The molecular and phenotypic makeup of fetal human skin T lymphocytes.

The adult human skin contains a vast number of T cells that are essential for skin homeostasis and pathogen defense. T cells are first observed in the skin at the early stages of gestation; however, our understanding of their contribution to early immunity has been limited by their low abundance and lack of comprehensive methodologies for their assessment. Here, we describe a new workflow for isolating and expanding significant amounts of T cells from fetal human skin. Using multiparametric flow cytometry and in situ immunofluorescence, we found a large population with a naive phenotype and small populations with a memory and regulatory phenotype. Their molecular state was characterized using single-cell transcriptomics and TCR repertoire profiling. Importantly, culture of total fetal skin biopsies facilitated T cell expansion without a substantial impact on their phenotype, a major prerequisite for subsequent functional assays. Collectively, our experimental approaches and data advance the understanding of fetal skin immunity and potential use in future therapeutic interventions.

Brainstem and cerebellar volumes at magnetic resonance imaging are smaller in fetuses with congenital heart disease.

BACKGROUND: Congenital heart disease is associated with an increased risk of smaller brain volumes and structural brain damage, and impaired growth of supratentorial brain structures in utero has been linked to poor neurodevelopmental outcomes. However, little is known on brainstem and cerebellar volumes in fetuses with congenital heart disease. Moreover, it is not clear whether impaired infratentorial growth, if present, is associated with only certain types of fetal cardiac defects or with supratentorial brain growth, and whether altered biometry is already present before the third trimester. OBJECTIVE: This study aimed to investigate brainstem and cerebellar volumes in fetuses with congenital heart disease and to compare them to infratentorial brain volumes in fetuses with normal hearts. Secondarily, the study aimed to identify associations between infratentorial brain biometry and the type of cardiac defects, supratentorial brain volumes, and gestational age. STUDY DESIGN: In this retrospective case-control study, 141 magnetic resonance imaging studies of 135 fetuses with congenital heart disease and 141 magnetic resonance imaging studies of 125 controls with normal hearts at 20 to 37 gestational weeks (median, 25 weeks) were evaluated. All cases and controls had normal birthweight and no evidence of structural brain disease or genetic syndrome. Six types of congenital heart disease were included: tetralogy of Fallot (n=32); double-outlet right ventricle (n=22); transposition of the great arteries (n=27); aortic obstruction (n=24); hypoplastic left heart syndrome (n=22); and hypoplastic right heart syndrome (n=14). First, brainstem and cerebellar volumes of each fetus were segmented and compared between cases and controls. In addition, transverse cerebellar diameters, vermian areas, and supratentorial brain and cerebrospinal fluid volumes were quantified and differences assessed between cases and controls. Volumetric differences were further analyzed according to types of cardiac defects and supratentorial brain volumes. Finally, volume ratios were created for each brain structure ([volume in fetus with congenital heart disease/respective volume in control fetus] × 100) and correlated to gestational age. RESULTS: Brainstem (cases, 2.1 cm3 vs controls, 2.4 cm3; P<.001) and cerebellar (cases, 3.2 cm3 vs controls, 3.4 cm3; P<.001) volumes were smaller in fetuses with congenital heart disease than in controls, whereas transverse cerebellar diameters (P=.681) and vermian areas (P=.947) did not differ between groups. Brainstem and cerebellar volumes differed between types of cardiac defects. Overall, the volume ratio of cases to controls was 80.8% for the brainstem, 90.5% for the cerebellum, and 90.1% for the supratentorial brain. Fetuses with tetralogy of Fallot and transposition of the great arteries were most severely affected by total brain volume reduction. Gestational age had no effect on volume ratios. CONCLUSION: The volume of the infratentorial brain, which contains structures considered crucial to brain function, is significantly smaller in fetuses with congenital heart disease than in controls from midgestation onward. These findings suggest that impaired growth of both supra- and infratentorial brain structures in fetuses with congenital heart disease occurs in the second trimester. Further research is needed to elucidate associations between fetal brain volumes and neurodevelopmental outcomes in congenital heart disease.

Risk and protective factors for obstetric anal sphincter injuries: A retrospective nationwide study.

BACKGROUND: In view of the reported increase in obstetric anal sphincter injuries, the objective of this study was to evaluate the incidence of such injuries over time and the associated risk and protective factors. METHODS: This was a retrospective cohort study from a national database of 168 137 primiparous women with term, singleton, cephalic, vaginal delivery between 2008 and 2014. The main outcome measure was obstetric anal sphincter injury. A multivariate regression model was used to identify risk and protective factors. RESULTS: Age >19 years, birthweight >4000 g, and operative vaginal delivery were independent risk factors for obstetric anal sphincter injuries. Mediolateral episiotomy increased the risk for obstetric anal sphincter injuries in spontaneous vaginal birth (number needed to harm 333), whereas it was protective in vacuum delivery (number needed to treat 50). From 2008 to 2014, there was an increase in the rate of obstetric anal sphincter injuries (2.1% vs 3.1%, P < .01), vacuum deliveries (12.1% vs 12.8%, P < .01), and cesarean delivery after labor (17.1% vs 19.4%, P < .01), while forceps deliveries (0.4% vs 0.1%, P < .01) and episiotomy rate decreased (35.9% vs 26.4%, P < .01). CONCLUSIONS: Episiotomy may be a risk or protective factor depending on the type of episiotomy and the clinical setting in which it is used. Our study supports a restrictive use of mediolateral episiotomy in spontaneous vaginal deliveries. In vacuum deliveries mediolateral episiotomy may help prevent obstetric anal sphincter injuries.

Maternal and neonatal omentin-1 levels in gestational diabetes.

PURPOSE: To evaluate the effect of gestational diabetes on omentin-1 in maternal and cord plasma. As a potent mediator of insulin resistance, Omentin-1, an adipokine derived from human adipose and placental tissue, may be an important player in the pathophysiology of gestational diabetes. METHODS: This was a prospective case-control study. The study included 96 women with gestational diabetes and 96 pregnant women without. Omentin-1 was measured at the time of the oral glucose tolerance test, at 32 weeks in maternal plasma and right after delivery in umbilical cord blood by ELISA assay. RESULTS: Over a period of 2 years, 200 patients were enrolled. Omentin-1 levels did not significantly differ between both groups throughout the pregnancy: omentin-1 levels were 157 ± 83 ng/ml in women with gestational diabetes and 158 ± 93 ng/ml in women without gestational diabetes (p = 0.94) at time of the oral glucose tolerance test and 118 ± 77 ng/ml in women with diabetes and 150 ± 89 ng/ml in women without (p = 0.12) at 32 weeks, respectively. Both groups showed a decrease in omentin-1 levels throughout pregnancy, with a more pronounced decrease in diabetic women (13 ± 53 versus 4 ± 48 ng/ml; p = 0.5). Neonatal omentin-1 levels were significantly lower in offspring of diabetic mothers: 106 ± 61 versus 134 ± 45 ng/ml (p = 0.03). CONCLUSIONS: There was no significant difference in omentin-1 levels between healthy and diabetic mothers throughout the pregnancy. However, we found significantly lower omentin-1 levels in offspring of diabetic mothers. This may indicate a risk for the development of insulin resistance in later life.

Reliability of sonographic fetal weight estimation in triplet pregnancies: a retrospective cohort study.

PURPOSE: To review our experience in ultrasound fetal weight estimation in our large population of triplet pregnancies. METHODS: Ninety-seven triplet pregnancies were retrospectively included between January 2003 and January 2017. Sonographic fetal weight estimation using Hadlock's and Schild's formulas was compared to actual birth weight in a tertiary-care center in Vienna, Austria. Statistical analyses were performed using a stepwise linear regression model and crosstabs. RESULTS: The median discrepancy between the sonographically estimated fetal weight by Hadlock's formula and the actual birth weight was 106 g (IQR 56-190). The percentage error and its standard deviation were - 2.5 ± 12.1%, and the median percentage error was - 3.6%. Concerning the use of Hadlock's formula, estimated fetal weight was the most important factor predictive of actual birth weight with an estimate of 0.920 (p < 0.001). Female neonates had been overestimated by a mean of 50.473 g per fetus. The sonographic prediction of small-for-gestational-age neonates was significantly reliable (p < 0.001), with positive and negative predictive values ranging from 81.3 to 100.0%. Similar results were obtained for Schild's formula. CONCLUSION: Even if sonographically estimated fetal weight in triplet pregnancies has a high overall accuracy of fetal weight estimation, there are some limitations in prediction of intrauterine growth restrictions, especially in female fetuses.

Epidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013 criteria among obese pregnant women in Europe.

AIMS/HYPOTHESIS: Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria. METHODS: Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies. RESULTS: The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24-28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35-37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not. CONCLUSIONS/INTERPRETATION: The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies.

Cerebral Lesions at Fetal Magnetic Resonance Imaging and Neurologic Outcome After Single Fetal Death in Monochorionic Twins.

BACKGROUND: Single fetal death (sFD) in monochorionic twin pregnancies is associated with substantial morbidity and mortality in the survivor. The aim of our study was to evaluate the rate of cerebral lesions detected at fetal Magnetic Resonance Imaging (MRI) and to correlate the results with the neurologic outcome of the survivors of monochorionic twin pregnancies after sFD. METHODS: Between 2005 and 2012, 11 monochorionic twin pregnancies with sFD and subsequent fetal MRI of the survivor were included. All neonates underwent neurologic assessment after birth and 56% of surviving infants underwent long-term neurologic assessment. MRI findings and neurologic outcome of the survivors were evaluated. RESULTS: Gestational age at sFD was 20.9 (±2.9) weeks; 55% (6/11) of survivors of monochorionic twin pregnancies after sFD showed cerebral lesions at fetal MRI; 72% (8/11) of all survivors had normal neonatal neurologic outcome: all survivors with normal fetal MRI and 50% of survivors with cerebral lesions at fetal MRI. Long-term neurologic assessment was normal in all tested patients with normal fetal MRI and in one of three tested patients with cerebral lesions at fetal MRI. CONCLUSION: Survivors of monochorionic twin pregnancies after sFD show a high rate of cerebral lesions at fetal MRI. The importance of cerebral lesions at fetal MRI in survivors after sFD in monochorionic twin pregnancies is uncertain. All tested survivors with normal fetal MRI showed normal neurologic outcome but only one of three survivors with cerebral lesions at fetal MRI showed normal long-term neurologic outcome.

Congenital heart disease in monochorionic twins with and without twin-to-twin transfusion syndrome.

OBJECTIVE: This study aims to evaluate the prevalence of congenital heart disease (CHD) in monochorionic (MC) twin pregnancies with and without twin-to-twin transfusion syndrome (TTTS) in an unselected cohort, which underwent prenatal and postnatal echocardiography. METHOD: This was a retrospective cohort study including 451 MC twin pregnancies between 2002 and 2012. Complete outcome data were available for 381 pregnancies. All patients had prenatal echocardiography, and postnatal echocardiography was performed in all newborns with symptoms or to follow-up on prenatal findings. Data from prenatal and postnatal echocardiography and autopsy were analyzed. The classification of Houyel et al. was used for structural CHD. RESULTS: Structural CHD was diagnosed in 5.5% of all MC twins (42/762). Twins with TTTS showed a significant higher rate of CHD than unaffected twins (9.3% vs 4.7%; p = 0.03). Prenatal detection rate of CHD was 48%. Most common abnormalities were ventricular septal defects (VSD) (2.1%) followed by anomalies of the ventricular outflow tracts (1.3%) in the overall population and VSD (2.9%) and anomalies of the great arteries (2.9%) in the group with TTTS. CONCLUSION: MC twin pregnancies show a high prevalence of structural CHD (5.5%), especially those affected by TTTS. A detailed prenatal and postnatal echocardiography could be considered in these pregnancies.

Native human and mouse skin infection models to study Candida auris-host interactions.

The World Health Organization (WHO) declared certain fungal pathogens as global health threats for the next decade. Candida auris (C. auris) is a newly emerging skin-tropic multidrug-resistant fungal pathogen that can cause life-threatening infections of high mortality in hospitals and healthcare settings. Here, we address an unmet need and present novel native ex vivo skin models, thus extending previous C. auris-host interaction studies. We exploit histology and immunofluorescence analysis of ex vivo skin biopsies of human adult and fetal, as well as mouse origin infected with C. auris via distinct routes. We demonstrate that an intact skin barrier efficiently protects from C. auris penetration and invasion. Although C. auris readily grows on native human skin, it can reach deeper layers only upon physical disruption of the barrier by needling or through otherwise damaged skin. By contrast, a barrier disruption is not necessary for C. auris penetration of native mouse skin. Importantly, we show that C. auris undergoes morphogenetic changes upon skin penetration, as it acquires pseudohyphal growth phenotypes in deeper human and mouse dermis. Taken together, this new human and mouse skin model toolset yields new insights into C. auris colonization, adhesion, growth and invasion properties of native versus damaged human skin. The results form a crucial basis for future studies on skin immune defense to colonizing pathogens, and offer new options for testing the action and efficacy of topical antimicrobial compound formulations.

Fetal Growth Restriction Is Associated with Pregnancy Associated Plasma Protein A and Uterine Artery Doppler in First Trimester.

Fetal growth restriction (FGR) is a major cause of stillbirth and poor neurodevelopmental outcomes. The early prediction may be important to establish treatment options and improve neonatal outcomes. The aim of this study was to assess the association of parameters used in first-trimester screening, uterine artery Doppler pulsatility index and the development of FGR. In this retrospective cohort study, 1930 singleton pregnancies prenatally diagnosed with an estimated fetal weight under the third percentile were included. All women underwent first-trimester screening assessing maternal serum pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin levels, fetal nuchal translucency and uterine artery Doppler pulsatility index (PI). We constructed a Receiver Operating Characteristics curve to calculate the sensitivity and specificity of early diagnosis of FGR. In pregnancies with FGR, PAPP-A was significantly lower, and uterine artery Doppler pulsatility index was significantly higher compared with the normal birth weight group (0.79 ± 0.38 vs. 1.15 ± 0.59, p < 0.001 and 1.82 ± 0.7 vs. 1.55 ± 0.47, p = 0.01). Multivariate logistic regression analyses demonstrated that PAPP-A levels and uterine artery Doppler pulsatility index were significantly associated with FGR (p = 0.009 and p = 0.01, respectively). To conclude, these two parameters can predict FGR < 3rd percentile.

Maxillary dental arch biometry: assessment with fetal MR imaging.

OBJECTIVE: To define normal growth of the fetal maxillary dental arch using magnetic resonance imaging. METHOD: Four hundred twenty-four consecutive fetuses (18 to 37 weeks) with a morphologically normal anatomy or only minor malformations, not affecting bone growth and face anatomy were included. On axial T2-weighted images the dental arch length and width were measured. The measurements were correlated with gestational age and the biparietal diameter (BPD) of the fetal head using correlation and regression analysis. RESULTS: A linear growth relationship was observed between the dental arch length and gestational age (r = 0.86; p = < 0.0001; y = -1.85 + 0.75 × gestational age) and the dental arch width and gestational age (r = 0.92; p = < 0.0001; y = -2.19 + 1.05 × gestational age). A significant correlation was found between the dental arch length and the BPD (r = 0.903; p = < 0.0001) and the dental arch width and the BPD (r = 0.927; p = < 0.0001). The interobserver variability showed good agreement for the dental arch length (intraclass coefficient 0.981; r = 0.963) and width (intraclass coefficient 0.987; r = 0.974), respectively. CONCLUSION: We present a nomogram for the in utero assessment of the fetal dental arch. These data may help in the early detection of abnormal dental arch development.

Low placental weight and risk for fetal distress at birth.

UNLABELLED: Abstract Objective: The objective of this study was to assess whether low placental weight is associated with higher risk of emergency delivery (cesarean section and vacuum-assisted delivery). METHODS: This was a retrospective cohort study, including 657 normally developed term pregnancies. A strict methodology was used to provide reliable and reproducible placental weight measurement. Fetal heart rate patterns were analyzed according to the guidelines of the Royal College of Obstetricians and Gynecologists. Linear and logistic multiple regression analyses were used to assess risk factors for emergency delivery. RESULTS: Nulliparity, placental weight <10th percentile, and delivery after 40 weeks of gestation remain significantly associated with higher risk of emergency delivery for non-reassuring fetal status in the multivariable model [odds ratio (OR) 5.13, 95% confidence interval (CI) 2.85-9.22, P<0.001; OR 2.46, 95% CI 1.49-4.06, P<0.001; OR 2.23, 95% CI 1.26-4.51, P=0.01, respectively]. In the group of women who had an emergency delivery, 17.3% had a placental weight <10th percentile, which was significantly different to the group of women who delivered normally (9.4%, P≤0.04). If only emergency cesarean sections were analyzed, the percentage of women with placental weight <10th percentile was 37.5% in the cesarean section group compared to 9.8% in women who delivered normally (P≤0.001). CONCLUSION: This study suggests that, in clinically normally developed term pregnancies, placental weight <10th percentile is associated with an increased risk for emergency delivery during labor. These results warrant further prospective studies for potential use in clinical practice.

Neutrophil Gelatinase-Associated Lipocalin and Hypertensive Disorders of Pregnancy: A Cohort Study in Twin Pregnancies.

Hypertensive disorders complicate more than 10% of twin pregnancies. Several studies showed increased neutrophil gelatinase-associated lipocalin (NGAL) values in women with singleton pregnancies and preeclampsia. This study aimed to assess NGAL values in twin pregnancies complicated by hypertensive disorders. We conducted a study of 242 consecutive twin pregnancies at the Medical University of Vienna. Serum NGAL was evaluated twice during pregnancy and once in the postpartum period. Furthermore, serum NGAL values were compared between women who developed hypertensive disorders and those who had normal blood pressure. In all twin pregnancies, mean NGAL values increased significantly from the first to the second visit (p = 0.004) and, further, after delivery (p < 0.001). NGAL was significantly higher in pregnancies that developed pregnancy hypertension or preeclampsia when compared to the control group at the first visit (109.2 ± 48.9 ng/mL vs. 91.9 ± 29.4 ng/mL, p = 0.04, respectively). The predictive power of first visit NGAL values for development of pregnancy hypertension or preeclampsia was evaluated. When using a cut-off value of 115 ng/mL, we obtained a sensitivity of 45% with a specificity of 77%. We conclude that women with twin pregnancies who develop hypertensive disorders of pregnancy showed increased NGAL values at 11−16 weeks.

Outcome after Prenatal Diagnosis of Trisomy 13, 18, and 21 in Fetuses with Congenital Heart Disease.

Fetal congenital heart disease (CHD) is often associated with chromosomal abnormalities. Our primary aim was to assess stillbirth and neonatal mortality rates for pregnancies complicated by trisomies 13, 18, and 21 in the presence of CHD, from a single tertiary referral center during 2000-2020 in a retrospective cohort study. The secondary aims were to investigate maternal morbidity in these pregnancies, and to study the gestational or neonatal age when mortality occurred. Inclusion criteria were the prenatal diagnosis of at least one structural CHD, together with prenatally diagnosed fetal trisomy 13, 18, or 21. One-hundred and sixty patients with fetal trisomy 13 (14.4%), fetal trisomy 18 (28.8%), and fetal trisomy 21 (56.9%) were evaluated. In total, 98 (61.3%) families opted for the termination of pregnancy (TOP). Of the remaining 62 (38.8%) pregnancies, 16 (25.8%) resulted in intrauterine fetal death/death during delivery. Ten out of twenty-one (47.6%) infants with trisomy 13 or 18 were born alive. The livebirth rate was 87.8% (36/41) for infants with trisomy 21. Early neonatal death was observed in nine (19.6%) infants. Thirty-one (86.1%) infants with trisomy 21 survived the first year of life. These data may be helpful for counseling affected parents when the decision to terminate or continue the pregnancy should be considered.

Vitamin D3 Supplementation in Overweight/Obese Pregnant Women: No Effects on the Maternal or Fetal Lipid Profile and Body Fat Distribution-A Secondary Analysis of the Multicentric, Randomized, Controlled Vitamin D and Lifestyle for Gestational Diabetes Prevention Trial (DALI).

Vitamin D deficiency is a common finding in overweight/obese pregnant women and is associated with increased risk for adverse pregnancy outcome. Both maternal vitamin D deficiency and maternal obesity contribute to metabolic derangements in pregnancy. We aimed to assess the effects of vitamin D3 supplementation in pregnancy versus placebo on maternal and fetal lipids. Main inclusion criteria were: women <20 weeks' gestation, BMI ≥ 29 kg/m2. Eligible women (n = 154) were randomized to receive vitamin D3 (1600 IU/day) or placebo. Assessments were performed <20, 24−28 and 35−37 weeks and at birth. Linear regression models were used to assess effects of vitamin D on maternal and cord blood lipids. In the vitamin D group significantly higher total 25-OHD and 25-OHD3 levels were found in maternal and cord blood compared with placebo. Adjusted regression models did not reveal any differences in triglycerides, LDL-C, HDL-C, free fatty acids, ketone bodies or leptin between groups. Neonatal sum of skinfolds was comparable between the two groups, but correlated positively with cord blood 25-OH-D3 (r = 0.34, p = 0.012). Vitamin D supplementation in pregnancy increases maternal and cord blood vitamin D significantly resulting in high rates of vitamin D sufficiency. Maternal and cord blood lipid parameters were unaffected by Vitamin D3 supplementation.

Mean, lowest, and highest pulsatility index of the uterine artery and adverse pregnancy outcome in twin pregnancies.

OBJECTIVE: The objective of the study was to assess the use of mean, lowest, and highest pulsatility index (PI) of the uterine arteries to screen for adverse pregnany outcome in twin pregnancies. STUDY DESIGN: This was a screening study of 423 twin pregnancies. Relationship between PI at 20-22 weeks and adverse pregnancy outcome was evaluated. RESULTS: Mean, lowest, and highest PI above the 95th centile were significant risk factors for preeclampsia and adverse pregnancy outcome in monochorionic and dichorionic twins. We calculated a sensitivity for preeclampsia for mean, highest, and lowest PI of 35%, 29%, and 27%, respectively. CONCLUSION: Increased mean, lowest, and highest PI is associated with a higher risk of preeclampsia and adverse pregnancy outcome in twins. We observed the highest sensitivity and specificity by using highest PI. The high incidence of preeclampsia in twins makes it attractive to use the PI of the uterine artery for risk stratification in twins.

αßγδ T cells play a vital role in fetal human skin development and immunity.

T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αß and γδ T cell receptors (TCRs) that was enriched in fetal skin and intestine but not detected in other fetal organs and peripheral blood. TCR sequencing data revealed that double-positive (DP) αßγδ T cells displayed little overlap of CDR3 sequences with single-positive αß T cells. Gene signatures, cytokine profiles and in silico receptor-ligand interaction studies indicate their contribution to early skin development. DP αßγδ T cells were phosphoantigen responsive, suggesting their participation in the protection of the fetus against pathogens in intrauterine infections. Together, our analyses unveil a unique cutaneous T cell type within the native skin microenvironment and point to fundamental differences in the immune surveillance between fetal and adult human skin.

The impact of fetal gender on prematurity in dichorionic twin gestations after in vitro fertilization.

BACKGROUND: Impact of fetal gender on prematurity has been primarily investigated in singleton pregnancies. In an attempt to understand better how fetal gender may affect gestational length in twin gestations after in vitro fertilization, same-sex twins and opposite twins were compared for pregnancy duration. METHODS: This study evaluated 113 women at ages 20 to 39 years with consecutive dichorionic-diamniotic twin gestations after assisted reproduction. All pregnancies were results of fresh in vitro fertilization (IVF) cycles with use of autologous oocytes and sperm and were delivered at up to 37 weeks of gestation at a University-based high-risk, maternal-fetal medicine unit. RESULTS: Both groups did not differ in baseline characteristics, such as maternal ages, indications for fertility treatments, number of previous IVF attempts, body mass index and parity. Opposite sex- twins, however, presented with significantly shorter gestational age at birth (32.9 +/- 3.4 weeks) than same-sex twins (34.3 +/- 2.5 weeks), (p < 0.05). Younger maternal age was also associated with shorter pregnancy duration (p < 0.05). CONCLUSIONS: Fetal gender mix serves as risk factor for more significant prematurity in dichorionic-diamniotic twins after assisted reproduction with opposite sex twins at higher risk than same sex-twins.

Influence of gestational diabetes mellitus on weight discrepancy in twin pregnancies.

OBJECTIVE: To evaluate the influence of gestational diabetes mellitus on weight discrepancy in twin pregnancies. METHODS: 200 twin pregnancies were included in the study. 157 nondiabetic pregnant women with twin gestations and 43 twin pregnancies with gestational diabetes mellitus (GDM) with viable fetuses born after 24 weeks of gestation were enrolled. Influence of maternal age, body-mass-index at the time of the oral glucose tolerance test, parity, smoking, chorionicity, gestational age at delivery and diagnosis of GDM on weight discrepancy of the twins was evaluated. RESULTS: Mean weight discrepancy of all analyzed twin pregnancies was 285 grams (+/- 231), relative weight discrepancy was 11.3% (+/- 8.6). Univariate regression analyses showed that GDM, chorionicity and gestational age at delivery were significantly associated with weight discrepancy. In the multivariate model only diagnosis of GDM was significantly associated with weight discrepancy. CONCLUSION: Twin pregnancies with insulin requiring gestational diabetes seem to have less birth weight discrepancy than twin pregnancies with normal glucose tolerance.

Does fetal sex influence the risk of preterm delivery in dichorionic twin pregnancies after spontaneous conception?

OBJECTIVE: The incidence of preterm delivery has been increasing, and our aim was to estimate the influence of fetal sex on the risk of preterm delivery in dichorionic twins after spontaneous conception. METHODS: 125 spontaneously conceived dichorionic twin gestations, with viable fetuses, born after 24 weeks and delivered spontaneously before 37 weeks, were enrolled. The impact of fetal sex, previous preterm delivery, maternal age, body-mass-index, smoking, and parity on gestational age at birth were evaluated. RESULTS: Despite similar baseline characteristics in all three groups, women with one or two male fetuses delivered significantly more often before 34 weeks than patients with two female fetuses, 48% (23/48) and 43% (19/44) vs 21% (7/33), p = .04. Regression analyses, including fetal sex, maternal age, maternal body-mass-index, smoking, previous preterm delivery and parity, revealed that only fetal sex was significantly associated with spontaneous preterm delivery (p = .03). CONCLUSION: Fetal sex appears to be a risk factor for preterm delivery in spontaneously conceived dichorionic twin gestations. Twin pregnancies with one or two male fetuses seem to be at higher risk for spontaneous preterm delivery than those with only females.