Growth and joint symptoms in children treated with nalidixic acid.

To analyze the effects of quinolones on growth and joints in children we identified 78 patients who had been receiving nalidixic acid for 116 days on the average (range, 3 to 570 days) from a random sample of 3094 of 16,409 children treated with long term medication because of recurrent urinary tract infection. Two controls per each index case, matched for sex and the age at which the first medication for recurrent urinary tract infection occurred, were chosen. Frequency of joint symptoms and examinations or possible treatments for arthropathies were similar in the index (n = 44) and control (n = 62) cases. Detailed growth data were analyzed from 39 case-control pairs after the mean follow-up time of 19.6 years (range, 14.8 to 24.7 years), and no growth disturbances were found. The final heights (age, > 18 years) of the index and control cases were similar (n = 31 case-control pairs). We conclude that nalidixic acid does not cause arthropathies or hamper growth in children, which supports the suggestion that at least short treatment periods with quinolones are safe.

Adverse reactions in children during long-term antimicrobial therapy.

BACKGROUND: It is difficult to obtain reliable date on the rate of adverse reactions caused by drugs in general use. Yet it would be important to compile data on adverse reactions to long-term antimicrobial therapy. METHODS: A sample of 1607 girls and 218 boys from 16 409 children younger than 16 years who had received long term antimicrobial therapy for recurrent urinary tract infections during 1976 to 1985 was analyzed with regard to adverse reactions. RESULTS: Altogether 5066 courses of treatment were given to female patients and 607 to male patients. Adverse reactions were reported in 589 courses of the 5673 (10.4%), and 463 courses (8.2%) were discontinued because of adverse reactions. None of the patients had serious life-threatening reactions, and none of those receiving nitrofurantoin had pulmonary problems. The most common adverse reactions associated with the use of nitrofurantoin were nausea and vomiting (rate, 4.4/100 person years at risk; 95% confidence interval, 3.4 to 5.4), whereas sulfonamides caused most commonly allergic skin reactions (rate, 4.6; 95% confidence interval, 3.2 to 6.5). Patients younger than the age of 2 years receiving nitrofurantoin had adverse reactions more often than those who received sulfonamides, but in the age group 2 to 15 years sulfonamides caused adverse reactions leading to discontinuation of treatment more often than did nitrofurantoin of treatment the adverse reactions occurred during the first 6 months of treatment. CONCLUSIONS: We found nitrofurantoin and sulfonamides to be safe drugs for use in long term preventive antimicrobial therapy.

Angiotensin converting enzyme gene insertion/deletion polymorphism, angiotensinogen gene polymorphisms, family history of hypertension, and childhood blood pressure.

Earlier epidemiologic studies have yielded inconsistent results on the extent and timing of the blood pressure (BP) increase in offspring of hypertensive parents. We hypothesized that a familial influence on the BP of the offspring exists from birth on, but becomes significant only later in childhood. We studied the influence of familial occurrence of hypertension on the BP of 3596 children aged 6 to 18 years during a 6-year follow-up. In addition, we examined the possible associations of BP variations with polymorphisms of two candidate genes for hypertension, ie, those coding for the angiotensin converting enzyme (ACE) and those coding for angiotensinogen. A positive family history of hypertension was reflected as the occurrence of higher systolic BP values from the age of 9 years and upward among the females and from the age of 12 years and upward among the males. The mean differences in BP varied from 3.2 to 5.8 mm Hg (systolic) and 2.1 to 5.9 mm Hg (diastolic) between the female offspring of normotensive and hypertensive parents and grandparents. The systolic BP values were significantly higher among females with a hypertensive history in two generations in comparison with females from normotensive families. Among the male offspring of hypertensive and normotensive families, the BP differences were inconsistent. The deletion/deletion males had higher systolic BP values than those with other ACE genotypes. In contrast, variation at the angiotensinogen gene locus was not significantly associated with BP. We conclude that parental history of hypertension is a risk factor for high blood pressure among the offspring from the ages of 9 to 12 years and upward, and hypertension within two generations may enhance this effect. Although the common genetic variation of ACE may influence blood pressure in male children and adolescents, our data do not suggest a role for the common variation of the angiotensinogen gene as a BP regulator during childhood.

Insulin and blood pressure among healthy children. Cardiovascular risk in young Finns.

We evaluated the role of insulin in regulating and predicting blood pressure among 3596 to 2799 Finnish children and adolescents aged 3 to 18 years who were followed from 1980 to 1986. Blood pressure, weight, and height were measured in three surveys 3 years apart. Fasting blood samples were drawn and serum insulin was analyzed. The effect of insulin on blood pressure was evaluated in each of the 3 study years, together with the effect of fasting insulin on future blood pressure and the effect of insulin on the change in blood pressure. We also analyzed the correlation between insulin and blood pressure in different age groups and the correlation between change in insulin and change in blood pressure. A constant positive correlation was found between insulin and both systolic and diastolic (Korotkoff's fifth phase) blood pressures measured in the respective years (correlation coefficients 0.10 to 0.41 and partial correlation coefficients 0.02 to 0.15), except between insulin and diastolic blood pressure in the first two surveys in terms of partial correlation and multiple regression analysis. Similarly insulin and blood pressure correlated positively in every age group. Insulin measured in 1980 or 1983 predicted systolic blood pressure as measured 3 and 6 years later (correlation coefficients 0.30 to 0.47 and partial correlation coefficients 0.06 to 0.13), and likewise diastolic blood pressure as measured 3 and 6 years later (correlation coefficients 0.17 to 0.35 and partial correlation coefficients 0.05 to 0.08), except among the males in 1983. Correlation between insulin and the change in blood pressure was not significant or remained marginal. Similarly, the correlation between change in insulin and change in blood pressure was not significant or remained marginal. We suggest that insulin seems to regulate actual blood pressure within the normal range and to predict future blood pressure among children and adolescents, independently of age and weight. However, insulin does not enhance the rise in blood pressure.

Lack of association between copper, zinc, selenium and blood pressure among healthy children.

Contradictory results have been published about the relation between copper, zinc and selenium and blood pressure (BP). To evaluate the role of these trace elements in BP regulation, we analysed the correlations between BP and copper, zinc and selenium, measured from serum, diet and hair among 3596 healthy children in a 6-year follow up. Fasting blood samples were used in serum copper, zinc and selenium analyses. The dietary intake of trace elements and energy were determined by the 48-h recall method. The hair copper and zinc analyses were performed from the naturally coloured hair samples. Correlation analysis was used to show the relation between BP and copper, zinc or selenium in each study year and during a 3- or 6-year follow-up period. The zinc-to-copper ratio in serum, diet and hair was calculated. In the correlation analyses the data was adjusted for weight and the daily intake of energy. Neither serum and diet copper or zinc, nor the zinc-to-copper ratio correlated uniformly with BP measured in the same year (correlation coefficients varying from -0.12 to 0.18) or in the subsequent years. Hair copper and zinc correlated weakly negatively with BP (correlation coefficients varying from -0.17 to -0.01). Serum selenium correlated weakly positively with systolic and diastolic BP measured in the same year (correlation coefficients varying from 0.03 to 0.14), but not with subsequent BP measured in the second or third survey. Dietary selenium had an inconsistent effect on BP (correlation coefficients varying from -0.14 to 0.26). In conclusion, copper, zinc, their ratio or selenium did not associate with BP, nor did they have any effect on subsequent BP.

Random-zero sphygmomanometer, Rose's tape, and the accuracy of the blood pressure measurements in children.

In the Cardiovascular Risk in Young Finns project, blood pressure (BP) was measured in 3549 randomly selected children aged 6-18 y in 1980, and 2887 and 2500 of the same individuals in 1983 and 1986, respectively. An ordinary mercury sphygmomanometer (OMS) was used in the first two surveys and a random-zero sphygmomanometer (RZS) in the third survey. Systolic and diastolic BP were lower when measured with an RZS than with an OMS and the shape of the age-related BP curve obtained with an RZS was significantly different from that obtained with an OMS, because low BP values were apparently measured more accurately with the former. Use of the RZS did not affect the distribution of the BP values. Rose's tape readings were used to evaluate the effect of training and to control the accuracy of the BP measurements. According to Rose's tape readings, Korotkoff's 4th phase BP was more difficult to measure accurately than 5th phase (p = 0.002). The mean values for the differences between the correct and actual BP readings on the Rose's tape were -1.2 mm Hg (SD 2.1) for systolic BP, 8.3 mm Hg (SD 13.6) for diastolic Korotkoff's 4th phase BP, and 1.2 mm Hg (SD 7.0) for diastolic Korotkoff's 5th phase BP, with a negative value indicating that the BP phase was measured lower than the correct value. Terminal digit preference was present in each survey to such an extent that it could have hampered the reaching of reliable conclusions from the data obtained with an OMS. The bias caused by terminal digit preference was obviated by the RZS.(ABSTRACT TRUNCATED AT 250 WORDS)

A meta-analytical approach to the pooling of blood pressure values in children.

Meta-analysis of blood pressure (BP) studies in children was performed in order to evaluate whether BP readings obtained in various studies may be pooled. In total 30 original reports on BP in children were analyzed and the age and sex-specific BP values reported for 12 and 15-year-old subjects in 11 of these were tested for homogeneity. The differences in sample size-weighted means between the devices used (with 95% confidence intervals) were evaluated. The BP values reported in different studies for systolic Korotkoffs first phase BP (K1) and diastolic Korotkoffs fourth (K4) and fifth (K5) phase BP were shown to be too heterogeneous (p < 0.001) to be pooled. Heterogeneity and measurement biases in the BP results were caused by differences between the devices and the diastolic BP indicator (K4 vs K5) and by observer biases such as uncontrolled terminal digit preference. The device-specific weighted means for K1, K4 and K5 BP in 12 and 15-year-old subjects showed statistically significant differences between random zero (RZS) and ordinary mercury (OMS) sphygmomanometer (p < 0.001) the difference (OMS-RZS) being from 0.7 to 6.6 mmHg for K1 (p < 0.001, except in 12-year-old girls), from 1.1 to 7.1 mmHg for K4 (p < 0.001, except in 12-year-old girls) and from 4.5 to 7.9 mmHg for K5 (p < 0.001). Such a discrepancy was also apparent between ordinary and automated mercury sphygmomanometer (AMS) in the case of diastolic K4 and K5 BP (p < 0.001), but not in K1. BP results obtained in different investigations using different BP devices and Korotkoffs phases as indicator of diastolic BP should not be pooled. More widely accepted recommendations are needed to standardize the measurement of BP in children.

Change in blood pressure during pubertal insulin resistance.

To examine the levels and relationship of blood pressure and insulin during puberty, blood pressure and serum insulin were measured in 3596 subjects, aged 3-18 y, whose pubertal status was graded according to the Tanner classification. The same study protocol was repeated in two follow-up surveys 3 and 6 y later for 2991 6-21-y-old subjects and 2799 9-24-y-old subjects, respectively. There was a 37-66% increase in insulin at Tanner stage 3 (pubic hair) among the female subjects and at Tanner stage 5 (pubic hair) among the male subjects, after which insulin started to decrease. The mean systolic and diastolic blood pressure increased steadily throughout puberty. The rise in blood pressure continued during early adulthood, despite the decrease in serum insulin. The correlation between systolic blood pressure and insulin measured in the same year was weak at each pubertal stage after standardization for weight, except among the female subjects at mid puberty. There was no relation between diastolic blood pressure and insulin. Adult systolic blood pressure could be predicted by pubertal insulin among the male subjects after adjustment for age and weight (partial correlation coefficient 0.21), but among the female subjects this relation was trivial (partial correlation coefficient 0.08). We conclude that the correlation between insulin and actual blood pressure vanishes during puberty, whereas pubertal insulin and future adult male systolic blood pressure seem to correlate.

Pulse sounds and measurement of diastolic blood pressure in children.

Controversy exists over the value of measuring diastolic blood pressure (BP) in children, and over whether this should be measured at Korotkoff's fourth phase (K4) or fifth phase (K5) of pulse sounds. We measured diastolic BP in 3012 randomly selected Finnish children aged 6-18 years in 1980, and in 2885 of the same individuals in 1983 and 2500 in 1986. BP was measured with a standard mercury sphygmomanometer in 1980 and 1983, and with a random-zero sphygmomanometer in 1986. K4 was consistently absent in 187 individuals (3.2%) in 1980 and 1983, and in 155 individuals (6.2%) in 1986. K5 was absent in only 34 individuals (0.6%) in 1980/83 and 5 (0.2%) in 1986. The difference between mean K4 and K5 diastolic BP varied from 6.5 to 9.2 mm Hg depending upon age. K4 and K5 BPs showed good correlation in all age groups. Reliable and repeatable BP measurements in all age groups of children are best achieved with K5 as the indicator of diastolic BP.

Prenatal and postnatal factors in predicting later blood pressure among children: cardiovascular risk in young Finns.

A negative correlation between birth weight and subsequent blood pressure has been reported, but in some studies this correlation has not been found. We analyzed the effect of birth weight and pubertal development and several pre- and postnatal factors on subsequent blood pressure among 2500 children and adolescents in a follow-up study with three surveys conducted with 3-y intervals. The correlations between birth weight and systolic blood pressure varied from -0.04 to 0.02 among the female subjects and from -0.05 to -0.04 among the male subjects in each survey. A somewhat stronger relation was found among the postpubertal female and male subjects (correlation coefficient -0.09 and -0.05) in the last survey. When adjusted for weight, the correlations became negative and more often significant. The decrease in the adjusted mean systolic blood pressure was about 2 mm Hg when birth weight increased from the lowest to the highest tertile. Other factors affecting systolic blood pressure were current age (mean change up to 1.8 mm Hg/ y) and weight (mean change up to 1.2 mm Hg/kg), the duration of breast feeding over 3 mo (mean change up to -6.5 mm Hg), and a birth rank order over four (mean change up to 5.0 mm Hg) presented as the mean difference from the baseline. According to the multiple regression analysis, a history of mother's high blood pressure during pregnancy (p < 0.05) predicted future blood pressure more eminently than birth weight. In conclusion, our results based on healthy children and adolescents offer support for the theory of low birth weight as a predicting factor for future blood pressure. However, other pre- and postnatal factors seem to be important as well.

Altered serum lipid profile after systemic infection in children: risk factor for CHD?

Systemic infections may thicken the intima of coronary arteries and modify the serum lipid profile. Infants and children are particularly susceptible to such intimal thickening, the signs of which are more pronounced in infants who have evidence of infection at death. The topography of the thickenings, their greater size in males, and in families with a history of coronary heart disease favours the idea that the thickenings are pre-atherosclerotic. Infections modify the serum lipid pattern: serum high density lipoprotein (HDL) cholesterol concentration decreases and stays low during convalescence. Thus repeated infections might prove to be a risk factor for atherosclerosis via their effect on HDL concentration.

Nutritional and genetic contributions to serum cholesterol concentration in a children's follow-up study.

In the Finnish multicentre study of cardiovascular risk in young Finns in 1980, 1983 and 1986, 2429, 2052 and 1841 9 to 18-year-old children and adolescents participated. In 1980, subjects of eastern origin living in the west had, despite their western diet, higher serum cholesterol concentrations than subjects both residing in and originating from the west. In males, eastern origin increased the east/west difference in serum cholesterol concentrations. Between 1980 and 1986 the mean serum total cholesterol of the study cohorts decreased by 5.5% and simultaneously the east/west differences in serum cholesterol concentrations disappeared in boys. The study suggests that genetic background is a separate factor determining serum total cholesterol level, but with declining serum cholesterol concentrations the effect of the genetic factor does not become manifest.

Diet, serum fatty acids, and atopic diseases in childhood.

BACKGROUND: The reasons behind the reported increase in the occurrence of childhood atopic sensitization rates are unclear. We wanted to evaluate the association between dietary fats, serum fatty acids, and the occurrence and development of atopic diseases. METHODS: From a longitudinal database of a population-based sample, 231 sex- and age-matched pairs in 1980 and 154 pairs in 1986 were chosen, between whom we compared the dietary data, serum fatty acid composition, and occurrence of atopic diseases. The same variables were also compared between those who developed atopic disease later and those who did not during the 9-year follow-up. RESULTS: Examination of the dietary data in 1980 for those who had developed atopic disease compared with those who had remained healthy showed that the atopic children had used less butter before the expression of atopy. According to the cross-sectional data, the children with atopic disease consumed more margarine (mean 8.6 vs 7.3 [P = 0.04]), and less butter (mean 9.4 vs 11.6 g/1000 kcal [P = 0.002]), than the nonatopic children in 1980. Differences supporting these dietary findings were similarly found in the serum fatty acid data. CONCLUSION: The diet of the atopic children differed from that of the nonatopic children in the consumption of polyunsaturated fat.

Blood pressure in children, adolescents and young adults.

The question of whether blood pressure is one of the main risk factors for cardiovascular diseases in childhood has been evaluated in a Study of Cardiovascular Risk in Young Finns. In the second follow-up study, carried out in 1986, blood pressure was successfully measured in 2500 individuals aged nine to 24 years using a random zero sphygmomanometer. The mean systolic blood pressure in girls rose from 102 mmHg (95th percentile 119 mmHg) at age nine to 116 mmHg (138 mmHg) at age 24 and that in boys from 102 mmHg (95th percentile 121 mmHg) to 128 mmHg (148 mmHg). Diastolic blood pressure was more often measurable using Korotkoff's 5th than the 4th phase. The values observed were similar to those reported by the Second Task Force on Blood Pressure Control in Children, but owing to differences in the methods used to measure blood pressure it cannot be reliably concluded that the blood pressures were similar in the two series. Even in childhood blood pressure measurement is important, and since it changes with the physical size of the child, observations should be compared with normal values such as those reported here. No data are yet available to suggest that children with blood pressure values in the high normal range would benefit from interventions. Thus normal blood pressure value curves should be applied with caution when assessing children.

Obesity in children, adolescents and young adults.

The prevalence of obesity in Finnish children, adolescents and young adults aged three to 24 years was estimated in three surveys performed within the multicentre project, "Cardiovascular Risk in Young Finns" (1980, 1983, 1986). Obesity was defined as either body mass index (weight/height) or skinfold thickness (triceps or subscapular) or both greater than 90th percentiles of age and sex-specific reference data for white children. Its mean prevalences among 9- to 18-year old boys and girls in three surveys (95% confidence limits) were 3.6% (3.1-4.2) and 2.1% (1.7-2.6) as estimated in terms of body mass index and triceps skinfold thickness or 4.3% (3.9-4.9) and 2.6% (2.2-3.1) according to body mass index and subscapular skinfold thickness. Thus the 9- to 18-year old boys were on average more often obese than the girls, but no statistically significant changes in the prevalence of obesity were observed over the period 1980-1986. Body mass index and triceps or subscapular skinfold thicknesses vary in sensitivity as indicators of obesity.