The Diagnostic Yield of Chromosomal Microarray Analysis in Third-Trimester Fetal Abnormalities.

OBJECTIVE: This study aimed to determine the diagnostic yield of chromosomal microarray analysis (CMA) performed in cases of fetal abnormalities detected during the third trimester of pregnancy. STUDY DESIGN: A retrospective review of medical records was conducted for women who underwent amniocentesis at or beyond 28 weeks of gestation between January 2017 and February 2023. CMA results of pregnancies with abnormal sonographic findings not detected before 28 weeks were included. RESULTS: A total of 482 fetuses met the inclusion criteria. The average maternal age was 31.3 years, and the average gestational age at amniocentesis was 32.3 weeks. The overall diagnostic yield of CMA was 6.2% (30 clinically significant copy number variations [CNVs]). The yield was 16.4% in cases with two or more fetal malformations, while cases with a single anomaly revealed a diagnostic yield of 7.3%. Cases presenting isolated polyhydramnios or isolated fetal growth restriction had a lower yield of 9.3 and 5.4%, respectively. Of the 30 clinically significant cases, 19 (or 63.4%) exhibited recurrent CNVs. The remaining 11 cases (or 36.6%) presented unique CNVs. The theoretical yield of Noninvasive Prenatal Testing (NIPT) in our cohort is 2% for aneuploidy, which implies that it could potentially miss up to 70% of the significant findings that could be identified by CMA. In 80% of the fetuses (or 24 out of 30) with clinically significant CNVs, the structural abnormalities detected on fetal ultrasound examinations corresponded with the CMA results. CONCLUSION: The 6.2% detection rate of significant CNVs in late-onset fetal anomalies confirms the value of CMA in third-trimester amniocentesis. The findings underscore the necessity of CMA for detecting CNVs potentially overlooked by NIPT and emphasize the importance of thorough genetic counseling. KEY POINTS: · CMA yields 6.2% for third-trimester anomalies.. · NIPT may miss 70% of CMA findings.. · Ultrasound matched 80% of CMA results..

Exploring inheritance, and clinical penetrance of distal Xq28 duplication syndrome: insights from 47 new unpublished cases.

BACKGROUND: Distal Xq28 duplication, or int22h1/int22h2-mediated Xq28 duplication syndrome, leads to cognitive impairment, neurobehavioral issues, and facial dysmorphisms. Existing literature has limited information on clinical traits and penetrance. METHODS: We identified cases of distal Xq28 duplication (chrX: 154,126,575-154,709,680, GRCh37/hg19) through a review of clinical records and microarray reports from five centers, encompassing both postnatal and prenatal cases, with no prior family knowledge of the duplication. RESULTS: Our search found 47 cases across 26 families, with duplications ranging from 208 to 935 Kb. In total, 8 out of 26 index cases featured a 200-300 kb partial duplication, mainly from Armenian/Caucasian Jewish backgrounds. Most prenatal cases showed no major fetal ultrasound malformations. Of cases with known inheritance mode (15 out of 26), maternal inheritance was more common (80%). The study identified seven male carriers of the duplication from six unrelated families, indicating partial penetrance in males. CONCLUSION: Our study provides key insights into distal Xq28 duplication. Most prenatal tests showed no major fetal ultrasound issues. Maternal inheritance was common, with unaffected mothers. In the postnatal group, a balanced gender distribution was observed. Among male family members, two fathers had ADHD, one was healthy, and one brother had mild symptoms, indicating partial penetrance in males.

Congenital diaphragmatic hernia: quality improvement using a maximal lung protection strategy and early surgery-improved survival.

To evaluate the effectiveness of a novel protocol, adopted in our institution, as a quality improvement project for congenital diaphragmatic hernia (CDH). A maximal lung protection (MLP) protocol was implemented in 2019. This strategy included immediate use of high-frequency oscillatory ventilation (HFOV) after birth, during the stay at the Neonatal Intensive Care Unit (NICU), and during surgical repair. HFOV strategy included low distending pressures and higher frequencies (15 Hz) with subsequent lower tidal volumes. Surgical repair was performed early, within 24 h of birth, if possible. A retrospective study of all inborn neonates prenatally diagnosed with CDH and without major associated anomalies was performed at the NICU of Schneider Children's Medical Center of Israel between 2009 and 2022. Survival rates and pulmonary outcomes of neonates managed with MLP were compared to the historical standard care cohort. Thirty-three neonates were managed with the MLP protocol vs. 39 neonates that were not. Major adverse outcomes decreased including death rate from 46 to 18% (p = 0.012), extracorporeal membrane oxygenation from 39 to 0% (p < 0.001), and pneumothorax from 18 to 0% (p = 0.013). CONCLUSION:  MLP with early surgery significantly improved survival and additional adverse outcomes of neonates with CDH. Prospective randomized studies are necessary to confirm the findings of the current study. WHAT IS KNOWN: • Ventilator-induced lung injury was reported as the main cause of mortality in neonates with congenital diaphragmatic hernia (CDH). • Conventional ventilation is recommended by the European CDH consortium as the first-line ventilation modality; timing of surgery is controversial. WHAT IS NEW: • A maximal lung protection strategy based on 15-Hz high-frequency oscillatory ventilation with low distending pressures as initial modality and early surgery significantly reduced mortality and other outcomes.

Overestimation of Oxygen Saturation Measured by Pulse Oximetry in Hypoxemia. Part 1: Effect of Optical Pathlengths-Ratio Increase.

On average, arterial oxygen saturation measured by pulse oximetry (SpO2) is higher in hypoxemia than the true oxygen saturation measured invasively (SaO2), thereby increasing the risk of occult hypoxemia. In the current article, measurements of SpO2 on 17 cyanotic newborns were performed by means of a Nellcor pulse oximeter (POx), based on light with two wavelengths in the red and infrared regions (660 and 900 nm), and by means of a novel POx, based on two wavelengths in the infrared region (761 and 820 nm). The SpO2 readings from the two POxs showed higher values than the invasive SaO2 readings, and the disparity increased with decreasing SaO2. SpO2 measured using the two infrared wavelengths showed better correlation with SaO2 than SpO2 measured using the red and infrared wavelengths. After appropriate calibration, the standard deviation of the individual SpO2-SaO2 differences for the two-infrared POx was smaller (3.6%) than that for the red and infrared POx (6.5%, p < 0.05). The overestimation of SpO2 readings in hypoxemia was explained by the increase in hypoxemia of the optical pathlengths-ratio between the two wavelengths. The two-infrared POx can reduce the overestimation of SpO2 measurement in hypoxemia and the consequent risk of occult hypoxemia, owing to its smaller increase in pathlengths-ratio in hypoxemia.

The association of neonatal SARS-CoV-2 anti-spike protein receptor-binding domain antibodies at delivery with infant SARS-CoV-2 infection under the age of 6 months: a prospective cohort study.

OBJECTIVES: The aim of this study was to assess the association between neonatal SARS-CoV-2 antibody level at delivery and infant SARS-CoV-2 infection under the age of 6 months and to identify predictive factors for neonatal antibody level at delivery. METHODS: In a prospective observational study, conducted between September 2021 and mid-February 2022, cord blood sera were tested for SARS-CoV-2 anti-spike receptor-binding domain antibodies after maternal BNT162b2 vaccination or infection. Infants were followed up for 6 months for SARS-CoV-2 infection. RESULTS: Sixty-seven mother-infant dyads were enrolled; nine of those did not meet the eligibility criteria. Of the 58 mother-infant dyads included, 6-month follow-up data were available for 57 mother-infant dyads. The mean ± standard deviation log SARS-CoV-2 anti-spike antibody level at delivery was lower among infants who were COVID-19 positive versus negative during follow-up (3.41 ± 0.74 AU/mL, n = 12; vs. 3.87 ± 0.84 AU/mL, n = 46; p 0.036); a log titre of ≥4.07 AU/mL (11 750) at delivery was associated with a significantly lower likelihood of infant infection (1/26 vs. 11/32 in infants with antibody level of <4.07 log AU/mL, OR = 0.076 [95% CI, 0.076, 0.64], p 0.018). A spline curve model showed a linear decrease in antibody levels when the last dose was administered at ≤30 weeks of gestation (50 days before delivery), after which the antibody levels increased (R2 = 0.50). In multivariate analysis, more vaccine doses, prior maternal infection, and last administered dose at ≥31 weeks of gestation were associated with higher antibody levels at delivery. DISCUSSION: Higher anti-spike antibodies at delivery were associated with decreased risk of COVID-19 at the age of <6 months; the antibody level decreased linearly when the last dose was administered at ≤30 weeks of gestation. Future research should assess the effectiveness of a second booster during pregnancy against infant infection.

Headache in Pediatric and Adolescent Patients With Chronic Kidney Disease and After Kidney Transplantation: A Comparative Study.

AIM: This study compared prevalence and characteristics of headaches between pediatric patients with chronic kidney disease and pediatric patients with transplanted kidneys and identify factors associated with headaches in the entire cohort. METHODS: We interviewed 87 children and adolescents with either chronic kidney disease or transplanted kidney, regarding the prevalence of headaches and their characteristics. We reviewed hospital charts for medical history and blood test. RESULTS: Twenty-two patients (25.3%) reported experiencing headaches, of them 15 (68%) had migraine. The prevalence was greater among those with chronic kidney disease than among those after kidney transplant: 36.6% vs 15.2%, P = .03. Headache, mostly migraine, was associated with lower glomerular filtration and higher phosphate level. CONCLUSIONS: In a pediatric population, headaches were less prevalent among patients after kidney transplantation than among patients with chronic kidney disease. The lower headache rate after kidney transplantation may be related to improvement in homeostasis and electrolyte balance.

[UNILATERAL MULTI-CYSTIC LUNG DISEASE IN A PRETERM INFANT].

INTRODUCTION: Cystic diseases of the lung are a rare spectrum of anomalies, commonly diagnosed prenatally. We present a case of a newborn twin, born at 29 weeks gestational. The infant was diagnosed with respiratory distress syndrome shortly after birth, treated with surfactant by the INSURE method (intubation, surfactant administration, extubation) and required only short-term non-invasive ventilation. On the 40th day of life an extensive single lung cystic disease was identified after respiratory deterioration occurred. The diagnostic approach is presented. The differential diagnosis of neonatal cystic lung disease includes congenital and acquired diseases. The most common cystic lesions presenting in the neonatal period include congenital pulmonary airway malformation (CPAM), pulmonary sequestration, bronchogenic cysts, congenital lobar emphysema and acquired lung damage resulting in cyst formation including pulmonary interstitial emphysema, damage secondary to infection disease. Follow-up showed gradual resolution of the cystic disease, supporting an acquired lung disease. The cystic lung disease may be due to barotrauma from non-invasive ventilation, unequal surfactant distribution, genetic susceptibility to the relatively mild barotrauma associated with non-invasive ventilation or a combination of these factors. The case report demonstrates that procedures considered "safe" such as non-invasive ventilation and surfactant administration may result in extensive lung damage.

Do Neonatal Infections Require a Positive Blood Culture?

Neonatal sepsis is a major cause of worldwide morbidity and mortality. Blood cultures are considered the gold standard for diagnosis, but results are often delayed for 24 to 48 hours, and sensitivity, although improved by modern techniques, such as automated blood cultures, is variable and affected by the bacterial load. For these reasons, empiric antibiotics are frequently administered to avoid potential devastating consequences of untreated sepsis. Unnecessary antibiotic treatment has been associated with increased mortality and other adverse outcomes; therefore, antibiotics should be discontinued as soon as sepsis has been ruled out. Negative cultures pose a challenge to clinicians, who must distinguish between real sepsis and sepsis-like conditions (noninfectious or viral) which do not require antibiotics. Focal infections with negative blood cultures do require antibiotic treatment. Ultra-low bacteremia, primary or secondary to recent antibiotic exposure, is often associated with negative cultures, and some consider a short course of empiric antibiotics sufficient for clearing of bacteremia. Biomarkers and molecular methods based on polymerase chain reaction are important add-ons to clinical signs or symptoms for establishing the diagnosis of sepsis. Other promising future potential adjuvants are metabolomics. Antibiotic stewardship should be implemented to avoid or discontinue unnecessary treatment. Prevention of infection still remains the most important step for dealing with neonatal sepsis. KEY POINTS: · Blood cultures are the gold standard diagnosis of neonatal sepsis but sometimes may be negative.. · Other bacterial, viral, and noninfectious conditions may mimic sepsis, prompting initiation of empiric antibiotic treatments.. · Since a definition of neonatal sepsis is lacking, recognizing real septic episodes may be challenging..