 4-1-4-4) have been discussed. For each statement, the levels of recommendation, evidence and consensus rates were determined. These guidelines will assist in the management of patients with cCMV infection.

The gaze characteristics in preterm children: The appropriate timing for an eye-tracking tool.

BACKGROUND: An objective screening tool for autism spectrum disorder (ASD), also known as an eye-tracking tool, assesses the patient's abnormal gaze patterns and detects the risk of ASD. As this tool is generally used for children born at term, this study aimed to clarify the appropriate timing for using the tool for preterm children, factors that influence the timing, and evaluate their gaze characteristics using the Gazefinder®. METHOD: In 90 preterm children, a total of 125 eye-tracking tasks were completed and analyzed in 3-6, 7-9, 10-12, 13-18, and 19-32 months of corrected age (CA). The Gazefinder® was used to compare the mean fixation time percentage (MFP) in each CA and evaluate the gaze patterns. Perinatal factors associated with low MFP were also analyzed. RESULTS: Only 50% of the children scored ≥70% MFP at 3-6 months of CA. The MFP increased significantly after 7 months of CA (p = 0.0003), reached 90% at 13-18 months, and 100% at 19-32 months of CA. Chronic lung disease (CLD) was a clinical factor associated with low MFP (p = 0.036). Preterm children gazed more at eyes but gazed at mouths when the mouth moved. CONCLUSION: It is necessary for preterm children to begin using Gazefinder® atleast at ≥13 months of age, especially those complicated with CLD. Preterm children prefer gazing at social information just as typically developing children.

Association of umbilical cord insulin-like growth factor 1 levels with severe retinopathy in extremely preterm infants.

BACKGROUND: The association between umbilical cord blood insulin-like growth factor 1 (IGF-1) levels and retinopathy of prematurity (ROP) remains unclear. This study aimed to investigate whether umbilical cord blood IGF-1 levels can predict the development of severe ROP in extremely preterm infants. METHODS: This hospital-based retrospective cohort study included infants born at <37 weeks gestational age (GA) between 2019 and 2021 and then classified them into the two GA groups: extremely preterm, <28 weeks and preterm infants, 28-36 weeks. Extremely preterm infants were further subclassified into two groups according to the laser treatment as follows: the severe ROP (ROP-Tx) and ROP (No ROP-Tx) groups. Median umbilical cord blood IGF-1 values were compared between the groups. Perinatal risk factors were identified by univariate and multivariate analyses. Finally, umbilical cord IGF-1 cut-off values requiring ROP treatment with laser were determined by receiver operating characteristic (ROC) curve analyses. RESULTS: A total of 205 infants were enrolled, with 32 being extremely preterm (ROP-Tx: n = 11; No ROP-Tx: n = 21) and 173 being preterm. IGF-1 levels were significantly lower in extremely preterm (13.5 ng/mL) than preterm infants (36 ng/mL, p < 0.001). In extremely preterm infants, IGF-1 levels were significantly lower in the ROP-Tx group than the No ROP-Tx group (10 vs. 19 ng/mL, respectively, p = 0.024). Only GA, umbilical cord blood IGF-1 levels, birth head circumference, and birth chest circumference were identified as risk factors by univariate analysis (p < 0.05). Multivariate analysis showed that only umbilical cord blood IGF-1 was an independent risk factor (odds ratio: 1.26, p = 0.021). ROC curves revealed an IGF-1 cut-off value of 14 ng/mL. CONCLUSION: The need of laser treatment for ROP was found to be associated with low umbilical cord blood IGF-1 levels in extremely preterm infants. Umbilical cord blood IGF-1 can be used as a biomarker for the risk of developing severe ROP.

Procalcitonin-Based Antibiotic Use for Neonatal Early-Onset Bacterial Infections: Pre- and Post-Intervention Clinical Study.

We previously reported the 95th percentile cutoff value of the serum procalcitonin (PCT) reference curve for diagnosing early-onset bacterial infection. We aimed to verify the effectivity of these novel diagnostic criteria by comparing antibiotic use and incidence of early-onset bacterial infection between pre- and post-introduction periods. We included newborns admitted to our neonatal intensive care unit who underwent blood tests within 72 h after birth between 2018 and 2022. The neonates were divided into the pre-intervention (admitted before the introduction, n = 737) or post-intervention (admitted after the introduction, n = 686) group. The days of antibiotics therapy (DOT) per 1000 patient days up to 6 days after birth, percentage of antibiotic use, and incidence of early-onset bacterial infection were compared between the groups. The post-intervention group had significantly lower DOT per 1000 patient days (82.0 days vs. 211.3 days, p < 0.01) and percentage of newborns receiving antibiotics compared with the pre-intervention group (79 (12%) vs. 280 (38%), respectively, p < 0.01). The incidence of early-onset bacterial infections did not differ between the groups (2% each, p = 0.99). In conclusion, our diagnostic criteria using the 95th percentile cutoff value of the serum PCT reference curve for early-onset bacterial infection were proven safe and effective, promoting appropriate use of antibiotics.

Clinical factors associated with extended hospitalization in pediatric patients ≥3 years of age with respiratory syncytial virus or human metapneumovirus infection: A Japanese single-center, retrospective study.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections are common in children worldwide. However, the clinical factors related to extended hospitalization in Japanese patients aged ≥3 years remain elusive. We aimed to elucidate the clinical risk factors contributing to hospital stays ≥7 days in patients with RSV and hMPV infections. Patients ≥3 years of age who were hospitalized due to RSV or hMPV infection between 2014 to 2020 were included. Twenty-one RSV- and 27 hMPV-infected patients were enrolled. Patients were divided into 2 groups: hospitalization for ≥ and <7 days. Univariate and multivariate analyses determined the clinical risk factors contributing to hospital stay ≥7 days. The RSV- and hMPV-infected patients had similar clinical characteristics. The clinical risk factors contributing to extended hospitalization were analyzed in the 48 infected patients of the 2 groups. The presence of prophylactic antibiotics usage, co-bacterial colonization, and underlying diseases were extracted by univariate analysis (P < .05). In multivariate analysis, underlying diseases were determined as an independent clinical risk factor (odds ratio 8.09, P = .005). Underlying diseases contributed to extended hospitalization in RSV- or hMPV-infected patients ≥3 years of age.

Changes in Cranial Shape and Developmental Quotient at 6 Months of Age in Preterm Infants.

The purpose of this study was to investigate changes in cranial shape among preterm neonates aged 1-6 months and the relationship between developmental quotient (DQ) and cranial shape at 6 months of age. Preterm infants who were hospitalized in our hospital were prospectively followed for 6 months. The cephalic index (CI) and cranial vault asymmetry index (CVAI) were evaluated at 1 (T1), 3 (T2), and 6 months (T3) of age and compared with those of the full-term infants. The relationship between CI or CVAI and DQ at T3 was analyzed using the Enjoji Scale of Infant Analytical Development. A total of 26 participants born at 34.7 ± 1.9 weeks of gestation were included. The CI increased with age (T1: 77.2%, T2: 82.9%, T3: 85.4%, p < 0.01). The prevalence of dolichocephaly at T3 did not significantly differ from that in full-term infants (15.4% vs. 4.5%, p = 0.08). CVAI did not significantly differ between preterm and full-term infants. The DQ showed no significant correlation with either the CI or CVAI (correlation coefficients: 0.23 for CI, -0.01; CVAI). Dolichocephaly improved over time in preterm infants and no relationship between cranial shape and development was observed in preterm infants at 6 months of age.

Correction: Go et al. Diagnostic Accuracy of Biomarkers for Early-Onset Neonatal Bacterial Infections: Evaluation of Serum Procalcitonin Reference Curves. Diagnostics 2020, 10, 839.

In the original publication [...].

Restriction of SARS-CoV-2 replication in the human placenta.

Although SARS-CoV-2 can infect human placental tissue, vertical transmission is rare. Therefore, the placenta may function as a barrier to inhibit viral transmission to the foetus, though the mechanisms remain unclear. In this study, we confirmed the presence of the SARS-CoV-2 genome in human placental tissue by in situ hybridization with antisense probes targeting the spike protein; tissue staining was much lower when using sense probes for the spike protein. To the best of our knowledge, this is the first evidence directly indicating inefficient viral replication in the SARS-CoV-2-infected placenta. Additional studies are required to reveal the detailed mechanisms.

Survey of physician knowledge of congenital cytomegalovirus infection and clinical practices in Japan: A web-based survey.

ABSTRACT: Congenital cytomegalovirus infection (cCMVi) can cause serious and long-term effects in newborns. Without available vaccines or antiviral prophylaxis, prevention strategies for cCMVi and cytomegalovirus disease during pregnancy are limited to hygiene and behavioral interventions to prevent transmission. The objective of this study was to assess cCMVi-related awareness, knowledge, and physicians' actual and preferred clinical practices in Japan. This web-based cross-sectional survey was conducted using online panels. Survey invitations were sent by email to physicians (pediatricians, obstetricians, otolaryngologists, and internists). Participants were asked about their awareness of congenital conditions, including cCMVi. Participants who were aware of cCMVi were then asked additional questions related to the study objectives. Participants included 292 pediatricians, 245 obstetricians, 245 otolaryngologists, and 279 internists. Awareness of cCMVi was generally high (69.2%-97.6%). Pediatricians and obstetricians were most knowledgeable about cCMVi; however, responses to specific questions such as those pertaining to risk factors, patient counseling, and clinical management of cCMVi varied. For example, correct identification of potential cytomegalovirus transmission routes among pediatricians ranged from 36.8% to 65.6%. Survey results showed a discrepancy between responses when physicians were asked about their actual and preferred clinical practices to manage cCMVi. For example, although around 90% of obstetricians and pediatricians considered it preferred practice to educate pregnant women about cCMVi, only 60.1% of obstetricians reported being able to actually do so in current practice.This survey revealed that knowledge about cCMVi among Japanese physicians could be improved and identified variability in clinical practice.