Obstetrical and neonatal outcomes in patients with surgically repaired heart disease.

BACKGROUND: Congenital and acquired heart disease complicate 1% to 4% of pregnancies in the United States. Beyond the risks of the underlying maternal congenital heart disease, cardiac surgery and its sequelae, such as surgical scarring resulting in higher rates of arrhythmias and implanted valves altering anticoagulation status, have potential implications that could affect gestation and delivery. OBJECTIVE: This study aimed to investigate whether history of maternal cardiac surgery is associated with adverse obstetrical or neonatal outcomes compared with patients without a history of cardiac disease or surgery, considered "healthy controls." STUDY DESIGN: This is a secondary analysis of retrospective cohort studies performed at a tertiary care facility in the United States comparing obstetrical outcomes in patients with a history of open cardiac surgery who delivered from January 2007 to December 2018 with healthy controls, who delivered from April 2020 to July 2020. There were 74 pregnancies in 61 patients with a history of open cardiac surgery that were compared with pregnancies in healthy controls. Of the 74 pregnancies, 65 were successfully matched based on gestational age to controls at a 1:3 (case-to-control) ratio. The remainder of cases were matched at a 1:2 or 1:1 ratio; therefore, a total of 219 control pregnancies were included in the analysis. Our primary outcome was the incidence of hypertensive disorders of pregnancy, as well as cesarean delivery, in patients with a history of open cardiac surgery compared with healthy controls. Our secondary outcome was the incidence of low-birthweight neonates in patients with a history of open cardiac surgery compared with healthy controls. RESULTS: Patients with a history of cardiac surgery were not more likely to have any hypertensive disorder diagnosed than healthy controls. Patients with a history of cardiac surgery were more likely to have an operative delivery (P<.0001) but equally likely to have a cesarean delivery (P=.528) compared with healthy controls. Birthweight was not statistically different of 2655±808 g in neonates born to patients with a history of cardiac surgery vs 2844±830 g born to healthy controls (P=.092). CONCLUSION: Patients with a history of cardiac surgery may not be at higher risk of hypertensive disorder diagnosis during pregnancy. Similarly, most patients with a history of cardiac surgery are also likely not at higher risk of cesarean delivery or low-birthweight neonates.

Evaluation of Early Screening for Diabetes Mellitus in Pregnancy with Hemoglobin A1c.

Early diabetes screening is recommended for high-risk pregnant women risk via a 1-hour glucose challenge test (1-hour GCT). Hemoglobin A1c (HbA1c) can be obtained with initial obstetric laboratories. We sought to examine the relationship between HbA1c and 1-hour GCT for early diabetes screening in pregnancy. This is a retrospective cohort study of 204 high-risk pregnant women who underwent early HbA1c and 1-hour GCT. Simple logistic regression analysis was performed to predict abnormal 1-hour GCT and diagnosis of diabetes using HbA1c. A total of 158 (77.5%), 44 (21.5%), and 2 (1%) women had HbA1c of less than 5.7, 5.7 to 6.4, and 6.5% or higher, respectively. Seven of 158 (4.4%) women with HbA1c less than 5.7% and 8 of 44 (18.2%) with HbA1c of 5.7 to 6.4% had a diagnosis of diabetes. A positive correlation between early HbA1c and 1-hour GCT was detected. Logistic regression showed HbA1c significantly predicted the risk of diabetes but was not a good predictor of abnormal 1-hour GCT. HbA1c of 5.5% or less had a 97% or higher negative predictive value for early diabetes in pregnancy. There is a positive correlation between HbA1c and 1-hour GCT for the early screening of diabetes in pregnancy. Women with early HbA1c ≤ 5.5% could forego further testing in early pregnancy.

Precision Medicine-A Demand Signal for Genomics Education.

Pressed by the accumulating knowledge in genomics and the proven success of the translation of cancer genomics to clinical practice in oncology, the Obama administration unveiled a $215 million commitment for the Precision Medicine Initiative (PMI) in 2016, a pioneering research effort to improve health and treat disease using a new model of patient-powered research. The objectives of the initiative include more effective treatments for cancer and other diseases, creation of a voluntary national research cohort, adherence to privacy protections for maintaining data sharing and use, modernization of the regulatory framework, and forging public-private partnerships to facilitate these objectives. Specifically, the DoD Military Health System joined other agencies to execute a comprehensive effort for PMI. Of the many challenges to consider that may contribute to the implementation of genomics-lack of familiarity and understanding, poor access to genomic medicine expertise, needs for extensive informatics and infrastructure to integrate genomic results, privacy and security, and policy development to address the unique requirements of military medical practice-we will focus on the need to establish education in genomics appropriate to the provider's responsibilities. Our hypothesis is that there is a growing urgency for the development of educational experiences, formal and informal, to enable clinicians to acquire competency in genomics commensurate with their level of practice. Several educational approaches, both in practice and in development, are presented to inform decision-makers and empower military providers to pursue courses of action that respond to this need.

Characterizing placental stiffness using ultrasound shear-wave elastography in healthy and preeclamptic pregnancies.

PURPOSE: To measure the stiffness of the placenta in healthy and preeclamptic patients in the second and third trimesters of pregnancy using ultrasound shear-wave elastography (SWE). We also aimed to evaluate the effect of age, gestational age, gravidity, parity and body mass index (BMI) on placental stiffness and a possible correlation of stiffness with perinatal outcomes. METHODS: In a case-control study, we recruited a total of 47 singleton pregnancies in the second and third trimesters of which 24 were healthy and 23 were diagnosed with preeclampsia. In vivo placental stiffness was measured once at the time of recruitment for each patient. Pregnancies with posterior placentas, multiple gestation, gestational hypertension, chronic hypertension, diabetes, autoimmune disease, fetal growth restriction and congenital anomalies were excluded. RESULTS: The mean placental stiffness was significantly higher in preeclamptic pregnancies compared to controls in the third trimester (difference of means = 16.8; 95% CI (9.0, 24.5); P < 0.001). There were no significant differences in placental stiffness between the two groups in the second trimester or between the severe preeclampsia and preeclampsia without severe features groups (difference of means = 9.86; 95% CI (-5.95, 25.7); P ≥ 0.05). Peripheral regions of the placenta were significantly stiffer than central regions in the preeclamptic group (difference of means = 10.67; 95% CI (0.07, 21.27); P < 0.05), which was not observed in the control group (difference of means = 0.55; 95% CI (- 5.25, 6.35); P > 0.05). We did not identify a correlation of placental stiffness with gestational age, maternal age, gravidity or parity. However, there was a statistically significant correlation with BMI (P < 0.05). In addition, pregnancies with higher placental stiffness during the 2nd and 3rd trimesters had significantly reduced birth weight (2890 ± 176 vs. 2420 ± 219 g) and earlier GA (37.8 ± 0.84 vs. 34.3 ± 0.98 weeks) at delivery (P < 0.05). CONCLUSION: Compared to healthy pregnancies, placentas of preeclamptic pregnancies are stiffer and more heterogeneous. Placental stiffness is not affected by gestational age or the severity of preeclampsia but there is a correlation with higher BMI and poor perinatal outcomes.

Neonatal and maternal outcomes of pregnancies with a fetal diagnosis of congenital heart disease using a standardized delivery room management protocol.

OBJECTIVE: We sought to determine if fetuses with prenatally diagnosed congenital heart disease (CHD) were more likely to undergo cesarean delivery in the setting of a non-reassuring fetal heart rate tracing (NRFHT) and to determine if those fetuses were more likely to have a fetal acidosis. STUDY DESIGN: A retrospective cohort study of neonates prenatally diagnosed with CHD from August 2010 to July 2016. The control group consisted of gestational age matched controls without CHD. RESULTS: Each group consisted of 143 patients. The most common reason for cesarean delivery was a NRFHT (control 31% vs CHD 35%, p = 0.67). Fetal acidosis was a rare outcome occurring in only five controls (3.5%) and 11 cases (7.7%) (p = 0.12). CONCLUSION: These findings demonstrate that with multidisciplinary care coordination, fetuses with a prenatal diagnosis of CHD have similar cesarean rates, labor and delivery management, and delivery room compromise as healthy fetuses.

Third trimester ultrasound for fetal macrosomia: optimal timing and institutional specific accuracy.

PURPOSE: To determine the performance of third trimester ultrasound in women with suspected fetal macrosomia. MATERIALS AND METHODS: We performed a retrospective cohort study of fetal ultrasounds from January 2004 to December 2014 with estimated fetal weight (EFW) between 4000 and 5000 g. We determined accuracy of birth weight prediction for ultrasound performed at less than and greater than 38 weeks, accounting for diabetic status and time between ultrasound and delivery. RESULTS: There were 405 ultrasounds evaluated. One hundred and twelve (27.7%) were performed at less than 38 weeks, 293 (72.3%) at greater than 38 weeks, and 91 (22.5%) were performed in diabetics. Sonographic identification of EFW over 4000 g at less than 38 weeks was associated with higher correlation between EFW and birth weight than ultrasound performed after 38 weeks (71.5 versus 259.4 g, p < .024). EFW to birth weight correlation was within 1.7% of birth weight for ultrasound performed less than 38 weeks and within 6.5% of birth weight for ultrasound performed at greater than 38 weeks. CONCLUSIONS: Identification of EFW with ultrasound performed less than 38 weeks has greater reliability of predicting fetal macrosomia at birth than measurements performed later in gestation. EFW to birth weight correlation was more accurate than previous reports.

Neonatal outcomes in fetuses with cardiac anomalies and the impact of delivery route.

BACKGROUND: Congenital fetal cardiac anomalies compromise the most common group of fetal structural anomalies. Several previous reports analyzed all types of fetal cardiac anomalies together without individualized neonatal morbidity outcomes based on cardiac defect. Mode of delivery in cases of fetal cardiac anomalies varies greatly as optimal mode of delivery in these complex cases is unknown. OBJECTIVE: We sought to determine rates of neonatal outcomes for fetal cardiac anomalies and examine the role of attempted route of delivery on neonatal morbidity. STUDY DESIGN: Gravidas with fetal cardiac anomalies and delivery >34 weeks, excluding stillbirths and aneuploidies (n = 2166 neonates, n = 2701 cardiac anomalies), were analyzed from the Consortium on Safe Labor, a retrospective cohort study of electronic medical records. Cardiac anomalies were determined using International Classification of Diseases, Ninth Revision codes and organized based on morphology. Neonates were assigned to each cardiac anomaly classification based on the most severe cardiac defect present. Neonatal outcomes were determined for each fetal cardiac anomaly. Composite neonatal morbidity (serious respiratory morbidity, sepsis, birth trauma, hypoxic ischemic encephalopathy, and neonatal death) was compared between attempted vaginal delivery and planned cesarean delivery for prenatal and postnatal diagnosis. We used multivariate logistic regression to calculate adjusted odds ratio for composite neonatal morbidity controlling for race, parity, body mass index, insurance, gestational age, maternal disease, single or multiple anomalies, and maternal drug use. RESULTS: Most cardiac anomalies were diagnosed postnatally except hypoplastic left heart syndrome, which had a higher prenatal than postnatal detection rate. Neonatal death occurred in 8.4% of 107 neonates with conotruncal defects. Serious respiratory morbidity occurred in 54.2% of 83 neonates with left ventricular outflow tract defects. Overall, 76.3% of pregnancies with fetal cardiac anomalies underwent attempted vaginal delivery. Among patients who underwent attempted vaginal delivery, 66.1% had a successful vaginal delivery. Women with a fetal cardiac anomaly diagnosed prenatally were more likely to have a planned cesarean delivery than women with a postnatal diagnosis (31.7 vs 22.8%; P < .001). Planned cesarean delivery compared to attempted vaginal delivery was not associated with decreased composite neonatal morbidity for all prenatally diagnosed (adjusted odds ratio, 1.67; 95% confidence interval, 0.85-3.30) or postnatally diagnosed (adjusted odds ratio, 0.99; 95% confidence interval, 0.77-1.27) cardiac anomalies. CONCLUSION: Most fetal cardiac anomalies were diagnosed postnatally and associated with increased rates of neonatal morbidity. Planned cesarean delivery for prenatally diagnosed cardiac anomalies was not associated with less neonatal morbidity.

Bioengineering Strategies to Treat Female Infertility.

Bioengineering strategies have demonstrated enormous potential to treat female infertility as a result of chemotherapy, uterine injuries, fallopian tube occlusion, massive intrauterine adhesions, congenital uterine malformations, and hysterectomy. These strategies can be classified into two broad categories as follows: (i) Transplantation of fresh or cryopreserved organs into the host and (ii) tissue engineering approaches that utilize a combination of cells, growth factors, and biomaterials that leverages the body's inherent ability to regenerate/repair reproductive organs. While whole organ transplant has demonstrated success, the source of the organ and the immunogenic effects of allografts remain challenging. Even though tissue engineering strategies can avoid these issues, their feasibilities of creating whole organ constructs are yet to be demonstrated. In this article we summarize the recent advancements in the applications of bioengineering to treat female infertility.

Glycemic control, compliance, and satisfaction for diabetic gravidas in centering group care.

PURPOSE: To determine if diabetic gravidas enrolled in Centering® group care have improved glycemic control compared to those attending standard prenatal care. To compare compliance and patient satisfaction between the groups. MATERIALS AND METHODS: We conducted a prospective cohort study of diabetics enrolled in centering group care from October 2013 to December 2015. Glycemic control, compliance and patient satisfaction (five-point Likert scale) were evaluated. Student's t-test, Chi-Square and mixed effects model were used to compare outcomes. RESULTS: We compared 20 patients in centering to 28 standard prenatal care controls. Mean fasting blood sugar was lower with centering group care (91.0 versus 105.5 mg/dL, p =0.017). There was no difference in change in fasting blood sugar over time between the two groups (p = 0.458). The percentage of time patients brought their blood glucose logs did not differ between the centering group and standard prenatal care (70.7 versus 73.9%, p = 0.973). Women in centering group care had better patient satisfaction scores for "ability to be seen by a physician" (5 versus 4, p = 0.041) and "time in waiting room" (5 versus 4, p =0.001). CONCLUSION: Fasting blood sugar was lower for patients in centering group care. Change in blood sugar over time did not differ between groups. Diabetic gravidas enrolled in centering group care report improved patient satisfaction.

A case of recurrent hyperreactio luteinalis in three spontaneous pregnancies.

Hyperreactio luteinalis is a rare condition in pregnancy characterized by enlarged ovaries with multiple theca luteal cysts, and recurrence of disease has seldom been documented in the literature. This is a case report of a woman who developed recurrent hyperreactio luteinalis with three spontaneous pregnancies. Endocrine evaluation was performed and revealed hyperandrogenism. Ultrasonography was used to assess the ovaries throughout each pregnancy. The ovarian cysts required drainage in the first pregnancy due to severe distention and shortness of breath. Cyst resolution occurred in the post-partum period following each pregnancy. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:502-505, 2016.

Catecholaminergic Ventricular Tachycardia, Pregnancy and Teenager: Are They Compatible?

Arrhythmias in pregnancy are becoming more common given more available and effective medical, ablation and device treatment options. Several changes associated with pregnancy, increased blood volume, cardiac output, and heart rate secondary to an increased sympathetic state, facilitate more frequent occurrences of arrhythmias throughout the pregnancy and during labor and delivery. We present a case of successful pregnancy in a teenage female with a previous diagnosis of CPVT, followed by a review of the literature.

Use of cell-free DNA in the investigation of intrauterine fetal demise and miscarriage.

OBJECTIVE: To estimate whether cell-free DNA is present in nonviable pregnancies and thus can be used in diagnostic evaluation in this setting. METHODS: We conducted a prospective cohort study of 50 participants at MedStar Washington Hospital Center, Washington, DC, between June 2013 and January 2014. Included were women with pregnancies complicated by missed abortion or fetal demise. All gestational ages were considered for study participation. Participants with fetal demise were offered the standard workup for fetal death per the American College of Obstetricians and Gynecologists. Maternal blood samples were processed to determine the presence of cell-free DNA, the corresponding fetal fractions, and genetic abnormalities. RESULTS: Fifty samples from nonviable pregnancies were analyzed. The average clinical gestational age was 16.9 weeks (standard deviation 9.2). The mean maternal body mass index was 30.3 (standard deviation 9.1). Seventy-six percent (38/50) of samples yielded cell-free DNA results, that is, had fetal fractions within the detectable range of 3.7-65%. Among the 38, 76% (29) were classified as euploid, 21% (8) as trisomies, and 3% (1) as microdeletion. A cell-free DNA result was obtained more frequently at ultrasonographic gestational ages of 8 weeks or greater compared with less than 8 weeks (87.9% [n=29/33, 95% confidence interval (CI) 72.7-95.2; and 52.9%, n=9/17, 95% CI 31.0-73.8] of the time, respectively, P=.012). Time from demise was not associated with obtaining a result. CONCLUSION: Among nonviable pregnancies, cell-free DNA is present in the maternal plasma with fetal fractions greater than 3.7% in more than three fourths of cases after an ultrasonographic gestational age of 8 weeks. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01916928. LEVEL OF EVIDENCE: III.

Understanding the Limitations of Circulating Cell Free Fetal DNA: An Example of Two Unique Cases.

Circulating cell free fetal DNA (cffDNA) is an effective screening modality for fetal aneuploidy. We report two cases of false positive results. The first case involves a female, with self-reported Down syndrome. CffDNA returned positive for trisomy 18 leading to a maternal diagnosis of mosaicism chromosome 18 with normal fetal karyotype. The second case involves a patient with an anomalous fetal ultrasound and cffDNA positive for trisomy 13. Amniocentesis demonstrated a chromosome 8p duplication/deletion. False positive cffDNA may arise in clinical scenarios where diagnostic testing is clearly indicated. Practitioners should recognize the limitations of cffDNA.

Multidisciplinary management of pregnancy in complex congenital heart disease: a model for coordination of care.

With advancements in medical care, many women with complex congenital heart disease (CHD) are now living into adulthood and childbearing years. The strains of pregnancy and parturition can be dangerous in such patients, and careful interdisciplinary plans must be made to optimize maternal and fetal health through this process. Several large studies have been published regarding risk prediction and medical management of pregnancy in complex CHD, though few case studies detailing clinical care plans have been published. The objective of this report is to describe the process of developing a detailed pregnancy and delivery care plan for three women with complex CHD, including perspectives from the multidisciplinary specialists involved in the process. This article demonstrates that collaboration between specialists in the fields of cardiology, anesthesiology, high-risk obstetrics, maternal fetal medicine, and neonatology results in clinically successful individualized treatment plans for the management of pregnancy in complex CHD. Multidisciplinary collaboration is a crucial element in the management of pregnancy in complex CHD. We provide a template used in three cases which can serve as a model for the design of future care plans.

Intrauterine fetal resuscitation following complications of closed fetal surgery.

BACKGROUND: With advances in prenatal diagnosis and surgical technique more fetal interventions are being performed. There are limited data about the etiology, incidence, management, or long-term outcomes of complications associated with these procedures. CASE: A gravida had a fetus diagnosed with posterior urethral valve syndrome. During placement of a peritoneal-amniotic shunt, profound fetal bradycardia was noted. Using closed fetal surgical techniques successful resuscitation was accomplished. CONCLUSION: Closed fetal surgical interventions carry the potential for significant complications of varying etiologies. Resuscitation can be accomplished. Preparation for potential complications may improve outcome.

Implementing prenatal screening for cystic fibrosis in routine obstetric practice.

OBJECTIVE: The purpose of this study was to assess the outcome of the type of prescreening counseling on choices for prenatal cystic fibrosis screening. STUDY DESIGN: From October 2001 to November 2002, regardless of ethnicity, all prenatal patients (n = 855) at the Air Force Medical Genetics Center, Biloxi, Miss, received education on prenatal screening for cystic fibrosis by group genetic counseling either by a presentation by a genetics professional (430 patients) or by a similar audiovisual presentation only (425 patients). A combination pretest/posttest document was used to evaluate learning and served as the consent. Partner testing was recommended for mutation-positive patients. RESULTS: Fifty-eight percent patients requested screening, of whom 68% were white. Regardless of the type of counseling, patients showed an improvement in knowledge based on pre- and posttest scores. There was no significant difference in choices to undergo screening on the basis of counseling method. Fifteen mutation carriers were identified. Only 6 partners of mutation-positive patients were available and consented to be tested. To date, no infants have been born with cystic fibrosis. CONCLUSION: Audio-visual counseling is an effective means to educate patients about genetic screening and does not require a trained genetics professional to administer. Partner testing in mobile populations may prove problematic.

Outcome of five years of accelerated surveillance in patients at high risk for inherited breast/ovarian cancer: report of a phase II trial.

OBJECTIVE: To assess the outcome of accelerated patient surveillance in patients at high risk for inherited breast or ovarian cancer. METHODS: Using stringent inclusion criteria, 57 high-risk patients (7 positive for BRCA1/2 mutations, 39 mutation negative, and 11 unaffected) were recruited from a genetic testing protocol for inherited breast/ovarian cancer and were followed for 5 years (192.5 total patient years). Patients received twice annual physical examinations, imaging studies, measurement of CA125 and CA15-3, psychometric measurements, and unstructured interviews by a psychologist. RESULTS: When mutation (+) and mutation (-) patients were compared, there were no significant differences in the development of disease metastasis, recurrence, or new cancers. No unaffected patients developed cancer. Management of osteoporosis, sexual function, and psychological distress were major concerns. CONCLUSIONS: Our data suggest that all patients with remarkable family history, regardless of their mutation status, may be at substantially increased risk for disease progression and development of new cancers, which is often not ovarian or recurrent breast cancer. Although prophylactic surgery is important in decreasing cancer recurrence in mutation carriers, increased surveillance with physical examinations and psychological support is also valuable and acceptable to such high-risk patients.

Guidelines for evaluation of patients at risk for inherited breast and ovarian cancer: recommendations of the Department of Defense Familial Breast/Ovarian Cancer Research Project.

Patients at high risk for inherited breast and/or ovarian cancer are frequently encountered in all medical specialties. Department of Defense, Health Affairs funding as part of the Breast Cancer Education and Awareness Program was used to develop a comprehensive program for the identification, counseling, genetic testing, and long-term follow-up of such high-risk patients. This article reports the recommendations for high-risk patient management based on 4 years of evaluation and care, including discussions of the approach to counseling, indications for genetic testing, post-testing counseling, patient surveillance with examination, imagining, and laboratory testing, and suggested options for surgical and chemoprophylaxis as well as lifestyle modifications.

Diagnostic criteria for testing for BRCA1 and BRCA2: the experience of the Department of Defense Familial Breast/Ovarian Cancer Research Project.

The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.