ABSTRACT
OBJECTIVE: To assess the effect of gestational age-based dosing of unfractionated heparin (UFH) compared with standard dosing of UFH for thromboprophylaxis on an elevated serum activated partial thromboplastin time (aPTT) during prolonged antepartum hospitalizations. METHODS: This was a randomized trial of pregnant persons who were admitted in the antepartum period for at least 72 hours. Participants were randomly allocated to the standard dose of UFH (5,000 units subcutaneously every 12 hours) or the gestational age-based dose of UFH (first trimester [less than 14 weeks]: 5,000 units subcutaneously every 12 hours; second trimester [14-27 6/7 weeks]: 7,500 units subcutaneously every 12 hours; third trimester (28 weeks or more): 10,000 units subcutaneously every 12 hours). The primary outcome was the proportion of antepartum patients who had an elevated serum aPTT value above the normal range (more than 36.2 seconds) 6 hours after an UFH dose. Secondary outcomes included the development of venous thromboembolism (VTE) and reported side effects of heparin administration. RESULTS: Between December 15, 2020, and April 1, 2022, 97 patients with antepartum hospitalizations were screened and 46 were randomized: 22 allocated to standard dosing and 24 allocated to gestational age-based dosing of UFH. A significantly greater proportion of antepartum patients who received gestational age-based dosing had an abnormal elevation in aPTT compared with those who received standard dosing (33.3% vs 4.8%, P =.02). Gestational age-based dosing resulted in higher maximum [interquartile range] aPTT (30.4 [27.4, 37.5] vs 26.6 [23.0, 29.6], P =.01) and anti-Xa levels (0.09 [0.09, 0.11] vs 0.09 [0.09, 0.09], P =.04). There was no significant difference in VTE between groups ( P =.47). CONCLUSION: Gestational age-based dosing of UFH for thromboprophylaxis of antepartum hospitalizations was associated with significantly increased rates of elevated coagulation parameters compared with standard fixed dosing. This study suggests a need for close monitoring if higher doses of UFH during pregnancy are used later in gestation. The efficacy of gestational age-based dosing compared with standard dosing for UFH to prevent thromboembolic events remains an area for future investigation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04635839.
Subject(s)
Anticoagulants , Gestational Age , Heparin , Hospitalization , Venous Thromboembolism , Humans , Female , Pregnancy , Heparin/administration & dosage , Adult , Anticoagulants/administration & dosage , Venous Thromboembolism/prevention & control , Hospitalization/statistics & numerical data , Partial Thromboplastin TimeABSTRACT
OBJECTIVES: Optimal management of placenta accreta spectrum (PAS) requires antenatal diagnosis. We sought to evaluate the sensitivity of ultrasound findings suggestive of PAS in detecting posterior PAS. METHODS: Cohort study of patients with posterior placentation and pathology-confirmed PAS from 2011 to 2020 at a tertiary center. Patients were excluded if ultrasound images were unavailable. Ultrasounds were reviewed for presence of lacunae, hypervascularity, myometrial thinning, loss of the hypoechoic zone, bridging vessels, abnormal uterine serosa-bladder interface, placental bulge, placental extension into/beyond the myometrium, and an exophytic mass. Risk factors, postpartum outcomes, and ultrasound findings were compared by antepartum suspicion for PAS. Sensitivity was calculated for each ultrasound finding. RESULTS: Thirty-three patients were included. PAS was not suspected antenatally in 70â¯% (23/33). Patients with unsuspected PAS were more likely to be non-Hispanic, have in vitro fertilization, no prior Cesarean deliveries, no placenta previa, and delivered later in gestation. Depth of invasion and estimated blood loss were less for unsuspected PAS, but there was no difference in hysterectomy between groups. Ultrasound findings were less frequently seen in those who were not suspected antenatally: lacunae 17.4 vs. 100â¯% (p<0.001), hypervascularity 8.7 vs. 80â¯% (p<0.001), myometrial thinning 4.4 vs. 70â¯% (p<0.001), and placental bridging vessels 0 vs. 60â¯% (p<0.001). There was poor sensitivity (0-42.4â¯%) for all findings. CONCLUSIONS: Posterior PAS is less likely to be detected antenatally due to a lower sensitivity of typical ultrasound findings in the setting of a posterior placenta. Further studies are needed to better identify reliable markers of posterior PAS.
Subject(s)
Placenta Accreta , Placenta , Pregnancy , Female , Humans , Placenta/diagnostic imaging , Placenta Accreta/diagnostic imaging , Cohort Studies , Ultrasonography, Prenatal , Placentation , Retrospective StudiesABSTRACT
More than 290 million people worldwide, and almost 2 million people in the United States, are infected with hepatitis B virus, which can lead to chronic hepatitis B, a vaccine-preventable communicable disease. The prevalence of chronic hepatitis B infection in pregnancy is estimated to be 0.7% to 0.9% in the United States, with >25,000 infants born annually at risk for chronic infection due to perinatal transmission. Given the burden of disease associated with chronic hepatitis B infection, recent national guidance has expanded both the indications for screening for hepatitis B infection and immunity and the indications for vaccination. The purpose of this document is to aid clinicians caring for pregnant patients in screening for hepatitis B infection and immunity status, discuss the perinatal risks of hepatitis B infection in pregnancy, determine whether treatment is indicated for maternal or perinatal indications, and recommend hepatitis B vaccination among susceptible patients. The following are the Society for Maternal-Fetal Medicine recommendations: (1) we recommend triple-panel testing (hepatitis B surface antigen screening, antibody to hepatitis B surface antigen, and total antibody to hepatitis B core antigen) at the initial prenatal visit if not previously documented or known to have been performed (GRADE 1C); (2) we recommend universal hepatitis B surface antigen screening alone at the initial prenatal care visit for all pregnancies where there has been a previously documented negative triple-panel test (GRADE 1B); (3) we recommend that individuals with unknown hepatitis B surface antigen screening status be tested on any presentation for care in pregnancy; we also recommend that those with clinical hepatitis or those with risk factors for acute hepatitis B infection be tested at the time of admission to a birthing facility when delivery is anticipated (GRADE 1B); (4) we do not recommend altering routine intrapartum care in individuals chronically infected with hepatitis B; administration of neonatal immunoprophylaxis is standard of care in these situations (GRADE 1B); (5) we do not recommend cesarean delivery for the sole indication of reducing perinatal hepatitis B virus transmission (GRADE 1B); (6) we recommend that individuals with HBV infection can breastfeed as long as the infant has received immunoprophylaxis at birth (GRADE 1C); (7) we suggest individuals with hepatitis B infection who desire invasive testing may have the procedure performed after an informed discussion on risks and benefits in the context of shared decision-making and in the context of how testing will affect clinical care (GRADE 2C); (8) in individuals with hepatitis viral loads >200,000 IU/mL (>5.3 log 10 IU/mL), we recommend antiretroviral therapy with tenofovir (tenofovir alafenamide at 25 mg daily or tenofovir disoproxil fumarate at 300 mg daily) in the third trimester (initiated at 28-32 weeks of gestation) as an adjunctive strategy to immunoprophylaxis to reduce perinatal transmission (GRADE 1B); (9) we recommend administering hepatitis B vaccine and hepatitis B immunoglobin within 12 hours of birth to all newborns of hepatitis B surface antigen-positive pregnant patients or those with unknown or undocumented hepatitis B surface antigen status, regardless of whether antiviral therapy has been given during the pregnancy to the pregnant patient (GRADE 1B); and (10) we recommend hepatitis B vaccination in pregnancy for all individuals without serologic evidence of immunity or documented history of vaccination (GRADE 1C).
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Pregnancy Complications, Infectious , Pregnancy , Infant , Female , Infant, Newborn , Humans , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/prevention & control , Hepatitis B, Chronic/drug therapy , Hepatitis B Surface Antigens/therapeutic use , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/drug therapy , Perinatology , Infectious Disease Transmission, Vertical/prevention & control , Hepatitis B/diagnosis , Hepatitis B/prevention & control , Hepatitis B/drug therapy , Hepatitis B virus , Tenofovir/therapeutic use , Hepatitis B Vaccines/therapeutic useABSTRACT
To decrease risk of early-onset neonatal sepsis from group B streptococcus (GBS), pregnant patients should undergo screening between 36 0/7 and 37 6/7 weeks' gestation. Patients with a positive vaginal-rectal culture, GBS bacteriuria , or history of newborn with GBS disease should receive intrapartum antibiotic prophylaxis (IAP) with an agent targeting GBS. If GBS status is unknown at time of labor, IAP should be administered in cases of preterm birth, rupture of membranes for >18 hours, or intrapartum fever. The antibiotic of choice is intravenous penicillin; alternatives should be considered in cases of penicillin allergy depending on allergy severity.
Subject(s)
Hypersensitivity , Pregnancy Complications, Infectious , Premature Birth , Streptococcal Infections , Pregnancy , Female , Humans , Infant, Newborn , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/prevention & control , Streptococcal Infections/diagnosis , Streptococcal Infections/drug therapy , Premature Birth/drug therapy , Antibiotic Prophylaxis , Streptococcus agalactiae , Penicillins/therapeutic use , Hypersensitivity/drug therapy , Infectious Disease Transmission, Vertical/prevention & control , Anti-Bacterial Agents/therapeutic useABSTRACT
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..
ABSTRACT
OBJECTIVE: This study was aimed to evaluate the role of intertwin discrepancy in middle cerebral artery peak systolic velocity (MCA-PSV) and cerebroplacental ratio (CPR) for the prediction of adverse outcomes in monochorionic-diamniotic (MCDA) twin pregnancies. STUDY DESIGN: A retrospective cohort study of MCDA pregnancies that underwent ultrasound surveillance at a perinatal referral center from 2007 to 2017. Intertwin MCA-PSV discrepancy (MCA-ΔPSV-MoM) was defined as the absolute difference of MCA-PSV multiple of the median (MoM) for gestational age between twins. Intertwin CPR discrepancy (CPR-Δ) was defined as the absolute difference of CPR between twins. The maximum MCA-ΔPSV-MoM and CPR-Δ before and after 26 weeks of gestation were assessed as predictors of pregnancy and neonatal outcomes through simple logistic regression models and Pearson's correlation coefficients. Receiver operating characteristic (ROC) curves were generated to determine the predictive value of maximum MCA-ΔPSV-MoM and CPR-Δ. RESULTS: A total of 143 MCDA pregnancies met inclusion criteria. There was a significant association between MCA-ΔPSV-MoM at <26 weeks and the development of twin anemia-polycythemia sequence (TAPS; p = 0.007), intrauterine fetal demise (IUFD; p = 0.009), and neonatal intensive care unit (NICU) admission (p < 0.05). MCA-ΔPSV-MoM at ≥26 weeks was associated with the development of TAPS (p < 0.001). CPR-Δ at <26 weeks was associated with the development of twin-twin transfusion syndrome (TTTS; p = 0.03) and NICU admission (p = 0.02). MCA-ΔPSV-MoM at ≥26 weeks was highly predictive of TAPS (area under curve [AUC] = 0.92). A cut-off of 0.44 would identify TAPS with 100% sensitivity and 73% specificity. CONCLUSION: In MCDA pregnancies, intertwin MCA and CPR discrepancies are associated with adverse pregnancy and neonatal outcomes, including TAPS, TTTS, IUFD, and NICU admission. Evaluation of intertwin MCA and CPR differences demonstrated the potential for clinical predictive utility in the surveillance of MCDA twin pregnancies. KEY POINTS: · Intertwin discrepancy of MCA-PSV and CPR is associated with adverse pregnancy outcomes.. · Intertwin differences in Doppler ultrasound may occur prior to meeting diagnostic criteria for TTTS or TAPS.. · There is potential clinical predictive utility in MCA and CPR surveillance of MCDA twin pregnancies..
Subject(s)
Blood Flow Velocity , Diseases in Twins , Middle Cerebral Artery/diagnostic imaging , Pregnancy Outcome , Twins, Monozygotic , Ultrasonography, Prenatal , Umbilical Arteries/diagnostic imaging , Anemia/epidemiology , Anemia/etiology , Diseases in Twins/diagnosis , Diseases in Twins/epidemiology , Female , Fetofetal Transfusion/epidemiology , Humans , Middle Cerebral Artery/physiology , Polycythemia/epidemiology , Pregnancy , Pregnancy, Twin , ROC Curve , Retrospective Studies , Ultrasonography, Doppler , Umbilical Arteries/physiologyABSTRACT
Extensive remodeling of the airways is a major characteristic of chronic inflammatory lung diseases such as asthma or chronic obstructive pulmonary disease (COPD). To elucidate the importance of a deregulated immune response in the airways for remodeling processes, we established a matching Drosophila model. Here, triggering the Imd (immune deficiency) pathway in tracheal cells induced organ-wide remodeling. This structural remodeling comprises disorganization of epithelial structures and comprehensive epithelial thickening. We show that these structural changes do not depend on the Imd pathway's canonical branch terminating on nuclear factor κB (NF-κB) activation. Instead, activation of a different segment of the Imd pathway that branches off downstream of Tak1 and comprises activation of c-Jun N-terminal kinase (JNK) and forkhead transcription factor of the O subgroup (FoxO) signaling is necessary and sufficient to mediate the observed structural changes of the airways. Our findings imply that targeting JNK and FoxO signaling in the airways could be a promising strategy to interfere with disease-associated airway remodeling processes.
Subject(s)
Airway Remodeling , Drosophila Proteins/metabolism , Drosophila melanogaster/immunology , Forkhead Transcription Factors/metabolism , Immunity , Mitogen-Activated Protein Kinase Kinases/metabolism , Animals , Epithelium/metabolism , Epithelium/microbiology , Hyperplasia , Life Cycle Stages , MAP Kinase Kinase Kinases/metabolism , Transcription Factors/metabolismABSTRACT
Pregnant women may be at risk for more severe manifestations and sequelae of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At this time, there remain significant evidence gaps to allow for comprehensive counseling of pregnant women and their families, specifically regarding the risks of gestational-age specific maternal outcomes and potential risks of intrauterine or peripartum viral transmission to the fetus or newborn. As maternal fetal medicine providers and consultants, we are uniquely positioned to mitigate the risks associated with maternal infection and to guide the care for infected pregnant women by being able to provide the most current evidence-based recommendations. Such care requires incorporating the rapidly evolving data regarding this virus and its impact on pregnancy, as well as taking a stand to advocate for best scientific and clinical practices to optimize both women's health and public health during this pandemic.
Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Coronavirus Infections/therapy , Perinatal Care/methods , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Pregnancy Complications, Infectious/virology , COVID-19 , COVID-19 Testing , Centers for Disease Control and Prevention, U.S. , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Critical Care/statistics & numerical data , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Obstetrics/methods , Pandemics , Pneumonia, Viral/diagnosis , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/therapy , Pregnancy Outcome , Pregnancy, High-Risk , Prenatal Care/methods , SARS-CoV-2 , United StatesABSTRACT
The emergence of beta-lactam-resistant pathogenic organisms has resulted in limitation or even elimination of drugs such as penicillin and ampicillin from available antibiotic choices for treating common infections in obstetrics and gynecology. In clinical situations for which penicillins and cephalosporins are appropriate or recommended first-line agents, the problem of patient-reported penicillin allergies has led to routine use of alternative but potentially less effective agents. The use of broader-spectrum and potentially suboptimal alternative antibiotic regimens for intrapartum antibiotic prophylaxis against group B streptococcus or for surgical prophylaxis for cesarean delivery in women with a reported penicillin allergy may affect these women during labor and birth. Most individuals who report a penicillin allergy are neither truly allergic nor at risk of developing a hypersensitivity reaction after exposure to penicillin. The available evidence suggests that there are important roles for both targeted history-taking, to determine the nature of drug allergies and penicillin allergy testing in pregnant women, to optimize their antibiotic-related treatment both during pregnancy and for their lifetimes. Wider consideration and adoption of penicillin allergy testing in pregnant women specifically, as well as the general population of women cared for by providers of obstetrics and gynecology, is recommended.
Subject(s)
Anti-Bacterial Agents/adverse effects , Antibiotic Prophylaxis/adverse effects , Drug Hypersensitivity/complications , Penicillins/adverse effects , Streptococcal Infections/prevention & control , Anti-Bacterial Agents/therapeutic use , Drug Hypersensitivity/epidemiology , Female , Humans , Infectious Disease Transmission, Vertical/prevention & control , Penicillins/therapeutic use , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Streptococcal Infections/microbiology , Streptococcus agalactiae/isolation & purificationABSTRACT
OBJECTIVES: The aim of this study was to evaluate inter- and intraobserver variability of first-trimester biometric measurements and crown-rump length (CRL) and to compare the accuracy and precision of CRL with these biometric measurements used in the interpretation of first-trimester nuchal translucency (NT). METHODS: Women presenting for a first trimester ultrasound were recruited. Both a sonographer, and a maternal fetal medicine specialist individually examined each participant. Each examiner obtained three independent measurements of CRL, a standardized set of biometric measurements (biparietal diameter, occipitofrontal diameter, head circumference, abdominal circumference, humerus length, and femur length), and an NT between 11 0/7 and 13 6/7 weeks of gestation. Biometry-specific expected NT values were calculated using linear and quadratic regression models and were used to convert results into multiples of the median. RESULTS: Fetal biometric measurements, CRL, and NT measurements were obtained in 356 consecutive pregnancies with singleton fetuses. CRL demonstrated the least intra- and interobserver variability as demonstrated by the smallest coefficient of variance. However, abdominal circumference and head circumference were not statistically different from CRL variance. CRL and abdominal circumference showed the smallest standard deviation when calculating multiples of the median for NT interpretation. CONCLUSION: First-trimester abdominal circumference demonstrates the most intra- and interobserver precision for dating and calculating NT multiples of the median, which could potentially be useful with obesity and in any setting with technical limitations of sonography.
Subject(s)
Crown-Rump Length , Ultrasonography, Prenatal/methods , Waist Circumference/physiology , Abdomen/anatomy & histology , Cohort Studies , Female , Humans , Observer Variation , Pregnancy , Pregnancy Trimester, First , Prospective Studies , Reproducibility of ResultsABSTRACT
OBJECTIVE: To investigate factors associated with abnormal cell-free DNA (cfDNA) results for sex chromosomes (SCs). STUDY DESIGN: This is a retrospective cohort study of abnormal cfDNA results for SC at a referral practice from March 2013 to July 2015. Cell-free DNA results were abnormal if they were positive for SC aneuploidy (SCA), inconclusive, or discordant with ultrasound (US) findings. Primary outcome was concordance with karyotype or postnatal evaluation. RESULTS: Of 50 abnormal cfDNA results for SC, 31 patients (62%) were positive for SCA, 13 (26%) were inconclusive, and 6 (12%) were sex discordant on US. Of SCA results, 19 (61%) were reported as 45,X and 12 (39%) were SC trisomy. Abnormal karyotypes were confirmed in 8/23 (35%) of SC aneuploidy and 1/5 (20%) of inconclusive results. Abnormal SC cfDNA results were associated with in vitro fertilization (P = .001) and twins (P < .001). Sex discordance between cfDNA and US was associated with twin gestation (P < .001). CONCLUSIONS: In our cohort, abnormal SC cfDNA results were associated with in vitro fertilization and twins. Our results indicate cfDNA for sex prediction in twins of limited utility. Positive predictive value and sensitivity for SC determination were lower than previously reported.
Subject(s)
Cell-Free Nucleic Acids/analysis , Maternal Serum Screening Tests , Sex Chromosome Aberrations , Adult , False Positive Reactions , Female , Humans , Pregnancy , Retrospective Studies , Sex ChromosomesABSTRACT
Antithrombin (AT) deficiency is a high-risk thrombophilia and a rare condition. Despite full anticoagulation during pregnancy and the postpartum period, women with AT deficiency may still be vulnerable to developing venous thromboembolism (VTE), including fatal events. There is limited guidance on the management of AT deficiency in pregnancy, including the role of AT concentrates. Following a comprehensive review of the state of the art with respect to recommendations and guidelines, our expert panel in maternal-fetal medicine, hematology and basic science reached consensus on key issues in the recognition and management of AT deficiency in pregnancy. This paper summarizes the state of the art and summarizes what we believe are best practices with special emphasis on a multidisciplinary approach involving obstetrics and hematology in the care of women with AT deficiency.
Subject(s)
Antithrombin III Deficiency/drug therapy , Antithrombin III Deficiency/pathology , Female , Humans , Postpartum Period , Pregnancy , Risk FactorsABSTRACT
OBJECTIVE: To describe a single U.S. perinatal center's ongoing experience with evaluating pregnant patients with potential exposure to Zika virus infection. METHODS: This is an institutional review board-approved longitudinal observational study from January to August 2016 from a single perinatal referral center. Patients who had traveled to or had sexual contact with a person who traveled to a region with documented local Zika virus transmission were included in the study. The aim of the study was to identify the rate of confirmed infection among pregnant women referred to our center with established risk factors for Zika virus acquisition. We also sought to characterize travel patterns that constituted risk, to identify rates of symptoms suggesting infection, and to potentially describe findings suggestive of congenital Zika virus infection in prenatal ultrasound evaluations. RESULTS: We evaluated 185 pregnant women with potential Zika virus exposure. Testing was offered in accordance with the version of the Centers for Disease Control and Prevention guidelines in place at the time of the consultation visit. Geographic exposure data showed Mexico (44%), the Caribbean (17%), North America (16%), South America (13%), and Central America (9%) to be the most common areas in which potential exposure occurred. One hundred twenty-three (67%) patients reported insect bites and 19 (10%) patients reported symptoms. Overall, five (3% of all) patients had prenatal ultrasound findings suggestive of possible fetal Zika virus infection; all their Zika virus test results returned negative. These findings included microcephaly, echogenic intracardiac foci, and ventricular calcifications. Of the 153 Zika virus screening tests ordered, eight (5%) immunoglobulin M results returned positive or equivocal with only one positive through confirmatory testing. Overall, 1 of 185 (0.5%) of all those consulted and 1 of 153 (0.7%) of those tested had a confirmed Zika virus infection with no confirmed fetal or neonatal infections. CONCLUSION: We identified low rates of confirmed maternal Zika virus infection in our cohort, but the number of patients described here demonstrates the magnitude of concern existing among both patients and physicians regarding possible perinatal Zika virus infection. It also underscores the need for health care providers to be prepared to answer questions, explain laboratory and ultrasound results, and describe testing options for concerned patients and their families.
Subject(s)
Disease Outbreaks , Practice Patterns, Physicians' , Pregnancy Complications, Infectious/epidemiology , Prenatal Diagnosis , Zika Virus Infection/epidemiology , Adult , Centers for Disease Control and Prevention, U.S. , Female , Humans , Middle Aged , Obstetrics , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Infectious/diagnosis , United States/epidemiology , Young Adult , Zika Virus Infection/diagnosisABSTRACT
OBJECTIVE: To describe the clinically relevant findings detected by the first trimester ultrasound (FTU) and to determine the additional value of the FTU compared to cell free DNA (cfDNA) alone. METHOD: Retrospective cohort study of patients undergoing a FTU at a maternal-fetal medicine referral practice. Fetal, gynecologic, and placental findings detected by ultrasound were analyzed with available cfDNA and diagnostic testing results. A subgroup analysis of positive ultrasound findings and cfDNA results was performed to assess the additional benefit of ultrasound evaluation in FT prenatal screening. RESULTS: There were 1906 FTU between 1 October 2013 and 1 October 2014. CfDNA results were available for 959 (50%) patients. FTU detected: 42 fetal (2.2%), 286 gynecologic (15.0%), and 317 placental (16.6%) findings. CfDNA results were discordant with invasive testing results in 8/61 cases (13%) and with ultrasound findings in 18/42 (42%) cases. There were six false positive and two false negative cfDNA results confirmed by diagnostic testing. Subgroup analysis revealed that cfDNA as the sole method of prenatal screening in the FT would miss 95% of the fetal findings detected with ultrasound. CONCLUSION: The comprehensive FTU provides valuable clinical information about fetal and maternal anatomy that cannot be detected with cfDNA alone. © 2016 John Wiley & Sons, Ltd.
Subject(s)
DNA/blood , Prenatal Diagnosis/methods , Ultrasonography, Prenatal , Adult , Diagnostic Errors/statistics & numerical data , Female , Fetus/chemistry , Gestational Age , Humans , Maternal Serum Screening Tests/methods , Middle Aged , Pregnancy , Pregnancy Trimester, First , Prenatal Diagnosis/statistics & numerical data , Retrospective StudiesABSTRACT
BACKGROUND: Since its commercial release in 2011 cell-free DNA screening has been rapidly adopted as a routine prenatal genetic test. However, little is known about its performance in actual clinical practice. OBJECTIVE: We sought to investigate factors associated with the accuracy of abnormal autosomal cell-free DNA results. STUDY DESIGN: We conducted a retrospective cohort study of 121 patients with abnormal cell-free DNA results from a referral maternal-fetal medicine practice from March 2013 through July 2015. Patients were included if cell-free DNA results for trisomy 21, trisomy 18, trisomy 13, or microdeletions (if reported by the laboratory) were positive or nonreportable. The primary outcome was confirmed aneuploidy or microarray abnormality on either prenatal or postnatal karyotype or microarray. Secondary outcomes were identifiable associations with in vitro fertilization, twins, ultrasound findings, testing platform, and testing laboratory. Kruskal-Wallis or Fisher exact tests were used as appropriate. RESULTS: A total of 121 patients had abnormal cell-free DNA results for trisomy 21, trisomy 18, trisomy 13, and/or microdeletions. In all, 105 patients had abnormal cell-free DNA results for trisomy 21, trisomy 18, and trisomy 13. Of these, 92 (87.6%) were positive and 13 (12.4%) were nonreportable. The results of the 92 positive cell-free DNA were for trisomy 21 (48, 52.2%), trisomy 18 (22, 23.9%), trisomy 13 (17, 18.5%), triploidy (2, 2.2%), and positive for >1 parameter (3, 3.3%). Overall, the positive predictive value of cell-free DNA was 73.5% (61/83; 95% confidence interval, 63-82%) for all trisomies (by chromosome: trisomy 21, 83.0% [39/47; 95% confidence interval, 69-92%], trisomy 18, 65.0% [13/20; 95% confidence interval, 41-84%], and trisomy 13, 43.8% [7/16; 95% confidence interval, 21-70%]). Abnormal cell-free DNA results were associated with positive serum screening (by group: trisomy 21 [17/48, 70.8%]; trisomy 18 [7/22, 77.8%]; trisomy 13 [3/17, 37.5%]; nonreportable [2/13, 16.7%]; P = .004), and abnormal first-trimester ultrasound (trisomy 21 [25/45, 55.6%]; trisomy 18 [13/20, 65%]; trisomy 13 [6/14, 42.9%]; nonreportable [1/13, 7.7%]; P = .003). There was no association between false-positive rates and testing platform, but there was a difference between the 4 laboratories (P = .018). In all, 26 patients had positive (n = 9) or nonreportable (n = 17) microdeletion results. Seven of 9 screens positive for microdeletions underwent confirmatory testing; all were false positives. CONCLUSION: The positive predictive value of 73.5% for cell-free DNA screening for autosomal aneuploidy is lower than reported. The positive predictive value for microdeletion testing was 0%. Diagnostic testing is needed to confirm abnormal cell-free DNA results for aneuploidy and microdeletions.
Subject(s)
Chromosome Deletion , Chromosome Disorders/diagnosis , Maternal Serum Screening Tests , Trisomy , Adult , Biomarkers/blood , Chromosome Disorders/genetics , DNA/blood , Female , Follow-Up Studies , Humans , Middle Aged , Predictive Value of Tests , Pregnancy , Retrospective StudiesABSTRACT
The Zika pandemic provides biomedical scientists, clinicians, public health advocates, and governments a unique opportunity to advance reproductive justice by addressing the paradoxes outlined in this essay. The circumstances in which pregnancies occur are morally relevant to women's reproductive life decisions, to the provision of reproductive health care, and to the development of reproductive health policy. Whether the Zika pandemic might foster context-driven reproductive pandemic planning and response is yet to be determined. Maintaining the status quo will surely increase a range of global health disparities and further stratify reproduction, producing predictable and preventable outcomes in which some people receive the necessary care and resources to achieve family building while others are neglected. Women and men should be able to count on biomedical researchers to answer the questions that need answering without undue influence from political agendas. Women should be able to continue pregnancies and count on public health assistance and help for children with Zika-related disabilities, or prevent or end a Zika-affected pregnancy. Pandemic responses that don't further these ends are morally unacceptable.
Subject(s)
Health Policy , Pregnancy Complications, Infectious/etiology , Reproduction , Zika Virus Infection/epidemiology , Zika Virus/physiology , Female , Humans , Male , Pandemics , Pregnancy , Pregnant Women , Zika Virus Infection/transmission , Zika Virus Infection/virologyABSTRACT
Between 800,000-1.4 million people in the United States and more than 240 million people worldwide are infected with hepatitis B virus (HBV). Specific to pregnancy, an estimated prevalence of 0.7-0.9% for chronic hepatitis B infection among pregnant women in the United States has been reported, with >25,000 infants at risk for chronic infection born annually to these women. Vertical transmission of HBV from infected mothers to their fetuses or newborns, either in utero or peripartum, remains a major source of perpetuating the reservoir of chronically infected individuals globally. Universal screening for hepatitis B infection during pregnancy has been recommended for many years. Identification of pregnant women with chronic HBV infection through universal screening has had a major impact in decreasing the risk of neonatal infection. The purpose of this document is to aid clinicians in counseling their patients regarding perinatal risks and management options available to pregnant women with hepatitis B infection in the absence of coinfection with HIV. We recommend the following: (1) perform routine screening during pregnancy for HBV infection with maternal HBsAg testing (grade 1A); (2) administer hepatitis B vaccine and HBV immunoglobulin within 12 hours of birth to all newborns of HBsAg-positive mothers or those with unknown or undocumented HBsAg status, regardless of whether maternal antiviral therapy has been given during the pregnancy (grade 1A); (3) In pregnant women with HBV infection, we suggest HBV viral load testing in the third trimester (grade 2B); (4) in pregnant women with HBV infection and viral load >6-8 log 10 copies/mL, HBV-targeted maternal antiviral therapy should be considered for the purpose of decreasing the risk of intrauterine fetal infection (grade 2B); (5) in pregnant women with HBV infection who are candidates for maternal antiviral therapy, we suggest tenofovir as a first-line agent (grade 2B); (6) we recommend that women with HBV infection be encouraged to breast-feed as long as the infant receives immunoprophylaxis at birth (HBV vaccination and hepatitis B immunoglobulin) (grade 1C); (7) for HBV infected women who have an indication for genetic testing, invasive testing (eg amniocentesis or chorionic villus sampling) may be offered-counseling should include the fact that the risk for maternal-fetal transmission may increase with HBV viral load >7 log 10 IU/mL (grade 2C); and (8) we suggest cesarean delivery not be performed for the sole indication for reduction of vertical HBV transmission (grade 2C).