Longitudinal associations between urinary biomarkers of phthalates and replacements with novel in vivo measures of placental health.

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.

Point-of-Care Ultrasound in Critical Care Obstetrics: A Scoping Review of the Current Evidence.

OBJECTIVES: To synthesize the current evidence of maternal point-of-care ultrasound (POCUS) in obstetrics. A scoping review was conducted using PubMed, Clinicaltrials.gov, and the Cochrane library from inception through October 2023. METHODS: Studies were eligible for inclusion if they described the use of POCUS among obstetric or postpartum patients. Two authors independently screened all abstracts. Quantitative, qualitative, and mixed-methods studies were eligible for inclusion. Case reports of single cases, review articles, and expert opinion articles were excluded. Studies describing detailed maternal nonobstetric sonograms or maternal first trimester sonograms to confirm viability and rule out ectopic pregnancy were also excluded. Data were tabulated using Microsoft Excel and summarized using a narrative review and descriptive statistics. RESULTS: A total of 689 publications were identified through the search strategy and 12 studies met the inclusion criteria. Nine studies evaluated the use of lung POCUS in obstetrics in different clinical scenarios. Lung ultrasound (LUS) findings in preeclampsia showed an excellent ability to detect pulmonary edema (area under the receiver operating characteristic 0.961) and findings were correlated with clinical evidence of respiratory distress (21 of 57 [37%] versus 14 of 109 [13%]; P = .001). Three studies evaluated abdominal POCUS, two of the inferior vena cava (IVC) to predict postspinal anesthesia hypotension (PSAH) and fluid receptivity and one to assess the rate of ascites in patients with preeclampsia. Patients with PSAH had higher IVC collapsibility (area under the curve = 0.950, P < .001) and, in patients with severe preeclampsia, there is a high rate of ascites (52%) associated with increased risk of adverse outcomes. There were no studies on the use of subjective cardiac POCUS. CONCLUSION: POCUS use in the management of high-risk obstetrics has increased. LUS has been the most studied modality and appears to have a potential role in the setting of preeclampsia complicated by pulmonary edema. Cardiac and abdominal POCUS have not been well studied. Trials are needed to evaluate its clinical applicability, reliability, and technique standardization before widespread use.

Neonatal Outcomes among Fetuses with an Abdominal Circumference <3rd %ile and Estimated Fetal Weight 3rd to 9th %ile Compared to Fetuses with an EFW <3rd %ile.

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 <3rd %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..

ChatGPT in maternal-fetal medicine practice: a primer for clinicians.

ChatGPT (Generative Pre-trained Transformer), a language model that was developed by OpenAI and launched in November 2022, generates human-like responses to prompts using deep-learning technology. The integration of large language processing models into healthcare has the potential to improve the accessibility of medical information for both patients and health professionals alike. In this commentary, we demonstrated the ability of ChatGPT to produce patient information sheets. Four board-certified, maternal-fetal medicine attending physicians rated the accuracy and humanness of the information according to 2 predefined scales of accuracy and completeness. The median score for accuracy of information was rated 4.8 on a 6-point scale and the median score for completeness of information was 2.2 on a 3-point scale for the 5 patient information leaflets generated by ChatGPT. Concerns raised included the omission of clinically important information for patient counseling in some patient information leaflets and the inability to verify the source of information because ChatGPT does not provide references. ChatGPT is a powerful tool that has the potential to enhance patient care, but such a tool requires extensive validation and is perhaps best considered as an adjunct to clinical practice rather than as a tool to be used freely by the public for healthcare information.

Rate of deterioration of umbilical artery Doppler indices in fetuses with severe early-onset fetal growth restriction.

BACKGROUND: Incorporation of umbilical artery Doppler in the surveillance of fetal growth restriction has been shown to reduce the risk of perinatal deaths. Systole/Diastole ratio, Pulsatility Index and Resistance Index are obtained upon Doppler interrogation of the umbilical artery however it is unknown which index predicts more advanced stages of placental deterioration. OBJECTIVE: This study aimed to examine risk factors for the development of absent or reversed end-diastolic velocity and the time intervals of deterioration from normal umbilical artery end-diastolic velocity (indicated by systole/diastole ratio, pulsatility index, or resistance index) to decreased and absent or reversed end-diastolic velocity in fetuses with early-onset severe fetal growth restriction. STUDY DESIGN: This was a retrospective cohort study performed from 2005 to 2020. All singleton pregnancies with severe (estimated fetal weight or abdominal circumference below the third percentile) and early-onset (diagnosed between 20 0/7 and 31 6/7 weeks of gestation) fetal growth restriction were included. Patients with fetal genetic or structural anomalies, suspected congenital infections, absent or reversed end-diastolic velocity at diagnosis, poor pregnancy dating, and absence of follow-up ultrasounds were excluded. Estimated fetal weight, abdominal circumference, and Doppler indices were reviewed longitudinally from diagnosis to delivery. To examine risk factors for absent or reversed end-diastolic velocity, we performed backward stepwise logistic regression and calculated odds ratios with 95% confidence intervals. Kaplan-Meier curves were compared using log-rank tests. RESULTS: A total of 985 patients met the inclusion criteria, and 79 (8%) progressed to absent or reversed end-diastolic velocity. Factors associated with development of absent or reversed end-diastolic velocity included gestational age at diagnosis (adjusted odds ratio, 4.88 [95% confidence interval, 2.55-9.37] at 20 0/7 to 23 6/7 weeks; adjusted odds ratio, 1.56 [95% confidence interval, 0.86-2.82] at 24 0/7 to 27 6/7 weeks compared with 28 0/7 to 31 6/7 weeks) and presence of chronic hypertension (adjusted odds ratio, 2.37 [95% confidence interval, 1.33-4.23]). Rates of progression from diagnosis of fetal growth restriction with normal umbilical artery Doppler to absent or reversed end-diastolic velocity were significant after 4 weeks from diagnosis (5.84% [95% confidence interval, 4.50-7.57]). Regarding the Doppler indices, the progression from normal values to abnormal indices was similar at 1 and 2 weeks. However, the rate of progression from normal to abnormal systole/diastole ratio compared with the rates of progression from normal to abnormal pulsatility index or resistance index was higher at 4 and 6 weeks. Deterioration from abnormal indices to absent or reversed end-diastolic velocity was shorter with abnormal resistance index and pulsatility index when compared with the systole/diastole ratio at 2, 4, and 6 weeks after diagnosis and at 6 weeks, respectively. CONCLUSION: Earlier gestational age at diagnosis and chronic hypertension are considered as risk factors for Doppler deterioration and development of absent or reversed end-diastolic velocity in the umbilical artery. With normal Doppler indices, significant deterioration and progression to absent or reversed end-diastolic velocity is unlikely until 4 weeks after diagnosis. Abnormal systole/diastole ratio seems to appear first. However, abnormal pulsatility index or resistance index was associated with absent or reversed end-diastolic velocity.

Personal care product use patterns in association with phthalate and replacement biomarkers across pregnancy.

BACKGROUND: Humans are exposed to phthalates, a class of non-persistent chemicals, through multiple products, including personal care and cosmetics. Associations between specific phthalates and product use have been inconsistent. However, determining these connections could provide avenues for exposure reduction. OBJECTIVE: Examine the association between patterns of personal care product use and associations with phthalate and replacement biomarkers. METHODS: In the Human Placenta and Phthalates Study, 303 women were enrolled in early pregnancy and followed for up to 8 visits across gestation. At each visit, women completed a questionnaire about product use in the prior 24 hours and contributed urine samples, subsequently analyzed for 18 phthalate and replacement metabolites. At early, mid-, and late pregnancy, questionnaire responses were condensed and repeated metabolite concentrations were averaged. Latent class analysis (LCA) was used to determine groups of women with similar use patterns, and weighted associations between group membership and biomarker concentrations were assessed. RESULTS: LCA sorted women into groups which largely corresponded to: (1) low fragranced product use (16-23% of women); (2) fragranced product and low body wash use (22-26%); 3) fragranced product and low bar soap use (26-51%); and (4) low product use (7-34%). Monoethyl phthalate (MEP) urinary concentrations were 7-10% lower and concentrations of summed di(2-ethylhexyl) terephthalate metabolites were 15-21% lower among women in the "low fragranced product use" group compared to the population mean. Few other consistent associations between group and biomarker concentrations were noted. IMPACT STATEMENT: Personal care products and cosmetics are a known exposure source for phthalates and potentially represent one of the most accessible intervention targets for exposure reduction. However, in this analysis accounting for concurrent use and fragranced status of products, we did not find any use patterns that corresponded to universally lower levels.