Short Term Coping-Behaviors and Postpartum Health in a Population-Based Study of Women with a Live Birth, Stillbirth, or Neonatal Death.

OBJECTIVE: Responding to the National Institutes of Health Working Group's call for research on the psychological impact of stillbirth, we compared coping-related behaviors by outcome of an index birth (surviving live birth or perinatal loss - stillbirth or neonatal death) and, among individuals with loss, characterized coping strategies and their association with depressive symptoms 6-36 months postpartum. METHODS: We used data from the Stillbirth Collaborative Research Network follow-up study (2006-2008) of 285 individuals who experienced a stillbirth, 691 a livebirth, and 49 a neonatal death. We conducted a thematic analysis of coping strategies individuals recommended following their loss. We fit logistic regression models, accounting for sampling and inverse probability of follow-up weights to estimate associations between pregnancy outcomes and coping-related behaviors and, separately, coping strategies and probable depression (Edinburgh Postnatal Depression Scale > 12) for those with loss. RESULTS: Compared to those with a surviving live birth and adjusting for pre-pregnancy drinking and smoking, history of stillbirth, and age, individuals who experienced a loss were more likely to report increased drinking or smoking in the two months postpartum (adjusted OR: 2.7, 95% CI = 1.4-5.4). Those who smoked or drank more had greater odds of probable depression at 6 to 36 months postpartum (adjusted OR 6.4, 95% CI = 2.5-16.4). Among those with loss, recommended coping strategies commonly included communication, support groups, memorializing the loss, and spirituality. DISCUSSION: Access to a variety of evidence-based and culturally-appropriate positive coping strategies may help individuals experiencing perinatal loss avoid adverse health consequences.

Placental Lesions Associated With Stillbirth by Gestational Age, as Related to Cause of Death: Follow-Up Results From the Stillbirth Collaborative Research Network.

BACKGROUND: We previously identified placental lesions associated with stillbirths of varying gestational ages (GA) using advanced feature analysis. We further investigated the relationships between placental lesions and cause of death in stillbirths within these GA ranges. METHODS: Using data from the Stillbirth Collaborative Research Network, we derived a sample of stillbirths who underwent placental examination and Initial Causes of Fetal Death (INCODE) evaluation for determining cause of death. We then compared the rates of causes of death within and among GA ranges (extreme preterm stillbirth [PTSB] [<28 weeks], early PTSB [28-336/7 weeks], late PTSB [34-366/7 weeks], term stillbirth [≥37 weeks]) according to the presence of these lesions. RESULTS: We evaluated 352 stillbirths. In extreme PTSB, obstetric complications and infections were associated with acute funisitis. In early PTSB, uteroplacental insufficiency was associated with parenchymal infarcts. In term stillbirth (vs early PTSB), increased syncytial knots were associated with umbilical cord causes and infection. CONCLUSIONS: Placental lesions of high importance in distinguishing stillbirths at different GAs are associated with specific causes of death. This information is important in relating the presence of placental lesions and fetal death and in helping to understand etiologies of stillbirths at different GAs.

Genetic Predisposition to Adverse Neurodevelopmental Outcome of Extremely Low Birth Weight Infants.

OBJECTIVE: This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants. STUDY DESIGN: We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case-control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with p < 0.01 were selected for validation in the replication cohort. Successful replication was defined as p < 0.05 in the replication cohort. RESULTS: Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with p < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis (p = 4.1 × 10-4) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2-1.0; p = 0.039). CONCLUSION: A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants. KEY POINTS: · Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay.. · A genetic variant in SERPINE1 is associated with CP or death among ELBW infants.. · The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor..

Assessing Intrauterine Retention according to Microscopic Stillbirth Features: A Cluster Analysis Approach.

Background: Previous studies identified microscopic changes associated with intrauterine retention of stillbirths based on clinical time of death. The objective of this study was to utilize unsupervised machine learning (not reliant on subjective measures) to identify features associated with time from death to delivery. Methods: Data were derived from the Stillbirth Collaborative Research Network. Features were chosen a priori for entry into hierarchical cluster analysis, including fetal and placental changes. Results: A four-cluster solution (coefficient = 0.983) correlated with relative time periods of "no retention," "mild retention," "moderate retention," and "severe retention." Loss of nuclear basophilia within fetal organs were found at varying rates among these clusters. Conclusions: Hierarchical cluster analysis is able to classify stillbirths based on histopathological changes, roughly correlating to length of intrauterine retention. Such clusters, which rely solely on objective fetal and placental findings, can help clinicians more accurately assess the interval from death to delivery.

Macroscopic lesions of maternal and fetal vascular malperfusion in stillborn placentas: Diagnosis in the absence of microscopic histopathological examination.

INTRODUCTION: Lesions of maternal vascular malperfusion (MVM) and fetal vascular malperfusion (FVM) are common in placentas associated with both stillbirth and live birth. The objective of this study was to identify lesions present more commonly in stillborn placentas and those most indicative of MVM and FVM without microscopic pathologic evaluation. METHODS: Data were derived from the Stillbirth Collaborative Research Network. Lesions were identified according to standard protocols published previously and categorized as either MVM or FVM according to the Amsterdam Placental Workshop Group Consensus Statement and macroscopic "umbilical cord at risk" findings. Multivariate logistic regression was used to determine the odds of stillbirth with macroscopic findings of MVM or FVM. RESULTS: 595 stillbirths and 1,305 live births were analyzed. FVM lesions (85.2%) were marginally more common (though not statistically different) in stillbirths compared to MVM lesions (81.3%). Macroscopic findings of both MVM and FVM were more common in stillbirths versus livebirths (p < 0.001). Odds ratios of macroscopic MVM and FVM lesions for stillbirth, adjusted for gestational age at delivery, maternal race (minority), ethnicity (Hispanic), age, and history of hypertension or diabetes, were 1.48 (95% CI 1.30-1.69) and 1.34 (95% CI 1.18-1.53), respectively. DISCUSSION: Macroscopic features of MVM and FVM are associated with higher odds of stillbirth versus live birth even when controlled for gestational age and maternal factors, which may be a useful clue in determining the pathophysiology of these events. This information is also useful for pathologists when microscopic examination is not available.

Identifying risk of stillbirth using machine learning.

BACKGROUND: Previous predictive models using logistic regression for stillbirth do not leverage the advanced and nuanced techniques involved in sophisticated machine learning methods, such as modeling nonlinear relationships between outcomes. OBJECTIVE: This study aimed to create and refine machine learning models for predicting stillbirth using data available before viability (22-24 weeks) and throughout pregnancy, as well as demographic, medical, and prenatal visit data, including ultrasound and fetal genetics. STUDY DESIGN: This is a secondary analysis of the Stillbirth Collaborative Research Network, which included data from pregnancies resulting in stillborn and live-born infants delivered at 59 hospitals in 5 diverse regions across the United States from 2006 to 2009. The primary aim was the creation of a model for predicting stillbirth using data available before viability. Secondary aims included refining models with variables available throughout pregnancy and determining variable importance. RESULTS: Among 3000 live births and 982 stillbirths, 101 variables of interest were identified. Of the models incorporating data available before viability, the random forests model had 85.1% accuracy (area under the curve) and high sensitivity (88.6%), specificity (85.3%), positive predictive value (85.3%), and negative predictive value (84.8%). A random forests model using data collected throughout pregnancy resulted in accuracy of 85.0%; this model had 92.2% sensitivity, 77.9% specificity, 84.7% positive predictive value, and 88.3% negative predictive value. Important variables in the previability model included previous stillbirth, minority race, gestational age at the earliest prenatal visit and ultrasound, and second-trimester serum screening. CONCLUSION: Applying advanced machine learning techniques to a comprehensive database of stillbirths and live births with unique and clinically relevant variables resulted in an algorithm that could accurately identify 85% of pregnancies that would result in stillbirth, before they reached viability. Once validated in representative databases reflective of the US birthing population and then prospectively, these models may provide effective risk stratification and clinical decision-making support to better identify and monitor those at risk of stillbirth.

Composition of the maternal gastrointestinal microbiome as a predictor of neonatal birth weight.

BACKGROUND: The biological mechanism by which the maternal gastrointestinal microbiota contributes to fetal growth and neonatal birth weight is currently unknown. The purpose of this study was to explore how the composition of the maternal microbiome in varying pre-gravid body mass index (BMI) groups are associated with neonatal birth weight adjusted for gestational age. METHODS: Retrospective, cross-sectional metagenomic analysis of bio-banked fecal swab biospecimens (n = 102) self-collected by participants in the late second trimester of pregnancy. RESULTS: Through high-dimensional regression analysis using principal components (PC) of the microbiome, we found that the best performing multivariate model explained 22.9% of the variation in neonatal weight adjusted for gestational age. Pre-gravid BMI (p = 0.05), PC3 (p = 0.03), and the interaction of the maternal microbiome with maternal blood glucose on the glucose challenge test (p = 0.01) were significant predictors of neonatal birth weight after adjusting for potential confounders including maternal antibiotic use during gestation and total gestational weight gain. CONCLUSIONS: Our results indicate a significant association between the maternal gastrointestinal microbiome in the late second trimester and neonatal birth weight adjusted for gestational age. Moderated by blood glucose at the time of the universal glucose screening, the gastrointestinal microbiome may have a role in the regulation of fetal growth. IMPACT: Maternal blood glucose in the late second trimester significantly moderates the relationship between the maternal gastrointestinal microbiome and neonatal size adjusted for gestational age. Our findings provide preliminary evidence for fetal programming of neonatal birth weight through the maternal gastrointestinal microbiome during pregnancy.

Placental lesions associated with stillbirth by gestational age, according to feature importance: Results from the stillbirth collaborative research network.

INTRODUCTION: Previous studies have identified lesions commonly found in placentas associated with stillbirth but have not distinguished across a range of gestational ages (GAs). The objective of this study was to identify lesions associated with stillbirths at different GAs by adapting methods from the chemical machine learning field to assign lesion importance based on correlation with GA. METHODS: Placentas from the Stillbirth Collaborative Research Network were examined according to standard protocols. GAs at stillbirth were categorized as: <28 weeks (extreme preterm stillbirth [PTSB]), 28-33'6 weeks (early PTSB), 34-36'6 weeks (late PTSB), ≥37 weeks (term stillbirth). We identified and ranked the most discriminating placental features, as well as those that were similar across GA ranges, using Kernel Principal Covariates Regression (KPCovR). RESULTS: These analyses included 210 (47.2%) extreme PTSB, 85 (19.1%) early PTSB, 62 (13.9%) late PTSB, and 88 (19.8%) term stillbirths. When we compute the KPCovR, the first principal covariate indicates that there are four lesions (acute funisitis & nucleated fetal red blood cells found in extreme PTSB; multifocal reactive amniocytes & multifocal meconium found in term stillbirth) that distinguish GA ranges among all stillbirths. DISCUSSION: There are distinct placental lesions present across GA ranges in stillbirths; these lesions are identifiable using sophisticated feature selection. Further investigation may identify histologic changes across gestations that relate to fetal mortality.

Noise in cesarean deliveries: a comprehensive analysis of noise environments in the Labor and Delivery operating room and evaluation of a visual alarm noise abatement program.

BACKGROUND: Cesarean delivery is the most common major surgery worldwide. Noise in healthcare settings leads to impaired communication and concentration, and stress among healthcare providers. Limited information is available about noise at cesarean delivery. OBJECTIVE: This study aimed to achieve a comprehensive analysis of noise that occurs during cesarean deliveries. Sound level meters are used to determine baseline noise levels and to describe the frequency of acute noise generated during a cesarean delivery that will cause a human startle response. Secondarily, we aimed to evaluate the effectiveness of a visual alarm system in mitigating excessive noise. STUDY DESIGN: We completed a preintervention/postintervention observational study of noise levels during cesarean deliveries before and after introduction of a visual alarm system for noise mitigation between February 15, 2021 and August 26, 2021. There were 156 cases included from each study period. Sound pressure levels were analyzed by overall case median decibel levels and by time epoch for relevant phases of the operation. Rapid increases in noise events capable of causing a human startle response, "startle events," were detected by retrospective analysis, with quantification for baselines and analysis of frequency by case type. Median noise levels with interquartile ranges are presented. Data are compared between epochs and case characteristics with nonparametric 2-tailed testing. RESULTS: The median acoustic pressure for all cesarean deliveries was 61.8 (58.8-65.9) (median [interquartile range]) dBA (A-weighted decibels). The median dBA for the full case time period was significantly higher in cases with neonatal intensive care unit team presence (62.1 [60.5-63.9]), admission to the neonatal intensive care unit (62.0 [60.4-63.9]), 5-minute Apgar score <7 (62.2 [61.1-64.3]), multiple gestations (62.6 [62.0-64.2]), and intraoperative tubal sterilization (62.8 [61.5-65.1]). The use of visual alarms was associated with a statistically significant reduction of median noise level by 0.7 dBA, from 61.8 (60.6-63.5) to 61.1 (59.8-63.7) dBA (P<.001). CONCLUSION: The noise intensities recorded during cesarean deliveries were commonly at levels that affect communication and concentration, and above the safe levels recommended by the World Health Organization. Although noise was reduced by 0.7 dBA, the reduction was not clinically significant in reaching a discernible amount (a 3-dB change) or in reducing "startle events." Isolated use of visual alarms during cesarean deliveries is unlikely to be a satisfactory noise mitigation strategy.

Comparative Diagnostic Performance of Estimated Fetal Weight and Isolated Abdominal Circumference for the Detection of Fetal Growth Restriction.

OBJECTIVES: To describe the comparative incidence, detection of small-for-gestational age (SGA), and composite perinatal morbidity (CPM) associated with diagnostic criteria of fetal growth restriction (FGR) by estimated fetal weight (EFW) <10% with those with isolated abdominal circumference (AC) measurements <10%. METHODS: We performed a retrospective cohort study of 1587 patients receiving prenatal care and delivery at our institution. We included all patients with ultrasounds and delivery outcomes available, and excluded terminations, second trimester losses, and pregnancies without ultrasounds. EFW was calculated from Hadlock and use of the Duryea centiles, and AC from Hadlock's reference curves. We determined SGA at birth and defined CPM as birthweight less than 3% or birthweight less than 10% with neonatal morbidity. RESULTS: Of 1587 patients, 28 (1.8%) were classified as FGR by EFW <10%. Three of 12 patients with isolated AC <10% developed EFW <10% later in pregnancy (25%). The performance of each diagnostic criteria were comparable for the outcomes of SGA and CPM, with similar sensitivities, but with decreased specificity for SGA outcome, and an increased false positive rate for patients classified as FGR by isolated AC <10, with a tradeoff of decreased false negatives. CONCLUSIONS: Broadening the diagnosis of FGR to include patients with isolated AC <10 did not significantly increase the detection of pregnancies at risk for SGA or CPM. Our conclusions may be limited by a lack of statistical power given a low frequency of SGA and CPM.

Copy number variants and fetal growth in stillbirths.

BACKGROUND: Fetal growth abnormalities are associated with a higher incidence of stillbirth, with small and large for gestational age infants incurring a 3 to 4- and 2 to 3-fold increased risk, respectively. Although clinical risk factors such as diabetes, hypertension, and placental insufficiency have been associated with fetal growth aberrations and stillbirth, the role of underlying genetic etiologies remains uncertain. OBJECTIVE: This study aimed to assess the relationship between abnormal copy number variants and fetal growth abnormalities in stillbirths using chromosomal microarray. STUDY DESIGN: A secondary analysis utilizing a cohort study design of stillbirths from the Stillbirth Collaborative Research Network was performed. Exposure was defined as abnormal copy number variants including aneuploidies, pathogenic copy number variants, and variants of unknown clinical significance. The outcomes were small for gestational age and large for gestational age stillbirths, defined as a birthweight <10th percentile and greater than the 90th percentile for gestational age, respectively. RESULTS: Among 393 stillbirths with chromosomal microarray and birthweight data, 16% had abnormal copy number variants. The small for gestational age outcome was more common among those with abnormal copy number variants than those with a normal microarray (29.5% vs 16.5%; P=.038). This finding was consistent after adjusting for clinically important variables. In the final model, only abnormal copy number variants and maternal age remained significantly associated with small for gestational age stillbirths, with an adjusted odds ratio of 2.22 (95% confidence interval, 1.12-4.18). Although large for gestational age stillbirths were more likely to have an abnormal microarray: 6.2% vs 3.3% (P=.275), with an odds ratio of 2.35 (95% confidence interval, 0.70-7.90), this finding did not reach statistical significance. CONCLUSION: Genetic abnormalities are more common in the setting of small for gestational age stillborn fetuses. Abnormal copy number variants not detectable by traditional karyotype make up approximately 50% of the genetic abnormalities in this population.

Holding a baby after stillbirth: the impact of fetal congenital and structural abnormalities.

OBJECTIVE: Stillbirth can result in numerous adverse psychosocial sequelae. Recommendations vary with regard to holding the baby after a stillbirth. Few studies have addressed the impact of fetal abnormalities on these outcomes. STUDY DESIGN: Analyses of singleton stillbirths within the Stillbirth Collaborative Research Network were conducted. Patient and stillbirth characteristics were compared between those who did and did not hold their baby. Results from psychometric surveys were compared between cases with and without visible fetal anomalies. RESULT: There were no significant differences between those who held and those who did not hold in any patient or stillborn characteristics. Visible fetal abnormalities were not associated with adverse psychological outcomes. CONCLUSION: Fetal abnormalities, including congenital and post-demise changes, do not differ between those who held and did not hold their baby after stillbirth. This suggests that patients should not be discouraged from holding their stillborn infant in the presence of visible abnormalities.

Metagenomic characterization of the maternal prenatal gastrointestinal microbiome by pregravid BMI.

OBJECTIVE: The incidence of women entering into pregnancy with BMI indicating overweight or obesity is rising with concurrent increases in adverse complications such as gestational diabetes. Although several studies have examined the compositional changes to the microbiome across BMI classifications, there has been no investigation regarding changes in microbial function during pregnancy. METHODS: A total of 105 gastrointestinal microbiome biospecimens were used in this analysis. Biospecimens were sequenced by using the Illumina NovaSeq 6000 shotgun metagenomics platform. RESULTS: Findings indicate an enrichment in microbiota from the phylum Firmicutes across all pregravid BMI groups with a decrease in α diversity in groups with BMI indicating obesity or overweight compared with a group with BMI indicating normal weight (p = 0.02). More specifically, women with BMI indicating obesity or overweight had enrichment in Bifidobacterium bifidum and B. adolescentis. Women with BMI > 25 kg/m2 had a higher abundance of microbiota that support biotin synthesis and regulate epithelial cells in the lower gastrointestinal tract. These epithelial cells are responsible for host adaptability to dietary lipid variation and caloric absorption. CONCLUSIONS: Our analysis suggests that there are differences in microbial composition and function between BMI groups. Future research should consider how these changes contribute to specific clinical outcomes during pregnancy.

Association between microbial composition, diversity, and function of the maternal gastrointestinal microbiome with impaired glucose tolerance on the glucose challenge test.

Over the last two decades, the incidence of gestational diabetes (GDM) has almost doubled resulting in almost 9% of pregnant women diagnosed with GDM. Occurring more frequently than GDM is impaired glucose tolerance (IGT), also known as pre-diabetes, but it has been understudied during pregnancy resulting in a lack of clinical recommendations of maternal and fetal surveillance. The purpose of this retrospective, cross-sectional study was to examine the association between microbial diversity and function of the maternal microbiome with IGT while adjusting for confounding variables. We hypothesized that reduced maternal microbial diversity and increased gene abundance for insulin resistance function will be associated with IGT as defined by a value greater than 140 mg/dL on the glucose challenge test. In the examination of microbial composition between women with IGT and those with normal glucose tolerance (NGT), we found five taxa which were significantly different. Taxa higher in participants with impaired glucose tolerance were Ruminococcacea (p = 0.01), Schaalia turicensis (p<0.05), Oscillibacter (p = 0.03), Oscillospiraceae (p = 0.02), and Methanobrevibacter smithii (p = 0.04). When we further compare participants who have IGT by their pre-gravid BMI, five taxa are significantly different between the BMI groups, Enterobacteriaceae, Dialister micraerophilus, Campylobacter ureolyticus, Proteobacteria, Streptococcus Unclassified (species). All four metrics including the Shannon (p<0.00), Simpson (p<0.00), Inverse Simpson (p = 0.04), and Chao1 (p = 0.04), showed a significant difference in alpha diversity with increased values in the impaired glucose tolerance group. Our study highlights the important gastrointestinal microbiome changes in women with IGT during pregnancy. Understanding the role of the microbiome in regulating glucose tolerance during pregnancy helps clinicians and researchers to understand the importance of IGT as a marker for adverse maternal and neonatal outcomes.

DLK1: A Novel Biomarker of Placental Insufficiency in Stillbirth and Live Birth.

OBJECTIVE: Delta-like homolog 1 (DLK1) is a growth factor that is reduced in maternal sera in pregnancies with small for gestational age neonates. We sought to determine if DLK1 is associated with stillbirth (SB), with and without placental insufficiency. STUDY DESIGN: A nested case-control study was performed using maternal sera from a multicenter case-control study of SB and live birth (LB). SB and LB were stratified as placental insufficiency cases (small for gestational age <5% or circulatory lesions on placental histopathology) or normal placenta controls (appropriate for gestational age and no circulatory lesions). Enzyme-linked immunosorbent assay (ELISA) was used to measure DLK1. The mean difference in DLK1 was compared on the log scale in an adjusted linear regression model with pairwise differences, stratified by term/preterm deliveries among DLK1 results in the quantifiable range. In exploratory analysis, geometric means were compared among all data and the proportion of "low DLK1" (less than the median value for gestational age) was compared between groups and modeled using linear and logistic regression, respectively. RESULTS: Overall, 234 SB and 234 LB were analyzed; 246 DLK1 values were quantifiable within the standard curve. Pairwise comparisons of case and control DLK1 geometric means showed no significant differences between groups. In exploratory analysis of all data, adjusted analysis revealed a significant difference for the LB comparison only (SB: 71.9 vs. 99.1 pg/mL, p = 0.097; LB: 37.6 vs. 98.1 pg/mL, p = 0.005). In exploratory analysis of "low DLK1," there was a significant difference between the odds ratio of having "low DLK1" between preterm cases and controls for both SB and LB. There were no significant differences in geometric means nor "low DLK1" between SB and LB. CONCLUSION: In exploratory analysis, more placental insufficiency cases in preterm SB and LB had "low DLK1." However, low DLK1 levels were not associated with SB. KEY POINTS: · Maternally circulating DLK1 is correlated with placental insufficiency.. · Maternally circulating DLK1 is not correlated with SB.. · DLK1 is a promising marker for placental insufficiency..

Prediction of Cerebral Palsy or Death among Preterm Infants Who Survive the Neonatal Period.

OBJECTIVE: To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death. STUDY DESIGN: This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes (n = 11) and demographic and clinical factors (n = 10) evident by the time of discharge among surviving infants (n = 1889) and the primary outcome of death or moderate/severe CP at age 2 (n = 73) was estimated, and a prediction model was created. RESULTS: Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67-0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1-13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6-104.6), and male gender (OR: 2.5, CI: 1.4-4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78-0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants. CONCLUSION: IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae. KEY POINTS: · Factors known at hospital discharge are identified which are independently associated with death or CP by age 2.. · A model was created and validated using these findings to counsel parents.. · The risk of death or CP can be calculated at the time of hospital discharge..