To characterize the incidence, management and short term outcomes of cardiovascular insufficiency (CVI) in mechanically ventilated newborns, evaluating 4 separate pre-specified definitions.
Multicenter, prospective cohort study of infants ≥34 weeks gestational age (GA) and on mechanical ventilation during the first 72 hours. CVI was prospectively defined as either (1) mean arterial pressure (MAP)
Of 647 who met inclusion criteria, 419 (65%) met ≥1 definition of CVI. Of these, 98% received fluid boluses, 36% inotropes and 17% corticosteroids. Of treated infants, 46% did not have CVI as defined by a MAP < GA ± signs of inadequate perfusion. Inotrope therapy was associated with increased mortality (11.1% vs. 1.3%; P < 0.05).
More than half of the infants met at least one definition of CVI. However, almost half of the treated infants met none of the definitions. Inotropic therapy was associated with increased mortality. These findings can help guide the design of future studies of CVI in newborns.
blood pressure; cardiovascular insufficiency; mechanical ventilation; inotrope; fluid bolus; glucocorticoid; outcomes; newborn
Diabetic kidney disease (DKD) remains the most common cause of end-stage kidney disease despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation of ATP-binding cassette transporter ABCA1 occurs in normal human podocytes exposed to the sera of patients with type 1 diabetes and albuminuria (DKD+) when compared with diabetic patients with normoalbuminuria (DKD−) and similar duration of diabetes and lipid profile. Glomerular downregulation of ABCA1 was confirmed in biopsies from patients with early DKD (n = 70) when compared with normal living donors (n = 32). Induction of cholesterol efflux with cyclodextrin (CD) but not inhibition of cholesterol synthesis with simvastatin prevented podocyte injury observed in vitro after exposure to patient sera. Subcutaneous administration of CD to diabetic BTBR (black and tan, brachiuric) ob/ob mice was safe and reduced albuminuria, mesangial expansion, kidney weight, and cortical cholesterol content. This was followed by an improvement of fasting insulin, blood glucose, body weight, and glucose tolerance in vivo and improved glucose-stimulated insulin release in human islets in vitro. Our data suggest that impaired reverse cholesterol transport characterizes clinical and experimental DKD and negatively influences podocyte function. Treatment with CD is safe and effective in preserving podocyte function in vitro and in vivo and may improve the metabolic control of diabetes.
In this secondary analysis of the AIM-HIGH trial, the objectives were to examine the relationship between niacin treatment, lipoproteins, and cardiovascular (CV) outcomes.
During 3-year follow-up in 3,414 patients with established CV disease and low HDL-C, combined niacin + LDL-lowering therapy did not reduce CV events versus LDL-lowering therapy alone.
Subjects taking simvastatin + ezetimibe were randomized to extended-release (ER) niacin 1500–2000 mg or minimal immediate-release niacin (<150 mg) as placebo at bedtime. LDL-C in both groups was maintained from 40 to 80 mg/dL. Hazard ratios (HR) were estimated by Cox proportional hazards for relationships between lipoproteins and the composite endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization.
CV outcomes were not associated with ER niacin in any baseline lipoprotein tertile. In a subset of patients in both the highest triglyceride (>198 mg/dl) and lowest HDL-C (<33 mg/dl) tertiles, ER niacin showed a trend toward benefit (HR=0.74, p=0.073). In-trial LDL-C, nonHDL-C, and TC/HDL-C ratio were positively associated with CV events in the control group, but these relationships were absent in the ER niacin group.
Baseline lipoprotein tertiles did not predict differential benefit or harm with ER niacin added to LDL-lowering therapy, but a small dyslipidemic subgroup may benefit. ER niacin attenuated expected relationships of lipoprotein risk factors with CV events, raising the possibility that nonlipoprotein actions of niacin could impact risk.
Clinical trial info
niacin; cardiovascular events; clinical trial; lipoproteins; GPR109A
Candida remains an important cause of late-onset infection in preterm infants. Mortality and neurodevelopmental outcome of extremely low birthweight (ELBW) infants enrolled in the Candida study was evaluated based on infection status.
ELBW infants born at NICHD Neonatal Research Network (NRN) centers between March 2004 and July 2007 screened for suspected sepsis were eligible for inclusion in the Candida study. Primary outcome data for neurodevelopmental impairment (NDI) or death were available for 1317/1515 (90%) of the infants enrolled in the Candida study. The Bayley Scales of Infant Development (BSID)-II or the BSID-III was administered at 18 months adjusted age. A secondary comparison with 864 infants registered with NRN enrolled during the same cohort never screened for sepsis and therefore not eligible for the Candida study was performed.
Among ELBW infants enrolled in the Candida study, 31% with Candida and 31% with late-onset non-Candida sepsis had NDI at 18 months. Infants with Candida sepsis and/or meningitis had an increased risk of death and were more likely to have the composite outcome of death and/or NDI compared with uninfected infants in adjusted analysis. Compared with infants in the NRN registry never screened for sepsis, overall risk for death were similar but those with Candida infection were more likely to have NDI (OR 1.83 (1.01,3.33, p=0.047).
In this cohort of ELBW infants, those with infection and/or meningitis were at increased risk for death and/or NDI. This risk was highest among those with Candida sepsis and/or meningitis.
Candida; Neonatal sepsis; Neurodevelopmental and Prematurity
It is unclear how lipids change in response to lifestyle modification or metformin among postmenopausal glucose intolerant women using and not using hormone therapy (HT). We examined the one-year changes in lipids among postmenopausal, prediabetic women in the Diabetes Prevention Program (DPP), and whether changes were mediated by sex hormones.
We performed a secondary analysis of a randomized controlled trial of 342 women who used HT at baseline and year 1 and 382 women who did not use HT at either time point. Interventions included intensive lifestyle (ILS) with goals of weight reduction of at least 7% of initial weight and 150 minutes per week of moderate intensity exercise, or metformin or placebo administered 850 mg up to twice a day. Women were not randomized to HT. Main outcome measures were changes between baseline and study year 1 in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides.
Compared to placebo, both ILS and metformin significantly reduced LDL-C and raised HDL-C among HT users, changes partially explained by change in estradiol and testosterone but independent of changes in waist circumference and 1/fasting insulin. In contrast, DPP interventions had no effect on LDL-C and HDL-C among non-HT users. ILS significantly lowered triglycerides among non-users but did not significantly change triglycerides among HT users. Metformin did not significantly change triglycerides among non-users but increased triglycerides among HT users.
The beneficial effects of ILS and metformin on lowering LDL-C and raising HDL-C differ depending upon concurrent HT use.
sex hormones; lifestyle intervention; hormone therapy; lipids; women
Adults with the apolipoprotein E gene (APOE) alleles e4 and e2 are at high risk of poor neurologic outcome after brain injury. The e4 allele has been associated with cerebral palsy and the e2 allele has been associated with worse neurologic outcome with congenital heart disease. This study was done to test the hypothesis that APOE genotype is associated with outcome among neonates who survive after hypoxic-ischemic encephalopathy (HIE).
We conducted a cohort study of infants who survived HIE and had 18 – 22 month standardized neurodevelopmental evaluations to assess associations between disability and APOE genotypes e3/e3, e4/-, and e2/-
139 survivors were genotyped. 86 (62%) were e3/e3, 41 (29%) were e4/-, and 14 (10%) were e2/-. 129 infants had genotype and follow-up data; 26% had moderate or severe disabilities. Disability prevalence was 30% and 19% among those with and without e3/e3 genotype, 25% and 26% among those with and without the e2 allele, and 18% and 29% among those with and without the e4 allele. None of the differences were statistically significant. Cerebral palsy prevalence was also similar among genotype groups.
Disability was not associated with APOE genotype in this cohort of HIE survivors.
This study aimed to determine the association between circulating leptin levels and total depressive symptoms as well as depressive symptom dimensions (cognitive and somatic) after controlling for important confounding factors.
The study sample was comprised of 135 participants with the metabolic syndrome. Depressive symptoms were measured using the Beck Depression Inventory - II. Leptin was measured using a leptin-specific enzyme immunoassay. Inflammation was assessed using C-reactive protein and interleukin-6 levels.
Leptin was significantly associated with somatic depressive symptoms (β=0.33, P=0.018) but not total depressive symptoms (β=0.27, P=0.067), or cognitive depressive symptoms (β=0.21, P=0.182), after controlling for age, gender, body mass index and insulin resistance. Further adjustment for C-reactive protein and interleukin-6 levels did not alter the relationship (β=0.32, P=0.023) between circulating leptin levels and somatic depressive symptoms.
Leptin is independently associated with somatic depressive symptoms in patients with the metabolic syndrome.
Depression; Leptin; Inflammation; Metabolic Syndrome; Blood Pressure; Body Weight; Insulin Resistance; Lipoproteins; Cardiovascular Disease
Determine effects of low-dose dopamine on urine output in very low birth weight premature neonates.
Retrospective cohort study of all low-dose (3-5 μg/kg/min) dopamine infusions >24 hours duration in neonates ≤1500 g and ≤32 weeks gestation from August 2009 through September 2011. Linear regression was used to estimate the impact of covariates on urine output.
We identified 91 episodes of low-dose dopamine use in 65 neonates. Increased urine output occurred with 64% of episodes. Low-dose dopamine use was associated with a 0.6 mL/kg/hr increase in urine output (p<0.001) and a 1.3 mL/kg/hr increase when baseline urine output was <1.5 mL/kg/hr (p<0.001). The improvement remained statistically significant after controlling for medications (diuretics and hydrocortisone) and fluid intake.
Low-dose dopamine use was associated with increased urine output in very low birth weight neonates.
renal dose; dopamine; urine output
To examine factors affecting center differences in mortality for extremely low birth weight (ELBW) infants.
We analyzed data for 5418 ELBW infants born at 16 Neonatal Research Network centers during 2006–2009. The primary outcomes of early mortality (≤12 hours after birth) and in-hospital mortality were assessed by using multilevel hierarchical models. Models were developed to investigate associations of center rates of selected interventions with mortality while adjusting for patient-level risk factors. These analyses were performed for all gestational ages (GAs) and separately for GAs <25 weeks and ≥25 weeks.
Early and in-hospital mortality rates among centers were 5% to 36% and 11% to 53% for all GAs, 13% to 73% and 28% to 90% for GAs <25 weeks, and 1% to 11% and 7% to 26% for GAs ≥25 weeks, respectively. Center intervention rates significantly predicted both early and in-hospital mortality for infants <25 weeks. For infants ≥25 weeks, intervention rates did not predict mortality. The variance in mortality among centers was significant for all GAs and outcomes. Center use of interventions and patient risk factors explained some but not all of the center variation in mortality rates.
Center intervention rates explain a portion of the center variation in mortality, especially for infants born at <25 weeks’ GA. This finding suggests that deaths may be prevented by standardizing care for very early GA infants. However, differences in patient characteristics and center intervention rates do not account for all of the observed variability in mortality; and for infants with GA ≥25 weeks these differences account for only a small part of the variation in mortality.
mortality rates; outcome; NICU; preterm infants; extremely preterm infants
To investigate the relationships among blood pressure (BP) values, antihypotensive therapies, and in-hospital outcomes to identify a BP threshold below which antihypotensive therapies may be beneficial.
Prospective observational study of infants 230/7 to 266/7 weeks’ gestational age. Hourly BP values and antihypotensive therapy use in the first 24 hours were recorded. Low BP was investigated by using 15 definitions. Outcomes were examined by using regression analysis controlling for gestational age, the number of low BP values, and illness severity.
Of 367 infants enrolled, 203 (55%) received at least 1 antihypotensive therapy. Treated infants were more likely to have low BP by any definition (P < .001), but for the 15 definitions of low BP investigated, therapy was not prescribed to 3% to 49% of infants with low BP and, paradoxically, was administered to 28% to 41% of infants without low BP. Treated infants were more likely than untreated infants to develop severe retinopathy of prematurity (15% vs 8%, P = .03) or severe intraventricular hemorrhage (22% vs 11%, P < .01) and less likely to survive (67% vs 78%, P = .02). However, with regression analysis, there were no significant differences between groups in survival or in-hospital morbidity rates.
Factors other than BP contributed to the decision to use antihypotensive therapies. Infant outcomes were not improved with antihypotensive therapy for any of the 15 definitions of low BP investigated.
extremely preterm infant; antihypotensive therapy; blood pressure; hypotension
To examine whether preterm very low birth weight (VLBW) infants have an increased risk of late-onset sepsis (LOS) following early-onset sepsis (EOS).
Retrospective analysis of VLBW infants (401-1500 g) born September 1998 through December 2009 who survived >72 hours and were cared for within the NICHD Neonatal Research Network. Sepsis was defined by growth of bacteria or fungi in a blood culture obtained ≤72 hr of birth (EOS) or >72 hr (LOS) and antimicrobial therapy for ≥5 days or death <5 d while receiving therapy. Regression models were used to assess risk of death or LOS by 120d and LOS by 120d among survivors to discharge or 120d, adjusting for gestational age and other covariates.
Of 34,396 infants studied 504 (1.5%) had EOS. After adjustment, risk of death or LOS by 120d did not differ overall for infants with EOS compared with those without EOS [RR:0.99 (0.89-1.09)] but was reduced in infants born at <25wk gestation [RR:0.87 (0.76-0.99), p=0.048]. Among survivors, no difference in LOS risk was found overall for infants with versus without EOS [RR:0.88 (0.75-1.02)], but LOS risk was shorter in infants with BW 401-750 g who had EOS [RR:0.80 (0.64-0.99), p=0.047].
Risk of LOS after EOS was not increased in VLBW infants. Surprisingly, risk of LOS following EOS appeared to be reduced in the smallest, most premature infants, underscoring the need for age-specific analyses of immune function.
Very low birth weight; early-onset sepsis; late-onset sepsis
Determine predictors of neurocognitive outcome in early school age congenital diaphragmatic hernia (CDH) survivors.
Prospective study of infants with CDH at Duke University Medical Center. Neurocognitive delay (NCD) at school age (4 to 7 years) was defined as a score < 80 in any of the following areas: Verbal Scale IQ, Performance Scale IQ, Expressive Language, or Receptive Language. Logistic regression, Fisher’s exact, and the Wilcoxon rank sum test were used to examine the relationship between NCD at early school age and 6 demographic and 18 medical variables.
Of 43 infants with CDH, twenty seven (63%) survived to hospital discharge, and 16 (59%) returned for school age testing at a median age of 4.9 years. Seven (44%) of the children evaluated had NCD. Patch repair (p=0.01), extracorporeal membrane oxygenation (ECMO; p=0.02), days on ECMO (p=0.01), days of mechanical ventilation (p=0.049), and post-operative use of inhaled nitric oxide (p=0.02) were found to be associated with NCD at early school age.
CDH survivors are at risk for neurocognitive delay persisting into school age. Perinatal factors such as patch repair and ECMO treatment may aid in identifying CDH survivors at high risk for continued learning difficulties throughout childhood.
hernia, diaphragmatic; follow-up studies; neurobehavioral manifestations; growth & development; infant nutrition disorders
Despite adiponectin’s independent relationship with many markers of vascular disease risk, its association with clinical outcomes is unclear and results of studies have been inconsistent. We examined the association between adiponectin, an adipocytokine secreted by adipose tissue, and vascular events (stroke, myocardial infarction (MI), vascular death) in the multi-ethnic prospective population-based Northern Manhattan Study (NOMAS).
Adiponectin was measured at baseline among 2900 participants free of MI and stroke (mean age 69±10 years, 37% men, 21% white, 53% Hispanic, 24% black). Over a mean 10 years follow-up, 692 incident vascular events accrued.
The mean adiponectin=11.4±6.2 μg/ml (median=9.8, range=2.1–53.3). In Cox models adjusting for demographics and vascular risk factors, a decreased risk of vascular events was suggested with lower adiponectin. Examination of quartiles suggested a non-linear relationship, with a reduction in risk observed among those in adiponectin quartiles 1–3 vs. 4, and the lowest effect estimates observed in quartile 2. Similar results were found when stroke, MI, and vascular death were examined separately. We saw no effect modification by baseline vascular health profile, but the positive association between adiponectin and vascular events was stronger among those with elevated waist circumference.
In NOMAS, low-moderate adiponectin was associated with a decreased risk of vascular events despite the fact that low adiponectin levels were associated with an elevated vascular risk profile. These counter-intuitive findings underscore the need for further research on adiponectin as a useful biomarker of vascular disease risk and mechanisms explaining the inconsistent observations in the literature.
adiponectin; myocardial infarction; stroke; epidemiology
Population-based data on serum adiponectin levels, an adipocytokine secreted from adipose tissue, are lacking, particularly across race–ethnic groups. Studies have suggested an inverse association between adiponectin and vascular risk factors, but data are limited and inconsistent. We examined the cross-sectional association between adiponectin, vascular risk factors and race–ethnicity in the population-based Northern Manhattan Study (NOMAS).
Blood samples, anthropomorphics, and vascular risk factors were collected at baseline. Multivariable linear regression analysis was conducted with log-transformed adiponectin as the dependent variable.
Adiponectin was measured among 2900 participants (age 69±10 years, body mass index (BMI) 28.0±5.6, 37% male, 21% white, 53% Hispanic, 24% black). The mean adiponectin was 11.4±6.2 μg/mL (median=9.8, range=2.1–53.3). After multivariable adjustment, adiponectin levels were greatest among whites, followed by Hispanics, and lowest among blacks. Lower adiponectin levels were observed in participants with the following characteristics: Male, former smoking, hypertension, diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), metabolic syndrome, moderate alcohol use, elevated waist circumference, BMI, estimated glomerular filtration rate (eGFR), triglycerides, low-density lipoprotein cholesterol (LDL-C), lower high-density lipoprotein cholesterol (HDL-C), and younger age. Obesity was a stronger risk factor for decreased adiponectin among blacks than among whites or Hispanics. The associations for several vascular risk factors, including hypertension, triglycerides, and low HDL-C, with low adiponectin were stronger among individuals who were not obese than among those who were obese.
Adiponectin levels were lower among blacks and Hispanics and among those with various vascular risk factors, and greater with older age. The association between BMI and adiponectin varied across race–ethnic groups. Investigation of whether differences in body fat distribution may explain race–ethnic differences in adiponectin is needed.
This review describes the effect of lifestyle change or metformin compared to standard care on incident diabetes and cardiometabolic risk factors in the Diabetes Prevention Program (DPP) and its Outcome Study. The DPP was a randomized, controlled clinical trial of intensive lifestyle and metformin treatments versus standard care in 3234 subjects at high risk for diabetes. At baseline, hypertension was present in 28%, and 53% had the metabolic syndrome, with considerable variation in risk factors by age, gender and race. Over 2.8 years, diabetes incidence fell by 58% and 31% in the lifestyle and metformin groups respectively, and metabolic syndrome prevalence fell by a third with lifestyle change but was not reduced by metformin. In placebo- and metformin-treated subjects the prevalence of hypertension and dyslipidemia increased during the DPP, while lifestyle intervention slowed these increases significantly. During long term follow up using modified interventions, diabetes incidence decreased to about 5% per year in all groups. This was accompanied by significant improvement in CVD risk factors over time in all treatment groups, in part associated with increasing use of lipid lowering and antihypertensive medications. Thus a program of lifestyle change significantly reduced diabetes incidence and metabolic syndrome prevalence in subjects at high risk for diabetes. Metformin had more modest effects.
prediabetes; metabolic syndrome; lifestyle; metformin
Adults at high risk for diabetes may have reduced health-related quality of life (HRQoL).
To assess changes in HRQoL after interventions aimed at diabetes risk reduction.
DESIGN, SETTING, AND PARTICIPANTS
A randomized clinical trial, the Diabetes Prevention Program, was conducted in 27 centers in the United States, in 3,234 non-diabetic persons with elevated fasting and post-load plasma glucose, mean age 51 years, mean BMI 34 Kg/m²; 68 % women, and 45 % members of minority groups.
Intensive lifestyle (ILS) program with the goals of at least 7 % weight loss and 150 min of physical activity per week, metformin (MET) 850 mg twice daily, or placebo (PLB).
HRQoL using the 36-Item Short-Form (SF-36) health survey to evaluate health utility index (SF-6D), physical component summaries (PCS) and mental component summaries (MCS). A minimally important difference (MID) was met when the mean of HRQoL scores between groups differed by at least 3 %.
After a mean follow-up of 3.2 years, there were significant improvements in the SF-6D (+0.008, p = 0.04) and PCS (+1.57, p < 0.0001) scores in ILS but not in MET participants (+0.002 and +0.15, respectively, p = 0.6) compared to the PLB group. ILS participants showed improvements in general health (+3.2, p < 0.001), physical function (+3.6, p < 0.001), bodily pain (+1.9, p = 0.01), and vitality (+2.1, p = 0.01) domain scores. Treatment effects remained significant after adjusting sequentially for baseline demographic factors, and for medical and psychological comorbidities. Increased physical activity and weight reduction mediated these ILS treatment effects. Participants who experienced weight gain had significant worsening on the same HRQoL specific domains when compared to those that had treatment-related (ILS or MET) weight loss. No benefits with ILS or MET were observed in the MCS score.
Overweight/obese adults at high risk for diabetes show small improvement in most physical HRQoL and vitality scores through the weight loss and increased physical activity achieved with an ILS intervention.
Electronic supplementary material
The online version of this article (doi:10.1007/s11606-012-2122-5) contains supplementary material, which is available to authorized users.
quality of life; lifestyle; metformin; diabetes risk; weight loss
Sepsis in older children and adults modifies immune system function. We compared serotype-specific antibody responses to heptavalent pneumococcal conjugate vaccine (PCV7) in very low birth weight infants (<1500g,VLBW) with and without blood stream infection (BSI) during their birth hospitalization.
Patients and Methods
Retrospective analysis of prospectively collected data for the Neonatal Research Network study of PCV7 responses among VLBWs. Infants received PCV7 at 2, 4, and 6 months after birth with blood drawn 4–6 weeks after 3rd dose. Serotype antibodies were compared between infants with or without a history of BSI. Regression models were constructed with birth-weight groups and other confounding factors identified in the primary study.
244 infants completed the vaccine series and had serum antibody available; 82 had BSI. After adjustment, BSI was not associated with reduced odds of serum antibody ≥0.35μg/mL.
BSI was not associated with reduced odds of WHO-defined protective PCV7 responses in VLBWs.
VLBW; immune response; vaccine; sepsis; blood stream infection
To assess the impact of emperic antifungal therapy of invasive candidiasis on subsequent outcomes in premature infants.
This was a cohort study of infants ≤1000 g birth weight cared for at Neonatal Research Network sites. All infants had at least 1 positive culture for Candida. Emperic antifungal therapy was defined as receipt of a systemic antifungal on the day of or the day before the first positive culture for Candida was drawn. We created Cox proportional hazards and logistic regression models stratified on propensity score quartiles to determine the effect of emperic antifungal therapy on survival, time to clearance of infection, retinopathy of prematurity, bronchopulmonary dysplasia, end-organ damage, and neurodevelopmental impairment (NDI).
136 infants developed invasive candidiasis. The incidence of death or NDI was lower for infants who received emperic antifungal therapy (19/38, 50%) compared with those who had not (55/86, 64%; odds ratio=0.27 [95% confidence interval 0.08–0.86]). There was no significant difference between the groups for any single outcome or other combined outcomes.
Emperic antifungal therapy was associated with increased survival without NDI. A prospective randomized trial of this strategy is warranted.
Candida; neonate; mortality; neurodevelopmental impairment
The effect of birth location on hypothermia-related outcomes has not been rigorously examined in the literature. In this study, we determined whether birth location had an impact on the benefits of whole-body cooling to 33.5 °C for 72 h in term infants (n = 208) with hypoxic–ischemic encephalopathy (HIE) who participated in the Neonatal Research Network (NRN) randomized controlled trial.
Heterogeneity by birth location was examined with respect to cooling treatment for the 18-mo primary outcomes (death, moderate disability, severe disability) and secondary outcomes (death, components of disability), and in-hospital organ dysfunction. Logistic regression models were used to generate adjusted odds ratios.
Infants bom at a location other than an NRN center (outborn) (n = 93) experienced significant delays in initiation of therapy (mean (SD): 5.5 (1.1) vs. 4.4 (1.2) h), lower baseline temperatures (36.6 (1.2) vs. 37.1 (0.9) °C), and more severe HIE (43 vs. 29%) than infants born in an NRN center (inborn) (n = 115). Maternal education <12 y (50 vs. 14%) and African-American ethnicity (43 vs. 25%) were more common in the inborn group. When adjusted for NRN center and HIE severity, there were no significant differences in 18-mo outcomes or in-hospital organ dysfunction between inborn and outborn infants.
Although limited by sample size and some differences in baseline characteristics, the study showed that birth location does not appear to modify the treatment effect of hypothermia after HIE.
The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic–ischaemic encephalopathy treated with hypothermia.
Design and patients
Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18–22 months of age.
Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability.
Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18–22 months following hypothermia for neonatal encephalopathy.
Permanent ductal closure involves anatomic remodeling, in which transforming growth factor (TGF)-β appears to play a role. Our objective was to evaluate the relationship, if any, between blood spot TGF-β on day 3 and day 7 of life and patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Prospective observational study involving ELBW infants (n = 968) in the National Institute of Child Health and Human Development Neonatal Research Network who had TGF-β measured on filter paper spot blood samples using a Luminex assay. Infants with a PDA (n = 493) were significantly more immature, had lower birth weights, and had higher rates of respiratory distress syndrome than those without PDA (n = 475). TGF-β on days 3 and 7 of life, respectively, were significantly lower among neonates with PDA (median 1,177 pg/ml [range 642–1,896]; median 1,386 pg/ml [range 868–1,913]) compared with others without PDA (median 1,334 pg/ml [range 760–2,064]; median 1,712 pg/ml [range 1,014–2,518 pg/ml]). The significant difference persisted when death or PDA was considered a composite outcome. TGF-β levels were not significantly different among subgroups of infants with PDA who were not treated (n = 51) versus those who were treated medically (n = 283) or by surgical ligation (n = 159). TGF-β was not a significant predictor of death or PDA (day 3 odds ratio [OR] 0.99, 95 % confidence interval [CI] 0.83–1.17; day 7 OR 0.88, 95 % CI 0.74–1.04) on adjusted analyses. Our results suggest that blood spot TGF-β alone is unlikely to be a reliable biomarker of a clinically significant PDA or its responsiveness to treatment.
Transforming growth factor; Patent ductus arteriosus; Preterm; Neonate
We sought to determine if a center’s approach to care of premature infants at the youngest gestational ages (22–24 weeks’ gestation) is associated with clinical outcomes among infants of older gestational ages (25–27 weeks’ gestation).
Inborn infants of 401 to 1000 g birth weight and 22 0/7 to 27 6/7 weeks’ gestation at birth from 2002 to 2008 were enrolled into a prospectively collected database at 20 centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Markers of an aggressive approach to care for 22- to 24-week infants included use of antenatal corticosteroids, cesarean delivery, and resuscitation. The primary outcome was death before postnatal day 120 for infants of 25 to 27 weeks’ gestation. Secondary outcomes were the combined outcomes of death or a number of morbidities associated with prematurity.
Our study included 3631 infants 22 to 24 weeks’ gestation and 5227 infants 25 to 27 weeks’ gestation. Among the 22- to 24-week infants, use of antenatal corticosteroids ranged from 28% to 100%, cesarean delivery from 13% to 65%, and resuscitation from 30% to 100% by center. Centers with higher rates of antenatal corticosteroid use in 22- to 24-week infants had reduced rates of death, death or retinopathy of prematurity, death or late-onset sepsis, death or necrotizing enterocolitis, and death or neurodevelopmental impairment in 25- to 27-week infants.
This study suggests that physicians’ willingness to provide care to extremely low gestation infants as measured by frequency of use of antenatal corticosteroids is associated with improved outcomes for more-mature infants.
low-birth weight infant; NICUs; treatment; patient outcome assessment
Information on cytokine profiles in fungal sepsis (FS), an important cause of mortality in extremely low birthweight infants (ELBW), is lacking. We hypothesized that cytokine profiles in the 1st 21 days of life in ELBW with FS differ from those with bacterial sepsis (BS) or no sepsis (NS).
In a secondary analyses of the NICHD Cytokine study, three groups were defined - FS (≥1 episode of FS), BS (≥1 episode of BS without FS), and NS. Association between 11 cytokines assayed in dried blood spots obtained on days 0-1, 3±1, 7±2, 14±3, and 21±3 and sepsis group was explored.
Of 1066 infants, 89 had FS and 368 had BS. Compared to BS, FS was more likely to be associated with lower birthweight, vaginal delivery, patent ductus arteriosus, postnatal steroids, multiple central lines, longer respiratory support and hospital stay, and higher mortality (p<0.05). Analyses controlling for covariates showed significant group differences over time for IFN-γ, IL-10, IL-18, TGF-β and TNF-α (p<0.05).
Significant differences in profiles for IFN-γ, IL-10, IL-18, TGF-β and TNF-α in FS, BS or NS in this hypothesis-generating secondary study require validation in rigorously designed prospective studies and may have implications for diagnosis and treatment.