Cost-effectiveness of ultrasound before non-invasive prenatal screening for fetal aneuploidy.

OBJECTIVE: To determine the cost-effectiveness of first-trimester ultrasound before fetal aneuploidy screening with cell-free DNA (cfDNA) compared with screening by cfDNA alone. METHODS: A decision analytic model was constructed for 400 000 pregnant individuals with advanced maternal age who desired first-trimester aneuploidy screening with cfDNA in the USA, to compare two screening strategies: (1) cfDNA only and (2) ultrasound performed within 4 weeks before cfDNA. Input parameters included probability of fetal aneuploidy, cfDNA performance, desire for diagnostic testing, pregnancy outcomes, and pregnancy and lifetime costs and utilities. The primary outcome measure was the incremental cost-effectiveness ratio (ICER), in terms of cost in 2020 US dollars (USD) per quality-adjusted life year (QALY) gained. Secondary outcomes included procedure-related loss, pregnancy termination, live birth with aneuploidy, live birth with structural anomaly and stillbirth. Discounting was performed at 3% per year with an estimated maternal lifespan of 81 years starting at the age of 35 years. One-way, multiway and Monte Carlo probabilistic sensitivity analyses were performed. All base-case estimates and ranges of uncertainty were derived from the literature. The willingness-to-pay threshold was set at 100 000 USD per QALY. RESULTS: In the base-case analysis, ultrasound before cfDNA screening was more cost-effective than cfDNA screening without pretest ultrasound, with an ICER of 12 588 USD and higher net monetary benefit (24 241 vs 20 466). The strategy involving ultrasound before cfDNA was more costly by 544 USD but also more effective (by 0.04 QALY) compared with cfDNA alone. Base-case results were robust in sensitivity analyses with the strategy involving ultrasound before cfDNA always remaining the most cost-effective approach with the highest net monetary benefit. CONCLUSION: First-trimester ultrasound before cfDNA is a more cost-effective strategy for non-invasive prenatal aneuploidy screening compared with cfDNA alone. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Frequency and prediction of persistent urinary tract dilation in third trimester and postnatal urinary tract dilation in infants following diagnosis in second trimester.

OBJECTIVE: To determine the frequency, associated characteristics and prognostic value of the current risk stratification system for prenatal urinary tract dilation (UTD) for predicting persistent UTD in the third trimester and subsequent postnatal UTD in the infant, following diagnosis in the second trimester. METHODS: This was a single-institution retrospective cohort study of singleton pregnancies diagnosed with unilateral or bilateral UTD in the second trimester (before 28 weeks' gestation) with follow-up in the third trimester (at or after 28 weeks) between January 2017 and May 2019. In all cases, the prenatal diagnosis and stratification to low-risk (Grade A1) or increased-risk (Grade A2-3) UTD was made using the 2014 UTD consensus classification system. The primary outcomes included persistent prenatal UTD in the third trimester and postnatal UTD up to 6 months of age. We performed multivariable analysis to assess whether patient and second- and third-trimester sonographic characteristics (such as UTD laterality, other renal abnormality (calyceal dilation, abnormal parenchymal appearance, abnormal ureter or bladder) and anteroposterior renal pelvic diameter (AP-RPD)) were associated with the study outcomes. We assessed the predictive value of the current risk stratification system (Grade A1 vs Grade A2-3) in the second and third trimesters for persistent prenatal UTD and postnatal UTD using the area under the receiver-operating-characteristics curve (AUC). RESULTS: Of 26 620 second-trimester ultrasound assessments in the study period, 347 patients were diagnosed with UTD in the second trimester and had third-trimester follow-up, of whom 150/347 (43% (95% CI, 38-49%)) had persistent UTD in the third trimester. Among the 282/347 (81%) patients with postnatal follow-up available, the frequency of postnatal UTD was 49/282 (17% (95% CI, 13-22%)), and among the subset with persistent UTD in the third trimester, the frequency of postnatal UTD was 46/102 (45% (95% CI, 35-55%)). The most frequent postnatal diagnosis was transient UTD (76%), followed by duplicated collecting system (10%). Of infants originally diagnosed with UTD in the second trimester, 2% (7/347) required surgery; stated differently, of the 49 infants with postnatal UTD, 14% (7/49) required surgery. At second-trimester diagnosis, sonographic predictors of both persistent prenatal UTD and postnatal UTD included the presence of other renal abnormality and UTD Grade A2-3. At third-trimester follow-up, predictors of postnatal UTD were larger mean AP-RPD and UTD Grade A2-3, while all cases had other renal abnormality. Second-trimester diagnosis of UTD Grade A2-3 had satisfactory discrimination for predicting persistent prenatal UTD (AUC, 0.64 (95% CI, 0.58-0.70)) and postnatal UTD (AUC, 0.72 (95% CI, 0.63-0.81)), as did third-trimester UTD Grade A2-3 for predicting postnatal UTD (AUC, 0.66 (95% CI, 0.56-0.76)). CONCLUSIONS: The majority of cases of prenatal UTD did not result in postnatal UTD, and of those that did, very few required surgery. Follow-up third-trimester assessment after a second-trimester diagnosis of UTD is warranted. The current risk stratification system by UTD grade, based on the 2014 UTD consensus classification, can be used to predict postnatal UTD with fair accuracy. Further research is needed to determine whether the predictive performance of this system can be improved by incorporating additional risk factors. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Association of chorioamnionitis and its duration with adverse maternal outcomes by mode of delivery: a cohort study.

OBJECTIVE: To investigate the association of chorioamnionitis and its duration with adverse maternal outcomes by mode of delivery. DESIGN: A retrospective cohort study. SETTING: Data from the Consortium on Safe Labor Study in the USA (2002-2008). POPULATION: Singleton deliveries at ≥23 weeks of gestation (221 274 assessed deliveries, 62 331 by caesarean section). METHODS: The association of chorioamnionitis, and secondarily the duration of chorioamnionitis estimated from intrapartum antibiotic use, with adverse maternal outcomes was analysed using logistic regression with generalised estimating equations, adjusting for age, parity, race, pregestational diabetes, chronic hypertension, gestational age at delivery, study site and delivery year. Analyses were stratified by vaginal versus caesarean delivery. MAIN OUTCOME MEASURES: The composite adverse maternal outcome included: postpartum transfusion, endometritis, wound/perineal infection/separation, venous thromboembolism, hysterectomy, admission to intensive care unit and/or death. RESULTS: Chorioamnionitis was associated with higher odds of the composite adverse maternal outcome with caesarean delivery (adjusted odds ratio 2.31; 95% CI 1.97-2.71); and the association persisted regardless of whether a woman had a trial of labour, preterm delivery or maternal group B streptococcus colonisation. The most common adverse outcomes after caesarean section were postpartum transfusion (56.0%) and wound/perineal infection or endometritis (38.6%). Chorioamnionitis was not associated with adverse maternal outcomes after vaginal delivery. The duration of chorioamnionitis as the exposure did not alter the association between chorioamnionitis and adverse maternal outcomes. CONCLUSIONS: Chorioamnionitis, but not the estimated duration, was associated with increased odds of adverse maternal outcomes with caesarean delivery. This finding has implications for care programmes to prevent maternal morbidity after a caesarean section complicated by chorioamnionitis. TWEETABLE ABSTRACT: Chorioamnionitis, but not its duration, increases the risk of adverse maternal outcomes with caesarean delivery.

Utility of ultrasound examination at 10-14 weeks prior to cell-free DNA screening for fetal aneuploidy.

OBJECTIVE: To estimate the frequency of unexpected first-trimester ultrasound findings that would alter prenatal management in pregnant women eligible for cell-free (cf) DNA screening because of advanced maternal age (AMA). METHODS: This was a retrospective cohort study of all AMA women at a tertiary care center who had a 10-14-week ultrasound examination between 1 January 2012 and 27 April 2015. Information on pregnancy dating, obstetric ultrasound examination, prenatal screening and genetic testing were collected from a perinatal database. The primary outcome was an unexpected ultrasound finding in the first trimester that would alter the prenatal screening/testing strategy. RESULTS: In total, 2337 women met the inclusion criteria, with a total of 2462 fetuses. Sixty-eight (2.9%) women had an anomalous fetus, of which 44 (64.7%) had diagnostic testing. In the entire cohort, a non-viable pregnancy was identified in 153 (6.5%) women. Multiple gestation was identified in 32 (1.4%) women; five had a cotwin demise. Gestational dating was revised for 126 (5.4%) women. Among those who opted for aneuploidy screening (n = 1806), 68.5% had cfDNA screening and 31.5% had first-trimester screening by analysis of maternal serum biomarkers and nuchal translucency thickness. Among those eligible for cfDNA screening, 16.1% (95% CI, 15.0-18.0%; 377/2337) had an ultrasound finding (anomaly, incorrect dating, multiple gestation, non-viable pregnancy) at the time of testing that would have altered the provider's counseling regarding the prenatal screening/testing strategy. CONCLUSIONS: A substantial proportion of AMA women eligible for cfDNA screening have fetal ultrasound findings that could alter genetic testing strategy and clinical management. This study recommends ultrasound examination prior to cfDNA screening in AMA women. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Vaginal birth after caesarean for women with three or more prior caesareans: assessing safety and success.

OBJECTIVE: To estimate the rate of success and risk of maternal morbidities in women with three or more prior caesareans who attempt vaginal birth after caesarean (VBAC). DESIGN: Retrospective cohort design. SETTING: Multicentre, from 1996 to 2000, including 17 tertiary and community delivery centres in north-eastern USA. POPULATION: A total of 25 005 women who had had at least one prior caesarean delivery. METHODS: Women who attempted VBAC with three or more prior caesareans were compared with those who attempted after one and two prior caesareans. Univariable and stratified analyses were used to select factors for multivariable analyses for maternal morbidity. Maternal characteristics were compared using a Student's t test, Mann-Whitney U test, chi-square test or Fisher's exact test, as appropriate. MAIN OUTCOME MEASURES: The primary outcome was composite maternal morbidity, defined as at least one of the following: uterine rupture, bladder or bowel injury, or uterine artery laceration. Secondary outcomes were VBAC success, blood transfusion and fever. RESULTS: Of 25 005 women, 860 had three or more prior caesarean deliveries: 89 attempted VBAC and 771 elected for repeat caesarean. Of the 89 who attempted VBAC, there were no cases of composite maternal morbidity. They were also as likely to have a successful VBAC as women with one prior caesarean (79.8% versus 75.5%, adjusted OR 1.4, 95% CI 0.81-2.41, P = 0.22). CONCLUSION: Women with three or more prior caesareans who attempt VBAC have similar rates of success and risk for maternal morbidity as those with one prior caesarean, and as those delivered by elective repeat caesarean.

Selective laser photocoagulation versus serial amniodrainage for the treatment of twin-twin transfusion syndrome: a cost-effectiveness analysis.

OBJECTIVE: To compare the cost-effectiveness of selective laser photocoagulation (SLP) with serial amniodrainage (AD) in the treatment of twin-to-twin transfusion syndrome (TTTS). STUDY DESIGN: Using decision-analysis modeling, we compared the cost-effectiveness of using laser photocoagulation with AD for the treatment of TTTS. The analysis was carried out from a societal perspective using a theoretical cohort of 1000 women with TTTS. Costs included the costs of procedures, perinatal complications from TTTS and of resources used for raising a child with cerebral palsy (CP) following TTTS. One-way, multiway and probabilistic (Monte Carlo) sensitivity analyses were carried out for all model variables. The main outcome measures were: cost per quality-adjusted life years (QALYs) gained from treating TTTS. RESULT: On the basis of the available data, the decision model favors SLP as the most cost-effective treatment option compared with AD. Using the theoretical cohort, laser photocoagulation will result in an overall perinatal survival of 59.3% compared with 51.5% for AD. The frequency of children with CP after laser would be 8.5% compared with 15.4% after AD. Sensitivity analyses showed the model to be robust over a wide range of values for the variables, except when the overall survival associated with AD is >62%. Above that survival rate, AD was the more cost-effective therapy. CONCLUSION: Under a wide range of circumstances, the most cost-effective therapy for TTTS is SLP.

The controversy surrounding indomethacin for tocolysis.

Indomethacin is a prostaglandin synthetase inhibitor sometimes used for tocolysis. Several placebo-controlled trials and trials comparing indomethacin to other potential first-line tocolytic agents support its efficacy for delaying delivery for >48 hours. Recent observational studies, however, have raised concerns about the safety of indomethacin, implicating it with increased rates of intraventricular hemorrhage and necrotizing enterocolitis. Careful analysis of these observational studies suggests that these results should be viewed with caution, because of uncontrolled confounding by indication. A recent decision analysis supports the risk/benefit analysis of indomethacin in this setting. Still, the future of indomethacin in preterm labor should be guided by well-designed prospective clinical trials. Such studies are underway.

Predicting outcomes of trials of labor in women attempting vaginal birth after cesarean delivery: a comparison of multivariate methods with neural networks.

OBJECTIVE: Our aim was to assess the utility and effectiveness of a neural network for predicting the likelihood of success of a trial of labor, relative to standard multivariate predictive models. STUDY DESIGN: We identified 100 failed trials of labor and 300 successful trials of labor in women with a prior cesarean delivery performed at our institution. Information was collected on >70 potential predictors of labor outcomes from the medical records, including demographic, historical, and past obstetric information, as well as information from the index pregnancy. Bivariate analyses comparing women in whom a trial of labor failed with those whose trial succeeded were performed. These initial analyses were used to select variables for inclusion into our muitivariate predictive model. From the same data we trained and tested a neural network, using a back-propagation algorithm. The test characteristics of the multivariate predictive model and the neural network were compared. RESULTS: From the bivariate analysis a history of substance abuse (adjusted odds ratio, 0.27; 95% confidence interval, 0.09-0.80), a successful prior vaginal birth after cesarean delivery (adjusted odds ratio, 0.13; 95% confidence interval, 0.05-0.31), cervical dilatation at admission (adjusted odds ratio, 0.53; 95% confidence interval, 0.31-0.88), and the need for labor augmentation (adjusted odds ratio, 2.15; 95% confidence interval, 1.14-4.06) were ultimately discovered to be important in predicting the likelihood of the success or failure of a trial of labor. With these variables in the predictive model the sensitivity of the derived rule for predicting failure was 77%, the specificity was 65%, and the overall accuracy was 69%. We also built a network using the 4 variables that were included in the final multivariate model. We were unable to achieve the same degree of sensitivity and specificity that we observed with the regression-based predictive model (sensitivity and specificity, 59% and 44%). CONCLUSION: In this study a standard multivariate model was better able to predict outcome in women ttempting a trial of labor.

Can antenatal clinical and biochemical markers predict the development of severe preeclampsia?

OBJECTIVE: This study was undertaken to develop a multivariable clinical predictive rule for severe preeclampsia using second-trimester clinical factors and biochemical markers. STUDY DESIGN: We performed a retrospective cohort study of all pregnant patients with single gestations from 1995 through 1997 for whom we had complete follow-up data. Through medical record review we determined whether patients had severe preeclampsia develop according to American College of Obstetricians and Gynecologists criteria. Case patients with severe preeclampsia were compared with control subjects with respect to clinical data and multiple-marker screening test results. With potential predictive factors identified in the bivariate and stratified analyses both an explanatory logistic regression model and a clinical prediction rule were created. Patients were assigned a predictive score according to the presence or absence of predictive factors, and receiver operating characteristic analysis was used to determine the optimal score cutoff point for prediction of severe preeclampsia with maximal sensitivity. RESULTS: Among the 1998 patients we found 49 patients with severe preeclampsia (prevalence, 2.5%). After we controlled for confounding variables, case patients and control subjects had similar human chorionic gonadotropin and alpha-fetoprotein levels, and the only variables that remained significantly associated with severe preeclampsia were nulliparity (relative risk, 3.8; 95% confidence interval, 1.7-8.3), history of preeclampsia (relative risk, 5.0; 95% confidence interval, 1.7-17.2), elevated screening mean arterial pressure (relative risk, 3.5; 95% confidence interval, 1.7-7.2), and low unconjugated estriol concentration (relative risk, 1.7; 95% confidence interval, 0.9-3.4). Our predictive model for severe preeclampsia, which included only these 4 variables, had a sensitivity of 76% and a specificity of 46%. CONCLUSION: Even after incorporation of the strongest risk factors, our predictive model had only modest sensitivity and specificity for discrimination of patients at risk for development of severe preeclampsia. The addition of the human chorionic gonadotropin and alpha-fetoprotein biochemical markers did not enhance the model's predictive value for severe preeclampsia.

Prediction of delivery among women with early preterm labor by means of clinical characteristics alone.

OBJECTIVE: This study was undertaken to assess whether individual clinical factors or combinations thereof could be used to accurately predict the risk of delivery within 1 week of admission among women with preterm labor and minimal cervical dilatation. STUDY DESIGN: We performed a case-control study of patients admitted to our institution with preterm labor and minimal cervical dilatation. A case patient was a patient who sought treatment with uterine contractions between 24 and 34 weeks' gestation with cervical dilatation 70 potential predictors was recorded. Statistical analysis consisted of bivariate and multivariable methods. We also generated a multivariable clinical predictive model with the purpose of detecting a proportion as high as possible of those destined to be delivered within 1 week (high sensitivity). We estimated that we would need 50 case patients and 150 control subjects to detect an odds ratio of 2.5 for risk factors with a prevalence of 20%, an alpha error of.05, a beta error of.20, and a control subject/case patient ratio of 3:1. RESULTS: Three variables were eligible for inclusion in our logistic models according to the bivariate analyses-bleeding on admission, substance abuse, and admission white blood cell count >/=14,000 cells/microL. The simplest and most favorable model included only 2 variables, bleeding and substance abuse, and yielded a sensitivity of 46% and a specificity of 76%. The full 3-variable model had similar test characteristics. For no model were we able to achieve a sensitivity >/=50%. CONCLUSION: The results of this case-control study suggest that combinations of clinical factors do not yield an adequate level of discrimination to be used alone for predicting the likelihood of delivery within 1 week among patients with minimal degrees of cervical dilatation.

Selection of delivery method in pregnancies complicated by autoimmune thrombocytopenia: a decision analysis.

OBJECTIVE: To compare three common strategies for selecting delivery methods in term pregnancies complicated by immune thrombocytopenia by contrasting their effects on the number of severely thrombocytopenic neonates delivered vaginally and total cesarean rates. METHODS: We used decision analysis to compare three strategies to select delivery method in women with autoimmune thrombocytopenia, funipuncture at term, intrapartum fetal scalp platelet sampling with delivery mode decisions based on platelet count in the first two strategies, and no testing of fetal platelets with delivery mode determined by standard obstetric criteria. We assumed that the goal of each strategy was to minimize the number of severely thrombocytopenic neonates delivered vaginally while maintaining an acceptable cesarean rate. Severe thrombocytopenia was defined as under 50,000 platelets per microL. Probabilities with ranges (used in sensitivity analyses) were derived from the medical literature. RESULTS: Of the two testing strategies, funipuncture was clearly preferable. Funipuncture resulted in zero cases of severely thrombocytopenic neonates delivered vaginally (as did scalp sampling), with a lower overall cesarean rate compared with fetal scalp sampling (36.6% versus 69.1%). Compared with the no-testing strategy, the funipuncture strategy reduced the number of severely thrombocytopenic neonates delivered vaginally (0 versus 82 per 1000) with a modest increase in the cesarean rate (1.9 cesareans to prevent vaginal delivery of one severely thrombocytopenic neonate). CONCLUSION: Fetal scalp sampling should be abandoned in favor of funipuncture when testing for thrombocytopenia.

Predicting delivery within 48 hours in women treated with parenteral tocolysis.

OBJECTIVE: To develop a prediction rule using clinical admission characteristics for women treated with parenteral tocolysis for preterm labor who are at highest risk of delivery within 48 hours. METHODS: We performed a case-control study of patients treated with magnesium sulfate for idiopathic preterm labor. A case was defined as a patient who received magnesium sulfate tocolysis and delivered within 48 hours of admission. We selected a 48-hour delay to delivery as a clinically relevant endpoint for the maximization of steroid benefit. Controls were patients who received magnesium sulfate tocolysis and remained undelivered 48 hours after admission. Cases and controls were identified by merging a pharmacy billing database with International Classification of Disease codes for premature labor. Medical records were reviewed and risk factor information was obtained. We focused on risk factors within the first hour of admission, because our goal was to identify patients at high risk of delivery early in their hospital course. Backward stepwise logistic regression was used to develop explanatory and predictive models. The focus of the predictive model was to maximize the test's sensitivity and negative predictive value. RESULTS: We identified 50 cases and 150 controls. The following six variables were included in the initial multivariable models based on bivariate analyses: white blood cell count at least 14.0 (1000/microL), cervical dilation at least 2 cm, bleeding, substance abuse, parity, and previous abortion. A two-variable model containing cervical dilation and bleeding had an overall accuracy of 73%, sensitivity of 62%, and specificity of 76%, and it was as sensitive and specific as more complex models. CONCLUSION: Cervical dilation of at least 2 cm and bleeding on admission had an overall accuracy of 73% in predicting the likelihood of delivery within 48 hours in women receiving magnesium sulfate.

Diagnosis of fetal renal anomalies.

Urinary tract abnormalities are fairly common in the perinatal period. Ultrasonography is an effective diagnostic tool for identifying fetal urinary tract anomalies and can be helpful in establishing prognosis and guiding treatment decisions. The sonographer is encouraged to characterize and localize the fetal urinary tract abnormality when identified. In doing so, the correct diagnosis can be selected from the differential possibilities, providing vital clinical information needed to develop a care plan for both the pregnant woman and her fetus.

Tocolysis of preterm contractions does not improve preterm delivery rate or perinatal outcomes.

To determine whether hospital admission and parenteral tocolysis of patients with threatened preterm labor results in a decreased preterm delivery rate and improved perinatal outcome, we performed a prospective cohort study comparing tocolytic treatment versus no tocolytic treatment. Women between 20 and 37 weeks' gestation who presented with at least eight uterine contractions per hour and a cervical examination <2 cm dilated, <80% effaced, and no cervical change over a 2-hr period were entered into the study. Exclusion criteria included cervical change, multiple gestation, chorioamnionitis, rupture of membranes, placenta previa or abruption, undiagnosed vaginal bleeding, and prior tocolytic therapy in the current pregnancy. Seventy-five patients were admitted to the hospital for tocolysis (tocolysis cohort) and 81 were observed and discharged to home (observation cohort). There was no significant difference in mean gestational age at delivery, mean birth weight, or in preterm delivery rate between the two cohorts. Four of the eight women in the observation cohort who delivered preterm had a history of preterm delivery. We conclude that discharging women with preterm contractions without objective evidence of labor does not result in an increase in preterm births. More importantly, tocolysis did not decrease the preterm delivery rate in this cohort.

Predictive factors for neonatal morbidity in neonates with an umbilical arterial cord pH less than 7.00.

OBJECTIVE: Fewer than 50% of neonates with an umbilical arterial pH < 7.00 have neonatal complications. Our objective was to identify clinical predictive factors for adverse outcomes in this group of neonates. STUDY DESIGN: In this case-control study both cases and controls had an umbilical arterial cord pH < 7.00. Cases were defined as those neonates who had seizures, grade 3 to 4 intraventricular hemorrhage, gastrointestinal dysfunction, respiratory distress syndrome requiring intubation, sepsis, or death. Controls had an umbilical arterial cord pH < 7.00 and no complications. A multivariable prediction model was created, with variables having an association with adverse outcome by bivariate analyses, attempting to predict which neonates in this umbilical arterial pH range are at greatest risk for adverse outcomes. RESULTS: We identified 73 of 10,705 neonates born between July 1992 and October 1996 with an umbilical arterial cord pH < 7.00. Thirty-five neonates met our case definition, and the remaining 38 composed the control group. Cases had significantly lower arterial pH values and 1- and 5-minute Apgar scores, greater arterial base deficit values, and a higher incidence of abruptio placentae and maternal cocaine use. More cases were delivered before 34 weeks. There were three neonatal deaths, two cases of grade 3 or 4 intraventricular hemorrhage, five cases of gastrointestinal dysfunction, and four cases of neonatal seizures. In our predictive model for adverse neonatal outcome, an arterial base deficit > or = 16 mmol/L and a 5-minute Apgar score < 7 had a sensitivity and a specificity of 79% and 80.8%, respectively. CONCLUSION: Neonatal morbidity in neonates with an umbilical arterial cord pH < 7.00 can be predicted by a high arterial base deficit value and low 5-minute Apgar score.