North American Fetal Therapy Network: intervention vs expectant management for stage I twin-twin transfusion syndrome.

BACKGROUND: Stage I twin-twin transfusion syndrome presents a management dilemma. Intervention may lead to procedure-related complications while expectant management risks deterioration. Insufficient data exist to inform decision-making. OBJECTIVE: The aim of this retrospective observational study was to describe the natural history of stage I twin-twin transfusion syndrome, to assess for predictors of disease behavior, and to compare pregnancy outcomes after intervention at stage I vs expectant management. STUDY DESIGN: Ten North American Fetal Therapy Network centers submitted well-documented cases of stage I twin-twin transfusion syndrome for analysis. Cases were retrospectively divided into 3 management strategies: those managed expectantly, those who underwent amnioreduction at stage I, and those who underwent laser therapy at stage I. Outcomes were categorized as no survivors, 1 survivor, 2 survivors, or at least 1 survivor to live birth, and good (twin live birth ≥30.0 weeks), mixed (single fetal demise or delivery between 26.0-29.9 weeks), and poor (double fetal demise or delivery <26.0 weeks) pregnancy outcomes. Outcomes were analyzed by initial management strategy. RESULTS: A total of 124 cases of stage I twin-twin transfusion syndrome were studied. In all, 49 (40%) cases were managed expectantly while 30 (24%) underwent amnioreduction and 45 (36%) underwent laser therapy at stage I. The overall fetal mortality rate was 20.2% (50 of 248 fetuses). Of those managed expectantly, 11 patients regressed (22%), 4 remained stage I (8%), 29 advanced in stage (60%), and 5 experienced spontaneous previable preterm birth (10%) during observation. The mean number of days from diagnosis of stage I to a change in status (progression, regression, loss, or delivery) was 11.1 (SD 14.3) days. Intervention by amniocentesis or laser therapy was associated with a lower risk of fetal loss (P = .01) than expectant management. The unadjusted odds of poor outcome were 0.33 (95% confidence interval, 0.09-01.20), for amnioreduction and 0.26 (95% confidence interval, 0.09-0.77) for laser therapy vs expectant management. Adjusting for nulliparity, recipient maximum vertical pocket, gestational age at diagnosis, and placenta location had negligible effect. Both amnioreduction and laser therapy at stage I decreased the likelihood of no survivors (odds ratio, 0.11; 95% confidence interval, 0.02-0.68 and odds ratio, 0.07; 95% confidence interval, 0.01-0.37, respectively). Only laser therapy, however, was protective against poor outcome in our data (odds ratio, 0.29; 95% confidence interval, 0.07-1.30 for amnioreduction vs odds ratio, 0.12, 95% confidence interval, 0.03-0.44 for laser), although the estimate for amnioreduction suggests a protective effect. CONCLUSION: Stage I twin-twin transfusion syndrome was associated with substantial fetal mortality. Spontaneous resolution was observed, although the majority of expectantly managed cases progressed. Progression was associated with a worse prognosis. Both amnioreduction and laser therapy decreased the chance of no survivors, and laser was particularly protective against poor outcome independent of multiple factors. Further studies are justified to corroborate these findings and to further define risk stratification and surveillance strategies for stage I disease.

Hemolytic disease of the fetus and newborn due to multiple maternal antibodies.

OBJECTIVE: The objective of the study was to determine whether women with combinations of red blood cell antibodies are more likely to develop significant hemolytic disease of the fetus and newborn than those with single antibodies. STUDY DESIGN: A retrospective exposure cohort study was conducted of pregnant women with red blood cell antibodies. The development of significant hemolytic disease of the fetus and newborn was then compared between patients with single antibodies and those with multiple antibodies. Data analysis was limited to pregnancies delivering since the year 2000. RESULTS: Thirteen percent of the patients referred to our program had multiple red blood cell antibodies. Odds of developing significant hemolytic disease of the fetus and newborn for patients with anti-Rh(D) combined with at least 1 additional red blood cell antibody were 3.65 times the odds for women with anti-Rh(D) antibodies in isolation (95% confidence interval, 1.84-7.33). In the setting of multiple antibodies including anti-Rh(D), Rh-positive fetuses/neonates have an increased odds of developing significant hemolytic disease even if the fetus is negative for the other corresponding red blood cell antigen. CONCLUSION: Women with multiple red blood cell antibodies are more likely to develop significant hemolytic disease of the fetus and newborn than those with a single antibody especially in the presence of anti-(Rh)D. This pathophysiology may suggest a more aggressive immune response in women who develop more than 1 red blood cell antibody.

Anti-D in Rh positive pregnancies.

OBJECTIVE: The purpose of this study was to review the clinical outcomes of anti-D isoimmunization in a series of women who typed Rh positive or Rh weak positive. STUDY DESIGN: This was a review of The Ohio State University Medical Center Fetal Therapy Program Database. RESULTS: Of 1068 pregnancies affected by anti-D, 5 pregnancies (0.47%) occurred in 4 women between 1994 and 2004, who were serologically typed as Rh positive or Rh weak positive. All 5 pregnancies delivered at term. All newborns were confirmed affected either by a positive direct antiglobulin test (DAT) or were Rh positive. Newborns were not anemic at birth and subsequently did not require transfusion. No newborns were treated for jaundice. All newborns were discharged home with their mothers. CONCLUSION: Anti-D hemolytic disease of the fetus and newborn (HDFN) is a rare complication of Rh positive and Rh weak positive pregnancies. Although the potential for severe HDFN exists in this clinical scenario, our experience suggests that in Rh positive or Rh weak positive pregnancies with anti-D isoimmunization, clinical HDFN is mild. Nonetheless, Rh positive or Rh weak positive patients with anti-D should be monitored for potentially significant HDFN.

Effects of antepartum therapy for fetal alloimmune thrombocytopenia on maternal lifestyle.

OBJECTIVE: The objective of this study is to describe the effects of antepartum therapy for fetal alloimmune thrombocytopenia (FAIT) on lifestyle. With the goal of preventing intraventricular hemorrhage in all fetuses without cordocentesis to measure fetal platelets, empiric treatment with intravenous immune globulin (IVIG), with or without prednisone, is recommended. It is hypothesized that these treatments negatively affect women's lifestyle. This information is needed for pre-conceptual counseling and developing management strategies. METHODS: A survey was mailed to 62 women treated by one provider from 2005 to 2013 asking if they experienced side effects from IVIG and prednisone, if their lives were negatively affected, if they would plan another affected pregnancy and if they needed help managing side effects. RESULTS: Three-quarters of 32 respondents reported that the treatments negatively affected their lifestyle. Thirty-one percent of women would not plan another pregnancy due to their experience and 22% were uncertain. All women experienced adverse effects and required additional medications or healthcare resources. Ninety-four percent contacted healthcare providers for help managing side effects. CONCLUSION: The significant negative effects on the lifestyle of women treated for FAIT emphasizes the need to identify the lowest effective doses and duration of pharmacotherapy and develop management strategies. Women undergoing treatment may need additional healthcare resources, including coordination of care.

Hemolytic Disease of the Fetus and Newborn due to Intravenous Drug Use.

Objectives The objective is to present a pregnancy complication associated with intravenous drug use, namely, that of red blood cell alloimmunization and hemolytic disease of the fetus and newborn. Methods An observational case series is presented including women with red blood cell alloimmunization most likely secondary to intravenous drug abuse Results Five pregnancies were identified that were complicated by red blood cell alloimmunization and significant hemolytic disease of the fetus and newborn, necessitating intrauterine transfusion, an indicated preterm birth, or neonatal therapy. Conclusions As opioid abuse continues to increase in the United States, clinicians should be aware of the potential for alloimmunization to red blood cell antibodies as yet another negative outcome from intravenous drug abuse.

Management of pregnancies complicated by anti-E alloimmunization.

OBJECTIVE: There is limited information published about anti-E alloimmunization. We review our experience at The Ohio State University to determine appropriate management strategies. METHODS: We reviewed records from June 1959 to April 2004 to identify pregnancies managed for anti-E alloimmunization. Information collected included antibody titers, DeltaOD450 values, Liley zones, middle cerebral artery peak systolic velocity, fetal and neonatal hemoglobin (Hb) and antigen typing, fetal and neonatal direct antiglobulin test, and outcomes. Pregnancies affected only by anti-E alloimmunization with a positive direct antiglobulin test or positive E antigen typing in the fetus or newborn were included. RESULTS: A total of 283 pregnancies were identified with anti-E. Of these, 32 pregnancies in 27 women were at risk for hemolytic disease of the fetus or newborn from anti-E only and had complete records. Sixteen of these pregnancies had titers greater than or equal to 1:32, with amniocenteses performed for DeltaOD450 in 15 pregnancies. Values of DeltaOD450 in zone IIB or zone III in combination with serologic titers identified all pregnancies with fetal or neonatal anemia. Five of 32 (15%) fetuses had Hb less than 10 g/dL and 1 fetus had hydrops fetalis due to anti-E alloimmunization. There was 1 perinatal death attributable to anti-E hemolytic disease of the fetus or newborn. Middle cerebral artery peak systolic velocity was measured in 2 cases and corroborated information obtained from amniocentesis. CONCLUSION: Anti-E alloimmunization can cause hemolytic disease of the fetus or newborn requiring prenatal intervention. Based on our population, clinical strategies developed for Rh D alloimmunization using maternal serology, amniotic fluid spectrophotometry, and fetal blood sampling are useful in monitoring E alloimmunization.

Monochorionic diamniotic infants without twin-to-twin transfusion syndrome.

BACKGROUND: Monochorionic-diamniotic twins (MoDi) occur in 0.3% of all pregnancies. Twin-to-twin transfusion syndrome (TTS) that occurs in 20% of MoDi pregnancies is associated with high perinatal morbidity and mortality. MoDi twins without TTS are more frequent (80%) but have been scarcely reported. OBJECTIVE: To study perinatal morbidity and mortality of 74 MoDi twin sets without TTS and to compare it to that of 38 sets of MoDi twins with TTS. METHODS: Chorionicity was determined by gender and placental examination. Gestational age (GA) was set by sonography and pediatric examination. TTS was diagnosed clinically and by sonography, discordance was defined by twins birth weight difference > or =20%, and fetal growth restriction was determined by using a twin-specific nomogram. RESULTS: MoDi twin pregnancies without and with TTS were similar in demographics, live births, history of preeclampsia, fetal distress and cesarean delivery. They were different (p<0.01) in discordant pregnancies (36 and 79%), GA at delivery (32 and 29 weeks) intrauterine growth restriction (39 and 89%) and neonatal mortality (12 and 36%). Concordant (47 sets) and discordant (27 sets) MoDi twins without TTS were clinically similar. CONCLUSIONS: MoDi twins without TTS have high rates of birth weight discordance, fetal growth restriction, fetal distress, prematurity and cesarean delivery. Although their perinatal mortality is low, the reported occurrence and the short- and long-term impacts of fetal and neonatal morbidities warrants attention.

Management of pregnancies complicated by anti-c isoimmunization.

OBJECTIVE: To review cases of anti-c isoimmunization and determine the most appropriate management strategies. METHODS: We performed a review of 102 pregnancies managed at The Ohio State University from 1967 to 2001 for anti-c isoimmunization. Of these, 55 had complete data and are included in this report. Information collected included serum titers, deltaOD450 values, Liley zones, fetal and neonatal hemoglobin levels and antigen typing, neonatal direct antiglobulin test, and neonatal outcomes. The appropriateness of traditional management was then evaluated. RESULTS: Of the 55 pregnancies, 46 had fetuses with positive direct antiglobulin test, and nine pregnancies had unaffected fetuses. Of the affected neonates, 12 (26%) had serious hemolytic disease of the newborn. Of these 12, 8 required fetal transfusion, and the remaining 4 newborns had hemoglobin levels of less than 10 g/dL at the time of delivery. A titer of 1:32 or greater or the presence of hydrops fetalis identified all such fetuses. There were 58 amniocenteses performed for deltaOD450 When plotted on modified Liley graphs, deltaOD450 values corresponded to disease severity. There were no perinatal deaths attributable to anti-c hemolytic disease of the newborn. CONCLUSION: Anti-c isoimmunization might cause significant fetal and newborn hemolytic disease. A titer of 1:32 or greater or evidence of hydrops fetalis identified all the serious hemolytic disease at our institution. The significance of antibody titers and deltaOD450 values was similar to Rh-D sensitized pregnancies, and management by the same modalities is appropriate.

Passively acquired treponemal antibody from intravenous immunoglobulin therapy in a pregnant patient.

Intravenous immunoglobulin is purified, concentrated immunoglobulin G antibodies pooled from human blood donors. The passive transmission of various antibodies from intravenous immunoglobulin has been reported. However, to the best of our knowledge, there are no reports of acquisition of treponemal antibody from immunoglobulin therapy. A woman with a pregnancy complicated by neonatal alloimmune thrombocytopenia was treated with intravenous immunoglobulin to manage her fetal thrombocytopenia. The patient had no history of a syphilis infection. The patient's blood was screened for syphilis antibodies regularly and routinely because she donated platelets for transfusion to her fetus. During her intravenous immunoglobulin treatments, a positive result on a fluorescence antibody absorption test was confirmed, but the result on a rapid plasma reagin test was negative. Eleven weeks after her final dose, results of the fluorescence antibody absorption test were negative, with a negative rapid plasma reagin test result, suggesting passive acquisition of the treponemal antibody. Clinicians and pathologists must be aware of the possible acquisition of this antibody during the treatment and counseling of patients receiving intravenous immunoglobulin.

Management of pregnancies complicated by anti-Fy(a) alloimmunization.

BACKGROUND: The objective was to evaluate the management and outcome of patients with anti-Fy(a) at the Ohio State University. STUDY DESIGN AND METHODS: A database search for patients with pregnancies complicated only by anti-Fy(a) from 1959 to 2004. Collected information included maternal testing, fetal therapy, and neonatal outcomes. RESULTS: The final data set included 18 pregnancies in 15 women where anti-Fy(a) was the only maternal alloantibody present and the fetus was Fy(a) antigen-positive. Maternal antibody titers of at least 32 and optical density at 450 nm values in modified Liley Zone IIB or III identified all fetuses or neonates with significant hemolytic disease (2/18, 11%). No fetuses had hydrops, and there were no deaths attributed to hemolytic disease of the fetus and newborn. CONCLUSION: Anti-Fy(a) has the potential to lead to significant fetal hemolysis. Management guidelines developed for D sensitization are appropriate for pregnancies complicated by anti-Fy(a) alloimmunization.