The perinatal consequences of SARS-CoV-2 infection are still largely unknown. This study aimed to describe the features and outcomes of pregnant women with or without SARS-CoV-2 infection after the ...universal screening was established in a large tertiary care center admitting only obstetric related conditions without severe COVID-19 in Mexico City. This retrospective case-control study integrates data between April 22 and May 25, 2020, during active community transmission in Mexico, with one of the highest COVID-19 test positivity percentages worldwide. Only pregnant women and neonates with a SARS-CoV-2 result by quantitative RT-PCR were included in this study. Among 240 pregnant women, the prevalence of COVID-19 was 29% (95% CI, 24% to 35%); 86% of the patients were asymptomatic (95% CI, 76%-92%), nine women presented mild symptoms, and one patient moderate disease. No pregnancy baseline features or risk factors associated with severity of infection, including maternal age > 35 years, Body Mass Index >30 kg/m2, and pre-existing diseases, differed between positive and negative women. The median gestational age at admission for both groups was 38 weeks. All women were discharged at home without complications, and no maternal death was reported. The proportion of preeclampsia was higher in positive women than negative women (18%, 95% CI, 10%-29% vs. 9%, 95% CI, 5%-14%, P<0.05). No differences were found for other perinatal outcomes. SARS-CoV-2 test result was positive for nine infants of positive mothers detected within 24h of birth. An increased number of infected neonates were admitted to the NICU, compared to negative neonates (44% vs. 22%, P<0.05) and had a longer length of hospitalization (2 2-18 days vs. 2 2-3 days, P<0.001); these are potential proxies for illness severity. This report highlights the importance of COVID-19 detection at delivery in pregnant women living in high transmission areas.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment and protection against any ...infectious challenge. The fetal membranes and placenta create a hyperprolactinemic milieu in which prolactin (PRL) synthesized by the maternal decidua is transported through the amnion-chorion and accumulated into the amniotic cavity, where the fetus is bedded in high concentrations during pregnancy. PRL is a pleiotropic immune-neuroendocrine hormone with multiple immunomodulatory functions mainly related to reproduction. However, the biological role of PRL at the maternal-fetal interface has yet to be fully elucidated. In this review, we have summarized the current information on the multiple effects of PRL, focusing on its immunological effects and biological significance for the immune privilege of the maternal-fetal interface.
Placentas from gestational diabetes mellitus (GDM) patients undergo significant metabolic and immunologic adaptations due to hyperglycemia, which results in an exacerbated synthesis of ...proinflammatory cytokines and an increased risk for infections. Insulin or metformin are clinically indicated for the treatment of GDM; however, there is limited information about the immunomodulatory activity of these drugs in the human placenta, especially in the context of maternal infections. Our objective was to study the role of insulin and metformin in the placental inflammatory response and innate defense against common etiopathological agents of pregnancy bacterial infections, such as
and
, in a hyperglycemic environment. Term placental explants were cultivated with glucose (10 and 50 mM), insulin (50-500 nM) or metformin (125-500 µM) for 48 h, and then they were challenged with live bacteria (1 × 10
CFU/mL). We evaluated the inflammatory cytokine secretion, beta defensins production, bacterial count and bacterial tissue invasiveness after 4-8 h of infection. Our results showed that a GDM-associated hyperglycemic environment induced an inflammatory response and a decreased beta defensins synthesis unable to restrain bacterial infection. Notably, both insulin and metformin exerted anti-inflammatory effects under hyperglycemic infectious and non-infectious scenarios. Moreover, both drugs fortified placental barrier defenses, resulting in reduced
counts, as well as decreased
and
invasiveness of placental villous trees. Remarkably, the double challenge of high glucose and infection provoked a pathogen-specific attenuated placental inflammatory response in the hyperglycemic condition, mainly denoted by reduced TNF-α and IL-6 secretion after
infection and by IL-1β after
infection. Altogether, these results suggest that metabolically uncontrolled GDM mothers develop diverse immune placental alterations, which may help to explain their increased vulnerability to bacterial pathogens.
An infectious process into the uterine cavity represents a major endangered condition that compromises the immune privilege of the maternal-fetal unit and increases the risk for preterm birth (PTB) ...and premature rupture of membranes (PROM). Fetal membranes are active secretors of antimicrobial peptides (AMP), which limit bacterial growth, such as
. Nevertheless, the antibacterial responses displayed by chorioamniotic membranes against a choriodecidual
infection have been briefly studied. The objective of this research was to characterize the profile of synthesis, activity, and spatial distribution of a broad panel of AMPs produced by fetal membranes in response to
choriodecidual infection. Term human chorioamniotic membranes were mounted in a two independent compartment model in which the choriodecidual region was infected with live
(1 × 10
CFU/mL). Amnion and choriodecidual AMP tissue levels and TNF-α and IL-1β secretion were measured by the enzyme-linked immunosorbent assay. The passage of bacterium through fetal membranes and their effect on structural continuity was followed for 24 h. Our results showed that
infection caused a progressive mechanical disruption of the chorioamniotic membranes and an activated inflammatory environment. After the challenge, the amnion quickly (2-4 h) induced production of human beta defensins (HBD)-1, HBD-2, and LL-37. Afterwards (8-24 h), the amnion significantly produced HBD-1, HBD-2, HNP-1-3, S100A7, sPLA2, and elafin, whereas the choriodecidua induced LL-37 synthesis. Therefore, we noticed a temporal- and tissue-specific pattern regulation of the synthesis of AMPs by infected fetal membranes. However, fetal membranes were not able to contain the collagen degradation or the bacterial growth and migration despite the battery of produced AMPs, which deeply increases the risk for PTB and PROM. The mixture of recombinant HBDs at low concentrations resulted in increased bactericidal activity compared to each HBD alone in vitro, encouraging further research to study AMP combinations that may offer synergy to control drug-resistant infections in the perinatal period.
(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold ...(CT) values. (2) This was a retrospective case-control study in a third-level health center in Mexico City with universal screening by RT-qPCR. The association of COVID-19 manifestations, preeclampsia, and preterm birth with maternal variables and CT values were assessed by logistic regression models and decision trees. (3) Accordingly, 828 and 298 women had a negative and positive test, respectively. Of those positive, only 2.6% of them presented mild to moderate symptoms. Clinical characteristics between both groups of women were similar. No associations between CT values were found for maternal features, such as pre-gestational BMI, age, and symptomatology. A significantly higher percentage of placental fibrinoid was seen with women with low CTs (<25; p < 0.01). Regarding perinatal outcomes, preeclampsia was found to be significantly associated with symptomatology but not with risk factors or CT values (p < 0.01, aOR = 14.72). Moreover, 88.9% of women diagnosed with COVID-19 at <35 gestational weeks and symptomatic developed preeclampsia. (4) The data support strong guidance for pregnancies with SARS-CoV-2 infection, in particular preeclampsia and placental pathology, which need further investigation.
Neonatal sepsis remains difficult to diagnose due to its non-specific signs and symptoms. Traditional scoring systems help to discriminate between septic or not patients, but they do not consider ...every single patient particularity. Thus, the purpose of this study was to develop an early- and late-onset neonatal sepsis diagnosis model, based on clinical maternal and neonatal data from electronic records, at the time of clinical suspicion. A predictive model was obtained by training and validating an artificial Neural Networks (ANN) algorithm with a balanced dataset consisting of preterm and term non-septic or septic neonates (early- and late-onset), with negative and positive culture results, respectively, using 25 maternal and neonatal features. The outcome of the model was sepsis or not. The performance measures of the model, evaluated with an independent dataset, outperformed physician's diagnosis using the same features based on traditional scoring systems, with a 93.3% sensitivity, an 80.0% specificity, a 94.4% AUROC, and a regression coefficient of 0.974 between actual and simulated results. The model also performed well-relative to the state-of-the-art methods using similar maternal/neonatal variables. The top 10 factors estimating sepsis were maternal age, cervicovaginitis and neonatal: fever, apneas, platelet counts, gender, bradypnea, band cells, catheter use, and birth weight.
Maternal obesity has been related to adverse neonatal outcomes and fetal programming. Oxidative stress and adipokines are potential biomarkers in such pregnancies; thus, the measurement of these ...molecules has been considered critical. Therefore, we developed artificial neural network (ANN) models based on maternal weight status and clinical data to predict reliable maternal blood concentrations of these biomarkers at the end of pregnancy. Adipokines (adiponectin, leptin, and resistin), and DNA, lipid and protein oxidative markers (8-oxo-2'-deoxyguanosine, malondialdehyde and carbonylated proteins, respectively) were assessed in blood of normal weight, overweight and obese women in the third trimester of pregnancy. A Back-propagation algorithm was used to train ANN models with four input variables (age, pre-gestational body mass index (p-BMI), weight status and gestational age). ANN models were able to accurately predict all biomarkers with regression coefficients greater than R² = 0.945. P-BMI was the most significant variable for estimating adiponectin and carbonylated proteins concentrations (37%), while gestational age was the most relevant variable to predict resistin and malondialdehyde (34%). Age, gestational age and p-BMI had the same significance for leptin values. Finally, for 8-oxo-2'-deoxyguanosine prediction, the most significant variable was age (37%). These models become relevant to improve clinical and nutrition interventions in prenatal care.
Preterm neonates are at high risk of infectious and inflammatory diseases which require antibiotic treatment. Antibiotics influence neonatal gut microbiome development, and intestinal dysbiosis has ...been associated with delayed gastrointestinal transit. Neonates who take less time to pass meconium have a better tolerance to enteral feeding. We analyzed the effect of neonatal antibiotic treatment on the stool pattern and oral tolerance in 106 preterm infants < 33 weeks gestational age. Neonates were classified in 3 groups according to neonatal antibiotic (ABT) treatment days: no antibiotics, 3−7 d ABT, and ≥8 d ABT. Preterm infants from the ≥8 d ABT group took longer to pass meconium and to start green and yellow stools, took longer to reach 100 and 150 mL/kg/day, and reached reduced volumes in enteral feeds at day of life 14 and 28 than infants from no ABT and 3−7 d ABT groups. Multiple linear regression models showed that neonatal antibiotic treatment, birth weight, invasive mechanical ventilation, surfactant, enteral feeding start day, neonatal parenteral nutrition, and neonatal fasting days are associated with the stool pattern and oral tolerance in preterm infants.
(1) Background: Size at birth is an important early determinant of health later in life. The prevalence of small for gestational age (SGA) newborns is high worldwide and may be associated with ...maternal nutritional and metabolic factors. Thus, estimation of fetal growth is warranted. (2) Methods: In this work, we developed an artificial neural network (ANN) model based on first-trimester maternal body fat composition, biochemical and oxidative stress biomarkers, and gestational weight gain (GWG) to predict an SGA newborn in pregnancies with or without obesity. A sensibility analysis to classify maternal features was conducted, and a simulator based on the ANN algorithm was constructed to predict the SGA outcome. Several predictions were performed by varying the most critical maternal features attained by the model to obtain different scenarios leading to SGA. (3) Results: The ANN model showed good performance between the actual and simulated data (R
= 0.938) and an AUROC of 0.8 on an independent dataset. The top-five maternal predictors in the first trimester were protein and lipid oxidation biomarkers (carbonylated proteins and malondialdehyde), GWG, vitamin D, and total antioxidant capacity. Finally, excessive GWG and redox imbalance predicted SGA newborns in the implemented simulator. Significantly, vitamin D deficiency also predicted simulated SGA independently of GWG or redox status. (4) Conclusions: The study provided a computational model for the early prediction of SGA, in addition to a promising simulator that facilitates hypothesis-driven constructions, to be further validated as an application.
The aim of this pilot study was to determine Clara cell protein (CC16) concentration in bronchoalveolar lavages (BAL) fluid from full-term and preterm (<37 weeks’ gestational age) neonates requiring ...respiratory support, having symptoms of neonatal respiratory distress syndrome, and at risk of bronchopulmonary dysplasia (BPD). We hypothesized that CC16 may be predictive of BPD diagnosis regardless of gestational age. BAL fluid CC16 was measured by ELISA at birth and at day 7 of life. Both groups that developed BPD showed significantly decreased BAL fluid CC16 levels compared to those infants that did not develop the disease. CC16 positively correlated with diagnosis of BPD and negatively with the severity of the disease. These results suggest that BAL fluid CC16 levels may have a diagnostic value at day 7 for BPD in both term and preterm infants. This study demonstrates the potential utility of BAL fluid CC16 levels as a biomarker for BPD in term infants.
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