Are bacteria, fungi, and archaea present in the midtrimester amniotic fluid?

OBJECTIVES: This study was conducted to determine whether bacteria, fungi, or archaea are detected in the amniotic fluid of patients who underwent midtrimester amniocentesis for clinical indications. METHODS: Amniotic fluid samples from 692 pregnancies were tested by using a combination of culture and end-point polymerase chain reaction (PCR) techniques. Intra-amniotic inflammation was defined as an interleukin-6 concentration >2,935 pg/mL. RESULTS: Microorganisms were detected in 0.3% (2/692) of cases based on cultivation, 1.73% (12/692) based on broad-range end-point PCR, and 2% (14/692) based on the combination of both methods. However, most (13/14) of these cases did not have evidence of intra-amniotic inflammation and delivered at term. Therefore, a positive culture or end-point PCR in most patients appears to have no apparent clinical significance. CONCLUSIONS: Amniotic fluid in the midtrimester of pregnancy generally does not contain bacteria, fungi, or archaea. Interpretation of amniotic fluid culture and molecular microbiologic results is aided by the assessment of the inflammatory state of the amniotic cavity. The presence of microorganisms, as determined by culture or a microbial signal in the absence of intra-amniotic inflammation, appears to be a benign condition.

Extracellular vesicle-associated miRNAs are an adaptive response to gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a serious public health issue affecting 9-15% of all pregnancies worldwide. Recently, it has been suggested that extracellular vesicles (EVs) play a role throughout gestation, including mediating a placental response to hyperglycaemia. Here, we investigated the EV-associated miRNA profile across gestation in GDM, assessed their utility in developing accurate, multivariate classification models, and determined the signaling pathways in skeletal muscle proteome associated with the changes in the EV miRNA profile. METHODS: Discovery: A retrospective, case-control study design was used to identify EV-associated miRNAs that vary across pregnancy and clinical status (i.e. GDM or Normal Glucose Tolerance, NGT). EVs were isolated from maternal plasma obtained at early, mid and late gestation (n = 29) and small RNA sequencing was performed. Validation: A longitudinal study design was used to quantify expression of selected miRNAs. EV miRNAs were quantified by real-time PCR (cases = 8, control = 14, samples at three times during pregnancy) and their individual and combined classification efficiencies were evaluated. Quantitative, data-independent acquisition mass spectrometry was use to establish the protein profile in skeletal muscle biopsies from normal and GDM. RESULTS: A total of 2822 miRNAs were analyzed using a small RNA library, and a total of 563 miRNAs that significantly changed (p < 0.05) across gestation and 101 miRNAs were significantly changed between NGT and GDM. Analysis of the miRNA changes in NGT and GDM separately identified a total of 256 (NGT-group), and 302 (GDM-group) miRNAs that change across gestation. A multivariate classification model was developed, based on the quantitative expression of EV-associated miRNAs, and the accuracy to correctly assign samples was > 90%. We identified a set of proteins in skeletal muscle biopsies from women with GDM associated with JAK-STAT signaling which could be targeted by the miRNA-92a-3p within circulating EVs. Interestingly, overexpression of miRNA-92a-3p in primary skeletal muscle cells increase insulin-stimulated glucose uptake. CONCLUSIONS: During early pregnancy, differently-expressed, EV-associated miRNAs may be of clinical utility in identifying presymptomatic women who will subsequently develop GDM later in gestation. We suggest that miRNA-92a-3p within EVs might be a protected mechanism to increase skeletal muscle insulin sensitivity in GDM.

New obstetric systemic inflammatory response syndrome criteria for early identification of high-risk of sepsis in obstetric patients.

OBJECTIVES: We aimed to establish new cut-off values for SIRS (Systemic Inflammatory Response Syndrome) variables in the obstetric population. METHODS: A prospective cohort study in pregnant and postpartum women admitted with systemic infections between December 2017 and January 2019. Patients were divided into three cohorts: Group A, patients with infection but without severe maternal outcomes (SMO); Group B, patients with infection and SMO or admission to the intensive care unit (ICU); and Group C, a control group. Outcome measures were ICU admission and SMO. The relationship between SIRS criteria and SMO was expressed as the area under the receiver operating characteristics curve (AUROC), selecting the best cut-off for each SIRS criterion. RESULTS: A total of 541 obstetric patients were enrolled, including 341 with infections and 200 enrolled as the reference group (Group C). The patients with infections included 313 (91.7%) in Group A and 28 (8.2%) in Group B. There were significant differences for all SIRS variables in Group B, compared with Groups A and C, but there were no significant differences between Groups A and C. The best cut-off values were the following: temperature 38.2 °C, OR 4.1 (1.8-9.0); heart rate 120 bpm, OR 2.9 (1.2-7.4); respiratory rate 22 bpm, OR 4.1 (1.6-10.1); and leukocyte count 16,100 per mcl, OR 3.5 (1.6-7.6). CONCLUSIONS: The cut-off values for SIRS variables did not differ between healthy and infected obstetric patients. However, a higher cut-off may help predict the population with a higher risk of severe maternal outcomes.

Fetal cardiac remodeling and dysfunction is associated with both preeclampsia and fetal growth restriction.

BACKGROUND: Preeclampsia and fetal growth restriction share some pathophysiologic features and are both associated with placental insufficiency. Fetal cardiac remodeling has been described extensively in fetal growth restriction, whereas little is known about preeclampsia with a normally grown fetus. OBJECTIVE: To describe fetal cardiac structure and function in pregnancies complicated by preeclampsia and/or fetal growth restriction as compared with uncomplicated pregnancies. STUDY DESIGN: This was a prospective, observational study including pregnancies complicated by normotensive fetal growth restriction (n=36), preeclampsia with a normally grown fetus (n=35), preeclampsia with fetal growth restriction (preeclampsia with a normally grown fetus-fetal growth restriction, n=42), and 111 uncomplicated pregnancies matched by gestational age at ultrasound. Fetal echocardiography was performed at diagnosis for cases and recruitment for uncomplicated pregnancies. Cord blood concentrations of B-type natriuretic peptide and troponin I were measured at delivery. Univariate and multiple regression analysis were conducted. RESULTS: Pregnancies complicated by preeclampsia and/or fetal growth restriction showed similar patterns of fetal cardiac remodeling with larger hearts (cardiothoracic ratio, median [interquartile range]: uncomplicated pregnancies 0.27 [0.23-0.29], fetal growth restriction 0.31 [0.26-0.34], preeclampsia with a normally grown fetus 0.31 [0.29-0.33), and preeclampsia with fetal growth restriction 0.28 [0.26-0.33]; P<.001) and more spherical right ventricles (right ventricular sphericity index: uncomplicated pregnancies 1.42 [1.25-1.72], fetal growth restriction 1.29 [1.22-1.72], preeclampsia with a normally grown fetus 1.30 [1.33-1.51], and preeclampsia with fetal growth restriction 1.35 [1.27-1.46]; P=.04) and hypertrophic ventricles (relative wall thickness: uncomplicated pregnancies 0.55 [0.48-0.61], fetal growth restriction 0.67 [0.58-0.8], preeclampsia with a normally grown fetus 0.68 [0.61-0.76], and preeclampsia with fetal growth restriction 0.66 [0.58-0.77]; P<.001). Signs of myocardial dysfunction also were observed, with increased myocardial performance index (uncomplicated pregnancies 0.78 z scores [0.32-1.41], fetal growth restriction 1.48 [0.97-2.08], preeclampsia with a normally grown fetus 1.15 [0.75-2.17], and preeclampsia with fetal growth restriction 0.45 [0.54-1.94]; P<.001) and greater cord blood B-type natriuretic peptide (uncomplicated pregnancies 14.2 [8.4-30.9] pg/mL, fetal growth restriction 20.8 [13.1-33.5] pg/mL, preeclampsia with a normally grown fetus 31.8 [16.4-45.8] pg/mL and preeclampsia with fetal growth restriction 37.9 [15.7-105.4] pg/mL; P<.001) and troponin I as compared with uncomplicated pregnancies. CONCLUSION: Fetuses of preeclamptic mothers, independently of their growth patterns, presented cardiovascular remodeling and dysfunction in a similar fashion to what has been previously described for fetal growth restriction. Future research is warranted to better elucidate the mechanism(s) underlying fetal cardiac adaptation in these conditions.

Long-term cardiovascular consequences of fetal growth restriction: biology, clinical implications, and opportunities for prevention of adult disease.

In the modern world, cardiovascular disease is a leading cause of death for both men and women. Epidemiologic studies consistently have suggested an association between low birthweight and/or fetal growth restriction and increased rate of cardiovascular mortality in adulthood. Furthermore, experimental and clinical studies have demonstrated that sustained nutrient and oxygen restriction that are associated with fetal growth restriction activate adaptive cardiovascular changes that might explain this association. Fetal growth restriction results in metabolic programming that may increase the risk of metabolic syndrome and, consequently, of cardiovascular morbidity in the adult. In addition, fetal growth restriction is strongly associated with fetal cardiac and arterial remodeling and a subclinical state of cardiovascular dysfunction. The cardiovascular effects ocurring in fetal life, includes cardiac morphology changes, subclinical myocardial dysfunction, arterial remodeling, and impaired endothelial function, persist into childhood and adolescence. Importantly, these changes have been described in all clinical presentations of fetal growth restriction, from severe early- to milder late-onset forms. In this review we summarize the current evidence on the cardiovascular effects of fetal growth restriction, from subcellular to organ structure and function as well as from fetal to early postnatal life. Future research needs to elucidate whether and how early life cardiovascular remodeling persists into adulthood and determines the increased cardiovascular mortality rate described in epidemiologic studies.

Performance of the Obstetric Early Warning Score in critically ill patients for the prediction of maternal death.

BACKGROUND: Every day, about 830 women die worldwide from preventable causes related to pregnancy and childbirth. Obstetric early warning scores have been proposed as a potential tool to reduce maternal morbidity and mortality, based on the identification of predetermined abnormal values in the vital signs or laboratory parameters, to generate a rapid and effective medical response. Several early warning scores have been developed for obstetrical patients, but the majority are the result of a clinical consensus rather than statistical analyses of clinical outcome measures (ie, maternal deaths). In 2013, the Intensive Care National Audit and Research Center Case Mix Program reported the first statistically validated early warning scoring system for pregnant women. OBJECTIVE: We sought to assess the performance of the Intensive Care National Audit and Research Center Obstetric Early Warning Score in predicting death among pregnant women who required admission to the intensive care unit. STUDY DESIGN: This retrospective cohort study included pregnant women admitted to the intensive care unit at a tertiary referral center from January 2006 through December 2011 in Colombia, a developing country, with direct and indirect obstetric-related conditions. The Obstetric Early Warning Score was calculated based on data collected during the first 24 hours of intensive care unit admission. The Obstetric Early Warning Score is calculated based on values of the following variables: systolic and diastolic blood pressure, respiratory rate, heart rate, fraction of inspired oxygen (FiO2) required to maintain an oxygen saturation ≥96%, temperature, and level of consciousness. The performance of the Obstetric Early Warning Score was evaluated using the area under the receiver operator characteristic curve. Outcomes selected were: maternal death, need for mechanical ventilation, and/or vasoactive support. Statistical methods included distribution appropriate univariate analyses and multivariate logistic regression. RESULTS: During the study period, 50,897 births were recorded. There were 724 obstetric admissions to critical care, for an intensive care unit admission rate of 14.22 per 1000 deliveries. A total of 702 women were included in the study, with 29 (4.1%) maternal deaths, and a mortality ratio of 56.98 deaths per 100,000 live births. The most frequent causes of admission were direct, obstetric-related conditions (n = 534; 76.1%). The Obstetric Early Warning Score value was significantly higher in nonsurvivors than in survivors [12 (interquartile range 10-13) vs 7 (interquartile range 4-9); P < .001]. Peripartum women with normal values of Obstetric Early Warning Score had 0% mortality rate, while those with high Obstetric Early Warning Score values (>6) had a mortality rate of 6.3%. The area under the receiver operator characteristic curve of the Obstetric Early Warning Score in discrimination of maternal death was 0.84 (95% confidence interval, 0.75-0.92). The overall predictive value of the Obstetric Early Warning Score was better when the main cause of admission was directly related to pregnancy or the postpartum state. The area under the receiver operator characteristic curve of the score in conditions directly related to pregnancy and postpartum was 0.87 (95% confidence interval, 0.79-0.95), while in indirectly related conditions the area under the receiver operator characteristic curve was 0.77 (95% confidence interval, 0.58-0.96). CONCLUSION: Although there are opportunities for improvement, Obstetric Early Warning Score obtained upon admission to the intensive care unit can predict survival in conditions directly related to pregnancy and postpartum. The use of early warning scores in obstetrics may be a highly useful approach in the early identification of women at an increased risk of dying.

Predictors of Maternal Mortality and Prognostic Models in Obstetric Patients.

The use of predictive models has been proposed as a potential tool to reduce maternal morbidity and mortality, by aiding in the timely identification of potential high-risk patients. Prognostic models in critical care have been used to characterize the severity of illness of specific diseases. Physiological changes in pregnancy may result in general critical illness prediction models overestimating mortality in obstetric patients. Models that specifically reflect the unique characteristics of obstetric patients may have better prognostic value. Recently developed tools have focused on identifying at-risk patients before they require intensive care unit (ICU) admission to target early interventions and prevent acute clinical decompensation. The aim of the newest scoring systems, specifically designed for groups of obstetric patients receiving non-ICU care, is to reduce maternal morbidity and mortality by identifying early high-risk patients and initiating prompt effective medical responses.

Clinical chorioamnionitis at term I: microbiology of the amniotic cavity using cultivation and molecular techniques.

INTRODUCTION: The objectives of this study were: 1) to determine the amniotic fluid (AF) microbiology of patients with the diagnosis of clinical chorioamnionitis at term using both cultivation and molecular techniques; and 2) to examine the relationship between intra-amniotic inflammation with and without microorganisms and placental lesions consistent with acute AF infection. METHODS: The AF samples obtained by transabdominal amniocentesis from 46 women with clinical signs of chorioamnionitis at term were analyzed using cultivation techniques (for aerobic and anerobic bacteria as well as genital mycoplasmas) and broad-range polymerase chain reaction (PCR) coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). The frequency of microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation [defined as an AF interleukin 6 (IL-6) concentration ≥2.6 ng/mL], and placental lesions consistent with acute AF infection (acute histologic chorioamnionitis and/or acute funisitis) were examined according to the results of AF cultivation and PCR/ESI-MS as well as AF IL-6 concentrations. RESULTS: 1) Culture identified bacteria in AF from 46% (21/46) of the participants, whereas PCR/ESI-MS was positive for microorganisms in 59% (27/46) ­ combining these two tests, microorganisms were detected in 61% (28/46) of patients with clinical chorioamnionitis at term. Eight patients had discordant test results; one had a positive culture and negative PCR/ESI-MS result, whereas seven patients had positive PCR/ESI-MS results and negative cultures. 2) Ureaplasma urealyticum (n=8) and Gardnerella vaginalis (n=10) were the microorganisms most frequently identified by cultivation and PCR/ESI-MS, respectively. 3) When combining the results of AF culture, PCR/ESI-MS and AF IL-6 concentrations, 15% (7/46) of patients did not have intra-amniotic inflammation or infection, 6.5% (3/46) had only MIAC, 54% (25/46) had microbial-associated intra-amniotic inflammation, and 24% (11/46) had intra-amniotic inflammation without detectable microorganisms. 4) Placental lesions consistent with acute AF infection were significantly more frequent in patients with microbial-associated intra-amniotic inflammation than in those without intra-amniotic inflammation [70.8% (17/24) vs. 28.6% (2/7); P=0.04]. CONCLUSION: Microorganisms in the AF were identified in 61% of patients with clinical chorioamnionitis at term; 54% had microbial-associated intra-amniotic inflammation, whereas 24% had intra-amniotic inflammation without detectable microorganisms.

Comparison of severity-of-illness scores in critically ill obstetric patients: a 6-year retrospective cohort.

OBJECTIVE: The purpose of this research was to evaluate the discrimination and calibration of mortality prediction of Simplified Acute Physiology Score 2, Simplified Acute Physiology Score 3, Mortality Probability Model II, and Mortality Probability Model III in peripartum women. DESIGN: A retrospective cohort study. SETTING: Rafael Calvo Maternity Hospital, a large teaching hospital in Cartagena (Colombia). PATIENTS: All obstetric patients admitted to the ICU from 2006 to 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Seven hundred twenty-six obstetric critical care patients were included. All scores showed good discrimination (area under the receiver operator characteristic curve > 0.86). Simplified Acute Physiology Score 2, Simplified Acute Physiology Score 3, and Mortality Probability Model III inaccurately estimated mortality. The only mortality prediction score that showed good calibration through mortality ratio and Hosmer-Lemeshow test was Mortality Probability Model II. Mortality ratio for Mortality Probability Model II was 0.88 (95% CI, 0.60-1.25). Hosmer-Lemeshow test was not significant (p = 0.571). CONCLUSIONS: Simplified Acute Physiology Score 2 and Simplified Acute Physiology Score 3 overestimate mortality in obstetric critical care patients. Mortality Probability Model III was inadequately calibrated. Mortality Probability Model II showed good fit to predict mortality in a developing country setting. Future studies in developed and developing countries are needed to further confirm our findings.

The peripheral whole-blood transcriptome of acute pyelonephritis in human pregnancya.

OBJECTIVE: Human pregnancy is characterized by activation of the innate immune response and suppression of adaptive immunity. The former is thought to provide protection against infection for the mother, and the latter, tolerance against paternal antigens expressed in fetal cells. Acute pyelonephritis is associated with an increased risk of acute respiratory distress syndrome and sepsis in pregnant (vs. nonpregnant) women. The objective of this study was to describe the gene expression profile (transcriptome) of maternal whole blood in acute pyelonephritis. METHOD: A case-control study was conducted to include pregnant women with acute pyelonephritis (n=15) and women with a normal pregnancy (n=34). Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA, USA) were used for gene expression profiling. A linear model was used to test the association between the presence of pyelonephritis and gene expression levels while controlling for white blood cell count and gestational age. A fold change of 1.5 was considered significant at a false discovery rate of 0.1. A subset of differentially expressed genes (n=56) was tested with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (cases, n=19; controls, n=59). Gene ontology and pathway analyses were applied. RESULTS: A total of 983 genes were differentially expressed in acute pyelonephritis: 457 were upregulated and 526 were downregulated. Significant enrichment of 300 biological processes and 63 molecular functions was found in pyelonephritis. Significantly impacted pathways in pyelonephritis included (a) cytokine-cytokine receptor interaction, (b) T-cell receptor signaling, (c) Jak-STAT signaling, and (d) complement and coagulation cascades. Of 56 genes tested by qRT-PCR, 48 (85.7%) had confirmation of differential expression. CONCLUSION: This is the first study of the transcriptomic signature of whole blood in pregnant women with acute pyelonephritis. Acute infection during pregnancy is associated with the increased expression of genes involved in innate immunity and the decreased expression of genes involved in lymphocyte function.

Prenatal Diagnosis of a Right Atrial Appendage Aneurysm: Case Report and Review of the Literature.

Introduction Congenital malformations of the right atrium are rare heart defects with only a few cases described prenatally. Early diagnosis of these anomalies is becoming increasingly important for proper follow-up and due to the possibility of serious complications such as supraventricular arrhythmia, thromboembolic events, and sudden death. Objective The atrial appendage aneurysm (AAA) is a dilatation of the atrial appendage. It is considered an extremely rare congenital anomaly. However, this condition is clinically significant because it leads to atrial arrhythmias, recurrent emboli, heart failure, and chest pain. In addition, it is possible to recognize AAA prenatally with fetal echocardiography, even if it rarely happens. However, few fetal AAA cases have been reported in the literature. Study Design We report a case of a fetal AAA; diagnosed prenatally and with postnatal confirmation. We undertook a systematic review of studies on fetal AAA to synthesize available knowledge on diagnosing and managing this rare condition. Results A total of eight studies describing 24 patients were identified and analyzed. Conclusion Despite their rarity, fetal atrial appendage aneurysms necessitate early detect on due to associated severe complications. Our findings emphasize the importance of prenatal diagnosis through fetal echocardiography and highlight the need for further research to optimize management strategies and improve outcomes for affected individuals.

Global health systems strengthening: FIGO's strategic view on reducing maternal and newborn mortality worldwide.

OBJECTIVE: To demonstrate that successful health systems strengthening (HSS) projects have addressed disparities and inequities in maternal and perinatal care in low-income countries. METHODS: A comprehensive literature review covered the period between 1980 and 2022, focusing on successful HSS interventions within health systems' seven core components that improved maternal and perinatal care. RESULTS: The findings highlight the importance of integrating quality interventions into robust health systems, as this has been shown to reduce maternal and newborn mortality. However, several challenges, including service delivery gaps, poor data use, and funding deficits, continue to hinder the delivery of quality care. To improve maternal and newborn health outcomes, a comprehensive HSS strategy is essential, which should include infrastructure enhancement, workforce skill development, access to essential medicines, and active community engagement. CONCLUSION: Effective health systems, leadership, and community engagement are crucial for a comprehensive HSS approach to catalyze progress toward universal health coverage and global improvements in maternal and newborn health.

A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix.

Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and is the most important challenge to modern obstetrics. A major obstacle has been that preterm birth is treated (implicitly or explicitly) as a single condition. Two thirds of preterm births occur after the spontaneous onset of labor, and the remaining one third after "indicated" preterm birth; however, the causes of spontaneous preterm labor and "indicated" preterm birth are different. Spontaneous preterm birth is a syndrome caused by multiple etiologies, one of which is a decline in progesterone action, which induces cervical ripening. A sonographic short cervix (identified in the midtrimester) is a powerful predictor of spontaneous preterm delivery. Randomized clinical trials and individual patient meta-analyses have shown that vaginal progesterone reduces the rate of preterm delivery at <33 weeks of gestation by 44%, along with the rate of admission to the neonatal intensive care unit, respiratory distress syndrome, requirement for mechanical ventilation, and composite neonatal morbidity/mortality score. There is no evidence that 17-α-hydroxyprogesterone caproate can reduce the rate of preterm delivery in women with a short cervix, and therefore, the compound of choice is natural progesterone (not the synthetic progestin). Routine assessment of the risk of preterm birth with cervical ultrasound coupled with vaginal progesterone for women with a short cervix is cost-effective, and the implementation of such a policy is urgently needed. Vaginal progesterone is as effective as cervical cerclage in reducing the rate of preterm delivery in women with a singleton gestation, history of preterm birth, and a short cervix (<25 mm).

Differences and similarities in the transcriptional profile of peripheral whole blood in early and late-onset preeclampsia: insights into the molecular basis of the phenotype of preeclampsiaa.

OBJECTIVE: Preeclampsia (PE) can be sub-divided into early- and late-onset phenotypes. The pathogenesis of these two phenotypes has not been elucidated. To gain insight into the mechanisms of disease, the transcriptional profiles of whole blood from women with early- and late-onset PE were examined. METHODS: A cross-sectional study was conducted to include women with: i) early-onset PE (diagnosed prior to 34 weeks, n=25); ii) late-onset PE (after 34 weeks, n=47); and iii) uncomplicated pregnancy (n=61). Microarray analysis of mRNA expression in peripheral whole blood was undertaken using Affymetrix microarrays. Differential gene expression was evaluated using a moderated t-test (false discovery rate <0.1 and fold change >1.5), adjusting for maternal white blood cell count and gestational age. Validation by real-time qRT-PCR was performed in a larger sample size [early PE (n=31), late PE (n=72) and controls (n=99)] in all differentially expressed genes. Gene ontology analysis and pathway analysis were performed. RESULTS: i) 43 and 28 genes were differentially expressed in early- and late-onset PE compared to the control group, respectively; ii) qRT-PCR confirmed the microarray results for early and late-onset PE in 77% (33/43) and 71% (20/28) of genes, respectively; iii) 20 genes that are involved in coagulation (SERPINI2), immune regulation (VSIG4, CD24), developmental process (H19) and inflammation (S100A10) were differentially expressed in early-onset PE alone. In contrast, only seven genes that encoded proteins involved in innate immunity (LTF, ELANE) and cell-to-cell recognition in the nervous system (CNTNAP3) were differentially expressed in late-onset PE alone. Thirteen genes that encode proteins involved in host defense (DEFA4, BPI, CTSG, LCN2), tight junctions in blood-brain barrier (EMP1) and liver regeneration (ECT2) were differentially expressed in both early- and late-onset PE. CONCLUSION: Early- and late-onset PE are characterized by a common signature in the transcriptional profile of whole blood. A small set of genes were differentially regulated in early- and late-onset PE. Future studies of the biological function, expression timetable and protein expression of these genes may provide insight into the pathophysiology of PE.

Coronavirus Disease-2019 in Pregnancy.

Coronavirus disease-2019 (COVID-19) infection during pregnancy is associated with severe complications and adverse effects for the mother, the fetus, and the neonate. The frequency of these outcomes varies according to the region, the gestational age, and the presence of comorbidities. Many COVID-19 interventions, including oxygen therapy, high-flow nasal cannula, and invasive mechanical ventilation, are challenging and require understanding physiologic adaptations of pregnancy. Vaccination is safe during pregnancy and lactation and constitutes the most important intervention to reduce severe disease and complications.

Maternal and perinatal health among pregnant patients in the context of a migratory crisis.

OBJECTIVE: To compare maternal and perinatal outcomes of migrant Venezuelan women with local pregnant patients in a Colombian institution in the context of a migratory crisis. STUDY DESIGN: This cross-sectional study included 11 304 deliveries from the Clínica de Maternidad Rafael Calvo in Cartagena de Indias, Colombia, a tertiary referral center on the north coast of Colombia. Data on maternal demographics and perinatal outcomes were obtained by chart review. RESULTS: In total, 595 patients were identified as Venezuelan migrants, and their perinatal outcomes were compared against those of 10 709 local pregnant patients. Despite similar baseline maternal conditions in both groups, poorer prenatal follow-up care (3 [1-5] vs. 5 [4-7] visits; P < 0.001) and severe complications were more common in Venezuelan migrant pregnant patients and their children. In addition, maternal hypertension was significantly more common in migrants (11.4% [68/595] vs. 8.3% [887/10709]; P = 0.009). Furthermore, in the group of pregnant migrant patients, the rates of severe maternal morbidity (13.4% [80/575] vs. 9.45%, [1013/10709]; P = 0.002), neonatal respiratory distress syndrome (22/595 [3.7%] vs. 237/10709 [2.23%]; P = 0.03), and perinatal mortality (11/586 [1.88%] vs. 67/10651 [0.63%]; P = 0.003) were significantly higher than in the local pregnant population. CONCLUSION: Forced migration during pregnancy may be associated with poorer prenatal care, which may predispose women and their newborns to more frequent adverse maternal and perinatal outcomes.

Similarity network fusion to identify phenotypes of small-for-gestational-age fetuses.

Fetal growth restriction (FGR) affects 5-10% of pregnancies, is the largest contributor to fetal death, and can have long-term consequences for the child. Implementation of a standard clinical classification system is hampered by the multiphenotypic spectrum of small fetuses with substantial differences in perinatal risks. Machine learning and multiomics data can potentially revolutionize clinical decision-making in FGR by identifying new phenotypes. Herein, we describe a cluster analysis of FGR based on an unbiased machine-learning method. Our results confirm the existence of two subtypes of human FGR with distinct molecular and clinical features based on multiomic analysis. In addition, we demonstrated that clusters generated by machine learning significantly outperform single data subtype analysis and biologically support the current clinical classification in predicting adverse maternal and neonatal outcomes. Our approach can aid in the refinement of clinical classification systems for FGR supported by molecular and clinical signatures.

Performance of the INTERGROWTH-21st and World Health Organization fetal growth charts for the detection of small-for-gestational age neonates in Latin America.

OBJECTIVE: To evaluate the performance of INTERGROWTH-21st (IG-21st ) and World Health Organization (WHO) fetal growth charts to identify small-for-gestational-age (SGA) and fetal growth restriction (FGR) neonates, as well as their specific risks for adverse neonatal outcomes. METHODS: Multicenter cross-sectional study including 67 968 live births from 10 maternity units across four Latin American countries. According to each standard, neonates were classified as SGA and FGR (birth weight <10th and less than third centiles, respectively). The relative risk (RR) and diagnostic performance for a low APGAR score and low ponderal index were calculated for each standard. RESULTS: WHO charts identified more neonates as SGA than IG-21st (13.9% vs 7%, respectively). Neonates classified as having FGR by both standards had the highest RR for a low APGAR (RR, 5.57 [95% confidence interval (CI), 3.99-7.78]), followed by those who were SGA by both curves (RR, 3.27 [95% CI, 2.52-4.24]), while neonates with SGA identified by WHO alone did not have an additional risk (RR, 0.87 [95% CI, 0.55-1.39]). Furthermore, the diagnostic odds ratio for a low APGAR was higher when IG-21st was used. CONCLUSION: In a population from Latin America, the WHO charts seem to identify more SGA neonates, but the diagnostic performance of the IG-21st charts for low APGAR score and low ponderal index is better.

The Interplay between Pathophysiological Pathways in Early-Onset Severe Preeclampsia Unveiled by Metabolomics.

INTRODUCTION: Preeclampsia is a multi-system disorder unique to pregnancy responsible for a great part of maternal and perinatal morbidity and mortality. The precise pathogenesis of this complex disorder is still unrevealed. METHODS: We examined the pathophysiological pathways involved in early-onset preeclampsia, a specific subgroup representing its most severe presentation, using LC-MS/MS metabolomic analysis based on multi-level extraction of lipids and small metabolites from maternal blood samples, collected at the time of diagnosis from 14 preeclamptic and six matched healthy pregnancies. Statistical analysis comprised multivariate and univariate approaches with the application of over representation analysis to identify differential pathways. RESULTS: A clear difference between preeclamptic and control pregnancies was observed in principal component analysis. Supervised multivariate analysis using orthogonal partial least square discriminant analysis provided a robust model with goodness of fit (R2X = 0.91, p = 0.002) and predictive ability (Q2Y = 0.72, p < 0.001). Finally, univariate analysis followed by 5% false discovery rate correction indicated 82 metabolites significantly altered, corresponding to six overrepresented pathways: (1) aminoacyl-tRNA biosynthesis; (2) arginine biosynthesis; (3) alanine, aspartate and glutamate metabolism; (4) D-glutamine and D-glutamate metabolism; (5) arginine and proline metabolism; and (6) histidine metabolism. CONCLUSION: Metabolomic analysis focusing specifically on the early-onset severe form of preeclampsia reveals the interplay between pathophysiological pathways involved in this form. Future studies are required to explore new therapeutic approaches targeting these altered metabolic pathways in early-onset preeclampsia.

Postnatal persistence of cardiac remodeling and dysfunction in late fetal growth restriction.

Fetal growth restriction is one of the most common obstetric complications, affecting 7-10% of all pregnancies. Affected fetuses are exposed to an adverse environment in utero during a critical time of development and may face long-term health consequences such as increased cardiovascular risk in adulthood. Growth restricted fetuses develop remodeled hearts with signs of systolic and diastolic dysfunction. Cardiac adaptations are more evident in early severe cases, but also present in late onset fetal growth restriction. Cardiovascular remodeling persists into postnatal life, from the neonatal period to adolescence, encompassing an increased susceptibility to adult disease. In this review, we summarize the current evidence on cardiovascular programming associated to fetal growth restriction, its postnatal consequences and potential strategies to reduce their cardiovascular risk.