Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study

ObjectiveTo 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 DesignNeurodevelopmental 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.ResultsA 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).ConclusionIncidence 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

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

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% (n = 215) were categorized as TTTS-only and 59.2% (n = 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), p = 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 (p = 0.385). Both sFGR (OR 1.5;95% CI 1.1–2.0, p = 0.013) and lower gestational age at laser (OR 1.1;95% CI 1.0–1.1, p = 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

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

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 (p < 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 (p < 0.0001). Perinatal survival was 77% (599/782) in the TTTS-only group and 83% (118/142) in the TTTS+AP group (p = 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 (p = 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 (p = 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

Impact of placental sharing and large bidirectional anastomoses on birthweight discordance in monochorionic twins: a retrospective cohort study in 449 cases

BACKGROUND: In monochorionic twin pregnancies, the fetuses share a single placenta. When this placenta is unequally shared, a discordant antenatal growth pattern ensues resulting in high rates of perinatal morbidity and mortality. Understanding placental pathophysiology is paramount in devising feasible antenatal management strategies. Unequal placental sharing is not the sole determinant of birthweight discordance as there is no one-to-one relationship with placental share discordance. Placental angioarchitecture, especially the presence of large bidirectional anastomoses, is thought to affect this relationship by allowing for a compensatory intertwin blood flow. OBJECTIVE: This study aimed to assess whether placental angioarchitecture can affect birthweight discordance in live-born monochorionic twins, the aim of our study was 2-fold: (1) to assess the relationship between birthweight discordance and placental share discordance and (2) to examine to what extent large bidirectional anastomoses can compensate for the effect of unequal placental sharing on birthweight discordance, with a subgroup analysis for umbilical artery Doppler flow patterns in cases with a birthweight discordance of ≥20%. STUDY DESIGN: This was a retrospective cohort study that included monochorionic twin pregnancies observed in our center between March 2002 and June 2021, in which twins with a birthweight discordance of ≥20% were classified according to umbilical artery Doppler flow patterns of the smaller twin. We excluded cases with twin-twin transfusion syndrome and twin anemia polycythemia sequence. Monochorionic placentas of live-born twins were injected with dye, and images were saved for computer measurements of placental sharing and the diameter of anastomoses. Univariate linear regressions of the relationship between placental share discordance and birthweight discordance (both calculated as weight or share larger twin-weight or share smaller twin/weight or share larger twin×100%) and the relationship between arterioarterial and venovenous diameters and birthweight ratio/placental territory ratio were performed. RESULTS: A total of 449 placentas were included in the analysis. Placental share discordance was positively correlated with birthweight discordance (β coefficient, 0.325; 95% confidence interval, 0.254-0.397; P<.0001). The arterioarterial diameter was negatively correlated with birthweight ratio/placental territory ratio (β coefficient, -0.041; 95% confidence interval, -0.059 to -0.023; P<.0001), meaning that an increase in arterioarterial diameter leads to less birthweight discordance than expected for the amount of placental share discordance. There was no relationship between venovenous diameter and birthweight ratio/placental territory ratio (β coefficient, -0.007; 95% confidence interval, -0.027 to 0.012; P=.473). CONCLUSION: Birthweight discordance in monochorionic twins was strongly associated with placental share discordance. Large arterioarterial anastomoses can mitigate the effect of unequal placental sharing

Long-term neurodevelopmental outcome in children after antenatal intravenous immune globulin treatment in fetal and neonatal alloimmune thrombocytopenia

Background: Children with fetal and neonatal alloimmune thrombocytopenia face increased risk of intracranial hemorrhage potentially leading to developmental impairment. To prevent intracranial hemorrhage, pregnant women with alloantibodies against fetal platelets are often treated with intravenous immunoglobulin. Intravenous immunoglobulin seems effective in vastly reducing the risk of fetal or neonatal bleeding complications. However, information on long-term neurodevelopment of these children is lacking. Objective: This study aimed to evaluate long-term neurodevelopmental outcome in children with fetal and neonatal alloimmune thrombocytopenia who were treated with intravenous immunoglobulin antenatally. Study Design: An observational cohort study was performed, including children of mothers treated with intravenous immunoglobulin during pregnancy because a previous child was diagnosed with fetal and neonatal alloimmune thrombocytopenia. Children were invited for a follow-up assessment including standardized cognitive and neurologic tests. The parents were asked to complete a behavioral questionnaire and school performance reports. The primary outcome was severe neurodevelopmental impairment, defined as severe cognitive impairment (intelligence quotient <70), cerebral palsy with Gross Motor Function Classification System Level ≥3, bilateral blindness, and/or bilateral deafness (requiring amplification). The secondary outcome was mild to moderate neurodevelopmental impairment, defined as either mild to moderate cognitive impairment (intelligence quotient <85), cerebral palsy with Gross Motor Function Classification System Level ≤2, minor neurologic dysfunction, vision loss, and/or hearing loss. Results: Between 2003 and 2017, 51 children were live-born after antenatal intravenous immunoglobulin treatment. One family moved abroad and was therefore not eligible for inclusion. In total, 82% (41/50) of the eligible cases were included for neurodevelopmental assessment at a median age of 9 years and 8 months. Severe neurodevelopmental impairment was not detected. The incidence of mild to moderate neurodevelopmental impairment was 14% (6/41; 95% confidence interval, 6%–29%). The children's mean cognitive score, behavioral scores, and academic achievement were not different from those observed in the Dutch norm groups. Neuroimaging was performed in 90% (37/41) of cases. Severe intracranial hemorrhage was diagnosed in 2 cases (5%), one antenatally before the start of intravenous immunoglobulin and the other case 1 day after birth. Both cases had a normal neurodevelopmental outcome. Conclusion: The risk of neurodevelopmental impairment in children whose mothers were treated for fetal and neonatal alloimmune thrombocytopenia with antenatal intravenous immunoglobulin is comparable to that reported in the general population