Franz Kainer

Assessment of the quality of general movements in fetuses and infants of women with type-I diabetes mellitus

The effect of type-I diabetes on the quality of general movements (GMs) was studied longitudinally in 12 human fetuses. GMs were analysed at two-weekly intervals from 16 weeks until delivery. A pregnancy optimality-score and a diabetes optimality-score were used to cover the course of the pregnancy and delivery and the severity of diabetes. GMs of infants were analysed 1, 4-6, and 12-18 weeks after birth and the Bayley developmental test was performed at 10 months. All fetuses showed normal GMs at 16 weeks. From 20 weeks onwards until delivery five fetuses developed abnormal GMs. The diabetes optimality-score was significantly lower in the group with abnormal GMs (P = 0.018) whereas the pregnancy optimality-score did not differ between fetuses with normal and abnormal GMs. Our results indicate that type-I diabetes can have a negative impact on prenatally observed GMs. Consistently normal GMs indicate normal neurodevelopmental outcome at 10 months whereas in the group with abnormal GMs reduced Bayley-scores may occur.

Fetal outcome in gestational diabetes with elevated amniotic fluid insulin levels: Dietary versus insulin treatment

Of 228 women with gestational diabetes between 28 and 32 gestational weeks, 195 had a normal amniotic fluid insulin level (4.8 +/- 3.6 microU/ml) while 33 (14.5%) had an elevated level (23.1 +/- 10 microU/ml). Women with a normal amniotic fluid insulin level were treated by diet alone. Fourteen of the women with an elevated level were treated by diet alone; 19 received insulin treatment additionally. The fetal outcome of patients with a normal amniotic fluid insulin level and dietary therapy and of those with an elevated level and insulin treatment was similar to that of metabolically healthy women. The newborns of gestational diabetics with elevated amniotic fluid insulin treated by diet alone showed a significantly higher incidence of neonatal hyperinsulinism, hypoglycemia, hyperbilirubinemia, high birth weight, respiratory distress syndrome and hypocalcemia. While 2/14 (14%) of the neonates in the dietary group had fatal respiratory distress syndrome, there were no deaths in the group with elevated amniotic fluid insulin and insulin treatment. The data demonstrate that in gestational diabetics with normal amniotic fluid insulin (low-risk group), dietary therapy is sufficient while insulin therapy is required to ensure healthy offspring in patients with elevated amniotic insulin (high-risk group).

Levels of amniotic fluid insulin and profiles of maternal blood glucose in pregnant women with diabetes type-I

The aim of this study was to investigate the relationship between amniotic fluid insulin (AF-insulin) measurements and maternal blood glucose levels in pregnancies complicated by insulin-dependent maternal diabetes mellitus (IDDM). Twenty-five patients with IDDM underwent amniocentesis (AC) in the third trimester. Twelve patients had a second amniocentesis after 2-3 weeks. The maternal blood glucose values (MBG) 2 weeks before amniocentesis were correlated with AF-insulin. Mean (+/-S.D.) MBG in the group with AF-insulin > 97th centile (n = 7) was 6.1 +/- 1 mmol/l. MBG in the group with AF-insulin < 97th centile (n = 18) was 5.3 +/- 1.2 mmol/l (r = 0.2948; P-value 0.162). In the group with repeated AC and AF-insulin > 97th centile (n = 6) the correlation coefficient was 0.722 (P = 0.043), whereas in the group with normal AF-insulin (n = 6) no correlation was found (r = -0.213; P = 0.686). These results indicate that no significant correlation exists between MBG values and concentration of AF-insulin. MBG is not appropriate for the diagnosis of fetal hyperinsulinism in well-controlled women with IDDM. In individual cases with AF-insulin > 97th centile a decrease of MBG causes lower AF-insulin levels. These results indicate that there seems to be an individual threshold for maternal MBG which causes hyperinsulinism. Fetal hyperinsulinism not only depends on blood glucose levels. Different fetal sensitivity to maternal glucose stimuli or a different glucose transport across the placenta in the individual fetus could be responsible for these results.

Altered release of endothelin‐1,2 and thromboxane B2 from trophoblastic cells in pre‐eclampsia

The aim of the study was to investigate whether pre‐eclampsia is associated with an altered release of vasoactive substances from trophoblastic cells in vitro. Trophoblastic cells from 15 uncomplicated control pregnancies and 18 pre‐eclamptic pregnancies at preterm (weeks 31–36; n = 12) and term (weeks 37–40; n = 21) were cultured for 5 days. The concentrations of angiotensin II (AII), endothelin‐1,2 (ET‐1,2), thromboxane B2 (TXB2), 6‐keto‐prostaglandin F1α (6‐keto‐PGF1α) and leukotriene B4 (LTB4) were measured daily in culture media for 5 days by radioimmunoassay. In pre‐eclampsia, concentrations of ET‐1,2 were decreased (P < 0.01) at both preterm and term, TXB2 concentrations were increased P < 0.05) only at preterm and the TXB2–6‐keto‐PGF1α ratio was increased at both preterm and term (P < 0.01) as compared with the controls. Concentrations of AII, 6‐keto‐PGF1α and LTB4 were similar to the controls. The data suggest that pre‐eclampsia is associated with a decreased release of ET‐1 and an increased release of TXB2 from trophoblastic cells in vitro

Anti-insulin antibodies and birth weight in pregnancies complicated by diabetes

Free insulin cannot cross the placenta but insulin complexed to anti-insulin antibodies has been demonstrated in cord blood. We studied whether antibody-bound insulin in diabetic patients can evoke fetal macrosomia independently of maternal metabolic control. In 457 non insulin-treated controls and 173 insulin-treated diabetic patients we measured 1187 anti-insulin antibody levels and maternal blood glucose, maternal fructosamine, cord blood insulin, cord blood C-peptide, cord blood fructosamine and amniotic fluid insulin. Mean anti-insulin antibody levels in maternal blood and cord blood were significantly higher in insulin treated diabetic patients (4.6 and 5.4 U/ml) than in controls (1.8 and 1.7 U/ml) with maxima of 89.2 in maternal and 120.0 U/ml in cord blood, respectively. In insulin treated diabetic patients 16.6% (maternal blood) and 22% (cord blood) anti-insulin antibody levels were above the 97th percentile. There was a high significant correlation between maternal and cord blood anti-insulin antibodies (R = 0.987, P = < 0.0001), but no correlation of anti-insulin antibodies with maternal (glucose, fructosamine) or fetal (insulin, C-peptide, and fructosamine in cord blood, amniotic fluid insulin) metabolic parameters. While maternal and fetal metabolic parameters correlated with birth weight neither maternal nor cord blood anti-insulin antibody levels correlated with birth weight. These findings do not support the hypothesis that maternal anti-insulin antibodies independently influence fetal weight.

Cord blood insulin to assess the quality of treatment in diabetic pregnancies

According to the Pedersen hypothesis, fetal hyperinsulinism is the major cause for adverse neonatal outcome. We investigated associations between insulin levels in cord blood and fetal complications. Three groups of 21 insulin-dependent diabetic patients with different insulin levels in cord blood were matched according to White Classes. Insulin levels in cord blood of < 20 microU/ml were considered normal (controls), 20-50 microU/ml intermediate group, and > 50 microU/ml high (cases). The mean (+/-S.D.) insulin level in cord blood in the three groups was 10.7+/-5.6, 28.6+/-8.1, and 104.0+/-61.0 microU/ml, respectively. Controls and cases showed significant differences in birth weight > 90th percentile (9.5% vs. 76.2%), premature birth < 37 weeks (4.8% vs. 71.4%), caesarean delivery (28.6% vs. 66.4%), hypoglycaemia of the neonate (14.3% vs. 61.9%), cushingoid appearance (4.8% vs. 42.9%) and respiratory distress syndrome (0% vs. 33.3%). The results of the intermediate group were between the controls and the cases. Insulin levels in cord blood > 20 microU/ml represent a continuum of increasing diabetogenic fetopathy. We consider neonates with insulin levels in cord blood < 20 microU/ml as metabolically healthy, those with 20-50 microU/ml as having mild fetopathy, and those with > 50 microU/ml as having marked fetopathy, respectively.

Ultrasound growth parameters in relation to levels of amniotic fluid insulin in women with diabetes type-I

The aim of the study was to investigate the correlation between ultrasound parameters and levels of amniotic fluid insulin (AF-insulin) in pregnancies complicated by insulin-dependent diabetes mellitus (IDDM). In 129 women with IDDM amniocentesis was performed between 28 and 35 weeks of gestation. The levels of AF-insulin were measured by radioimmunoassay (Pharmacia RIA 100) and were correlated with biparietal diameter (BPD), abdominal diameter (AD), abdominal circumference (AC), and femur length (FL). The women were maintained at good glycemic control (fructosamine level: mean +/- S.D.: 236.3 +/- 40 micromol/l) and delivered infants with a mean (+/- S.D.) birth weight of 3477 +/- 640 g. The sensitivity of BPD, AD, AC and FL to detect fetuses with pathological levels of AF-insulin was 50%, 62%, 67% and 49%, respectively. The sensitivities of AD and AC in a selected group (n = 14) with highly pathological levels of AF-insulin (> 20 microU/ml) were both 80%, whereas the specificity was 56% and 46%, respectively. In women with IDDM, fetal biparietal diameter, abdominal diameter, abdominal circumference, and femur length are not reliable markers for the identification of fetal hyperinsulinism. Only cases with highly pathological levels of AF-insulin can be detected by abdominal measurements.

PRE-ECLAMPSIA AND GESTATIONAL AGE DIFFERENTLY ALTER BINDING OF ENDOTHELIN-1 TO PLACENTAL AND TROPHOBLAST MEMBRANE PREPARATIONS

The aim of the study was to compare the binding of endothelin-1 (ET-1) to membranes from placental tissue and trophoblast cells in normal and pre-eclamptic pregnancies. Plasma membranes from placental tissue and trophoblastic cells were prepared from 15 control and 18 pre-eclamptic pregnancies at either preterm (weeks 31-36) or term (weeks 37-40). ET-1 binding to tissue membranes was measured by a radioreceptor assay. In addition, binding of 56 nmol/l [125I]ET-1 to plasma membranes of trophoblastic cells was determined. In pre-eclampsia, placental membranes bound less (P < 0.01) ET-1 owing to fewer (P < 0.01) receptors at preterm than in the corresponding preterm controls. In contrast, binding of [125I]ET-1 to plasma membranes of trophoblast cells was higher (P < 0.01) in pre-eclampsia at both gestational stages than in the controls. Incubation of trophoblast cells with hydralazine reduced binding by 70%. We conclude that pre-eclampsia is associated with changes in the binding of ET-1 to its placental receptors. Moreover, the data suggest that pre-eclampsia affects non-trophoblast cells in the opposite manner to the trophoblast.

AMNIOTIC FLUID INSULIN LEVELS IN NONDIABETIC PREGNANT WOMEN : AN UPDATE

Abstract. Elevated amniotic fluid insulin levels in diabetes are frequently described but there are few systematic data on metabolically healthy women to define normal ranges. Previous studies had too high normal ranges because they were based on unspecific insulin binding radioimmunoassays. The aim of the study was to update normal amniotic fluid insulin data and to define a reliable normal range in the course of a nondiabetic pregnancy. Amniotic fluid insulin levels were measured in 841 amniotic fluid samples of 707 nondiabetic women undergoing amniocentesis for hydramnios, suspected malformation, determination of lung maturation, Rhesus antibodies and cordocentesis. Mean (±SD) of amniotic fluid insulin level was 3.6 (±2.1) μU/mL at 31.5 (±4.9) weeks of pregnancy. The 97th percentile was 8.2 μU/mL. Insulin levels show a biphasic course between 16th and 42nd weeks of pregnancy with a zenith at 30th week. Only two cases (0.3%) had unexplicably elevated amniotic fluid insulin levels ≥10 μU/mL. Thus, in nondiabetic women amniotic fluid insulin levels >10 μU/mL are unlikely.

Fetale Ultraschallbiometrie und Fruchtwasserinsulinkonzentration bei diabetischen Schwangeren

OBJECTIVE The aim of the study was to prove the sensitivity of sonographic measurements for the presence of a fetal hyperinsulinism. METHODS In a longitudinal examination of 102 insulin-dependent diabetics we show the correlation between the amniotic fluid insulin level and the biparietal diameter, abdominal diameter and femur length in the third trimester. The control of the maternal metabolic state was done by measuring the glycosylated hemoglobin and fructosamine at the time of the amniocentesis. RESULTS The sensitivity, specificity, positive and negative predictive value of sonographic measurements > 75th percentile in fetal hyperinsulinism was for the biparietal diameter 21, 96, 81 and 62%, for the abdominal diameter 48, 82, 69 und 66%, and for the femur length 22, 90, 67 and 57%. The maternal glycoproteins did not show any correlation with the amniotic fluid insulin level. CONCLUSIONS The results demonstrate that fetal hyperinsulinism cannot be proved by fetal biometry or evaluation of the maternal metabolic state.