Kari Teramo

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 A1 c 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 HbA1 c was only slightly raised (5.6 to 6.8 %, ie 2.0 to 5.9 standard deviation units) showed a relative risk of 3.0 (95 % confidence interval: 1.2 to 7.5). Haemoglobin A1 c retained its statistically significant association with the occurrence of malformations after adjusting for Whites class, age at onset of diabetes, duration of diabetes, parity, smoking and participation in pre-pregnancy counselling.¶Conclusions/interpretation. Even a slightly raised HbA1 c 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. [Diabetologia (2000) 43: 79–82]

Risk of minor and major fetal malformations in diabetics with high haemoglobin A1c values in early pregnancy.

Maternal haemoglobin A1c (HbA1c) values were measured before the end of the 15th week of gestation in 142 pregnancies in women with insulin dependent diabetes. In pregnancies complicated by fetal malformations (n = 17) the mean initial HbA1c value was 9.5 (SD 1.8)% of the total haemoglobin concentration, which was significantly (p less than 0.001) higher than in pregnancies without malformations (8.0 (SD 1.4)%; n = 125). HbA1c values did not differ between pregnancies complicated by minor and major fetal malformations, but the rate of malformations showed a positive relation to the HbA1c value in early pregnancy (chi 2 = 11.9; p = 0.001). Fetal malformations occurred in six out of 17 pregnancies (35.3%) in mothers whose initial HbA1c value was 10% or more, in eight out of 62 pregnancies (12.9%) in mothers with initial values between 8.0% and 9.9%, and in only three out of 63 pregnancies (4.8%) in mothers with an initial value below 8.0%. These data support the hypothesis that the increased incidence of fetal malformations in mothers with insulin dependent diabetes is associated with maternal hyperglycaemia during organogenesis. Hence diabetic women who are planning to have a child--especially those with a high HbA1c value--should receive intensified metabolic control.

Glycaemic control is associated with pre-eclampsia but not with pregnancy-induced hypertension in women with Type I diabetes mellitus

Aims/hypothesis. To investigate the association between glycaemic control and hypertensive pregnancy complications. Methods. From 1988 to 1997, we followed up 683 consecutive non-selected pregnancies in women with Type I (insulin-dependent) diabetes mellitus. Glycaemic control was assessed by assay of HbA1 c. Pre-eclampsia was defined as diastolic blood pressure of 90 mmHg or more at the end of pregnancy after an increase of 15 mmHg or more, combined with proteinuria of 0.3 g or more for 24 h. Pregnancy-induced hypertension was defined similarly but without proteinuria. The same criteria were applied to a control group of 854 non-selected non-diabetic women. Results. Pre-eclampsia developed in 12.8 % of the women with diabetes (excluding those with nephropathy before pregnancy) and in 2.7 % of the control women (odds ratio 5.2; 95 % CI 3.3–8.4). In multiple logistic regression, glycaemic control, nulliparity, retinopathy and duration of diabetes emerged as statistically significant independent predictors of pre-eclampsia. The adjusted odds ratios for pre-eclampsia were 1.6 (95 % CI 1.3–2.0) for each 1 % increment in the HbA1 c value at 4–14 (median 7) weeks of gestation and 0.6 (0.5–0.8) for each 1 % decrement achieved during the first half of pregnancy. Changes in glycaemic control during the second half of pregnancy did not significantly alter the risk of pre-eclampsia. Unlike pre-eclampsia, the risk of pregnancy-induced hypertension was not associated with glycaemic control. Conclusion/interpretation. In women with Type I diabetes, poor glycaemic control is associated with an increased risk of pre-eclampsia but not with a risk of pregnancy-induced hypertension. [Diabetologia (2000) 43: 1534–1539]

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.

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

Aims/hypothesisIn 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.MethodsA 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.ResultsThe median amniotic fluid erythropoietin level was 14.0xa0mU/ml (range 2.0–1975.0) in diabetic pregnancies and 6.3xa0mU/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 63.0xa0mU/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 (>63.0xa0mU/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 (<15.0xa0mmxa0Hg) was explained by amniotic fluid erythropoietin (p<0.0001) and birthweight z score (p=0.004).Conclusions/interpretationAntenatal high amniotic fluid erythropoietin levels can identify Type 1 diabetic pregnancies at increased risk of severe perinatal complications.

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 × 109/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 4489 infants, 84.9% of the study population. Eighty-nine infants had platelet counts below 150 × 109/L (2.0%; 95% CI 1.5, 2.3) in cord blood and 11 were less than 50 × 109/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.

Pregnancy in lupus nephropathy

The purpose of this study was to obtain information about the fetal and maternal outcome of pregnancy in patients with pre‐existing lupus nephritis and to evaluate risk factors for poor fetal outcome. Twenty‐six pregnancies in 16 patients were retrospectively analyzed. Induced abortions were performed in two patients and one patient had a spontaneous abortion. Of the 23 completed pregnancies, all clinically established on inactive lupus nephritis with normal renal function, seven (30%) were complicated by pre‐eclampsia. Two of the three patients with severe pre‐eclampsia had increased levels of antiphospholipid antibodies (aPL). Of the 23 newborns, seven (30%) were premature (> 37 weeks) and seven (30%) had neonatal complications. Six of the seven pregnancies associated with neonatal complications were hypertensive. There was one early neonatal death. Four newborns (16%) were severely growth retarded (>— 2 SD). The presence of hypertension before pregnancy tended to correlate with low relative birth weight in the newborns (p = 0.079). Flares of systemic lupus erythematosus (SLE) during pregnancy and six months post partum occurred in two (9%) of the 23 completed pregnancies. Renal function was not affected irreversibly in any patient. Thus, the outlook for pregnancy in patients with stable lupus nephritis at conception is good. However, the risk of obstetric complications is greater and fetal morbidity, especially in hypertensive pregnancies, is common.

Primary Sphincter Repair: Are the Results of the Operation Good Enough?

PURPOSE:nThis study was designed to evaluate the clinical outcome of primary anal sphincter repair caused by obstetric tears and to analyze possible risk factors associated with sphincter rupture during vaginal delivery.nMETHODS:nA total of 52 females with a third-degree or fourth-degree perineal laceration during vaginal delivery were examined. The symptoms of anal incontinence were obtained by a standard questionnaire. In addition to a clinical examination, endoanal ultrasound, anal manometry, and pudendal nerve terminal motor latency examinations were performed. A control group consisted of 51 primiparous females with no clinically detectable perineal laceration after vaginal delivery.nRESULTS:nAfter primary sphincter repair, 31 females (61 percent) had symptoms of anal incontinence. Fecal incontinence occurred in 10 females (20 percent). According to Hardcastle and Parks’ and Jorge and Wexner’s classifications, the study group had more severe symptoms of anal incontinence than the control group (P < 0.001 in both classification groups). In endoanal ultrasound examination, a persistent defect of the external anal sphincter was found in 39 females (75 percent) in the rupture group compared with 10 females (20 percent) in the control group (P < 0.001). Anal sphincter pressures were significantly lower in the rupture group than in the control group. An abnormal presentation was the only risk factor for anal sphincter rupture during vaginal delivery.nCONCLUSIONS:nAfter primary sphincter repair, persistent external anal sphincter defect and symptoms of anal incontinence are common in females who have had a primary sphincter repair after vaginal delivery. The means of improving the results of primary repair should be studied further.n

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

Aims/hypothesisOur 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.MethodsWe 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.ResultsMaternal BMI increased significantly during 1989–2008 (pu2009<u20090.001). The mean HbA1c in the first trimester remained unchanged, but the midpregnancy and the last HbA1c before delivery increased (pu2009=u20090.009 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 HbA1c value before delivery was associated with delivery before 37xa0weeks’ gestation, UA pH <7.15, 1xa0min Apgar score <7, macrosomia, NICU admission and neonatal hypoglycaemia.Conclusions/interpretationSelf-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.

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

Aims/hypothesisOur aim was to study whether pre-eclampsia and pregnancy-induced hypertension are predictors of diabetic nephropathy in type 1 diabetic women.Materials and methodsA 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 11xa0years within the nationwide, multi-centre Finnish Diabetic Nephropathy Study. Diabetic nephropathy was defined as microalbuminuria, macroalbuminuria or end-stage renal disease.ResultsPatients 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 HbA1c (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/interpretationThese data suggest that a history of pre-eclamptic pregnancy but not pregnancy-induced hypertension is associated with an elevated risk of diabetic nephropathy.