Fetal ciliopathies: a retrospective observational single-center study.

PURPOSE: Report on the diagnosis of prenatally suspected multisystem ciliopathies in a single center between 2002 and 2020. METHODS: Retrospective observational single-center study including pregnancies with prenatal ultrasound features of multisystem ciliopathies, such as hyperechogenic kidneys together with polydactyly and/or other skeletal and extraskeletal findings. Cases were compared according to their prenatal findings and outcomes. RESULTS: 36 cases of multisystem ciliopathies were diagnosed. Meckel-Gruber syndrome (MKS) was the most common ciliopathy (n = 19/36, 52.8%), followed by disorders that belong to the group of short-rib thoracic dysplasia (SRTD, n = 10/36, 27.8%) McKusick-Kaufmann syndrome (MKKS, n = 4/36, 11.1%), Bardet-Biedl syndrome (BBS, n = 2/36, 5.5%) and Joubert syndrome (n = 1/36, 2.8%). All cases showed abnormalities of the kidneys, most often hyperechogenic parenchyma (n = 26/36, 72.2%), cystic dysplasia (n = 24/36, 66.7%), and/or bilateral kidney enlargement (n = 22/36, 61.1%). Oligohydramnios was mainly present in fetuses with MKS. Polydactyly (n = 18/36), abnormalities of the CNS (n = 25/36), and heart defects (n = 10/36) were associated in 50%, 69.4%, and 27.8%, respectively. CONCLUSION: Prenatal detection of renal abnormalities associated with skeletal or brain abnormalities should raise the suspicion for multisystem ciliopathies. Prenatal ultrasound can help to differentiate between different diseases and pave the way for subsequent targeted genetic testing.

Approach to the sonographic evaluation of fetal ventriculomegaly at 11 to 14 weeks gestation.

BACKGROUND: The aim of the study was to report the prevalence and associated findings of fetal ventriculomegaly between 11 + 0 and 13 + 6 gestational weeks and to evaluate a sonographic approach to classify first trimester ventriculomegaly in the standard axial plane used for biparietal diameter (BPD) measurement. METHODS: The ratio between choroid plexus and lateral ventricle diameter (PDVDR), between the choroid plexus and lateral ventricle length (PLVLR) and between the choroid plexus and lateral ventricle area (PAVAR) were calculated from stored 2D images of the axial head plane in 100 normal fetuses and 17 fetuses with ventriculomegaly. RESULTS: The PDVDR, the PLVLR and the PAVAR were below the 5(th) percentile in 82.4%, 94.1% and 94.1% of the cases with ventriculomegaly. Ventriculomegaly was isolated in 29.4% and associated with further anomalies in 70.6% at the initial evaluation. The mean PLVLR in euploid compared to aneuploid fetuses was significantly lower (0.40 versus 0.53 (p = 0.0332)). CONCLUSIONS: The measurements of PDVDR, PLVLR and PAVAR are helpful to objectify ventriculomegaly at 11-14 gestational weeks. The PLVLR and PAVAR were superior to PDVDR, since there seems to be rather shrinkage of the choroid plexus than an increased width of the lateral ventricles in the first trimester.

The association of crown-rump length discrepancy with birthweight discordance in spontaneous versus IVF monochorionic twins: a multicenter study.

OBJECTIVE: The objective of this study was to compare the associations of crown-rump length (CRL) discrepancy with birthweight discordance in spontaneous versus in vitro fertilization (IVF) monochorionic (MC) twin pregnancies. METHOD: This is a multicenter retrospective study on women with twin pregnancies assessed for nuchal translucency between January 1997 and July 2013. The study group was subdivided into MC twins conceived spontaneously and after IVF. Pregnancies with later fetal death or twin transfusion syndrome were excluded. A large-weight discordance was defined as a difference of birthweights of >15%. RESULTS: The study group included 171 pregnancies; of them, 142 (83%) were spontaneous and 29 (17%) were IVF conceived. In the entire cohort, we found a significant correlation between birthweight discordance and CRL discrepancy (r = 0.173, P < 0.05). While a significant correlation was found between CRL discrepancy and birthweight discordance in spontaneous-conceived pregnancies (n = 142, r = 0.24, P = 0.005), such correlation was not present in IVF pregnancies (n = 29, r = -0.7, P = 0.724). A logistic regression analysis found significant odds of larger-weight discordance for each increase of 1% in CRL discrepancy among spontaneously conceived pregnancies (odds ratio = 1.1, confidence interval = 1.03-1.2, P = 0.005). A receiver operating characteristic (ROC) for large-weight discordance in the spontaneously conceived pregnancies demonstrated an area under the ROC curve of 0.613 (P = 0.039). CONCLUSION: The significant correlation between CRL discrepancy and birthweight discordance in spontaneous versus IVF MC twin pregnancies might suggest differential monozygotic twinning process.

Resistin in pregnancy: Analysis of determinants in pairs of umbilical cord blood and maternal serum.

OBJECTIVE: Despite intensive research on the cytokine resistin only few studies investigated mother-newborn-pairs during healthy pregnancy and reported about interactions with clinical obstetric variables or other cytokines. Comparison of existing studies is difficult due to differences between assays, sample collection, gestational age, definition of healthy controls and patient characteristics. Furthermore, differences between rodent models and humans do not allow for a direct comparison. METHODS: In this cross-sectional, prospective study 109 healthy mother-newborn pairs were analyzed. Maternal venous blood samples were taken on admission to the labor ward; newborn venous blood samples were drawn from the placental part of the umbilical cord (UC), immediately after clamping. Resistin, leptin, adiponectin, TNF-α, IL-6 and brain derived neurotrophic factor (BDNF) serum concentrations were measured with commercially available immunoassays. Determinants of maternal and newborn resistin levels were analyzed using simple and multiple linear regression. RESULTS: UC resistin levels were higher than maternal concentrations (median 17.69 ng/mL, IQR 7.36 vs. median 8.04 ng/mL, IQR 4.30). Correlation between UC and maternal resistin levels was moderate (R = 0.503, p < 0.01). In multiple regression analysis levels of maternal resistin and newborn TNF-α remained significant determining factors for UC resistin levels. Gestational age and maternal BDNF-levels remained significant factors for maternal resistin levels. CONCLUSION: In healthy, term newborns and their respective mothers a positive correlation between maternal and newborn levels and an association with gestational age around term can be found and point to a placental source of resistin. Further investigations are needed to clarify the possible contribution of transplacental transport of resistin into the fetal circulation. Except for gestational age most of the clinical obstetric variables tested do not seem to be determining factors for fetal or maternal resistin. Interactions of resistin with other cytokines like TNF-α and BDNF could be the missing link for the conflicting results in literature.