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

Restless Legs Syndrome During Pregnancy and 12 Weeks Postpartum and Its Links to Cardiovascular Diseases, Stressful Life Events, and Psychiatric History

Restless legs syndrome (RLS) is highly prevalent among pregnant women. In the present study, a neurological–obstetrical sample of 561 postpartum women was retrospectively screened for RLS symptoms during pregnancy and in the first 12 weeks postpartum. The first screening took place within 1 to 6 days of delivery (T0) and the second 12 weeks after childbirth (T1). The pregnancy-related RLS prevalence rate was found to be 21% (n = 119), with the women suffering from RLS being more often affected by psychiatric history and having been more exposed to stressful life events. They were also found to have experienced baby blues more frequently shortly after childbirth. However, RLS in pregnancy did not appear to have any effect on the development of postpartum depression. Additionally, a positive trend was observed toward an association between pregnancy-related RLS and gestational diabetes and hypertension. Of the 119 women, 23 (19.3%) remained affected by RLS 12 weeks postpartum. Body mass index (BMI), weight gain, parity, childbearing history, or chronic stress exposure in pregnancy as measured by hair cortisol were not found to be linked to RLS. In summary, a comprehensive understanding of the interaction of clinical, environmental, and anamnestic factors can help shed valuable light on this pregnancy-related condition

Sertraline in pregnancy - Therapeutic drug monitoring in maternal blood, amniotic fluid and cord blood

Rationale: This study is the first to measure and correlate sertraline concentrations in maternal blood, amniotic fluid and umbilical cord blood and account for distribution of the drug between these three compartments. Methods: Concentrations of sertraline were measured in six mother infant pairs at the time of delivery. Data are provided as median values, first and third quartiles as well as ranges. To account for the penetration ratio into amniotic fluid and cord blood, the concentration of sertraline in both environments was divided by the concentration in maternal serum. Daily doses were correlated with maternal serum- and umbilical cord bloodconcentrations, and serum levels were correlated with levels in amniotic fluid. Results: The median daily dose of sertraline was 75 mg (Q1: 43.75 mg, Q3: 100 mg; range 25–100 mg). Amniotic fluid concentrations of sertraline strongly correlated with the daily dose (r=0.833, p=0.039) while neither maternal serum concentrations nor cord blood concentrations correlated with the daily dose (p > 0.05). The median penetration ratio for sertraline into amniotic fluid was 0.57 (Q1: 0.28, Q3: 0.75; range: 0.22–0.88). The median penetration ratio into the fetal circulation, calculated on the basis of umbilical cord bloodconcentrations, was found to be 0.36 (Q1: 0.28, Q3: 0.49; range: 0.17–0.65). Conclusions: Sertraline concentrations in amniotic fluid gave evidence that maternally administered sertraline is constantly accessible to the fetus via amniotic fluid in a manner not previously appreciated. A relatively low penetration into fetal circulation may contribute to a sufficient safety profile of sertraline during pregnancy although in our study APGAR Scores were relatively low in three infants. Our data support the important role of therapeutic drug monitoring in maintaining the safety of pregnant women and exposed infants

iPSC-derived mesenchymal stromal cells are less supportive than primary MSCs for co-culture of hematopoietic progenitor cells

Abstract In vitro culture of hematopoietic stem and progenitor cells (HPCs) is supported by a suitable cellular microenvironment, such as mesenchymal stromal cells (MSCs)—but MSCs are heterogeneous and poorly defined. In this study, we analyzed whether MSCs derived from induced pluripotent stem cells (iPS-MSCs) provide a suitable cellular feeder layer too. iPS-MSCs clearly supported proliferation of HPCs, maintenance of a primitive immunophenotype (CD34+, CD133+, CD38-), and colony-forming unit (CFU) potential of CD34+ HPCs. However, particularly long-term culture-initiating cell (LTC-IC) frequency was lower with iPS-MSCs as compared to primary MSCs. Relevant genes for cell-cell interaction were overall expressed at similar level in MSCs and iPS-MSCs, whereas VCAM1 was less expressed in the latter. In conclusion, our iPS-MSCs support in vitro culture of HPCs; however, under the current differentiation and culture conditions, they are less suitable than primary MSCs from bone marrow