Search

Preeclampsia has many characteristics similar to the metabolic syndrome. One of these is aberrant lipid metabolism. We studied free fatty acid (FFA) profiles at baseline and after oral glucose load in 21 preeclamptic and 11 normotensive pregnant women. Insulin sensitivity was measured by intravenous glucose tolerance test. We found that serum total FFA concentrations at baseline were 67% higher in preeclamptic than in normotensive pregnancies (P=0.0002). The difference between the two groups was largest in the concentrations of oleic (75%), linoleic (129%) and arachidonic (315%) acids. Oral intake of glucose suppressed total FFA in preeclamptic women by 40% (95% CI 32.1-46.1%, P<0.0001) but only 24% in control women (95% CI 0.01-42.0%, P=0.045). Insulin sensitivity, which in preeclamptic women was 37% lower (P=0.009), was unrelated to total or any individual FFA concentration. We concluded that preeclamptic women have higher circulating FFA concentrations, which despite insulin resistance are suppressed by oral glucose loading.

Context: Physiologic changes of pregnancy include insulin resistance, thrombophilia, immunosuppression, and hypervolemia. These changes may herald the development of disease in later life., Objective: To summarize current evidence on how pregnancy reveals risk of chronic disease., Evidence Acquisition: MEDLINE was searched for articles published between 1990 and 2005 relating pregnancy conditions to the development of chronic disease. Bibliographies and the Web sites of the International Society of Obstetric Medicine and International Society for the Study of Hypertension in Pregnancy were also reviewed., Evidence Synthesis: Pregnancy exaggerates atherogeniclike responses, including insulin resistance and dyslipidemia, manifesting as preeclampsia or gestational diabetes. These complications herald an increased risk of postpartum cardiovascular disease, with a 2-fold increased risk of coronary artery disease and stroke. Women with gestational diabetes mellitus can progress to type 2 diabetes mellitus. The rate of progression varies from 6% to 92% depending on diagnostic criteria, race/ethnicity, and duration of surveillance (from 6 months to 28 years). Pregnancy increases risk of venous thrombosis by 7- to 10-fold. Heritable thrombophilia is present in at least 15% of Western populations and underlies at least 50% of gestational venous thromboses. Thus, the procoagulant changes during pregnancy can unmask hereditary thrombophilia. An important adaptation leading to immunotolerance of the fetoplacental unit is a switch from helper T-cell (T(H)) 1 dominance to T(H)2 dominance. Patients with a T(H)1-dominant immune disease, such as rheumatoid arthritis or multiple sclerosis, improve during pregnancy. However, rheumatoid arthritis is 5 times more likely to develop after delivery than at any other time. During pregnancy, there is a 50% increase in plasma volume, which can unmask glomerulopathies, peripartum cardiomyopathy, arterial aneurysms, or arteriovenous malformations. Development of intrahepatic cholestasis of pregnancy predicts increased risk of later cholelithiasis., Conclusions: The physiologic changes of pregnancy can reveal risk of chronic diseases. Exaggerated responses reflective of the metabolic syndrome are seen in preeclampsia and gestational diabetes and can herald future cardiovascular and metabolic disease. Pregnancy is therefore an important screening opportunity for cardiovascular and metabolic disease risk factors, with the possibility of early intervention.

Background: Women suffering from fear of labor have reduced pain tolerance during a cold pressor test (CPT) during and after pregnancy., Methods: We compared levels of norepinephrine, adrenocorticotropin (ACTH), cortisol and beta-endorphin before and during the CPT up to 60 min in 20 normotensive women with and 20 without fear of labor at 37.4 +/- 0.2 (mean +/- SE) gestational weeks and at 41.9 +/- 1.6 weeks after delivery., Results: Baseline levels of norepinephrine in the pregnant fear group (1.63 +/- 0.18 nmol/L) were higher (p = 0.068) than in controls (1.38 +/- 0.14 nmol/L) but after delivery they were lower in the fear group (1.75 +/- 0.31 nmol/L vs. 2.31 +/- 0.26 nmol/L, p = 0.064). ACTH, cortisol and beta-endorphin did not differ between pregnant and nonpregnant groups. The CPT caused a 28.4% smaller response in norepinephrine in the pregnant fearful women than in controls, whereas the responses of ACTH and beta-endorphin were similar between groups during and after pregnancy. The CPT caused no significant response in cortisol. Pregnant fearful women had higher diastolic blood pressure (85.6 +/- 4.5 mmHg, mean +/- SE) than the controls (74.9 +/- 3.4 mmHg, p = 0.065)., Conclusions: Women with fear of labor were characterized by changes in norepinephrine but not in ACTH, cortisol or beta-endorphin before and during the CPT, indicating a normal pituitary-adrenal axis function.

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.

Ceramides contribute to the development of type 2 diabetes but it is uncertain whether they predict gestational diabetes (GDM). In this multicentre case–control study including 1040 women with GDM and 958 non-diabetic controls, early pregnancy (mean 10.7 gestational weeks) concentrations of four ceramides—Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)—were determined by a validated mass-spectrometric method from biobanked serum samples. Traditional lipids including total cholesterol, LDL, HDL and triglycerides were measured. Logistic and linear regression and the LASSO logistic regression were used to analyse lipids and clinical risk factors in the prediction of GDM. The concentrations of four targeted ceramides and total cholesterol, LDL and triglycerides were higher and HDL was lower among women with subsequent GDM than among controls. After adjustments, Cer(d18:1/24:0), triglycerides and LDL were independent predictors of GDM, women in their highest quartile had 1.44-fold (95% CI 1.07–1.95), 2.17-fold (95% CI 1.57–3.00) and 1.63-fold (95% CI 1.19–2.24) odds for GDM when compared to their lowest quartiles, respectively. In the LASSO regression modelling ceramides did not appear to markedly improve the predictive performance for GDM alongside with clinical risk factors and triglycerides. However, their adverse alterations highlight the extent of metabolic disturbances involved in GDM. [ABSTRACT FROM AUTHOR]

Objective: To assess the frequency and perinatal outcomes of gestational diabetes mellitus (GDM) defined by the criteria according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) and the National Institute for Health and Care Excellence (NICE) diagnostic criteria for GDM. Design: A retrospective cohort study. Setting: Six secondary and tertiary delivery hospitals in Finland in 2009. Population: Pregnant women (N = 4,033) and their offspring. Methods: We used data on comprehensive screening of pregnant women with a 2-h 75-g oral glucose tolerance test (OGTT), performed between gestational weeks 24 and 40. OGTT glucose concentrations were used to identify women who fulfilled IADPSG and NICE criteria. While cut-offs according to Finnish national criteria partly overlapped with both criteria, a subgroup of IADPSG- or NICE-positive GDM women remained undiagnosed by Finnish criteria and hence non-treated. They were analysed as subgroups and compared to controls who were negative with all cut-offs. Main outcome measures: GDM prevalence, birth weight SD score (BWSDS), large for gestational age (LGA) and caesarean section (CS) rates. Results: Among the 4,033 women screened for GDM, 1,249 (31.0%) and 529 (13.1%) had GDM according to the IADPSG and NICE criteria, respectively. The LGA rate was similar in both groups. Regardless of the diagnostic criteria, women with GDM had a higher risk of induced delivery and CSs than controls. In IADPSG-positive non-treated women, offspring's BWSDS and CS rate were higher than in controls. Conclusions: GDM prevalence was 2.4-fold higher according to the IADPSG compared with the NICE criteria but the LGA rate did not differ. BWSDS and CS rate were increased already with mild untreated hyperglycaemia. [ABSTRACT FROM AUTHOR]

Introduction: The awareness of the incidence and timing of postpartum venous thromboembolic events guides the use of thromboprophylaxis. Our aims were to assess the incidence and mortality of venous thromboembolic events and identify its associated risk factors during different postpartum periods.Material and Methods: A population-based controlled cohort study by combining four large registers in 2001-2011. All women with a recent delivery were identified. The incidence, risk factors and mortality of venous thromboembolic events 0-180 days after delivery were assessed by using all healthy delivered women as the control group. The incidence was compared with that of the nonpregnant women.Results: Among the 634 292 delivered women, 1169 had venous thromboembolic events 0-180 days postpartum. The incidence of venous thromboembolic events was highest during the first week postpartum: 37-fold compared with nonpregnant women, declining to two-fold immediately after that. Almost half of the venous thromboembolic events occurred between 43 and 180 days postpartum. The incidence of venous thromboembolic events was four-fold compared with that of nonpregnant women. Three venous thromboembolic events-related deaths occurred. Older age, higher body mass index, thrombophilia, multiple pregnancy, gestational diabetes, anemia, chorioamnionitis, threatening premature birth, in vitro fertilization with ovarian hyperstimulation, primiparity, cesarean section, cardiac/renal diseases, and varicose veins were associated with an increased risk for postpartum venous thromboembolic events. The risk remained elevated for 180 days in women with thrombophilia, cesarean section, multiple pregnancy, varicose veins, and cardiac disease.Conclusions: The risk of venous thromboembolic events remained elevated compared with that of the nonpregnant women after the usually defined postpartum period (6 weeks). The results might assist in selecting women in need of thromboprophylaxis. [ABSTRACT FROM AUTHOR]

Abstract: Studies in the early 1990s suggested that a hormone identical to ouabain or an isomer of ouabain is secreted by the adrenal glands into the circulation and plays a role in the regulation of arterial pressure and cardiac and renal function. This hormone, known as endogenous ouabain (EO), was claimed to contribute to the pathophysiology of a number of disorders including heart failure, renal failure, pregnancy‐induced, and essential hypertension. However, some research groups have been unable to confirm the presence of EO in the human circulation and the issue remains in dispute. In that the implications are of considerable importance to clinicians who, like the authors, lack biochemical expertise, it would be useful if the dispute could be addressed by disinterested scientists with long‐standing and acknowledged expertise in analytical chemistry who could opine as to whether the evidence is, or is not, sufficient to state categorically that EO does (or does not) exist in the circulation in man. This brief review does not present new data but, rather, recommends that adjudication is needed regarding this important issue. © 2018 BioFactors, 44(3):219–221, 2018 [ABSTRACT FROM AUTHOR]

Background: Maternal overweight, obesity and consequently the incidence of gestational diabetes are increasing rapidly worldwide. The objective of the study was to assess the efficacy and cost-effectiveness of a combined diet and physical activity intervention implemented before, during and after pregnancy in a primary health care setting for preventing gestational diabetes, later type 2 diabetes and other metabolic consequences. Methods: RADIEL is a randomized controlled multi-center intervention trial in women at high risk for diabetes (a previous history of gestational diabetes or prepregnancy BMI ≥30 kg/m²). Participants planning pregnancy or in the first half of pregnancy were parallel-group randomized into an intervention arm which received lifestyle counseling and a control arm which received usual care given at their local antenatal clinics. All participants visited a study nurse every three months before and during pregnancy, and at 6 weeks, 6 and 12 months postpartum. Measurements and laboratory tests were performed on all participants with special focus on dietary and exercise habits and metabolic markers. Of the 728 women [mean age 32.5 years (SD 4.7); median parity 1 (range 0-9)] considered to be eligible for the study 235 were non-pregnant and 493 pregnant [mean gestational age 13 (range 6 to 18) weeks] at the time of enrollment. The proportion of nulliparous women was 29.8% (n = 217). Out of all participants, 79.6% of the non-pregnant and 40.4% of the pregnant women had previous gestational diabetes and 20.4% of the non-pregnant and 59.6% of the pregnant women were recruited because of a prepregnancy BMI ≥30 kg/m². Mean BMI at first visit was 30.1 kg/m² (SD 6.2) in the non-pregnant and 32.7 kg/m² (SD 5.6) in the pregnant group. Discussion: To our knowledge, this is the first randomized lifestyle intervention trial, which includes, besides the pregnancy period, both the prepregnancy and the postpartum period. This study design also provides an opportunity to focus upon the health of the next generation. The study is expected to produce novel information on the optimal timing and setting of interventions and for allocating resources to prevent obesity and diabetes in women of reproductive age. [ABSTRACT FROM AUTHOR]

The relapse rate of multiple sclerosis (MS) is typically reduced during late pregnancy but increases in the postpartum period. The reasons for the increased postpartum activity are not entirely clear, but factors such as the abrupt decrease in oestrogen levels immediately after the delivery and the loss of the immunosuppressive state of pregnancy are likely of importance. There is a general view that MS does not affect the course or outcome of pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study the safety of low-molecular-weight heparin (LMWH) treatment during pregnancy for the mother and the foetus. Study design: Retrospective controlled cohort study. Six hundred and forty-eight pregnancies exposed to LMWH were compared with 626 unexposed pregnancies. Principal characteristics, indications for LMWH use, and maternal and foetal complications were reported for each pregnancy. Data were obtained from patients’ electronic hospital records and analysed using Statistical Package for the Social Sciences Version 17.0. Results: The incidence rates of various pregnancy complications did not differ between the groups (LMWH group vs control group): 1.56% vs 1.1% for thrombocytopenia, 8.7% vs 6.5% for preterm delivery, 0.7% vs 0.3% for stillbirth, 1.4% vs 1.0% for severe pre-eclampsia, 2.7% vs 2.2% for foetal growth restriction, and 10.7% vs 7.8% for antenatal bleeding. One serious antenatal maternal haemorrhage occurred in the LMWH group (0.15%), but this was unrelated to LMWH use. The caesarean section rate and the amount of bleeding during delivery were similar in the two groups (21% vs 19% and 500 vs 450ml, respectively). The risk of major blood loss during labour (>1000ml) was no higher in the LMWH group compared with the control group. The incidence of allergic skin reactions was 0.3% in the LMWH group. No heparin-induced thrombocytopenia or symptomatic osteoporotic fractures were observed. Recurrent venous thromboembolic events occurred in 2.5% of patients in the LMWH group. Conclusion: This study indicates that the use of LMWH is safe during pregnancy. [Copyright &y& Elsevier]

This retrospective case report describes 11 pregnancies in five women. All of the women were carriers of the lamin A/C gene mutation known to cause dilated cardiomyopathy, often together with atrioventricular conduction disturbances. The penetrance of these mutations is age-dependent but almost complete. We found no major adverse effects or worsening in the cardiac condition during or after the pregnancy in these patients. All babies were healthy except for one with a small ventricular septal defect, one diagnosed with tracheobronchomalasia, and one with a patent ductus arteriosus. None of these defects have been associated with lamin A/C mutations. [ABSTRACT FROM PUBLISHER]

OBJECTIVE -- A recent randomized trial compared prandial insulin aspart (IAsp) with human insulin in type 1 diabetic pregnancy. The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled during early pregnancy. RESEARCH DESIGN AND METHODS -- IAsp administered immediately before each meal was compared with human insulin administered 30 min before each meal in 99 subjects (44 to IAsp and 55 to human insulin) randomly assigned preconception and in 223 subjects (113 for IAsp and 110 for human insulin) randomly assigned in early pregnancy (<10 weeks). NPH insulin was the basal insulin. Severe hypoglycemia (requiring third-party assistance) was recorded prospectively preconception (where possible), during pregnancy, and postpartum. Relative risk (RR) of severe hypoglycemia was evaluated with a gamma frailty model. RESULTS -- Of the patients, 23% experienced severe hypoglycemia during pregnancy with the peak incidence in early pregnancy. In the first half of pregnancy, the RR of severe hypoglycemia in women randomly assigned in early pregnancy/preconception was 1.70 (95 % CI 0.913.18, P = 0.097); the RR in the second half of pregnancy was 1.35 (0.38-4.77, P = 0.640). In women randomly assigned preconception, severe hypoglycemia rates occurring before and during the first and second halves of pregnancy and postpartum for IAsp versus human insulin were 0.9 versus 2.4, 0.9 versus 2.4, 0.3 versus 1.2, and 0.2 versus 2.2 episodes per patient per year, respectively (NS). CONCLUSIONS -- These data suggest that initiation of insulin analog treatment preconception rather than during early pregnancy may result in a lower risk of severe hypoglycemia in women with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Objective. It has been suggested that poor oral health and periodontal disease, in particular, associate with adverse birth outcomes. However, previous reports on the topic are conflicting. The objective of the present cross-sectional study was therefore to compare the oral health parameters of a racially and socio-economically homogeneous group of women who gave birth before 259 gestational days (37 weeks) with those of women who went full-term. Material and Methods. We studied various dental parameters, including prevalence of dental caries, gingival bleeding on probing, the probing periodontal pocket depths, and the carriage of periodontal pathogens in 328 all-Caucasian women with singleton births. Seventy-seven of the women had preterm births, while 251 had full-term. Dental data were recorded within 2 days postpartum and analyzed with data from medical history, prenatal care, and delivery records. Results. Preterm mothers had more dental caries (93.5%) than full-term mothers (85.3%) when assessed as carious teeth in the mouth (p=0.06). In clinical and microbiological periodontal health parameters, however, no differences could be seen between the preterm and full-term mothers. Primiparity, low weight-gain, and antimicrobial drug use during pregnancy were the significant predictors for preterm birth. Conclusions. Although we cannot make any causal linkage, the oral health parameters were no different in women who experienced preterm births compared with those who had full-term births in this cohort. Only established systemic risk factors explained the preterm birth. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. Good metabolic control maintained throughout pregnancy reduces maternal and fetal complications in diabetic women. The long-acting insulin analogue glargine has 24-h persistence and a peakless action profile, and could contribute to more stable daily plasma glucose levels and improved glycemic control. We evaluated the metabolic control associated with insulin glargine during pregnancy in comparison with conventional basal insulin therapy. Methods. Retrospective case-control analysis of glycemic control and pregnancy complications in 100 type 1 diabetic pregnancies with intermediate-acting NPH insulin or insulin glargine prior to conception and throughout pregnancy. Results. Overall, glycemic control was not different between the groups, though the decrease in HbA1c from the first to the third trimester was greater with insulin glargine (0.8 versus 0.3%, p=0.04). The rate of hypoglycemia was comparable. Conclusions. Our findings suggest that, as regards metabolic control, insulin glargine in women with type 1 diabetes is comparable with NPH insulin as basal insulin therapy. No adverse effects were associated with glargine use at the time of conception and during pregnancy. [ABSTRACT FROM AUTHOR]

Background. Isolated systolic hypertension (ISH) is known to be a strong predictor of cerebrovascular and cardiac events, especially in women. Metabolic and hormonal changes associated with reproductive history may contribute to the development of cardiovascular diseases. The aim of this study was to identify associations between pregnancy-related factors and ISH. Methods. A cross-sectional study based on a random sample of 3937 Finnish women aged 30-99 was carried out. Associations between pregnancy-related factors and ISH were analyzed using multivariate analyses. Results. Of 3470 subjects, 26% had ISH. Younger age at first delivery predicted a higher risk of ISH (odds ratio after adjustment for age, education, smoking, height and weight = 1.31, 95% CI 1.07-1.61). Age at first and last delivery was significantly associated with age, education, marital status and use at any time of hormone replacement therapy (HRT); age at first delivery was also associated with toxemia in any pregnancy, weight and body mass index (BMI). In the univariate analyses, ISH was significantly associated with age, height, weight, BMI, education, marital status, oral contraceptive pills use at any time and HRT use at any time. Conclusion. This population-based study showed that early age at first delivery increased the risk of ISH, which may in turn increase cerebrovascular and cardiac events after menopause. Age at first delivery is heavily dependent on education, which may be linked to the risk of developing of cardiovascular disease throughout adulthood. The other plausible mechanism may be adiposity due to pregnancy. [ABSTRACT FROM AUTHOR]

Objective. Disturbed maternal endothelial function is believed to be central in the pathogenesis of preeclampsia and has been observed to persist for several years following the preeclamptic pregnancy. Endothelial dysfunction has been reported to cause increased pulse wave reflection, a measure of systemic arterial stiffness. This study tested the hypothesis that preeclampsia and a history of preeclampsia are associated with increased pulse wave reflection. Design and Methods. We carried out a cross-sectional case-control study of 26 pregnant women with preeclampsia, 26 pregnant controls, 22 normotensive nonpregnant previously preeclamptic women, and 22 nonpregnant controls. Pulse wave reflection was assessed by applanation tonometry on the radial artery. Results. Pregnant preeclamptic women had a significantly higher heart rate–adjusted augmentation index than did pregnant controls (23 ± 1 vs. 8 ± 1%, P 2 = 0.76) the augmentation index of pregnant women was independently associated with a diagnosis of preeclampsia ( P [ABSTRACT FROM AUTHOR]

Niittyvuopio R, Juvonen E, Kaaja R, Oksanen K, Hallman H, Timonen T, Ruutu T. Pregnancy in essential thrombocythaemia: experience with 40 pregnancies. Eur J Haematol 2004: 73: 431–436.© Blackwell Munksgaard 2004.In this study, the course of 40 pregnancies in 16 women with essential thrombocythaemia (ET) was analysed retrospectively. Of the pregnancies, 45% were complicated, 55% uncomplicated, and 62% resulted in live birth. The most common complication was spontaneous abortion during the first trimester seen in 33% of all pregnancies and comprising 72% of all complications. Two intrauterine foetal deaths occurred at weeks 22 and 28. Three pregnancies were complicated by eclampsia or pre-eclampsia. Nine of 16 women with 29 pregnancies had at least one complicated pregnancy. In seven of 16 women, all 11 pregnancies were uneventful. The non-pregnancy-related symptoms of ET or the platelet count before conception or during pregnancy did not correlate with the risk of pregnancy complications. Treatment with low-dose acetylsalicylic acid (ASA) alone during pregnancy or platelet-lowering drugs before or during pregnancy reduced the risk of complications. [ABSTRACT FROM AUTHOR]

Inherited thrombophilias, suggested to be risk factors for ovarian hyperstimulation syndrome and known to be associated with venous thromboembolism during pregnancy, may also increase the risk for preeclampsia (PE). We describe the case of a 29‐year‐old woman with primary infertility with no history of thrombosis, hypertension or renal disorders. In her first pregnancy, achieved by frozen embryo transfer, she developed severe early‐onset (23rd gestational week) PE with heavy proteinuria, and at the same time was found to have enlarged ovaries with hyperreactio luteinalis. After admission we found that she was a heterozygotic carrier of the factor V Leiden mutation. After administering low molecular weight heparin (LMWH) therapy, her blood pressure normalized, proteinuria diminished and her d‐dimer values returned to that of a normal pregnant level. The fetus grew normally. Her ovaries normalized during the pregnancy, as determined by ultrasound examinations. At term she delivered spontaneously a normal weight, healthy girl. Previously, only prophylactic LMWH, in subsequent pregnancy, have been administered in patients with thrombophilia and a history of severe PE. We describe a case of spontaneous hyperreactio luteinalis, where the clinical characteristics of PE improved after beginning LMWH therapy in severe, very early onset PE. Inherited thrombophilia, spontaneous hyperreactio luteinalis and PE may be associated phenomena. [ABSTRACT FROM AUTHOR]

OBJECTIVE — To evaluate the progression of retinopathy during pregnancy and postpartum in (insulin-dependent) women with type 1 diabetes treated with insulin lispro or with regular human insulin. RESEARCH DESION AND METHODS — A prospective open study of 69 pregnant women with diabetes was performed. A total of 36 of the women were treated with insulin lispro (lispro group) and 33 were treated with conventional short-acting human insulin (regular insulin group). The retinopathy level was estimated by color fundus photography every trimester and postpartum. Glycemic control during pregnancy, hypoglycemia (blood glucose level <3 mmol/l) in 24-h glucose profile, blood pressure, and proteinuria were registered. RESULTS — HbA[sub 1c] values were similar at baseline in the first trimester but thereafter were lower in the lispro group than in the regular insulin group throughout pregnancy (P = 0.022, repeated-measures ANOVA). The number of hypoglycemic episodes did not differ between the treatment groups. In multivariable logistic regression analysis with retinopathy severity (Diabetes Control and Complications Trial level) in the third trimester as the dependent variable, only nulliparity qualified as a predictor in the model [Exp(B) = 4.0, 95% CI 1.1-13.7, P = 0.030]. Factors such as duration of diabetes, type of insulin used, mean HbA[sub 1c] level throughout pregnancy, blood pressure (systolic or diastolic), preeclampsia in the current pregnancy, smoking, or prepregnancy planning did not explain the retinopathy progression. CONCLUSIONS — Insulin lispro improves glycemic control during diabetic pregnancy compared with regular insulin with no adverse impact on progression of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

We investigated the production of prostacyclin and thromboxane in pregnant women with a previous venous thromboembolic event before, during and after the use of unfractionated heparin and low molecular weight heparin (dalteparin). Twenty women were studied before starting heparin prophylaxis (before 20 weeks of gestation), during heparin prophylaxis (at 30 weeks of gestation) and after heparin prophylaxis (16 weeks after delivery). Ten pregnant women with no history of thromboembolism were studied as the control group. Urinary output of the stable metabolite of prostacyclin (2,3-dinor-6-keto-PGF1α) and that of thromboxane A2 (2,3-dinor-TxB2), as well as a number of markers of thrombophilia were measured and expressed as mean (±SEM). Women with a history of thromboembolism were characterized by normal prostacyclin production but elevated thromboxane production (44·0 ± 4·1 versus 19·0 ± 3·6 ng/mmol creatinine, P < 0·001) at 12 weeks of pregnancy. Heparin prophylaxis (regardless of the type) had abolished elevated thromboxane concentrations at 30 weeks of gestation. Four months after delivery, thromboxane dominance had returned (25·2 ± 3·5 versus 13·6 ± 2·1 ng/mmol creatinine, P < 0·01). The presence of hereditary thrombophilia (9/20) was not associated with any changes in prostanoid concentrations. Thus, women with a history of venous thromboembolic events have thromboxane dominance during and after pregnancy, but this dominance can be eliminated through the use of heparins. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Fetal outcome in systemic lupus erythematosus (SLE) was retrospectively analysed in 242 pregnancies in 112 unselected patients, and the outcome was compared with that of 417 pregnancies in 192 control women matched for age, parity and socio-economic status. Relative risk for fetal loss after the diagnosis of SLE was 2.5 (95% confidence interval (CI), 1.4-4.5), for prematurity 5.8 (3.2-10.5) and for intra-uterine growth retardation (IUGR) 8.6 (3.0-24.3). Fetal outcome of pregnancy in patients with pre-existing stable lupus nephritis was no worse than in other SLE pregnancies.Relations of three lupus anticoagulant (LA) assays and three anticardiolipin (aCL) enzyme-linked immunosorbent assays to fetal outcome were studied. Patients positive by any LA assay had a previous fetal loss more often than patients negative by all LA assays (odds ratio 3.4; 95% CI, 1.3-9.0; P = 0.01). Of the 41 patients whose antiphospholipid antibody (aPL) tests were all negative, five (12%) had a history of fetal loss (16% in controls). As a group, aCL was more sensitive for fetal loss than LA (64% vs 50%), but LA was more specific (77% vs 52%). Combinations of one aCL assay with one LA assay had a 41-73% sensitivity and a 64-73% specificity for a history of fetal loss. aPL did not correlate to prematurity or fetal growth retardation.In conclusion, fetal loss in SLE is 2.5 times more prevalent than in the normal population. The presence of LA indicates a high risk for fetal loss, and the absence of aPL is an indication of a favorable pregnancy outcome. Prematurity and IUGR are common in SLE, but they are not associated with aPL. [ABSTRACT FROM PUBLISHER]

Objective: The objective of the study was a comparison of insulin aspart (IAsp) with human insulin (HI) in basal-bolus therapy with neutral protamine Hagedorn for fetal and perinatal outcomes of type 1 diabetes in pregnancy. Study Design: This was a randomized, parallel, open-label, controlled, multicenter, multinational study. Subjects were pregnant (gestational age; <10 weeks) or planning pregnancy at enrollment. Three hundred twenty-two women with type 1 diabetes received IAsp (n = 157) or HI (n = 165). Results: For IAsp and HI, respectively, there were 137 and 131 live births and 14 and 21 fetal losses. Perinatal mortality was 14 and 22 per 1000 births; number of congenital malformations were 6 and 9; mean (SEM) birthweight corrected for gestational age was 3438 g (71.5) and 3555 g (72.9; P = .091). Mean gestational age was 37.6 vs 37.4 weeks. Preterm delivery occurred in 20.3% (IAsp) and 30.6% (HI) of pregnancies (P = .053). Conclusion: The fetal outcome using IAsp was comparable with HI with a tendency toward fewer fetal losses and preterm deliveries. [Copyright &y& Elsevier]

Abstract: 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 50g OGCT test was performed prospectively in 532 unselected women at 26–28 weeks of gestation. The 1-h venous plasma glucose concentration of >7.3mmol/l was considered as a positive screening result. Patients with a positive OGCT underwent a 75g 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 2h after the 75g 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 75g OGTT regardless of the result of the OGCT. Results:: A positive 50g 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 50g 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. [Copyright &y& Elsevier]

Low-molecular-weight (LMW) heparins have been shown to be at least as effective as unfractionated (UF) heparin in the treatment of deep venous thrombosis (DVT) in nonpregnant subjects. LMW heparins have been shown to be safe when used during pregnancy as they do not cross the placenta. Up to now, they have been used mainly in thromboprophylaxis during pregnancy and rarely in the treatment of acute DVT in pregnant women. In a prospective observational study, we compared the effectiveness and safety of the LMW heparin, dalteparin, with UF heparin in the initial treatment (first week) of DVT during pregnancy. After confirmation of DVT by ultrasonography, 10 women were treated with UF heparin (25,430 IU/day, mean) and 21 women with dalteparin (16,000 IU/day, mean) for 7 days and, thereafter, all women were given treatment doses of LMW heparin for another 2 weeks. The dose was then gradually decreased and kept at a high prophylactic dose until delivery. One patient in the dalteparin group had recurrence of DVT 2 weeks after starting the treatment. No differences were observed between the groups in symptoms or bleeding complications during pregnancy and delivery. Our results indicate that LMW heparin is as effective and safe as UF heparin for the first week of treatment, but LMW heparin has the advantage of being easily administered and few laboratory controls are required. [Copyright &y& Elsevier]

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) 4–7 years 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 (1.22 g/cm 2 vs. 1.27 g/cm 2 ; p = 0.03), and in the treatment group (1.20 g/cm 2 vs. 1.27 g/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. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Stillbirth is a relatively uncommon pregnancy complication in developed countries yet causing strong emotional burden. Thrombophilia has been associated with stillbirth but population-based studies are few. We assessed selected genetic and acquired parameters for the risk of unexplained stillbirth, including FV Leiden. Materials and methods: We performed a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers and accepted according to strict criteria after checking their medical records. Stillbirth was defined as intrauterine fetal death ≥22weeks of gestation. We excluded stillbirths due to lethal congenital developmental conditions, umbilical cord complications, and infections. We studied 44 cases of unexplained stillbirth and 766 controls. Results: FV Leiden was associated with 3.8-fold (95% CI 1.2-11.6) risk for unexplained stillbirth, 3.9-fold (95% CI 1.1-13.9) risk for unexplained late stillbirth (≥28weeks of gestation), and 10.8-fold (95% CI 2.1-55.3) risk for unexplained stillbirth with placental lesions. The same figures for singleton pregnancies were 3.1-fold (95% CI 0.9-10.9), 4.3-fold (95% CI 1.2-15.3), and 10.6-fold (95% CI 2.1-54.3). Slightly increased risk associated with blood group O was not statistically significant. We found a trend for increased risk in advanced maternal age and smoking during pregnancy. High pre-pregnancy BMI was not associated with increased risk, nor was low educational level or first pregnancy. Conclusions: Our population-based study from a country with comprehensive prenatal care confirms the association between FV Leiden and unexplained stillbirth. [Copyright &y& Elsevier]

Abstract: Introduction: Pre-eclampsia is an important cause of maternal morbidity and mortality. Its etiology is still unknown. Clinical symptoms correlate with activation of coagulation and inherited thrombophilia has been associated with pre-eclampsia. ABO blood group has been associated with thrombotic disorders and pre-eclampsia. We assessed ABO blood group, seven thrombophilia associated polymorphisms, and anti-beta2-glycoprotein I antibodies as risk factors for pre-eclampsia. Materials and methods: We performed a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers and medical records were reviewed. We studied 248 cases fulfilling strict criteria for pre-eclampsia and 679 controls. Severe pre-eclampsia, early pre-eclampsia, and pre-eclampsia with intra-uterine growth restriction (IUGR) were analyzed separately. Results: Blood group AB increased the risk for pre-eclampsia as a whole (OR 2.1, 95% CI 1.3-3.5), and in the three subgroups (OR 2.3, 3.8, 3.4; 95% CI 1.3-3.9, 2.0-7.1, 1.6-7.1). FV Leiden increased the risk as a whole (OR 1.7, 95% CI 0.8-3.9), and in the three subgroups, although not statistically significantly. Anti-beta2-glycoprotein I antibodies were not associated with pre-eclampsia. High body mass index, diabetes, first pregnancy, and twin pregnancy increased the risk from 1.5-fold to 8.2-fold. Conclusions: Our results confirm and extend the prior observation of blood group AB being a risk factor for pre-eclampsia. ABO blood group is known from all pregnant women. The value of blood group as risk factor for pre-eclampsia should be further assessed in prospective studies. In this study, FV Leiden was not statistically significant risk factor. [Copyright &y& Elsevier]

Abstract: Introduction: Hereditary and acquired risk factors increase the risk for thrombosis among pregnant women. Few risk estimates are, however, well established. The aim of the present study was to assess risk for pregnancy-associated venous thrombosis of factor V Leiden (FVL), FII G20210A, FV A4070G, MTHFR C677T, TFPI C536T, PROC T38853G, FXIII V34L, blood group, age, and body mass index (BMI), and their interactions and public health impact. Materials and methods: Study design is a population-based nested case–control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers. Thirty four cases with objectively diagnosed venous thrombosis and 641 controls were studied. Results: FVL (OR 11.6, 95% CI 3.6–33.6), age >35 vs. <25 (OR 6.3, 95% CI 1.7–23.1), and BMI >30 vs. <25 (OR 5.6, 95% CI 2.3–13.9) were associated with thrombosis. Overall absolute risk of a FVL carrier was 1 in 314. FVL interacted with age, BMI, and blood group. Population attributable risk proportion was 19% for FVL, 23% for age >35, 33% for BMI >25, and 35% for non-O blood group. Unexpectedly, the prevalence of FVL increased with age in controls. Conclusions: FVL appeared as a strong risk factor for pregnancy-associated venous thrombosis. Especially in elderly overweight mothers, FVL may cause a substantial thrombosis risk. Further studies are needed to confirm the increased prevalence of FVL in elderly mothers with normal pregnancies. [Copyright &y& Elsevier]

To evaluate the role of various vasoactive hormones in the evolution of diabetic retinopathy during pregnancy and postpartum.Retinopathy was graded from fundus photographs of 45 pregnant women with type 1 diabetes and seven pregnant women without diabetes in a prospective study. Markers of renin-angiotensin-system (RAS), plasma renin activity (PRA), angiotensin II (AngII), aldosterone, natriuretic peptides (ANP, BNP, CNP) and adreonomedullin (AM) were measured during the first and third trimesters and at 3 months postpartum. The women with diabetes were grouped by progression of retinopathy during pregnancy and postpartum.Levels of PRA (p = 0.001) and ANP (p = 0.03) were significantly lower in diabetes than in non-diabetes subjects throughout pregnancy and postpartum. No significant differences appeared in levels of AngII, aldosterone, AM, BNP or CNP between the two groups. In multivariate logistic regression analyses with retinopathy progression by the third trimester as the dependent variable, only duration of diabetes qualified in the model (p = 0.027, R = 0.227, Exp(B) = 1.28).Diabetic pregnancy is associated with lower levels of PRA and ANP compared to non-diabetic pregnancy. Lowered RAS activity may contribute to the hyperdynamic blood flow and progression of DR during diabetic pregnancy. Within the power of this study no clear associations between the vasoactive hormones and progression of retinopathy could be detected. [ABSTRACT FROM AUTHOR]