Prenatal Phenotype of Alkuraya-Kucinskas Syndrome: A Novel Case and Systematic Literature Review.

Alkuraya-Kucinskas syndrome (AKS) is an autosomal recessive multisystem disorder resulting from mutations in the BLTP1 gene, formerly known as KIAA1109. Primary manifestations include brain malformations, arthrogryposis, and clubfeet. Cardiac, renal, and ophthalmologic abnormalities may also be observed, while nonimmune hydrops is rare. We present a case of two novel BLTP1 canonical splice-site variants in a fetus with multiple congenital anomalies, including hydrops, a kinked brainstem, and joint contractures. A systematic literature review was conducted to describe the prenatal phenotype of AKS, which was inspired by our case. Our systematic literature review of the prenatal phenotype in 19 cases, including our additional case, demonstrated joint contractures in 90% (18/20), ventriculomegaly in 60% (12/20), brainstem dysgenesis in 50% (10/20), cerebellar hypoplasia in 50% (10/20), parenchymal thinning with lissencephalic aspect in 60% (12/20), and facial dysmorphism in 70% (14/20) of reported AKS cases. In addition to our case, hydrops was reported in two other families. AKS should be considered in fetal presentations with characteristic features, especially brainstem kinking and joint contractures. Exome sequencing, including coverage of canonical intronic splice-site variants, can clarify the diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT03911531.

Propranolol to decrease time to delivery: a meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the effect of propranolol on time to delivery among patients undergoing induction or augmentation of labor. DATA SOURCES: PubMed, Scopus, Cochrane Library, ClinicalTrials.gov, and CINAHL (EBSCO) were searched from inception to December 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) that examined the impact of propranolol on time to delivery among patients undergoing induction or augmentation of labor were included. RCTs that included stillbirth before randomization, non-randomized trials, observational, cohort, case control, or studies in which the control group included an intervention other than standard care were excluded. STUDY APPRAISAL AND SYNTHESIS METHODS: Primary outcome was time to delivery after administration of propranolol among patients undergoing induction or augmentation of labor. The summary measures were reported as summary mean difference (MD) or relative risk with 95% confidence interval (CI). RESULTS: Nine RCTs including 1,182 patients were included in this meta-analysis. Five studies investigated the effect of propranolol among patients undergoing induction of labor (IOL) and demonstrated a significant decrease in time to delivery (MD, -91.5 minutes, 95% CI -110.6 to -72.4). Four studies investigated the effect of propranolol among patients undergoing augmentation of labor and showed no significant decrease in time to delivery (MD, -2.98 minutes, 95% CI -21.6 to 15.6). Our pooled analysis demonstrated that the use of propranolol in IOL and augmentation was associated with a decrease in time to delivery from administration of propranolol compared to placebo (mean difference, -46.15 minutes, 95% CI -59.48 to -32.81). The meta-analysis found no increased risk of PPH, blood transfusion, cesarean delivery rates, or NICU admission with the use of propranolol during labor. CONCLUSION: The use of propranolol during induction of labor shortens overall time to delivery by about 91 minutes and did not significantly decrease time to delivery in those undergoing augmentation of labor.

Recombinant erythropoietin for the treatment of iron deficiency anemia in pregnancy: A systematic review.

BACKGROUND: Treatment options for severe, refractory iron deficiency anemia are limited in pregnancy. OBJECTIVE: To review the available literature on the use of recombinant erythropoietin in the treatment of iron deficiency anemia in pregnancy. SEARCH STRATEGY: An electronic search of seven databases from inception to March 2022 was performed using a combination of keywords. SELECTION CRITERIA: We included all randomized controlled or observational studies of pregnant patients with iron deficiency anemia who received recombinant erythropoietin or control. The primary outcome was a change in hematologic parameters (hemoglobin or hematocrit) after treatment. Studies were appraised using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. DATA COLLECTION AND ANALYSIS: Data were summarized using narrative synthesis and descriptive statistics as appropriate. This study was registered with PROSPERO, CRD42022313328. MAIN RESULTS: Of 234 studies screened, five studies met the inclusion criteria and had sufficient data for analysis (n = 103 recombinant erythropoietin and n = 104 controls). All patients in the intervention group received iron supplementation (intravenous or oral) in addition to recombinant erythropoietin. All patients in the control group received iron supplementation (intravenous or oral) alone. As the result of variance between studies in inclusion criteria, the timing of repeat blood draws, and data reporting, a meta-analysis could not be performed. Three studies found that serial recombinant erythropoietin combined with iron supplementation was more effective at raising hematologic laboratory parameters (hemoglobin or hematocrit) than iron alone. One study reported no difference in hemoglobin or hematocrit levels between groups at day 28. However, patients in this study only received one dose of recombinant erythropoietin, whereas those in the other studies received serial doses. Another study also found no difference in hemoglobin levels by day 28, but patients in the recombinant erythropoietin group had lower hemoglobin levels at baseline and a more rapid rise in hemoglobin than iron alone. This is demonstrated by a more significant rise in hemoglobin at day 11 in the recombinant erythropoietin group than in the control group. CONCLUSIONS: Serial recombinant erythropoietin administration and iron supplementation may be more effective at treating refractory iron deficiency anemia in pregnancy than iron supplementation alone.

DNA methylation patterns in umbilical cord blood from infants of methadone maintained opioid dependent mothers.

Methadone maintenance treatment for opioid dependent mothers is standard of care. Infants of methadone maintained opioid dependent (MMOD) mothers have better outcomes compared to infants of opioid dependent mothers without treatment. However, when compared to non-exposed infants, infants of MMOD mothers are associated with worse outcomes. We conducted a pilot study to examine genome wide differential DNA methylation using cord blood samples from sixteen term and near-term infants of MMOD and opioid naïve mothers, excluding Infants with chorioamnionitis. A total of 152 differentially methylated loci were identified at a difference > + 2, < - 2 and p-value < 0.05. There were 90 hypermethylated loci (59 annotated genes) and 62 hypomethylated loci (38 annotated genes) observed. The hypermethylated and hypomethylated DNA changes involved multiple genes, pathways and networks that may explain some of the changes seen in infants of MMOD mothers. Top hypermethylated and hypomethylated genes involved areas of cell growth, neurodevelopment, vision and xenobiotic metabolism functions. Our data may explain the role of key pathways and genes relevant to neonatal outcomes seen from methadone exposure in pregnancy. Functional studies on the identified pathways and genes could lead to improved understanding of the mechanisms and identify areas for intervention.

Glucose-6-phosphate dehydrogenase deficiency as a cause for nonimmune hydrops fetalis and severe fetal anemia: A systematic review.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive disorder that predisposes individuals to hemolysis due to an inborn error of metabolism. We performed a systematic literature review to evaluate G6PD deficiency as a possible etiology of nonimmune hydrops fetalis (NIHF) and severe fetal anemia. METHODS: PubMed, OVID Medline, Scopus, and clinicaltrials.gov were queried from inception until 31 April 2023 for all published cases of NIHF and severe fetal anemia caused by G6PD deficiency. Keywords included "fetal edema," "hydrops fetalis," "glucose 6 phosphate dehydrogenase deficiency," and "fetal anemia." Cases with workup presuming G6PD deficiency as an etiology for NIHF and severe fetal anemia were included. PRISMA guidelines were followed. RESULTS: Five cases of G6PD-related NIHF and one case of severe fetal anemia were identified. Four fetuses (4/6, 66.7%) were male and two fetuses (2/6, 33.3%) were female. Mean gestational age at diagnosis of NIHF/anemia and delivery was 32.2 ± 4.9 and 35.7 ± 2.4 weeks, respectively. Four cases (66.7%) required a cordocentesis for fetal transfusion, and two cases (33.3%) received blood transfusions immediately following delivery. Among the four multigravida cases, two (50%) noted previous pregnancies complicated by neonatal anemia. When reported, the maternal cases included two G6PD deficiency carrier patients and two G6PD-deficient patients. Exposures to substances known to cause G6PD deficiency-related hemolysis occurred in 3/6 (50%) cases. CONCLUSION: Six cases of NIHF/severe fetal anemia were associated with G6PD deficiency. While G6PD deficiency is an X-linked recessive condition, female fetuses can be affected. Fetal G6PD deficiency testing can be considered if parental history indicates, particularly if the standard workup for NIHF is negative.

Trends in Preeclampsia Risk Factors in the US From 2010 to 2021.

This population-based retrospective study uses data from the National Vital Statistics System to evaluate trends in risk factors for preeclampsia in the US between 2010 and 2021.

Antenatal steroids and neonatal outcomes in late preterm births with pregestational diabetes.

OBJECTIVE: To evaluate if antenatal steroid use was associated with a lower rate of respiratory complications in neonates born late preterm to patients with pregestational diabetes mellitus (PGDM). METHODS: This was a retrospective cohort study of live, singleton, non-anomalous, late preterm births complicated by PGDM using data from the Centers for Disease Control and National Vital Statistics System from 2017 to 2021. The primary (assisted ventilation use >6 h) and secondary neonatal outcomes (immediate assisted ventilation, Apgar score, neonatal intensive care unit [NICU] admission, and surfactant use) were compared between births that received steroids and those that did not. Multivariable analyses were performed to adjust for differences in demographic and clinical characteristics. RESULTS: There were 24 323 late preterm births with PGDM, of which 4613 received antenatal steroids and 19 710 did not receive steroids. After adjusting for the differences among the two groups, the need for assisted neonatal ventilation for more than 6 h (adjusted odds ratio [aOR] 1.69, 95% confidence interval [CI] 1.53-1.86), immediate assisted neonatal ventilation (aOR 1.67, 95% CI 1.55-1.80), NICU admission (aOR 1.95, 95% CI 1.81-2.10), and surfactant use (aOR 1.68, 95% CI 1.40-2.02) were higher in the births that received steroids compared with those that did not. These findings did not differ when examining outcomes at each gestational week of delivery between 34 weeks 0 days and 36 weeks 6 days. CONCLUSIONS: Antenatal steroid use in late preterm births complicated with PGDM was associated with worse immediate respiratory neonatal outcomes. Our findings support current recommendations against the use of steroids in the late preterm period in pregnancies with PGDM.

The genetic etiologies of bilateral renal agenesis.

OBJECTIVE: The goal of this study was to review and analyze the medical literature for cases of prenatal and/or postnatally diagnosed bilateral renal agenesis (BRA) and create a comprehensive summary of the genetic etiologies known to be associated with this condition. METHODS: A literature search was conducted as a scoping review employing Online Mendeliain Inheritance in Man, PubMed, and Cochrane to identify cases of BRA with known underlying genetic (chromosomal vs. single gene) etiologies and those described in syndromes without any known genetic etiology. The cases were further categorized as isolated versus non-isolated, describing additional findings reported prenatally, postnatally, and postmortem. Inheritance pattern was also documented when appropriate in addition to the reported timing of diagnosis and sex. RESULTS: We identified six cytogenetic abnormalities and 21 genes responsible for 20 single gene disorders associated with BRA. Five genes have been reported to associate with BRA without other renal anomalies; sixteen others associate with both BRA as well as unilateral renal agenesis. Six clinically recognized syndromes/associations were identified with an unknown underlying genetic etiology. Genetic etiologies of BRA are often phenotypically expressed as other urogenital anomalies as well as complex multi-system syndromes. CONCLUSION: Multiple genetic etiologies of BRA have been described, including cytogenetic abnormalities and monogenic syndromes. The current era of the utilization of exome and genome-wide sequencing is likely to significantly expand our understanding of the underlying genetic architecture of BRA.

Maternal outcomes of a cohort of pregnancies affected by non-immune hydrops fetalis.

OBJECTIVE: To describe the maternal outcomes of a prospective cohort of non-immune hydrops fetalis (NIHF) pregnancies with negative standard-of-care evaluations. METHODS: This study was a secondary analysis of a prospective cohort study of NIHF pregnancies with negative work-ups (infection, alloimmune anemia, fetomaternal hemorrhage, and chromosomal disorders). Outcomes were obstetric complications, including pre-eclampsia, mirror syndrome, preterm birth, polyhydramnios, postpartum hemorrhage, and maternal mental health. RESULTS: Forty pregnancies were included. Four patients developed pre-eclampsia (4/40, 10.0%); three occurred postpartum. None was diagnosed with mirror syndrome. Of the 31 continued pregnancies, 16 (51.6%) resulted in early fetal death or stillbirth and 15 (48.4%) resulted in live births. Of the 15 live births, 8 (53.3%) were delivered by primary cesarean delivery; 5 (62.5%) were for hydrops fetalis. Eleven live births (73.3%) were delivered preterm; 9 (81.8%) were indicated, most commonly for fetal indications (7/9, 77.8%). Polyhydramnios occurred in 14/40 (35.0%) cases. Where EBL was recorded (n=37), there were 5 (13.5%) cases of postpartum hemorrhage and an additional 3 (8.1%) had uterine atony without hemorrhage. Eighteen patients (18/40, 45.0%) had new-onset or exacerbated depression or anxiety symptoms. CONCLUSION: Our study identified several important adverse outcomes of pregnancies complicated by NIHF with negative standard-of-care evaluations, including a high rate of postpartum pre-eclampsia and worsened mental health. We identified a higher rate of cesarean delivery and preterm birth, both primarily for fetal indications. We also observed the known relationship between polyhydramnios, hemorrhage, and atony, but noted that this risk included pregnancies concluding in dilation and evacuation. Counseling after a diagnosis of NIHF should include these adverse outcomes.

RASopathies are the most common set of monogenic syndromes identified by exome sequencing for nonimmune hydrops fetalis: A systematic review and meta-analysis.

RASopathies are a group of malformation syndromes known to lead to nonimmune hydrops fetalis (NIHF) in severe presentations. Pathogenic variants can be de novo or parentally inherited. Despite being a known frequent presentation, the fraction of monogenic NIHF cases due to RASopathies is limited in the literature. Also, the specific parental contribution of RASopathies to NIHF is not well described. Our objective was to review pooled exome sequencing (ES) diagnostic yield of RASopathies for NIHF and to determine the parental contribution of RASopathy to NIHF. We performed a systematic review of prenatal ES studies from January 1, 2000 to August 1, 2022. Thirty-six studies met inclusion criteria. Cases with RASopathy gene variants were reviewed. NIHF cases were further classified as isolated or non-isolated. Thirty-six ES studies including 46 pregnancies with NIHF and a diagnosed RASopathy were reviewed. Forty-four diagnostic variants and 2 variants of uncertain significance in 12 RASopathy genes were identified. Expanding on what was previously published, a total of 506 NIHF cases were extracted with 191 cases yielding a positive diagnosis by ES. The overall rate of RASopathy diagnosis in clinically diagnosed NIHF cases was 9% (44/506). The rate of RASopathy diagnosis among NIHF cases with positive genetic diagnosis by ES was 23% (44/191). Of the 46 cases identified, 13 (28%) variants were parentally inherited; specifically, 5/13 (38%) maternal, 3/13 (23%) paternal, 2/13 (15%) biparental, and 3/13 (23%) unspecified. Majority of NIHF cases 29/46 (63%) were isolated. Among NIHF cases with positive ES diagnoses, RASopathy diagnostic yield by ES was 23%. NIHF secondary to RASopathies was parentally inherited in 28% of cases. Most cases of NIHF due to RASopathy were isolated, with no prenatal detection of associated anomalies.

Use of cell salvage at the time of cesarean delivery: a meta-analysis of randomized controlled trials.

OBJECTIVE: Excess blood loss from obstetrical hemorrhage requires transfusion of donor blood, a finite resource. Intraoperative cell salvage collects a patient's own blood that has been lost during cesarean delivery and returns it to their own circulation. We performed a meta-analysis to examine the perioperative outcomes in patients receiving cell salvage at the time of cesarean delivery. DATA SOURCES: Scopus, PubMed, Cochrane Central Register of Controlled Trials, Ovid Medline, and clinicaltrials.gov were searched from database inception through October 2023. STUDY ELIGIBILITY CRITERIA: Eligible studies included randomized controlled trials comparing the use of cell salvage to standard-of-care during cesarean delivery. METHODS: Two authors independently extracted data. Preferred Reporting Items of Systematic Reviews and Meta-Analysis guidelines were used for data extraction and quality assessment. The primary outcomes were the rate of donor blood transfusion and change in hemoglobin level. The secondary outcomes included transfusion reaction, amniotic fluid embolism, and length of hospital stay. Results were summarized as weighted mean difference or risk ratio with associated 95% confidence intervals. Heterogeneity was measured using Higgins I2. RESULTS: A total of 5 randomized controlled trials (n=3361) comparing cell salvage to standard care during cesarean delivery met the inclusion criteria. Primary analysis showed a significant decrease in receiving allogeneic blood transfusion with intraoperative cell salvage use vs standard care (odds ratio, 0.32; 95% confidence interval, 0.23-0.46), with no change in hemoglobin drop (mean difference, -0.77; 95% confidence interval, -1.67 to -0.14). The secondary outcomes showed no difference in transfusion reaction (odds ratio, 0.56; 95% confidence interval, 0.06-5.59), and length of hospital stay (mean difference, -1.90; 95% confidence interval, -4.85 to 1.06). No cases of amniotic fluid embolism were reported among the 1685 patients who received cell salvage. CONCLUSION: Use of cell salvage during cesarean delivery reduced the overall need for allogeneic blood transfusion without increasing the risk of complications, including no cases of amniotic fluid embolism.

Imaging and outcomes of fetal adrenal hemorrhage: A systematic review.

OBJECTIVE: To describe prenatal and postnatal imaging findings of fetal adrenal hemorrhage (FAH) and its associated perinatal outcomes, including frequency of postnatal surgical intervention. METHOD: A systematic literature review of seven electronic databases was conducted from inception until January 2022, with 2008 articles identified reporting prenatally identified fetal adrenal masses. Studies with confirmed FAH diagnosis were included. Quality and risk assessment were evaluated. RESULTS: Thirty-five studies, including 102 FAH cases, were analyzed. FAH was commonly described as cystic (28/90, 31%), anechoic (25/90, 28%), or mixed echogenic (14/90, 16%) on ultrasound. Outcome data were available for 65 cases (64%) of FAH: 9% (6/65) resolved prenatally, 35% (23/65) resolved postnatally, 34% (22/65) regressed in size after birth, and 22% (14/65) persisted postnatally. Overall, 25% (16/65) of cases underwent postnatal surgical intervention. Neuroblastoma was suspected in all 16 surgical cases. Only one case (1/16, 6%) confirmed a cystic hematoma with microscopic islets of neuroblastoma in situ on pathology. CONCLUSION: Prenatal diagnosis of FAH is challenging due to the significant heterogeneity of ultrasound findings. Final pathology did not support the need for surgical intervention. Persistent postnatal FAH warrants shared decision making for further management based on the clinical presentation.

PIEZO1 is the most common monogenic etiology of non-immune hydrops fetalis detected by prenatal exome sequencing.

OBJECTIVE: To clarify the relevance of PIEZO1 variants detected by prenatal exome in the context of non-immune hydrops fetalis (NIHF). METHODS: A systematic review of prenatal exome studies from 1/1/2000-8/1/2022 was performed. Thirty-six studies met the inclusion criteria. PIEZO1 variants were categorized by disease mode (dominant (AD) versus recessive (AR)) and classified by the American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: Twenty-two pregnancies with 35 distinct PIEZO1 variants were included. We deemed PIEZO1 variants to be "likely diagnostic" in 12/22 pregnancies, "possibly diagnostic" in 7/22, and "unlikely diagnostic" in 3/22. In total, 19 of 191 NIHF cases diagnosed by prenatal exome were attributed to PIEZO1. Among likely diagnosed cases, the disease mode was AR in eight and AD in four. PIEZO1 variants causing AR NIHF were characterized by loss of function and isolated NIHF phenotype. PIEZO1 variants causing AD NIHF were characterized by gain of function in red blood cells, scarcity in databases, and sporadic inheritance. Missense variants associated with NIHF were clustered in three domains: transmembrane helical unit 4 (THU4), THU5, and the Cap. CONCLUSION: PIEZO1 variants were reported in 10% of NIHF cases diagnosed by prenatal exome, making PIEZO1 the most common single gene reported in NIHF.

Misoprostol with balloon vs oxytocin with balloon in high-risk pregnancy induction: a randomized controlled trial.

BACKGROUND: Pregnancies at high risk for maternal, fetal, or placental complications often necessitate induction of labor in the late preterm or early term period for delivery. Limited data exist on the safest method of induction to use in this specific patient population. OBJECTIVE: This study aimed to compare the combination of oxytocin plus a Cook balloon vs misoprostol plus a Cook balloon for induction of labor in high-risk pregnancies. STUDY DESIGN: We conducted an open-label, randomized controlled trial at a single institution from July 2020 to May 2022. The study was approved by the institutional review board and registered with ClinicalTrials.gov (NCT04492072). Individuals with a high-risk pregnancy, at least ≥22 weeks' gestation, with a singleton in cephalic presentation, Bishop score ≤6, and intact membranes were offered enrollment. A high-risk pregnancy was defined as a pregnancy with any of the following complications: hypertensive disease of pregnancy, fetal growth restriction, oligohydramnios, suspected placental abruption requiring delivery, uncontrolled pregestational diabetes, or abnormal biophysical profile or nonstress test requiring delivery. The primary outcome was the rate of cesarean delivery. Secondary maternal outcomes included induction to delivery interval, number of vaginal deliveries within 24 hours, rates of uterine tachysystole, intraamniotic infection, operative vaginal delivery, and postpartum hemorrhage. Secondary fetal outcomes included fetal heart rate abnormalities, stillbirth, Apgar scores <7 at 5 minutes, admission to the neonatal intensive care unit, arterial umbilical blood pH <7.1, sepsis, and neonatal death. A subgroup analysis was planned for the primary outcome to assess the different indications for cesarean delivery. An intent-to-treat analysis was performed. RESULTS: During the 22 months of the trial, a total of 150 patients were randomized, and 73 (49%) of those were induced with oxytocin and a Cook balloon and 77 (51%) were induced with misoprostol and a Cook balloon. There was no significant difference in the overall rate of cesarean delivery between the study groups, (21.9% vs 31.1%; relative risk, 0.70; 95% confidence interval, 0.41-1.21), nor among those for which the cesarean delivery was performed for a specific indication. There were no differences in the secondary maternal and fetal or neonatal adverse outcomes. CONCLUSION: In high-risk pregnancies, the rate of cesarean delivery and adverse maternal and fetal outcomes were similar for induction of labor with oxytocin and a Cook balloon and for induction with misoprostol and a Cook balloon.

Genetic counseling practices among outpatient obstetric providers in the Northeast.

BACKGROUND: The American College of Obstetricians and Gynecologists recommends all pregnant people be offered genetic screening and diagnostic testing regardless of risk factors. Previous studies have demonstrated disparities in referrals for genetic testing by race outside of pregnancy, but limited data exist regarding genetic counseling practices during pregnancy. OBJECTIVE: This study aimed to describe how patient, provider, and practice demographics influence the offering of diagnostic prenatal genetic testing by outpatient prenatal care providers. STUDY DESIGN: This was a multicenter anonymous survey study conducted between October 2021 and March 2022. Outpatient prenatal care providers, including family medicine and obstetrics attendings, residents, maternal-fetal medicine fellows, nurse practitioners, physician assistants, and midwives, were surveyed about their genetic counseling practices and practice demographics. The primary outcome was the proportion of respondents who answered "yes, all patients" to the survey question "Do you offer diagnostic genetic testing to all patients?" The secondary outcomes included the association between patient and practice demographics and offering diagnostic testing. Diagnostic testing was defined as chorionic villus sampling or amniocentesis. Screening genetic tests were defined as sequential screen, quadruple screen, cell-free DNA screening, or "other." The chi-square test or Fisher exact test was used as appropriate. For the outcome answers of diagnostic testing, logistic regression was performed to assess the association between the answer of diagnostic genetic testing and the current training level of providers, race and ethnicity, and insurance status variables. Multivariable analysis was performed to adjust for confounders. RESULTS: A total of 635 outpatient prenatal care providers across 7 sites were sent the survey. Overall, 419 providers responded for a total response rate of 66%. Of the providers who responded, most were attendings (44.9%), followed by residents (37.5%). Providers indicated the race, insurance status, and primary language of their patient population. Screening genetic testing was offered by 98% of providers. Per provider report, 37% offered diagnostic testing to all patients, 18% did not offer it at all, and 44% only offered it if certain patient factors were present. Moreover, 54.8% of attendings reported universally offering diagnostic testing. On univariable analysis, residents were less likely to offer diagnostic testing than attendings (odds ratio, 0.18; 95% confidence interval, 0.11-0.30). Providers who serve non-Hispanic Black, Hispanic Black, and other Hispanic patients were less likely to report offering diagnostic testing than other patient populations. Providers who served non-Hispanic Whites were more likely to offer diagnostic testing (odds ratio, 2.26; 95% confidence interval, 1.51-3.39). Patient populations who were primarily privately insured were more likely to be offered diagnostic testing compared with primarily publicly insured patients (odds ratio, 6.25; 95% confidence interval, 3.60-10.85). Providers who served a primarily English-speaking population were more likely to offer diagnostic genetic testing than other patient populations (odds ratio, 0.43; 95% confidence interval, 0.26-0.69). On multivariable analysis, the factors that remained significantly associated with offering diagnostic testing included level of training (resident odds ratio, 0.33; 95% confidence interval, 0.17-0.62; P=.0006; advanced practice provider odds ratio, 0.34; 95% confidence interval, 0.15-0.82; P=.02), having at least one-third of the patient population identify as "other Hispanic" (odds ratio, 0.42; 95% confidence interval, 0.23-0.77; P=.005), and having private insurance instead of public insurance (primarily private insured odds ratio, 2.84; 95% confidence interval, 1.20-6.74; P=.02). CONCLUSION: Although offering genetic screening and diagnostic testing to all patients is recommended, no provider group universally offers diagnostic testing. Providers who serve populations from a racial and ethnic minority, those with public insurance, and those whose primary language is not English are less likely to report universally offering diagnostic genetic testing.

Management of a Retained Broken Suture Needle During Cerclage Placement.

BACKGROUND: Broken suture needles with unintentional foreign body retention are an uncommon occurrence during obstetric procedures. Few reports exist in the literature of cases in pregnant patients. We report a case with the pregnancy management of a broken needle during cerclage placement that was retained in the cervix until repeat cesarean delivery. CASE: A 36-year-old woman, gravida 12 para 5, presented at 13 weeks of gestation for a history-indicated cerclage. The suture needle broke during the cerclage procedure, leaving a 35-mm needle fragment inside the cervical stroma between the 11 and 2 o'clock position that could not be recovered after multiple attempts. The procedure continued without needle recovery. Intraoperative pelvic X-ray was performed, demonstrating the retained fragment. No further attempts at recovery were made during the pregnancy, and a plan was made to proceed with removal at the patient's repeat cesarean delivery. The patient presented in labor at 32 1/7 weeks of gestation and underwent an uncomplicated cesarean delivery. The retained needle was subsequently removed after manual palpation of the fragment transvaginally. CONCLUSION: Retained broken suture needles during obstetric procedures require careful management decisions in pregnant patients. Retention of a needle fragment until delivery may be considered if risks of removal outweigh the anticipated benefits.

Changes in Rates of Hypertensive Disorders of Pregnancy Among Nulliparous Patients After the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) Trial.

The ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial demonstrated lower rates of hypertensive disorders of pregnancy (HDP) among low-risk nulliparous patients undergoing labor induction at 39 weeks of gestation. We conducted a population-based cohort study in which we evaluated the association between the routinization of 39-week induction and the rate of HDP by comparing rates before and after the ARRIVE trial publication, using the National Vital Statistics System. Logistic regression models were used to project what the HDP rate would have been based on trends seen pre-ARRIVE. Despite an overall increase in the rate of HDP from pre-ARRIVE to post-ARRIVE (4.9% pre vs 6.3% post, adjusted odds ratio [aOR] 1.26, 95% CI 1.24-1.27), the HDP rate was significantly lower in the post-ARRIVE group among patients undergoing induction at 39 weeks of gestation (14.7% pre vs 14.1% post, aOR 0.91, 95% CI 0.90-0.93), decreasing by 12.0% per year (P<.001). The rate of HDP among all other delivering patients was higher in the post-ARRIVE group (4.1% pre vs 5.5% post, aOR1.32, 95% CI 1.30-1.34). Our findings may suggest that, as the overall HDP rate rises, the relative advantage of 39-week induction will rise similarly.

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.

SARS-CoV-2 Covid-19 Infection During Pregnancy and Differential DNA Methylation in Human Cord Blood Cells From Term Neonates.

Background: The global pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). About 18.4% of total Covid-19 cases were reported in children. Even though vertical transmission from mother to infant is likely to occur at a low rate, exposure to COVID-19 during fetal life may alter DNA methylation patterns with potential long-term effects. Objective: To determine if COVID-19 infection during pregnancy alters the DNA methylation patterns in umbilical cord blood cells from term infants and to identify potential pathways and genes affected by exposure to COVID-19 infection. Methods: Umbilical cord blood was collected from 8 infants exposed to COVID-19 during pregnancy and 8 control infants with no COVID-19 exposure. Genomic DNA was isolated from umbilical cord blood cells and genome-wide DNA methylation was performed using Illumina Methylation EPIC Array. Results: 119 differentially methylated loci were identified at the FDR level of 0.20 (64 hypermethylated loci and 55 hypomethylated loci) in umbilical cord blood cells of COVID-19 exposed neonates compared to the control group. Important canonical pathways identified by Ingenuity Pathway Analysis (IPA) were related to stress response (corticotropin releasing hormone signaling, glucocorticoid receptor signaling, and oxytocin in brain signaling pathway), and cardiovascular disease and development (nitric oxide signaling in the cardiovascular system, apelin cardiomyocyte signaling pathways, factors promoting cardiogenesis, and renin-angiotensin signaling). The genes affected by the differential methylations were associated with cardiac, renal, hepatic, neurological diseases, developmental and immunological disorders. Conclusions: COVID-19 induces differential DNA methylation in umbilical cord blood cells. The differentially methylated genes may contribute to hepatic, renal, cardiac, developmental and immunological disorders in offspring born to mothers with COVID-19 infection during pregnancy, and their developmental regulation.