Long-Term Survival of Individuals Born Small and Large for Gestational Age

Background

Little is known on long-term survival and causes of death among individuals born small or large for gestational age. This study investigates birth weight in relation to survival and causes of death over time.

Methods

A national cohort of 1.7 million live-born singletons in Denmark was followed during 1979–2011, using the Danish Civil Registration System, the Medical Birth Registry and the Cause of Death Registry. Cox proportional hazards were estimated for the impact of small (SGA) and large (LGA) gestation weight and mortality overall, by age group and birth cohort.

Results

Compared to normal weight children, SGA children were associated with increased risk of dying over time. Though most of the deaths occurred during the first year of life, the cumulative mortality risk was increased until 30 years of age. The hazard ratios [HR] for dying among SGA children ages <2 years were: 3.47 (95% CI, 3.30–3.64) and 1.06 (95% CI, 0.60–1.87) in 30 years and older. HR for dying among SGA adults (20–29 years) were: 1.20 (95% CI, 0.99–1.46) in years 1979–1982 and 1.61 (95% CI, 1.04–2.51) in years 1989–1994. The SGA born had increased risk of dying from infection, heart disease, respiratory disease, digestive disease, congenital malformation, perinatal conditions, and accidents, suicide, and homicide. Individuals born LGA were associated with decreased mortality risk, but with increased risk of dying from malignant neoplasm.

Conclusions

Survival has improved independently of birth weight the past 30 years. However, children born SGA remain at significantly increased risk of dying up till they turn 30 years of age. Individuals born LGA have lower mortality risk but only in the first two years of life.     

Methylphenidate and the Response to Growth Hormone Treatment in Short Children Born Small for Gestational Age

Background

Growth hormone (GH) treatment has become a frequently applied growth promoting therapy in short children born small for gestational age (SGA). Children born SGA have a higher risk of developing attention deficit hyperactivity disorder (ADHD). Treatment of ADHD with methylphenidate (MP) has greatly increased in recent years, therefore more children are being treated with GH and MP simultaneously. Some studies have found an association between MP treatment and growth deceleration, but data are contradictory.

Objective

To explore the effects of MP treatment on growth in GH-treated short SGA children

Methods

Anthropometric measurements were performed in 78 GH-treated short SGA children (mean age 10.6 yr), 39 of whom were also treated with MP (SGA-GH/MP). The SGA-GH/MP group was compared to 39 SGA-GH treated subjects. They were matched for sex, age and height at start of GH, height SDS at start of MP treatment and target height SDS. Serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels were yearly determined. Growth, serum IGF-I and IGFBP-3 levels during the first three years of treatment were analyzed using repeated measures regression analysis.

Results

The SGA-GH/MP group had a lower height gain during the first 3 years than the SGA-GH subjects, only significant between 6 and 12 months of MP treatment. After 3 years of MP treatment, the height gain was 0.2 SDS (±0.1 SD) lower in the SGA-GH/MP group (P = 0.17). Adult height was not significantly different between the SGA-GH/MP and SGA-GH group (−1.9 SDS and −1.9 SDS respectively, P = 0.46). Moreover, during the first 3 years of MP treatment IGF-I and IGFBP-3 measurements were similar in both groups.

Conclusion

MP has some negative effect on growth during the first years in short SGA children treated with GH, but adult height is not affected.     

Trends in All-Cause Mortality across Gestational Age in Days for Children Born at Term

Background

Term birth is a gestational age from 259 days to 293 days. However trends in mortality according to gestational ages in days have not yet been described in this time period.

Methods and Findings

Based on nation-wide registries, we conducted a population-based cohort study among all children born at term in Denmark from 1997 to 2004 to estimate differences in mortality across gestational ages in days among singletons born at term. We studied early-neonatal mortality, neonatal mortality, infant mortality, and five-year mortality. Children were followed from birth up to the last day of the defined mortality period or December 31, 2009. A total of 360,375 singletons born between 259 and 293 days of gestation were included in the study. Mortality decreased with increasing gestational age in days and the highest mortality was observed among children born at 37 week of gestation. A similar pattern was observed when analyses were restricted to children born to by mothers without pregnancy complications.

Conclusions

This study demonstrates heterogeneity in mortality rates even among singletons born at term. The highest mortality was observed among children born 37 weeks of gestation, which call for cautions when inducing labor in term pregnancies just reaching 37 weeks of gestation. The findings support that 37 weeks of gestation should be defined as early term.     

Maternal Antioxidant Levels in Pregnancy and Risk of Preeclampsia and Small for Gestational Age Birth: A Systematic Review and Meta-Analysis

Background

Oxidative stress in preeclampsia and small for gestational age (SGA) birth suggests antioxidant supplementation could prevent these conditions. However, it remains unclear whether maternal antioxidant levels are systematically lower in these pregnancies.

Objective

To conduct a systematic review of the association between maternal antioxidant levels during pregnancy and preeclampsia or SGA.

Methods

We searched PubMed, Embase, and several other databases from 1970–2013 for observational studies that measured maternal blood levels of non-enzymatic antioxidants (vitamins A, C, E, and carotenoids) during pregnancy or within 72 hours of delivery. The entire review process was done in duplicate. Study quality was assessed using the Newcastle-Ottawa Scale and additional questions. We pooled the standardized mean difference (SMD) across studies, stratified by outcome and pregnancy trimester, and investigated heterogeneity using meta-regression.

Results

We reviewed 1,882 unique citations and 64 studies were included. Most studies were small with important risk of bias. Among studies that addressed preeclampsia (n = 58) and SGA (n = 9), 16% and 66%, respectively, measured levels prior to diagnosis. The SMDs for vitamins A, C, and E were significantly negative for overall preeclampsia, but not for mild or severe preeclampsia subtypes. Significant heterogeneity was observed in all meta-analyses and most could not be explained. Evidence for lower carotenoid antioxidants in preeclampsia and SGA was limited and inconclusive. Publication bias appears likely.

Conclusions

Small, low-quality studies limit conclusions that can be drawn from the available literature. Observational studies inconsistently show that vitamins C and E or other antioxidants are lower in women who develop preeclampsia or SGA. Reverse causality remains a possible explanation for associations observed. New clinical trials are not warranted in light of this evidence; however, additional rigorous observational studies measuring antioxidant levels before clinical detection of preeclampsia and SGA may clarify whether levels are altered at a causally-relevant time of pregnancy.     

Gestational Age and Neonatal Brain Microstructure in Term Born Infants: A Birth Cohort Study

Objective

Understanding healthy brain development in utero is crucial in order to detect abnormal developmental trajectories due to developmental disorders. However, in most studies neuroimaging was done after a significant postnatal period, and in those studies that performed neuroimaging on fetuses, the quality of data has been affected due to complications of scanning during pregnancy. To understand healthy brain development between 37–41 weeks of gestational age, our study assessed the in utero growth of the brain in healthy term born babies with DTI scanning soon after birth.

Methods

A cohort of 93 infants recruited from maternity hospitals in Singapore underwent diffusion tensor imaging between 5 to 17 days after birth. We did a cross-sectional examination of white matter microstructure of the brain among healthy term infants as a function of gestational age via voxel-based analysis on fractional anisotropy.

Results

Greater gestational age at birth in term infants was associated with larger fractional anisotropy values in early developing brain regions, when corrected for age at scan. Specifically, it was associated with a cluster located at the corpus callosum (corrected p<0.001), as well as another cluster spanning areas of the anterior corona radiata, anterior limb of internal capsule, and external capsule (corrected p<0.001).

Conclusions

Our findings show variation in brain maturation associated with gestational age amongst ‘term’ infants, with increased brain maturation when born with a relatively higher gestational age in comparison to those infants born with a relatively younger gestational age. Future studies should explore if these differences in brain maturation between 37 and 41 weeks of gestational age will persist over time due to development outside the womb.     

孕期被动吸烟与小于胎龄儿关系的Meta分析

目的:应用Meta分析方法探讨孕期被动吸烟与小于胎龄儿之间的关联.方法:利用计算机检索中国生物医学文献数据库、中国期刊全文数据库、维普期刊全文数据库检索文献,采用Cochrane协作网提供的Review Manager4.2分析软件,对符合纳入标准的4篇有关孕期被动吸烟与小于胎龄儿关系的病例-对照研究结果进行了随机效应模型的Meta分析.结果:孕期被动吸烟与小于胎龄儿的发生关联明显,合并OR值为3.74,OR值的95%置信区间为1.75-8.00.结论:孕期被动吸烟与小于胎龄儿的发生有一定关联.     

Aortic Intima-Media Thickness and Aortic Diameter in Small for Gestational Age and Growth Restricted Fetuses

ObjectiveThe objective of this study is to measure aortic intima-media thickness (aIMT) and aortic diameter (AD) in appropriate for gestational age (AGA) fetuses, small for gestational age (SGA) fetuses, and intrauterine growth restricted (IUGR) fetuses.MethodsCase-control study performed between June 2011 and June 2012. Forty-nine AGA fetuses, 40 SGA fetuses, and 35 IUGR fetuses underwent concomitant measurement of aIMT and AD at a mean gestational age of 34.4 weeks.ResultsMedian aIMT was higher in fetuses with IUGR (0.504 mm [95%CI: 0.477-0.530 mm]), than in SGA fetuses (0.466 mm [95% CI: 0.447–0.485 mm]), and AGA fetuses (0.471 mm [95% CI: 0.454-0.488 mm]) (p = 0.023). Mean AD was significantly lower in fetuses with IUGR (4.451 mm [95% CI: 4.258–4.655 mm]), than in AGA fetuses (4.74 mm [95% CI: 4.63-4.843 mm]) (p = 0.028).ConclusionsGrowth restricted fetuses have a thicker aortic wall than AGA and SGA fetuses, which possibly represents preclinical atherosclerosis and a predisposition to later cardiovascular disease.     

Trend of Cardio-Metabolic Risk Factors in Polycystic Ovary Syndrome: A Population-Based Prospective Cohort Study

Objective

To see the changes of cardio-metabolic risk factors overtime in polycystic ovary syndrome vs. control women.

Methods

This study was conducted on 637 participants (85 PCOS and 552 control reproductive aged, 18–45 years) of Tehran Lipid and Glucose Study (TLGS), an ongoing population-based cohort study with 12 years of follow-up. The cardiovascular risk factors of these groups were assessed in three-year intervals using standard questionnaires, history taking, anthropometric measures, and metabolic/endocrine evaluation. Generalized estimating equation was used to analyze the data.

Results

Overall mean of insulin (3.55, CI: 0.66–6.45), HOMA-IR (0.63, CI: 0.08–1.18), and HOMA-β (45.90, CI: 0.86–90.93) were significantly higher in PCOS than in healthy women after adjustment for age, BMI, and baseline levels. However, the negative interaction (follow-up years × PCOS status) of PCOS and normal women converged overtime. Comparing third follow-up with first, insulin and HOMA-IR decreased 10.6% and 5%, respectively in PCOS women; and increased 6.7% and 14.6%, respectively in controls (P<0.05). The results did not show any significant result for other cardio-metabolic variables including WC, lipid profile, FPG, 2-h PG, SBP, and DBP.

Conclusion

While the insulin level and insulin resistance rate were higher in reproductive aged PCOS than in healthy women, the difference of these risk factors decreased overtime. Thus, the metabolic consequences of PCOS women in later life may be lower than those initially anticipated.     

Effect of Pregnancy for Females Born Small on Later Life Metabolic Disease Risk

There is a strong inverse relationship between a females own birth weight and her subsequent risk for gestational diabetes with increased risk of developing diabetes later in life. We have shown that growth restricted females develop loss of glucose tolerance during late pregnancy with normal pancreatic function. The aim of this study was to determine whether growth restricted females develop long-term impairment of metabolic control after an adverse pregnancy adaptation. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) in late pregnancy (E18) in F0 female rats. F1 Control and Restricted female offspring were mated with normal males and allowed to deliver (termed Ex-Pregnant). Age-matched Control and Restricted Virgins were also studied and glucose tolerance and insulin secretion were determined. Pancreatic morphology and hepatic glycogen and triacylglycerol content were quantified respectively. Restricted females were born lighter than Control and remained lighter at all time points studied (p<0.05). Glucose tolerance, first phase insulin secretion and liver glycogen and triacylglycerol content were not different across groups, with no changes in β-cell mass. Second phase insulin secretion was reduced in Restricted Virgins (−34%, p<0.05) compared to Control Virgins, suggestive of enhanced peripheral insulin sensitivity but this was lost after pregnancy. Growth restriction was associated with enhanced basal hepatic insulin sensitivity, which may provide compensatory benefits to prevent adverse metabolic outcomes often associated with being born small. A prior pregnancy was associated with reduced hepatic insulin sensitivity with effects more pronounced in Controls than Restricted. Our data suggests that pregnancy ameliorates the enhanced peripheral insulin sensitivity in growth restricted females and has deleterious effects for hepatic insulin sensitivity, regardless of maternal birth weight.     

妊娠糖尿病饮食相关危险因素分析

目的：通过分析妊娠糖尿病患者与正常孕妇的饮食行为,探讨妊娠糖尿病发病饮食相关的危险因素,为孕期妇女提供科学 合理膳食指导。方法：采用多阶段连续等比例抽样,选取确诊GDM的孕妇150 例为病例组,同期就诊非GDM孕妇150 例为对照 组,利用24 小时膳食回顾法进行饮食行为和一般情况的问卷调查。采用Logistic 回归筛选GDM 饮食相关危险因素。结果：多因 素Logistic 回归分析显示,怀孕年龄( OR=1.157)、孕前BMI(OR=1.780)、糖尿病家族史(OR=2.448)、产次(OR=1.157)、总能量、水果 摄入量(OR=4.109)、豆类（OR=0.998）与妊娠糖尿病发生相关（OR=0.998）。采用多变量模型具体分析水果的摄入量,同时调整与妊 娠糖尿病发生的相关因素结果显示：与水果摄入量小于200 g/d 相比,水果的摄入量200 ~ 400 g/d,400 ~ 600 g/d 和超过600 g/d 其OR值分别为0.38、2.48、2.63（P<0.01）。结论：除高龄、肥胖、糖尿病家族史等妊娠糖尿病高危因素外,饮食行为与GDM存在一 定的相关性。针对高危人群早期干预,同时对孕期妇女进行科学合理的饮食指导,调整饮食结构,控制食物摄入量,以减少GDM 的发病。     

Secular Trends of Gestational Diabetes Mellitus and Changes in Its Risk Factors

Objective

The aim of this study was to evaluate the secular trends of incidence of gestational diabetes mellitus (GDM) and insulin treatment for GDM in a Korean population and to determine the factors that contribute to the trends in the incidence of GDM.

Study Design

We used data collected by the Health Insurance Review & Assessment Service of Korea and analyzed data from women who had given birth from 2006 to 2010. We evaluated the trends in the incidence of GDM and GDM requiring insulin treatment and the changes in risk factors.

Results

There were 1,824,913 births during the study period, which included 129,666 cases of GDM, an incidence of 7.11% over this period. The incidence of GDM increased from 3.86% in 2007 to 11.83% in 2010, with a continuous increase after adjustment for age. However, the number of GDM cases that required insulin treatment decreased significantly from 13.87% in 2007 to 5.94% in 2010. The proportion of patients who were at an older age and multiparity, 2 GDM risk factors, increased during the study period.

Conclusions

In Korea, the incidence of GDM, especially mild GDM, increased dramatically during the period from 2006 to 2010. Further efforts are needed to monitor this trend and to identify associated factors.     

Differences in Muscle and Adipose Tissue Gene Expression and Cardio-Metabolic Risk Factors in the Members of Physical Activity Discordant Twin Pairs

High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50–74 years) who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing active vs. inactive co-twin gene expression ratios. Our findings showed that among the physically active members of twin pairs, as compared to their inactive co-twins, gene expression in the muscle tissue samples was chronically up-regulated for the central pathways related to energy metabolism, including oxidative phosphorylation, lipid metabolism and supportive metabolic pathways. Up-regulation of these pathways was associated in particular with aerobic fitness and high HDL cholesterol levels. In fat tissue we found physical activity-associated increases in the expression of polyunsaturated fatty acid metabolism and branched-chain amino acid degradation gene sets both of which associated with decreased ‘high-risk’ ectopic body fat and plasma glucose levels. Consistent with other findings, plasma lipidomics analysis showed up-regulation of the triacylglycerols containing the polyunsaturated fatty acids. Our findings identified skeletal muscle and fat tissue pathways which are associated with the long-term physical activity and reduced cardio-metabolic disease risk, including increased aerobic fitness. In particular, improved skeletal muscle oxidative energy and lipid metabolism as well as changes in adipocyte function and redistribution of body fat are associated with reduced cardio-metabolic risk.     

Obesity and Cardio-Metabolic Risk Factors in an Urban and Rural Population in the Ashanti Region-Ghana: A Comparative Cross-Sectional Study

There is a surge in chronic diseases in the developing world, driven by a high prevalence of cardio-metabolic risk factors. This study described differences in prevalence of obesity and cardio-metabolic risk factors between urban and rural settlements in the Ashanti Region of Ghana. This comparative cross-sectional study included 672 participants (median age 50 years), of which 312 were from Kumasi (urban) and 360 from Jachie-Pramso (rural). Demographic, anthropometric and other cardio-metabolic risk factors were gathered and venous blood samples were drawn for biochemical assays. Results suggested significant differences in diastolic blood pressure (80.0 mmHg vs 79.5 mmHg; p = 0.0078), and fasting blood sugar (5.0 mmo/l vs 4.5 mmol/l; p < 0.0001) between the two groups. Further differences in anthropometric measures suggested greater adiposity amongst participants in the urban area. Participants in the urban area were more likely than rural participants, to have high total cholesterol and LDL-c (p < 0.0001 respectively). Risk factors including BMI ≥ 25 (p < 0.0001), BMI ≥ 30 (p < 0.0001), high waist circumference (p < 0.0001), high waist-to-height ratio (p < 0.0001) and alcohol consumption (p = 0.0186) were more prevalent amongst participants in the urban area. Markers of adiposity were higher amongst females than males in both areas (p < 0.05). In the urban area, hypertension, diabetes and lifestyle risk factors were more prevalent amongst males than females. Differences in risk factors by urban / rural residence remained significant after adjusting for gender and age. Obesity and cardio-metabolic risk factors are more prevalent amongst urban settlers, highlighting an urgent need to avert the rise of diet and lifestyle-related chronic diseases.     

Separate and Joint Associations of Occupational and Leisure-Time Sitting with Cardio-Metabolic Risk Factors in Working Adults: A Cross-Sectional Study

Background

The workplace is a main setting for prolonged sitting for some occupational groups. Convincing evidence has recently accumulated on the detrimental cardio-metabolic health effects of leisure-time sitting. Yet, much less is known about occupational sitting, and the potential health risk attached compared to leisure-time sitting.

Objective

To explore the separate and joint associations of occupational and leisure-time sitting with cardio-metabolic risk factors in working adults.

Methods

All working adults (N = 2544) from the Health2006, a Danish population-based study, were included in this cross-sectional study. Participants reported hours of sitting during work, during leisure-time along with socio-demographic and behavioral characteristics, including physical activity. Cardio-metabolic risk factors (waist circumference, body mass index, body fat percentage, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, insulin, hemoglobin A1c and plasma glucose) were measured. Associations were explored by linear regression for leisure-time, occupational, and overall sitting time.

Results

Statistically significant (p<.05) detrimental associations of leisure-time sitting were observed with all cardio-metabolic risk factors, except hemoglobin A1c and plasma glucose. Similarly, occupational sitting time was significantly detrimentally associated with HDL cholesterol, triglycerides, and insulin. For categories of sitting time, a joint adverse association of sitting much during both work-time and leisure-time was observed.

Conclusion

The associations of occupational sitting time with cardio-metabolic risk factors were fewer and weaker compared to leisure-time sitting. Yet, the joint associations of occupational and leisure-time sitting with cardio-metabolic risk factors were higher than the separate. Our findings amplify the need for further focus in this area prior to making assumptions about equivalent health risks across sedentary behaviors. To our knowledge, this is the first study to contrast the deleterious associations of prolonged occupational and leisure-time sitting, both separately and jointly.     

新诊断标准下妊娠期糖尿病高危因素研究

目的:调查新诊断标准下国内妊娠期糖尿病(Gestational diabetes mellitus GDM)的发病情况,分析影响GDM发生的高危因素,为新标准下国内GDM孕妇临床早期管理、诊断和干预提供理论依据。方法:对2011年1月至2011年9月我院接受产前建卡检查的所有孕妇1152例进行临床资料的收集及回顾性研究,排除孕前糖尿病患者16例,采用GDM诊断新标准进行一步法诊断,收集包括年龄、孕产次、体质指数(body mass index BMI)、糖尿病家族史、多囊卵巢综合征等13种影响GDM发生的危险因素,并综合分析。结果:新标准下GDM检出率为10.39%(118/1136)2)单因素分析结果发现年龄≥35岁(X2=10.2814,P=0.0013)、肥胖(孕前BMI≥28kg/m2()X2=36.2384,P<0.0001)、多囊卵巢综合征(X2=20.6725,P<0.0001)、糖尿病家族史(X2=7.8783,P=0.0050)在GDM组与非GDM组有统计学差异,多因素逐步Logistic回归分析肥胖(OR=7.546 95%CI=2.356~20.129 P=0.0002)、多囊卵巢综合征(OR=6.342 95%CI=1.783~16.329,P=0.0019)、年龄(OR=3.021 95%CI=0.983~6.459 P=0.0108)、糖尿病家族史(OR=2.43895%CI=0.612~5.231 P=0.0256)为GDM的高危因素。结论:新标准下报告GDM检出率为10.39%。肥胖、多囊卵巢综合征、年龄、糖尿病家族史为影响GDM发生的高危因素。加强GDM筛查并对具有高危因素的妊娠期妇女早期诊断,早期干预、早期管理可改善妊娠结局,提高人口素质。     

Toll 样受体4在小于胎龄儿生后发生胰岛素抵抗的作用研究

目的:探讨Toll样受体4在小于胎龄儿生后发生胰岛素抵抗的作用。方法:建立动物模型,分为小于胎龄儿追赶生长组(S1组)、小于胎龄儿无追赶生长组(S2组)、适于胎龄儿组(AGA组)。生后4周和12周取血、肝脏和脂肪组织,检测血糖、胰岛素、甘油三酯、游离脂肪酸和总胆固醇,计算胰岛素抵抗指数(Homeostasis model assessment for insulin resistance index,HOMA-IR);ELISA法检测血清白介素-6、肿瘤坏死因子-α;实时定量RT-PCR法检测相同体质量肝脏和脂肪组织中Toll样受体4、髓细胞样分化因子88、核因子κB、肿瘤坏死因子-α和白介素-6 mRNA的表达。结果:与适于胎龄儿组和小于胎龄儿无追赶生长组相比,小于胎龄儿追赶生长组随年龄增长血糖、血清胰岛素、游离脂肪酸、甘油三酯和HOMA-IR逐渐增高(P0.05),相同体质量肝脏和脂肪组织中Toll样受体4、髓细胞样分化因子88、核因子κB、肿瘤坏死因子-α和白介素-6 mRNA表达量也逐渐升高(P0.05);肝脏和脂肪组织中Toll样受体4信号通路与胰岛素抵抗指数HOMA-IR呈显著正相关(P0.05),脂肪组织中的相关性显著高于肝脏组织(P0.05)。结论:SGA生后追赶生长者随年龄增长出现糖脂代谢异常;肝脏和脂肪组织Toll样受体4信号途径激活,诱发以TNF-α和IL-6为炎性介质的慢性炎症,促进胰岛素抵抗发生发展;脂肪组织在胰岛素抵抗发生发展中作用更强。     

Resting Brain Perfusion and Selected Vascular Risk Factors in Healthy Elderly Subjects

Background and Purpose

Both cerebral hypoperfusion and vascular risk factors have been implicated in early aging of the brain and the development of neurodegenerative disease. However, the current knowledge of the importance of cardiovascular health on resting brain perfusion is limited. The aim of the present study was to elucidate the relation between brain perfusion variability and risk factors of endothelial dysfunction and atherosclerosis in healthy aged subjects.

Methods

Thirty-eight healthy subjects aged 50–75 years old were included. Mean global brain perfusion was measured using magnetic resonance phase contrast mapping and regional brain perfusion by use of arterial spin labeling.

Results

Mean global brain perfusion was inversely correlated with caffeine and hematocrit, and positively with end-tidal P_CO2. Furthermore, the mean global brain perfusion was inversely correlated with circulating homocysteine, but not with asymmetric dimethylarginine, dyslipidemia or the carotid intima-media thickness. The relative regional brain perfusion was associated with circulating homocysteine, with a relative parietal hypoperfusion and a frontal hyperperfusion. No effect on regional brain perfusion was observed for any of the other risk factors. A multiple regression model including homocysteine, caffeine, hematocrit and end-tidal P_CO2, explained nearly half of the observed variability.

Conclusion

Both intrinsic and extrinsic factors influenced global cerebral perfusion variation between subjects. Further, the results suggest that the inverse relation between homocysteine and brain perfusion is owing to other mechanisms, than reflected by asymmetric dimethylarginine, and that homocysteine may be a marker of cerebral perfusion in aging brains.     

Low Birth Weight Is a Risk Factor for Severe Retinopathy of Prematurity Depending on Gestational Age

Objective

To evaluate the impact of low birth weight as a risk factor for retinopathy of prematurity (ROP) that will require treatment in correlation with gestational age at birth (GA).

Study design

In total, 2941 infants born <32 weeks GA were eligible from five cohorts of preterm infants previously collected for analysis in WINROP (Weight IGF-I Neonatal ROP) from the following locations: Sweden (EXPRESS) (n = 426), North America (n = 1772), Boston (n = 338), Lund (n = 52), and Gothenburg (n = 353). Data regarding GA at birth, birth weight (BW), gender, and need for ROP treatment were retrieved. Birth weight standard deviation scores (BWSDS) were calculated with Swedish as well as Canadian reference models. Small for gestational age (SGA) was defined as BWSDS less than −2.0 SDS using the Swedish reference and as BW below the 10^th percentile using the Canadian reference charts.

Results

Univariate analysis showed that low GA (p<0.001), low BW (p<0.001), male gender (p<0.05), low BWSDS_Canada (p<0.001), and SGA_Canada (p<0.01) were risk factors for ROP that will require treatment. In multivariable logistic regression analysis, low GA (p<0.0001), male gender (p<0.01 and p<0.05), and an interaction term of BWSDS*GA group (p<0.001), regardless of reference chart, were risk factors. Low BWSDS was less important as a risk factor in infants born at GA <26 weeks compared with infants born at GA ≥26 weeks calculated with both reference charts (BWSDS_Sweden, OR = 0.80 vs 0.56; and BWSDS_Canada, OR = 0.72 vs 0.41).

Conclusions

Low BWSDS as a risk factor for vision-threatening ROP is dependent on the infant''s degree of immaturity. In more mature infants (GA ≥26 weeks), low BWSDS becomes a major risk factor for developing ROP that will require treatment. These results persist even when calculating BW deficit with different well-established approaches.     

Neonatal Mortality and Long-Term Outcome of Infants Born between 27 and 32 Weeks of Gestational Age in Breech Presentation: The EPIPAGE Cohort Study

Objective

To determine whether breech presentation is an independent risk factor for neonatal morbidity, mortality, or long-term neurologic morbidity in very preterm infants.

Design

Prospective population-based cohort.

Population

Singletons infants without congenital malformations born from 27 to 32 completed weeks of gestation enrolled in France in 1997 in the EPIPAGE cohort.

Methods

The neonatal and long-term follow-up outcomes of preterm infants were compared between those in breech presentation and those in vertex presentation. The relation of fetal presentation with neonatal mortality and neurodevelopmental outcomes was assessed using multiple logistic regression models.

Results

Among the 1518 infants alive at onset of labor included in this analysis (351 in breech presentation), 1392 were alive at discharge. Among those eligible to follow up and alive at 8 years, follow-up data were available for 1188 children. Neonatal mortality was significantly higher among breech than vertex infants (10.8% vs. 7.5%, P = 0.05). However the differences were not significant after controlling for potential confounders. Neonatal morbidity did not differ significantly according to fetal presentation. Severe cerebral palsy was less frequent in the group born in breech compared to vertex presentation but there was no difference after adjustment. There was no difference according to fetal presentation in cognitive deficiencies/learning disabilities or overall deficiencies.

Conclusion

Our data suggest that breech presentation is not an independent risk factor for neonatal mortality or long-term neurologic deficiencies among very preterm infants.