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.

Multisystem inflammatory syndrome in children (MIS-C), a new condition related to coronavirus disease 2019 (COVID-19) in the pediatric population, was recognized by physicians in the United Kingdom in April 2020. Given those up to the age of 21 years can be affected, pregnant adolescents and young adults are susceptible. However, there is scant information on how MIS-C may affect pregnancy and whether the presentation differs in the pregnant population. We report a case of a pregnant adolescent with COVID-19 and MIS-C with a favorable outcome. This case highlights the considerations in managing a critically ill pregnant patient with a novel illness and the importance of a multidisciplinary team in coordinating care.

OBJECTIVE:This study aimed to estimate the perinatal mortality associated with prenatally diagnosed vasa previa and to determine what proportion of those perinatal deaths are directly attributable to vasa previa. DATA SOURCES/METHODS:The following databases have been searched from January 1, 1987, to January 1, 2023: PubMed, Scopus, Web of Science, and Embase. STUDY ELIGIBILITY CRITERIA/METHODS:Our study included all studies (cohort studies and case series or reports) that had patients in which a prenatal diagnosis of vasa previa was made. Case series or reports were excluded from the meta-analysis. All cases in which prenatal diagnosis was not made were excluded from the study. METHODS:. The publication bias was evaluated using a funnel plot and the Peters regression test. The Newcastle-Ottawa scale was used to assess the risk of bias. RESULTS:=0.0%) of pregnancies, respectively. CONCLUSION/CONCLUSIONS:Perinatal death is uncommon after a prenatal diagnosis of vasa previa. Approximately half of the cases of perinatal mortality are not directly attributable to vasa previa. This information will help in guiding physicians in counseling and will provide reassurance to pregnant individuals with a prenatal diagnosis of vasa previa.

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/METHODS: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/CONCLUSIONS: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.

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.

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.

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..

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/METHODS: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/CONCLUSIONS: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.

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/METHODS: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/CONCLUSIONS: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.