Objective The role of placental inflammation in neonatal morbidities is underestimated due to lack of placental examination. This meta-analysis aims to assess the association between histological... Show moreObjective The role of placental inflammation in neonatal morbidities is underestimated due to lack of placental examination. This meta-analysis aims to assess the association between histological chorioamnionitis (HCA) with and without funisitis (FUN) and risk of retinopathy of prematurity (ROP).Study Design Forty-five studies reporting (unadjusted) data on HCA without FUN and HCA with FUN in neonates with ROP were included. Primary outcomes were any stage ROP and severe ROP. Potential confounders explored were gestational age (GA) at birth, birthweight, maternal steroid use, necrotizing enterocolitis, sepsis (suspected/proven) and mechanical ventilation duration.Results Neonates with HCA had increased risk for any stage ROP (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.3-2.4) and severe ROP (OR 1.5; 95% CI 1.2-1.8) compared with neonates without HCA. The rates of any stage ROP (OR 1.8; 95% CI 1.4-2.2) and severe ROP (OR 1.4; 95% CI 1.1-1.6) were higher in neonates with FUN compared with neonates without FUN. Multivariate meta-regression analysis suggests that lower GA increases the effect size between FUN and severe ROP.Conclusion This meta-analysis confirms that presence of HCA and FUN are risk factors for any stage ROP and severe ROP. Structured histological placental examination of HCA and FUN may be a tool to further refine the ROP risk profile. Show less
Vos, T.W.D.; Winkelhorst, D.; Porcelijn, L.; Beaufort, M.; Oldert, G.; Bom, J.G. van der; ... ; Schoot, E. van der 2023
Background Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare disease that untreated can lead to intracranial haemorrhage or death. The natural history of FNAIT is still unclear;... Show moreBackground Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a rare disease that untreated can lead to intracranial haemorrhage or death. The natural history of FNAIT is still unclear; therefore, the benefits of screening cannot be estimated and no routine screening is yet in place. We aimed to assess the incidence of clinically detectable FNAIT among pregnancies in human platelet antigen-1a (HPA-1a)-immunised women. Methods We did a prospective observational cohort study of pregnant women negative for rhesus D (RhD) and rhesus c (Rhc) antigens, without age limits, who underwent routine antenatal screening for red cell antibodies at 27 weeks' gestation and were typed for HPA-1a between March 1, 2017, and May 1, 2020. HPA-1a-negative women were tested for HPA alloantibodies. Health-care professionals were masked to all test results. The main outcome was the proportion of neonates with severe, clinically detectable FNAIT, defined as having an intracranial bleed, organ bleed, or bleeding-related death observed during pregnancy or within the first week of life. Cases of clinically detectable FNAIT not categorised as severe were categorised as mild. This study is registered with ClinicalTrials.gov (NCT04067375). Findings Of 153 106 women typed for HPA-1a, 3722 (2 center dot 4%) were negative for HPA-1a. 913 HPA-1a-negative women gave informed consent, underwent HPA-1a antibody screening, and were included in the study. Anti-HPA-1a antibodies were detected in 85 HPA-1a-negative participants, among whom three with HPA-1a-negative fetuses and one with a previous child with FNAIT were excluded. As controls, 820 HPA-1a-negative, non-immunised pregnancies and 2704 randomly selected pregnancies of women negative for RhD and Rhc who were typed HPA-1a positive were included. Of 81 fetuses included, one (1 center dot 2%) was diagnosed with severe HPA-1a-mediated intracranial haemorrhage and three (3 center dot 7%) had mild FNAIT. Gravidity and parity did not seem to be risk factors for HPA-1a immunisation. 73 (90 center dot 1%) of 81 HPA-1a-immunised women were positive for HLA-DRB3*01:01. Interpretation Our data suggest that, without intervention, the incidence of major clinically detectable bleeding in FNAIT is estimated as 11 (95% CI 0-32) per 10 000 HPA-1a-negative pregnancies. These findings imply that severe bleeding is a rare event that potentially could be prevented by a screening programme. Show less
Todtenhaupt, P.; Franken, L.A.; Groene, S.G.; Hoolwerff, M. van; Meeren, L.E. van der; Klink, J.M.M. van; ... ; Pel, M. van 2023
Background aimsHuman umbilical cord–derived mesenchymal stromal cells (hUC-MSCs) are increasingly used in research and therapy. To obtain hUC-MSCs, a diversity of isolation and expansion methods... Show moreBackground aimsHuman umbilical cord–derived mesenchymal stromal cells (hUC-MSCs) are increasingly used in research and therapy. To obtain hUC-MSCs, a diversity of isolation and expansion methods are applied. Here, we report on a robust and standardized method for hUC-MSC isolation and expansion.MethodsUsing 90 hUC donors, we compared and optimized critical variables during each phase of the multi-step procedure involving UC collection, processing, MSC isolation, expansion and characterization. Furthermore, we assessed the effect of donor-to-donor variability regarding UC morphology and donor attributes on hUC-MSC characteristics.ResultsWe demonstrated robustness of our method across 90 UC donors at each step of the procedure. With our method, UCs can be collected up to 6 h after birth, and UC-processing can be initiated up to 48 h after collection without impacting on hUC-MSC characteristics. The removal of blood vessels before explant cultures improved hUC-MSC purity. Expansion in Minimum essential medium α supplemented with human platelet lysate increased reproducibility of the expansion rate and MSC characteristics as compared with Dulbecco's Modified Eagle's Medium supplemented with fetal bovine serum. The isolated hUC-MSCs showed a purity of ∼98.9%, a viability of >97% and a high proliferative capacity. Trilineage differentiation capacity of hUC-MSCs was reduced as compared with bone marrow-derived MSCs. Functional assays indicated that the hUC-MSCs were able to inhibit T-cell proliferation demonstrating their immune-modulatory capacity.ConclusionsWe present a robust and standardized method to isolate and expand hUC-MSCs, minimizing technical variability and thereby lay a foundation to advance reliability and comparability of results obtained from different donors and different studies. Show less
Van't Oever, R.M.; Zwiers, C.; Haas, M. de; Cessie, S. le; Lopriore, E.; Oepkes, D.; Verweij, E.J.T. 2023
ObjectivePregnant women who received at least one intrauterine transfusion (IUT) for haemolytic disease of the fetus and newborn (HDFN) in the preceding pregnancy are presumed to have a high... Show moreObjectivePregnant women who received at least one intrauterine transfusion (IUT) for haemolytic disease of the fetus and newborn (HDFN) in the preceding pregnancy are presumed to have a high likelihood of requiring IUTs again, often starting at an earlier gestational age. Our aim was to quantify these risks in a large national cohort.DesignRetrospective cohort study of a nationwide Dutch database.SettingThe Netherlands.PopulationAll women treated in The Netherlands with IUTs for Rhesus D (RhD)- or Kell-mediated HDFN between 1999 and 2017 and their follow-up pregnancies were included. Pregnancies with an antigen-negative fetus were excluded.MethodsElectronic patient files were searched for the number and gestational age of each IUT, and analysed using descriptive statistics and linear regression.Main outcome measuresPercentage of women requiring one or more IUTs again in the subsequent pregnancy, and gestational age at first IUT in both pregnancies.ResultsOf the 321 women in our study population, 21% (69) had a subsequent ongoing pregnancy at risk. IUTs were administered in 86% (59/69) of cases. In subsequent pregnancies, the median gestational age at first IUT was 3 weeks earlier (interquartile range -6.8 to 0.4) than in the preceding pregnancy.ConclusionsOur study shows that pregnant women with a history of IUTs in the previous pregnancy are highly likely to require IUTs again, and on average 3 weeks earlier. Clinicians need to be aware of these risks and ensure timely referral, and close surveillance from early pregnancy onwards. Additionally, for women with a history of IUT and their caregivers, this information is essential to enable adequate preconception counselling. Show less
Groene, S.G.; Gremmen, I.J.; Zwet, E.W. van; Roest, A.A.W.; Haak, M.C.; Klink, J.M.M. van; ... ; Bruin, C. de 2023
ObjectiveResearch suggests that postnatal catch-up growth after fetal growth restriction (FGR) occurs frequently. Yet, postnatal growth in singletons may be influenced by multiple factors.... Show moreObjectiveResearch suggests that postnatal catch-up growth after fetal growth restriction (FGR) occurs frequently. Yet, postnatal growth in singletons may be influenced by multiple factors. Identical twins with discordant prenatal growth, termed selective FGR (sFGR), can be regarded as a natural experiment eliminating these sources of bias.DesignObservational cohort study.MethodsMonochorionic twins with sFGR born between 2002 and 2017 (aged 3-17 years) were eligible. Growth measurements (height, weight, head circumference, and body mass index) were performed at follow-up. Detailed growth curves documented by a systematic primary care system in the Netherlands were collected. Measurements were converted to standard deviation scores (SDSs). A mixed-effects model was used to assess within-pair SDS difference and individual height SDS relative to target height SDS.ResultsForty-seven twin pairs (94 children) were included at a median age of 11 (interquartile range 8-13) years. At the last measurement, smaller twins at birth had a lower height SDS [−0.6 vs −0.3, P < .001, median difference 0.5 (95%CI 0.4-0.7)], lower weight SDS [−0.5 vs −0.1, P < .001, median difference 0.8 (95%CI 0.5-1.0)], and lower head circumference SDS [−0.5 vs 0.2, P < .001, median difference 0.8 (95%CI 0.6-0.9)] compared to larger twins. These differences persisted until the age of 17. Smaller twins showed rapid catch-up growth in the first 2 years and reached their target height range between 8 and 11 years.ConclusionsIdentical twins with discordant prenatal growth maintain a modest but significant difference in height, weight, and head circumference, indicating a persistent, inhibitory effect of an adverse intrauterine environment on childhood growth. Show less
Introduction: Perforation of the intertwin membrane can occur as a complication of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS). Data on the occurrence and the risk of... Show moreIntroduction: Perforation of the intertwin membrane can occur as a complication of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS). Data on the occurrence and the risk of subsequent cord entanglement is limited. The objective of this study is to assess the prevalence, risk factors and outcome of intertwin membrane perforation and cord entanglement after laser surgery for TTTS. Methods: In this multicenter retrospective study, we included all TTTS pregnancies treated with laser surgery in two fetal therapy centers, Shanghai (China) and Leiden (The Netherlands) between 2002 and 2020. We evaluated the occurrence of intertwin membrane perforation and cord entanglement after laser, based on routine fortnightly ultrasound examination and investigated the risk factors and the association with adverse short- and long-term outcome. Results: Perforation of the intertwin membrane occurred in 118 (16%) of the 761 TTTS pregnancies treated with laser surgery and was followed by cord entanglement in 21% (25/118). Perforation of the intertwin membrane was associated with higher laser power settings, 45.8 Watt versus 42.2 Watt (p=0.029) and a second fetal surgery procedure 17% versus 6% (p<0.001). The group with intertwin membrane perforation had a higher rate of caesarean section (77% versus 31%, p<0.001) and a lower gestational age at birth (30.7 versus 33.3 weeks of gestation, p<0.001) compared to the group with an intact intertwin membrane. Severe cerebral injury occurred more often in the group with intertwin membrane perforation, 9% (17/185) versus 5% (42/930) respectively (p=0.019). Neurodevelopmental outcome at two years of age was similar between the groups with and without perforation of the intertwin membrane and between the subgroups with and without cord entanglement. Conclusion: Perforation of the intertwin membrane after laser occurred in 16% of TTTS cases treated with laser and led to cord entanglement in at least one in five cases. Intertwin membrane perforation was associated with a lower gestational age at birth and a higher rate of severe cerebral injury in surviving neonates. Show less
BackgroundResearch in singletons identified fetal growth restriction (FGR) as a risk factor for retinopathy of prematurity (ROP), but is generally subject to confounding by genetic, obstetric, and... Show moreBackgroundResearch in singletons identified fetal growth restriction (FGR) as a risk factor for retinopathy of prematurity (ROP), but is generally subject to confounding by genetic, obstetric, and maternal factors. We investigated the effect of FGR on ROP in growth-discordant identical twins, thereby controlling for confounding factors.MethodsAll data of monochorionic (MC) twin pairs with a birth weight discordance >= 20% born in our center between 2010 and 2021 were retrospectively reviewed for the presence of ROP. Potential risk factors for ROP were analyzed. Outcomes were compared between the smaller and larger twin.ResultsWe included 88 MC twin pairs with growth discordance. In 34% (30/88), both neonates were at risk of ROP. Prevalence of ROP was higher among the smaller twin compared to the larger twin, 30% (9/30) versus 13% (4/30), respectively (OR 2.8, 95% CI: 1.2-6.6). The smaller twin had a longer duration of mechanical ventilation (8 (1-20) versus 2 (1-4) days) and received their first red blood cell transfusion at an earlier postmenstrual age (29.6 (28.1-31.6) versus 30.4 (29.7-32.6) weeks).ConclusionsIn this identical twin model, FGR is associated with almost tripled odds of ROP development, suggesting that both unfavorable antenatal growth conditions and adverse neonatal outcomes affect postnatal retinal vascular proliferation.ImpactFetal growth restriction in growth-discordant identical twins is associated with almost tripled odds of developing retinopathy of prematurity in the smaller twin.Since these twins do not only differ in birth weight but also duration of mechanical ventilation and timing of the first red blood cell transfusion, both unfavorable antenatal growth conditions and adverse neonatal outcomes can affect postnatal retinal vascular proliferation.More attention for preventing retinopathy of prematurity is needed in those with fetal growth restriction who received prolonged duration of mechanical ventilation, oxygen supplementation, or a first red blood cell transfusion Show less
ObjectiveTo assess the perinatal outcome after fetal reduction in complicated monochorionic (MC) twin pregnancies by comparing different techniques. MethodsA retrospective cohort study at a... Show moreObjectiveTo assess the perinatal outcome after fetal reduction in complicated monochorionic (MC) twin pregnancies by comparing different techniques. MethodsA retrospective cohort study at a national referral center comparing data between four techniques: interstitial laser coagulation, radiofrequency ablation (RFA), fetoscopic laser coagulation (FLC) and bipolar cord coagulation (BCC). The primary outcome was the mortality of the co-twins. Secondary outcomes were preterm pre-labor rupture of membranes (PPROM), gestational age at delivery and neonatal morbidity. Results259 MC twin pregnancies underwent selective fetal reduction: 29 IL, 64 RFA, 85 FLC and 81 BCC. The perinatal mortality rate was 29% and fetal demise of the co-twins occurred in 19%. The lowest mortality rate was seen after BCC (17%, p = 0.012). PPROM occurred in 18% patients without significant differences between techniques. The mean gestational age at delivery in liveborn children was 35 weeks and did not differ between techniques. Severe cerebral injury and neonatal morbidity were reported in 4% and 14%, respectively, without significant differences between techniques. ConclusionsSelective fetal reductions in MC twins are precarious procedures with an increased risk of perinatal mortality of the co-twins. Our results show the lowest mortality rates after BCC. However, high PPROM rates were seen irrespective of the technique. Show less
Emrani, S. el; Groene, S.G.; Spekman, J.A.; Slaghekke, F.; Meeren, L.E. van der; Schalij-Delfos, N.E.; Lopriore, E. 2023
Introduction: The purpose of this study was to evaluate the within-pair difference in retinopathy of prematurity (ROP) between donors and recipients with twin-to-twin transfusion syndrome (TTTS)... Show moreIntroduction: The purpose of this study was to evaluate the within-pair difference in retinopathy of prematurity (ROP) between donors and recipients with twin-to-twin transfusion syndrome (TTTS) and to identify risk factors for ROP development.Methods: This retrospective cohort study included 147 TTTS twin pairs managed between 2002-2022 and eligible for ROP screening. Primary outcomes were any stage ROP and severe ROP. Secondary outcomes were hemoglobin at birth, red blood cell transfusions, mechanical ventilation days, postnatal steroids and neonatal morbidity.Results: Rates of any stage ROP (23% vs. 14%) and severe ROP (8% vs. 3%) were significantly higher in donors compared to recipients. Donors received a higher number of blood transfusions (1 (+/- 1.9) vs. 0.7 (+/- 1.5)). Five factors were univariately associated with any stage ROP: donor status (OR 1.9; 95% CI 1.3-2.9), lower GA at birth (OR 1.7; 95% CI 1.4-2.1), small for GA (OR 2.1; 95% CI 1.3-3.5), mechanical ventilation days (OR 1.1; 95% CI 1.1-1.2) and blood transfusions in phase 1 (OR 2.3; 95% CI 1.2-4.3). Three factors were independently associated with any stage ROP: donor status (OR 1.8; 95% CI 1.1-2.9), lower GA at birth (OR 1.6; 95% CI 1.2-2.1) and mechanical ventilation days (OR 1.1, 95% CI 1.0-1.1). Donor status was univariately associated with severe ROP (OR 2.3, 95% CI 1.1-5.0). Conclusion: Any stage ROP and severe ROP are detected twice as frequently in donors compared to recipients. Increased awareness for ROP is needed in donors, especially those with lower GA at birth and longer duration of mechanical ventilation. Show less
Tollenaar, L.S.A.; Slaghekke, F.; Middeldorp, J.M.; Lopriore, E. 2023
Introduction: Monochorionic twins may develop fetal anemia when blood is unequally distributed via the placental vascular anastomoses. This review focuses on the causes of fetal anemia in... Show moreIntroduction: Monochorionic twins may develop fetal anemia when blood is unequally distributed via the placental vascular anastomoses. This review focuses on the causes of fetal anemia in complicated monochorionic twins and highlights the differences in management and outcome. Areas: coveredFetal anemia can occur in the context of twin anemia polycythemia sequence (TAPS), chronic twin-twin transfusion syndrome (TTTS) and acute peripartum TTTS, and in cotwins after single fetal demise. Diagnosis of fetal anemia is based on abnormal Doppler ultrasound measurements. Management options include fetoscopic laser surgery, intrauterine blood transfusion, or expectant management, depending on the type of complication and the severity of the disease. In all complications, fetal anemia may lead to perinatal mortality, neonatal morbidity, severe cerebral injury, and long-term neurodevelopmental impairment. In TAPS specifically, anemic donors may also show bilateral deafness.Expert opinion: Knowledge on the diagnosis and optimal treatment in TTTS is nowadays widespread, but caregivers often fail to distinguish TAPS from acute peripartum TTTS at birth. A full blood count including reticulocyte count is required, and placental dye injection is extremely helpful to reach the correct diagnosis and establish the optimal management. Show less
Winter, D.P. de; Hulzebos, C.; Oever, R.M. van 't; Haas, M. de; Verweij, E.J.T.; Lopriore, E. 2022
Since the discovery of the Rh blood group system in 1940, a greater understanding of hemolytic disease of the fetus and newborn (HDFN) was gained. In the years thereafter, researchers and... Show moreSince the discovery of the Rh blood group system in 1940, a greater understanding of hemolytic disease of the fetus and newborn (HDFN) was gained. In the years thereafter, researchers and clinicians came to the current understanding that fetal and neonatal red blood cells (RBC) are hemolyzed by maternal alloantibodies directed against RBC antigens potentially leading to severe disease. Preventative measures, such as Rhesus(D) immunoprophylaxis (RhIG), have greatly decreased the prevalence of Rh(D)-mediated HDFN, although a gap between high-income countries and middle- to low-income countries was created largely due to a lack in availability and high costs of RhIG. Other important developments in the past decades have improved the identification, monitoring, and care of pregnancies, fetuses, and neonates with HDFN. Prenatally, fetal anemia may occur and intrauterine transfusions may be needed. Postnatally, pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for anemia in the late phase of the disease. Through this review, we aim to provide an overview of important historic events and to provide hands-on guidelines for the delivery and postnatal management of neonates with HDFN. Secondarily, we aim to describe recent scientific findings and evidence gaps. Conclusion: Multiple developments have improved the identification, monitoring, and care of pregnancies and neonates with HDFN throughout the centuries. Pediatricians should be aware of the (antenatally determined) risk of hemolysis in RBC alloimmunization and should provide treatment for hyperbilirubinemia in the early phase and monitor for late anemia in the late phase of the disease. Future studies should be set in an international setting and ultimately aim to eradicate HDFN on a global scale. What is Known: Developments have led to a greater understanding of the pathophysiology, an improved serological identification and monitoring of at-risk cases and the current pre- and postnatal treatment. What is New: This review provides the pediatrician with hands-on guidelines for the delivery and postnatal management of neonates with HDFN. Future studies should be set in an international setting with the ultimate aim of eradicating HDFN. Show less
Aim: To evaluate the inter-and intraindividual variation of predicted nasogastric tube insertion lengths by nurses working in two neonatal intensive care units in the Netherlands, using a mannequin... Show moreAim: To evaluate the inter-and intraindividual variation of predicted nasogastric tube insertion lengths by nurses working in two neonatal intensive care units in the Netherlands, using a mannequin model. Methods: A total of 110 nurses (55 nurses from Center A and 55 from Center B) were asked to predict the nasogastric tube insertion length on a neonatal mannequin. We evaluated the length and prediction method used by the nurses. We also estimated the number of tubes that would have correctly been placed in the stomach of a neonate according to the seize of the mannequin.Results: The mean predicted insertion length of the nasogastric tube was 30.0 cm with an inter -individual variation of 12 cm (range 24-36 cm). The mean intraindividual variation was 0.75 cm. The two centers used two different prediction methods in their local guidelines, but overall at least 6 different methods were used by the nurses. We estimated that 77% (85/110) of the tubes would have ended in the body of the mannequins stomach, while 10% (11/110) would have ended in the esophagus and 13% (14/110) would have ended against the stomach lining or in the duodenum.Conclusion: Nurses in two neonatal intensive care units used many different methods which lead to a large interindividual variation in predicted insertion lengths of the nasogastric tubes. Regular evaluations using this mannequin model could lead to more uniformity and reduce the risk of tube misplacement in neonates. Show less
Jansen, S.J.; Ree, I.M.C.; Broer, L.; Winter, D. de; Haas, M. de; Bekker, V.; Lopriore, E. 2022
Background: Among neonates with hemolytic disease of the fetus and newborn (HDFN), we aimed to describe the frequency of central-line use, indications for insertion, and incidence of confirmed and... Show moreBackground: Among neonates with hemolytic disease of the fetus and newborn (HDFN), we aimed to describe the frequency of central-line use, indications for insertion, and incidence of confirmed and suspected sepsis, including antibiotic treatment over a 10-year surveillance period. Study Design and Methods: All neonates with HDFN admitted to our neonatal intensive care unit between January 2012 and December 2021 were included in this retrospective, cohort study. Annual proportions of infants with a central-line and central-line-associated bloodstream infection (CLABSI) rates (per 1000 central-line days and per 100 infants) were evaluated. Numbers of confirmed and suspected early- and late-onset sepsis episodes were assessed over the entire study period. Results: Of the 260 included infants, 25 (9.6%) were evaluated for suspected sepsis, with 16 (6.2%) having >= 1 confirmed sepsis episode. A total of 123 central-lines were placed in 98 (37.7%) neonates, with impending exchange transfusion (ET) being the most frequent indication. Of the 34 (34.7%) neonates in whom a central-line was placed due to impending ET, 11 (32.4%) received no ET. Overall CLABSI incidence was 13.58 per 1000 central-line days. Neonates with a central-line had a higher risk for confirmed late-onset infection (RR 1.11, 95% CI: 1.04-1.20) and sepsis work-up (RR 1.10, 95% CI: 1.03-1.17) compared to infants without a central-line. Conclusions: Sepsis incidence among neonates with HDFN remains high, in particular in those with a central-line. Considering the substantial proportion of neonates with a central-line without eventual ET, central-line placement should be delayed until the likelihood of ET is high. Show less
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... Show moreBACKGROUND: 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 larger weight or share- smaller weight or share/larger weight or sharex 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 (b coefficient, 0.325; 95% confidence interval, 0.254-0.397; P<.0001). The arterioarterial diameter was negatively correlated with birthweight ratio/placental territory ratio (b 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 (b 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. Show less
Background: Psychosocial development in monochorionic (MC) twins born after selective fetal growth restriction (sFGR) has been unreported to date, despite its importance for daily functioning and... Show moreBackground: Psychosocial development in monochorionic (MC) twins born after selective fetal growth restriction (sFGR) has been unreported to date, despite its importance for daily functioning and future relationships. Aims: To investigate psychosocial development, attachment and school functioning in MC twins with sFGR and compare outcomes with the general population and between smaller and larger twins. Study design: Observational cohort study. Subjects: MC twins with sFGR (defined as a birth weight discordance >= 20 %) born between 2002 and 2017 and aged 3-17 years. Outcome measures: Multiple parent report questionnaires: the Child Behavior Checklist (social-emotional devel-opment and behavior), the (Early) Childhood Behavior Questionnaire Very Short Form (temperament), the Attachment Insecurity Screening Inventory (attachment) and a school functioning questionnaire. Results: Median age for the 48 twin pairs was 11 (interquartile range (IQR) 8-13) years. Attachment insecurity for both twins was higher than in the general population for ambivalence/resistance (34 % (21/62) vs. 16 %, p = 0.024) and total attachment insecurity (35 % (22/62) vs. 16 %, p = 0.016). Smaller twins had more internalizing behavioral problems, i.e. negative emotions and behaviors turned inwards (22 % (10/46) vs. 11 % (5/46), p = 0.021) and a higher negative affect, i.e. more likely to experience negative emotions (3.2 (2.9-3.7) vs. 2.9 (2.2-3.2), p = 0.009) than larger twins, as well as a lower secondary school level (p = 0.031). Conclusion: MC twins with sFGR have more ambivalent/resistant attachment insecurity following the compli-cated pregnancy course. Smaller twins have a tendency towards negative emotions and internalizing behaviors compared to larger twins, indicating an increased sensitivity for depression and anxiety. Show less
Vos, T.W. de; Winkelhorst, D.; Arnadottir, V.; Bom, J.G. van der; Suris, C.C.; Caram-Deelder, C.; ... ; Lopriore, E. 2022
Background Children affected by fetal and neonatal alloimmune thrombocytopenia (FNAIT) are at risk of severe intracranial haemorrhage. Management in the postnatal period is based on sparse evidence... Show moreBackground Children affected by fetal and neonatal alloimmune thrombocytopenia (FNAIT) are at risk of severe intracranial haemorrhage. Management in the postnatal period is based on sparse evidence. We aimed to describe the contemporary management and outcomes of patients with FNAIT in high-income countries.Methods In this multicentre, retrospective, cohort study, we set up a web-based registry for the collection of deidentified data on the management and course of neonates with FNAIT. Eight centres from seven countries (Australia, Norway, Slovenia, Spain, Sweden, the Netherlands, and the USA) participated. Eligibility criteria comprised neonates with FNAIT being liveborn between Jan 1, 2010, and Jan 1, 2020; anti-human platelet antigen (HPA) alloantibodies in maternal serum; confirmed maternal and fetal HPA incompatibility; and bleeding detected at antenatal ultrasound, neonatal thrombocytopenia (<150 x 10(9) platelets per L), or both in the current or previous pregnancy. Clinical data were retrieved from local medical records of the first neonatal admission and entered in the registry. The key outcome was the type of postnatal treatment given to neonates with FNAIT. Other outcomes were daily median platelet counts in the first week of life, median platelet count increment after first unmatched versus first matched transfusions, and the proportion of neonates with mild or severe bleeding.Findings 408 liveborn neonates with FNAIT were entered into the FNAIT registry, of whom 389 from Australia (n=74), Norway (n=56), Slovenia (n=19), Spain (n=55), Sweden (n=31), the Netherlands (n=138), and the USA (n=16) were included in our analyses. The median follow-up was 5 days (IQR 2-9). More neonates were male (241 [64%] of 379) than female (138 [36%]). Severe thrombocytopenia (platelet count <50 x 10(9) platelets per L) was reported in 283 (74%) of 380 neonates, and extreme thrombo-cytopenia (<10 x 10(9) platelets per L) was reported in 92 (24%) neonates. Postnatal platelet count nadir was higher in the no-treatment group than in all other groups. 163 (42%) of 389 neonates with FNAIT received no postnatal treatment. 207 (53%) neonates received platelet transfusions, which were either HPA-unmatched (88 [43%] of 207), HPA-matched (84 [41%]), or a combination of both (35 [17%]). The proportion of neonates who received HPA-matched platelet transfusions varied between countries, ranging from 0% (Slovenia) to 63% (35 of 56 neonates; Norway). Postnatal intravenous immunoglobulin treatment was given to 110 (28%) of 389 neonates (alone [n=19] or in combination with platelet transfusions [n=91]), with the proportion receiving it ranging from 12% (17 of 138 neonates; the Netherlands) to 63% (ten of 16 neonates; the USA) across countries. The median platelet increment was 59 x 10(9) platelets per L (IQR 35-94) after HPA-unmatched platelet transfusions and 98 x 10(9) platelets per L (67-134) after HPA-matched platelet transfusions (p<0 center dot 0001). Severe bleeding was diagnosed in 23 (6%) of 389 liveborn neonates, with one having a severe pulmonary haemorrhage and 22 having severe intracranial haemorrhages. Mild bleeding was diagnosed in 186 (48%) neonates.Interpretation Postnatal management of FNAIT varies greatly between international centres, highlighting the absence of consensus on optimal treatments. Our data suggest that HPA-matched transfusions lead to a larger median platelet count increment than HPA-unmatched transfusions, but whether HPA matching is also associated with a reduced risk of bleeding remains unknown. Copyright (c) 2022 Published by Elsevier Ltd. All rights reserved. Show less
Knijnenburg, P.J.C.; Lopriore, E.; Slaghekke, F.; Klink, J.M.M. van 2022
Monochorionic twin pregnancies have an increased risk of morbidity and mortality. Due to the advancements in screening and treatment strategies, mortality rates have decreased. Improving survival... Show moreMonochorionic twin pregnancies have an increased risk of morbidity and mortality. Due to the advancements in screening and treatment strategies, mortality rates have decreased. Improving survival rates demands a shift in scope toward long-term outcomes. In this review, we focus on neurodevelopmental outcome in survivors from complicated monochorionic twin pregnancies, including twinetwin transfusion syndrome (TTTS), twin anemia-polycythemia sequence (TAPS), acute peripartum TTTS, acute perimortem TTTS, selective fetal growth restriction (sFGR) and monoamnionicity. Our aim is to provide an overview of the current knowledge on the long-term outcome in survivors, including psychomotor development and quality of life, and provide recommendations for future research and follow-up programs. (c) 2022 Published by Elsevier Ltd. Show less
Groene, S.G.; Tollenaar, L.S.A.; Middeldorp, J.M.; Lopriore, E. 2022
Monochorionic (MC) twin pregnancies are at increased risk of neonatal morbidity and mortality due to the shared placenta with vascular connections that can give rise to various complications,... Show moreMonochorionic (MC) twin pregnancies are at increased risk of neonatal morbidity and mortality due to the shared placenta with vascular connections that can give rise to various complications, including twin-twin transfusion syndrome, twin anemia polycythemia sequence (TAPS), selective fetal growth restriction, and other hematological imbalances at birth. Each complication presents its own challenges and considerations in the neonatal period. Measurement of hemoglobin levels and reticulocyte count is required to establish a correct diagnosis. Placenta dye injection is needed to properly distinguish between the various conditions. Risk factors for adverse outcome in MC twins include prematurity, severe cerebral injury, and the type of MC pregnancy complication. We, therefore, recommend cerebral ultrasound examinations in all complicated MC twins at birth to rule out a severe brain injury. Lastly, we strongly encourage screening for hearing loss using automated auditory brainstem response in all spontaneous TAPS donors to prevent permanent speech development delay. Show less
Oever, R.M. van 't; Zwiers, C.; Winter, D. de; Haas, M. de; Oepkes, D.; Lopriore, E.; Verweij, E.J. 2022
Introduction Hemolytic disease of the fetus and newborn (HDFN) is a condition caused by maternal alloantibodies against fetal red blood cells (RBCs) that can cause severe morbidity and mortality in... Show moreIntroduction Hemolytic disease of the fetus and newborn (HDFN) is a condition caused by maternal alloantibodies against fetal red blood cells (RBCs) that can cause severe morbidity and mortality in the fetus and newborn. Adequate screening programs allow for timely prevention and intervention resulting in significant reduction of the disease over the last decades. Nevertheless, HDFN still occurs and with current treatment having reached an optimum, focus shifts toward noninvasive therapy options. Areas covered This review focusses on the timely identification of high risk cases and antenatal management. Furthermore, we elaborate on future perspectives including improvement of screening, identification of high risk cases and promising treatment options. Expert opinion In high-income countries mortality and morbidity rates due to HDFN have drastically been reduced over the last decades, yet worldwide anti-D mediated HDFN still accounts for 160,000 perinatal deaths and 100,000 patients with disabilities every year. Much of these deaths and disabilities could have been avoided with proper identification and prophylaxis. By implementing sustainable prevention, screening, and disease treatment measures in all countries this will systemically reduce unnecessary perinatal deaths. There is a common responsibility to engage in this cause. Show less
Henricks, L.M.; Huisman, E.J.; Lopriore, E.; Luken, J.S.; Haas, M. de; Ootjers, C.S.; Albersen, A. 2022
Background Plasma is a commonly used blood product and is available in the form of fresh frozen plasma (FFP) or pooled solvent/detergent-treated plasma. In the Netherlands, solvent/detergent... Show moreBackground Plasma is a commonly used blood product and is available in the form of fresh frozen plasma (FFP) or pooled solvent/detergent-treated plasma. In the Netherlands, solvent/detergent-treated plasma has become the standard product in the adult population since several years, but for neonatal use, FFP remains the product of preference. Description A preterm neonate developed lung bleeding at day 8 postpartum, for which intubation and mechanical ventilation was required and transfusions with packed red blood cells and plasma, in the form of FFP, were given. Five hours after transfusion, a red discoloration of the urine occurred. An acute haemolytic transfusion was suspected, confirmed by laboratory investigations (fast decrease in haemoglobin, increased free haemoglobin, decreased haptoglobin, increased lactate dehydrogenase and a positive direct antiglobulin test [IgG 2+]). Additional research showed that the FFP product contained nonspecific auto-antibodies that reacted with the transfused erythrocytes, most test erythrocytes and the donor's own erythrocytes. Conclusion A neonate experienced an acute haemolytic reaction, most probably caused by administrating a FFP product containing auto-antibodies. If transfused with solvent/detergent-treated plasma, such antibodies would have been diluted or captured. This case adds a new argument to the discussion on expanding the use of solvent/detergent-treated plasma to the paediatric population. Show less
