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The racial disparity associated with preterm birth is a public health concern in the United States. The placenta is the principal metabolic, respiratory, and endocrine organ of the fetus and a key route by which environmental exposures are transmitted from mother to offspring. Available at every delivery, it may serve as a marker of differences in prenatal exposures that manifest differently by race. Recently, we described differences in placental pathology between African-American and White preterm births: the prevalence of chronic inflammation was higher among African-American women's placentas compared with those of White women. Similarly, racial differences have been shown in placental malperfusion and placental weight. Social determinants such as poverty and stress from discrimination have been implicated in racial disparities in preterm birth. To date, however, the underlying biological mechanisms, whether through inflammatory, oxidative stress, or other pathways involving epigenetic programming, remain largely unknown. The placenta, complemented by maternal and umbilical cord blood biomarkers, may provide important information on the perinatal environment that explains the origins of racial disparities in preterm birth rates and subsequent health outcomes. This article reviews existing literature and current research gaps. Opportunities are discussed for future placental research that may reveal novel mechanisms leading to the development of new approaches in the prevention and management of preterm birth and its outcomes.

BACKGROUND: Intrauterine growth restriction is often accompanied by placental vascular disease, of which histologic maternal vascular malperfusion is prominent. Maternal vascular malperfusion is characterized by accelerated villous maturation consistent with placental aging. Alpha klotho is an anti-aging protein produced by the placenta. We hypothesize that cord blood alpha klotho varies with maternal vascular malperfusion and small for gestational age infants through dysregulated angiogenesis. METHODS: Nested case-control study of 54 preterm infants (N=22 small for gestational age infants, 32 appropriate for gestational age infants, mean gestational age=33.7±2.7 weeks) and validation sample (N=39) from a longitudinal birth cohort at Prentice Women’s Hospital, Chicago, IL. Cord blood alpha klotho was measured via enzyme-linked immunoassay; concentrations were linked to multiplex data of cord blood angiogenic growth factors. RESULTS: Median cord blood alpha klotho was decreased in small for gestational age infants (1200 [859, 2083] pg/mL) versus controls (3193 [1703, 3963] pg/mL; p

A 33-year-old gravida 2, para 1 woman was noted to have early intrauterine growth restriction at 22 weeks gestation and subsequently developed severe pre-eclampsia. She delivered a 460 g male neonate at 28 weeks. The infant was managed on non-invasive ventilatory support and was gaining weight on enteral feeds for the first eight weeks of life, at which point he developed necrotizing enterocolitis. He then developed severe pulmonary hypertension that was refractory to maximal medical management. He died at 10 weeks of life due to hypoxemic respiratory and heart failure. Placental pathology revealed a constellation of findings consistent with maternal vascular malperfusion. Lung autopsy revealed muscularized and hypertrophied pulmonary arterioles consistent with severe pulmonary hypertension. Von Willebrand factor immunofluorescent staining of autopsy specimens suggest parallels in extent of endothelial injury. This case study illustrates our evolving knowledge of the fetal origins of neonatal lung diseases.

Prenatal stress exposure increases vulnerability to virtually all forms of psychopathology. Based on this robust evidence base, we propose a "Mental Health, Earlier" paradigm shift for prenatal stress research, which moves from the documentation of stress-related outcomes to their prevention, with a focus on infant neurodevelopmental indicators of vulnerability to subsequent mental health problems. Achieving this requires an expansive team science approach. As an exemplar, we introduce the Promoting Healthy Brain Project (PHBP), a randomized trial testing the impact of the Wellness-4-2 personalized prenatal stress-reduction intervention on stress-related alterations in infant neurodevelopmental trajectories in the first year of life. Wellness-4-2 utilizes bio-integrated stress monitoring for just-in-time adaptive intervention. We highlight unique challenges and opportunities this novel team science approach presents in synergizing expertise across predictive analytics, bioengineering, health information technology, prevention science, maternal-fetal medicine, neonatology, pediatrics, and neurodevelopmental science. We discuss how innovations across many areas of study facilitate this personalized preventive approach, using developmentally sensitive brain and behavioral methods to investigate whether altering children's adverse gestational exposures, i.e., maternal stress in the womb, can improve their mental health outlooks. In so doing, we seek to propel developmental SEED research towards preventive applications with the potential to reduce the pernicious effect of prenatal stress on neurodevelopment, mental health, and wellbeing.

Preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) have accelerated lung aging and poor long-term outcomes. Klotho is an antiaging protein that modulates oxidative stress, angiogenesis and fibrosis. Here we test the hypothesis that decreased cord Klotho levels in preterm infants predict increased BPD–PH risk and early Klotho supplementation prevents BPD-like phenotype and PH in rodents exposed to neonatal hyperoxia. In experiment 1, Klotho levels were measured in cord blood of preterm infants who were enrolled in a longitudinal cohort study. In experiment 2, using an experimental BPD–PH model, rat pups exposed to room air or hyperoxia (85% O2) were randomly assigned to receive every other day injections of recombinant Klotho or placebo. The effect of Klotho on lung structure, PH and cardiac function was assessed. As compared to controls, preterm infants with BPD or BPD–PH had decreased cord Klotho levels. Early Klotho supplementation in neonatal hyperoxia-exposed rodents preserved lung alveolar and vascular structure, attenuated PH, reduced pulmonary vascular remodeling and improved cardiac function. Together, these findings have important implications as they suggest that perinatal Klotho deficiency contributes to BPD–PH risk and strategies that preserve Klotho levels, may improve long-term cardiopulmonary outcomes in preterm infants.

Pulmonary hypertension (PH) is a common consequence of bronchopulmonary dysplasia (BPD) and remains a primary contributor to increased morbidity and mortality among preterm infants. Unfortunately, at the present time, there are no reliable early predictive markers for BPD-associated PH. Considering its health consequences, understanding in utero perturbations that lead to the development of BPD and BPD-associated PH and identifying early predictive markers is of utmost importance. As part of the discovery phase, we applied a multiplatform metabolomics approach consisting of untargeted and targeted methodologies to screen for metabolic perturbations in umbilical cord blood (UCB) plasma from preterm infants that did ( n = 21; cases) or did not ( n = 21; controls) develop subsequent PH. A total of 1,656 features were detected, of which 407 were annotated by metabolite structures. PH-associated metabolic perturbations were characterized by reductions in major choline-containing phospholipids, such as phosphatidylcholines and sphingomyelins, indicating altered lipid metabolism. The reduction in UCB abundances of major choline-containing phospholipids was confirmed in an independent validation cohort consisting of UCB plasmas from 10 cases and 10 controls matched for gestational age and BPD status. Subanalyses in the discovery cohort indicated that elevations in the oxylipins PGE1, PGE2, PGF2a, 9- and 13-HOTE, 9- and 13-HODE, and 9- and 13-KODE were positively associated with BPD presence and severity. This expansive evaluation of cord blood plasma identifies compounds reflecting dyslipidemia and suggests altered metabolite provision associated with metabolic immaturity that differentiate subjects, both by BPD severity and PH development.

BackgroundNonspecific clinical signs and suboptimal diagnostic tests limit accurate identification of late onset sepsis (LOS) and necrotizing enterocolitis (NEC) in premature infants, resulting in significant morbidity and antibiotic overuse. An infant’s systemic inflammatory response may be identified earlier than clinical suspicion through analysis of multiple vital signs by a computerized algorithm (RALIS).AimTo evaluate the revised RALIS algorithm for detection of LOS and NEC in preterm infants.MethodsIn this nested case-control study, VS data (heart rate, respiratory rate, temperature, desaturations, bradycardias) were extracted from medical records of infants 23-32 weeks gestation. RALIS generated an output, with score >5 triggering an alert. Patient episodes were classified based on culture, radiograph, and antibiotic data into categories: LOS, expanded LOS, NEC, and controls. Paired t-tests, linear regression and cross-validation analyses were used to evaluate the relationship between RALIS alert and LOS/NEC.ResultsAmong 155 infants with 161 episodes, there were 41 expanded LOS (+ blood, CSF, urine, respiratory culture), 31 LOS (+ blood, CSF, urine), 9 NEC, and 93 controls. RALIS alert was 43.1+/-79 hours before culture in LOS (p=0.012). There was a significant association between RALIS alert and LOS/NEC (β=0.72, pConclusionsFor infants

To assess whether cord blood biomarkers associated with placental maternal vascular underperfusion (MVU) are predictive of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH).Premature infants enrolled in a longitudinal cohort study were randomly sampled from 4 gestational age strata (n?=?190, range 23-36 weeks). Fifteen factors from a human angiogenesis panel were measured in cord blood using multiplex immunoassay. Multivariate linear regression was used to compare biomarker levels according to placental histologic MVU, taking into account acute/chronic inflammation and fetal vascular pathology. Biomarkers associated with MVU were further evaluated in the subgroup of extremely low gestational age infants (gestational age ? 28 weeks; n?=?48), and measured by enzyme-linked immunoassay in an additional 39 infants to determine associations with BPD (defined using the National Institutes of Health workshop criteria) and PH (identified by echocardiogram at 36 weeks of gestation).Cord blood placental growth factor (PIGF), granulocyte-colony stimulating factor (G-CSF), and vascular endothelial growth factor-A were decreased with MVU (P??.003), and decreased with BPD-PH (P??.05). The findings were validated for PIGF and G-CSF in 39 additional extremely low gestational age infants. In the combined group (n?=?87), PIGF was decreased in infants with BPD-PH (n?=?21) versus controls without PH (median 3 pg/mL [IQR 2-7] vs median 15 pg/mL [IQR 6-30], respectively; P??.001). G-CSF was similarly decreased with BPD-PH (median, 55 pg/mL [IQR 38-85] vs median 243 pg/mL [IQR 48-1593], respectively; P?=?.001). Receiver operator curve analysis revealed that decreased PIGF and G-CSF were predictive of BPD-PH (area under the curve 0.83 and 0.76, respectively).Cord blood angiogenic factors that are decreased with placental MVU may serve as predictors of BPD-PH.

Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) may either be concordant or discordant between multiple gestation births. Abnormal placental development, particularly maternal vascular malperfusion, may account for discordance in BPD-PH through fetal programming mechanisms. Maternal vascular malperfusion is a placental histologic lesion associated with intrauterine growth restriction and BPD-PH. We conducted a retrospective longitudinal cohort study of infants born

Objective: To test the hypothesis that umbilical cord blood-derived CD34+ hematopoietic stem cells (HPSC), cord tissue-derived CD90+ and CD105+ mesenchymal stem cells (MSC) vary with bronchopulmonary dysplasia (BPD).Methods: We conducted a prospective longitudinal study at a large birth center (Prentice Women's Hospital in Chicago, IL). Premature infants (N = 200) were enrolled in 2:1:1 ratio based on gestational age (GA): mildly preterm (31–32 weeks), moderately preterm (29–30 weeks), and extremely preterm (23–28 weeks). Cord blood (CB) and cord tissues (CT) were collected at birth using commercial banking kits, and analyzed for collection blood volume, tissue mass, CD34+, CD90+, CD105+ counts, and concentrations. Multiplex immunoassay was used to measure 12 cytokines and growth factors in CB plasma of 74 patients. BPD severity was defined according to NIH consensus definitions. Univariate and multivariate regression models were used to identify perinatal covariates and assess associations between stem cell concentrations, cytokines, and BPD outcomes.Results: Of 200 patients enrolled (mean GA = 30 ± 2 weeks), 30 developed mild, 24 moderate, and 19 severe BPD. Concentrations of HPSC and MSC, as measured by %CD34+, %CD90+, and %CD105+ of total cells, increased with degree of prematurity. Collection parameters varied with GA, birth weight (BW), gender, prolonged rupture of membranes, mode of delivery, chorioamnionitis, and multiple gestation. Moderate-severe BPD or death was increased with lower GA, BW, Apgar scores, and documented delayed cord clamping. %CD34+ and %CD90+ were increased with BPD and directly correlated with BPD severity. Severe BPD was positively associated with %CD34+ (beta-coefficient = 0.9; 95% CI = 0.4–1.5; P < 0.01) and %CD90+ (beta-coefficient = 0.4; 95% CI = 0.2–0.6; P < 0.001) after adjustment for covariates. CB plasma granulocyte-colony stimulating factor (G-CSF) was inversely associated with %CD90+, and decreased with BPD. Below median G-CSF combined with elevated %CD90+ predicted BPD (positive predictive value = 100%).Conclusions: CB and CT collections yielded high concentrations of HPSCs and MSCs in BPD infants, accompanied by low circulating G-CSF. These variations suggest possible mechanisms by which stem cell differentiation and function predict BPD.

Infants born large-for-gestational age (LGA) are at risk f or early childhood obesity. The aims of this study were to investigate factors associated with LGA status and their relationship to inflammatory biomarkers that have been impl icated in the LGA infant at birth. Included were 364 mother-infant pairs enrolled as part of an ongoing longitudinal cohort study of infant birth weight being conducted at Boston Medical Center (BMC). LGA was defined as birth weight (BW) > 90th percentile of the reference population at BMC (N = 45). Appropriate-for-gestational age (AGA) was defined as B W 10th percentile (N = 319). Cord blood IL-6, IL-8, TNF-alpha and RANTES levels were analyzed from a larger panel of immune biomarkers measured using multiplex immunoassay. Multivariate regression models were used to determine the associations between LGA status, maternal BMI and diabetes (DM), which included either gestational or type 2 diabetes (T2DM), and cord blood biomarkers, with adjustment for important demographic and clinical variables. Maternal pre-pregnancy BMI within the obesity range (> 30 kg/m 2 ), as well as DM, were each associated with increased risk of LGA (OR = 2.64, 95%CI 1.31-6.20; OR = 5.58, 95%CI 2.06-15.13, respectively). Among the 4 biomarkers, only RANTES (regulated on activation, normal T cell express and secreted upon uptake), which is a chemokine secreted by white adipose tissue, was significantly increased in LGA infants (beta-coefficient = 0.37; 95%CI: 0.09, 0.65; P < 0.01). This association remained essentially unchanged after adjustment for maternal DM and BMI (beta-coefficient = 0.37; 95%CI: 0.08, 0.65; P = 0.01). Ponderal index (PI = BWx100/length 3 ) was also positively correlated with RANTES. Cord blood RANTES is selectively elevated with fetal macrosomia, independent of maternal factors. Further investigation of RANTES as a marker of LGA and future childhood health is warranted.

Elevated levels of the phosphate-regulating hormone, fibroblast growth factor-23 (FGF-23) are associated with skeletal and cardiovascular disease. Levels of FGF-23 are elevated in neonates, but the mechanisms are poorly understood. Iron deficiency is a recently described stimulus for FGF-23 production.To test the hypothesis that lower fetal iron status, as measured by lower cord blood ferritin, is independently associated with elevated FGF-23 levels in neonates.This is a cross-sectional study of 64 full-term, healthy neonates.This study took place in a university-based, tertiary care center.Plasma levels of second generation C-terminal FGF-23 (cFGF-23) and intact FGF-23 (iFGF-23).Levels of cFGF-23 ranged from 108 to 7508 reference units (RU)/ml (median, 824 RU/ml), and iFGF-23 from undetectable (8.5) to 135.4 pg/ml (median,8.5 pg/mL). Ferritin ranged from 58 to 719 ng/ml (mean, 203 ng/ml). Lower cord blood ferritin levels were associated with higher cFGF-23 (r = −0.320; P = .014), but not iFGF-23 levels (r = −0.222; P = .082). In multivariate analyses adjusted for glycemic indices, maternal race, and parity, lower ferritin levels remained independently associated with higher cFGF-23 levels (B = −0.261, P = .01). In the full models, higher cord blood glucose and C-peptide levels were also independently associated with higher cFGF-23 levels.cFGF-23, but not iFGF-23 levels, are elevated in cord blood of healthy term neonates and independently associated with lower serum ferritin and higher glycemic indices.

Background Chorioamnionitis is a risk factor for future asthma development. Animal models of chorioamnionitis demonstrate increased TH17-to-Treg ratios associated with proinflammatory cytokine elevations. The association of chorioamnionitis on human neonatal immune cells systemically and within tissues is not known. Methods We enrolled two cohorts to evaluate TH17 and regulatory T cell (Treg) phenotypic markers in chorioamnionitis. From a cohort of 19 live birth infants, we collected cord blood and placenta samples to evaluate for signs of acute and chronic histologic inflammation and cell phenotype characterization. We analyzed a second cohort of stillborn infants with and without chorioamnionitis to classify and enumerate cell infiltrate phenotypes in the spleen, thymus, and lung. We used linear regression analysis determine the association of retinoic acid-related orphan receptor gamma t positive (RORγt+) and Treg cell frequency with different types of inflammation seen in the live cohort subjects. Using linear mixed models, we evaluated for any associations between chorioamnionitis and T- and B-cell with a logarithmic scale for level of expression of cellular markers. We then performed Wilcoxon rank sum tests to assess the associations between cell count and chorioamnionitis. Results In the live birth subjects with chronic placental inflammation we observed an increased proportion of RORγt+ cells in Foxp3+ cells, regardless of the presence of acute inflammation, compared to subjects with neither acute nor chronic inflammation. We also found an increased proportion of RORγt+ cells within Foxp3+ cells in subjects with acute high stage fetal and maternal inflammation compared to those without acute or chronic inflammation. In the stillborn subjects with chorioamnionitis, we observed a decrease in splenic Foxp3+ cells and an increase in lung CD3+ cells compared with subjects that did not have chorioamnionitis. Conclusion Exposure to chorioamnionitis in utero may affect immune activation in neonates with an increased frequency of RORγt+ cells systemically as well as lymphocytic infiltrate in the lung. Our findings suggest an increase in RORγt+ cells during chorioamnionitis and thus may support the known associations between chorioamnionitis with asthma. Electronic supplementary material The online version of this article (10.1186/s13223-018-0297-y) contains supplementary material, which is available to authorized users.

The past decade of neonatal care has been highlighted by increased survival rates in smaller and more premature infants. Despite reduction in mortality associated with extreme prematurity, long term pulmonary morbidities remain a concern, with growing recognition of the clinical burden attributable to infants with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH). Recent publications shed light on the critical contributions of maternal placental pathology and compromised intrauterine growth to fetal pulmonary vascular development. A body of literature has further clarified postnatal risk factors for PH, most notably the severity of BPD but surprisingly the additional presence of non-pulmonary morbidities including necrotizing enterocolitis (NEC). Limitations of current diagnostics persist with growing consideration of novel echocardiographic approaches as well as complementary non-invasive biomarkers to better identify infants at risk. In 2015, a joint report published by the American Heart Association and American Thoracic Society provided the first guidelines for the care of children with PH with limited content to address BPD-associated PH. These guidelines were expanded upon in an expert consensus report produced by the Pediatric Pulmonary Hypertension Network (PPHNet). These recommendations encouraged the use of standardized screening protocols and emphasized the importance of evaluation and treatment of comorbidities when PH is identified. Cardiac catheterization was recommended prior to initiation of therapy for more accurate quantification of pulmonary pressures, clarification of anatomy and guidance in the use of pharmacotherapy. Despite these guidelines, significant practice variation persists and gaps remain with respect to optimal evaluation and management of BPD-associated PH.

African American women are at higher risk for preterm birth compared to white women, but no placental pathology has characterized this disparity. The objective of this study was to examine the association of race with placental pathology among very preterm births.We conducted an eight-year retrospective cohort study of very preterm infants born at ≤32 weeks at Northwestern Prentice Women's Hospital in Chicago, Illinois. Archived placental slides underwent standardized masked histopathologic review. Logistic regression was performed for placental pathology, adjusting for available relevant covariates and stratified by infant sex and gestational age.Placentas were available for 296 white and 224 African American mother-infant pairs among births at ≤32 weeks gestation. Compared to placentas from white births, the adjusted OR (aOR) for acute inflammation in placentas from African American births was 1.95 (95% CI 0.87-4.37), the aOR for chronic inflammation was 3.35 (1.49-7.54), the aOR for fetal vascular pathology was 0.82 (0.29-2.32), and the aOR for maternal vascular pathology was 1.01 (0.51-1.99). Stratified analysis showed associations between all placental pathologies and race among male births. Across gestational age groups (28 and ≥ 28 weeks), the association between race and placental pathology was present for chronic inflammation and fetal vascular pathology.Race is associated with placental pathology, and in particular, with chronic inflammation among very preterm births. The effect is modified by infant sex and gestational age. Placental histopathology may be useful markers for understanding the biological processes that shape disparities in pregnancy outcomes.

The placenta is a vital organ, shared by a mother and fetus, which houses valuable information on the events and processes occurring before birth. Often these processes can have a negative impact on any or all organ systems, leading to neonatal instability and infant morbidity and mortality. Therefore, the placenta may serve as an important clinical tool for the neonatologist and pediatrician in the diagnosis and management of several complex neonatal diseases. These diagnoses range from neonatal sepsis to congenital infections, sequelae of intrauterine growth abnormalities, neurologic signs, and a wide range of complications accompanying prematurity. The purpose of this review is to provide baseline information on the processes obtainable from the perinatal pathologist’s placental examination. We describe common anatomic and histologic lesions of the placenta that are associated with the aforementioned clinical problems, and describe how such placental findings can help the clinician in routine diagnosis and management. We discuss the current gaps in diagnostic usefulness of the placenta, and how ongoing research is the key to optimizing the placental examination to improve neonatal outcomes.

The development of pulmonary hypertension (PH) is a serious complication of bronchopulmonary dysplasia (BPD) among infants born at extremely low gestational ages. Bronchopulmonary dysplasia-associated PH is characterized by persistent pulmonary vasoconstriction, progressive right heart dysfunction, and an increased risk of death. We have shown previously that certain placental vascular lesions are associated with BPD-associated PH. Further evaluation of the villous and vascular morphometry of these placentas is warranted. Using digital image analysis (DIA), we compared villous and vascular morphometric parameters of placentas from infants with and without BPD-associated PH. We conducted a case-control study of placentas from 14 infants born at ≤28 weeks' gestational age (GA). Cases with PH ( N = 7) and non-PH controls ( N = 7) were identified using echocardiogram screening at 36 weeks' corrected GA. Central parenchymal sections from each placenta were stained for CD31. Digital image analysis was used to measure vessel and villous capillary number, perimeter, diameter, and area. Mean villous vascularity (number of vessels per villus) was calculated for each patient. Mean vessel and villous number as well as area were similar between the two groups. Villous vascularity was decreased in placentas from infants who ultimately had PH disease compared to non-PH controls (5.5 ± 1.0 vs 7.1 ± 1.6; P < 0.05). Placental villous vascularity is decreased in infants with BPD-associated PH. Further studies should assess whether placental morphometric markers may allow clinicians to better predict BPD and provide earlier and more targeted management.

Background : Preterm infants often receive prolonged empiric antibiotics for culture-negative presumed early onset sepsis. We investigated 16S rDNA PCR of cord blood (CB) as a culture-independent method of bacterial detection to improve EOS diagnosis. Methods : Preterm infants were classified into 4 categories: confirmed EOS (cEOS), culture-negative presumed sepsis (PS), late onset sepsis (LOS), and no sepsis (control). Sanger and next generation sequencing (NGS) of 16S rDNA amplicons from CB buffy coat were compared to peripheral blood culture and CB acute phase reactants (APRs). Results : Twelve of 12 cEOS patients had a positive CB Sanger-based 16S rDNA result; 8 were concordant with the peripheral blood culture. Twenty-three of 30 controls and 14 of 15 LOS had negative Sanger sequencing (NPV=92.5%). Known pathogens were identified by Sanger-based 16S rDNA PCR in 8 of 30 PS patients. These infants had elevated CB APRs. NGS demonstrated complex bacterial rDNA species in all CB samples. Controls had significantly higher alpha diversity than cEOS. Some cEOS and PS had high % abundance of known pathogenic neonatal bacteria. Conclusions : CB Sanger-based 16S rDNA amplicon sequencing correctly identifies bacterial pathogens in cEOS. PS with positive PCR and elevated APRs may indicate infection where culture remains negative. NGS indicates altered microbial diversity in infection and in utero microbial exposures. CB PCR could provide early organism-specific information in cases of culture-negative sepsis, improving targeted antibiotic use.

To identify the association between birth weight (BW)-for-gestational age (GA) and pulmonary hypertension (PHTN) at 36 weeks in infants with moderate-severe bronchopulmonary dysplasia (BPD).In this retrospective cohort study, we followed 138 premature infants (≤ 28 weeks) with moderate and severe BPD (National Institutes of Health consensus definition) born at Prentice Women's Hospital between 2005 and 2009. BW percentiles were calculated using the Fenton growth curve for premature infants. PHTN was determined using a standardized algorithm of echocardiogram review at 36 weeks. Logistic regression was used to evaluate the associations between BW percentile subgroups and PHTN, taking into account antenatal and neonatal factors that were related to PHTN.PHTN was associated with small BW-for-GA, ranging from thresholds of10th to25th percentile (P0.001). These associations remained significant when comparing BW25th percentile to the reference group (50 to 89 th percentile); after adjustment for GA, gender, multiple gestation, race/ethnicity (odds ratio (OR)=4.2; 95% confidence interval (CI)=1.5, 12.1); and after further adjustment for maternal vascular disease, intrauterine infection, oligohydramnios and relevant postnatal factors (OR=5.7; 95% CI=1.5, 21.2). Longitudinal follow-up of this cohort showed a trend toward higher morbidity and death among PHTN infants with BW25th percentile.BW-for-GA is an important predictor of PHTN in premature infants with moderate-severe BPD. Our findings contribute to the growing evidence supporting fetal mechanisms of later onset pulmonary vascular disease.

Current clinical and laboratory diagnostics for neonatal infection are inadequate. An infant’s systemic inflammatory response may be identified earlier than clinical suspicion by a computerized algorithm (RALIS) incorporating multiple vital signs (VS). We tested the ability of RALIS to detect late onset infection (LOI) earlier than clinically suspected.We conducted a retrospective review of infants enrolled in a birth cohort study at Prentice Women’s Hospital. VS data (heart rate, respirations, temperature, desaturation, bradycardia) were extracted from electronic records of 73 premature infants (born ≤28 weeks’ gestation; survived first month). RALIS generated a continuous output for the first 28 days of life. A score ≥5 for 6 h triggered an alert. The time of RALIS alert to time of clinical suspicion of infection (time culture sent) was measured for each episode of suspected and/or confirmed LOI.Among the 73 infants followed with RALIS, there were 34 episodes of culture-positive LOI, seven culture-negative but treated episodes, and 13 false-positive culture (untreated) episodes. Twenty-five infants had no culture-positive or treated sepsis events during the observation period. There was a positive linear association between alert and culture (β=0.88, PThe RALIS algorithm is a sensitive indicator for early detection of infection in preterm infants. Further modifications to improve the specificity of the algorithm are needed prior to application of VS modeling to patient antibiotic treatment decisions.

Supplemental Digital Content is available in the text, Previous genetic studies of food allergy (FA) have mainly focused on inherited genotypic effects. The role of parental genotypic effects remains largely unexplored. Leveraging existing genome-wide association study (GWAS) data generated from the Chicago Food Allergy Study, we examined maternal genotypic and parent-of-origin (PO) effects using multinomial likelihood ratio tests in 588 complete and incomplete Caucasian FA trios. We identified 1 single nucleotide polymorphism with significant (P

Background Early onset sepsis (EOS) is a major cause of morbidity and mortality in preterm infants, yet diagnosis remains inadequate resulting in missed cases or prolonged empiric antibiotics with adverse consequences. Evaluation of acute phase reactant (APR) biomarkers in umbilical cord blood at birth may improve EOS detection in preterm infants with intrauterine infection. Methods In this nested case-control study, infants (29.7 weeks gestation, IQR: 27.7–32.2) were identified from a longitudinal cohort with archived cord blood and placental histopathology. Patients were categorized using culture, laboratory, clinical, and antibiotic treatment data into sepsis groups: confirmed sepsis (cEOS, n = 12); presumed sepsis (PS, n = 30); and no sepsis (controls, n = 30). Nine APRs were measured in duplicate from cord blood using commercially available multiplex immunoassays (Bio-Plex Pro™). In addition, placental histopathologic data were linked to biomarker results. Results cEOS organisms were Escherichia coli, Streptococcus agalactiae, Proteus mirabilis, Haemophilus influenzae and Listeria monocytogenes. C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), serum amyloid P and ferritin were significantly elevated in cEOS compared to controls (p

Human genome sequencing is the process by which the exact order of nucleic acid base pairs in the 24 human chromosomes is determined. Since the completion of the Human Genome Project in 2003, genomic sequencing is rapidly becoming a major part of our translational research efforts to understand and improve human health and disease. This article reviews the current and future directions of clinical research with respect to genomic sequencing, a technology that is just beginning to find its way into clinical trials both nationally and worldwide. We highlight the currently available types of genomic sequencing platforms, outline the advantages and disadvantages of each, and compare first- and next-generation techniques with respect to capabilities, quality, and cost. We describe the current geographical distributions and types of disease conditions in which these technologies are used, and how next-generation sequencing is strategically being incorporated into new and existing studies. Lastly, recent major breakthroughs and the ongoing challenges of using genomic sequencing in clinical research are discussed.