Publications by authors named "Monique C Haak"

81 Publications

Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy.

J Clin Invest 2021 Mar;131(5)

Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences.

Congenital heart disease is the most common type of birth defect, accounting for one-third of all congenital anomalies. Using whole-exome sequencing of 2718 patients with congenital heart disease and a search in GeneMatcher, we identified 30 patients from 21 unrelated families of different ancestries with biallelic phospholipase D1 (PLD1) variants who presented predominantly with congenital cardiac valve defects. We also associated recessive PLD1 variants with isolated neonatal cardiomyopathy. Furthermore, we established that p.I668F is a founder variant among Ashkenazi Jews (allele frequency of ~2%) and describe the phenotypic spectrum of PLD1-associated congenital heart defects. PLD1 missense variants were overrepresented in regions of the protein critical for catalytic activity, and, correspondingly, we observed a strong reduction in enzymatic activity for most of the mutant proteins in an enzymatic assay. Finally, we demonstrate that PLD1 inhibition decreased endothelial-mesenchymal transition, an established pivotal early step in valvulogenesis. In conclusion, our study provides a more detailed understanding of disease mechanisms and phenotypic expression associated with PLD1 loss of function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI142148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919725PMC
March 2021

Respiratory distress syndrome and bronchopulmonary dysplasia after fetal growth restriction: Lessons from a natural experiment in identical twins.

EClinicalMedicine 2021 Feb 29;32:100725. Epub 2021 Jan 29.

Neonatology, Dept. of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.

Background: Fetal growth restriction (FGR) is thought to negatively affect lung development resulting in increased respiratory morbidity. However, research performed in singletons is often limited by a certain level of bias caused by individual differences in genetic constitution, obstetrical and maternal factors.

Methods: Respiratory morbidity was compared between the smaller and the larger twin in monochorionic twins with selective fetal growth restriction (sFGR), defined as a birth weight discordance ≥ 20%, born in our center between 2010 and 2019 in this retrospective study. Respiratory distress syndrome (RDS) was diagnosed based on the clinical picture of a neonate with respiratory failure requiring mechanical ventilation and/or surfactant, confirmed by a chest X-ray. Bronchopulmonary dysplasia (BPD) was diagnosed when the neonate required treatment with >21% oxygen for at least 28 days.

Findings: Median gestational age at birth for the 94 included pregnancies was 32.4 (IQR 30.4-34.3) weeks. Within-pair analyses showed that the prevalence of RDS was lower in the smaller twin compared to the larger twin, 19.1% (18/94) vs 34.0% (32/94), respectively ( = 0.004). The odds of RDS for the larger twin was doubled (OR 2.1 (CI95% 1.3-3.5). In contrast, the rate of BPD in the smaller twin was higher as opposed to the larger twin, 16.7% (15/90) vs 6.7% (6/89), respectively ( = 0.008), with a more than doubled odds (OR 2.5 (CI95% 1.3-4.9)).

Interpretation: Despite being genetically identical, sFGR twins have different respiratory outcomes. Adverse growth condition in the smaller twin is associated with a reduced odds of RDS at birth but a more than doubled odds of BPD, reflecting the pathophysiologic adverse effect of growth restriction on lung development.

Funding: The Dutch Heart Foundation (2017T075).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2021.100725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851769PMC
February 2021

The prognosis of common arterial trunk from a fetal perspective: A prenatal cohort study and systematic literature review.

Prenat Diagn 2021 Jan 22. Epub 2021 Jan 22.

Department of Obstetrics and Fetal Medicine, Leiden University Medical Center, Leiden, Netherlands.

Objective: The limited number of large fetal cohort studies on common arterial trunk (CAT) impedes prenatal counseling at midgestation. This study evaluates the prognosis of CAT from a fetal perspective.

Method: Fetuses with a prenatally diagnosed CAT were extracted from the PRECOR registry (2002-2016). We evaluated fetal and postnatal survival and the presence of additional morbidity at last follow-up. Literature databases were searches systematically for additional cases.

Results: Thirty-eight cases with a prenatal diagnosis of CAT were identified in our registry, of which 18/38 (47%) opted for pregnancy termination (TOP). Two cases resulted in spontaneous intrauterine demise (10%, 2/20), six cases demised postnatally (33%, 6/18), leaving 60% (12/20) alive, after exclusion of TOP, at a mean age of six (range: 2-10 years). Additional morbidity was found in 42% (5/12) of survivors, including 22q11.2 deletion syndrome, Adams-Oliver syndrome and intestinal atresia, whereas 8% (1/12) had developmental delay. The remaining 30% (6/12) of survivors appeared isolated with normal development. All of whom six required replacement of the initial right ventricle to pulmonary artery conduit. Additionally, we reviewed 197 literature cases on short-term outcome.

Conclusion: The risk of fetal and neonatal demise, as well as significant morbidity amongst survivors, should be included in prenatal counseling for CAT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.5907DOI Listing
January 2021

The association between flow and oxygenation and cortical development in fetuses with congenital heart defects using a brain-age prediction algorithm.

Prenat Diagn 2021 Jan 7;41(1):43-51. Epub 2020 Sep 7.

Department of Obstetrics and Prenatal Diagnosis, Leiden University Medical Center, Leiden, The Netherlands.

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 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.5813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891604PMC
January 2021

Quality assessment of ultrasonic foetal biometry during the IUGR Risk Selection (IRIS) trial: A cross sectional study.

Midwifery 2020 Dec 22;91:102842. Epub 2020 Sep 22.

Amsterdam University Medical Centre, Vrije Universiteit Amsterdam, Department of Midwifery Science, AVAG/Amsterdam Public Health, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands; Zorginstituut Nederland, Willem Dudokhof 1, 1112 ZA Diemen, the Netherlands. Electronic address:

Objective: Intrauterine growth restriction is a major risk factor for perinatal morbidity and mortality. Ultrasonic foetal biometry is an important tool to monitor foetal growth. Therefore, the quality of these biometry scans is vital to achieve good diagnostic accuracy. We assessed the quality of foetal biometry during a nationwide trial and explored its association with sonographer's characteristics.

Methods: Four scans from every sonographer (n = 154), performed at 29 and 35 weeks gestational age were collected. Two assessors scored these scans according to a national audit system. A quality score ≥ 65% was considered 'adequate'. We compared the quality scores per scoring criterion (i.e. foetal head measurements, abdominal circumference and femur length with regard to magnification, correctness of the plane and calliper placement) and gestational age. We analysed the associations between characteristics of the sonographers and their scores. In a subsample of scans of 30 sonographers we determined the interrater agreement on the quality scores given by the two assessors independently.

Findings: The mean score was 81.3%. Thirteen sonographers (8.4%) failed to achieve 'adequate quality'. Scores for femur length (83.8%) were significantly higher than those for head (77.9%) and abdominal circumference (78.6%) (both P < 0.05). Scores for correctness of the plane (73.4%) were lower than those for magnification (81.2%) and calliper placement (85.7%) (both P < 0.05). Gestational age did not affect the quality scores. Only the number of scans performed in the previous year was positively associated with the scores (β = 0.01; P < 0.05). The mean interrater difference in quality scoring was 11.1%, with 77.6% agreement on scans of 'adequate quality', but with no agreement on scans with 'insufficient quality'.

Key Conclusions And Implications For Practice: Most sonographers achieved an 'adequate quality' score. Highest quality scores were attained for femur length, lowest quality scores for the correct plane. The number of scans one performs is associated with the quality scores, yet the minimum number of scans to perform for guaranteed quality still needs to be determined. Further research is needed to develop a standardized method to assess and maintain good ultrasonic foetal biometry quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.midw.2020.102842DOI Listing
December 2020

Response to Thibodeau and Langlois.

Genet Med 2021 Jan 27;23(1):244-245. Epub 2020 Sep 27.

Department of Obstetrics and Fetal Medicine, Leiden University Medical Center, Leiden, Netherlands.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-020-00965-2DOI Listing
January 2021

Critical Coarctation of the Aorta in Selective Fetal Growth Restriction and the Role of Coronary Stent Implantation.

Fetal Diagn Ther 2020 Jul 27:1-9. Epub 2020 Jul 27.

Department of Development and Regeneration, Cluster Woman and Child, Biomedical Sciences, KU Leuven, Leuven, Belgium,

Introduction: Monochorionic twins are at increased risk of congenital heart defects (CHDs). Up to 26% have a birth weight <1,500 g, a CHD requiring neonatal surgery, therefore, poses particular challenges.

Objective: The aim of the study was to describe pregnancy characteristics, perinatal management, and outcome of monochorionic twins diagnosed with critical coarctation of the aorta (CoA).

Methods: We included monochorionic twins diagnosed with critical CoA (2010-2019) at 2 tertiary referral centers, and we systematically reviewed the literature regarding CoA in monochorionic twins.

Results: Seven neonates were included. All were the smaller twin of pregnancies complicated by selective fetal growth restriction. The median gestational age at birth was 32 weeks (28-34). Birth weight of affected twins ranged as 670-1,800 g. One neonate underwent coarctectomy at the age of 1 month (2,330 g). Six underwent stent implantation, performed between day 8 and 40, followed by definitive coarctectomy between 4 and 9 months in 4. All 7 developed normally, except for 1 child with neurodevelopmental delay. Three co-twins had pulmonary stenosis, of whom 1 required balloon valvuloplasty. The literature review revealed 10 cases of CoA, all in the smaller twin. Six cases detected in the first weeks after birth were treated with prostaglandins alone, by repeated transcatheter angioplasty or by surgical repair, with good outcome in 2 out of 6.

Conclusions: CoA specifically affects the smaller twin of growth discordant monochorionic twin pairs. Stent implantation is a feasible bridging therapy to surgery in these low birth weight neonates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000508305DOI Listing
July 2020

A low incidence of preoperative neurosonographic abnormalities in neonates with heart defects.

Early Hum Dev 2020 09 1;148:105097. Epub 2020 Jun 1.

Leiden University Medical Center, Willem Alexander Children's Hospital, Department of Neonatology, Leiden, the Netherlands. Electronic address:

Background And Aim: To investigate whether neonates with prenatally detected congenital heart defects (CHD) demonstrate cerebral abnormalities on early preoperative cranial ultrasound (CUS), compared to healthy neonates, and to measure brain structures to assess brain growth and development in both groups.

Study Design, Subjects And Outcome Measures: Prospective cohort study with controls. Between September 2013 and May 2016 consecutive cases of prenatally detected severe isolated CHD were included. Neonatal CUS was performed shortly after birth, before surgery and in a healthy control group. Blinded images were reviewed for brain abnormalities and various measurements of intracranial structures were compared.

Results: CUS was performed in 59 healthy controls and 50 CHD cases. Physiological CUS variants were present in 54% of controls and in 52% of CHD cases. Abnormalities requiring additional monitoring (both significant and minor) were identified in four controls (7%) and five CHD neonates (10%). Significant abnormalities were only identified in four CHD neonates (8%) and never in controls. A separate analysis of an additional 8 CHD neonates after endovascular intervention demonstrated arterial stroke in two cases that underwent balloon atrioseptostomy (BAS). Cerebral measurements were smaller in CHD neonates, except for the cerebrospinal fluid measurements, which were similar to the controls.

Conclusions: The prevalence of significant preoperative CUS abnormalities in CHD cases was lower than previously reported, which may be partially caused by a guarding effect of a prenatal diagnosis. Arterial stroke occurred only in cases after BAS. As expected, neonates with CHD display slightly smaller head size and cerebral growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.earlhumdev.2020.105097DOI Listing
September 2020

Post-Laser Twin Anemia Polycythemia Sequence: Diagnosis, Management, and Outcome in an International Cohort of 164 Cases.

J Clin Med 2020 Jun 5;9(6). Epub 2020 Jun 5.

Department of Obstetrics, Division of Fetal therapy, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

The aim of this study was to investigate the management and outcome in the post-laser twin anemia polycythemia sequence (TAPS). Data of the international TAPS Registry, collected between 2014 and 2019, were used for this study. The primary outcomes were perinatal mortality and severe neonatal morbidity. Secondary outcomes included a risk factor analysis for perinatal mortality and severe neonatal morbidity. A total of 164 post-laser TAPS pregnancies were included, of which 92% (151/164) were diagnosed antenatally and 8% (13/164) postnatally. The median number of days between laser for TTTS and detection of TAPS was 14 (IQR: 7-28, range: 1-119). Antenatal management included expectant management in 43% (62/151), intrauterine transfusion with or without partial exchange transfusion in 29% (44/151), repeated laser surgery in 15% (24/151), selective feticide in 7% (11/151), delivery in 6% (9/151), and termination of pregnancy in 1% (1/151). The median gestational age (GA) at birth was 31.7 weeks (IQR: 28.6-33.7; range: 19.0-41.3). The perinatal mortality rate was 25% (83/327) for the total group, 37% (61/164) for donors, and 14% (22/163) for recipients ( < 0.001). Severe neonatal morbidity was detected in 40% (105/263) of the cohort and was similar for donors (43%; 51/118) and recipients (37%; 54/145), = 0.568. Independent risk factors for spontaneous perinatal mortality were antenatal TAPS Stage 4 (OR = 3.4, 95%CI 1.4-26.0, = 0.015), TAPS donor status (OR = 4.2, 95%CI 2.1-8.3, < 0.001), and GA at birth (OR = 0.8, 95%CI 0.7-0.9, = 0.001). Severe neonatal morbidity was significantly associated with GA at birth (OR = 1.5, 95%CI 1.3-1.7, < 0.001). In conclusion, post-laser TAPS most often occurs within one month after laser for TTTS, but may develop up to 17 weeks after initial surgery. Management is mostly expectant, but varies greatly, highlighting the lack of consensus on the optimal treatment and heterogeneity of the condition. Perinatal outcome is poor, particularly due to the high rate of perinatal mortality in donor twins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9061759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355738PMC
June 2020

Intermittent absent and reversed umbilical artery flows in appropriately grown monochorionic diamniotic twins in relation to proximate cord insertion: A harmful combination?

Prenat Diagn 2020 09 9;40(10):1284-1289. Epub 2020 Jul 9.

Division of Fetal Medicine, Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.

Objective: To compare the prevalence of intermittent absent or reversed end-diastolic flow (iAREDF) in the umbilical artery in appropriately grown monochorionic diamniotic (MCDA) pregnancies with and without proximate cord insertion (PCI), and to evaluate pregnancy outcome.

Methods: The prevalence of iAREDF in MCDA pregnancies with PCI (n = 11) was compared with a control group without PCI (n = 33). PCI was defined as a distance between the cord insertions below the fifth percentile. Placental sharing, number, and diameter of anastomoses were assessed by placental examination. Pregnancy outcome was evaluated.

Results: iAREDF was present in 7/11 PCI pregnancies, compared with 0/33 in the control group (P ≤ .01). All PCI pregnancies and 94% of controls had arterioarterial (AA)-anastomoses (P = .56), the diameter was larger in the PCI group, respectively 3.3 vs 2.1 mm (P = .03). Three cases with iAREDF had adverse outcome, two resulted in fetal death of which one with brain damage in the co-twin, another underwent early premature emergency section for fetal distress.

Conclusion: iAREDF occurs in a large proportion of MCDA pregnancies with PCI and is related to the diameter of the AA anastomosis. We hypothesize that iAREDF in appropriately grown MCDA twin pregnancies reflects an unstable hemodynamic balance with an increased risk for fetal deterioration. Whether outcome in these pregnancies can be improved by altered management requires further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.5736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539996PMC
September 2020

The prevalence of genetic diagnoses in fetuses with severe congenital heart defects.

Genet Med 2020 Jul 28;22(7):1206-1214. Epub 2020 Apr 28.

Department of Obstetrics and Fetal Medicine, Leiden University Medical Center, Leiden, Netherlands.

Purpose: Congenital heart defects (CHD) are associated with genetic syndromes. Rapid aneuploidy testing and chromosome microarray analysis (CMA) are standard care in fetal CHD. Many genetic syndromes remain undetected with these tests. This cohort study aims to estimate the frequency of causal genetic variants, in particular structural chromosome abnormalities and sequence variants, in fetuses with severe CHD at mid-gestation, to aid prenatal counselling.

Methods: Fetuses with severe CHD were extracted from the PRECOR registry (2012-2016). We evaluated pre- and postnatal genetic testing results retrospectively to estimate the frequency of genetic diagnoses in general, as well as for specific CHDs.

Results: 919 fetuses with severe CHD were identified. After exclusion of 211 cases with aneuploidy, a genetic diagnosis was found in 15.7% (111/708). These comprised copy number variants in 9.9% (70/708). In 4.5% (41/708) sequence variants were found that would have remained undetected with CMA. Interrupted aortic arch, pulmonary atresia with ventricular septal defect and atrioventricular septal defect were most commonly associated with a genetic diagnosis.

Conclusion: In case of normal CMA results, parents should be offered exome sequencing sequentially, if time allows for it, especially if the CHD is accompanied by other structural malformations due to the large variety in genetic syndromes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-020-0791-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332415PMC
July 2020

Prevalence, risk factors, and outcome of postprocedural amniotic band disruption sequence after fetoscopic laser surgery in twin-twin transfusion syndrome: a large single-center case series.

Am J Obstet Gynecol 2020 10 23;223(4):576.e1-576.e8. Epub 2020 Apr 23.

Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.

Background: Postprocedural amniotic band disruption sequence is a condition that is associated with intrauterine interventions, and it is characterized by a constriction of the limbs or umbilical cord by fibrous strands, leading to edema, amputation, and/or fetal demise.

Objective: To evaluate the prevalence of, risk factors for, and the outcome of postprocedural amniotic band disruption sequence after fetoscopic laser surgery in twin-twin transfusion syndrome cases.

Study Design: All consecutive cases of twin-twin transfusion syndrome treated with fetoscopic laser coagulation of the vascular anastomoses at our center between January 2002 and March 2019 were included in the study. The occurrence of postprocedural amniotic band disruption sequence in these cases was recorded, and the potential risk factors were analyzed.

Results: Postprocedural amniotic band disruption sequence was detected, at birth, in 2.2% (15/672) of twin-twin transfusion syndrome cases treated with fetoscopic laser surgery, in both the recipients (10/15, 67%) and the donors (5/15, 33%). Postprocedural amniotic band disruption sequence primarily affected the lower extremities (11/15, 73%) and, less frequently, the upper extremities (2/15, 13%), both the upper and lower extremities (1/15, 7%), or the umbilical cord (1/15, 7%). Postprocedural amniotic band disruption sequence led to the amputation of toes in 5 of 15 cases (33%) and resulted in fetal demise because of constriction of the umbilical cord in 1 case (7%). The independent risk factors identified for postprocedural amniotic band disruption sequence were lower gestational age at laser surgery (odds ratio per week, 1.43; 95% confidence interval, 1.12-1.79; P=.003) and the presence of postprocedural chorioamniotic membrane separation on antenatal ultrasound examination (odds ratio, 41.66; 95% confidence interval, 5.44-319.25; P<.001).

Conclusion: The prevalence of postprocedural amniotic band disruption sequence is low, but, when present, it may lead to severe consequences, with amputation of extremities or fetal demise occurring in more than one-third of the cases. Lower gestational age at the time of laser therapy and chorioamniotic membrane separation are independent risk factors for the postprocedural amniotic band disruption sequence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2020.04.016DOI Listing
October 2020

Perioperative fetal hemodynamic changes in twin-twin transfusion syndrome and neurodevelopmental outcome at two years of age.

Prenat Diagn 2020 06 15;40(7):825-830. Epub 2020 Apr 15.

Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, Leiden, The Netherlands.

Objective: To investigate whether perioperative fetal hemodynamic changes in twin-to-twin transfusion syndrome (TTTS) are associated with neurodevelopmental impairment (NDI) at two years.

Methods: Doppler parameters of three sonograms (day before, first day after and 1 week after laser surgery for TTTS) were assessed for correlation with neurodevelopmental outcome at two years (2008-2016). NDI was defined as: cerebral palsy, deafness, blindness, and/or a Bayley-III cognitive/motor developmental test-score > 2SD below the mean.

Results: Long-term outcome was assessed in 492 TTTS survivors. NDI was present in 5% (24/492). After adjustment for severe cerebral injury (present in 4%), associated with NDI were: middle cerebral artery peak systolic velocity (MCA-PSV) >1.5 multiples of the median (MoM) 1 day after surgery (odds ratio [OR] 4.96; 95% confidence interval [CI]: 1.17-21.05, P = .03), a change from normal umbilical artery pulsatility index (UA-PI) presurgery to UA-PI >p95 postsurgery (OR 4.19; 95% CI: 1.04-16.87, P = .04), a change from normal to MCA-PSV >1.5MoM (OR 4.75; 95% CI: 1.43-15.77, P = .01).

Conclusion: Perioperative fetal hemodynamic changes in TTTS pregnancies treated with laser are associated with poor neurodevelopmental outcome. Prospective research on the cerebrovascular response to altered hemodynamic conditions is necessary to further understand the cerebral autoregulatory capacity of the fetus in relation to neurodevelopmental outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.5690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383478PMC
June 2020

Early postnatal cardiac follow-up of survivors of twin-twin transfusion syndrome treated with fetoscopic laser coagulation.

J Perinatol 2020 09 9;40(9):1375-1382. Epub 2020 Mar 9.

Division of Pediatric Cardiology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

Objective: To assess the cardiac function and prevalence of congenital heart defects (CHD) in twin-twin transfusion syndrome (TTTS) survivors.

Study Design: Prospective follow-up of TTTS pregnancies treated with laser surgery (2015-2018). Echocardiography was performed 1 day and 1 month after birth (corrected for prematurity). Results were compared with a control group of age-matched uncomplicated monochorionic twin-pairs at 1 month.

Result: Eighty-nine TTTS (168 neonates) and nine control pregnancies (18 neonates) were enrolled. CHD birth prevalence was 9.2% (8/87) in recipients and 13.6% (11/81) in donors (p = 0.37). Four of 19 (21%) were detected prenatally, all pulmonary stenosis. Donors had lower aortic peak velocities compared with recipients at day 1 (0.66 ± 0.15 m/s vs 0.71 ± 0.19 m/s, p = 0.04) and 1 month (1.04 ± 0.21 m/s vs 1.11 ± 0.18 m/s, p = 0.02), but not compared with controls.

Conclusion: CHD prevalence in TTTS survivors is high, with a low prenatal detection of minor abnormalities. Follow-up fetal echocardiograms and a postnatal echocardiogram should be offered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41372-020-0645-xDOI Listing
September 2020

TRIDENT-2: National Implementation of Genome-wide Non-invasive Prenatal Testing as a First-Tier Screening Test in the Netherlands.

Am J Hum Genet 2019 12 7;105(6):1091-1101. Epub 2019 Nov 7.

Department of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081HV Amsterdam, the Netherlands.

The Netherlands launched a nationwide implementation study on non-invasive prenatal testing (NIPT) as a first-tier test offered to all pregnant women. This started on April 1, 2017 as the TRIDENT-2 study, licensed by the Dutch Ministry of Health. In the first year, NIPT was performed in 73,239 pregnancies (42% of all pregnancies), 7,239 (4%) chose first-trimester combined testing, and 54% did not participate. The number of trisomies 21 (239, 0.33%), 18 (49, 0.07%), and 13 (55, 0.08%) found in this study is comparable to earlier studies, but the Positive Predictive Values (PPV)-96% for trisomy 21, 98% for trisomy 18, and 53% for trisomy 13-were higher than expected. Findings other than trisomy 21, 18, or 13 were reported on request of the pregnant women; 78% of women chose to have these reported. The number of additional findings was 207 (0.36%); these included other trisomies (101, 0.18%, PPV 6%, many of the remaining 94% of cases are likely confined placental mosaics and possibly clinically significant), structural chromosomal aberrations (95, 0.16%, PPV 32%,) and complex abnormal profiles indicative of maternal malignancies (11, 0.02%, PPV 64%). The implementation of genome-wide NIPT is under debate because the benefits of detecting other fetal chromosomal aberrations must be balanced against the risks of discordant positives, parental anxiety, and a potential increase in (invasive) diagnostic procedures. Our first-year data, including clinical data and laboratory follow-up data, will fuel this debate. Furthermore, we describe how NIPT can successfully be embedded into a national screening program with a single chain for prenatal care including counseling, testing, and follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2019.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904791PMC
December 2019

Long-Term Neurodevelopmental Outcome in Twin-to-Twin Transfusion Syndrome: Is there still Room for Improvement?

J Clin Med 2019 Aug 15;8(8). Epub 2019 Aug 15.

Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, J7-48, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

Despite many developments in its management, twin-to-twin transfusion syndrome (TTTS) remains an important risk factor for long-term neurodevelopmental impairment (NDI). Our objective was to compare the incidence of severe NDI in a recent cohort of TTTS survivors, treated with laser surgery from 2011 to 2014, with a previous cohort treated from 2008 to 2010. Neurological, cognitive, and motor development were assessed at two years of age. We determined risk factors associated with Bayley-III scores. Severe NDI occurred in 7/241 (3%) survivors in the new cohort compared to 10/169 (6%) in the previous cohort ( = 0.189). Disease-free survival (survival without severe impairment) did not significantly differ. Low birth weight and being small for gestational age (SGA) were independently associated with lower cognitive scores (both < 0.01). Severe cerebral injury was related to decreased motor scores (B = -14.10; 95% CI -3.16, -25.04; = 0.012). Children with severe NDI were born ≥32 weeks' gestation in 53% of cases and had no evidence of cerebral injury on cranial ultrasound in 59% of cases. Our results suggest that improvement in outcome of TTTS has reached a plateau. Low birth weight, SGA, and cerebral injury are risk factors for poor neurodevelopmental outcome. Neither gestational age above 32 weeks nor the absence of cerebral injury preclude severe NDI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8081226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723379PMC
August 2019

Twin-Twin Transfusion Syndrome with Anemia-Polycythemia: Prevalence, Characteristics, and Outcome.

J Clin Med 2019 Jul 30;8(8). Epub 2019 Jul 30.

Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

The aim of this study was to estimate the prevalence of co-existing anemia-polycythemia (AP) in twin pregnancies with twin-twin transfusion syndrome (TTTS) prior to laser surgery, and to evaluate the characteristics and outcomes in TTTS twins with and without AP. All TTTS cases treated with laser between 2001 and 2019 were retrospectively reviewed for the presence of AP before surgery. AP was defined as delta middle cerebral artery-peak systolic velocity > 0.5 multiples of the median. The primary outcome was a composite of perinatal survival and severe neurodevelopmental impairment (NDI). Secondary outcomes included procedure-related characteristics, severe neonatal morbidity, and disease-free survival. In total, 66% (461/696) of TTTS twin pregnancies were eligible for analysis. AP was detected in 15% (70/461) of the TTTS twins prior to laser surgery. Gestational age at laser was higher in the TTTS+AP group compared to the TTTS-only group-21.0 weeks (interquartile rage (IQR): 18.8-24.0) versus 19.3 weeks (IQR: 17.3-21.9), respectively ( < 0.0001). Fewer placental anastomoses were detected in the TTTS+AP group than in the TTTS-only group-five (IQR: 4-6) versus six (IQR: 5-8), respectively ( < 0.0001). Perinatal survival was 77% (599/782) in the TTTS-only group and 83% (118/142) in the TTTS+AP group ( = 0.130). Severe NDI was 8% (28/370) in TTTS-only and 3% (2/74) in TTTS+AP. TTTS-only twins showed more severe neonatal morbidity than twins with TTTS+AP-23% (132/575) versus 11% (13/115), respectively ( = 0.005). Disease-free survival was lower in the TTTS-only group compared to the TTTS+AP group-62% (341/548) versus 73% (72/98), respectively ( = 0.046). Thus, AP complicates 15% of TTTS twins prior to laser. TTTS+AP twins show a different placental angioarchitecture, a later time of onset of the disease, and a more favorable outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8081129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723740PMC
July 2019

: The win ongitudinal nvestigation of tal Discordance.

Twin Res Hum Genet 2019 12 25;22(6):617-622. Epub 2019 Jul 25.

Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.

Lifelong health is thought to be partially set during intrauterine life by persistent epigenetic changes induced by the prenatal environment. To evaluate this hypothesis, we initiated a prospective longitudinal study in monochorionic (MC) twins: the TwinLIFE study. MC twins are monozygotic, thus in origin genetically identical, and share a single placenta. Although MC twins have many environmental factors in common, in one-third of the MC twin pairs, one fetus has significantly less access to nutrients and resources during pregnancy than its co-twin often resulting in a significant discordance in prenatal growth. Hence, MC twins constitute a unique natural experiment to study the influence of the prenatal environment on health. In TwinLIFE, we will chart intrapair differences in DNA methylation focusing on mesenchymal stromal cells isolated from cord as an advanced proxy of epigenetic dysregulation relevant for long-term health consequences. Next, we will follow up the MC twins for growth, cardiovascular and neurodevelopmental outcomes during childhood and evaluate the impact of an epigenetic signature at birth on future health. The current target is to include 100 MC twin pairs, but we aim to continue enrollment after procuring additional funding. TwinLIFE will not only address an unmet clinical need in the high-risk group of MC twins, but may also advance early-life strategies to prevent adverse growth, cardiovascular and neurodevelopmental outcomes in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/thg.2019.38DOI Listing
December 2019

Cortical development in fetuses with congenital heart defects using an automated brain-age prediction algorithm.

Acta Obstet Gynecol Scand 2019 12 24;98(12):1595-1602. Epub 2019 Aug 24.

Department of Obstetrics and Prenatal Diagnosis, Leiden University Medical Center, Leiden, The Netherlands.

Introduction: Congenital heart defects are associated with neurodevelopmental delay. It is hypothesized that fetuses affected by congenital heart defect have altered cerebral oxygen perfusion and are therefore prone to delay in cortical maturation. The aim of this study was to determine the difference in fetal brain age between consecutive congenital heart defect cases and controls in the second and third trimester using ultrasound.

Material And Methods: Since 2014, we have included 90 isolated severe congenital heart defect cases in the Heart And Neurodevelopment (HAND)-study. Every 4 weeks, detailed neurosonography was performed in these fetuses, including the recording of a 3D volume of the fetal brain, from 20 weeks onwards. In all, 75 healthy fetuses underwent the same protocol to serve as a control group. The volumes were analyzed by automated age prediction software which determines gestational age by the assessment of cortical maturation.

Results: In total, 477 volumes were analyzed using the age prediction software (199 volumes of 90 congenital heart defect cases; 278 volumes of 75 controls). Of these, 16 (3.2%) volume recordings were excluded because of imaging quality. The age distribution was 19-33 weeks. Mixed model analysis showed that the age predicted by brain maturation was 3 days delayed compared with the control group (P = .002).

Conclusions: This study shows that fetuses with isolated cases of congenital heart defects show some delay in cortical maturation as compared with healthy control cases. The clinical relevance of this small difference is debatable. This finding was consistent throughout pregnancy and did not progress during the third trimester.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aogs.13687DOI Listing
December 2019

Twin-Twin Transfusion Syndrome with and without Selective Fetal Growth Restriction Prior to Fetoscopic Laser Surgery: Short and Long-Term Outcome.

J Clin Med 2019 Jul 3;8(7). Epub 2019 Jul 3.

Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

As twin-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR) are both prevalent complications of monochorionic (MC) twin pregnancies, its coexistence is not uncommon. The aim of this study is to evaluate the short and long-term outcome in TTTS with and without sFGR prior to fetoscopic laser coagulation. All TTTS cases treated with laser surgery at our center between 2001-2019 were retrospectively reviewed for the presence of sFGR, defined as an estimated fetal weight (EFW) <10th centile. We compared two groups: TTTS-only and TTTS + sFGR. Primary outcomes were perinatal survival and long-term severe neurodevelopmental impairment (NDI). Of the 527 pregnancies eligible for analysis, 40.8% ( = 215) were categorized as TTTS-only and 59.2% ( = 312) as TTTS + sFGR. Quintero stage at presentation was higher in the TTTS + sFGR group compared to the TTTS-only group (57% compared to 44% stage III). Separate analysis of donors showed significantly lower perinatal survival for donors in the TTTS + sFGR group (72% (224/311) compared to 81% (173/215), = 0.027). Severe NDI at follow-up in long-term survivors in the TTTS-only and TTTS + sFGR group was present in 7% (13/198) and 9% (27/299), respectively ( = 0.385). Both sFGR (OR 1.5;95% CI 1.1-2.0, = 0.013) and lower gestational age at laser (OR 1.1;95% CI 1.0-1.1, = 0.001) were independently associated with decreased perinatal survival. Thus, sFGR prior to laser surgery is associated with a more severe initial presentation and decreased donor perinatal survival. The long-term outcome was not affected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8070969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679158PMC
July 2019

Congenital Heart Defects in Monochorionic Twins: A Systematic Review and Meta-Analysis.

J Clin Med 2019 Jun 24;8(6). Epub 2019 Jun 24.

Division of Fetal Medicine, Department of Obstetrics, Leiden University Medical Center, PO Box 9600, NL-2300 RC Leiden, The Netherlands.

Monochorionic (MC) twins are at an increased risk of developing congenital heart defects (CHDs) compared to singletons and dichorionic twins. The development of acquired CHDs in this specific group of twins is associated with twin-twin transfusion syndrome (TTTS). We performed a systematic review and meta-analysis to provide an overview of the reported birth prevalence of CHDs in liveborn MC twins with and without TTTS. Twelve studies were included in this review. Compared to the reference population, MC twins were 6.3 times more likely to be born with a CHD (59.3 per 1000 liveborn twins; relative risk (RR) 6.3; 95% confidence interval (CI): 4.4-9.1), and TTTS twins had a 12-fold increased risk of having a CHD at birth (87.3 per 1000 live births; RR 12.4, 95% CI: 8.6-17.8). The increased incidence of CHDs can mainly be attributed to the risk of right ventricular outflow tract obstruction (35/1000 TTTS twin live births vs. 0.5/1000 singleton live births). We recommend an expert fetal echocardiogram in all MC twins, follow-up scans in the event of TTTS, and a postnatal cardiac evaluation in all TTTS survivors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm8060902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617007PMC
June 2019

The value of echocardiography and Doppler in the prediction of fetal demise after laser coagulation for TTTS: A systematic review and meta-analysis.

Prenat Diagn 2019 09 17;39(10):838-847. Epub 2019 Jul 17.

Department of Obstetrics, Division of Fetal Medicine, Leiden University Medical Center, Leiden, The Netherlands.

This study aimed to investigate the value of echocardiography and Doppler before fetoscopic laser coagulation for twin-twin transfusion syndrome (TTTS) in the prediction of intrauterine fetal demise (IUFD). We performed a systematic review and meta-analysis to compare preoperative parameters between fetuses with and without demise after laser surgery. Eighteen studies were included. Recipient twins have an increased risk of demise in case of preoperative absent/reversed flow (A/REDF) in the umbilical artery (odds ratio [OR] 2.76, 95% confidence interval [CI], 1.78-4.28), absent or reversed a-wave in the ductus venosus (OR 2.32, 95% CI, 1.70-3.16), or a middle cerebral artery peak systolic velocity > 1.5 multiples of the median (MoM) (OR 7.59, 95% CI, 2.56-22.46). In donors, only A/REDF in the umbilical artery (OR 3.40, 95% CI, 2.68-4.32) and absent or reversed a-wave in the ductus venosus (OR 1.66, 95% CI, 1.12-2.47) were associated with IUFD. No association was found between donor-IUFD and preoperative myocardial performance index (MPI). Two studies found an association between abnormal MPI and recipient demise. With this study, we have identified a set of preoperative Doppler parameters predictive of fetal demise after laser surgery. More research is needed to assess the utility of preoperative echocardiographic parameters such as the MPI in predicting IUFD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.5511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771838PMC
September 2019

From diagnostic yield to clinical impact: a pilot study on the implementation of prenatal exome sequencing in routine care.

Genet Med 2019 10 28;21(10):2303-2310. Epub 2019 Mar 28.

Department of Clinical Genetics, Leiden University Medical Centre, Leiden, the Netherlands.

Purpose: Exome sequencing (ES) is an efficient tool to diagnose genetic disorders postnatally. Recent studies show that it may have a considerable diagnostic yield in fetuses with structural anomalies on ultrasound. We report on the clinical impact of the implementation of prenatal ES (pES) for ongoing pregnancies in routine care.

Methods: We retrospectively analyzed the impact of pES on pregnancy outcome and pre- or perinatal management in the first 22 patients counseled for pES because of one or more structural anomalies on fetal ultrasound.

Results: In two cases, a diagnosis was made by chromosomal microarray analysis after ES counseling. The remaining 20 cases were divided in three groups: (1) pES to aid parental decision making (n = 12), (2) pES in the context of late pregnancy termination requests (n = 5), and (3) pES to guide pre- or perinatal management (n = 3). pES had a clinical impact in 75% (9/12), 40% (2/5), and 100% (3/3) respectively, showing an overall clinical impact of pES of 70% (14/20).

Conclusion: We show that clinical implementation of pES is feasible and affects parental decision making or pre- and perinatal management supporting further implementation of ES in the prenatal setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-019-0499-9DOI Listing
October 2019

Amnioinfusion Compared With No Intervention in Women With Second-Trimester Rupture of Membranes: A Randomized Controlled Trial.

Obstet Gynecol 2019 01;133(1):129-136

Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, the Departments of Obstetrics and Gynecology and Pediatrics, Grow, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Department of Obstetrics, Leiden University Medical Center, Leiden, the Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, the Department of Obstetrics and Gynecology, Maxima Medical Center, Veldhoven, the Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, the Department of Neonatology, Emma Children's Hospital Academic Medical Center, Amsterdam, the Department of Obstetrics and Gynecology, Martini Hospital, Groningen, the Department of Obstetrics and Gynecology, University Medical Center Groningen, Groningen, and the Department of Obstetrics and Gynecology and the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands; and Robinson Research Institute, School of Medicine, University of Adelaide, Adelaide, Australia.

Objective: To assess the effectiveness of amnioinfusion in women with second-trimester preterm prelabor rupture of membranes.

Methods: We performed a nationwide, multicenter, open-label, randomized controlled trial, the PPROM: Expectant Management versus Induction of Labor-III (PPROMEXIL-III) trial, in women with singleton pregnancies and preterm prelabor rupture of membranes at 16 0/7 to 24 0/7 weeks of gestation with oligohydramnios (single deepest pocket less than 20 mm). Participants were allocated to transabdominal amnioinfusion or no intervention in a one-to-one ratio by a web-based system. If the single deepest pocket was less than 20 mm on follow-up visits, amnioinfusion was repeated weekly until 28 0/7 weeks of gestation. The primary outcome was perinatal mortality. We needed 56 women to show a reduction in perinatal mortality from 70% to 35% (β error 0.20, two-sided α error 0.05).

Results: Between June 15, 2012, and January 13, 2016, we randomized 28 women to amnioinfusion and 28 to no intervention. One woman was enrolled before the trial registration date (June 19, 2012). Perinatal mortality rates were 18 of 28 (64%) in the amnioinfusion group vs 21 of 28 (75%) in the no intervention group (relative risk 0.86, 95% CI 0.60-1.22, P=.39).

Conclusion: In women with second-trimester preterm prelabor rupture of membranes and oligohydramnios, we found no reduction in perinatal mortality after amnioinfusion.

Clinical Trial Registration: NTR Dutch Trial Register, NTR3492.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/AOG.0000000000003003DOI Listing
January 2019

Fatal Umbilical Cord Strangulation in the Remaining Co-Twin after Selective Foeticide with Radiofrequency Ablation for Twin-Twin Transfusion Syndrome.

Fetal Diagn Ther 2019 12;45(6):441-444. Epub 2018 Nov 12.

Division of Neonatology, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.

We report a case of a monochorionic diamniotic twin diagnosed with twin-twin transfusion syndrome (TTTS; stage 3) with co-existing severe cerebral damage in the donor twin at 18 + 4 weeks' gestation. After counselling, the parents opted for selective foeticide of the donor twin. For the procedure, radiofrequency ablation (RFA) was used. Serial ultrasound examinations at 20 + 1 and 21 + 1 weeks' gestation showed good recovery of the ex-recipient, after which the patient was sent back to the referring hospital. At 29 + 5 weeks' gestation, an unexpected foetal death was diagnosed. On macroscopic placental examination, (iatrogenic) monoamnionicity was detected. In addition, the umbilical cord of the recipient was found to be constricted by the macerated umbilical cord of the ex-donor. This case demonstrates that iatrogenic monoamnionicity can be a serious complication of RFA in monochorionic twins complicated by TTTS, with a subsequent risk for cord entanglement leading to a fatal outcome for the remaining co-twin. Although the actual incidence of iatrogenic monoamnionicity after RFA remains unknown, increased attention to the intactness of the inter-twin membrane even weeks after the RFA may be required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000493790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604266PMC
January 2020

Acquired right ventricular outflow tract obstruction in twin-to-twin transfusion syndrome; a prospective longitudinal study.

Prenat Diagn 2018 12 28;38(13):1013-1019. Epub 2018 Nov 28.

Department of Obstetrics, Division of Fetal Medicine, Leiden University Medical Center, Leiden, Netherlands.

Objective: The pathophysiology of right ventricular outflow tract obstruction (RVOTO) in twin-to-twin transfusion syndrome (TTTS) recipients is incompletely understood. We aimed to investigate the development and spectrum of RVOTO in TTTS recipients.

Methods: A prospective longitudinal cohort study was conducted between 2015 and 2017. Echocardiographic assessment was performed in recipients from TTTS diagnosis until the neonatal period.

Results: Prenatal RVOTO, defined as abnormal flow velocity waveforms across the pulmonary valve (PV), was diagnosed in 12.9% (16/124) of recipients at TTTS diagnosis. Postnatal RVOTO was found in 6.7% (7/105) of surviving recipients. All recipients with severe postnatal RVOTO showed prenatal RVOTO at TTTS diagnosis. In 5.6% (6/108) of cases, prenatal RVOTO appeared only after laser therapy, and in 1.9% (2/108), this progressed to mild postnatal pulmonary stenosis. Elevated peak systolic PV velocities were more frequently associated with postnatal RVOTO compared with prenatal finding of functional pulmonary atresia. Postnatal RVOTO was associated with early manifestation of TTTS but was equally found in all Quintero stages.

Conclusion: In the spectrum of postnatal RVOTO, severe cases show prenatal RVOTO at TTTS diagnosis. However, RVOTO can develop after laser or even in the neonatal period and in all Quintero stages. A potential risk factor for postnatal RVOTO is early TTTS manifestation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.5378DOI Listing
December 2018

Persistent pulmonary hypertension of the newborn after fetomaternal hemorrhage.

Transfusion 2018 12 13;58(12):2819-2824. Epub 2018 Oct 13.

Division of Fetal Medicine, Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands.

Background: Newborns with anemia are at increased risk of persistent pulmonary hypertension of the newborn (PPHN), yet reports on the association between fetomaternal hemorrhage (FMH) and PPHN are rare. To optimize care for pregnancies complicated by FMH, clinicians should be aware of the risks of FMH and the possible diagnostic and therapeutic options. To increase the current knowledge, the incidence of PPHN and short-term neurologic injury in FMH cases were studied.

Study Design And Methods: We included all FMH cases (≥30 mL fetal blood transfused into the maternal circulation) admitted to our neonatal unit between 2006 and 2018. First, we evaluated the incidence of PPHN and short-term neurologic injury. Second, we studied the potential effect of intrauterine transfusion (IUT).

Results: PPHN occurred in 37.9% of newborns (11 of 29), respectively, 14.3% (one of seven) and 45.5% (10 of 22) in the IUT group and no-IUT group (p = 0.20). The mortality rate was 13.8% (4 of 29). Severe brain injury occurred in 34.5% (10 of 29), respectively, and 14.3% (one of seven) and 40.9% (nine of 22) in the IUT group and no-IUT group (p = 0.37).

Conclusion: Awareness should be raised among perinatologists and neonatologists about the possible life-threatening consequences of FMH, as more than one-third of neonates with anemia due to FMH experience PPHN and suffer from severe brain injury. Antenatal treatment with IUT seems to reduce these risks. Specialists should therefore always consider fetal anemia in FMH cases and refer patients to a fetal therapy center. If anemia is present at birth, it should be corrected promptly and neonatologists should be aware of signs of PPHN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.14932DOI Listing
December 2018

The effect of the introduction of the three-vessel view on the detection rate of transposition of the great arteries and tetralogy of Fallot.

Prenat Diagn 2018 11 11;38(12):951-957. Epub 2018 Sep 11.

Department of Obstetrics and Fetal Medicine, Leiden University Medical Center, Leiden, The Netherlands.

Objectives: The 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.

Methods: All 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.

Results: In 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).

Conclusions: In 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pd.5347DOI Listing
November 2018

Systematic review and meta-analysis of the performance of second-trimester screening for prenatal detection of congenital heart defects.

Int J Gynaecol Obstet 2018 Feb 22;140(2):137-145. Epub 2017 Nov 22.

Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, Netherlands.

Background: The prenatal detection rate of congenital heart defects (CHDs) is increasing, but reported rates vary.

Objectives: To determine the performance of the second-trimester anomaly scan to detect CHD.

Search Strategy: PubMed and Embase were searched for relevant studies in any language from inception to February 3, 2017. The search terms included "prenatal diagnosis" or "pregnancy," "cardiovascular diseases" or "cardiac defects," "congenital," and "specificity," or "sensitivity," or "cohort study."

Selection Criteria: Cohort studies assessing the detection rate of CHD during population-based prenatal screening from 1995 were eligible for inclusion.

Data Collection And Analysis: Data were collected from identified studies; authors were approached for additional data when necessary. A review and meta-analysis were performed. When possible, separate analyses were undertaken for isolated CHD cases.

Main Results: Meta-analysis of seven studies showed the pooled detection rate of CHD in unselected populations as 45.1% (95% confidence interval 33.5%-57.0%). However, the rate of detection of univentricular defects and heterotaxy was above 85%. Similar rates were found among cases of isolated CHD.

Conclusions: Prenatal detection showed a strong correlation with CHD severity. The detection of conotruncal anomalies needs to improve. A thoroughly organized screening program will be essential to achieve a higher detection rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijgo.12373DOI Listing
February 2018