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Biomedical subjects

J G Koppe

Publications and source records attributed to J G Koppe.

At least 37 records · Page 2Linked to original sources

Clinical laboratory manifestations of exposure to background levels of dioxins in the perinatal period.

The effects of exposure to low levels of dioxins in infants (intrauterine and via breast milk) were studied. In a group of 35 babies, specially selected, laboratory tests were performed in cord blood and in blood sampled at 7 days and 11 weeks of age. The outcome of these laboratory tests was related to dioxin concentrations in milk fat and cumulative dioxin intake. At 11 weeks of age, alanine aminotransferase and aspartate aminotransferase activities in plasma were significantly related to cumulative dioxin intake. A significant negative relation was found between platelet count and cumulative dioxin intake. The results of this study suggest that exposure to background levels of dioxins, both intrauterine and via breast milk, may have effects in newborns.

Adult↗

Studies on long-lasting consequences of prenatal exposure to anticonvulsant drugs.

Based on neonatal examination at birth, it has been estimated that epileptic women have a 2-3 times greater risk of giving birth to an infant with congenital anomalies. But anticonvulsant drugs may also have more subtle influences on the developing foetus which are not visible at birth but only emerge later in life. Evidence for these functional teratogenic influences has been provided by animal research and follow-up studies in young children. This article discusses these findings in human and animal studies. In addition, the outline of a study carried out at the Department of Obstetrics and Neonatology, Academic Medical Centre, Amsterdam, is described. In this study cognitive functioning, fertility and gender role behaviour of young adults, who had been prenatally exposed to barbiturates and/or hydantoins was examined.

Abnormalities, Drug-Induced↗

Influence of short-term dietary measures on dioxin concentrations in human milk.

Breast-feeding may expose infants to high levels of toxic chlorinated dioxins. To diminish intake of these lipophilic compounds by the baby, two diets were tested for their ability to reduce concentrations of dioxins in human milk. The diets were a low-fat/high- carbohydrate/low-dioxin diet. (about 20% of energy intake derived from fat) and a high fat /low-carbohydrate/low-dioxin diet. These diets were tested in 16 and 18 breast-feeding women, respectively. The test diets were followed for 5 consecutive days in the fourth week after delivery. Milk was sampled before and at the end of the dietary regimen, and dioxin concentrations and fatty acid concentrations were determined. Despite significant influences of these diets on the fatty acid profiles, no significant influence on the dioxin concentrations in breast milk could be found. We conclude that short-term dietary measures will not reduce dioxin concentration in human milk.

Adult↗

The Dutch famine birth cohort study: design, validation of exposure, and selected characteristics of subjects after 43 years follow-up.

A historical birth cohort study of 1116 women born between August 1 1944 and April 15 1946 in the Wilhelmina Gasthuis hospital in Amsterdam, the Netherlands, was set up to study the short- and long-term effects of a limited period of extreme nutritional deprivation in the winter of 1944-1945 in the Western Netherlands. The degree of food deprivation is evidenced by a dramatic decline in third trimester pregnancy weight gain and infant birthweight. All women were traced and 84% (683/813) of survivors presently resident in the Netherlands agreed to be interviewed in their homes. There were no differences in characteristics at birth between interviewed and uninterviewed survivors. The women who were interviewed had 1299 offspring and were able to recall birthweight of all of them. Additional birthweight information from hospital and well-baby clinic (WBC) records is available for about half of the offspring. Since the famine was imposed on the entire population of a well-defined area, whose opportunities to obtain food elsewhere were severely restricted, and the women from this hospital cohort were predominantly lower middle class, the relationship between fetal nutrition and subsequent health outcomes in this cohort is not likely to be confounded by unmeasured attributes related to social class. In addition, selective losses to follow-up could be excluded, which makes the Dutch famine birth cohort a valuable resource for future studies in perinatal epidemiology.

Adult↗

Effects of pre- and postnatal exposure to chlorinated dioxins and furans on human neonatal thyroid hormone concentrations.

Animal studies have shown that dioxins influence plasma thyroid hormone concentrations. To investigate the effect of chlorinated dioxins and furans on thyroid hormone concentrations in humans, we studied 38 healthy breast-fed infants. The study population was divided into two groups according to the dioxin concentrations in milk fat of their mothers. Blood samples were taken at birth and at the ages of 1 and 11 weeks. At birth a tendency to higher total thyroxine (tT4) concentrations was found in the high exposure group. At the ages of 1 and 11 weeks the increase of mean tT4 concentrations and tT4/thyroxine-binding globulin ratios in the high exposure group reached significance as compared to the low exposure group. At birth and 1 week after birth, mean thyrotropin (TSH) concentrations were similar in both groups, but at the age of 11 weeks the mean TSH concentrations were significantly higher in the high exposure group. We postulate that the observed plasma tT4 elevation in infants exposed to dioxins before and after birth is the result of an effect on the thyroid hormone regulatory system.

Adult↗

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin or 2,2',4,4',5,5'-hexachlorobiphenyl on vitamin K-dependent blood coagulation in female germfree WAG/Rij-rats.

Newborn infants are susceptible to bleeding disorders caused by a vitamin K deficiency, so called 'haemorrhagic disease of the newborn' (HDN). These bleedings often occur in infants after medication of the mother with antiepileptics, such as phenobarbital or phenytoin. It has been suggested that an increase in the late type of HDN in exclusively breast-fed infants might be related to the presence of cytochrome P450-inducing polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in human milk. In order to study this possible mechanistic relationship 5-week-old, germfree, female WAG/Rij-rats were exposed to a single oral dose of either 1 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin/kg body weight (TCDD) or 30 mg 2,2',4,4',5,5'-hexachlorobiphenyl/kg body weight (HxCB), representing cytochrome P-450 1A (3-methylcholanthrene type) and 2B (phenobarbital type) inducers. During the experiment blood coagulation time from each rat was measured. Also, hepatic 7-ethoxy-(EROD) and 7-pentoxyresorufin O-dealkylating (PROD) activities and total cytochrome P450 content were measured. Blood coagulation time (Thrombotest) in the HxCB-treated rats was significantly prolonged and positively correlated to PROD activity and total P450 content. No clear effect of TCDD on coagulation time could be observed under these experimental conditions. These results suggest involvement of P450 2B isoenzymes in vitamin K metabolism.

Animals↗

Placental transport of dioxins from mother to fetus. II. PCBs, dioxins and furans and vitamin K metabolism.

Placental transport of dioxins and furans from mother to fetus takes place. It is probably related to the fatty acid transport. Between 10 and 20% of fatty acids in a full-term baby are of maternal origin. In adipose tissue of children that died in the early neonatal period concentrations of +/- 25% were found of three dioxin and furan congeners 12378 P5CDD, 123678 H6CDD, and 23478 P5CDF in relation to a mean concentration of these congeners in the fat of 14 breastmilk samples. Data of concentrations are given as measured in liver and adipose tissue. In the placenta of a Dutch woman an accumulation of dioxins and furans is found in relation to blood. Animal studies support the hypothesis that polychlorobifenyls play a role in the cause of the late hemorrhagic disease in the newborn, in particular the 2, 4, 5, 2, 4, 5-hexachlorobifenyl that is present in relatively high concentrations in breastmilk.

Dioxins↗

Breast milk, dioxins and the possible effects on the health of newborn infants.

The concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the fat of breast milk of 14 Dutch mothers varied from 5.35 to 17.0 ng kg-1 (nanograms per kilogram fat). Expressed as toxic equivalents the concentrations of the 17 different congeners of dioxin and furans in the fat of the breast milk were between 29.85 and 92.88 ng kg-1. These levels are sufficient to induce enzyme formation in the livers of infants. (The acceptable daily intake is 4 pg/kg bodyweight/day). Dioxin induces the same enzyme production in the liver as phenobarbital; therefore, because phenobarbital affects fat-soluble vitamins, such as vitamins D and K, a similar response was anticipated in response to exposure to dioxin. Consequently, one aim of this study was to investigate blood coagulation parameters. We found a statistically significant relationship with the mean concentration of TCDD in the breast milk of mothers whose babies suffered from bleeding problems. This association was not found for 2,3,4,7,8-pentachlorodibenzofuran concentrations, nor for the remaining congeners expressed as toxic equivalents. A simple laboratory test for measuring dioxins and furans is urgently needed.

Adult↗

[Breast feeding, PCBs and dioxins].

In breastmilk of 14 Dutch mothers and 5 Polish mothers the content of dioxins and furans is measured. The study in Dutch mothers is started to relate the level of these xenobiotics to bleeding in the perinatal and late neonatal period. Interference with coagulation is hypothesized in analogon to phenobarbital. A relation is seen between bleeding in four babies and the mean content of 2, 3, 7, 8 TCDD (= tetrachloordibenzodioxin) (P = 0.02) in their breastmilk. This relation however is not found for the content of 2, 3, 4, 7, 8 PnCDF (= pentachloordibenzofuran) or the total amount of toxic equivalents. The fact that the prenatal gradient from mother to baby is different for T4CDD and PnCDF, respectively 2:1 and 10:1, may be an explanation for the dissociation between T4CDD on one side and PnCDF and total amount of toxic equivalents on the other side. Polish breastmilk was significantly lower (about four times) for dioxins and furans than Dutch breastmilk. This means that for these chemicals pollution in Holland is much higher than in Poland.

Adult↗

[Transcutaneous PCO2 determination in neonatology].

Transcutaneous PCO2 studies were performed in 21 healthy preterm infants and in 12 preterm infants with respiratory problems, in order: I. to evaluate the feasibility of transcutaneous PCO2 measurements in the clinical situation; 2. to collect normal values for preterm infants, and 3. to compare transcutaneous tcPCO2 values with PCO2 measured in capillary or arterial blood samples. Normal tcPCO2, measured in 21 healthy preterm infants, mean gestational age 32.5 +/- 2.3 weeks (range 26 6/7-36 1/7, mean birth weight 1547 +/- 498 gram (range 820-2840), postnatal age 2.2 +/- 2.1 days (range 0-6) was 41.2 +/- 5.5 mm Hg. The relation between transcutaneous PCO2 and PCO2 in arterial or capillary blood samples was studied in 12 patients with respiratory problems, 7 boys and 5 girls, mean gestational age 31 4/7, birth weight 1600 gram (range 885-3050). We found a good linear relation between tcPCO2 and arterial PaCO2 (regression coëfficient between 0.66 and 0.96) and a bad correlation between tcPCO2 and capillary PCO2 (regression coefficient 0.14-0.89). We conclude that tcPCO2 measurement is reliable and feasible for clinical use and is more reliable than PCO2 measurement in capillary blood.

Birth Weight↗

Circadian rhythms in preterm infants: a preliminary study.

A method has been developed for long-term continuous recordings of several physiological variables in humans, including body movements, core temperature, heart rate and respiratory rate. This method enabled us to study circadian rhythms of body temperature and rest-activity in preterm infants. In 5 out of 9 infants (recorded at 28-34 weeks conceptional age) circadian rhythms were found in body temperature. We conclude that circadian rhythmicity is present during the early neonatal period in certain physiological variables (body temperature) but not in others (rest-activity).

Circadian Rhythm↗

Lung function 8-18 years after intermittent positive pressure ventilation for hyaline membrane disease.

Lung function and respiratory symptoms were studied in 40 children aged 8-18 years who had been ventilated for hyaline membrane disease after birth; 11 had had bronchopulmonary dysplasia. Also studied were 38 age matched children who had had hyaline membrane disease but had not required ventilation, 25 unmatched children who were born prematurely but did not develop hyaline membrane disease, and 39 randomly selected pupils of similar age. There was no difference in thoracic gas volume, total lung capacity, inspiratory vital capacity, residual volume, or transfer factor for carbon monoxide between the groups. Respiratory symptoms during the three years before the study and the frequency of clinically diagnosed asthma in patients and their family were similar in all the children with hyaline membrane disease irrespective of whether they had been ventilated or had had bronchopulmonary dysplasia. The children with bronchopulmonary dysplasia, however, had a lower forced expiratory volume in one second (FEV1) before bronchodilator (73% predicted) than the other groups (88-95% predicted). Children who had required ventilation had lower values for specific airways conductance (sGaw) and a greater increase in FEV1 (delta FEV1) after salbutamol (13%) than non-ventilated children (6%); delta FEV1 was associated with the peak pressure of intermittent positive pressure ventilation, a family history of asthma and a history of wheezing, recurrent respiratory illnesses, and a doctor's diagnosis of asthma during the three years before the study. These findings indicate that after eight years of age patients with bronchopulmonary dysplasia have more reversible airways obstruction, compatible with increased bronchial smooth muscle tone.

Adolescent↗

Psychological development of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome.

Potential side effects of antenatal administration of corticosteroids to prevent neonatal respiratory distress syndrome were studied in 10- to 12-year-old children whose mothers had participated in a randomized, double-blind, placebo-controlled trial of betamethasone. Aspects of the children's intellectual and motor development, school achievement, and social-emotional functioning were investigated. There were no differences between the corticoid group and the placebo group on these variables, nor were there more children with learning difficulties and behavioral disturbances in either of the groups.

Betamethasone↗

Physical development and medical history of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome: a 10- to 12-year follow-up.

Potential side effects of antenatal administration of corticosteroids to prevent neonatal respiratory distress syndrome were studied in 10- to 12-year-old children whose mothers had participated in a randomized, double-blind, placebo-controlled trial of betamethasone. The children had a general physical examination; parents were interviewed about the medical history of their child with special attention to infectious diseases; growth data were collected; and a developmental neurological examination, an ophthalmological examination, and a lung function test were conducted. In the corticosteroid group significantly more hospital admissions because of infectious diseases during the first years of life were reported. On the other variables no differences between the corticoid and the placebo groups were found.

Betamethasone↗