Faculty Bibliography

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: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: 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: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.

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: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.