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Abstract Introduction Fetal growth restriction (FGR) is associated with an increased risk of neonatal morbidity and mortality. Current diagnostic criteria for FGR do not discriminate between constitutionally small and pathologically restricted fetuses. Following FGR diagnosis, umbilical artery (UA) Doppler is utilized to monitor fetal well‐being, but its limitations have increased interest in investigating growth velocity as an adjunctive tool. The objective of this study is to compare the predictive ability of UA Doppler studies and growth velocity for adverse neonatal outcomes in growth‐restricted fetuses. Methods This is a secondary analysis of a cohort of pregnancies delivered in a single healthcare network from August 2017 to December 2022, diagnosed antenatally with FGR. The cohort was restricted to those with baseline estimated fetal weight (EFW) between the 3rd and 50th percentiles. All subjects had growth velocity measured (defined as EFW percentile change per week between baseline and subsequent ultrasound). The primary outcome was a composite of neonatal morbidity (neonatal intensive care unit [NICU] admission, low 5‐min Appearance, Pulse, Grimace, Activity, Respiration score [<7], intraventricular hemorrhage, necrotizing enterocolitis, or metabolic acidosis) and severe adverse perinatal events (stillbirth or neonatal death, hypoxic ischemic encephalopathy, mechanical ventilation, or severe metabolic acidosis [pH < 7.0]). Neonatal morbidity and severe adverse perinatal events were analyzed separately as secondary outcomes. Independence between growth velocity and S/D ratio was evaluated. Univariate logistic regression models were then performed, with each outcome of interest as the dependent variable and S/D ratio and growth velocity as independent variables. Receiver operating characteristic (ROC) curves were generated to compare the performance of both tests. Results A total of 172 patients were included in the analysis. UA Doppler data were available for 165 patients, 15.3% of whom had S/D ratio >95th percentile; none demonstrated absent or reversed end‐diastolic flow. There was no correlation observed between S/D ratio percentile and growth velocity, suggesting independence. ROC analysis demonstrated that the discriminatory ability of growth velocity was higher across outcomes with areas under the curve (AUC) ranging from 0.65 to 0.69 while AUC for S/D ratio percentiles ranged from 0.51 to 0.53, approximating the performance of chance. Higher growth velocity was significantly associated with reduced odds of the composite outcome (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.69–0.90), and neonatal morbidity (OR, 0.84; 95% CI, 0.73–0.95). S/D ratio percentile was not associated with these outcomes. Conclusion In pregnancies complicated by growth restriction with forward UA flow, growth velocity outperformed S/D ratio percentile in predicting adverse outcomes. The two tests were independent, indicating that growth velocity may reflect a component of fetal development not captured by UA Doppler. These results suggest that growth velocity could be used in addition to UA Doppler studies for fetal risk assessment, especially in fetuses with forward arterial flow.

Introduction Out‐of‐hospital community births account for 1.6% to 2% of births in the United States and are associated with fewer obstetric interventions but increased neonatal risk. Little is known about how maternity care providers’ characteristics, values, and prior exposure to community birth influence attitudes toward community birth. Methods We conducted an observational cross‐sectional survey using a 40 to 43 item Research Electronic Data Capture questionnaire distributed October 2 to 30, 2024. Eligible participants (“providers”) included in‐hospital physicians, midwives, community birth providers, and registered nurses. The survey assessed demographics, practice characteristics, provider values, prior community birth experience, and attitudes toward community birth. Descriptive statistics were used to summarize characteristics. Group comparisons between in‐hospital and community birth providers were conducted using analysis of variance and χ 2 or Fisher exact tests. Associations between attitudes and provider values were evaluated using linear models with Bonferroni correction. Results Sixty‐seven providers completed the survey (51 in hospital, 16 community based). Most respondents were female (89.6%) and White (77.6%), with a median of 7 years in practice (IQR, 3‐14.5). Attitudes significantly differed by role ( P = .007) and credentials ( P = .002). In‐hospital providers reported safety concerns about community birth and perceived antenatal counseling to be inadequate. Perceived patient distrust during transfer was common among both in‐hospital and community‐based providers (69% and 81%, respectively). After adjustment for provider role and multiple comparisons, no significant differences in personal values were noted by attitude group; however, providers with positive attitudes toward community birth were more likely to believe that patients value compassion (β = 2.3, P = .004). Discussion Provider attitudes toward community birth appear to be shaped more by professional role and clinical experience than by differences in underlying value systems. High levels of perceived patient distrust during transfer highlight the need for interventions that strengthen compassion across maternity care settings.

Background: Pregnancies complicated by fetal growth restriction are at increased risk of fetal demise and adverse neonatal outcomes. Distinguishing growth-restricted fetuses from constitutionally small ones remains challenging. Given the variability in current diagnostic criteria and the importance of identifying at-risk fetuses, fetal growth velocity has emerged as a predictor of adverse neonatal outcomes. Objective: To evaluate whether percentile-based fetal growth velocity, defined as change in estimated fetal weight percentile per week, predicts adverse neonatal outcomes in pregnancies affected by fetal growth restriction or small-for-gestational-age neonates. The primary aim was to determine the relationship between growth velocity and a composite of adverse neonatal outcomes. Study Design: This was a retrospective cohort study of pregnant patients 18 - 45 years old who delivered between August 2017 to December 2022 in a single healthcare system. Patients were excluded who had fewer than 2 ultrasounds after 16 weeks gestation, genetic or anatomic abnormalities, or a multiple gestation. Results: 300 patients met all inclusion criteria, and most patients (n=199) delivered at the tertiary care center. Three had an intrauterine fetal demise at a mean gestational age of 35w3d. 74 neonates were admitted to the NICU with a mean length of stay of 8.5 days; 29 required respiratory support. No neonatal deaths occurred. In fetuses with initial estimated fetal weight <3rd percentile (n=33), the probability of composite outcome was increased (50%, 95% CI 44.8-55.2) compared to those >50th percentile (5%, 95% CI 3.7-6.6). In the 3-10th and 10 - 50th percentile subgroups with decelerated growth, composite outcome rates were also increased (56.2% and 44.1%) compared to those with neutral or increased growth velocity. Conclusion: Percentile-based fetal growth velocity is a simple calculation that correlates with adverse neonatal outcomes regardless of initial estimated fetal weight. As fetal growth velocity decreased, our cohort saw increased rates of adverse outcomes. Change in EFW percentile normalizes for gestational age and allows ease of clinical interpretation. Decelerated growth identified fetuses at highest risk, suggesting growth velocity as a useful metric in routine surveillance.

Abstract Background Preterm premature rupture of membranes (PPROM) and preterm labor (PTL) are adverse obstetrical outcomes that are strongly associated with cervical high-risk human papilloma virus (cHPV) infection at the time of pregnancy. Persistent cHPV may lead to oncogenic changes in the cervico-vaginal tract and can cause inflammation in gestational tissues, but it is unknown how persistent cHPV infection may affect obstetrical outcomes. The aim of this study is to evaluate whether persistent cHPV infection is associated with recurrent PPROM or PTL among patients with a prior spontaneous preterm birth due to PPROM/PTL, and to examine clinical and pathologic characteristics of cHPV infection in this population. Methods We conducted a retrospective cohort study of patients delivering at Mayo Clinic Rochester or Mayo Clinic Health System (5/1/2018–12/31/2023). Eligible patients had ≥ 1 spontaneous preterm birth due to PPROM/PTL and positive cHPV testing. Demographics and pregnancy outcomes from index and subsequent pregnancies were abstracted. Persistent cHPV was defined as > 1 pregnancy with positive cHPV testing. Results Of 191 index pregnancies, 90 (47.1%) and 30 (33.3%) had one and two subsequent pregnancies, respectively. Patients were predominantly White (91.3%), non‑Hispanic (94.2%), non-smokers (72.0%), and 34.8% were unvaccinated for HPV. Approximately one‑third (31%) experienced recurrent PPROM/PTL in the second pregnancy, with recurrence in 40.7% of those with persistent cHPV and 27.4% without (p = 0.69). Excisional procedures occurred before 12.0% of index pregnancies and 20–24% of subsequent pregnancies; recurrence of PTL/PPROM remained high regardless of procedure history. HPV strain data were available for 132 index pregnancies, and types 16 and 18 were more likely to persist into a subsequent pregnancy (p = 0.0043). CIN persistence occurred at similar rates in patients with and without persistent cHPV infection. Placental inflammation rates were high in both patients with persistent and non-persistent cHPV. Conclusion Recurrent PPROM/PTL, CIN persistence, and placental inflammation were common; a finding independent of persistent cHPV infection, excisional procedure history, or HPV vaccination status. These findings suggest that factors other than cHPV persistence may play a larger role in recurrent preterm birth. Larger studies with higher cHPV prevalence and subsequent pregnancies are needed to provide clarity.

ABSTRACTObjectivesPrior studies have raised concerns about postpartum hemorrhage (PPH) risk associated with selective serotonin and serotonin‐norepinephrine reuptake inhibitors (SSRIs and SNRIs), although limitations include possible confounding by maternal indications. The current study examined the risk of PPH associated with prenatal S/NRIs accounting for diagnosed maternal depression during pregnancy.MethodsThe current study is a secondary analysis of data from a cohort of 2213 pregnancies (1997–2010) identified from a large electronic medical record‐linkage system. Exposures were identified from electronic prescriptions records and resulted in three main groups: S/NRI‐exposed pregnancies (S/NRI users), antidepressant‐unexposed pregnancies (non‐users), and S/NRI exposure in the year prior to (but not during) pregnancy (former users). Data used to identify PPH occurrences included obstetrician chart diagnoses, diagnosis codes, and recorded estimated blood loss (EBL). The risk of PPH by exposure group was estimated using unadjusted, minimally adjusted (maternal age at delivery, delivery year, parity, and maternal smoking), and depression‐adjusted models (previous covariates and maternal depression). Supplemental analyses included an examination of PPH risk with prenatal bupropion monotherapy.ResultsThe study cohort consisted of 837 S/NRI users, 401 former users, and 786 non‐users, as well as 114 bupropion users identified for additional analyses. The frequency of PPH was 11.6% in the overall cohort, and was 14.7% for S/NRI users, 10.2% for former users, and 8.7% for non‐users. The risk of PPH was significantly higher for S/NRI users than non‐users in unadjusted (OR 1.82 [95% CI 1.33, 2.49]), minimally adjusted (aOR 1.66 [1.19, 2.31]), and depression‐adjusted models (aOR 1.46 [1.02, 2.10]). The risk of PPH was also higher for S/NRI former users than non‐users in unadjusted models (OR 1.54 [1.05, 2.26]) but not minimally adjusted (aOR 1.42 [0.95, 2.11]) or depression‐adjusted models (aOR 1.41 [0.95, 2.10]). No significant differences in PPH risk were observed between S/NRI users and former users, between bupropion users and non‐users, or between S/NRI users and bupropion users.ConclusionsPrenatal S/NRI exposure was associated with an increased risk of PPH after adjusting for maternal depression, although residual confounding and confounding by other factors (including unmeasured factors) may be possible, as the risk of PPH appeared to be similar between S/NRI users and former users. Best‐practice PPH risk management strategies should be adhered to for depressed patients, especially those who require treatment with antidepressants during pregnancy.

Introduction: Despite advances in obstetric care, postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Prior reviews of studies published through 2016 suggest an association of antidepressant use during late pregnancy and increased risk of PPH. However, a causal link between prenatal antidepressants and PPH remains controversial. Objectives: This systematic literature review aimed to synthesize the empirical evidence on the association of antidepressant exposure in late pregnancy with the risk of PPH, including studies published before and after 2016. Methods: A systematic literature search was conducted using PubMed, OVID Medline, EMBASE, SCOPUS, PsycINFO, and CINAHL from inception to September 9, 2023. Original, peer-reviewed studies (published in English) that reported on the frequency or risk of PPH in women with evidence of antidepressant use during pregnancy and included at least one control group were included. Results: Twenty studies (eight published after 2016) met inclusion criteria, most of which focused on the risks of PPH associated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). The main findings from the individual studies were mixed, but the majority documented statistically significant associations of PPH with late prenatal exposure, especially for exposures occurring within 30 days of delivery, compared with unexposed deliveries. Fourteen studies addressed underlying antidepressant indications or their correlates. Few studies focused on prenatal antidepressants and the risk of well-defined severe PPH or on antidepressant dose changes and general PPH risk. None examined competing risks of antidepressant discontinuation on mental health outcomes. Conclusions: Late pregnancy exposure to antidepressants may be a minor risk factor for PPH, but it is unclear to what extent reported associations are causal in nature, as opposed to correlational (effects related to nonpharmacological factors including maternal indication). For patients needing antidepressants during pregnancy, current evidence does not favor routinely discontinuing antidepressants specifically to reduce the risk of PPH.

INTRODUCTION: Perinatal mental illness imparts a significant health burden. A multitude of factors are hypothesized to increase the incidence of perinatal mood and anxiety disorders (PMADs) in the fetal surgical population, including uncertain fetal prognosis and the inherent risks of surgery and preterm delivery. We sought to determine the disease course of PMADs in the fetal surgery population. METHODS: A retrospective chart review was conducted of fetal surgery patients from 2017 to 2021 at a tertiary care center. Demographics, surgical, obstetric, and psychiatric diagnoses were recorded. Standard descriptive analyses were performed. RESULTS: One hundred nineteen eligible patients were identified. Fetal surgery was performed at a median gestational age of 23.0 (range 16.0–34.0) weeks. Laser ablation of placental anastomoses (n=51) and in utero myelomeningocele repair (n=22) were the most common procedures. 26.8% (32/119) had preexisting mood disorders, with 59.3% (19/32) and 53.1% (17/32) on a baseline medication for depression or anxiety, respectively, prior to surgery. 26.4% (23/87) of patients without a history of anxiety or depression had a new diagnosis of PMAD. Two patients experienced suicidal ideation. 6.7% (8/119) and 10.1% (12/119) initiated a new psychiatric medication during or post-pregnancy, respectively. 19.8% (21/113) received a therapy referral. Among patients with baseline anxiety or depression, 62.5% (20/32) experienced an exacerbation postpartum with 25.0% (8/32) referred for therapy, and 34.3% (11/32) changing dose or medication for anxiety and 37.5% (12/32) for depression. CONCLUSION: Among patients undergoing fetal surgery, a high incidence of PMAD was identified. Most patients with prepregnancy anxiety or depression experienced an exacerbation postpartum. Further research into effective supportive interventions is warranted.

INTRODUCTION: While focal-occult placenta accreta spectrum (PAS) is known to lead to adverse outcomes, little is known of the morbidity in comparison to previa-associated PAS. METHODS: After IRB approval, retrospective review was conducted of pathologically confirmed (decidual layer absence or basal-plate myometrial fibers) PAS from 2018 to 2021 at a tertiary care center. Baseline characteristics and surgical, obstetric, and subsequent pregnancy outcomes were recorded. Focal-occult PAS was compared with previa-associated PAS using Kruskal-Wallis/Chi-square tests; P<.05 was considered significant. RESULTS: A total of 56 cases were identified: 22 previa-associated and 34 focal-occult PAS. All patients with previa-associated and 26.5% of those with focal-occult PAS underwent hysterectomy. Of the previa-associated PAS patients, 20 of 22 were diagnosed antenatally, as was 1 of 34 focal-occult PAS patients. Mean maternal age (32.5 vs. 33.1 year), number of previous dilation and curettage procedures (0.4 vs. 0.3), and in vitro fertilization rates (4.5% vs. 23.5%) were not significantly different between groups. Mean parity (3.7 vs. 1.4), gestational age at delivery (34.3 vs. 35.7 weeks), any previous cesarean delivery (95.5% vs. 29.4%), mean number of previous cesareans (2.5 vs. 0.5), and placental locations were significantly different between groups. All measures of morbidity, including postpartum hemorrhage rates (81.0% vs. 75.8%), median qualitative blood loss (1,500cc, range: 500–9,516cc vs. 1,660cc, range: 350–12,220cc), mean units of red blood cells transfused (1.8 vs. 1.9), massive transfusion (9.1% vs. 20.6%), ICU admission (9.1% vs. 14.7%), and reoperation rates (9.1% vs. 32.4%) were similar between groups. Six focal-occult PAS patients had a subsequent pregnancy, and two had recurrent PAS. CONCLUSION: Despite representing lower grade PAS, focal-occult PAS has similar measures of morbidity when compared to previa-associated PAS, potentially attributable to lack of antenatal detection.

Abstract Objectives: We hypothesize that a validated panel of methylated DNA markers (MDMs) for HPV(+)CSCC will be similar to but distinct from a cohort of HPV(+)OPSCC. Methods: Patients were excluded for recurrent tumor, prior pelvic or head or neck cancer/neoplasia, chemotherapy &lt; 1 year, prior therapeutic radiation to the target region, prior transplant, insufficient target tissue (&lt;5mm), or if &lt;18 yrs. MDMs identified from sequenced differentially methylated regions were selected from a panel validated for HPV(+)CSCC and evaluated on DNA from independent FFPE HPV(+)OPSCC, HPV(+)CSCC, normal oropharynx tonsil, and normal cervix tissue using methylation-specific PCR. White blood cells (WBCs) were used as a background control. Results: 34 HPV(+)OPSCC, 36 HPV(+)CSCC, 26 normal tonsil tissue, and 24 normal cervical tissue patients met criteria. The HPV(+)OPSCC cohort was older (57 vs 44 yrs, p=0.027), had more frequent alcohol exposure (85% vs 64%, p=0.02), but similar ACE-27 comorbidity scores (p=0.078) and tobacco use (p=0.066). Tumor stages were stage I (47% and 83%), stage II (44% and 11%) and stage III (9% and 6%) for HPV(+)OPSCC and HPV(+)CSCC, respectively. Twenty-one MDMs were evaluated and areas under the receiver operator characteristic curve (AUC) are reported (Table 1). 95% confidence intervals excluded a non-diagnostic null hypothesis AUC of 0.5. 5/21 (24%) achieved an AUC ≥ 0.90, 15/21 (71%) achieved an AUC ≥ 0.8, and 19/21 (90%) exhibited better than chance classifications relative to control tonsil tissue (all p&lt;0.001). Conclusion: MDMs have the potential to discriminate both HPV(+)OPSCC and HPV(+)CSCC from their normal tissue controls. 90% of the MDMs discovered for HPV(+)CSCC had better than chance discrimination in HPV(+)OPSCC suggesting a distinct signature between the two subtypes. Future discovery efforts specific to HPV(+)OPSCC is warranted. Methylated DNA Markers in HPV(+)OPSCC and HPV(+)CSCC CSCC AUC (95% CI) OPSCC AUC (95% CI) AUC CSCC vs AUC OPSCC Pvalue GRIN2D 0.72 (0.59-0.85) 0.91 (0.83-0.99) 0.019 EMX1 0.93 (0.86-0.99) 0.77 (0.65-0.89) 0.0191 VWC2 0.88 (0.79-0.97) 0.57 (0.42-0.72) 0.0001 ZNF610 0.99 (0.98-1) 0.89 (0.8-0.97) 0.0162 ZNF781.F 0.92 (0.86-0.99) 0.79 (0.67-0.91) 0.0585 TBX15 0.99 (0.96-1) 0.82 (0.72-0.93) 0.0025 TSPYL5 0.94 (0.87-1) 0.82 (0.72-0.93) 0.058 LOC645323 0.95 (0.89-1) 0.88 (0.8-0.97) 0.1952 ASCL1 0.98 (0.93-1) 0.86 (0.76-0.95) 0.0187 ABCB1 0.97 (0.93-1) 0.74 (0.61-0.86) 0.0001 ZNF69 0.89 (0.8-0.97) 0.95 (0.9-1) 0.2017 MAX.chr9 0.97 (0.92-1) 0.82 (0.72-0.93) 0.0113 ARHGAP12 0.91 (0.83-0.99) 0.9 (0.81-1) 0.9223 C1orf114 0.94 (0.86-1) 0.88 (0.8-0.97) 0.3366 MAX.chr6 0.99 (0.97-1) 0.86 (0.76-0.96) 0.0099 NEUROG3 0.95 (0.89-1) 0.7 (0.57-0.83) 0.0001 NID2 0.98 (0.95-1) 0.86 (0.77-0.95) 0.0207 TMEM200C 0.95 (0.89-1) 0.54 (0.39-0.69) 0.0001 TTYH1 0.99 (0.98-1) 0.82 (0.71-0.93) 0.0023 ZNF773 0.93 (0.86-1) 0.9 (0.82-0.98) 0.5696 ZNF781.R 1 (1-1) 0.92 (0.86-0.99) 0.0198 Citation Format: Kathryn M. Van Abel, David M. Routman, Daniel J. Ma, Karen A. Doering, Kelli N. Burger, Patrick H. Foote, William R. Taylor, Douglas W. Mahoney, Calise K. Berger, Xiaoming Cao, Sara S. Then, Alyssa M. Larish, Eric J. Moore, Joaquin G. Garcia, Rondell P. Graham, Jamie N. Bakkum-Gamez, John B. Kisiel. Comparison of methylated DNA markers between human papillomavirus mediated carcinoma in oropharynx and cervical cancer: A pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3742.