Congenital diaphragmatic hernia: improved surgical results should influence abortion decision making.

AIMS: To compare surgical results for congenital diaphragmatic hernia (CDH) in two Scandinavian university hospitals and to evaluate the effects of abortions on the clinical profile of CDH in Iceland. METHODS: A retrospective study including all CDH-cases in Iceland 1983-2002 and children referred to Lund University Hospital 1993-2002. Aborted fetuses with CDH from a nation-wide Icelandic abort-registry were also included. RESULTS: In Iceland, 19 out of 23 children with CDH were diagnosed < 24 hours from delivery, one with associated anomalies. Eight fetuses were diagnosed prenatally and seven of them aborted, three having isolated CDH at autopsy. In Iceland, 15 of 18 children operated on survived surgery (83% operative survival). In Lund 28 children were treated with surgery, 23 of them diagnosed early after birth or prenatally. Four children did not survive surgery (86% operative survival) and 9 (31%) had associated anomalies. All the discharged children treated in Iceland and Lund are alive, 3-22 years postoperatively. CONCLUSION: CDH is a serious anomaly where morbidity and mortality is directly related to other associated anomalies and pulmonary hypoplasia. However, majority of CDH patients do not have other associated anomalies. In spite of improved surgical results (operative mortality < 20%), a large proportion of pregnancies complicated with CDH are terminated. We conclude that the improved survival rate after corrective surgery must be emphasized when giving information to parents regarding abortion of fetuses with a prenatally diagnosed CDH.

A molecular survey of phenylketonuria in Iceland: identification of a founding mutation and evidence of predominant Norse settlement.

Iceland was settled during the late 9th and early 10th centuries AD by Vikings who arrived from Norway and the British Isles. Although it is generally acknowledged that the Vikings brought with them Celtic slaves, the relative contribution of these peoples to the modern Icelandic gene pool has been a matter of considerable discussion. Most population genetic studies using classical markers have indicated a large Irish genetic contribution. We have investigated the molecular basis of phenylketonuria (PKU) in 17 Icelandic patients and found 9 different mutations in the phenylalanine hydroxylase gene. One novel mutation, Y377fsdelT, accounts for more than 40% of the mutant chromosomes. Haplotype data support a common ancestral origin of the mutation, and genealogical examination extending back more than 5 generations shows that this mutation has probably arisen in an isolated part of southern Iceland and was enriched by a founder effect. At least 7 PKU mutations have originated outside iceland. The almost exclusively Scandinavian background of these mutations and the complete absence of common Irish PKU mutations strongly support historical and linguistic evidence of a predominant Scandinavian heritage of the Icelandic people.

Bacterial meningitis: diagnosis and initial antibiotic therapy.

Despite advances in antibiotic treatment, bacterial meningitis remains a significant cause of mortality and morbidity among children. In population-based studies in the United States, the incidence of bacterial meningitis is estimated to be 4.6 to 10 per 100,000 population per year. Every year more than two thousand deaths due to bacterial meningitis are reported in the United States, most of these in previously healthy children. This article reviews diagnosis and management of this puzzling disease entity.

Maternal treatment with a cardioselective beta-blocking agent--consequences for the ovine fetus during intermittent asphyxia.

To evaluate the effect of chronic beta 1-adrenoceptor blockade on physiological adaptation to asphyxia a study was done on exteriorized sheep fetuses of 127-142 days gestational age. Eleven pregnant ewes were infused with metoprolol for 5 days prior to experiment. Another 10 ewes were infused with saline and served as controls. Asphyxia was induced by intermittent complete obstruction of maternal placental blood flow. Fetal electro-cardiogram, heart rate, cardiac output, myocardial contractility and cerebral blood flow were measured together with blood pH, lactate and hypoxanthine. Neurophysiological responses were evaluated by changes in somatosensory evoked electroencephalogram. The beta 1-blocked fetuses showed less responsiveness in myocardial contractility and heart rate during reoxygenation. This curtailed reaction resulted in accelerated lactic acidosis, increased break-down of intracellular energy rich substances and impaired cerebral function. Nine of the ten controls survived the experiment and 8 of them regained their somatosensory evoked EEG potentials, whereas 7 of the 11 beta-blocked fetuses survived and only 3 regained original somatosensory evoked EEG potentials. It is concluded that beta 1-adrenoceptor blockade impairs the adaptive responses to asphyxia in the ovine fetus and decreases its ability to survive severe asphyxia.

Acute blockade of beta 1-receptors in the asphyxiated sheep fetus.

The effects of acute beta 1-blockade on fetal cardiovascular reactions during asphyxia were evaluated in 11 exteriorized sheep fetuses. Gestational age was 110-142 days. Asphyxia was induced either by ventilating the mother with low oxygen gas mixture or by mechanical reduction of placental blood flow. During asphyxia all fetuses reacted to metoprolol injection with a decrease in heart rate, myocardial contractility, cardiac output and arterial blood pressure. Five experiments resulted in irreversible fetal cardiovascular collapse. Isoprenaline was given to the fetuses during hypoxia to test the ability to further increase heart rate and activate myocardial beta-adrenoceptors. In those experiments with fetal cardiovascular demise after metoprolol, the isoprenaline injection did not result in a significant tachycardia. The surviving fetuses could increase their heart rate as a sign of a capacity to further increase the sympatho-adrenergic drive.

[Feeding patterns and risk factors in an epidemic of neonatal necrotizing enterocolitis.].

OBJECTIVE: To study the relationship between neonatal feeding patterns and the emergence of neonatal necrotizing enterocolitis during the epidemic of this disease in Iceland in 1987-1990. MATERIAL AND METHODS: This was a retrospective case-controlled study of 18 newborns that developed neonatal necrotizing enterocolitis during a four year epidemic of the disease. Two newborns of similar weight and gestational age served as controls for each case. The amount of food given per kilogram of body weigth was recorded every 12 hours for each group and plotted against time. The differences in amount of food for the individuals of each group were calculated, regression lines found and these compared by t-test. The type of food the children received was also noted and compared, as was the presence of several other possible risk factors. RESULTS: The statistical calculation (t-test) showed that there was no significant difference between the patients and the controls as regards the amount of food given and the increase in the amount of each feeding (p=0.6). Sixteen (88.9%) of the patients had been fed before the occurrence of the disease. All had been fed through a gastric tube but only 20 (55.6%) of the controls, this is a significant difference (p=0.03). Three (18.8%) of the patients and 18 (50%) of the controls were given breast milk at their first feed. This difference however is not statistically significant (p=0.07). Comparison was also made of the occurrence of the following risk factors: umbilical catheter, perinatal asphyxia, polycythemia, acute or semiacute cesarian section, respiratory distress and being small for gestational age. Only births by cesarian section showed a significant difference between the groups (p= 0.004). Comparison of the number of risk factors did not show a statistically significant difference (p= 0.05). However there was a linear trend towards the patients having more risk factors than the controls (p=0.01). CONCLUSION: The study did not show that the epidemic of neonatal necrotizing enterocolitis in Iceland in 1987-1990 was caused by the increments in feeding given prior to the development of the disease. Two possible risk factors, feeding by gastric tube and birth by acute or semiacute cesarian section, were significantly more often found in the patient group than in the control group.

The relationship between circulating catecholamines and ST waveform in the fetal lamb electrocardiogram during hypoxia.

Previous studies from this laboratory have shown that changes in the ST waveform in the fetal electrocardiogram are a sign of fetal asphyxia. In the present study, seven chronically instrumented fetal lambs between 117 and 143 days' gestation were studied during 16 one-hour periods of maternally induced hypoxia. The aim was to test the hypothesis of a relationship between the concentration of circulating catecholamines and T-wave amplitude. The response to hypoxia was aged-dependent. Fetuses below 126 days of gestation did not react with electrocardiographic changes and output of epinephrine unless acidosis occurred. In more mature fetuses, hypoxia per se would induce a surge of epinephrine and changes in the ST waveform. Overall there was a strong correlation between the T/QRS ratio and the level of circulating epinephrine. During normoxia, epinephrine was undetectable (less than 0.1 nmol/L) in most fetuses; norepinephrine showed an increase at term. The analysis showed one fetus with chronic changes in the ST waveform (T/QRS ratio greater than 0.30) related to a marked increase in the plasma level of epinephrine in spite of normal blood gas values. These findings complement previous results in the acute and chronically instrumented fetal lamb and suggest that changes in the ST waveform expressed as T/QRS ratio identify a change to anaerobic myocardial metabolism mediated by beta-adrenergic stimulation.

Beta-adrenoceptor agonists and hypoxia in sheep fetuses.

Sheep fetuses, near term, were studied to test the influence of a tocolytic beta agonist, terbutaline, on fetal responses to hypoxia. After fetal exteriorization the drug was administered intravenously to the mother in three different doses: The max group comprised 11 ewes receiving 67-134 micrograms min-1. Seven ewes were given 30 micrograms min-1 and eight ewes were infused with 10 micrograms min-1. Seventeen fetuses served as controls. Hypoxia was induced by intermittent complete occlusions of the maternal abdominal aorta. Maternal terbutaline levels were high (range 50-748 nmol l-1) in the max group and the 30-micrograms group, whereas those in the 10-micrograms group were in the clinical range (range 11-58 nmol l-1). Fetuses in the max and 30-micrograms groups reacted to moderate hypoxia with excessive responses of heart rate, blood pressure myocardial contractility and ST waveform changes and a 50% mortality rate during severe hypoxia as compared with 12% in the control animals. Ten micrograms min-1 did not decrease the survival but caused an increase in myocardial workload and a negative energy balance during severe hypoxia.

[Height and weight of Icelandic children 6-20 years of age.].

INTRODUCTION: Monitoring growth rate in children reflects the state of health and nutrition of the individual as well as the state of health of a nation. Until now little information has been available about the growth pattern of Icelandic children. We report here the results of a nationwide cross-sectional study of growth in Icelandic children aged 6-20 years. MATERIAL AND METHODS: Height, standing and sitting and weight were measured in a total of 6500 schoolchildren, 3173 girls and 3327 boys. The measurements were performed 1983-1987. Children were randomly selected from The National Registry according to date of birth from both urban and rural areas of the whole country of Iceland. Stature was measured by a Harpenden stadiometer and the children were weighed in underwear only using a standardized scale. RESULTS: The mean values and standard deviations for height, standing and sitting and weight are presented in tables. Growth charts for height weigt and sitting height are presented. No difference in height and weight was found between children from rural and urban areas. The results show that the growth of Icelandic children is in all age groups almost identical to the growth of Norwegian children. Compaired to other Nordic and WHO growth standards, Icelandic children are tall, especially during early pubertal development. CONCLUSIONS: Icelandic children are tall and the growth of Icelandic and Norwegian children follows the same pattern wich supports the theory that the two nations are closely related.

[Puberty in Icelandic girls.].

In a crosssectional study, 2775 healthy Icelandic girls, aged 6-16 years, were examined for physical signs of puberty. The study was performed in 1983-1987 and was a part of a larger crosssectional study of growth and development of 5526 Icelandic children all of whom were examined by the authors. Breast development stage 2 according to Tanner (B 2) was considered the first sign of puberty in girls. The mean age of Icelandic girls reaching B 2 was 10.84 years (SD 1.43). The mean time interval between B 2 and menarche was 2.42 years. The first signs of pubic hair growth, Tanner stage 2 (PH 2) were found at 11.46 years (SD 1.25). The mean time interval between PH 2 and PH 5 was 3.40 years. Comparison with studies from other countries is difficult because of different methods and different study designs, but the timing and tempo of puberty in Icelandic girls seems to be similar to what has been reported from other Nordic countries and countries in Western-Europe.

[Puberty in Icelandic boys.].

In a crosssectional study, 2751 healthy Icelandic boys aged 6-16 years, were examined for physical signs of puberty. The study was performed in 1983-1987 and was a part of a larger crosssectional growth study of 5526 Icelandic children all of whom were examined by the authors. Testicular volume of 4 ml (T 4) was considered the first sign of puberty in boys. The mean age of Icelandic boys reaching T 4 was 11.89 years (SD 1.08). The mean time interval between T 4 and T 12 was 2.21 years. The first signs of pubic hair growth, Tanner stage 2 (PH 2), were found at 12.74 years (SD 1.37). The mean time interval between PH 2 and PH 5 was 2.43 years. Even though comparison with studies from other countries is difficult because of different methods and different study design, we find that the timing and tempo of puberty in Icelandic boys is similar to what has been reported from other Nordic countries and countries in Western-Europe.

Maternal beta-adrenoceptor blockade reduces fetal tolerance to asphyxia. A study in pregnant sheep.

Maternal and fetal beta 1-adrenoceptor blockade was induced in sheep by infusing i.v. 11 pregnant ewes with metoprolol in doses producing maternal plasma concentrations of metoprolol comparable to those obtained in clinical use. Ten other ewes and their fetuses served as controls. Under acute anaesthesia the fetus was exteriorized and subjected to two levels of controlled asphyxia by intermittent, complete obstruction of the maternal placental blood flow. Fetal haemodynamic reactions were assessed by measuring fetal heart rate, cardiac contractility, cardiac output and cerebral blood flow. The metabolic reactions were evaluated from blood gases, pH, lactate and hypoxanthine concentrations, while the electrophysiological status of the brain was evaluated from the somatosensory evoked EEG potentials (SEP). Already during the period of moderate asphyxia the beta-blocked fetuses demonstrated a blunted haemodynamic response, in comparison with the control fetuses, resulting in an accelerating lactic acidosis, signs of a breakdown of intra-cellular energy-rich phosphates and an impaired cerebral function. During the period of severe asphyxia, both groups of fetuses exhibited signs of extensive cerebral deterioration. During the ensuing recovery phase, 80% of the control fetuses regained their brain function, as assessed by SEP, whereas this was true for only 30% of the beta 1-blocked fetuses. It is concluded that the ovine fetus relies heavily on greatly increased sympatho-adrenal activity to adapt itself to asphyxia and that blockade of the fetal beta 1-adrenoreceptors by maternal medication is a hazard to the potentially asphyctic fetus.

[Puberty in Icelandic boys.].

In a crosssectional study, 2751 healthy Icelandic boys aged 6-16 years, were examined for physical signs of puberty. The study was performed in 1983-1987 and was a part of a larger crosssectional growth study of 5526 Icelandic children all of whom were examined by the authors. Testicular volume of 4 ml (T 4) was considered the first sign of puberty in boys. The mean age of Icelandic boys reaching T 4 was 11.89 years (SD 1.08). The mean time interval between T 4 and T 12 was 2.21 years. The first signs of pubic hair growth, Tanner stage 2 (PH 2), were found at 12.74 years (SD 1.37). The mean time interval between PH 2 and PH 5 was 2.43 years. Even though comparison with studies from other countries is difficult because of different methods and different study design, we find that the timing and tempo of puberty in Icelandic boys is similar to what has been reported from other Nordic countries and countries in Western-Europe. Key words: puberty, growth, Icelandic boys. Correspondence: Arni V. Thorsson. E-mail: arniv@shr.is.

[Height and weight of Icelandic children 6-20 years of age.].

INTRODUCTION: Monitoring growth rate in children reflects the state of health and nutrition of the individual as well as the state of health of a nation. Until now little information has been available about the growth pattern of Icelandic children. We report here the results of a nationwide cross-sectional study of growth in Icelandic children aged 6-20 years. MATERIAL AND METHODS: Height, standing and sitting and weight were measured in a total of 6500 schoolchildren, 3173 girls and 3327 boys. The measurements were performed 1983-1987. Children were randomly selected from The National Registry according to date of birth from both urban and rural areas of the whole country of Iceland. Stature was measured by a Harpenden stadiometer and the children were weighed in underwear only using a standardized scale. RESULTS: The mean values and standard deviations for height, standing and sitting and weight are presented in tables. Growth charts for height weigt and sitting height are presented. No difference in height and weight was found between children from rural and urban areas. The results show that the growth of Icelandic children is in all age groups almost identical to the growth of Norwegian children. Compaired to other Nordic and WHO growth standards, Icelandic children are tall, especially during early pubertal development. CONCLUSIONS: Icelandic children are tall and the growth of Icelandic and Norwegian children follows the same pattern wich supports the theory that the two nations are closely related. KEYWORDS: Icelandic children, growth, height, weight. Correspondance: Atli Dagbjartsson. E-mail: atlid@rsp.is Arni V. Thorsson. E-mail: arniv@shr.is.