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K Teramo

Publications and source records attributed to K Teramo.

At least 19 recordsLinked to original sources

Glycaemic control during early pregnancy and fetal malformations in women with type I diabetes mellitus.

AIMS/HYPOTHESIS: To assess the relation between glycaemic control in early pregnancy and the risk of congenital malformations in offspring of mothers with Type I (insulin-dependent) diabetes mellitus. METHODS: From 1988-1997, we prospectively collected data from 691 pregnancies and 709 offspring of 488 women with Type I diabetes in a specific geographic area in Southern Finland. Glycated haemoglobin A1c at less than 14 weeks of gestation was used as the indicator of glycaemic control. The malformations were diagnosed either by ultrasonography in pregnancy or during the neonatal period. We also studied 729 non-selected control pregnancies in women without diabetes. RESULTS: The numbers of major fetal malformations were 30 (4.2%) in patients with Type I diabetes and 10 (1.2%) in the control subjects (relative risk 3.1; 95% confidence interval: 1.6 to 6.2). Even women whose HbA1c was only slightly raised (5.6 to 6.8%, i.e. 2.0 to 5.9 standard deviation units) showed a relative risk of 3.0 (95% confidence interval: 1.2 to 7.5). Haemoglobin A1c retained its statistically significant association with the occurrence of malformations after adjusting for White's class, age at onset of diabetes, duration of diabetes, parity, smoking and participation in pre-pregnancy counselling. CONCLUSIONS/INTERPRETATION: Even a slightly raised HbA1c during early pregnancy in women with Type I diabetes carries an increased risk for fetal malformations. Therefore normoglycaemia should be strived for during early pregnancy.

Biomarkers↗

Increased fetal leptin in type I diabetes mellitus pregnancies complicated by chronic hypoxia.

AIMS/HYPOTHESIS: The purpose of this study was to examine whether fetal leptin concentration correlates with severity of chronic or subchronic fetal hypoxia as indicated by increased fetal concentrations of erythropoietin in fetuses of mothers with Type I (insulin dependent) diabetes mellitus. METHODS: We measured leptin and erythropoietin concentrations in cord plasma and amniotic fluid with radioimmunoassay in 25 pregnancies (gestational age 37.2 +/- 1.0 weeks). Fetuses with amniotic fluid erythropoietin over 22.5 mU/ml were classified as hypoxic (n = 9) and those with amniotic fluid erythropoietin below 22.5 mU/ml (n = 16) as non-hypoxic. RESULTS: The hypoxic fetuses had significantly higher cord leptin concentrations than non-hypoxic fetuses (median 36.8; range, 12.5-135.1 vs median 16.2; range, 3.7-52.2 micrograms/l), (p = 0.0066). Cord plasma leptin (n = 25) correlated directly with amniotic fluid erythropoietin (r = 0.727, p = 0.0001), with cord plasma erythropoietin (r = 0.644, p = 0.0005) and with the maternal last trimester HbA1C (r = 0.612, p = 0.0019) and negatively with cord artery pO2 (r = -0.440, p = 0.032), and pH (r = -0.414, p = 0.040). CONCLUSION/INTERPRETATION: Fetal leptin concentrations increased concomitantly with erythropoietin during chronic or subchronic hypoxia. This phenomenon could indicate a role for leptin in fetal adaptation to hypoxia.

Amniotic Fluid↗

Thrombocytopenia in term infants: a population-based study.

OBJECTIVE: To assess the prevalence and causes of thrombocytopenia among full-term infants. METHODS: We conducted a 1-year, population-based surveillance study involving all full-term infants (at least 37 weeks' gestation) born to native Finnish women in Helsinki. In cases of thrombocytopenia (cord platelet count less than 150 x 10(9)/L) clinical risk factors were evaluated and immunologic studies were performed on both parents and on the infant; 95% confidence intervals (CIs) were calculated on the basis of binomial distribution. RESULTS: Platelet counts were done in cord blood from 4,489 infants, 84.9% of the study population. Eighty-nine infants had platelet counts below 150 x 10(9)/L (2.0%; 95% CI 1.5, 2.3) in cord blood and 11 were less than 50 x 10(9)/L (0.24%; 95% CI 0.10, 0.38). All causes of clinically important thrombocytopenia, those presenting with bleeding and requiring treatment, were related to fetomaternal alloimmune thrombocytopenia. The incidence of severe alloimmune thrombocytopenia was one in 1500 live births and one in 900 of all thrombocytopenia. An immunologic mechanism was involved in ten of 65 (15.4%; 95% CI 6.6, 24.2) infants studied and in four of 15 (26.7%; 95% CI 4.3, 49.1) cases of severe thrombocytopenia. CONCLUSION: Immunologic studies should be considered in all cases of severe neonatal thrombocytopenia for careful monitoring and prevention of potentially severe complications in subsequent pregnancies.

Female↗

Detection of reticulated platelets: estimating the degree of fluorescence of platelets stained with thiazole orange.

The primary problem in the measurement of reticulated platelets (RP) stained with thiazole orange (TO) by flow cytometry is the definition of a threshold limit for fluorescence positivity. We evaluated settings for the threshold gate for TO positivity based on two principles: a fluorescence histogram (median FL1, Relative FL1) or a plot of forward light scatter (FSC; reflecting the distribution of the platelet size) versus fluorescence intensity (% RP). These methods were applied prospectively in examination of 54 healthy blood donors (16 females) and a total of 50 blinded patient samples: pregnant women with thrombocytopenia (Group 1A, n = 11), thrombocytopenic women after delivery (Group 1B, n = 9) and healthy women with a thrombocytopenic newborn (Group 2, n = 30). Group 1A displayed higher median FL1 (mean 306, CI 279-332) as compared to that of Group 2 (mean 266, CI 255-277; p = 0.0038) or to that of the female controls (mean 249, CI 231-268; p < 0.001). Relative FL1 was also higher in the patients of Group 1A than those of Group 2 (p = 0.037). When analysing the % RP, the difference between these groups was not significant. In the patients (n = 50), the median FSC (mean 407, SD 40, CI 395-418) was also higher than that of the controls (n = 54; mean 383, SD 25, CI 376-390; Mann-Whitney U-test, p = 0.0015). In Group 1A, a significant correlation was observed between the Patient median FL1 and Patient median FSC (r = 0.62, p = 0.043). When developing methods for the measurement of RP, it seems to be useful to analyse the data with more than one principle to define the threshold limit for TO positivity.

Adult↗

Thrombopoietin levels in cord blood plasma and amniotic fluid in fetuses with alloimmune thrombocytopenia and healthy controls.

To extend our knowledge of the kinetics of fetal thrombopoietin (TPO), we studied TPO levels in cord blood plasma and amniotic fluid collected from 15 fetuses considered to be at risk of fetomaternal alloimmune thrombocytopenia and also from 10 healthy controls at caesarean delivery. In the plasma of all 25 fetuses and newborn infants studied, TPO was detected above the lower limit of detection (7 pg/ml) and correlated inversely with platelet counts (r = -0.53, P = 0.006). At term, TPO detected in amniotic fluid was at significantly lower levels (7 pg/ml; range 0-22 pg/ml) than simultaneously obtained cord plasma TPO (114 pg/ml; range 43-201 pg/ml; P < 0.001). There was no correlation between levels of TPO in amniotic fluid and cord plasma or platelet counts. In the serial samples collected from the five fetuses with HPA-1a alloimmunization before 37 weeks' gestation, the TPO levels in amniotic fluid were significantly higher than at term (P = 0.013): from 22 to 28 weeks' gestation, 42 pg/ml (30-78 pg/ml); from 32 weeks', 24 pg/ml (17-33 pg/ml); at term, 8 pg/ml (4-13 pg/ml), correlating inversely with gestational age (r = -0.81, P = 0.003). Thus, TPO is present in amniotic fluid at levels apparently inversely related to gestational age. Whether these high levels seen early in pregnancy are normal or are associated with the HPA-1 alloimmunization remains to be shown.

Amniotic Fluid↗

Neonatal thrombocytopenia in two of six human platelet alloantigen (HPA) 5a-positive children of an HPA-5a-immunized mother.

We describe a human platelet alloantigen (HPA) 5a-alloimmunized HPA-5b5b mother. The children were obligatory heterozygotes for HPA-5a but despite IgG class maternal anti-HPA-5a antibodies only two (second and fifth) of the six children developed neonatal thrombocytopenia. Throughout the 4-year follow-up the mother had anti-HPA-5a antibodies (confirmed in the 8th Platelet serology workshop of International Society of Blood Transfusion in 1996). Antibodies against glycoproteins (GP) IIbIIIa or IbIX were not detected. Differences in the children's HPA type (HPA-1, -2, -3, -5) did not correlate with thrombocytopenia. We hypothesized that different expression of GPIaIIa recently associated with two silent polymorphisms (C807T and G873A) of GPIa could explain the unpredictable recurrence pattern of neonatal alloimmune thrombocytopenia (NAIT). Both parents were homozygous for the silent polymorphisms (C807 and G873) associated with the low expression of GP Ia. Thus, the inheritance pattern of the silent polymorphisms (C807T and G873A) did not help in predicting the recurrence risk of thrombocytopenia in the offspring. More detailed comprehension of the natural history of NAIT would be necessary to enable directing fetal blood sampling to the cases at the highest risk of thrombocytopenia.

Adult↗

Prenatal treatment of severe fetomaternal alloimmune thrombocytopenia.

Prenatal treatment of fetomaternal alloimmune thrombocytopenia (FMAIT) in previously affected families is of great clinical importance. We report here our experience in the prenatal treatment of 15 severely thrombocytopenic fetuses. Thrombocytopenia was in 13 cases due to immunization to HPA-1a, in one case to HPA-5b, and in one case to HPA-6b. Thirteen fetuses received altogether 34 intrauterine platelet transfusions, seven of them in combination with maternal-administered intravenous gammaglobulin (IVIG) and two in combination with IVIG and prednisone. Six of the 13 fetuses had only one transfusion just prior to delivery. In our experience, IVIG seemed to be less effective than reported; only two fetuses of eight treated initially with weekly maternal-administered IVIG responded, and these were the mildest affected cases in the study. On the other hand, owing to the short survival time, weekly platelet transfusions could only partly maintain a safe platelet count in the four fetuses treated with serial intrauterine platelet transfusions. The number of transfusions needed to be limited because of the high cumulative risk associated with repeated procedures. Three of 34 intrauterine platelet transfusions were associated with near-loss of three different fetuses due to prolonged fetal bradycardia after the transfusion. In conclusion, overall neonatal outcome was good, with no mortality; among the study group there was no intracranial haemorrhage (evaluated by postnatal ultrasonography) compared with one case in their untreated siblings. However, the problem of the optimal treatment of FMAIT remains to be solved. For the moment, the treatment of choice is a combination of maternal IVIG and platelet transfusions in severely affected cases. Serial fetal blood samplings (FBS) are needed in order to monitor the fetus with sufficient care.

Antigens, Human Platelet↗

Effects of transdermal nitroglycerin on impedance to flow in the uterine, umbilical, and fetal middle cerebral arteries in pregnancies complicated by preeclampsia and intrauterine growth retardation.

OBJECTIVE: We studied whether transdermal nitroglycerin, a donor of nitric oxide, affects uterine, umbilical, and fetal cerebral blood flow in pregnancies complicated by preeclampsia and impaired uteroplacental blood flow. STUDY DESIGN: Seventeen patients with preeclampsia were treated with a nitroglycerin patch, 10 mg per 24 hours, for three consecutive days between 28 and 36 weeks' gestation. The uterine, umbilical, and fetal middle cerebral artery pulsatility index and resistance index were assessed by color Doppler ultrasonography before the start of treatment, daily during treatment, and on the first 2 days after the removal of the last patch. RESULTS: The nitroglycerin patch caused a significant fall in the mean uterine pulsatility index and resistance index that reached its maximum (18% +/- 4% and 17% +/- 3%, respectively, from baseline) on the last treatment day. After the removal of the last patch, uterine pulsatility index and resistance index rose to the pretreatment value within 12 hours. No significant changes in umbilical or middle cerebral artery pulsatility index and resistance index were observed during treatment. Maternal mean arterial pressure fell from 122 +/- 8 to 117 +/- 7 mm Hg (P = .05). CONCLUSION: Transdermal administration of nitroglycerin may offer a potential for treatment for patients with preeclampsia who have increased uteroplacental impedance.

Administration, Cutaneous↗

Idiopathic thrombocytopenic purpura in pregnancy.

OBJECTIVE: The aim of this study was to evaluate retrospectively our strategies in monitoring and treating pregnant women with idiopathic thrombocytopenic purpura (ITP). METHODS: Medical records were reviewed for diagnosis, clinical course, treatment, and neonatal outcome in 35 Finnish women with ITP giving birth to 55 neonates during 53 pregnancies. The outcome of the first (i.e. index) pregnancy was used in the statistical analyses. The platelet immunofluorescence test (PIFT) was used for detection of platelet autoantibodies. The correlation between neonatal platelet counts and results of PIFT was calculated with the Pearson's correlation coefficient and the Fisher's exact test. RESULTS: There were no serious bleeding complications although five of 35 women had platelet counts of less than 50 x 10(9)/l in the third trimester of the index pregnancy. Prophylactic platelet transfusions were given to six of 15 women delivered by cesarean section. Five of 35 (14.3%; 95% confidence interval, 2.6 to 25.8%) neonates had platelet counts of less than 50 x 10(9)/l median 3 days after delivery versus only one of 28 (3.6%; 95% confidence interval, 0.1 to 10.5%) at birth. No infant showed any clinical signs of intracranial hemorrhage. No significant correlation was encountered between neonatal thrombocytopenia and maternal platelet autoantibodies. The history of a previous infant with thrombocytopenia was the only important information in estimating the risk of fetal thrombocytopenia. CONCLUSIONS: To avoid unnecessary and possibly harmful monitoring and treatment, we need further tests for predicting the perinatal risks in pregnant women with ITP.

Autoantibodies↗

Mother's weight in pregnancy and coronary heart disease in a cohort of Finnish men: follow up study.

OBJECTIVE: To determine whether restricted growth in utero is associated with an increased risk of coronary heart disease are among men in Finland, where rates of the disease are among the highest in the world. DESIGN: Follow up study. SETTING: Helsinki, Finland. SUBJECTS: 3302 men born in Helsinki University Central Hospital during 1924-33 who went to school in the city of Helsinki and were resident in Finalnd in 1971. MAIN OUTCOME MEASURES: Standardised mortality ratios for coronary heart disease. RESULTS: Men who were thin at birth, with low placental weight, had high death rates from coronary heart disease. Men whose mothers had a high body mass index in pregnancy also had high death rates. In a multivariate analysis the hazard ratio for coronary heart disease was 1.37 (95% confidence interval 1.20 to 1.57) (P < 0.0001) for every standard deviation decrease in ponderal index at birth and 1.24 (1.10 to 1.39) (P = 0.0004) for every standard deviation increase in mother's body mass index. The effect of mother's body mass index was restricted to mothers of below average stature. CONCLUSION: These findings suggest a new explanation for the epidemics of coronary heart disease that accompany Westernisation. Chronically malnourished women are short and light and their babies tend to be thin. The immediate effect of improved nutrition is that women become fat, which seems to increase the risk of coronary heart disease in the next generation. With continued improvements in nutrition, women become taller and heavier; their babies are adequately nourished; and maternal fatness no longer increases the risk of coronary heart disease, which therefore declines.

Aged↗

Contrast sensitivity in diabetic pregnancy.

PURPOSE: To evaluate the correlation between the changes in contrast sensitivity and retinopathy throughout pregnancy in diabetic women with mild background diabetic retinopathy. METHODS: Contrast sensitivity (Vistech 6500 Contrast Test System) was measured in 22 type I diabetic women with mild background retinopathy [0-16 microaneurysms (MAs)/eye and occasional small intraretinal hemorrhages] and 10 healthy pregnant women at the 12th and 32nd weeks of pregnancy and 3 months after delivery. Red-free fundus photography was also performed at all visits. RESULTS: Throughout pregnancy contrast sensitivity was lower in the diabetics than in the controls at 1.5, 3.0, and 6.0 cycles per degree (cpd). During the course of pregnancy, contrast sensitivity decreased at 1.5 and 6.0 cpd in patients with more than five new MAs compared to those with fewer than five new MAs during pregnancy. Likewise, contrast sensitivity decreased at 6 cpd in patients with an increase in MA count during pregnancy and at 6 and 12 cpd in patients with a baseline MA count of two or more MAs. CONCLUSIONS: Contrast sensitivity, especially at low to mid-range spatial frequencies, is decreased in diabetic women with mild retinopathy. Even small changes in retinopathy are reflected in a decrease in contrast sensitivity during and after pregnancy. Thus, contrast sensitivity seems to be a sensitive indicator of changes in minimal background retinopathy.

Adult↗

The effect of pregnancy on mild diabetic retinopathy.

PURPOSE: To study microaneurysm (MA) formation and disappearance rates during pregnancy and postpartum in diabetic women with mild diabetic retinopathy. METHODS: Red-free photographs were taken at the 12th, 24th and 32nd-36th weeks of pregnancy and 3 and 6 months postpartum from 21 type 1 diabetics with mild diabetic retinopathy. In a subset of 13 patients follow-up was continued until 1 year after pregnancy. Fundus photographs were analysed using a computer-assisted fundus lesion localization system. RESULTS: In the whole material the total MA count was 3.1 +/- 3.6 (mean +/- SD) at the 12th week, 3.4 +/- 3.1 at the 24th week, 4.1 +/- 4.9 at the 32nd-36th week, 5.4 +/- 6.2 at 3 months postpartum and 5.2 +/- 5.8 at 6 months postpartum. We found that MA count increased during pregnancy, but it was highest 3 months postpartum. Both the rate of MA formation and the rate of MA disappearance increased during pregnancy, with the disappearance rate exceeding the formation rate 6 months postpartum. In patients having mean HbA1c levels below the median value of 6.38 mmol/l there was a flare-up of MAs during pregnancy, levelling by 3 months postpartum. Patients with a higher than the median (0.76 mmol/l) decrease in HbA1c level compared to pre-pregnancy HbA1c also developed more MAs during the course of pregnancy. CONCLUSIONS: These data suggest that there is continuous turnover of MAs during pregnancy. MA count increases during pregnancy but the MA count was highest 3 months postpartum, after which the formation rate started to decline. Temporary aggravation of mild retinopathy occurs in diabetic patients after normalization of blood glucose levels.

Adult↗

Granulocyte-macrophage colony-stimulating factor in amniotic fluid and in airway specimens of newborn infants.

Granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that promotes white cell maturation, participates in the metabolism of pulmonary surfactant. Little is known on the production of GM-CSF during pregnancy or the neonatal period. We studied how the concentrations of GM-CSF in amniotic fluid (AF) or in tracheal aspirates (TA) of newborn infants are influenced by length of gestation, postnatal age, as well as conditions affecting the mother or the fetus. One hundred and forty-three AF samples from 143 pregnant patients (gestational age range, 28-42 wk) and 202 TA samples from 82 neonates (gestational age, 24-42.5 wk, postnatal age 0.2 d to 4 wk) were analyzed for GM-CSF using ELISA. In patients with intact membranes, AF GM-CSF increased as a function of gestational age; the concentrations were below 7.5 ng/L (detection limit of the assay) (n = 5), 18.6 +/- 2.3 ng/L (n = 56), and 56.7 +/- 7.9 ng/L (n = 58) at gestational ages between 28 and 32 wk, between 32 and 37 wk, and in term patients, respectively (linear regression: r = 0.404, p = 0.001). Among patients at less than 33 wk of gestation, those with intact membranes had a median AF GM-CSF concentration under the detection limit (n = 7), whereas in those with preterm premature rupture of membranes, the concentration was 50.1 +/- 22.2 ng/L (n = 16) (p = 0.002). Among term patients, those in labor had higher AF GM-CSF than those without signs of labor. TA GM-CSF at less than 12 h of age correlated with gestational age (r = 0.654, p = 0.0002, n = 28); thereafter, TA GM-CSF increased, and gestation dependence disappeared. We conclude that GM-CSF in AF and in fetal lung liquid is developmentally regulated and GM-CSF production increases in inflammatory conditions during pregnancy.

Amniotic Fluid↗

Maternal serum screening for Down's syndrome on population basis.

BACKGROUND: The favorable attitude among the public towards prenatal diagnostics in Finland allowed us to start a trial on population basis when screening for Down's syndrome by maternal serum markers and age was introduced. METHODS: Screening by maternal serum markers for Down's syndrome was offered to all 17,200 pregnant women in the Helsinki area during the study period of 2.5 years. Screening due to advanced maternal age, 37 years or more, was continued as previously, and 1133 pregnant mothers used this option. Alpha-fetoprotein, human chorionic gonadotrophin, and during the first year also unconjugated estriol were used as markers. RESULTS: The uptake of serum screening was 84%. The proportion of false positive results i.e. risk for Down's syndrome, 1:350 or more at term, was initially 5.7%. After ultrasound scan 4.1% of the mothers remained 'screen positive'. The amniocentesis or chorionic villus sampling uptake was 98.4%. Ten out of eighteen cases of Down's syndrome were detected by maternal serum screening, sensitivity 56%, 95% CI 31-79%. Other chromosomal abnormalities were found in three cases, and there were four cases of mosaicisms confined to the placenta. These were trisomies 16, 7 and 2, and tetraploidy. Elevated serum alpha-fetoprotein was found initially in 0.7% of the cases. One case of congenital nephrosis of the Finnish type and ten other, mainly structural, abnormalities were detected by high AFP. CONCLUSIONS: The screening was well received by the mothers. The detection rate of 56% is in the same range as in previous studies. Ultrasound scan before the test would effectively lower the false positive rate caused by incorrect timing.

Adult↗

Long-term effects of pregnancy on diabetic complications.

The aim of our study was to establish whether pregnancy affects long-term development and progression of retinopathy and nephropathy in diabetic women compared to nulliparous diabetic women. Twenty-eight diabetic women who had delivered in 1983-85 at Helsinki University Central Hospital and 17 nulliparous controls matched according in age, duration of diabetes, and degree of vascular complications were personally interviewed and the current retinal status and renal function were assessed 7 years later, in 1990-92. Serum creatinine, creatinine clearance, nocturnal albuminuria, and HbA1c were measured and colour fundus photography carried out. The results were compared to the status in 1983-85. Of those who had been pregnant, 5 of 26 (19.2%) had experienced worsening of retinopathy. In 3 of these, proliferative retinopathy had developed from only minimal background changes. In the control group, progression had occurred in 8 cases of 16 (50%, p < 0.05). The groups did not differ from each other regarding progression or development of nephropathy. This suggests that pregnancy does not seem to affect development or progression of diabetic nephropathy whereas progression of retinopathy seems to occur less often after pregnancy compared to nulliparous women.

Adult↗

Macular blood flow during pregnancy in patients with early diabetic retinopathy measured by blue-field entoptic simulation.

PURPOSE: To study macular capillary blood flow velocity during pregnancy and postpartum in diabetic women with minimal diabetic retinopathy. METHODS: Macular capillary blood velocity was measured using the blue-field entoptic simulation technique in 17 type I diabetic pregnant women with minimal background retinopathy and 10 healthy pregnant women at the 12th and 32nd-36th weeks of pregnancy and 3 months after delivery. Red-free fundus photography was also performed at all visits. RESULTS: Capillary blood velocities at the 12th week of pregnancy were 1.09 +/- 0.37 mm/s in the diabetic women and 0.81 +/- 0.21 mm/s in the controls(P = 0.017), at the 32nd week 0.93 +/- 0.19 mm/s and 0.94 +/- 0.24 mm/s (P = 0.880), and 3 months postpartum 0.98 +/- 0.25 mm/s and 0.75 +/- 0.17 mm/s (P = 0.016), respectively. Analysis of variance indicated that there was a significant difference in leukocyte velocities during the course of pregnancy, with the flow being constantly elevated in diabetic women, but increasing by term in nondiabetic women (P = 0.039). Capillary flow velocity showed a statistically non-significant tendency to be higher in patients with HbA1c levels > 6.4%. Capillary flow velocity levels were not connected with changes in the number of microaneurysms. Capillary leukocyte density in the pregnant diabetic women did not differ from that of nondiabetic pregnant women. CONCLUSIONS: These data suggest that during pregnancy there is a difference in retinal capillary blood flow between diabetic women with minimal background retinopathy and normal women. The lack of increase in blood flow in macular capillaries during diabetic pregnancy may reflect redistribution of retinal capillary flow during diabetic pregnancy or be due to altered rheological properties of blood components in diabetic pregnancy.

Adult↗

Disease-associated antibodies in offspring of mothers with IDDM.

We studied 20 infants of mothers with IDDM participating in a pilot study for a dietary intervention trial, testing the hypothesis that avoidance of cow's milk proteins early in life will reduce the risk of subsequent IDDM. The aim was to evaluate the elimination of IDDM-associated antibodies from the peripheral circulation of the infants, the possible emergence of autoantibodies indicating beta-cell destruction, and the influence of the dietary intervention and genetic disease susceptibility on the development of these autoantibodies. Transplacentally transferred islet cell antibodies (ICAs) and antibodies to the 65-kDa isoform of glutamic acid decarboxylase (GAD65As) disappeared from the peripheral circulation of most infants over the first few months of life and in all infants before the age of 9 months. Insulin antibodies were eliminated before the same age in all cases but one. The higher the initial antibody level was, the longer the time required for elimination. Four infants tested positive for insulin autoantibodies (IAAs) on at least one occasion during the first year of life, and 5 out of 16 unaffected subjects (31%) had IAAs at the age of 2 years. One infant became positive for IAA before the age of 6 months, with increasing levels later, seroconverted to positivity for ICAs and GAD65As between 6 and 9 months and presented with clinical IDDM at the age of 14 months. He had the HLA DQB1*0302/x genotype, which predisposes carriers to IDDM, and had been given the casein hydrolysate formula as supplementary milk. There were no significant differences in the levels of various autoantibodies between two groups of subjects defined either on the type of dietary intervention or the degree of genetic susceptibility. The findings indicate that transplacentally transferred antibodies related to IDDM are usually eliminated from the peripheral circulation of infants before 9 months of age and that IDDM-associated autoantibodies may emerge before the age of 6 months. Our results also illustrate that avoidance of cow's milk proteins over the first 9 months of life does not provide total protection against IDDM.

Adult↗