Decreased Alpha Klotho Expression in Placentas Exposed to Severe Maternal Vascular Malperfusion.

BACKGROUND: Placental maternal vascular malperfusion (MVM) is characterized by accelerated villous maturation and has been associated with a decrease in the antiaging protein, alpha-klotho (AK). Our aim was to characterize AK protein and gene expression in the placenta and fetal organs. METHODS: We utilized 2 cohorts. First, we characterized AK protein expression in an autopsy cohort where cases were defined as MVM as the cause of fetal death compared to a stillborn control population. Second, we characterized placental and umbilical cord blood AK gene expression in a liveborn population with and without MVM. RESULTS: We found decreased protein expression in the villous trophoblastic cells of placentas exposed to severe MVM and decreased AK gene expression in placental tissue exposed to MVM. We did not see any statistically significant differences in fetal organ or umbilical cord blood AK expression based on the presence or absence of MVM. Furthermore, in liveborn infants, we also found increased odds of preterm birth with lower placental AK expression. CONCLUSIONS: Decreased AK gene and protein expression in the placenta in the setting of MVM is consistent with the theory of placental aging in MVM and is associated with increased odds of preterm birth.

Reducing severe maternal morbidity for birthing persons with severe hypertension through a statewide quality improvement initiative.

BACKGROUND: Hypertensive disorders of pregnancy are a leading preventable cause of severe maternal morbidity and maternal mortality worldwide. OBJECTIVE: To assess the improvement in hospital care processes and patient outcomes associated with hypertensive disorders of pregnancy after introduction of a statewide Severe Maternal Hypertension Quality Improvement Initiative. STUDY DESIGN: A prospective cohort design comparing outcomes before and after introduction of the Illinois Perinatal Quality Collaborative statewide hypertension quality improvement initiative among 108 hospitals across Illinois. Participating hospitals recorded data for all cases of new-onset severe hypertension (>160 mm Hg systolic or >110 mm Hg diastolic) during pregnancy through 6 weeks postpartum from May 2016 to December 2017. Introduction of the statewide quality improvement initiative included implementation of severe maternal hypertension protocols, standardized patient education and discharge planning, rapid access to medications and standardized treatment order sets, and provider and nurse education. The main outcome measure was the reduction of severe maternal morbidity for pregnant/postpartum patients with severe hypertension. Key process measures include time to treatment of severe hypertension, frequency of provider/nurse debriefs, appropriate patient education, and early postpartum follow-up. RESULTS: Data were reported for 8073 cases of severe maternal hypertension. The frequency of patients with new-onset severe hypertension treated within 60 minutes increased from 41% baseline to 87% (P<.001) at the end of the initiative. The initiative was associated with increased proportion of patients receiving preeclampsia education at discharge (41% to 89%; P<.001), scheduling follow-up appointments within 10 days of discharge (68% to 83%; P<.001), and having a care team debrief after severe hypertension was diagnosed (17% to 59%; P<.001). Conversely, severe maternal morbidity was reduced from 11.5% baseline to 8.4% (P<.002) at the end of the study period. Illinois hospitals have achieved time to treatment goal regardless of hospital characteristics including geography, birth volume, and patient mix. CONCLUSION: Introduction of a statewide quality improvement effort was associated with improved time to treatment of severe hypertension and increased frequency of provider/nurse debriefs, appropriate patient education, and early postpartum follow-up scheduled at discharge, and reduced severe maternal morbidity.

Implementation of a clinically integrated breastfeeding peer counselor program.

OBJECTIVE: Reflecting disparities across the US, in 2015 publicly insured patients of the NorthShore Community Health Center (NSCHC) in Evanston, Illinois had lower breastfeeding rates than commercially insured patients. We used the Replicating Effective Programs framework to describe the design and implementation of a clinically-integrated breastfeeding peer counseling (ci-BPC) program to address these disparities. STUDY DESIGN: Patient focus groups and surveys informed program design, and a multidisciplinary clinical support team developed workflows that integrated the breastfeeding peer counselor (BPC) into the clinic and the postpartum unit. RESULTS: ci-BPC improved breastfeeding intensity and duration by providing every NSCHC patient with (1) prenatal lactation education; (2) hands on lactation care in the hospital; and (3) on-demand postpartum support. Total cost per patient was $297-386. The program was sustained after demonstrating potential cost-savings. CONCLUSION: An evidence-based, multidisciplinary collaboration resulted in a sustainable clinically integrated breastfeeding peer counseling program that improved breastfeeding outcomes.

Using quality improvement to address social determinants of health needs in perinatal care.

There are unacceptable racial inequities in perinatal outcomes in the United States. Social determinants of health (SDOH) are associated with health outcomes and contribute to disparities in maternal and newborn health. In this article, we (1) review the literature on SDOH improvement in the perinatal space, (2) describe the SDOH work facilitated by the Illinois Perinatal Quality Collaborative (ILPQC) in the Birth Equity quality improvement initiative, (3) detail a hospital's experience with implementing strategies to improve SDOH screening and linkage to needed resources and services and (4) outline a framework for success for addressing SDOH locally. A state-based quality improvement initiative can facilitate implementation of strategies to increase screening for SDOH. Engaging patients and communities with specific actionable strategies is key to increase linkage to needed SDOH resources and services.

The role of clinic-based breastfeeding peer counseling on breastfeeding rates among low-income patients.

BACKGROUND: Despite the benefits of breastfeeding (BF), rates remain lower than public health targets, particularly among low-income Black populations. Community-based breastfeeding peer counselor (BPC) programs have been shown to increase BF. We sought to examine whether implementation of a BPC program in an obstetric clinical setting serving low-income patients was associated with improved BF initiation and exclusivity. METHODS: This is a quasi-experimental time series study of pregnant and postpartum patients receiving care before and after implementation of a BPC program in a teaching hospital affiliated prenatal clinic. The role of the BPC staff included BF classes, prenatal counseling and postnatal support, including in-hospital assistance and phone triage after discharge. Records were reviewed at each of 3 time points: immediately before the hire of the BPC staff (2008), 1-year post-implementation (2009), and 5 years post-implementation (2014). The primary outcomes were rates of breastfeeding initiation and exclusivity prior to hospital discharge, secondary outcomes included whether infants received all or mostly breastmilk during inpatient admission and by 6 weeks post-delivery. Bivariable and multivariable analyses were utilized as appropriate. RESULTS: Of 302 patients included, 52.3% identified as non-Hispanic Black and 99% had Medicaid-funded prenatal care. While there was no improvement in rates of BF initiation, exclusive BF during the postpartum hospitalization improved during the 3 distinct time points examined, increasing from 13.7% in 2008 to 32% in 2014 (2009 aOR 2.48, 95%CI 1.13-5.43; 2014 aOR 1.82, 95%CI 1.24-2.65). This finding was driven by improved exclusive BF for patients who identified as Black (9.4% in 2008, 22.9% in 2009, and 37.9% in 2014, p = 0.01). CONCLUSION: Inpatient BF exclusivity significantly increased with the tenure of a BPC program in a low-income clinical setting. These findings demonstrate that a BPC program can be a particularly effective method to address BF disparities among low-income Black populations.

Implementation of perinatal quality collaborative statewide initiative improves obstetrical opioid use disorder care and outcomes.

BACKGROUND: Maternal deaths resulting from opioid use disorder have been increasing across the United States. Opioid use disorder among pregnant persons is associated with adverse pregnancy outcomes, including preterm birth, along with racial disparities in optimal opioid use disorder care. OBJECTIVE: This study aimed to evaluate whether the Illinois Perinatal Quality Collaborative implementation of the Mothers and Newborns affected by Opioids - Obstetric quality improvement initiative was associated with improvement in opioid use disorder identification, provision of optimal opioid use disorder care for birthing patients, and reduction in racial gaps in optimal opioid use disorder care. STUDY DESIGN: Using a prospective cohort design, hospitals reported monthly key measures for all patients with opioid use disorder at delivery between July 2018 and December 2020. The Illinois Perinatal Quality Collaborative facilitates collaborative learning opportunities, rapid response data, and quality improvement support. Generalized linear mixed-effects regression models were used to evaluate improvement in optimal opioid use disorder care, including increases in linkages to medication-assisted treatment, recovery treatment services, and naloxone counseling across time, and to determine whether optimal opioid use disorder care was associated with positive outcomes, such as lower odds of preterm birth. RESULTS: A total of 91 hospitals submitted data on 2095 pregnant persons with opioid use disorder. For the primary outcomes, the rates of patients receiving medication-assisted treatment and recovery treatment services improved across the initiative from 41% to 78% and 48% to 67%, respectively. For the secondary outcomes, the receipt of recovery treatment services and both recovery treatment services and medication-assisted treatment provided prenatally before delivery admission was associated with lower odds of preterm birth (adjusted odds ratio: 0.67 [95% confidence interval, 0.50-0.91] and 0.49 [95% confidence interval, 0.31-0.75], respectively). During the first quarter of the initiative, Black patients with opioid use disorder were less likely to be linked to medication-assisted treatment than White patients (23% vs 48%, respectively); however, an increase in medication-assisted treatment rates across the initiative occurred for all patients, with the greatest improvement for Black patients with an associated reduction in this disparity gap with >70% of both Black and White patients linked to medication-assisted treatment. CONCLUSION: The Mothers and Newborns affected by Opioids - Obstetric initiative was associated with improvement in optimal opioid use disorder care for pregnant patients across Illinois hospitals, additionally racial disparities in opioid use disorder care was reduced across the initiative. Our findings implicate how optimal opioid use disorder care can improve pregnancy outcomes and close persistent racial gaps for pregnant individuals with opioid use disorder.

Optimizing accuracy of birth certificate data through a statewide quality improvement initiative in Illinois.

OBJECTIVE: This study examines improvement in birth certificate accuracy during a statewide quality improvement initiative. STUDY DESIGN: Participating hospitals systematically sampled 10 delivery medical records per month and compared them to corresponding birth certificates for accuracy. Accuracy was computed before implementing the initiative (Aug-Oct 2014), end of phase 1 (July 2015) and end of phase 2 (Nov-Dec 2015). Accuracy data was aggregated and compared across time points using a linear mixed model and by hospital characteristics. RESULTS: 105 hospitals participated. Birth certificate accuracy increased between baseline (89.59%) and end of phase 2 (97.00%, p < 0.001). Percent accuracy at baseline was lowest in hospitals serving at-risk populations (p < 0.01). These hospitals showed relatively greater increases in overall accuracy with no difference in accuracy by the end of the initiative. CONCLUSIONS: A statewide QI effort contributed to improvements in birth certificate accuracy. Hospitals serving at-risk populations exhibited the greatest benefit and improvement.

Inflammatory markers in serum and placenta in a randomized controlled trial of group prenatal care.

BACKGROUND: Racial and socioeconomic disparities in preterm birth and small for gestational age births are growing in the United States, increasing the burden of morbidity and mortality particularly among Black women and birthing persons and their infants. Group prenatal care is one of the only interventions to show potential to reduce the disparity, but the mechanism is unclear. OBJECTIVE: The goal of this project was to identify if group prenatal care, when compared with individual prenatal care, was associated with a reduction in systemic inflammation during pregnancy and a lower prevalence of inflammatory lesions in the placenta at delivery. STUDY DESIGN: The Psychosocial Intervention and Inflammation in Centering Study was a prospective cohort study that exclusively enrolled participants from a large randomized controlled trial of group prenatal care (the Cradle study, R01HD082311, ClinicalTrials.gov: NCT02640638) that was performed at a single site in Greenville, South Carolina, from 2016 to 2020. In the Cradle study, patients were randomized to either group prenatal care or individual prenatal care, and survey data were collected during the second and third trimesters. The Psychosocial Intervention and Inflammation in Centering Study cohort additionally provided serum samples at these 2 survey time points and permitted collection of placental biopsies for inflammatory and histologic analysis, respectively. We examined associations between group prenatal care treatment and a composite of z scored serum inflammatory biomarkers (C-reactive protein, interleukin-6, interleukin-1 receptor antagonist, interleukin-10, and tumor necrosis factor α) in both the second and third trimesters and the association with the prevalence of acute and chronic maternal placental inflammatory lesions. Analyses were conducted using the intent to treat principle, and the results were also examined by attendance of visits in the assigned treatment group (modified intent to treat and median or more number of visits) and were stratified by race and ethnicity. RESULTS: A total of 1256 of 1375 (92%) Cradle participants who were approached enrolled in the Psychosocial Intervention and Inflammation in Centering Study, which included 54% of all the Cradle participants. The Psychosocial Intervention and Inflammation in Centering Study cohort did not differ from the Cradle cohort by demographic or clinical characteristics. Among the 1256 Psychosocial Intervention and Inflammation in Centering Study participants, 1133 (89.6%) had placental data available for analysis. Among those, 549 were assigned to group prenatal care and 584 of 1133 were assigned to individual prenatal care. In the intent to treat and modified intent to treat cohorts, participation in group prenatal care was associated with a higher serum inflammatory score, but it was not associated with an increased prevalence of placental inflammatory lesions. In the stratified analyses, group prenatal care was associated with a higher second trimester inflammatory biomarker composite (modified intent to treat: B=1.17; P=.02; and median or more visits: B=1.24; P=.05) among Hispanic or Latine participants. CONCLUSION: Unexpectedly, group prenatal care was associated with higher maternal serum inflammation during pregnancy, especially among Hispanic or Latine participants.

Maternal plasma and salivary anelloviruses in pregnancy and preterm birth.

Introduction: Human anelloviruses, including torque teno virus (TTV) and torque teno mini virus (TTMV), are ubiquitous in the general population and have no known pathogenicity. We investigated the prevalence and viral load of TTV and TTMV in plasma and saliva over pregnancy, and assessed their association with spontaneous or medically indicated preterm birth. Methods: This is a secondary analysis of the Measurement of Maternal Stress (MOMS) study, which recruited 744 individuals with singleton pregnancies from 4 US sites (Chicago, Pittsburgh, San Antonio, and rural Pennsylvania). Baseline outpatient visits took place in the second trimester (between 12'0 and 20'6/7 weeks' gestation), and follow-up visits in the third trimester (between 32'0 and 35'6/7 weeks' gestation). In a case-control study design, participants who delivered preterm (<37 weeks) resulting from spontaneous labor and/or preterm premature rupture of membranes ("sPTB") were compared with participants experiencing medically indicated preterm birth ("iPTB"), or delivery at term ("controls"). Plasma and saliva samples obtained during the second and third trimesters were tested for the presence and quantity of TTV and TTMV using real-time PCR. Demographic data were obtained via self-report, and clinical data via medical record review by trained research personnel. Results: TTV was detected in plasma from 81% (second trimester) and 77% (third trimester) of participants, and in saliva from 64 and 60%. Corresponding detection rates for TTMV were 59 and 41% in plasma, and 35 and 24% in saliva. TTV and TTMV concentrations were similar between matched plasma and saliva samples. TTV prevalence and concentrations were not significantly different between groups (sPTB, iPTB, and controls). However, plasma TTMV in the third trimester was associated with sPTB and earlier gestational age at delivery. The iPTB group was not different from either the sPTB or the control group. In saliva, concentrations of TTV and TTMV were similar among the three groups. Both TTV and TTMV were more prevalent with increasing parity and were more common in Black and Hispanic participants compared to non-Hispanic White participants. Conclusion: Anellovirus presence (specifically, TTMV) in the third trimester may be associated with preterm birth. Whether this association is causative remains to be determined.

Clinically Integrated Breastfeeding Peer Counseling to Promote Breastfeeding Equity.

OBJECTIVE: This study aimed to determine whether clinically integrated Breastfeeding Peer Counseling (ci-BPC) added to usual lactation care reduces disparities in breastfeeding intensity and duration for Black and Hispanic/Latine participants. STUDY DESIGN: This study is a pragmatic, randomized control trial (RCT) of ci-BPC care at two ci-BPC-naïve obstetrical hospital facilities in the greater Chicago area. Participants will include 720 patients delivering at Hospital Site 1 and Hospital Site 2 who will be recruited from eight prenatal care sites during midpregnancy. Participants must be English or Spanish speaking, planning to parent their child, and have no exposure to ci-BPC care prior to enrollment. Randomization will be stratified by race and ethnicity to create three analytic groups: Black, Hispanic/Latine, and other races. RESULTS: The primary outcome will be breastfeeding duration. Additional outcomes will include the proportion of breastmilk feeds during the delivery admission, at 6-week postdelivery, and at 6-month postdelivery. A process evaluation will be conducted to understand implementation outcomes, facilitators, and barriers to inform replication and scaling of the innovative ci-BPC model. CONCLUSION: This research will produce findings of relevance to perinatal patients and their families, the vast majority of whom desire to provide breastmilk to their infants and require support to succeed with their feeding goals. As the largest RCT of ci-BPC in the United States to date, this research will improve the quality of evidence available regarding the effectiveness of ci-BPC at reducing disparities. These findings will help patients and stakeholders determine the benefits of accepting and adopting the program and inform policies focused on improving perinatal care and reducing maternal/child health disparities. This study is registered with Clinical Trial (identifier: NCT05441709). KEY POINTS: · Ci-BPC can promote racial breastfeeding equity.. · Ci-BPC has not been tested as a generalized lactation strategy in prior trials and is underused.. · This RCT will identify if ci-BPC can reduce breastfeeding disparities for Black and Hispanic patients..

Adaptation of Screening Tools for Social Determinants of Health in Pregnancy: A Pilot Project.

OBJECTIVES: Social determinants of health (SDOH) and stress during pregnancy may contribute to adverse pregnancy outcomes. The objective of this in the field pilot project was to develop a comprehensive screening tool by combining existing validated screeners. Additionally, implement use of this tool within routine prenatal visits and assess feasibility. METHODS: Pregnant patients accessing prenatal care at a single site of an urban Federally Qualified Health Center were recruited during prenatal visits to complete a Social Determinants of Health in Pregnancy Tool (SIPT). SIPT combines a series of questions from existing and well-validated tools and consists of five domains: (1) perceived stress, (2) relationship and family stress, (3) domestic violence, (4) substance abuse, and (5) financial stress. RESULTS: Between April 2018 and March 2019, 135 pregnant participants completed SIPT. Ninety-one percent of patients scored positive on at least one screener, 54% to three or more screeners. CONCLUSIONS: Despite guidelines to screen for SDOH during pregnancy there is no universal tool. Our pilot project demonstrated the concurrent use of adapted screening tools where participants reported at least one area of potential stress, and that linking to resources at the time of a visit is plausible. Future work should examine if screening and point of care linkages of services improves maternal child outcomes.

Maternal exposure to childhood maltreatment and adverse birth outcomes.

Exposure to traumatic events during pregnancy may influence pregnancy and birth outcomes. Growing evidence suggests that exposure to traumatic events well before pregnancy, such as childhood maltreatment (CM), also may influence the course of pregnancy and risk of adverse birth outcomes. We aimed to estimate associations between maternal CM exposure and small-for-gestational-age birth (SGA) and preterm birth (PTB) in a diverse US sample, and to examine whether common CM-associated health and behavioral sequelae either moderate or mediate these associations. The Measurement of Maternal Stress (MOMS) Study was a prospective cohort study that enrolled 744 healthy English-speaking participants ≥ 18 years with a singleton pregnancy, who were < 21 weeks at enrollment, between 2013 and 2015. CM was measured via the Childhood Trauma Questionnaire (CTQ) and participants above the moderate/severe cut-off for any of the five childhood abuse and neglect scales were assigned to the CM-exposed group. Common CM-associated health (obesity, depressive symptoms, hypertensive disorders) and behavioral (substance use) sequelae were obtained from standardized questionnaires and medical records. The main outcomes included PTB (gestational age < 37 weeks at birth) and SGA (birthweight < 10%ile for gestational age) abstracted from the medical record. Multivariable logisitic regression was used to test associations between CM, sequeale, and birth outcomes, and both moderation and mediation by CM-related sequelae were tested. Data were available for 657/744 participants. Any CM exposure was reported by 32% of participants. Risk for SGA birth was 61% higher among those in the CM group compared to the non-CM group (14.1% vs. 7.6%), and each subsequent form of CM that an individual was exposed to corresponded with a 27% increased risk for SGA (aOR 1.27, 95% CI 1.05, 1.53). There was no significant association between CM and PTB (9.3% vs. 13.0%, aOR 1.07, 95% CI 0.58, 1.97). Of these sequelae only hypertensive disorders were associated with both CM and SGA and hypertensive disorders of pregnancy did not mediate the association between CM and SGA. Our findings indicate that maternal CM exposure is associated with increased risk for SGA birth and highlight the importance of investigating the mechanisms whereby childhood adversity sets the trajectory for long-term and intergenerational health issues.

Group vs traditional prenatal care for improving racial equity in preterm birth and low birthweight: the Centering and Racial Disparities randomized clinical trial study.

BACKGROUND: The United States has persistently high rates of preterm birth and low birthweight and is characterized by significant racial disparities in these rates. Innovative group prenatal care models, such as CenteringPregnancy, have been proposed as a potential approach to improve the rates of preterm birth and low birthweight and to reduce disparities in these pregnancy outcomes. OBJECTIVE: This study aimed to test whether participation in group prenatal care would reduce the rates of preterm birth and low birthweight compared with individual prenatal care and whether group prenatal care would reduce the racial disparity in these rates between Black and White patients. STUDY DESIGN: This was a randomized controlled trial among medically low-risk pregnant patients at a single study site. Eligible patients were stratified by self-identified race and ethnicity and randomly allocated 1:1 between group and individual prenatal care. The primary outcomes were preterm birth at <37 weeks of gestation and low birthweight of <2500 g. The primary analysis was performed according to the intent-to-treat principle. The secondary analyses were performed according to the as-treated principle using modified intent-to-treat and per-compliance approaches. The analysis of effect modification by race and ethnicity was planned. RESULTS: A total of 2350 participants were enrolled, with 1176 assigned to group prenatal care and 1174 assigned to individual prenatal care. The study population included 952 Black (40.5%), 502 Hispanic (21.4%), 863 White (36.8%), and 31 "other races or ethnicity" (1.3%) participants. Group prenatal care did not reduce the rate of preterm birth (10.4% vs 8.7%; odds ratio, 1.22; 95% confidence interval, 0.92-1.63; P=.17) or low birthweight (9.6% vs 8.9%; odds ratio, 1.08; 95% confidence interval, 0.80-1.45; P=.62) compared with individual prenatal care. In subgroup analysis, greater attendance in prenatal care was associated with lower rates of preterm birth and low birthweight. This effect was most noticeable for the rates of low birthweight for Black participants in group care: intent to treat (51/409 [12.5%]), modified intent to treat (36/313 [11.5%]), and per compliance (20/240 [8.3%]). Although the rates of low birthweight were significantly higher for Black participants than White participants seen in individual care (adjusted odds ratio, 2.00; 95% confidence interval, 1.14-3.50), the difference was not significant for Black participants in group care compared with their White counterparts (adjusted odds ratio, 1.58; 95% confidence interval, 0.74-3.34). CONCLUSION: There was no difference in the overall rates of preterm birth or low birthweight between group and individual prenatal care. With increased participation in group prenatal care, lower rates of preterm birth and low birthweight for Black participants were observed. The role of group care models in reducing racial disparities in these birth outcomes requires further study.

Complaints about excessive use of police force in women's neighborhoods and subsequent perinatal and cardiovascular health.

There are substantial, unexplained racial disparities in women's health. Some of the most pronounced involve elevated rates of preterm delivery (PTD) and cardiovascular disease (CVD) among Black women. We hypothesized that stress associated with excessive use of force by police may contribute to these disparities. In two prospective cohorts derived from electronic health records (pregnancy cohort, N = 67,976; CVD cohort, N = 6773), we linked formal complaints of excessive police force in patients' neighborhoods with health outcomes. Exposed Black women were 1.19 times as likely to experience PTD [95% confidence interval (CI): 1.04 to 1.35] and 1.42 times as likely to develop CVD (95% CI: 1.12 to 1.79), even after adjustment for neighborhood disadvantage and homicide. The excess risks of PTD were also observed in maternal fixed-effects analyses comparing births to the same woman. These findings suggest police violence may be an unrecognized contributor to health inequity for Black women.

The intersection of race and socioeconomic status is associated with inflammation patterns during pregnancy and adverse pregnancy outcomes.

BACKGROUND: Preterm birth rates are higher among individuals of lower socioeconomic status and non-White race, which is possibly related to life-course stressors. It is important to understand the underlying mechanisms of these health disparities, and inflammation is a possible pathway to explain the disparities in birth outcomes. OBJECTIVE: In this study, we aimed to determine whether patterns of inflammation differed by maternal race and socioeconomic status. STUDY DESIGN: Seven hundred and forty-four participants in a multi-site, prospective study of pregnancy and birth outcomes provided biological and psychological data between 12'0-20'6 weeks gestation. Participants with recent infection, fever, antibiotics or steroid treatment were excluded. Cytokines including INFÉ£, IL-10, IL-13, IL-6, IL-8, and TNFα, and the acute phase protein CRP were measured in serum and values and were log-transformed for normality when appropriate, and a non-orthogonal rotation (Oblimid) was performed to allow the extracted factor to inter-correlate. IFNγ, IL-8, IL-10, IL-6, TNF-a, and IL-13 loaded onto Inflammatory Factor 1 (IF-1), while CRP and IL-6 loaded onto Inflammatory Factor 2 (IF-2). Race and education were collected via self-report during an in-person study visit. Multivariable models were used to determine the association of race and SES with IF-1 and IF-2 during the second trimester, and a mediation model was used to examine if inflammation is on the causal pathway. Models were adjusted for study site, prenatal age, pre-pregnancy BMI, smoking during pregnancy, and gestational age at the time of blood collection. RESULTS: Six hundred and five participants were included in our final analysis, with 61.2% of low or moderate SES, and 35.5% identifying as a person of color (POC). Identifying as a POC, being of low and moderate SES, and being both low-SES and POC or moderate-SES and POC were associated with higher odds of preterm birth and lower birth weight percentile infants. Low SES POC participants had significantly higher IF-1 and IF-2 scores when compared to high-SES White participants. Additionally, higher IF-1 and IF-2 were associated with shorter gestation. In the mediation analysis, we observed a significant direct effect of race/SES on preterm birth; however, the results did not support an indirect pathway where IF-1 or IF-2 acted as mediators. CONCLUSION: Maternal race and SES are significantly associated with inflammatory biomarkers during pregnancy, and when race and SES are considered in combination, they are stronger predictors of adverse pregnancy outcomes than when evaluated separately.

Living in a block group with a higher eviction rate is associated with increased odds of preterm delivery.

BACKGROUND: Housing instability is associated with adverse pregnancy outcomes. Recent studies indicate that eviction, which may affect a larger segment of the population than other forms of housing instability, is also associated with adverse pregnancy outcomes. However, these studies evaluate eviction across large areas, such as counties, so it remains unclear whether these patterns extend to individual-level pregnancy outcomes. METHODS: We used data on a cohort of all singleton live births at a single Chicago hospital between March 2008 and March 2018 to investigate the associations between block-group eviction rates and individual adverse pregnancy outcomes. Eviction data were obtained from the Eviction Lab at Princeton University. Generalised estimating equations were used to estimate associations and account for correlations among individuals living in the same block groups. RESULTS: Individuals living in block groups in the highest quartile for eviction filing rate were 1.17 times as likely to deliver preterm (95% CI: 1.08 to 1.27) and 1.13 times as likely to deliver a small for gestational age infant (95% CI: 1.03 to 1.25) as compared with individuals living in block groups in the lowest quartile. Further, tests for linear trend indicated that for each quartile increase in eviction filing rate, there was a corresponding increase in odds of adverse outcomes (p<0.05). Results were strongest in magnitude for those with low neighbourhood and individual socioeconomic status, who are most likely to be renters and affected by local eviction policies. CONCLUSION: Our results suggest that individuals living in block groups with higher eviction rates are more likely to deliver preterm. Future research should explore associations of individual experience with eviction on adverse pregnancy outcomes and examine whether policies to improve tenant protections also impact pregnancy outcomes.

Using principal component analysis to examine associations of early pregnancy inflammatory biomarker profiles and adverse birth outcomes.

OBJECTIVE: Inflammation as a risk factor for preterm birth is well-established. The primary objective of this analysis was to examine whether individual cytokines versus a composite indicator of mid-pregnancy inflammation are significantly associated with risk for adverse birth outcomes. STUDY DESIGN: A multi-site prospective study was conducted in a socio-demographically diverse cohort of 610 pregnant participants. At a study visit between 12 and 20 6/7 weeks' gestation, low-grade inflammation was measured via log-transformed serum concentrations of the biomarkers IFN-γ, IL-10, IL-13, IL-6, IL-8, TNF-α, and CRP. Principal component analysis (PCA) was used to identify underlying dimensions of inflammatory activity from the seven biomarkers measured. Gestational age and birth weight at delivery were obtained from medical chart review. The associations between inflammatory profiles and birth outcomes were assessed via linear and logistic regression models. Results were compared with those from individual inflammatory biomarkers, and model fit was assessed using Akaike's Information Criterion (AIC). RESULTS: Principal component analysis analysis yielded a two-factor solution, with the first factor (IF1) composed of IL-8, IL-10, IL-13, IFN-É£, and TNF-α, and the second factor (IF2) containing IL-6 and CRP. When adjusted for race, education, BMI, smoking status, gestational age at time of blood draw, and study site, a one standard deviation (SD) increase in IF1 remained significantly associated with a decrease in standardized gestational age (ß = -.13, 95% CI: -.21, -.05) and an increase in odds of preterm delivery (OR = 1.46, 95% CI: 1.13, 1.88) (Table 3). A one SD increase in IF2 was similarly associated with a decrease in standardized gestational age at delivery (ß = -.13, 95% CI: -.23, -.04) and an increase in odds of preterm delivery (OR: 1.46, 95% CI: 1.04, 2.05). Neither IF1 nor IF2 was associated with measures of fetal growth. AIC identified that IL-6 was a slightly better fit for length of gestation compared to either composite measure, though all performed similarly. CONCLUSION: Independent of known sociodemographic risk factors, an elevated mid-pregnancy inflammatory profile was associated with a nearly 50% increase in odds of preterm delivery. The composite performed similarly to IL-6. These results suggest that maternal low-grade inflammation is a risk factor for preterm delivery, and that mid-pregnancy inflammatory biomarkers may be useful in predicting risk for preterm delivery.

Racial differences across pregnancy in maternal pro-inflammatory immune responsivity and its regulation by glucocorticoids.

BACKGROUND: The distribution of adverse pregnancy, birth and subsequent child developmental and health outcomes in the U.S. is characterized by pronounced racial (particularly Black-white) disparities. In this context, chronic stress exposure represents a variable of considerable importance, and the immune/inflammatory system represents a leading candidate biological pathway of interest. Previous pregnancy studies examining racial disparities in immune processes have largely utilized circulating cytokine levels, and have yielded null or mixed results. Circulating cytokines primarily represent basal secretion and do not necessarily represent functional features of immune responsivity and regulation. Thus, in order to conduct a more in-depth characterization of racial differences in functional immune properties during pregnancy, we utilized an ex vivo stimulation assay, a dynamic measure of immune function at the cellular level, to investigate Black-white racial differences in in mid- and late-gestation in i) pro-inflammatory (IL-6) responsivity of leukocytes to antigen [lipopolysaccharide (LPS)] challenge, and ii) regulation (dampening) of this pro-inflammatory response by glucocorticoids. METHOD: 177 women (N = 42 Black (24%), n = 135 white (76%)) with a singleton, intrauterine pregnancy provided 20 mL venous blood in mid- (16.6 ± 2.4 wks) and late (33.3 ± 1.1 wks) pregnancy. Maternal pro-inflammatory responsivity of leukocytes was quantified by assessing the release of the pro-inflammatory cytokine IL-6 in response to LPS stimulation, and regulation of the pro-inflammatory response was quantified by assessing the suppression of the stimulated IL-6 response after co-incubation with progressively increasing levels of dexamethasone [10-7, 10-6, 10-5 M] (i.e., glucocorticoid receptor resistance (GRR)). A priori model covariates included maternal age, parity, SES (socioeconomic status), and pre-pregnancy BMI. RESULTS: Maternal pro-inflammatory responsivity (LPS-stimulated IL-6) and GRR increased significantly across mid- and late gestation (adjusted ß = 0.157, p = 0.007; ß = 0.627, p < 0.001, respectively). Across both time points in pregnancy Black women exhibited significantly higher LPS-stimulated IL-6 release and reduced glucocorticoid regulation of the IL-6 response (i.e., higher GRR) relative to white women, before and after adjusting for covariates (ß = 0.381, p = 0.0030; ß = 0.391, p = 0.0075, respectively). There was no racial difference in the concentrations of circulating IL-6 (p = 0.9199). CONCLUSION: Our findings support the hypothesis postulating significant racial (Black-white) differences in key functional properties of the maternal immune system in pregnancy, which were not apparent using circulating cytokine measures. These data elucidate a potentially important physiological mechanism underlying the transduction of environmental conditions into racial disparities in reproductive and subsequent child health outcomes, and the use of these ex vivo measures should be considered in future studies.

Clinically integrated breastfeeding peer counseling and breastfeeding outcomes.

OBJECTIVE: To evaluate whether clinically integrated breastfeeding peer counseling (ci-BPC) improved breastfeeding outcomes for a diverse cohort of Medicaid-enrolled patients. STUDY DESIGN: Medical records were reviewed for a random subset of patients delivering 2014-2015 (baseline, N = 147) and 2017-2019 (post-implementation, N = 281). Chi-squared and logistic regression evaluated differences in breastfeeding initiation, exclusivity, and duration, and results were stratified by race/ethnicity. RESULTS: Post-implementation, 90.4% of patients received ci-BPC. Compared to baseline, documented prenatal breastfeeding counseling increased from 5 to 84% (<0.001), and inpatient counseling increased from 12 to 55% (p < 0.001). Breastfeeding initiation was similar (86 to 89%, p = 0.28), while exclusivity increased from 21 to 31% (p = 0.03). Any breastfeeding ≥6 weeks increased from 29 to 65% (p < 0.001) and was most improved for Black (32 to 50%, p < 0.01) and Latinx patients (37 to 71%, p < 0.01). CONCLUSIONS: ci-BPC was associated with significant improvement in breastfeeding exclusivity and duration, and may address breastfeeding disparities.

Time-dependent changes in placental mRNA expression after delivery due to delayed specimen collection.

PROBLEM: Current scientific guidelines recommend collecting placental specimens within two hours of delivery for gene expression analysis. However, collecting samples in a narrow time window is a challenge in the dynamic and unpredictable clinical setting, so delays in placental specimen collection are possible. The purpose of our analysis was to investigate temporal changes in placental gene expression by longitudinally sampling placentas over a 24 h period. METHOD OF STUDY: Eight placentas from individuals with uncomplicated, term pregnancies delivered by scheduled cesarean section were collected and sampled following the placental delivery and again at 1, 2, 4, 6, and 24 h post-delivery. At each time point, biopsies of chorionic villous tissue were taken from 3 cotyledons to account for intra-placental heterogeneity. The 3 biopsies from each time point were pooled prior to RNA extraction. Expression of 382 mRNA transcripts was quantified using the NanoString nCounter System. Fold change values were calculated for each time point relative to delivery, and a fold change threshold of 1.25 was used to determine a meaningful change from delivery. RESULTS: Based on a fold change threshold of 1.25, 84.3% of transcripts were stable for at least 1 h, 80.2% were stable for at least two hours, and 20.6% of transcripts were stable through the collection at 24 h. CONCLUSION: Our results suggest that for some mRNA transcripts, expression changes as time to sample collection increases. We have developed a Web application to allow investigators to explore transcripts relevant to their research interests and to set appropriate thresholds to aid in determining whether placentas with delayed sample collection can be included in analyses (https://placentaexpression.foundationsofhealth.org/).