Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

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.

How to choose a test for prenatal genetic diagnosis: a practical overview.

Establishing the diagnosis of a fetal genetic disease in utero expands decision-making opportunities for individuals during pregnancy and enables providers to tailor prenatal care and surveillance to disease-specific risks. The selection of prenatal genetic tests is guided by key details from fetal imaging, family and obstetrical history, suspected diagnoses and mechanisms of disease, an accurate understanding of what abnormalities each test is designed to detect, and, at times, the gestational age at which testing is initiated. Pre- and posttest counseling, by or in conjunction with providers trained in genetics, ensure an accurate understanding of genetic tests, their potential results and limitations, estimated turnaround time for results, and the clinical implications of their findings. As prenatal diagnosis and testing options continue to expand rapidly, it is increasingly important for obstetrical providers to understand how to choose appropriate genetic testing and contextualize the clinical implications of their results.

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.

Connecting the dots: Carrier screening and the Genetic Information Nondiscrimination Act in the United States.

OBJECTIVE: To highlight the possibility of genetic discrimination in the United States with respect to carrier screening under limitations of the Genetic Information Nondiscrimination Act (GINA) and to encourage providers to educate patients about this possibility during pretest counseling. METHODS: Review of current professional guidelines and practice resources regarding the necessary components of pretest counseling for carrier screening in the context of GINA's limitations and the potential impact of carrier screening results on life, long-term care and disability insurance. RESULTS: Current practice resources advise that patients in the United States should be informed that their employer or health insurance company generally cannot use their genetic information during the underwriting process. However, these resources do not elaborate on GINA's limitations or explain why there may be adverse consequences to patients regarding these limitations. Studies have demonstrated significant gaps in provider knowledge of GINA, especially for those without formal genetic training. CONCLUSION: Enhanced education and provision of GINA educational resources for providers and patients will help ensure that patients have the opportunity to prioritize their insurance needs prior to undergoing carrier screening.

Prenatal Genetic Screening in Twin Pregnancy.

Twin pregnancy presents unique considerations for aneuploidy screening. Pre-test counseling regarding benefits, alternatives, and options for aneuploidy screening should be provided to all patients carrying twin pregnancy. This article aims to review the options for aneuploidy screening in twin pregnancy including the potential benefits and limitations.

First Trimester Ultrasound and Aneuploidy Screening in Twins.

All patients with twin pregnancy should have first trimester ultrasound and be offered screening for chromosomal aneuploidy as well as diagnostic testing. Screening for aneuploidy in twins presents unique challenges compared with singletons. Cell-free DNA screening should be considered first-line; however, this option may not be available or may have limitations in certain clinical scenarios, such as vanishing twins. If cell-free DNA screening is not available, maternal serum marker screening in conjunction with nuchal translucency assessment should be offered. Patients with positive aneuploidy screening tests or fetal structural abnormalities should be offered diagnostic testing.

Adverse Perinatal Outcomes Associated with Stage 1 Hypertension in Pregnancy: A Retrospective Cohort Study.

OBJECTIVE: To determine if women who newly met criteria for stage 1 hypertension in early pregnancy were at increased risk for adverse perinatal outcomes compared with normotensive women. STUDY DESIGN: We conducted a retrospective cohort study of women who had prenatal care at a single institution and subsequently delivered a live infant between December 2017 and August 2019. Women with a singleton gestation who had at least two prenatal visits prior to 20 weeks of gestation were included. We excluded women with known chronic hypertension or other major maternal illness. Two groups were identified: (1) women newly diagnosed with stage 1 hypertension before 20 weeks of gestation (blood pressure [BP]: 130-139/80-89 on at least two occasions) and (2) women with no known history of hypertension and normal BP (<130/80 mm Hg) before 20 weeks of gestation. The primary outcome was any hypertensive disorder of pregnancy; secondary outcomes were indicated preterm birth and small for gestational age. Generalized linear models were used to compare risk of adverse outcomes between the groups. RESULTS: Of the 1,630 women included in the analysis, 1,443 women were normotensive prior to 20 weeks of gestation and 187 women (11.5%) identified with stage 1 hypertension. Women with stage 1 hypertension were at significantly increased risk for any hypertensive disorder of pregnancy (adjusted risk ratio [aRR]: 1.86, 95% confidence interval [CI]: 1.12-3.04) and indicated preterm birth (aRR: 1.83, 95% CI: 1.12-3.02). Black women and obese women with stage 1 hypertension were at increased for hypertensive disorder of pregnancy compared with white women and nonobese women, respectively (aRR: 1.32, 95% CI: 1.11-1.57; aRR: 1.69, 95% CI: 1.39-2.06). CONCLUSION: These results provide insight about the prevalence of stage 1 hypertension and inform future guidelines for diagnosis and management of hypertension in pregnancy. Future research is needed to assess potential interventions to mitigate risk. KEY POINTS: · Stage 1 hypertension increased risk for hypertensive disorders of pregnancy and indicated preterm birth.. · Among women with stage 1 hypertension, risk of severe preeclampsia was 2.6 times higher than normotensive women.. · Black and obese women with stage 1 hypertension were at additional risk for adverse outcomes..

PROMPT: Prospective Meta-analysis for Pessary Trials Study Protocol.

OBJECTIVE: Preterm birth, defined as birth before 37 weeks of gestation, is a leading cause of perinatal and infant mortality throughout the world. Preterm birth is also associated with long-term neurological disabilities and other significant health issues in children. A short cervix in the second trimester has been noted to be one of the strongest predictors of subsequent spontaneous preterm birth in both singleton and multiple pregnancies. Some studies have shown that cervical support in the form of an Arabin pessary lowers the risk of preterm birth in women with a singleton gestation and short cervical length; however, other studies have conflicting results. Our objective was to form an international collaborative of planned or ongoing randomized trials of pessary in singleton and twin gestations with a short cervix. STUDY DESIGN: In November 2014, an international group of investigators, who had initiated or were planning randomized trials of pessary for pregnant people with a short cervix and singleton or twin gestation to prevent preterm birth, formed a collaboration to plan a prospective individual patient data (IPD) meta-analysis of randomized trials (PROspective Meta-analysis of Pessary Trials [PROMPT]). The PROMPT investigators agreed on meta-analysis IPD hypotheses for singletons and twins, eligibility criteria, and a set of core baseline and outcome measures. The primary outcome is a composite of fetal death or preterm delivery before 32 weeks' gestation. Secondary outcomes include maternal and neonatal morbidities. The PROMPT protocol may be viewed as a written agreement among the study investigators who make up the PROMPT consortium (PROSPERO ID# CRD42018067740). RESULTS: Results will be published in phases as the individual participating studies are concluded and published. Results of the first phase of singleton and twin pessary trials are expected to be available in late 2022. Updates are planned as participating trials are completed and published. KEY POINTS: · Short cervical length predicts preterm birth.. · Results of prior cervical pessary trials are mixed.. · Meta-analysis of pessary trials protocol..

Cervical Pessary for Prevention of Preterm Birth in Individuals With a Short Cervix: The TOPS Randomized Clinical Trial.

Importance: A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting. Objective: To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix. Design, Setting, and Participants: We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded. Interventions: Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians. Main Outcome and Measures: The primary outcome was delivery or fetal death prior to 37 weeks. Results: A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32). Conclusions and Relevance: Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02901626.

Cell-free DNA screening positive for monosomy X: clinical evaluation and management of suspected maternal or fetal Turner syndrome.

Initially provided as an alternative to evaluation of serum analytes and nuchal translucency for the assessment of pregnancies at high risk of trisomy 21, cell-free DNA screening for fetal aneuploidy, also referred to as noninvasive prenatal screening, can now also screen for fetal sex chromosome anomalies such as monosomy X as early as 9 to 10 weeks of gestation. Early identification of Turner syndrome, a sex chromosome anomaly resulting from the complete or partial absence of the second X chromosome, allows medical interventions such as optimizing obstetrical outcomes, hormone replacement therapy, fertility preservation and support, and improved neurocognitive outcomes. However, cell-free DNA screening for sex chromosome anomalies and monosomy X in particular is associated with high false-positive rates and low positive predictive value. A cell-free DNA result positive for monosomy X may represent fetal Turner syndrome, maternal Turner syndrome, or confined placental mosaicism. A positive screen for monosomy X with discordant results of diagnostic fetal karyotype presents unique interpretation and management challenges because of potential implications for previously unrecognized maternal Turner syndrome. The current international consensus clinical practice guidelines for the care of individuals with Turner syndrome throughout the lifespan do not specifically address management of individuals with a cell-free DNA screen positive for monosomy X. This study aimed to provide context and expert-driven recommendations for maternal and/or fetal evaluation and management when cell-free DNA screening is positive for monosomy X. We highlight unique challenges of cell-free DNA screening that is incidentally positive for monosomy X, present recommendations for determining if the result is a true-positive, and discuss when diagnosis of Turner syndrome is applicable to the fetus vs the mother. Whereas we defer the subsequent management of confirmed Turner syndrome to the clinical practice guidelines, we highlight unique considerations for individuals initially identified through cell-free DNA screening.

Obesity and no call results: optimal timing of cell-free DNA testing and redraw.

BACKGROUND: Fetal fraction of cell-free DNA decreases with increasing maternal weight. Consequently, cell-free DNA screening for fetal aneuploidy has higher screen failures or "no call" rates in women with obesity owing to a low fetal fraction. The optimal timing of testing based on maternal weight is unknown. OBJECTIVE: This study aimed to identify the optimal timing of initial cell-free DNA testing based on maternal weight and to identify the optimal timing of repeat cell-free DNA testing in cases with an initial screen failure. STUDY DESIGN: This was a retrospective cohort study of women undergoing cell-free DNA for fetal aneuploidy screening between 9 and 18 weeks through a single laboratory over 1 year from 2018 to 2019. Fetal fraction change per week was calculated, and generalized linear models were used to calculate relative risk and 95% confidence interval of a no call result at given maternal weights and gestational ages. RESULTS: The vast majority of samples (99.22%) received a test result. The risk of a no call result owing to a low fetal fraction was higher with increasing maternal weight. At 9 to 12 weeks, the rate of a no call result owing to a low fetal fraction in women who weighed <150 lb was 0.14% compared with 17.39% in women weighing >400 lb. Fetal fraction increased with increasing gestational age, although the incremental increase in fetal fraction over time is inversely proportional to maternal weight. At 13 to 18 weeks' gestation, 6.45% of women weighing >400 lb received a no call result owing to a low fetal fraction. In women in the highest weight category, >400 lb, fetal fraction increased 0.5% with each week of gestation. CONCLUSION: Although the risk of a no call result increases with maternal weight, cell-free DNA screening should be offered to all women at 9 to 12 weeks' gestation, allowing the option to have chorionic villus sampling after a positive test result. Pretest counseling for women with obesity should include the increased chance for a test failure. Most women weighing less than 400 lb will receive a test result and more than 80% of women with a weight of >400 lb will receive a test result at 9 to 12 weeks' gestation. Data regarding the expected increase in cell-free DNA fetal fraction per week may help guide the timing of a redraw to optimize test success.

Screening for Aneuploidy in the Patient With Diabesity: Pearls and Pitfalls.

The American College of Obstetrics & Gynecology (ACOG) recommends offering aneuploidy screening to all pregnant women. Obesity and diabetes are not associated with an increased risk of aneuploidy; however, they can complicate and compromise testing options. As the prevalence of obesity and diabetes, or "diabesity" increases, counseling women regarding potential limitations in testing performance of aneuploidy screening is of paramount importance. This chapter reviews options for aneuploidy screening for women with diabesity including sonography/nuchal translucency, serum analyte screening, and cell-free DNA. Potential challenges associated with diagnostic testing with amniocentesis and chorionic villus sampling in women with obesity are also discussed.

Association between cell-free DNA fetal fraction and gestational diabetes.

OBJECTIVE: To determine the association between cell-free DNA (cfDNA) fetal fraction and gestational diabetes (GDM) in a cohort of women presenting for cfDNA screening for fetal aneuploidy. METHODS: A retrospective cohort study of women with singleton pregnancies who had cfDNA screening at a single institution at 10 to 20 weeks gestation between October 2011 and October 2017. Fetal fractions were adjusted for gestational age (GA) using multiples of the median (MoM). Multivariable logistic regression was used to estimate the odds ratio (OR) of GDM controlling for potential confounders. RESULTS: Two thousand six hundred twenty-three pregnancies met criteria. Women with GDM had a lower fetal fraction (0.93 MoM vs. 1.05 MoM, P = .002). However, the association between fetal fraction and GDM was not significant after adjusting for body mass index (BMI) [OR 0.84, 95% confidence interval (CI) 0.52-1.36; P = .48]. Since insulin resistance increases at later GAs, separate analysis on women with GA 14 to 20 weeks was performed. Again, the association between fetal fraction and GDM was not significant after adjusting for BMI, (OR 0.81, 95% CI 0.31-2.12; P = .67). CONCLUSION: Low or high fetal fraction of cfDNA was not associated with GDM. Although fetal fraction was lower among women diagnosed with GDM, this relationship was no longer statistically significant once maternal BMI was taken into account.

Cell-free DNA for Down syndrome screening in obese women: Is it a cost-effective strategy?

OBJECTIVE: Determine cost differences between cell-free DNA (cfDNA) and serum integrated screening (INT) in obese women given the limitations of aneuploidy screening in this population. METHODS: Using a decision-analytic model, we estimated the cost-effectiveness of trisomy 21 screening in class III obese women using cfDNA compared with INT. Primary outcomes of the model were cost, number of unnecessary invasive tests, procedure-related fetal losses, and missed cases of trisomy 21. RESULTS: In base case, the mean cost of cfDNA was $498 greater than INT ($1399 vs $901). cfDNA resulted in lower probabilities of unnecessary invasive testing (2.9% vs 3.5%), procedure-related loss (0.015% vs 0.019%), and missed cases of T21 (0.00013% vs 0.02%). cfDNA cost $87 485 per unnecessary invasive test avoided, $11 million per procedure-related fetal loss avoided, and $2.2 million per missed case of T21 avoided. In sensitivity analysis, when the probability of insufficient fetal fraction is assumed to be >25%, cfDNA is both costlier than INT and results in more unnecessary invasive testing (a dominated strategy). CONCLUSION: When the probability of insufficient fetal fraction more than 25% (a maternal weight of ≥300 lbs), cfDNA is costlier and results in more unnecessary invasive testing than INT.

Predicting asymptomatic cervical dilation in pregnant patients with short mid-trimester cervical length: A secondary analysis of a randomized controlled trial.

INTRODUCTION: Second trimester asymptomatic cervical dilation is a significant risk factor for early preterm birth. The objective of this study is to evaluate whether transvaginal ultrasound cervical length (CL) predicts asymptomatic cervical dilation on physical exam in women with short cervix (CL ≤25 mm) and no prior preterm birth. MATERIAL AND METHODS: Secondary analysis of a randomized trial on pessary in asymptomatic singletons without prior preterm birth diagnosed with CL ≤25 mm between 18+0/7 and 23+6/7  weeks. Participants had transvaginal ultrasound and physical cervical exam and were randomized to pessary or no pessary with all patients with cervical length ≤20 mm offered vaginal progesterone. The primary outcome was to determine whether CL was predictive of asymptomatic physical cervical dilation ≥1 cm using receiver operating characteristic curve. RESULTS: In all, 119 women were included. Based on receiver operating characteristic curve, CL ≤11 mm was best predictive of cervical dilation ≥1 cm, with 75% sensitivity, 80% specificity, and area under the curve 0.73 (0.55-0.91), P = 0.009. Cervical length ≤11 mm had increased incidence of cervical dilation ≥1 cm on physical exam (30% vs 3%, odds ratio 12.29 (3.05-49.37) P < 0.001) with a negative predictive value of 97%. Patients with ≥1 cm dilation had increased preterm birth <37 weeks (75% vs 39%, P = 0.03) compared to those not dilated. Women with a CL ≤11 mm had increased preterm birth <37 weeks (77% vs 31%, P < 0.001), preterm birth <34 weeks (63% vs 22%, P < 0.001), and lower birthweight (1552 ± 1047 vs 2560 ± 1072 g, P < 0.001) compared to women with CL >11 mm. CONCLUSIONS: Among singletons without prior preterm birth diagnosed with short cervix (≤25 mm), CL ≤11 mm may identify a subgroup of patients at high risk for asymptomatic cervical dilation and poor perinatal outcome. Physical exam should be considered and adjunctive preterm birth prevention measures should be studied in singletons with CL ≤11 mm.

Association of Fetal Fraction of Cell-Free DNA and Hypertensive Disorders of Pregnancy.

OBJECTIVE: The objective of this study is to examine the relationship between fetal fraction and hypertensive disorders of pregnancy. STUDY DESIGN: This is a retrospective cohort study of women with singleton pregnancies who had cell-free DNA (cfDNA) screening at 10 to 20 weeks of gestation. The primary outcome was the development of gestational hypertension (gHTN), preeclampsia (PEC), and PEC with severe features. Multinomial logistic regression was performed to assess the relationship between fetal fraction and pregnancy outcomes of interest while controlling for potential confounders. RESULTS: Among 2,701 women meeting inclusion criteria, 387 (14.3%) were diagnosed with hypertensive disorders of pregnancy. First-trimester fetal fraction was significantly lower in women diagnosed with hypertensive disorders of pregnancy (10.9 vs. 12.4, p < 0.0001). An increased risk of gHTN and PEC, PEC with severe features with delivery > 34 weeks, and PEC with severe features with delivery ≤ 34 weeks was seen with lower first-trimester fetal fractions (odds ratio [OR]: 0.55, 95% confidence interval [CI] [0.36-0.83], p = 0.005; OR: 0.59, 95% CI [0.35-0.99], p = 0.048; and OR: 0.27, 95% CI [0.08-0.96], p = 0.044). The relationship between fetal fraction and hypertensive disorders of pregnancy was not statistically significant after adjusting for maternal age, race, body mass index, and chronic hypertension. CONCLUSION: Fetal fraction of cfDNA at 10 to 20 weeks of gestation was not associated with the development of hypertensive disorders of pregnancy.

The benefits and limitations of cell-free DNA screening for 22q11.2 deletion syndrome.

Cell-free DNA testing is increasingly being used to screen pregnant women for fetal aneuploidy. This technology may also identify microdeletion syndromes, including 22q11.2 deletion syndrome, the most common microdeletion syndrome, and the 22q11.2 duplication syndrome. The purpose of this paper is to provide an overview of the 22q11.2 deletion syndrome, to review the early experience with cell-free DNA screening for this deletion and to consider the potential benefits that may be associated with prenatal detection of the deletion. © 2016 John Wiley & Sons, Ltd.