Objective To evaluate the microbial load and the inflammatory response in the distal and proximal parts of the cervical mucus plug. Design Experimental research. Population Twenty women with a normal, singleton pregnancy. Sample Vaginal swabs and specimens from the distal and proximal parts of the cervical mucus plug. Methods. Immunohistochemistry, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and histology. Results The total bacterial load (16S rDNA) was significantly lower in the cervical mucus plug compared with the vagina (p = 0.001). Among women harboring Ureaplasma parvum, the median genome equivalents/g were 1574 (interquartile range 2526) in the proximal part, 657 (interquartile range 1620) in the distal part and 60 240 (interquartile range 96 386) in the vagina. Histological examinations and quantitative polymerase chain reaction revealed considerable amounts of lactobacilli and inflammatory cells in both parts of the cervical mucus plug. The matrix metalloproteinase-8 concentration was decreased in the proximal part of the plug compared with the distal part (p = 0.08). Conclusion The cervical mucus plug inhibits, but does not block, the passage of Ureaplasma parvum during its ascending route from the vagina through the cervical canal.

Identification of fetal kidney anomalies invites questions about underlying causes and recurrence risk in future pregnancies. We therefore investigated the diagnostic yield of next-generation sequencing in fetuses with bilateral kidney anomalies and the correlation between disrupted genes and fetal phenotypes. Fetuses with bilateral kidney anomalies were screened using an in-house-designed kidney-gene panel. In families where candidate variants were not identified, whole-exome sequencing was performed. Genes uncovered by this analysis were added to our kidney panel. We identified likely deleterious variants in 11 of 56 (20%) families. The kidney-gene analysis revealed likely deleterious variants in known kidney developmental genes in 6 fetuses and TMEM67 variants in 2 unrelated fetuses. Kidney histology was similar in the latter 2 fetuses-presenting a distinct prenatal form of nephronophthisis. Exome sequencing identified ROBO1 variants in one family and a GREB1L variant in another family. GREB1L and ROBO1 were added to our kidney-gene panel and additional variants were identified. Next-generation sequencing substantially contributes to identifying causes of fetal kidney anomalies. Genetic causes may be supported by histological examination of the kidneys. This is the first time that SLIT-ROBO signaling is implicated in human bilateral kidney agenesis.

This study has identified a new heterozygous de novo mutation in the Cx26 gene (c.263C>T; p.Ala88Val) leading to KID syndrome.

Our study supports the view that GBCA is a major risk factor for NSF. Importantly, we found that patients with CKD stage 3 and 4 can be at risk of NSF. NSF may also be triggered by macrocyclic GBCA. Further, we observed a trend for higher phosphate levels in NSF cases compared with controls. The important findings drawn from this case-control study indicate that NSF is not an overlooked condition among patients with renal insufficiency not exposed to GBCA.

We report on two sibships with four fetuses of 12, 15, 17, and 20 weeks of gestation, respectively, and 1 preterm baby of 31 weeks of gestation affected by a multiple congenital disorder with manifestation suggestive of Fryns syndrome. In addition to the characteristic malformation pattern in Fryns syndrome, they presented with fetal hydrops, cystic hygroma, and multiple pterygias, allowing prenatal ultrasound diagnosis as early as in the 11th week of gestation. The two affected fetuses of family 1 showed severe craniofacial anomalies with bilateral cleft lip and palate, acral hypoplasia, postaxial oligodactyly, persistent truncus arteriosus, and interrupted aortic arch, asplenia sequence, and complex central nervous system midline malformations. In family 2 with three affected sibs, ear anomalies with atresia of the auditory canals, postaxial hexadactyly, intestinal atresias, callosal defects, and eye colobomas were the most outstanding features. On the basis of the present findings and former reports, the inter- and intrafamiliar phenotypic variability in Fryns syndrome, possible pathogenetic mechanisms, and the value of prenatal diagnosis are discussed. In the pathogenetic discussion, a special emphasis is put on the neural crest cell developmental field.