The patient experience of a postpartum readmission for hypertension: a qualitative study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are the most common cause of postpartum readmission. Prior research led to clinical guidelines for postpartum management; however, the patient experience is often missing from this work. The objective of this study is to understand the perspective of patients readmitted for postpartum hypertension. METHODS: This was a qualitative study with data generated through semi-structured interviews. Patients readmitted with postpartum HDP at an urban academic medical center from February to December 2022 were approached and consented for an interview. The same researcher conducted all interviews and patient recruitment continued until thematic saturation was reached (n = 9). Two coders coded all interviews using Nvivo software with both deductive and inductive coding processes. Discrepancies were discussed and resolved with consensus among the two coders. Themes were identified through an initial a priori template of codes which were expanded upon using grounded theory, and researchers were reflexive in their thematic generation. RESULTS: Six themes were generated: every pregnancy is different, symptoms of preeclampsia are easily dismissed or minimized by both patient and providers, miscommunication regarding medical changes can increase the risk of readmissions, postpartum care coordination and readmission logistics at our hospital could be improved to facilitate caring for a newborn, postpartum care is often considered separately from the rest of pregnancy, and patient well-being improved when conversations acknowledged the struggles of readmission. CONCLUSIONS: This qualitative research study revealed patient-identified gaps in care that may have led to readmission for hypertensive disorders of pregnancy. The specific recommendations that emerge from these themes include addressing barriers to blood pressure management prior to discharge, improving postpartum discharge follow-up, providing newborn care coordination, and improving counseling on the risk of postpartum preeclampsia during discharge. Incorporating these patient perspectives in hospital discharge policy can be helpful in creating patient-centered systems of care and may help reduce rates of readmission.

Prenatal vs postnatal diagnosis of 22q11.2 deletion syndrome: cardiac and noncardiac outcomes through 1 year of age.

BACKGROUND: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis. OBJECTIVE: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome. STUDY DESIGN: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 deletion syndrome by 1 year of age with or without congenital heart disease; those with prenatal diagnosis or suspicion (suggestive ultrasound findings and/or high-risk cell-free fetal DNA screen for 22q11.2 deletion syndrome with postnatal confirmation) were compared with those with postnatal diagnosis. Perinatal management, cardiac and noncardiac morbidity, and mortality by 1 year were assessed. Outcomes were adjusted for presence of critical congenital heart disease, gestational age at birth, and site. RESULTS: A total of 625 fetuses, neonates, or infants with 22q11.2 deletion syndrome (53.4% male) were included: 259 fetuses were prenatally diagnosed (156 [60.2%] were live-born) and 122 neonates were prenatally suspected with postnatal confirmation, whereas 244 infants were postnatally diagnosed. In the live-born cohort (n=522), 1-year mortality was 5.9%, which did not differ between groups but differed by the presence of critical congenital heart disease (hazard ratio, 4.18; 95% confidence interval, 1.56-11.18; P<.001) and gestational age at birth (hazard ratio, 0.78 per week; 95% confidence interval, 0.69-0.89; P<.001). Adjusting for critical congenital heart disease and gestational age at birth, the prenatal cohort was less likely to deliver at a local community hospital (5.1% vs 38.2%; odds ratio, 0.11; 95% confidence interval, 0.06-0.23; P<.001), experience neonatal cardiac decompensation (1.3% vs 5.0%; odds ratio, 0.11; 95% confidence interval, 0.03-0.49; P=.004), or have failure to thrive by 1 year (43.4% vs 50.3%; odds ratio, 0.58; 95% confidence interval, 0.36-0.91; P=.019). CONCLUSION: Prenatal detection of 22q11.2 deletion syndrome was associated with improved delivery management and less cardiac and noncardiac morbidity, but not mortality, compared with postnatal detection.

Unique Challenges of NIPT for Sex Chromosome Aneuploidy.

Noninvasive prenatal testing (NIPT) for the sex chromosome aneuploidies (45,X, 47,XXY, 47,XXX, and 47,XYY) differs significantly from that for the autosomal aneuploidies (trisomy 13, 18, and 21). As a group, sex chromosome aneuploidies occur more commonly (1/400) than any one isolated autosomal aneuploidy, the phenotypic variation is greater, the role of mosaicism more challenging, and the positive predictive value of a high-risk NIPT result is substantially lower. These considerations should be identified during pretest counseling, the inclusion of sex chromosome testing offered separately, and the differences from autosomal aneuploidy NIPT clearly delineated.

Postnatal genetic testing on cord blood for prenatally identified high-probability cases.

OBJECTIVE: To evaluate the utility of postnatal genetic testing on umbilical cord blood (CB) for prenatally identified high-probability fetuses. METHOD: CB for genetic testing was offered to individuals who met one of the following criteria: (i) fetal anomaly, (ii) positive non-invasive prenatal screening by cfDNA or biochemical analysis, or (iii) family history. Individuals with diagnostic testing, but not microarray, were also included when recommended by society guidelines. CB was collected at Brigham and Women's and Emerson Hospitals between 2016 and 2021. RESULTS: 448 individuals consented for cord blood testing (370 (82.6%) for fetal anomalies, 51 (11.4%) for high-probability cfDNA, and 27 (6.0%) for family history) and a total of 393 (87.7%) samples were analyzed. Genetic testing yielded a diagnosis in 92 (23.4%) neonates by karyotype (n = 37), chromosomal microarray (CMA) (n = 32), and other molecular analysis (n = 23). Testing averaged 10.3 days (range 1-118 days). 68 (73.9%) diagnoses potentially impacted neonatal management. MCC could not be definitively excluded in only 1.4% (6/418) of samples. CONCLUSION: Prenatal identification of high-probability fetuses and genetic testing on CB facilitates timely genetic diagnoses and neonatal management. Testing provides reassurance and reduces a postnatal diagnostic odyssey for high-probability neonates.

Single gene non-invasive prenatal screening for autosomal dominant conditions in a high-risk cohort.

PURPOSE: To determine the utility of single gene non-invasive prenatal screening (NIPS-SGD) in a high-risk reproductive genetics clinic. METHODS: A clinical pilot for NIPS-SGD was conducted from March 2020 to November 2021. A NIPS-SGD panel assessing pathogenic variants in 30 genes was offered to pregnant individuals for the following indications: (1) advanced sperm age ≥40 years, (2) nuchal translucency (NT) ≥ 3.5 mm, (3) fetal anomaly, or (4) family history of a condition covered by the panel. Diagnostic testing was offered concurrently. RESULTS: NIPS-SGD was ordered for 253 individuals: 88 (34.8%) for fetal anomalies, 96 (37.9%) for advanced sperm age, 37 (14.6%) for increased NT, and 5 (2.0%) for family history. Among 228 (90.1%) completed tests, 8 (3.5%) were positive. Diagnostic testing for 78 individuals revealed no false positive or negative results. Of 41 (25.9%) individuals who received a molecular diagnosis, 34 (82.9%) were outside the scope of NIPS-SGD. Positive NIPS-SGD altered medical management in five cases. CONCLUSIONS: NIPS-SGD in a high-risk population can lead to earlier prenatal diagnosis, enhanced surveillance, and targeted genetic analysis, but should not replace clinically indicated diagnostic testing. Potential incidental findings include parental diagnoses and misattributed parentage.

Redesigning Care for the Management of Postpartum Hypertension: How Can Ob-Gyns and Primary Care Physicians Partner in Caring for Patients after a Hypertensive Pregnancy?

The standard care model in the postpartum period is ripe for disruption and attention. Hypertensive disorders of pregnancy (HDPs) can continue to be a challenge for the postpartum person in the immediate postpartum period and is a harbinger of future health risks. The current care approach is inadequate to address the needs of these women. We propose a model for a multidisciplinary clinic and collaboration between internal medicine specialists and obstetric specialists to shepherd patients through this high-risk time and provide a bridge for lifelong care to mitigate the risks of a HDP. KEY POINTS: · HDPs are increasing in prevalence.. · The postpartum period can be more complex for women with HDPs.. · A multidisciplinary clinic could fill the postpartum care gap for women with HDP..

Overcoming roadblocks in clinical innovation via high fidelity simulation: use of a phantom simulator to achieve FDA and IRB approval of a clinical trial of fetal embolization of vein of Galen malformations.

BACKGROUND: Vein of Galen malformation (VOGM) is a rare, life-threatening vascular malformation in neonates and is treated with embolization. However, even at the most experienced centers, patients face high mortality and morbidity. In utero treatment options have been limited by lack of animal models or simulations. OBJECTIVE: To create a novel ultrasound phantom simulator for a preclinical feasibility study of in utero fetal intervention for VOGM. METHODS: Novel phantoms were designed and built in two configurations of spherical and windsock shape from cryogel material to mimic the salient vasculature of the fetal VOGM, based on real-patient fetal MR imaging dimensions. Critical anatomy was realistically mimicked within this model and transtorcular ultrasound-guided coil deployment was simulated. Each phantom model was assessed before and after treatment to evaluate coil mass deposition within the target. RESULTS: The two phantoms underwent pretreatment T2-weighted MR imaging assessment, ultrasound-guided embolization, post-treatment MR and fluoroscopic imaging, and visual inspection of the sliced phantoms for target embolization verification. Postoperative MR scans confirmed realistic compact deposition of the coil masses within the central cavity. Phantom embolization results were submitted as part of the institutional review board and US Food and Drug Administration investigative device exemption approval for a first-in-humans clinical trial of fetal intervention for VOGM. CONCLUSIONS: A phantom simulator for fetal intervention of VOGM produces lifelike results during trial interventions, removing obstacles to feasibility and safety evaluations, typically precluded by non-availability of appropriate animal models. The study provides a proof of concept for potentially wider applications of medical simulation to enable novel procedural advancements in neurointerventions.

Prenatal diagnosis of sex chromosome aneuploidy-What do we tell the prospective parents?

Sex chromosome aneuploidy (SCA) can be detected on prenatal diagnostic testing and cell free DNA screening (cfDNA). High risk cfDNA results should be confirmed with diagnostic testing. This summary article serves as an update for prenatal providers and assimilates data from neurodevelopmental, epidemiologic, and registry studies on the most common SCA. This information can be helpful for counseling after prenatal diagnosis of sex chromosome aneuploidy. Incidence estimates may be influenced by ascertainment bias and this article is not a substitute for interdisciplinary consultation and counseling.

The hypergonadotropic hypogonadism conundrum of classic galactosemia.

BACKGROUND: Hypergonadotropic hypogonadism is a burdensome complication of classic galactosemia (CG), an inborn error of galactose metabolism that invariably affects female patients. Since its recognition in 1979, data have become available regarding the clinical spectrum, and the impact on fertility. Many women have been counseled for infertility and the majority never try to conceive, yet spontaneous pregnancies can occur. Onset and mechanism of damage have not been elucidated, yet new insights at the molecular level are becoming available that might greatly benefit our understanding. Fertility preservation options have expanded, and treatments to mitigate this complication either by directly rescuing the metabolic defect or by influencing the cascade of events are being explored. OBJECTIVE AND RATIONALE: The aims are to review: the clinical picture and the need to revisit the counseling paradigm; insights into the onset and mechanism of damage at the molecular level; and current treatments to mitigate ovarian damage. SEARCH METHODS: In addition to the work on this topic by the authors, the PubMed database has been used to search for peer-reviewed articles and reviews using the following terms: 'classic galactosemia', 'gonadal damage', 'primary ovarian insufficiency', 'fertility', 'animal models' and 'fertility preservation' in combination with other keywords related to the subject area. All relevant publications until August 2022 have been critically evaluated and reviewed. OUTCOMES: A diagnosis of premature ovarian insufficiency (POI) results in a significant psychological burden with a high incidence of depression and anxiety that urges adequate counseling at an early stage, appropriate treatment and timely discussion of fertility preservation options. The cause of POI in CG is unknown, but evidence exists of dysregulation in pathways crucial for folliculogenesis such as phosphatidylinositol 3-kinase/protein kinase B, inositol pathway, mitogen-activated protein kinase, insulin-like growth factor-1 and transforming growth factor-beta signaling. Recent findings from the GalT gene-trapped (GalTKO) mouse model suggest that early molecular changes in 1-month-old ovaries elicit an accelerated growth activation and burnout of primordial follicles, resembling the progressive ovarian failure seen in patients. Although data on safety and efficacy outcomes are still limited, ovarian tissue cryopreservation can be a fertility preservation option. Treatments to overcome the genetic defect, for example nucleic acid therapy such as mRNA or gene therapy, or that influence the cascade of events are being explored at the (pre-)clinical level. WIDER IMPLICATIONS: Elucidation of the molecular pathways underlying POI of any origin can greatly advance our insight into the pathogenesis and open new treatment avenues. Alterations in these molecular pathways might serve as markers of disease progression and efficiency of new treatment options.

Hemodynamic and anatomic changes after fetal aortic valvuloplasty are associated with procedural success and postnatal biventricular circulation.

BACKGROUND: There are minimal data characterizing the trajectory of left heart growth and hemodynamics following fetal aortic valvuloplasty (FAV). METHODS: This retrospective study included patients who underwent FAV between 2000 and 2019, with echocardiograms performed pre-FAV, immediately post-FAV, and in late gestation. RESULTS: Of 118 fetuses undergoing FAV, 106 (90%) underwent technically successful FAV, of which 55 (52%) had biventricular circulation. Technically successful FAV was associated with improved aortic valve growth (p < 0.001), sustained antegrade aortic arch (AoA) flow (p = 0.02), improved mitral valve (MV) inflow pattern (p = 0.002), and favorable patent foramen ovale (PFO) flow pattern (p = 0.004) from pre-FAV to late gestation. Compared to patients with univentricular outcome, patients with biventricular outcome had less decrement in size of the left ventricle (LV) (p < 0.001) and aortic valve (p = 0.005), as well as more physiologic PFO flow (p < 0.001) and antegrade AoA flow (p < 0.001) from pre-FAV to late gestation. In multivariable analysis, echocardiographic predictors of biventricular outcome were less decline in LV end diastolic dimension (p < 0.001), improved PFO flow (p = 0.004), and sustained antegrade AoA flow (p = 0.002) from pre-FAV to late gestation. CONCLUSION: Stabilization of left heart growth and improved hemodynamics following successful FAV through late gestation are associated with postnatal biventricular circulation.

Percutaneous transuterine fetal cerebral embolisation to treat vein of Galen malformations at risk of urgent neonatal decompensation: study protocol for a clinical trial of safety and feasibility.

INTRODUCTION: Although endovascular techniques have improved outcomes in vein of Galen malformations (VOGM), there is still a high rate of morbidity and mortality, particularly among cases with decompensation in the neonatal period. The dimension of the draining venous sinus on fetal imaging correlates with the risk of neonatal decompensation. In fetuses within this high-risk group who do not have end-organ injury, there is a theoretical therapeutic opportunity to reduce the arteriovenous shunt before the normal physiological changes of birth precipitate decompensation. This study investigates the safety and potential benefit of treating a VOGM in utero, which has not been previously studied. METHODS AND ANALYSIS: This study aims to enroll 20 subjects: pregnant women with a fetus harbouring a high-risk VOGM (defined on MRI by a narrowest medial-lateral width greater than 8 mm in the draining venous sinus). Unfortunately, the subset of fetuses with in utero end-organ injury is ineligible, because the late stage of pathology is not amenable to recovery from a cerebrovascular intervention, likely not even in utero. This study aims to alter the physiology before such developments accrue.At or after 23 weeks of gestation, a transuterine transposterior fontanelle needle puncture to the torcular allows ultrasound-guided deployment of coils to embolise the draining venous malformation.This study has 97.5% power to detect major safety events at 30% or greater, and 80% power to detect a reduction in the rate of neonatal intervention from 80% to 30%. In the staged study design, an interval evaluation after 11 patients invokes study termination if safety events occur above the allowed threshold. ETHICS AND DISSEMINATION: The institutional review boards at Mass General Brigham and Boston Children's Hospital (BCH) reviewed and approved this protocol. The BCH Department of Radiology and a patient family philanthropic donation fund this study. The trial results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04434729.

International Society for Prenatal Diagnosis Updated Position Statement on the use of genome-wide sequencing for prenatal diagnosis.

The research and clinical use of genome-wide sequencing for prenatal diagnosis of fetuses at risk for genetic disorders have rapidly increased in recent years. Current data indicate that the diagnostic rate is comparable and for certain indications higher than that of standard testing by karyotype and chromosomal microarray. Responsible clinical implementation and diagnostic use of prenatal sequencing depends on standardized laboratory practices and detailed pre-test and post-test counseling. This Updated Position Statement on behalf of the International Society for Prenatal Diagnosis recommends best practices for the clinical use of prenatal exome and genome sequencing from an international perspective. We include several new points for consideration by researchers and clinical service and laboratory providers.

ISPD 2021 debate - All in vitro fertilization cycles should involve pre-implantation genetic testing to improve fetal health and pregnancy outcomes.

For 3 decades, couples at increased risk for a genetic disorder have been offered preimplantation genetic testing (PGT). Simultaneously, PGT for aneuploidy (PGT-A) to improve in vitro fertilization (IVF) outcomes was introduced, but evidence of value-added remains inconsistent. Recently, lower genetic testing costs and shorter turnaround time have reinvigorated PGT-A. Additionally, a shift from blastomere (day 3) to blastocyst (day 5) transfer and embryo freezing advances support PGT without the time constraints of immediate transfer. PGT-A transformed from a time-constrained analysis of 1-2 cells to an "add on" study for all IVF. But should it be offered to all IVF patients? And if not, under what conditions? Pre-debate polling found 64% opposed to PGT for all IVF cycles with concerns voiced about cost, informed consent, and a "slippery slope". Leaving aside the inconsistent evidence of IVF improvement whether measured as miscarriage or livebirths with PGT-A, the debaters grappled with patient and provider desires versus the ethical concerns for the unborn child. However, the audience was not swayed; two thirds remained opposed to PGT for all IVF cycles.

Counseling for personal health implications identified during reproductive genetic carrier screening.

OBJECTIVE: Preconception and prenatal carrier screening is designed to provide reproductive risk information, but carriers for some autosomal recessive or X-linked conditions also have personal health risks. This study investigated the prevalence of and inclusion of personal health implications in pre- and post-test counseling. METHODS: Twelve genetic conditions with personal health risks for carriers included on carrier screening panels but not otherwise screened routinely were identified (e.g., Gaucher disease with Parkinson's disease risk). A retrospective review was performed of patients with a positive carrier screen for one of these conditions at our center from 2012 to 2019. RESULTS: Of 6147 individuals that had carrier screening for one of the twelve conditions, 96 (1.56%) did not report a known family history and screened positive for one of the conditions. Testing was ordered largely by reproductive endocrinologists (51.0%) and genetic counselors (35.4%). Most individuals did not receive pre- (96.8%) or post-test (64.6%) counseling about personal health risks. Post-test counseling was performed principally by genetic counselors (97.1%). For carriers of conditions with guidelines for specialist referral, most individuals (75.9%) were referred. CONCLUSION: Expanded genetic carrier screening increasingly identifies individuals with personal health implications, but patients are frequently not counseled before or after testing. These findings stress the importance of developing guidelines for practitioners about expanded carrier screening counseling and follow-up.

Problems with Using Polygenic Scores to Select Embryos.

Companies have recently begun to sell a new service to patients considering in vitro fertilization: embryo selection based on polygenic scores (ESPS). These scores represent individualized predictions of health and other outcomes derived from genomewide association studies in adults to partially predict these outcomes. This article includes a discussion of many factors that lower the predictive power of polygenic scores in the context of embryo selection and quantifies these effects for a variety of clinical and nonclinical traits. Also discussed are potential unintended consequences of ESPS (including selecting for adverse traits, altering population demographics, exacerbating inequalities in society, and devaluing certain traits). Recommendations for the responsible communication about ESPS by practitioners are provided, and a call for a society-wide conversation about this technology is made. (Funded by the National Institute on Aging and others.).

General practitioners' knowledge about pregnancy complications associated with long-term cardiovascular risk.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of mortality in women; preeclampsia (PE) and gestational diabetes mellitus (GDM) are associated with an increased risk of CVD. OBJECTIVE: To evaluate general practitioners (GP) knowledge about complicated pregnancies and their association with CVD. METHODS: An anonymous case-based electronic questionnaire designed to assess the level of understanding on the influence of a history of pregnancy complications on long-term cardiovascular risk and general knowledge about CVD risk was sent to GPs. RESULTS: The response rate was 35 % (161/465). The participants recognized that PE and GDM are risk factors for CVD (98 and 83 %, respectively), and reported the following CVD screening strategies in women with a history of PE and GDM: blood pressure monitoring (PE 100 %, GDM 46 %), body mass index calculation (PE 68 %, GDM 57 %), lipid profile evaluation (PE 71 %, GDM 57 %), glycated hemoglobin (PE 26 %, GDM 92 %), and fasting glucose (PE 28 %, GDM 91 %). CONCLUSION: GP-reported screening strategies to identify CVD in women with a history of PE and GDM were variable.

INTRODUCCIÓN: La enfermedad cardiovascular (ECV) constituye la principal causa de mortalidad en mujeres; la preeclampsia (PE) y la diabetes mellitus gestacional (DMG) están asociadas a incremento en el riesgo de ECV. OBJETIVO: Evaluar el conocimiento de los médicos generales (MG) sobre complicaciones obstétricas asociadas a ECV. MÉTODOS: Se envió a los MG un cuestionario electrónico anónimo basado en casos, diseñado para evaluar el entendimiento de la influencia de la historia obstétrica en el riesgo cardiovascular a largo plazo y el conocimiento general sobre riesgo de ECV. RESULTADOS: La tasa de respuesta fue de 35 % (161/465). Los participantes reconocieron que la PE y la DMG son factores de riesgo para ECV (98 y 83 %, respectivamente) y reportaron las siguientes estrategias de tamizaje de ECV en mujeres con historial de PE y DMG: monitoreo de presión arterial (PE 100 %, DMG 46 %), cálculo de índice de masa corporal (PE 68 %, DMG 57 %), evaluación del perfil de lípidos (PE 71 %, DMG 57 %), hemoglobina glucosilada (PE 26 %, DMG 92 %) y glucosa en ayuno (PE 28 %, DMG 91 %). CONCLUSIÓN: Las estrategias de tamizaje para identificar ECV en mujeres con antecedentes de PE y DMG reportadas por los MG fueron variables.

Utility of noninvasive genome-wide screening: a prospective cohort of obstetric patients undergoing diagnostic testing.

PURPOSE: Copy-number variant (CNV) assessment is recommended for patients undergoing prenatal diagnostic testing. Noninvasive screening tests have not been extensively validated for CNV detection. The objective of this study was to compare the ability of genome-wide noninvasive prenatal screening (NIPS) to chromosomal microarray to detect clinically significant findings. METHODS: We prospectively enrolled 198 subjects at the time of consent for diagnostic prenatal testing. Genome-wide NIPS results were compared with diagnostic testing results to assess NIPS test performance (n = 160, 38 subjects without microarray results excluded). Cohen's kappa statistic was used to assess test agreement. RESULTS: Genome-wide NIPS did not detect clinically significant chromosomal abnormalities at the same rate as diagnostic testing, κ = 0.75 (95% confidence interval [CI], 0.62-0.87). When excluding CNVs <7 Mb and findings outside the limits of genome-wide NIPS, test agreement improved, κ = 0.88 (0.79-0.97) driven by agreement for common aneuploidies (κ = 1.0). However, among patients with an abnormal fetal survey, agreement was only fair, κ = 0.38 (0.08-0.67). CONCLUSION: While NIPS is an excellent screening test for common aneuploidies, genome-wide NIPS misses clinically significant findings detected on routine diagnostic testing. False positive and false negative cases highlight the importance of pretest counseling regarding NIPS limitations, especially in the setting of fetal anomalies.