Monique C. Haak

A systematic analysis of the feasibility of four‐dimensional ultrasound imaging using spatiotemporal image correlation in routine fetal echocardiography

To investigate the feasibility of incorporating spatiotemporal image correlation (STIC) into a tertiary fetal echocardiography program.

Induction of Labor versus Expectant Management in Women with Preterm Prelabor Rupture of Membranes between 34 and 37 Weeks: A Randomized Controlled Trial

In a randomized controlled trial David van der Ham and colleagues investigate induction of labor versus expectant management for women with preterm prelabor rupture of membranes.

Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta‐analysis

To estimate the incremental yield of detecting copy number variants (CNVs) by genomic microarray over karyotyping in fetuses with increased nuchal translucency (NT) diagnosed by first‐trimester ultrasound.

Fetal cardiac function assessed with four-dimensional ultrasound imaging using spatiotemporal image correlation

The goal of this study was to use spatiotemporal image correlation (STIC) to provide reference values for left and right ventricle volumes, and indices of fetal cardiac function.

Array comparative genomic hybridization and fetal congenital heart defects: a systematic review and meta‐analysis

Array comparative genomic hybridization (aCGH) is a molecular cytogenetic technique that is able to detect the presence of copy number variants (CNVs) within the genome. The detection rate of imbalances by aCGH compared to standard karyotyping and 22q11 microdeletion analysis by fluorescence in‐situ hybridization (FISH), in the setting of prenatally‐diagnosed cardiac malformations, has been reported in several studies. The objective of our study was to perform a systematic literature review and meta‐analysis to document the additional diagnostic gain of using aCGH in cases of congenital heart disease (CHD) diagnosed by prenatal ultrasound examination, with the aim of assisting clinicians to determine whether aCGH analysis is warranted when an ultrasonographic diagnosis of CHD is made, and to guide counseling in this setting.

Abnormal lymphatic development in trisomy 16 mouse embryos precedes nuchal edema

Ultrasound measurement of increased nuchal translucency is a method of risk assessment for heart malformations and trisomy 21 in human pregnancy. The developmental background of this nuchal edema is still not sufficiently understood. We have studied the process in trisomy 16 mice that show nuchal edema and heart malformations. We used trisomy 16 and wild‐type (WT) embryos from embryonic day (E) 12.5 to E18.5. In WT embryos at E13, bilateral jugular lymphatic sacs are visible that share a lymphatic–venous membrane with the jugular vein. We could not in any case discern a valve between these vessels. At E14 in the TS16 embryos, the lymphatic sacs become enlarged showing abnormally thickened endothelium, specifically at the site of the membrane. In these embryos, severe edema develops in the nuchal region. There is a very close colocalisation of the nerves with the vascular structures. The start of reorganization of the jugular lymphatic sac to a lymph node is observed in both wild‐type and TS16 but is diminished in the latter. In conclusion, abnormal size and structure of the jugular lymphatic sacs coincides with the development of nuchal edema. A disturbance of lymphangiogenesis might be the basis for increased nuchal translucency that is often observed in diseased human fetuses. Developmental Dynamics 230:378–384, 2004.

Increased nuchal translucency and distended jugular lymphatic sacs on first-trimester ultrasound

To investigate the presence and volume of jugular lymphatic sacs (JLS) in first‐trimester fetuses with normal nuchal translucency thickness (NT) and in those with increased NT.

Interobserver agreement in detailed prenatal diagnosis of congenital heart disease by telemedicine using four‐dimensional ultrasound with spatiotemporal image correlation

To evaluate the clinical accuracy of four‐dimensional (4D) echocardiography in the detailed prenatal diagnosis of congenital heart disease (CHD) in a telemedicine setting.

Nuchal edema and venous-lymphatic phenotype disturbance in human fetuses and mouse embryos with aneuploidy

Objective: Nuchal edema (NE) is a clinical indicator for aneuploidy, cardiovascular anomalies, and several genetic syndromes. Its etiology, however, is unknown. In the nuchal area, the endothelium of the jugular lymphatic sacs (JLS) develops by budding from the blood vascular endothelium of the cardinal veins. Abnormal distension of the jugular sacs is associated with NE. We hypothesize that a disturbed lymphatic endothelial differentiation and sac formation causes NE. We investigated endothelial differentiation of the jugular lymphatic system in human and mouse species with NE. Methods: Aneuploid human fetuses (trisomy 21; trisomy 18) were compared with euploid controls (gestational age 12 to 18 weeks). Trisomy 16 mouse embryos were compared with wild type controls (embryonic day 10 to 18). Trisomy 16 mice are considered an animal model for human trisomy 21. Endothelial differentiation was investigated by immunohistochemistry using lymphatic markers (prox-1, podoplanin, lymphatic vessel endothelial hyaluronan receptor [LYVE]-1) and en blood vessel markers (neuropilin [NP]-1 and ligand vascular endothelial growth factor [VEGF]-A). Smooth muscle actin (SMA) was included as a smooth muscle cell marker. Results: We report a disturbed venous-lymphatic phenotype in aneuploid human fetuses and mouse embryos with enlarged jugular sacs and NE. Our results show absent or diminished expression of the lymphatic markers Prox-1 and podoplanin in the enlarged jugular sac, while LYVE-1 expression was normal. Additionally, the enlarged JLS showed blood vessel characteristics, including increased NP-1 and VEGF-A expression. The lumen contained blood cells and smooth muscle cells lined the wall. Conclusion: A loss of lymphatic identity seems to be the underlying cause for clinical NE. Also, abnormal endothelial differentiation provides a link to the cardiovascular anomalies associated with NE.

First‐trimester fetuses with increased nuchal translucency do not show altered intracardiac flow velocities

To study intracardiac flow velocities in first‐trimester fetuses with normal nuchal translucency thickness (NT) and those with increased NT.