Introduction Neurodevelopmental delay is more common in children born with congenital heart defects (CHD), even with optimal perinatal and peri-operative care. It is hypothesized that fetuses with... Show moreIntroduction Neurodevelopmental delay is more common in children born with congenital heart defects (CHD), even with optimal perinatal and peri-operative care. It is hypothesized that fetuses with CHD are prone to neurological impairment in utero due to their cardiac defect, possibly leading to delayed cortical development. Methods Cerebral cortical maturation was assessed with advanced neurosonographic examinations every 4 weeks in fetuses with CHD and compared to control fetuses. Five different primary fissures and four areas were scored (ranging 0-5) by blinded examiners using a cortical maturation scheme. Results Cortical staging was assessed in 574 ultrasound examinations in 85 CHD fetuses and 61 controls. Small differences in grading were seen in Sylvian and cingulate fissures. (Sylvian fissure: -0.12 grade, 95% CI (-0.23; -0.01) p = 0.05, cingulate fissure: -0.24 grade, 95% CI (-0.38; -0.10) p = <0.001. Other cortical areas showed normal maturation as compared to control fetuses. Conclusion Small differences were seen in three of the nine analyzed cortical areas in CHD fetuses, in contrast to previous reports on progressive third-trimester delay. The clinical implications of the small differences however, remain unknown. Show less
Objectives Presumably, changes in fetal circulation contribute to the delay in maturation of the cortex in fetuses with congenital heart defect (CHD). The aim of the current study is to analyze... Show moreObjectives Presumably, changes in fetal circulation contribute to the delay in maturation of the cortex in fetuses with congenital heart defect (CHD). The aim of the current study is to analyze fetal brain development based on hemodynamic differences, using novel brain-age prediction software. Methods We have performed detailed neurosonography, including acquiring 3D volumes, prospectively in cases with isolated CHD from 20 weeks onwards. An algorithm that assesses the degree of fetal brain-age automatically was used to compare CHD cases to controls. We stratified CHD cases according to flow and oxygenation profiles by lesion physiology and performed subgroup analyses. Results A total of 616 ultrasound volumes of 162 CHD cases and 75 controls were analyzed. Significant differences in maturation of the cortex were observed in cases with normal blood flow toward the brain (-3.8 days, 95%CI [-5.5; -2.0],P = <.001) and low (-4.0 days, 95% CI [-6.7; -1.2]P = <.05; hypoplastic left heart syndrome[HLHS]) and mixed (-4.4 days, 95%CI [-6.4; -2.5]p = <.001) oxygen saturation in the ascending aorta (TGA) and in cardiac mixing (eg, Fallot) cases. Conclusion The current study shows significant delay in brain-age in TGA and Fallot cases as compared to control cases. However, the small differences found in this study questions the clinical relevance. Show less
ObjectivesThe aim of this study was to analyze the annual detection rate (DR) of transposition of the great arteries (TGA) and tetrology of Fallot (ToF), after the introduction of the three‐vessel... Show moreObjectivesThe aim of this study was to analyze the annual detection rate (DR) of transposition of the great arteries (TGA) and tetrology of Fallot (ToF), after the introduction of the three‐vessel view as a mandatory plane in 2012.MethodsAll registered TGA and ToF cases were retrospectively extracted from our registry between 2007 and 2016. We compared the DR in a 10‐year period, before 2011, with the DR of TGA and ToF after 2012.ResultsIn the period before 2012, 23 of the 52 TGA cases were prenatally detected (44.2%), compared with 42 of the 51 cases (82.4%) after 2012. For ToF, the DRs increased from 28 of 64 cases (43.8%) to 42 of 62 cases (67.7%) in the aforementioned periods. The increase in DRs for both defects was statistically significant (P ≤ 0.001 and P ≤ 0.05).ConclusionsIn this nationally organized prenatal screening program with a quality monitoring system and a uniform protocol, DRs of 82.4% for TGA and 67.7% for ToF were reached after the introduction of the three‐vessel view as a mandatory item. The three‐vessel view significantly contributes to the detection of these conotruncal anomalies. Show less
OBJECTIVE To determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT).... Show moreOBJECTIVE To determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT). STUDY DESIGN Neurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests, including the Bayley Scales of Infant Development, the Wechsler Preschool and Primary Scale of Intelligence, and the Wechsler Intelligence Scale for Children, according to the children's age. Primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe developmental delay, bilateral deafness, and/or blindness. RESULTS A total of 291 children were evaluated at a median age of 8.2 years (range, 2-17 years). Cerebral palsy was detected in 6 (2.1%) children, severe developmental delay in 9 (3.1%) children, and bilateral deafness in 3 (1.0%) children. The overall incidence of neurodevelopmental impairment was 4.8% (14/291). In a multivariate regression analysis including only preoperative risk factors, severe hydrops was independently associated with neurodevelopmental impairment (odds ratio, 11.2; 95% confidence interval, 1.7-92.7). CONCLUSION Incidence of neurodevelopmental impairment in children treated with intrauterine transfusion for fetal alloimmune anemia is low (4.8%). Prevention of fetal hydrops, the strongest preoperative predictor for impaired neurodevelopment, by timely detection, referral and treatment may improve long-term outcome. Show less
During pregnancy, maternal lymphocytes at the fetal-maternal interface play a key role in the immune acceptance of the allogeneic fetus. Recently, CD4(+) CD25(bright) regulatory T cells have been... Show moreDuring pregnancy, maternal lymphocytes at the fetal-maternal interface play a key role in the immune acceptance of the allogeneic fetus. Recently, CD4(+) CD25(bright) regulatory T cells have been shown to be concentrated in decidual tissue, where they are able to suppress fetus-specific and nonspecific immune responses. Decidual CD8(+) T cells are the main candidates to recognize and respond to fetal HLA-C at the fetal-maternal interface, but data on the characteristics of these cells are limited. In this study we examined the decidual and peripheral CD8(+) T cell pool for CD45RA, CCR7, CD28, and CD27 expression, using nine-color flow cytometry. Our data demonstrate that decidual CD8(+) T cells mainly consist of differentiated CD45RA(-)CCR7(-) effector-memory (EM) cells, whereas unprimed CD45RA(+) CCR7(+) naive cells are almost absent. Compared with peripheral blood EM CD8(+) T cells, the decidual EM CD8(+) T cells display a significantly reduced expression of perforin and granzyme B, which was confirmed by immunohistochemistry of decidual tissue sections. Interestingly, quantitative PCR analysis demonstrates an increased perforin and granzyme B mRNA content in decidual EM CD8(+) T cells in comparison with peripheral blood EM CD8(+) T cells. The presence of high levels of perforin and granzyme B mRNA in decidual EM T cells suggests that decidual CD8(+) T cells pursue alternative means of EM cell differentiation that may include a blockade of perforin and granzyme B mRNA translation into functional perforin and granzyme B proteins. Regulation of decidual CD8(+) T cell differentiation may play a crucial role in maternal immune tolerance to the allogeneic fetus. The Journal of Immunology, 2010, 185: 4470-4477. Show less
During pregnancy, maternal lymphocytes at the fetal-maternal interface play a key role in the immune acceptance of the allogeneic fetus. Recently, CD4(+) CD25(bright) regulatory T cells have been... Show moreDuring pregnancy, maternal lymphocytes at the fetal-maternal interface play a key role in the immune acceptance of the allogeneic fetus. Recently, CD4(+) CD25(bright) regulatory T cells have been shown to be concentrated in decidual tissue, where they are able to suppress fetus-specific and nonspecific immune responses. Decidual CD8(+) T cells are the main candidates to recognize and respond to fetal HLA-C at the fetal-maternal interface, but data on the characteristics of these cells are limited. In this study we examined the decidual and peripheral CD8(+) T cell pool for CD45RA, CCR7, CD28, and CD27 expression, using nine-color flow cytometry. Our data demonstrate that decidual CD8(+) T cells mainly consist of differentiated CD45RA(-)CCR7(-) effector-memory (EM) cells, whereas unprimed CD45RA(+) CCR7(+) naive cells are almost absent. Compared with peripheral blood EM CD8(+) T cells, the decidual EM CD8(+) T cells display a significantly reduced expression of perforin and granzyme B, which was confirmed by immunohistochemistry of decidual tissue sections. Interestingly, quantitative PCR analysis demonstrates an increased perforin and granzyme B mRNA content in decidual EM CD8(+) T cells in comparison with peripheral blood EM CD8(+) T cells. The presence of high levels of perforin and granzyme B mRNA in decidual EM T cells suggests that decidual CD8(+) T cells pursue alternative means of EM cell differentiation that may include a blockade of perforin and granzyme B mRNA translation into functional perforin and granzyme B proteins. Regulation of decidual CD8(+) T cell differentiation may play a crucial role in maternal immune tolerance to the allogeneic fetus. The Journal of Immunology, 2010, 185: 4470-4477. Show less
Bakker, J.J.H.; Verhoeven, C.J.M.; Janssen, P.F.; Lith, J.M. van; Oudgaarden, E.D. van; Bloemenkamp, K.W.M.; ... ; Post, J.A.M. van der 2010
OBJECTIVE: To estimate whether multiplex ligation-dependent probe amplification (MLPA), a molecular technique used for detecting the most common chromosomal aneuploidies, is comparable with... Show moreOBJECTIVE: To estimate whether multiplex ligation-dependent probe amplification (MLPA), a molecular technique used for detecting the most common chromosomal aneuploidies, is comparable with karyotyping for the detection of aneuploidies of chromosomes X, Y, 13, 18, and 21 in routine clinical practice and to estimate the costs differences of both techniques. METHODS: In this prospective, nationwide cohort study, we consecutively included 4,585 women who had an amniocentesis because of their age (36 years or older), increased risk after prenatal screening, or maternal anxiety. Amniotic fluid samples were tested independently with both MLPA and karyotyping. The primary outcome was diagnostic accuracy of MLPA to detect aneuploidies of chromosomes X, Y, 13, 18, and 21. Secondary outcome Measures were turnaround time for test results and costs. A sample size was calculated using a critical noninferiority margin of 0.002; therefore, at least 4,497 paired test results were needed (one-sided alpha 0.05, power 0.90). RESULTS: Diagnostic accuracy of MLPA was 1.0 (95% confidence interval [CI] 0.99-1.0), sensitivity was 100% (95% CI 0.96-1.0) and specificity was 100% (95% CI 0.999-1.0). Diagnostic accuracy of MLPA was statistically similar (noninferior) to that of karyotyping (P<.001). In 75 cases, MLPA failed (1.6%); karyotyping failed once (0.02%). Compared with karyotyping, MLPA shortened the waiting time by 14.5 days (P<.001, 95% Cl 14.3-14.6) and cost less (-47, P<.001). CONCLUSION: In routine clinical practice, diagnostic accuracy of MLPA for detection of trisomies X, Y, 13, 18, and 21 is comparable with that of karyotyping, and it reduces waiting time at lower costs. (Obstet Gynecol 2010,115:297-303) Show less
Bakker, J.J.H.; Verhoeven, C.J.M.; Janssen, P.F.; Lith, J.M. van; Oudgaarden, E.D. van; Bloemenkamp, K.W.M.; ... ; Post, J.A.M. van der 2010
BACKGROUND It has been hypothesized that internal tocodynamometry, as compared with external monitoring, may provide a more accurate assessment of contractions and thus improve the ability to... Show moreBACKGROUND It has been hypothesized that internal tocodynamometry, as compared with external monitoring, may provide a more accurate assessment of contractions and thus improve the ability to adjust the dose of oxytocin effectively, resulting in fewer operative deliveries and less fetal distress. However, few data are available to test this hypothesis. METHODS We performed a randomized, controlled trial in six hospitals in the Netherlands to compare internal tocodynamometry with external monitoring of uterine activity in women for whom induced or augmented labor was required. The primary outcome was the rate of operative deliveries, including both cesarean sections and instrumented vaginal deliveries. Secondary outcomes included the use of antibiotics during labor, time from randomization to delivery, and adverse neonatal outcomes (defined as any of the following: an Apgar score at 5 minutes of less than 7, umbilical-artery pH of less than 7.05, and neonatal hospital stay of longer than 48 hours). RESULTS We randomly assigned 1456 women to either internal tocodynamometry (734) or external monitoring (722). The operative-delivery rate was 31.3% in the internal-tocodynamometry group and 29.6% in the external-monitoring group (relative risk with internal monitoring, 1.1; 95% confidence interval [CI], 0.91 to 1.2). Secondary outcomes did not differ significantly between the two groups. The rate of adverse neonatal outcomes was 14.3% with internal monitoring and 15.0% with external monitoring (relative risk, 0.95; 95% CI, 0.74 to 1.2). No serious adverse events associated with use of the intrauterine pressure catheter were reported. CONCLUSIONS Internal tocodynamometry during induced or augmented labor, as compared with external monitoring, did not significantly reduce the rate of operative deliveries or of adverse neonatal outcomes. (Current Controlled Trials number, ISRCTN13667534; Netherlands Trial number, NTR285.) Show less
Boormans, E.M.; Birnie, E.; Oepkes, D.; Galjaard, R.J.; Schuring-Blom, G.H.; Lith, J.M. van; MLP Karyotyping Evaluation MAKE St 2010
OBJECTIVE: To estimate whether multiplex ligation-dependent probe amplification (MLPA), a molecular technique used for detecting the most common chromosomal aneuploidies, is comparable with... Show moreOBJECTIVE: To estimate whether multiplex ligation-dependent probe amplification (MLPA), a molecular technique used for detecting the most common chromosomal aneuploidies, is comparable with karyotyping for the detection of aneuploidies of chromosomes X, Y, 13, 18, and 21 in routine clinical practice and to estimate the costs differences of both techniques. METHODS: In this prospective, nationwide cohort study, we consecutively included 4,585 women who had an amniocentesis because of their age (36 years or older), increased risk after prenatal screening, or maternal anxiety. Amniotic fluid samples were tested independently with both MLPA and karyotyping. The primary outcome was diagnostic accuracy of MLPA to detect aneuploidies of chromosomes X, Y, 13, 18, and 21. Secondary outcome measures were turnaround time for test results and costs. A sample size was calculated using a critical noninferiority margin of 0.002; therefore, at least 4,497 paired test results were needed (one-sided alpha 0.05, power 0.90). RESULTS: Diagnostic accuracy of MLPA was 1.0 (95% confidence interval [CI] 0.99-1.0), sensitivity was 100% (95% CI 0.96-1.0) and specificity was 100% (95% CI 0.999-1.0). Diagnostic accuracy of MLPA was statistically similar (noninferior) to that of karyotyping (P<.001). In 75 cases, MLPA failed (1.6%); karyotyping failed once (0.02%). Compared with karyotyping, MLPA shortened the waiting time by 14.5 days (P<.001, 95% CI 14.3-14.6) and cost less (-47, P<.001). CONCLUSION: In routine clinical practice, diagnostic accuracy of MLPA for detection of trisomies X, Y, 13, 18, and 21 is comparable with that of karyotyping, and it reduces waiting time at lower costs. Show less
