Utilisation of supplementary prenatal screening and diagnostics in Germany: cross-sectional study using data from the KUNO Kids Health Study.

BACKGROUND: Appropriate health system utilisation during pregnancy is fundamental for maintaining maternal and child's health. To study the use and determinants of supplementary prenatal screening and diagnostics in Germany this study provides comprehensive data. METHODS: We obtained data from a recently established prospective German birth cohort study, the KUNO Kids Health Study. Analyses are based on Andersen's Behavioural Model of health system use, which distinguishes between predisposing (e.g. country of birth), enabling (e.g. health insurance) and need factors (e.g. at-risk pregnancy). We examined bi- and multivariate association with the use of supplementary prenatal screening and diagnostics using logistic regression. RESULTS: The study has a sample size of 1886 participating mothers. One fifth of the mothers investigated did not use any supplementary prenatal screening or diagnostics. Notably, the chance of using supplementary prenatal screening and diagnostics more than doubled if the pregnant woman had a private health insurance (OR 2.336; 95% CI 1.527-3.573). Higher maternal age (OR 1.038; 95% CI 1.006-1.071) and environmental tobacco smoke exposure (OR 1.465 95% CI 1.071-2.004) increased the use of supplementary prenatal screening and diagnostics. However, regarding need factors only having an at-risk-pregnancy (OR 1.688; 95% CI 1.271-2.241) showed an independent association. CONCLUSION: The important role of the type of health insurance and the relatively small influence of need factors was surprising. Especially with respect to equity in accessing health care, this needs further attention.

The reproductive microbiome - clinical practice recommendations for fertility specialists.

The interest in and understanding of the human microbiome has grown remarkably over recent years. Advances in molecular techniques have allowed researchers to identify and study the microbiota and also use this information to develop therapeutic solutions for a spectrum of conditions. Alongside the growing interest in the microbiome, societal changes have resulted in many couples looking to start families later in life, therefore increasing the demand for assisted reproductive technologies. Combining these trends, it makes sense that clinicians are eager to understand and exploit the microbiome of their patients, i.e. the reproductive microbiome, in order to help them achieve their goal of becoming parents. This paper aims to provide an overview of the current and future research into the reproductive microbiome in relation to fertility and also share clinical practice recommendations for physicians who are new to this field or unsure about how they can utilise what is known to help their patients.

Variability in COVID-19 Symptom Presentation During Pregnancy and its Impact on Maternal and Infant Outcomes Across the Pandemic.

BACKGROUND: With the dominance of different SARS-CoV-2 variants, the severity of COVID-19 has evolved. We aimed to investigate the difference in symptom prevalence and the association between symptoms and adverse pregnancy outcomes during the dominance of Wild-type/Alpha, Delta, and Omicron. METHODS: COVID-19 related symptom prevalence, maternal and specific neonatal outcomes of 5431 pregnant women registered in this prospective study were compared considering the dominant virus variant. Logistic regression models analyzed the association between specific symptoms and intensive care unit (ICU) admission or preterm birth. RESULTS: Infection with the Delta variant led to an increase in the symptom burden compared to the Wild-type/Alpha variant and the highest risk for respiratory tract symptoms, feeling of sickness, headache, and dizziness/drowsiness. An infection with the Omicron variant was associated with the lowest risk of dyspnea and changes in smell/taste but the highest risk for nasal obstruction, expectoration, headaches, myalgia, and fatigue compared to the Wild-type/Alpha and Delta variant dominant periods. With the progression of the Wild-type/Alpha to the Delta variant neonatal outcomes worsened. Dyspnea and fever were strong predictors for maternal ICU admission and preterm birth independent of vaccination status or trimester of infection onset. CONCLUSION: The symptom burden increased during the Delta period and was associated with worse pregnancy outcomes than in the Wild-type/Alpha area. During the Omicron dominance there still was a high prevalence of less severe symptoms. Dyspnea and fever can predict a severe maternal illness.

Implementation of safe infant sleep recommendations during night-time sleep in the first year of life in a German birth cohort.

The aim of our study was to assess the extent to which families followed recommendations, issued by the German society for sleep medicine, for the prevention of sudden infant death syndrome (SIDS) during night-time sleep. Analyzing longitudinal data from a birth cohort located at the University Children's Hospital Regensburg in Bavaria (Germany), we determined data regarding the infant's sleep location, sleep settings and body position, and exposure to environmental factors. Data were collected in a structured interview after birth and by standardized questionnaires at 4 weeks, 6 months, and 1 year of life, respectively. The majority of 1,400 surveyed infants (94% at 4 weeks) were reported to sleep in the parents' sleeping room during the first months of life. While the most common furniture was a bedside sleeper (used by 48%), we also observed a considerable proportion of families who regularly practiced bed-sharing and, for 16% of infants, the parents' bed was the default sleeping place. 12% of infants were still put regularly in the prone position. The vast majority (87%) of the infants were breastfed at some timepoint and 17% lived in a household with one or more smokers. Although most parents implemented many SIDS recommendations, our analysis illustrates a considerable gap between recommendations and intentions after birth on the one hand and actual implementation in real life on the other. The number-one deviation from the current SIDS guidelines during night-time sleep was bed-sharing with an adult.

A prospective longitudinal cohort study: evolution of GERD symptoms during the course of pregnancy.

BACKGROUND: Symptoms of gastro-esophageal reflux disease (GERD) in pregnancy are reported with a prevalence of 30-80%. The aim of this study was to assess the prevalence and severity of GERD symptoms during the course of pregnancy. Furthermore current practice in medical care for GERD during pregnancy was assessed. METHODS: We performed a prospective longitudinal cohort study on 510 pregnant women (mean age 28.12, SD 5.3). Investigations for reflux symptoms where based on the use of validated reflux-disease questionnaire (RDQ). Additional information was collected about the therapy. A group of non-pregnant women (mean age 24.56, SD 5.7) was included as controls. Frequency and severity of reflux symptoms were recorded in each trimester of pregnancy. RESULTS: The prevalence of GERD symptoms in pregnant women increased from the first trimester with 26.1 to 36.1% in the second trimester and to 51.2% in the third trimester of pregnancy. The prevalence of GERD symptoms in the control group was 9.3%.Pregnant women received medication for their GERD symptoms in 12.8% during the first, 9.1% during the second and 15.7% during the third trimester. Medications used >90% antacids, 0% PPI. CONCLUSION: GERD symptoms occur more often in pregnant women than in non-pregnant and the frequency rises in the course of pregnancy. Medical therapy is used in a minority of cases and often with no adequate symptom relief.

Human chorionic gonadotropin attracts regulatory T cells into the fetal-maternal interface during early human pregnancy.

Regulatory T cells (Treg) expand during pregnancy and are present at the fetal-maternal interface at very early stages in pregnancy. The migration mechanisms of Treg to the pregnant uterus are still unclear. Human chorionic gonadotropin (hCG) is secreted by the blastocyst immediately after fertilization and has chemoattractant properties. Therefore, we sought to analyze whether hCG secreted by early trophoblasts attracts Treg to the uterus and hence contributes to maternal tolerance toward the fetus. Decidua and placenta tissue samples from patients having spontaneous abortions or ectopic pregnancies were employed to evaluate Treg and hCG levels. Age-matched samples from normal pregnant women served as controls. We further performed in vitro studies with primary first trimester trophoblast cells and a choriocarcinoma cell line (JEG-3) aiming to evaluate the ability of secreted hCG to attract Treg. Patients having miscarriages or ectopic pregnancy presented significantly decreased hCG mRNA and protein levels associated with decreased Foxp3, neuropilin-1, IL-10, and TGF-beta mRNA levels as compared with normal pregnant women. Using migration assays we demonstrated that Treg were attracted by hCG-producing trophoblasts or choriocarcinoma cells. Treg migration toward cells transfected with hCG expression vectors confirmed the chemoattractant ability of hCG. Our data clearly show that hCG produced by trophoblasts attracts Treg to the fetal-maternal interface. High hCG levels at very early pregnancy stages ensure Treg to migrate to the site of contact between paternal Ags and maternal immune cells and to orchestrate immune tolerance toward the fetus.

Improving Neonatal and Maternal Outcome by Inducing Mild Labor before Elective Cesarean Section: The Lacarus Randomized Controlled Trial.

BACKGROUND: Newborns delivered by elective cesarean section (CS) are at higher respiratory risk than those delivered vaginally or by CS proceeded by labor (secondary CS). The oxytocin challenge test (OCT) induces uterine contractions that trigger the release of fetal hormones regulating lung fluid clearance during transition from the uterine to an air-breathing environment. OBJECTIVES: The aim is to summarize current evidence and outline the Lacarus trial protocol. METHODS: Literature review informed the design of a randomized placebo-controlled multicenter trial of OCT preceding elective CS in 1,450 women with a singleton pregnancy due for CS at >35 weeks gestation, without preceding contractions, rupture of the membranes, or antenatal steroids. OCT comprises the infusion of oxytocin 5 IU/500 mL Ringer lactate at a rate of 12 mL/h, doubling every 10 min until inducing 5 uterine contractions per 15-min interval. The primary endpoint is the occurrence of neonatal respiratory morbidity within 24 h after birth. Secondary endpoints include biochemical and physiological parameters of fetal and maternal well-being, such as breastfeeding rate and fetal plasma copeptin concentrations. CONCLUSION: This is the first trial to test the hypothesis that oxytocin-induced contractions before elective CS is a promising application of physiologic principles gleaned from natural birth to improve neonatal and maternal outcomes.

Estradiol and progesterone regulate the migration of mast cells from the periphery to the uterus and induce their maturation and degranulation.

BACKGROUND: Mast cells (MCs) have long been suspected as important players for implantation based on the fact that their degranulation causes the release of pivotal factors, e.g., histamine, MMPs, tryptase and VEGF, which are known to be involved in the attachment and posterior invasion of the embryo into the uterus. Moreover, MC degranulation correlates with angiogenesis during pregnancy. The number of MCs in the uterus has been shown to fluctuate during menstrual cycle in human and estrus cycle in rat and mouse indicating a hormonal influence on their recruitment from the periphery to the uterus. However, the mechanisms behind MC migration to the uterus are still unknown. METHODOLOGY/PRINCIPAL FINDINGS: We first utilized migration assays to show that MCs are able to migrate to the uterus and to the fetal-maternal interface upon up-regulation of the expression of chemokine receptors by hormonal changes. By using a model of ovariectomized animals, we provide clear evidences that also in vivo, estradiol and progesterone attract MC to the uterus and further provoke their maturation and degranulation. CONCLUSION/SIGNIFICANCE: We propose that estradiol and progesterone modulate the migration of MCs from the periphery to the uterus and their degranulation, which may prepare the uterus for implantation.