Receipt of RhD-positive whole blood for life-threatening bleeding in female children: A survey in alloimmunized mothers regarding minimum acceptable survival benefit relative to risk of maternal alloimmunization to anti-D.

BACKGROUND: Low-titer group O whole blood (LTOWB) for treatment of hemorrhagic shock sometimes necessitates transfusion of RhD-positive units due to short supply of RhD-negative LTOWB. Practitioners must choose between using RhD-positive LTOWB when RhD-negative is unavailable against the risk to a female of childbearing potential of becoming RhD-alloimmunized, risking hemolytic disease of the fetus and newborn (HDFN) in future children, or using component therapy with RhD-negative red cells. This survey asked females with a history of red blood cell (RBC) alloimmunization about their risk tolerance of RhD alloimmunization compared to the potential for improved survival following transfusion of RhD-positive blood for an injured RhD negative female child. STUDY DESIGN AND METHODS: A survey was administered to RBC alloimmunized mothers. Respondents were eligible if they were living in the United States with at least one red cell antibody known to cause HDFN and if they had at least one RBC alloimmunized pregnancy. RESULTS: Responses from 107 RBC alloimmmunized females were analyzed. There were 32/107 (30%) with a history of severe HDFN; 12/107 (11%) had a history of fetal or neonatal loss due to HDFN. The median (interquartile range) absolute improvement in survival at which the respondents would accept RhD-positive transfusions for a female child was 4% (1%-14%). This was not different between females with and without a history of severe or fatal HDFN (p = .08 and 0.38, respectively). CONCLUSION: Alloimmunized mothers would accept the risk of D-alloimmunization in a RhD-negative female child for improved survival in cases of life-threatening bleeding.

Hemoglobin Electrophoresis versus Kleihauer-Betke to Determine Bone Marrow Suppression in Fetuses Undergoing Intrauterine Transfusion.

OBJECTIVE: Mainstay therapy for fetuses affected by maternal red cell alloimmunization is serial intrauterine transfusion (IUT). Testing to determine when fetal red cells have been replaced with donor cells historically involves the use of the Kleihauer-Betke (KB) test. Hemoglobin (Hgb) electrophoresis testing may be more rapid with a reduced cost of analysis. We aimed to determine the correlation between fetal Hgb electrophoresis versus the traditional KB test. STUDY DESIGN: This is a retrospective analysis of all alloimmunized singleton pregnancies undergoing IUT between January 1, 2021, and July 1, 2023. Maternal and fetal characteristics were collected along with the indication for IUT. A final fetal blood sample was obtained at the conclusion of each transfusion and sent for KB testing and Hgb electrophoresis. The primary outcome was the assessment of these parameters in their ability to predict the replacement of the fetal circulating red cell population with donor cells. Linear regression analysis and repeated measures analysis of variance were performed, and p-values less than 0.05 were considered significant. RESULTS: A total of 56 IUTs were performed in 16 patients. There were 39 (69.6%) final KB test values collected and compared with 30 (53.6%) final Hgb electrophoresis values. Hgb electrophoresis when compared with the KB test demonstrated a significant correlation (R 2 = 0.93; 95% confidence interval, 0.61-0.76; p < 0.001). This same finding held true when examining the correlation at each individual IUT as well. The final KB test and Hgb electrophoresis values significantly decreased with each transfusion (p = 0.003). A predominance of adult donor blood was noted by the third transfusion for both laboratory indices. CONCLUSION: Fetal Hgb electrophoresis obtained at the time of IUT demonstrates a significant correlation with the traditional KB test. KEY POINTS: · Fetal Hgb electrophoresis following IUT is underexplored. · Hgb electrophoresis is an automated evaluation. · The traditional KB test is a manual evaluation. · These two tests demonstrate significant correlation.

Immunomodulation for early-onset haemolytic disease of the fetus/newborn: Can we delay the need for intrauterine transfusions?

When cases of severe fetal anaemia due to maternal red-cell alloimmunization present in the early second trimester, standard treatment with intrauterine transfusion often results in fetal loss. The report by Vlachodimitropoulou et al. offers new insight into the use of maternal intravenous immune globulin to delay the need for intrauterine transfusion. Performing these procedures at a later gestational age increases the likelihood of technical success and subsequent perinatal survival. Commentary on: Vlachodimitropoulou et al. Intravenous immune globulin in the management of severe early onset of red cell alloimmunization. Br J Haematol 2023; 200:97-103.

The Special Delivery Unit: A Novel Concept for Mother-Baby Continuity for Major Fetal Abnormalities.

OBJECTIVE: This article describes the experience in the planning and development of a special delivery unit (SDU) at our free-standing children's hospital in Austin, Texas. STUDY DESIGN: Description of various aspects of the development of the SDU. In addition, telephone surveys were obtained from five other institutions regarding the planning and current status of their SDUs. RESULTS: Since the advent of the SDU at Children's Hospital of Philadelphia in 2008, several free-standing children's hospitals have opened similar units at their institutions. Developing an obstetrical unit in a children's hospital can be a daunting task on many fronts. The costs of providing 24-hour obstetrical, nursing, and anesthesiology coverage must be considered. Although most SDUs are associated with a fetal center and fetal surgery/interventions, some units function exclusively for the delivery of pregnancies complicated by major fetal conditions where the neonate will require immediate surgical care or other interventions. CONCLUSION: Research on the cost-effectiveness and the effect of SDUs on clinical outcome, teaching, and patient satisfaction is warranted. KEY POINTS: · Specialized delivery units are becoming more common at free-standing children's hospitals.. · The primary aim of the SDU is to maintain mother-baby continuity in cases of congenital anomalies.. · Developing an obstetrical unit at a pediatric hospital is a daunting task..

Congenital myotonic dystrophy: An overlooked diagnosis not amenable to detection by sequencing.

OBJECTIVE: To increase the clinical awareness of the need for genetic evaluation for congenital myotonic dystrophy (CDM1) in cases of fetal akinesia sequence and idiopathic polyhydramnios. METHODS: Retrospective case review. RESULTS: A 27 y.o. G1P0 with no significant family history presented for ultrasound at 25 weeks gestation. Notable findings included lack of extension of the fetal arms and legs with bilateral talipes consistent with fetal akinesia sequence. Polyhydramnios with an amniotic fluid index of 32.2 cm was also present. Amniotic fluid obtained by amniocentesis was sent for chromosomal microarray and a next generation sequencing fetal akinesia panel which both returned normal. The patient underwent serial amnioreductions for recurrent severe polyhydramnios with removal of a total of 9.3 L. Further amniotic fluid testing for CDM1 identified >200 repeats in one copy of the fetal DMPK gene, consistent with a diagnosis of CDM1. The patient was delivered at 35 weeks gestation and neonatal demise occurred on the second day of life. CONCLUSION: Congenital myotonic dystrophy should be a consideration for cases of severe polyhydramnios identified by ultrasound. Myotonic dystrophy is detected using PCR and southern blot and is not typically included on next generation sequencing (NGS) panels that test for similar conditions. Clinicians should consider more specialized genetic testing than microarray and NGS in these cases.

Medical therapy to attenuate fetal anaemia in severe maternal red cell alloimmunisation.

Haemolytic disease of the fetus and newborn (HDFN) remains an important cause of fetal mortality with potential neonatal and longer-term morbidity. HDFN is caused by maternal red cell alloimmunisation, with IgG antibodies crossing the placenta to destroy fetal erythroid cells expressing the involved antigen. Intrauterine fetal blood transfusion is the therapy of choice for severe fetal anaemia. Despite a strong evidence base and technical advances, invasive fetal therapy carries risk of miscarriage and preterm birth. Procedure-related risks are increased when invasive, in utero transfusion is instituted prior to 22 weeks to treat severe early-onset fetal anaemia. This review focuses upon this cohort of HDFN and discusses intravenous immunoglobin (IVIg) and novel monoclonal antibody (M281, nipocalimab) treatments which, if started at the end of the first trimester, may attenuate the transplacental passage and fetal effects of IgG antibodies. Such therapy has the ability to improve fetal survival in this severe presentation of HDFN when early in utero transfusion may be required and may have wider implications for the perinatal management in general.

Predicting fetal and neonatal demise after fetoscopy for twin-twin transfusion syndrome using recursive partitioning.

OBJECTIVE: Donor demise after laser surgery for twin-twin transfusion syndrome (TTTS) is well-characterized, but recipient demise is not, nor is neonatal death. This study aims to characterize factors associated with recipient death, donor death, and dual twin death after laser, both before and after birth. METHODS: This is a prospective cohort study of monochorionic twin pairs who underwent laser ablation for TTTS. Risk factors for fetal and neonatal death of both twins were identified using univariable analysis and recursive partitioning, a novel statistical method to quantify contributions of each factor to outcomes. RESULTS: In 413 twin pairs, death of both twins occurred in 9.2% (38/413), donor death in 12.1% (50/413), and recipient death in 2.4% (10/413). Recursive partitioning showed that gestational age at delivery predicts dual twin death (below 23.7 weeks, likely [p < 0.001], above 28.3 weeks, unlikely [p = 0.004]). Abnormal umbilical artery Doppler and weight discordance predict donor demise (p < 0.001 and p = 0.033, respectively). Cervical length under 16 mm predicts neonatal death of both twins (p < 0.001). CONCLUSIONS: Parents can gain individualized information about the survival of each fetus based on variables available from preoperative and delivery variables. Short cervix and premature delivery cause significant mortality in TTTS.

Low Transverse versus Midline Abdominal Skin Incisions for in utero Spina Bifida Repair.

OBJECTIVE: The 2 types of maternal skin incisions for in utero spina bifida repair are low transverse (LT) incision perceived to be cosmetic benefit and midline longitudinal (ML) incision, typically associated with a reduction in surgical time and lower blood loss. Our objective was to compare short- and long-term outcomes associated with these 2 types of skin incisions following in utero spina bifida repair. METHODS: Prospective observational cohort of 72 patients undergoing fetal spina bifida repair at a single institution between September 2011 and August 2018. The decision for the type of incision was at the discretion of the surgeons. The primary outcome was total operative time. Secondary outcomes included an analog scale of wound pain score on postoperative day 3, duration of postoperative stay, and postoperative wound complications within the first 4 weeks. The Patient Scar Assessment Questionnaire, a validated questionnaire, was obtained for all patients (≥6 months from delivery) using 4 categories (appearance, consciousness, satisfaction with appearance and with symptoms), with higher scores reflecting a poorer perception of the scar. RESULTS: There were 43 women (59.7%) in the LT group and 29 (40.3%) in the ML group. In all patients, the same incision was used during cesarean delivery. The total operative time was higher in the LT group by 33 min (p < 0.001), primarily due to abdominal wall incision time (open and closure). No significant differences were found between the groups in pain score, length of postoperative stay, or the rate of wound complications. Fifty-three patients (73.6%) responded to the questionnaire, 36/43 from the LT group and 17/29 from the ML group. There was no difference in the scores of appearance, consciousness, and satisfaction with appearance and symptoms between the groups. CONCLUSION: ML incisions shorten operative times without altering long-term incision-related satisfaction when compared to LT incisions.

Pregnancy outcomes associated with chorioamnion membrane separation severity following fetoscopic laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: We tested the hypothesis that increasing severity of chorioamnion membrane separation (CAS) after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) is associated with worse pregnancy outcomes. METHODS: Prospective cohort of patients undergoing FLS for TTTS between 2011 and 2018. CAS was defined as separation of fetal membranes from the uterine wall on post-operative ultrasound. Patient groups were defined: Group 1: No CAS; Group 2: CAS lower than 50th centile; Group 3: CAS upper than 50th centile or complete CAS. Comparative analysis was performed. RESULTS: Of 387 patients meeting inclusion criteria, 29 (7.5%) had CAS (median 9.8 mm [4.9-30.8 mm]). Group 1 patients were more likely to undergo FLS at later gestational age, had increased recipient maximum vertical pocket, and higher amnioreduction volume than Group 3. Group 3 had higher rates of preterm premature rupture of membrane, delivered earlier and were more likely to terminate than Group 1. Group 2 had fewer neonatal survivors than Group 1. Survival analysis for gestational age at delivery and Cox proportional hazards model indicated increased risk for early delivery in Groups 2 and 3 compared with Group 1. CONCLUSIONS: Patients with CAS ≥9.8 mm or complete CAS after FLS for TTTS had worse obstetric and neonatal outcomes.

Prenatal and Postnatal Imaging Findings After Fetal Repair of Spinal Dysraphisms Using Cryopreserved Human Umbilical Cord Patch: A Case Series of 4 Patients.

We describe a case series of imaging findings of 4 patients who underwent spinal dysraphisms repair in utero with novel patch material, cryopreserved human umbilical cord, in our institution. In our study, the prenatal and postnatal magnetic resonance imaging and ultrasound are reviewed and showed cord tethering and syrinx progression in all cases. Our report is the first description of magnetic resonance imaging and ultrasound findings in the context of using this novel patch in severe cases of spinal dysraphisms.

Fortnightly surveillance of monochorionic diamniotic twins for twin to twin transfusion syndrome: Compliance and effectiveness.

OBJECTIVES: To determine the compliance and effectiveness of fortnightly ultrasound surveillance for detection of twin-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MCDA) twin gestations. METHODS: This is a retrospective study of ultrasound surveillance of MCDA twins for TTTS. Our surveillance protocol requires fortnightly ultrasounds starting at 16 weeks of gestational age (GA) continuing until delivery. Compliance was assessed by determining the GA of surveillance initiation and time between ultrasounds. GA and Quintero Stage at diagnosis were evaluated to determine whether TTTS was detected prior to advanced disease (Quintero Stage III +) or fetal demise. RESULTS: Of 442 women, 264 (59.7%) initiated surveillance after 16 weeks; follow-up ultrasounds were late in 17.4% of cases. TTTS was diagnosed in 43 (9.7%) women at a median GA of 19.7 [17.4, 23.9] weeks. Of 25/43 (58.1%) cases diagnosed during protocol compliance, 12 had advanced disease and two had fetal demise. A similar proportion of diagnoses (n = 18), made while non-compliant, exhibited advanced disease (11/18, 61.1%, P = .40). Thirteen diagnoses occurred during periods of increased ultrasound frequency due to abnormalities (ie, fluid/estimated fetal weight discrepancies or Doppler abnormalities). CONCLUSIONS: In this population, fortnightly ultrasound compliance was suboptimal. Advanced disease and fetal demise occurred during protocol compliance.

Steroid Hormone Levels in Recipient Amniotic Fluid in Twin-Twin Transfusion Syndrome and Their Association with Preterm Delivery.

OBJECTIVE: Preterm delivery following fetoscopic laser surgery (FLS) of twin-twin transfusion syndrome (TTTS) is associated with severe perinatal morbidity and mortality. The role of steroid hormones in amniotic fluid (AF) after FLS remains unknown. STUDY DESIGN: A prospective cohort study of consecutive case series of FLS for TTTS was performed from April 2012 to February 2017. Cases were divided into early (≤27 weeks) spontaneous preterm delivery (ED) and late delivery (LD; ≥34 weeks) following FLS and compared. AF supernatants were assessed for protein, estradiol, progesterone and cortisol levels (using the ELISA kit), and normalized to total protein levels to adjust for dilution. RESULTS: A total of 294 consecutive cases of FLS for TTTS in monochorionic-diamniotic twins were performed during the study period. AF was available in 44 ED patients and 50 LD patients. On logistic regression, ED was associated with higher normalized progesterone levels (odds ratio [OR]: 1.25; 95% confidence interval [CI]: 1.12-1.41), lower normalized cortisol (OR: 0.78; 95% CI: 0.64-0.96), and higher estradiol levels (OR: 1.3; 95% CI: 1.03-1.63). CONCLUSION: Elevated AF normalized progesterone and estradiol, and lower normalized cortisol levels were associated with ED. This novel finding requires further exploration to establish the molecular mechanism operational in pregnancies complicated by TTTS to potentially prevent early preterm birth after fetal surgery.

Fractional Limb Volume in Spina Bifida Fetuses as an Assessment Tool for Postnatal Ambulation.

BACKGROUND: Prenatal fractional limb volume (FLV) can be used to assess muscle atrophy in fetuses with myelomeningocele. OBJECTIVE: We hypothesize that FLV in fetal myelomeningocele (fMMC) repair is different from postnatal repair (PNR). Assessing intrauterine muscle development can predict ambulation. METHODS: A prospective observational study was performed from July 2012 to April 2016. Demographics, clinical outcomes, and FLV of the fetal thigh were assessed by ultrasound. Ambulation videos were collected from patients over 30 months of age. FLV was compared between the fMMC and PNR groups and between ambulators and non-ambulators. Two-sample t test, ANOVA, Spearman's rho correlation, and Bland-Altman plots were used for analysis. A p value <0.05 was used for statistical significance. RESULTS: Fifty-nine patients were included, 24 had fMMC and 35 had PNR. Videos were obtained in 47 cases (73%). There was no difference in baseline demographics between the groups. There was no significant change in the fMMC group between the FLV at initial presentation and the repeat at 34 weeks gestation (54.5 ± 28.2 and 62.2% ± 16.4; p = 0.6). In contrast, the FLV in the PNR decreased between the initial evaluation and the repeat at 34 weeks (54.1 ± 27.7 to 35.8 ± 34.1%; p = 0.04). FLV at 34 weeks gestation was higher in the fMMC group as compared to the PNR group (62.2 ± 16.4 vs. 35.8 ± 34.1%; p = 0.02). There was no difference in FLV between ambulators and non-ambulators either at initial evaluation (p = 0.8) or at 34 weeks gestation (p = 0.6). CONCLUSION: Lower FLV in the PNR group compared to fMMC may suggest in utero muscle atrophy. No correlation was seen between FLV and subsequent ambulation; however, future larger studies may be needed.

Distance Traveled to a Fetal Center and Pregnancy Outcomes in Twin-Twin Transfusion Syndrome.

BACKGROUND: Fetoscopic laser photocoagulation (FLP) is the definitive treatment for twin-twin transfusion syndrome (TTTS). Due to variability in geographic proximity to high-volume fetal centers, many patients travel great distances to receive experienced care. We sought to determine whether distance traveled (DT) is associated with gestational age (GA) at delivery and neonatal survival. METHODS: A prospective cohort study of patients within the continental United States referred to our center between September 23, 2011 and July 25, 2018 undergoing planned FLP for TTTS (n = 393; GA 20.6 ± 2.5 weeks; stage I: n = 50; stage II: n = 118; stage III: n = 208; stage IV: n = 17) was performed. The great-circle distance to our center was calculated using patients' home zip codes. DT was stratified into groups containing equal patient numbers and pregnancy outcomes assessed. RESULTS: A total of 393 patients met the inclusion criteria. The threshold distance from our center was <250 miles (n = 181), 250-499 miles (n= 119), and ≥500 miles (n = 93). There was no significant difference between any of the preoperative variables among the three groups, with the exception of race and rural status. Furthermore, there was no significant association between DT and GA at delivery (p = 0.34), time interval from procedure to delivery (p = 0.37), and the number of neonatal survivors (p= 0.21). Preterm premature rupture of membranes (PPROM) at <34 weeks was highest (47.9%, p = 0.04) in the group traveling 250-499 miles. CONCLUSION: To our knowledge, this is the largest study to show that in TTTS, DT is not associated with GA at delivery, time interval from procedure to delivery, or neonatal survival. Although PPROM at <34 weeks was higher in the group traveling 250-499 miles, there was no significant difference in GA at delivery. While patients with advanced disease may choose to seek treatment based on proximity, traveling long distances does not adversely affect pregnancy outcomes.

Neonatal Outcomes and Maternal Characteristics in Monochorionic Diamniotic Twin Pregnancies: Uncomplicated versus Twin-to-Twin Transfusion Syndrome Survivors after Fetoscopic Laser Surgery.

Preterm birth remains a major complication of fetal laser surgery (FLS) due to twin-to-twin transfusion syndrome (TTTS). OBJECTIVES: We tested the hypothesis that neonatal outcomes in fetuses born at >24 weeks are worse in TTTS survivors compared to uncomplicated monochorionic diamniotic (MCDA) twins. METHODS: 196 patients with TTTS treated with laser therapy and 91 uncomplicated MCDA gestations were compared. Neonatal outcomes included respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal death. Risk factors assessed were TTTS, maternal age, maternal body mass index, race, premature prolonged rupture of membranes, stage of TTTS, parity, and gestational age (GA) at delivery. RESULTS: GA at delivery was lower in the TTTS group (31.0 ± 4.6 vs. 33.5 ± 2.4 weeks, p < 0.001). RDS and TTN occurred at higher rates in the TTTS than in the uncomplicated MCDA group. After multivariate logistic regression, the only factor significantly associated with the composite adverse outcome was GA at delivery (OR 0.61; 95% CI: 0.58-0.7). CONCLUSION: TTTS twins treated with FLS are deliver 2.5 weeks earlier than uncomplicated MCDA twins. Respiratory complications were significantly higher in TTTS twins and were mainly the consequence of the early GA at delivery.

Cell free fetal DNA to triage antenatal rhesus immune globulin: Is it really cost-effective in the United States?

OBJECTIVE: To compare the efficacy and costs of three different strategies of antenatal rhesus immune globulin (RhIG) administration in a US population. METHODS: A decision tree analysis was undertaken for universal antenatal RhIG administration based on RhD serologic paternity testing, universal administration without paternity, and selective antenatal RhIG administration using cell free fetal DNA (cfDNA) for RHD fetal typing. Rates of alloimmunization were calculated. Charges were determined for laboratory testing and obstetrical and neonatal treatments for the first pregnancy and cases of alloimmunization in the following pregnancy. RESULTS: The largest number of new RhD alloimmunization cases resulted from a strategy of universal RhIG that included paternity. Fewer cases resulted from a selective strategy; the least number of cases were associated with a universal approach that discounted paternity. When the costs of first pregnancies and alloimmunized second pregnancies were combined, a universal strategy that excludes paternity had the least costs followed by a selective strategy followed by a universal strategy that included paternity. CONCLUSION: The use of cfDNA to determine the selective use of antenatal RhIG would not be cost-effective in the United States. Universal antenatal RhIG without paternity is more effective in preventing new cases of alloimmunization than the current ACOG guideline.

Early Administration of Magnesium Sulfate during Open Fetal Myelomeningocele Repair Reduces the Dose of Inhalational Anesthesia.

INTRODUCTION: Optimal uterine relaxation is achieved through higher minimum alveolar concentration (MAC) of inhalational anesthetics, increasing risks to mother and fetus. Our objective was to determine if earlier administration of magnesium sulfate would reduce the requirement of inhalational anesthetics in fetal myelomeningocele repair. MATERIALS AND METHODS: Prospective observational study of fetal myelomeningocele repair was performed from September 2011 to August 2017. Groups compared were: (1) magnesium sulfate at uterine closure; (2) magnesium sulfate at maternal skin incision. Maternal demographics, anesthetic agents, intraoperative complications, and pregnancy outcomes were reviewed. A Student t test was used for analysis. RESULTS: There were 30 cases in group 1 and 21 cases in group 2. There was no difference in gestational age at intervention (24.92 ± 0.62 vs. 25.22 ± 0.47 weeks, p = 0.07) or at delivery (34.83 ± 2.77 vs. 33.98 ± 3.83 weeks, p = 0.38) between groups 1 and 2, respectively. The maximum MAC of sevoflurane was significantly lower in group 2 (1.84 ± 0.25 vs. 1.05 ± 0.28, p < 0.0001). There was no difference in the average dose of phenylephrine used. DISCUSSION: Magnesium sulfate infusion initiated earlier in open fetal surgery reduces the total anesthetic exposure to the fetus.

Clinical Monitoring of Sacrococcygeal Teratoma.

BACKGROUND: Sacrococcygeal teratomas (SCT) are often highly vascularized and may result in high-output cardiac failure, polyhydramnios, fetal hydrops, and demise. Delivery is guided by the SCT to fetus volume ratio (SCTratio), SCT growth rate, and cardiac output indexed for weight (CCOi). METHODS: We compared measurements and outcome in 12 consecutive fetuses referred with SCT. Adverse outcomes were: fetal surgery, delivery < 32 gestational weeks or neonatal demise. Only SCTratio and CCOi were used to manage the cases. SCT vascularization index (VI%) was derived from the 3D virtual organ computer-aided analysis (VOCAL) software. The SCTModel (modified from acardiac twins) calculated a hypothetical SCT draining vein size and derived a risk line, using diameters of the superior and inferior vena cava, the azygous and umbilical veins. VI% and a model of systemic and umbilical venous volumes (SCTModel) were tested as indicators for outcome in SCT. RESULTS: Fetuses were monitored from 20.1 to 36.4 gestational weeks and 5/12 had adverse outcomes: 1 had successful open fetal surgery at 23.8 weeks and delivered at term, 4 delivered at < 32 weeks with 3/4 having neonatal demise between 25 and 29 weeks. VI% was significantly higher in cases with adverse outcomes (mean 10.3 [8.9-11.6] vs. 4.4 [3.4-5.3], p < 0.0001). The additional fraction of the fetal cardiac output required to perfuse the SCT-draining vein (XSCO%) (p = 0.46), SCTratio (p = 0.08), and CCOi (p = 0.64) were not significant. All cases with adverse outcome had VI% > 8%. The SCTModel risk line predicted nonadverse outcomes well but lacked data in 2/5 cases with adverse outcomes. CONCLUSIONS: VI% is a significant indicator of SCT cases with adverse outcomes and combined with SCTratio may guide timing of delivery better than current measures.

Successful management of severe red blood cell alloimmunization in pregnancy with a combination of therapeutic plasma exchange, intravenous immune globulin, and intrauterine transfusion.

BACKGROUND: Antibodies to Rhesus and Kell antigens have been associated with severe hemolytic disease of the fetus and newborn (HDFN) necessitating intrauterine transfusion (IUT) of red blood cells (RBCs). We report a case series of five women with severe HDFN secondary to maternal RBC alloimmunization who were successfully managed with therapeutic plasma exchange (TPE), intravenous immune globulin (IVIG), and IUT. STUDY DESIGN AND METHODS: This is a retrospective case series of five women with severe HDFN who underwent a total of three TPE procedures during Weeks 10 to 13 of pregnancy, followed by weekly IVIG infusions. They were followed with serial middle cerebral artery peak systolic velocity studies beginning at 16 weeks' gestation to detect fetal anemia. For IUT, fetuses were administered RBC units that fully matched the maternal phenotype to D, C, E, K, Fy, Jk, and S antigen groups. The delivery outcomes and newborn information were followed. RESULTS: Anti-D and anti-K alloantibodies were implicated in HDFN. A two- to fourfold dilution reduction in anti-D and anti-K titers was observed after TPE. IUT was initiated between 21 to 27 weeks' gestation. The total number of IUTs for each patient ranged from four to seven. All five women delivered healthy infants at 33 to 38 weeks' gestation. CONCLUSION: A combined regimen of TPE and IVIG early in pregnancy and IUT later in pregnancy results in successful management of severe maternal RBC alloimmunization and HDFN. IUT with fully phenotypically matched RBC units may help prevent further RBC alloimmunization in complex cases of HDFN.