Addressing anti-black racism in an academic preterm birth initiative: perspectives from a mixed methods case study.

BACKGROUND: Growing recognition of racism perpetuated within academic institutions has given rise to anti-racism efforts in these settings. In June 2020, the university-based California Preterm Birth Initiative (PTBi) committed to an Anti-Racism Action Plan outlining an approach to address anti-Blackness. This case study assessed perspectives on PTBi's anti-racism efforts to support continued growth toward racial equity within the initiative. METHODS: This mixed methods case study included an online survey with multiple choice and open-ended survey items (n = 27) and key informant interviews (n = 8) of leadership, faculty, staff, and trainees working within the initiative. Survey and interview questions focused on perspectives about individual and organizational anti-racism competencies, perceived areas of initiative success, and opportunities for improvement. Qualitative interview and survey data were coded and organized into common themes within assessment domains. RESULTS: Most survey respondents reported they felt competent in all the assessed anti-racism skills, including foundational knowledge and responding to workplace racism. They also felt confident in PTBi's commitment to address anti-Blackness. Fewer respondents were clear on strategic plans, resources allocated, and how the anti-racism agenda was being implemented. Suggestions from both data sources included further operationalizing and communicating commitments, integrating an anti-racism lens across all activities, ensuring accountability including staffing and funding consistent with anti-racist approaches, persistence in hiring Black faculty, providing professional development and support for Black staff, and addressing unintentional interpersonal harms to Black individuals. CONCLUSIONS: This case study contributes key lessons which move beyond individual-level and theoretical approaches towards transparency and accountability in academic institutions aiming to address anti-Black racism. Even with PTBi's strong commitment and efforts towards racial equity, these case study findings illustrate that actions must have sustained support by the broader institution and include leadership commitment, capacity-building via ongoing coaching and training, broad incorporation of anti-racism practices and procedures, continuous learning, and ongoing accountability for both short- and longer-term sustainable impact.

Estimating the effect of timing of earned income tax credit refunds on perinatal outcomes: a quasi-experimental study of California births.

BACKGROUND: The largest poverty alleviation program in the US is the earned income tax credit (EITC), providing $60 billion to over 25 million families annually. While research has shown positive impacts of EITC receipt in pregnancy, there is little evidence on whether the timing of receipt may lead to differences in pregnancy outcomes. We used a quasi-experimental difference-in-differences design, taking advantage of EITC tax disbursement each spring to examine whether trimester of receipt was associated with perinatal outcomes. METHODS: We conducted a difference-in-differences analysis of California linked birth certificate and hospital discharge records. The sample was drawn from the linked CA birth certificate and discharge records from 2007-2012 (N = 2,740,707). To predict eligibility, we created a probabilistic algorithm in the Panel Study of Income Dynamics and applied it to the CA data. Primary outcome measures included preterm birth, small-for-gestational age (SGA), gestational diabetes, and gestational hypertension/preeclampsia. RESULTS: Eligibility for EITC receipt during the third trimester was associated with a lower risk of preterm birth compared with preconception. Eligibility for receipt in the preconception period resulted in improved gestational hypertension and SGA. CONCLUSION: This analysis offers a novel method to impute EITC eligibility using a probabilistic algorithm in a data set with richer sociodemographic information relative to the clinical and administrative data sets from which outcomes are drawn. These results could be used to determine the optimal intervention time point for future income supplementation policies. Future work should examine frequent income supplementation such as the minimum wage or basic income programs.

Cultural considerations and beliefs surrounding preterm birth in Kenya and South Africa.

BACKGROUND: Preterm birth (PTB) is a global health epidemic, sub-Saharan Africa is severely impacted due to its limited healthcare resources. Pregnancy knowledge, cultural beliefs and practices play a role in the identification of risk and management of PTB. This study explored knowledge, understandings, cultural beliefs and attitudes to pregnancy and PTB, as well as cultural considerations for the introduction of an intravaginal device which could be used to identify PTB risk. METHODS: Qualitative research was conducted in South Africa and Kenya. In-depth interviews were conducted using semi-structured guides with women with a history of PTB (n = 10), healthcare providers (n = 16) and health systems experts (n = 10); and 26 focus group discussions with pregnant women seeking antenatal care (n = 132) and community male partners/fathers (n = 54). Interviews/discussions were transcribed, translated, and analysed thematically. RESULTS: Pregnancy knowledge, especially for first time pregnancies was poor, with many reporting late entry to antenatal care. Knowledge about PTB was understood in terms of gestational age, weight or small size of baby, with concerns about long term health and stigma. Various risk factors for PTB were described, including those related to traditions and beliefs of witchcraft/curses. Cultural practices, such as the use of traditional medicines and pica, and religion and its impact on health seeking behaviour were also viewed as risk factors. Although insertion of intravaginal devices was not widely acceptable in traditional communities, especially during pregnancy, it was felt that the use of one to detect risk of PTB would be accepted if proven effective in reducing PTB risk. CONCLUSIONS: Various culturally-informed beliefs exist which explain understandings of and attitudes toward pregnancy, pregnancy risk, and PTB. An inclusive exploratory process is critical to facilitate an understanding of the beliefs and traditions which could impact the introduction and design of a product to detect the risk of PTB.

Using Community-Based Participatory Research to Design a Patient and Practitioner-Centered Group Prenatal Care Model.

In response to disproportionately high rates of infant mortality and preterm birth among women of color and women in poverty in Fresno County, California, community and academic partners coordinated a community-based participatory research (CBPR) project with local residents. Social isolation and stress, inaccessible prenatal care, and dissatisfaction with care experiences were identified as leading predictors of poor birth outcomes. The PRECEDE-PROCEED framework was used to lead the CBPR effort that resulted in the development of a model of group prenatal care, named Glow! Group Prenatal Care Program (Glow! Program). Group prenatal care (GPNC), which focuses on pregnancy health assessments, education, and peer support, has the potential to address the health and social priorities of women during pregnancy. As a result of the employed CBPR process and the extensive participation from stakeholders, this modified GPNC model responds to the unique needs of the at-risk community members, the agencies aiming to improve maternal-child health experiences and outcomes, and the prenatal care providers offering it to their patients. The methods from this study can be applied in the design and implementation of community-based health care interventions. Returning to community partners throughout the design, implementation, and evaluation phases underscored that health care interventions cannot be designed in silos, and require flexibility to respond to factors that promote improved maternal and infant outcomes, which affect the end goal for the intervention.

Risk of early birth by body mass index in a propensity score-matched sample: A retrospective cohort study.

OBJECTIVE: Evaluate the risk of preterm (<37 weeks) or early term birth (37 or 38 weeks) by body mass index (BMI) in a propensity score-matched sample. DESIGN: Retrospective cohort analysis. SETTING: California, USA. POPULATION: Singleton live births from 2011-2017. METHODS: Propensity scores were calculated for BMI groups using maternal factors. A referent sample of women with a BMI between 18.5 and <25.0 kg/m2 was selected using exact propensity score matching. Risk ratios for preterm and early term birth were calculated. MAIN OUTCOME MEASURES: Early birth. RESULTS: Women with a BMI <18.5 kg/m2 were at elevated risk of birth of 28-31 weeks (relative risk [RR] 1.2, 95% CI 1.1-1.4), 32-36 weeks (RR 1.3, 95% CI 1.2-1.3), and 37 or 38 weeks (RR 1.1, 95% CI 1.1-1.1). Women with BMI ≥25.0 kg/m2 were at 1.2-1.4-times higher risk of a birth <28 weeks and were at reduced risk of a birth between 32 and 36 weeks (RR 0.8-0.9) and birth during the 37th or 38th week (RR 0.9). CONCLUSION: Women with a BMI <18.5 kg/m2 were at elevated risk of a preterm or early term birth. Women with BMI ≥25.0 kg/m2 were at elevated risk of a birth <28 weeks. Propensity score-matched women with BMI ≥30.0 kg/m2 were at decreased risk of a spontaneous preterm birth with intact membranes between 32 and 36 weeks, supporting the complexity of BMI as a risk factor for preterm birth. TWEETABLE ABSTRACT: Propensity score-matched women with BMI ≥30 kg/m2 were at decreased risk of a late spontaneous preterm birth.

Toward an intravaginal device to detect risk of preterm labor: a user-centered design approach in Sub-Saharan Africa.

BACKGROUND: Prematurity and its complications are the leading cause of death and disability in children under five in Africa and North America, affecting as many as one in ten pregnancies. Screening tests to predict preterm birth (PTB) are insensitive, costly, and often unavailable in low resource settings. In parallel with early-stage U.S.-based testing of a novel self-placed intravaginal device to predict PTB risk, we elicited key stakeholder input from two sub-Saharan African countries to ensure local contextual factors inform future development of the device and its acceptability. METHODS: A qualitative study was conducted in Kiambu County, Kenya and KwaZulu-Natal Province, South Africa. We conducted 26 focus group discussions with pregnant women (n = 132) and males from the community (n = 54); in-depth interviews with women who had a history of PTB (n = 10), healthcare providers (n = 16), and health system experts (n = 10). Interviews were transcribed and thematic analysis was performed using an iterative coding technique. In addition, we facilitated user-centered design sessions to generate prototype preferences. RESULTS: Women with a personal history of PTB were almost unanimous in support of the proposed device, whereas those with no experience of PTB expressed the greatest degree of reservation. Healthcare providers anticipated that women with a history of PTB would accept the device. However, various potential challenges were identified, including potential discomfort with device insertion, hygiene, and sexual activity, as well as need for provider training, and attention to country-specific regulatory processes. Both community participants and providers expressed a preference for a provider inserted device. Design recommendations included preference for a small, soft, pliable device, with a shape that could facilitate easy removal. CONCLUSIONS: Use of an intravaginal device to detect risk of PTB was generally acceptable, however stakeholders expressed a notable preference for insertion by providers. This reflects the significance of end-user consultation in device design and use. Recommended device modifications as well as educational messaging and provider technical assistance may facilitate utilization.

Prematurity and its complications are the leading cause of death and disability in children under 5 years of age. Up to ten percent of pregnancies in North America and Africa are affected. Screening tests to predict preterm birth (PTB) are insensitive, costly, and often unavailable in low resource settings. A U.S.-based study has developed an intravaginal device to detect preterm labor. In order to assess acceptability and guide development for a low-resource setting, a qualitative study was conducted in Kenya and South Africa. We conducted focus group discussions and interviews with pregnant women, male community members, health care providers and health systems experts. Participants with a personal history of PTB were almost unanimous in support of the proposed device; women with no experience of PTB expressed the greatest degree of reservation. Various potential challenges were identified: discomfort, hygiene, and sexual activity, the need for provider training and attention to country-specific regulatory processes. Design recommendations included preference for a small, soft, pliable device, with a shape that could facilitate easy removal. Stakeholders expressed a strong preference for insertion by providers. These findings reflect the significance of end-user consultation in device design and use.

Association of Maternal Immune Activation during Pregnancy and Neurologic Outcomes in Offspring.

OBJECTIVE: To evaluate neurologic morbidity among offspring during their first year of life in association with prenatal maternal immune activation (MIA), using an inclusive definition. STUDY DESIGN: This retrospective cohort study included singletons born in California between 2011 and 2017. MIA was defined by International Classification of Diseases diagnosis of infection, autoimmune disorder, allergy, asthma, atherosclerosis, or malignancy during pregnancy. Neurologic morbidity in infants was defined by International Classification of Diseases diagnosis of intraventricular hemorrhage, periventricular leukomalacia, seizures, abnormal neurologic examination, or abnormal neurologic imaging. Outcomes of delayed developmental milestones during the first year of life were also explored. Risk of neurologic morbidity in offspring was approximated for women with and without MIA using log link binary regression. RESULTS: Demographic characteristics among 3 004 166 mother-infant dyads with or without MIA were similar in both groups. Rate of preterm delivery in mothers with MIA (9.4%) was significantly higher than those without MIA (5.6%). Infants of mothers with MIA were more likely to experience neurologic morbidities across all gestational ages. Adjusted relative risk (95% CI) in the exposed infants was 2.0 (1.9-2.1) for abnormal neurologic examination; 1.6 (1.5-1.7) for seizures, and 1.6 (1.4-1.8) for periventricular leukomalacia. CONCLUSIONS: Our results demonstrate that MIA during pregnancy may be associated with considerably higher risk of neurologic morbidity in offspring.

Mortality and Major Neonatal Morbidity in Preterm Infants with Serious Congenital Heart Disease.

OBJECTIVE: To investigate the trends of 1-year mortality and neonatal morbidities in preterm infants with serious congenital heart disease (CHD). STUDY DESIGN: This cohort study used a population-based administrative dataset of all liveborn infants of 26-36 weeks gestational age with serious CHD born in California between 2011 and 2017. We assessed 1-year mortality and major neonatal morbidities (ie, retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage grade >2, and periventricular leukomalacia) across the study period and compared these outcomes with those in infants without CHD. RESULTS: We identified 1921 preterm infants with serious CHD. The relative risk (RR) of death decreased by 10.6% for each year of the study period (RR, 0.89; 95% CI, 0.84-0.95), and the RR of major neonatal morbidity increased by 8.3% for each year (RR, 1.08; 95% CI, 1.02-1.15). Compared with preterm neonates without any CHD (n = 234 522), the adjusted risk difference (ARD) for mortality was highest at 32 weeks of gestational age (9.7%; 95% CI, 8.3%-11.2%), that for major neonatal morbidity was highest at 28 weeks (21.9%; 95% CI, 17.0%-26.9%), and that for the combined outcome was highest at 30 weeks (26.7%; 95% CI, 23.3%-30.1%). CONCLUSIONS: Mortality in preterm neonates with serious CHD decreased over the last decade, whereas major neonatal morbidities increased. Preterm infants with a gestational age of 28-32 weeks have the highest mortality or morbidity compared with their peers without CHD. These results support the need for specialized and focused medical neonatal care in preterm neonates with serious CHD.

Newborn metabolic vulnerability profile identifies preterm infants at risk for mortality and morbidity.

BACKGROUND: Identifying preterm infants at risk for mortality or major morbidity traditionally relies on gestational age, birth weight, and other clinical characteristics that offer underwhelming utility. We sought to determine whether a newborn metabolic vulnerability profile at birth can be used to evaluate risk for neonatal mortality and major morbidity in preterm infants. METHODS: This was a population-based retrospective cohort study of preterm infants born between 2005 and 2011 in California. We created a newborn metabolic vulnerability profile wherein maternal/infant characteristics along with routine newborn screening metabolites were evaluated for their association with neonatal mortality or major morbidity. RESULTS: Nine thousand six hundred and thirty-nine (9.2%) preterm infants experienced mortality or at least one complication. Six characteristics and 19 metabolites were included in the final metabolic vulnerability model. The model demonstrated exceptional performance for the composite outcome of mortality or any major morbidity (AUC 0.923 (95% CI: 0.917-0.929). Performance was maintained across mortality and morbidity subgroups (AUCs 0.893-0.979). CONCLUSIONS: Metabolites measured as part of routine newborn screening can be used to create a metabolic vulnerability profile. These findings lay the foundation for targeted clinical monitoring and further investigation of biological pathways that may increase the risk of neonatal death or major complications in infants born preterm. IMPACT: We built a newborn metabolic vulnerability profile that could identify preterm infants at risk for major morbidity and mortality. Identifying high-risk infants by this method is novel to the field and outperforms models currently in use that rely primarily on infant characteristics. Utilizing the newborn metabolic vulnerability profile for precision clinical monitoring and targeted investigation of etiologic pathways could lead to reductions in the incidence and severity of major morbidities associated with preterm birth.

Outcomes of Monochorionic, Diamniotic Twin Pregnancies with Prenatally Diagnosed Intertwin Weight Discordance.

OBJECTIVE: Monochorionic, diamniotic (MCDA) twin pairs are predisposed to various pregnancy complications due to the unique placental angioarchitecture of monochorionicity. Few studies have evaluated the outcomes of weight-discordant MCDA pairs without selective fetal growth restriction (SFGR) or the risk factors for development of SFGR. This study aims to describe the natural history of expectant, noninvasive management of weight-discordant MCDA twins and to evaluate risk factors associated with progression to SFGR. STUDY DESIGN: This was a retrospective cohort study at a single, tertiary care center in the United States. All MCDA twins with isolated intertwin weight discordance (ITWD) ≥ 20% diagnosed before 26 weeks' gestational age (GA) were included. The primary outcome of descriptive analyses was overall pregnancy outcome, incorporating both survival to delivery and GA at delivery, as defined by the North American Fetal Therapy Network. The secondary outcome was SFGR in one twin (defined as estimated fetal weight < 10% for GA) and factors associated with this progression. Only those with fetal ultrasound (US) within 4 weeks of delivery were included in this secondary analysis. RESULTS: Among 73 MCDA pairs with ITWD, 73% had a good pregnancy outcome, with dual live delivery at a median GA of 33 weeks. Among the 34 pairs with adequate US follow-up, 56% developed SFGR. There were no differences in GA at delivery or discordance at birth between those who did and those who did not develop SFGR. There was a nonsignificant association between increasing ITWD at diagnosis and subsequent development of SFGR. CONCLUSION: Expectant, noninvasive management can be considered in MCDA twin pregnancies with ITWD ≥ 20% diagnosed before 26 weeks. This approach is associated with a good pregnancy outcome in the majority of cases, even after the development of SFGR in the smaller twin. KEY POINTS: · Nearly 75% of weight-discordant mo/di twins have a good pregnancy outcome.. · Weight-discordant mo/di twins deliver at a mean gestational age of 33 weeks without invasive therapy.. · Noninvasive management should be considered for weight-discordant mo/di twins..

Research priorities of women at risk for preterm birth: findings and a call to action.

BACKGROUND: Traditional hierarchical approaches to research give privilege to small groups with decision-making power, without direct input from those with lived experience of illness who bear the burden of disease. A Research Justice framework values the expertise of patients and communities as well as their power in creating knowledge and in decisions about what research is conducted. Preterm birth has persisted at epidemic levels in the United States for decades and disproportionately affects women of color, especially Black women. Women of color have not been included in setting the agenda regarding preterm birth research. METHODS: We used the Research Priorities of Affected Communities protocol to elicit and prioritize potential research questions and topics directly from women of color living in three communities that experience disproportionately high rates of preterm birth. Women participated in two focus group sessions, first describing their healthcare experiences and generating lists of uncertainties about their health and/or healthcare during pregnancy. Women then participated in consensus activities to achieve 'top-priority' research questions and topic lists. The priority research questions and topics produced by each group were examined within and across the three regions for similarities and differences. RESULTS: Fifty-four women participated in seven groups (14 sessions) and generated 375 researchable questions, clustered within 22 topics and four overarching themes: Maternal Health and Care Before, During, and After Pregnancy; Newborn Health and Care of the Preterm Baby; Understanding Stress and Interventions to Prevent or Reduce Stress; and Interpersonal and Structural Health Inequities. The questions and topics represent a wide range of research domains, from basic science, translational, clinical, health and social care delivery to policy and economic research. There were many similarities and some unique differences in the questions, topics and priorities across the regions. CONCLUSIONS: These findings can be used to design and fund research addressing unanswered questions that matter most to women at high risk for preterm birth. Investigators and funders are strongly encouraged to incorporate women at the front lines of the preterm birth epidemic in research design and funding decisions, and more broadly, to advance methods to deepen healthcare research partnerships with affected communities.

An Evaluation of Sexually Transmitted Infection and Odds of Preterm or Early-Term Birth Using Propensity Score Matching.

BACKGROUND: Few studies have examined the relationship between sexually transmitted infections (STIs) and preterm birth (<37 weeks gestation) by subtype (<32 weeks, 32-36 weeks, spontaneous, provider-initiated). Here, we evaluate the odds of preterm (by subtype) and early-term (37 and 38 weeks gestation) birth in women with an STI compared with a propensity score-matched reference population. METHODS: The sample was selected from California births in 2007 to 2012. Sexually transmitted infection was defined as a maternal diagnosis of chlamydia, gonorrhea, or syphilis in the birth certificate or hospital discharge record. A reference sample of women without an STI was selected using exact propensity score matching on maternal factors. Odds of preterm and early-term birth were calculated. RESULTS: Sixteen thousand three hundred twelve women were identified as having an STI during pregnancy and an exact propensity score-matched control was identified for 97.2% (n = 15,860). Women with an indication of syphilis during pregnancy were at 1.6 times higher odds of having a preterm birth and, in particular, at elevated odds of a birth less than 32 weeks due to preterm premature rupture of the membranes or provider-initiated birth (odds ratios 4.0-4.2). Women with gonorrhea were at increased odds of a preterm birth, a birth less than 32 weeks, or an early-term birth (odds ratios 1.2-1.8). Chlamydia did not raise the odds of either a preterm or early-term birth. CONCLUSIONS: Gonorrhea and syphilis increased the odds of a preterm birth. Gonorrhea also increased the odds of an early-term birth. Chlamydia did not raise the odds of an early birth.

High risk of spontaneous preterm birth among infants with gastroschisis.

We examined the association between gastroschisis and preterm birth (PTB, <37 weeks) by subtype. The sample was drawn from singleton live births in California from 2007 to 2012 contained in a birth cohort file maintained by the California Office of Statewide Health Planning and Development (n = 2,891,965; 1,421 with gastroschisis). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for PTB by gestational age (<34, 34-36, and any <37 weeks) and by type (spontaneous labor with intact membranes, preterm premature rupture of the membranes [PPROM], provider initiated) and were adjusted for maternal characteristics. Over 44.5% of infants with gastroschisis were born preterm because of spontaneous etiologies; notably, 8.4% of infants with gastroschisis were born <34 weeks because of spontaneous etiologies (adjusted RRs 9.1-12.2). Overall, 53.7% of infants with gastroschisis were born preterm compared with only 6.9% of infants without gastroschisis (adjusted RR 15.2, 95% CI 13.6-19.5) and are at particularly high risk of spontaneous PTB. Nearly 9% of infants with gastroschisis delivered <34 weeks, regardless of preterm etiology, indicating that these infants are at great risk for PTB morbidities in addition to the complications from gastroschisis.

Previous Adverse Outcome of Term Pregnancy and Risk of Preterm Birth in Subsequent Pregnancy.

Objective Evaluate risk of preterm birth (PTB, < 37 completed weeks' gestation) among a population of women in their second pregnancy with previous full term birth but other adverse pregnancy outcome. Methods The sample included singleton live born infants between 2007 and 2012 in a birth cohort file maintained by the California Office of Statewide Health Planning and Development. The sample was restricted to women with two pregnancies resulting in live born infants and first birth between 39 and 42 weeks' gestation. Logistic regression was used to calculate the risk of PTB in the second birth for women with previous adverse pregnancy outcome including: small for gestational age (SGA) infant, preeclampsia, placental abruption, or neonatal death (≤ 28 days). Risks were adjusted for maternal factors recorded for second birth. Results The sample included 133,622 women. Of the women with any previous adverse outcome, 4.7% had a PTB while just 3.0% of the women without a previous adverse outcome delivered early (relative risk adjusted for maternal factors known at delivery 1.4, 95% CI 1.3-1.5). History of an SGA infant, placental abruption, or neonatal death increased the adjusted risk of PTB in their second birth by 1.5-3.7-fold. History of preeclampsia did not elevate the risk of a preterm birth in the subsequent birth. Conclusions for Practice The findings indicate that women with previous SGA infant, placental abruption, or neonatal death, despite a term delivery, may be at increased risk of PTB in the subsequent birth. These women may be appropriate participates for future interventions aimed at reduction in PTB.

Initial Metabolic Profiles Are Associated with 7-Day Survival among Infants Born at 22-25 Weeks of Gestation.

OBJECTIVE: To evaluate the association between early metabolic profiles combined with infant characteristics and survival past 7 days of age in infants born at 22-25 weeks of gestation. STUDY DESIGN: This nested case-control consisted of 465 singleton live births in California from 2005 to 2011 at 22-25 weeks of gestation. All infants had newborn metabolic screening data available. Data included linked birth certificate and mother and infant hospital discharge records. Mortality was derived from linked death certificates and death discharge information. Each death within 7 days was matched to 4 surviving controls by gestational age and birth weight z score category, leaving 93 cases and 372 controls. The association between explanatory variables and 7-day survival was modeled via stepwise logistic regression. Infant characteristics, 42 metabolites, and 12 metabolite ratios were considered for model inclusion. Model performance was assessed via area under the curve. RESULTS: The final model included 1 characteristic and 11 metabolites. The model demonstrated a strong association between metabolic patterns and infant survival (area under the curve [AUC] 0.885, 95% CI 0.851-0.920). Furthermore, a model with just the selected metabolites performed better (AUC 0.879, 95% CI 0.841-0.916) than a model with multiple clinical characteristics (AUC 0.685, 95% CI 0.627-0.742). CONCLUSIONS: Use of metabolomics significantly strengthens the association with 7-day survival in infants born extremely premature. Physicians may be able to use metabolic profiles at birth to refine mortality risks and inform postnatal counseling for infants born at <26 weeks of gestation.

Altered metabolites in newborns with persistent pulmonary hypertension.

BACKGROUND: There is an emerging evidence that pulmonary hypertension is associated with amino acid, carnitine, and thyroid hormone aberrations. We aimed to characterize metabolic profiles measured by the newborn screen (NBS) in infants with persistent pulmonary hypertension of the newborn (PPHN) METHODS: Nested case-control study from population-based database. Cases were infants with ICD-9 code for PPHN receiving mechanical ventilation. Controls receiving mechanical ventilation were matched 2:1 for gestational age, sex, birth weight, parenteral nutrition administration, and age at NBS collection. Infants were divided into derivation and validation datasets. A multivariable logistic regression model was derived from candidate metabolites, and the area under the receiver operator characteristic curve (AUROC) was generated from the validation dataset. RESULTS: We identified 1076 cases and 2152 controls. Four metabolites remained in the final model. Ornithine (OR 0.32, CI 0.26-0.41), tyrosine (OR 0.48, CI 0.40-0.58), and TSH 0.50 (0.45-0.55) were associated with decreased odds of PPHN; phenylalanine was associated with increased odds of PPHN (OR 4.74, CI 3.25-6.90). The AUROC was 0.772 (CI 0.737-0.807). CONCLUSIONS: In a large, population-based dataset, infants with PPHN have distinct, early metabolic profiles. These data provide insight into the pathophysiology of PPHN, identifying potential therapeutic targets and novel biomarkers to assess the response.

Risk of preterm birth by maternal age at first and second pregnancy and race/ethnicity.

We examined the risk of preterm birth (PTB, <37 weeks' gestation) in a second pregnancy and analyzed the extent to which this risk varies by maternal age and race/ethnicity. The sample included nulligravida mothers in California who delivered two singletons between 2005 and 2011. Logistic regression was used to calculate the odds of PTB in the second pregnancy. Within each race/ethnicity stratum, women delivering term infants in their first pregnancy and between 25 and 34 years old for both pregnancies served as the referent group. There were 2,90,834 women included in the study. Among women who delivered their first infant at term, the odds of delivering their second infant early differed by race and age. Hispanic, Black and Asian non-Hispanic women who were <18 years for both pregnancies were at higher odds of having a PTB in their second pregnancy (adjusted odds ratios 1.7, 3.3 and 2.9, respectively). Asian non-Hispanic women who were <18 years for their first delivery at term and between 18 and 24 years for their second delivery, or were >34 years for both, were also at higher odds of delivering their second baby prematurely (adjusted odds ratios 1.9 and 1.3, respectively). Women who deliver their first infant at <37 weeks of gestation are at 3 to 7 times higher odds of delivering their second infant preterm. Providers should consider including information about these risks in counseling their patients.

Polyhydramnios Affecting a Recipient-like Twin: Risk of Progression to Twin-Twin Transfusion Syndrome and Outcomes.

OBJECTIVE: The significance of polyhydramnios of one twin in the absence of oligohydramnios of the cotwin in monochorionic diamniotic (MCDA) twin pregnancies (polyhydramnios affecting a recipient-like twin [PART]) is unknown. Our aim is to assess the risk of progression to twin-twin transfusion syndrome (TTTS) with PART, progression to ≥ stage II TTTS, and neonatal survival. STUDY DESIGN: This study was a retrospective cohort study of MCDA twin pregnancies with PART evaluated at a referral center from 2008 to 2015. RESULTS: Sixty-four MCDA twin pregnancies with PART were identified. Fifteen (23.4%) progressed to TTTS, including 10 (15.6%) who progressed to ≥ stage II TTTS. Three pregnancies were terminated and one underwent selective reduction by radiofrequency ablation. Overall survival was 113 out of 128 (88.3%). Of those who remained stable, 91.8% (N = 45) had survival of both neonates. In multivariate analysis, the presence of arterioarterial (A-A) anastomosis by in utero Doppler ultrasound was associated with decreased risk of progression to TTTS (odds ratio: 0.12, p = 0.03, 95% confidence interval: 0.02-0.78). CONCLUSION: Most MCDA twin pregnancies with PART do not progress to TTTS and have a favorable prognosis. Progression rates are higher than observed in uncomplicated MCDA twins; however, so close surveillance is warranted. The presence of an A-A anastomosis appears to confer decreased risk of progression to TTTS.

Stage I Twin-Twin Transfusion Syndrome: Outcomes of Expectant Management and Prognostic Features.

OBJECTIVE: This article describes the natural history of stage I twin-twin transfusion syndrome (TTTS) including risk of progression to higher stage TTTS and pregnancy outcomes, and to identify risk factors for progression. STUDY DESIGN: Retrospective cohort study of monochorionic diamniotic (MCDA) twin pregnancies from 2006 to 2016 with expectantly managed Quintero stage I TTTS. RESULTS: A total of 30 MCDA twin pregnancies with expectantly managed stage I TTTS were identified. Of these, eight (26.7%) progressed to higher stage TTTS. Median gestational age (GA) at diagnosis for those that progressed was 18.9 ± 2.9 weeks versus 21.4 ± 3.4 weeks in those that remained stable (p = 0.06). Presence of an arterioarterial (A-A) anastomosis was assessed for 20/30 patients, and eight A-A were identified. Of those, 7/8 (87.5%) remained stable. In the complete cohort, a tiny or transiently visible bladder was noted in seven donor twins. Of these, 4/7 (57.1%) progressed. Excluding one termination, 47/58 (81.0%) fetuses survived. CONCLUSION: With expectant management of stage I TTTS, nearly three-fourths of pregnancies remain stable and most have survival of ≥ 1 twin. A-A anastomoses were not associated with progression to higher stage TTTS, whereas earlier GA at diagnosis or a small or intermittently visible donor bladder may herald greater risk of progression.

The Management of Myelomeningocele Study: obstetrical outcomes and risk factors for obstetrical complications following prenatal surgery.

BACKGROUND: The Management of Myelomeningocele Study was a multicenter randomized trial to compare prenatal and standard postnatal closure of myelomeningocele. The trial was stopped early at recommendation of the data and safety monitoring committee and outcome data for 158 of the 183 randomized women published. OBJECTIVE: In this report, pregnancy outcomes for the complete trial cohort are presented. We also sought to analyze risk factors for adverse pregnancy outcome among those women who underwent prenatal myelomeningocele repair. STUDY DESIGN: Pregnancy outcomes were compared between the 2 surgery groups. For women who underwent prenatal surgery, antecedent demographic, surgical, and pregnancy complication risk factors were evaluated for the following outcomes: premature spontaneous membrane rupture ≤34 weeks 0 days (preterm premature rupture of membranes), spontaneous membrane rupture at any gestational age, preterm delivery at ≤34 weeks 0 days, nonintact hysterotomy (minimal uterine wall tissue between fetal membranes and uterine serosa, or partial or complete dehiscence at delivery), and chorioamniotic membrane separation. Risk factors were evaluated using χ2 and Wilcoxon tests and multivariable logistic regression. RESULTS: A total of 183 women were randomized: 91 to prenatal and 92 to postnatal surgery groups. Analysis of the complete cohort confirmed initial findings: that prenatal surgery was associated with an increased risk for membrane separation, oligohydramnios, spontaneous membrane rupture, spontaneous onset of labor, and earlier gestational age at birth. In multivariable logistic regression of the prenatal surgery group adjusting for clinical center, earlier gestational age at surgery and chorioamniotic membrane separation were associated with increased risk of spontaneous membrane rupture (odds ratio, 1.49; 95% confidence interval, 1.01-2.22; and odds ratio, 2.96, 95% confidence interval, 1.05-8.35, respectively). Oligohydramnios was associated with an increased risk of subsequent preterm delivery (odds ratio, 9.21; 95% confidence interval, 2.19-38.78). Nulliparity was a risk factor for nonintact hysterotomy (odds ratio, 3.68; 95% confidence interval, 1.35-10.05). CONCLUSION: Despite the confirmed benefits of prenatal surgery, considerable maternal and fetal risk exists compared with postnatal repair. Early gestational age at surgery and development of chorioamniotic membrane separation are risk factors for ruptured membranes. Oligohydramnios is a risk factor for preterm delivery and nulliparity is a risk factor for nonintact hysterotomy at delivery.