A Common OXTR Risk Variant Alters Regulation of Gene Expression by DNA Hydroxymethylation in Pregnant Human Myometrium.

Postpartum hemorrhage, or excessive bleeding after birth, is a leading cause of maternal morbidity. A major cause of postpartum hemorrhage is uterine atony, tiring of the uterus which leads to ineffective contractions. Uterine contractions depend on oxytocin signaling in the myometrium, which in turn depends on expression of the oxytocin receptor (OXTR). Both genetic and epigenetic factors related to the oxytocin receptor are associated with risk of postpartum hemorrhage, but a mechanism relating these factors to oxytocin receptor activity in myometrium remains unclear. We report a genetic by epigenetic interaction whereby the relationship between DNA hydroxymethylation and OXTR gene expression depends on a common OXTR gene variant (rs53576). We also provide evidence that a similar genetic by epigenetic interaction using blood-derived DNA methylation is associated with relevant clinical outcomes: quantity of oxytocin administration and odds for postpartum hemorrhage. These results provide new avenues for predicting how women will respond to pharmacological agents in the prevention and treatment of postpartum hemorrhage.

Examining Cesarean Among Individuals of Advanced Maternal Age in Nurse-Midwifery Care.

INTRODUCTION: Cesarean rates are rising, especially for individuals of advanced maternal age (AMA), defined as aged 35 or older. The Robson 10-Group Classification System (TGCS) facilitates assessment and comparison of cesarean rates among individuals in different settings. In midwifery-led care, in which pregnant people are typically healthier and seek a vaginal birth, it is unknown whether individuals of AMA have different antecedents leading to cesarean compared with younger counterparts. This study aimed to examine antecedents contributing to cesarean using Robson TGCS for individuals across age groups in midwifery care. METHODS: This study was a secondary analysis of 2 cohort data sets from Oregon Health & Science University (OHSU) and University of Michigan Health Systems (UMHS) hospitals. The samples were individuals in midwifery-led care birthing at either OHSU from 2012 to 2019 or UMHS from 2007 to 2019. RESULTS: A total of 11,951 individuals were studied. Overall cesarean rates were low; however, the rate for individuals of AMA was higher than the rate of their younger counterparts (18.30% vs 15.10%). The Robson groups were similar; however, the primary contributor among AMA individuals was group 5 (multiparous with previous cesarean), followed by group 2 [nulliparous with labor induced or prelabor cesarean], and group 1 [nulliparous with spontaneous labor]. In contrast, the primary contributors for younger individuals were groups 1, 2, and 5, respectively. In addition, prelabor cesarean and induced labor partly mediated the relationship between AMA and cesarean among nulliparous individuals, whereas prelabor cesarean was the key contributor to cesarean among multiparous people. DISCUSSION: The cesarean rate in midwifery-led care was low. Using Robson TGCS provided additional insight into the antecedents to cesarean, rather than viewing cesarean as a single outcome. Future studies should continue to use Robson TGCS and investigate antecedents to cesarean, including factors influencing successful vaginal birth after cesarean in individuals of AMA.

Deep Learning Model Using Continuous Skin Temperature Data Predicts Labor Onset.

Background: Changes in body temperature anticipate labor onset in numerous mammals, yet this concept has not been explored in humans. Methods: We evaluated patterns in continuous skin temperature data in 91 pregnant women using a wearable smart ring. Additionally, we collected daily steroid hormone samples leading up to labor in a subset of 28 pregnancies and analyzed relationships among hormones and body temperature trajectory. Finally, we developed a novel autoencoder long-short-term-memory (AE-LSTM) deep learning model to provide a daily estimation of days until labor onset. Results: Features of temperature change leading up to labor were associated with urinary hormones and labor type. Spontaneous labors exhibited greater estriol to α-pregnanediol ratio, as well as lower body temperature and more stable circadian rhythms compared to pregnancies that did not undergo spontaneous labor. Skin temperature data from 54 pregnancies that underwent spontaneous labor between 34 and 42 weeks of gestation were included in training the AE-LSTM model, and an additional 40 pregnancies that underwent artificial induction of labor or Cesarean without labor were used for further testing. The model was trained only on aggregate 5-minute skin temperature data starting at a gestational age of 240 until labor onset. During cross-validation AE-LSTM average error (true - predicted) dropped below 2 days at 8 days before labor, independent of gestational age. Labor onset windows were calculated from the AE-LSTM output using a probabilistic distribution of model error. For these windows AE-LSTM correctly predicted labor start for 79% of the spontaneous labors within a 4.6-day window at 7 days before true labor, and 7.4-day window at 10 days before true labor. Conclusion: Continuous skin temperature reflects progression toward labor and hormonal status during pregnancy. Deep learning using continuous temperature may provide clinically valuable tools for pregnancy care.

The Role of Passive Descent and Epidural Analgesia in Outcomes Associated With Prolonged Pushing Among Nulliparous Individuals in Midwifery Care.

INTRODUCTION: Efforts to reduce primary cesarean birth may include supporting longer second stages of labor. Although midwifery-led care is associated with lower cesarean use, little has been published on associated outcomes of prolonged second stage (≥3 hours of pushing) for nulliparous individuals in US hospital-based midwifery care. Epidural analgesia and the role of passive descent in midwifery-led care are also underexplored in relation to the second stage. In this study, we report the incidence of prolonged second stage stratified by epidural analgesia and/or passive descent. Secondary aims included calculating the odds of cesarean birth, obstetric anal sphincter injury (OASI), postpartum hemorrhage (PPH), and neonatal complications. METHODS: Data were collected prospectively from a single academic center in the United States from 2012 through 2019. Our cohort analysis of labors attended by midwives for nulliparous, term, singleton, and vertex pregnancies included both descriptive and inferential statistics comparing outcomes between prolonged versus nonprolonged pushing groups. We stratified the sample and quantified second stage outcomes by epidural analgesia and by use of passive descent. RESULTS: Of the 1465 births, 17% (n = 247) included prolonged pushing. Cesarean ranged from 2.2% without prolonged pushing to 26.7% with prolonged pushing. Fetal malposition, epidural analgesia, and longer passive descent were more common among those with prolonged active pushing. Despite these factors, neither odds for PPH nor poor neonatal outcomes were associated with prolonged pushing. Those with more than one hour of passive descent in the second stage who also had prolonged active pushing had lower odds for cesarean but higher odds for OASI relative to those who had little passive descent before pushing for more than 3 hours. DISCUSSION: Prolonged pushing occurred in nearly 2 of 10 nulliparous labors. Fetal malposition, epidural analgesia, and prolonged pushing were commonly observed with longer passive descent, cesarean, and OASI. Passive descent in these data likely reflects individualized midwifery care strategies when pushing was complicated by fetal malposition or other complexities.

Maternal outcomes related to Genetic and epigenetic Variation in the oxytocin system: A scoping review.

Purpose: In this scoping review, we synthesize the literature on oxytocin and oxytocin receptor genetic and epigenetic variation in relationship to breastfeeding, maternal caregiving behavior, and maternal mental health. Methods: A literature search was conducted in early 2022, and updated in 2023, utilizing the PRISMA scoping review reporting method, using the following MeSH headings and key terms: oxytocin, oxytocin receptor, genetics, epigenetics, methylation, pregnancy, postnatal, breastfeeding, lactation, mother-infant relations and perinatal outcomes. The search was conducted using PubMed, EMBASE, CINAHL, Google Scholar, SCOPUS, and the Cochrane Library. Inclusion criteria included: human literature which was peer reviewed and found in primary sources, printed in the English language. In addition, the study must have reported genetic/epigenetic data in either the oxytocin or oxytocin receptor gene (maternal or infant up to 12 months after birth) in relation to a breastfeeding, maternal caregiving behavior or a maternal mental health outcome. There was no date limitation. Four authors reviewed studies for eligibility. Data was extracted using a structured data extraction form. Results: A total of 23 studies met inclusion criteria for this review (breastfeeding n = 4, maternal caregiving behavior n = 7, and maternal mental health n = 16). Seventeen papers reported on oxytocin or oxytocin receptor genotype and nine reported epigenetic associations (namely DNA methylation). These totals are greater than 23, as studies reported on multiple outcomes. One paper assessed the interaction between genotype and methylation. While a number of genotype variations were reported, the single nucleotide polymorphism rs53576 on the oxytocin receptor gene was the most studied. Overall, variation in this polymorphism was related to postnatal depression symptoms. Among numerous epigenetic markers, site -934 was the most studied methylation site, and methylation status was associated with maternal depression and maternal caregiving behavior outcomes. Results suggest that early life experiences impact adult maternal caregiving behaviors and mental health outcomes, and vary based on genetic vulnerability. Breastfeeding outcomes were minimally studied. Conclusion: This scoping review found that genetic and epigenetic variation at the oxytocin and oxytocin receptor genes were associated with maternal caregiving behavior and mental health, likely through complex gene and environment interactions. The findings suggest that maternal early life experiences and stress impact later caregiving behaviors and mental health in the postnatal period. The findings highlight potential pathways by which environment, experiences, and genes interact to impact maternal caregiving behavior and maternal mental health.

Predicting labor onset relative to the estimated date of delivery using smart ring physiological data.

The transition from pregnancy into parturition is physiologically directed by maternal, fetal and placental tissues. We hypothesize that these processes may be reflected in maternal physiological metrics. We enrolled pregnant participants in the third-trimester (n = 118) to study continuously worn smart ring devices monitoring heart rate, heart rate variability, skin temperature, sleep and physical activity from negative temperature coefficient, 3-D accelerometer and infrared photoplethysmography sensors. Weekly surveys assessed labor symptoms, pain, fatigue and mood. We estimated the association between each metric, gestational age, and the likelihood of a participant's labor beginning prior to (versus after) the clinical estimated delivery date (EDD) of 40.0 weeks with mixed effects regression. A boosted random forest was trained on the physiological metrics to predict pregnancies that naturally passed the EDD versus undergoing onset of labor prior to the EDD. Here we report that many raw sleep, activity, pain, fatigue and labor symptom metrics are correlated with gestational age. As gestational age advances, pregnant individuals have lower resting heart rate 0.357 beats/minute/week, 0.84 higher heart rate variability (milliseconds) and shorter durations of physical activity and sleep. Further, random forest predictions determine pregnancies that would pass the EDD with accuracy of 0.71 (area under the receiver operating curve). Self-reported symptoms of labor correlate with increased gestational age and not with the timing of labor (relative to EDD) or onset of spontaneous labor. The use of maternal smart ring-derived physiological data in the third-trimester may improve prediction of the natural duration of pregnancy relative to the EDD.

A prolonged latent phase: An early career in oxytocin during birth.

•The author, a nurse-midwife scientist, shares her path to the study of the causes and consequences of clinical oxytocin use.•This paper highlights mentors and key research that informed new thinking about the role of oxytocin during parturition.•Future directions for improving maternal care during childbirth are presented, including genetic and epigenetic perspectives.

Disparities by race/ethnicity in unplanned cesarean birth among healthy nulliparas: a secondary analysis of the nuMoM2b dataset.

BACKGROUND: Racial disparities exist in maternal morbidity and mortality, with most of these events occurring in healthy pregnant people. A known driver of these outcomes is unplanned cesarean birth. Less understood is to what extent maternal presenting race/ethnicity is associated with unplanned cesarean birth in healthy laboring people, and if there are differences by race/ethnicity in intrapartum decision-making prior to cesarean birth. METHODS: This secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) dataset involved nulliparas with no significant health complications at pregnancy onset who had a trial of labor at ≥ 37 weeks with a singleton, non-anomalous fetus in cephalic presentation (N = 5,095). Logistic regression models were used to examine associations between participant-identified presenting race/ethnicity and unplanned cesarean birth. Participant-identified presenting race/ethnicity was used to capture the influence of racism on participant's healthcare experiences. RESULTS: Unplanned cesarean birth occurred in 19.6% of labors. Rates were significantly higher among Black- (24.1%) and Hispanic- (24.7%) compared to white-presenting participants (17.4%). In adjusted models, white participants had 0.57 (97.5% CI [0.45-0.73], p < 0.001) lower odds of unplanned cesarean birth compared to Black-presenting participants, while Hispanic-presenting had similar odds as Black-presenting people. The primary indication for cesarean birth among Black- and Hispanic- compared to white-presenting people was non-reassuring fetal heart rate in the setting of spontaneous labor onset. CONCLUSIONS: Among healthy nulliparas with a trial of labor, white-presenting compared to Black or Hispanic-presenting race/ethnicity was associated with decreased odds of unplanned cesarean birth, even after adjustment for pertinent clinical factors. Future research and interventions should consider how healthcare providers' perception of maternal race/ethnicity may bias care decisions, leading to increased use of surgical birth in low-risk laboring people and racial disparities in birth outcomes.

Oxytocin receptor DNA methylation is associated with exogenous oxytocin needs during parturition and postpartum hemorrhage.

BACKGROUND: The oxytocin receptor gene (OXTR) is regulated, in part, by DNA methylation. This mechanism has implications for uterine contractility during labor and for prevention or treatment of postpartum hemorrhage, an important contributor to global maternal morbidity and mortality. METHODS: We measured and compared the level of OXTR DNA methylation between matched blood and uterine myometrium to evaluate blood as an indicator of uterine methylation status using targeted pyrosequencing and sites from the Illumina EPIC Array. Next, we tested for OXTR DNA methylation differences in blood between individuals who experienced a postpartum hemorrhage arising from uterine atony and matched controls following vaginal birth. Bivariate statistical tests, generalized linear modeling and Poisson regression were used in the analyses. RESULTS: Here we show a significant positive correlation between blood and uterine DNA methylation levels at several OXTR loci. Females with higher OXTR DNA methylation in blood had required significantly more exogenous oxytocin during parturition. With higher DNA methylation, those who had oxytocin administered during labor had significantly greater relative risk for postpartum hemorrhage (IRR 2.95, 95% CI 1.53-5.71). CONCLUSIONS: We provide evidence that epigenetic variability in OXTR is associated with the amount of oxytocin administered during parturition and moderates subsequent postpartum hemorrhage. Methylation can be measured using a peripheral tissue, suggesting potential use in identifying individuals susceptible to postpartum hemorrhage. Future studies are needed to quantify myometrial gene expression in connection with OXTR methylation.

Oxytocin is a hormone produced by the body during childbirth and can cause contractions of the uterus (womb). Synthetic oxytocin is used as a medicine for stimulating or increasing uterine contractions and controlling bleeding after birth. The oxytocin receptor gene, which enables the body to use oxytocin, can be altered by a chemical modification called DNA methylation. We found that the those who bled more during childbirth had higher oxytocin receptor gene DNA methylation compared to those who had normal bleeding. Higher methylation was also linked to needing greater amounts of oxytocin during labor to achieve vaginal birth and control bleeding. These findings identify that certain problems during birth may be related to oxytocin receptor gene methylation. This research could lead to improvements in how versions of oxytocin are used during the birth process by using the amount of oxytocin receptor gene methylation to predict people who may have problems with uterine contractions or bleeding.

Oxytocin receptor single nucleotide polymorphism predicts atony-related postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage remains a key contributor to overall maternal morbidity in the United States. Current clinical assessment methods used to predict postpartum hemorrhage are unable to prospectively identify about 40% of hemorrhage cases. Oxytocin is a first-line pharmaceutical for preventing and treating postpartum hemorrhage, which acts through oxytocin receptors on uterine myocytes. Existing research indicates that oxytocin function is subject to variation, influenced in part by differences in the DNA sequence within the oxytocin receptor gene. One variant, rs53576, has been shown to be associated with variable responses to exogenous oxytocin when administered during psychological research studies. How this variant may influence myometrial oxytocin response in the setting of third stage labor has not been studied. We tested for differences in the frequency of the oxytocin receptor genotype at rs53576 in relationship to the severity of blood loss among a sample of individuals who experienced vaginal birth. METHODS: A case-control prospective design was used to enroll 119 postpartum participants who underwent vaginal birth who were at least 37 weeks of gestation. Cases were defined by either a 1000 mL or greater blood loss or instances of heavier bleeding where parturients were given additional uterotonic treatment due to uterine atony. Controls were matched to cases on primiparity and labor induction status. Genotype was measured from a maternal blood sample obtained during the 2nd postpartum month from 95 participants. Statistical analysis included bivariate tests and generalized linear and Poisson regression modeling. RESULTS: The distribution of the genotype across the sample of 95 participants was 40% GG (n = 38), 50.5% AG (n = 48) and 9.5% AA (n = 9). Blood loss of 1000 mL or greater occurred at a rate of 7.9% for GG, 12.5% for AG and 55.6% for AA participants (p = 0.005). Multivariable models demonstrated A-carriers (versus GG) had 275.2 mL higher blood loss (95% CI 96.9-453.4, p < 0.01) controlling for parity, intrapartum oxytocin, self-reported ancestry, active management of third stage or genital tract lacerations. Furthermore, A-carrier individuals had a 79% higher risk for needing at least one second-line treatment (RR = 1.79, 95% CI = 1.08-2.95) controlling for covariates. Interaction models revealed that A-carriers who required no oxytocin for labor stimulation experienced 371.4 mL greater blood loss (95% CI 196.6-546.2 mL). CONCLUSIONS: We provide evidence of a risk allele in the oxytocin receptor gene that may be involved in the development of postpartum hemorrhage among participants undergoing vaginal birth, particularly among those with fewer risk factors. The findings, if reproducible, could be useful in studying pharmacogenomic strategies for predicting, preventing or treating postpartum hemorrhage.

Advancing understanding of maternal age: correlating epigenetic clocks in blood and myometrium.

Background: Advanced maternal age is currently a term defined by chronological age. However, a group of biomarkers known as epigenetic clocks, which can predict morbidity and mortality, has been used to estimate measures of biological aging. Uterine myometrial function during the process of parturition may be influenced by aging, as labor dystocia, unplanned intrapartum cesarean birth, and postpartum hemorrhage are more common in older individuals. The purpose of this study was to evaluate the use of epigenetic clocks in maternal myometrium and blood for predicting age and to evaluate the correlation of epigenetic age between the tissues. Results: We compared epigenetic age in blood and myometrial samples provided by women undergoing planned cesarean birth at term gestation. Chronological age ranged from 20 to 50 with a median (IQR) age of 35.5(8) years. The MethylationEPIC BeadChip was used to obtain DNA methylation data, and then epigenetic age was calculated using the Horvath, Hannum, GrimAge, and PhenoAge clocks. Spearman correlations of epigenetic age with chronological age were calculated. We tested the relationship of epigenetic age in maternal blood to epigenetic age in myometrium. Age acceleration, for each clock, was also correlated between tissues. Twenty-seven participants provided samples, and 21 matched specimens were included in the final analysis after quality control. Spearman correlation between maternal chronological age and epigenetic age were significant in three of the four clocks (pan-tissue Horvath, Hannum, and GrimAge), for both myometrium and blood samples. Correlations between blood epigenetic age and maternal age ranged from 0.72 to 0.87 (all p < 0.001). Correlations between myometrial epigenetic age and maternal age were also significant (0.62-0.70, p = 0.002), though lower than correlations seen in blood. Maternal blood epigenetic age also correlated with epigenetic age in myometrium with each of these three clocks 0.60 (p = 0.004, Horvath), 0.63 (p = 0.003, Hannum), and 0.80 (p < 0.001, GrimAge). GrimAge age acceleration had the highest correlation between tissues among the clocks (0.49, p = 0.02). Conclusions: Given the limited sample, this study provides insight into the potential use of epigenetic age derived from blood as a proxy for myometrial epigenetic age, which may be a useful biomarker in estimating myometrial biological age in relationship to myometrial dysfunction. GrimAge outperformed the other tested clocks in terms of concordance of epigenetic age and age acceleration between tissues; however, the Horvath and Hannum clocks may be useful depending on the outcome of interest in pregnancy.

Birth, love, and fear: Physiological networks from pregnancy to parenthood.

Pregnancy and childbirth are among the most dramatic physiological and emotional transformations of a lifetime. Despite their central importance to human survival, many gaps remain in our understanding of the temporal progression of and mechanisms underlying the transition to new parenthood. The goal of this paper is to outline the physiological and emotional development of the maternal-infant dyad from late pregnancy to the postpartum period, and to provide a framework to investigate this development using non-invasive timeseries. We focus on the interaction among neuroendocrine, emotional, and autonomic outputs in the context of late pregnancy, parturition, and post-partum. We then propose that coupled dynamics in these outputs can be leveraged to map both physiologic and pathologic pregnancy, parturition, and parenthood. This approach could address gaps in our knowledge and enable early detection or prediction of problems, with both personalized depth and broad population scale.

Maternal Morbidity Predicted by an Intersectional Social Determinants of Health Phenotype: A Secondary Analysis of the NuMoM2b Dataset.

Maternal race, ethnicity and socio-economic position are known to be associated with increased risk for a range of poor pregnancy outcomes, including maternal morbidity and mortality. Previously, researchers seeking to identify the contributing factors focused on maternal behaviors and pregnancy complications. Less understood is the contribution of the social determinants of health (SDoH) in observed differences by race/ethnicity in these key outcomes. In this secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) dataset, latent mixture modeling was used to construct groups of healthy, nulliparous participants with a non-anomalous fetus in a cephalic presentation having a trial of labor (N = 5763) based on SDoH variables. The primary outcome was a composite score of postpartum maternal morbidity. A postpartum maternal morbidity event was experienced by 350 individuals (6.1%). Latent class analysis using SDoH variables revealed six groups of participants, with postpartum maternal morbidity rates ranging from 8.7% to 4.5% across groups (p < 0.001). Two SDoH groups had the highest odds for maternal morbidity. These higher-risk groups were comprised of participants with the lowest income and highest stress and those who had lived in the USA for the shortest periods of time. SDoH phenotype predicted MM outcomes and identified two important, yet distinct groups of pregnant people who were the most likely have a maternal morbidity event.

Innovations in Prospective Perinatal Research as a Result Of the COVID-19 Pandemic.

In 2020, in-person research activities were stopped because of the spread of the novel coronavirus, severe acute respiratory syndrome coronavirus 2, and the resulting disease, coronavirus disease 2019. Our collaborative team of nurse and midwife scientists at universities across the United States adapted research activities to continue prospective perinatal research during the pandemic. These adaptations included development of new research techniques and the implementation of previously developed, but underused, strategies to conduct research from a distance. These strategies included online recruitment, virtual enrollment and consent, qualitative data collection via video conferencing, new applications of smart phone technology, wearable biological measurement, and participant self-collection of biological samples. In addition to allowing research to continue during the pandemic, these innovative strategies may increase access to research for low-income, rural, and racially diverse pregnant and postpartum populations. Decreased travel requirements, flexible scheduling, wearable devices, and the capacity to self-collect biologic samples may improve recruitment and the experience of research participation. The rapid implementation of these research strategies has advanced innovation toward wider, more inclusive and increasingly diverse perinatal research access, and many of these strategies will continue to be used and refined.

Mucosal-Associated Invariant T Cell Response to Acute Exercise and Exercise Training in Older Obese Women.

(1) Background: Obesity is a major global public health concern as it is associated with many of the leading causes of preventable deaths. Exercise reduces obesity-induced inflammation; however, it is unknown how exercise training may impact mucosal associated invariant T (MAIT) cells in overweight/obese (OW) post-menopausal women. Therefore, the purpose of this study was to investigate (i) circulating MAIT-cells at rest in OW vs. Lean women, (ii) the response of MAIT-cells to a single bout of combined aerobic and resistance exercise, and (iii) the effects of 12 weeks of exercise training (EX) or educational program (ED) on the MAIT-cell response in OW. (2) Methods: OW completed an acute exercise session or sitting control, underwent 12 weeks of exercise training or received educational materials, and then repeated the exercise session/sitting control. Lean post-menopausal women provided a baseline comparison. (3) Results: OW had lower circulating MAIT-cells at rest than Lean prior to exercise training; however, after training EX displayed improved MAIT-cell frequency. Additionally, prior to training EX did not exhibit MAIT-cell mobilization/egress, however, both improved after training. (4) Conclusions: Reduced MAIT-cell frequency and ability to mobilize/egress were potentially partially rescued in EX after 12 weeks of exercise training; however, further research is needed to elucidate age or obesity-induced attenuations in MAIT-cells.

Induction of labor or expectant management? Birth outcomes for nulliparous individuals choosing midwifery care.

BACKGROUND: Induction of labor (IOL) has been studied as a strategy to reduce rates of cesarean birth (CB). Midwifery care models are also associated with lower CB rates, even considering that midwives perform fewer IOLs. In this study, we examined childbirth outcomes among individuals undergoing IOL in certified nurse-midwifery (CNM) care as compared to two categories of expectant management (EM). METHODS: Data were from two CNM practices in the United States (2007-2018). The sample was limited to term nulliparous, nondiabetic, singleton, vertex pregnancies. Individuals having an IOL in each week of gestation (37th, 38th, etc) were compared with those having EM. Two methods for defining EM were considered as each method when used alone limits interpretation. Inclusive EM included all births starting in the same week as IOL. The exclusive EM group was comprised of all births occurring in the next gestational age week relative to the IOL cases (ie, 39th week IOL versus all births occurring at 40 weeks or later). Adjusted regression models were used to examine differences in CB by IOL versus EM (inclusive or exclusive) at each week of gestation. RESULTS: Among 4057 CNM-attended pregnancies, the overall rate of IOL was 28.9% (95% CI 27.5%-30.3%) and CB was 19.4% (95% CI 18.1%-20.6%). Most IOLs involved obstetric indications. CB rates did not differ by IOL versus inclusive EM when performed between 37 and 40 weeks, though post hoc power calculations indicate these comparisons were low-powered. In multivarable models, IOL in the 40th week was associated with lower odds for CB versus exclusive EM definition (ie, births occurring at 41 0/7 weeks or later, OR (95% CI) = 0.57 (0.36-0.90)). This finding is explained by the large increase in CB rates after IOL during the 41st week (34.3%, up from 21.9% in the 40th week). Furthermore, the adjusted odds for CB in the 41st week were 55% higher relative to inclusive EM (all labors 41st week and later), OR (95% CI) = 1.55(1.11-2.15). Neonatal outcomes (aside from macrosomia) did not differ by IOL/EM at any gestational age. DISCUSSION: Outcomes for nulliparous individuals having IOL or EM in the context of a midwifery model of care include low overall use of CB and low frequency of IOL before 41 weeks. In this model, IOL in the 40th week may lower CB odds, especially in comparison to those who do not have spontaneous labor and later undergo an IOL in the 41st week.

Predicting Postpartum Hemorrhage After Low-Risk Vaginal Birth by Labor Characteristics and Oxytocin Administration.

OBJECTIVE: To determine the odds of postpartum hemorrhage (PPH) in low-risk women who gave birth vaginally and were exposed to different durations and dosages of oxytocin across a range of labor durations during spontaneous or induced labor. DESIGN: A retrospective cross-sectional analysis of data from the Consortium for Safe Labor. SETTING: Data were gathered from 12 clinical institutions across the United States from 2002 to 2008. PARTICIPANTS: After exclusion of high-risk conditions associated with PPH, we examined data from 27,072 women who gave birth vaginally. METHODS: PPH was defined as estimated blood loss of greater than 500 ml at the time of birth and/or a diagnostic code for PPH before hospital discharge. We included covariates were if they were associated with oxytocin use and PPH and did not mediate oxytocin use. We used regression models to determine the likelihood of PPH overall and within the induced and spontaneous labor groups separately. We used subgroup analyses within specific durations of labor to clarify the findings. RESULTS: The overall rate of PPH was 3.9%. Women with induced labor experienced PPH more frequently than women who labored spontaneously. Labor augmentation was associated with greater adjusted odds for PPH when oxytocin was infused for more than 4 hours. Longer duration of spontaneous labor and the second stage of labor did not change this association. Oxytocin use during labor induction increased the odds for PPH when administered for more than 7 hours. The odds further increased when induction lasted longer than 12 hours and/or the second stage of labor was longer than 3 hours. CONCLUSION: Strategies for judicious oxytocin administration may help mitigate PPH in low-risk women having vaginal birth.

Factors affecting third-stage management and postpartum hemorrhage in planned midwife-led home and birth center births in the United States.

BACKGROUND: Postpartum hemorrhage (PPH) is a potential childbirth complication. Little is known about how third-stage labor is managed by midwives in the United States, including use of uterotonic medication during community birth. Access to uterotonic medication may vary based on credentials of the midwife or state regulations governing midwifery. METHODS: Using data from the Midwives of North America 2.0 database (2004-2009), we describe the PPH incidence for women giving birth in the community, their demographic and clinical characteristics, and methods used by midwives to address PPH. We also examined PPH rates by midwifery credentials and by the presence of regulations for legal midwifery practice. RESULTS: Of the 17 836 vaginal births, 15.9% had blood loss of over 500 mL and 3.3% had 1000 mL or greater blood loss. Midwives used pharmaceuticals to prevent or treat postpartum bleeding in 6.3% and 13.9% of births, respectively, and the rate of hospital transfer after birth was 1.4% (n = 247). In adjusted analyses, PPH was less likely when births occurred at home vs a birth center, if the midwife had a CNM/CM credential vs a CPM/LM/LDM credential, or if the woman was multiparous without a history of PPH or prior cesarean birth. PPH was more likely in states with barriers to midwifery practice compared with regulated states (OR: 1.26; 95% CI, 1.16-1.38). CONCLUSIONS: Women giving birth in the community experienced low overall incidence of PPH-related hospital transfer. However, the occurrence of PPH itself would likely be reduced with improved legal access to uterotonic medication.

COVID-19: Challenges and Lessons Learned from Early Career Investigators.

In March 2020, the United States experienced an unprecedented event that suddenly demanded that researchers cease all nonessential activities to mitigate the rapid spread of the SARS-CoV2. Within the research community, the impact of this cessation on early career investigators was significant, in part because the support systems (i.e., mentors and institutions) that early career investigators typically rely on were also significantly impacted. This article presents the stories of the impact of COVID-19 on early career investigators within the NIH Building Interdisciplinary Research Careers in Women's Health and Women's Reproductive Health Research K12 career development programs. We discuss the common challenges that we faced across our respective fields ranging from basic to clinical to epidemiological women's health research, including the impact it had on our career trajectories. In addition, we share lessons learned in an effort to strengthen our research workforce and increase our resiliency during this and future challenges.

Predicting Postpartum Hemorrhage After Vaginal Birth by Labor Phenotype.

INTRODUCTION: Postpartum hemorrhage (PPH) is an important contributor to maternal morbidity and mortality. Predicting which laboring women are likely to have a PPH is an active area of research and a component of quality improvement bundles. The purpose of this study was to identify phenotypes of labor processes (ie, labors that have similar features, such as duration and type of interventions) in a cohort of women who had vaginal births, estimate the likelihood of PPH by phenotype, and analyze how maternal and fetal characteristics relate to PPH risk by phenotype. METHODS: This study utilized the Consortium for Safe Labor dataset (2002-2008) and examined term, singleton, vaginal births. Using 16 variables describing the labor and birth processes, a latent class analysis was performed to describe distinct labor process phenotypes. RESULTS: Of 24,729 births, 1167 (4.72%) women experienced PPH. Five phenotypes best fit the data, reflecting labor interventions, duration, and complications. Women who had shorter duration of admission after spontaneous labor onset (admitted in latent or active labor) had the lowest rate of PPH (3.8%-3.9%). The 2 phenotypes of labor progress characterized by women who had complicated prolonged labors (spontaneous or induced) had the highest rate of PPH (8.0% and 12.0%, respectively). However, the majority of PPH (n = 881, 75%) occurred in the phenotypes with fewer complications. Prepregnancy body mass index did not predict PPH. Overall, the odds of PPH were highest among nulliparous women (odds ratio [OR], 1.52; 95% CI, 1.30-1.77), as well as Black women (OR, 1.39; 95% CI, 1.13-1.73) and Hispanic women (OR, 1.85; 95% CI, 1.56-2.20). Within phenotypes, maternal race and ethnicity, nulliparity, macrosomia, hypertension, and depression were associated with increased odds of PPH. DISCUSSION: Women who were classified into a lower-risk labor phenotype and still experienced PPH were more likely to be nulliparous, a person of color, or diagnosed with hypertension.