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Exposure to synthetic and natural chemicals is a major environmental risk factor in the etiology of many chronic diseases. Investigating complex co-exposures is necessary for a holistic assessment in exposome-wide association studies. In this work, a sensitive liquid chromatography-tandem mass spectrometry approach was developed and validated. The assay enables the analysis of more than 80 highly-diverse xenobiotics in urine, serum/plasma, and breast milk; with detection limits generally in the pg-ng mL −1 range. In plasma of extremely-premature infants, 27 xenobiotics are identified; including contamination with plasticizers, perfluorinated alkylated substances and parabens. In breast milk samples collected longitudinally over the first 211 days post-partum, 29 analytes are detected, including pyrrolizidine- and tropane alkaloids which have not been identified in this matrix before. A preliminary estimation of daily toxicant intake via breast milk is conducted. In conclusion, we observe significant early-life co-exposure to multiple toxicants, and demonstrate the method’s applicability for large-scale exposomics-type cohort studies. Exposure to synthetic and natural toxicants is a major risk factor in the etiology of disease. Here, authors describe the development of a method to quantify >80 xenobiotics and apply it to assess early-life exposure in vulnerable infants.

To determine the effect of different types of probes for lung ultrasound in neonates. Prospective, blinded, randomized, comparative study between 2020 and 2022. Single-center study at a third level neonatal unit. Hemodynamically stable infants with either nasal continuous positive airway pressure, high flow nasal cannula or without respiratory support. Lung ultrasound using either an echo or microconvex probe. As control, the linear probe was used. Primary outcome measure was neonatologist performed lung ultrasound (NPLUS) score. Secondary outcome measures were number of B-Lines, thickness of the pleural line and subjective image quality. Furthermore, correlation between NPLUS results and clinical data was assessed. A total of 1584 video loops from 66 patients, with a mean corrected gestational age of 33.8 weeks (SD 4.23) and weight of 1950g (SD 910), respectively, were analyzed. NPLUS score was estimated lower with the echo- and microconvex probe compared to the linear probe, with a coefficient of -2.95 (p < 0.001) and -1.09 (p = 0.19), respectively. Correlation between the pulse oximetric saturation/fraction of inspired oxygen ratio and NPLUS score was moderately strong and best using the microconvex probe (Spearman's rho = -0.63, p<0.001). Our results not only confirm the current recommendations, but also demonstrate the extent of the varying results when different probes are used. The differences we discovered call for caution in interpreting scores, especially in the context of guiding therapies and communicating prognoses. Finally, the correlation between NPLUS score and clinical parameters contributes to validating the use of this diagnostic tool.

Assessing pain in newborns in the NICU is crucial due to their frequent exposure to painful stimuli, yet it's challenging due to the subjective nature of current methods. This study aimed to evaluate the effectiveness of an AI system designed for automatic facial recognition by comparing its performance with the expert opinion of health care provider. This is a secondary analysis from an eye-tracking study, assessing neonatal pain evaluations by healthcare professionals. The performance of AI software, FaceReader 9, was compared to experts' evaluations using a visual-analog scale, focusing on identifying specific facial action units associated with different pain levels. The study found significant differences in AI-generated metrics—arousal and valence—across three stimulus types: non-noxious thermal, short-noxious, and prolonged-noxious, with p -values below 0.001. A strong correlation (r = 0.84, p  ≤ .001) was observed between AI metrics and expert ratings. Eleven facial action units were identified as relevant to describe neonatal pain. The findings highlight the AI system's potential in accurately detecting and analyzing newborn facial expressions in response to varying pain intensities, demonstrating a significant correlation with healthcare professionals' assessments. This suggests that AI technology could enhance objective pain assessment in neonates.

Rationale Lung recruitment and continuous distending pressure (CDP) titration are critical for assuring the efficacy of high-frequency ventilation (HFOV) in preterm infants. The limitation of oxygenation (peripheral oxygen saturation, SpO 2 ) in optimizing CDP calls for evaluating other non-invasive bedside measurements. Respiratory reactance (Xrs) at 10 Hz measured by oscillometry reflects lung volume recruitment and tissue strain. In particular, lung volume recruitment and decreased tissue strain result in increased Xrs values. Objectives In extremely preterm infants treated with HFOV as first intention, we aimed to measure the relationship between CDP and Xrs during SpO 2 -driven CDP optimization. Methods In this prospective observational study, extremely preterm infants born before 28 weeks of gestation undergoing SpO 2 -guided lung recruitment maneuvers were included in the study. SpO 2 and Xrs were recorded at each CDP step. The optimal CDP identified by oxygenation (CDP Opt_SpO2 ) was compared to the CDP providing maximal Xrs on the deflation limb of the recruitment maneuver (CDP Xrs ). Results We studied 40 infants (gestational age at birth = 22 + 6 -27 + 5 wk; postnatal age = 1–23 days). Measurements were well tolerated and provided reliable results in 96% of cases. On average, Xrs decreased during the inflation limb and increased during the deflation limb. Xrs changes were heterogeneous among the infants for the amount of decrease with increasing CDP, the decrease at the lowest CDP of the deflation limb, and the hysteresis of the Xrs vs. CDP curve. In all but five infants, the hysteresis of the Xrs vs. CDP curve suggested effective lung recruitment. CDP Opt_SpO2 and CDP Xrs were highly correlated (ρ = 0.71, p < 0.001) and not statistically different (median difference [range] = -1 [-3; 9] cmH 2 O). However, CDP Xrs were equal to CDP Opt_SpO2 in only 6 infants, greater than CDP Opt_SpO2 in 10, and lower in 24 infants. Conclusions The Xrs changes described provide complementary information to oxygenation. Further investigation is warranted to refine recruitment maneuvers and CPD settings in preterm infants.

Diagnosis of neonatal sepsis remains a major challenge in neonatology. Most molecular-based methods are not customized for neonatal requirements. The aim of the present study was to assess the diagnostic accuracy of a modified multiplex PCR protocol for the detection of neonatal sepsis using small blood volumes. 212 episodes of suspected neonatal late onset sepsis were analyzed prospectively using the Roche SeptiFast® MGRADE PCR with a modified DNA extraction protocol and software-handling tool. Results were compared to blood culture, laboratory biomarkers and clinical signs of sepsis. Of 212 episodes, 85 (40.1%) were categorized as \"not infected\". Among these episodes, 1 was false positive by blood culture (1.2%) and 23 were false positive by PCR (27.1%). Of 51 (24.1%) episodes diagnosed as \"culture proven sepsis\", the same pathogen was detected by blood culture and PCR in 39 episodes (76.5%). In 8 episodes, more pathogens were detected by PCR compared to blood culture, and in 4 episodes the pathogen detected by blood culture was not found by PCR. One of these episodes was caused by Bacillus cereus, a pathogen not included in the PCR panel. In 76/212 (35.8%) episodes, clinical sepsis was diagnosed. Among these, PCR yielded positive results in 39.5% of episodes (30/76 episodes). For culture-positive sepsis, PCR showed a sensitivity of 90.2% (95%CI 86.2-94.2%) and a specificity of 72.9% (95%CI 67.0-79.0%). The Roche SeptiFast® MGRADE PCR using a modified DNA extraction protocol showed acceptable results for rapid detection of neonatal sepsis in addition to conventional blood culture. The benefit of rapid pathogen detection has to be balanced against the considerable risk of contamination, loss of information on antibiotic sensitivity pattern and increased costs.

Parents of very low birth weight (VLBW) infants in a neonatal intensive care unit experienced additional stress during the SARS-CoV-2 pandemic due to the related restrictions in hospital visiting policies. Our study aimed to compare parents' burdens before and during the pandemic. This survey included 121 parents of 76 VLBW infants in two European Level IV perinatal centers before and during the pandemic. We performed standardized parent questionnaires with mothers and fathers separately to evaluate their emotional stress and well-being. The pandemic worsened the emotional well-being of parents of VLBW infants, particularly of mothers. During the pandemic, mothers reported significantly higher state anxiety levels (48.9 vs. 42.9, p  = 0.026) and hampered bonding with the child (6.3 vs. 5.2, 0 = 0.003) than before. In addition, mothers felt more personally restricted than fathers (6.1 vs. 5.2, p  = 0.003). Fathers experienced lower levels of stress than mothers; they were equally burdened before and during the pandemic. Restrictions in visiting policies for families of VLBW infants during the SARS-CoV-2 pandemic have a significant negative impact on parental stress and should therefore be applied cautiously.

Background Providing optimal pain relief is a challenging task when caring for premature infants. The aim of this study was to compare the long-term cognitive, motor, and behavioral outcomes of preterm infants before and after the implementation of a pain and sedation protocol. In addition, we investigated whether the increased opiate administration resulting after the implementation process had an impact on these outcomes. Methods Cognitive outcomes were evaluated using the Kaufman Assessment Battery for Children (KABC), neuromotor examinations were based on Amiel-Tison, and behavioral outcomes were assessed using the parent-reported Child Behavior Checklist (CBCL). Results One hundred extremely preterm infants were included in the study (control group, n  = 53; intervention group, n  = 47). No significant differences were found in cognitive and motor outcomes at preschool age. However, every increase in the cumulative opiate exposure for each 100 mg/kg was weakly significantly associated with a higher risk for autism spectrum features (adjusted odds ratio (aOR) = 1.822, 95% confidence interval (CI) [1.231–2.697]; P  = 0.03) and withdrawn behavior (aOR = 1.822, 95% CI [1.231–2.697]; P  = 0.03) at preschool age. Conclusion Increased neonatal cumulative opiate exposure did not alter cognitive and motor outcomes but may represent a risk factor for autism spectrum and withdrawn behavior at preschool age. Impact The implementation of a protocol for the management of pain and sedation in preterm infants resulted in increased cumulative opiate exposure. Our study adds further evidence that increased neonatal opiate exposure did  not alter cognitive and motor outcomes but may yield a potential risk factor for autism spectrum disorders and withdrawn behavior at preschool age. A vigilant use of opiates is recommended. Further studies are needed looking for novel pain management strategies and drugs providing optimal pain relief with minimal neurotoxicity.

Infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in pregnancy are associated with the development of preeclampsia and fetal growth restriction (FGR). Recently, preeclampsia was linked to impaired maternal hemodynamic function. This retrospective study evaluated singleton pregnancies with COVID-19 during pregnancy and healthy pregnant controls matched for gestational age from November 2020 to March 2022. Non-invasive assessment of maternal hemodynamics by continuous wave Doppler ultrasound measurements (USCOM-1A® Monitor) and oscillometric arterial stiffness (Arteriograph) was performed. Overall, 69 pregnant women were included—23 women after COVID-19 during pregnancy and 46 healthy controls. While two women (8.7%) were admitted to the hospital due to COVID-19-related symptoms, none required intensive care unit admission or non-invasive/invasive ventilation. There were no statistically significant differences in the majority of hemodynamic parameters between the two cohorts. The prevalence of FGR was significantly higher in the COVID-19 during pregnancy group (9.5% vs. healthy controls: 0.0%; p = 0.036), especially in nulliparous women. No difference in angiogenic markers and neonatal outcomes were observed between pregnant women after COVID-19 and healthy controls. In conclusion, no significant differences in hemodynamic parameters or neonatal outcome were observed in women with COVID-19 during pregnancy. However, an increased prevalence of FGR could be described.

Parents' meaningful activities (occupations) and occupational balance are relevant to neonatal care. Valid and reliable self-reported measurement instruments are needed to assess parents' occupational balance and to evaluate occupational balance interventions in neonatal care. The aims of this study were to develop a self-reported questionnaire on occupational balance in informal caregivers (OBI-Care) and to examine its measurement properties including construct validity and internal consistency. A mixed method multicenter study design was employed. Items of the OBI-Care were created with parents of preterm infants based on qualitative research methods. Measurement properties were analyzed with quantitative data of parents of preterm infants. Construct validity was assessed by determining dimensionality, overall and item fit to a Rasch model, differential item functioning and threshold ordering. Internal consistency was examined by determining inter-item and item-total correlations, Cronbach's alpha and Rasch's person separation index. Fourteen parents participated in item creation. Measurement properties were explored in data of 304 parents. Twenty-two items, summarized in three subscales were compiled to the OBI-Care. Items showed an overall fit and except one item, an item fit to the Rasch model. There was no evidence of differential item functioning and all items displayed ordered thresholds. Each subscale had good values of person separation indices and Cronbach's alpha. The OBI-Care demonstrates construct validity and internal consistency and is thus a suitable measurement instrument to assess occupational balance of parents of preterm infants in neonatal care. OBI-Care is generic and can be applied in various health care settings.

The agreement between invasive and non-invasive blood pressure (BP) readings in the first days of life of preterm infants is contentiously debated. To compare mean, systolic and diastolic invasive (IBP) and non-invasive BP (NBP) readings obtained during routine care in the first four weeks of life of extremely preterm infants. We extracted pairs of IBP and NBP readings obtained from preterm infants born below 28 weeks of gestation from the local database. After exclusion of erroneous measurements, we investigated the repeated measures correlation and analyzed the agreement (bias) and precision adjusted for multiple measurements per individual. Among 335 pairs of IBP and NBP readings obtained from 128 patients, we found correlation coefficients >0.65 for mean, systolic and diastolic BP values. The bias for mean BP readings was -0.4 mmHg (SD 6.1), for systolic BP readings 6.2 mmHg (SD 8.1), and for diastolic BP readings -4.3 mmHg (SD 6.5). Overestimation of systolic IBP and underestimation of diastolic IBP by the non-invasive measurement were found both in the group with gestational age from 23 to 25.9 weeks and in the group with gestational age from 26 to 27.9 weeks. Systolic NBP readings tended to exceed invasive readings in the range <50 mmHg (bias 9.9 mmHg) whereas diastolic NBP readings were lower than invasive values particularly in the range >30 mmHg (bias -5.5 mmHg). The disagreement between invasive and non-invasive BP readings in infants extends to the first four weeks of life. Biases differ for mean, systolic and diastolic BP values. Our observation implies that they may depend on the range of the blood pressure. Awareness of these biases and preemptive concomitant use of IBP and NPB readings may contribute to reducing over- or under-treatment.