Association of ApoE Genotypes and Recovery From Intracerebral Hemorrhage in Very Low Birth Weight Infants

Background and Purpose: Associations of APOE genotypes with intracerebral hemorrhage (ICH) in preterm infants were previously described. In adults, APOE-ε4 genotype has been proposed as susceptibility factor for impaired recovery after cerebral insult. We here aim to determine APOE genotype-specific neurological consequences of neonatal ICH at school age. Methods: In this multicenter observational cohort study, very low birth weight (<1500 g, <32 weeks gestational age) children were studied for cerebral palsy (CP) after ultrasound diagnosed ICH stratified by APOE genotype. Follow-up examination was done at the age of 5 to 6 years. Study personnel were blinded for perinatal information and complications. Participants were born between January 1, 2009 and December 31, 2013 and enrolled in the German Neonatal Network. Of 8022 infants primarily enrolled, 2467 children were invited for follow-up between January 1, 2014 and December 31, 2019. Univariate analyses and multivariate logistic regression models were used to assess the impact of APOE genotype (APOE-ε2, APOE-ε3, APOE-ε4) on CP after ICH. Results: Two thousand two hundred fifteen children participated at follow-up, including 363 children with ultrasound diagnosed neonatal ICH. In univariate analyses of children with a history of ICH, APOE-ε3 carriers had lower frequencies of CP (n=33/250; 13.2 [95% CI, 9.4%–17.8%]), as compared to APOE-ε2 (n=15/63; 23.8 [14.6%–35.3%], P =0.037) and –ε4 carriers (n=31/107; 29.0 [21.0%–38.0%], P <0.001), respectively. Regression models revealed an association of APOE-ε4 genotype and CP development (odds ratio, 2.77 [1.44–5.32], P =0.002) after ICH. Notably, at low-grade ICH (grade I) APOE-ε4 expression resulted in an increased rate of CP (n=6/39; 15.4 [6.7–29.0]) in comparison to APOE-ε3 (n=2/105; 1.9 [0.4%–6.0%], P =0.002). Conclusions: APOE-ε4 carriers have an increased risk for long-term motor deficits after ICH. We assume an effect even after low-grade neonatal ICH, but more data are needed to clarify this issue.

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Abstract WP359: Higher Risk of Intracerebral Hemorrhage Recurrence Among African American and Latino/Hispanic Individuals

Stroke ◽

10.1161/str.48.suppl_1.wp359 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Axana Rodriguez-Torres ◽

Christina Kourkoulis ◽

Kristin Schwab ◽

Alison M Ayres ◽

M. Edip Gurol ◽

...

Keyword(s):

Risk Factors ◽

African American ◽

Intracerebral Hemorrhage ◽

Cox Regression ◽

Apoe Genotype ◽

Recurrence Risk ◽

Single Center ◽

Apoe Ε4 ◽

Phone Calls

Introduction: Intracerebral hemorrhage (ICH) is more prevalent among African American (AA) and Latino/Hispanic (LH) individuals. While ICH survivors are at high risk for rebleeding, it is unclear whether recurrence risk differs based on race / ethnicity. Hypothesis: We sought to clarify: 1) whether ICH recurrence risk is higher for AA and LH patients; 2) whether this disparity is explained by the most potent ICH risk factors, i.e. hypertension severity and the APOE gene variant ε4. Methods: We conducted a single-center longitudinal study enrolling 738 ICH survivors presenting to a single center from January 2006 to December 2014. Participants had APOE genotype determined at enrollment, and were followed via phone calls and review of medical records. We captured hypertension severity as absolute blood pressure (BP) measures, as well as BP variability (average percent variation during follow-up). We created univariable and multivariable (Cox regression) models to identify risk factors for ICH recurrence. Results: Systolic BP (SBP) was associated with increased ICH recurrence risk ( Hazard Ratio [HR]=1.30, 95% Confidence Interval [CI] 1.02 -1.66, p=0.036), as was SBP variation (HR=1.75 per variation quartile, 95% CI 1.09-2.81, p=0.021). APOE ε4 was also associated with ICH recurrence (HR=1.66, 95% CI 1.10-2.50, p=0.016). After adjusting for BP and APOE ε4, both LH ( HR=1.68, 95% CI 1.01-2.78, p = 0.045 ) and AA ( HR= 2.12, 95% CI 1.14-3.95, p = 0.019 ) patients when at higher risk for ICH recurrence. Both AA and LH patients had a significantly higher systolic BP (SBP) during follow-up (Figure, A); AA individuals also had greater SBP variation during follow up (Figure, B ). Conclusions: AA and LH patients are at higher risk for ICH recurrence, and hypertension severity / APOE ε4 did not fully account for this disparity. Additional studies will be required to further elucidate biological determinants for this health

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20 Jahre Follow-up von «very low-birth-weight»-Kindern

Praxis ◽

10.1024/0369-8394.92.13.612 ◽

2003 ◽

Vol 92 (13) ◽

pp. 612-613

Author(s):

M. Koller

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Very Low Birth Weight

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Primary Follow-up Care in a Multidisciplinary Setting Enhances Catch-up Growth of Very-low-birth-weight Infants

Journal of the American Dietetic Association ◽

10.1016/s0002-8223(97)00096-5 ◽

1997 ◽

Vol 97 (4) ◽

pp. 386-390 ◽

Cited By ~ 7

Author(s):

STEPHANIE R. BRYSON ◽

LEA THERIOT ◽

NELL J. RYAN ◽

JANET POPE ◽

NANCY TOLMAN ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Very Low Birth Weight ◽

Low Birth Weight Infants ◽

Follow Up Care ◽

Catch Up

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Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

The Journal of Pediatrics ◽

10.1016/j.jpeds.2006.12.013 ◽

2007 ◽

Vol 150 (4) ◽

pp. 345-350 ◽

Cited By ~ 33

Author(s):

Patricia A. Nixon ◽

Lisa K. Washburn ◽

Michael S. Schechter ◽

T. Michael O’Shea

Keyword(s):

Randomized Controlled Trial ◽

Birth Weight ◽

Low Birth Weight ◽

Very Low Birth Weight ◽

Controlled Trial ◽

Low Birth Weight Infants ◽

Follow Up Study ◽

Randomized Controlled ◽

Dexamethasone Therapy

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Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

Yearbook of Pediatrics ◽

10.1016/s0084-3954(08)79235-2 ◽

2009 ◽

Vol 2009 ◽

pp. 429-431

Author(s):

J.A. Stockman

Keyword(s):

Randomized Controlled Trial ◽

Birth Weight ◽

Low Birth Weight ◽

Very Low Birth Weight ◽

Controlled Trial ◽

Low Birth Weight Infants ◽

Follow Up Study ◽

Randomized Controlled ◽

Dexamethasone Therapy

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GROWTH OF VERY LOW BIRTH WEIGHT PRETERM UNTIL 12 MONTHS OF CORRECTED AGE

Journal of Human Growth and Development ◽

10.7322/jhgd.90228 ◽

2015 ◽

Vol 25 (3) ◽

pp. 351 ◽

Cited By ~ 2

Author(s):

Milene De Moraes Sedrez Rover ◽

Cláudia Silveira Viera ◽

Beatriz Rosana G. de Oliveira Toso ◽

Sabrina Grassiolli ◽

Bruna Maria Bugs

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Neonatal Intensive Care ◽

Very Low Birth Weight ◽

Progressive Increase ◽

Z Score ◽

Monitoring Methods ◽

Male Birth ◽

Growth Changes

Introduction: facing the progressive increase in the survival of premature ta infants, a concern for health professionals would be related to the possible consequences arising from prematurity, among them the growth changes. Objectives: to describe the anthropometric variables of newborns Premature Very Low Birth Weight in the follow-up monitoring. Methods: observational, longitudinal and retrospective study, involving 71 children who left Neonatal Intensive Care Unit (NICU), with a weight lower than 1500 g who were treated between 2006 and 2013. They should have at least three outpatient visits within twelve months of corrected age after NCAU discharge, in the following periods: period I up to 3 months of corrected age; period II between 4-6 months of corrected age and period III between 7-12 months of corrected age. Results: the mean Gestational Age (GA) was 29.4 weeks, 51% male, birth weight 1073.2 g, 70% with appropriate GA. The hospitalization stay was 68.73 days. Weight Z score at birth -0.95; at discharge -3.05; in period I -2.4; period II -1.8; period III -1.2. Height at birth -1.21, at discharge -2.23; -2.5; -1.8 and -1.1 for the periods I, II and III , respectively. Regarding the PT Z score at birth -0.71; at discharge -1.5; and monitoring -1.1; - 0.8 and -0.5 respectively in the periods I, II and III. Conclusions: despite of the great Z score reduction in NICU, there was a progressive improvement during follow-up in the Z score in the three anthropometric variables.

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Neurodevelopmental Outcome at 36 Months' Corrected Age of Preterm Infants in the Multicenter Indomethacin Intraventricular Hemorrhage Prevention Trial

PEDIATRICS ◽

10.1542/peds.98.4.714 ◽

1996 ◽

Vol 98 (4) ◽

pp. 714-718 ◽

Cited By ~ 5

Author(s):

Laura R. Ment ◽

Betty Vohr ◽

William Oh ◽

David T. Scott ◽

Walter C. Allan ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Intraventricular Hemorrhage ◽

Maternal Education ◽

Low Dose ◽

Very Low Birth Weight ◽

Cranial Ultrasound ◽

The Mean ◽

English Monolingual

Objectives. Low-dose indomethacin has been shown to prevent intraventricular hemorrhage (IVH) in very low birth weight neonates, and long-term neurodevelomental follow-up data are needed to validate this intervention. We hypothesized that the early administration of low-dose indomethacin would not be associated with adverse cognitive outcome at 36 months' corrected age (CA). Methods. We enrolled 431 neonates of 600 to 1250 g birth weight with no IVH at 6 to 12 hours in a randomized, prospective trial to determine whether low-dose indomethacin would prevent IVH. A priori, neurodevelopmental follow-up examinations, including the Stanford-Binet Intelligence Scale and Peabody Picture Vocabulary Test-Revised, and standard neurologic examinations were planned at 36 months' CA. Results. Three hundred eighty-four of the 431 infants survived (192 [92%] of 209 infants receiving indomethacin versus 192 [86%] of 222 infants receiving saline), and 343 (89%) children were examined at 36 months' CA. Thirteen (8%) of the 166 infants who received indomethacin and 14 (8%) of 167 infants receiving the placebo were found to have cerebral palsy. There were no differences in the incidence of deafness or blindness between the two groups. For the 248 English-monolingual children for whom IQ data follow, the mean gestational age was significantly younger for the infants who received indomethacin than for those who received the placebo. None of the 115 infants who received indomethacin was found to have ventriculomegaly on cranial ultrasound at term, compared with 5 of 110 infants who received the placebo. The mean ± SD Stanford-Binet IQ score for the 126 English-monolingual children who had received indomethacin was 89.6 ± 18.92, compared with 85.0 ± 20.79 for the 122 English-monolingual children who had received the placebo. Although maternal education was strongly correlated with Stanford-Binet IQ at 36 months' CA, there was no difference in educational levels between mothers of the infants receiving indomethacin and the placebo. Conclusions. Indomethacin administered at 6 to 12 hours as prophylaxis against IVH in very low birth weight infants does not result in adverse cognitive or motor outcomes at 36 months' CA.

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Factors Predictive of Follow-up Clinic Attendance and Developmental Outcome in a Regional Cohort of Very Low Birth Weight Infants

American Journal of Epidemiology ◽

10.1093/oxfordjournals.aje.a116908 ◽

1993 ◽

Vol 138 (9) ◽

pp. 704-713 ◽

Cited By ~ 39

Author(s):

M. K. Campbell ◽

E. Halinda ◽

M. J. Carlyle ◽

A. M. Fox ◽

L. A. Turner ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Very Low Birth Weight ◽

Developmental Outcome ◽

Clinic Attendance ◽

Low Birth Weight Infants

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Convexity subarachnoid hemorrhage in lobar intracerebral hemorrhage

Neurology ◽

10.1212/wnl.0000000000009036 ◽

2020 ◽

Vol 94 (9) ◽

pp. e968-e977 ◽

Cited By ~ 1

Author(s):

Nicolas Raposo ◽

Andreas Charidimou ◽

Duangnapa Roongpiboonsopit ◽

Michelle Onyekaba ◽

M. Edip Gurol ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Intracerebral Hemorrhage ◽

Regression Models ◽

Cox Regression ◽

Bleeding Risk ◽

Superficial Siderosis ◽

Amyloid Angiopathy ◽

Increased Risk ◽

Cortical Superficial Siderosis

ObjectiveTo investigate whether acute convexity subarachnoid hemorrhage (cSAH) associated with acute lobar intracerebral hemorrhage (ICH) increases the risk of ICH recurrence in patients with cerebral amyloid angiopathy (CAA).MethodsWe analyzed data from a prospective cohort of consecutive survivors of acute spontaneous lobar ICH fulfilling the Boston criteria for possible or probable CAA (CAA-ICH). We analyzed baseline clinical and MRI data, including cSAH (categorized as adjacent or remote from ICH on a standardized scale), cortical superficial siderosis (cSS), and other CAA MRI markers. Multivariable Cox regression models were used to assess the association between cSAH and recurrent symptomatic ICH during follow-up.ResultsWe included 261 CAA-ICH survivors (mean age 76.2 ± 8.7 years). Of them, 166 (63.6%, 95% confidence interval [CI] 57.7%–69.5%) had cSAH on baseline MRI. During a median follow-up of 28.3 (interquartile range 7.2–57.0) months, 54 (20.7%) patients experienced a recurrent lobar ICH. In Cox regression, any cSAH, adjacent cSAH, and remote cSAH were independent predictors of recurrent ICH after adjustment for other confounders, including cSS. Incidence rate of recurrent ICH in patients with cSAH was 9.9 per 100 person-years (95% CI 7.3–13.0) compared with 1.2 per 100 person-years (95% CI 0.3–3.2) in those without cSAH (adjusted hazard ratio 7.5, 95% CI 2.6–21.1).ConclusionIn patients with CAA-related acute ICH, cSAH (adjacent or remote from lobar ICH) is commonly observed and heralds an increased risk of recurrent ICH. cSAH may help stratify bleeding risk and should be assessed along with cSS for prognosis and clinical management.

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