Identification of Endometrial Cancer-Specific microRNA Biomarkers in Endometrial Fluid.

Abnormal uterine bleeding is a common benign gynecological complaint and is also the most common symptom of endometrial cancer (EC). Although many microRNAs have been reported in endometrial carcinoma, most of them were identified from tumor tissues obtained at surgery or from cell lines cultured in laboratories. The objective of this study was to develop a method to detect EC-specific microRNA biomarkers from liquid biopsy samples to improve the early diagnosis of EC in women. Endometrial fluid samples were collected during patient-scheduled in-office visits or in the operating room prior to surgery using the same technique performed for saline infusion sonohysterography (SIS). The total RNA was extracted from the endometrial fluid specimens, followed by quantification, reverse transcription, and real-time PCR arrays. The study was conducted in two phases: exploratory phase I and validation phase II. In total, endometrial fluid samples from 82 patients were collected and processed, with 60 matched non-cancer versus endometrial carcinoma patients used in phase I and 22 in phase II. The 14 microRNA biomarkers, out of 84 miRNA candidates, with the greatest variation in expression from phase I, were selected to enter phase II validation and statistical analysis. Among them, three microRNAs had a consistent and substantial fold-change in upregulation (miR-429, miR-183-5p, and miR-146a-5p). Furthermore, four miRNAs (miR-378c, miR-4705, miR-1321, and miR-362-3p) were uniquely detected. This research elucidated the feasibility of the collection, quantification, and detection of miRNA from endometrial fluid with a minimally invasive procedure performed during a patient in-office visit. The screening of a larger set of clinical samples was necessary to validate these early detection biomarkers for endometrial cancer.

Protocol of the Snuggle Bug/Acurrucadito Study: a longitudinal study investigating the influences of sleep-wake patterns and gut microbiome development in infancy on rapid weight gain, an early risk factor for obesity.

BACKGROUND: Overweight, obesity, and associated comorbidities are a pressing global issue among children of all ages, particularly among low-income populations. Rapid weight gain (RWG) in the first 6 months of infancy contributes to childhood obesity. Suboptimal sleep-wake patterns and gut microbiota (GM) have also been associated with childhood obesity, but little is known about their influences on early infant RWG. Sleep may alter the GM and infant metabolism, and ultimately impact obesity; however, data on the interaction between sleep-wake patterns and GM development on infant growth are scarce. In this study, we aim to investigate associations of infant sleep-wake patterns and GM development with RWG at 6 months and weight gain at 12 months. We also aim to evaluate whether temporal interactions exist between infant sleep-wake patterns and GM, and if these relations influence RWG. METHODS: The Snuggle Bug/ Acurrucadito study is an observational, longitudinal study investigating whether 24-h, actigraphy-assessed, sleep-wake patterns and GM development are associated with RWG among infants in their first year. Based on the Ecological Model of Growth, we propose a novel conceptual framework to incorporate sleep-wake patterns and the GM as metabolic contributors for RWG in the context of maternal-infant interactions, and familial and socio-physical environments. In total, 192 mother-infant pairs will be recruited, and sleep-wake patterns and GM development assessed at 3 and 8 weeks, and 3, 6, 9, and 12 months postpartum. Covariates including maternal and child characteristics, family and environmental factors, feeding practices and dietary intake of infants and mothers, and stool-derived metabolome and exfoliome data will be assessed. The study will apply machine learning techniques combined with logistic time-varying effect models to capture infant growth and aid in elucidating the dynamic associations between study variables and RWG. DISCUSSION: Repeated, valid, and objective assessment at clinically and developmentally meaningful intervals will provide robust measures of longitudinal sleep, GM, and growth. Project findings will provide evidence for future interventions to prevent RWG in infancy and subsequent obesity. The work also may spur the development of evidence-based guidelines to address modifiable factors that influence sleep-wake and GM development and prevent childhood obesity.

Development and validation of a spontaneous preterm delivery predictor in asymptomatic women.

BACKGROUND: Preterm delivery remains the leading cause of perinatal mortality. Risk factors and biomarkers have traditionally failed to identify the majority of preterm deliveries. OBJECTIVE: To develop and validate a mass spectrometry-based serum test to predict spontaneous preterm delivery in asymptomatic pregnant women. STUDY DESIGN: A total of 5501 pregnant women were enrolled between 17(0/7) and 28(6/7) weeks gestational age in the prospective Proteomic Assessment of Preterm Risk study at 11 sites in the United States between 2011 and 2013. Maternal blood was collected at enrollment and outcomes collected following delivery. Maternal serum was processed by a proteomic workflow, and proteins were quantified by multiple reaction monitoring mass spectrometry. The discovery and verification process identified 2 serum proteins, insulin-like growth factor-binding protein 4 (IBP4) and sex hormone-binding globulin (SHBG), as predictors of spontaneous preterm delivery. We evaluated a predictor using the log ratio of the measures of IBP4 and SHBG (IBP4/SHBG) in a clinical validation study to classify spontaneous preterm delivery cases (<37(0/7) weeks gestational age) in a nested case-control cohort different from subjects used in discovery and verification. Strict blinding and independent statistical analyses were employed. RESULTS: The predictor had an area under the receiver operating characteristic curve value of 0.75 and sensitivity and specificity of 0.75 and 0.74, respectively. The IBP4/SHBG predictor at this sensitivity and specificity had an odds ratio of 5.04 for spontaneous preterm delivery. Accuracy of the IBP4/SHBG predictor increased using earlier case-vs-control gestational age cutoffs (eg, <35(0/7) vs ≥35(0/7) weeks gestational age). Importantly, higher-risk subjects defined by the IBP4/SHBG predictor score generally gave birth earlier than lower-risk subjects. CONCLUSION: A serum-based molecular predictor identifies asymptomatic pregnant women at risk of spontaneous preterm delivery, which may provide utility in identifying women at risk at an early stage of pregnancy to allow for clinical intervention. This early detection would guide enhanced levels of care and accelerate development of clinical strategies to prevent preterm delivery.

Interpregnancy intervals and the risk for infant mortality: a case control study of Arizona infants 2003-2007.

There is well-documented evidence on how interpregnancy interval (IPI) is associated with adverse perinatal outcomes and how short and long IPIs are associated with increased risk for preterm birth, low birth weight, and intra-uterine growth restriction. However, the extremes of IPI on infant mortality are less well documented. The current study builds on the existing evidence on IPI to examine if extremes of IPI are associated with infant mortality, and also examines if IPI is associated with both neonatal and post-neonatal mortality after adjusting for several known confounders. Matched birth and death certificate data for Arizona resident infants was drawn for 2003-2007 cohorts. The analysis was restricted to singleton births among resident mothers with a previous live birth (n = 1,466) and a randomly selected cohort of surviving infants during the same time-frame was used as a comparison group (n = 2,000). Logistic regression models were utilized to assess the odds for infant mortality at monthly interpregnancy intervals (<6, 6-11, 12-17, 18-23, 24-59, ≥60), while adjusting for established predictors of infant mortality (i.e., preterm birth, low birth weight, and small for gestational age), and other potential confounders. Unadjusted analysis showed greater clustering at extreme IPIs of <6 months and ≥60 months for infants that died (32%) compared to infants that survived (24.7%). Shorter IPI (i.e., <6 months, 6-11 months, and 12-17 months) compared to 'ideal' IPI (i.e., 18-23 months), were associated with infant mortality even after adjusting for confounders. Short intervals were significantly associated with neonatal, but not post-neonatal deaths. IPI above 23 months were not associated with infant mortality in our analyses. Shorter IPIs (18 months or less) significantly increases the risk for neonatal infant mortality even after controlling for known confounders, and our study adds to the existing evidence on adverse perinatal outcomes. Counseling women of reproductive age on the benefits of spacing pregnancies to at least 18 months addresses one preventable risk for early infant mortality.

Inhibition of uterine contractility with various tocolytics with and without progesterone: in vitro studies.

OBJECTIVE: Various tocolytics are used to suppress uterine contractility in patients in preterm labor. Progesterone (P4) is used in patients at high risk for preterm delivery. In this study, we evaluated the effects of various tocolytics with and without P4 to examine effects on uterine contractility. STUDY DESIGN: Uterine tissues (n = 280) from women undergoing cesarean at term were exposed in vitro to various agents (vehicle, magnesium sulfate [MgSO(4)], nifedipine, indomethacin, or pinacidil-all with and without P4). Contractility was measured before and after addition of the various agents. RESULTS: P4 alone at 10(-5) mol/L concentration has little effect to inhibit contractility (P ≥ .05). MgSO(4) (2-8 × 10(-3) mol/L) inhibits uterine contractility (P < .05) but there is no change when combined with P4 (P > .05). Nifedipine (10(-8) mol/L) and indomethacin (10(-5) mol/L) inhibit contractions alone (P < .05) and to a greater extent when combined with P4 (P < .05). P4 significantly (P < .05) reduced the effects of pinacidil (10(-6.5) mol/L). CONCLUSION: Combinations of P4 with nifedipine or indomethacin, but not MgSO(4), might be used to effectively suppress preterm labor.

Acculturation and health care utilization among Mexican heritage women in the United States.

With the increasing Latino population in the United States, it is critical to examine the influence of the process of acculturation on health care practices and utilization. The purpose of this study was to evaluate the relationship between acculturation level and post-partum visit (PPV) compliance among Latinas participating in a larger psycho-educational intervention aimed at encouraging women to engage in positive healthcare practices. Acculturation was measured with the Bicultural Involvement Questionnaire which assigned participants to five categories: Assimilated, Separated, Moderate, Bicultural and Alienation. Logistic Regression analyses were conducted to predict post-partum visit attendance. Odds ratios and relative risk of not attending the post-partum visit are presented. Results suggest women in the Separation and Assimilation groups were less likely than bicultural group members to attend the PPV. The only other variable that was significant in this analysis is the group condition, indicating that the intervention group was more likely to attend the PPV than the control group. Women identifying as bicultural seem to participate more actively in their own healthcare as they draw on the cultural assets that have a positive influence on informal health practices, such as healthy eating and refraining from drug use. Bicultural group members can also use formal skills related to language and knowledge of the dominant culture to help effectively navigate the healthcare system. Implications for research, intervention and practice are discussed to improve healthcare practices and increase utilization among Latinas.

Sentinel surveillance of SARS-CoV-2 rates and equity impacts using labor and delivery patients in Phoenix, Arizona.

Proactive management of SARS-CoV-2 requires timely and complete population data to track the evolution of the virus and identify at risk populations. However, many cases are asymptomatic and are not easily discovered through traditional testing efforts. Sentinel surveillance can be used to estimate the prevalence of infections for geographical areas but requires identification of sentinels who are representative of the larger population. Our goal is to evaluate applicability of a population of labor and delivery patients for sentinel surveillance system for monitoring the prevalence of SARS-CoV-2 infection. We tested 5307 labor and delivery patients from two hospitals in Phoenix, Arizona, finding 195 SARS-CoV-2 positive. Most positive cases were associated with people who were asymptomatic (79.44%), similar to statewide rates. Our results add to the growing body of evidence that SARS-CoV-2 disproportionately impacts people of color, with Black people having the highest positive rates (5.92%). People with private medical insurance had the lowest positive rates (2.53%), while Medicaid patients had a positive rate of 5.54% and people without insurance had the highest positive rates (6.12%). With diverse people reporting for care and being tested regardless of symptoms, labor and delivery patients may serve as ideal sentinels for asymptomatic detection of SARS-CoV-2 and monitoring impacts across a wide range of social and economic classes. A more robust system for infectious disease management requires the expanded participation of additional hospitals so that the sentinels are more representative of the population at large, reflecting geographic and neighborhood level patterns of infection and risk.

Racism, COVID-19, and Health Inequity in the USA: a Call to Action.

The current national COVID-19 mortality rate for Black Americans is 2.1 times higher than that of Whites. In this commentary, we provide historical context on how structural racism undergirds multi-sector policies which contribute to racial health inequities such as those highlighted by the COVID-19 pandemic. We offer a concrete, actionable path forward to address structural racism and advance health equity for Black Americans through anti-racism, implicit bias, and cultural competency training; capacity building; community-based participatory research (CBPR) initiatives; validated metrics for longitudinal monitoring of efforts to address health disparities and the evaluation of those interventions; and advocacy for and empowerment of vulnerable communities. This necessitates a multi-pronged, coordinated approach led by clinicians; public health professionals; researchers; social scientists; policy-makers at all governmental levels; and local community leaders and stakeholders across the education, legal, social service, and economic sectors to proactively and systematically advance health equity for Black Americans across the USA.

Better Estimation of Spontaneous Preterm Birth Prediction Performance through Improved Gestational Age Dating.

The clinical management of pregnancy and spontaneous preterm birth (sPTB) relies on estimates of gestational age (GA). Our objective was to evaluate the effect of GA dating uncertainty on the observed performance of a validated proteomic biomarker risk predictor, and then to test the generalizability of that effect in a broader range of GA at blood draw. In a secondary analysis of a prospective clinical trial (PAPR; NCT01371019), we compared two GA dating categories: both ultrasound and dating by last menstrual period (LMP) (all subjects) and excluding dating by LMP (excluding LMP). The risk predictor's performance was observed at the validated risk predictor threshold both in weeks 191/7-206/7 and extended to weeks 180/7-206/7. Strict blinding and independent statistical analyses were employed. The validated biomarker risk predictor showed greater observed sensitivity of 88% at 75% specificity (increases of 17% and 1%) in more reliably dated (excluding-LMP) subjects, relative to all subjects. Excluding dating by LMP significantly improved the sensitivity in weeks 191/7-206/7. In the broader blood draw window, the previously validated risk predictor threshold significantly stratified higher and lower risk of sPTB, and the risk predictor again showed significantly greater observed sensitivity in excluding-LMP subjects. These findings have implications for testing the performance of models aimed at predicting PTB.

Clinical and economic evaluation of a proteomic biomarker preterm birth risk predictor: cost-effectiveness modeling of prenatal interventions applied to predicted higher-risk pregnancies within a large and diverse cohort.

OBJECTIVES: Preterm birth occurs in more than 10% of U.S. births and is the leading cause of U.S. neonatal deaths, with estimated annual costs exceeding $25 billion USD. Using real-world data, we modeled the potential clinical and economic utility of a prematurity-reduction program comprising screening in a racially and ethnically diverse population with a validated proteomic biomarker risk predictor, followed by case management with or without pharmacological treatment. METHODS: The ACCORDANT microsimulation model used individual patient data from a prespecified, randomly selected sub-cohort (N = 847) of a multicenter, observational study of U.S. subjects receiving standard obstetric care with masked risk predictor assessment (TREETOP; NCT02787213). All subjects were included in three arms across 500 simulated trials: standard of care (SoC, control); risk predictor/case management comprising increased outreach, education and specialist care (RP-CM, active); and multimodal management (risk predictor/case management with pharmacological treatment) (RP-MM, active). In the active arms, only subjects stratified as higher risk by the predictor were modeled as receiving the intervention, whereas lower-risk subjects received standard care. Higher-risk subjects' gestational ages at birth were shifted based on published efficacies, and dependent outcomes, calibrated using national datasets, were changed accordingly. Subjects otherwise retained their original TREETOP outcomes. Arms were compared using survival analysis for neonatal and maternal hospital length of stay, bootstrap intervals for neonatal cost, and Fisher's exact test for neonatal morbidity/mortality (significance, p < .05). RESULTS: The model predicted improvements for all outcomes. RP-CM decreased neonatal and maternal hospital stay by 19% (p = .029) and 8.5% (p = .001), respectively; neonatal costs' point estimate by 16% (p = .098); and moderate-to-severe neonatal morbidity/mortality by 29% (p = .025). RP-MM strengthened observed reductions and significance. Point estimates of benefit did not differ by race/ethnicity. CONCLUSIONS: Modeled evaluation of a biomarker-based test-and-treat strategy in a diverse population predicts clinically and economically meaningful improvements in neonatal and maternal outcomes.

Preterm birth, defined as delivery before 37 weeks' gestation, is the leading cause of illness and death in newborns. In the United States, more than 10% of infants are born prematurely, and this rate is substantially higher in lower-income, inner-city and Black populations. Prematurity associates with greatly increased risk of short- and long-term medical complications and can generate significant costs throughout the lives of affected children. Annual U.S. health care costs to manage short- and long-term prematurity complications are estimated to exceed $25 billion.Clinical interventions, including case management (increased patient outreach, education and specialist care), pharmacological treatment and their combination can provide benefit to pregnancies at higher risk for preterm birth. Early and sensitive risk detection, however, remains a challenge.We have developed and validated a proteomic biomarker risk predictor for early identification of pregnancies at increased risk of preterm birth. The ACCORDANT study modeled treatments with real-world patient data from a racially and ethnically diverse U.S. population to compare the benefits of risk predictor testing plus clinical intervention for higher-risk pregnancies versus no testing and standard care. Measured outcomes included neonatal and maternal length of hospital stay, associated costs and neonatal morbidity and mortality. The model projected improved outcomes and reduced costs across all subjects, including ethnic and racial minority populations, when predicted higher-risk pregnancies were treated using case management with or without pharmacological treatment. The biomarker risk predictor shows high potential to be a clinically important component of risk stratification for pregnant women, leading to tangible gains in reducing the impact of preterm birth.

Severe acute respiratory syndrome coronavirus 2: a canary in the coal mine for public safety net hospitals.

BACKGROUND: The coronavirus disease 2019 pandemic has exposed disproportionate health inequities among underserved populations, including refugees. Public safety net healthcare systems play a critical role in facilitating access to care for refugees and informing coordinated public health prevention and mitigation efforts during a pandemic. OBJECTIVE: This study aimed to evaluate the prevalence ratios of severe acute respiratory syndrome coronavirus 2 infection between refugee women and nonrefugee parturient patients admitted to the hospital for delivery. Here, we suspected that the burden of infection was disproportionately distributed across refugee communities that may act as sentinels for community outbreaks. STUDY DESIGN: A cross-sectional study was conducted examining parturient women admitted to the maternity unit between May 6, 2020, and July 22, 2020, when universal testing for severe acute respiratory syndrome coronavirus 2 was first employed. Risk factors for severe acute respiratory syndrome 2 positivity were ascertained, disaggregated by refugee status, and other clinical and sociodemographic variables examined. Prevalence ratios were calculated and comparisons made to county-level community prevalence over the same period. RESULTS: The positive test percentage at the county-level during this study period was 21.6%. Of 350 women admitted to the hospital for delivery, 33 (9.4%) tested positive for severe acute respiratory syndrome 2. When refugee status was determined, 45 women (12.8%) were identified as refugees. Of the 45 refugee women, 8 (17.8%) tested positive for severe acute respiratory syndrome 2 compared with 25 nonrefugee patients (8.19%) who tested positive for severe acute respiratory syndrome 2 (prevalence ratio, 2.16; 95% confidence interval, 1.04-4.51). In addition, 7 of the refugee women who tested positive for severe acute respiratory syndrome coronavirus 2 were from Central Africa. CONCLUSION: The severe acute respiratory syndrome coronavirus 2 outbreak has disproportionately affected refugee populations. This study highlighted the utility of universal screening in mounting a rapid response to an evolving pandemic and how we can better serve refugee communities. Focused response may help achieve more equitable care related to severe acute respiratory syndrome 2 among vulnerable communities. The identification of such populations may help mitigate the spread of the disease and facilitate a timely, culturally, and linguistically enhanced public health response.

Transient tachypnea of the newborn: is labor prior to cesarean delivery protective?

Transient tachypnea of the newborn (TTN) is a common respiratory problem in newborns. This study aims to determine if cesarean delivery (CD) is a risk factor for TTN, and if labor prior to CD decreases this risk. A linked data set consisting of Arizona birth certificates (1994 to 1998) and infants enrolled in a high-risk perinatal program provided 800 TTN cases and 800 controls, stratified by year. The relationships of CD and labor to TTN were examined using logistic regression. CD was associated with an increased risk of TTN, whether it was accompanied by labor (odds ratio [OR] 2.68; 95% confidence interval [CI] 1.62 to 4.45) or not accompanied by labor (OR 2.88; 95% CI 2.01 to 4.13), even after adjusting for confounding variables. Labor did not affect the development of TTN, nor did it modify the association of CD with increased risk for TTN. CD is a risk factor for TTN. Labor prior to CD is not protective for TTN.

Performance of a proteomic preterm delivery predictor in a large independent prospective cohort.

BACKGROUND: Preterm birth remains a common and devastating complication of pregnancy. There remains a need for effective and accurate screening methods for preterm birth. Using a proteomic approach, we previously discovered and validated (Proteomic Assessment of Preterm Risk study, NCT01371019) a preterm birth predictor comprising a ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin. OBJECTIVE: To determine the performance of the ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin to predict both spontaneous and medically indicated very preterm births, in an independent cohort distinct from the one in which it was developed. STUDY DESIGN: This was a prospective observational study (Multicenter Assessment of a Spontaneous Preterm Birth Risk Predictor, NCT02787213) at 18 sites in the United States. Women had blood drawn at 170/7 to 216/7 weeks' gestation. For confirmation, we planned to analyze a randomly selected subgroup of women having blood drawn between 191/7 and 206/7 weeks' gestation, with the results of the remaining study participants blinded for future validation studies. Serum from participants was analyzed by mass spectrometry. Neonatal morbidity and mortality were analyzed using a composite score by a method from the PREGNANT trial (NCT00615550, Hassan et al). Scores of 0-3 reflect increasing numbers of morbidities or length of neonatal intensive care unit stay, and 4 represents perinatal mortality. RESULTS: A total of 5011 women were enrolled, with 847 included in this planned substudy analysis. There were 9 preterm birth cases at <320/7 weeks' gestation and 838 noncases at ≥320/7 weeks' gestation; 21 of 847 infants had neonatal composite morbidity and mortality index scores of ≥3, and 4 of 21 had a score of 4. The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio was substantially higher in both preterm births at <320/7 weeks' gestation and there were more severe neonatal outcomes. The ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin ratio was significantly predictive of birth at <320/7 weeks' gestation (area under the receiver operating characteristic curve, 0.71; 95% confidence interval, 0.55-0.87; P=.016). Stratification by body mass index, optimized in the previous validation study (22

Knowledge and attitudes regarding preconception care in a predominantly low-income Mexican American population.

OBJECTIVE: The objective of the study was to determine knowledge and attitudes regarding preconception care in a low-income Mexican American population. STUDY DESIGN: This was a cross-sectional survey of 305 reproductive-age women at an urban public hospital. RESULTS: The sample was mostly Hispanic (88%) and pregnant (68%); 35% had not completed high school. Eighty-nine percent agreed that improving preconception health benefits pregnancy. Seventy-seven percent expressed some interest in preconception health care with the obstetrics gynecology office at the preferred location. The average knowledge of preconception care score was 76% (higher score more favorable). Areas of higher knowledge included the effects on pregnancy of folic acid; alcohol use; substance use; and verbal, physical, and sexual abuse; lower knowledge was found for the effects of cat litter and fish products. CONCLUSION: There was interest in preconception education and agreement that preconception health has a positive effect on pregnancy. Fewer respondents agreed that it had a good effect than a suburban sample in the same region (89% vs 98%).

Nulliparous term singleton vertex cesarean delivery rates: institutional and individual level predictors.

OBJECTIVE: This study was undertaken to determine individual and institutional level variables predictive of variations in nulliparous term singleton vertex cesarean delivery rates. STUDY DESIGN: Retrospective cohort study of 28,863 nulliparous term singleton vertex births at 40 Arizona hospitals. RESULTS: The average nulliparous term singleton vertex cesarean delivery rate was 22.0%, the lowest hospital rate was 10.3%, high, 34.2%. The following individual level variables increased the nulliparous term singleton vertex cesarean delivery rate in a multivariable model: increased mother's age, African American race, increased birthweight, labor induction, and the presence of medical conditions such as diabetes and hypertension. Of the institutional variables, after adjustment, the highest level of nursery or a higher percentage of government-paid births was associated with lower risks, whereas delivery at a hospital with the lowest level of care or with an obstetric and gynecology residency was associated with an increased risk of cesarean delivery. CONCLUSION: Substantial variations in nulliparous term singleton vertex cesarean delivery rates were seen in this comparative analysis of 40 hospitals.

The clinical content of preconception care: an overview and preparation of this supplement.

In June 2005, the Select Panel on Preconception Care established implementation workgroups in 5 areas (clinical, public health, consumer, policy and finance, and research and surveillance) to develop strategies for the implementation of the Centers for Disease Control and Prevention recommendations on preconception health and healthcare. In June 2006, members of the clinical workgroup asked the following questions: what are the clinical components of preconception care? What is the evidence for inclusion of each component in clinical activities? What health promotion package should be delivered as part of preconception care? Over the next 2 years, the 29 members of the clinical workgroup and > 30 expert consultants reviewed in depth > 80 topics that make up the content of the articles that are contained in this supplement. Topics were selected on the basis of the effect of preconception care on the health of the mother and/or infant, prevalence, and detectability. For each topic, the workgroup assigned a score for the strength of the evidence that supported its inclusion in preconception care and assigned a strength of the recommendation. This article summarizes the methods that were used to select and review each topic and provides a summary table of the recommendations.

The clinical content of preconception care: care of psychosocial stressors.

In the period before conceiving, many women are under considerable psychosocial stress, which may affect their ability to conceive and to carry a pregnancy successfully to term. Thus, health care providers who interact with women in the preconception and interconception period should ask their patients about possible psychosocial risks. It is no longer sufficient to wait until the woman mentions a problem or seeks advice; the provider must be proactive, because many women do not realize the potential impact of stressors on their pregnancy outcomes nor are they always aware that their provider is interested in their psychosocial as well as their physical health. An income that puts women below or near the federal poverty level is one such stress. If a woman's economic situation can be improved before the pregnancy, she is more likely to be healthy after conception, because increased income can reduce financial stress, improve food security, and improve well-being in other ways. Therefore, all women should be asked about their economic status and those who appear to be struggling financially should be referred to an agency that can check their eligibility for various types of financial assistance. Many women of childbearing age have difficulty accessing the primary care services needed for preconception care. Usually this is due to lack of insurance, but it may also be caused by living in an area with an insufficient number of providers. Certainly all women who are uninsured, and possible many who are on Medicaid and have difficulty finding providers who will accept Medicaid, have access problems. All women should be asked about their health insurance coverage and their usual source of care. If they do not have health insurance, they should be referred to an agency that can determine their eligibility. If they do not have a usual source of care, one should be established that will accept their insurance coverage or provide care free of charge or on a sliding fee basis. Intimate partner violence, sexual violence outside of an intimate relationship (usually rape), and maltreatment (abuse or neglect) as a child or adolescent place a woman at elevated risk during a pregnancy, as well as having possible adverse impacts on the fetus, the infant, and the child. Studies show that women believe it is appropriate for health care providers to ask about interpersonal violence, but that they will not report it spontaneously. Therefore, screening for ongoing and historical interpersonal violence, sexual violence, and child maltreatment should be incorporated into routine care by all health care providers.

The clinical content of preconception care: reproductive history.

A history of previous birth of a low birthweight infant, previous cesarean sections, multiple previous spontaneous abortions, prior stillbirth, or uterine anomaly identifies women at increased risk for recurrent abortion, preterm birth, or stillbirth. We review the evidence for the potential benefit of reproductive history in identifying strategies for evaluation and treatment to prevent recurrent adverse pregnancy outcome. We offer evidence-based recommendations for management of women with these histories.

Where is the "W"oman in MCH?

Scientific evidence indicates that improving a woman's health before pregnancy will improve pregnancy outcomes. However, for many years, our efforts have focused primarily on prenatal care and on caring for infants after birth. The concept of preconception care has been identified repeatedly as a priority for improving maternal and infant health. Preconception care is not something new that is being added to the already overburdened healthcare provider, but it is a part of routine primary care for women of reproductive age. Many opportunities exist for preconception intervention, and much of preconception care involves merely the provider reframing his or her thinking, counseling, and decisions in light of the reproductive plans and sexual and contraceptive practices of the patient. With existing scientific evidence that improving the health of "W"omen will improve the health of mothers and children, we must focus on improving the health of "W"omen before pregnancy and put the "W" in Maternal and Child Health.

Healthier women, healthier reproductive outcomes: recommendations for the routine care of all women of reproductive age.

By addressing the reproductive intentions and contraceptive practices and needs of every patient, providers may be able to decrease women's chances of experiencing unintended pregnancies and support women in achieving planned and well-timed pregnancies. By addressing the health promotion needs of every patient and examining and addressing her health profile for reproductive risks, irrespective of her desires for pregnancy, it is likely that more women will enter pregnancy with high levels of preconception wellness and that healthier women and healthier pregnancies and infants will result. The importance of the integration of reproductive planning and health promotion into women's routine healthcare is further emphasized when the potentially far-reaching effects of reproductive outcomes (such as unintended pregnancies, adverse pregnancy outcomes, pregnancy complications, and sexually transmitted infections) on women's health, well-being, and life circumstances are considered.