Comparison of Serial Amnioinfusion Strategies for Isolated Early-Onset Fetal Renal Anhydramnios.

INTRODUCTION: The optimal protocol for serial amnioinfusions to maintain amniotic fluid in pregnancies with early-onset fetal renal anhydramnios before 22 weeks is not known. We compared the performance of two different approaches. METHODS: A secondary analysis was conducted of serial amnioinfusions performed by a single center during the external pilot and feasibility phases of the Renal Anhydramnios Fetal Therapy (RAFT) trial. During the external pilot, higher amnioinfusion volumes were given less frequently; in the feasibility study, smaller volume amnioinfusions were administered more frequently. Procedural details, complications, and obstetric outcomes were compared between the two groups using Pearson's χ2 or Fisher's exact tests for categorical variables and Student's t tests or Wilcoxon rank-sum tests for continuous variables. The adjusted association between procedural details and chorioamniotic separation was obtained through a multivariate repeated measure logistic regression model. RESULTS: Eleven participants underwent 159 amnioinfusions (external pilot: 3 patients, 21 amnioinfusions; feasibility: 8 patients, 138 amnioinfusions). External pilot participants had fewer amnioinfusions (7 vs. 19.5 in the feasibility group, p = 0.04), larger amnioinfusion volume (750 vs. 500 mL, p < 0.01), and longer interval between amnioinfusions (6 [4-7] vs. 4 [3-5] days, p < 0.01). In the external pilot, chorioamniotic separation was more common (28.6% vs. 5.8%, p < 0.01), preterm prelabor rupture of membranes (PPROM) occurred sooner after amnioinfusion initiation (28 ± 21.5 vs. 75.6 ± 24.1 days, p = 0.03), and duration of maintained amniotic fluid between first and last amnioinfusion was shorter (38 ± 17.3 vs. 71 ± 19 days, p = 0.03), compared to the feasibility group. While delivery gestational age was similar (35.1 ± 1.7 vs. 33.8 ± 1.5 weeks, p = 0.21), feasibility participants maintained amniotic fluid longer. CONCLUSION: Small volume serial amnioinfusions performed more frequently maintain normal amniotic fluid volume longer because of delayed occurrence of PPROM.

Treatment of Twin Anemia Polycythemia Sequence with Donor Transfusion and Partial Recipient Exchange Transfusion: Procedural Considerations and Outcomes.

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We aimed to provide a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe setup. Procedural characteristics and outcomes as well as the accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9-6.0]). One pET was stopped due to fetal deceleration. The patients were delivered at 33.0 weeks [IQR 31.9-33.3] with two survivors and no neonatal transfusion requirements. The IUT volume was 48 mL [IQR 39-63 mL] and the pET volume was 32 mL [IQR 20-50], utilizing aliquots of 5-20 mL for the latter (p = 0.021). For the IUTs, the assumption of a fetal blood volume below 150 mL/kg underestimated the required transfusion volume. For the pETs, all formulas required adjustment of the dilution volume based on bedside testing (p < 0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin.

First-trimester detection of fetal anomalies in pregestational diabetes using nuchal translucency, ductus venosus Doppler, and maternal glycosylated hemoglobin.

OBJECTIVE: The frequency of fetal anomalies in women with pregestational diabetes correlates with their glycemic control. This study aimed to assess the predictive performance of first-trimester fetal nuchal translucency (NT), ductus venosus (DV) Doppler, and hemoglobin A1c (HbA1c) to predict fetal anomalies in women with pregestational diabetes. STUDY DESIGN: This was a prospective observational study of patients undergoing first-trimester NT with DV Doppler. Screening performance was tested for first-trimester parameters to detect fetal anomalies. RESULTS: Of 293 patients, 17 had fetal anomalies (11 cardiac, 7 major, 3 multisystem). All anomalous fetuses were suspected prenatally. One had NT >95th centile, 2 had reversed DV a-wave, and 13 had HbA1c >7.0%. The HbA1c was the primary determinant of anomalies (r(2), 0.15; P < .001) and >8.35% was the optimal cutoff for prediction of anomalies with an area under the curve of 0.72 (95% confidence interval, 0.57-0.88). Therefore, first-trimester prediction of anomalies was best in women with increased NT or HbA1c >8.3% (sensitivity 70.6%, specificity 77.4%, positive predictive value 16.2%, negative predictive value 97.7%, P < .001). CONCLUSION: In women with pregestational diabetes and poor glycemic control, an increased NT increases risks for major fetal anomalies. Second-trimester follow-up is required to achieve accurate prenatal diagnosis.

Dichorionic diamniotic heterotopic twin gestation with cesarean section scar implantation and placenta increta.

Heterotopic cesarean scar pregnancy is an extremely rare form of pregnancy and is defined as an intrauterine pregnancy coexisting with an ectopic pregnancy implanted in the cesarean scar. Cesarean scar ectopic pregnancy can also be a precursor for placenta accreta spectrum, a potentially life-threatening condition in which the placenta is abnormally adherent to the uterine myometrium and possibly adjacent organs. Although cesarean scar ectopic pregnancies are rare, there has been an increase in their incidence due to the rise in cesarean deliveries. We present the case of a 35-year-old patient with a heterotopic pregnancy with ectopic implantation in a cesarean scar and associated placenta increta, as well as the radiologic evaluation of placenta accreta spectrum and subsequent management.

Predictors of necrotizing enterocolitis in preterm growth-restricted neonates.

OBJECTIVE: The purpose of this study was to test the hypothesis that multivessel fetal Doppler imaging provides enhanced prediction of necrotizing enterocolitis (NEC) in preterm placental insufficiency. STUDY DESIGN: Placental-based growth-restricted fetuses (abdominal circumference <5%, abnormal umbilical artery [UA] Doppler imaging) were examined. UA, middle cerebral artery, ductus venosus, and umbilical vein (UV) were evaluated prenatally and were assessed for their ability to predict NEC in neonates who were delivered at <37 weeks of gestation. RESULTS: Thirty-nine of 404 neonates (9.7%) experienced NEC. Among these, the mortality rate was 15.4% (6/39 neonates; odds ratio, 2.7; 95% CI, 1.03-7.11). NEC cases had higher UA Doppler indices prenatally (P = .023), lower gestational ages and birthweight at delivery (P < .0001, respectively), 5-minute Apgar scores of <7, and higher umbilical cord artery base deficit (P < .01, respectively). NEC was more likely after prenatal UV pulsations (odds ratio, 2.4; 95% CI, 1.13-5.14; P = .028) and severe cardiovascular abnormality (composite variable incorporating UA- absent or reversed end diastolic velocity, absent or reversed ductus venosus a-wave, or UV pulsations; odds ratio, 2.1; 95% CI, 1.06-4.05; P = .029) Logistic regression revealed birthweight and base deficit as the main contributors of NEC (r(2) = 0.20; P < .0001). Receiver operating characteristic analyses revealed birthweight of <790 g (sensitivity, 74.4%; specificity, 72.9%; P < .0001) and gestational age of < or =32.2 weeks (sensitivity, 94.9%; specificity, 45.8%; P < .0001) as optimal cut-offs that provide an odds ratio for NEC of 8.2 (95% CI, 3.9-17.6; P < .0001). CONCLUSION: Placental disease predisposes the severely growth-restricted neonate to necrotizing enterocolitis. Even when arterial and venous Doppler variables are taken into consideration, birthweight remains the predominant risk factor for NEC. Further research should focus on the critical transition to neonatal life to identify relevant triggers in predisposed neonates.

Gravid hysterectomy: a decade of experience at an academic referral center.

OBJECTIVE: To evaluate the incidence of gravid hysterectomy (GH) and to examine the indications as well as risk factors and complications associated with the procedure at an academic perinatal referral center. STUDY DESIGN: Retrospective chart review of all patients who underwent GH from 1991 to 2001. Demographics, obstetric history, delivery information, complications and outcome were analyzed. RESULTS: There were 34 GHs out of 19,491 deliveries (1.74/1000). The preoperative indications were hemorrhage associated with atony (32.4%), placenta accreta (20.6%) and uncontrolled bleeding (17.6%). Of the patients, 87.5% were parous and 53.1% had previous cesarean section. GH was performed prior to viability in 3. GH followed cesarean delivery in 24 (68.6%). Uterine and/or hypogastric artery ligation were performed in 11 (32.4%). Postoperative complications included surgical re-exploration for recurrent hemorrhage in 5, transfusion of blood products in 30, disseminated intravascular coagulopathy in 15, prolonged (> 24 hours) ventilation in 10 and admission to the SICU for prolonged intensive care in 12. There were 2 maternal deaths (5.9%). A significant rise in GH rate from 1/800 to 1/299 occurred over the past 5 years despite constant cesarean rates (chi2, p < 0.05). CONCLUSION: Rates of GH increased over the period examined. Placenta accreta associated with previous cesarean section is the predominant risk factor for GH.

Nucleated red blood cell counts in the first week of life: a critical appraisal of relationships with perinatal outcome in preterm growth-restricted neonates.

OBJECTIVE: Nucleated red blood cells (NRBC) are fetal hematologic markers for placental dysfunction, hypoxemia, and asphyxia. NRBC count elevation at birth or persistence is linked statistically to adverse outcome, but clinical predictive value is variable. We studied novel indices to better define overall magnitude of NRBC response. STUDY DESIGN: Peripheral NRBC count was obtained from preterm (<34 weeks of gestation) growth-restricted neonates within 2 hours of life. Daily counts and duration of NRBC count >30/100 white blood cells were determined. Mean counts (NRBC-mean), area under the curve (NRBC-AUC), and declination (NRBC-slope) were analyzed over week 1. NRBC parameters were related to major morbidity (bronchopulmonary dysplasia, grade III/IV intraventricular hemorrhage, necrotizing enterocolitis included) and neonatal death (NND). RESULTS: Twenty-two of 176 patients (12.5%) had acidosis. Complications included bronchopulmonary dysplasia (n = 36; 20.5%), intraventricular hemorrhage (n = 18; 10.2%), necrotizing enterocolitis (n = 18; 10.2%), NND (n = 18; 10.2%). NRBC-AUC and NRBC-mean correlated most strongly with pH, birthweight, and gestational age (Pearson coefficient -0.45 to -0.18; all P < .001). NRBC-AUC varied most between nonmorbid and morbid; NRBC-mean varied most between survivors and NND (all P < .001). NRBC persistence strongly predicted NND: clearance by day 4 was achieved by 80% of survivors and only 35% of NNDs. Logistic regression identified prematurity and persistent NRBC counts as primary morbidity determinants (r2 = 0.56; P < .01). Although the importance of individual NRBC counts varied, day-4 NRBC counts of >70 predicted morbidity best (sensitivity, 82%; specificity, 96%). Presence of morbidity and birthweight were prime determinants of death (r2 = 0.42; P < .01). CONCLUSION: Simple daily NRBC counts provide clinical information that is equivalent to more complicated methods. The importance of prematurity and growth are emphasized, but elevated NRBC counts beyond day 3 are relevant independent predictors of adverse outcome.

Determinants of the middle cerebral artery peak systolic velocity in the human fetus.

OBJECTIVE: The purpose of this study was to identify physiologic determinants of the peak systolic blood flow velocity (PSV) of the middle cerebral artery (MCA) in the human fetus. STUDY DESIGN: MCA PSV was measured with pulsed wave Doppler ultrasound in human fetuses who underwent cordocentesis. Hemoglobin, hematocrit, and blood gas values were analyzed from umbilical venous blood, and the data were normalized for gestational age. Total oxygen content of fetal venous blood was calculated from oxygen saturation, hemoglobin value, and pO2. Correlation and logistic regression analyses were performed to identify primary physiologic determinants of MCA PSV. RESULTS: In 136 fetuses who underwent cordocentesis (predominantly for alloimmune disease), hematocrit, hemoglobin, and blood oxygen content correlated significantly with the MCA PSV (P < .01). Logistic regression modeling demonstrated that fetal hemoglobin content (odds ratio, 7.1; 95% CI, 3.71-13.7) and pCO2, but not pO2 or fetal blood oxygen content, accounted for increases in MCA PSV. CONCLUSION: Under physiologic circumstances, fetal hemoglobin, and not fetal oxygenation, primarily determines the middle cerebral artery peak systolic velocity.

Sustained hematological consequences in the first week of neonatal life secondary to placental dysfunction.

OBJECTIVE: To evaluate the relationship between umbilical artery end diastolic velocity in growth restricted fetuses and neonatal hematologic parameters. STUDY DESIGN: Growth restricted fetuses were studied with ultrasound and Doppler evaluations. Neonates were analyzed in two groups based on umbilical artery Doppler status: positive end-diastolic velocities (PEDV) and absent or reversed end-diastolic velocities (AEDV). At birth and throughout the first week of life, groups were compared for anemia and thrombocytopenia; transfusion of red blood cells, platelets, and fresh frozen plasma; and intraventricular hemorrhage (IVH). RESULTS: Seventy-three neonates met inclusion criteria, 38 with PEDV, 35 with AEDV. Those with AEDV were delivered 3 weeks earlier, were 450 g smaller, had lower cord arterial pH values, and greater cord artery base deficits (p<0.05, respectively). AEDV neonates were twice as likely to be anemic and thrombocytopenic at birth and remain so during the first week, requiring more red blood cell and platelet transfusions. There was no difference in occurrence of severe IVH between groups. CONCLUSION: Hematological alterations associated with intrauterine growth restriction appear to continue into the first week of neonatal life. These are proportional to the degree of placental dysfunction and are predicted by fetal Doppler status. SUMMARY: Abnormal development of the placental vascular tree is the primary step in a cascade of fetal compromises leading to intrauterine growth restriction (IUGR). Doppler ultrasound evaluation of fetal and placental blood flows provides a non-invasive assessment of the fetal condition which reflects the impact of placental vascular abnormalities. The degree of placental dysfunction determines the severity of fetal disease, which can affect many fetal organ systems. In addition to disturbances in placental respiratory function, abnormal umbilical artery Doppler status is also indicative of hematologic abnormalities during fetal life and at birth. Neonates who had more severe placental dysfunction, as depicted by absent umbilical artery end diastolic velocity, were more likely to be anemic and thrombocytopenic at birth and remain so during the first week of life, and required more transfusions than those with positive end diastolic velocities. The severity of hematologic alterations during the first week of life in growth restricted neonates was proportional to and predicted by the antenatal umbilical artery end diastolic velocity Doppler status.

Persistent fetal hemoglobin in maternal circulation complicating the diagnosis of fetomaternal hemorrhage.

BACKGROUND: Transplacental hemorrhage can be life threatening to a fetus and has important maternal treatment implications. In contrast, hereditary persistence of fetal hemoglobin is a condition that has little consequence. The Kleihauer-Betke test, which is routinely used to document transplacental hemorrhage, will be positive in either case. CASES: We report two cases in which maternal persistence of fetal hemoglobin was unknown and led to the erroneous diagnosis of fetomaternal hemorrhage. These cases highlight both the limitations of the Kleihauer-Betke test and the role of flow cytometry in diagnosing fetomaternal hemorrhage. CONCLUSION: The use of flow cytometry can clarify Kleihauer-Betke test results when there is known maternal persistence of fetal hemoglobin and can more precisely quantify a fetomaternal hemorrhage for accurate Rh immune globulin dosing.

Lethal progression of a fetal intracranial arteriovenous malformation.

Fetal intracranial vascular tumors present unique clinical challenges. Accurate diagnosis of the lesion, as well as an understanding of the local and systemic impacts, will guide the antenatal surveillance and the treatment plan and will determine the prognosis. Management will be altered by and dependent on intrauterine progression, gestational age, and fetal condition at birth. In addition, large vascular tumors can lead to the development of the Kasabach-Merritt sequence in the fetus and to either fetal or maternal hemodynamic impairment. Vascular tumors are either malformations or neoplasms. Color and pulsed wave Doppler sonography are useful for the identification of vascular lesions and help narrow the differential diagnosis. Once a vascular malformation is identified, a comprehensive anatomic survey is mandatory to determine whether there are coexistent malformations that impact either the diagnosis or prognosis. These lesions can have local mass effects, systemic hemodynamic effects, or both. Therefore, longitudinal assessment of the fetus is focused on the detection of lesion progression and on any fetal or maternal status changes. We report the prenatal diagnosis of an intracranial arteriovenous malformation (AVM) with a dramatic progression affecting both mother and fetus.

Venous Doppler in the prediction of acid-base status of growth-restricted fetuses with elevated placental blood flow resistance.

OBJECTIVE: This study was undertaken to test which venous Doppler parameter offers the best prediction of acid-base status at birth in pregnancies complicated by intrauterine growth restriction (IUGR) caused by placental dysfunction. STUDY DESIGN: A prospective cross-sectional Doppler study of IUGR fetuses with abnormal umbilical artery Doppler and birth weight less than the 10th percentile. Absence of atrial systolic forward velocities in the ductus venosus (DV) (DV-RAV) and umbilical vein (UV) pulsations were noted and multiple venous indices were calculated for the inferior vena cava (IVC) and DV (IVC and DV preload index, peak velocity index [PVIV] and pulsatility index [PIV] and the DV S/a ratio). Doppler indices, UV pulsations, and DV- RAV were related to an umbilical artery cord pH <7.20, and a pH <7.00 and/or base deficit greater than -13 (severe metabolic compromise) in neonates delivered by cesarean section without labor. RESULTS: In 122 fetuses all venous Doppler indices were equally predictive of a pH <7.20, with the exception of the IVC PVIV. No Doppler index predicted severe metabolic compromise. Bayesian analysis of individual Doppler parameters showed comparable outcome prediction with the highest sensitivity for the IVC PIV (76%) and the highest specificity for DV-RAV (96%). Combined assessment of the IVC, DV, and UV provided the most accurate outcome prediction. Doppler abnormality in either vessel identified 89% of neonates with pH <7.20 (negative predictive value 92%) and 10 of 11 neonates with severe metabolic compromise. Prediction was most specific (84%) when Doppler parameters were abnormal in all 3 vessels. CONCLUSION: IVC, DV, and UV Doppler parameters correctly predict acid-base status in a significant proportion of IUGR neonates. Combination, rather than single vessel assessment provides the best predictive accuracy. While the choice of Doppler index can be guided by operator preference, familiarity with the examination technique of all 3 vessels is encouraged to offer the highest flexibility in clinical practice.