Manon Gijtenbeek

BACKGROUND: The relationship between fetal aortic valvuloplasty procedural volume and outcomes is crucial to understand whether regionalization should be advised worldwide. This study utilizes the International Fetal Cardiac Intervention Registry to examine the relationship between center volume for fetal aortic valvuloplasty and outcome metrics including procedure success, complications, and fetal death. METHODS: Data were included from institutions performing ≥3 procedures (2001–2018). The primary outcome was technical success, defined as ≥1 balloon inflation across the aortic valve, with increased antegrade flow across the valve and new aortic regurgitation. Secondary end points were procedural complications and fetal periprocedural death (within 48 hours). Univariable and Classification and Regression Tree analyses were performed. RESULTS: Eleven centers, with volumes ranging from 6 to 31 cases, performed 162 fetal aortic valvuloplasties with a technical success rate of 80.2%. Higher volume was not associated with better technical success or fewer complications but was associated with fewer periprocedural fetal deaths. Employing Classification and Regression Tree modeling, the largest drivers of improved outcomes for all measures were greater estimated fetal weight and gestational age. A single cardiac puncture was associated with greater technical success and fewer procedural complications after accounting for fetal estimated fetal weight and gestational age. CONCLUSIONS: In this registry cohort, higher-volume centers did not have greater fetal aortic valvuloplasty technical success or fewer complications but did have fewer periprocedural fetal deaths. Fetal gestational age and number of cardiac punctures influenced outcomes, suggesting that unmeasured fetal selection criteria, such as different referral patterns, and technical expertise, indicative of overall center/team experience, may influence fetal survival.

Objectives: To assess maternal complications after fetoscopic laser surgery (FLS) for the twin‐to‐twin transfusion syndrome (TTTS).Methods: All consecutive cases treated with FLS for TTTS between 2008 and 2021 at the Leiden University Medical Center (LUMC) were included. We allocated complications in three timeframes: “Admission for laser surgery,” “pregnancy after laser,” and “delivery and third stage of labor.” Maternal complications were graded according to the Maternal and Fetal Adverse Event Terminology (MFAET) and for intra‐abdominal hemorrhage, the Common Terminology Criteria for Adverse Events (CTCAE).Results: In the study period, 637 mothers were treated for TTTS with FLS. There were 1559 occurrences of maternal complications. The rate of severe maternal complications (grade 3 or 4) was 8.0%. Severe complications consisted of six cases of severe intra‐abdominal hemorrhage, nine cases of severe hemorrhage in pregnancy, one with severe chorioamnionitis, 10 with severe preeclampsia/HELLP syndrome, and 25 with a severe postpartum hemorrhage.Conclusions: Even though it is the gold standard for treating TTTS, FLS comes at a risk to the mother which should not be neglected. And even though not all complications have serious consequences to the mother, the severe maternal complication rate of 8.0% should be added to the inherent risks for the fetus, and should be discussed with patients eligible for surgery in order to make an informed decision on treatment options.

Objectives: This systematic review explores cardiac adaptation in monochorionic (MC) twins with twin–twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) and assesses the risk of congenital heart defects (CHDs).Methods: Adhering to PRISMA guidelines, 63 studies were reviewed (49 on cardiac adaptation, 13 on CHD, one on both). A narrative synthesis of cardiac adaptation patterns was performed. Additionally, a meta‐analysis compared the livebirth prevalence of CHD in TTTS and sFGR against uncomplicated MC twins.Results: In TTTS recipients, cardiac function may be impaired for diastolic, systolic, as well as global functions, while in donors, cardiac function is generally preserved. In sFGR, large twins may show hypertrophic cardiomyopathy, and small twins may show impaired systolic function. Co‐occurrence of TTTS and sFGR magnifies cardiac impact but is often underreported. Meta‐analysis for CHD prevalence revealed a relative risk ratio of 3.5 (95% CI: 2.5–4.9) for TTTS and 2.2 (95%CI: 1.3–3.5) for sFGR compared with uncomplicated MC twins.Conclusions: This study highlights the well‐documented cardiac adaptation in TTTS, contrasting with limited understanding in sFGR. Elevated CHD risks were observed in both conditions. Enhanced cardiovascular surveillance is warranted in complicated MC twin pregnancies. Future research should explore cardiac adaptation in sFGR and its long‐term consequences.

Objectives: To explore whether intertwin discordance in myocardial performance index (MPI) or cardiac time intervals enables the prediction of twin–twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) pregnancies with amniotic fluid discordance.Methods: Prospective cohort study of MCDA pregnancies with amniotic fluid discordance ≥4 cm. Serial ultrasound examinations consisted of evaluation of amniotic fluid, fetal Dopplers and fetal cardiac function.Results: We included 21 “future‐TTTS” (group I), 18 selective fetal growth restriction (sFGR; group II) and 20 uncomplicated MCDA twin pairs (group III). Group I had a higher intertwin difference in left ventricle (LV) MPI and right ventricle (RV) MPI compared to group II and III. The intertwin difference in global heart relaxation time was significantly higher in group I compared to group III. Future recipient twins had significantly higher contraction times of the global heart and RV and lower relaxation times of the global heart and RV compared to the “expected recipients” in group II and III.Conclusion: Intertwin discordance in LV‐MPI and RV‐MPI differentiate between TTTS and MCDA pregnancies with transient discordant amniotic fluid volume. Cardiac time intervals identify future recipient twins. The clinical utility of cardiac time intervals and MPI should be investigated in large prospective studies.

Introduction: Monochorionic twins are at increased risk of congenital heart defects (CHDs). Up to 26% have a birth weight 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.

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.

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.

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.

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.

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.