Preterm birth, birthweight, and subsequent risk for depression.

An individual's birthweight, a marker of in utero exposures, was recently associated with certain psychiatric conditions. However, studies investigating the relationship between an individual's preterm birth status and/or birthweight and risk for depression during adulthood are sparse; we used data from the Women's Health Initiative (WHI) to investigate these potential associations. At study entry, 86,925 postmenopausal women reported their birthweight by category (<6 lbs., 6-7 lbs. 15 oz., 8-9 lbs. 15 oz., or ≥10 lbs.) and their preterm birth status (full-term or ≥4 weeks premature). Women also completed the Burnham screen for depression and were asked to self-report if: (a) they had ever been diagnosed with depression, or (b) if they were taking antidepressant medications. Linear and logistic regression models were used to estimate unadjusted and adjusted effect estimates. Compared to those born weighing between 6 and 7 lbs. 15 oz., individuals born weighing <6 lbs. (ßadj = 0.007, P < 0.0001) and ≥10 lbs. (ßadj = 0.006, P = 0.02) had significantly higher Burnam scores. Individuals born weighing <6 lbs. were also more likely to have depression (adjOR 1.21, 95% CI 1.11-1.31). Individuals born preterm were also more likely to have depression (adjOR 1.18, 95% CI 1.02-1.35); while attenuated, this association remained in analyses limited to only those reportedly born weighing <6 lbs. Our research supports the role of early life exposures on health risks across the life course. Individuals born at low or high birthweights and those born preterm may benefit from early evaluation and long-term follow-up for the prevention and treatment of mental health outcomes.

The co-occurrence and cumulative prevalence of hypertension, rheumatoid arthritis, and hypothyroidism in preterm-born women in the Women's Health Initiative.

Emerging evidence suggests that preterm-born individuals (<37 weeks gestation) are at increased risk of developing chronic health conditions in adulthood. This study compared the prevalence, co-occurrence, and cumulative prevalence of three female predominant chronic health conditions - hypertension, rheumatoid arthritis [RA], and hypothyroidism - alone and concurrently. Of 82,514 U.S. women aged 50-79 years enrolled in the Women's Health Initiative, 2,303 self-reported being born preterm. Logistic regression was used to analyze the prevalence of each condition at enrollment with birth status (preterm, full term). Multinomial logistic regression models analyzed the association between birth status and each condition alone and concurrently. Outcome variables using the 3 conditions were created to give 8 categories ranging from no disease, each condition alone, two-way combinations, to having all three conditions. The models adjusted for age, race/ethnicity, and sociodemographic, lifestyle, and other health-related risk factors. Women born preterm were significantly more likely to have any one or a combination of the selected conditions. In fully adjusted models for individual conditions, the adjusted odds ratios (aORs) were 1.14 (95% CI, 1.04, 1.26) for hypertension, 1.28 (1.12, 1.47) for RA, and 1.12 (1.01, 1.24) for hypothyroidism. Hypothyroidism and RA were the strongest coexisting conditions [aOR 1.69, 95% CI (1.14, 2.51)], followed by hypertension and RA [aOR 1.48, 95% CI (1.20, 1.82)]. The aOR for all three conditions was 1.69 (1.22, 2.35). Perinatal history is pertinent across the life course. Preventive measures and early identification of risk factors and disease in preterm-born individuals are essential to mitigating adverse health outcomes in adulthood.

Association of Preterm Birth With Prevalent and Incident Hypertension, Early-Onset Hypertension, and Cardiovascular Disease in the Women's Health Initiative.

Increasing evidence suggests preterm birth is a risk factor for hypertension and cardiovascular disease (CVD) in adulthood. Whether there is effect modification by hypertension on CVD risk is unknown. To investigate the associations between preterm birth, hypertension, and incident CVD, we identified 2,303 women aged 50 to 79 years who self-reported being born preterm from the Women's Health Initiative. Using multivariable logistic regression, prevalent hypertension at enrollment, age at hypertension diagnosis, and antihypertensive medication use were compared by birth status (preterm, full-term). Risk of incident hypertension, coronary heart disease, and CVD were analyzed using multivariable Cox proportional-hazard models. Both models adjusted for age, race/ethnicity, education, smoking, physical activity, body mass index, and diabetes mellitus. Significant associations were found between preterm birth and prevalent hypertension (37% vs 33.1%; adjusted odds ratio 1.26 [95% confidence interval (CI) 1.15 to 1.28] p = <0.0001), early-onset hypertension (<50 years) (14.7% vs 11.7%; adjusted odds ratio 1.31, 95% CI 1.15 to 1.48, p = <0.0001), and incident hypertension (53.2% vs 51%; ajusted hazard ratio 1.10, 95% CI 1.03 to 1.19, p = 0.008). Preterm-born women reported taking more antihypertensive medications (2.9% vs 2.6%, p = 0.04). Preterm birth had a nonsignificant association with CVD risk, but when stratified by prevalent hypertension, women born preterm without hypertension had elevated CVD risk compared with women born full-term without prevalent hypertension. Women with prevalent hypertension, preterm and full-term, had similar magnitudes of elevations in CVD risk. In conclusion, preterm birth increases the risk of hypertension and coronary heart disease. With 10% of the population born preterm, birth history should be assessed as a CVD risk factor.

Differential Susceptibility: An Explanation for Variability in Life Course Health and Developmental Outcomes.

Differential susceptibility theory posits that some individuals, with specific characteristics, are more, or less susceptible than others, to both adverse and beneficial environmental influences. It offers a perspective for understanding the directional trajectories across the life course affected by daily context and individual characteristics, in order to identify influential components. The aim of this article is to describe differential susceptibility theory, critically evaluate research findings in which the theory is tested, and consider implications of differential susceptibility theory as a theoretical framework for nursing science. Preterm birth trajectories and outcomes research are used as a lens for this examination.

A test of differential susceptibility in behavior trajectories of preterm infants from preschool to adulthood.

Preterm birth predisposes children to internalizing and externalizing behaviors that may persist into adolescence resulting in adult mental health conditions. Social and caregiving contexts, particularly for vulnerable infants born preterm, influence long-term outcomes, but mechanisms are not clearly understood. Healthcare teams caring for those born preterm face difficulty predicting who will be most affected by risk, who will most benefit, and the optimal timing of intervention. Differential susceptibility theory offers an alternative to the traditional risk-only assessments and theories by positing that individuals may be more, or less, susceptible to environmental influences. A sample of preterm- and term-born infants were followed from birth to 23 years of age. Mixed model repeated measures analyses of internalizing and externalizing behaviors were utilized for the comparison groups (N = 214; observations = 1070). Environmental contexts were indexed as proximal protection (low, moderate, high) and medical risk (low, moderate, high). Personal characteristic covariates of sex, race, socioeconomic status, and cognition were modeled. Internalizing behavior trajectories varied significantly over time. Early proximal protective environments conferred a sustained positive influence on behaviors. There is partial support for differential susceptibility theory suggesting that prematurity, as a malleability characteristic enables absorption of both the positive and negative influences of the environment, with greater intensity that those without malleability. The current analyses suggest lasting effects of the preschool age proximal environment on internalizing and externalizing behaviors in young adulthood for those born preterm. Understanding these nuances may aid healthcare professionals in the promotion and timing of interventions to support the child and family. The current manuscript reflects ongoing analyses of longitudinal data. No patient or public contribution to the analyses were required for testing the differential susceptibility theory. The authors would solicit patient or public contribution when implementing practice or policy changes based on the results.

A new cardiovascular disease risk factor for young adults: Preterm birth.

ABSTRACT: Adults born preterm (birth <37 weeks' gestation) have a two-fold increased risk of early cardiovascular mortality. With 10% of the U.S. population born prematurely and perinatal advancements dramatically improving survival rates, millions of survivors are now reaching adulthood. This phenomenon has introduced a whole new population of individuals with a history of preterm birth. Although the prevailing notion has been that preterm birth is a condition confined only to infancy and early childhood, we now know preterm birth is a risk for lifelong chronic health conditions. Despite almost a decade of epidemiological evidence showing increased cardiovascular risk for those born preterm, this has not yet been translated into clinical practice. As a result, clinicians are caring for adults born prematurely without screening and treatment guidelines for this at-risk population and few inquire about birth history during clinical encounters. This brief report presents growing evidence about disrupted cardiogenesis and consequential structural and functional modifications. By asking the question "Were you born preterm?," nurse practitioners can take the first step of increasing their awareness of this at-risk population and mitigate adverse cardiovascular outcomes by using preterm birth as a risk factor when determining health promotion and treatment decisions.

A Protocol to Assess Adult Outcomes at 30 Years Following Preterm Birth.

BACKGROUND: Among the most intense adversity experiences for infants is premature birth. Early birth marks the beginning of a life course that broadly affects families, healthcare, education, social systems, and the survivors themselves. For many, the transition to adulthood is challenging and often hampered by cognitive, physical and mental health, and motor and independence difficulties. OBJECTIVES: The aim of this study was to share a comprehensive protocol of a 10th follow-up study of premature infants in their 30s. The protocol accounts for stress during the neonatal period, the cumulative context (risk and protection) of development, biological and epigenetic mechanisms, and individual resilience. METHODS: The prospective, five-group longitudinal design includes 215 term-born and preterm-born individuals with various neonatal morbidities at ages 30-35 years. Adult outcomes include health, adaptive, executive function, work, and social competence. Novel measures are four system indicators of allostatic load (AL) and epigenetics. Contextual measures include socioeconomic risk and individual resilience. All measures were selected based on coherence with constructs of the scientific aims, strong psychometrics, continuity for repeated measures, and minimal subject burden. Objective assessments include body composition imaging, exercise testing, blood and saliva collection, and actigraphy. The two-phase protocol takes approximately 8 hours. DISCUSSION: After an 11-month COVID-19 pause, participant response has been strong. As of May 2022, 75 participants have completed the full protocol, and 99 have consented to participate. When socioeconomic risk is controlled, we hypothesize that life course trajectories in physical and psychological health, adaptive function, and executive function will differ between term and preterm neonatal morbidity groups. AL will vary across groups and contribute to outcomes. We expect proximal protection and resilience to mediate the cumulative medical and socioeconomic risk and AL. Epigenome-wide DNA methylation, with estimates of age acceleration, will be examined across groups and explored in longitudinal associations with medical risk, socioeconomic status, and protection. To our knowledge, this is the only U.S. study of premature infants aged 30-35 years. With millions of preterm-born individuals reaching adulthood, the protocol incorporates molecular and genetic biomarkers in a life course developmental examination to inform the timing and content of interventions.

Allostatic Load and Mortality: A Systematic Review and Meta-Analysis.

INTRODUCTION: Allostatic load, a measure of stress-related physiologic dysregulation, is associated with numerous mortality risk factors. This systematic review and meta-analysis examines the relationship between high allostatic load (i.e., increased dysregulation versus low dysregulation) and mortality (cardiovascular disease and all-cause mortality). METHODS: Systematic searches of 2 databases conducted in May 2021 yielded 336 unique records; 17 eligible studies (2001-2020) were included. RESULTS: High allostatic load was associated with increased risk of all-cause mortality across all the 17 individual studies (hazard ratio=1.08-2.75) and in 6 of 8 studies examining cardiovascular disease mortality (hazard ratio=1.19-3.06). Meta-analyses indicated that high allostatic load was associated with increased risk of all-cause mortality, overall (hazard ratio=1.22, 95% CI=1.14, 1.30, n=10) and across subgroups (hazard ratio=1.11-1.41), and similarly for cardiovascular disease mortality (hazard ratio=1.31, 95% CI=1.10, 1.57, n=6). Although studies were generally of good quality (n=13), heterogeneity was high in most pooled estimates (I2>90%). DISCUSSION: In this review of relatively good-quality studies, high allostatic load was associated with an increased mortality risk of 22% for all-cause mortality and 31% for cardiovascular disease mortality. Thus, allostatic load is an emerging and potent modifiable risk factor for all-cause and cardiovascular disease mortality that shows promise as a prognostic indicator for mortality. The heterogeneity in allostatic load assessment across studies highlights the need for standardized measurement. The findings underscore the importance of allostatic load's dynamic nature, which may be especially relevant for mitigating mortality risk in younger adults. Because older adults are oversampled, future allostatic load research should prioritize younger adults and longitudinal monitoring and specific cardiovascular disease mortality risk associations and individualize behavioral and lifestyle targets for reducing allostatic load.

Molding influences of prematurity: Interviews with adults born preterm.

BACKGROUND: Tremendous medical advancements over the last several decades have supported the survival of younger and sicker newborns. Substantial quantitative research exists about health and developmental outcomes following preterm birth, however, limited published literature has explored what this experience means to the survivors. AIM: The purpose was to describe, interpret and understand how adults born preterm perceive prematurity to have affected their lives. STUDY DESIGN: Qualitative thematic analysis. METHODS: Semi-structured interviews were conducted with 33 adults born preterm from the RHODE Study, a longitudinal preterm birth cohort. A cross-section of participants with high and low early life medical and environmental risk was interviewed. Data were analyzed using a constructionist method of latent theme analysis. RESULTS: From the data, 3 themes were identified: 1) My parents call me their miracle, 2) It's not a big deal, I'm the same as everyone else, 3) I've overcome a lot. Themes represent a continuum of experience, from positive to neutral to negative. Common life experiences of family, education, friends, and health are subthemes that help to illuminate how participants assign meaning to their prematurity. Meaning was linked to how typical or not participants perceive their health, learning and friends compared to peers. CONCLUSION: Perceptions about prematurity and adversity are influenced by the ways parents and families represent prematurity in shared stories and actions. These findings should inform future research with adult survivors of prematurity. Participants identified ongoing need for support and advocacy, particularly from healthcare and education communities.

Mathematical performance in childhood and early adult outcomes after very preterm birth: an individual participant data meta-analysis.

AIM: To investigate the strength of the independent associations of mathematics performance in children born very preterm (<32wks' gestation or <1500g birthweight) with attending postsecondary education and their current employment status in young adulthood. METHOD: We harmonized data from six very preterm birth cohorts from five different countries and carried out one-stage individual participant data meta-analyses (n=954, 52% female) using mixed effects logistic regression models. Mathematics scores at 8 to 11 years of age were z-standardized using contemporary cohort-specific controls. Outcomes included any postsecondary education, and employment/education status in young adulthood. All models were adjusted for year of birth, gestational age, sex, maternal education, and IQ in childhood. RESULTS: Higher mathematics performance in childhood was independently associated with having attended any postsecondary education (odds ratio [OR] per SD increase in mathematics z-score: 1.36 [95% confidence interval {CI}: 1.03, 1.79]) but not with current employment/education status (OR 1.14 per SD increase [95% CI: 0.87, 1.48]). INTERPRETATION: Among populations born very preterm, childhood mathematics performance is important for adult educational attainment, but not for employment status.

Determinants of Neonatal Readmission in Healthy Term Infants: Results from a Nested Case-Control Study.

OBJECTIVE: The aim of this study was to estimate the incidence and identify the factors associated with neonatal readmission among healthy term infants. STUDY DESIGN: A nested case-control study with matching was conducted at a large level III perinatal hospital with approximately 8,700 deliveries each year. Each case infant (n = 130) was matched to two control infants (n = 260) on the case infant's date of birth (±7 days) and the mother's maternal age (<20 years, 20-29, 30-39, and >39 years). All infants were selected from a cohort of eligible term, healthy, in-state infants admitted to the newborn unit postdelivery from January 1, 2016 to May 8, 2017. Data were analyzed using hierarchical conditional logistic regression. RESULTS: The incidence of neonatal readmission was 2.2%, and all readmissions occurred within 8.6 days of birth. Earlier gestational age (37 weeks; odds ratio [OR]: 4.11, 95% confidence interval [CI]: 1.79-9.45; 38 weeks OR: 1.29, CI 0.60-2.75; [ref] 39 weeks), jaundice on day two of life (OR: 2.45; CI: 1.40-4.30), maternal group B streptococcus chemoprophylaxis (OR: 2.55; CI: 1.23-5.28 [Ref N/A]) were associated with readmission. Delivery by cesarean section (OR: 0.31, CI: 0.12-0.79) and each milliliter of formula [first three days] (OR: 0.96; CI: 0.993-0.999) were protective. CONCLUSION: Neonatal readmission in healthy term infants may potentially be reduced with identification of modifiable determinants of readmission prior to discharge. Policies to capture the true incidence of neonatal readmissions should include admissions to hospitals other than the birth hospital.

Late adolescent & young adult functioning and participation outcomes after prematurity.

There has been an increased emphasis on optimizing health, developmental, and behavioral outcomes over the life course after prematurity. An important framework for examining adolescent and young adult outcomes is the International Classification of Functioning Disability and Health Children (ICF) developed by the World Health Organization (WHO) in 2001 and expanded to children and youth (ICF-CY) under age 19 years in 2007. The ICF and the ICF-CY can be used as a statistical tool in population studies, a research tool to measure outcomes, quality of life, and environmental factors, a clinical tool for outcomes of rehabilitation and vocation training, and as a social policy-educational tool to raise awareness and promote social action for equity. In this review we describe how functioning and participation can help inform transitional outcomes at age 17 years and emerging adult independence at 23 years. We highlight outcomes in adolescence and adulthood of former preterm infants using the ICF domains of functioning and participation. We include current standardized adaptive assessments (Vineland Adaptive Behavior Scales-3rd Edition; VABS3) and Adaptive Behavior Assessment Scale-3; ABAS3) that measure self-care daily living skills, applied learning, and social functioning. We also emphasize that participation involves life activities of higher education attainment, completing vocational training, experiencing employment, living independently, and relationship experiences with partners as well as family formation.

Prematurity and cardiovascular risk at early adulthood.

BACKGROUND: Theories of early stress exposure and allostatic load offer a lifespan perspective to adult health after prematurity based on these early stressors affecting endocrine and metabolic systems. In this study, we examine cardiovascular and metabolic risk by comparing two groups of preterm infants who experienced a full spectrum of neonatal illness and a term-born group at age 23. METHODS: Of the 215 infants recruited at birth, 84% participated at age 23. The cohort included 45 full-term (FT), 24 healthy preterm (HPT), and 111 sick preterm (SPT) infants. Socio-economic status was equivalent across groups. Cardiovascular and metabolic outcomes were as follows: blood pressure (BP), fasting glucose and lipid profiles, weight, waist-hip ratio (WHR), and body mass index (BMI). Clinical and subclinical ranges were compared across neonatal groups and gender. RESULTS: At age 23, the HPT and SPT groups had higher systolic BP compared with the FT group. The SPT group had lower weight compared with the FT and HPT groups. No group differences were found on diastolic BP, glucose, total cholesterol, high-density lipids, low-density lipids, triglycerides, BMI, or WHR. Preterm males had more systolic hypertension and low high-density lipids than FT males. Former preterm males and females had high WHR ratios and BMI at 23 years. Subclinical prehypertensive rates were highest for the HPT female group, followed by the SPT females. Only one (4.2%) HPT adult male was clinically diabetic. CONCLUSIONS: As young adults, HPT and SPT infants had early indicators of cardiovascular risk but no indicators of metabolic risk. There is utility in using clinical and subclinical ranges to identify early cardiovascular risk in early adulthood.

Development of growth equations from longitudinal studies of body weight and height in the full term and preterm neonate: From birth to four years postnatal age.

Physiologically based pharmacokinetic (PBPK) models are developed from compound-independent information to describe important anatomical and physiological characteristics of an individual or population of interest. Modeling pediatric populations is challenging because of the rapid changes that occur during growth, particularly in the first few weeks and months after birth. Neonates who are born premature pose several unique challenges in PBPK model development. To provide appropriate descriptions for body weight (BW) and height (Ht) for age and appropriate incremental gains in PBPK models of the developing preterm and full term neonate, anthropometric measurements collected longitudinally from 1,063 preterm and 158 full term neonates were combined with 2,872 cross-sectional measurements obtained from the NHANES 2007-2010 survey. Age-specific polynomial growth equations for BW and Ht were created for male and female neonates with corresponding gestational birth ages of 25, 28, 31, 34, and 40 weeks. Model-predicted weights at birth were within 20% of published fetal/neonatal reference standards. In comparison to full term neonates, postnatal gains in BW and Ht were slower in preterm subgroups, particularly in those born at earlier gestational ages. Catch up growth for BW in neonates born at 25, 28, 31, and 34 weeks gestational age was complete by 13, 8, 6, and 2 months of life (males) and by 10, 6, 5, and 2 months of life (females), respectively. The polynomial growth equations reported in this paper represent extrauterine growth in full term and preterm neonates and differ from the intrauterine growth standards that were developed for the healthy unborn fetus.

Theory and Theorizing in Nursing Science: Commentary from the Nursing Research Special Issue Editorial Team.

BACKGROUND: Articles from three landmark symposia on theory for nursing-published in Nursing Research in 1968-1969-served as a key underpinning for the development of nursing as an academic discipline. The current special issue on Theory and Theorizing in Nursing Science celebrates the 50th anniversary of publication of these seminal works in nursing theory. OBJECTIVE: The purpose of this commentary is to consider the future of nursing theory development in light of articles published in the anniversary issue. APPROACH: The Editorial Team for the special issue identified core questions about continued nursing theory development, as related to the nursing metaparadigm, practice theory, big data, and doctoral education. Using a dialogue format, the editors discussed these core questions. DISCUSSION: The classic nursing metaparadigm (health, person, environment, nursing) was viewed as a continuing unifying element for the discipline but is in need of revision in today's scientific and practice climates. Practice theory and precision healthcare jointly arise from an emphasis on individualization. Big data and the methods of e-science are challenging the assumptions on which nursing theory development was originally based. Doctoral education for nursing scholarship requires changes to ensure that tomorrow's scholars are prepared to steward the discipline by advancing (not reifying) past approaches to nursing theory. CONCLUSION: Ongoing reexamination of theory is needed to clarify the domain of nursing, guide nursing science and practice, and direct and communicate the unique and essential contributions of nursing science to the broader health research effort and of nursing to healthcare.

Trajectories of problem behaviors from 4 to 23 years in former preterm infants.

Premature infants have significant risk for later behavior problems. This study examined growth trajectories of three problem behaviors across five developmental age points from preschool to early adulthood in a well-characterized sample of premature infants. The effects of neonatal risk, gender, and socioeconomic context were modeled on these trajectories. The longitudinal sample was comprised of preterm infants (N = 160) with full variation of neonatal morbidity and birth weight (640-1950 grams). Trajectories of externalizing, internalizing and attention problem behaviors from 4 to 23 years, measured by the Child Behavior Checklist, were tested using latent growth curve modeling. The results indicate individual variation in the number of externalizing and internalizing problems over time. Externalizing problems were not significantly different for males and females, but male scores were consistently higher. Neonatal risk was significantly associated with higher internalizing problems at age 4, but was not predictive at school age and beyond. Attention problem scores increased from early preschool through adolescence for males, but females had little change over the same ages. SES was not predictive of any problem behavior trajectories and no significant two-way interactions were found. The results advance understanding of stability and change of three important problem behaviors through preschool, childhood and adolescence to young adulthood in prematurely born infants in order to inform clinicians about timely assessment and the refinement of effective interventions.

Long-Term Effects of Prematurity, Cumulative Medical Risk, and Proximal and Distal Social Forces on Individual Differences in Diurnal Cortisol at Young Adulthood.

This study examined the effects of prematurity, cumulative medical risk, and proximal and distal social forces on individual differences in the activity of the hypothalamic-pituitary-adrenal (HPA) axis in young adulthood. A prospective sample of 149 infants born healthy preterm (PT; n = 22), sick PT ( n = 93, medical illness, neurological illness, small for gestational age), and full term ( n = 34) was recruited from a Level III neonatal intensive care unit in southern New England between 1985 and 1989 and followed to age 23 years. Cumulative medical risk was indexed across seven assessment waves (spanning 17 years) using medical and neurological health status at birth, toddlerhood (ages 18 and 30 months), childhood (ages 4 and 8 years), and adolescence (ages 12 and 17 years). Distal risk included socioeconomic status (SES) at birth. Proximal social factors were indexed from assessments of the home environment and measures of child vulnerability and maternal self-esteem, involvement, and control style from birth, 4 years, 8 years, and 12 years. At age 23 years, five saliva samples were collected upon awakening, 45 min after waking, 4 hr after waking, 8 hr after waking, and bedtime (later assayed for cortisol). Results reveal effects of cumulative medical risk on the diurnal pattern of HPA axis activity, with moderating effects of SES and proximal social factors. Findings are discussed in terms of implications for contemporary theories related to developmental sensitivity and susceptibility to context and the developmental origins of health and disease theory.

Prematurity and perinatal adversity effects hypothalamic-pituitary-adrenal axis reactivity to social evaluative threat in adulthood.

This study examined the long-term effects of prematurity and perinatal adversity on individual differences in stress-related reactivity and regulation of the HPA axis. A prospective sample of 155 infants born preterm and healthy (n = 20), medical illness (n = 48), neurological illness (n = 26), and small for gestational age (n = 24) and full-term (n = 37) were recruited between 1985 and 1989. At age 23 years, multiple saliva samples were collected before and after participation in the Trier Social Stress Test and later assayed for cortisol. Results reveal that at age 23 years, infants born premature with neurological complications showed higher cortisol reactivity to social evaluative threat compared to either their full-term, small for gestation age, medically ill, or healthy preterm peers. Findings are discussed in terms of implications for contemporary theories that propose effects of early adversity on biological sensitivities and susceptibilities, which translate experience into developmental outcomes related to poor health and risk for disease.

Relationship Between a Sepsis Intervention Bundle and In-Hospital Mortality Among Hospitalized Patients: A Retrospective Analysis of Real-World Data.

BACKGROUND: Sepsis is a systemic response to infection that can lead to tissue damage, organ failure, and death. Efforts have been made to develop evidence-based intervention bundles to identify and manage sepsis early in the course of the disease to decrease sepsis-related morbidity and mortality. We evaluated the relationship between a minimally invasive sepsis intervention bundle and in-hospital mortality using robust methods for observational data. METHODS: We performed a retrospective cohort study at the University of California, San Francisco, Medical Center among adult patients discharged between January 1, 2012, and December 31, 2014, and who received a diagnosis of severe sepsis/septic shock (SS/SS). Sepsis intervention bundle elements included measurement of blood lactate; drawing of blood cultures before starting antibiotics; initiation of broad spectrum antibiotics within 3 hours of sepsis presentation in the emergency department or 1 hour of presentation on an inpatient unit; administration of intravenous fluid bolus if the patient was hypotensive or had a lactate level >4 mmol/L; and starting intravenous vasopressors if the patient remained hypotensive after fluid bolus administration. Poisson regression for a binary outcome variable was used to estimate an adjusted incidence-rate ratio (IRR) comparing mortality in groups defined by bundle compliance measured as a binary predictor, and to estimate an adjusted number needed to treat (NNT). RESULTS: Complete bundle compliance was associated with a 31% lower risk of mortality (adjusted IRR, 0.69, 95% confidence interval [CI], 0.53-0.91), adjusting for SS/SS presentation in the emergency department, SS/SS present on admission (POA), age, admission severity of illness and risk of mortality, Medicaid/Medicare payor status, immunocompromised host status, and congestive heart failure POA. The adjusted NNT to save one life was 15 (CI, 8-69). Other factors independently associated with mortality included SS/SS POA (adjusted IRR, 0.55; CI, 0.32-0.92) and increased age (adjusted IRR, 1.13 per 10-year increase in age; CI, 1.03-1.24). CONCLUSIONS: The University of California, San Francisco, sepsis bundle was associated with a decreased risk of in-hospital mortality across hospital units after robust control for confounders and risk adjustment. The adjusted NNT provides a reasonable and achievable goal to observe measureable improvements in outcomes for patients diagnosed with SS/SS.