Richard O'Shaughnessy

Management of pregnancies complicated by anti-E alloimmunization.

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, ΔOD450 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 ΔOD450. When plotted on modified Liley graphs, ΔOD450 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 ΔOD450 values was similar to Rh-D sensitized pregnancies, and management by the same modalities is appropriate. LEVEL OF EVIDENCE: II-3

Management of pregnancies complicated by anti-Kell isoimmunization.

OBJECTIVE To assess the efficacy of managing pregnancies complicated by anti-Kell isoimmunization using the methods developed for evaluating anti-Rh-D isoimmunization. METHODS We reviewed 156 anti-Kell-positive pregnancies seen from 1959 to 1995, which were managed with serial maternal titers, amniotic fluid deltaOD450 determination, and funipuncture. Data on maternal titers, paternal phenotypes, invasive fetal testing and therapies, and neonatal outcomes were collected and analyzed to determine whether severely affected pregnancies were identified in time for successful fetal and neonatal therapy. RESULTS Twenty-one fetuses were affected, eight with severe disease, and two fetuses in this group died. All of the severely affected fetuses were associated with maternal serum titers of at least 1:32. A critical titer of 1:32 was found to be 100% sensitive for identifying the affected pregnancies. The affected group had significantly higher amniotic fluid deltaOD450 values over the range of gestational ages than did the unaffected group (P < .001). The upper Liley curve was a specific discriminator for the diagnosis of affected fetuses, and the lower curve was specific for the diagnosis of unaffected or mild cases. CONCLUSION Fetal anemia due to anti-Kell isoimmunization might be due in part to erythropoietic suppression, but it is still largely a hemolytic process. The methods based on a hemolytic process, including use of a critical maternal serum titer of 1:32, serial amniotic fluid analyses when the titer was exceeded, and liberal use of funipuncture, were successful in identifying severely affected fetuses.

Glycosylated hemoglobins and diabetes mellitus in pregnancy

The glycosylated hemoglobins (HA1) were measured in the blood of normal nonpregnant (n = 50) and pregnant (n = 29) volunteers and pregnant diabetic patients (n = 21). HA1 in normal pregnancy (6.7% +/- 1.03%) did not differ significantly from values in nonpregnancy (7.5% +/- 0.73%) and did not vary with the stage of gestation. HA1 was increased in diabetic pregnancy (8.4+ +/- 2.15%) and was positively correlated with serial fasting blood sugar (FBS) mean values in samples drawn up to 16 weeks (r = 0.57) prior to the measurement of HA1, although the highest correlation (r = 0.73, p less than 0.001) was with FBS levels over the prior 8 weeks. A large standard error of the estimate (26.9 mg/100 ml) showed HA1 to be insensitive as an indicator of prior FBS. There was a large overlap of HA1 from known diabetic patients with the normal range for pregnancy. There was no correlation of third-trimester HA1 and newborn birth weight. It was concluded that (1) normal pregnancy does not alter HA1; (2) HA1 is proportional to prior mean FBS; (3) marked elevations of HA1 (greater than 10%) reliably predict poor diabetic control, but HA1 is not useful for fine control of FBS; (4) HA1 is not useful as a screen for diabetes mellitus; (5) HA1 is not predictive of newborn birth weight.

Retrospective comparison of blood pressure course during preeclamptic and matched control pregnancies

A decrease in systemic blood pressure by midtrimester of normal pregnancy has been observed by many investigators. To examine the timing of onset of this decline and to study early behavior of blood pressure in pregnancies complicated by preeclampsia, we reviewed the outpatient charts of all patients with preeclampsia who received prenatal care at our clinics during the past 3 years. The 30 patients who met our criteria for preeclampsia were matched for age, race, and parity with normotensive control subjects. We found that in normal pregnancies, decline in blood pressure occurred before the second trimester and blood pressure remained low throughout gestation, rising insignificantly near term. Both systolic and diastolic blood pressures were significantly higher (p less than 0.05) for patients with preeclampsia than for normal control subjects beginning in the first trimester. This difference persisted throughout pregnancy and was also present at the 6-week postpartum visit (p less than 0.025).

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 ≥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.

Immunohistochemical evaluation of human placental implantation: An initial study

Immunohistochemical staining for human chorionic gonadotropin and factor VIII-related antigen with the avidin-biotin complex immunoperoxidase technique was used as a marker for syncytiotrophoblast and endothelial cells, respectively, in the human placental bed. Material from placental implantation sites at varying stages of gestation (8 weeks to term) was studied. Trophoblastic invasion of the uterine stroma and blood vessels were evaluated. Syncytiotrophoblasts lining placental villi and anchoring villi were positive for human chorionic gonadotropin at all stages of gestation studied. Endothelial cells lining maternal uterine blood vessels were positive for factor VIII-related antigen. At early stages of intrauterine placentation (8 and 11 weeks) trophoblastic invasion of uterine blood vessels and trophoblastic incorporation in the walls of dilated vessels were present. An unexpected finding, however, was the large number of giant cells in the superficial placental bed which had morphology suggestive of syncytiotrophoblast but which were negative for human chorionic gonadotropin. In addition, many enlarged, rather pleomorphic cells lining superficial blood vessels were found to be positive for factor VIII-related antigen, which identified them as endothelial cells and not migrating trophoblastic elements. This study demonstrates that human chorionic gonadotropin and factor VIII-related antigen immunoperoxidase staining is a helpful adjunct in evaluating human placentation and suggests extension of the technique with use of other antibodies to evaluate components of the placental bed.

Adrenergic innervation of uterine vasculature in human term pregnancy

The adrenergic innervation to the vasculature of the pregnant human uterus was studied by means of glyoxylic acid histofluorescence staining. Catecholamine fluorescent nerves are observed in the myometrium and walls of the vasculature in deep biopsies taken from the uterine isthmus and placental bed.

Circulating cell-free fetal DNA for the detection of RHD status and sex using reflex fetal identifiers†

To determine the sensitivity and specificity of circulating cell‐free fetal DNA in determining the fetal RHD status and fetal sex.

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 patients 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.

Antepartum versus intrapartum selective screening for maternal group B streptococcal colonization

Selective antepartum culturing was performed in pregnant women at high risk for low-birth-weight delivery and neonatal infection, in order to identify the presence of the group B streptococcus (GBS). Intrapartum culturing was performed in an additional group of gravid women when they presented either in premature labor or with prematurely ruptured membranes. Antepartum screening for GBS offered no additional advantage over intrapartum culturing in predicting pregnancies that resulted in neonatal infection. Therefore, an intrapartum approach is recommended.