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Biomedical subjects

Diederick E Grobbee

Publications and source records attributed to Diederick E Grobbee.

At least 37 records · Page 2Linked to original sources

Non-transferrin-bound iron and risk of coronary heart disease in postmenopausal women.

BACKGROUND: Epidemiological studies aimed at correlating coronary heart disease (CHD) with serum ferritin levels have thus far yielded inconsistent results. We hypothesized that a labile iron component associated with non-transferrin-bound iron (NTBI) that appears in individuals with overt or cryptic iron overload might be more suitable for establishing correlations with CHD. METHODS AND RESULTS: We investigated the relation of NTBI, serum iron, transferrin saturation, and serum ferritin with risk of CHD and acute myocardial infarction (AMI). The cohort used comprised a population-based sample of 11 471 postmenopausal women aged 49 to 70 years at enrollment in 1993 to 1997. During a median follow-up of 4.3 years (quartile limits Q1 to Q3: 3.3 to 5.4), 185 CHD events were identified, including 66 AMI events. We conducted a case-cohort study using all CHD cases and a random sample from the baseline cohort (n=1134). A weighted Cox proportional hazards model was used to estimate hazard ratios for tertiles of iron variables in relation to CHD and AMI. Adjusted hazard ratios of women in the highest NTBI tertile (range 0.38 to 3.51) compared with the lowest (range -2.06 to -0.32) were 0.84 (95% confidence interval 0.61 to 1.16) for CHD and 0.47 (95% confidence interval 0.31 to 0.71) for AMI. The results were similar for serum iron, transferrin saturation, and serum ferritin. CONCLUSIONS: Our results show no excess risk of CHD or AMI within the highest NTBI tertile compared with the lowest but rather seem to demonstrate a decreased risk. Additional studies are warranted to confirm our findings.

Aged↗

Risk and determinants of myocardial injury during off-pump coronary artery bypass grafting.

Perioperative myocardial injury (PMI) after coronary revascularization (bypass surgery using cardiopulmonary bypass or percutaneous intervention) is strongly associated with future adverse events, such as death, myocardial infarction, and coronary intervention. The incidence, determinants, and prognostic significance of PMI after bypass surgery without cardiopulmonary bypass (off-pump surgery) are unknown. The study population comprised the patients who were randomized to off-pump surgery in the Octopus Study. PMI was defined by a creatine kinase isoenzyme-MB/total creatine kinase ratio of >5% during the first 48 hours, postoperatively. PMI occurred in 137 of 260 patients (52%). Using multivariate regression analysis, age, female gender, previous myocardial infarction, preoperative nitrate use, preoperative diuretic use, and number of grafts were independently associated with an increased risk of PMI during off-pump surgery. The presence of preoperative coronary collaterals showed a negative association with PMI. The occurrence of PMI had a crude odds ratio of 7.53 (95% confidence interval 1.59 to 35.63) for an adverse cardiac event at 1 year after off-pump surgery. This odds ratio changed little after adjustment for confounders (odds ratio 6.39, 95% confidence interval 1.41 to 28.93). In conclusion, more severe atherosclerotic disease and female gender were associated with an increased risk of perioperative myocardial injury during off-pump bypass surgery, although the presence of coronary collaterals appeared to be protective. Patients with perioperative myocardial injury during off-pump surgery were at a higher risk of adverse cardiac outcomes at 1 year.

Age Factors↗

Heart failure and chronic obstructive pulmonary disease: An ignored combination?

AIMS: To quantify the prevalence of heart failure and left ventricular systolic dysfunction (LVSD) in chronic obstructive pulmonary disease (COPD) patients and vice versa. Further, to discuss diagnostic and therapeutic implications of the co-existence of both syndromes. METHODS AND RESULTS: We performed a Medline search from 1966 to March 2005. The reported prevalence of LVSD among COPD patients varied considerably, with the highest prevalence (10-46%) among those with an exacerbation. One single study assessed the prevalence of heart failure in COPD patients. A prevalence of 21% of previously unknown heart failure was reported in patients with a history of COPD or asthma. We did not find any report on COPD in heart failure or LVSD patients. Diagnosing heart failure in COPD patients or vice versa is complicated by overlap in signs and symptoms, and diminished diagnostic value of additional investigations. In general, pulmonary and heart failure 'drug cocktails' can be administered safely to patients with concomitant COPD and heart failure, although (short acting) beta2-adrenoreceptor agonists and digitalis have potentially deleterious effects on cardiac and pulmonary function, respectively. CONCLUSION: Although knowledge about the prevalence of concomitant heart failure in COPD patients and vice versa is scarce, it seems that the combined presence is rather common. In view of diagnostic and therapeutic implications, more attention should be paid to the concomitant presence of both syndromes in clinical practice and research.

Adrenergic beta-Agonists↗

Relations between body composition, functional and hormonal parameters and quality of life in healthy postmenopausal women.

OBJECTIVE: To investigate whether body composition, functional status and serum hormone levels are associated with quality of life in healthy postmenopausal women. DESIGN: A cross-sectional study among 402 women aged 56-73 years, 8-30 years postmenopausal. Quality of life (QoL) was assessed using the questionnaire on life satisfaction (QLS), with two modules directed at general factors (QLS-general) and health factors (QLS-health). Muscle strength was measured using dynamometry. Functional ability was estimated by physical performance (PPS), physical activity during the preceding year, and impairment in activities of daily living (ADL). Bone mineral density, lean mass and fat mass were assessed by dual-energy X-ray absorptiometry. Fasting levels of serum oestradiol, oestrone, and sex hormone-binding globulin (SHBG), testosterone, cortisol, androstenedione, DHEA and DHEAS, insulin-like growth factor (IGF-1), its binding proteins (IGFBP-1 and -3) and insulin, were determined. RESULTS: Both QLS modules did not decrease with age. The major positive predictor of QLS-general module was the presence of a partner. Higher physical performance and higher educational level of participants' partners were significantly related to higher QLS-general, while smoking and presence of co-morbidities were significantly associated with a lower QLS-general. The determinants studied were mostly related to the QLS-health module, the major negative predictor of QLS-health being the presence of co-morbidities, followed by physical activity, physical performance and grip strength. Higher educational level of participants was related with higher QLS-health module, while higher BMI, fat mass and presence of disability were associated with significantly lower QLS-health. No consistent relation was found between serum levels of hormones measured and both QLS modules. CONCLUSIONS: The most important and specific determinant for psychological well-being was having a partner. Physical and psychological well-being are further strongly associated in this population of healthy postmenopausal women below 75 years of age, while increasing fat mass was related to decreased well-being. Our results suggest that in elderly and late postmenopausal women hormonal factors do not predict quality of life.

Absorptiometry, Photon↗

Reduced risk of surgical site infections through surveillance in a network.

OBJECTIVE: To estimate the effect of multicentre surveillance for nosocomial infections on patients' risk of surgical site infection (SSI). DESIGN: Prospective multi-centre cohort study, from January 1996 to December 2000. SETTING: Acute care hospitals in The Netherlands. STUDY PARTICIPANTS: All 50 hospitals performing surveillance for one of seven selected procedures in the Dutch surveillance network for nosocomial infections PREZIES were invited. Thirty-seven hospitals participated (74%) and provided information on 21 920 operations, after which 885 (4%) SSI occurred. INTERVENTIONS: The surveillance comprised the following: Development of surveillance methodology by multidisciplinary team; use of a standardized registration protocol and software; regular training of data collectors; anonymous inter-hospital comparison of infection rates and feedback of results; appointment of one contact person per hospital, responsible for data collection; and dissemination of results to other health care professionals. Regular discussion of both successful and failing prevention strategies that had been instituted based on the surveillance results. OUTCOME MEASURE: Risk of SSI. RESULTS: The risk of infection was reduced for patients who had an operation during the fourth surveillance year (RR = 0.69; 95% confidence interval (CI) = 0.52-0.89) and decreased further for patients operated on during the fifth surveillance year (RR = 0.43; CI = 0.24-0.76) as compared with patients who underwent surgery within one year of the start of surveillance in their hospital. No significant risk reduction was observed for patients operated on during the second and third surveillance years. CONCLUSION: Surveillance, supported by participation in a surveillance network, reduced the risk of SSI in surgical patients registered in the Dutch surveillance network PREZIES. Our results suggest that infection control teams need to be perseverant and that surveillance programmes should be given time before evaluation.

Adult↗

The effect of tibolone and continuous combined conjugated equine oestrogens plus medroxyprogesterone acetate on progression of carotid intima-media thickness: the Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) study.

AIMS: At the time of the design of the Osteoporosis Prevention and Arterial effects of tiboLone (OPAL) study in 1996, oral hormone therapy (HT) was assumed to reduce cardiovascular risk. The evidence mainly came from the effects of combined conjugated equine oestrogens plus medroxyprogesterone acetate (CEE/MPA) therapy. Other HT regimes had not been studied widely. Tibolone, a selective tissue oestrogenic activity regulator, has several effects on cardiovascular risk factors, one of which is HDL lowering. Because the overall effect of tibolone on cardiovascular risk was unknown, the OPAL study was designed. METHODS AND RESULTS: The OPAL study was a three-arm, randomized, placebo-controlled, double-blind study to determine the effect of tibolone (2.5 mg daily) and of CEE/MPA (0.625/2.5 mg daily) over 3 years on progression of carotid intima-media thickness (CIMT) in 866 healthy post-menopausal women. The women were recruited from six US and five European centres. The primary outcome was change in mean common CIMT. Annual common CIMT progression rates in the tibolone and CEE/MPA groups were higher than in the placebo group: 0.0077 mm [95% confidence interval (CI) 0.0051-0.0103] in the tibolone group, 0.0074 mm (0.0048-0.0099) in the CEE/MPA group, and 0.0035 mm (0.009-0.0061) in the placebo group. The differences with placebo (0.0042 mm/year for tibolone and 0.0039 mm/year for CEE/MPA) were statistically significant. HDL cholesterol increased in CEE/MPA group and was lowered in the tibolone group. CONCLUSION: Both tibolone and CEE/MPA showed increased progression of common CIMT. Translation of the increased common CIMT progression of the CEE/MPA group into cardiovascular disease risk could not fully explain the observed increased cardiovascular risk as observed in the Women's Health Initiative study. This suggests that the net effect of tibolone and CEE/MPA on cardiovascular events may depend on the combined effects on the arterial wall, clotting factors, and possibly inflammation.

Aged↗

Distraction from randomization in diagnostic research.

The ultimate goal of medical care, including diagnostic testing, is to improve patient outcome. Accordingly, it has been advocated widely that when establishing a test's diagnostic accuracy, the impact of the test on patient outcome subsequently must be quantified. When studying patient outcome in medical research, the use of randomized comparisons comes into perspective. In our view, randomized studies often are not necessary to validly estimate the effect of the diagnostic test on patient outcome. Results of cross-sectional diagnostic studies, combined with results from therapeutic studies, often will suffice.

Cross-Sectional Studies↗

Prediction of mortality risk in the elderly.

PURPOSE: Ways to predict the risk of cardiovascular (CV) events or all-cause mortality have largely been derived from populations in which old and very old subjects were underrepresented. We set out to estimate the incremental prognostic utility of inflammation and atherosclerosis markers in the prediction of all-cause and CV mortality in elderly men. METHODS: In a prospective population-based cohort study, conventional CV risk factors were documented in 403 independently living elderly men. C-reactive protein (CRP) and interleukin (IL)-6 levels were measured. Carotid plaques were assessed by ultrasound. Analyses were performed with proportional hazards analyses, and bootstrapping was used for internal validation. Main outcome was CV and all-cause mortality occurring during 4 years of follow-up. RESULTS: Increasing tertiles of CRP, IL-6, and number of plaques were independently associated with all-cause and CV mortality. With information on age, carotid plaques, IL-6, and CRP yielded good discriminatory power for all-cause and CV mortality: area under the receiver operating characteristic curve (95% confidence interval), 0.76 (0.70-0.82) and 0.74 (0.68-0.80), respectively. Combined use of only IL-6 and plaque burden allowed identification of subjects with low and high mortality risk. The Framingham PROCAM and a Dutch Risk Function poorly predicted mortality risk, similar or worse than a model using age alone. CONCLUSION: In the old and very old, IL-6 and number of carotid plaques are powerful predictors of mortality risk in the years to come. Conventional risk scores seem to perform unsatisfactorily.

Aged↗

HFE genotypes and dietary heme iron: no evidence of strong gene-nutrient interaction on serum ferritin concentrations in middle-aged women.

BACKGROUND AND AIM: Hereditary hemochromatosis (HH) is a disorder characterized by inappropriately high intestinal iron absorption. In populations of Northern European descent, HH is most commonly caused by mutations (C282Y/H63D) in the HFE gene. METHODS AND RESULTS: We investigated the effects of dietary heme iron intake and HFE mutations on serum ferritin concentrations in a population-based random sample of 1611 women aged >50 years using analysis of covariance (ANCOVA). Higher heme iron intake was associated with significantly higher serum ferritin concentrations (P(trend) < 0.001). Also, women with the compound or C282Y homozygous genotype had significantly higher serum ferritin concentrations (geometric mean 115.2 microg/L (95% CI 81.4-162.9 microg/L) than women carrying normal alleles (geometric mean 76.6 microg/L (95% CI 72.5-80.9 microg/L). We observed the highest serum ferritin concentrations among postmenopausal women who are compound heterozygous or C282Y homozygous, and who consume relatively high amounts of heme iron (geometric mean 183.9 microg/L (95% CI 97.2-347.8 microg/L). CONCLUSIONS: Even when there are currently no clinical signs, women with the compound or C282Y homozygous genotype may still be at risk for developing iron overload sometime after menopause.

Aged↗

Validating and updating a prediction rule for neurological sequelae after childhood bacterial meningitis.

Recently, a prediction rule for developing neurological sequelae after childhood bacterial meningitis was developed on a small derivation set. Before implementing in practice a prediction rule must first be tested in new patients (external validation). Our aim was to study the external validity of this rule and, if necessary, to update the rule. The prediction rule was tested on newly available data (validation set) by assessing the rule's calibration and discrimination. We updated the prediction rule by adding extra predictors and re-estimating the regression coefficients of the original predictors in the combined datasets. The rule showed poor agreement between predicted risks and observed frequencies. The ROC area was 0.65 (95% CI 0.57-0.72), which was statistically significantly lower than in the derivation set (0.87 (0.78-0.96)), p-value<0.01. The updated prediction rule showed adequate performance in the combined data sets; the ROC area was 0.77 (95% CI 0.72-0.82). Further study of the generalizability of this updated rule may stimulate application in clinical practice.

Child↗

Depression and cardiovascular mortality: a role for n-3 fatty acids?

BACKGROUND: Recent studies indicate that depression plays an important role in the occurrence of cardiovascular diseases (CVDs). The underlying mechanisms are not well understood. OBJECTIVE: We investigated whether dietary intake of the n-3 fatty acids (FAs) eicosapentaenic acid and docosahexaenoic acid could explain the relation between depressive symptoms and cardiovascular mortality. DESIGN: The Zutphen Elderly Study is a prospective cohort study conducted in the Netherlands. Depressive symptoms were measured in 1990 with the Zung Self-rating Depression Scale in 332 men aged 70-90 y and free from CVD and diabetes. Dietary factors were assessed with a cross-check dietary history method in 1990. Mortality data were collected between 1990 and 2000. Logistic and Cox regression analyses were performed, with adjustment for demographics and CVD risk factors. RESULTS: Compared with a low intake (x: 21 mg/d), a high intake (x: 407 mg/d) of n-3 FAs was associated with fewer depressive symptoms [odds ratio: 0.46; 95% CI: 0.22, 0.95; P for trend = 0.04] at baseline and no significant reduced risk of 10-y CVD mortality [hazard ratio (HR): 0.88; 95% CI: 0.51, 1.50]. The adjusted HR for an increase in depressive symptoms with 1 SD for CVD mortality was 1.28 (95% CI: 1.03, 1.57) and did not change after additional adjustment for the intake of n-3 FAs. CONCLUSION: An average intake of approximately 400 mg n-3 FA/d may reduce the risk of depression. Our results, however, do not support the hypothesis that the intake of n-3 FAs explains the relation between depression and CVD.

Aged↗

Spurious systolic hypertension in young adults; prevalence of high brachial systolic blood pressure and low central pressure and its determinants.

OBJECTIVE: To investigate the prevalence and determinants of spurious systolic hypertension (SSH) in a population-based sample of young adults and estimate their 20-year risk of coronary heart disease. POPULATION AND METHODS: Seven hundred and fifty young adults (352 men and 398 women), aged 26-31 years, from the Atherosclerosis Risk in Young Adults study were studied. Blood pressure levels were measured twice and central (aortic) pressures were derived by applanation tonometry on the radial artery using a generalized transfer function. SSH was defined as brachial systolic blood pressure (SBP) > or = 140 mmHg, brachial diastolic blood pressure (DBP) < 90 mmHg, and central SBP < 124 mmHg for men and < 120 mmHg for women. The Framingham risk score was calculated. Analysis of variance models were used to compare SSH individuals with normotensive and hypertensive males for cardiovascular risk factors. RESULTS: SSH was diagnosed in 57 men (16.1%; 95% confidence interval, 12.3-20.0) versus only three women (8%; 95% confidence interval, 0-1.6). The female population was excluded from further analysis. Compared with normotensive males, SSH individuals were heavier (88.7 versus 81.8 kg, P < 0.05) had a higher body mass index (25.8 versus 24.2 kg/m, P < 0.01) and significantly higher brachial and central SBP, DBP, pulse pressure, and mean arterial pressure. They had significantly higher pulse pressure amplification. Twenty-year Framingham risk scores based on DBP did not differ significantly between SSH subjects and normotensive individuals (2.72 versus 2.10%, respectively). CONCLUSION: SSH is predominantly found among young adult men. Apart from weight and body mass index, no other cardiovascular risk factors differed significantly between subjects with SSH and normotension or hypertension. When calculating the 20-year risk of coronary heart disease based on brachial DBP, SSH individuals were at intermediate risk between normotensive and hypertensive participants, but differences were not statistically significant.

Adult↗

Aortic stiffness is associated with atherosclerosis of the coronary arteries in older adults: the Rotterdam Study.

OBJECTIVE: Aortic stiffness can lead to low diastolic blood pressure, thereby possibly limiting coronary perfusion. Therefore, the simultaneous occurrence of both aortic stiffness and coronary atherosclerosis can lead to an increased risk of subendocardial ischaemia. The aim of the present study was to investigate the association between aortic stiffness and coronary atherosclerosis. METHODS: The study was performed in 1757 subjects of the Rotterdam Study, a population-based study of elderly individuals. Aortic stiffness was assessed by measuring carotid-femoral pulse wave velocity (PWV). Coronary atherosclerosis was assessed by measuring coronary calcification using electron beam tomography and expressed as a total calcium score. The total calcium score was log-transformed because of its skewed distribution. The association between PWV and coronary calcification was first evaluated after adjustment for age, sex, mean arterial blood pressure and heart rate. RESULTS: Linear regression analyses showed that increased PWV was associated with a higher log total coronary calcium score [beta-regression coefficient 0.11, 95% confidence interval (CI) 0.07-0.15]. Compared with the lowest quartile of PWV, multivariate odds ratios and corresponding 95% CI for advanced coronary calcification in the second, third and fourth highest quartiles were 1.17 (0.79-1.74), 1.58 (1.07-2.34) and 2.12 (1.40-3.20), respectively. CONCLUSIONS: In this large population-based study performed in elderly subjects aortic stiffness was strongly and independently associated with coronary atherosclerosis.

Aged↗

Depressive symptoms as risk factor of cardiovascular mortality in older European men: the Finland, Italy and Netherlands Elderly (FINE) study.

BACKGROUND: Depressive symptoms have been suggested to increase the risk of cardiovascular diseases, but this may reflect reversed causality. We investigated to what extent depressive symptoms are a true risk factor for cardiovascular mortality in elderly men. DESIGN: The Finland, Italy and Netherlands Elderly (FINE) study is a prospective cohort study conducted in Finland, Italy and The Netherlands. METHODS: Depressive symptoms were measured with the Zung self-rating Depression Scale in 799 elderly men, aged 70-90 years, free from cardiovascular diseases. Using Cox models, hazard ratios (HRs) were calculated for specific cardiovascular mortality endpoints. The analyses were adjusted for potential confounders, stratified on country and repeated after exclusion of men who died from cardiovascular diseases up to 5 years after baseline. RESULTS: During 10-years of follow-up 224 (28%) men died from cardiovascular diseases. The adjusted hazard for a five-point increase in depressive symptoms was 1.15 [95% confidence interval (CI) 1.08-1.23] for cardiovascular mortality. This risk was stronger for mortality from stroke (HR 1.35; 95% CI 1.19-1.53) and heart failure (HR 1.16; 95% CI 1.00-1.35) in comparison with mortality from coronary heart disease (HR 1.08; 95% CI 0.97-1.20) and other degenerative heart diseases (HR 1.06; 95% CI 0.91-1.23). Exclusion of men who died from cardiovascular diseases within 5 years after baseline did not change the strength of the associations. There were no significant differences in HRs between northern and southern Europe. CONCLUSIONS: This study provides further and more convincing prospective evidence for depressive symptoms as a risk factor for cardiovascular mortality in elderly men.

Adult↗

Impaired fasting glucose is associated with increased arterial stiffness in elderly people without diabetes mellitus: the Rotterdam Study.

OBJECTIVES: To study the association between impaired fasting glucose (IFG) and arterial stiffness in older adults. DESIGN: Cross-sectional population-based study. SETTING: The Rotterdam Study, a Dutch population-based cohort study. PARTICIPANTS: Two thousand nine hundred eighty-seven subjects aged 60 and older. MEASUREMENTS: Arterial stiffness assessed by measuring common carotid arterial distensibility and glucose status classified into three categories: normal fasting glucose (NFG) (fasting glucose <6.1 mmol/L), IFG (fasting glucose 6.1-6.9 mmol/L), and diabetes mellitus (DM). RESULTS: In the total cohort, common carotid distensibility decreased with increasing impairment of glucose metabolism. Subjects younger than 75 with IFG were comparable with subjects with NFG with respect to arterial stiffness. Subjects aged 75 and older with IFG had stiffer arteries than subjects with NFG, reaching the same arterial stiffness as subjects with DM. For subjects younger than 75, mean difference in distensibility coefficient between subjects with NFG and with IFG was 0.1 (95% confidence interval (CI)=-0.04-0.05, P=.88) and between subjects with NFG and with DM was 1.2 (95% CI=0.7-1.7, P<.001). For subjects aged 75 and older, the mean difference between these groups was 0.7 (95% CI=0.2-1.2, P=.007) and 0.8 (0.3-1.4; P=.002), respectively. In the total cohort, fasting glucose was strongly associated with carotid distensibility (beta-coefficient=-0.29, P<.001). CONCLUSION: IFG is related to arterial stiffness in elderly subjects. An advanced stage of arterial stiffness, comparable with that of subjects with DM, is only reached at the age of 75.

Aged↗

Influence of estrogen receptor alpha and progesterone receptor polymorphisms on the effects of hormone therapy on mammographic density.

Postmenopausal hormone therapy increases mammographic density, a strong breast cancer risk factor, but effects vary across women. We investigated whether the effect of hormone therapy use is modified by polymorphisms in the estrogen receptor (ESR1) and progesterone receptor (PGR) genes in the Dutch Prospect-EPIC and the English EPIC-Norfolk cohorts. Information on hormone therapy use was obtained through questionnaires at recruitment and after 5 years. Blood samples were collected and consecutive mammograms were available through breast cancer screening programs. For 795 hormone therapy users, one mammogram before and a second mammogram during hormone therapy use was included. For 781 never hormone therapy users, mammograms with similar time intervals were included. Mammographic density was assessed using a computer-assisted method. Changes in density were analyzed using linear regression. A statistically significant difference in percentage density change between hormone therapy users and never users was seen in women with the ESR1 PvuII Pp or pp genotype (2.24%; P < 0.01), but not in those with the PP genotype (0.90%; P = 0.47). Similarly, effects of hormone therapy on percentage density were observed in women with the ESR1 XbaI Xx or xx genotype (2.20%; P < 0.01), but not in those with the XX genotype (-0.65%; P = 0.70). Also, effects were seen in women with the PGR +331 GG genotype (2.04%; P < 0.01), but not in those with the GA or AA genotype (0.98%; P = 0.53). The PGR PROGINS polymorphism did not seem to make women more susceptible to the effects of hormone therapy use. In conclusion, our results suggest that specific polymorphisms in the ESR1 and PGR genes may make women more susceptible to the effects of hormone therapy use on mammographic density.

Aged↗

Neonatal hydrocortisone treatment related to 1H-MRS of the hippocampus and short-term memory at school age in preterm born children.

Animal studies have shown that corticosteroids (dexamethasone) cause neuronal loss in the hippocampus and deficits in short term memory. Proton magnetic resonance spectroscopy can measure brain metabolites in vivo and give an indication of neuronal integrity. We investigated whether prolonged administration of hydrocortisone during the neonatal period for bronchopulmonary dysplasia (BPD) in preterm born children changes the metabolism in the hippocampus, measured at school age. Secondly, we investigated whether hippocampal metabolism and short-term memory and neurodevelopmental outcome are related. In this observational study 37 preterm born children (< or = 32 wk (range 25.0-33.0) and/or a birth weight < or = 1500 g) underwent proton spectroscopy of the hippocampus at school age. Eighteen children were treated with hydrocortisone for BPD (starting dose 5 mg/kg/d tapered over a minimum period of 22 d, median duration 28 d) and 19 never received corticosteroids during the perinatal period. N-acetyl aspartate/ Choline + Creatine/phosphocreatine (NAA/(Cho + Cr)) ratios were determined. A 15-word recall memory test and an IQ measurement were obtained on the same day. Hydrocortisone treated children were younger, lighter and sicker than their nonsteroid treated counterparts. Mean NAA/(Cho + Cr) ratios in the hippocampus were not significantly different in the hydrocortisone group compared with the non-steroid group. Performance on the 15-word memory test and IQ were similar in the two groups. There was no relation between NAA/(Cho + Cr) ratios and memory nor between NAA/(Cho + Cr) ratios and IQ. We conclude that hydrocortisone in the mentioned dose, administered in the neonatal period for BPD, does not appear to have any long-term effects on memory and/or hippocampal metabolism.

Hippocampus↗