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.

Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus.

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: This study aimed to systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions and a Delphi technique. STUDY DESIGN: A 4-round focus group discussion and a 3-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected on the basis of their publication record on vasa previa. First, we convened a focus group discussion panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A 3-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa, which 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 were deemed to have had no consensus and were excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and nonconsensus statements were then aggregated. RESULTS: A total of 68 international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on 5 continents and have contributed to >80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, and 91% for the first, second, and third rounds, respectively, and 71% completed all 3 rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including the following: (1) although there is no agreement on the 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 approximately 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 delivery 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. CONCLUSION: Through focus group discussion 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.

Association of Commonly Prescribed Antepartum Medications and Incidence of Orofacial Clefting.

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: 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.

Performance of prenatal cfDNA screening for sex chromosomes.

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

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

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

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.

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

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

Acceptance of Routine Vaccines in Pregnancy during the COVID-19 Pandemic.

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: This was a retrospective cohort study comparing rates of Tdap and influenza vaccination in pregnant people who received care at NYU Langone Health and delivered from September 1, 2020, to January 31, 2021 ("COVID cohort") to the same period the prior year ("2019 cohort"). Demographic information, trimester of initiation of prenatal care, insurance status, and medical comorbidities were evaluated. Outcomes were analyzed using chi-square, Fisher's exact test, and multivariable logistic regression, with significance of p < 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: 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: · 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..

Grand Multiparity and Obstetric Outcomes in a Contemporary Cohort: The Role of Increasing Parity.

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: Multicenter retrospective cohort of patients with parity ≥ 5 who delivered a singleton gestation in New York City from 2011 to 2019. Outcomes included postpartum hemorrhage, preterm delivery, hypertensive disorders of pregnancy, shoulder dystocia, birth weight > 4,000 and <2,500 g, and neonatal intensive care unit (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 prespecified adverse outcomes. Odds of postpartum hemorrhage increased with history (adjusted odds ratio [aOR]: 2.65, 95% confidence interval [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 (aOR: 5.89 [3.22, 10.79]) and birth weight > 4,000 g (aOR: 9.94 [6.32, 15.65]). Birth weight > 4,000 g was associated with maternal obesity (aOR: 2.92 [2.22, 3.84]). Birth weight < 2,500 g 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 [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: 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. KEY POINTS: · Increasing parity is not associated with adverse obstetric outcomes among grand multiparas.. · Prior adverse pregnancy outcome is a risk factor for the outcome among grand multiparas.. · Advanced maternal age is associated with adverse obstetric outcomes among grand multiparas..

Comparing outcomes of fetal growth restriction defined by estimated fetal weight versus isolated abdominal circumference.

PURPOSE: 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: This was a retrospective cohort study of singleton gestations who underwent growth ultrasounds and delivered at a single health system from 1/1/19-9/4/20. The study group was comprised of patients with AC < 10th percentile and EFW ≥ than the 10th percentile (iAC group). The control group included patients with overall EFW < 10th percentile (EFW group). Outcomes evaluated included GA at delivery, mode of delivery, fetal and neonatal outcomes. Data was analyzed using Mann Whitney U, X2, 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: 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.

Timing of birth and adverse pregnancy outcomes in cases of prenatally diagnosed vasa previa: a systematic review and meta-analysis.

OBJECTIVE: The ideal time for birth in pregnancies diagnosed with vasa previa remains unclear. We conducted a systematic review aiming to identify the gestational age at delivery that best balances the risks for prematurity with that of pregnancy prolongation in cases with prenatally diagnosed vasa previa. DATA SOURCES: Ovid MEDLINE, PubMed, CINAHL, Embase, Scopus, and Web of Science were searched from inception to January 2022. STUDY ELIGIBILITY CRITERIA: The intervention analyzed was delivery at various gestational ages in pregnancies prenatally diagnosed with vasa previa. Cohort studies, case series, and case reports were included in the qualitative synthesis. When summary figures could not be obtained directly from the studies for the quantitative synthesis, authors were contacted and asked to provide a breakdown of perinatal outcomes by gestational age at birth. METHODS: Study appraisal was completed using the National Institutes of Health quality assessment tool for the respective study types. Statistical analysis was performed using a random-effects meta-analysis of proportions. RESULTS: The search identified 3435 studies of which 1264 were duplicates. After screening 2171 titles and abstracts, 140 studies proceeded to the full-text screen. A total of 37 studies were included for analysis, 14 of which were included in a quantitative synthesis. Among 490 neonates, there were 2 perinatal deaths (0.4%), both of which were neonatal deaths before 32 weeks' gestation. In general, the rate of neonatal complications decreased steadily from <32 weeks' gestation (4.6% rate of perinatal death, 91.2% respiratory distress, 11.4% 5-minute Apgar score <7, 23.3% neonatal blood transfusion, 100% neonatal intensive care unit admission, and 100% low birthweight) to 36 weeks' gestation (0% perinatal death, 5.3% respiratory distress, 0% 5-minute Apgar score <7, 2.9% neonatal blood transfusion, 29.2% neonatal intensive care unit admission, and 30.9% low birthweight). Complications then increased slightly at 37 weeks' gestation before decreasing again at 38 weeks' gestation. CONCLUSION: Prolonging pregnancies until 36 weeks' gestation seems to be safe and beneficial in otherwise uncomplicated pregnancies with antenatally diagnosed vasa previa.

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

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

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

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

Pregnant women with severe or critical coronavirus disease 2019 have increased composite morbidity compared with nonpregnant matched controls.

BACKGROUND: In March 2020, as community spread of severe acute respiratory syndrome coronavirus 2 became increasingly prevalent, pregnant women seemed to be equally susceptible to developing coronavirus disease 2019. Although the disease course usually appears mild, severe and critical cases of coronavirus disease 2019 seem to lead to substantial morbidity, including intensive care unit admission with prolonged hospital stay, intubation, mechanical ventilation, and even death. Although there are recent reports regarding the impact of coronavirus disease 2019 on pregnancy, there is a lack of information regarding the severity of coronavirus disease 2019 in pregnant vs nonpregnant women. OBJECTIVE: We aimed to describe the outcomes of severe and critical cases of coronavirus disease 2019 in pregnant vs nonpregnant, reproductive-aged women. STUDY DESIGN: This is a multicenter, retrospective, case-control study of women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection hospitalized with severe or critical coronavirus disease 2019 in 4 academic medical centers in New York City and 1 in Philadelphia between March 12, 2020, and May 5, 2020. The cases consisted of pregnant women admitted specifically for severe or critical coronavirus disease 2019 and not for obstetrical indications. The controls consisted of reproductive-aged, nonpregnant women admitted for severe or critical coronavirus disease 2019. The primary outcome was a composite morbidity that includes the following: death, a need for intubation, extracorporeal membrane oxygenation, noninvasive positive pressure ventilation, or a need for high-flow nasal cannula O2 supplementation. The secondary outcomes included intensive care unit admission, length of stay, a need for discharge to long-term acute care facilities, and discharge with a home O2 requirement. RESULTS: A total of 38 pregnant women with severe acute respiratory syndrome coronavirus 2 polymerase chain reaction-confirmed infections were admitted to 5 institutions specifically for coronavirus disease 2019, 29 (76.3%) meeting the criteria for severe disease status and 9 (23.7%) meeting the criteria for critical disease status. The mean age and body mass index were markedly higher in the nonpregnant control group. The nonpregnant cohort also had an increased frequency of preexisting medical comorbidities, including diabetes, hypertension, and coronary artery disease. The pregnant women were more likely to experience the primary outcome when compared with the nonpregnant control group (34.2% vs 14.9%; P=.03; adjusted odds ratio, 4.6; 95% confidence interval, 1.2-18.2). The pregnant patients experienced higher rates of intensive care unit admission (39.5% vs 17.0%; P<.01; adjusted odds ratio, 5.2; 95% confidence interval, 1.5-17.5). Among the pregnant women who underwent delivery, 72.7% occurred through cesarean delivery and the mean gestational age at delivery was 33.8±5.5 weeks in patients with severe disease status and 35±3.5 weeks in patients with critical coronavirus disease 2019 status. CONCLUSION: Pregnant women with severe and critical coronavirus disease 2019 are at an increased risk for certain morbidities when compared with nonpregnant controls. Despite the higher comorbidities of diabetes and hypertension in the nonpregnant controls, the pregnant cases were at an increased risk for composite morbidity, intubation, mechanical ventilation, and intensive care unit admission. These findings suggest that pregnancy may be associated with a worse outcome in women with severe and critical cases of coronavirus disease 2019. Our study suggests that similar to other viral infections such as severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, pregnant women may be at risk for greater morbidity and disease severity.

Differential Uptake of Telehealth for Prenatal Care in a Large New York City Academic Obstetrical Practice during the COVID-19 Pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic in New York City, telehealth was rapidly implemented for obstetric patients. Though telehealth for prenatal care is safe and effective, significant concerns exist regarding equity in access among low-income populations. We performed a retrospective cohort study evaluating utilization of telehealth for prenatal care in a large academic practice in New York City, comparing women with public and private insurance. We found that patients with public insurance were less likely to have at least one telehealth visit than women with private insurance (60.9 vs. 87.3%, p < 0.001). After stratifying by borough, this difference remained significant in Brooklyn, one of the boroughs hardest hit by the pandemic. As COVID-19 continues to spread around the country, obstetric providers must work to ensure that all patients, particularly those with public insurance, have equal access to telehealth. KEY POINTS: · Telehealth for prenatal care is frequently utilized during the COVID-19 pandemic.. · Significant concerns exist regarding equity in access among lower-income populations.. · Women with public insurance in New York City were less likely to access telehealth for prenatal care..

A Survey of Labor and Delivery Practices in New York City during the COVID-19 Pandemic.

Recently, a novel coronavirus, precisely severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), that causes the disease novel coronavirus disease 2019 (COVID-19) has been declared a worldwide pandemic. Over a million cases have been confirmed in the United States. As of May 5, 2020, New York State has had over 300,000 cases and 24,000 deaths with more than half of the cases and deaths occurring in New York City (NYC). Little is known, however, of how this virus impacts pregnancy. Given this lack of data and the risk for severe disease in this relatively immunocompromised population, further understanding of the obstetrical management of COVID-19, as well as hospital level preparation for its control, is crucial. Guidance has come from expert opinion, professional societies and public health agencies, but to date, there is no report on how obstetrical practices have adapted these recommendations to their local situations. We therefore developed an internet-based survey to elucidate the practices put into place to guide the care of obstetrical patients during the COVID-19 pandemic. We surveyed obstetrical leaders in four academic medical centers in NYC who were implementing and testing protocols at the height of the pandemic. We found that all sites made changes to their practices, and that there appeared to be agreement with screening and testing for COVID-19, as well as labor and delivery protocols, for SARS-CoV-2-positive patients. We found less consensus with respect to inpatient antepartum fetal surveillance. We hope that this experience is useful to other centers as they formulate their plans to face this pandemic. KEY POINTS: · Practices changed to accommodate public health needs.. · Most practices are screened for novel COVID-19 on admission.. · Fetal testing in COVID-19 patients varied..

Prehypertension in Early Pregnancy: What is the Significance?

Objective Hypertensive disorders play a significant role in maternal morbidity and mortality. There is limited data on prehypertension (pre-HTN) during the first half of pregnancy. We sought to examine the risk of adverse pregnancy outcomes in patients with prehypertension in early pregnancy (<20 weeks' gestational age). Study Design A retrospective cohort study of 377 patients between 2013 and 2014. Patients were divided based on the highest blood pressure in early pregnancy, as defined per the JNC-7 criteria. There were 261 control patients (69.2%), 95 (25.2%) pre-HTN patients, and 21 (5.6%) chronic hypertension (CHTN) patients. The groups were compared using X2, Fisher's Exact, Student t-test, and Mann-Whitney U test with p < 0.05 used as significance. Results Patients with pre-HTN delivered earlier (38.8 ± 1.9 weeks vs 39.3 ± 1.7 weeks), had more pregnancy related hypertension (odds ratio [OR], 4.62; confidence interval [CI], 2.30-9.25; p < 0.01) and composite maternal adverse outcomes (OR, 2. 10; 95% CI, 1.30-3.41; p < 0.01), NICU admission (OR, 2.21; 95% CI, 1.14-4.26; p = 0.02), neonatal sepsis (OR, 6.12; 95% CI, 2.23-16.82; p < 0.01), and composite neonatal adverse outcomes (OR, 2.05; 95% CI, 1.20-3.49; p < 0.01). Conclusion Although women with pre-HTN are currently classified as normal in obstetrics, they are more similar to women with CHTN. Pre-HTN in the first half of pregnancy increases the likelihood of adverse outcomes.

Two cases of maternal alloimmunization against human neutrophil alloantigen-4b, one causing severe alloimmune neonatal neutropenia.

BACKGROUND: Human neutrophil antigen (HNA)-4a/4bw is encoded by 230G>A in ITGAM, which results in an Arg61His substitution of the αM chain (CD11b) of complement receptor 3 (CR3; CD11b/18 or Mac-1). HNA-4a antibodies have been detected in the sera of female blood donors and in maternal sera that caused alloimmune neonatal neutropenia (ANN), in which maternal immunoglobulin (Ig)G antibodies against a paternally inherited HNA cross the placenta and destroy fetal and neonatal neutrophils. However, to date, antibodies specific for HNA-4b have not been reported. Here, we report the first two examples of HNA-4b antibodies. STUDY DESIGN AND METHODS: The two sera studied were both from previously pregnant females, one a multiparous female blood donor implicated in two separate transfusion reactions and the second a mother whose first pregnancy resulted in the birth of a severely neutropenic (0 × 10(6) neutrophils/L) infant affected with ANN. Serum neutrophil antibody testing was by flow cytometry and CD11b/18 monoclonal antibody immobilization of granulocyte antigens assay, and HNA genotyping was performed by polymerase chain reaction with sequence-specific priming and allele-specific 5' exonuclease assays. RESULTS: Sera from both women contained IgG antibodies reactive only with HNA-4b+ neutrophils and both typed HNA-4a/a. Both were immunized through pregnancy since their husbands and children all typed HNA-4a/b. CONCLUSIONS: The serologic results, together with the genotype results, confirm that these are the first reported cases of neutrophil antibodies specific for HNA-4b.

Uterocervical angle: a novel ultrasound screening tool to predict spontaneous preterm birth.

BACKGROUND: Mechanical alteration of the cervical angle has been proposed to reduce spontaneous preterm birth. Performance of the uterocervical angle as measured by ultrasound for predicting spontaneous preterm birth is poorly understood. OBJECTIVE: We sought to determine whether a novel ultrasonographic marker, uterocervical angle, correlates with risk of spontaneous preterm birth in a general population. STUDY DESIGN: We conducted a retrospective cohort study from May 2014 through May 2015 of singleton gestations between 16 0/7-23 6/7 weeks undergoing transvaginal ultrasound for cervical length screening. Images were remeasured for uterocervical angle between the lower uterine segment and the cervical canal. Primary outcome was prediction of spontaneous preterm birth <34 weeks and <37 weeks by uterocervical angle and secondary outcome evaluated cervical length and spontaneous preterm birth. RESULTS: A total of 972 women were studied. The rate of spontaneous preterm birth in this cohort was 9.6% for delivery <37 weeks and 4.5% for <34 weeks. Uterocervical angle of ≥95 degrees was significantly associated with spontaneous preterm birth <37 weeks with sensitivity of 80% (P < .001; confidence interval, 0.70-0.81; negative predictive value, 95%). Uterocervical angle of ≥105 degrees predicted spontaneous preterm birth <34 weeks with sensitivity of 81% (P < .001; confidence interval, 0.72-0.86; negative predictive value, 99%). Cervical length ≤25 mm significantly predicted spontaneous preterm birth <37 weeks (P < .001; sensitivity, 62%; negative predictive value, 95%) and <34 weeks (P < .001; sensitivity, 63%; negative predictive value, 97%). Regression analysis revealed a significant association of maternal age, nulliparity, race, and obesity at conception with spontaneous preterm birth and uterocervical angle. There was no correlation identified between history of dilation and curettage, abnormal Pap smear results, excisional cervical procedures, smoking, or obesity at delivery on spontaneous preterm birth and uterocervical angle. CONCLUSION: A wide uterocervical angle ≥95 and ≥105 degrees detected during the second trimester was associated with an increased risk for spontaneous preterm birth <37 and <34 weeks, respectively. Uterocervical angle performed better than cervical length in this cohort. Our data indicate that uterocervical angle is a useful, novel transvaginal ultrasonographic marker that may be used as a screening tool for spontaneous preterm birth.