Early changes in S100B maternal blood levels can predict fetal intrauterine growth restriction.

OBJECTIVES: Intrauterine growth restriction (IUGR) represents one of the main causes of perinatal mortality and morbidity. Nowadays, IUGR early diagnosis is mandatory in order to limit the occurrence of multiorgan failure, especially the brain. Therefore, we investigated whether longitudinal S100B assessment in maternal blood could be a trustable predictor of IUGR. METHODS: We conducted a prospective study in 480 pregnancies (IUGR: n=40; small for gestational age, SGA: n=40; controls: n=400) in whom S100B was measured at three predetermined monitoring time-points (T1: 8-18 GA; T2: 19-23 GA; T3: 24-28 GA). RESULTS: Lower S100B in IUGR fetuses than SGA and controls (p<0.05, for all) at T1-T3. Receiver operating characteristic curve showed that S100B at T1 was the best predictor of IUGR (sensitivity: 100 %; specificity: 81.4 %) than T2, T3. CONCLUSIONS: The early lower S100B concentration in pregnant women lately complicated by IUGR support the notion that non-invasive early IUGR diagnosis and monitoring is becoming feasible. Results open the way to further studies aimed at diagnosing and monitoring fetal/maternal diseases at earliest time.

Co-Occurrence of a Pathogenic HSD3B2 Variant and a Duplication on 10q22.3-q23.2 Detected in Newborn Twins with Salt-Wasting Congenital Adrenal Hyperplasia.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by enzyme deficiencies required for cortisol biosynthesis in the adrenal cortex. The majority of CAH are due to the deficiency of the 21-hydroxylase enzyme, while 3ß-hydroxysteroid dehydrogenase type 2 deficiency accounts for less than five percent of all CAH cases. We report two Moroccan twins from a spontaneous triplet pregnancy. The 46,XY newborn exhibited a disorder of sexual differentiation (DSD) with hypo virilization, while the 46,XX newborn had normal female external genitalia. In the first week of life, they showed hyponatremia and primary adrenal insufficiency with a slight 17OHP elevation and increased DHEAS and renin levels. The aCGH-SNP analysis disclosed a 8.36 Mb long contiguous stretch of homozygosity (LCSH) on chromosome 1p13.2-p11.2 including the candidate HSD3B2 gene, a LCSH of 7.3 Mb on 14q31.1-q32.11, and a 7 Mb duplication on 10q22.3-q23.2. Clinical exome sequencing revealed the biallelic c.969T > G (p.Asn323Lys) HSD3B2, likely pathogenic, variant in both of the affected twins. This case emphasizes the importance of a prompt molecular diagnosis performed through the combination of aCGH and clinical exome, both for establishment of correct therapy and for follow-up, as the newborns also carry a genomic rearrangement with possible clinical implications.

Perinatal asphyxia partly affects presepsin urine levels in non-infected term infants.

OBJECTIVES: Standard of care sepsis biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) can be affected by several perinatal factors, among which perinatal asphyxia (PA) has a significant role. In this light, new early sepsis biomarkers such as presepsin (P-SEP) are needed to enact therapeutic strategies at a stage when clinical and laboratory patterns are still silent or unavailable. We aimed at investigating the potential effects of PA on longitudinal P-SEP urine levels. METHODS: We conducted an observational case-control study in 76 term infants, 38 with PA and 38 controls. Standard clinical, laboratory, radiological monitoring procedures and P-SEP urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. RESULTS: Higher (p<0.05) CRP and PCT blood levels at T1-T3 were observed in PA than control infants whilst no differences (p>0.05, for all) at T0 were observed between groups. P-SEP urine levels were higher (p<0.05) in PA at first void and at 24 h while no differences (p>0.05) at 48 and 96 h were observed. No significant correlations were found (p>0.05) between P-SEP and urea (R=0.11) and creatinine (R=0.02) blood levels, respectively. CONCLUSIONS: The present results, showed that PA effects on P-SEP were limited up to the first 24 h following birth in absence of any kidney function bias. Data open the way to further investigations aimed at validating P-SEP assessment in non-invasive biological fluids as a reliable tool for early EOS and LOS detection in high-risk infants.

S100B Maternal Blood Levels in Gestational Diabetes Mellitus Are Birthweight, Gender and Delivery Mode Dependent.

Gestational Diabetes Mellitus (GDM) is one of the main causes of perinatal mortality/morbidity. Today, a parameter offering useful information on fetal central nervous system (CNS) development/damage is eagerly awaited. We investigated the role of brain-protein S100B in the maternal blood of GDM pregnancies by means of a prospective case-control study in 646 pregnancies (GDM: n = 106; controls: n = 530). Maternal blood samples for S100B measurement were collected at four monitoring time-points from 24 weeks of gestation to term. Data was corrected for gender and delivery mode and correlated with gestational age and weight at birth. Results showed higher (p < 0.05) S100B from 24 to 32 weeks and at term in GDM fetuses than controls. Higher (p < 0.05) S100B was observed in GDM male new-borns than in females from 24 to 32 weeks and at term, in GDM cases delivering vaginally than by caesarean section. Finally, S100B positively correlated with gestational age and weight at birth (R = 0.27; R = 0.37, respectively; p < 0.01). The present findings show the usefulness of S100B in CNS to monitor high-risk pregnancies during perinatal standard-of-care procedures. The results suggest that further investigations into its potential role as an early marker of CNS growth/damage in GDM population are needed.

S100B in cardiac surgery brain monitoring: friend or foe?

Recent advances in perioperative management of adult and pediatric patients requiring open heart surgery (OHS) and cardiopulmonary bypass (CPB) for cardiac and/or congenital heart diseases repair allowed a significant reduction in the mortality rate. Conversely morbidity rate pattern has a flat trend. Perioperative period is crucial since OHS and CPB are widely accepted as a deliberate hypoxic-ischemic reperfusion damage representing the cost to pay at a time when standard of care monitoring procedures can be silent or unavailable. In this respect, the measurement of neuro-biomarkers (NB), able to detect at early stage perioperative brain damage could be especially useful. In the last decade, among a series of NB, S100B protein has been investigated. After the first promising results, supporting the usefulness of the protein as predictor of short/long term adverse neurological outcome, the protein has been progressively abandoned due to a series of limitations. In the present review we offer an up-dated overview of the main S100B pros and cons in the peri-operative monitoring of adult and pediatric patients.

High-Fidelity simulation-based program improves flow state scale in the perinatal team.

BACKGROUND: We aimed to evaluate the degree of realism and involvement, stress management and awareness of performance improvement in practitioners taking part in high fidelity simulation (HFS) training program for delivery room (DR) management, by means of a self-report test such as flow state scale (FSS). METHODS: This is an observational pretest-test study. Between March 2016 and May 2019, fourty-three practitioners (physicians, midwives, nurses) grouped in multidisciplinary teams were admitted to our training High Fidelity Simulation center. In a time-period of 1 month, practitioners attended two HFS courses (model 1, 2) focusing on DR management and resuscitation maneuvers. FSS test was administred at the end of M1 and M2 course, respectively. RESULTS: FSS scale items such as unambiguous feed-back, loss of self consciousness and loss of time reality, merging of action and awareness significantly improved (P < 0.05, for all) between M1 and M2. CONCLUSIONS: The present results showing the high level of practitioner involvement during DR management-based HFS courses support the usefulness of HFS as a trustworthy tool for improving the awareness of practitioner performances and feed-back. The data open the way to the usefulness of FSS as a trustworthy tool for the evaluation of the efficacy of training programs in a multidisciplinary team.

Determinants of exhaled nitric oxide levels (FeNO) in childhood atopic asthma: evidence for neonatal respiratory distress as a factor associated with low FeNO levels.

BACKGROUND: In allergic asthmatic children exhaled nitric oxide (FeNO) levels are related to eosinophilic inflammation by correlation analysis. Whether FeNO can be modified by factors potentially influencing the natural history of asthma in early life is not known. OBJECTIVE: To evaluate the frequency of anamnestic factors influencing the natural history of asthma and to identify potential determinants for elevated or low FeNO levels by multivariate analysis. METHODS: One hundred seventy-one children with mild-moderate asthma were stratified according to their FeNO levels into three groups: low (<20 ppb), mid (20-40 ppb), and high (>40 ppb). The frequency of nine anamnestic factors together with indices of allergic sensitization (total and allergen-specific immunoglobulin E [IgE], blood eosinophil counts) and of airflow limitation (forced expiratory volume in one second [FEV(1)]% predicted) were evaluated. Results. Among factors related to the patient history, neonatal respiratory distress was reported only in children with low FeNO levels, whereas this factor was never reported in children with mid-to-high FeNO levels (p = .008). As compared with low FeNO group, mid and high FeNO groups showed higher eosinophil counts and a tendency to have lower FEV(1) values. By multivariate analysis, four factors (eosinophils >300 cells/mm(3), cat-specific IgE, house dust mites [HDM]-specific IgE, FEV(1) ≤ 86% predicted) turned out to be significantly associated with mid-high FeNO levels and two factors (eosinophils >600 cells/mm(3), total IgE >355 kU/L) with high FeNO levels. CONCLUSIONS: Besides confirming the well-known tight association between blood eosinophilia and/or allergic sensitization and FeNO, these data provide new evidence for neonatal respiratory distress as potential factor associated with low FeNO levels in childhood atopic asthma.