The immune system of neonates is immature and therefore knowledge of possible early-life protection against SARS-CoV-2 infection, such as breastfeeding, is of great importance. Few studies have investigated the presence and duration of SARS-CoV-2 antibodies in breastmilk in relation to the trimester of maternal infection during pregnancy, and none with successful participation from all three trimesters. This study has dual objectives (1) in relation to the trimester of infection to examine the frequency, concentration and duration of IgA and IgG antibodies in breastmilk and blood serum in the third and sixth month post-partum in former SARS-CoV-2-infected mothers and (2) to examine the association in pediatric emergency admission of children within the first six months of life compared to children of non-SARS-CoV-2-infected women. The first objective is based on a prospective cohort and the second is based on a nested case–control design. The study participants are women with a former SARS-CoV-2 infection during pregnancy, whose serology IgG tests at delivery were still positive. Maternal blood and breastmilk samples were collected at three and six months postpartum. Serum IgA frequency three months pp was 72.7% (50%, 90% and 60% in the first, second and third trimester) and 82% six months pp (67%, 91% and 82% in the first, second and third trimester). Breastmilk IgA frequency three months pp was 27% (16.6%, 36% and 20% in first, second and third trimester) and 28% six months pp (0%, 38% and 28% in the first, second and third trimester). The highest IgA concentration in breastmilk was found six months post-partum with infection in the third trimester. Serum IgA was detectable more than 400 days post infection, and serum IgG above threshold was found 430 days after date of infection. We found no correlation between serum IgA and breastmilk IgA, nor between serum IgG and breastmilk IgA regardless of the trimester of infection.
Recurrent pregnancy loss is characterized by three or more consecutive pregnancy losses. Although the causes of recurrent pregnancy loss are often unknown, chromosomal defects and fetal anomalies account for a significant proportion of cases. Previous research has primarily focused on maternal factors, but recent attention has shifted to the role of male lifestyle factors.
Abstract Background Pregnancy is a complex biological process and serious complications can arise when the delicate balance between the maternal immune system and the semi-allogeneic fetal immune system is disrupted or challenged. Gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth, and low birth weight, pose serious threats to maternal and fetal health. Identification of early biomarkers through an in-depth understanding of molecular mechanisms is critical for early intervention. Methods We analyzed the associations between 47 proteins involved in inflammation, chemotaxis, angiogenesis, and immune system regulation, maternal and neonatal health outcomes, and the baseline characteristics and pre-existing conditions (diseases and obstetric history) of the mother in a prospective cohort of 1,049 pregnant women around the 20th gestational week. Bayesian linear regression models were used to examine the impact of risk factors on biomarker levels and Bayesian cause-specific parametric proportional hazards models were used to analyze the effect of biomarkers on maternal and neonatal health outcomes. Finally, we evaluated the predictive value of baseline characteristics and the 47 proteins using machine-learning models. Shapley additive explanation (SHAP) scores were used to dissect the machine learning models to identify biomarkers most important for predictions. Results Associations were identified between specific inflammatory markers and existing conditions, including maternal age and pre-pregnancy BMI, chronic diseases, complications from prior pregnancies, and COVID-19 exposure. Smoking during pregnancy significantly affected GM-CSF and 9 other biomarkers. Distinct biomarker patterns were observed for different ethnicities. In obstetric complications, IL-6 inversely correlated with pre-eclampsia risk, while acute cesarean section and birth weight to gestational age ratio were linked to markers such as VEGF or PlGF. GDM was associated with IL-1RA, IL-17D, and Eotaxin-3. Severe PPH correlated with CRP and proteins of the IL-17 family. Predictive modeling using MSD biomarkers yielded ROC-AUC values of 0.708 and 0.672 for GDM and pre-eclampsia, respectively. Significant predictive biomarkers for GDM included IL-1RA and Eotaxin-3, while pre-eclampsia prediction yielded highest predictions when including MIP-1β, IL-1RA, and IL-12p70. Conclusion Our study provides novel insights into the interplay between preexisting conditions and immune dysregulation in pregnancy. These findings contribute to our understanding of the pathophysiology of obstetric complications and the identification of novel biomarkers for early intervention(s) to improve maternal and fetal health.
Per- and polyfluoroalkyl substances (PFAS) are a group of thousands of highly persistent anthropogenic chemicals widely used in many industries. Therefore, they are, ubiquitously present in various types of environments. Despite their omnipresence, ecotoxicological studies of most PFAS are scarce, and those available often assess the effects of long chain PFAS. In this study, we present the results of an exposure experiment in which wild aquatic amphipod Gammarus spp. was exposed to the short chain perfluorinated substance perfluorobutanoic acid (PFBA) at very low and environmentally relevant concentrations of 0, 10 and 100 ng/L. The exposure lasted for 12 days, and food intake and non-reproductive behavior were analyzed. Exposure to 10 and 100 ng/L PFBA resulted in a lower consumption of food during exposure but no effect on behavior was found.
Abstract Background Pregnancy is a complex biological process and serious complications can arise when the delicate balance between the maternal and semi-allogeneic fetal immune systems is disrupted or challenged. Gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth, and low birth weight pose serious threats to maternal and fetal health. Identification of early biomarkers through an in-depth understanding of molecular mechanisms is critical for early intervention. Methods We analyzed the associations between 47 proteins involved in inflammation, chemotaxis, angiogenesis, and immune system regulation, maternal and neonatal health outcomes, and the baseline characteristics and pre-existing conditions of the mother in a prospective cohort of 1049 pregnant women around the 20th gestational week. We used Bayesian linear regression models to examine the impact of risk factors on biomarker levels and Bayesian cause-specific parametric proportional hazards models to analyze the effect of biomarkers on maternal and neonatal outcomes. We evaluated the predictive value of baseline characteristics and 47 proteins using machine-learning models and identified the most predictive biomarkers using Shapley additive explanation scores. Results Associations were identified between specific inflammatory markers and several conditions, including maternal age and pre-pregnancy body mass index, chronic diseases, complications from prior pregnancies, and COVID-19 exposure. Smoking during pregnancy affected GM-CSF and 9 other biomarkers. Distinct biomarker patterns were observed for different ethnicities. Within obstetric complications, IL-6 inversely correlated with pre-eclampsia risk, while birth weight to gestational age ratio was linked to markers including VEGF and PlGF. GDM was associated with IL-1RA, IL-17D, and eotaxin-3. Severe postpartum hemorrhage correlated with CRP, IL-13, and proteins of the IL-17 family. Predictive modeling yielded area under the receiver operating characteristic curve values of 0.708 and 0.672 for GDM and pre-eclampsia, respectively. Significant predictive biomarkers for GDM included IL-1RA and eotaxin-3, while pre-eclampsia prediction yielded the highest predictions when including MIP-1β, IL-1RA, and IL-12p70. Conclusions Our study provides novel insights into the interplay between preexisting conditions and immune dysregulation in pregnancy. These findings contribute to our understanding of the pathophysiology of obstetric complications and the identification of novel biomarkers for early intervention(s) to improve maternal and fetal health.
Intrauterine growth restriction (IUGR) is a potential complication associated with maternal SARS-CoV-2 infection. Danish guidelines recommend ultrasound follow-up from gestational age (GA) 24+0 in SARS-CoV-2-positive pregnant women who experience reduced fetal movements. This is a case report of severe IUGR (-51%) after maternal infection at GA 22+1 in a healthy unvaccinated 28-year-old woman. Positive PCR-tests for SARS-CoV-2 from placenta and child, along with massive placental inflammatory findings, suggested IUGR caused by maternal infection. This implies that follow-up from earlier GA may be warranted.
Microtubules can regulate GPCR (G protein–coupled receptor) signaling in various cell types. In vascular smooth muscle, activation of the β-adrenoceptor leads to production of cAMP to mediate a vasorelaxation. Little is known about the role of microtubules in smooth muscle, and given the importance of this pathway in vascular smooth muscle cells, we investigated the role of microtubule stability on β-adrenoceptor signaling in rat renal and mesenteric arteries. In isometric tension experiments, incubation with the microtubule inhibitors colchicine and nocodazole enhanced isoprenaline-mediated relaxations of renal and mesenteric arteries that the microtubule stabilizer, paclitaxel, prevented. Sharp microelectrode experiments showed that colchicine treatment caused increased hyperpolarization of mesenteric artery segments in response to isoprenaline. Application of the Kv7 channel blocker, XE991, attenuated the effect of colchicine on isoprenaline relaxations, whereas iberiotoxin—a BKCa channel blocker—had no effect. In addition, colchicine improved the relaxations to the Kv7.2 to 7.5 activator, S-1, in both renal and mesenteric artery segments compared with dimethyl sulfoxide incubation. We determined that increased mesenteric artery myocytes treated with colchicine showed increased Kv7.4 membrane expression, but Western blot analysis showed no change in total Kv7.4 protein. This study is the first to show microtubule disruption improves the β-adrenoceptor–mediated relaxations of mesenteric and renal arteries and determine this enhancement to be because of increased membrane expression of the Kv7 voltage-gated potassium channels.
