Blood pressure levels but not hypertensive complications have increased in Type 1 diabetes pregnancies during 1989-2010.

AIMS: The pre-pregnancy BMI and the third trimester HbA(1c) levels increased in Finnish parturients with Type 1 diabetes during 1989-2008. The aim of the present study was to investigate whether these trends have been accompanied by increases in blood pressure or hypertensive complications. Hypertension trends were analysed using the definitions of hypertension of both the American College of Obstetricians and Gynecologists and the American Diabetes Association. The associations of hypertension, as defined by the latter criteria, with perinatal complications were also studied. METHODS: The records of a cohort of 1007 consecutive patients with Type 1 diabetes with a singleton live childbirth during 1989-2010 at the Helsinki University Central Hospital were studied. RESULTS: The frequencies of hypertensive pregnancy complications did not change, but the mean diastolic blood pressure increased in normotensive parturients in all trimesters. The proportion of patients with systolic blood pressure > 130 mmHg or diastolic blood pressure > 80 mmHg in the first, second and third trimesters of pregnancy increased from 25 to 33%, from 26 to 35% and from 57 to 71%, respectively. Systolic blood pressure of 131-139 mmHg or diastolic blood pressure of 81-89 mmHg in the third trimester was associated with umbilical artery pH < 7.15. CONCLUSIONS: Blood pressure of patients with Type 1 diabetes during pregnancy is increasing. A growing proportion of women with Type 1 diabetes exceed the American Diabetes Association's definition of hypertension during pregnancy.

Trends in maternal BMI, glycaemic control and perinatal outcome among type 1 diabetic pregnant women in 1989-2008.

AIMS/HYPOTHESIS: Our objective was to examine the trends in prepregnancy BMI and glycaemic control among Finnish type 1 diabetic patients and their relation to delivery mode and perinatal outcome. METHODS: We analysed the obstetric records of 881 type 1 diabetic women with a singleton childbirth during 1989-2008. Maternal prepregnancy weight and height were obtained from the maternity cards, where they are recorded as reported by the mother. RESULTS: Maternal BMI increased significantly during 1989-2008 (p < 0.001). The mean HbA(1c) in the first trimester remained unchanged, but the midpregnancy and the last HbA(1c) before delivery increased (p = 0.009 and 0.005, respectively). Elective Caesarean sections (CS) decreased (p for trend <0.001), while emergency CS increased (p for trend <0.001). The mean umbilical artery (UA) pH decreased in vaginal deliveries (p for trend <0.001). The frequency of UA pH <7.15 and <7.05 increased (p for trend <0.001 and 0.008, respectively). The macrosomia rate remained at 32-40%. Neonatal intensive care unit (NICU) admissions increased (p for trend 0.03) and neonatal hypoglycaemia frequency decreased (p for trend 0.001). In multiple logistic regression analysis, maternal BMI was associated with macrosomia and NICU admission. The last HbA(1c) value before delivery was associated with delivery before 37 weeks' gestation, UA pH <7.15, 1 min Apgar score <7, macrosomia, NICU admission and neonatal hypoglycaemia. CONCLUSIONS/INTERPRETATION: Self-reported pregestational BMI has increased and glycaemic control during the second half of pregnancy has deteriorated. Poor glycaemic control seems to be associated with the observed increases in adverse obstetric and perinatal outcomes.

Feasibility and compliance in a nutritional primary prevention trial in infants at increased risk for type 1 diabetes.

AIM: The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) was launched to determine whether weaning to a highly hydrolysed formula in infancy reduces the incidence of type 1 diabetes in children at increased genetic disease susceptibility. We describe here the findings on feasibility and compliance from the pilot study. METHODS: The protocol was tested in 240 children. The diet of the participating children was assessed by self-administered dietary forms, a structured questionnaire and a food record. Blood samples were taken and weight and height measured at birth and at 3, 6, 9, 12, 18 and 24 months. RESULTS: A majority of the subjects (84%) were exposed to the study formula at least for 2 months. Linear growth or weight gain over the first 2 years of life was similar in the two study groups. The levels of IgA and IgG antibodies to cow's milk and casein were higher in the cow's milk-based formula group than in the hydrolysed formula group during the intervention period (p<0.05), reflecting the difference in the intake of cow's milk protein. CONCLUSION: This randomized trial on infant feeding turned out to be feasible, and dietary compliance was acceptable. Valuable experience was gained for the planning and sample size estimation of the study proper.

Pre-eclampsia but not pregnancy-induced hypertension is a risk factor for diabetic nephropathy in type 1 diabetic women.

AIMS/HYPOTHESIS: Our aim was to study whether pre-eclampsia and pregnancy-induced hypertension are predictors of diabetic nephropathy in type 1 diabetic women. MATERIALS AND METHODS: A total of 203 type 1 diabetic women, who were pregnant between 1988 and 1996 and followed at the Department of Obstetrics and Gynaecology in Helsinki, were re-assessed after an average of 11 years within the nationwide, multi-centre Finnish Diabetic Nephropathy Study. Diabetic nephropathy was defined as microalbuminuria, macroalbuminuria or end-stage renal disease. RESULTS: Patients with prior pre-eclampsia had diabetic nephropathy more often than patients with a normotensive pregnancy (diabetic nephropathy vs normal albumin excretion rate: 41.9% vs 8.9%; p<0.001), whereas patients with a history of pregnancy-induced hypertension did not (10.3% vs 8.9%; p=0.81). CHD was more prevalent in patients with a history of pre-eclampsia than in patients with a normotensive pregnancy (12.2% vs. 2.2%; p=0.03). Pre-eclampsia (odds ratio [OR] 7.7, 95% CI 1.6-36.1; p=0.01) and HbA(1c) (OR 2.0, 95% CI 1.1-3.8; p<0.05) were associated with incident diabetic nephropathy even when adjusted for follow-up time, BMI, smoking, diabetes duration and age. CONCLUSIONS/INTERPRETATION: These data suggest that a history of pre-eclamptic pregnancy but not pregnancy-induced hypertension is associated with an elevated risk of diabetic nephropathy.

Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study.

AIMS/HYPOTHESIS: We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood. METHODS: We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles. After exclusive breastfeeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen; Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence. RESULTS: The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group, suggesting the need for a larger well-powered study. After adjustment for duration of study formula feeding, life-table analysis showed a significant protection by the intervention from positivity for ICA (p=0.02) and at least one autoantibody (p=0.03). CONCLUSIONS/INTERPRETATION: The present study provides the first evidence ever in man, despite its limited power, that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy.

Effect of maternal diabetes on phosphorylation of insulin-like growth factor binding protein-1 in cord serum.

AIMS: The insulin-like growth factor (IGF) system is considered important in the regulation of fetal growth. Binding of IGFs to specific binding proteins (IGFBPs) modifies their actions. In fetal blood, IGFBP-1 is the primary IGF binding protein whose phosphorylation generates proteins with different affinities for IGF-I. We studied cord serum IGFBP-1 phosphoisoform profiles in normal pregnancies and in diabetic pregnancies, which are frequently complicated by macrosomia. RESEARCH DESIGN AND METHODS: Cord serum IGFBP-1 phosphoisoform concentrations were measured at birth by two immunoenzymometric assays in 67 pregnancies complicated by Type 1 diabetes, in 28 pregnancies complicated by insulin-treated gestational diabetes, and in 62 normal pregnancies. RESULTS: Cord serum highly phosphorylated IGFBP-1 (hpIGFBP-1) concentrations were lower in pregnancies complicated by Type 1 diabetes (204 +/- 36 microg/l, P = 0.032) and in pregnancies complicated by gestational diabetes (170 +/- 28 microg/l, P = 0.031) than in controls (316 +/- 34 microg/l). Cord serum lesser phosphorylated IGFBP-1 (lpIGFBP-1) concentrations were similar in diabetic and normal pregnancies (P = 0.692 between groups by analysis of variance). Relative birth weight correlated negatively with cord serum hpIGFBP-1 and lpIGFBP-1 in diabetic pregnancies, and with cord serum lpIGFBP-1 in normal pregnancies. CONCLUSIONS: Maternal diabetes is associated with suppressed hpIGFBP-1 but unaltered lpIGFBP-1 concentrations in cord serum, suggesting that IGFBP-1 phosphoisoforms are differentially regulated in the fetus. Because hpIGFBP-1 has a higher affinity for IGF-I than does lpIGFBP-1, diabetes-related changes in fetal IGFBP-1 phosphorylation may increase IGF-I bioavailability and, consequently, stimulate fetal growth. This may partly explain the increased occurrence of macrosomia in diabetic pregnancies.

Diurnal blood glucose profiles in women with gestational diabetes with or without hypertension.

AIM: The aim of the study was to establish whether diurnal blood glucose profiles differed in women with gestational diabetes (GDM) with different forms of hypertensive complications. METHODS: The subjects were patients diagnosed at 26-32 gestational weeks as having GDM (n = 178). They were classified as being normotensive, having chronic hypertension (with or without superimposed pre-eclampsia on chronic hypertension) or pregnancy-induced hypertension (with or without proteinuria). We compared diurnal blood glucose profiles (blood glucose taken every 4 h over 24 h) in these three groups. RESULTS: Hypertension complicated 43% of the women with GDM. The glucose profiles were similar between the three groups, except that in early morning hours (from 04:00 to 08:00 h) blood glucose concentrations increased in mothers with chronic hypertension, whereas they decreased in the normotensive women. In univariate regression analysis, both obesity (BMI > or = 28 kg/m(2)) and chronic hypertension showed significant association with blood glucose rise from 04:00 to 08:00 h, but in a multiple regression model neither showed significant independent effect. CONCLUSIONS: The rise in blood glucose levels during the early morning hours in women with GDM and chronic hypertension could reflect greater insulin resistance and sympathetic overactivity.

High amniotic fluid erythropoietin levels are associated with an increased frequency of fetal and neonatal morbidity in type 1 diabetic pregnancies.

AIMS/HYPOTHESIS: In this study we investigated whether chronic fetal hypoxia, as indicated by amniotic fluid erythropoietin levels, is associated with perinatal morbidity in type 1 diabetic pregnancies. METHODS: A total of 331 women with type 1 diabetes had at least one childbirth between 1995 and 2000. The amniotic fluid erythropoietin concentration was measured in 156 diabetic singleton pregnancies at a median time of 1 day before Caesarean section without labour contractions and in 19 healthy control subjects at Caesarean section. RESULTS: The median amniotic fluid erythropoietin level was 14.0 mU/ml (range 2.0-1975.0) in diabetic pregnancies and 6.3 mU/ml (range 1.7-13.7) in controls (p<0.0001). Of the 156 diabetic patients, 21 (13.5%) had amniotic fluid erythropoietin levels higher than 63.0 mU/ml. Amniotic fluid erythropoietin levels correlated negatively with umbilical artery pH (r=-0.49, p<0.0001) and pO2 (r=-0.62, p<0.0001) at birth and neonatal lowest blood glucose level (r=-0.47, p<0.0001). Positive correlations were found between amniotic fluid erythropoietin levels and umbilical artery pCO2 (r=0.49, p<0.0001) and last maternal HbA1c (r=0.43, p<0.0001). Furthermore, a U-shaped correlation was demonstrated between amniotic fluid erythropoietin levels and birthweight z score (z score below -0.6 SD units: r=-0.63, p=0.0007; z score above +1.0 SD units: r=0.32, p=0.0014). Neonatal hypoglycaemia, hypertrophic cardiomyopathy and admission to the neonatal intensive care unit occurred significantly more often in cases with high amniotic fluid erythropoietin levels (>63.0 mU/ml) than in those with normal levels. Multivariate logistic regression analysis revealed that amniotic fluid erythropoietin was the only variable independently related to low umbilical artery pH (<7.21; p<0.0001) and neonatal hypoglycaemia (p=0.002). Low umbilical artery pO2 (<15.0 mm Hg) was explained by amniotic fluid erythropoietin (p<0.0001) and birthweight z score (p=0.004). CONCLUSIONS/INTERPRETATION: Antenatal high amniotic fluid erythropoietin levels can identify type 1 diabetic pregnancies at increased risk of severe perinatal complications.

Birthweight of full-term infants is associated with cord blood CD34+ cell concentration.

AIM: CD34+ cell counts are used to define the haematopoietic stem cell potential of a given cord blood transplant. The aim was to test the hypothesis that high concentration of cord blood haematopoietic progenitor and stem cells could be a reflection of intrauterine growth, of which birthweight is an indicator. METHODS: Simple and multiple regression analyses were applied to test cord blood bank data on 1368 infants for associations of selected obstetric factors and cellular contents of cord blood. RESULTS: When groups were formed based on the extreme values (5th versus 95th percentiles) of a given variable, e.g. birthweight, the term infants having the highest birthweights were found to have statistically significantly higher median cord blood CD34+ cell concentrations. Also, infants in the top 50th percentile of relative birthweight had higher median CD34+ cell concentration than infants in the low 50th percentile. In multiple regression analysis, the correlation between birthweight and CD34+ cell concentration was statistically clearly significant. Notably, while an expected correlation between gestational age and nucleated cell concentration was found, there was no association between infant gestational age and CD34+ cell concentration. CONCLUSION: Haematopoietic progenitor and stem cells may reflect intrauterine growth and have a more central role in foetal development than has been reported earlier.

Angiopoietic factors and retinopathy in pregnancies complicated with Type 1 diabetes.

AIMS: To evaluate the role of systemic angiopoietic factors in the progression of diabetic retinopathy during pregnancy. METHODS: In a prospective study of 26 pregnant women with diabetes and eight non-diabetic pregnant women, retinopathy was graded from fundus photographs. Plasma levels of angiopoietin-1, angiopoietin-2, human vascular endothelial growth factor A (hVEGF-A), and total soluble receptor of vascular endothelial growth factor (sVEGF) receptor-1 were measured during the first and third trimester and 3 months postpartum. RESULTS: In diabetic women, levels of angiopoietin-2 were 26.5 ng/ml (12.1-47.7) (median and range) during the first trimester, 2.9 ng/ml (0.6-3.5) during the third trimester, and 0.5 ng/ml (0.3-0.7) 3 months postpartum, compared with 44.3 (38.3-61.9), 5.7 (3.1-8.4) and 0.9 (0.6-4.9) ng/ml, respectively, in non-diabetic women (P = 0.002 between groups). Levels of angiopoietin-1 and sVEGF receptor-1 did not differ between the groups. Postpartum hVEGF-A levels were lowest in women with progression of retinopathy. In logistic regression analyses, progression of retinopathy during pregnancy was not explained by the levels of the angiopoietic factors. CONCLUSIONS: The circulating levels of angiopoietic factors in pregnant diabetic women were either lower than (Ang-2) or similar to (Ang-1, hVEGF-A, VEGFR-1) those levels observed in non-diabetic pregnant women. The levels of angiopoietic factors measured here appear not to be connected with the progression of retinopathy during pregnancy.

High birth weight is associated with human leukocyte antigen (HLA) DRB1*13 in full-term infants.

In cord blood banking, substantial amounts of data on infants and cord blood are gathered at high cost, including birth weights and human leukocyte antigen (HLA) genotypes. As certain HLA alleles have been associated with protective host responses, it is possible that an HLA allele, or another factor linked to it, might even affect normal intrauterine growth. We explored cord blood bank data (n = 1381 infants) to elucidate whether there is an association between birth weight and HLA class II (DRB1) alleles. HLA DRB1 data were available from 1263 infants. We observed an association between birth weight and HLA DRB1*13, which was over-represented among full-term infants with the highest birth weights. The association remained when the birth weight was corrected for varying gestational age (relative birth weight) according to gender (P = 0.015). After correction of the P-value for multiple comparisons, the association was not statistically significant. However, when the birth weights of all infants were analysed for the effect of DRB1*13, infants positive for HLA DRB1*13 (n = 319) were found to have higher birth weights than infants negative for this allele (n = 944; median 3690 g vs. 3650 g, respectively; P = 0.044). Although the difference in median birth weight was only 40 g, it may be considered significant because it appeared after segregation of the infants into two groups according to the single HLA class II allele group earlier associated with protection against, for example, childhood type 1 diabetes and certain infectious diseases. The present finding may thus suggest identification of a new factor affecting normal intrauterine growth.

Associations among nucleated cell, CD34+ cell and colony-forming cell contents in cord blood units obtained through a standardized banking process.

BACKGROUND AND OBJECTIVES: Nucleated cell content is one of the main components used when evaluating cord blood (CB) units for clinical use. However, other indicators of the haematopoietic potential of a CB unit, such as CD34+ cell and colony-forming cell (CFU-TOT) content, have also been investigated. The aim of this study was to determine whether the CD34+ cell content could be used in selecting CB collections for banking. MATERIALS AND METHODS: The collection data, as well as cellular contents of 588 CB collections obtained using a standardized CB banking process, were analysed. RESULTS: Altogether, 526 CB units from the 588 collections accepted for processing were included in international search registries. The volume collected was, as expected, 69 ml (range 28-116 ml). The correlation between total CD34+ cell and CFU-TOT (n = 88) content in the CB collection was higher (r = 0.87) than the correlation between the total nucleated cell and CFU-TOT content (r = 0.69, both P < 0.0001). The correlations of pre- and postvolume reduction values of the total nucleated cell and CD34+ cell numbers were highly significant (r = 0.96, P < 0.0001, both). The total CFU-TOT content of the CB collection correlated significantly with the total CD34+ cell content of the CB unit before cryopreservation (but after volume reduction) (r = 0.89, P < 0.0001). CONCLUSIONS: CD34+ cell content predicts the haematopoietic potential of a CB unit better than nucleated cell content. Accordingly, the CD34+ cell content of CB could be used to select CB for banking purposes and for transplantation.

Sleep-related disordered breathing during pregnancy in obese women.

STUDY OBJECTIVES: This study was designed to evaluate sleep-related disordered breathing in obese women during pregnancy. Obesity is known to predispose to sleep-related breathing disorders. During pregnancy, obese mothers gain additional weight, but other mechanisms may counteract this effect. DESIGN: A case-control study to compare sleep-related breathing in obese pregnant women (mean prepregnancy body mass index [BMI] > 30 kg/m(2)) with pregnant women of normal weight (mean BMI, 20 to 25 kg/m(2)). SETTING: University teaching hospital with a sleep laboratory. PARTICIPANTS: We recruited 11 obese women (BMI, 34 kg/m(2); mean age 31 years) and 11 control women (BMI, 23 kg/m(2); mean age 32 years). INTERVENTIONS: Overnight polysomnography was performed during early (after 12 weeks) and late (after 30 weeks) pregnancy. MEASUREMENTS AND RESULTS: During pregnancy, obese mothers gained 13 kg and control women gained 16 kg. Sleep characteristics did not differ between the groups. During late pregnancy, the women in both groups slept more poorly and slept in supine position less. During early pregnancy, their apnea-hypopnea indexes (1.7 events per hour vs 0.2 events per hour; p < 0.05), 4% oxygen desaturations (5.3 events per hour vs 0.3 events per hour; p < 0.005), and snoring times (32% vs 1%, p < 0.001) differed significantly. These differences between the groups persisted in the second polysomnography, with snoring time further increasing in the obese. Preeclampsia and mild obstructive sleep apnea were diagnosed in one obese mother. One obese mother delivered a baby showing growth retardation (weight - 3 SD). CONCLUSIONS: We have shown significantly more sleep-related disordered breathing occurring in obese mothers than in subjects of normal weight, despite similar sleeping characteristics.

Congenital complete heart block in the fetus: hemodynamic features, antenatal treatment, and outcome in six cases.

Congenital heart block (CHB) can result in intrauterine cardiac failure leading to fetal or neonatal loss. To establish perinatal hemodynamic factors which might predict adverse outcome, six fetuses with CHB diagnosed between 20 and 30 gestational weeks were examined by echocardiography at 2-week intervals. Neonatal morbidity and outcome in infancy are detailed. The fetuses showed a significant decrease in ventricular rate (VR) with advancing gestation (60 +/- 7 vs 51 +/- 4 beats/min, p = 0.03). Cardiac decompensation defined as hydrops or pericardial effusion was associated with VR of lower than 55 beats/min in two fetuses. Three mothers had a therapeutic trial with a sympathomimetic and digoxin. Salbutamol increased VR 10% in one of three fetuses treated. Digoxin decreased pericardial effusion in one hydropic fetus with autoimmune myocarditis. In this fetus, poor left ventricular fractional shortening (LVFS) was accompanied with high umbilical artery resistance index (RI). High amniotic fluid erythropoietin indicated severe hypoxia preceding death. Pacemaker was indicated in all the newborns. At the age of 2 weeks all the surviving infants had tricuspid regurgitation and a shunt through foramen ovale due to asynchronized atrioventricular contraction. During the 12-month follow-up two of five surviving infants had no symptoms. One had symptomatic neonatal lupus. Two infants had patent ductus arteriosus, one with dilated cardiomyopathy. In conclusion, poor fetal outcome was associated with low VR, low LVFS, and high RI. Despite early pacing, morbidity was high in infancy due to cardiomyopathy and associated heart defects. Regular echocardiographic monitoring during pregnancy and after delivery is required in order to optimize care and timing of any interventions.

Fetal shoulder measurements by fast and ultrafast MRI techniques.

The purpose of this study was to evaluate magnetic resonance imaging (MRI) of fetal shoulder measurements of fetuses with suspected macrosomia. The actual fetal shoulder measurements made immediately after birth were compared with measurements obtained by fast and ultrafast MRI techniques antepartum. Eight singleton diabetic pregnant mothers underwent MRI examination with fast imaging in steady-state precession (TrueFISP) and spin-echo (SE) and gradient-echo (GE) echo-planar (EPI) sequences to show the fetal shoulder width. The actual shoulder width was measured immediately postpartum by a neonatologist. There was a statistically significant correlation between the MRI measurements and the actual shoulder width (P < 0.001 - P < 0.05) for all sequences. TrueFISP (r = 0.98, P < 0.001) was superior to EPI sequences (r = 0.88, P < 0.01 for SE EPI and r = 0.80, P < 0.05 for GE EPI). The images of all three sequences used were free of major motion artifacts. Fast and ultrafast sequences seem to be reliable for fetal shoulder measurements and the TrueFISP was the most accurate sequence compared to SE and GE echo-planar sequences. J. Magn. Reson. Imaging 2001;13:938-942.

Maternal thrombocytopenia at term: a population-based study.

BACKGROUND: Thrombocytopenia is a common problem during pregnancy and often inappropriately managed. This study aimed to assess the prevalence and causes of maternal thrombocytopenia at term with special attention to immune mechanisms of thrombocytopenia and the need for assessing fetal risks. METHODS: We conducted a 1-year population-based surveillance study involving 4,382 fullterm (at least 37 weeks' gestation) women (83.8% of the study population) and their infants from the city of Helsinki. Maternal and cord platelet counts were performed at delivery. Immune studies were performed if maternal platelet counts were less than 100 x 10(9)/l; 95% confidence intervals (CIs) were calculated from the binomial distribution. RESULTS: A total of 317 women (7.3%; 95% CI 6.5, 8.1) had platelet counts of less than 150 x 10(9)/l. Most cases (81%) of maternal thrombocytopenia at term were due to gestational thrombocytopenia, which had no impact on either the mother or the fetus unless associated with some other medical or obstetric disorder. Other causes of thrombocytopenia were preeclampsia (16%) and idiopathic thrombocytopenic purpura (ITP) (3%). There was no association between maternal and fetal platelet counts: of the infants born to thrombocytopenic mothers, 2.1%, had thrombocytopenia in the cord blood, which did not differ significantly from the 2.0% of thrombocytopenic infants born to non-thrombocytopenic mothers. CONCLUSION: Women with gestational thrombocytopenia do not require alteration of their treatment. Fetal blood sampling is not considered necessary when thrombocytopenia is discovered unexpectedly at term.

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.

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.