Objective Congenital anomalies are increasingly diagnosed before birth, which may lead to psychological distress in expectant parents. While the presence of significant symptoms of depression and stress in these parents is established, understanding their context within parents' other life stressors has not been fully investigated. We sought to characterize the socioeconomic profile and depression symptoms of expectant parents in a quaternary care academic hospital's fetal care clinic. Methods This prospective observational study enrolled pregnant persons and their partners in our fetal care clinic. The Edinburgh Postpartum Depression Scale (EPDS), Tool Assessing Patient Stress (TAPS), and a sociodemographic survey were utilized to assess parent psychological distress and socioeconomic stressors. Results were analyzed by the severity of the fetal anomaly. EPDS was repeated at two weeks postpartum. Results 21.7% of pregnant subjects and 25.0% of co-parents had a positive screen on the EPDS at enrollment during their pregnancy. Mothers' EPDS scores correlated with the severity of the fetal anomaly. Many parents reported socioeconomic stressors including: living remotely from the medical center, low household income, food insecurity, unemployment, or other employment concerns, and difficulty affording living expenses. Most also reported factors that can mitigate psychological distress including social support and participation in a religion or faith. Conclusions Expectant parents with fetal anomalies should be screened for depression as well as social and economic risk factors that place them and their infants at higher risk for poor health outcomes. Further work is needed to determine the optimum interventions for addressing their depression symptoms and reducing socioeconomic stressors.

OBJECTIVE:We investigated the cost-effectiveness of three sequential prenatal cystic fibrosis (CF) carrier screening strategies: genotyping both partners, genotyping one partner then sequencing the second, and sequencing both partners.METHOD:A decision-analytic model compared the strategies in a theoretical cohort of four million pregnant couples in the US population and five racial/ethnic sub-populations. Inputs were obtained from literature and varied in sensitivity analysis. Outcomes included cost per quality-adjusted life year (QALY), missed carrier couples, affected newborns, missed prenatal diagnoses, terminations, and procedure-related losses. The cost-effectiveness threshold was $100,000/QALY.RESULTS:Sequencing both partners identified 1099 carrier couples that were missed by genotyping both partners, leading to 273 fewer missed prenatal diagnoses, 152 more terminations, and 152 fewer affected newborns. A similar trend was observed in the genotyping followed by sequencing strategy. The incremental cost-effectiveness ratio of genotyping followed by sequencing compared to genotyping both partners was $180,004/QALY and the incremental cost-effectiveness ratio of sequencing both partners compared to genotyping followed by sequencing was $17.6 million/QALY. Sequencing both partners was cost-effective below $339 per test, genotyping/sequencing between $340 and $1837, and genotyping both partners above $1838. Sequencing was not cost-effective among five racial/ethnic sub-populations.CONCLUSION:Despite improved outcomes, sequencing for prenatal CF carrier screening was not cost-effective compared to genotyping. The clinical significance of the incremental cost-effectiveness of CF carrier screening is a matter of deliberation for public policy debate.

Objective To compare the recommended three-view fetal heart screening method to detect major congenital heart disease (CHD) with more elaborate screening strategies to determine the cost-effective strategy in unselected (low-risk) pregnancies. Methods A decision-analytic model was designed to compare four screening strategies to identify fetuses with major CHD in a theoretical cohort of 4 000 000 births in the USA. The four strategies were: (1) three views: four-chamber view (4CV) and views of the left (LVOT) and right (RVOT) ventricular outflow tracts; (2) five views: 4CV, LVOT, RVOT and longitudinal views of the ductal arch and aortic arch; (3) five axial views: 4CV, LVOT, RVOT, three-vessel (3V) view and three-vessels-and-trachea view; and (4) six views: 4CV, LVOT, RVOT and 3V views and longitudinal views of the ductal arch and aortic arch. Outcomes related to neonatal mortality and neurodevelopmental disability were evaluated. The analysis was performed from a healthcare-system perspective, with a cost-effectiveness willingness-to-pay threshold set at $100 000 per quality-adjusted life year (QALY). Baseline analysis, one-way sensitivity analysis and Monte-Carlo simulation were performed. Results In our baseline model, screening with five axial views was the optimal strategy, detecting 3520 more CHDs, and resulting in 259 fewer children with neurodevelopmental disability, 40 fewer neonatal deaths and only slightly higher costs, compared with screening with the currently recommended three views. Screening with six views was more effective, but also cost considerably more, compared with screening with five axial views, and had an incremental cost of $490 023/QALY, which was over the willingness-to-pay threshold. The five-view strategy was dominated by the other three strategies, i.e. it was more costly and less effective in comparison. The data were robust when tested with Monte-Carlo and one-way sensitivity analysis. Conclusion Although current guidelines recommend a minimum of three views for detecting CHD during the mid-trimester anatomy scan, screening with five axial views is a cost-effective strategy thatmay lead to improved outcome compared with three-view screening. Copyright (c) 2020 ISUOG. Published by John Wiley & Sons Ltd.

ABSTRACT Objective To perform a cost‐effectiveness analysis of different follow‐up strategies for non‐obese and obese women who had incomplete fetal cardiac screening for major congenital heart disease (CHD). Methods Three decision‐analytic models, one each for non‐obese, obese and Class‐III‐obese women, were developed to compare five follow‐up strategies for initial suboptimal fetal cardiac screening. The five strategies were: (1) no follow‐up ultrasound (US) examination but direct referral to fetal echocardiography (FE); (2) one follow‐up US, then FE if fetal cardiac views were still suboptimal; (3) up to two follow‐up US, then FE if fetal cardiac views were still suboptimal; (4) one follow‐up US and no FE; and (5) up to two follow‐up US and no FE. The models were designed to identify fetuses with major CHD in a theoretical cohort of 4 000 000 births in the USA. Outcomes related to neonatal mortality and neurodevelopmental disability were evaluated. A cost‐effectiveness willingness‐to‐pay threshold was set at US$100 000 per quality‐adjusted life year (QALY). Base‐case and sensitivity analysis and Monte‐Carlo simulation were performed. Results In our base‐case models for all body mass index (BMI) groups, no follow‐up US, but direct referral to FE led to the best outcomes, detecting 7%, 25% and 82% more fetuses with CHD in non‐obese, obese and Class‐III‐obese women, respectively, compared with the baseline strategy of one follow‐up US and no FE. However, no follow‐up US, but direct referral to FE was above the US$100 000/QALY threshold and therefore not cost‐effective. The cost‐effective strategy for all BMI groups was one follow‐up US and no FE. Both up to two follow‐up US with no FE and up to two follow‐up US with FE were dominated (being more costly and less effective), while one follow‐up US with FE was over the cost‐effectiveness threshold. One follow‐up US and no FE was the optimal strategy in 97%, 93% and 86% of trials in Monte‐Carlo simulation for non‐obese, obese and Class‐III‐obese models, respectively. Conclusion For both non‐obese and obese women with incomplete fetal cardiac screening, the optimal CHD follow‐up screening strategy is no further US and immediate referral to FE; however, this strategy is not cost‐effective. Considering costs, one follow‐up US and no FE is the preferred strategy. For both obese and non‐obese women, Monte‐Carlo simulations showed clearly that one follow‐up US and no FE was the optimal strategy. Both non‐obese and obese women with initial incomplete cardiac screening examination should therefore be offered one follow‐up US. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

INTRODUCTION: Our study models the trade-off between preterm neonatal morbidity and stillbirth for women with intrahepatic cholestasis of pregnancy (ICP) with total bile acids (TBA) between 40 and 99 µmol/L in order to determine the optimal gestational age for delivery. METHODS: A decision analytic model was created to compare the outcomes of delivery at 33 through 40 weeks gestation in women with TBA between 40 and 99 µmol/L. Baseline morbidity and mortality risks were derived from the literature and adjusted where appropriate for peak TBA and administration of antenatal steroids. We assumed a population of 10,000 women with ICP and calculated total quality-adjusted life years (QALYs) for each strategy, taking into account both maternal and neonatal perspectives. Univariate sensitivity analysis was performed for all variables to test the robustness of the model. RESULTS: In women with TBA between 40 and 99 µmol/L, delivery at 39 weeks maximized QALYs, resulting in 700.6 more QALYs but 5.3 more stillbirths than delivery at 36 weeks. Sensitivity analysis demonstrated that delivery at 38 weeks became optimal when the relative risk of stillbirth given TBA between 40 and 99 µmol/L rose from a baseline of 1.00 to 4.91. Monte Carlo analysis demonstrated that when variation was incorporated into the model, delivery at 39 weeks was optimal 38% of the time and delivery at 38 weeks 25% of the time. CONCLUSION: In women with ICP with TBA between 40 and 99 µmol/L, delivery between 38 and 39 weeks may be optimal.

INTRODUCTION: Our study models the trade-off between preterm neonatal morbidity and stillbirth for women with intrahepatic cholestasis of pregnancy (ICP) with total bile acids ≥100 µmol/L in order to determine the optimal gestational age for delivery. METHODS: A decision analytic model was created to compare the outcomes of delivery at 33 through 40 weeks gestation in women with total bile acids (TBA) ≥100 µmol/L. Baseline risks of stillbirth and spontaneous delivery were derived from the literature and adjusted for peak TBA. It was assumed that betamethasone was given within 48 hours of all planned preterm deliveries and before a percentage of spontaneous ones. We assumed a population of 10,000 women with ICP and calculated total quality-adjusted life years (QALYs) for each strategy, taking into account both maternal and neonatal perspectives. Univariate sensitivity analysis was performed for all variables to test the robustness of the model. RESULTS: In women with peak TBA ≥100 µmol/L, delivery at 34 weeks maximized QALYs. Compared to delivery at 36 weeks, it resulted in 1302.4 more QALYs, 98.2 fewer stillbirths, and 21 more cases of cerebral palsy in our theoretical cohort of 10,000 women. Sensitivity analysis demonstrated that when the relative risk of stillbirth given TBA ≥100 µmol/L fell from a baseline of 30.5 to below 26.2, delivery at 35 weeks became optimal. Monte Carlo analysis demonstrated that when variation was incorporated into the model, delivery at 34 weeks was the dominant strategy 45% of the time. CONCLUSION: In women with ICP with TBA ≥100 µmol/L, delivery at 34 weeks maximizes QALYs.

Objectives Cell-free fetal DNA (cfDNA) has been increasingly incorporated into prenatal aneuploidy screening paradigms given its relatively high sensitivity for Down syndrome (DS). This is often the case when fetal ultrasonographic soft markers are present, such as the relatively common echogenic intracardiac focus (EIF). We sought to evaluate the cost-effectiveness of a screening strategy that included cfDNA screening when an isolated EIF is identified in a low-risk population with prior aneuploidy screening. Methods A decision-analytic model was constructed using TreeAge software with probabilities derived from the literature. Our model compared cfDNA screening following isolated EIF detection in women less than 35 years with prior reassuring first trimester screen compared to a strategy of no further aneuploidy screening. Strategies were compared to generate an incremental cost-effectiveness ratio with a threshold of $100 000/quality-adjusted life year (QALY) and applied to a theoretical cohort. Results The cfDNA strategy resulted in 21 fewer DS births and 52 additional QALYs, however, increased costs by $51.3 million. This yielded an incremental cost-effectiveness ratio of $986 503; therefore, it was not a cost-effective strategy. Conclusion In a low-risk population with prior reassuring aneuploidy screening, it is not cost effective to offer cfDNA after identification of an isolated EIF.

There is increasing utilization of cell free DNA (cfDNA) for prenatal genetic screening. With increased use of cfDNA, the utility of concurrent use of nuchal translucency (NT) ultrasound has been questioned. There are no studies examining the cost of NT ultrasound compared to the difference in pregnancy outcomes. We sought to estimate the cost-effectiveness of adjunct NT ultrasound in women who had previously had low risk cfDNA screening. A decision-analytic model was created using TreeAge software to compare outcomes for women with low risk cfDNA screening with and without addition of NT ultrasound. Probabilities were derived from the literature. Outcomes included miscarriage after diagnostic procedure, termination, stillbirth, neonatal death, and aneuploidy. Maternal utilities were applied to generate maternal quality adjusted life years (QALYs). The cost-effectiveness threshold was set at $100,000 per QALY. Sensitivity analyses were performed to assess the robustness of our assumptions. When applied to a theoretic cohort of 3 million women who had low risk cfDNA screening, use of adjunctive NT ultrasound resulted in 402 fewer stillbirths and 1,251 fewer neonatal deaths when compared to not using adjunctive NT ultrasound. There were 610 more procedure-related losses and 1,108 more terminations performed in the NT ultrasound arm. Additionally, use of NT ultrasound resulted in 256,314 maternal QALYs, at a cost savings of $51,670,400,000 when applied across our theoretic cohort of 3 million women. Use of adjunctive NT ultrasound in women with low risk cfDNA screening is cost-saving and results in higher maternal outcomes when compared to no adjunctive NT ultrasound. This study did not account for additional ultrasound findings which can be identified at time of NT ultrasound, which would likely increase the utility of adjunctive ultrasound. Additional studies are warranted to determine possible additional benefits of first trimester ultrasound in women with low risk cfDNA genetic screening.

While the cell-free DNA (cfDNA) test for Down syndrome is a screening test, many individuals do not want an amniocentesis with a positive screen. In this study, we compared the addition of ultrasound (US) as a second screen versus proceeding directly to amniocentesis for prenatal detection of trisomy 21 (T21). A decision-analytic model was constructed to compare US as a second screening test versus amniocentesis for prenatal detection of T21 in a theoretical cohort of 4 million women undergoing cfDNA testing for aneuploidy. All probabilities, costs, and utilities were derived from literature and varied in sensitivity analysis. The sensitivity and specificity of cfDNA for T21 was 99.7% and 99.6%, respectively. The prenatal detection rate of US for T21 was 64.4%. Primary outcomes included incremental cost per quality-adjusted life year (QALY), neonates born with T21, fetal loss, elective abortion, and neonatal death. The cost-effectiveness threshold was set at $100,000/QALY. Adding US as a second screen in women with positive cfDNA for T21 would result in 825 more neonates with Down syndrome as compared to proceeding directly to amniocentesis (Table 1). This is explained by the suboptimal sensitivity of US for prenatal detection of T21, leading to 1,754 missed true positive cases. We also observed 945 fewer elective abortions, 71 more spontaneous fetal losses, and 58 more infant deaths in this cohort. US as a second screen, however, improved detection of those with false positive cfDNA results and led to 67 fewer amniocentesis-related losses, 58 of which were normal fetuses. Overall, US as a second screen resulted in decreased effectiveness by 4,448 QALYs and increased costs by $890 million. When we varied the sensitivity of US for prenatal detection of T21, US as a second screen became cost-effective only above 99.9% (Figure 1). In women undergoing cfDNA screening for T21, incorporating US as a second screen for positive results is not a cost-effective strategy compared to proceeding directly to amniocentesis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Cystic fibrosis (CF) is one of the most prevalent inherited conditions, with 1,000 new cases/year in the United States. Current guidelines recommend genotyping for prenatal carrier screening, however next generation sequencing (NGS) has recently been developed which performs with high sensitivity. Our study investigated the cost-effectiveness of genotyping and NGS strategies for prenatal CF carrier couple screening. A decision-analytic model was constructed using TreeAge software to compare cost-effectiveness of four screening strategies for CF in 4 million pregnant people and their partners: genotyping both partners, genotyping then NGS, NGS then genotyping, and NGS for both partners. All probabilities, costs, and utilities were derived from literature. The primary outcome was incremental cost per quality-adjusted life year (QALY). Additional outcomes included missed at-risk couples and missed CF. Cost of NGS was varied in sensitivity analysis with a cost-effectiveness threshold of $100,000/QALY. In our theoretical cohort, genotyping both partners was the cost-effective strategy. However, it failed to identify 1,096 more at risk couples and resulted in 273 more missed prenatal CF cases when compared to NGS for both partners. Given these outcomes, genotyping both partners was less costly but least effective (Table 1). In comparison, NGS for both partners was most effective but associated with higher costs and false positive rate. We found the cost of NGS (baseline $2,104) was a large driver of the model. When we varied this cost in sensitivity analysis, NGS for both partners was cost-effective below $318 per test (Figure 1). Between $318-$2,067, genotyping then NGS was cost-effective. Above $2,067, genotyping both partners was cost-effective. Genotyping both partners for prenatal CF carrier screening is cost-effective compared to strategies with NGS. As the cost of NGS improves, carrier screening with genetic sequencing may become an optimal screening strategy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

SMFM and ACOG guidelines recommend comprehensive prenatal diagnosis in pregnancy. Upon detection of structural abnormalities during the anatomic ultrasound, it is recommended that women undergo counseling including the opportunity for additional diagnostic testing including chromosomal microarray analysis (CMA). With the added prognostic value of a significant CMA abnormality, some women may desire pregnancy termination. However, twenty states have enacted laws prohibiting abortion beyond 20 weeks' gestation; currently 17 are active. We sought to estimate the effect of 20-week abortion bans on health outcomes and costs in the setting of a fetal diagnosis from microarray with an underlying structural anomaly. A decision-analytic model was built using TreeAge software to evaluate the impact of a 20-week ban on abortion in a theoretical cohort of 10,000 women with abnormal CMA after identification of structural abnormalities on ultrasound. Outcomes included number of abortions, maternal death, neonatal death, intrauterine fetal demise, and a child with moderate or severe chromosomal microdeletions, in addition to cost and quality-adjusted-life-years (QALY). The threshold for cost-effectiveness was set to $100,000 per QALY. Sensitivity analyses were performed broadly. In this hypothetical cohort, a 20-week abortion ban results in an additional 217 stillbirths, 337 neonatal deaths. There would be 1,823 fewer terminations of pregnancy. The presence of a ban results in 48,148 fewer maternal QALYs and costs society over $3.3 billion. Among the 5,958 women who would consider termination, 1,650 would still travel out of state to obtain the abortion. In sensitivity analyses, not having a ban in place remained the cost-effective strategy until abortion cost over 920 times its current cost. Policies prohibiting termination of pregnancy after 20 weeks' gestation are associated with significant societal costs and worsened maternal outcomes when considering a population of women with abnormal ultrasound and CMA. With increased utilization and improved resolution of CMA testing, the magnitude of this impact may increase.

We describe twins with an interstitial deletion of chromosome 1 with a severe phenotype compared to previously described cases. As genetic testing is more frequently performed, it is important for clinicians to understand the spectrum of clinical findings that can occur with this particular deletion.

BackgroundAbsence of the cavum septi pellucidi (CSP) on prenatal imaging is historically associated with additional anomalies; however, recent cases of isolated absent CSP have also been identified. This study seeks to assess the accuracy of prenatal imaging in evaluating isolated absent CSP and to describe the spectrum of clinical outcomes. MethodsThis is a retrospective observational study of all prenatally diagnosed absent CSP cases between 2011 and 2016 at our institution. Cases with additional structural parenchymal abnormalities were excluded. Clinical outcomes were abstracted from available records. ResultsWe identified 15 cases of prenatally diagnosed isolated absent CSP. All patients were initially diagnosed on ultrasound (US) and 11/15 patients had fetal magnetic resonance imaging (MRI) confirming the diagnosis. Prenatal US and MRI were concordant in all cases. Of the continuing pregnancies, 2 neonatal deaths occurred related to extreme prematurity. Two cases of septo-optic dysplasia were identified in our cohort. DiscussionIn this study, fetal MRI and US had a high degree of accuracy with concordant postnatal imaging. Our study is similar to other case series suggesting that a range of clinical outcomes is possible with isolated absent CSP, but long-term patient follow up is necessary.

INTRODUCTION: The 2014 Fetal Imaging Workshop endorses obtaining a quad screen or cell-free fetal DNA (cfDNA) test in fetuses identified to have an isolated echogenic intracardiac foci (EIF) without prior aneuploidy screening. Our goal was to compare estimated outcomes and costs of the recommendation. We additionally hoped to gain information to assist providers in offering patient specific recommendations. METHODS: A decision-analytic model was constructed using TreeAge software and probabilities derived from the literature. The model compared use of quad testing to cfDNA in women with an isolated EIF identified on screening ultrasound, with T21 sensitivities assumed at 81% and 99% respectively. Baseline risk of T21 was assumed at 1/400. Positive likelihood ratio for T21 with an isolated EIF, was assumed to be 1.5. Outcomes of interest included T21 diagnosis, procedure related loss, termination, spontaneous abortion, and T21 live births. Strategies were compared to generate an incremental cost-effectiveness ratio, with a $100,000/QALY threshold, and applied to a theoretical cohort of 100,000. RESULTS: When compared to aneuploidy screening using quad testing, the strategy that utilized cfDNA after detection of an isolated EIF resulted in 47 fewer live T21 births and 85 additional QALYs with cost savings of $525,964 per 100,000 pregnancies; a dominant strategy in cost-effectiveness analysis. CONCLUSION: In a population with an isolated EIF identified on screening US without prior aneuploidy screening it is cost effective to offer cfDNA as compared to a quad screening test. Despite the higher cost of cfDNA, these results likely stem from the increased sensitivity and decreased false positive rate.

We aimed to characterize the impact of Prader Willi Syndrome on perinatal outcomes in a cohort of affected pregnancies. This is a retrospective cohort of Prader Willi Syndrome affected deliveries in California using linked vital statistics and ICD-9 data. We compared pregnancies affected by Prader Willi Syndrome to those unaffected by the diagnosis. Outcomes of interest include gestational diabetes (GDM), fetal cardiac anomaly, preterm delivery at 32 weeks (PTD), hypoglycemia, small for gestational age (SGA), infant death, caesarean section (CS), and cost. We used X2 and paired t-tests to compare outcomes, and multiple logistic regression to characterize risks and control for potential confounders. In our cohort of 2,029,004 pregnancies, 39 were affected by Prader Willi Syndrome. Compared to pregnancies not complicated by Prader Willi, having a fetus with Prader Willi Syndrome was associated with a greater rate of PTD (5.1% vs 1.4%, p=0.05), hypoglycemia (20.5% vs 0.9%, p<0.0001), SGA (40.5% vs 6.3%, p<0.0001), infant death (2.6% vs 0.4%, p = 0.022), and CS (69.2% vs 30.2%, p<0.0001) (Table 1). Prader Willi Syndrome was associated with a greater cost for the infant ($88,715.01 vs $5,066.56, p<0.0001) and mother ($10,599.52 vs $7,727.93, p=0.0181). There were no significant differences in gestational diabetes and fetal cardiac anomaly. A pregnancy affected by Prader Willi Syndrome results in increased risk for adverse fetal outcomes and costs.

OBJECTIVE: To estimate the effect of 20-week abortion bans on maternal and consequent neonatal health outcomes and costs in the setting of fetal congenital diaphragmatic hernia. METHODS: A decision-analytic model was built using TreeAge software to evaluate the effect of a 20-week ban on abortion in a theoretical cohort of 921 women diagnosed with fetal congenital diaphragmatic hernia. Probabilities, utilities, and costs were derived from the literature. The cohort size was based on the annual rate of prenatal diagnoses of congenital diaphragmatic hernia and live births among the 20 states with bans. The threshold for cost-effectiveness was set at $100,000 per quality-adjusted life-year. Analysis was completed from the maternal perspective. Clinical outcomes included mode of delivery, maternal death, intrauterine fetal death, neonatal death, neurodevelopmental disability, and use of extracorporeal membrane oxygenation. One-way sensitivity analysis was used on all variables and Monte Carlo simulation was performed. RESULTS: A policy restricting termination was associated with higher costs, at an additional $158,419,623, with decreased quality of life and 674 fewer quality-adjusted life-years. With 20-week bans in place, 60 women would travel out of state to obtain abortions. There would be 158 more live births affected by congenital diaphragmatic hernia. Of these births, 45 neonates would die before 28 days after birth and an additional 37 would have long-term neurodevelopmental disability. CONCLUSION: In this model, bans that limit abortions beyond 20 weeks of gestation were associated with worse health outcomes and increased costs for women with pregnancies complicated by congenital diaphragmatic hernia. The restriction of health care access should be considered in terms of the long-term outcomes and economic effect on individuals and society.

Cell Free DNA screening (cfDNA) has expanded the options for prenatal genetic screening. As this technology has advanced, single gene assessment has been utilized in those at increased risk for an abnormality, however given the low prevalence of these disorders, it is unclear if this strategy should be offered to all pregnant women. Thus, we sought to estimate the cost-effectiveness of cfDNA screening for single gene disorders in a general obstetric population. A decision-analytic model was created using TreeAge software to compare costs and outcomes for women undergoing genetic screening with standard cfDNA versus cfDNA screening with single gene analysis. Probabilities were derived from the literature. Outcomes included were miscarriage after diagnostic procedure, termination, stillbirth, neonatal death, and the 25 conditions single gene cfDNA tests for. Maternal utilities were applied to discounted life expectancy at a rate of 3% to generate combined quality adjusted life years (QALYs). The cost-effectiveness threshold was set at $100,000 per QALY. Sensitivity analyses were then performed in order to assess the robustness of our assumptions. When applied to a theoretic cohort of 4 million women, cfDNA screening for single gene disorders resulted in 108 fewer stillbirths and 136 fewer neonatal deaths when compared to standard cfDNA. There were 912 more procedure-related losses and 2312 more terminations performed in the single-gene cfDNA arm. While cfDNA with single gene assay resulted in 4,452 additional QALYs compared with standard cfDNA screening, it cost an additional $372,814, making it not cost-effective for the general population. When sensitivity analysis on the cost of single gene cfDNA was performed, the test became cost-effective at a cost of $491 (compared to the base cost of $795) and became the dominant strategy (improved outcomes at lower costs) at $380. According to this CEA, cfDNA screening for single gene disorders is not useful as a screening tool for a low risk population due to the low prevalence, inevitable accumulation of false positive rates and additional cost. Prospective studies are needed to determine test characteristics in the general obstetric population.

We aimed to characterize the impact of 22q11.2 Deletion Syndrome (22q11) on neonatal outcomes in a cohort of affected pregnancies. This is a retrospective cohort of 22q11 affected deliveries in California using linked vital statistics and ICD-9 data. We compared pregnancies affected by 22q11 to those unaffected by the diagnosis and stratified outcomes by presence fetal cardiac anomaly. Outcomes of interest included fetal cardiac anomaly, preterm delivery (PTD), respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), hypoglycemia, small for gestational age (SGA), neonatal death, infant death, and cost. We used X∧2 and paired t-tests to compare outcomes, and multiple logistic regression to characterize risks and control for potential confounders. In our cohort of 2,029,004 deliveries, 64 fetuses were affected by 22q11 Deletion Syndrome, 35 of which had fetal cardiac anomalies. Compared to pregnancies not complicated by 22q11, having 22q11 was associated with a greater rate of fetal cardiac anomaly (54.6% vs 0.5%, p<0.0001), PTD (7.8% vs 1.4%, p<0.0001), RDS (10.9% vs 1.3%, p<0.0001), IVH (4.7% vs 0.2%, p<0.0001), NEC (3.1% vs 0.1%, p<0.0001), hypoglycemia (3.1% vs 0.9%, p=0.049), SGA (18.6% vs 6.3%, p<0.0001), neonatal death (1.6% vs 0.2%, p=0.02), infant death (10.9% vs 0.4%, p<0.0001) and cost ($216,147.50 vs $5,062.02, p<0.0001) (Table 1). These outcomes, except neonatal death and SGA, were also greater in 22q11 affected fetuses with no cardiac anomalies compared to those unaffected by 22q11. In 22q11 affected fetuses with cardiac anomalies, SGA was the only increased outcome. Cost was increased for all neonates affected with 22q11, regardless cardiac anomaly. 22q11 affected pregnancies have increased risk of adverse neonatal outcomes and higher costs. This is similarly true in the setting of 22q11 affected neonates without a cardiac anomaly, but there were minimal differences between neonatal outcomes of fetal cardiac anomalies comparing those with and without 22q11.

Purpose: To describe the rate and severity of gestational hypertensive disorders (GHDs) in pregnancies complicated by trisomy 13 (T13).Materials and methods: Retrospective cohort study of singleton deliveries in California from 2005 to 2008 using vital statistics and ICD-9 data. We were interested in gestational hypertension (gHTN), preeclampsia with and without severe features (sPREX and PREX), and gestational age at delivery. Pregnancies and maternal complications affected by prenatally diagnosed T13 were compared to unaffected pregnancies. Regression models were used to compute adjusted odds ratios for pregnancy outcomes by T13 status.Results: Of the 2,029,004 deliveries, 142 women had prenatally diagnosed T13. A diagnosis of GHD occurred in 26.8% of the T13 pregnancies versus 6% of the non-T13 pregnancies (p < .001). This remained true for gHTN (9.2% versus 3.2%, p=.001), PREX (12% versus 2.2%, p < .001), and sPREX (8.5% versus 0.9%, p < .001). After adjusting for confounders, T13 pregnancies were 6.3-times more likely to be affected by GHD, and 12.5-times more likely to have sPREX. Delivery <37 and <32 weeks in the setting of GHD was 14.1-times and 11.2-times likely among women with T13.Conclusions: Women with T13 pregnancies were significantly more likely to have gHTN, preeclampsia, sPREX, and to deliver <32 weeks.