Clinical implications of crown-rump length discordance at 11 to 14 weeks in dichorionic twins.

BACKGROUND: Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance. OBJECTIVE: This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance. STUDY DESIGN: This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders. RESULTS: Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance. CONCLUSION: Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.

Cell-free DNA screening for trisomy 21 in twin pregnancy: a large multicenter cohort study.

BACKGROUND: Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. OBJECTIVE: This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13. STUDY DESIGN: This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. RESULTS: A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. CONCLUSION: Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.

Is Amniocentesis after CVS Risky?

OBJECTIVE: Approximately, 2% of women who undergo chorionic villi sampling (CVS) will subsequently undergo amniocentesis due to placental mosaicism or sampling/laboratory issues. Our objective was to compare obstetric outcomes in women who underwent both procedures with those who had CVS alone. STUDY DESIGN: Retrospective case-control study of patients with singleton pregnancies undergoing invasive testing from 2010 to 2020 was performed. All women who underwent CVS followed by amniocentesis were compared with a control group who underwent CVS alone matched (2:1) for age and year of pregnancy. Women with pregnancy loss at <16 weeks were excluded from the control group. Pregnancies terminated for genetic abnormalities were excluded. Obstetric outcomes were compared between cases and controls. Student t-test and Fisher's exact test were used for statistical comparison. RESULTS: During the study period 2,539 women underwent CVS, and 66 (2.6%) subsequently underwent amniocentesis. The 66 cases were compared with 132 age-matched controls who underwent CVS alone. Mean maternal age was 36.8 ± 3.4 years, and 43% of women were nulliparous. Amniocentesis was performed due to sampling or laboratory issues in 33% of cases, placental mosaicism in 44%, and further diagnostic testing in 23%. There were no pregnancy losses or stillbirths in either group. Those who had two invasive procedures delivered at similar gestational ages and birthweights and did not have higher rates of adverse outcomes compared with those who underwent CVS alone. CONCLUSION: Patients considering CVS who are concerned about the possibility that a second invasive procedure could be required should be reassured that this does not appear to be associated with higher rates of adverse outcomes. Due to study size, we cannot exclude the possibility of small differences in uncommon outcomes, such as pregnancy loss or stillbirth. KEY POINTS: · Amniocentesis may be recommended after CVS due to mosaicism, sampling issues, or further testing.. · Amniocentesis after CVS is not associated with pregnancy loss or other adverse outcomes compared.. · Patients who have both CVS and amniocentesis deliver at similar gestational ages and birthweights..

Ultrasound detection rates of the placenta accreta spectrum with prior myomectomy.

OBJECTIVE: To describe the performance of ultrasound in detecting placenta accreta spectrum (PAS) in patients with history of prior myomectomy. METHODS: A retrospective cohort study of patients who were referred for sonographic evaluation of the placenta and delivered at a tertiary academic center from 2012 to 2019. Demographic, obstetric, sonographic findings, and pathology information were collected and analyzed using Chi-square, t-tests, and ANOVA analysis. RESULTS: 640 patients met inclusion criteria, including 46 (7.2%) with histologically confirmed PAS. Groups for comparison included those with C-section only (CS), CS-Myomectomy, and Myomectomy-only. Those with CS-Myomectomy were older (38.7 years vs. 35.7 years or 35.5 years, p = .003) and those with CS only were more likely to have an anterior placenta (63.4% vs. 54.5% or 41.8%, p = .005). The rate of PAS was highest in those with Myomectomy only (14.5% vs. 6.1% or 11.4%, p = 0.04). Sensitivity, Specificity, and Predictive Values were lowest in the CS-Myomectomy group, with detection rate and PPV of only 40%. Accuracy, defined as the rate of clinical outcome consistent with imaging, was significantly higher in those with CS only compared to the CS with myomectomy or myomectomy-only groups. Of the histologically confirmed PAS, 11 (23.9%) did not have a placenta previa, and the majority of these occurred in women with prior myomectomy. In the cohort with CS only, the proportion of cases with PAS without placenta previa was 5 of 33 (15.2%) compared to 6 of 13 (46.2%) of PAS in those with prior myomectomy, with or without CS (p = .05). CONCLUSION: In patients with prior uterine surgery referred for sonographic evaluation of the placenta, rates of histology-confirmed PAS were highest in those with prior myomectomy, though ultrasound accuracy was lower in these patients. As ultrasound findings of PAS may be clearer in the presence of placenta previa, the absence of previa in a higher proportion of PAS with prior myomectomy may be related to the observed lower sonographic accuracy in these patients.

Potentially Preventable Primary Cesarean Sections in Future Placenta Accreta Spectrum.

OBJECTIVE: Prior cesarean delivery is a well-known risk factor for placenta accreta spectrum disorders. While primary cesarean section is unavoidable in some patients, in others it may not be clearly indicated. The aim of the study is to determine the proportion of patients with placenta accreta spectrum who had a potentially preventable primary cesarean section and to identify factors associated with preventable placenta accreta spectrum. STUDY DESIGN: This was a single-center retrospective cohort study of women with pathology-confirmed placenta accreta spectrum from 2007 to 2019. Primary cesarean sections were categorized as potentially preventable or unpreventable based on practice consistent with the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine "Safe Prevention of the Primary Cesarean Delivery" recommendations. Fisher's exact test and Mann-Whitney U-test were used for comparison with p <0.05 considered statistically significant. RESULTS: Seventy-two patients had pathology-confirmed placenta accreta spectrum over the course of the study period, 15 (20.8%) of whom required a cesarean hysterectomy at the time of primary cesarean section. Fifty-seven patients had placenta accreta spectrum in a pregnancy following their primary cesarean section. Of these, 29 (50.9%) were considered potentially preventable. Most were performed without clear medical indication (37.9%) or for fetal malpresentation without attempted external cephalic version (37.9%). The remainder were due to arrest of labor not meeting criteria (17.2%) and abnormal or indeterminate fetal heart patterns with documented recovery (6.9%). Of the 11 patients without clear medical indication for primary cesarean section, eight (72.7%) were patient-choice cesarean sections and three (27.3%) were for suspected fetal macrosomia with estimated fetal weights not meeting criteria for cesarean delivery. There was no difference in the incidence of potentially preventable primary cesarean sections before and after the ACOG-SMFM "Safe Prevention of the Primary Cesarean Delivery" publication (48.8 vs. 57.1%, p = 0.59). Privately insured patients were more likely to have a potentially preventable primary cesarean section than those with Medicaid (62.5 vs. 23.5%, p = 0.008) and were more likely to have a primary cesarean section without clear medical indication (81.8 vs. 18.2%, p = 0.004). CONCLUSION: Many patients with placenta accreta spectrum had a potentially preventable primary cesarean section. Most were performed without clear medical indication or for malpresentation without attempted external cephalic version, suggesting that at least a subset of placenta accreta spectrum cases may be preventable. This was particularly true for privately insured patients. These findings call for continued investigation of potentially preventable primary cesarean sections with initiatives to address concerns at the patient, provider, and hospital level. KEY POINTS: · Many patients with placenta accreta spectrum have potentially preventable primary cesarean sections.. · Privately insured patients are more likely to have potentially preventable primary cesarean sections.. · Our findings suggest that at least a subset of placenta accreta spectrum cases may be preventable..

Suspected Placenta Accreta: Using Imaging to Stratify Risk of Morbidity.

OBJECTIVE: This study was aimed to compare clinical outcomes and use of interventions in women with suspected accreta based on the degree of antenatal suspicion. STUDY DESIGN: This was a retrospective cohort study of women with suspected accreta from 2007 to 2019. Included patients had one or more imaging studies suggestive of accreta. Cases were classified as "lower risk" if imaging showed possible signs of accreta including mild or superficial myometrial infiltration, an abnormal uterine contour, an abnormal uteroplacental interface, or loss of the retroplacental hypoechoic zone and "higher risk" if there was clear evidence of more than superficial myometrial infiltration, placental tissue extruding beyond the uterine serosa, bridging vessel(s), or placental lacunae with high velocity and/or turbulent flow. The primary study outcome was a composite maternal morbidity including cesarean hysterectomy, transfusion of blood or blood products, unintentional cystotomy, or intensive care unit (ICU) admission. Chi-square, Fisher's exact test, and Mann-Whitney U-test were used for analysis. RESULTS: A total of 78 women had a suspected accreta on imaging, 36 with "lower risk" features and 42 with "higher risk" features. There were no differences in baseline maternal demographics. Women in the "higher risk" group were more likely to have a placenta previa (p < 0.01) and preoperative consultation with gynecologic oncology (p = 0.04). There was a significant difference in composite maternal morbidity between patients with "lower risk" and "higher risk" features of accreta on imaging (50 vs. 92.9%, p < 0.01). Median gestational age at planned and actual delivery were earlier in the "higher risk" group (36.6 vs. 34.9 weeks, p < 0.01; 36.0 vs. 34.7 weeks, p < 0.01). CONCLUSION: Stratification of women with suspected accreta based on imaging corresponded to rates of maternal morbidity and operative complications, and appears to have been used clinically in selecting timing of delivery and interventions. KEY POINTS: · Increased morbidity with high risk accreta imaging.. · Interventions correlate with accreta imaging risk.. · Imaging can be used to stratify accreta cases..

Maternal morbidity of induction of labor compared to planned cesarean delivery in twin gestations.

OBJECTIVE: To compare maternal morbidity associated with induction of labor (IOL) with planned cesarean delivery (CD) in twin gestations. METHODS: This was a retrospective cohort study of vertex-presenting twin pregnancies ≥24-week gestation delivering at our institution from 2016 to 2017. We compared patients undergoing IOL with patients undergoing planned CD. Demographic and pregnancy outcome data were abstracted from the medical record. Our primary outcome was composite maternal morbidity including severe postpartum hemorrhage (PPH) (EBL >1500 cc), hysterectomy, transfusion, ICU admission, use of ≥2 uterotonic medications or maternal death. These morbidities were also assessed independently. Secondary analyses of maternal morbidity among unplanned CD versus planned CD and successful IOL versus planned CD was also performed. Chi-square, Mann-Whitney U and multivariate logistic regression were used in statistical analysis. RESULTS: Of 211 twin gestations included, 70.6% were nulliparous, the median age was 35.5 years [32-38], and the median gestational age at delivery was 37 weeks [35-38]. One hundred and five underwent IOL and 106 had a planned CD. Composite morbidity was higher in the IOL group versus planned CD group (30.5 versus 11.3%, p = .001). In the IOL group, 64 (61.0%) achieved a vaginal delivery. Patients in the planned CD group were more likely to be >35 years of age (62.3 versus 48.6%, p = .045), nulliparous (80.2 versus 61.0%, p = .002) and deliver preterm (53.8 versus 38.1%, p = .022). Patients with a planned CD had a significantly lower risk of composite morbidity compared to those who had CD after failed IOL (11.3 versus 48.8%, p ≤ .001) and there was no significant difference in composite morbidity in the successful IOL compared to the planned CD group (18.8 versus 11.3%, p = .18). There were four peri-partum hysterectomies, all within the IOL group. CONCLUSION: Labor induction in twins was associated with increased maternal morbidity compared to planned CD. The increase in adverse maternal outcomes was due to those who underwent an IOL and ultimately required CD.

Prenatally diagnosed vasa previa: association with adverse obstetrical and neonatal outcomes.

BACKGROUND: Vasa previa represents a rare prenatal finding with potentially life-threatening risk to the fetus. OBJECTIVE: This study aimed to describe the natural history of prenatally diagnosed vasa previa and evaluate the association between antenatally diagnosed vasa previa and adverse obstetrical and neonatal outcomes. STUDY DESIGN: This was a multicenter descriptive and retrospective study of patients diagnosed prenatally with vasa previa on transvaginal ultrasound in the New York City Maternal-Fetal Medicine Research Consortium centers between 2012 and 2018. Outcomes evaluated included persistence of vasa previa at the time of delivery, gestational age at delivery, indications for unplanned unscheduled delivery, and neonatal course. RESULTS: A total of 165 pregnancies with vasa previa were included, of which 16 were twin gestations. Forty-three cases (26.1%) were noted to resolve on subsequent ultrasound. Of the remaining 122 cases with persistent vasa previa, 46 (37.7%) required unscheduled delivery. Twin gestations were nearly 3 times as likely to require unscheduled delivery as singleton gestations (73.3% vs 25.2%; P<.001). Most infants (70%) were admitted to the neonatal intensive care unit. There was 1 neonatal death (0.9%) because of complications related to prematurity. CONCLUSION: Despite the low neonatal mortality rate with prenatal detection of vasa previa, one-third of patients required unscheduled delivery, and more than half of neonates experienced complications related to prematurity.

Obstetrical Complications and Long-Term Cardiovascular Outcomes.

PURPOSE OF REVIEW: Obstetrical complications including indicated preterm birth (PTB), hypertension (HTN), IUGR, and GDM are risk factors for future cardiovascular disease. To identify patients at risk, the American Heart Association recommends obtaining a detailed obstetric history. Our objective was to determine if non-OB-GYN physicians-in-training obtain an obstetric history when assessing a risk profile for cardiovascular disease and to identify differences based on level of training. In 2019, an anonymous survey was distributed to trainees in internal medicine, cardiology, endocrinology, nephrology, and neurology. Subjects were queried about frequency of asking a history of PTB, IUGR, GDM, and HTN in pregnancy. Survey options were always/frequently/sometimes/rarely/never and were categorized into two groups: "ask" (always/frequently/sometimes) vs. "do not ask" (rarely/never). Comparisons between specialties and levels of training were made using chi-square and Fisher's exact test. Comparisons within subjects were made using McNemar's test. RECENT FINDINGS: The response rate was 64% (210 total possible participants), including 98 internal medicine residents and 37 fellows in cardiology (21), endocrinology (3), nephrology (8), and neurology (5). Asking about medical complications (HTN + GDM) was significantly more common than asking about OB complications (PTB + IUGR) (p < 0.001). Internal medicine residents were less likely than subspecialty fellows to ask about HTN (31% vs. 70%; p < 0.001). There were no differences in likelihood of eliciting OB history based on PGY level. An OB history can identify risk factors for cardiovascular morbidity. Our data demonstrates that physicians caring for women lack awareness on the association between complications in pregnancy and cardiovascular health.

Preeclampsia and low sodium (PALS): A case and systematic review.

Normal physiologic changes in pregnancy include mild hyponatremia. In some cases of preeclampsia, more significant hyponatremia has been associated with syndrome of inappropriate antidiuretic hormone secretion and hypervolemic hyponatremia. A 45-year-old gravida 2, para 0010 with a dichorionic twin gestation was diagnosed with preeclampsia at 30 weeks 6 days and noted to have concomitant hyponatremia of 125 mEq/L at our institution. Her hyponatremia was initially managed with furosemide and water restriction. She was delivered at 33 weeks 5 days due to worsening preeclampsia and continued significant hyponatremia despite treatment. Her hyponatremia resolved within 48 h after delivery. Our objectives were to discuss trends, treatment, and outcomes of cases with hyponatremia in preeclampsia. We performed a systematic review of the literature using Ovid Medline (1963-2017), Scopus (1962-2017), and PubMed (1963-2017, including Cochrane database). Relevant articles describing any case report of hyponatremia in preeclampsia were identified from the above databases without any time, language, or study limitations. Studies were deemed eligible for inclusion if they described a case of hyponatremia in the setting of preeclampsia. 18 manuscripts detailing 55 cases were identified. Pertinent demographic data and laboratory values were extracted. Maternal management strategy, diagnosis, delivery, and neonatal outcome data were also collected. Mean, range, standard deviation, and percentage calculations were used as applicable. Advanced maternal age (46 %), nulliparity (79 %), and multifetal gestation (34 %) were noted in patients with preeclampsia and low sodium. Hyponatremia was detected on average at 34 weeks gestation. 64 % were diagnosed with preeclampsia with severe features. When reported, diagnoses related to hyponatremia were syndrome of inappropriate antidiuretic hormone secretion (41 %) or hypervolemic hyponatremia (59 %). Indications for delivery included severe hyponatremia unresponsive to conservative measures in addition to other known obstetric or preeclamptic indications. Hyponatremia resolved within 48 h on average in cases where postpartum resolution was reported. It may be prudent to screen women with preeclampsia for electrolyte disturbances as part of their evaluation, especially in the setting of severe features. Initially, hyponatremia may be treated with medical management. In addition to established obstetric or preeclamptic indications, delivery may be considered if severe hyponatremia no longer responds to conservative measures.

Abortion for Fetal Genetic Abnormalities: Type of Abnormality and Gestational Age at Diagnosis.

Background Advances in genetic screening can identify patients at high risk for common genetic conditions early in pregnancy and can facilitate early diagnosis and early abortion. Less common abnormalities might only be diagnosed with invasive testing is performed after structural abnormalities are identified. Objective Our objective was to compare gestational age (GA) at diagnosis and abortion for genetic abnormalities identified based on screening with abnormalities that were not discovered after screening. Study Design All prenatal diagnostic procedures from 2012 to 2017 were reviewed, and singleton pregnancies terminated following diagnosis of genetic abnormalities were identified. Cases diagnosed as the result of screening tests were compared with remaining cases. Conditions were considered "screened for" if they can be suspected by cell-free DNA testing, biochemistry, carrier screening, or if the patient was a known carrier of a single-gene disorder. When abnormal karyotype, microarray, or Noonan's syndrome was associated with abnormal NT, these cases were considered "screened for." GA at abortion was the primary outcome. Fisher's exact test and Mann-Whitney's U test were used for statistical comparison. Results In this study, 268 cases were included. A total of 227 (85%) of abortions were performed for "screened for" disorders, with 210 (93%) of these for karyotype abnormalities, 5 (2%) for microarray abnormalities, and 12 (5%) for single-gene disorders. Forty-one (15%) of abortions were performed for conditions not included in screening, with 8 (19%) of those for karyotype abnormalities, 25 (61%) for microarray abnormalities, and 8 (19%) for single-gene disorders. Invasive testing and abortion occurred at earlier median GA for those with conditions that were screened for: 12 2/7 versus 15 5/7 weeks, p ≤0.001 and 13 5/7 versus 20 0/7 weeks; p ≤0.001. Conclusion Most abortions were for abnormalities that can be suspected early in pregnancy. As many structural abnormalities associated with rare conditions are not identifiable until the mid-trimester, prenatal diagnosis and abortion occurred significantly later. Physicians and patients should be aware of the limitations of genetic screening.

Abortion for fetal indications: Timing of prenatal diagnosis and abortion for structural and genetic abnormalities.

OBJECTIVE: To compare diagnoses in patients undergoing abortion for fetal indications at 15-0/7 to 21-6/7 vs. ≥22-0/7 weeks' gestation. STUDY DESIGN: This retrospective cohort study included women undergoing abortion at ≥15-0/7 weeks' gestation for fetal indications from 2012 to 2018 at our institution. We compared indications (genetic vs. structural only) between groups by gestational age (15-0/7 to 21-6/7 vs. ≥22-0/7 weeks). We performed statistical analysis using Fisher's exact and Mann-Whitney U tests. RESULTS: The 158 women identified included 97 (61.4%) at 15-0/7 to 21-6/7 and 61 (38.6%) at ≥22-0/7 weeks' gestation. Women at an earlier gestational age more commonly had an initial diagnosis of a genetic disorder (41 [42.3%)] vs.10 [16.4%], respectively, p < .001). In 69 cases with initial or subsequent diagnosis of a genetic disorder, there were differences in the types of genetic abnormalities, with common chromosomal abnormalities (including Trisomies 13, 18, and 21) the most frequent diagnosis in those who underwent abortion at 15-0/7 to 21-6/7 weeks and microarray abnormalities more common at ≥22-0/7 weeks (22 [44.9%] vs. 4 [18.2%]) and 7 [14.9%] vs. 11 [50.0%], respectively, p = .01). Routine ultrasonography for fetal anomaly surveillance occurred one week earlier in women undergoing abortion for structural anomalies at 15-0/7 to 21-6/7weeks (median 19-2/7 weeks [interquartile range (IQR) 19 0/7 to 19-5/7 weeks]) compared to ≥22-0/7 weeks (median 20-2/7 weeks [IQR 19 6/7 to 20 4/7 weeks]), p < .001. CONCLUSION: Abortions for genetic indications are performed earlier in gestation compared to those performed for structural abnormalities. Timing of fetal anatomy ultrasound examination correlated with gestational age at abortion for structural abnormalities. IMPLICATIONS: Many states impose gestational-age based abortion bans, with 20-weeks post-fertilization the most common. However, we may not identify fetal abnormalities until close to 22 weeks gestation (20-weeks post-fertilization). Optimizing timing of prenatal diagnosis might mitigate the impact of gestational-age based abortion bans.

Pregnancy Outcomes in Women with Incidentally Detected Unicornuate Uteri.

OBJECTIVE: To estimate the incidence of adverse pregnancy outcomes in women with incidentally detected unicornuate uteri. STUDY DESIGN: This is a descriptive study. Database review identified patients with unicornuate uteri and singleton pregnancies at ≥12 weeks' gestation. Patients were excluded if the diagnosis of unicornuate uterus was made after a midtrimester loss or preterm delivery. Records were reviewed to obtain clinical outcomes. Chi-square test, Fisher's exact test, and Mann-Whitney U-test were used for statistical analysis. RESULTS: Forty patients with 67 pregnancies were included. Most diagnoses were made during infertility work-up (76.2%). There was one midtrimester loss (1.5%). In the remaining 66 pregnancies, median gestational age at delivery was 38 weeks. There were 20 (30.3%) preterm births, 9 (13.6%) spontaneous preterm births, and 11 (16.7%) indicated preterm births. Women with indicated preterm births were more likely to have placental abnormalities. Of the available placental pathology, 45.2% had histological lesions of malperfusion. Cesarean delivery was performed in 77.3% of cases. CONCLUSION: Most women with incidentally detected unicornuate uteri gave birth at term. More than half the preterm births were indicated, with relatively high rates of placental abnormalities. In patients without a poor obstetrical history, rates of midtrimester loss and spontaneous preterm birth were lower than previously described.

Abnormal nuchal translucency: residual risk with normal cell-free DNA screening.

Objective: To determine the proportion of genetic abnormalities that could be identified by cell-free DNA screening in pregnancies with an abnormal nuchal translucency.Methods: From 2015-2017, pregnancies with nuchal translucency ≥ 3.0 mm on ultrasounds were identified. Pregnancies with genetic testing results were included, whether or not cell-free DNA screening was performed. Comparisons of the proportion of genetic abnormalities detectable on cell-free DNA screening versus not detectable were made based on nuchal translucency values (3.0-3.4 mm; ≥3.5 mm) and maternal age (≥35 versus <35 years). Chi-square analysis, Fisher's exact test, and Mann-Whitney U were used for statistical comparison.Results: One hundred ten patients were included, 60 had genetic abnormalities (54.5%), with 44 (73.3%) detectable on cell-free DNA screening and 16 (26.7%) not. In those with nuchal translucency ≥3.5 mm, only 40 of 56 (71.4%) of abnormalities could be detected by cell-free DNA screening. Cell-free DNA screening could identify 27 of 31 abnormalities with nuchal translucency ≥3.5 mm in women ≥35 years but could identify only 13 of 25 genetic abnormalities in younger women (87.1 versus 52.0%; p = .005).Conclusion: A significant proportion of abnormalities in those with nuchal translucency ≥3.5 mm would not be detected by cell-free DNA, especially in younger women.

Diagnostic accuracy of isolated clubfoot in twin compared to singleton gestations.

Background Our objective was to determine the predictive value of the prenatal diagnosis of isolated clubfoot in twin gestations compared to singleton gestations. Methods A prospectively entered ultrasound database was reviewed for all pregnancies scanned at our institution from 2002 to 2014. Cases of suspected clubfoot were identified. Neonates with associated anomalies or aneuploidy, and patients who delivered at other institutions were excluded. Neonatal charts were reviewed for the confirmation of clubfoot. The chi-squared (χ2) test, Fisher's exact test and the Mann-Whitney U test were used in the analysis, with p < 0.05 considered significant. Results Of those women who had prenatal ultrasound and subsequently delivered at our hospital, 84 pregnancies had isolated clubfoot suspected in the antenatal period. Of these pregnancies, 20 were twin gestations and 64 were singleton gestations. Overall, 51/84 (60.7%) pregnancies had clubfoot confirmed during the neonatal period. Of the twin pregnancies, only 35% (7/20) had a confirmed diagnosis of clubfoot at birth compared to 68.8% (44/64) of the singleton pregnancies (P = 0.008). Gestational age at diagnosis, breech presentation, neonatal gender, unilateral vs. bilateral clubfoot and suspicion of clubfoot in the presenting twin (Twin A) vs. the non-presenting twin (Twin B) did not correlate with an accurate diagnosis of clubfoot in twins. Conclusion False-positive prenatal diagnosis of isolated clubfoot is more common in twin gestations compared to singletons. This may be due to transient malpositioning or a result of diminished space. Obstetric providers should consider the possibility of a false-positive diagnosis and use caution when counseling patients about a prenatal suspicion for clubfoot, especially in twin gestations.

Isolated Fetal Cardiac Abnormalities: Are They Really Isolated?

Objective To determine the rate of unsuspected noncardiac abnormalities in newborns suspected to have isolated cardiac abnormalities in the second trimester. Study Design A review of the ultrasound database from the Weill Cornell Medical Center identified fetuses with a suspected cardiac abnormality from January 2006 to November 2016. Cases with prenatally suspected noncardiac structural abnormalities, abnormal fetal or neonatal karyotype or microarray, and those who delivered at an outside institution or underwent abortion were excluded. Neonatal records were reviewed to confirm prenatal findings and to identify anomalies not suspected in the second trimester. Results Sixty-eight live births met the inclusion criteria. Five newborns (7.4%) had major abnormalities not identified in the second trimester. Three newborns had an imperforate anus. One newborn had left hydronephrosis and absent right lung, and one had hemifacial microsomia and fused ribs. All five newborns with unsuspected anomalies were in the group with suspected conotruncal anomalies, with a 11.9% rate of unsuspected anomalies versus 0% in those with nonconotruncal cardiac anomalies ( p = 0.15). Conclusion Patients with a suspected isolated fetal cardiac anomaly on ultrasound should be aware of the possibility of other major structural abnormalities, especially in cases of conotruncal cardiac anomalies.

The Use of Ultrasound as a Potential Adjunct to Cell-Free Fetal DNA Screening for Aneuploidy at Weill Cornell Medical College, New York, USA.

Objective To evaluate the utility of ultrasound in identifying fetuses with uncommon chromosomal abnormalities that would be considered not detectable by cell-free fetal deoxyribonucleic acid (cfDNA). Study Design We performed a retrospective study of fetuses with chromosomal abnormalities that would be undetectable by cfDNA, who underwent an 11- to 14-week ultrasound from 2006 to 2016. Results There were 43 pregnancies included. First-trimester ultrasound revealed a fetal abnormality in 19 (44.2%) cases, of which 13 (30.2%) had a thickened nuchal translucency. There were an additional four fetuses with second-trimester sonographic abnormalities. Overall, 23 (53.5%) fetuses were found to have a major anomaly diagnosed by ultrasound. The rate of first-trimester sonographic abnormalities varied widely based on category of chromosomal abnormalities with high rates seen with triploidy (87.5%) and autosomal trisomy (80%) and lower rates seen with structurally abnormal chromosomes (33.3%), trisomy mosaicism (27.3%), other forms of mosaicism (11.1%), and deletions or duplications (25.0%), p < 0.001. Conclusion The majority of fetuses with uncommon chromosomal abnormalities in our cohort had major sonographic anomalies. The use of first-trimester ultrasound with nuchal translucency measurement may offer utility in identifying fetuses with risk of aneuploidy that would not be detectable with cfDNA.

Testing for Noonan syndrome after increased nuchal translucency.

OBJECTIVE: The aim of this study was to report the prevalence of Noonan syndrome (NS) in a cohort of fetuses that presented with increased nuchal translucency (NT) thickness in the first trimester of pregnancy. METHODS: This is a retrospective chart review. INCLUSION CRITERIA: (1) first trimester NT measurement ≥3 mm, (2) normal karyotype by either a CVS or an amniocentesis procedure, and (3) prenatal molecular genetic testing for NS completed. Results with known pathogenic variants were considered positive, while those with variants of unknown clinical significance, or with no variants, were considered negative. RESULTS: A total of 804 fetuses had an NT measurement of ≥3 mm, with a median NT thickness of 3.6 mm. Of these, 302 had karyotyping by CVS or amniocentesis, 200 (66.23%) with normal results. Of fetuses with a normal karyotype, 39 with a median NT thickness of 4.0 mm had a NS gene sequencing panel done, and 161 fetuses with a mean NT thickness of 4.3 mm were not tested for NS (p = 0.05). Of the 39 fetuses who were tested for NS, four (10.3%) had variants consistent with this diagnosis. CONCLUSION: In euploid fetuses, increased NT is associated with a 10% risk of NS. © 2017 John Wiley & Sons, Ltd.