Canine pulmonary clearance during feto-neonatal transition according to the type of delivery.

The success of immediate adaptation to extrauterine life depends on appropriate lung function, however, elective cesarean section can increase the risk of respiratory distress as a result of reduced pulmonary fluid absorption. This study aimed to evaluate the influence of birth mode on pulmonary clearance and respiratory performance of canine neonates in the transition period. For this purpose, 37 neonates were selected according to the obstetric condition: Vaginal Eutocia (n = 17) and Elective C-section (n = 20). Neonates were evaluated for neonatal vitality score, as well as evaluation of heart and respiratory rates, body temperature and body weight, venous hemogasometric evaluation, blood lactate and glucose, pulse oximetry and radiographic evaluation during the first 24 h of life. Additionally, amniotic fluid electrolyte composition of each puppy was evaluated. There was no influence of the type of delivery on electrolyte composition of canine amniotic fluid and neonatal pulmonary liquid content, analyzed by thoracic X-Rays. On the other hand, elective cesarean section delayed pulmonary adaptation, resulting in hypoxemia and less efficient compensatory response to acid-base imbalance and thermoregulation. In conclusion, elective c-section does not delay pulmonary clearance, whilst alters pulmonary adaptation by less efficient gas exchange and lower oxygenation, hindering the compensatory response to acid-base imbalance during the fetal-neonatal transition in dogs.

Canine and feline foetal fluids: Volume, hormonal and biochemical characterization during pregnancy.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the volume, the concentration of steroid hormones, and biochemical composition of the foetal fluids at different gestational ages in dogs and cats. METHODS: Following the ovariohysterectomy, the allantoic and amniotic fluid samples were collected from pregnant bitches and queens and were assigned to different groups according to their gestational age. RESULTS: The canine and feline allantoic fluid volume increased during pregnancy, reached its maximum values on days 40-49 and then decreased. The canine and feline amniotic fluid volume increased steadily by the last days of pregnancy. In spite of significant changes of sex hormones in the foetal fluids, their concentration and ratios were not significantly different between male and female fetuses. The canine amniotic cortisol concentration increased until days 40-49 and decreased significantly afterwards. The maximum cortisol concentrations in the feline allantoic and amniotic fluids were observed on days 50-60 and 40-49, respectively. During the canine pregnancy, the concentrations of calcium, phosphorus, chloride, sodium, triglyceride, cholesterol, total protein, albumin and the activities of aminotransferase (AST), alkaline phosphatase (ALP), amylase and gamma-glutamyl transferase (GGT) in the amniotic fluid were higher than the allantoic fluid. The magnesium, potassium, lactate dehydrogenase (LDH) activity, creatine and lipase were higher in the allantoic fluid. In the feline allantoic fluid, potassium, magnesium, phosphorus, creatinine, albumin and glucose concentrations and the activities of creatine kinase (CK), GGT, LDH and lipase were higher. The ALP, AST activities, sodium and calcium concentrations were higher in the amniotic fluid (p < 0.05). CONCLUSION: Volume of foetal fluids was determined in dogs and cats. Concentration of sex hormones did not different between male and female fetuses.

Temporal metabolomics state in pregnant rat: Analysis of amniotic fluid, placenta, and maternal plasma at embryonic and fetal time points.

INTRODUCTION: During pregnancy, the dynamic metabolic demands for fetal growth require a continuous supply of essential metabolites. Understanding maternal metabolome changes during gestation is crucial for predicting disease risks in neonates. METHODS: The study aimed to characterize the placental and amniotic fluid (AF) metabolomes during gestation in rats at gestational days GD-13 and 19 reflecting the end of the embryonic and fetal periods, respectively, and the maternal plasma, using metabolomics (LC-MS) and chemometrics. The objective was to highlight, through univariate and multivariate analyses, the complementarity of the data obtained from these different biological matrices. RESULTS: The biological matrix had more impact on the metabolome composition than the gestational stage. The placental and AF metabolomes showed specific metabolome evolving over the two gestational stages. Analyzing the three targeted metabolomes revealed evolving pathways in arginine and proline metabolism/glutathione metabolism and phenylalanine metabolism; purine metabolism; and carbohydrate metabolism. Significantly, lipid metabolism in the placenta exhibited substantial changes with higher levels of certain phosphatidylethanolamine and sphingomyelins at GD19 while some cholesteryl esters and some glycosphingolipids levels being in higher levels at GD13. DISCUSSION: These data highlight the metabolic gradients (mainly in placenta, also in AF, but only a few in plasma) observed through embryonic patterning and organ development during mid-to late gestation.

Association of Fetal Catecholamines With Neonatal Hypoglycemia.

Importance: Perinatal stress and fetal growth restriction increase the risk of neonatal hypoglycemia. The underlying pathomechanism is poorly understood. In a sheep model, elevated catecholamine concentrations were found to suppress intrauterine insulin secretion, followed by hyperresponsive insulin secretion once the adrenergic stimulus subsided. Objective: To determine whether neonates with risk factors for hypoglycemia have higher catecholamine concentrations in umbilical cord blood (UCB) and/or amniotic fluid (AF) and whether catecholamines are correlated with postnatal glycemia. Design, Setting, and Participants: In a prospective cohort study of 328 neonates at a tertiary perinatal center from September 2020 through May 2022 in which AF and UCB were collected immediately during and after delivery, catecholamines and metanephrines were analyzed using liquid chromatography with tandem mass spectrometry. Participants received postnatal blood glucose (BG) screenings. Exposure: Risk factor for neonatal hypoglycemia. Main Outcomes and Measures: Comparison of catecholamine and metanephrine concentrations between at-risk neonates and control participants, and correlation of concentrations of catecholamines and metanephrines with the number and severity of postnatal hypoglycemic episodes. Results: In this study of 328 neonates (234 in the risk group: median [IQR] gestational age, 270 [261-277] days; and 94 in the control group: median [IQR] gestational age, 273 [270-278] days), growth-restricted neonates showed increased UCB median (IQR) concentrations of norepinephrine (21.10 [9.15-42.33] vs 10.88 [5.78-18.03] nmol/L; P < .001), metanephrine (0.37 [0.13-1.36] vs 0.12 [0.08-0.28] nmol/L; P < .001), and 3-methoxytyramine (0.149 [0.098-0.208] vs 0.091 [0.063-0.149] nmol/L; P = .001). Neonates with perinatal stress had increased UCB median (IQR) concentrations of norepinephrine (22.55 [8.99-131.66] vs 10.88 [5.78-18.03] nmol/L; P = .001), normetanephrine (1.75 [1.16-4.93] vs 1.25 [0.86-2.56] nmol/L; P = .004), and 3-methoxytyramine (0.120 [0.085-0.228] vs 0.091 [0.063-0.149] nmol/L; P = .008) (P < .0083 was considered statistically significant). Concentrations of UCB norepinephrine, metanephrine, and 3-methoxytyramine were negatively correlated with AF C-peptide concentration (rs = -0.212, P = .005; rs = -0.182, P = .016; and rs = -0.183, P = .016, respectively [P < .017 was considered statistically significant]). Concentrations of UCB norepinephrine, metanephrine, and 3-methoxytyramine were positively correlated with the number of hypoglycemic episodes (BG concentration of 30-45 mg/dL) (rs = 0.146, P = .01; rs = 0.151, P = .009; and rs = 0.180, P = .002, respectively). Concentrations of UCB metanephrine and 3-methoxytyramine were negatively correlated with the lowest measured BG concentration (rs = -0.149, P = .01; and rs = -0.153, P = .008, respectively). Conclusions and Relevance: Neonates at risk for hypoglycemia displayed increased catecholamine and metanephrine concentrations that were correlated with postnatal hypoglycemic episodes and lower BG levels; these results are consistent with findings in a sheep model that fetal catecholamines are associated with neonatal ß-cell physiology and that perinatal stress or growth restriction is associated with subsequent neonatal hyperinsulinemic hypoglycemia. Improving the pathomechanistic understanding of neonatal hypoglycemia may help to guide management of newborns at risk for hypoglycemia.

Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

Evaluation of Congenital Cytomegalovirus Infection in Pregnant Women Admitted to a University Hospital in Istanbul.

Cytomegalovirus (CMV) can cause serious complications in immunocompromised individuals and fetuses with congenital infections. These can include neurodevelopmental impairments and congenital abnormalities in newborns. This paper emphasizes the importance of concurrently evaluating ultrasonography findings and laboratory parameters in diagnosing congenital CMV infection. To examine the prenatal characteristics of CMV DNA-positive patients, we assessed serum and amniotic fluid from 141 pregnant women aged 19-45 years, each with fetal anomalies. ELISA and PCR tests, conducted in response to these amniocentesis findings, were performed at an average gestational age of 25 weeks. Serological tests revealed that all 141 women were CMV IgG-positive, and 2 (1.41%) had low-avidity CMV IgG, suggesting a recent infection. CMV DNA was detected in 17 (12.05%) amniotic fluid samples using quantitative PCR. Of these, 82% exhibited central nervous system abnormalities. Given that most infections in pregnant women are undetectable and indicators non-specific, diagnosing primary CMV in pregnant women using clinical findings alone is challenging. We contend that serological tests should not be the sole means of diagnosing congenital CMV infection during pregnancy.

Microplastics in maternal amniotic fluid and their associations with gestational age.

Microplastics (MPs) pollution is a growing global concern due to its potential threat to human health, particularly concerning fetal health. Nevertheless, few studies have examined the sources of fetal MPs exposure and its impact on fetal development. In this study, MPs levels in maternal amniotic fluid (AF) and their associations with measures of fetal growth were investigated. Specifically, 40 human AF samples were collected to determine the presence and characteristics of MPs using laser direct infrared (LD-IR) spectroscopy. MPs were found in 32 out of 40 AF samples, with an average abundance of 2.01 ± 4.19 particles/g. Polyethylene (PE, 38.80 %) and chlorinated polyethylene (CPE, 26.98 %) were the most prevalent polymers. The majority of MPs (87.56 %) were 20-100 µm in size, and fragments (71.23 %) evidently prevailed in morphology. Additionally, a questionnaire was designed to explore the associations between MPs levels in the AF and maternal dietary habits, aiming at unveiling the potential sources of MPs in AF. The MPs levels in the AF were positively associated with the frequency of seafood consumption (r = 0.781, P < 0.001) and bottled water intake (r = 0.386, P = 0.014). Moreover, the associations between MPs levels in maternal AF and measures of fetal growth were evaluated. The abundance of total MPs in maternal AF were significantly negatively associated with gestational age (ß = -0.44, 95 % CI, -0.83, -0.05). This study confirms the presence of MPs in human AF and provides compelling evidence linking them to gestational age, while highlighting the potential risks associated with dietary habits. These findings underscore the need for further investigation into the mechanisms of MPs transmission from mother to fetus and the potential health implications during fetal development, offering valuable insights for future policies aimed at safeguarding maternal and fetal health.

Relationship between the 2D:4D and prenatal testosterone, adult level testosterone, and testosterone change: Meta-analysis of 54 studies.

The ratio between the hands' second to the fourth finger (2D:4D) is commonly hypothesized to result from prenatal testosterone. The 2D:4D has also been hypothesized to relate to adult-level testosterone and, more recently, to the testosterone response to a challenging situation. In the present work, we tested these core assumptions. Drawing from, in total, 54 studies and 8077 participants, we investigated whether the 2D:4D is related to adult level testosterone (44 studies), testosterone change (6 studies), and prenatal testosterone (10 studies). We found no evidence of the relationship between the above testosterone types and digit ratios. Furthermore, there was no relationship between testosterone and the right and left 2D:4D, male and female 2D:4D, and the 2D:4D and testosterone measurement (i.e., measured in blood or saliva). However, we found some evidence that prenatal testosterone measured in amniotic fluid (but not cord blood) might be related to the digit ratios-further studies are necessary to validate this observation. In summary, considering the current state of knowledge, any conclusions drawn from the assumption of the digit ratios as the proxy for testosterone (prenatal, adult level, or testosterone change under a challenging situation) warrant great caution.

The correlation with abnormal fetal outcome and a high level of amniotic fluid alpha-fetoprotein in mid-trimester.

OBJECTIVE: To evaluate the correlation of high levels [>2.0 multiples of median (MoM)] of amniotic fluid alpha-fetoprotein (AFAFP) in midtrimester with abnormal fetal outcome. MATERIALS AND METHODS: We retrospectively studied 6245 pregnant women with singleton pregnancy who had undergone amniocentesis between 15 and 27 weeks' gestation at Mackay Memorial Hospital between January 2014 and June 2020. Fifty-five cases had high AFAFP levels (>2.0 MoM). We investigated the abnormal fetal outcomes. RESULTS: Among the fifty-five cases with high AFAFP levels (>2.0 MoM), thirty (54.5%) had fetal chromosomal abnormalities, major structural abnormalities, and/or adverse obstetric events. Eight cases (14.5%) had chromosomal abnormalities including trisomy 21 (3 cases), trisomy 18 (3 cases), mosaic trisomy 18 (1 cases), and mosaic ring 13 (1 case). Seventeen cases (30.9%) had major structural abnormalities including abdominal wall defect (6 cases) and central nervous system (5 cases), gastrointestinal tract (3 cases), cardiovascular (2 cases), and genitourinary tract (2 cases) abnormalities. Fifteen cases (27%) had adverse obstetric events, including preterm delivery (5 cases), intrauterine fetal demise (4 cases), small for gestational age (4 cases), preeclampsia (4 cases), gestational diabetes mellitus (2 cases), gestational hypertension (1 case), preterm prelabor rupture of membrane (1 case), prolonged labor (1 case), and preterm uterine contraction (1 case). CONCLUSION: A high AFAFP level (>2.0 MoM) in midtrimester can be associated with abnormal fetal outcome, including chromosomal abnormalities, major structural abnormalities, and adverse obstetric events. Women with a prenatal diagnosis of high AFAFP levels (>2.0 MoM) should be alerted of the possibility of abnormal fetal outcomes, and further detailed genetic studies and serial sonographic examinations are recommended.

Association between interleukin-6 and preterm birth: a meta-analysis.

BACKGROUND: Interleukin (IL)-6 is a pro-inflammatory cytokine that plays an important role in preterm birth (PTB), Several meta-analyses investigated the association between IL-6 and PTB, but definitive conclusion has not yet been achieved. This updated meta-analysis aimed to ascertain the association between IL-6 and PTB by examining IL-6 levels in both normal birth and PTB groups. MATERIAL AND METHODS: Prospective cohort studies were retrieved in PubMed, Embase, and the Cochrane library from their inception until 18 February 2020. The primary outcome was the association between IL-6 and PTB, and secondary outcomes were the association between IL-6 and spontaneous PTB. RESULTS: Nine studies involving 1904 patients were included. Overall, IL-6 from different sample types (maternal blood, amniotic fluid and cervicovaginal fluid) was associated with PTB (standard mean difference [SMD]: 0.86, 95% confidence interval [CI]: 0.32 to 1.39, p < 0.001). Furthermore, the association was significant for IL-6 only in amniotic fluid (SMD: 1.87, 95%CI: 0.82 to 2.93, p < 0.001) and cervicovaginal fluid (SMD: 0.46, 95%CI: 0.09 to 0.84, p = 0.022), but not significant in maternal blood (SMD: -0.11, 95%CI: -0.57 to 0.34, p = 0.623). In addition, IL-6 was also associated with spontaneous PTB (SMD: 1.57, 95% CI: 0.18 to 2.95, p < 0.001). CONCLUSIONS: Based on the available evidence, IL-6 in amniotic fluid and cervicovaginal fluid might be useful for predicting preterm birth.

KEY MESSAGESBased on the available evidenceIL-6 in amniotic fluid and cervicovaginal fluid might be useful for predicting preterm birth.

Pharmacological blockade of the interleukin-1 receptor suppressed Escherichia coli lipopolysaccharide-induced neuroinflammation in preterm fetal sheep.

BACKGROUND: Intraamniotic inflammation is associated with preterm birth, especially in cases occurring before 32 weeks' gestation, and is causally linked with an increased risk for neonatal mortality and morbidity. Targeted anti-inflammatory interventions may assist in improving the outcomes for pregnancies impacted by intrauterine inflammation. Interleukin-1 is a central upstream mediator of inflammation. Accordingly, interleukin-1 is a promising candidate target for intervention therapies and has been targeted previously using the interleukin-1 receptor antagonist, anakinra. Recent studies have shown that the novel, noncompetitive, allosteric interleukin-1 receptor inhibitor, rytvela, partially resolved inflammation associated with preterm birth and fetal injury. In this study, we used a preterm sheep model of chorioamnionitis to investigate the anti-inflammatory efficacy of rytvela and anakinra, administered in the amniotic fluid in the setting of intraamniotic Escherichia coli lipopolysaccharide exposure. OBJECTIVE: We hypothesized that both rytvela and anakinra would reduce lipopolysaccharide-induced intrauterine inflammation and protect the fetal brain. STUDY DESIGN: Ewes with a singleton fetus at 105 days of gestation (term is ∼150 days) were randomized to one of the following groups: (1) intraamniotic injections of 2 mL saline at time=0 and time=24 hours as a negative control group (saline group, n=12); (2) intraamniotic injection of 10 mg Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 2 mL saline at time=0 hours and time=24 hours as an inflammation positive control group (lipopolysaccharide group, n=11); (3) intraamniotic injection of Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 2.5 mg rytvela at time=0 hours and time=24 hours to test the anti-inflammatory efficacy of rytvela (lipopolysaccharide + rytvela group, n=10); or (4) intraamniotic injection of Escherichia coli lipopolysaccharide in 2 mL saline and intraamniotic injections of 100 mg anakinra at time=0 hours and time=24 hours to test the anti-inflammatory efficacy of anakinra (lipopolysaccharide + anakinra group, n=12). Amniotic fluid was sampled at time 0, 24, and 48 hours (ie, at each intervention and at delivery). Fetal umbilical cord blood was collected at delivery for differential blood counts and chemical studies. Inflammation was characterized by the analysis of fetal tissue cytokine and chemokine levels using quantitative polymerase chain reaction, enzyme-linked inmmunosorbent assay, and histology. The primary study outcome of interest was the assessment of anakinra and rytvela brain-protective effects in the setting of Escherichia coli lipopolysaccharide-induced intrauterine inflammation. Secondary outcomes of interest were to assess protection from fetal and intrauterine (ie, amniotic fluid, chorioamnion) inflammation. RESULTS: Intraamniotic administration of lipopolysaccharide caused inflammation of the fetal lung, brain, and chorioamnionitis in preterm fetal sheep. Relative to treatment with saline only in the setting of lipopolysaccharide exposure, intraamniotic administration of both rytvela and anakinra both significantly prevented periventricular white matter injury, microglial activation, and histologic chorioamnionitis. Anakinra showed additional efficacy in inhibiting fetal lung myeloperoxidase activity, but its use was associated with metabolic acidaemia and reduced fetal plasma insulin-like growth factor-1 levels at delivery. CONCLUSION: Intraamniotic administration of rytvela or anakinra significantly inhibited fetal brain inflammation and chorioamnionitis in preterm fetal sheep exposed to intraamniotic lipopolysaccharide. In addition, anakinra treatment was associated with potential negative impacts on the developing fetus.

Meconium Stained Amniotic Fluid and Associated Factors among Women Who Gave Birth at Term in Adama Hospital Medical College, Ethiopia.

Background: Meconium stained amniotic fluid (MSAF) is a commonly observed phenomenon in day-to-day practice of obstetrics. The reported prevalence of MSAF was 7-22% of all term deliveries. Some of the factors that increases the risk of meconium stained amniotic fluid includes; advanced gestational age at delivery, prolonged rupture of membranes, intra-amniotic infection, pre-eclampsia, oligohydroamnios, and diabetes mellitus. The study aimed to determine the prevalence of meconium stained amniotic fluid and its associated factors among women who gave birth at term, from January 1st to July 30th, 2020, at Adama Hospital Medical College. Methods: Institutional based cross-sectional study was conducted on 314 laboring women who gave birth at term. Systematic random sampling was used to select the study participants. Data entry and analysis were made by using Epi- info 7 and SPSS version 20, respectively. Results: The prevalence of meconium stained amniotic fluid was 23.9%. Late term pregnancy, Oligohydraminos, Antepartum hemorrhage, Premature rupture of membrane, and Non-reassuring fetal heart rate pattern were significantly associated with meconium-stained amniotic fluid. Conclusions: The prevalence of MSAF was comparable with other studies. Late-term pregnancy, oligohydramnios, antepartum hemorrhage, non-reassuring fetal heart rate pattern, and premature rupture of the membrane were factors associated with an increased risk of MSAF.

Meconium-stained amniotic fluid.

Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard. The condition has been attributed to the passage of fetal colonic content (meconium), intraamniotic bleeding with the presence of heme catabolic products, or both. The frequency of green-stained amniotic fluid increases as a function of gestational age, reaching approximately 27% in post-term gestation. Green-stained amniotic fluid during labor has been associated with fetal acidemia (umbilical artery pH <7.00), neonatal respiratory distress, and seizures as well as cerebral palsy. Hypoxia is widely considered a mechanism responsible for fetal defecation and meconium-stained amniotic fluid; however, most fetuses with meconium-stained amniotic fluid do not have fetal acidemia. Intraamniotic infection/inflammation has emerged as an important factor in meconium-stained amniotic fluid in term and preterm gestations, as patients with these conditions have a higher rate of clinical chorioamnionitis and neonatal sepsis. The precise mechanisms linking intraamniotic inflammation to green-stained amniotic fluid have not been determined, but the effects of oxidative stress in heme catabolism have been implicated. Two randomized clinical trials suggest that antibiotic administration decreases the rate of clinical chorioamnionitis in patients with meconium-stained amniotic fluid. A serious complication of meconium-stained amniotic fluid is meconium aspiration syndrome. This condition develops in 5% of cases presenting with meconium-stained amniotic fluid and is a severe complication typical of term newborns. Meconium aspiration syndrome is attributed to the mechanical and chemical effects of aspirated meconium coupled with local and systemic fetal inflammation. Routine naso/oropharyngeal suctioning and tracheal intubation in cases of meconium-stained amniotic fluid have not been shown to be beneficial and are no longer recommended in obstetrical practice. A systematic review of randomized controlled trials suggested that amnioinfusion may decrease the rate of meconium aspiration syndrome. Histologic examination of the fetal membranes for meconium has been invoked in medical legal litigation to time the occurrence of fetal injury. However, inferences have been largely based on the results of in vitro experiments, and extrapolation of such findings to the clinical setting warrants caution. Fetal defecation throughout gestation appears to be a physiologic phenomenon based on ultrasound as well as in observations in animals.

Reference values for interleukin-6 in the amniotic fluid of asymptomatic pregnant women.

INTRODUCTION: Nowadays, proinflammatory factors are considered to play an important role in the pathophysiology of threatened preterm labor or chorioamnionitis. The aim of this study was to establish the normal reference range for interleukin-6 (IL-6) levels in the amniotic fluid and to identify factors which may alter this value. MATERIAL AND METHODS: Prospective study in a tertiary-level center including asymptomatic pregnant women undergoing amniocentesis for genetic studies from October 2016 to September 2019. IL-6 measurements in amniotic fluid were performed using a fluorescence immunoassay with microfluidic technology (ELLA Proteinsimple, Bio Techne). Maternal history and pregnancy data were also recorded. RESULTS: This study included 140 pregnant women. Of those, women who underwent termination of pregnancy were excluded. Therefore, a total of 98 pregnancies were included in the final statistical analysis. The mean gestational age was 21.86 weeks (range: 15-38.7) at the time of amniocentesis, and 38.6 weeks (range: 30.9-41.4) at delivery. No cases of chorioamnionitis were reported. The log10 IL-6 values follow a normal distribution (W = 0.990, p = 0.692). The median, and the 5th, 10th, 90th, and 95th percentiles for IL-6 levels were 573, 105, 130, 1645, and 2260 pg/mL, respectively. The log10 IL-6 values were not affected by gestational age (p = 0.395), maternal age (p = 0.376), body mass index (p = 0.551), ethnicity (p = 0.467), smoking status (p = 0.933), parity (p = 0.557), method of conception (p = 0.322), or diabetes mellitus (p = 0.381). CONCLUSIONS: The log10 IL-6 values follow a normal distribution. IL-6 values are independent of gestational age, maternal age, body mass index, ethnicity, smoking status, parity and method of conception. Our study provides a normal reference range for IL-6 levels in the amniotic fluid that can be used in future studies. We also observed that normal IL-6 values were higher in the amniotic fluid than in serum.

Transfer of anticonvulsants and lithium into amniotic fluid, umbilical cord blood & breast milk: A systematic review & combined analysis.

OBJECTIVE: Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a series of matrices from combined samples of pregnant/breastfeeding women treated with anticonvulsants or lithium. METHODS: We conducted a systematic literature search in PubMed/EMBASE for studies with concentrations of anticonvulsants/lithium from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal concentrations. When data from multiple studies were available, we calculated combined penetration ratios, weighting studies' mean by study size. RESULTS: Ninety-one eligible studies for brivaracetam, carbamazepine, clonazepam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, lithium, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproate, vigabatrin and zonisamide were identified. For amniotic fluid, the highest penetration ratios were estimated for levetiracetam (mean 3.56, range 1.27-5.85, n = 2) and lowest for valproate (mean 0.11, range 0.02-1.02, n = 57). For umbilical cord plasma, oxcarbazepine had the highest ratio (mean 1.59, range 0.11-4.33, n = 12) with clonazepam having the lowest (mean 0.55, range 0.52-0.59, n = 2). For breast milk, the highest ratios were observed for oxcarbazepine (mean 3.75, range 0.5-7.0, n = 2), whereas the lowest were observed for valproate (mean 0.04, range 0.01-0.22, n = 121). DISCUSSION: We observed substantial variability between anticonvulsants and lithium regarding their ability to enter fetal/newborn circulation. Assessing concentrations of anticonvulsants and lithium in maternal samples can provide a surrogate of fetal/infant exposure, although patterns of concentration-dependent effects for maternal/neonatal safety are lacking.

The Association between the Bisphenols Residues in Amniotic Fluid and Fetal Abnormalities in Polish Pregnant Women-Its Potential Clinical Application.

The present study aimed to investigate the relationship between the concentrations of bisphenols residues in the amniotic fluid (AF) samples collected during amniocentesis and fetal chromosomal abnormalities in pregnant women. A total of 33 pregnant Polish women aged between 24 and 44 years, and screened to detect high risk for chromosomal defects in the first trimester, were included in this study. Samples were collected from these patients during routine diagnostic and treatment procedures at mid-gestation. The concentrations of various bisphenols residues in the samples were determined by liquid chromatography coupled with triple quadrupole tandem mass spectrometry (LC-ESI-QqQ-MS/MS). Residues of eight analytes (BPS, BPF, BPA, BPAF, BADGE, BADGE•2H2O, BADGE•H2O•HCl and BADGE•2HCl) were detected in amniotic fluid samples in the range 0.69 ng/mL to 3.38 ng/mL. Fetuses with chromosomal abnormalities showed a slightly higher frequency of occurrence of selected bisphenols residues in the AF samples collected between 15-26 weeks of pregnancies. Finally, the proposed method was applied in the simultaneous determination of several endocrine-disrupting chemicals from bisphenol group in 33 human AF samples. BADGE•H2O•HCl has been identified in the AF samples taken from women older than average in the examined group. The number of detected compounds has been significant for the following analytes: BPS, BPAF, BADGE•H2O•HCl and BADGE. The proposed method may be an attractive alternative for application in large-scale human biomonitoring studies.

Steroid Profiling in the Amniotic Fluid: Reference Range for 12 Steroids and Interest in 21-Hydroxylase Deficiency.

CONTEXT: Determination of steroid levels in the amniotic fluid gives some insight on fetal adrenal and gonadal functions. OBJECTIVE: Our objectives were to establish reference ranges of 12 steroid levels throughout pregnancy and to compare them with steroid levels from pregnancies with fetuses presenting with 21-hydroxylase deficiency (21OHD). METHODS: Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was applied to 145 "control" amniotic fluid samples from gynecology activity (12 + 6 to 32 + 4 gestational weeks, GW). The following steroids were analyzed according to gestational age and compared to 23 amniotic fluid samples from fetuses with classic 21OHD confirmed by molecular studies: delta-4-androstenedione (D4), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17OHP), 11-deoxycortisol (11OH), 21-deoxycortisol (21OH), corticosterone, deoxycorticosterone (DOC), testosterone, pregnenolone, 17-hydroxypregnenolone (17Pregn), cortisol, and cortisone. Chromosomal sex was determined by karyotype and gestational age by biometric measurements. RESULTS: Analysis of control samples showed a statistically significant difference for D4 and testosterone levels according to fetal sex. Cortisol, corticosterone, and DOC had lower concentrations before 20 GW than after 20 GW, whereas 17Pregn and pregnenolone had higher concentrations before 20 GW. This allowed us to establish age- and sex-dependent reference values. We observed higher 21OH, 17Pregn, D4, and testosterone levels in females with 21OHD than female controls. The ratios 17OHP/17Pregn, D4/DHEA, and 11OH/17OHP appeared discriminant for the diagnosis of 21OHD. CONCLUSION: Our study provides information on fetal steroidogenesis and suggests reference values for 12 steroids during pregnancy. This allows a prenatal diagnosis of 21OHD within 24 hours and might be useful in the diagnosis of other variations of sex development.

Non-Nutritive Sweeteners in Human Amniotic Fluid and Cord Blood: Evidence of Transplacental Fetal Exposure.

OBJECTIVE: This study aimed to investigate human fetal exposure to non-nutritive sweeteners (NNS) by analyzing amniotic fluid and umbilical cord blood. STUDY DESIGN: Concentrations of four NNS (acesulfame-potassium [ace-K], saccharin, steviol glucuronide, and sucralose) were measured in amniotic fluid (n = 13) and cord blood samples (n = 15) using liquid chromatography-mass spectrometry. Amniotic fluid samples were obtained for research purposes at the time of term elective cesarean birth or clinically indicated third trimester amnioreduction at Mercy Hospital for Women (Melbourne, Australia). All except four women were in the fasting state. Cord blood samples were obtained from an independent cohort of newborns whose mothers were enrolled in a separate clinical trial at the National Institutes of Health. RESULTS: Ten of 13 amniotic fluid samples contained at least one NNS (ace-K, saccharin, steviol glucuronide, and/or sucralose). Maximum amniotic fluid NNS concentrations of ace-K, saccharin, steviol glucuronide, and sucralose were 78.9, 55.9, 93.5, and 30.6 ng/mL, respectively. Ace-K and saccharin were present in 100% and 80% of the cord blood samples, with maximal concentrations of 6.5 and 2.7 ng/mL, respectively. Sucralose was not detected and steviol glucuronide was not measurable in any of the cord blood samples. CONCLUSION: Our results provide evidence of human transplacental transmission of NNS. Based on results predominantly obtained from rodent models, we speculate that NNS exposure may adversely influence the offsprings' metabolic health. Well-designed, prospective clinical trials are necessary to understand the impact of NNS intake during pregnancy on human development and long-term health. KEY POINTS: · NNS consumption during pregnancy has increased in recent years.. · Maternal NNS intake during pregnancy is associated with preterm birth and higher infant weight gain in epidemiologic studies.. · In rodents, in utero NNS exposure induces metabolic abnormalities in mothers and their offspring, alters offspring gut microbiota composition, and promotes sweet taste preference in adulthood.. · It is presently unknown whether and to what degree maternal NNS ingestion in humans leads to direct in utero exposure.. · This study provides the first evidence of in utero NNS exposure in humans and highlights the urgent need to investigate clinical consequences of early life NNS exposure on metabolism, weight, taste preference, and general health..

High-Risk Pregnancy Is Associated With Increased Alpha-Fetoprotein Concentrations in the Amniotic Fluid and Foal Plasma.

This study aimed to determine alpha-fetoprotein (AFP) concentrations in amniotic fluid, plasma of mares and respective foals: carrying normal pregnancies and delivering healthy foals (n = 20; Group 1); carrying apparently normal pregnancies and delivering sick foals (n = 15; Group 2); carrying high-risk pregnancies and delivering sick foals (n = 14; Group 3). High-risk pregnancy was defined by a history of premature udder development/lactation or increased of the combined thickness of the uterus and placenta, or vulvar discharge and/or mares' systemic illness. Sick foals were affected by neonatal encephalopathy, sepsis, prematurity/dysmaturity, or hypoxic-ischemic encephalopathy. Based on histological examination of the chorioallantois, AFP trend was analyzed in pregnancies with pathologic (PFM) and normal fetal membranes (NFM). Concentrations of AFP were measured using a commercially available immunoassay previously validated for horses. Mares' plasma AFP did not change during the last 15-20 days of pregnancy in the three groups, and there was no difference among them. Amniotic fluid AFP was higher in Group 3 (P = .014). Foals' plasma AFP concentration was higher from birth to 72hours in foals of Group 2 and 3 than in healthy ones, and foals of Group 3 had the highest value. The strong association (r = 0.84; P < .0001) between AFP in amniotic fluid and foals' plasma at birth is likely due to the presence of AFP in fetal urine. AFP was higher in pregnancy with PFM than with NFM in mare's plasma at admission (P = .031), amniotic fluid (P = .004), foal's plasma at birth (P = .002), at 24 (P = .005) and at 72 hours of life (P = .004). AFP is higher in pregnancy with histopathological lesions of the chorioallantois providing the evidence of the differences between pregnancy with a normal placental barrier and the more compromised ones. The increased AFP concentration in the amniotic fluid and plasma of high-risk foals suggests upregulation.

Estimated time to emergence of secondary intra-amniotic infection or inflammation since the onset of the preterm premature rupture of membranes.

OBJECTIVE: Prematurity is the most important prognostic factor for infants born following preterm premature rupture of membranes (PPROM). Therefore, when PPROM occurs between 22 and 33 weeks of gestation, prolonging pregnancy is recommended. Determination of management strategies requires screening for the presence of intra-amniotic infection or inflammation at the time of PPROM diagnosis. If intra-amniotic infection/inflammation is not detected, it is important to monitor the patient to diagnose any new infection/inflammation. We examined the period from PPROM to secondary intra-amniotic infection/inflammation and associated factors. MATERIALS AND METHODS: This retrospective study was conducted at a single facility. We examined 26 patients who experienced PPROM between 26 and 33 weeks of gestation and were negative for intra-amniotic infection/inflammation at the time of diagnosis and underwent serial amniocentesis. Antibiotic therapy comprising ampicillin, amoxicillin, and clarithromycin for 7 days was started after the first amniocentesis. The period from PPROM to secondary intra-amniotic infection/inflammation was analyzed using a Kaplan-Meier survival curve. The onset of intra-amniotic infection/inflammation was considered as the time at which amniotic fluid bacterial culture results became positive, the time when amniotic fluid Interleukin (IL)-6 increased beyond 2.6 ng/mL, or the day of delivery if histological chorioamnionitis was observed in the delivered placenta. Patients were treated as censored if no intra-amniotic infection/inflammation could be confirmed in the amniotic fluid and delivered placenta. RESULTS: The median time from PPROM to secondary intra-amniotic infection/inflammation was 18 days. Six patients developed intra-amniotic infection/inflammation, while 13 patients without intra-amniotic infections/inflammation delivered fewer than 7 days after PPROM. No confounding factors at the time of PPROM diagnosis were associated with the time from PPROM until secondary intra-amniotic infection/inflammation. CONCLUSIONS: The time between PPROM and onset of secondary intra-amniotic infection/inflammation appears prolonged. Treatments other than antimicrobial agents may need to be added to prolong pregnancy.