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BACKGROUND: The cause of most fetal anomalies is not determined prenatally. Exome sequencing has transformed genetic diagnosis after birth, but its usefulness for prenatal diagnosis is still emerging. Nonimmune hydrops fetalis (NIHF), a fetal abnormality that is often lethal, has numerous genetic causes; the extent to which exome sequencing can aid in its diagnosis is unclear. METHODS: We evaluated a series of 127 consecutive unexplained cases of NIHF that were defined by the presence of fetal ascites, pleural or pericardial effusions, skin edema, cystic hygroma, increased nuchal translucency, or a combination of these conditions. The primary outcome was the diagnostic yield of exome sequencing for detecting genetic variants that were classified as either pathogenic or likely pathogenic according to the criteria of the American College of Medical Genetics and Genomics. Secondary outcomes were the percentage of cases associated with specific genetic disorders and the proportion of variants that were inherited. RESULTS: In 37 of the 127 cases (29%), we identified diagnostic genetic variants, including those for disorders affecting the RAS-MAPK cell-signaling pathway (known as RASopathies) (30% of the genetic diagnoses); inborn errors of metabolism and musculoskeletal disorders (11% each); lymphatic, neurodevelopmental, cardiovascular, and hematologic disorders (8% each); and others. Prognoses ranged from a relatively mild outcome to death during the perinatal period. Overall, 68% of the cases (25 of 37) with diagnostic variants were autosomal dominant (of which 12% were inherited and 88% were de novo), 27% (10 of 37) were autosomal recessive (of which 95% were inherited and 5% were de novo), 1 was inherited X-linked recessive, and 1 was of uncertain inheritance. We identified potentially diagnostic variants in an additional 12 cases. CONCLUSIONS: In this large case series of 127 fetuses with unexplained NIHF, we identified a diagnostic genetic variant in approximately one third of the cases. (Funded by the UCSF Center for Maternal-Fetal Precision Medicine and others; ClinicalTrials.gov number, NCT03412760.).
Subject(s)
Exome Sequencing , Genetic Variation , Hydrops Fetalis/diagnosis , Hydrops Fetalis/genetics , Prenatal Diagnosis , Female , Humans , Pregnancy , PrognosisABSTRACT
PURPOSE OF REVIEW: Chronic hypertension affects up to 10% of pregnancies in the United States and the incidence of hypertensive diseases of pregnancy has more than doubled in the past decade, affecting minority women at disproportionate rates. Recent data show potential benefit by lowering the threshold of blood pressure treatment for pregnant women to >140/90âmmHg. RECENT FINDINGS: In April 2022, the results of the Chronic Hypertension and Pregnancy (CHAP) trial was published and demonstrated that lower thresholds (>140/90 vs. >160/110âmmHg) for the initiation of antihypertensive therapy during pregnancy resulted in better pregnancy outcomes without negative impacts to foetal growth. In addition, professional societies, such as the American College of Obstetrics and Gynecology (ACOG) and the Society of Maternal Fetal Medicine (SMFM), have released statements supporting the initiation of antihypertensive therapy at elevations above 140/90âmmHg for pregnant women with chronic hypertension based upon these recent reports. SUMMARY: Treatment of hypertension in pregnant women is controversial, but recent data are emerging that treatment at lower blood pressure thresholds may be associated with improved perinatal outcomes without an increased risk of poor foetal growth. Although these recommendations may be applied to women with chronic hypertension, more research is needed to determine how these guidelines should be applied to other hypertensive diseases of pregnancy.
Subject(s)
Hypertension , Pre-Eclampsia , Female , Pregnancy , Humans , Blood Pressure/physiology , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/pharmacology , Hypertension/drug therapy , Pregnancy OutcomeABSTRACT
OBJECTIVES: Measles immunity testing, unlike that for rubella, is not currently part of prenatal screening even though immunity to both is conferred by the measles-mumps-rubella (MMR) vaccine. Although endemic transmission of measles was declared eliminated in the United States in 2001, outbreaks have continued to occur. Given the risks associated with measles infection during pregnancy, we sought to identify risk factors for measles nonimmunity (MNI) in rubella-immune (RI) pregnant individuals. METHODS: We performed a retrospective observational cross-sectional study of patients receiving prenatal care and delivering at two university hospitals and a county hospital in Southern California from April 1, 2019 to February 1, 2021. Inclusion criteria were pregnant individuals ≥18 years old who had serological testing for rubella and measles during pregnancy. Demographic data were extracted from electronic medical records, including results of serological testing and chronic medical conditions. All subjects were rubella immune, and we compared measles-immune (MI) with MNI groups. RESULTS: In total, 1,813 RI individuals were identified, with 1,467 (81%) MI and 346 (19%) MNI individuals. Variables associated with an increased risk of MNI included having public health insurance (adjusted relative risk [aRR]: 1.56; 95% confidence interval [CI]: 1.24, 1.97) and Hispanic ethnicity (aRR: 1.37; 95% CI: 1.06, 1.78). Black race was associated with a decreased risk of MNI (aRR: 0.52; 95% CI: 0.29, 0.91). Birth year before 1989 demonstrated a trend toward increased risk of MNI, but this did not reach statistical significance (aRR 1.23; 95% CI: 1.00, 1.52). No differences were seen between the two groups for medical comorbidities. CONCLUSION: Our study is the first to demonstrate risk factors for measles MNI in patients with documented rubella immunity. In the absence of universal measles serological screening recommendations, the risk factors identified could help guide clinicians in selective screening for those at risk of needing postpartum MMR vaccination. KEY POINTS: · The rate of measles nonimmunity is higher than previously reported.. · Hispanic ethnicity and use of public insurance are risk factors for measles nonimmunity.. · The current recommendation for history-based screening for measles immunity is likely insufficient..
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OBJECTIVE: To review the pathophysiology of rhabdomyomas and the emerging option of prenatal treatment of fetal cardiac rhabdomyomas. METHODS: We present a case of fetal rhabdomyomas causing significant hemodynamic compromise that received in utero treatment of maternal sirolimus. Genetic amniocentesis confirmed a TSC2 mutation. A treatment program was initiated with a 10-mg loading dose titrated to a goal maternal trough of 10 to 15 ng/dL. In order to follow fetal cardiac function, a sophisticated method of speckle tracking echocardiography was used before and after treatment. Obstetric ultrasound was used to monitor fetal growth, and clinical surveillance, echocardiography, and brain MRI were used to monitor postnatal growth and development through 6 months of neonatal life. RESULTS: Sirolimus was initiated from 28 to 36 weeks of gestation with improvement of cardiac status. During this period, intrauterine growth restriction developed. Postnatally, the infant has had stable rhabdomyomas and cardiac function without reinitiating sirolimus. Brain MRI demonstrated scattered cortical tubers and subependymal nodules, and the infant has not had seizure-like activity. At 6 months of age, the infant has achieved appropriate developmental milestones. CONCLUSION: In counseling cases of prenatal onset large obstructing rhabdomyomas and cardiac compromise, in utero sirolimus treatment can be considered.
Subject(s)
Heart Neoplasms/drug therapy , Heart Neoplasms/embryology , Rhabdomyoma/drug therapy , Rhabdomyoma/embryology , Sirolimus/administration & dosage , Adult , Amniocentesis , Echocardiography , Female , Genetic Testing , Gestational Age , Heart Neoplasms/genetics , Humans , Mutation , Pregnancy , Prenatal Diagnosis , Rhabdomyoma/genetics , TOR Serine-Threonine Kinases/antagonists & inhibitors , Treatment Outcome , Tuberous Sclerosis Complex 2 Protein/geneticsABSTRACT
OBJECTIVE: This study aims to evaluate the utility of social media to distribute a patient survey on differences in management and outcomes of monochorionic-diamniotic (MCDA) pregnancies. STUDY DESIGN: A cross-sectional survey was posted to an English-language MCDA twins patient-centered support group within the social media site, Facebook from April 2, 2018 to June 26, 2018. Subjects were recruited through a technique called "snowballing," whereby individuals shared the survey to assist with recruiting. Patient reported data were analyzed using Chi-square and Kruskal-Wallis's tests to explore characteristics associated with surveillance and outcomes as related to region and provider type. RESULTS: Over 3 months, the post "reached" 14,288 Facebook users, among which 5,653 (40%) clicked on the post. A total of 2,357 respondents with MCDA pregnancies completed the survey. Total 1,928 (82%) were from the United States (US) and 419 (18%) from other countries. Total 85% of patients had co-management with maternal-fetal medicine (MFM), more in the US compared with the rest of the world (87 vs. 74%, p < 0.01). MFM involvement led to increased adherence to biweekly ultrasounds (91 vs. 65%, p < 0.01), diagnosis of monochorionicity by 12 weeks (74 vs. 69%, p < 0.01) and better education about twin-twin transfusion syndrome (90 vs. 66%, p < 0.01). Pregnancies with MFM involvement had a higher take-home baby rate for both babies (92 vs. 89%, p < 0.01) or for at least one baby (98 vs. 93%, p < 0.01) compared with those without MFM involvement. CONCLUSION: A survey distributed via social media can be effective in evaluating real-life management and outcomes of an uncommon obstetrical diagnosis. This survey elucidates wide international variation in adherence to guidelines, management, and outcomes.
Subject(s)
Fetofetal Transfusion/epidemiology , Pregnancy, Twin , Social Media , Adolescent , Adult , Cross-Sectional Studies , Female , Guideline Adherence , Humans , Internationality , Middle Aged , Perinatology , Pregnancy , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Ultrasound training is a vital component of maternal-fetal medicine fellowships in the United States. Of the 18 months of core clinical training, the American Board of Obstetrics and Gynecology currently requires a minimum of 3 months to be dedicated to ultrasound to be eligible for board certification. However, the experience and degree of hands-on training differ among the fellowship programs and have not been reassessed for nearly a decade. OBJECTIVE: To assess regional heterogeneity in the ultrasound training experience during maternal-fetal medicine fellowship in the United States. STUDY DESIGN: A survey was distributed to postgraduate year (PGY)-6 maternal-fetal medicine fellows registered to attend an annual ultrasound training course before the conference (n=114). For programs with >1 fellow attending (n=39), only 1 of them completed the survey to represent the program. The questions included demographics of the program, ultrasound training structure, the fellows' self-perception of ultrasound capabilities, research, mentorship, and technical aspects of sonography. RESULTS: Seventy two postgraduate year 6 fellows with a wide geographic distribution as follows completed the survey (96% response rate): 10 (14%) from the West, 16 (22%) from the Midwest, 17 (24%) from the South, and 29 (40%) from the Northeast. Respondents undergoing training in the South were less likely to report feeling comfortable performing nuchal translucency and detailed anatomic surveys than those from other regions (nuchal translucency: P=.046; anatomy: P=.011). Most of the respondents reported feeling comfortable performing growth (78%) and umbilical artery Doppler (58%) and feeling uncomfortable with three-dimensional ultrasound, neurosonography, and fetal echocardiography. Respondents in the Northeast were more likely to report feeling comfortable performing chorionic villus sampling (P=.001). There was no difference among fellowship programs in the presence or absence of ultrasound curriculum, bedside teaching, ultrasound-focused research mentorship, or months of ultrasound training. CONCLUSION: Despite the standardization of ultrasound training structure across the United States, there remains regional heterogeneity in fellow self-reported comfort with specific ultrasound techniques and chorionic villus sampling at a midpoint in their fellowship training. The maternal-fetal medicine attending involvement at the bedside did not affect the fellow self-reported comfort with ultrasound surveys. This study highlights the need for further optimization of maternal-fetal medicine fellowship ultrasound training, especially in advanced sonography and diagnostic procedures.
Subject(s)
Obstetrics , Perinatology , Fellowships and Scholarships , Female , Humans , Obstetrics/education , Perception , Pregnancy , Prenatal Diagnosis , United StatesABSTRACT
Objective The objective of the study was to review the obstetric outcomes of complete hydatidiform molar pregnancies with a coexisting fetus (CHMCF), a rare clinical entity that is not well described. Materials and Methods We performed a retrospective case series with pathology-confirmed HMCF. The cases were collected via solicitation through a private maternal-fetal medicine physician group on social media. Each contributing institution from across the United States ( n = 9) obtained written informed consent from the patients directly, obtained institutional data transfer agreements as required, and transmitted the data using a Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliant modality. Data collected included maternal, fetal/genetic, placental, and delivery characteristics. For descriptive analysis, continuous variables were reported as median with standard deviation and range. Results Nine institutions contributed to the 14 cases collected. Nine (64%) cases of CHMCF were a product of assisted reproductive technology and one case was trizygotic. The median gestational age at diagnosis was 12 weeks and 2 days (9 weeks-19 weeks and 4 days), and over half were diagnosed in the first trimester. The median human chorionic gonadotropin (hCG) at diagnosis was 355,494 mIU/mL (49,770-700,486 mIU/mL). Placental mass size universally enlarged over the surveillance period. When invasive testing was performed, insufficient sample or no growth was noted in 40% of the sampled cases. Antenatal complications occurred in all delivered patients, with postpartum hemorrhage (71%) and hypertensive disorders of pregnancy (29%) being the most frequent outcomes. Delivery outcomes were variable. Four patients developed gestational trophoblastic neoplasia. Conclusion This series is the largest report of obstetric outcomes for CHMCF to date and highlights the need to counsel patients about the severe maternal and fetal complications in continuing pregnancies, including progression to gestational trophoblastic neoplastic disease. Key Points CHMCF is a rare obstetric complication and may be associated with the use of assisted reproductive technology.Universally, patients with CHMCF who elected to manage expectantly developed antenatal complications.The risk of developing gestational trophoblastic neoplasia after CHMCF is high, and termination of the pregnancy did not decrease this risk.
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BACKGROUND: The postpartum period is critical, and women are at highest risk of perinatal complications; however, patient attendance at postpartum clinic visits is low. OBJECTIVE: This study aimed to determine whether decreasing the time to an initial postpartum visit from 6 weeks to 2 weeks can increase the attendance rates of patients in routine postpartum visits. STUDY DESIGN: We conducted a parallel, randomized, nonblinded trial at a publicly insured clinic comparing a single 6-week postpartum visit (control) with 2 visits at 2 and 6 weeks after delivery (intervention). The primary outcome was attendance at 1 or more routine postpartum visits. Secondary outcomes were emergency department visits within 30 days after delivery and nonroutine clinic visits. Multivariable regression was performed to identify predictors of clinic nonattendance. To demonstrate a significant increase from the baseline clinic attendance rate of 70% to 85%, 250 participants were needed. RESULTS: Between November 2018 and March 2020, 250 patients were randomized and analyzed. The patient population had multiple comorbidities, notably obesity (53%), diabetes mellitus (30%), mental health disorders (22%), and hypertensive disorders (21%). The attendance at 1 or more postpartum visits was not significantly different among the control and intervention arms (58% vs 70%; P=.065). The 2-week visit had an attendance rate of 41% (51 of 125), and the 6-week visit had an attendance rate of 60% (151 of 250). After adjusting for confounders, significant predictors of postpartum visit nonattendance included younger age, multiparity, and being a patient from the high-risk obstetrical clinic. The rate of emergency department visits was similar between the control and intervention arms (8% vs 6%; P=.635). However, more patients in the control arm come to the clinic for nonroutine visits (30% vs 16%; P=.010). In response to a patient satisfaction survey on the optimal timing of the postpartum visit, most respondents (59%) would have preferred both the 2- and 6-week visits. CONCLUSION: The addition of a 2-week postpartum visit to the 6-week postpartum visit did not increase the likelihood of attendance of patients in a routine visit but did decrease the number of urgent clinic visits.
Subject(s)
Postnatal Care , Postpartum Period , Ambulatory Care , Female , Humans , Parity , Patient Satisfaction , PregnancyABSTRACT
Background: Mental health disorders are becoming more recognized in pregnancy. Whether mental health disorders are associated with health services utilization after child birth is not completely understood. Objective: This study aimed to investigate postpartum emergency department use within 30 days of delivery among women with preexisting mental health disorders during pregnancy. Study Design: This was a retrospective cohort study evaluating emergency department use among postpartum women with or without mental health disorders who delivered at an academic center between January 2014 and June 2018. Demographic and outcome data were medical record abstracted and analyzed. Multivariate regression was performed to adjust for covariates. Results: During the study period, 13,605 women delivered at the institution, 2355 of whom (17.3%) had an underlying mental health disorder. The primary diagnoses of mental health disorder were anxiety (48.8%), depression (34.8%), substance use disorder (11.4%), bipolar disorder (3.4%), psychosis (0.7%), and other (0.8%). There were a total of 565 emergency department visits within 30 days of delivery. Women who presented to the emergency department after delivery were more likely to have public insurance, identify as black or Asian, and have an underlying mental health disorder. Among women with mental health disorders, 155 (6.6%) used the emergency department within 30 days of their delivery compared with 410 (3.6%) of patients without mental health disorder (adjusted odds ratio, 1.74; 95% confidence interval, 1.42-2.13; P<.001). When assessing the risk of emergency department usage per the type of mental health disorder, anxiety (adjusted odds ratio, 1.73; 95% confidence interval, 1.31-2.27) and depression (adjusted odds ratio, 2.13; 95% confidence interval, 1.59-2.86) carried the highest risk. Compared with women without mental health disorders, women with underlying mental health disorders had more presentations for hypertension (15.5% vs 11.2%) and psychiatric evaluations (4.5% vs 0.2%; both P<.001). Conclusion: Women with mental health disorders use the emergency department during the postpartum period for psychiatric and obstetrical reasons more frequently than women without mental health disorders. Increased surveillance, treatment, and follow-up during pregnancy and the early postpartum period may be warranted for this high-risk population.
Subject(s)
Mental Health , Postpartum Period , Child , Emergency Service, Hospital , Female , Humans , Odds Ratio , Pregnancy , Retrospective StudiesABSTRACT
BACKGROUND: Gastroschisis is often complicated by fetal growth restriction, preterm delivery, and prolonged neonatal hospitalization. Prenatal management and delivery decisions are often based on estimated fetal weight and interval growth; however, appropriate interval growth from week to week across gestation for these fetuses is poorly understood. OBJECTIVE: This study aimed to determine the median increase in overall estimated fetal weight and individual biometric measurements across each week of gestation in pregnancies with fetal gastroschisis and to assess whether lower in utero fetal weight gain is predictive of postnatal growth or adverse neonatal outcomes. STUDY DESIGN: This was a retrospective cohort study of pregnancies with gastroschisis evaluated at 5 institutions of the University of California Fetal-Maternal Consortium from December 2014 to December 2019. The inclusion criteria were prenatally diagnosed gastroschisis with at least 1 ultrasound performed at a University of California Fetal-Maternal Consortium institution. Estimated fetal weight and individual biometric measurements were recorded for each ultrasound performed at a University of California Fetal-Maternal Consortium institution from the time of gastroschisis diagnosis to delivery. Median estimated fetal weight and biometric measurements were calculated for each gestational age in 1-week increments. Neonatal outcomes collected were birthweight, length of stay, complications of gastroschisis (bowel atresia, bowel stricture, ischemic bowel before closure, or severe pulmonary hypoplasia), and growth failure at discharge. RESULTS: We identified 95 pregnancies with fetal gastroschisis who, in aggregate, had 360 growth ultrasounds at a University of California Fetal-Maternal Consortium institution. The median interval growth was 130 g/wk. The median estimated fetal weight and abdominal circumference in fetal gastroschisis cases were approximately the tenth percentile on the Hadlock growth curve across gestation. Moreover, the median biparietal diameter, head circumference, and femur length measurements remained below the 50th percentile on the Hadlock growth curve across gestation. The median birthweight for neonates with less than the median weekly prenatal weight gain was less than for those with greater than the median weekly prenatal weight gain (2185 g vs 2780 g; P<.01). There was no difference in prenatal weight gain trajectory when comparing neonates who had or did not have bowel complications of gastroschisis. CONCLUSION: In this multicenter cohort of pregnancies with fetal gastroschisis, the median interval growth was 130 g/wk, and overall, in utero growth closely followed the tenth percentile on the Hadlock curve. Poor prenatal growth in cases of fetal gastroschisis correlates with lower neonatal weights but did not predict a more complicated course.
Subject(s)
Gastroschisis , Female , Fetal Growth Retardation , Fetus , Gastroschisis/diagnostic imaging , Humans , Infant, Newborn , Pregnancy , Retrospective Studies , Ultrasonography, PrenatalABSTRACT
Background Prenatal diagnosis of congenital heart disease has been associated with early-term delivery and cesarean delivery (CD). We implemented a multi-institutional standardized clinical assessment and management plan (SCAMP) through the University of California Fetal-Maternal Consortium. Our objective was to decrease early-term (37-39 weeks) delivery and CD in pregnancies complicated by fetal congenital heart disease using a SCAMP methodology to improve practice in a high-risk and clinically complex setting. Methods and Results University of California Fetal-Maternal Consortium site-specific management decisions were queried following SCAMP implementation. This contemporary intervention group was compared with a University of California Fetal-Maternal Consortium historical cohort. Primary outcomes were early-term delivery and CD. A total of 496 maternal-fetal dyads with prenatally diagnosed congenital heart disease were identified, 185 and 311 in the historical and intervention cohorts, respectively. Recommendation for later delivery resulted in a later gestational age at delivery (38.9 versus 38.1 weeks, P=0.01). After adjusting for maternal age and site, historical controls were more likely to have a CD (odds ratio [OR],1.8; 95% CI, 2.1-2.8; P=0.004) and more likely (OR, 2.1; 95% CI, 1.4-3.3) to have an early-term delivery than the intervention group. Vaginal delivery was recommended in 77% of the cohort, resulting in 61% vaginal deliveries versus 50% in the control cohort (P=0.03). Among pregnancies with major cardiac lesions (n=373), vaginal birth increased from 51% to 64% (P=0.008) and deliveries ≥39 weeks increased from 33% to 48% (P=0.004). Conclusions Implementation of a SCAMP decreased the rate of early-term deliveries and CD for prenatal congenital heart disease. Development of clinical pathways may help standardize care, decrease maternal risk secondary to CD, improve neonatal outcomes, and reduce healthcare costs.