The Role of cfDNA Biomarkers and Patient Data in the Early Prediction of Preeclampsia: Artificial Intelligence Model.

OBJECTIVE: Accurate individualized assessment of preeclampsia risk enables the identification of patients most likely to benefit from initiation of low-dose aspirin at 12-16 weeks' gestation when there is evidence for its effectiveness, as well as guiding appropriate pregnancy care pathways and surveillance. The primary objective of this study was to evaluate the performance of artificial neural network models for the prediction of preterm preeclampsia (<37 weeks' gestation) using patient characteristics available at the first antenatal visit and data from prenatal cell-free DNA (cfDNA) screening. Secondary outcomes were prediction of early onset preeclampsia (<34 weeks' gestation) and term preeclampsia (≥37 weeks' gestation). METHODS: This secondary analysis of a prospective, multicenter, observational prenatal cfDNA screening study (SMART) included singleton pregnancies with known pregnancy outcomes. Thirteen patient characteristics that are routinely collected at the first prenatal visit and two characteristics of cfDNA, total cfDNA and fetal fraction (FF), were used to develop predictive models for early-onset (<34 weeks), preterm (<37 weeks), and term (≥37 weeks) preeclampsia. For the models, the 'reference' classifier was a shallow logistic regression (LR) model. We also explored several feedforward (non-linear) neural network (NN) architectures with one or more hidden layers and compared their performance with the LR model. We selected a simple NN model built with one hidden layer and made up of 15 units. RESULTS: Of 17,520 participants included in the final analysis, 72 (0.4%) developed early onset, 251 (1.4%) preterm, and 420 (2.4%) term preeclampsia. Median gestational age at cfDNA measurement was 12.6 weeks and 2,155 (12.3%) had their cfDNA measurement at 16 weeks' gestation or greater. Preeclampsia was associated with higher total cfDNA (median 362.3 versus 339.0 copies/ml cfDNA; p<0.001) and lower FF (median 7.5% versus 9.4%; p<0.001). The expected, cross-validated area under the curve (AUC) scores for early onset, preterm, and term preeclampsia were 0.782, 0.801, and 0.712, respectively for the LR model, and 0.797, 0.800, and 0.713, respectively for the NN model. At a screen-positive rate of 15%, sensitivity for preterm preeclampsia was 58.4% (95% CI 0.569, 0.599) for the LR model and 59.3% (95% CI 0.578, 0.608) for the NN model.The contribution of both total cfDNA and FF to the prediction of term and preterm preeclampsia was negligible. For early-onset preeclampsia, removal of the total cfDNA and FF features from the NN model was associated with a 6.9% decrease in sensitivity at a 15% screen positive rate, from 54.9% (95% CI 52.9-56.9) to 48.0% (95% CI 45.0-51.0). CONCLUSION: Routinely available patient characteristics and cfDNA markers can be used to predict preeclampsia with performance comparable to other patient characteristic models for the prediction of preterm preeclampsia. Both LR and NN models showed similar performance.

Impact of high-risk prenatal screening results for 22q11.2 deletion syndrome on obstetric and neonatal management: Secondary analysis from the SMART study.

OBJECTIVE: One goal of prenatal genetic screening is to optimize perinatal care and improve infant outcomes. We sought to determine whether high-risk cfDNA screening for 22q11.2 deletion syndrome (22q11.2DS) affected prenatal or neonatal management. METHODS: This was a secondary analysis from the SMART study. Patients with high-risk cfDNA results for 22q11.2DS were compared with the low-risk cohort for pregnancy characteristics and obstetrical management. To assess differences in neonatal care, we compared high-risk neonates without prenatal genetic confirmation with a 1:1 matched low-risk cohort. RESULTS: Of 18,020 eligible participants enrolled between 2015 and 2019, 38 (0.21%) were high-risk and 17,982 (99.79%) were low-risk for 22q11.2DS by cfDNA screening. High-risk participants had more prenatal diagnostic testing (55.3%; 21/38 vs. 2.0%; 352/17,982, p < 0.001) and fetal echocardiography (76.9%; 10/13 vs. 19.6%; 10/51, p < 0.001). High-risk newborns without prenatal diagnostic testing had higher rates of neonatal genetic testing (46.2%; 6/13 vs. 0%; 0/51, P < 0.001), echocardiography (30.8%; 4/13 vs. 4.0%; 2/50, p = 0.013), evaluation of calcium levels (46.2%; 6/13 vs. 4.1%; 2/49, P < 0.001) and lymphocyte count (53.8%; 7/13 vs. 15.7%; 8/51, p = 0.008). CONCLUSIONS: High-risk screening results for 22q11.2DS were associated with higher rates of prenatal and neonatal diagnostic genetic testing and other 22q11.2DS-specific evaluations. However, these interventions were not universally performed, and >50% of high-risk infants were discharged without genetic testing, representing possible missed opportunities to improve outcomes for affected individuals.

Performance of prenatal cfDNA screening for sex chromosomes.

PURPOSE: The aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation. METHODS: This was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies. RESULTS: A total of 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs, and fetal sex was determined in 17,297, 10,333, and 14,486 pregnancies, respectively. Sensitivity, specificity, and positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%. CONCLUSION: Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.

Obstetrical, perinatal, and genetic outcomes associated with nonreportable prenatal cell-free DNA screening results.

BACKGROUND: The clinical implications of nonreportable cell-free DNA screening results are uncertain, but such results may indicate poor placental implantation in some cases and be associated with adverse obstetrical and perinatal outcomes. OBJECTIVE: This study aimed to assess the outcomes of pregnancies with nonreportable cell-free DNA screening in a cohort of patients with complete genetic and obstetrical outcomes. STUDY DESIGN: This was a prespecified secondary analysis of a multicenter prospective observational study of prenatal cell-free DNA screening for fetal aneuploidy and 22q11.2 deletion syndrome. Participants who underwent cell-free DNA screening from April 2015 through January 2019 were offered participation. Obstetrical outcomes and neonatal genetic testing results were collected from 21 primary-care and referral centers in the United States, Europe, and Australia. The primary outcome was risk for adverse obstetrical and perinatal outcomes (aneuploidy, preterm birth at <28, <34, and <37 weeks' gestation, preeclampsia, small for gestational age or birthweight <10th percentile for gestational week, and a composite outcome that included preterm birth at <37 weeks, preeclampsia, small for gestational age, and stillbirth at >20 weeks) after nonreportable cell-free DNA screening because of low fetal fraction or other causes. Multivariable analyses were performed, adjusting for variables known to be associated with obstetrical and perinatal outcomes, nonreportable results, or fetal fraction. RESULTS: In total, 25,199 pregnant individuals were screened, and 20,194 were enrolled. Genetic confirmation was missing in 1165 (5.8%), 1085 (5.4%) were lost to follow-up, and 93 (0.5%) withdrew; the final study cohort included 17,851 (88.4%) participants who had cell-free DNA, fetal or newborn genetic confirmatory testing, and obstetrical and perinatal outcomes collected. Results were nonreportable in 602 (3.4%) participants. A sample was redrawn and testing attempted again in 427; in 112 (26.2%) participants, results were again nonreportable. Nonreportable results were associated with higher body mass index, chronic hypertension, later gestational age, lower fetal fraction, and Black race. Trisomy 13, 18, or 21 was confirmed in 1.6% with nonreportable tests vs 0.7% with reported results (P=.013). Rates of preterm birth at <28, 34, and 37 weeks, preeclampsia, and the composite outcome were higher among participants with nonreportable results, and further increased among those with a second nonreportable test, whereas the rate of small for gestational age infants was not increased. After adjustment for confounders, the adjusted odds ratios were 2.2 (95% confidence interval, 1.1-4.4) and 2.6 (95% confidence interval, 0.6-10.8) for aneuploidy, and 1.5 (95% confidence interval, 1.2-1.8) and 2.1 (95% confidence interval, 1.4-3.2) for the composite outcome after a first and second nonreportable test, respectively. Of the patients with nonreportable tests, 94.9% had a live birth, as opposed to 98.8% of those with reported test results (adjusted odds ratio for livebirth, 0.20 [95% confidence interval, 0.13-0.30]). CONCLUSION: Patients with nonreportable cell-free DNA results are at increased risk for a number of adverse outcomes, including aneuploidy, preeclampsia, and preterm birth. They should be offered diagnostic genetic testing, and clinicians should be aware of the increased risk of pregnancy complications.

Selective fetal termination for preeclampsia treatment in a dichorionic gestation with a triploid fetus: A case report.

Background: Triploidy is commonly associated with the development of early-onset preeclampsia. While previable preeclampsia is often a contraindication to prolonging pregnancy, there may be rare circumstances in which an alternative approach may be offered. Case: A nulliparous patient with a dichorionic twin gestation, recently diagnosed triploidy in one twin, and history of chronic hypertension presented at 18 weeks of gestation with signs and symptoms suggestive of preeclampsia. After symptomatic therapy and laboratory evaluations, selective fetal termination of the affected twin was elected and performed without complications. The patient subsequently delivered a healthy newborn at 37 weeks of gestation. Conclusion: Selective fetal termination may be considered a management option for previable preeclampsia in a dichorionic gestation with triploid fetus and was associated with a favorable outcome in this case.

Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome.

BACKGROUND: Historically, prenatal screening has focused primarily on the detection of fetal aneuploidies. Cell-free DNA now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2 deletion syndrome, large cohort studies with confirmatory postnatal testing to assess test performance have not been reported. OBJECTIVE: This study aimed to assess the performance of single-nucleotide polymorphism-based, prenatal cell-free DNA screening for detection of 22q11.2 deletion syndrome. STUDY DESIGN: Patients who underwent single-nucleotide polymorphism-based prenatal cell-free DNA screening for 22q11.2 deletion syndrome were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation using chromosomal microarrays. The primary outcome was sensitivity, specificity, positive predictive value, and negative predictive value of cell-free DNA screening for the detection of all deletions, including the classical deletion and nested deletions that are ≥500 kb, in the 22q11.2 low-copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2 deletion syndrome and performance of an updated cell-free DNA algorithm that was evaluated with blinding to the pregnancy outcome. RESULTS: Of the 20,887 women enrolled, a genetic outcome was available for 18,289 (87.6%). A total of 12 22q11.2 deletion syndrome cases were confirmed in the cohort, including 5 (41.7%) nested deletions, yielding a prevalence of 1 in 1524. In the total cohort, cell-free DNA screening identified 17,976 (98.3%) cases as low risk for 22q11.2 deletion syndrome and 38 (0.2%) cases as high risk; 275 (1.5%) cases were nonreportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% confidence interval, 42.8-94.5); specificity of 99.84% (95% confidence interval, 99.77-99.89); positive predictive value of 23.7% (95% confidence interval, 11.44-40.24), and negative predictive value of 99.98% (95% confidence interval, 99.95-100). None of the cases with a nonreportable result was diagnosed with 22q11.2 deletion syndrome. The updated algorithm detected 10 of 12 cases (83.3%; 95% confidence interval, 51.6-97.9) with a lower false positive rate (0.05% vs 0.16%; P<.001) and a positive predictive value of 52.6% (10/19; 95% confidence interval, 28.9-75.6). CONCLUSION: Noninvasive cell-free DNA prenatal screening for 22q11.2 deletion syndrome can detect most affected cases, including smaller nested deletions, with a low false positive rate.

Cell-free DNA screening for trisomies 21, 18, and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation.

BACKGROUND: Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a lack of follow-up genetic testing to confirm the outcomes and accurately assess test performance, particularly in women at a low risk for aneuploidy. OBJECTIVE: To measure and compare the performance of cell-free DNA screening for trisomies 21, 18, and 13 between women at a low and high risk for aneuploidy in a large, prospective cohort with genetic confirmation of results STUDY DESIGN: This was a multicenter prospective observational study at 21 centers in 6 countries. Women who had single-nucleotide-polymorphism-based cell-free DNA screening for trisomies 21, 18, and 13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. The test performance and test failure (no-call) rates were assessed for the cohort, and women with low and high previous risks for aneuploidy were compared. An updated cell-free DNA algorithm blinded to the pregnancy outcome was also assessed. RESULTS: A total of 20,194 women were enrolled at a median gestational age of 12.6 weeks (interquartile range, 11.6-13.9). The genetic outcomes were confirmed in 17,851 cases (88.4%): 13,043 (73.1%) low-risk and 4808 (26.9%) high-risk cases for aneuploidy. Overall, 133 trisomies were diagnosed (100 trisomy 21; 18 trisomy 18; 15 trisomy 13). The cell-free DNA screen positive rate was lower in the low-risk vs the high-risk group (0.27% vs 2.2%; P<.0001). The sensitivity and specificity were similar between the groups. The positive predictive value for the low- and high-risk groups was 85.7% vs 97.5%; P=.058 for trisomy 21; 50.0% vs 81.3%; P=.283 for trisomy 18; and 62.5% vs 83.3; P=.58 for trisomy 13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. The trisomy rate was higher in the 287 cases with no-call results than patients with a result on a first draw (2.8% vs 0.7%; P=.001). The updated algorithm showed similar sensitivity and specificity to the study algorithm with a lower no-call rate. CONCLUSION: In women at a low risk for aneuploidy, single-nucleotide-polymorphism-based cell-free DNA has high sensitivity and specificity, positive predictive value of 85.7% for trisomy 21 and 74.3% for the 3 common trisomies. Patients who receive a no-call result are at an increased risk of aneuploidy and require additional investigation.

Adherence and acceptability of telehealth appointments for high-risk obstetrical patients during the coronavirus disease 2019 pandemic.

Background: Telehealth has been successfully implemented for the delivery of obstetrical care. However, little is known regarding the attitudes and acceptability of patients and providers in high-risk obstetrics and whether the implementation of a telehealth model improves access to care in nonrural settings. Objective: This study aimed to describe patient and provider attitudes toward telehealth for the delivery of high-risk obstetrical care in a large healthcare system with both urban and suburban settings and to determine whether the implementation of a telehealth model improves patient adherence to scheduled appointments in this patient population. Study Design: Two self-administered surveys were designed. The first survey was sent to all high-risk obstetrical patients who received a telehealth visit between March 1, 2020, and May 30, 2020. The second survey was designed for providers who participated in these visits. We also compared the attended, cancelled, and no-show visit rates before (March 1 to May 30, 2019) and after (March 1 to May 30, 2020) the telehealth implementation and telehealth vs in-person visits in 2020. We reviewed scheduled high-risk prenatal care appointments, diabetes mellitus education sessions, and genetic counseling and Maternal-Fetal Medicine consultations. Results: A total of 91 patient surveys and 33 provider surveys were analyzed. Overall, 86.9% of patients were satisfied with the care they received and 78.3% would recommend telehealth visits to others. Notably, 87.8% of providers reported having a positive experience using telehealth, and 90.9% believed that telehealth improved patients' access to care. When comparing patient and provider preference regarding future obstetrical care after experiencing telehealth, 73.8% of patients desired a combination of in-person and telehealth visits during their pregnancy. However, a significantly higher rate of providers preferred in-person than telehealth visits (56% vs 23%, P=.024, respectively). When comparing visits between 2019 and 2020, there was a significantly lower rate of no-show appointments (8.49% vs 4.61%, P<.001), patient-cancelled appointments (7.06% vs 4.96%, P<.001), and patient same-day cancellations (2.30% vs 1.35%, P<.001) with the implementation of telehealth. There was also a significantly lower rate of patient-cancelled appointments (3.82% vs 5.44%, P=.021) and patient same-day cancellations (0.60% vs 1.65%, P=.002) with those receiving telehealth visits than in-person visits in 2020. Conclusion: The implementation of a telehealth model in high-risk obstetrics has the potential to improve access to high-risk obstetrical care, by reducing the rate of missed appointments. Both patients and providers surveyed expressed a high rate of satisfaction with telehealth visits and a desire to integrate telehealth into the traditional model of high-risk obstetrical care.

The care of pregnant women during the COVID-19 pandemic - response of a large health system in metropolitan New York.

The rapid progression of the coronavirus disease 2019 (COVID-19) outbreak presented extraordinary challenges to the US health care system, particularly straining resources in hard hit areas such as the New York metropolitan region. As a result, major changes in the delivery of obstetrical care were urgently needed, while maintaining patient safety on our maternity units. As the largest health system in the region, with 10 hospitals providing obstetrical services, and delivering over 30,000 babies annually, we needed to respond to this crisis in an organized, deliberate fashion. Our hospital footprint for Obstetrics was dramatically reduced to make room for the rapidly increasing numbers of COVID-19 patients, and established guidelines were quickly modified to reduce potential staff and patient exposures. New communication strategies were developed to facilitate maternity care across our hospitals, with significantly limited resources in personnel, equipment, and space. The lessons learned from these unexpected challenges offered an opportunity to reassess the delivery of obstetrical care without compromising quality and safety. These lessons may well prove valuable after the peak of the crisis has passed.

Recurrence of extreme serum analytes in consecutive pregnancies and association with obstetrical outcomes.

OBJECTIVE: To evaluate if presence of extreme maternal serum biochemical analytes recurs in consecutive pregnancies. We hypothesized that presence of >1 extreme analyte in prior pregnancy is associated with increased risk of adverse pregnancy outcome in subsequent pregnancy. METHODS: Retrospective cohort study of singleton pregnancies evaluated and delivered in 2 consecutive pregnancies (2011-2015). Adverse outcomes were defined as indicated preterm delivery before 37 completed weeks due to preeclampsia, fetal growth restriction or other complications. RESULTS: First and second trimester maternal serum analytes were assessed in 1434 patients in 2 consecutive pregnancies. The presence of >1 extreme serum analyte in prior pregnancy significantly increased likelihood of >1 extreme analyte in subsequent pregnancy. The likelihood increased as number of prior extreme markers increased. In patients with normal outcomes and 2 or more extreme serum analytes in prior pregnancy, there was an increased incidence of adverse pregnancy outcomes in subsequent pregnancy with relative risk (RR) of 5.42 [95% CI 1.6-18.3]. CONCLUSIONS: The presence of more than 1 extreme serum marker in one pregnancy increases likelihood of recurrence in subsequent pregnancies. Risk of adverse outcomes in subsequent pregnancy can be evaluated based on biochemistry results as well as prior pregnancy outcomes.

Elevated maternal serum-free ß-human chorionic gonadotropin (ß-hCG) and reduced risk of spontaneous preterm delivery.

Objective: To evaluate the relationship between first and second trimester maternal serum-free ß-hCG and the risk of spontaneous preterm delivery (PTD). Study design: This was a case-control study of women evaluated and delivered at our institution from 2011 to 2015. Spontaneous PTD was defined as delivery before 37 weeks due to spontaneous preterm labor or premature rupture of membranes. Patient with multifetal gestation and those with medically indicated term or PTD were excluded. Results: Of 877 women meeting the inclusion criteria, 173 delivered preterm and 704 delivered at term, and 8.1% had high free ß-hCG in one or both trimesters. High maternal first and/or second trimester free ß-hCG (≥95th percentile) was associated with lower rates of PTD. Thirty-two women with high free ß-hCG in both first and second trimesters delivered at term. Gestational age at delivery and birth weights were lower in women who did not have high free ß-hCG in any trimester. Low free ß-hCG (≤5th percentile) in either trimester was not associated with an increased or decreased likelihood of PTD. Logistic regression demonstrated an independent association of high free ß-hCG (≥95th percentile) with a reduced likelihood of PTD. Stratified analysis revealed a stronger impact of this association in women with no prior history of PTD. Conclusions: High free ß-hCG, in the absence of risk factors for medically indicated PTD, is associated with a reduced likelihood of spontaneous PTD and may represent a marker indicating lower risk.

Quantitative Ultrasound Analysis of Proximal and Distal Cervical Tissue Echogenicity in Premature Cervical Remodeling.

OBJECTIVES: To determine whether a novel, noninvasive quantitative ultrasound (US) technique can detect differences in proximal and distal cervical tissue echogenicity in women with and without a shortened cervical length (CL). METHODS: We conducted a retrospective case-control study of singleton pregnancies at 16 to 26 weeks' gestation in which a transvaginal US examination was performed to measure CL from 2013 to 2015. Initial CLs in cases and controls were less than 2.5 cm and 2.5 cm or greater, respectively. For each US image, a region of interest was selected in the proximal and distal cervical stroma, in both the anterior and posterior cervical lips. The Floyd-Steinberg dithering algorithm transformed grayscale pixels in each region of interest into a binary map. A histogram tabulated the number of black and white pixels, allowing determination of the percent echogenicity. The difference in the percent echogenicity was calculated by subtracting the distal cervical echogenicity (average of anterior and posterior lips) from the proximal cervical echogenicity (average of anterior and posterior lips). RESULTS: Ultrasound images from 177 women were analyzed. There was a difference in the percent echogenicity (P < .0001) when comparing women with a short cervix (mean ± SD, 9.8 ± 10.1; n = 102) to women with a normal CL (17.2 ± 9.5; n = 75). Differences were attributable to changes in proximal (P < .008) rather than distal cervical echogenicity. Regardless of CL, the proximal cervix was more echogenic than the distal cervix. CONCLUSIONS: A quantitative US analysis of cervical tissue can detect differences in echogenicity between the proximal and distal cervix in the second trimester. Proximal cervical echogenicity is lower with CL of less than 2.5 cm compared to a normal CL.

Effect of Maternal Body Mass Index and Amniotic Fluid Index on the Accuracy of Sonographic Estimation of Fetal Weight in Late Gestation.

OBJECTIVE: The objective of this study was to determine the effect, if any, of maternal body mass index (BMI) and amniotic fluid index (AFI) on the accuracy of sonographic estimated fetal weight (EFW) at 40 to 42 weeks' gestation. METHODS: This was a retrospective cohort study of singleton gestations with ultrasound performed at 40 to 42 weeks from 2010 to 2013. In this study, patients with documented BMI and sonographic EFW and AFI, concurrently, within 7 days of delivery were included. Chronic medical conditions and fetal anomalies were excluded from this study. The primary variable of interest was the rate of substantial error in EFW, defined as absolute percentage error (APE) >10%. RESULTS: A total of 1,000 pregnancies were included. Overall, the APE was 6.0 ± 4.5% and the rate of substantial error was 17.4% (n = 174). There was no significant difference in APE or rate of substantial error between BMI groups. In the final multivariable logistic regression model, the rate of substantial error was increased in women with oligohydramnios (OR 1.79; 95% CI: 1.10-2.92). Furthermore, oligohydramnios was significantly more likely to overestimate EFW while polyhydramnios was more likely to underestimate EFW. Maternal BMI did not affect the accuracy of sonographic EFW. CONCLUSION: Sonographic EFW may be affected by extremes of AFI in the postdates period. Maternal BMI does not affect EFW accuracy at 40 to 42 weeks.

Prenatal sonographic findings in a case of Wolman's disease.

No published case of Wolman's disease has described the prenatal sonographic findings. We present a case in which a third-trimester sonographic examination demonstrated fetal hepatomegaly and bilateral adrenal echogenicity suggestive of diffuse calcification. Wolman's disease, also known as lysosomal acid lipase (LIPA) deficiency, is a rare autosomal-recessive disorder characterized by complete absence of the LIPA enzyme. The diagnosis of Wolman's disease was made postnatally by biochemical testing, which indicated absence of LIPA enzyme activity and gene sequencing, which confirmed homozygosity for the G66V mutation within the LIPA gene. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:66-68, 2018.

Maternal Body Mass Index and Amniotic Fluid Index in Late Gestation.

OBJECTIVES: To determine the effect, if any, of an increasing maternal body mass index (BMI) on sonographically diagnosed oligohydramnios in late gestation and how it subsequently affects obstetric and neonatal outcomes. METHODS: This retrospective cohort study evaluated all women with singleton gestations who had a sonographic examination at 40 to 42 weeks' gestational age at North Shore University Hospital from 2010 through 2013. Underweight women (prepregnancy BMI < 18.5 kg/m2 ) were excluded because of higher rates of oligohydramnios and fetal growth restriction. Patients were classified into 5 groups by late-pregnancy BMI. The primary variable of interest was the diagnosis of oligohydramnios (amniotic fluid index < 5 cm). Secondary variables of interest included the mode of delivery and indication for primary cesarean delivery. A multivariable logistic regression analysis was performed. RESULTS: Oligohydramnios was identified in 189 of 1671 patients (11.3%). There was no significant difference in the amniotic fluid index between BMI groups. The rate of primary cesarean delivery increased with each successive BMI group (P < .001) such that women in the class III obesity group had an approximately 3-fold higher rate of primary cesarean delivery than women in the normal BMI group and a 2-fold higher rate than women in the overweight BMI group. In the final multivariable logistic regression model, a high BMI, nulliparity, and excessive gestational weight gain were associated with primary cesarean delivery. However, oligohydramnios did not contribute significantly to the model. CONCLUSIONS: The maternal BMI is not associated with oligohydramnios in late gestation. An increasing maternal BMI significantly increases the risk of primary cesarean delivery.

Ultrasonic Assessment of Cervical Heterogeneity for Prediction of Spontaneous Preterm Birth: A Feasibility Study.

BACKGROUND: In a normal pregnancy, cervical collagen fibers remain organized in predictable patterns throughout most of the gestation. Cervical remodeling reflects a rearrangement of collagen fibers in which they become increasingly disordered and contribute to the pathogenesis of spontaneous preterm birth. Quantitative ultrasound analysis of cervical tissue echotexture may have the capacity to identify microstructural changes before the onset of cervical shortening. OBJECTIVE: The primary objective of this study was to examine the utility of a novel quantitative sonographic marker, the cervical heterogeneity index (HI), which reflects the relative organization of cervical collagen fibers. Also, we aimed to determine an optimal HI cut-point to predict spontaneous preterm birth. STUDY DESIGN: This retrospective cohort study employed a novel image-processing technique on transvaginal ultrasound images of the cervix in gestations between 14 and 28 completed weeks. The transvaginal sonography images were analyzed in MATLAB (MathWorks, Natick, MA) using a custom image-processing technique that assessed the relative heterogeneity of the cervical tissue. RESULTS: A total of 151 subjects were included in the study. The mean HI in subjects who delivered preterm and at term was 8.28 ± 3.73 and 12.35 ± 5.80, respectively (p < 0.0001). Thus, decreased tissue heterogeneity was associated with preterm birth, and increased tissue heterogeneity was associated with delivery at term. In our study population, preterm birth was associated with a short cervix (<2.5 cm), history of preterm birth and lower HI, and our findings indicate that HI may improve prediction of preterm birth. CONCLUSION: Quantitative ultrasound measurement of the cervical HI is a promising, noninvasive tool for early prediction of spontaneous preterm birth.

Maternal Serum Analytes as Predictors of Fetal Growth Restriction with Different Degrees of Placental Vascular Dysfunction.

Abnormal levels of maternal serum analytes have been associated with fetal growth restriction (FGR) and preeclampsia secondary to placental vascular dysfunction. Accurately identifying the FGR fetuses at highest risk for adverse outcomes remains challenging. Placental function can be assessed by Doppler analysis of the maternal and fetal circulation. Although the combination of multiple abnormal maternal serum analytes and abnormal Doppler findings is strongly associated with adverse outcomes, the predictive value remains too low to be used as a screening test in a low-risk population. Stratification of cases based on the severity of Doppler abnormalities may improve predictive models.

Uterine fibroids at routine second-trimester ultrasound survey and risk of sonographic short cervix.

OBJECTIVE: To determine whether women with sonographically identified uterine fibroids are at higher risk for a short cervix. METHODS: This retrospective cohort study evaluated all women with singleton gestations who had a routine second-trimester ultrasound at 17-23 weeks gestational age from 2010 to 2013. When fibroids were noted, their presence, number, location and size were recorded. Exclusion criteria included a history of cervical conization or loop electrosurgical excision procedure (LEEP), uterine anomalies, maternal age greater than 40 years, and a previously placed cerclage. The primary variable of interest was short cervix (<25 mm). Secondary variables of interest included gestational age at delivery, mode of delivery, indication for cesarean, malpresentation, birth weight, and Apgar scores. A multivariable logistic regression analysis was performed. RESULTS: Fibroids were identified in 522/10 314 patients (5.1%). In the final multivariable logistic regression model, short cervix was increased in women with fibroids (OR 2.29, 95% CI: 1.40, 3.74). The number of fibroids did not affect the frequency of short cervix. Fibroids were significantly associated with preterm delivery (<37 weeks), primary cesarean, breech presentation, lower birth weight infants, and lower Apgar scores. CONCLUSIONS: Women with uterine fibroids may be at higher risk for a short cervix. Fibroids are also associated with several adverse obstetric and neonatal outcomes.

Maternal serum analytes as predictors of IUGR with different degrees of placental vascular dysfunction.

OBJECTIVES: Our primary objective was to determine the association of maternal serum analytes in pregnancies complicated by intrauterine growth restriction (IUGR) stratified by umbilical artery (UA) Doppler versus pregnancies with appropriately grown for gestational age (AGA) and its potential use as screening model. METHODS: Retrospective cohort evaluating first and second trimester maternal serum aneuploidy screening markers in women complicated with IUGR [90 with absent or reversed end diastolic velocity (AREDV), 46 with UA systolic/diastolic ratio ≥95th percentile and 215 with normal UA Doppler] versus 2590 women with AGA fetuses (control). RESULTS: Extreme levels of each analyte were significantly more common in the IUGR/AREDV group than in AGA group: inhibin A >97th percentile [≥2.27 multiples of the median (MoM)], OR: 41 (95% CI: 21-80); unconjugated estriol <3rd percentile (≤0.6 MoM), OR: 17.2 (95% CI: 8.1-42); AFP >97th percentile (≥1.88 MoM), OR: 15 (95% CI: 8.2-27); PAPP-A <3rd percentile (≤0.33 MoM), OR: 13 (95% CI: 6.6-25.5); and free-beta human chorionic gonadotrophin second trimester >97th percentile (≥3.24 MoM), OR: 11.6 (95% CI: 4.2-32). In a subgroup of pregnancies in which all markers were evaluated on each patient, a combination of abnormal markers detected 73% (95% CI: 54-87%) of IUGR/AREDV fetuses. When maternal risk factors were included into the risk calculation, it increased to 91% (95% CI: 76-98%). CONCLUSIONS: Abnormal maternal serum aneuploidy markers preferentially identify those pregnancies at greatest risk of IUGR with AREDV in the UA.

Placental mesenchymal dysplasia with hepatic mesenchymal hamartoma: a case report and literature review.

Placental mesenchymal dysplasia (PMD) is characterized by placentomegaly and grapelike vesicles resembling a partial molar pregnancy and in most cases, a phenotypically normal fetus. Hepatic mesenchymal hamartoma (HMH) is a benign hamartomatous proliferation of mesenchymal liver tissue. PMD has been associated with HMH. Although rare, in combination, it is known to carry a poorer prognosis than in fetuses without structural abnormalities. There are only a few reported cases of PMD and associated HMH with varying management strategies and outcomes, precluding ascertainment of the most appropriate treatment plan. We present a case of PMD with associated cystic HMH resulting in fetal death. We also reviewed the published literature on this issue and explored possible management strategies to prevent adverse fetal and neonatal outcomes.