The Impact of Spontaneous versus Indicated Preterm Birth on Neonatal Outcomes among Extremely Premature Neonates.

OBJECTIVE: This study aimed to investigate whether neonatal morbidity differs in spontaneous compared with indicated preterm births in extremely premature neonates. STUDY DESIGN: This is a retrospective cohort study including births ≤28 weeks at a single institution from 2011 to 2020. Births were categorized as either medically indicated or spontaneous preterm deliveries. The primary outcome was inhospital mortality and serious morbidity in survivors. t-tests, Fisher's exact tests, chi-square tests, and logistic regression models were utilized as appropriate. p < 0.05 was significant. RESULTS: Two hundred and twenty-seven births were included, with two-thirds representing spontaneous births (65.6%, 149/227) and one-third categorized as medically indicated births (34.4%, 78/227). Inhospital mortality was more common in the spontaneous preterm birth group (p = 0.04), while inhospital morbidity did not significantly vary between the medically indicated and spontaneous birth groups (p = 0.32). There was no difference in inhospital morbidity or mortality by maternal race. In multivariate models of inhospital morbidity and mortality, gestational age was the only significant predictor of adverse outcomes. CONCLUSION: Despite inhospital mortality being more common in spontaneous preterm births, inhospital mortality and significant morbidity are best accounted for by gestational age alone. KEY POINTS: · Inhospital death is more common in spontaneous preterm births.. · Perinatal outcomes do not differ on the basis of racial/ethnic group.. · Gestational age is the best predictor of inhospital morbidity and mortality..

Placental transcriptome analysis of hypertensive pregnancies identifies distinct gene expression profiles of preeclampsia superimposed on chronic hypertension.

BACKGROUND: The pathogenesis of preeclampsia superimposed on chronic hypertension (SI) is poorly understood relative to preeclampsia (PreE) occurring in pregnant people without chronic hypertension. Placental transcriptomes in pregnancies complicated by PreE and SI have not been previously compared. METHODS: We identified pregnant people in the University of Michigan Biorepository for Understanding Maternal and Pediatric Health with hypertensive disorders affecting singleton, euploid gestations (N = 36) along with non-hypertensive control subjects (N = 12). Subjects were grouped as: (1) normotensive (N = 12), (2) chronic hypertensive (N = 13), (3) preterm PreE with severe features (N = 5), (4) term PreE with severe features (N = 11), (5) preterm SI (N = 3), or (6) term SI (N = 4). Bulk RNA sequencing of paraffin-embedded placental tissue was performed. The primary analysis assessed differential gene expression relative to normotensive and chronic hypertensive placentas, where Wald adjusted P values < 0.05 were considered significant. Unsupervised clustering analyses and correlation analyses were performed between conditions of interest, and a gene ontology was constructed. RESULTS: Comparing samples from pregnant people with hypertensive diseases to non-hypertensive controls, there were 2290 differentially expressed genes. The log2-fold changes in genes differentially expressed in chronic hypertension correlated better with term (R = 0.59) and preterm (R = 0.63) PreE with severe features than with term (R = 0.21) and preterm (R = 0.22) SI. A relatively poor correlation was observed between preterm SI and preterm PreE with severe features (0.20) as well as term SI and term PreE with severe features (0.31). The majority of significant genes were downregulated in term and preterm SI versus normotensive controls (92.1%, N = 128). Conversely, most term and preterm PreE with severe features genes were upregulated compared to the normotensive group (91.8%, N = 97). Many of the upregulated genes in PreE with the lowest adjusted P values are known markers of abnormal placentation (e.g., PAAPA, KISS1, CLIC3), while the downregulated genes with the greatest adjusted P values in SI have fewer known pregnancy-specific functions. CONCLUSIONS: We identified unique placental transcriptional profiles in clinically relevant subgroups of individuals with hypertension in pregnancy. Preeclampsia superimposed on chronic hypertension was molecularly distinct from preeclampsia in individuals without chronic hypertension, and chronic hypertension without preeclampsia, suggesting that preeclampsia superimposed on hypertension may represent a distinct entity.

Urinary metabolites as a predictive marker for perinatal depression: A secondary analysis of the mothers, Omega-3 & Mental Health Study.

Background: Perinatal depression has been associated with unfavorable pregnancy and childhood development outcomes; however, no objective markers exist to identify perinatal mood disorders. We investigated whether metabolites in maternal urine during pregnancy can predict increased depressive symptoms in late pregnancy and postpartum among pregnant women at risk for perinatal depression. Methods: We evaluated metabolomic markers in urine collected at 12-20 and 34-36 weeks' gestation. We analyzed 49 urinary metabolites using ion pairing reversed-phase liquid chromatography-mass spectrometry. Depressive symptom severity was identified using Beck Depression Inventory (BDI) scores from 105 participants at 12-20 and 34-36 weeks' gestation, and 6-8 weeks' postpartum. Mixed model repeated measures analysis evaluated associations between changes in maternal urinary metabolites and BDI scores across pregnancy. Results: Increases in urinary xanthine and hypoxanthine were positively associated with increases in maternal depressive symptoms throughout pregnancy (p = 0.03 and 0.02, respectively). This finding did not persist after false discovery rate correction. None of the urinary metabolites examined were significantly associated with development of postpartum depressive symptoms. Limitations: This study is an exploratory secondary biologic sample analysis from a trial whose sample size was determined by a different primary outcome and expected effect size, which may have limited statistical power to detect associations between urinary metabolites, depressive symptoms, and mood trajectory over time. Conclusions: Increasing concentrations of xanthine and hypoxanthine were associated with increasing depressive symptoms throughout pregnancy. Further research is needed to evaluate the utility of these metabolic markers in identifying women at risk for perinatal depressive symptoms.

Delivering equity: preterm birth by socioeconomic class before and after coverage of 17-hydroxyprogesterone caproate.

OBJECTIVE: We compare the preterm birth rate across socioeconomic strata in Michigan before and after the decision by Michigan Medicaid to provide coverage for 17-hydroxyprogesterone caproate (17-OHP), a costly medication for recurrent preterm birth prevention. STUDY DESIGN: We retrospectively analyzed births recorded in the Michigan Department of Health & Human Services database from 2008-2016, comparing the rate of preterm birth stratified by standardized US Census Bureau socioeconomic levels (affluent, higher-middle class, lower-middle class, and poverty) across three time periods: pre-Federal Drug Administration approval of 17-OHP (2008-2011), pre-Medicaid coverage (2012-2014), and post-Medicaid coverage (2015-2016). RESULTS: Of 1,034,901 total live births, 10% (N = 103,869) were premature. An ANOVA with post-hoc testing showed the preterm birth rate was highest for those living in poverty, lower for the lower-middle class, and lowest for the collective higher-middle and affluent classes. The preterm birth rate dropped for all classes after Michigan Medicaid began paying for 17-OHP, but inter-class gaps remained. CONCLUSION: Extended financial coverage for 17-OHP may have contributed to modest decreases in preterm birth rates, but this policy did not equalize outcomes between those with disparate resources.

The gender authorship gap in gynecologic oncology research.

Female first authorship and senior authorship in academic obstetrics and gynecology has increased over time but gender-specific publishing data are lacking within gynecologic oncology. We examined contribution by gender to the subspecialty's flagship journal, Gynecologic Oncology, over five decades, from 1972 to 2014, to identify trends in gender representation. Chi-square tests were used to compare gender distributions within and between the first and last years studied (1972-73 and 2014) as well as linear regression to model trends over time. Female first and senior authorship increased significantly from 1972 to 2014 (first: χ2 = 20.9, p < .01; senior: χ2 = 9.9, p < .01). The number of female first authors increased markedly after 2000. Male senior authors still outnumber female senior authors. Papers with senior female authors were more likely to have female first authors, suggesting a mentorship role. Subspecialty-wide gender equity initiatives should encourage continued mentorship of women by female colleagues.

Breaking Down Barriers in Pediatric Mental Health Consultations: Understanding Patients' Use of I DON'T KNOW.

Barriers to effective provider-patient communication take many forms that can be difficult to recognize and appropriately address. This paper offers probabilistic indicators for one such form, patient-produced "I don't know" (IDK), distinguishing its use as a cognitive claim and its use as a strategy for resisting discussion of sensitive topics. A total of 95 audio-recorded psychiatrist-child interactions are drawn from a US-wide corpus of physician-patient consultations. From these, 376 patient-produced IDKs are extracted and coded for linguistic/social factors, including form, function, prosody, age, gender, and primary diagnosis. Two multiple logistic regressions are performed to determine the predictors of cognitive and resistive IDK functions respectively. Cognitive IDK uses are associated with the full form (p < 0.01) and unstressed prosody (p < 0.01). Use of resistive IDK is correlated with decreasing patient age (p < 0.01) and emotionally labile mental health diagnoses (p < 0.01). Cognitive and resistive IDK uses have distinctive linguistic and social distributions in psychiatrist-child interactions, where cognitive uses have two objectively identifiable linguistic characteristics and resistive uses are associated with certain patient types. Providers may learn to recognize cognitive and resistive IDK uses, thus acquiring the ability to correctly interpret interactional cues relevant to the diagnosis and treatment of pediatric mental health conditions.

Interpreting "I don't know" use by persons living with dementia in Mini-Mental State Examinations.

OBJECTIVE: We investigate dementia patients' use of "I don't know" (IDK) in Mini-Mental State Exams (MMSEs) using objective linguistic indicators to differentiate IDK signalling lack of knowledge (LOK) from IDK used to hedge responses, affect exam progression etc. We hypothesize that increased proportional use of LOK-IDK correlates with worsening dementia severity. METHODS: 189 IDK tokens were extracted from 72 MMSE interactions and coded for linguistic/social characteristics. A data-driven, discourse position/relation-based functional taxonomy for IDK in MMSE was developed and the resulting functional distribution was subjected to multiple logistic regression. RESULTS: Use of LOK-IDK (vs. non-LOK-IDK) is significantly correlated (p=0.01) with clinicians' subjective ratings of patients' dementia as 'severe' vs. 'mild'/'moderate', indicating that objective sociolinguistic criteria approximate physician judgments. 92% of 'severe' patients' IDKs signalled LOK, compared to only 68% of 'mild' patients', suggesting that uncritical interpretation of IDK as signalling LOK would result in 8-32% of IDK responses being mis-scored. CONCLUSION: LOK and non-LOK uses distinguished on the basis of reliable, objective usage patterns are differentially distributed among dementia severity groups. PRACTICE IMPLICATIONS: LOK-IDK serves as a supplemental indicator of dementia severity. Correct interpretation may improve diagnostic accuracy and allow clinicians to respond supportively during cognitive assessment.

Patient-centered interviewing is associated with decreased responses to painful stimuli: an initial fMRI study.

OBJECTIVE: To identify the functional magnetic resonance imaging (fMRI) changes associated with a patient-centered interview (PCI) and a positive provider-patient relationship (PPR). METHODS: Nine female patients participated, five randomly selected to undergo a replicable, evidence-based PCI, the other four receiving standard clinician-centered interviews (CCI). To verify that PCI differed from CCI, we rated the interviews and administered a patient satisfaction with the provider-patient relationship (PPR) questionnaire. Patients were then scanned as they received painful stimulation while viewing pictures of the interviewing doctor and control images (unknown doctor). RESULTS: Interview ratings and questionnaire results confirmed that PCIs and CCIs were performed as planned and PCIs led to a much more positive PPR. We found significantly reduced pain-related neural activation in the left anterior insula region in the PCI group when the interviewing doctor's picture was shown. CONCLUSION: This study identifies an association between a PCI that produced a positive PPR and reduced pain-related neural responses in the anterior insula. This is an initial step in understanding the neural underpinnings of a PCI. PRACTICE IMPLICATIONS: If confirmed, our results indicate one neurobiological underpinning of an effective PCI, providing an additional scientific rationale for its use clinically.

A linguistic study of patient-centered interviewing: emergent interactional effects.

OBJECTIVES: To evaluate interactional effects of patient-centered interviewing (PCI) compared to isolated clinician-centered interviewing (CCI). METHODS: We conducted a pilot study comparing PCI (N=4) to CCI (N=4) for simulated new-patient visits. We rated interviews independently and measured patient satisfaction with the interaction via a validated questionnaire. We conducted interactional sociolinguistic analysis on the interviews and compared across three levels of analysis: turn, topic, and interaction. RESULTS: We found significant differences between PCI and CCI in physician responses to patients' psychosocial cues and concerns. The number and type of physician questions also differed significantly across PCI and CCI sets. Qualitatively, we noted several indicators of physician-patient attunement in the PCI interviews that were not present in the CCI interviews. They spanned diverse aspects of physician and patient speech, suggesting interactional accommodation on the part of both participants. CONCLUSIONS: This small pilot study highlights a variety of interactional variables that may underlie the effects associated with patient-centered interviewing (e.g., positive relationships, health outcomes). Question form, phonological accommodation processes, and use of stylistic markers are relatively unexplored in controlled studies of physician-patient interaction. PRACTICE IMPLICATIONS: This study characterizes several interactional variables for larger scale studies and contributes to models of patient-centeredness in practice.