Timing and Mode of Delivery in Prenatally Diagnosed Congenital Heart Disease- an Analysis of Practices within the University of California Fetal Consortium (UCfC).

Prenatal diagnosis of critical congenital heart disease (CHD) is associated with decreased morbidity. It is also associated with lower birth weights and earlier gestational age at delivery. The University of California Fetal Consortium (UCfC) comprises five tertiary medical centers, and was created to define treatment practices. We utilized this consortium to assess delivery patterns and outcomes in subjects with prenatal and postnatal diagnosis of CHD. A retrospective cohort study was conducted on maternal-neonatal pairs diagnosed with complex CHD prenatally (n = 186) and postnatally (n = 110) from 2011 to 2013. Outcomes were assessed between groups after adjusting for disease severity. Prenatally diagnosed subjects were born earlier (38.1 ± 0.11 vs. 39 ± 0.14 weeks, p = < 0.001), and had lower birth weights (2853 ± 49 vs. 3074 ± 58 g, p = 0.005) as compared to postnatal diagnosis. For every week increase in gestational age and 100 g increase in birth weight, length of stay decreased by 12.3 ± 2.7% (p < 0.001) and 3.9 ± 0.9% (p < 0.001). Subjects with prenatal diagnosis were more often born via cesarean both planned (35.6 vs. 26.2%, p = 0.004) and after a trial of labor (13 vs. 7.8%, p = 0.017). Neonates with cesarean delivery trended toward a longer length of stay (2.6 days longer), and were born earlier as compared to other modalities (37.7 ± 0.22 weeks, p = 0.001). Management after prenatal diagnosis of CHD appears to have modifiable disadvantages for maternal and neonatal outcomes. The UCfC provides a platform to study best practices and standardization of care for future studies.

Anomalous Pulmonary Venous Return: Insights Into Prenatal Detection.

OBJECTIVES: To review all cases of total anomalous pulmonary venous return (TAPVR) or partial anomalous pulmonary venous return (PAPVR) identified prenatally or postnatally at a single institution and to identify factors that may lead to a correct or missed diagnosis in both high- and low-risk fetuses on screening examinations. METHODS: Fetal images from 16 cases of prenatally or postnatally diagnosed T/PAPVR were retrospectively reviewed to analyze factors that influenced interpretations and diagnoses. RESULTS: Sixteen diagnoses of T/PAPVR were made, with a final number of 10 confirmed cases, 1 of which was PAPVR. Ten fetuses with a presumptive diagnosis of T/PAPVR before delivery were at an average gestational age of 24.7 weeks, with 5 cases diagnosed postnatally. None of the diagnoses of isolated TAPVR were made during a screening examination. Twelve of the pregnancies were complicated by complex cardiac defects, including 6 with heterotaxy syndromes. Of the 5 abnormal cases identified in the postpartum period, 3 had isolated TAPVR. In the 3 patients with isolated defects, prenatal echocardiography was not performed; the anatomy scan interpretations were confounded by multiple factors. In retrospect, there was no obvious sonographic evidence of TAPVR in these patients; however, color flow Doppler imaging of the pulmonary veins was not performed on any of them. CONCLUSIONS: Although fetal echocardiography has improved the overall detection of TAPVR or PAPVR, this abnormality continues to elude prenatal diagnosis during screening in both low- and high-risk patients. We hypothesize that the use of color flow Doppler imaging in the 4-chamber view may assist in diagnosing TAPVR in screening low-risk patients, especially in those with difficult scans.

Aspirin resistance in pregnancy is associated with reduced interleukin-2 (IL-2) concentrations in maternal serum: Implications for aspirin prophylaxis for preeclampsia.

OBJECTIVES: To evaluate the impact of aspirin resistance on the incidence of preeclampsia and maternal serum biomarker levels in pregnant individuals at high-risk of preeclampsia receiving low dose aspirin (LDA). STUDY DESIGN: We performed a secondary analysis of a randomized, placebo-controlled trial of LDA (60 mg daily) for preeclampsia prevention in high-risk individuals (N = 524) on pregnancy outcomes and concentrations of PLGF, IL-2, IL-6, thromboxane B2 (TXB2), sTNF-R1 and sTNF-R2 from maternal serum. MAIN OUTCOME MEASURES: LDA-resistant individuals were defined as those having a TXB2 concentration >10 ng/ml or <75 % reduction in concentration at 24-28 weeks after LDA administration. Comparisons of outcomes were performed using a Fisher's Exact Test. Mean concentrations of maternal serum biomarkers were compared using a Student's t-test. Pearson correlation was calculated for all pairwise biomarkers. Longitudinal analysis across gestation was performed using linear mixed-effects models accounting for repeated measures and including BMI and maternal age as covariates. RESULTS: We classified 60/271 (22.1 %) individuals as LDA-resistant, 179/271 (66.1 %) as LDA-sensitive, and 32/271 (11.8 %) as non-adherent. The prevalence of preeclampsia was not significantly different between the LDA and placebo groups (OR = 1.43 (0.99-2.28), p-value = 0.12) nor between LDA-sensitive and LDA-resistant individuals (OR = 1.27 (0.61-2.8), p-value = 0.60). Mean maternal serum IL-2 concentrations were significantly lower in LDA-resistant individuals relative to LDA-sensitive individuals (FDR < 0.05). CONCLUSIONS: These results suggest a potential role for IL-2 in the development of preeclampsia modulated by an individuals' response to aspirin, presenting an opportunity to optimize aspirin prophylaxis on an individual level to reduce the incidence of preeclampsia.

Cardiovascular Risk Assessment as a Quality Measure in the Pregnancy and Postpartum Period.

Background: Cardiovascular disease (CVD) is the leading cause of maternal mortality in the United States, accounting for over one-third of all pregnancy-related deaths. Contributing factors such as lack of recognition and delayed diagnosis of CVD are primarily due to the overlap of signs and symptoms of a normal pregnancy with those of CVD. Objectives: This study aimed to demonstrate the feasibility of introducing CVD risk assessment into clinical practice using the California Maternal Quality Care Collaborative algorithm to detect CVD during pregnancy and postpartum periods. Methods: We implemented the CVD risk assessment algorithm into electronic health records at 3 large hospital networks serving over 14,000 patients at 23 sites. We determined the percentage of pregnant and/or postpartum patients who were screened for CVD risk and the follow-up rate for patients in whom the tool recommended a follow-up assessment. Rates were stratified according to clinical site characteristics. We obtained clinician feedback regarding the feasibility and acceptability of the tool. Results: The rate of patients screened for CVD risk in the 3 hospital networks was 57.1%, 71.5%, and 98.7%. For those with a positive screen, follow-up rates were 65.8%, 72.5%, and 55.9% in the 3 networks. The rates of screening and follow-up varied based on the clinic size and specialty. Clinician-identified barriers were busy clinics, competing priorities, and the type of clinical practice. Conclusions: This innovative population-based approach for universal CVD risk assessment during pregnancy is feasible and may be a helpful strategy to decrease CVD-related maternal morbidity and mortality.

Congenital cardiac anomalies: prenatal readings versus neonatal outcomes.

OBJECTIVE: The purpose of this study was to determine the variation between prenatal and postnatal diagnosis of congenital cardiac lesions diagnosed by both fetal center primary physicians and fetal pediatric cardiologists at a single tertiary referral center in the United States and evaluate why cases were misdiagnosed. METHODS: A retrospective review of all cardiac abnormalities identified prenatally by level II sonography at a tertiary referral fetal center between January 2006 and December 2008 was performed to include any patient with a fetal cardiac abnormality and with a documented autopsy or neonatal follow-up. Congenital heart disease diagnoses were classified as correct, incorrect, or incorrect but within the same spectrum of disease. Cases of correct diagnosis by primary physicians and pediatric cardiologists were compared. RESULTS: Sixty patients with fetal heart abnormalities were identified among 8894 patients who had level II sonography. The combined detection rate for fetal heart abnormalities for both primary physicians and pediatric cardiologists together was 81.7%. The detection rates of congenital heart disease were not statistically different between primary physicians and pediatric cardiologists: 77.9% (46 of 59) versus 85.0% (34 of 40; P = .3). The most common cardiac abnormalities misdiagnosed in our study population included pulmonic stenosis, ventricular septal defect, myxoma, truncus arteriosus, and coarctation of the aorta. CONCLUSIONS: Congenital heart disease is misdiagnosed in tertiary care centers by both pediatric cardiologists and fetal imaging specialists. We believe that this occurrence is related to multiple factors, including evolution of congenital heart disease, maternal body habitus, associated congenital anomalies, decreased amniotic fluid volume, gestational age at evaluation, imaging techniques, and, most importantly, the experience of the sonographer.

Chronic myelocytic leukemia in pregnancy: a case report describing successful treatment using multimodal therapy.

Leukemia during pregnancy is rare, posing a complex series of questions, including appropriate therapy and maternal counseling. Management of chronic myelocytic leukemia (CML) during pregnancy is limited. Our patient presented at 30 weeks' gestation with anemia, leukocytosis, and a non-productive cough. Polymerase chain reaction performed on a peripheral blood sample confirmed presence of the breakpoint cluster region-Abl1 chromosomal translocation and the diagnosis of CML. Therapy included acute leukocytapheresis, followed by α-interferon and imatinib mesylate. The patient responded to treatment and delivered a viable female infant at term weighing 2613 g. Continued imatinib mesylate chemotherapy post-delivery resulted in complete clinical remission. Successful antepartum management of newly diagnosed CML is possible utilizing leukocytapheresis, α-interferon and, more recently, imatinib mesylate. Definitive treatment should not be delayed due to pregnancy.

Use of multiplanar 3-dimensional ultrasonography for prenatal sex identification.

OBJECTIVE: Determination of fetal sex is an important part of detailed second-trimester ultrasonography. This task can be hindered by the fetal position, a low amniotic fluid volume, and advanced gestational age. Identification of fetal sex is further important in multiple gestations and prior histories of indeterminate-sex pregnancies. The goal of the study was to compare the effectiveness of 2-dimensional ultrasonography (2DUS) versus 3-dimensional ultrasonography (3DUS) at sex identification and to determine how genitalia measurements taken with 3DUS technology compare with measurements taken with 2DUS. METHODS: A total of 111 patients at or beyond 16 weeks' gestation were recruited. Assignments of fetal sex using 2DUS and 3DUS were compared by the test of proportions. The actual neonatal sex was obtained after delivery. Given such small number of misdiagnoses by either 2DUS or 3DUS, the accuracies of the two modalities were not found to be statistically distinguishable from one another (P = .5585). The penile length, scrotal width, and bilabial diameter according to gestational age were measured and compared with previously published 2DUS data by t tests. RESULTS: Sexes were assigned and interpreted in 65 cases. Ranges of genitalia measurements were plotted against gestational age and were found to be comparable with published data. There was a dramatic difference between the bilabial diameter and scrotal width with advancing gestational age that made sex determination much easier in the third trimester. CONCLUSIONS: Although 3DUS did not have better prediction of fetal sex when compared with 2DUS, it may be a useful tool in conjunction with traditional imaging techniques in assigning fetal sex.

Three-dimensional obstetric ultrasound.

Three-dimensional ultrasound has gained a significant popularity in obstetrical practice in recent years. The advantage of this modality in some cases is in question, however. This article provides a basic review of volume acquisition, mechanical positioning, and display modalities. Multiple uses of this technique in obstetrical care including first trimester applications and its utility in clarification of fetal anatomy such as brain, face, heart, and skeleton is discussed.

Proteomic analyses of Urine Exosomes reveal New Biomarkers of Diabetes in Pregnancy.

OBJECTIVE: To evaluate 24 hour urine exosome protein content changes among pregnant US subjects with diabetes and obesity during early pregnancy. METHODS: The exosome proteome content from 24 hour urine samples of pregnant subjects with gestational diabetes mellitus (GDM, N=8) and pre-gestational Type 2 diabetes (PGD, N = 10) were compared with control samples (CTRL, N = 10) obtained at week 20 of pregnancy. Differences in exosome protein load between groups was identified by liquid chromatography/mass spectrometry, analyzed by linear regression in negative binomial distribution, visualized in MetaboAnalyst (version 3.0), and validated by western immunoblotting. RESULTS: At the 20th week of pregnancy, we identified 646, 734 and 856 proteins in exosomes from 24 hour urine samples of patients from the CTRL, GDM and PGD groups, respectively. S100 calcium binding protein A9, damage associated molecular pattern (DAMP) signal, was found to be significantly increased in both GDM and PGD subjects. In GDM subjects the peptide counts for S100A9 protein independently correlated with maternal obesity and macrosomia of the newborn infants. Early to late pregnancy developmental changes in the GDM group were shown to utilize pathways and protein expression levels differently from those in PGD or CTRL groups. CONCLUSIONS: Urinary exosome proteomic analysis non-invasively provides insights into maternal changes during diabetic pregnancy. Exosome biomarkers early in pregnancy can be potentially used to better understand pathophysiologic mechanisms of diabetes at a cellular level, and to distinguish between gestational and pre-gestational diabetes at the pathway level. This information can aid intervention efforts to improve pregnancy outcomes in women with diabetes.