Maternal Inflammatory Response Research Articles

Linoleic acid and linoleate diols in neonatal cord blood influence birth weight.

BackgroundLow-birth-weight infants exhibit a high risk for postnatal morbidity. Cytochrome P450 (CYP) and epoxide hydrolase (EH) are involved in the metabolism of factors responsible for low-birth-weight in infants. Both CYPs and EHs have high substrate specificity and are involved in polyunsaturated fatty acid (PUFA) metabolism. The CYP pathway produces epoxy fatty acids (EpFAs), which are further degraded by soluble EH (sEH). Additionally, sEH inhibition enhances the action of EpFAs and suppresses inflammatory responses. During pregnancy, excessive activation of maternal inflammatory response is a significant factor associated with low-birth-weight. However, the association of EpFAs, which have potential anti-inflammatory properties, with the low-birth-weight of infants remains uninvestigated. This study aimed to clarify the association between the umbilical cord serum EpFA and low-birth-weight using data obtained from the Hamamatsu Birth Cohort for Mothers and Children (HBC Study) by analyzing the umbilical cord blood samples.MethodWe selected a subgroup of 200 infants (106 boys and 94 girls), quantified EpFA concentration in their cord blood samples collected at birth, and examined its correlation with birth weight.ResultsThe comparison between the low-birth-weight and normal-birth-weight groups revealed no significant correlation between PUFA and EpFA concentrations, but a significant correlation was observed in the linoleate diol concentrations of the two groups. Furthermore, birth weight did not significantly correlate with PUFA, EpFA, and diol concentrations in cord blood; however, multiple regression analysis showed a significant negative correlation of birth weight with the concentration of linoleic acid (LA) (r = −0.101, p = 0.016) as well as LA-derived dihydroxyoctadecenoic acid (diHOME) (r = −0.126, p = 0.007), 9,10-diHOME (r = −0.115, p = 0.014), and 12,13-diHOME (r = −0.126, p = 0.007) after adjusting for obstetric factors, including gestational age, infant’s sex, childbirth history, delivery method, and maternal height.ConclusionsBirth weight was significantly correlated with the concentration of LA and linoleate diol diHOME after adjusting for obstetric confounders. Our results show that CYP and sEH involved in PUFA metabolism may influence the birth weight of infants. Further validation is needed to provide insights regarding maternal intervention strategies required to avoid low-birth-weight in infants in the future.

Intrauterine Ureaplasma is associated with small airway obstruction in extremely preterm infants.

The long-term follow-up of lung function (LF) in extremely preterm (EP) infants with bronchopulmonary dysplasia (BPD) has shown a worldwide increase in small airway obstructions (SAO). We investigated the relationships between intrauterine Ureplasma infection in EP infants and bubbly/cystic lung, BPD, and SAO at school age. Placental pathology, placental Ureaplasma DNA (pU-DNA), and cord blood immunoglobulin M (IgM) (C-IgM) were investigated in 360 EP infants born from 1981 to 2004. Maternal amniotic inflammatory response (M-AIR) scores and hemosiderin deposition (HD) were estimated in the chorioamnion. The study subjects were divided into groups based on their M-AIR scores. Their LF at school age was compared with those of 33 healthy siblings. pU-DNA and C-IgM were significantly related to SAO at school age (p < 0.012). M-AIR score 3 and pU-DNA >1000 units had an odds ratio (OR) of 35 (95% confidence interval: 10-172) and 18 (5.6-67) for bubbly/cystic lung, and 11 (3.1 - 43) and 31 (4.5-349) for severe BPD, and 5.3 (2.1-11) and 12 (2.4-74) for SAO, respectively. The ORs of surfactant treatment, BPD grade III, O2 at 40 weeks, HD, and C-IgM >30 mg/dl for SAO were 0.21 (0.075-0.58), 5.3 (2.1-15), 2.5 (1.4-4.6), 3.6 (1.5-9.1) and 2.5 (1.0-5.2). 84% (90/107) SAO infants showed no or mild BPD in infancy, and 61% of infants had no severe CAM. Our long-term cohort study of LF in EP infants revealed that intrauterine Ureaplasma was associated with bubbly/cystic lung, severe BPD, and SAO at school age.

Association between Chorioamnionitis Severity and Procalcitonin Levels in Umbilical Venous Blood

Background: Procalcitonin can effectively differentiate between bacterial sepsis and a systemic inflammatory response syndrome of noninfectious origins in the adult. However, the usefulness of procalcitonin in perinatal field is not determined. Thus, the purpose of this study was to determine whether procalcitonin levels in the umbilical blood reflect the severity of chorioamnionitis and to assess their correlation with perinatal outcomes. Methods: A retrospective study was conducted in 145 pregnant women with singleton pregnancies and their neonates at a tertiary center between September 2010 and March 2013. Procalcitonin levels in the umbilical blood were measured by an immunoluminometric assay. The severity of chorioamnionitis was classified by the histological stage and grade for maternal and fetal inflammatory responses. Procalcitonin levels were evaluated according to the severity of chorioamnionitis; and the association with neonatal sepsis, intraventricular hemorrhage (IVH), neonatal death within 28 days of life, and periventricular leukomalacia was investigated. Results: In total, 28 women (19%) had chorioamnionitis, of which 21 (75%) delivered at less than 34 weeks of gestation. Fetal response in those with chorioamnionitis was correlated with maternal response. Procalcitonin levels in the group with fetal stage 2 and 3 or grade 2 responses were significantly higher than those infants with any other stage or grade. The frequency of neonatal sepsis, IVH stage III or IV, and neonatal death significantly increased (p &lt; 0.01), when a Procalcitonin level of ≥2 ng/mL was obtained. Conclusions: Procalcitonin levels in the umbilical blood reflect the severity of chorioamnionitis and are associated with neonatal outcomes such as neonatal sepsis, neonatal death, and severe IVH. When PCT level in umbilical venous blood show the high value of ≥2 ng/mL, it might be required that antibiotics therapy is initiated immediately after birth.

O-189 The effect of endometriosis on placental histopathology and perinatal outcome in singleton live births resulting from in vitro fertilization

Abstract Study question Does endometriosis have an effect on the placental histopathology patterns in singleton live births resulting from in-vitro fertilization? Summary answer Endometriosis is associated with acute chorioamnionitis, placenta previa, subchorionic fibrin deposition, intervillous thrombosis, fetal vascular malperfusion, as well as with failed labour induction. What is known already Endometriosis is a common chronic benign disease that affects reproductive age women and causes chronic pelvic pain and infertility. The effect of endometriosis on the reproduction and perinatal outcomes may be explained by the impact on the implantation decreasing the pregnancy rate and by causing abnormal placentation. Suboptimal placentation in the presence of endometriosis was previously explained by the altered uterine contractility, increased progesterone resistance, increased secretion of interleukins, and chronic inflammation. However, the spectrum of certain anatomical, inflammation, vascular, and villous maturation features of placentas introduced by the presence of endometriosis has not been previously evaluated. Study design, size, duration We conducted a retrospective analysis of all live births following IVF treatment during 2009-2017 from one tertiary hospital. All women with either surgically confirmed endometriosis or persistent ovarian cysts (for at least 12-weeks duration) consistent with endometriomas in ultrasound appearance were included in the endometriosis group. Placental histopathology results, obstetrical, and perinatal outcomes from pregnancies complicated by endometriosis were compared with those without signs of adenomyosis or endometriosis. Participants/materials, setting, methods Full gross and histopathology assessment of all placentas irrelevant of complication status was performed. The pathologic findings were categorized according to the Amsterdam Placental Workshop Group Consensus. The primary outcomes included anatomical, inflammation, vascular malperfusion, and villous maturation placental disorders. The secondary outcomes included fetal, maternal, perinatal, and delivery complications. A multivariate logistic model was used to adjust the results for confounding factors potentially associated with significant placental and perinatal characteristics. Main results and the role of chance A total of 1057 live births were included in the final analysis and were allocated to the group of women with endometriosis (n = 75) and without endometriosis (n = 982). Demography, obstetric history, distribution of chronic co-morbidities, the results of infertility evaluation including ovarian reserve, infertility factor, and partner’s semen parameters were similar between the groups. Placental weight, cord length as well as the prevalence of small (&amp;lt;10 percentile) and large (&amp;gt;90 percentile) placentas were also similarly distributed. After the adjustment for confounding factors endometriosis was found to be significantly associated with acute chorioamnionitis with moderate to severe maternal (OR 2.2; 95% CI 1.1–4.6) and fetal (OR 4.9; 95% CI 1.8–13.1) inflammatory response, placenta previa (OR 3.1; 95% CI 1.2–7.8), subchorionic fibrin deposition (OR 3.4; 95% CI 1.2–9.1), intervillous thrombosis (OR 3.4; 95% CI 1.5–8.1), fetal vascular malperfusion (OR 5.1; 95% CI 1.4–18.1), as well as with failed labour induction (OR 4.2; 95% CI 1.2–16.7). Limitations, reasons for caution It is possible that control group may contain some women with endometriosis who went unrecognized. However, we would expect this possibility to decrease the likelihood of significant findings when comparing the control group to women with endometriosis. This would suggest that significant findings in the endometriosis group represent real differences. Wider implications of the findings This was the first clinical study evaluating the effect of endometriosis on the placental pattern according to the Amsterdam Placental Workshop criteria. Our study demonstrates new insights into the pathophysiology of endometriosis which has an impact on the reproductive potential and pregnancy outcomes by causing abnormal placentation. Trial registration number not applicable (observation study)

Acute respiratory distress and amniotic fluid embolism in pregnancy.

Respiratory failure in pregnant and postpartum women is uncommon, but it is one of the leading causes of maternal admission into the intensive care unit and is associated with high mortality. The underlying causes include sequelae of underlying medical conditions, such as congenital heart diseases, but it is more often related to acute respiratory distress syndrome from obstetric complications like pre-eclampsia, effect of treatment like tocolysis, coincidental to pregnancy like transfusion-related acute lung injury, and accidental like amniotic fluid embolism. The pathophysiological mechanisms involved in many of these conditions remain to be clearly established, but maternal inflammatory response and activation of the immune and complement systems appear to play leading roles. Prompt recognition of maternal respiratory distress and related manifestations and aggressive and adequate supportive treatment, especially cardiopulmonary resuscitation, ventilation, maintenance of circulation, and timely termination of the pregnancy, play key roles in achieving survival of both mother and foetus.

The Impact of Maternal SARS-CoV-2 Infection Next to Pre-Immunization with Gam-COVID-Vac (Sputnik V) Vaccine on the 1-Day-Neonate’s Blood Plasma Small Non-Coding RNA Profile: A Pilot Study

The antenatal and postnatal effects of maternal SARS-CoV-2 on the fetus outcomes, especially in the case of maternal pre-vaccination against this infection, are still under investigation. Such effects may be due to placental insufficiency caused by maternal hypoxia and inflammatory response associated with SARS-CoV-2, and/or be a direct cytopathic effect of the virus. In this work, we studied the profile of small non-coding RNAs (sncRNAs) in the blood plasma of a newborn from a mother who had SARS-CoV-2 at the 22nd week of gestation after immunization with Gam-COVID-Vac (Sputnik V). The fetus had ultrasound signs of hypertrophy of the right heart and hydropericardium 4 weeks after infection of the mother with SARS-CoV-2, as well as cysts of the cerebral vascular plexuses by the time of birth. Taking this into account, we compared the sncRNA profile of this newborn on the first postpartum day with that of neonates born to COVID-19-negative women with different perinatal outcomes: severe cardiovascular and/or neurological disorders, or absence of any perinatal complications. According to next-generation sequencing data, we found that the fetus born to a COVID-19-affected mother pre-immunized with Gam-COVID-Vac (Sputnik V) vaccine differs from newborns with severe cardiovascular and/or nervous system abnormalities either in multidirectional changes in circulating sncRNAs or in less pronounced unidirectional changes in the level of sncRNAs relative to control samples. Considering this, it can be concluded that maternal vaccination against SARS-CoV-2 before pregnancy has a protective effect in preventing antenatal development of pathological processes in the cardiovascular and nervous systems of the neonate associated with COVID-19.

Does Maternal SARS-CoV-2 Infection or SARS-CoV-2 Vaccination Trigger an Inflammatory Response in the Fetus? A Prospective Cohort Study

Objectives: SARS-CoV-2 infection triggers a significant maternal inflammatory response. There is a dearth of information regarding whether maternal SARS-CoV-2 infection at admission for delivery or SARS-CoV-2 vaccination triggers an inflammatory response in the fetus. This study aims at evaluating fetal inflammatory response to maternal SARS-CoV-2 infection or SARS-CoV-2 vaccination compared to control group. Design, Participants, Setting, and Methods: A prospective cohort study was performed with a total of 61 pregnant women who presented for delivery at a single medical center (William Beaumont Hospital, Royal Oak, MI). All mothers were tested for SARS-CoV-2 infection using polymerase chain reaction (PCR) on admission to labor and delivery unit. Three groups were evaluated: 22 pregnant with a positive SARS-CoV-2 test (case group), 23 pregnant women with a negative SARS-CoV-2 test (control group), and 16 pregnant women who had recent SAR-CoV-2 vaccination and a negative SARS-CoV-2 test (vaccine group). At delivery, cord blood was collected to determine the levels of IL-6, C-reactive protein (CRP), and SARS-CoV-2 nucleocapsid IgG and IgM antibodies. In all cases, the newborn had a negative PCR test or showed no clinical findings consistent with SARS-CoV-2 infection. Results: Mean (SD) IL-6 level was not significantly different for the three groups: case group 9.00 ± 3.340 pg/mL, control group 5.19 ± 0.759 pg/mL, and vaccine group 7.11 ± 2.468 pg/mL (p value 0.855). Pairwise comparison also revealed no statistical difference for IL-6 concentrations with p values for case versus control, case versus vaccine, and control versus vaccine = 0.57, 0.91, and 0.74, respectively. Similarly, there was no statistically significant difference in the frequency of elevated IL-6 (>11 pg/mL) between groups (p value 0.89). CRP levels across the three groups were not statistically significant different (p value 0.634). Pairwise comparison of CRP levels among the different groups was also not statistically different. SARS-CoV-2 nucleocapsid IgG was positive in 12 out of 22 cord blood samples in the case group, 2 out of 23 of the control group (indicating old resolved maternal infection), and 0 out of 16 of the vaccine group. SARS-CoV-2 nucleocapsid IgM was negative in all cord blood samples of the case group, control group, and vaccine group. Limitations: A total number of 61 mothers enrolled in the study which represents a relatively small number of patients. Most patients with positive SARS-CoV-2 PCR were mainly asymptomatic. In addition, our vaccine group received the mRNA-based vaccines (mRNA1273 and BNT162b2). We did not study fetal response to other SARS-CoV-2 vaccines. Conclusion: In our prospective cohort, neither IL-6 nor CRP indicated increased inflammation in the cord blood of newborns of SARS-CoV-2-infected or vaccinated mothers.

Placental Vascular and Inflammatory Findings from Pregnancies Diagnosed with Coronavirus Disease 2019: A Systematic Review and Meta-analysis.

We aimed to perform a meta-analysis of the literature concerning histopathologic findings in the placentas of women with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection during pregnancy. Searches for articles in English included PubMed, Web of Science, Google Scholar, and reference lists (up to April 2021). Studies presenting data on placental histopathology according to the Amsterdam Consensus Group criteria in SARS-CoV-2 positive and negative pregnancies were identified. Lesions were categorized into: maternal and fetal vascular malperfusion (MVM and FVM, respectively), acute placental inflammation with maternal and fetal inflammatory response (MIR and FIR, respectively), chronic inflammatory lesions (CILs), and increased perivillous fibrin deposition (PVFD). A total of 15 studies reporting on 19,025 placentas, n = 699 of which were derived from women who were identified as being infected with SARS-CoV-2 and 18,326 as SARS-CoV-2-negative controls, were eligible for analysis. No significant difference in incidence of MVM (odds ratio [OR]: 1.18, 95% confidence interval [CI]: 0.73-1.90), FVM (OR: 1.23, 95% CI: 0.63-2.42), MIR (OR: 0.66, 95% CI: 0.29-1.52) or FIR (OR: 0.85, 95% CI: 0.44-1.63), and CILs (OR: 0.97, 95% CI: 0.55-1.72) was found between placentae from gravida identified as being SARS-CoV-2 infected. However, placenta from gravida identified as being infected with SARS-CoV-2 were associated with significantly increased occurrence of PVFD (OR: 2.77, 95% CI: 1.06-7.27). After subgroup analyses based on clinical severity of COVID-19 infection, no significant difference was observed in terms of reported placental pathology between symptomatic or asymptomatic SARS-CoV-2 gravidae placenta. Current evidence based on the available literature suggests that the only pathologic finding in the placentae of women who are pregnant identified as having been infected with SARS-CoV-2 was an increased prevalence of PVFD. KEY POINTS: · No association between SARS-CoV-2 and maternal or fetal placental malperfusion.. · No association between SARS-CoV-2 and maternal or fetal inflammatory response.. · SARS-CoV-2 is associated with increased perivillous fibrin deposition in placenta..

Association of CRP Levels in 3rd Trimester with Fetal Birth Weight in Normotensive and Preeclamptic Pregnant Females

Aim: To assess the level of C-reactive protein, which is an inflammatory marker, in pregnant women with pre-eclampsia and with normal blood pressure, and to assess its relationship with fetal weight at birth. Study design: An analytical and Cross-sectional study. Place and duration of study: In the Obstetrics and Gynecology department of Chandka Medical Hospital, Larkana and Murshid Hospital, Karachi for nine months duration from January to September 2021. Methodology: A total 70 cases of pre-eclampsia and 70 pregnant women with normal blood pressure participated, all in the 3rd trimester of gestation. All females were in the 20-40 years of age group and had a BMI ranging from 18 to 25. Highly sensitive levels of C-reactive protein (hsCRP) were evaluated using the Enzyme Link immunosorbent assay. Statistical analysis was performed with SPSS program 20.0. The values were taken as significant at the significance level of 0.05. Results: C-reactive protein levels were significantly advanced in the pre-eclampsia group with a mean value of 8.4 (0.4 to 24.2) compared to 5.1 (0.21 to 10.1) mg / L in women with normal blood pressure (p-value &lt;0.001). Spearman's correlation coefficient between birth weight and CRP was -0.405 in the pre-eclampsia group (p = 0.001) and 0.118 in the normal blood pressure group. In the group with pre-eclampsia, the birth weights of children were also significantly lower. High CRP levels in the preeclampsia group were negatively correlated with fetal birth weight. Conclusions: High levels of C-reactive protein in pregnant women with pre-eclampsia are part of the excessive systemic maternal inflammatory response and are associated with low fetal weight. Keywords: Pre-eclampsia. C-reactive protein. Pregnancy. Third trimester

Single-cell RNA sequencing reveals immunological rewiring at the maternal-fetal interface following asymptomatic/mild SARS-CoV-2 infection.

While severe coronavirus 2019 (COVID-19) is associated with immune activation at the maternal-fetal interface, responses to asymptomatic/mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain unknown. Here, we assess immunological adaptations in blood and term decidua in response to asymptomatic/mild disease in pregnant women. We report attenuated antigen presentation and type I interferon (IFN) signaling pathways, loss of tissue-resident decidual macrophages, and upregulated cytokine/chemokine signaling in monocyte-derived decidual macrophages. Furthermore, we describe increased frequencies of activated tissue-resident T cells and decreased abundance of regulatory T cells with infection while frequencies of cytotoxic CD4/CD8 T cells are increased in the blood. In contrast to decidual macrophages, type I IFN signaling is higher in decidual T cells. Finally, infection leads to a narrowing of T cell receptor diversity in both blood and decidua. Collectively, these observations indicate that asymptomatic/mild COVID-19 during pregnancy results in remodeling of the immunological landscape of the maternal-fetal interface, with a potential for long-term adverse outcomes for the offspring.

Histological severity of maternal and fetal inflammation is correlated with the prevalence of maternal clinical signs.

To evaluate whether there is a stepwise increase in the prevalence of maternal clinical signs according to the severity of histological inflammation in the chorioamniotic membranes, placenta, and umbilical cord in preterm deliveries. This retrospective study, conducted between January 2007 and May 2017, included patients with preterm delivery between 22 and 33 weeks. The histological findings of maternal/fetal inflammatory responses were staged and graded according to the Amsterdam Placental Workshop Group consensus statement. Correlations between the histological severity of maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and clinical signs were evaluated using the Cochran-Armitage trend test. A total of 138 patients were included. The stage and grade of the maternal inflammatory response were correlated with earlier gestational weeks at delivery and lighter birth weight. The prevalence of clinical chorioamnionitis was significantly correlated with a higher stage and grade of the maternal inflammatory response (Gibbs/Lencki criteria: 15.8%/15.8% in Stage 3, 16.3%/14% in Grade 2). No significant correlations were observed between gestational weeks at delivery and birth weight and stage/grade of fetal inflammatory response. The prevalence of clinical chorioamnionitis was significantly correlated with higher stage and grade of fetal inflammatory response (Gibbs/Lencki criteria: 25%/25% in Stage 3 and 29.4%/29.4% in Grade 2). Correlations exist between the severity of histological maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and positive maternal clinical signs in preterm deliveries. However, the prevalence of clinical chorioamnionitis was 20%-30% even in the most severe fetal inflammatory responses.

Gene Expression of Pregnancy Neutrophils Differs for Protease versus Lipopolysaccharide Stimulation.

Neutrophils, which extensively infiltrate maternal systemic blood vessels in preeclampsia, express protease-activated receptor 1 (PAR-1) but only during pregnancy. Neutrophils are generally considered to be non-specific in their response, but the pregnancy-specific expression of PAR-1 could result in a gene expression profile unique to pregnancy, which could help explain why the maternal inflammatory response in preeclampsia is systemic rather than localized. We sought to determine if gene expression of pregnancy neutrophils would differ if stimulated by a protease versus bacterial lipopolysaccharide (LPS). We isolated neutrophils from normal pregnant women at 30 weeks’ gestation and cultured them with elastase or LPS. We used elastase because it is a protease elevated in women with preeclampsia, and it activates pregnancy neutrophils via PAR-1. RNA was isolated from the neutrophils for sequencing of the transcriptomes. We discovered many differences in the gene expression profiles. For example, exposure to elastase resulted in three times more uniquely expressed genes than LPS, and the number of significantly differentially upregulated and downregulated genes was greater for elastase. Analysis of canonical pathways revealed similarities for innate immunity but also differences. LPS treatment enriched more pathways, but elastase activated more genes in each pathway. Elastase treatment enriched the MAPK signaling pathway, whereas LPS did not. This is significant because MAPK is a key mediator of transcriptional responses. These findings indicate that protease stimulation of pregnancy neutrophils results in a different profile than stimulation with LPS, which may help explain why the sterile inflammatory response of preeclampsia is systemic and unique to pregnancy.

Association between preeclampsia and HIV: a case-control study in urban South Africa

BACKGROUNDPreeclampsia is a considerable cause of maternal and infant morbidity and mortality. Although its etiology is unknown, preeclampsia has been described as a state of exaggerated maternal inflammatory response. Therefore, it has been hypothesized that preeclampsia would occur less commonly in states of immune deficiency.OBJECTIVEThis study aimed to compare the prevalence of treated and untreated HIV infections among preeclamptic cases and controls, determine infant outcomes, and evaluate the association between HIV and preeclampsia after adjusting for known predictor variables, including maternal age, gravidity, body mass index, and smoking.STUDY DESIGNThis case-control study investigated the association between preeclampsia and HIV infection using secondary data from an unrelated study. We defined preeclamptic cases as pregnant women who were normotensive until 20 weeks of gestation and thereafter had at least 1 high blood pressure measurement either before or at delivery and proteinuria, defined as protein excretion of ≥300 mg within 24 hours or >2 protein on dipstick urinalysis. The prevalence of HIV infection was compared between cases and controls. Multivariate logistic regression analysis was used to assess the association between preeclampsia and potential confounding variables and reported using odds ratios and 95% confidence intervals.RESULTSThere were 571 cases with preeclampsia and 596 normotensive controls included in this study. The median age was 27 years for cases and 26 years for controls (P=.008). Most participants (69%) had ≥2 previous pregnancies with no difference between the cases and controls (P=.176). Overall, 43% of the participants were obese, with a mean body mass index of 29 (interquartile range, 24.5–34.2), with higher proportions of women who were overweight and obese in the group with preeclampsia (P=.031). The prevalence of HIV was significantly lower in cases than in controls (24% vs 30%, respectively; P=.014). Compared with 16% of infants born preterm to normotensive controls, 48% of infants were born preterm born to women with preeclampsia (P<.001). Compared with 14% of infants born with low birthweight to normotensive controls, 53% of infants were born with low birthweight to women with preeclampsia (P<.0001). Untreated HIV infection was negatively associated with preeclampsia (unadjusted odds ratio, 0.330; 95% confidence interval, 0.197–0.552; P<.0001), whereas factors associated with preeclampsia were advanced maternal age (odds ratio, 1.673; 95% confidence interval, 1.209–2.316; P=.002) and obesity (odds ratio, 1.611; 95% confidence interval, 1.023–2.537; P=.040). After adjusting for maternal age, gravidity, smoking, and body mass index in the multivariate regression, only obesity remained significantly associated with preeclampsia (adjusted odds ratio, 1.624; 95% confidence interval, 1.024–2.575; P=.039).CONCLUSIONBefore the large-scale rollout of antiretroviral therapy in a setting with a high burden of HIV and preeclampsia, untreated HIV infection was found to have a protective effect against preeclampsia. The protective effect against preeclampsia was not apparent for HIV infection treated with antiretroviral therapy.

Molecular Advances in Preeclampsia and HELLP Syndrome.

Preeclampsia (PE) constitutes one of the principal reasons for maternal and perinatal morbidity and mortality worldwide. The circumstance typically implicates formerly healthful normotensive women, after 20 weeks of gestation, typically withinside the third trimester, without regarded threat elements or past deliveries. PE can be further complicated with hemolysis and thrombocytopenia, leading to the emergence of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low platelets). Both conditions are classified as hypertensive diseases of pregnancy (HDP), and their pathogenesis has been linked to an excessive maternal inflammatory response, accompanied by enhanced endothelial activation. Several studies have found that in pregnancies affected by PE/HELLP, von Willebrand factor (vWF) antigen levels (vWF:Ag) are significantly elevated, while its cleaving protease (ADAMTS-13, A Disintegrin-like and Metalloprotease with Thrombospondin type 1 motif, member 13) activity is normal to decreased. Furthermore, the higher urine excretion of the terminal complement complex C5b-9, as well as its greater deposition in the placental surface in preeclamptic women, imply that the utero-placental unit’s distinctive deficits are intimately tied to disproportionate complement activation. The goal of this updated evaluation is to provide the most up-to-date molecular advances in the pathophysiology of PE/HELLP syndromes. Recent medical data on vWF:Ag levels in patients with PE, ADAMTS-13, and dysregulation of the complement system, are highlighted and evaluated. Furthermore, we discuss the relationship between those entities and the progression of the disease, as well as their significance in the diagnostic process. Finally, considering the difficulties in analyzing and controlling those symptoms in pregnant women, we can provide a current diagnostic and therapeutic algorithm.

Acute Histological Chorioamnionitis and Birth Weight in Pregnancies With Preterm Prelabor Rupture of Membranes: A Retrospective Cohort Study.

Aim: To assess the association between the birth weight of newborns from pregnancies with preterm prelabor rupture of membranes (PPROM) and the presence of acute histological chorioamnionitis (HCA) with respect to the: i) fetal and maternal inflammatory responses and ii) acute inflammation of the amnion. Material and Methods: This retrospective cohort study included 818 women with PPROM. A histopathological examination of the placenta was performed. Fetal inflammatory response was defined as the presence of any neutrophils in umbilical cord (histological grades 1–4) and/or chorionic vasculitis (histological grade 4 for the chorionic plate). Maternal inflammatory response was defined as the presence of histological grade 3–4 for the chorion-decidua and/or grade 3 for the chorionic plate and/or grade 1–4 for the amnion. Acute inflammation of the amnion was defined as the presence of any neutrophils in the amnion (histological grade 1–4 for the amnion). Birth weights of newborns were expressed as percentiles derived from INTERGROWTH-21st standards for the i) estimated fetal weight and ii) newborn birth weight. Results: No difference in percentiles of birth weights of newborns was found among the women with the women with HCA with fetal inflammatory response, with HCA with maternal inflammatory response and those without HCA. Women with HCA with acute inflammation of the amnion had lower percentiles of birth weights of newborns, derived from the estimated fetal weight standards, than women with HCA without acute inflammation of the amnion and those with the absence of HCA in the crude (with acute inflammation: median 46, without acute inflammation: median 52, the absence of HCA: median 55; p = 0.004) and adjusted (p = 0.02) analyses. The same subset of pregnancies exhibited the highest rate of newborns with a birth weight of ≤25 percentile. When percentiles were derived from the newborn weight standards, no differences in birth weights were observed among the subgroups. Conclusion: Acute inflammation of the amnion was associated with a lower birth weight in PPROM pregnancies, expressed as percentiles derived from the estimated fetal weight standards.

Gardnerella vaginalis infection in pregnancy: Effects on placental development and neonatal outcomes.

Gardnerella vaginalis (GV)-associated bacterial vaginosis is recognised for its detrimental effects on pregnancy resulting in poor obstetric and neonatal outcomes. There is limited knowledge of the effects on placental histomorphology following GV infection in pregnancy. We investigated the effects of GV infection on the placenta, particularly with regards to the syncytiotrophoblasts and vascular development, and related these to neonatal outcomes. A prospective cohort study involving GV-positive pregnant women presented with abnormal vaginal discharge, with gestational age-matched healthy pregnant women controls. Placental sampling was performed upon delivery and examined histologically. Vascular endothelial growth factor-A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) mRNA and protein expression were analysed by real-time PCR and immunohistochemistry respectively. The standard measures in neonatal outcomes were recorded. Placentas from GV-positive mothers were found to have significant histological evidence of maternal and/or fetal inflammatory response compared with the controls (17/28: 60.7% vs 2/20: 10%) (p=0.0011). There was an increase in the percentage of syncytial nuclear aggregates (SNAs) per villus (47.4±11.09%) in placentas from GV-positive mothers (p<0.0001). VEGF-A was significantly increased in specifically, the villous endothelial cells of placentas with GV infection, but no difference in the immunoexpression of HIF-1α in these cells between groups. However, these were not associated with adverse neonatal outcomes. Increased placental VEGF-A expression associated with increased SNAs in pregnant women with GV infection of the genital tract may be an intrauterine response towards placental vascular remodeling, that may also serve as a protective role in moderating birth outcomes.

Placental pathology associated with maternal age and maternal obesity in singleton pregnancy

Objective Maternal age, maternal obesity and neonatal sex dimorphism are known to affect pregnancy and neonatal outcome. However, the effects of these factors on specific placental pathology are less well-documented. Study design Clinical information, placental pathology and neonatal data from singleton delivery were collected at our hospital in March 2020 to October 2021 and correlation studies were performed. Results A total 3,119 singleton placentas were examined between March 2020 and October 2021 in conjunction with clinical information and neonatal birth data. Advanced maternal age (>35) was significantly associated with a variety of pregnancy complications and placental pathology including preeclampsia/pregnancy induced hypertension (Pre/PIH), gestational diabetes mellitus (GDM2), intrauterine growth restriction (IUGR), and increased maternal body mass index (BMI) at delivery. Maternal obesity (BMI >30 at the time of delivery) was significantly associated with a variety of clinical features and placental pathology including PRE/PIH, GDM2 and decidual vasculopathy (mural arterial hypertrophy). No specific placental pathology was associated with neonatal sex except for more maternal inflammatory response (MIR, chronic deciduitis) in neonates of male sex. Conclusion Maternal age and maternal obesity were associated with not only clinical complications of pregnancy and neonatal birth weight but also specific placental pathology. Understanding the effects of maternal and environmental factors will help improve pregnancy outcome.

Prenatal and neonatal complications of COVID-19: A systematic review.

Background and AimsThe outbreak of coronavirus disease 2019 (COVID‐19) over the past year has affected public health worldwide. During pregnancy, the maternal immune system and inflammatory responses are widely suppressed. Pregnancy‐related immune system suppression could make the mother vulnerable to infectious diseases like SARS‐COV‐2. However, current data suggest little to no possibility of COVID‐19 transmission in pregnant women to the fetus during pregnancy or childbirth. This systematic review focused on the possible complications of COVID‐19 infection in the fetus and newborn babies including the possibility and evidence of vertical transmission by reviewing articles published during the first year of the COVID‐19 pandemic.MethodsWe conducted a systematic search using keywords on PubMed, Embase, and Scopus databases. The studies followed a title/abstract and a full‐text screening process, and the eligible articles were included in the study.ResultsIn total, 238 published papers were identified using a systematic search strategy (44 articles met the inclusion criteria and were included in the final review). In all studies, a total of 2375 women with signs and symptoms of COVID‐19, who were in the second and third trimester of pregnancy, were assessed mild to moderate pneumonia was one of the most common symptoms. Seventy‐three percent of the women did not present any comorbidity, 19% had a fever, 17% had to cough as the most frequent clinical signs and symptoms, 7.5% had pulmonary changes with chest scans, 8% had increased C reactive protein, and 9.4% had decreased lymphocytes (lymphocytopenia). A total of 2716 newborns and fetal were assessed; the delivery method of 1725 of them was reported, 913 (53%) through C‐section delivery, and 812 through normal vaginal delivery (47%). Of total newborns, 13 died (five died along with the mother), and 1965 were tested for SARS‐CoV‐2:118 tested positive. In a study, vertical transmission in seven cases was reported in total of 145 cases assessed.ConclusionIt appeared that most pregnant COVID patients were mildly ill, and there is currently no convincing evidence to support the vertical transmission of COVID‐19 disease. Therefore, neonates do not represent any additional risk for adverse outcomes neither during the prenatal period nor after birth.

Transmitted Fetal Immune Response in Cases of SARS-CoV-2 Infections during Pregnancy.

(1) Background: Little is known about the effects of SARS-CoV-2 on the placenta, and whether the maternal inflammatory response is transmitted vertically. This research aims to provide information about the effects of SARS-CoV-2 infection on maternal and fetal immunity. (2) Methods: We have studied placental changes and humoral and cellular immunity in maternal and umbilical cord blood (UCB) samples from a group of pregnant women delivering after the diagnosis of SARS-CoV-2 infection during pregnancy. IgG and IgM SARS-CoV-2 antibodies, Interleukin 1b (IL1b), Interleukin 6 (IL6), and gamma-Interferon (IFN-γ), have been studied in the UCB samples. Lymphocyte subsets were studied according to CD3, CD8, CD4, CD34, and invariant natural Killer T cells (iNKT) markers. We used in situ hybridization techniques for the detection of viral RNA in placentas. (3) Results: During the study period, 79 pregnant women and their corresponding newborns were recruited. The main gestational age at the time of delivery was 39.1 weeks (SD 1.3). We did not find traces of the SARS-CoV-2 virus RNA in any of the analyzed placental samples. Detectable concentrations of IgG anti-SARS-CoV-2 antibodies, IL1b, IL6, and IFN-γ, in UCB were found in all cases, but IgM antibodies anti-ARS-CoV-2 were systematically undetectable. We found significant correlations between fetal CD3+ mononuclear cells and UCB IgG concentrations. We also found significant correlations between UCB IgG concentrations and fetal CD3+/CD4+, as well as CD3+/CD8+ T cells subsets. We also discovered that fetal CD3+/CD8+ cell counts were significantly higher in those cases with placental infarctions. (4) Conclusion: we have not verified the placental transfer of SARS-CoV-2. However, we have discovered that a significant immune response is being transmitted to the fetus in cases of SARS-CoV-2 maternal infection.

MiR-21 differentially regulates IL-1β and IL-10 expression in human decidual cells infected with streptococcus B

Intrauterine infections caused by bacteria like group B streptococcus (GBS) and the subsequent activation of the maternal inflammatory response have been long suspected to be the underlying cause of preterm labor. The inflammatory network triggered by maternal decidua has been widely described and includes the secretion of pro- and anti-inflammatory cytokines as IL-1β and IL-10; however, the mechanisms that regulate their secretion have not been completely elucidated. MicroRNAs (miRNAs) are critical modulators of the inflammatory response by regulating cytokine expression in several cell types. Here, we explored the role of miR-21 in the expression of IL-1β and IL-10 in human decidual stromal cells (DSCs) exposed in vitro to GBS. We observed that IL1B and IL10 expression at the mRNA level was increased in DSCs after GBS infection. IL-10 but not IL-1β secretion was detected in the culture supernatants. We found a higher miR-21 expression (22-fold) in infected DSCs as compared with non-infected cells. miR-21 functional analysis revealed that DSCs transfected with an antagomiR vs. miR-21 significantly increased the secretion of IL-1β but decreased that of IL-10 in DSCs cells infected with GBS. Our results suggest that miR-21 participates in balancing the inflammatory response in infected decidua through at least IL-1β and IL-10 regulation. This is the first study attributing a functional role of miR-21 in the regulation of key molecules involved in the inflammatory response in infected DSCs, providing new insights into the epigenetic control of human decidual inflammation.