Meconium Aspiration Syndrome, Hypoxic-Ischemic Encephalopathy and Therapeutic Hypothermia-A Recipe for Severe Pulmonary Hypertension?

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality among term newborns globally. Infants born through meconium-stained amniotic fluid are at risk of developing meconium aspiration syndrome (MAS) and HIE. Simultaneous occurrence of MAS and HIE is a perilous combination for newborns due to the risk of persistent pulmonary hypertension of the newborn (PPHN). Moreover, therapeutic hypothermia (TH), which is the current standard of care for the management of HIE, may increase pulmonary vascular resistance (PVR) and worsen PPHN. Infants with MAS and HIE require close cardiorespiratory and hemodynamic monitoring for PPHN. Therapeutic strategies, including oxygen supplementation, ventilation, use of surfactant, inhaled nitric oxide and other pulmonary vasodilators, and systemic vasopressors, play a critical role in the management of PPHN in MAS, HIE, and TH. While TH reduces death or disability in infants with HIE, infants with MAS and HIE undergoing TH need close hemodynamic monitoring for PPHN.

Diagnosis and Management of Simple and Complicated Meconium Ileus in Cystic Fibrosis, a Systematic Review.

The early management of neonates with meconium ileus (MI) and cystic fibrosis (CF) is highly variable across countries and is not standardized. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The protocol was registered in PROSPERO (CRD42024522838). Studies from three providers of academic search engines were checked for inclusion criteria, using the following search terms: meconium ileus AND cystic fibrosis OR mucoviscidosis. Regarding the patient population studied, the inclusion criteria were defined using our predefined PICOT framework: studies on neonates with simple or complicated meconium which were confirmed to have cystic fibrosis and were conservatively managed or surgically treated. Results: A total of 566 publications from the last 10 years were verified by the authors of this review to find the most recent and relevant data, and only 8 met the inclusion criteria. Prenatally diagnosed meconium pseudocysts, bowel dilation, and ascites on ultrasound are predictors of neonatal surgery and risk factor for negative 12-month clinical outcomes in MI-CF newborns. For simple MI, conservative treatment with hypertonic solutions enemas can be effective in more than 25% of cases. If repeated enemas fail to disimpact the bowels, the Bishop-Koop stoma is a safe option. No comprehensive research has been conducted so far to determine the ideal surgical protocol for complicated MI. We only found three studies that reported the types of stomas performed and another study comparing the outcomes of patients depending on the surgical management; the conclusions are contradictory especially since the number of cases analyzed in each study was small. Between 18% and 38% of patients with complicated MI will require reoperation for various complications and the mortality rate varies between 0% and 8%. Conclusion: This study reveals a lack of strong data to support management decisions, unequivocally shows that the care of infants with MI is not standardized, and suggests a great need for international collaborative studies.

Fetal Appendiceal Perforation Masquerading as Meconium Peritonitis: A Report of a Rare Case.

Intrauterine appendicular perforation leading to meconium peritonitis is exceptionally rare, with few reported cases in the literature. This case underscores the diagnostic challenges and high mortality associated with neonatal appendicular perforation. Neonatal appendicitis and subsequent perforation are uncommon due to the funnel shape of the fetal appendix, which reduces susceptibility to luminal obstruction. While advances in neonatal care and diagnostic modalities have improved outcomes, challenges persist in timely diagnosis and management. We present the case of a preterm infant, one of dichorionic-diamniotic (DCDA) twins delivered via cesarean section, who developed gross abdominal distension and respiratory distress shortly after birth. Diagnostic abdominocentesis revealed meconium-stained fluid, prompting further investigation with imaging and subsequent exploratory laparotomy. Extensive adhesions and cecal perforation were observed, necessitating a cecostomy. Despite interventions, the infant's condition deteriorated, leading to a fatal outcome. Intrauterine appendicular perforation leading to meconium peritonitis is a rare and difficult-to-diagnose condition. Antenatal suspicion and early surgical intervention are crucial for improving outcomes. Factors contributing to neonatal appendicular perforation include ischemia, obstruction, and infective etiologies. Neonatal appendicular perforation is a rare but life-threatening condition requiring a high index of suspicion for prompt diagnosis and management. Advances in diagnostic tools and antenatal monitoring have contributed to improved outcomes, highlighting the importance of considering this diagnosis in cases of unexplained neonatal abdominal distension.

Investigations, management and outcome of neonates presenting with distal intestinal obstruction: challenging the need for contrast enemas.

PURPOSE: To characterise the investigations, management and ultimate diagnosis of neonates with distal intestinal obstruction. METHODS: Retrospective review of term (> 37 weeks) neonates with admission diagnosis of distal intestinal obstruction over 10 years (2012-2022). Patient pathways were identified and associations between presentations, response to treatments and outcome investigated. RESULTS: A total of 124 neonates were identified and all included. Initial management was colonic irrigation in 108, contrast enema in 4, and laparotomy in 12. Of those responding to irrigations none underwent contrast enema. Ultimately, 22 neonates proceeded to laparotomy. Overall, 106 had a suction rectal biopsy and 41 had genetic testing for cystic fibrosis. Final diagnosis was Hirschsprung disease (HD) in 67, meconium ileus with cystic fibrosis (CF) in 9, meconium plug syndrome in 19 (including 3 with CF), intestinal atresia in 10 and no formal diagnosis in 17. Median length of neonatal unit stay was 11 days (7-19). CONCLUSIONS: Initial management of neonates with distal bowel obstruction should be colonic irrigation since this is therapeutic in the majority and significantly reduces the need for contrast enema. These infants should all have suction rectal biopsy to investigate for HD unless another diagnosis is evident. If a meconium plug is passed, testing for CF is recommended. Evaluation and therapy are multimodal and time consuming, placing burden on resources and families.

MR Imaging of the Fetal Gastrointestinal Anomalies.

Fetal MR imaging has been shown to be a useful tool for the diagnosis of fetal gastro-intestinal pathologies. To recognize the various pathologies, it is, however, essential to know the normal MR imaging appearance of the fetal bowel at various gestational ages. By providing additional information to ultrasound in case of a fetal gastrointestinal anomaly, MR imaging helps to improve planning for the delivery, postnatal management, and improves parental counseling.

Intratracheal instillation of budesonide suspension versus normal saline on oxidative stress in neonates with meconium aspiration syndrome.

BACKGROUND: Presently, the efficacy of neonatal resuscitation techniques via interventions such as oral, nasal, and endotracheal suction for preventing meconium aspiration syndrome (MAS) after delivery has not been satisfactory. OBJECTIVE: This study aimed to investigate the role of intratracheal instillation of budesonide on oxidative stress in MAS. METHODS: Sixty-two neonates with MAS admitted to Huai'an Maternity and Child Healthcare Hospital from January 2018 to June 2020 were divided into a study group (intratracheal instillation of 2 ml budesonide suspension; n = 31) and a control group (intratracheal instillation of 2 ml normal saline; n = 31). Collect data from two groups of patients and evaluate clinical outcomes, including oxygenation index (OI), as well as serum total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI) and 8-Isoprostane before treatment and 72h after admission. RESULTS: We found no statistical differences in mortality, complication rate, total oxygen inhalation time, OI before treatment and 72h after admission between the two groups of neonates with MAS, while the duration of invasive respiratory support in the study group was significantly shorter than in the control group. Also, serum TAC, TOS, OSI and 8-isoprostane levels were not statistically different before treatment between the two groups. After 72h of admission, OSI and 8-Isoprostane in neonates with MAS in the study group were much lower than those in the control group. TOS, OSI, 8-Isoprostane in the control group and 8-Isoprostane in the study group were significantly higher than those before treatment. As for TAC and TOS, no significant differences were observed between the two groups. CONCLUSION: Intratracheal instillation of budesonide was shown to alleviate oxidative stress and shorten invasive ventilation time in neonates with MAS.

Transitional Hemodynamics in Neonates Born Through Meconium-Stained Amniotic Fluid: A Prospective Observational Study.

Neonates born through meconium-stained amniotic fluid (MSAF) are at increased risk of altered cardiopulmonary transition at birth. There is a paucity of literature evaluating the transitional hemodynamics in these neonates. We aimed to evaluate transitional hemodynamics via echocardiography in neonates born through MSAF, compared to healthy neonates. The primary objective was to assess pulmonary vascular resistance using left pulmonary artery-velocity time integral (LPA-VTI). The secondary objectives were to assess other pulmonary vascular parameters and myocardial function. We enrolled 35 MSAF-born and 35 healthy neonates. Echocardiography was performed at 24 and 48 h of life by a pediatric cardiologist. Echocardiographic parameters were compared between MSAF-born and healthy neonates, and between MSAF-born neonates who developed meconium aspiration syndrome (MAS) and who did not (non-MAS). Among 35 MSAF-born neonates, 14 (40%) were non-vigorous, 18 (51%) required admission to neonatal intensive care unit, 8 (23%) developed MAS, 3 (9%) pulmonary hypertension and 1 (3%) air leak. On echocardiography, LPA-VTI (cm; mean ± SD) was significantly decreased at 24 and 48 h in MSAF-born neonates (14.38 ± 2.48; 15.55 ± 2.48), compared to healthy neonates (16.60 ± 2.14; 17.66 ± 2.71), respectively. Further, LPA-VTI was significantly reduced at 24 and 48 h among MAS (11.81 ± 3.0; 12.43 ± 2.5), compared to non-MAS neonates (15.15 ± 1.72; 16.48 ± 1.55), respectively. Other pulmonary vascular and myocardial function parameters were comparable between the two groups. Pulmonary adaptation was significantly delayed in neonates with MSAF, which was more pronounced in MAS neonates. Further studies should explore the utility of these parameters for early prediction of cardiorespiratory morbidities in this population.

A Less Invasive Technique for Surfactant Administration in a Full-Term Newborn With Moderate Meconium Aspiration Syndrome.

Meconium aspiration syndrome (MAS) presents significant challenges in neonatal care, particularly in the context of respiratory distress. This report explores the efficacy of administering surfactant through a less invasive surfactant administration (LISA) technique in a full-term neonate with MAS. Our case highlights the potential of this method in reducing the need for mechanical ventilation, drawing parallels with its established benefits in preterm neonates with respiratory distress syndrome. The successful application of LISA in this case suggests a promising avenue for managing MAS in full-term neonates, warranting further investigation.

Long-Term Pulmonary and Neurodevelopmental Outcomes of Meconium Aspiration Syndrome Affected Infants: A Retrospective National Population-Based Study in Taiwan.

INTRODUCTION: Meconium aspiration syndrome (MAS) may cause severe pulmonary and neurologic injuries in affected infants after birth, leading to long-term adverse pulmonary or neurodevelopmental outcomes. METHODS: This retrospective population-based cohort study enrolled 1,554,069 mother-child pairs between 2004 and 2014. A total of 8,049 infants were in the MAS-affected group, whereas 1,546,020 were in the healthy control group. Children were followed up for at least 3 years. According to respiratory support, MAS was classified as mild, moderate, and severe. With the healthy control group as the reference, the associations between MAS severity and adverse pulmonary outcomes (hospital admission, intensive care unit (ICU) admission, length of hospital stay, or invasive ventilator support during admission related to pulmonary problem) or adverse neurodevelopmental outcomes (cerebral palsy, needs for rehabilitation, visual impairment, or hearing impairment) were accessed. RESULTS: MAS-affected infants had a higher risk of hospital and ICU admission and longer length of hospital stay, regardless of severity. Infants with severe MAS had a higher risk of invasive ventilator support during re-admission (odds ratio: 17.50, 95% confidence interval [CI]: 7.70-39.75, p < 0.001). Moderate (hazard ratio [HR]: 1.66, 95% CI: 1.30-2.13, p < 0.001) and severe (HR: 4.94, 95% CI: 4.94-7.11, p < 0.001) MAS groups had a higher risk of adverse neurodevelopmental outcome, and the statistical significance remained remarkable in severe MAS group after adjusting for covariates (adjusted HR: 2.28, 95% CI: 1.54-3.38, p < 0.001) Conclusions: Adverse pulmonary or neurodevelopmental outcomes could occur in MAS-affected infants at birth. Close monitoring and follow-up of MAS-affected infants are warranted.

Gestational Exposure to PM2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study.

Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.

Meconium aspiration syndrome: from pathophysiology to treatment.

Meconium aspiration syndrome (MAS) is a clinical condition characterized by respiratory distress in neonates born through meconium-stained amniotic fluid (MSAF). Despite advances in obstetric practices and perinatal care, MAS remains an important cause of morbidity and mortality in term and post-term newborns. Since the 1960s, there have been significant changes in the perinatal and postnatal management of infants born through MSAF. Routine endotracheal suctioning is no longer recommended in both vigorous and non-vigorous neonates with MSAF. Supportive care along with new treatments such as surfactant, inhaled nitric oxide, and high-frequency ventilation has significantly improved the outcome of MAS patients. However, determining the most appropriate approach for this condition continues to be a topic of debate. This review offers an updated overview of the epidemiology, etiopathogenesis, diagnosis, management, and prognosis of infants with MAS.

Pancreatic enzymes digest obstructive meconium from cystic fibrosis pig intestines.

Introduction: Meconium ileus (MI) is a life-threatening obstruction of the intestines affecting ∼15% of newborns with cystic fibrosis (CF). Current medical treatments for MI often fail, requiring surgical intervention. MI typically occurs in newborns with pancreatic insufficiency from CF. Meconium contains mucin glycoprotein, a potential substrate for pancreatic enzymes or mucolytics. Our study aim was to determine whether pancreatic enzymes in combination with mucolytic treatments dissolve obstructive meconium using the CF pig model. Methods: We collected meconium from CF pigs at birth and submerged it in solutions with and without pancreatic enzymes, including normal saline, 7% hypertonic saline, and the reducing agents N-acetylcysteine (NAC) and dithiothreitol (DTT). We digested meconium at 37 °C with agitation, and measured meconium pigment release by spectrophotometry and residual meconium solids by filtration. Results and discussion: In CF pigs, meconium appeared as a solid pigmented mass obstructing the ileum. Meconium microscopically contained mucus glycoprotein, cellular debris, and bile pigments. Meconium fragments released pigments with maximal absorption at 405 nm after submersion in saline over approximately 8 h. Pancreatic enzymes significantly increased pigment release and decreased residual meconium solids. DTT did not improve meconium digestion and the acidic reducing agent NAC worsened digestion. Pancreatic enzymes digested CF meconium best at neutral pH in isotonic saline. We conclude that pancreatic enzymes digest obstructive meconium from CF pigs, while hydrating or reducing agents alone were less effective. This work suggests a potential role for pancreatic enzymes in relieving obstruction due to MI in newborns with CF.

Correlation analysis between the amniotic fluid contamination and clinical grading of neonatal hypoxic-ischemic encephalopathy and biomarkers of brain damage.

BACKGROUND: Amniotic fluid contamination (AFC) is a risk factor for neonatal hypoxic ischemic encephalopathy (HIE); however, the correlation between AFC level and the incidence and clinical grading of HIE, in addition to relevant biomarkers of brain damage, have not been assessed. METHODS: This single-center observational study included 75 neonates with moderate-to-severe HIE. The neonates with HIE were divided into four subgroups according to the AFC level: normal amniotic fluid with HIE group (NAF-HIE), I°AFC with HIE group (I°AFC-HIE), II°AFC with HIE group (II°AFC-HIE), and III°AFC with HIE group (III°AFC-HIE). The control groups consisted of 35 healthy neonates. The clinical grading of neonatal HIE was performed according to the criteria of Sarnat and Sarnat. Serum tau protein and S100B were detected by enzyme-linked immunosorbent assay kits. Correlations of serum tau protein and S100B were evaluated using the Pearson correlation analysis. RESULTS: (1) The incidence of neonatal HIE in the NAF-HIE group was 20 cases (26. 7%), I°AFC-HIE was 13 cases (17.3%), II°AFC-HIE was 10 cases (13.3%), and III°AFC-HIE was 32 cases (42. 7%). The incidence of moderate-to-severe HIE in the I°-III°AFC-HIE groups was 73.3% (55/75). (2) In 44 cases with severe HIE, 26 cases (59.1%) occurred in the III°AFC-HIE group, which had a significantly higher incidence of severe HIE than moderate HIE (p < 0.05). In NAF-HIE and I°AFC-HIE groups, the incidence of moderate HIE was 45.2% and 29.0%, respectively, which was higher than that of severe HIE (X2 = 9.2425, p < 0.05; X2 = 5.0472, p < 0.05, respectively). (3) Serum tau protein and S100B levels in the HIE groups were significantly higher than in the control group (all p < 0.05), and were significantly higher in the III°AFC-HIE group than in the NAF-HIE and I°AFC-HIE groups (all p < 0.05). (4) Serum tau protein and S100B levels in the severe HIE group were significantly higher in the moderate HIE group (all p < 0.05). (5) Serum tau protein and S100B levels were significantly positively correlated (r = 0.7703, p < 0.0001). CONCLUSION: Among children with severe HIE, the incidence of III°AFC was higher, and the levels of serum tau protein and S100B were increased. AFC level might be associated with HIE grading.

Does prenatal diagnosis of meconium peritonitis have the better recovery? A single-center over 10 years of experience.

OBJECTIVE: To evaluate whether infants with prenatal diagnosis of meconium peritonitis (MP) have a poorer prognosis. METHODS: A retrospective analysis of data from infants treated with surgery from January 2008 to December 2020 was conducted. The patients were divided into prenatal diagnosis group and postnatal diagnosis group based on the timing of diagnosis. The intraoperative and postoperative parameters of the two groups of patients were compared. RESULTS: A total of 71 cases of MP were included in the study, with 48 cases in the prenatal diagnosis group and 23 cases in the postnatal diagnosis group. The comparison of preoperative indicators between the two groups of patients showed no statistically significant differences in baseline (p > 0.05). Intraoperative indicators, including blood loss, anastomosis, retained intestinal tube length and excised intestinal tube length, showed no statistically significant differences between the two groups (p > 0.05). However, the postnatal diagnosis group had a significantly shorter operation time than the prenatal diagnosis group (p < 0.05). Postoperative indicators, including fasting time, albumin usage, complications, and abandonment or mortality rates, show no difference (p > 0.05). Nevertheless, the postnatal diagnosis group exhibited significantly shorter hospital stay and time to first bowel movement compared to the prenatal diagnosis group (p < 0.05). CONCLUSION: Prenatal diagnosis of meconium peritonitis is associated with increased surgical complexity, prolonged hospital stay, and delayed recovery of intestinal function. However, there is no evidence of higher mortality or more complications compared to infants diagnosed postnatally, and there is no significant difference in long-term prognosis.

First Insight into Fetal Exposure to Legacy and Emerging Plasticizers Revealed by Infant Hair and Meconium: Occurrence, Biotransformation, and Accumulation.

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.

Analysis of the clinical diagnosis and treatment of fetal meconium peritonitis.

BACKGROUND: The purpose of this study was to improve diagnostic and therapeutic standards by examining the clinical features, treatment, and prognosis of fetal meconium peritonitis (FMP), as well as the diagnostic efficacy of ultrasound for FMP. METHODS: The clinical data of 41 infants and pregnant women diagnosed with meconium peritonitis (MP) and treated at the Fujian Maternal and Child Health Hospital from January 2013 to January 2020 were analyzed retrospectively. Clinical data, imaging data, complications, treatment strategies, pregnancy outcomes, neonatal prognoses, and follow-up outcomes were all analyzed. RESULTS: The MP prenatal diagnosis rate was 56.1% (23/41), the neonatal surgery rate was 53.7% (22/41), and the survival rate was 85.4% (35/41). Intraperitoneal calcification (23 pregnant women, 56.1%), intestinal dilatation (13 pregnant women, 31.7%), peritoneal effusion (22 pregnant women, 53.7%), intraperitoneal pseudocyst (7 pregnant women, 17.1%), and polyhydramnios were diagnosed via prenatal ultrasound (18 pregnant women, 43.9%). Twenty-two pregnant women were assigned to the surgical treatment (operation) group, while 18 were assigned to the conservative treatment group. In the operation group, there were 9 cases of ileal atresia (40.9%), 7 cases of jejunal atresia (31.8%), 2 cases of atresia at the jejunum-ileum junction (9.1%), 2 cases of ileal perforation (9.1%), 1 case of ileal necrosis (4.5%), and 1 case of adhesive obstruction (4.5%). There was no statistically significant difference (p > .05) in the occurrence of various prenatal ultrasound findings by etiology. CONCLUSION: Multiple prenatal ultrasound markers have been identified for MP. To improve the efficacy of newborn treatment for FMP and reduce neonatal mortality, dynamic monitoring of ultrasound image alterations and strengthened integrated perinatal management are necessary.

PRRSV-2 viral load in critical non-lymphoid tissues is associated with late gestation fetal compromise.

The impact of late gestation PRRSV-2 infection is highly variable within a litter, with a subset of fetuses displaying varying degrees of compromise following infection while others remain viable despite significant systemic viral load. To understand the underlying cause of this variation, we examined the susceptibility, distribution and impact of viral infection within non-lymphoid tissues. Samples of brain, heart, kidney, liver, lung, and skeletal muscle were obtained from fetuses of pregnant gilts at gestation day 86, and the presence and distribution of CD163+ cells within each tissue evaluated via immunohistofluorescence. Equivalent samples were collected from phenotypic extremes representing resistant, resilient and susceptible fetuses at 21 days following infection of pregnant gilts with PRRSV-2 at day 86 of gestation. Viral load and its impact in each tissue was evaluated by a combination of qPCR, in vitro viral recovery, and local expression of IFNG and CD163. Resting populations of CD163+ cells were observed in all six non-lymphoid tissues from healthy day 86 fetuses, though the apparent density and the morphology of positive cells varied between tissue. Viral RNA was detected in all six tissues derived from fetuses previously classified as highly infected, and infectious viral particles successfully recovered. Significantly more viral RNA was detected in heart, brain, lung and skeletal muscle of susceptible fetuses, relative to their viable counterparts. Infection was associated with an increase in the expression of CD163 in brain, kidney and lung. In addition, the presence of virus in each tissue coincided with a significant upregulation in the expression of IFNG, but the scale of this response was not associated with fetal susceptibility. Thus, PRRSV-2 is widely distributed across these susceptible non-lymphoid fetal tissues, and fetal outcome is associated with local viral load in critical fetal organs.

Assessment of Fetal Exposure and Elimination of Perfluoroalkyl and Polyfluoroalkyl Substances: New Evidence from Paired Serum, Placenta, and Meconium Samples.

Multiple pieces of evidence have shown that prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) is closely related to adverse birth outcomes for infants. However, difficult access to human samples limits our understanding of PFASs transport and metabolism across the human placental barrier, as well as the accurate assessment of fetal PFASs exposure. Herein, we assess fetal exposure to 28 PFASs based on paired serum, placenta, and meconium samples. Overall, 21 PFASs were identified first to be exposed to the fetus prenatally and to be metabolized and excreted by the fetus. In meconium samples, 25 PFASs were detected, with perfluorooctane sulfonate and perfluorohexane sulfonic acid being the dominant congeners, suggesting the metabolism and excretion of PFASs through meconium. Perfluoroalkyl sulfonic acids might be more easily eliminated through the meconium than perfluorinated carboxylic acids. Importantly, based on molecular docking, MRP1, OATP2B1, ASCT1, and P-gp were identified as crucial transporters in the dynamic placental transfer of PFASs between the mother and the fetus. ATSC5p and PubchemFP679 were recognized as critical structural features that affect the metabolism and secretion of PFASs through meconium. With increasing carbon chain length, both the transplacental transfer efficiency and meconium excretion efficiency of PFASs showed a structure-dependent manner. This study reports, for the first time, that meconium, which is a noninvasive and stable biological matrix, can be strong evidence of prenatal PFASs exposure.

Multiclass Determination of Endocrine-Disrupting Chemicals in Meconium: First Evidence of Perfluoroalkyl Substances in This Biological Compartment.

Major concerns have been raised about human exposure to endocrine-disrupting chemicals (EDCs) during pregnancy. Effective methodologies for the assessment of this exposure are needed to support the implementation of preventive measures and the prediction of negative health effects. Meconium has proven a valuable non-invasive matrix for evaluating cumulative exposure to xenobiotics during the last two trimesters of pregnancy. The study objective was to develop a novel method to determine the presence in meconium of perfluoroalkyl substances (PFASs), bisphenols, parabens, and benzophenones, EDCs that are widely used in the manufacture of numerous consumer goods and personal care products, including cosmetics. Ten PFASs, two bisphenols, four parabens, and four benzophenones were measured in meconium samples prepared by using a combination of Captiva Enhanced Matrix Removal (EMR) lipid cartridges with salt-assisted liquid-liquid extraction (SALLE) and dispersive liquid-liquid microextraction (DLLME) before the application of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Experimental parameters were optimized by applying different chemometric techniques. Limits of detection ranged from 0.05 to 0.1 ng g-1, and between-day variabilities (relative standard deviations) ranged from 6.5% to 14.5%. The method was validated by matrix-matched standard calibration followed by a recovery assay with spiked samples, obtaining percentage recoveries of 89.9% to 114.8%. The method was then employed to measure compounds not previously studied in this matrix in 20 meconium samples. The proposed analytical procedure yields information on cumulative in utero exposure to selected EDCs.