Intensive Care Unit Network Research Articles

A Multifaceted Intervention for Quality Improvement in a Network of Intensive Care Units

Evidence-based practices improve intensive care unit (ICU) outcomes, but eligible patients may not receive them. Community hospitals treat most critically ill patients but may have few resources dedicated to quality improvement. To determine the effectiveness of a multicenter quality improvement program to increase delivery of 6 evidence-based ICU practices. Pragmatic cluster-randomized trial among 15 community hospital ICUs in Ontario, Canada. A total of 9269 admissions occurred during the trial (November 2005 to October 2006) and 7141 admissions during a decay-monitoring period (December 2006 to August 2007). We implemented a videoconference-based forum including audit and feedback, expert-led educational sessions, and dissemination of algorithms to sequentially improve delivery of 6 practices. We randomized ICUs into 2 groups. Each group received this intervention, targeting a new practice every 4 months, while acting as control for the other group, in which a different practice was targeted in the same period. MAIN MEASURE OUTCOMES: The primary outcome was the summary ratio of odds ratios (ORs) for improvement in adoption (determined by daily data collection) of all 6 practices during the trial in intervention vs control ICUs. Overall, adoption of the targeted practices was greater in intervention ICUs than in controls (summary ratio of ORs, 2.79; 95% confidence interval [CI], 1.00-7.74). Improved delivery in intervention ICUs was greatest for semirecumbent positioning to prevent ventilator-associated pneumonia (90.0% of patient-days in last month vs 50.0% in first month; OR, 6.35; 95% CI, 1.85-21.79) and precautions to prevent catheter-related bloodstream infection (70.0% of patients receiving central lines vs 10.6%; OR, 30.06; 95% CI, 11.00-82.17). Adoption of other practices, many with high baseline adherence, changed little. In a collaborative network of community ICUs, a multifaceted quality improvement intervention improved adoption of care practices. clinicaltrials.gov Identifier: NCT00332982.

Neurobehavioral Abnormalities in Newborns with Congenital Heart Disease Requiring Open-Heart Surgery

In a prospective study, we evaluated the perioperative application of the Neonatal Intensive Care Unit Network Neurobehavioral Scale in a cohort of newborns with congenital heart disease (CHD). Infants with CHD were found to have suboptimal neurobehavioral performance compared with healthy infants without CHD, with particular vulnerability in the Regulation and Stress subscales.

Quality in quality improvement research - a new benchmark

Expanded abstractCitationScales DC, Dainty K, Hales B, Pinto R, Fowler RA, Adhikari NK, Zwarenstein M: A multifaceted intervention for quality improvement in a network of intensive care units: a cluster randomized trial. JAMA 2011, 305:363-72.ContextEvidence-based practices improve intensive care unit (ICU) outcomes, but eligible patients may not receive them. Community hospitals treat most critically ill patients but may have few resources to devote to quality improvement.ObjectiveTo determine the effectiveness of a multicenter quality improvement program to increase delivery of 6 evidence-based ICU practices.Design, setting, and participantsPragmatic, cluster-randomized trial among 15 community hospital ICUs in Ontario, Canada. A total of 9269 admissions occurred during the trial (November 2005 to October 2006) and 7141 admissions during a decay-monitoring period (December 2006 to August 2007).InterventionThe authors implemented a videoconference-based forum including audit and feedback, expert-led educational sessions, and dissemination of algorithms to sequentially improve delivery of 6 practices. The ICUs were randomized into 2 groups. Each group received this intervention, targeting a new practice every 4 months, while acting as control for the other group, in which a different practice was targeted in the same period.Main outcomesThe primary outcome was the summary ratio of odds ratios (ORs) for improvement in adoption (determined by daily data collection) of all 6 practices during the trial in intervention vs control ICUs.ResultsOverall, adoption of the targeted practices was greater in intervention ICUs than in controls (summary ratio of ORs, 2.79; 95% confidence interval [CI], 1.00-7.74). Improved delivery in intervention ICUs was greatest for semi recumbent positioning to prevent ventilator-associated pneumonia (90.0% of patient-days in last month vs. 50.0% in first month; OR, 6.35; 95% CI, 1.85-21.79) and precautions to prevent catheter-related bloodstream infection (70.0% of patients receiving central lines vs. 10.6%; OR, 30.06; 95% CI, 11.00-82.17). Adoption of other practices, many with high baseline adherence, changed little.ConclusionIn a collaborative network of community ICUs, a multi-faceted quality improvement intervention improved adoption of care practices.

Common variants of TLR1 associate with organ dysfunction and sustained pro-inflammatory responses during sepsis.

BackgroundToll-like receptors (TLRs) are critical components for host pathogen recognition and variants in genes participating in this response influence susceptibility to infections. Recently, TLR1 gene polymorphisms have been found correlated with whole blood hyper-inflammatory responses to pathogen-associated molecules and associated with sepsis-associated multiorgan dysfunction and acute lung injury (ALI). We examined the association of common variants of TLR1 gene with sepsis-derived complications in an independent study and with serum levels for four inflammatory biomarkers among septic patients.Methodology/Principal FindingsSeven tagging single nucleotide polymorphisms of the TLR1 gene were genotyped in samples from a prospective multicenter case-only study of patients with severe sepsis admitted into a network of intensive care units followed for disease severity. Interleukin (IL)-1β, IL-6, IL-10, and C-reactive protein (CRP) serum levels were measured at study entry, at 48 h and at 7th day. Alleles -7202G and 248Ser, and the 248Ser-602Ile haplotype were associated with circulatory dysfunction among severe septic patients (0.001≤p≤0.022), and with reduced IL-10 (0.012≤p≤0.047) and elevated CRP (0.011≤p≤0.036) serum levels during the first week of sepsis development. Additionally, the -7202GG genotype was found to be associated with hospital mortality (p = 0.017) and ALI (p = 0.050) in a combined analysis with European Americans, suggesting common risk effects among studies.Conclusions/SignificanceThese results partially replicate and extend previous findings, supporting that variants of TLR1 gene are determinants of severe complications during sepsis.

Neurobehavior of Late Preterm Infants of Adolescent Mothers

Background: Late preterm infants have higher morbidity in the neonatal period and difficulties at school age. There are few data about neonatal neurobehavior performance that may interfere in their development. Objectives: To compare the neurobehavior of healthy late preterm and full-term neonates born to adolescent mothers. Methods: This prospective cross-sectional study included infants with a gestational age of 40^0/7–40^6/7 weeks (full term) and 34^0/7–36^6/7 weeks (late preterm) aged 24–72 h without exposure to alcohol, tobacco, drugs or infections and free of clinical problems during the first 3 days of life. Infants were assessed with the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS). Outcomes were analyzed by ANOVA. Results: From July 2001 to November 2002, 3,685 infants were born, 928 of adolescent mothers. After exclusion, 36 late preterm and 96 term infants were enrolled. Adjusted for anesthesia type, delivery mode, gender, age at NNNS examination, time between last feeding and examination, and examination duration, late preterm, compared to term neonates, presented lower scores for attention (p = 0.041), arousal (p = 0.011), regulation (p < 0.001), quality of movements (p < 0.001) and higher scores for non-optimal reflexes (p < 0.001) and hypotonicity (p = 0.029). Conclusion: Late preterm infants of adolescent mothers have a more immature neurobehavioral performance at 24–72 h of life in multiple areas compared to term neonates suggesting a need for careful follow-up.

Infant Neurobehavior Following Prenatal Exposure to Methadone or Buprenorphine: Results From the Neonatal Intensive Care Unit Network Neurobehavioral Scale

This study examined the neurobehavioral functioning of neonates prenatally exposed to methadone (n = 11) or buprenorphine (n = 10), who underwent the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) examinations on days 3, 5, 7, 10, and 14 post-delivery. Linear mixed model analyses revealed that NNNS scores of arousal and excitability showed significant differences between medications over time. Compared to neonates who did not require medication to treat neonatal abstinence syndrome (NAS), neonates receiving pharmacotherapy for NAS showed differences over time in quality of movement, excitability, and lethargy. Results suggest the NNNS may detect subtle differences over time between both neonates prenatally exposed to methadone or buprenorphine and neonates pharmacologically treated or untreated for NAS.

Neurobehavioral Assessment Predicts Motor Outcome in Preterm Infants

To determine whether Neonatal Intensive Care Unit Network Neurobehavior Scales (NNNS) at 44 weeks predict motor outcome at 2 years in preterm infants from the Maternal Lifestyles Study (MLS). Data were collected on all preterm infants (<36 weeks) in the MLS who underwent an NNNS at 44 weeks (n = 395) and neurologic examination at 12 to 36 months or Bayley Psychomotor Development Index (PDI) at 24 months (n = 270). Logistic regression analyzed NNNS summary scores associated with cerebral palsy (CP) or PDI <70, while controlling for birth weight </=1250 g. Eighteen of 395 infants (5%) had CP; 24 of 270 infants (9%) had PDI <70. CP was associated with low quality of movement (odds ratio [OR], 1.95; 95% CI, 1.24-3.06; P = .004) and high lethargy (OR, 1.67; 95% CI, 1.01-2.76; P = .045). The model contributed 19% of the variance in CP diagnosis at 12 to 36 months (R(2) = .19, P < .001). Low PDI was associated with low handling (OR, 1.83; 95% CI, 1.12-2.99; P = .017), low quality of movement (OR, 2.16; 95% CI, 1.38-3.38; P = .001), and hypotonia (OR, 1.63; 95% CI, 1.14-2.32; P = .007). The model contributed 26% of the variance in PDI <70 at 24 months (R(2) = 0.26, P < .001). The neurobehavioral profile of under-arousal in 44-week-old preterm infants may predict poor motor outcome.

Neurobehavior at Term and White and Gray Matter Abnormalities in Very Preterm Infants

To examine the relationship between very preterm infant neurobehavior at term and concurrent magnetic resonance-defined cerebral abnormalities. 168 very preterm infants (birth weight <1250 g or gestation <30 weeks) were examined at term with 2 standardized neurobehavioral assessments, the Revised Hammersmith Neonatal Neurological Examination and the Neonatal Intensive Care Unit Network Neurobehavioral Scale. The relationship between composite neurobehavioral scores and qualitative white and gray matter abnormalities on magnetic resonance imaging was determined. Poorer neurobehavioral performance related to magnetic resonance-defined cerebral abnormalities. Composite neurobehavioral scores related to the total grade of white matter abnormality, and worse neurobehavior related most strongly to 2 components of this grade: white matter signal abnormalities and reduction in white matter volumes. Neurobehavior was not related to the total grade of gray matter abnormality. However, delayed gyral maturation, a component of the total gray matter grade, was related to poorer performance on both neurobehavioral scales. Very preterm infant neurobehavior at term is related to concurrent cerebral abnormalities in both white and gray matter defined by qualitative magnetic resonance imaging.

Prevention and Diagnosis of Ventilator-Associated Pneumonia

Prevention and Diagnosis of Ventilator-Associated Pneumonia

Neurocomportamento de recém-nascidos a termo, pequenos para a idade gestacional, filhos de mães adolescentes

OBJETIVO: Comparar o neurocomportamento de recém-nascidos a termo pequenos (PIG) e adequados (AIG) para a idade gestacional, filhos de mães adolescentes. MÉTODOS: Estudo transversal prospectivo de nascidos a termo AIG e PIG, com 24-72 horas de vida, sem afecções do sistema nervoso central. Os neonatos foram avaliados por meio da Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) para: habituação, atenção, despertar, controle, manobras para a orientação, qualidade dos movimentos, excitabilidade, letargia, reflexos não ótimos, assimetria, hipertonia, hipotonia e sinais de estresse e abstinência. A comparação dos grupos AIG e PIG foi feita por análise de variância e teste do qui-quadrado. Aplicou-se a regressão multivariada para analisar os fatores associados ao escore de cada variável do NNNS. RESULTADOS: Dos 3.685 nascidos no local do estudo, 928 (25%) eram de mães adolescentes. Desses, 477 satisfizeram os critérios de inclusão, sendo 419 (88%) AIG e 58 (12%) PIG. A análise univariada não mostrou diferença em nenhuma das variáveis da NNNS entre os PIG e os AIG. Na análise multivariada, os PIG nascidos de parto vaginal apresentaram menor escore na variável qualidade de movimentos do que os nascidos por cesárea. Os PIG nascidos com anestesia local ou sem anestesia apresentaram maior escore na variável excitabilidade do que os nascidos sob anestesia loco-regional. Os PIG femininos tiveram menor escore na variável sinais de estresse/abstinência que os masculinos. CONCLUSÃO: Os recém-nascidos PIG de mães adolescentes mostraram menor qualidade de movimento, mais excitabilidade e mais sinais de estresse, em associação com o sexo do neonato e com variáveis relacionadas ao parto.

Neurobehavior of full-term small for gestational age newborn infants of adolescent mothers

To compare the neurobehavior of small (SGA) and adequate (AGA) for gestational age full-term neonates born to adolescent mothers. This prospective cross-sectional study included full-term newborn infants aged 24-72 hours, free from central nervous system malformations and born to adolescent mothers at a single center in Brazil. Infants were assessed with the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) for: habituation, attention, arousal, regulation, handling, quality of movement, excitability, lethargy, nonoptimal reflexes, asymmetry, hypertonia, hypotonia, and stress/abstinence signals. The chi-square test and analysis of variance were used to compare SGA and AGA infants. Multivariate regression was used to analyze factors associated with the score of each NNNS variable. Of 3,685 infants born in the study hospital, 928 (25%) had adolescent mothers. Of these, 477 infants met the inclusion criteria: 419 (88%) were AGA and 58 (12%) were SGA. Univariate analysis did not show any differences between AGA and SGA neonates in terms of NNNS variables. Multivariate analysis showed that SGA neonates born by vaginal delivery had lower scores for quality of movements than those born by caesarean section. The SGA neonates born with local or without anesthesia had higher scores for excitability than those born with spinal anesthesia. Additionally, female SGA neonates had lower scores for stress/abstinence signals than males. SGA neonates born to adolescent mothers showed poorer quality of movements, more excitability and more signals of stress in association with sex of infant and variables related to delivery.

Another Look at Steroid Therapy for Septic Shock

Another Look at Steroid Therapy for Septic Shock

Mortality and Morbidities Among Very Premature Infants Admitted After Hours in an Australian Neonatal Intensive Care Unit Network

Mortality and Morbidities Among Very Premature Infants Admitted After Hours in an Australian Neonatal Intensive Care Unit Network

Neurobehavioral profile of healthy full-term newborn infants of adolescent mothers

Background: The Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) is used to assess neurological integrity, behavioral function and the existence of stress and abstinence signs in newborn infants. Aim: To determine the neurobehavioral profile of healthy term neonates of adolescent mothers. Design: Cross-sectional study with prospective collection of data. Subjects: 419 healthy newborns without analgesic/sedative use at labor, intra-uterine drug exposure, multiple gestation, congenital malformations or infections. The NNNS was applied with 33 ± 7 hours of life in a quiet and dark room, between feedings. Outcome measures: Mean, SD, and 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles for each of 13 NNNS variables were determined and compared according to maternal age (12–14 years vs. 15–17 years vs. 18–19 years) by ANOVA. Results: Mothers had 17 ± 1.5 years, 50% white, 7.1 ± 2.2 years of education, prenatal care in 96%, vaginal delivery in 73%, and local/regional anesthesia in 75%. Neonates had birth weight 3205 ±299 g, gestational age 39.4 ± 1.1 weeks, 55% male, 1 min Apgar 8.2 ± 1.3, and 5 min Apgar 9.6 ±0.6. NNNS scores (mean ± SD): habituation: 6.86 ± 1.49; attention: 5.73 ± 1.32; arousal: 3.70 ± 0.70; regulation: 6.06 ± 0.74; orientation handling procedures: 0.36 ± 0.26; quality of movements: 5.11 ±0.49; excitability: 2.48 ± 1.68; lethargy: 4.04 ± 1.82; non-optimal reflexes: 3.67 ± 1.35; asymmetry: 0.71 ± 0.94; hypertonicity: 0.18 ± 0.39; hypotonicity: 0.13 ± 037; and stress/abstinence signs: 0.07 ± 0.05. Infants of younger adolescent mothers were less lethargic than infants of older ones. Conclusion The description of the neurobehavioral profile of healthy term newborns of adolescent mothers is important to establish normal standards for this population.

Impact of a five-year surveillance of central venous catheter infections in the REACAT intensive care unit network in France

Central venous catheter (CVC)-related infections (CRIs) are a key target for infection control in intensive care units (ICUs). The aim of this study was to describe temporal trends of CRI incidence in a network of volunteer ICUs in Northern France. During a 4 month surveillance period each year, all CVCs in place for more than 48h were prospectively followed until removal or patient discharge. Standard clinical and microbiological criteria were used to define colonization and CRI. The standardized incidence ratio (SIR) was estimated by dividing the number of observed CRIs by the number of expected CRIs, which was computed using a logistic regression model including risk factors for CRI. CRI incidence and SIR were fed back to ICUs as a benchmark at the end of each period. From 2001 to 2005, 135 ICUs participated for at least one surveillance period. Overall, 11 703 CVC in 9182 patients (122 495 CVC-days) were included. CRI incidence was 2.8 per 1000 CVC-days. Among 35 ICUs that participated for three or more consecutive periods, CRI incidence decreased significantly by 58.6%. SIR also decreased significantly from the first to the third surveillance period in these ICUs. These results suggest that surveillance programmes have a significant impact on CRI risk in ICUs and remain an important strategy for combating nosocomial infections in these settings.

Alterations in Neurobehavior at Term Reflect Differing Perinatal Exposures in Very Preterm Infants

Preterm infants have higher rates of cognitive and behavioral difficulties at school age than their term-born peers. We hypothesized that neurobehavior at term would be different in very preterm infants compared with term infants and that perinatal exposures would be associated with these alterations in neurobehavior. Two standardized neurobehavioral evaluations were completed on 207 infants at term equivalent, including 168 very preterm infants (<1250 g or <30 weeks' gestation) and 39 term control infants. The assessments used were the Neonatal Intensive Care Unit Network Neurobehavioral Scale and the revised Hammersmith Neonatal Neurologic Examination. The relationship of perinatal variables to preterm infant neurobehavioral scores for both evaluations was examined. Compared with term-born infants, preterm infant neurobehavior was significantly altered for the Hammersmith Neonatal Neurologic Examination total score and all of the subtotals. Similarly, preterm infants displayed altered neurobehavior for the majority of the Neonatal Intensive Care Unit Network Neurobehavioral Scale summary scores. Complete perinatal data were available for 157 of 168 very preterm infants. The perinatal variables most strongly associated with altered preterm infant neurobehavior on multivariate regression analysis included the total number of days of assisted ventilation, intraventricular hemorrhage, and necrotizing enterocolitis. Positive perinatal influences on neurobehavioral performance at term on multivariate analysis included maternal antenatal steroids, female gender, and infants receiving breast milk at discharge home. Preterm infants at term equivalent showed alterations in motor behavior and higher cortically integrated functions. The pattern of abnormality in neurobehavior differed in relation to perinatal exposures. Neurobehavioral examination at term equivalent age is useful in evaluating the impact of neonatal intensive care.

Exposure to marijuana during pregnancy alters neurobehavior in the early neonatal period

To assess the neurobehavior of full-term neonates of adolescent mothers exposed to marijuana during pregnancy. This prospective cross-sectional study included full-term infants within 24 to 72 hours of life born to adolescent mothers at a single center in Brazil. Data on sociodemographic and obstetrical and neonatal characteristics were collected. The mothers underwent the Composite International Diagnostic Interview, and the infants were assessed with the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS). Maternal hair and neonatal meconium were analyzed. Neonates exposed in utero to tobacco, alcohol, cocaine, and/or any other drugs except marijuana were excluded. Of 3685 infants born in the study hospital, 928 (25%) were born to adolescent mothers. Of these, 561 infants met the inclusion criteria and were studied. Marijuana exposure was detected in 26 infants (4.6%). Infants exposed (E) or not exposed (NE) to marijuana differed in the following NNNS variables: arousal (E, 4.05 +/- 1.19 vs NE, 3.68 +/- 0.70), regulation (E, 5.75 +/- 0.62 vs NE, 6.04 +/- 0.72), and excitability (E, 3.27 +/- 1.40 vs NE, 2.40 +/- 1.57). After controlling for confounding variables, the effect of marijuana exposure on these scores remained significant. Marijuana exposure during pregnancy alters the neurobehavioral performance of term newborn infants of adolescent mothers.

Mortality and Morbidities Among Very Premature Infants Admitted After Hours in an Australian Neonatal Intensive Care Unit Network

To assess risk-adjusted early (within 7 days) mortality and major morbidities of newborn infants at < 32 weeks' gestation who are admitted after office hours to a regional Australian network of NICUs where statewide caseload is coordinated and staffed by on-floor registrars working in shift rosters. We hypothesize that adverse sequelae are increased in these infants. We conducted a database review of the records of infants (n = 8654) at < 32 weeks' gestation admitted to a network of 10 tertiary NICUs in New South Wales and the Australian Capital Territory from 1992 to 2002. Multivariate logistic regression analysis was performed to adjust for case-mix and significant baseline characteristics. Sixty-five percent of infants were admitted to the NICUs after hours. These infants did not have an increase in early neonatal mortality or major neonatal sequelae compared with their office-hours counterparts. Admissions during late night hours after midnight or fatigue risk periods before the end of a medical 12-hour shift were not associated with higher early mortality. Risk factors significantly predictive of early neonatal death were lack of antenatal steroid treatment, Apgar score < 7 at 5 minutes, male gender, gestation age, and being small for gestation. Current staffing levels, specialization, and networking are associated with lower circadian variation in adverse outcomes and after-hours admission to this NICU network and have no significant impact on early neonatal mortality and morbidity.

Continuous Positive Airway Pressure for Treatment of Postoperative Hypoxemia

Hypoxemia complicates the recovery of 30% to 50% of patients after abdominal surgery; endotracheal intubation and mechanical ventilation may be required in 8% to 10% of cases, increasing morbidity and mortality and prolonging intensive care unit and hospital stay. To determine the effectiveness of continuous positive airway pressure compared with standard treatment in preventing the need for intubation and mechanical ventilation in patients who develop acute hypoxemia after elective major abdominal surgery. Randomized, controlled, unblinded study with concealed allocation conducted between June 2002 and November 2003 at 15 intensive care units of the Piedmont Intensive Care Units Network in Italy. Consecutive patients who developed severe hypoxemia after major elective abdominal surgery. The trial was stopped for efficacy after 209 patients had been enrolled. Patients were randomly assigned to receive oxygen (n = 104) or oxygen plus continuous positive airway pressure (n = 105). The primary end point was incidence of endotracheal intubation; secondary end points were intensive care unit and hospital lengths of stay, incidence of pneumonia, infection and sepsis, and hospital mortality. Patients who received oxygen plus continuous positive airway pressure had a lower intubation rate (1% vs 10%; P = .005; relative risk [RR], 0.099; 95% confidence interval [CI], 0.01-0.76) and had a lower occurrence rate of pneumonia (2% vs 10%, RR, 0.19; 95% CI, 0.04-0.88; P = .02), infection (3% vs 10%, RR, 0.27; 95% CI, 0.07-0.94; P = .03), and sepsis (2% vs 9%; RR, 0.22; 95% CI, 0.04-0.99; P = .03) than did patients treated with oxygen alone. Patients who received oxygen plus continuous positive airway pressure also spent fewer mean (SD) days in the intensive care unit (1.4 [1.6] vs 2.6 [4.2], P = .09) than patients treated with oxygen alone. The treatments did not affect the mean (SD) days that patients spent in the hospital (15 [13] vs 17 [15], respectively; P = .10). None of those treated with oxygen plus continuous positive airway pressure died in the hospital while 3 deaths occurred among those treated with oxygen alone (P = .12). Continuous positive airway pressure may decrease the incidence of endotracheal intubation and other severe complications in patients who develop hypoxemia after elective major abdominal surgery.

Introduction

The purpose of this supplement is to facilitate researchers’ and clinicians’ use of the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS). The NNNS was developed for the National Institutes of Health (NIH) to assess the neurobehavior of drug-exposed and high-risk infants. In the early 1990s, the NIH began the multisite (Detroit, Michigan; Memphis, Tennessee; Miami, Florida; and Providence, Rhode Island) Maternal Lifestyle Study (MLS), a prospective longitudinal study of in utero cocaine exposure, under the auspices of the National Institute of Child Health and Human Development Neonatal Research Network. The NNNS was developed for use in the MLS under a separate “Neurobehavioral Contract” from the National Institute on Drug Abuse to provide measures for the MLS that were sensitive to drug effects. Part of the mission of the contract was also the dissemination of the measures, a mission fulfilled, in part, by this supplement. The material provided here will enable readers to determine their interest in using the exam. Procedures for learning the exam are described in this issue, and a training manual and assessment kit will be published by Brookes Publishing.This issue includes a preface by T. Berry Brazelton, MD, followed by a history and description of the NNNS and the NNNS procedures, which shows how to perform and score the exam. This is followed by two articles providing NNNS data from the MLS and a low-risk term sample. We then provide an article on clinical uses of the NNNS. Appendices are also included with information on how to compute summary scores.The NNNS represents the combined knowledge of many scientist-clinicians as well as examiners with extensive experience in the neurobehavioral assessment of normal and at-risk infants.We thank the National Institutes of Health for permission to disseminate this material, with special thanks to Linda Wright, National Institute of Child Health and Human Development project officer, and Vincent Smeriglio, National Institute on Drug Abuse project officer, whose combined vision helped lead to the development of this exam. We also thank the Johnson & Johnson Pediatric Institute for generous financial support of this supplement. This work was supported by National Institute of Child Health and Human Development grant 1U10-HD279004 and contract NO1-HD-2-3159, jointly supported by National Institute on Drug Abuse and National Institute of Child Health and Human Development.We thank our mentor, T. Berry Brazelton, for insight, guidance, and support. Other individuals who contributed to the development of the NNNS include Kevin Nugent, Zackariah Boukydis, and Rosemarie Bigsby. From the Maternal Lifestyle Study, we acknowledge the contribution of the other principal investigators, Charles Bauer, Seetha Shankaran, and Henrietta Bada, and the examiners in the 4 sites who provided valuable feedback during the pilot testing and training phase with the NNNS, including Andrea Nadra, Rebecca Van Vorst, Laura Dietz, Lisa Eisen, Susan Gauthier, Kim Yolton, and Eunice Woldt. Kim Yolton was involved from the beginning and has provided new input along with Melissa Fallone and Lynne Andriozzi. Special thanks go to Linda LaGasse for scientific as well as editorial input. Elizabeth Rahdert from the National Institute on Drug Abuse helped start this project. We also thank Dan Griffith.