Faculty Bibliography

BACKGROUND:There are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. OBJECTIVE:(s): To systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions (FGD) and a Delphi technique. STUDY DESIGN/METHODS:A four-round FGD and a three-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected based on their publication record on vasa previa. First, we convened an FGD panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A three-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa that the experts were asked to rate on a 5-point Likert scale (from strongly disagree = 1 to strongly agree = 5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of 3 or less were deemed to have had no consensus and excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and non-consensus statements were then aggregated. RESULTS:Sixty-eight international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on five continents and have contributed to over 80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, 91% for the first, second, and third rounds, respectively, and 71% completed all three rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including: 1) While there is no agreement on a distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2 cm distance; 2) All pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; 3) When a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at around 32 weeks to rule out vasa previa; 4) Outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; 5)Asymptomatic patients with vasa previa should be delivered by scheduled cesarean between 35- and 37-weeks of gestation; and 6) There was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa. CONCLUSIONS:Through FGD and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines.

BACKGROUND:Accurate individualized assessment of preeclampsia risk enables the identification of patients most likely to benefit from initiation of low-dose aspirin at 12 to 16 weeks of gestation when there is evidence for its effectiveness, and enables the guidance of appropriate pregnancy care pathways and surveillance. OBJECTIVE: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 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 cell-free DNA screening study (SMART) included singleton pregnancies with known pregnancy outcomes. Thirteen patient characteristics that are routinely collected at the first prenatal visit and 2 characteristics of cell-free DNA (total cell-free DNA and fetal fraction) 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 model. We also explored several feedforward (nonlinear) neural network architectures with ≥1 hidden layers, and compared their performance with the logistic regression model. We selected a simple neural network model built with 1 hidden layer and made up of 15 units. RESULTS:Of the 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 cell-free DNA measurement was 12.6 weeks, and 2155 (12.3%) had their cell-free DNA measurement at ≥16 weeks' gestation. Preeclampsia was associated with higher total cell-free DNA (median, 362.3 vs 339.0 copies/mL cell-free DNA; P<.001) and lower fetal fraction (median, 7.5% vs 9.4%; P<.001). The expected, cross-validated area under the curve scores for early-onset, preterm, and term preeclampsia were 0.782, 0.801, and 0.712, respectively, for the logistic regression model, and 0.797, 0.800, and 0.713, respectively, for the neural network model. At a screen-positive rate of 15%, sensitivity for preterm preeclampsia was 58.4% (95% confidence interval, 0.569-0.599) for the logistic regression model and 59.3% (95% confidence interval, 0.578-0.608) for the neural network model. The contribution of both total cell-free DNA and fetal fraction to the prediction of term and preterm preeclampsia was negligible. For early-onset preeclampsia, removal of the total cell-free DNA and fetal fraction features from the neural network model was associated with a 6.9% decrease in sensitivity at a 15% screen-positive rate, from 54.9% (95% confidence interval, 52.9-56.9) to 48.0% (95% confidence interval, 45.0-51.0). CONCLUSION/CONCLUSIONS:Routinely available patient characteristics and cell-free DNA markers can be used to predict preeclampsia with performance comparable to that of other patient characteristic models for the prediction of preterm preeclampsia. Logistic regression and neural network models showed similar performance.

We present a case of a vein of Galen aneurysmal malformation (VGAM), a rare congenital arteriovenous malformation, in one fetus of a monochorionic-diamniotic twin pregnancy. The diagnosis was made with color Doppler ultrasonography at 28 weeks and the affected fetus was found to have worsening cardiomegaly on subsequent fetal echocardiograms. She was emergently delivered at 32 weeks for abnormal fetal heart rate tracing of the affected twin. Magnetic resonance imaging of the brain findings after delivery demonstrated severe neurological injury; therefore, postnatal embolization was not performed. The neonate died on day of life 9. The cotwin survived without neurological complications. This is the first case in the literature of a VGAM diagnosed prenatally in a monochorionic-diamniotic twin pregnancy and demonstrates the challenge of delivery timing with prenatal diagnosis in a twin pregnancy.

PURPOSE/OBJECTIVE:The objective of this study was to compare maternal and neonatal outcomes when the diagnosis of FGR was based on isolated abdominal circumference < 10th percentile for gestational age (GA) (iAC group) versus overall estimated fetal weight < 10th percentile (EFW group). METHODS:, and Fisher exact tests with significance defined as p < 0.05. RESULTS:635 women met the inclusion criteria, 259 women in the iAC group and 376 women in the EFW group. The iAC group was noted to have a later GA at diagnosis and delivery. iAC was associated with lower rates of preterm birth (PTB), NICU admission, SGA at delivery and umbilical artery cord gas < 7.0. CONCLUSION/CONCLUSIONS:Using iAC as a definition of FGR increased the number of FGR cases by 1.69-fold over EFW criteria alone. However, obstetrical and neonatal outcomes for the iAC group appear to be significantly better than those in the EFW group, with low rates of PTB, NICU admission, and umbilical artery cord gas < 7.0.

BACKGROUND:Biologically active cervical glands provide a mucous barrier while influencing the composition and biomechanical strength of the cervical extracellular matrix. Cervical remodeling during ripening may be reflected as loss of the sonographic cervical gland area. As sonographic cervical length remains suboptimal for universal screening, adjunctive evaluation of other facets of the mid-trimester cervix may impart additional screening benefit. OBJECTIVE:To sonographically assess the cervical gland area at universal cervical length screening for preterm birth. STUDY DESIGN/METHODS:We performed a retrospective cohort study of singletons with transvaginal cervical length screening universally performed during anatomic survey between 18 0/7 and 23 6/7 weeks and subsequent live delivery at a single institution in 2018. Uterine anomalies, cerclage, suboptimal imaging, or medically indicated preterm birth were excluded. Ultrasound images were assessed for cervical length and cervical gland area (with quantitative measurements when present). The primary outcome was spontaneous preterm birth <37 weeks. Absent and present gland groups were compared using χ2, Fisher's exact, T-test, and multivariate logistic regression (adjusting for parity and progesterone use, as well as the gestational age, cervical length, and gland absence at screening ultrasound). Gland measurements were evaluated using the Mann-Whitney-U Test and Spearman's correlation. RESULTS:Among the cohort of 772 patients, absent and present CGA groups were overall similar. Patients were on average 33 years old, ∼20 weeks gestation at screening ultrasound, and overall, 2.5% had history of prior spontaneous preterm birth. The absent gland group was more likely to have been taking progesterone (17% vs 4%, p=0.04). Overall rate of preterm birth was 2.6%. However, the 2.3% of patients with absent cervical gland area were significantly more likely to deliver <37 weeks (aOR 23.9, 95% CI 6.4-89, p<0.001). Multivariate logistic regression demonstrated better performance of a cervical length screening model for preterm birth prediction with the addition of qualitative gland evaluation (p<0.001). Qualitative gland assessment was reproducible (PABAK 0.89), but quantitative gland measurements did not correlate with preterm birth. CONCLUSION/CONCLUSIONS:Qualitative gland absence at mid-gestation cervical length screening was associated with subsequent spontaneous preterm birth, whereas quantitative gland measurements were not. Multifaceted ultrasound screening may be needed to adequately evaluate the multiple biologic functions of the cervix.

OBJECTIVE: This study aimed to evaluate the rates of vaccination against infectious diseases (Tetanus, Diphtheria, and Pertussis [Tdap] and influenza) in pregnancy during the coronavirus disease 2019 (COVID-19) pandemic compared to contemporary historical controls. STUDY DESIGN/METHODS: < 0.05. RESULTS: In total, 1,713 pregnant people were included. Compared to historical controls, the COVID cohort differed in age, race, timing of initiation of prenatal care, insurance status, and medical comorbidities. After adjusting for these covariates, pregnant people were significantly more likely to accept influenza vaccine in the COVID cohort (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 1.27-2.29) and had similar Tdap acceptance (aOR 1.5, 95% CI 0.99-2.17). However, this trend was not observed for the entire obstetric population; public insurance status and medical comorbidities were associated with lower vaccine rates during the pandemic. For those who had public insurance, rates of influenza vaccination decreased from 83% in 2019 to 40% during COVID (aOR 0.16, 95% CI 0.10-0.24) and for Tdap rates decreased from 93 to 54% (aOR 0.13, 95% CI 0.08-0.21). CONCLUSION/CONCLUSIONS: During the COVID-19 pandemic era, pregnant people at large were more likely to accept the influenza vaccine. However, this trend did not apply to Tdap, and high-risk groups with public insurance and medical comorbidities. This study highlights potential disparities in vaccination rates, which need to be accounted for when evaluating national vaccine trends. These data support increased efforts in vaccine counseling for high-risk populations. KEY POINTS/CONCLUSIONS:· Antenatal flu vaccination increased during the pandemic.. · Antenatal Tdap vaccination was unchanged during the pandemic.. · High-risk pregnant patients had decreased vaccine uptake.. · High-risk subgroups were not included in overarching vaccination trends..

OBJECTIVE:Evidence is inconsistent regarding grand multiparity and its association with adverse obstetric outcomes. Few large American cohorts of grand multiparas have been studied. We assessed if increasing parity among grand multiparas is associated with increased odds of adverse perinatal outcomes. STUDY DESIGN/METHODS:Multi-center retrospective cohort of patients with parity ≥5 who delivered a singleton gestation in New York City from 2011-2019. Outcomes included postpartum hemorrhage, preterm delivery, hypertensive disorders of pregnancy, shoulder dystocia, birthweight >4000 grams and <2500 grams, and NICU admission. Parity was analyzed continuously, and multivariate analysis determined if increasing parity and other obstetric variables were associated with each adverse outcome. RESULTS:There were 2,496 patients who met inclusion criteria. Increasing parity among grand multiparas was not associated with any of the pre-specified adverse outcomes. Odds of postpartum hemorrhage increased with history (aOR 2.65 [1.83, 3.84]) and current cesarean delivery (aOR 4.59 [3.40, 6.18]). Preterm delivery was associated with history (aOR 12.36 [8.70-17.58]) and non-White race (aOR 1.90 [1.27, 2.84]). Odds of shoulder dystocia increased with history (OR 5.89 [3.22, 10.79]) and birth weight >4000g (aOR 9.94 [6.32, 15.65]). Birthweight >4000 grams was associated with maternal obesity (aOR 2.92 [2.22, 3.84]). Birthweight <2500 grams was associated with advanced maternal age (aOR 1.69 [1.15, 2.48]), chronic hypertension (aOR 2.45 [1.32, 4.53]) and non-White race (aOR 2.47 95% CI [1.66, 3.68]). Odds of hypertensive disorders of pregnancy increased with advanced maternal age (aOR 1.79 [1.25, 2.56]), history (aOR 10.09 [6.77-15.04]) and non-White race (aOR 2.79 [1.95, 4.00]). NICU admission was associated with advanced maternal age (aOR 1.47 [1.06, 2.02]) and non-White race (aOR 2.57 [1.84, 3.58]). CONCLUSION/CONCLUSIONS:Among grand multiparous patients, the risk factor for adverse maternal, obstetric and neonatal outcomes, appears to be occurrence of those adverse events in a prior pregnancy and not increasing parity itself.

BACKGROUND:Pharmacologic agents are often used in the antepartum period, however, studies on their effect on fetal development are limited. Thus, this study aims to examine the effect of commonly prescribed antepartum medications on the development of orofacial clefting. METHODS:Utilizing EPIC Cosmos deidentified data from approximately 180 US institutions was queried. Patients born between January 1, 2013, to January 1, 2023, were included. Eight OC cohorts were identified. Gestational medication use was identified by medications prescribed, provider-administered, or reported use by mothers. Medications used in at least 1 in 10,000 pregnancies were included in this analysis. RESULTS:A total of 12 098 newborns with available maternal pharmacologic data were born with any type of orofacial clefting. Prevalence for all oral clefts, any cleft palate, and any cleft lip were 20.56, 18.10, and 10.60 per 10 000 individuals, respectively. Notable significant exposures include most anticonvulsants, such as lamotrigine (OR1.33, CI 1.10-1.62), and topiramate (OR1.35, CI 1.13-1.62), as well as nearly all SSRIs/SNRIs, including fluoxetine (OR1.34, CI 1.19-1.51), sertraline (OR1.25, CI 1.16-1.34), and citalopram (OR1.28, CI 1.11-1.47). Corticosteroids were also correlated including dexamethasone (OR1.19, CI 1.12-1.27), and betamethasone (OR1.64, CI 1.55-1.73), as were antibiotics, including amoxicillin (OR1.22, CI 1.14-1.30), doxycycline (OR1.29, CI 1.10-1.52), and nitrofuran derivatives (OR1.10, CI 1.03-1.17). CONCLUSION/CONCLUSIONS:New associations between commonly prescribed antepartum medications and orofacial clefting were found. These findings should be confirmed as causality is not assessed in this report. Practitioners should be aware of the potential increased risk associated with these medications.

Although cell-free DNA (cfDNA) prenatal screening is widely used and has high sensitivity and specificity, there are circumstances in which the screening does not provide an interpretable result. Although this is relatively uncommon, it happens enough that clinical implications and potential reasons for follow-up should be studied and assessed. This study was designed to evaluate outcomes for pregnancies with nonreportable results on cfDNA screening tests. This study was a secondary analysis of the data from a multicenter prospective observational study of cfDNA screening for aneuploidy and 22q11.2 deletion syndrome. All patients were tested for trisomies 13, 18, and 21, as well as the 22q11.2 deletion syndrome, and all patients had confirmatory testing on the newborns in addition to collecting obstetric and perinatal outcomes. Inclusion criteria were women older than 18 years and at greater than 9 weeks of gestation with a singleton pregnancy. Exclusion criteria were having received cfDNA screening results before enrollment, organ transplant, ovum donation, vanishing twin, or being unwilling to provide a newborn sample. The primary outcome was the rate of adverse obstetrical and perinatal outcomes, including aneuploidy; preterm birth at less than 28, 34, or 37 weeks' gestation; preeclampsia; small for gestational age birth; and a composite outcome that included preterm birth before 37 weeks, preeclampsia, stillbirth at greater than 20 weeks, and small for gestational age. Final analyses included 17,851 individuals who had cfDNA screening, confirmatory genetic testing on the newborn, and obstetrical and perinatal outcomes recorded. Nonreportable results were found in 602 individuals (3.4%) after the first draw, with 32.2% of these due to low fetal fraction. Another third of the cohort had patterns where the risk of aneuploidy was uninterpretable but with an adequate fetal fraction, and in the final third, the fetal fraction could not be measured. Of the original 602 cases of nonreportable findings, 427 had a second draw, with 112 of these (26.2%) again having nonreportable results. There were no significant differences in baseline characteristics of age and parity for those with successful versus nonreportable test results; gestational age was significantly higher in individuals with nonreportable results (14.4 vs 13.4 weeks, P < 0.001), as was body mass index (26.2 vs 31.3), and the rate of chronic hypertension (4.0% vs 9.7%). In this cohort, there were 133 genetically confirmed trisomies, with 100 fetuses with trisomy 21, 18 individuals with trisomy 18, and 15 individuals with trisomy 13. Overall, the rate of aneuploidy was 1.7% in individuals with nonreportable results, versus 0.7% in those with reported results (P = 0.013; adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI], 1.1-4.0). Rates of preterm birth were also higher in those with nonreportable test results, with delivery at less than 34 weeks at 1.5% in those with a test result, 4.6% in those with one nonreportable test result and 6.9% in those with a second nonreportable test result (aOR, 2.2 and 2.7; 95% CI, 1.4-3.4 and 1.2-6.0, respectively). Preeclampsia showed a similar trend, with rates climbing from 3.9% in those with a reported result to 9.4% with 1 nonreportable result and 16.8% with 2 (aOR, 1.4 and 2.0; 95% CI, 1.0-1.9 and 1.1-3.7, respectively). Chances of live birth were significantly reduced in pregnancies with a nonreportable results (aOR, 0.20; 95% CI, 0.13-0.30), with the chances decreasing more after a second nonreportable test result (aOR, 0.11; 95% CI, 0.06-0.23). The study found that nonreportable cfDNA screening results are associated with an increased risk for aneuploidy, preterm birth, and preeclampsia, with a gradient of increased risk with a second failed test. This adds to literature with conflicting findings surrounding obstetrical complications in those with altered cfDNA levels and with most studies largely focused on characteristics that may be predictive of a nonreportable result rather than outcomes associated with nonreportable results. These results can inform clinicians who have patients with nonreportable test results in a way that may help them provide better care; future research should focus on more fully understanding the adverse outcomes associated with nonreportable tests to maximize this ability for clinicians in the future. Further research should also focus on specific populations or diagnoses to understand if there are fundamental differences in different groups of individuals.