Blood Pressure in 6-Year-Old Children Born Extremely Preterm

Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (<27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.Peer reviewe

Hypertension, Diabetes and Overweight: Looming Legacies of the Biafran Famine

Early life environment has in previous research been linked to risk of disease in adulthood. This thesis investigated three types of early life exposures and their potential associations with adult life cardiovascular risk. It has been proposed that early life malnutrition underpins the ongoing epidemic of lifestyle-related diseases in Sub-Saharan Africa. We examined the association between exposure to the Biafra famine (1968-1970) and cardiovascular risk in 1,339 Nigerians. Individuals exposed to famine in fetal-infant life had higher blood pressure, plasma glucose and BMI compared to individuals born after the famine. Malnutrition in early life may contribute to the burden of lifestyle- related disease in Sub-Saharan Africa (Paper I). Vitamin D deficiency is prevalent among women of childbearing age worldwide. Adult vitamin D deficiency has been linked to increased risk of cardiovascular disease, impaired glucose tolerance and obesity. We aimed to assess whether vitamin D status at birth is related to cardiovascular risk in adulthood. In paper II, neonatal vitamin D concentrations from stored blood samples were measured and cardiovascular risk markers assessed in 275 individuals aged 35 years born either in the end of the summer or in the end of the winter. We found no associations between low neonatal vitamin D status and cardiovascular risk at 35 years of age. However, men and women in the highest neonatal vitamin D quintile were at higher risk of being overweight (Paper II). The prime determinant of vitamin D status is exposure to sunlight. Month of birth is a proxy for a number of seasonally dependent environmental exposures including nutrition, infections, lifestyle factors – and vitamin D. At high latitudes, vitamin D levels in populations are lower in the winter compared to the summer due to scarce sunlight exposure. In the Swedish population aged 30 or above (>6 million individuals), followed from 1991 during 20 years, individuals born during autumn months lived longer than those born during spring months. The association between month of birth and mortality was particularly pronounced in the age-span 50 to 80 years and not significant before 50 years (Paper III). In the age-span 50 to 80 years, cardiovascular mortality was increased among spring-born compared to autumn-born. (Paper IV) Although individuals born in Sweden during the spring had an increased risk of cardiovascular mortality in ages 50 to 80 years (paper IV), the effect sizes were small. The lack of an association between low neonatal vitamin D status and adult cardiovascular risk in paper II indicate that vitamin D levels at birth may not be of sizeable importance to adult life cardiovascular health

Philosophy of the world and philosophy of Karl Löwith as a precursor and incentive to the idea of integrative bioethics

Traditional cosmology, once used to explain the world, was suppressed by the domination of science over philosophy which happened after their separation. Nowadays, scientific (in terms of natural sciences) cosmology is given the advantage in answering the question what is the world, while the "non-empirical" catholicity (the basic characteristic of traditional cosmology) became useless. Encouragement of one’s effort to re-establish the category of catholicity can be found in the idea of integrative bioethics on one side and in the philosophy of the world on the other. In this paper the relation between the idea of integrative bioethics and the philosophy of the world will be established through philosophical discussions which were held in Augsburg and in Zagreb (1988, 1990, 1993) and also with reliance on understanding the world in philosophy of Karl Löwith

Potencijalna korist meteoroloških informacija u prometu

U uvodu se ukazuje na ulogu i značaj meteorološke službe u valorizaciji prometa Republike Hrvatske. U drugom poglavlju daju se ciljevi i nabrajaju korisnici meteoroloških informacija u prometu, objašnjava priroda korisničkih zahtjeva i njihova identifikacija, vrste i sadržaj meteoroloških informacija, odnos korisnika prema ovim informacijama, te načini ostvarenja potencijalnih koristi u prometu. U trećem poglavlju obrazlaže se potreba upoznavanja meteorologa s djelatnostima korisnika informacija te osposobljavanje korisnika, i svih onih koji po prirodi posla dolaze u dodir s meteorološkim informacijama na putu od meteorologa do korisnika, kako bi se one optimalno koristile. U četvrtom poglavlju prikazan je sastav simulacijskog modela za istraživanje i primjenu potencijalnih koristi meteoroloških informacija u prometu, te se ukratko opisuje metodologija za njihovo efikasno korištenje od strane korisnika primjenom cost/benefit analize na jednostavnom primjeru

Long-term cardiovascular follow-up after preterm birth

Cardiovascular disease is a leading cause of morbidity and mortality worldwide. A large number of studies show that the risk of cardiovascular disease is increased in people born with low birth weight. The aim of this thesis is to study the contribution of preterm birth, the most common cause of low birth weight, to later cardiovascular function and disease risk. Clinical follow-up studies of children and adolescents born very preterm (total n=118) in the 1980 s and 1990 s were performed. Vascular endothelial function was assessed using Laser-Doppler measurements of skin perfusion responses to acetylcholine, an endothelium-dependent vasodilator (paper I-II). Dermal capillary density was studied using intra-vital video microscopy (paper II). Arterial stiffness was measured using pulse wave analysis, pulse wave velocity and ultrasound techniques (paper I and III). Arterial dimensions were studied using ultrasound and magnetic resonance imaging (paper I, III and IV). Paper I shows that adolescent girls, born at a mean gestational age of 29 w, had narrower abdominal aorta and lower skin perfusion, as compared to controls born at term. No signs of arterial stiffening were found and the endothelial function was unaffected after preterm birth. Paper II demonstrates that in 9-year old children born very preterm, the skin capillary density was reduced, but not the endothelial function, as compared to controls. Paper III shows that the 9-year old children born very preterm had the same carotid dimensions and stiffness as controls. Paper IV reports results from magnetic resonance imaging of the aorta in 86 healthy adolescents, of whom half were born very preterm. This study confirms the findings from paper I, showing lasting aortic narrowing after preterm birth. In addition, the aortic size was also strongly and independently associated with maternal smoking in pregnancy. Papers I, II and IV also show that children and adolescents born preterm have increased blood pressure. In paper II-III, the heart rate was higher in preterm children, but the heart rate was not related to their blood pressure. Paper V investigates the association between preterm birth and fetal growth restriction and later risk of hypertension in a cohort of 6,425 men and women born 1925-1949 in Sweden, of whom 2,931 were born preterm. At follow-up in 1987 through 2006, the risk of hypertension was increased by 53% in those born small for gestational age. Preterm birth was not associated with risk of subsequent hypertension. In conclusion, young subjects born very preterm exhibit altered vascular development, as illustrated by a lower capillary density and aortic narrowing. They also have higher blood pressure and heart rate. No signs of premature arterial stiffening or endothelial dysfunction early markers of atheromatous disease were found. The significance of these findings for future cardiovascular disease risk is not yet known

Cause-specific infant mortality in a population-based Swedish study of term and post-term births : the contribution of gestational age and birth weight

OBJECTIVE: To investigate infant mortality and causes of infant death in relation to gestational age (GA) and birth weight for GA in non-malformed term and post-term infants. DESIGN: Observational, retrospective nationwide cohort study. SETTING: Sweden 1983-2006. PARTICIPANTS: 2 152 738 singleton non-malformed infants born at 37 gestational weeks or later. MAIN OUTCOME MEASURES: Infant, neonatal and postneonatal mortality and causes of infant death. RESULTS: Infant mortality rate was 0.12% (n=2687). Compared with infants born at 40 weeks, risk of infant mortality was increased among early term infants (37 weeks, adjusted OR 1.70, 95% CI 1.43 to 2.02). Compared with infants with normal birth weight for GA, very small for gestational age (SGA; &lt;3rd percentile) infants faced a doubled risk of infant mortality (adjusted OR 2.13, 95% CI 1.80 to 2.53), and corresponding risk was also increased among moderately SGA infants (3rd to &lt;10th percentile; adjusted OR 1.46, 95% CI 1.26 to 1.68). Sudden infant death syndrome (SIDS) was the most common cause of death, accounting for 39% of all infant mortality. Compared with birth at 40 weeks, birth at 37 weeks was associated with increased risks of death by infections, cardiovascular disorders, SIDS and malignant neoplasms. Very and moderately SGA were associated with increased risks of death by neonatal respiratory disorders, infections, cardiovascular disorders, SIDS and neuromuscular disorders. High birth weight for GA was associated with increased risks of death by asphyxia and malignant neoplasms. CONCLUSION: Early term birth and very to moderately low birth weight for GA are independent risk factors for infant mortality among non-malformed term infants

Maternal Snuff Use and Smoking and the Risk of Oral Cleft Malformations - A Population-Based Cohort Study

Objective: To determine if maternal use of snuff (containing high levels of nicotine, low levels of nitrosamines and no combustion products) is associated with an increased risk of oral cleft malformations in the infant and whether cessation of snuff use or smoking before the antenatal booking influences the risk. Method: A population-based cohort study was conducted on all live born infants, recorded in the Swedish Medical Birth Register from 1999 through 2009 (n = 1 086 213). Risks of oral clefts were evaluated by multivariate logistic regression analyses (using adjusted odds ratios, with 95% confidence intervals [CI]). Results: Among 975 866 infants that had information on maternal tobacco use, 1761 cases of oral clefts were diagnosed. More than 50% of the mothers who used snuff or smoked three months prior pregnancy stopped using before the antenatal booking. Almost 8% of the mothers were smoking at the antenatal booking and 1,1% of the mothers used snuff. Compared with infants of non-tobacco users, the adjusted odds ratios (95% CI) of any oral cleft for infants of mothers who continued to use snuff or to smoke were 1.48 [1.00-2.21] and 1.19 [1.01-1.41], respectively. In contrast, in infants of mothers who stopped using snuff or stopped smoking before the antenatal booking, the corresponding risks were not increased (adjusted odds ratios [95% CI] were 0.71 [0.44-1.14] and 0.88 [0.73-1.05], respectively). Conclusion: Maternal snuff use or smoking in early pregnancy is associated with an increased risk of oral clefts. Infants of mothers who stopped using snuff or stopped smoking before the antenatal booking had no increased risk of oral cleft malformations. Oral snuff or other sources of nicotine should not be recommended as an alternative for smoke-cessation during pregnancy

Human- Versus Machine Learning-Based Triage Using Digitalized Patient Histories in Primary Care : Comparative Study

BACKGROUND: Smartphones have made it possible for patients to digitally report symptoms before physical primary care visits. Using machine learning (ML), these data offer an opportunity to support decisions about the appropriate level of care (triage).OBJECTIVE: The purpose of this study was to explore the interrater reliability between human physicians and an automated ML-based triage method.METHODS: After testing several models, a naïve Bayes triage model was created using data from digital medical histories, capable of classifying digital medical history reports as either in need of urgent physical examination or not in need of urgent physical examination. The model was tested on 300 digital medical history reports and classification was compared with the majority vote of an expert panel of 5 primary care physicians (PCPs). Reliability between raters was measured using both Cohen κ (adjusted for chance agreement) and percentage agreement (not adjusted for chance agreement).RESULTS: Interrater reliability as measured by Cohen κ was 0.17 when comparing the majority vote of the reference group with the model. Agreement was 74% (138/186) for cases judged not in need of urgent physical examination and 42% (38/90) for cases judged to be in need of urgent physical examination. No specific features linked to the model's triage decision could be identified. Between physicians within the panel, Cohen κ was 0.2. Intrarater reliability when 1 physician retriaged 50 reports resulted in Cohen κ of 0.55.CONCLUSIONS: Low interrater and intrarater agreement in triage decisions among PCPs limits the possibility to use human decisions as a reference for ML to automate triage in primary care

Number of deaths and excess hazard ratio (EHR) in ‰ compared to November (95% confidence interval) in the age-span >30: crude model, adjusted for sex and education, male (adjusted for education) and female (adjusted for education) and with p-value for type 3-test.

<p>Number of deaths and excess hazard ratio (EHR) in ‰ compared to November (95% confidence interval) in the age-span >30: crude model, adjusted for sex and education, male (adjusted for education) and female (adjusted for education) and with p-value for type 3-test.</p

Multi-Fetal Pregnancy, Preeclampsia, and Long-Term Cardiovascular Disease

This Swedish register-based cohort study determined the separate and joint contribution of preeclampsia and multi-fetal pregnancy on a woman's risk of cardiovascular disease (CVD) later in life. The study included 892 425 first deliveries between 1973 and 2010 of women born 1950 until 1971, identified in the Swedish Medical Birth Register. A composite outcome of CVD was retrieved through linkage with the National Patient and Cause of Death Registers. Cox proportional hazard regression was used to assess the risk of CVD in women who had preeclampsia in a singleton or multi-fetal pregnancy, adjusting for potential confounders, and presented as adjusted hazard ratios. Compared with women who had a singleton pregnancy without preeclampsia (the referent group), women with preeclampsia in a singleton pregnancy had an increased risk of CVD (adjusted hazard ratio 1.75 [95% CI, 1.64-1.86]). Women who had a multi-fetal pregnancy without or with preeclampsia did not have an increased risk of future CVD (adjusted hazard ratios 0.94 [95% CI, 0.79-1.10] and 1.25 [95% CI, 0.83-1.86], respectively). As opposed to preeclampsia in a first singleton pregnancy, preeclampsia in a first multi-fetal pregnancy was not associated with increased risk of future CVD. This may support the theory that preeclampsia in multi-fetal pregnancies more often occurs as a result of the larger pregnancy-related burden on the maternal cardiovascular system and excessive placenta-shed inflammatory factors, rather than the woman's underlying cardiovascular phenotype