White's classification and pregnancy outcome in women with type 1 diabetes: a population-based cohort study.

AIMS/HYPOTHESIS: Our aim was to examine the association of White's classification with obstetric and perinatal risk factors and outcomes in type 1 diabetic patients. METHODS: Obstetric records of a population-based cohort of 1,094 consecutive type 1 diabetic patients with a singleton childbirth during 1988-2011 were studied. The most recent childbirth of each woman was included. RESULTS: The prepregnancy and the first trimester HbA1c increased from White's class B to F (p for trend <0.001). Systolic and diastolic blood pressure and pre-eclampsia frequencies increased stepwise from class B to F (p for trends <0.001). Vaginal deliveries decreased and Caesarean sections and deliveries before 37 weeks increased from class B to F (p for trends <0.001). Fetal macrosomia (p for trend=0.003) decreased and small-for-gestational age infants (p for trend=0.002) and neonatal intensive care unit admissions (p for trend=0.001) increased from class B to F. In logistic regression analysis, White's classes were associated with pre-eclampsia but, with the exception of class R (proliferative retinopathy) and F (nephropathy), not with other adverse outcomes when adjusted for first trimester HbA1c ≥7% (≥53 mmol/mol) and blood pressure ≥140/90 mmHg. First trimester HbA1c ≥7% was associated with pre-eclampsia, preterm delivery, fetal macrosomia and neonatal intensive care unit admission. CONCLUSIONS/INTERPRETATION: White's classification is useful in estimating the risk of pre-eclampsia in early pregnancy independently of suboptimal glycaemic control and hypertension. However, its utility in predicting adverse perinatal outcomes seems limited when information on first trimester HbA1c, blood pressure and diabetic microvascular complications is available.

Obstetric and perinatal outcome in type 1 diabetes patients with diabetic nephropathy during 1988-2011.

AIMS/HYPOTHESIS: Our aim was to analyse possible changes in the glycaemic control, BP, markers of renal function, and obstetric and perinatal outcomes of parturients with diabetic nephropathy during 1988-2011. METHODS: The most recent childbirth of 108 consecutive type 1 diabetes patients with diabetic nephropathy and a singleton pregnancy were studied. Two periods, 1988-1999 and 2000-2011, were compared. RESULTS: The prepregnancy and the first trimester median HbA1c values persisted at high levels (8.2% [66 mmol/mol] vs 8.5% [69 mmol/mol], p = 0.16 and 8.3% [67 mmol/mol] vs 8.4% [68 mmol/mol], p = 0.67, respectively), but decreased by mid-pregnancy (6.7% [50 mmol/mol] vs 6.9% [52 mmol/mol], p = 0.11). Antihypertensive medication usage increased before pregnancy (34% vs 65%, p = 0.002) and in the second and third trimesters of pregnancy (25% vs 47%, p = 0.02, and 36% vs 60%, p = 0.01, respectively). BP exceeded 130/80 mmHg in 62% and 61% (p = 0.87) of patients in the first trimester, and in 95% and 93% (p = 0.69) in the third trimester, respectively. No changes were observed in the markers of renal function. Pre-eclampsia (52% vs 42%, p = 0.29) and preterm birth rates before 32 and 37 gestational weeks (14% vs 21%, p = 0.33, and 71% vs 77%, p = 0.49, respectively) remained high. The elective and emergency Caesarean section rates were 71% and 45% (p = 0.01) and 29% and 48% (p = 0.05), respectively. Neonatal intensive care unit admissions increased from 26% to 49% (p = 0.02). CONCLUSIONS/INTERPRETATION: Early pregnancy glycaemic control and hypertension management were suboptimal in both time periods. Pre-eclampsia and preterm delivery rates remained high in patients with diabetic nephropathy.

Male fetal sex is associated with earlier onset of placental abruption.

OBJECTIVE: Placental abruption is an important cause of preterm birth, and perinatal morbidity and mortality. Although more common with male fetuses, outcomes have not been evaluated by sex. Our aim was to find out whether short-term morbidity differs by infant sex in cases with placental abruption and in controls. DESIGN: Register-based case-control study. SETTING: National Hospital Discharge Register and Medical Birth Register data 1987-2005. POPULATION: The study population consisted of 4,081 women with placental abruption and singleton infant. Three control women without placental abruption were selected for each case matched by maternal age, parity, year of birth, and hospital district. A total of 3,688 cases and 12,695 controls had liveborn infants. METHODS: Data on pregnancy, delivery, and perinatal outcomes were collected. MAIN OUTCOME MEASURE: Placental abruption. RESULTS: The sex ratio (proportion of male) of cases was 0.548 and of controls 0.516 (p = 0.001). Compared with females, male fetuses in the placental abruption group were born earlier (p = 0.018). Compared with controls, cases with placental abruption were born earlier (p < 0.001), had lower birthweight (p < 0.001), were more often growth restricted (p < 0.001), had lower Apgar scores (p < 0.001) and pH (p < 0.001). Newborn cases needed special care, respirator treatment, antimicrobial and phototherapy more often (p < 0.001) than controls. There was no difference in perinatal outcomes between female and male infants in the placental abruption group. CONCLUSIONS: Placental abruption occurred earlier in pregnancy with male fetal sex but otherwise the outcomes were similar. Compared with controls newborns in the placental abruption group had a worse outcome.

Self-reported smoking habits and serum cotinine levels in women with placental abruption.

OBJECTIVE: smoking is an important risk factor for placental abruption with strong dose-dependency. Pregnant smokers often underreport tobacco use which can be objectively assessed by measuring serum cotinine levels. We examined the accuracy between self-reported smoking habits and early pregnancy serum cotinine levels in women with or without placental abruption. DESIGN: retrospective case-control study. SETTING: university Hospital. POPULATION: a total of 175 women with placental abruption and 370 control women. METHODS: serum samples collected during the first trimester were analyzed for serum cotinine levels. Cotinine concentration over 15 ng/ml was considered as the cutoff indicating active smoking. Smoking habits of the women and their partners were recorded at the same visit. MAIN OUTCOME MEASURE: placental abruption. RESULTS: of the cases of women with placental abruption, 27.4% reported smoking compared with 14.3% of the controls (p < 0.001). Based on serum cotinine levels, 30.3% of the case women and 17.6% of the control women were considered smokers (p = 0.003). Serum cotinine levels among smokers were higher in the abruption group than in the control group (median 229.5 ng/ml (interquartile range 169.8-418.1) vs. 153.5 ng/ml (56.6-241.4), p = 0.002). Self-reported number of cigarettes smoked daily correlated well with the cotinine levels (r = 0.68, p < 0.001). Of the women reporting as nonsmokers, approximately 7% were considered smokers based on cotinine testing. CONCLUSION: pregnant women with subsequent placental abruption are heavier smokers than pregnant control women. Self-reported smoking habits correlate well with serum cotinine levels in Finland. Therefore, self-reported smoking can be considered as a risk marker for placental abruption.

Hormonal and metabolic characteristics of premenopausal women with a history of preeclamptic pregnancy.

OBJECTIVE: To investigate whether women with a history of preeclampsia have more signs of hyperandrogenism and insulin resistance in the premenopausal period than women with history of normotensive pregnancies. DESIGN: Case-control study. SETTING: University Hospital. SAMPLE: Eighteen women with a history of preeclamptic first pregnancy and 19 women with prior normotensive first pregnancy studied 23-24 years after delivery. METHODS: Diagnosis of metabolic syndrome was based on the International Diabetes Federation (IDF) criteria. Matsuda's whole-body insulin sensitivity index, serum concentrations of follicle-stimulating hormone (FSH), sex hormone-binding globulin, and total and free calculated testosterone were assessed. Polycystic ovary syndrome (PCOS) phenotype was defined using Rotterdam criteria. MAIN OUTCOME MEASURES: Insulin sensitivity, metabolic syndrome and signs of hyperandrogenism. RESULTS: Insulin sensitivity and total and free testosterone were similar in the two groups. However, in women with prior preeclampsia and FSH below the median, calculated free testosterone levels were higher than in women with prior preeclampsia and FSH above the median (median 13.4 range (8.0-22.5) vs. 7.1 (5.1-20.5), p = 0.03). Of the women with previous preeclampsia, 17% (3/18) had metabolic syndrome and 11% (2/18) PCOS, versus 11% (2/19) and 0% of the controls, respectively. CONCLUSIONS: In women with prior preeclampsia, premenopause was not associated with insulin resistance, but signs of hyperandrogenism were present if FSH was within a premenopausal level.

Saltatory Pattern of Fetal Heart Rate during Labor Is a Sign of Fetal Hypoxia.

BACKGROUND: While late decelerations and major bradycardia episodes in intrapartum cardiotocography (CTG) recordings are known to correlate with fetal distress,little is known of the importance of the saltatory pattern. OBJECTIVE: The aim of the study was to examine whether the fetal heart rate (FHR) saltatory pattern in intrapartum CTG registration is associated with fetal hypoxia during the last 2 h of labor. DESIGN: The study group consisted of CTG recordings from 194 births with a 1-min Apgar score of <8 (birth weight 3,614 ± 512 g; gestational age 40.6 ± 0.7 weeks). The comparison group included 51 infants with a 1-min Apgar score of ≥9 (birth weight 3,624 ± 400 g; gestational age 40.5 ± 0.4 weeks). FHR patterns were evaluated blindly by 2 experienced perinatologists. The pH, base excess (BE), pO2 and erythropoietin (EPO) were measured from umbilical cord blood at birth as outcome variables. RESULTS: Saltatory pattern occurred in 31/194 (16.0%) of the study group and in 1/51 (2.0%) of the comparison group. Umbilical artery pH, BE, and pO2 were lower and umbilical vein (UV) EPO higher in the study group than in the comparison group. In the study group, UV EPO level was significantly higher in cases where the saltatory pattern was present (median 241 mU/mL, 95% CI 39.4-16,484), than in those without the saltatory pattern (median 39.4 mU/mL, 95% CI 11-282) (p < 0.0001, for difference). In the study group, no differences in EPO levels were found in cases where episodes of bradycardia, tachycardia, reduced variability, or uterine tachysystole were present or absent. In the study group, saltatory pattern preceded late decelerations in 82.8%. CONCLUSION: Saltatory pattern in an intrapartum FHR recording is an early sign of fetal hypoxia.

Maternal deaths in Finland: focus on placental abruption.

OBJECTIVE. To study placental abruption-associated maternal deaths out of all maternal deaths in Finland. DESIGN. Register-based study. SETTING. The Finnish Medical Birth Register (MBR), the Hospital Discharge Register (HDR), and the Cause-of-Death Register data during 1972-2005. METHODS. The maternal deaths were identified by linking data from the MBR, the HDR, and the Cause-of-Death Register. The clinical data were collected from the case records and death certificates. MAIN OUTCOME MEASURES. Cause-specific maternal death with special reference to placental abruption. RESULTS. During the study period, a total of 2,104,436 live births and 117 direct maternal deaths (caused by a disease or its management unique to the pregnancy) occurred in Finland. The direct maternal mortality ratio (MMR) was 5.6 per 100,000 live births. The two leading causes were thromboembolism (24.0%) and hemorrhage (22.3%) representing almost half of all maternal deaths. Altogether 7,735 placental abruptions were identified with three maternal deaths giving a case fatality rate of 0.4 per 1,000 cases. The MMR (38.8 per 100,000) was nearly seven times higher than the overall MMR (5.7 per 100,000) (p=0.010). CONCLUSION. The direct MMR in Finland is at the level generally seen in Western Europe. The main causes to maternal death are thromboembolism and obstetric hemorrhage. Deaths to placental abruption are rare, but still seven times higher than the overall MMR.

Increased plasma levels of inflammatory markers and upper airway resistance during sleep in pre-eclampsia.

OBJECTIVES: To evaluate pregnancy-associated sleep disorders, pregnancy outcomes and inflammatory markers in pre-eclampsia and normal pregnancy (control). PATIENTS AND METHODS: We studied 15 consecutive pre-eclamptic women and 14 controls. Pre-eclamptic women underwent overnight pulse oximetry and nasal pressure measurements at a university teaching hospital, and the sleep study for the controls was performed at home. Mean gestation was 31 weeks. Nasal airflow was carefully analyzed visually, and the time with flow limitation was calculated as a percentage of total recording time. At the time of the sleep study, the subjects were clinically evaluated, they answered sleep questionnaires, and fasting blood samples were drawn for tumor necrosis factor alpha TNF-alpha, interleukin 6 (IL-6) and sensitive C-reactive protein. Pregnancy outcomes were collected after delivery. RESULTS: Pre-eclampsia patients spent significantly more time with flow limitation (mean+/-SD: 21+/-18% vs. 4+/-9%), had higher plasma levels of TNF-alpha (6.2+/-2.3 ng/l vs. 4.1+/-ng/l) and IL-6 (4.4+/-ng/l vs. 1.2+/-0.4 ng/l), had more generalized edema, had increased fatigue and snoring, and had poorer pregnancy outcomes than did controls. Age, gestational age, mean SpO2 and body mass index did not differ between the groups. CONCLUSIONS: Pregnant women with pre-eclampsia showed significantly more nasal flow limitation during the night, higher fasting IL-6 and TNF-alpha plasma levels, more edema and worse pregnancy outcomes than did healthy pregnant women.

Detection of pregnancies with high risk of fetal macrosomia among women with gestational diabetes mellitus.

OBJECTIVE: To compare the frequency of fetal macrosomia and Erb's palsy in two groups of women with gestational diabetes mellitus (GDM) and in healthy controls. DESIGN: Retrospective clinical study of women with GDM. SETTING: Pregnant women in Greater Helsinki area. POPULATION: Nine hundred and five pregnancies and newborn infants of women with GDM and 805 non-diabetic controls. METHODS: GDM was diagnosed by a 2-hour oral glucose tolerance test (OGTT) among women with risk factors for GDM. The treatment of GDM was resolved by a 24-hour glucose profile obtained after 2 or 3 abnormal glucose values in the OGTT. Patients with a history of insulin-treated GDM in a previous pregnancy and those with a fasting glucose over 6 mmol/l underwent a 24-h glucose profile directly without a preceding OGTT. MAIN OUTCOME MEASURES: Fetal macrosomia, defined as a birth weight (adjusted for sex and gestational age) of >2.0 SD above the mean of a Finnish standard population. Erb's palsy. RESULTS: 385 women (42.5%) were treated with insulin and diet and 520 (57.5%) with diet only. Macrosomia occurred more often in the insulin-treated group (18.2%, p<0.001) compared with the diet-treated group (4.4%) and the controls (2.2%). The rate of Erb's palsy was 2.7% in the insulin-treated group, 2.4% in the diet-treated group, compared with 0.3% in the controls (p<0.001). CONCLUSION: The 24-hour glucose profile performed after the diagnosis of GDM clearly distinguishes between low-risk (diet-treated) and high-risk (insulin-treated) for fetal macrosomia in GDM pregnancies.

The relationship between human fetal cardiovascular hemodynamics and serum erythropoietin levels in growth-restricted fetuses.

OBJECTIVE: We hypothesized that in growth restricted fetuses, erythropoietin (EPO) secretion is increased in proportion to the severity of cardiovascular compromise. STUDY DESIGN: Thirty-eight growth restricted fetuses underwent Doppler ultrasonography of cardiovascular hemodynamics. An umbilical artery (UA) blood sample was taken at delivery for EPO analysis. Group 1 fetuses (n=9) had normal UA and ductus venosus (DV) velocimetries. Group 2 fetuses (n=18) showed an abnormal UA and a normal DV velocimetry. Group 3 fetuses (n=11) had abnormal UA and DV velocimetries. Normal EPO values were determined in 19 uncomplicated pregnancies (control group). RESULTS: In group 3, EPO levels were higher (P<.05) than in groups 1 and 2. All fetuses in group 3 had EPO concentrations above the 90th percentile EPO value in the control group. The corresponding incidences were 44% and 50% in groups 1 and 2. Fetuses with retrograde aortic isthmus net blood flow had greater (P<.001) EPO levels than fetuses with antegrade net blood flow. Descending aorta, UA, DV and left hepatic vein pulsatility index values correlated significantly with EPO concentrations. CONCLUSION: In fetal growth restriction, serum EPO concentration is increased in proportion to the severity of fetal cardiovascular compromise. Furthermore, in fetuses with retrograde aortic isthmus net blood flow, EPO levels are increased.

Plasma levels of annexins IV and V in relation to antiphospholipid antibody status in women with a history of recurrent miscarriage.

INTRODUCTION: The presence of antiphospholipid (aPL) antibodies increases the risk for recurrent miscarriage (RM). Annexins are a family of structurally related proteins which all bind to anionic phospholipids (PLs) preventing clotting on vascular phospholipid surfaces. The aim of our study was to define plasma concentrations of circulating annexins IV and V at the beginning of pregnancy among women with a history of RM, and in connection to their aPL antibody status. MATERIALS AND METHODS: Sixty-eight women with RM and 25 controls without history of adverse pregnancy outcome were included in the study. Concentrations of annexins IV and V in plasma were determined by using a sandwich ELISA technique. RESULTS: Hereditary or acquired thrombophilic disorders were found in 53% (36/68) of the patients with RM. Plasma levels of annexin V were significantly higher at the beginning of pregnancy (P=0.03), at the 6th (P=0.01) and 8th week of pregnancy in women with aPL antibodies compared with those without aPL antibodies. A tendency towards higher plasma levels of annexin V was observed in those whose pregnancies ended in miscarriage compared with those with successful pregnancy, although the results did not reach statistical significance (P=0.10). Plasma levels of annexin IV at the first visit in women with aPL antibodies were similar to those at 6 and 8 weeks of gestation. There were no significant differences in plasma annexin IV levels between women with and without aPL antibodies. CONCLUSIONS: Patients with RM show elevated plasma levels of annexin V in presence of aPL antibodies. These antibodies could displace annexin from anionic phospholipid surfaces of syncytiotrophoblasts (STBs) and hereby promote coagulation activation.

Prolonged low-molecular-weight heparin use during pregnancy and subsequent bone mineral density.

INTRODUCTION: In contrast to unfractionated heparin (UFH), use of low-molecular weight heparin (LMWH) during pregnancy has not been reported to be associated with a significant decrease in bone mineral density (BMD). The aim of this study was to investigate whether long-term use of LMWH during pregnancy is associated with subsequent decrease in BMD or with increased number of osteoporotic fractures. MATERIALS AND METHODS: In this observational cohort study BMD was measured by dual energy X-ray absorptiometry (DEXA) 4-7years after the last delivery in 152 women. Ninety-two women had prolonged LMWH-exposure during pregnancy - 75 as prophylaxis and 17 as treatment for venous thromboembolic event (VTE). Dalteparin and enoxaparin were the LMWH-preparations used. Sixty women without LMWH-exposure served as controls. A questionnaire about lifestyle factors and medical history was filled out by the subjects. RESULTS: Lumbar spine BMD in the LMWH users was lower than that in the controls both in the prophylactic group (1.22g/cm(2) vs. 1.27g/cm(2); p=0.03), and in the treatment group (1.20g/cm(2) vs. 1.27g/cm(2); p=0.07). BMD in femoral neck did not differ between the LMWH-users and controls. However, after adjusting for potential confounding factors, LMWH-exposure did not remain associated with decreased BMD in lumbar spine. Use of contraceptive pills was positively associated with BMD in lumbar spine. Incidence of osteopenia was 13% in the LMWH-group and 8% in the control-group, (p=0.4). No osteoporosis or osteoporotic fractures were found. CONCLUSIONS: Prolonged use of LMWH during pregnancy was not associated with subsequent decrease in BMD, osteopenia, osteoporosis, or osteoporotic fractures.

The insulin-like growth factor system and Type 1 diabetic retinopathy during pregnancy.

AIMS/HYPOTHESIS: To find out whether the levels of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1), highly phosphorylated IGFBP-1 (hpIGFBP-1), and IGF binding protein-3 (IGFBP-3) are related to the progression of diabetic retinopathy (DR) during pregnancy and postpartum. METHODS: In a prospective study of 42 pregnant women with Type 1 diabetes and 9 nondiabetic controls, DR was graded from fundus photographs. Levels of serum total IGF-I and two different phosphoisoform patterns of IGFBP-1 and IGFBP-3 were measured during the first and third trimester of pregnancy and 3 months postpartum. RESULTS: Both the levels of serum total IGF-I (P<.0001) and IGFBP-3 (P=.003) were lower in the diabetic than in the nondiabetic women during pregnancy and postpartum (repeated-measures ANOVA between the groups). Additionally, the IGF-I and IGFBP-3 levels tended to be lower in the diabetic women with more severe DR at baseline than in those with less severe DR. There were no statistically significant differences in the levels of IGF-I and IGFBP-3 in the diabetic women with progression of DR compared with those without. No statistical differences appeared in the IGFBP-1 phosphoisoform patterns between the groups. CONCLUSIONS/INTERPRETATION: In diabetic women, mean serum levels of IGF-1 and IGFBP-3 are lower than in nondiabetic controls during pregnancy and/or postpartum. Because there was no clear connection between the IGF system and progression of DR during pregnancy, it is unlikely that these substances mediate the tendency of DR to progress during pregnancy.

50gram oral glucose challenge test combined with risk factor-based screening for gestational diabetes.

OBJECTIVE: Our aim was to study whether universal screening of all pregnant women by Oral Glucose Challenge Test (OGCT) would identify a higher number of women with Gestational Diabetes (GDM) than risk factor based screening. STUDY DESIGN: A 50 g OGCT test was performed prospectively in 532 unselected women at 26-28 weeks of gestation. The 1-h venous plasma glucose concentration of >7.3 mmol/l was considered as a positive screening result. Patients with a positive OGCT underwent a 75 g 2-h OGTT, which was used as the actual diagnostic test for GDM. When two or all three of the glucose concentrations in OGTT (measured at fasting state and 1 and 2 h after the 75 g glucose load) were above the 97.5th percentile the patient was considered as having GDM. In addition, women with risk factors for GDM also underwent a 75 g OGTT regardless of the result of the OGCT. RESULTS: A positive 50 g OGCT was obtained in 123 (23%) of the women. In 15 (12%) of these, a diagnosis of GDM was established by the subsequent OGTT. Out of the 409 remaining women with a normal OGCT, 148 (36%) had risk factors for GDM. An OGTT performed in these patients identified 4 additional women with a GDM. Seventy-nine percent of GDM was thus found with 50g OGCT without regarding risk factors. Forty-seven percent of the women with GDM would have been missed in screening by risk factors only. CONCLUSIONS: In our population 50 g OGCT appears to identify a higher number of GDM than risk factor based screening. Combined with risk factor screening a few more cases of GDM would be found.

Enzyme-inducing antiepileptic drugs in pregnancy and the risk of bleeding in the neonate.

BACKGROUND: Case reports suggest that maternal hepatic enzyme-inducing antiepileptic drugs (AED) increase the risk for neonatal bleeding. Antenatal administration of vitamin K(1) to mothers using these drugs therefore is widely recommended. There are, however, no studies on the incidence of this complication. OBJECTIVE: To assess the occurrence of bleeding complications in newborns exposed to maternal enzyme-inducing AED in utero. METHODS: The authors prospectively followed 662 pregnancies in women with epilepsy who used enzyme-inducing AED. Of the 667 neonates, 463 were exposed to carbamazepine, 212 to phenytoin, 44 to phenobarbital, 11 to primidone, and 7 to oxcarbazepine. The control subjects were 1,324 nonepileptic pregnancies (1,334 neonates) matched for maternal age, parity, number of fetuses, and delivery date. None of the mothers received vitamin K(1) during pregnancy, but all infants received 1 mg vitamin K(1) intramuscularly at birth. RESULTS: A bleeding complication was observed in five (0.7%) of the offspring exposed to maternal enzyme-inducing AED and in five (0.4%) control subjects (p = 0.3). After logistic regression analysis was performed, bleeding was associated with birth at <32 weeks of gestation (adjusted OR = 13; 95% CI = 2.7 to 64) and alcohol abuse (adjusted OR = 17; 95% CI = 1.8 to 162) but not with exposure to enzyme-inducing AED (adjusted OR = 1.1; 95% CI = 0.3 to 4.6; p = 0.8). CONCLUSIONS: These data do not support the hypothesis that maternal enzyme-inducing AED increase the risk for bleeding in the offspring. Antenatal administration of vitamin K to these mothers may still be needed in selected cases.

Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin.

Venous thromboembolism remains an important cause of maternal mortality. In a randomised open study, 44 pregnant women with confirmed previous or current thromboembolism were randomised to receive either low-molecular-weight heparin, dalteparin (N = 21) once daily subcutaneously or unfractionated sodium heparin (UF heparin, N = 23) twice daily subcutaneously for thromboprophylaxis during pregnancy and puerperium. Bone mineral density (BMD) in the lumbosacral spine was measured with dual X-ray absorptiometry (DEXA) 1, 6, 16, 52 weeks and, if possible, 3 years after delivery. BMD values were also compared with those of healthy, delivered women (N = 19). Mean BMD of the lumbar spine was significantly lower in the unfractionated heparin group compared with the dalteparin and with the control groups (repeated measures ANOVA p = 0.02). BMD in the dalteparin group did not differ from BMD of healthy delivered women. Multiple logistic regression analysis revealed that therapy was the only independent factor influencing BMD at weeks 16 and 52. Therefore we recommend use of dalteparin instead of UF heparin for long-term thromboprophylaxis during and after pregnancy.

Risk for subsequent coronary artery disease after preeclampsia.

We studied the history of hypertensive pregnancies and conventional risk factors in 141 relatively young (<66 years) parous women with angiographically documented coronary artery disease and in age-matched controls. Our study showed that hypertension, diabetes, hypercholesterolemia, advanced age, smoking, and preeclampsia are independent risk factors for subsequent coronary artery disease.

Is there any link between insulin resistance and inflammation in established preeclampsia?

Both insulin resistance and inflammation may contribute to the onset of preeclampsia. They also could be interrelated. We studied the relationship between inflammatory cytokines and markers of insulin resistance. During their third trimester, 22 proteinuric preeclamptic women and 16 normotensive controls underwent intravenous glucose tolerance test (minimal model). Preeclamptic women were more insulin-resistant (P = .009), and they had higher levels of serum soluble tumor necrosis alpha receptor II (TNFalpha RII) (P = .002), triglycerides (P = .006), uric acid (P = .001), and leptin (P = .002) than did the controls. However, the study groups did not differ in serum TNFalpha, C-reactive protein (CRP), interleukin-6 (IL-6), sex hormone-binding globulin (SHBG), and high-density lipoprotein-2 (HDL(2))-cholesterol. In multiple regression analysis only SHBG (P = .01) and triglycerides (P = .0036) were associated with insulin sensitivity independently of body mass index (BMI), weight gain, HDL(2)-cholesterol, CRP, TNFalpha, and TNFalpha RII, IL-6, and leptin. We conclude that insulin resistance and the inflammatory markers studied were not associated in established preeclampsia.

Learning curve in ultrasonographic screening for selected fetal structural anomalies in early pregnancy.

OBJECTIVE: To assess the value of first trimester screening by ultrasonography in detecting structural anomalies of the fetus in a general obstetric population. METHODS: During 1993-1998, 20,465 consecutive pregnant women who resided in a defined geographic area participated in ultrasonographic screening for major malformations. These included anomalies of the central nervous system, urinary tract, abdominal wall, and long bones. Heart anomalies were not expected to be detected. The examinations were offered at 13-14 weeks' gestation as part of routine maternal care and were done by specially trained midwives. The pregnancy outcomes were ascertained from obstetric and pediatric records, and the data were completed by information from the national birth and malformation registries. RESULTS: A total of 307 fetuses (1.5%) with a major malformation were found; 67 fetuses (0.3%) had noncardiac major structural defects expected to be detectable by ultrasonography in early pregnancy. Thirty-five of 67 (52%) were identified at the early scan. Sensitivity for these defects increased from 22% to 79% from the first to the last (sixth) study year (P =.009). CONCLUSION: In a low-risk population, adequate sensitivity in screening for major malformations by early ultrasonography can be achieved after a learning curve of 3-4 years.

Serum highly sensitive C-reactive protein in preterm premature rupture of membranes.

OBJECTIVE: Low-grade inflammation may raise serum C-reactive protein (CRP) concentrations. We studied whether serum CRP is altered in preterm premature rupture of membranes (PPROM), which is frequently associated with an asymptomatic intrauterine infection. STUDY DESIGN: CRP was quantitated with highly sensitive immunofluorometric (IFMA) and immunoenzymometric (IEMA) assays in 32 women with PPROM at 30.7+/-0.4 gestational weeks (mean+/-standard error of the mean) and in 27 gestational age-matched healthy women. The results were compared to those obtained by the conventional immunoturbidimetric method. RESULTS: Twenty-three PPROM patients had a normal CRP value (