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STUDY QUESTION What is the longitudinal association between gestational phthalate exposure and in vivo placental outcomes? SUMMARY ANSWER Phthalates were adversely associated with placental microvasculature, stiffness, and presence of calcification, with different metabolites associated with different outcomes. WHAT IS KNOWN ALREADY Phthalate exposure is ubiquitous and implicated as a contributor to adverse pregnancy outcomes, possibly through impacts on the placenta. STUDY DESIGN, SIZE, DURATION A total of 303 women were recruited in early pregnancy and prospectively followed for up to eight visits across gestation in the Human Placenta and Phthalates study. PARTICIPANTS/MATERIALS, SETTING, METHODS At each visit, women provided urine samples and underwent placental ultrasounds. Urine was analyzed for 18 metabolites of phthalates and replacements. We took the geometric mean of repeated measurements to reflect pregnancy-averaged phthalate or replacement exposure for each participant (n = 303). Placental microvasculature, stiffness, and microcalcification presence were quantified from ultrasounds at each visit. Higher scores reflected worse placental function for all measures. Generalized linear mixed models were created to estimate the association between pregnancy-averaged exposure biomarker concentrations and repeated outcome measurements for microvasculature and stiffness. Gestational age at the time of calcification detection was modeled using Cox proportional hazards models. MAIN RESULTS AND THE ROLE OF CHANCE Monocarboxyisononyl phthalate and summed di(2-ethylhexyl) phthalate metabolites were associated with impaired microvasculature development, such that an interquartile range increase in concentration was associated with 0.11 standard deviation increase in the microvasculature ratio, indicating poorer vascularization (95% CI: 0.00, 0.22); 0.11 [95% CI: −0.01, 0.22], respectively. Monoethyl phthalate was associated with increased placental stiffness (0.09 [95% CI: −0.01, 0.19]) while summed di-iso-butyl phthalate metabolites and monobenzyl phthalate were associated with increased hazard of calcification detection (hazard ratios: 1.18 [95% CI: 0.98, 1.42]; 1.13 [95% CI: 0.96, 1.34]). LIMITATIONS, REASONS FOR CAUTION Outcomes used in this study are novel and further investigation is needed to provide clinical context and relevance. WIDER IMPLICATIONS OF THE FINDINGS We found evidence of associations between select phthalate biomarkers and various aspects of in vivo placental health, although we did not observe consistency across placental outcomes. These findings could illustrate heterogeneous effects of phthalate exposure on placental function. STUDY FUNDING/COMPETING INTEREST(S) This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZIA ES103344), and NIEHS T32ES007018. The authors declare that they have no competing interests to disclose. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Objective Fetal growth restriction (FGR) is defined as an estimated fetal weight (EFW) or abdominal circumference (AC) <10th percentile (%ile) for gestational age (GA). An EFW <3rd %ile for GA is considered severe FGR (sFGR). It remains unknown if fetuses with isolated AC <3rd %ile should be considered sFGR. Our primary objective was to assess composite neonatal outcomes in fetuses with an AC <3 rd %ile and overall EFW 3rd to 9th %ile compared with those with an EFW <3rd %ile. Study Design This retrospective cohort study was undertaken at a tertiary academic center from January 2016 to December 2021. Inclusion criteria were singleton fetuses with an EFW <3rd %ile (Group 1) or AC <3rd %ile with EFW 3rd to 9th %ile (Group 2) at 28 weeks' gestation or greater. Exclusion criteria were multiple gestations, presence of a major fetal anomaly, resolution of FGR, genetic syndrome, or infection. Composite neonatal outcome was defined by any of the following: neonatal intensive care unit admission >48 hours, necrotizing enterocolitis, sepsis, respiratory distress syndrome, mechanical ventilation, retinopathy of prematurity, seizures, intraventricular hemorrhage, stillbirth, or death before discharge. Small for gestational age (SGA) was defined as birth weight <10th %ile for GA. Results A total of 743 patients fulfilled our study criteria, with 489 in Group 1 and 254 in Group 2. The composite neonatal outcome occurred in 281 (57.5%) neonates in Group 1 and 53 (20.9%) in Group 2 (p < 0.01). The rates of SGA at birth were 94.9 and 75.6% for Group 1 and Group 2, respectively (OR 5.99, 95% confidence interval 3.65–9.82). Conclusion Although AC <3rd %ile with EFW 3rd to 9th %ile is associated with a lower frequency of SGA and neonatal morbidity than EFW <3 %ile, fetuses with AC <3 %ile still exhibited moderate rates of these adverse perinatal outcomes. Consideration should be given to inclusion of an AC <3rd %ile with EFW 3rd to 9th %ile as a criterion for sFGR. However, prospective studies comparing delivery at 37 versus 38 to 39 weeks' gestation are needed to ensure improved outcomes before widespread adaptation in clinical practice. Key Points The composite neonatal outcome occurred in 57.5% of fetuses with an overall EFW <3rd %ile and 20.9% of fetuses with an AC <3rd %ile but EFW 3rd to 9th %ile. Both groups demonstrated a high positive predictive value for SGA birth weight. Consideration should be given to inclusion of an AC <3rd %ile as a criterion for sFGR. [ABSTRACT FROM AUTHOR]

BackgroundThe goal of this statement is to review available literature and to put forth a scientific statement on the current practice of fetal cardiac medicine, including the diagnosis and management of fetal cardiovascular disease.Methods and resultsA writing group appointed by the American Heart Association reviewed the available literature pertaining to topics relevant to fetal cardiac medicine, including the diagnosis of congenital heart disease and arrhythmias, assessment of cardiac function and the cardiovascular system, and available treatment options. The American College of Cardiology/American Heart Association classification of recommendations and level of evidence for practice guidelines were applied to the current practice of fetal cardiac medicine. Recommendations relating to the specifics of fetal diagnosis, including the timing of referral for study, indications for referral, and experience suggested for performance and interpretation of studies, are presented. The components of a fetal echocardiogram are described in detail, including descriptions of the assessment of cardiac anatomy, cardiac function, and rhythm. Complementary modalities for fetal cardiac assessment are reviewed, including the use of advanced ultrasound techniques, fetal magnetic resonance imaging, and fetal magnetocardiography and electrocardiography for rhythm assessment. Models for parental counseling and a discussion of parental stress and depression assessments are reviewed. Available fetal therapies, including medical management for arrhythmias or heart failure and closed or open intervention for diseases affecting the cardiovascular system such as twin-twin transfusion syndrome, lung masses, and vascular tumors, are highlighted. Catheter-based intervention strategies to prevent the progression of disease in utero are also discussed. Recommendations for delivery planning strategies for fetuses with congenital heart disease including models based on classification of disease severity and delivery room treatment will be highlighted. Outcome assessment is reviewed to show the benefit of prenatal diagnosis and management as they affect outcome for babies with congenital heart disease.ConclusionsFetal cardiac medicine has evolved considerably over the past 2 decades, predominantly in response to advances in imaging technology and innovations in therapies. The diagnosis of cardiac disease in the fetus is mostly made with ultrasound; however, new technologies, including 3- and 4-dimensional echocardiography, magnetic resonance imaging, and fetal electrocardiography and magnetocardiography, are available. Medical and interventional treatments for select diseases and strategies for delivery room care enable stabilization of high-risk fetuses and contribute to improved outcomes. This statement highlights what is currently known and recommended on the basis of evidence and experience in the rapidly advancing and highly specialized field of fetal cardiac care.

To investigate outcomes of fetuses with hypoplastic left heart syndrome (HLHS) with an intact or restrictive atrial septum (I/RAS) managed expectantly or with fetal atrial septal intervention (FASI PubMed, Scopus, and Web of Science were searched systematically from inception until April 2023. Outcomes were classified by those who had FASI and those who had expectant management (EM). To estimate the overall proportion of each endpoint, a meta‐analysis of proportions was employed using a random‐effects model. Heterogeneity was assessed using the I2 value. Thirty‐two studies reporting on 746 fetuses with HLHS and I/RAS met our inclusion criteria. Eleven studies (123 fetuses) were in the FASI group and 21 studies (623 fetuses) were in the EM group. Among the 123 FASI cases, 107 (87%) were reported to be technically successful. The mean gestational age (GA) at diagnosis was comparable between the groups (26.2 weeks FASI vs. 24.4 weeks EM group). The mean GA at FASI was 30.4 weeks (95% CI 28.5, 32.5). The mean GA at delivery was also comparable (37.7 weeks FASI vs. 38.1 weeks EM group). Neonatal outcomes, including live birth, neonatal death, and survival to hospital discharge pooled proportions, were also comparable between groups (live birth: 92% (95% CI 64, 99) FASI versus 93% (95% CI 79, 98) in EM, neonatal death: 32% (95% CI 11, 65) FASI versus 30% (95% CI 21, 41) EM, survival to hospital discharge: 37% (95% CI 25, 52) FASI versus 52% (95% CI 42, 61) EM). Age at neonatal death was higher in the FASI group (mean: 17 days FASI vs. 7.2 days EM group). There was a lower rate of postnatal atrial restrictive septum in the FASI group 38% (95% CI 17, 63) compared to the EM group 88% (95% CI 57, 98). Our review shows variations across centers in the selection criteria and techniques used for FASI. Although survival including livebirth, neonatal death, and survival to hospital discharge did not differ between groups, the procedure may translate into a less restrictive septum at birth. Future multicenter studies are needed to better identify the subset of cases that might have improved outcomes, use standardized definitions, unified techniques, utilize core outcome set, and assess long‐term benefits. Key points: What's already known about this topic? In the setting of hypoplastic left heart syndrome (HLHS), the patency of the inter‐atrial septum is essential to ensure unobstructed drainage of pulmonary venous blood from the left to the right atrium.Prenatal consequences of HLHS with severe atrial restriction include marked elevation in left atrial and pulmonary venous pressures, reduced lung perfusion, and pulmonary lymphangiectasia.Left atrial decompression by the fetal atrial septal intervention (FASI) may offer a means of avoiding or reversing severe pulmonary damage and, thus, a more favorable postnatal outcome. What does this study add? Our review shows variations across centers in their selection criteria and techniques used for fetal atrial septal intervention (FASI) for prenatal hypoplastic left heart syndrome (HLHS) with intact or restrictive atrial septum (I/RAS).There was slightly higher fetal demise in the FASI group.GA at delivery was comparable between FASI and expectant management.Survival outcomes including livebirth, neonatal death, and survival to hospital discharge pooled proportions were also comparable between the two groups.Age at neonatal death was later in the FASI group (mean: 17 days in the FASI vs. 7.5 days in the EM group).47% of FASI cases had postnatal atrial restrictive septum compared to 89% in the expectant group. [ABSTRACT FROM AUTHOR]

Objective Pregnancy outcomes of individuals receiving cervical cerclage when the cervix is dilated are not well known. We sought to examine preterm birth rates after ultrasound or physical examination-indicated cerclage placement according to the degree of cervical dilation. Study Design This was a retrospective cohort study of individuals with singleton pregnancies undergoing ultrasound or physical examination-indicated cerclage before 24 0/7 weeks of gestation from 2004 to 2018. Individuals were categorized based on the degree of cervical dilation at the time of cerclage. Our primary outcome was preterm delivery at less than 37 weeks of gestation. Multivariable logistic regression was performed to calculate adjusted odds ratios (aOR) with 95th confidence intervals (95% CI), controlling for predefined covariates. Results Of 147 individuals undergoing ultrasound or physical examination-indicated cerclage, 90/147 (61%) had a closed or 0.5 cm dilated cervix at the time of cerclage placement, 45/147 (31%) had a cervical dilation of 1 to 2.5 cm, and 12/147 (8%) had a cervical dilation of 3 to 4 cm at the time of placement. Individuals with a cervical dilation of 1 to 2.5 cm compared with those who had a closed cervix did not have increased odds of preterm delivery (58 vs. 42%; aOR: 1.95; 95% CI: 0.93–4.07). However, individuals with a cervical dilation of 3 to 4 cm compared with individuals who had a closed cervix had significantly increased odds of preterm delivery (75 vs. 42%; aOR: 4.33; 95% CI: 1.05–17.77). Conclusion The rate of preterm birth increases with increasing cervical dilation at the time of cerclage placement. However, individuals who have a cerclage placed when the cervix is 1 to 2.5 cm can achieve an outcome that is not significantly different from those who had a cerclage placed when the cervix is closed. Key Points Time from cerclage placement to delivery decreases as cervical dilation increases. Individuals 1 to 2.5 cm dilated at the time of cerclage can achieve a favorable outcome. A cervical dilation of ≥3 cm at cerclage placement was associated with extreme prematurity. [ABSTRACT FROM AUTHOR]

Objective: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti‐SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second‐degree atrioventricular block (AVB). Methods: Women with anti‐SSA/Ro autoantibodies by commercial testing were stratified into high and low anti–52‐kD and/or 60‐kD SSA/Ro titers applying at‐risk thresholds defined by previous evaluation of AVB pregnancies. The high‐titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17–26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB. Results: Anti–52‐kD and/or 60‐kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti–60‐kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non‐AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second‐degree AVB, all <12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third‐degree and two participants with third‐degree AVB were diagnosed by urgent echocardiogram >17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal. Conclusion: High‐titer antibodies are associated with an increased incidence of AVB. Anti‐SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms. [ABSTRACT FROM AUTHOR]