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.

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.

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.

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.

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.

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.

Mirror syndrome: a systematic literature review.

OBJECTIVE: This study aimed to review the diagnostic criteria for mirror syndrome and describe its clinical presentation. DATA SOURCES: Databases from PubMed, Scopus, Cochrane Library, ClinicalTrials.gov, and CINAHL were inquired for case series containing ≥2 cases of mirror syndrome from inception to February 2022. STUDY ELIGIBILITY CRITERIA: Studies were included if they reported ≥2 cases of mirror syndrome and included case reports, case series, cohort studies, and case-control studies. STUDY APPRAISAL AND SYNTHESIS METHODS: The studies' quality and risk of bias were independently assessed. Data were tabulated using Microsoft Excel and summarized using narrative review and descriptive statistics. This systematic review was conducted according to the Preferred Reporting Item for Systematic Reviews and Meta-Analyses statement. All eligible references were assessed. Screening of records and data extraction were independently performed, and a third author resolved disagreements. RESULTS: Of 13 citations, 12 studies (n=82) reported diagnostic criteria for mirror syndrome: maternal edema (11/12), fetal hydrops (9/12), placental edema (6/12), placentomegaly (5/12), and preeclampsia (2/12); 12 studies (n=82) described the clinical presentation of mirror syndrome as maternal edema (62.2%), hypoalbuminemia (54.9%), anemia (39.0%), and new-onset hypertension (39.0%); 4 studies (n=36) reported that hemodilution was present in all patients; 8 studies (n=36) reported the etiology of fetal hydrops, with the most common being structural cardiac malformations (19.4%), alpha thalassemia (19.4%), Rh isoimmunization (13.9%), and nonimmune hydrops fetalis (13.9%); and 6 studies (n=47) reported maternal complications, 89.4% of which were major: postpartum hemorrhage (44.7%), hemorrhage requiring blood transfusion (19.1%), intensive care unit admission (12.8%), heart failure (10.6%), pulmonary edema (8.5%), and renal dysfunction (8.5%). In 39 cases, the reported fetal outcomes were stillbirth (66.6%) and neonatal or infant death (25.6%). The overall survival rate among continued pregnancies was 7.7%. CONCLUSION: The diagnostic criteria of mirror syndrome differed considerably among studies. Mirror syndrome clinical presentation overlapped with preeclampsia. Only 4 studies discussed hemodilution. Significant maternal morbidity and fetal mortality were associated with mirror syndrome. Further research is warranted to elucidate the pathogenesis of mirror syndrome to better guide clinicians in identifying and managing the condition.

HELLP syndrome at <23 weeks' gestation: a systematic literature review.

OBJECTIVE: We performed a systematic review to evaluate the clinical presentation and maternal and fetal outcomes in pregnancies with early-onset HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. DATA SOURCES: PubMed, Ovid MEDLINE, Scopus, CINAHL, Cochrane Library, and ClinicalTrials.gov were queried from inception through January 1, 2023 with the following terms: "HELLP syndrome," "HELLP," "hemolysis, elevated liver enzymes, low platelets," "hemolysis, elevated liver enzymes, low platelets syndrome," "pre-viable," "peri-viable," "previable," "periviable," "first trimester," "second trimester," "before 23 weeks," "<23 weeks," "<23 week gestation," and "before 23 weeks gestation." We also included an additional case from our institution. STUDY ELIGIBILITY CRITERIA: Abstracts, unpublished studies, and review articles were excluded, yielding 46 studies that met our inclusion criteria. METHODS: Two reviewers (N.S.I. and M.H.M.) performed the study selection and subsequent data extraction independently, after which the results were reviewed together. PRISMA guidelines were followed, and our study was registered at PROSPERO (CRD42021292692). RESULTS: A total of 55 patients had 58 pregnancies complicated by early-onset HELLP syndrome, including 3 with recurrent HELLP. The most common presenting signs/symptoms were abdominal pain (35/45; 78%), hypertension (32/49; 65%), nausea/vomiting (16/45; 36%), headache (13/45; 29%), and edema (8/45; 18%). Lactate dehydrogenase ≥600 IU/L was observed in 21 of 31 (68%) cases, whereas liver enzyme abnormalities and thrombocytopenia were reported in 48 of 51 (94%) and 50 of 54 (93%) cases, respectively. Maternal complications were encountered in 25 of 56 (45%) cases. The most common complications were hepatic (13/56; 23%), central nervous system-related (11/56; 20%), and respiratory (11/56; 20%). In 36 of 57 (63%) cases, pregnancy was terminated. Of the 21 continued pregnancies, early fetal death (at <20 weeks' gestation) was reported in 10 (48%), stillbirth in 6 (28%), and neonatal demise in 2 (10%). Living neonates were reported in 3 of 21 (14%) cases, all delivered at 23 weeks. The perinatal mortality rate was 73% (8/11). One case (2%) reported maternal death. Antiphospholipid syndrome was diagnosed in 14 of 29 (48%) cases. CONCLUSION: Early-onset HELLP syndrome presents with symptoms similar to those observed in later gestation. Maternal complications are life-threatening, with the most common complications being hepatic, central nervous system-related, and respiratory. Fetal outcomes are poor.

Diagnostic yield from prenatal exome sequencing for non-immune hydrops fetalis: A systematic review and meta-analysis.

Non-immune hydrops fetalis (NIHF) has multiple genetic etiologies diagnosable by exome sequencing (ES). We evaluated the yield of prenatal ES for NIHF, and the contribution of additional clinical findings and history. Systematic review was performed with PROSPERO tag 232951 using CINAHL, PubMed, and Ovid MEDLINE from January 1, 2000 through December 1, 2021. Selected studies performed ES to augment standard prenatal diagnostic approaches. Cases meeting a strict NIHF phenotype were tabulated with structured data imputed from papers or requested from authors. Genetic variants and diagnostic outcomes were harmonized across studies using current ACMG and ClinGen variant classification guidelines. Thirty-one studies reporting 445 NIHF cases had a 37% (95% CI: 32%-41%) diagnostic rate. There was no significant difference between isolated NIHF and NIHF with fetal malformations or between recurrent and simplex cases. Diagnostic rate was higher for consanguineous than non-consanguineous cases. Disease categories included RASopathies (24%), neuromuscular (21%), metabolic (17%), lymphatic (13%), other syndromes (9%), cardiovascular (5%), hematologic (2%), skeletal (2%), and other categories (7%). Inheritance patterns included recessive (55%), dominant (41%), and X-linked (4%). ES should be considered in the diagnostic workup of NIHF with and without associated ultrasound findings regardless of history of recurrence or consanguinity.

Implications for Prenatal Genetic Testing in the United States After the Reversal of Roe v Wade.

Prenatal genetic screening and diagnostic testing should be offered to every pregnant individual, with methods varying based on gestational age. Since Roe v Wade was overturned in June 2022, many states have implemented gestational age-based abortion restrictions. It is critical that reproductive health care professionals be aware of the interaction between the timing of genetic screening and diagnostic testing and the availability of legal abortion services in their state. We examined individual state abortion restrictions per publicly available data from The New York Times and the Guttmacher Institute and reviewed which genetic screening and diagnostic tests could be performed to provide results in time for individuals to decide whether to terminate their pregnancies legally in each state. As of December 11, 2022, 14 states have restrictions in which no diagnostic testing could be completed before gestational age-based cutoffs. Gestational age-based abortion restrictions may also influence a patient to favor chorionic villous sampling (CVS) over amniocentesis. There are two states, Florida and Arizona, where CVS would be feasible before the state's gestational age limit on abortion but amniocentesis would not. Both CVS and amniocentesis are feasible in 35 states, with legal challenges pending in 8 of the 35. Seven states specifically prohibit abortion for fetuses with genetic abnormalities. Clinicians may be placed in the suboptimal position of counseling patients with screening results alone before the gestational age-based ban in their state. There are several potential downstream consequences of gestational age-based termination restrictions for current genetic screening and testing paradigms, from adjustments to counseling options to potentially higher CVS procedure rates. Clinicians should be prepared for practice patterns to change to best serve patients in this evolving legal context.

Prenatal phenotype of 47, XXY (Klinefelter syndrome).

OBJECTIVE: There is a paucity of knowledge regarding the prenatal presentation of Klinefelter syndrome, or 47, XXY. Accurate prenatal counseling is critical and in utero diagnosis is currently limited by a poor understanding of the prenatal phenotype of this condition. METHODS: This is a case series of fetuses with cytogenetically confirmed 47, XXY in the prenatal period or up to age 5 years, with prenatal records available for review from four academic institutions between 2006 and 2019. Ultrasound reports were reviewed in detail to assess for increased nuchal translucency and structural abnormalities. Additionally, we reviewed results of cell-free DNA and serum analyte testing when performed to inform our understanding of the detection of fetal 47, XXY through standard genetic screening tests. RESULTS: Forty-one cases with confirmed cytogenetic diagnosis of 47, XXY and prenatal records available for review were identified: 37 had a prenatal diagnosis and 4 had a postnatal diagnosis. Nuchal translucency was increased ≥3.0 mm in 23.1% (6/26) of cases with a documented measurement. In 29.2% (7/24) of cases with a second trimester anatomical ultrasound available for review, a fetal abnormality was identified (3 brain anomalies, 1 cardiac abnormality, 1 echogenic bowel, and 2 limb abnormalities). Among those who had cell-free DNA and serum analytes performed, 92.6% (25/27) and 36.3% (4/11) had an abnormal result respectively. CONCLUSION: This case series expands our knowledge of the prenatal presentation of 47, XXY by identifying first and second trimester fetal sonographic abnormalities. Prenatal identification of this condition enables accurate counseling, focused prenatal management, and early postnatal interventions to ameliorate some of the known complications.