Prenatal Genetic Screening in Twin Pregnancy.

Twin pregnancy presents unique considerations for aneuploidy screening. Pre-test counseling regarding benefits, alternatives, and options for aneuploidy screening should be provided to all patients carrying twin pregnancy. This article aims to review the options for aneuploidy screening in twin pregnancy including the potential benefits and limitations.

First Trimester Ultrasound and Aneuploidy Screening in Twins.

All patients with twin pregnancy should have first trimester ultrasound and be offered screening for chromosomal aneuploidy as well as diagnostic testing. Screening for aneuploidy in twins presents unique challenges compared with singletons. Cell-free DNA screening should be considered first-line; however, this option may not be available or may have limitations in certain clinical scenarios, such as vanishing twins. If cell-free DNA screening is not available, maternal serum marker screening in conjunction with nuchal translucency assessment should be offered. Patients with positive aneuploidy screening tests or fetal structural abnormalities should be offered diagnostic testing.

Standard-Dose Azithromycin in Class III Obese Patients Undergoing Unscheduled Cesarean Delivery.

OBJECTIVE: Perioperative antibiotic prophylaxis reduces cesarean wound complications. This study investigates whether integration of standard-dose (500 mg) azithromycin prophylaxis reduced wound complications in patients with class III obesity (body mass index [BMI] ≥ 40 kg/m2) undergoing unscheduled cesarean delivery. STUDY DESIGN: Retrospective cohort study of patients with class III obesity undergoing unscheduled cesarean delivery in single hospital system from January 1, 2017, to January 1, 2020. A standard dose (500 mg) of azithromycin was integrated into system order sets in 2018. Medical history and postoperative wound outcomes were compared in pre- and postintegration cohorts. Wound complication was defined as composite of wound seroma, hematoma, superficial or deep infection. RESULTS: A total of 1,273 patients met inclusion criteria, 303 patients in the preorder set group, and 970 patients in the postorder set group. Demographics were similar between the pre- and postintegration cohorts, including BMI (median: 44.4 kg/m2, p = 0.84) and weight at delivery (mean: 121.2 ± 17.8 kg, p = 0.57). Patients in the postintegration cohort had lower rates of composite postpartum wound complication (7.9 vs. 13.9%, p = 0.002), superficial infection or deep infection/abscess (6.7 vs. 10.2%, p = 0.042), and postpartum readmission or unscheduled visits (18.7 vs. 24.4%, p < 0.029). Rates of chorioamnionitis and endometritis were similar between the pre- and postintegration groups (8.6 vs. 6.9%, p = 0.33, and 1.7 vs. 1.9%, p = 0.81, respectively). Patients in the postintegration cohort had lower risk of postoperative composite wound complication (unadjusted odds ratio [OR]: 0.54, confidence interval [CI]: 0.36-0.80, p = 0.002) and lower rates of wound infection (unadjusted OR: 0.63, 95% CI: 0.40-0.99, p = 0.044). When comparing patients who received azithromycin at delivery and patients who did not, standard-dose azithromycin reduced risk of postoperative wound complication (unadjusted OR: 0.67, 95% CI: 0.46-0.99, p = 0.043). CONCLUSION: A standard dose of azithromycin provides adequate perioperative prophylaxis in class III obese patients, decreasing rates of postcesarean wound complications and unscheduled postpartum outpatient visits. KEY POINTS: · Class III obese patients undergoing unscheduled cesarean have high rates of wound complications.. · Standard-dose azithromycin reduces risk of postcesarean wound infection in class III obese patients.. · Standard-dose azithromycin reduces readmission, unscheduled visits in class III obese patients..

Screening Echocardiogram in High-Risk Women with Class III Obesity to Predict the Risk of Preeclampsia.

OBJECTIVE: Women with obesity and other comorbidities such as hypertension and diabetes are at an increased risk of preeclampsia and perinatal morbidity. This study evaluates whether screening echocardiogram can identify women with obesity at a higher risk of preeclampsia. METHODS: We conducted a retrospective cohort study of women with class III obesity (body mass index [BMI] ≥40 kg/m2) and one or more medical comorbidities associated with an increased risk of preeclampsia (such as diabetes, hypertension, and rheumatologic disease) undergoing screening echocardiogram. Abnormal findings were defined as the presence of one or more of the following: diastolic dysfunction, ejection fraction of ≤45%, or cardiac chamber enlargement or hypertrophy. Multivariable logistic regression was used to estimate the odds ratio (OR) of gestational hypertension/mild preeclampsia, severe preeclampsia, and any preterm delivery <37 weeks associated with abnormal echocardiographic findings when controlling for potential confounders. RESULTS: Of 267 eligible women, 174 (64%) underwent screening echocardiograms. Sixty-nine women (40%) had abnormal echocardiograms. Maternal clinical characteristics were similar between women with normal echocardiographic findings and women with abnormal findings. Women with abnormal echocardiograms were more likely to have chronic hypertension (78 vs. 62%, p = 0.04) and a history of preeclampsia (27 vs. 10%, p = 0.02). After controlling for confounders, women with abnormal echocardiogram were at an increased risk of hypertensive disorders of pregnancy, OR 6.80 (95% confidence interval [CI] 3.32-13.93, p = 0.01), and in particular severe preeclampsia, OR 8.77 (95% CI 3.90-19.74, p = 0.01). CONCLUSION: Among pregnant women with class III obesity and medical comorbidities, screening echocardiogram may help identify a subset of women at the highest risk of developing preeclampsia. KEY POINTS: · Women with obesity and comorbid conditions are at a high risk of abnormal echocardiogram.. · Women with obesity, medical comorbid conditions, and abnormal echo are at a high risk of preeclampsia.. · Screening echocardiogram can help identify obese women at the highest risk of severe preeclampsia..

Obesity and no call results: optimal timing of cell-free DNA testing and redraw.

BACKGROUND: Fetal fraction of cell-free DNA decreases with increasing maternal weight. Consequently, cell-free DNA screening for fetal aneuploidy has higher screen failures or "no call" rates in women with obesity owing to a low fetal fraction. The optimal timing of testing based on maternal weight is unknown. OBJECTIVE: This study aimed to identify the optimal timing of initial cell-free DNA testing based on maternal weight and to identify the optimal timing of repeat cell-free DNA testing in cases with an initial screen failure. STUDY DESIGN: This was a retrospective cohort study of women undergoing cell-free DNA for fetal aneuploidy screening between 9 and 18 weeks through a single laboratory over 1 year from 2018 to 2019. Fetal fraction change per week was calculated, and generalized linear models were used to calculate relative risk and 95% confidence interval of a no call result at given maternal weights and gestational ages. RESULTS: The vast majority of samples (99.22%) received a test result. The risk of a no call result owing to a low fetal fraction was higher with increasing maternal weight. At 9 to 12 weeks, the rate of a no call result owing to a low fetal fraction in women who weighed <150 lb was 0.14% compared with 17.39% in women weighing >400 lb. Fetal fraction increased with increasing gestational age, although the incremental increase in fetal fraction over time is inversely proportional to maternal weight. At 13 to 18 weeks' gestation, 6.45% of women weighing >400 lb received a no call result owing to a low fetal fraction. In women in the highest weight category, >400 lb, fetal fraction increased 0.5% with each week of gestation. CONCLUSION: Although the risk of a no call result increases with maternal weight, cell-free DNA screening should be offered to all women at 9 to 12 weeks' gestation, allowing the option to have chorionic villus sampling after a positive test result. Pretest counseling for women with obesity should include the increased chance for a test failure. Most women weighing less than 400 lb will receive a test result and more than 80% of women with a weight of >400 lb will receive a test result at 9 to 12 weeks' gestation. Data regarding the expected increase in cell-free DNA fetal fraction per week may help guide the timing of a redraw to optimize test success.

Screening for Aneuploidy in the Patient With Diabesity: Pearls and Pitfalls.

The American College of Obstetrics & Gynecology (ACOG) recommends offering aneuploidy screening to all pregnant women. Obesity and diabetes are not associated with an increased risk of aneuploidy; however, they can complicate and compromise testing options. As the prevalence of obesity and diabetes, or "diabesity" increases, counseling women regarding potential limitations in testing performance of aneuploidy screening is of paramount importance. This chapter reviews options for aneuploidy screening for women with diabesity including sonography/nuchal translucency, serum analyte screening, and cell-free DNA. Potential challenges associated with diagnostic testing with amniocentesis and chorionic villus sampling in women with obesity are also discussed.

Labor and Delivery Outcomes with the Sequential Use of Misoprostol Followed by Cervical Foley Catheter.

OBJECTIVE: Studies demonstrate shorter time to delivery with concurrent use of misoprostol and cervical Foley catheter. However, concurrent placement may not be feasible. If misoprostol is used to start an induction, little is known regarding the benefit of sequentially using Foley catheter. We examine obstetrical outcomes in women with Foley catheter placed after misoprostol compared with those only requiring misoprostol. STUDY DESIGN: Retrospective cohort study of singleton pregnancies, intact membranes, and an unfavorable cervix (Bishop score of ≤6 and dilation ≤2 cm) undergoing term induction May 2013 to June 2015. We compared obstetrical outcomes between women receiving misoprostol alone versus those that had a Foley catheter placed after misoprostol. Outcomes are mode of delivery, time to delivery, chorioamnionitis, admission to neonatal intensive care unit, and maternal morbidity. Chi-square and Fisher's exact tests were used for categorical variables, Mann-Whitney U-tests compared continuous variables. RESULTS: Among 364 women, 281 began induction with misoprostol alone. A total of 135 (48%) subsequently had a Foley catheter placed. Characteristics were similar between the groups, although nulliparity and cervical dilation <1 cm at start of induction were more likely to have subsequent Foley catheter. Women with Foley catheter placement after misoprostol had a longer median time to delivery (15 vs. 11 hours, p < 0.001), twofold higher rate of cesarean (42 vs. 26%, odds ratio: 2.1, 95% confidence interval: 1.26-3.44, p = 0.004), and increased risk of neonatal intensive care unit (NICU) admission (21 vs. 11%, p = 0.024). There was a nonsignificant increased risk of chorioamnionitis (12 vs. 7%, p = 0.1) and maternal morbidity (15 vs. 8%, p = 0.08) in the misoprostol followed by Foley catheter group. CONCLUSION: In women receiving misoprostol for induction, nulliparas and those with dilation <1 cm are more likely to have subsequent Foley catheter placement. Sequential use of cervical Foley catheter after misoprostol is associated with longer labor, higher cesarean rate, and increased NICU admission. Requirement of Foley catheter after misoprostol confers higher risk and may guide counseling. KEY POINTS: · Little is known regarding efficacy of misoprostol followed by cervical Foley catheter.. · Nulliparas and dilation <1 cm increases need for Foley after misoprostol.. · Complications were more common in women requiring Foley after misoprostol..

Cell-free DNA for Down syndrome screening in obese women: Is it a cost-effective strategy?

OBJECTIVE: Determine cost differences between cell-free DNA (cfDNA) and serum integrated screening (INT) in obese women given the limitations of aneuploidy screening in this population. METHODS: Using a decision-analytic model, we estimated the cost-effectiveness of trisomy 21 screening in class III obese women using cfDNA compared with INT. Primary outcomes of the model were cost, number of unnecessary invasive tests, procedure-related fetal losses, and missed cases of trisomy 21. RESULTS: In base case, the mean cost of cfDNA was $498 greater than INT ($1399 vs $901). cfDNA resulted in lower probabilities of unnecessary invasive testing (2.9% vs 3.5%), procedure-related loss (0.015% vs 0.019%), and missed cases of T21 (0.00013% vs 0.02%). cfDNA cost $87 485 per unnecessary invasive test avoided, $11 million per procedure-related fetal loss avoided, and $2.2 million per missed case of T21 avoided. In sensitivity analysis, when the probability of insufficient fetal fraction is assumed to be >25%, cfDNA is both costlier than INT and results in more unnecessary invasive testing (a dominated strategy). CONCLUSION: When the probability of insufficient fetal fraction more than 25% (a maternal weight of ≥300 lbs), cfDNA is costlier and results in more unnecessary invasive testing than INT.

Association between cell-free DNA fetal fraction and gestational diabetes.

OBJECTIVE: To determine the association between cell-free DNA (cfDNA) fetal fraction and gestational diabetes (GDM) in a cohort of women presenting for cfDNA screening for fetal aneuploidy. METHODS: A retrospective cohort study of women with singleton pregnancies who had cfDNA screening at a single institution at 10 to 20 weeks gestation between October 2011 and October 2017. Fetal fractions were adjusted for gestational age (GA) using multiples of the median (MoM). Multivariable logistic regression was used to estimate the odds ratio (OR) of GDM controlling for potential confounders. RESULTS: Two thousand six hundred twenty-three pregnancies met criteria. Women with GDM had a lower fetal fraction (0.93 MoM vs. 1.05 MoM, P = .002). However, the association between fetal fraction and GDM was not significant after adjusting for body mass index (BMI) [OR 0.84, 95% confidence interval (CI) 0.52-1.36; P = .48]. Since insulin resistance increases at later GAs, separate analysis on women with GA 14 to 20 weeks was performed. Again, the association between fetal fraction and GDM was not significant after adjusting for BMI, (OR 0.81, 95% CI 0.31-2.12; P = .67). CONCLUSION: Low or high fetal fraction of cfDNA was not associated with GDM. Although fetal fraction was lower among women diagnosed with GDM, this relationship was no longer statistically significant once maternal BMI was taken into account.

Are prediction models for vaginal birth after cesarean accurate?

BACKGROUND: The use of trial of labor after cesarean delivery calculators in the prediction of successful vaginal birth after cesarean delivery gives physicians an evidence-based tool to assist with patient counseling and risk stratification. Before deployment of prediction models for routine care at an institutional level, it is recommended to test their performance initially in the institution's target population. This allows the institution to understand not only the overall accuracy of the model for the intended population but also to comprehend where the accuracy of the model is most limited when predicting across the range of predictions (calibration). OBJECTIVE: The purpose of this study was to compare 3 models that predict successful vaginal birth after cesarean delivery with the use of a single tertiary referral cohort before continuous model deployment in the electronic medical record. STUDY DESIGN: All cesarean births for failed trial of labor after cesarean delivery and successful vaginal birth after cesarean delivery at an academic health system between May 2013 and March 2016 were reviewed. Women with a history of 1 previous cesarean birth who underwent a trial of labor with a term (≥37 weeks gestation), cephalic, and singleton gestation were included. Women with antepartum intrauterine fetal death or fetal anomalies were excluded. The probability of successful vaginal birth after cesarean delivery was calculated with the use of 3 prediction models: Grobman 2007, Grobman 2009, and Metz 2013 and compared with actual vaginal birth after cesarean delivery success. Each model's performance was measured with the use of concordance indices, Brier scores, and calibration plots. Decision curve analysis identified the range of threshold probabilities for which the best prediction model would be of clinical value. RESULTS: Four hundred four women met the eligibility criteria. The observed rate of successful vaginal birth after cesarean delivery was 75% (305/404). Concordance indices were 0.717 (95% confidence interval, 0.659-0.778), 0.703 (95% confidence interval, 0.647-0.758), and 0.727 (95% confidence interval, 0.669-0.779), respectively. Brier scores were 0.172, 0.205, and 0.179, respectively. Calibration demonstrated that Grobman 2007 and Metz vaginal birth after cesarean delivery models were most accurate when predicted probabilities were >60% and were beneficial for counseling women who did not desire to have vaginal birth after cesarean delivery but had a predicted success rates of 60-90%. The models underpredicted actual probabilities when predicting success at <60%. The Grobman 2007 and Metz vaginal birth after cesarean delivery models provided greatest net benefit between threshold probabilities of 60-90% but did not provide a net benefit with lower predicted probabilities of success compared with a strategy of recommending vaginal birth after cesarean delivery for all women . CONCLUSION: When 3 commonly used vaginal birth after cesarean delivery prediction models are compared in the same population, there are differences in performance that may affect an institution's choice of which model to use.

Induction of Labor versus Scheduled Cesarean in Morbidly Obese Women: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess the costs, complication rates, and harm-benefit tradeoffs of induction of labor (IOL) compared to scheduled cesarean delivery (CD) in women with class III obesity. STUDY DESIGN: We conducted a cost analysis of IOL versus scheduled CD in nulliparous morbidly obese women. Primary outcomes were surgical site infection (SSI), chorioamnionitis, venous thromboembolism, blood transfusion, and readmission. Model outcomes were mean cost of each strategy, cost per complication avoided, and complication tradeoffs. We assessed the costs, complication rates, and harm-benefit tradeoffs of IOL compared with scheduled CD in women with class III obesity. RESULTS: A total of 110 patients underwent scheduled CD and 114 underwent IOL, of whom 61 (54%) delivered via cesarean. The group delivering vaginally experienced fewer complications. SSI occurred in 0% in the vaginal delivery group, 13% following scheduled cesarean, and 16% following induction then cesarean. In the decision model, the mean cost of induction was $13,349 compared with $14,575 for scheduled CD. Scheduled CD costs $9,699 per case of chorioamnionitis avoided, resulted in 18 cases of chorioamnionitis avoided per additional SSI and 3 cases of chorioamnionitis avoided per additional hospital readmission. In sensitivity analysis, IOL is cost saving compared with scheduled CD unless the cesarean rate following induction exceeds 70%. CONCLUSION: In morbidly obese women, induction of labor remains cost-saving until the rate of cesarean following induction exceeds 70%.

Perioperative Antibiotic Choice in Labored versus Unlabored Cesareans and Risk of Postcesarean Infectious Morbidity.

OBJECTIVE: This study aims to estimate postcesarean infectious morbidity in women receiving perioperative ß-lactam versus non-ß-lactam antibiotics. METHODS: We conducted a retrospective cohort analysis of the Maternal-Fetal Medicine Unit Cesarean Registry. The exposure was ß-lactam perioperative antibiotics versus non-ß-lactam regimens at cesarean delivery (CD). We stratified by labored versus unlabored CD. The primary composite outcome included wound infection, seroma, hematoma, endometritis, readmission due to wound complication, or debridement. Multivariable logistic regression estimated odds of wound complication by antibiotic regimen after adjusting for relevant confounders. RESULTS: Our analysis included 43,735 women who delivered via CD, 48% following labor. In both groups, 95% of women received ß-lactam antibiotics. In the labored CD group (n = 20,860), there was no significant difference in primary outcome by ß-lactam versus non-ß-lactam antibiotics (10.5 vs. 9.9%, p = 0.53). In the unlabored CD group (n = 22,875), women receiving non-ß-lactam antibiotics were more likely to experience a wound complication compared with those in the ß-lactam group (6.2 vs. 4.7%, p = 0.02, adjusted odds ratio: 1.39, 95% confidence interval: 1.08-1.80) after adjustment for clinical confounders. CONCLUSION: In unlabored CD, non-ß-lactam antibiotics have a higher risk of wound complications compared with ß-lactam regimens. Further study to optimize antibiotic prophylaxis for ß-lactam allergic women undergoing unlabored CD is warranted.

The Evolving Landscape of Genetic Carrier Screening: Clinical Considerations and Challenges.

Importance: Genetic carrier screening is performed to identify carriers of rare genetic diseases. Identification of carriers allows patients to make informed reproductive health choices and can decrease the incidence of genetic disorders with serious medical implications. Objective: This review aims to provide an overview of the history of prenatal genetic screening and the various forms of carrier screening, a synopsis of recent changes in society recommendations and current practice guidelines, and discussion of clinical challenges associated with carrier screening. Evidence Acquisition: Published practice guidelines from relevant professional societies were reviewed and synthesized. PubMed search was performed for relevant history and clinical considerations of carrier screening. Results: Information and evidence summarized in this review include professional society practice guidelines, review articles, and peer-reviewed research articles. Conclusions and Relevance: Current practice guidelines differ between stakeholder professional organizations. Expanded carrier screening offers increased identification of rare disease carriers allowing for more informed reproductive choices. However, there are several barriers to the implementation of expanded carrier screening for all patients.

Anaphylaxis in Pregnancy.

Anaphylaxis in pregnancy is a rare event, but has important implications for the pregnant patient and fetus. The epidemiology, pathophysiology, diagnosis, and treatment all carry important considerations unique to the pregnant patient. Common culprits of anaphylaxis are primarily medications, particularly antibiotics and anesthetic agents. Diagnosis can be difficult given the relative lack of cutaneous symptoms, and normal physiologic changes in pregnancy such as low blood pressure and tachycardia. Apart from patient positioning, treatment is similar to that of the general population, with a focus on prompt epinephrine administration.

Real-World Utilization of an Intrauterine, Vacuum-Induced, Hemorrhage-Control Device.

OBJECTIVE: To assess the real-world effectiveness and safety of a U.S. Food and Drug Administration (FDA)-cleared intrauterine vacuum-induced-hemorrhage control device for postpartum hemorrhage (PPH) management. METHODS: Sixteen centers in the United States participated in this observational, postmarket registry medical record review (October 2020 through March 2022). The primary effectiveness outcome was treatment success , defined as bleeding control after insertion with no treatment escalation or bleeding recurrence. Additional outcomes included blood loss, time to device insertion, indwelling time, bleeding recurrence, and time to bleeding control. Treatment success and severe maternal morbidity measures (transfusion of 4 or more units of red blood cell, intensive care unit admission, and hysterectomy) were evaluated by blood loss before insertion. To assess safety, serious adverse events (SAEs) and adverse device effects were collected. All outcomes were summarized by mode of delivery; treatment success was summarized by bleeding cause (all causes, any atony, isolated atony, nonatony). RESULTS: In total, 800 individuals (530 vaginal births, 270 cesarean births) were treated with the device; 94.3% had uterine atony (alone or in combination with other causes). Median total blood loss at device insertion was 1,050 mL in vaginal births and 1,600 mL in cesarean births. Across all bleeding causes, the treatment success rate was 92.5% for vaginal births and was 83.7% for cesarean births (95.8% [n=307] and 88.2% [n=220], respectively, in isolated atony). Median indwelling time was 3.1 hours and 4.6 hours, respectively. In vaginal births, 14 SAEs were reported among 13 individuals (2.5%). In cesarean births, 22 SAEs were reported among 21 individuals (7.8%). Three (0.4%) SAEs were deemed possibly related to the device or procedure. No uterine perforations or deaths were reported. CONCLUSION: For both vaginal and cesarean births in real-world settings, rapid and effective bleeding control was achieved with an FDA-cleared intrauterine vacuum-induced hemorrhage-control device. The safety profile was consistent with that observed in the registrational trial (NCT02883673), and SAEs or adverse device effects were of the nature and severity expected in the setting of PPH. This device is an important new tool for managing a life-threatening condition, and timely utilization may help to improve obstetric hemorrhage outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04995887.

Screening for aneuploidy in twins.

All pregnant women should be offered screening for aneuploidy. Twin pregnancies present unique challenges in aneuploidy screening. This review describes available aneuploidy screening options and their benefits and limitations in twin pregnancy, along with describing special circumstances, such as vanishing twins and diagnostic testing in twin pregnancy. No method of aneuploidy screening is as accurate in twin pregnancies as singleton pregnancies. Cell-free DNA screening should be considered a first-line approach; however, this option may not be available or may have limitations in certain clinical scenarios, such as vanishing twins. If cell-free DNA screening is not available, nuchal translucency and/or maternal serum marker screening can be offered.

Guidelines for Cystic Fibrosis Carrier Screening in the Prenatal/Preconception Period.

Importance: Cystic fibrosis (CF) is one of the most common autosomal recessive disorders. Carrier screening for CF should be offered to all women considering becoming pregnant or who are pregnant. Understanding the available screening tests, their limitations, and the benefits of screening is of paramount importance to the obstetrician-gynecologist. Objectives: The objective is to review the current guidelines for CF carrier screening including the options for carrier screening, the potential complexities associated with carrier screening for CF, and indications for referral to certified genetic counselors or maternal-fetal medicine specialists. Evidence Acquisition: A MEDLINE search of "cystic fibrosis," "cystic fibrosis carrier screening pregnancy," and "inheritance of cystic fibrosis" in the review was performed. Results: The evidence cited in this review includes 2 medical society committee opinions and 15 additional peer-reviewed journal articles that were original research or expert opinion summaries. Conclusions and Relevance: The American College of Obstetricians and Gynecologists recommends that obstetricians offer CF carrier screening to all pregnant women or women considering becoming pregnant. Based on recent guidelines from ACMG, additional expanded carrier screening can be recommended to patients in the future, with additional CF variants and other autosomal or X-linked recessive conditions. It is important for the prenatal care provider to understand the guidelines for carrier screening as well as the potential complexities associated with carrier screening due to the multiple pathogenic variants in the CFTR gene that may be associated with varying phenotypes. With the options for CF carrier screening, screening performance in different populations, a basic understanding of the disease and interpretation of carrier screening results is of paramount importance to the prenatal care provider.

Spinal Muscular Atrophy: Inheritance, Screening, and Counseling for the Obstetric Provider.

IMPORTANCE: Spinal muscular atrophy (SMA) confers significant risk of neonatal and infant morbidity and mortality. Screening women during or before pregnancy for carrier status of SMA presents an opportunity to identify pregnancies at risk for this potentially devastating condition. OBJECTIVE: The objective of this review is to describe the different forms of SMA and their inheritance. In addition, this review guides obstetric providers in interpreting results of carrier screening. EVIDENCE ACQUISITION: A MEDLINE search of "prenatal genetic testing," "spinal muscular atrophy," and "inheritance of spinal muscular atrophy" in the review was performed. RESULTS: The evidence cited in this review includes 4 medical society committee opinions and 14 additional peer-reviewed journal articles that were original research or expert opinion summaries. CONCLUSIONS AND RELEVANCE: Spinal muscular atrophy is a severe, heterogeneous neurodegenerative disorder. The American College of Obstetricians and Gynecologists recommends that obstetricians offer carrier screening for SMA to all pregnant women. Given the different types and inheritance of SMA, understanding of the disease and interpreting carrier screening results is of paramount importance to the prenatal care provider.

Exome Sequencing and Its Emerging Role in Prenatal Genetic Diagnosis.

IMPORTANCE: Prenatal genetic diagnosis can guide pregnancy management and decision making. Genetic diagnosis has advanced rapidly, and chromosomal microarray has become widely used, in addition to conventional karyotype. Exome sequencing may provide an even higher detection rate of genetic anomalies and may be more commonly applied in the future. OBJECTIVES: The objectives of this manuscript are to review current practices in prenatal genetic diagnosis, define exome sequencing, identify scenarios in which exome sequencing may be indicated, identify potential concerns regarding exome sequencing, and review the importance for the general obstetrician-gynecologist to understand exome sequencing technology and its uses. EVIDENCE ACQUISITION: A MEDLINE search of "prenatal genetic testing," "chromosomal microarray," "conventional karyotype," or "exome sequencing" in the review was performed. RESULTS: The evidence cited in this review includes 6 medical society committee opinions and 17 additional peer-reviewed journal articles that were original research or expert opinion summaries. CONCLUSIONS AND RELEVANCE: Exome sequencing may be a useful prenatal genetic diagnostic tool in cases with ultrasound anomalies with previously normal chromosomal microarray and/or karyotype. As more data become available, technology improves, and costs fall, exome sequencing may become more widely used in prenatal genetic diagnosis.