Predicting Intrauterine Transfusion Interval and Perinatal Outcomes in Alloimmunized Pregnancies: Time-to-Event Survival Analysis.

BACKGROUND: The risk factors determining the frequency of intrauterine transfusions (IUTs) for severely affected red blood cell alloimmunized singleton pregnancies are not well known. OBJECTIVE: To assess factors associated with IUT frequency and adverse pregnancy outcomes in transfused pregnancies. METHODS: Retrospective cohort analysis of 246 consecutive cases between 1991 and 2014. Time-to-event survival analysis for repeated events was used to evaluate risk of subsequent IUT. Multivariable logistic regression assessed odds of a composite adverse pregnancy outcome (intrauterine fetal death, termination of pregnancy, neonatal death, preterm birth <34 weeks' gestation). RESULTS: Full information was available on232 cases (94.3%) and 716 IUTs. Fetal hydrops was associated with increased frequency (hazard ratio [HR] 1.29 [95% CIs 1.15-1.47, p < 0.001]) while higher fetal hemoglobin (Hb) pre-IUT (HR) 0.99 (95% CI 0.99-1.00, p = 0.021) and post-IUT (HR 0.99 [95% CI 0.99-1.00] p = 0.042), and higher transfused blood volume (HR 0.98 [95% CI 0.97-0.99] p < 0.001) were associated with reduced IUT frequency. Adverse pregnancy outcomes were more likely with lower gestational age (GA) at initial IUT. Antibody type was not associated with IUT frequency or adverse pregnancy outcomes. CONCLUSIONS: Hydrops is associated with increased IUT frequency while lower GA at initial IUT is associated with higher adverse pregnancy outcomes in alloimmunized pregnancies.Higher transfused blood volumes, pre- and post-IUT Hb are associated with lower IUT frequency.

Management and Neonatal Outcomes of Pregnancies with Fetal/Neonatal Alloimmune Thrombocytopenia: A Single-Center Retrospective Cohort Study.

BACKGROUND: There is no consensus regarding the optimal antenatal treatment of fetal/neonatal alloimmune thrombocytopenia (F/NAIT). We aimed to review the fetal blood sampling (FBS)-related risk, fetal response to maternal intravenous immunoglobulin (IVIG), and cesarean section (CS) rate in pregnancies with a history of F/NAIT. METHODS: Maternal demographics, alloantibodies, pregnancy management, fetal and neonatal outcomes, and index case characteristics were collected. Responders (R) and non-responders (NR) were defined as women treated with IVIG in whom fetal platelets (PLTs) were normal or low (< 50 × 109/L). RESULTS: An FBS-related risk occurred in 1.6% (2/119) of procedures. Maternal characteristics did not differ between responders (n = 21) and non-responders (n = 21). HPA-1a antibody was detected in all non-responders and in 72% of responders (p < 0.01). The index case had a significantly lower PLT count at birth in non-responders versus responders (median PLT count: R = 20 × 109/L [IQR 8-43] vs. NR = 9 × 109/L [IQR 4-18], p < 0.02). No differences were found in IVIG treatment duration or dosage. PLTs at birth were significantly lower in non-responders compared to responders. No intracranial hemorrhages occurred. CSs were performed for obstetric indications only in all but two cases. CONCLUSION: Maternal IVIG can elicit different fetal responses. The lack of prognostic factors to predict responders or non-responders suggests that there remains a role for FBS in F/NAIT in experienced hands.

Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model.

BACKGROUND: Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care. METHODS: A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration. RESULTS: Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08). CONCLUSIONS: The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.

Obstetrical and neonatal outcomes of triplet births - spontaneous versus assisted reproductive technology conception.

OBJECTIVE: To determine the average gestational age at birth and to compare obstetrical and neonatal outcomes of triplet births conceived spontaneously versus via assisted reproductive technology (ART). METHODS: A retrospective chart review of triplet pregnancies that resulted in three live babies was conducted at Mount Sinai Hospital (Toronto, Canada) from January 2000 to June 2013. RESULTS: A total of 230 women and 690 fetuses were identified. The mean gestational age at birth was 32.0 ± 3.8 weeks. Obstetrical outcomes included preterm premature rupture of the membranes in 29%, preterm labor in 26%, preeclampsia or HELLP syndrome in 19% and gestational diabetes in 10%. The mean birth weight of infants born after 24 weeks was 1655 ± 550 g and the rate of small for gestational age was 28%. The neonatal mortality rate prior to discharge was 7%. Aside from respiratory distress syndrome (30.6 versus 46.6%; p = 0.02), there were no differences in gestational age at birth, obstetrical or neonatal outcomes between spontaneous versus ART triplet conception. Monochorionicity carried a higher risk of small for gestational age, congenital anomalies and neonatal mortality compared to trichorionicity. CONCLUSION: Rates of preterm birth and related complications remain high in triplet gestation. However, obstetrical and neonatal outcomes were similar for triplets conceived spontaneously versus via ART.

Fetal thrombocytopenia in pregnancies with fetal human parvovirus-B19 infection.

OBJECTIVE: Fetal infection with human parvovirus B19 (hParvo-B19) has been associated mainly with fetal anemia, although data regarding other fetal hematologic effects are limited. Our aim was to assess the rate and consequences of severe fetal thrombocytopenia after fetal hParvo-B19 infection. STUDY DESIGN: We conducted a retrospective study of pregnancies that were complicated by fetal hParvo-B19 infection that underwent fetal blood sampling (FBS). The characteristics and outcomes of fetuses with severe thrombocytopenia (<50 × 10(9)/L) were compared with those of fetuses with a platelet concentration of ≥50 × 10(9)/L (control fetuses). Fetuses in whom 3 FBSs were performed (n = 4) were analyzed to assess the natural history of platelet levels after fetal hParvo-B19 infection. RESULTS: A total of 37 pregnancies that were affected by fetal hParvo-B19 infection were identified. Of the 29 cases that underwent FBS and had information regarding fetal platelets, 11 cases (38%) were complicated by severe fetal thrombocytopenia. Severely thrombocytopenic fetuses were characterized by a lower hemoglobin concentration (2.6 ± 0.9 g/dL vs 5.5 ± 3.6 g/dL; P = .01), lower reticulocyte count (9.1% ± 2.8% vs 17.3% ± 10.6%; P = .02), and lower gestational age at the time of diagnosis (21.4 ± 3.1 wk vs 23.6 ± 2.2 wk; P = .03). Both the fetal death rate within 48 hours of FBS (27.3% vs 0%; P = .02) and the risk of prematurity (100.0% vs 13.3%; P < .001) were higher in fetuses with severe thrombocytopenia. Fetal thrombocytopenia was more common during the second trimester but, in some cases, persisted into the third trimester. Intrauterine transfusion (IUT) of red blood cells resulted in a further mean decrease of 40.1% ± 31.0% in fetal platelet concentration. CONCLUSION: Severe fetal thrombocytopenia is relatively common after fetal hParvo-B19 infection, can be further worsened by IUT, and may be associated with an increased risk of procedure-related fetal loss after either FBS or IUT.

Fetal outcome in the critically ill pregnant woman.

Management of the critically ill pregnant woman is complicated by potential adverse effects of both maternal illness and ICU interventions on the fetus. This paper reviews the potential risks to the fetus of maternal critical illness, including shock, hypoxemia, and fever, as well as the effects of critical care management, such as drug therapy and radiological investigations. The authors' recommended approach to management is provided. Prior publications and new data presented identify that there is insufficient information to prognosticate accurately on fetal outcome after maternal critical illness, although maternal shock, hypoxemia and early gestational age are likely significant risk factors.

Fetoscopic laser therapy for twin-twin transfusion syndrome before 17 and after 26 weeks' gestation.

OBJECTIVE: The purpose of this study was to compare perinatal outcomes of pregnancies that undergo "early" (<17 weeks' gestation) or "late" (>26 weeks' gestation) fetoscopic laser ablation of placental vascular anastomoses for twin-twin transfusion syndrome (TTTS) with "conventional" cases that were treated at 17-26 weeks' gestation. STUDY DESIGN: We conducted a single center, retrospective analysis of 325 consecutive pregnancies that underwent fetoscopic laser therapy for severe TTTS. RESULTS: Twenty-four "early," 18 "late," and 283 "conventional" pregnancies with severe TTTS underwent laser therapy. Fetoscopy duration, gestation at delivery, survival rate, and complications were comparable among groups, except for preterm premature rupture of membranes at <7 days after laser therapy, which was more common in the "early" group than in either of the other 2 groups. CONCLUSION: Laser therapy for TTTS at <17 or >26 weeks' gestation has similar outcomes to procedures done at 17-26 weeks' gestation. We suggest that conventional gestational age guidelines of 16-26 weeks for laser therapy for TTTS should be reevaluated.

Gastroschisis: what is the average gestational age of spontaneous delivery?

BACKGROUND/PURPOSE: To consolidate what is known about pregnancies complicated by fetal gastroschisis through analysis of one of the largest series yet reported and to define the average gestational age of spontaneous delivery. METHODS: From 1980 to 2001, 159 pregnancies complicated by fetal gastroschisis were identified at a tertiary care center. Gestational age at delivery, birth weight, preterm delivery rate, and maternal age were compared to the 2001 general population statistics. Patients with pregnancies complicated by gastroschisis who went into spontaneous labor (n = 86) were subdivided into 2 groups based on gestational age (< 37 weeks and > or = 37 weeks). Operative delivery rates for nonreassuring fetal status and Apgar scores were assessed. RESULTS: Gastroschisis occurred more often in younger mothers (< 21 years) (42% vs 7.3%), was more frequently associated with preterm labor and delivery (28% vs 6%), and was associated with more low-birth-weight babies (36% vs 10%). The mean gestational age at spontaneous labor was 36.6 weeks. In those patients who labored spontaneously, there were no significant differences in the operative delivery rates for fetal distress; however, there was a trend to lower Apgar scores in babies born at 37 weeks or more. CONCLUSION: Our data provide a framework for further studies to determine the optimal timing and mode of delivery for fetuses with gastroschisis.

When it comes to pregnant women sleeping, is left right?

Pregnant women who lie in a supine position may develop syncopal symptoms. However, of those women who become symptomatic, only 2% to 4% have significant aortocaval compression. Even in this small minority of symptomatic women, there is no evidence of fetal compromise. The advice often given to pregnant women to lie on the left side is therefore not relevant. In some women, experiencing a pre-syncopal episode will cause them to avoid lying in the supine position.

A randomized controlled trial of a bedside partogram in the active management of primiparous labour.

OBJECTIVE: The partogram is a pictorial representation of the progress of labour, used in an effort to enhance early recognition of dystocia and help avoid Caesarean section (CS). The objective of this study was to evaluate the effect of partogram use on the CS and obstetric intervention rates. METHODS: We conducted a randomized controlled trial of use of the partogram in 1932 primiparous women with uncomplicated pregnancies at term. Patients were randomly assigned to one of two groups: the standard group, who had the progress of labour charted in written notes, or the partogram group, whose progress in labour was recorded using a bedside graphical partogram as well as in written notes. Outcomes were stratified according to whether labour was spontaneous or induced and whether membranes were initially intact or ruptured. The primary outcome was the rate of CS; secondary outcome measures were rates of obstetric intervention for dystocia. RESULTS: There was no significant difference between the groups in rates of CS (partogram 24%, standard notes 25%), rates of other interventions, amniotomy, oxytocin use, or the mean cervical dilatation in labour. CONCLUSION: In this study, the use of a partogram without a mandatory management of labour protocol had no effect on rates of CS or other intrapartum interventions in healthy primiparous women at term.

Doppler ultrasonography versus amniocentesis to predict fetal anemia.

BACKGROUND: Pregnancies complicated by Rh alloimmunization have been evaluated with the use of serial invasive amniocentesis to determine bilirubin levels by measuring in the amniotic fluid the change in optical density at a wavelength of 450 nm (DeltaOD450); however, this procedure carries risks. Noninvasive Doppler ultrasonographic measurement of the peak velocity of systolic blood flow in the middle cerebral artery also predicts severe fetal anemia, but this test has not been rigorously evaluated in comparison with amniotic-fluid DeltaOD450. METHODS: We performed a prospective, international, multicenter study including women with RhD-, Rhc-, RhE-, or Fy(a)-alloimmunized pregnancies with indirect antiglobulin titers of at least 1:64 and antigen-positive fetuses to assess whether Doppler ultrasonographic measurement of the peak systolic velocity of blood flow in the middle cerebral artery was at least as sensitive and accurate as measurement of amniotic-fluid DeltaOD450 for diagnosing severe fetal anemia. The results of the two tests were compared with the incidence of fetal anemia, as determined by measurement of hemoglobin levels in fetal blood. RESULTS: Of 165 fetuses, 74 had severe anemia. For the detection of severe fetal anemia, Doppler ultrasonography of the middle cerebral artery had a sensitivity of 88 percent (95 percent confidence interval, 78 to 93 percent), a specificity of 82 percent (95 percent confidence interval, 73 to 89 percent), and an accuracy of 85 percent (95 percent confidence interval, 79 to 90 percent). Amniotic-fluid DeltaOD450 had a sensitivity of 76 percent (95 percent confidence interval, 65 to 84 percent), a specificity of 77 percent (95 percent confidence interval, 67 to 84 percent), and an accuracy of 76 percent (95 percent confidence interval, 69 to 82 percent). Doppler ultrasonography was more sensitive, by 12 percentage points (95 percent confidence interval, 0.3 to 24.0), and more accurate, by 9 percentage points (95 percent confidence interval, 1.1 to 15.9), than measurement of amniotic-fluid DeltaOD450. CONCLUSIONS: Doppler measurement of the peak velocity of systolic blood flow in the middle cerebral artery can safely replace invasive testing in the management of Rh-alloimmunized pregnancies. (ClinicalTrials.gov number, NCT00295516.).

Impact of selective laser ablation of placental anastomoses on the cardiovascular pathology of the recipient twin in severe twin-twin transfusion syndrome.

OBJECTIVES: We investigated the impact of selective laser ablation on the cardiovascular pathology of the recipient twin in twin-twin transfusion syndrome. STUDY DESIGN: Fetal echocardiograms and medical records were reviewed from 22 pregnancies with severe twin-twin transfusion syndrome where echocardiography was performed before and after laser. RESULTS: Before laser, cardiomegaly associated with right and/or left ventricular hypertrophy without ventricular dilatation, was observed in most cases. Right ventricular and left ventricular systolic dysfunction (shortening fraction <28%) was present in 59% and 27%, respectively, and diastolic dysfunction (based on inflow and venous Dopplers) in 73%. Shortly after laser, biventricular systolic function improved significantly and diastolic function tended to improve (50%, P = .06). Functional pulmonary atresia, secondary to right ventricular systolic dysfunction, resolved in 2 of 2 cases at post-laser echocardiography. On serial assessment, diastolic function was normal in 7 of 10, hydrops regressed in 4 of 5, and neither progressive myocardial hypertrophy nor anatomical right ventricular outflow obstruction were found. CONCLUSIONS: Selective laser ablation in severe twin-twin transfusion syndrome acutely improves biventricular systolic function and tends to improve diastolic function in the recipient twin.

The association between early membrane rupture, latency, clinical chorioamnionitis, neonatal infection, and adverse perinatal outcomes in twin pregnancies complicated by preterm prelabour rupture of membranes.

The objective of this study was to evaluate associations between adverse outcomes in twin pregnancies and preterm prelabour rupture of membranes (PPROM). A chart review of 246 consecutive twin pregnancies with confirmed PPROM was conducted. Regression analysis (beta [natural log of the odds ratio] and odds ratio [OR]) was performed to identify independent predictors. Two hundred and forty-six twin pregnancies, 492 liveborns, and 20 neonatal deaths. Mean (SD) PPROM gestational age (GA): 31.3 (3.8) wk; delivery GA: 32.0 (3.3) wk. PPROM < 30 wk was associated with increased parity (OR: 2.66), and log (admission leukocyte count) (OR: 9.99). Shortened latency was associated with PPROM GA (beta = -0.17) and chorioamnionitis (beta = 0.95). Neonatal sepsis was predicted by lower delivery GA (OR: 2.04). Adverse perinatal outcomes were protected against by older GA at PPROM (OR 0.53) and shortened latency (OR 0.73). It was concluded that increased leukocytosis and parity implies an infectious aetiology in earlier PPROM. Increased risk for neonatal sepsis at earlier delivery GA is consistent with gestation-dependent fetal immunocompetence. Early PPROM and long latencies were associated with increased adverse perinatal outcomes.

Maternal anti-Ro and anti-La antibody-associated endocardial fibroelastosis.

BACKGROUND: Maternal anti-Ro and anti-La antibodies are associated with congenital heart block (CHB). Although endocardial fibroelastosis (EFE) has been described in isolated cases of autoantibody-mediated CHB, the natural history and pathogenesis of this disease are poorly understood. METHODS AND RESULTS: We retrospectively reviewed the clinical history, echocardiography, and pathology of fetuses and children with EFE associated with CHB born to mothers positive for anti-Ro or anti-La antibodies at 5 centers. Thirteen patients were identified, 6 with a prenatal and 7 with a postnatal diagnosis. Six mothers were positive for anti-Ro and anti-La antibodies, and 7 were positive for anti-Ro antibodies only. Only 1 mother had autoimmune disease. Severe ventricular dysfunction was seen in all fetal and postnatal cases. Four fetal and 3 postnatal cases had EFE at initial presentation. However, 2 fetal and 4 postnatal cases developed EFE 6 to 12 weeks and 7 months to 5 years from CHB diagnosis, respectively, even despite ventricular pacing in 6 postnatal cases. Eleven (85%) either died (n=9) or underwent cardiac transplantation (n=2) secondary to the EFE. Pathologic assessment of the explanted heart, available in 10 cases, revealed moderate to severe EFE in 7 and mild EFE in 3 cases, predominantly involving the left ventricle. Immunohistochemistry in 4 cases (including 3 fetuses) demonstrated deposition of IgG in 4 and IgM in 3 and T-cell infiltrates in 3 cases, suggesting an immune response by the affected fetus or child. CONCLUSIONS: EFE occurs in the presence of autoantibody-mediated CHB despite adequate ventricular pacing. Autoantibody-associated EFE has a very high mortality rate, whether developing in fetal or postnatal life.