Effect of mothers' health literacy on early childhood allergy prevention behaviours: results from the KUNO-Kids health study.

BACKGROUND: Parents can engage in several behaviours with regard to early childhood allergy prevention (ECAP). These can be related to diet of mother/child and the modification of the home environment; not all of them are justified by current evidence. Previous studies showed that parental health literacy (HL) is related to favourable health behaviours directed at the child. This study aimed to investigate the causal effect of mothers' HL on ECAP behaviours and to test different moderators of this effect. METHODS: One thousand six hundred sixty-two mothers participating in the KUNO-Kids health study in the area of Regensburg, Germany were surveyed on HL (assessed via the health care scale of the Health Literacy Survey-EU questionnaire, HLS-EU-Q47) and ECAP behaviours implemented during pregnancy and the child's first year of life. Patterns in ECAP behaviours were identified by latent class analysis. Multinomial regression modelling was performed with HL as exposure, ECAP as outcome variable, allergy risk, parental competence and bonding, anxiety and depression as moderators as well as potentially confounding variables. RESULTS: We identified three classes of ECAP behaviours (class 1: "breastfeeding " N = 871; class 2: "allergen-avoidance " N = 490; class 3: "mixed behaviours " N = 301). In univariable as well as fully adjusted regression models, compared to class 1, class 2 was negatively, and class 3 was not associated with HL. None of the tested moderating variables altered the association between HL and ECAP significantly. CONCLUSIONS: We found an effect of mothers' HL on ECAP behaviours: lower HL of mothers increased allergen-avoiding behaviour directed at their child, while decreasing the chance of exclusive breastfeeding. Improving HL could contribute to the implementation of recommended ECAP behaviours in families, especially to the reduction of allergen-avoiding behaviours.

Fetoscopic laser coagulation for twin-to-twin transfusion syndrome: a comparison of flexible 1.0/1.2 mm fetoscopes with curved sheaths of 2.7/3.3 mm2 vs. 2 mm fetoscopic lens technique with sheaths of 6.6/11.3 mm2.

OBJECTIVES: Fetoscopic laser coagulation of placental anastomoses is usually performed for a treatment of twin-to-twin transfusion syndrome (TTTS). A common complication of fetoscopic laser coagulation for TTTS is preterm preliminary rupture of fetal membranes (PPROM) aggravating the neonatal outcome significantly. However, use of an flexible 1 mm fetoscope with an curved sheath could reduce iatrogenic damage of the amniotic membrane and improve neonatal outcomes after laser treatment. The aim of this study was to compare neonatal outcomes using this flexible fetoscope with curved sheath vs. use of a standard lens technique. METHODS: Outcomes were retrospective analyzed after use of a standard lens fetoscope of 2 mm (sheath 6.63 mm2 or 11.27 mm2 for anterior placenta) and a flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2) in two German centers of fetal surgery, performed during 2006-2019. RESULTS: Neonatal outcome of 247 TTTS patients were analyzed including the rates of double and single fetal survival. The survival of at least one fetus was 97.2 % in the group with the ultrathin technique (n=154) compared to 88.3 % (n=93) in the group with the standard lens fetoscope (p=0.008). Survival of both fetuses was not different between groups (81.0 vs. 75.3 %). The procedure to delivery interval was significantly increased using the ultrathin fetoscope (89.1±35.0 d vs. 71.4±35.4 d, p=0.001) resulting in an increased gestational age at delivery by 11 days on average (231.9±28.1 d vs. 221.1±32.7 d, p=0.012). CONCLUSIONS: Fetal survival can be significantly increased following TTTS using flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2).

Alteration in sB7-H4 Serum Levels and Placental Biomarker Expression after Therapeutic Plasma Exchange in Early-Onset Preeclampsia Patients.

Therapeutic plasma exchange (TPE) is a widely used treatment for numerous diseases including pregnancy-related conditions. Our prior study on 20 early-onset preeclampsia patients undergoing TPE revealed a significant extension in pregnancy duration and reduced serum levels of sFlt-1, sFlt-1/PlGF, and sEndoglin. Here, we investigated the impact of TPE on serum sB7-H4, an immunological checkpoint molecule, and placental proteins (Flt-1, Eng, B7-H4, iNOS, TNF-α) in TPE-treated early-onset preeclampsia patients (N = 12, 23 + 2-28 + 5 weeks), conventionally treated counterparts (N = 12, 23 + 5-30 weeks), and gestational age-matched controls (N = 8, 22 + 4-31 + 6 weeks). Immunoblotting, ELISA, and co-immunohistochemistry were used for biomarker analysis, including placental inflammation factors (iNOS, TNF-α). The results showed that TPE extended pregnancy by a median of 6.5 days in this cohort of early-onset preeclampsia. Serum sB7-H4, sFlt-1, and sEndoglin levels decreased, along with reduced expression of their membrane-bound proteins in placental tissue upon TPE treatment. Moreover, TPE-treated patients displayed reduced placental inflammation compared to preeclampsia patients receiving standard-of-care treatment. In conclusion, TPE may improve pregnancy outcomes in early-onset preeclampsia by lowering circulating levels of sB7-H4, sFlt-1, and sEndoglin, as well as reducing placental inflammation. This translational approach holds promise for enhancing placental function and extending gestation in high-risk pregnancies including very preterm PE or HELLP cases.

Human Cord Blood B Cells Differ from the Adult Counterpart by Conserved Ig Repertoires and Accelerated Response Dynamics.

Neonatal and infant immune responses are characterized by a limited capability to generate protective Ab titers and memory B cells as seen in adults. Multiple studies support an immature or even impaired character of umbilical cord blood (UCB) B cells themselves. In this study, we provide a comprehensive molecular and functional comparison of B cell subsets from UCB and adult peripheral blood. Most UCB B cells have a mature, naive B cell phenotype as seen in adults. The UCB Ig repertoire is highly variable but interindividually conserved, as BCR clonotypes are frequently shared between neonates. Furthermore, UCB B cells show a distinct transcriptional program that confers accelerated responsiveness to stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into Ab-secreting cells, presumably limiting memory B cell formation. Humanized mice suggest that the distinctness of UCB versus adult B cells is already reflected by the developmental program of hematopoietic precursors, arguing for a layered B-1/B-2 lineage system as in mice, albeit our findings suggest only partial comparability to murine B-1 cells. Our study shows that UCB B cells are not immature or impaired but differ from their adult mature counterpart in a conserved BCR repertoire, efficient IgA class switching, and accelerated, likely transient response dynamics.

Cervical ectopic pregnancy - the first case of live birth and uterus-conserving management.

A 37-old III gravida II para with two previous cesarean sections (CS) presented in 7 + 3 weeks of pregnancy with cervical ectopic pregnancy (CEP). At 12th week of pregnancy, a cerclage was performed to avoid cervical distention by the expanding placenta. Due to missing experience in CEP management and to avoid emergency operation, we recommended CS in 30th week of pregnancy due to unspecific pain of the patient. Vaginal bleeding never occured.After transverse laparotomy, the urinary bladder was sharply dissected from the anterior uterine and cervical wall. The baby was delivered by transverse cervicotomy caudally of the placenta. The placenta was left in situ. The patient then got prophylactic embolization of the uterine arteries to prevent further severe hemorrhage. 48 h later, ultrasound showed a floating, avascular placenta within a poor echogenic fluid-filled cervical space as well as macrohematuria. After re-laparotomy and cervicotomy at the same day, the placenta was completely and easily evacuated. A bladder injury was recognized and closed. We performed a cervical internal os plasty by inverting the cervical lips and suturing their distal ends on the proximal cervical tissue, resulting in complete bleeding cessation. Although, the patient got 8 erythrocyte concentrates at all, she was always in a stable condition without hemorrhagic shock.This case demonstrates for the first time a live-birth with uterus-conserving management in CEP.

Prevalence of genital Mycoplasma in pregnancies with shortened cervix.

OBJECTIVE: To determine whether colonisation with genital Mycoplasma species (spp.) in patients presenting with a shortened cervix before 34th week of pregnancy is associated with preterm birth. METHODS: The collection of this retrospective study consisted of 100 pregnant women who presented to a German Tertiary Perinatal Center between 2017 and 2020 due to a shortened cervix defined as a cervical length of 25 mm or shorter measured by transvaginal ultrasound before 34 weeks of gestation. At the time of admission, gestational age ranged from 18 + 4 to 33 + 3 weeks (+ days) of pregnancy. All patients underwent urine polymerase chain reaction (PCR) for genital Mycoplasma [Ureaplasma (U.) urealyticum, U. parvum, M. hominis or M. genitalium]. Patients who were tested positive underwent a therapy with macrolides (azithromycin or clarithromycin). RESULTS: 37% of the patients were positive for Ureaplasma spp., whereas 5% (5 patients) were Mycoplasma spp.-positive. All the latter were simultaneously colonised with Ureaplasma spp. Ureaplasma-positive patients were significantly younger than those who were tested negative. Median maternal age at examination was 30 years (a) versus 31a (p = 0.04). There was no difference between Ureaplasma-positive and -negative patients regarding median maternal body mass index (BMI) (kg/m2) (23.4 versus 22.3, p = 0.41), cervical length at admission (mm) (15 versus 17, p = 0.17), gestational age at examination (days, d) (198 versus 197, p = 0.97) or gestational age at birth (d) (250 versus 257, p = 0.33), respectively. Comparing U. parvum-positive and U. urealyticum-positive patients, there was some weak indication that U. parvum-positive patients may get a shortening of the cervix earlier in pregnancy, as the median gestational age at examination was 196d versus 215d (p = 0.06). Regarding Mycoplasma-positive and -negative patients, there was no difference in all examined parameters. CONCLUSIONS: Overall, one-third of all women in our study with a shortened cervix before 34th week of pregnancy were colonised with genital Mycoplasma spp. We were able to show that pregnant women, who were treated with antibiotics when tested positive for genital Mycoplasma, gave birth at the same gestational age as patients with a shortened cervix without detected Mycoplasma. This raises the question of whether routine testing and early antibiotic treatment should be established in prenatal care.

Food allergy in infants assessed in two German birth cohorts 10 years after the EuroPrevall Study.

BACKGROUND: The prevalence of food allergies (FA) in children increased rapidly at the turn of the century. The EuroPrevall study identified Germany as a country with very high prevalence of FA at that time. Using two large German birth cohorts, we provide an update of the status quo 10 years later. METHODS: KUNO Kids and Ulm SPATZ Health studies are two ongoing prospective birth cohorts. Information on FA was obtained by questionnaires at birth and after 6, 12, and 24 months. Univariable and multivariable logistic regression analyses were performed to investigate risk factors during pregnancy, birth, and early childhood. RESULTS: In 1139 and 1006 children from KUNO Kids and SPATZ, the point prevalence of parent-reported FA symptoms at the ages of 1 and 2 years was 13.2% (95% CI: 11.2-15.2) and 13.9% (95% CI: 11.5-17.2) in KUNO Kids. Doctor's diagnosed FA at 1 and 2 years was 2.4% (95% CI: 1.6-3.4) and 2.7% (95% CI: 1.2-4.3) in KUNO Kids and 2.3% (95% CI: 1.3-3.6) and 3% (95% CI: 2.0-4.5) in SPATZ. Cow's milk and citrus fruits were most frequently suspected by parents to cause FA symptoms. Atopy in the child was associated with a higher frequency of FA at any time, whereas atopy in first-degree relatives was only associated with FA at year 1. Smoke exposure during pregnancy was a risk for FA at age 2. CONCLUSION: The prevalence of food allergy seems to have plateaued in the last 10 years in Germany. FA is often suspected by parents but only rarely diagnosed by oral food challenge. Risk factor analysis may help to establish personalized health approaches.

Latency duration of preterm premature rupture of membranes and neonatal outcome: a retrospective single-center experience.

In preterm premature rupture of membranes (PPROM), a decision between early delivery with prematurity complications and pregnancy prolongation bearing the risk of chorioamnionitis has to be made. To define disadvantages of delayed prolongation, latency duration of PPROM in expectantly managed pregnancies was investigated. We included those PPROMs > 48 h leading to preterm birth prior 37 weeks' gestation and retrospectively analyzed 84 preterm infants fulfilling these criteria. The association between latency duration/appearance of PPROM and respiratory outcome (primary outcomes) and neurological outcome (secondary outcomes) was investigated. The study showed that latency duration of PPROM is not associated with clinical or histological chorioamnionitis (p = 0.275; p = 0.332). As the numerous clinical parameters show multicollinearity between each other, we performed a multiple regression analysis to consider this fact. Respiratory distress syndrome is significantly associated with gestational age at PPROM (p < 0.001), and surfactant application is significantly associated with PPROM duration (p = 0.014). The other respiratory parameters including steroids and diuretics therapy, bronchopulmonary dysplasia, and the neurological parameters (intraventricular hemorrhage, Bayley II testing at a corrected age of 24 months) were not significantly associated with PPROM duration or gestational age at PPROM diagnosis.Conclusion: Latency duration of PPROM was not associated with adverse neonatal outcome in expectantly and carefully managed pregnancies, but respiratory distress syndrome was pronounced. The observed effect of pronounced respiratory distress syndrome can be treated with surfactant preparations and was not followed by increased rate of bronchopulmonary dysplasia. What is Known: • In case of preterm premature rupture of membranes, a decision between pregnancy prolongation with the risk of chorioamnionitis and early delivery with prematurity complications has to be made. • Chorioamnionitis is a dangerous situation for the pregnant woman and the fetus. • Impaired neurodevelopmental outcome is strongly correlated with pronounced prematurity due to the increased rate of serious complications. What is New: • Respiratory distress syndrome is significantly associated with gestational age at PPROM, and surfactant application is significantly associated with PPROM duration. • Latency duration of PPROM is not associated with adverse respiratory neonatal outcome (therapy with continuous positive airway pressure, therapy with diuretics and/or steroids, bronchopulmonary dysplasia) in expectantly and carefully managed pregnancies. • Intraventricular hemorrhage and Bayley II testing at a corrected age of 24 months are not associated with latency duration of PPROM when pregnancies are carefully observed.

[Parental intention to vaccinate their children against COVID-19]. / COVID-19-Impfintention von Eltern bezogen auf ihre Kinder.

BACKGROUND: With the start of the vaccination campaign, a new phase in the management of the coronavirus pandemic has begun. Approval and recommendation for COVID-19 vaccination of children followed gradually; to date (4 October 2022), vaccination for children under five years of age has not been approved in Germany. AIM OF THE STUDY: The aim was to investigate how parents' intention to vaccinate their children against COVID-19 developed from May 2020 to February 2021 (from the first to the second wave of the COVID-19 pandemic) and to analyse the determinants of the intention to vaccinate. METHODS: In May 2020, 612 families participating with their children aged 1.5-6 years in the KUNO Kids Health Study completed an online survey (participation rate 51%), and 507 completed the second survey in February 2021. Determinants of the intention to vaccinate were analysed for both time points using univariable and multivariable logistic regression models. RESULTS: While 51% of parents reported wanting their children vaccinated against COVID-19 in May 2020, this proportion decreased to 41% by February 2021. At least at one of the two time points, health literacy and perceived competence regarding protective measures against the virus were significantly positively associated with higher vaccination intentions, while belonging to a risk group and the perception that the political measures were exaggerated were associated with lower vaccination intentions. DISCUSSION: Parents' intention to have their children vaccinated against COVID-19 was low and decreased further from the first to the second wave of the coronavirus pandemic. Attitudinal and competence-related determinants were important at both time points and could be targeted in a future vaccination campaign addressing parents of younger children.

Uterine Artery Embolization in the Twentieth Week of Pregnancy in Abnormally Invasive Placenta with Live Birth.

An abnormally invasive placenta is an increasing and potentially life-threatening pregnancy complication. The case presented herein is a heterotopic dichorial pregnancy with implantation of 1 placenta within the isthmocervical area, which caused vaginal bleeding during the 20th week of pregnancy, requiring a blood transfusion. To stop the bleeding, a bilateral embolization of the cervical branches of the uterine arteries was performed. The embolization was well tolerated and resulted in the abrupt and lasting cessation of bleeding for more than 10 weeks, resulting in the live birth of 1 child.

Reliability of prenatal detection of X-linked hypohidrotic ectodermal dysplasia by tooth germ sonography.

OBJECTIVE: In X-linked hypohidrotic ectodermal dysplasia (XLHED), dysfunction of ectodysplasin A1 (EDA1) due to EDA mutations results in malformation of hair, teeth, and sweat glands. Hypohidrosis, which can cause life-threatening hyperthermia, is amenable to intrauterine therapy with recombinant EDA1. This study aimed at evaluating tooth germ sonography as a noninvasive means to identify affected fetuses in pregnant carrier women. METHODS: Sonography, performed at 10 study sites between gestational weeks 18 and 28, led to the diagnosis of XLHED if fewer than six tooth germs were detected in mandible or maxilla. The assessment was verified postnatally by EDA sequencing and/or clinical findings. Estimated fetal weights and postnatal weight gain of boys with XLHED were assessed using appropriate growth charts. RESULTS: In 19 of 38 sonographic examinations (23 male and 13 female fetuses), XLHED was detected prenatally. The prenatal diagnosis proved to be correct in 37 cases; one affected male fetus was missed. Specificity and positive predictive value were both 100%. Tooth counts obtained by clinical examination corresponded well with findings on panoramic radiographs. We observed no weight deficits of subjects with XLHED in utero but occasionally during infancy. CONCLUSION: Tooth germ sonography is highly specific and reliable in detecting XLHED prenatally.

Is Afamin a novel biomarker for gestational diabetes mellitus? A pilot study.

BACKGROUND: In search of potential early biomarkers for timely prediction of gestational diabetes mellitus (GDM), we focused on afamin, a vitamin E-binding protein in human plasma.. Afamin plays a role in anti-apoptotic cellular processes related to oxidative stress and is associated with insulin resistance and other features of metabolic syndrome. During uncomplicated pregnancy its serum concentrations increase linearly. The aim of this study was to investigate the suitability of afamin as early marker for predicting GDM. METHODS: In a first-trimester cohort from a prospective observational study of adverse pregnancy outcomes we secondarily analyzed afamin concentrations in 59 patients diagnosed with GDM and 51 controls. Additionally, afamin concentrations were cross-sectionally examined in a mid-trimester cohort of 105 women and compared with results from a simultaneously performed oral glucose tolerance test (OGTT). Subgroup analysis comparing patients treated with either insulin (iGDM) or dietary intervention (dGDM) was performed in both cohorts. Patients were recruited at the University Hospital Essen, Germany, between 2003 and 2016. RESULTS: Results were adjusted for body-mass-index (BMI) and gestational age. First and mid-trimester cohorts yielded significantly elevated afamin concentrations in patients with pathological OGTT compared to patients without GDM (first trimester cohort: mean, 113.4 mg/l; 95% CI, 106.4-120.5 mg/l and 87.2 mg/l; 95% CI, 79.7-94.7 mg/l; mid-trimester cohort: mean, 182.9 mg/l; 95% CI, 169.6-196.2 mg/l and 157.3 mg/l; 95% CI, 149.1-165.4 mg/l, respectively). In the first-trimester cohort, patients developing iGDM later in pregnancy presented with significantly higher afamin concentrations compared to patients developing dGDM and compared to patients without GDM. In the mid-trimester cohort, mean concentrations of afamin differed significantly between patients with dGDM compared to controls and between patients with iGDM and controls. Patients with iGDM showed only slightly higher afamin levels compared to patients with dGDM. CONCLUSION: Afamin may serve as a new early biomarker for pathological glucose metabolism during pregnancy. Further research is needed to determine afamin's concentrations during pregnancy, its predictive value for early detection of pregnancies at high risk to develop GDM and its diagnostic role during the second trimester.

Trends in anti-Müllerian hormone concentrations across different stages of pregnancy in women with polycystic ovary syndrome.

RESEARCH QUESTION: What are the trends in anti-Müllerian hormone (AMH) concentrations from pre-conception to the third trimester of pregnancy in women with polycystic ovary syndrome (PCOS)? DESIGN: Observational study including cross-sectional and longitudinal data analysis. The Beckman Coulter AMH Gen II Assay was used to determine AMH levels longitudinally before pregnancy from 52 women with PCOS and 51 controls during all trimesters. Differences in AMH levels across successive stages of pregnancy were examined with the Wilcoxon signed-rank test for paired values. Linear regression models, adjusted for body-mass index (BMI), gestational and maternal age were used to compare AMH levels of PCOS and controls. RESULTS: AMH levels decreased significantly (all P < 0.05) from pre-pregnancy level throughout each trimester in women with PCOS and healthy controls. After adjusting for maternal age, gestational age and maternal BMI, AMH levels before pregnancy were 1.89 (95% CI 1.46 to 2.44; P < 0.0001) times higher among women with PCOS compared with controls (median 7.66 versus 2.67 ng/ml). During the first trimester, AMH levels were 1.61 (95% CI 1.22 to 2.13; P = 0.001) times higher among women with PCOS compared with controls (median 5.33 versus 2.48 ng/ml). Differences in AMH levels between women with PCOS and controls in the second trimester (1.68 times higher; 95% CI 0.94 to 3.01; median: 5.50 versus 2.20 ng/ml) and the third trimester (1.45 times higher; 95% CI 1.01 to 2.07; median: 1.36 versus 1.06 ng/ml) were not statistically significant. CONCLUSION: These findings indicate a pregnancy-associated AMH-decline independent of pre-pregnancy elevated AMH levels.

Vasospasm-related complications after subarachnoid hemorrhage: the role of patients' age and sex.

BACKGROUND: Outcome of aneurysmal subarachnoid hemorrhage (SAH) depends strongly on occurrence of symptomatic vasospasm (SV) leading to delayed cerebral ischemia (DCI). Various demographic, radiographic, and clinical predictors of SV have been reported so far, partially with conflicting results. The aim of this study was to analyze the role of patients' age and sex on SV/DCI risk, especially to identify age and sex-specific risk groups. METHODS: All patients admitted with acute SAH during a 14-year-period ending in 2016 were eligible for this study. The study endpoints were the following: SV requiring spasmolysis, occurrence of DCI in follow-up computed tomography scans and unfavorable outcome at 6 months (modified Rankin scale > 2). RESULTS: Nine hundred ninety-four patients were included in this study. The majority was female (666; 67%). SV, DCI, and unfavorable outcomes were observed in 21.5, 21.8, and 43.6% of the patients, respectively. Younger age (p < 0.001; OR = 1.03 per year decrease) and female sex (p = 0.025; OR = 1.510) were confirmed as independent predictors of SV. Regarding the sex differences, there were three age groups for SV/DCI risk ≤ 54, 55-74, and ≥ 75 years. Male patients showed earlier decrease in SV risk (at ≥ 55 vs. ≥ 75 years in females). Therefore, SAH females aged between 55 and 74 years were at the highest risk for DCI and unfavorable outcome, as compared to younger/older females (p = 0.001, OR = 1.77/p = 0.001, OR = 1.80). In contrast, their male counterparts did not show these risk alterations (p = 0.445/p = 0.822). CONCLUSION: After acute SAH, female and male patients seem to show different age patterns for the risk of SV and DCI. Females aged between 55 and 74 years are at particular risk of vasospasm-related SAH complications, possibly due to onset of menopause. CLINICAL TRIAL REGISTRATION NUMBER: DRKS, Unique identifier: DRKS00008749.

Tight interplay in early pregnancy between follistatin and anti-mullerian hormone in women with polycystic ovarian syndrome (PCOS).

PURPOSE: Follistatin levels increase during the course of pregnancy and may play a role in ovarian arrest, reflected by the simultaneous decrease of anti-mullerian-hormone (AMH) levels. The aim of the study was to investigate AMH and follistatin levels during the hormonal window at the beginning of pregnancy. Since both parameters are described as deregulated in polycystic ovarian syndrome (PCOS), subgroup analysis of PCOS patients may additionally elucidate their interplay and effects on ovarian activity. METHODS: Serum samples were retrospectively analyzed using the AMH Gen II ELISA and the Human Follistatin Quantikine ELISA Kit. Samples were collected longitudinally from 57 patients (32 with PCOS and 25 controls) before conception and during the first trimester. In 18 patients, measurements from the early and the late first trimester were available. Potential associations of AMH and follistatin levels with PCOS-related parameters were compared between the subgroups as well as longitudinally before and in the first trimester of pregnancy. For statistical analysis, the Spearman's correlation, Wilcoxon test, t test, Friedman test and multiple linear regression analysis was performed. RESULTS: In contrast to AMH, follistatin levels differed not between controls and PCOS patients before and in pregnancy. In both subgroups, AMH levels significantly decreased and follistatin levels significantly increased in longitudinally performed measurements before conceiving and in the first trimester of pregnancy. CONCLUSION: Follistatin levels are not suited as a biomarker for PCOS, but could be involved in suppressing ovarian activity, as reflected by AMH levels at the beginning of pregnancy.

Afamin: an early predictor of preeclampsia.

PURPOSE: Oxidative stress is involved in the pathogenesis of hypertensive disorders such as preeclampsia (PE) and associated with the human vitamin E-binding protein afamin. The aim of this study was, therefore, to analyse afamin in the first trimester of patients developing PE later in pregnancy and in control subjects without pregnancy complications. METHODS: In this retrospective study, 137 serum samples from the first trimester of pregnancy were analysed in a case-control study design. 39 patients developed PE (10 patients with early-onset and 29 patients with late onset disease) and 98 women had an uncomplicated pregnancy. Mann-Whitney U test, t test, logistic regression and ROC analyses were performed for statistical evaluation. RESULTS: Pregnant women developing PE presented with higher afamin concentrations in the first trimester [median 101.81 mg/L; interquartile range (IQR) 88.94-113.26] compared to subjects with uncomplicated pregnancy (median 86.40; IQR 75.26-96.92; p < 0.001). After adjusting for confounders, the odds ratio per afamin standard deviation was 1.60 (95% CI: 1.04-2.58; p = 0.04). An afamin threshold concentration of 87.8 mg/L exhibited the best sensitivity (79.5%) and specificity (57.1%) in predicting PE. Subgroup analysis of early- and late-onset disease resulted in substantially higher afamin concentrations in women with developing late-onset PE compared to controls (p < 0.001) with an odds ratio per afamin standard deviation of 1.62 (95% CI: 0.98-2.70; p = 0.06). CONCLUSIONS: Serum afamin concentrations are elevated in the first trimester among patients developing PE compared to controls. Substantial differences were observed mainly among patients with late-onset PE.

Oxygen Sensitivity of Placental Trophoblast Connexins 43 and 46: A Role in Preeclampsia?

Several gap junction connexins have been shown to be essential for appropriate placental development and function. It is known that the expression and distribution of connexins change in response to environmental oxygen levels. The placenta develops under various oxygen levels, beginning at a low oxygen tension of approximately 2% and increasing to a tension of 8% after the onset of the uteroplacental circulation. Moreover, it has been shown that during preeclampsia (PE) placentas are subjected to chronic hypoxia. Therefore, we investigated oxygen sensitivity of placental connexins 43 and 46. Using the trophoblast cell line Jar, we demonstrated that the expression of connexin43 increased during acute hypoxia but decreased during chronic hypoxia. Chronic hypoxia resulted in the translocation of connexin43 from the membrane to the cytoplasm and in a reduction in its communication properties. In contrast, the expression of connexin46 was down-regulated during chronic hypoxia and was translocated from perinuclear areas to the cell membrane. Hypoxia-inducible factor (HIF) knockdown showed that the translocation of connexin43 but not that of connexin46 was HIF-2α dependent and was mediated by phosphoinositide 3-kinase. The up-regulation of connexin43 in combination with the down-regulation of connexin46 was confirmed in placental explants cultivated under low oxygen and in placentas with early-onset PE. Taken together, in Jar cells, placental connexins 43 and 46 are regulated during periods of low oxygen in opposite manners. The oxygen sensing of connexins in the trophoblast may play a role in physiological and pathophysiological oxygen conditions and thus may contribute to PE.

CD133 allows elaborated discrimination and quantification of haematopoietic progenitor subsets in human haematopoietic stem cell transplants.

The success of haematopoietic stem cell (HSC) transplantation largely depends on numbers of transplanted HSCs, which reside in the CD34(+) populations of bone marrow (BM), peripheral blood stem cells (PBSC) and umbilical cord blood (UCB). More specifically HSCs reside in the CD38(low/-) subpopulation, which cannot be objectively discriminated from mature CD34(+)  CD38(+) progenitors. Thus, better marker combinations for the quantification of more primitive haematopoietic stem and progenitor cells in transplants are required. Recently, by combining CD34 and CD133 we could clearly distinguish CD133(+)  CD34(+) multipotent and lympho-myeloid from CD133(low)  CD34(+) erythro-myeloid progenitors in UCB samples. To qualify the assessment of CD133 for routine quality control of adult HSC sources, we analysed the developmental potentials of CD133(+) and CD133(low) subpopulations in BM and PBSC. Similar to UCB, CD133 expression objectively discriminated functionally distinct subpopulations in adult HSC sources. By implementing anti-CD45RA staining, which separates multipotent (CD133(+)  CD34(+)  CD45RA(-) ) from lympho-myeloid (CD133(+)  CD34(+)  CD45RA(+) ) progenitor fractions, UCB was found to contain 2-3 times higher multipotent progenitor frequencies than BM and PBSC. To test for the consistency of CD133 expression, we compared CD133(+)  CD34(+) contents of 128 UCB samples with maternal and obstetrical factors and obtained similar correlations to related studies focusing on CD34(+) cell contents. In conclusion, implementation of anti-CD133 staining into existing routine panels will improve the quality control analyses for HSC transplants.

Maternal serum copeptin, MR-proANP and procalcitonin levels at 11-13 weeks gestation in the prediction of preeclampsia.

PURPOSE: We investigated the potential value of maternal serum copeptin, midregional proatrial natriuretic peptide (MR-proANP) and Procalcitonin (PCT) levels at 11-13 weeks' gestation in the prediction of preeclampsia (PE) in a case-control study. MATERIALS AND METHODS: Maternal serum concentration of copeptin, MR-proANP and PCT were measured at 11-13 weeks' gestation in cases of PE (n = 35) and controls (n = 100). The PE group was divided into early-onset PE (EO-PE) and late-onset PE (LO-PE). From the regression model, the value in each case and control was expressed as a multiple of the expected median (MoM). The Mann-Whitney test was used to determine the significance of differences in the median MoM in each outcome group from that in the controls. RESULTS: In the PE group, compared to controls, maternal serum concentrations of copeptin, MR-proANP and PCT were not significantly different. CONCLUSION: The maternal serum copeptin, MR-proANP and PCT levels are higher in EO-PE and LO-PE patients, but the difference is not significant. Thus, their levels in first trimester are not proven to be effective markers to screen for PE.