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Background: Gestational diabetes mellitus (GDM) is a common pregnancy-related disorder and a well-known risk factor for adverse pregnancy outcomes. There are conflicting findings on the association of GDM with the risk of congenital anomalies (CAs) in offspring. In this study, we aimed to determine study whether maternal GDM is associated with an increased risk of major CAs in offspring., Methods: This Finnish Gestational Diabetes (FinnGeDi) register-based study included 6,597 women with singleton pregnancies and a diagnosis of GDM and 51,981 singleton controls with no diabetes identified from the Finnish Medical Birth Register (MBR) in 2009. Data from MBR were combined in this study with the Register of Congenital Malformations, which includes the data of CAs. We used logistic regression to calculate odds ratios (OR) for CAs, together with their 95% confidence intervals (CIs), adjusting for maternal age, parity, pre-pregnancy body mass index (BMI), and maternal smoking status., Results: The risk of major CAs was higher in the GDM-exposed (n = 336, 5.09%) than in the non-exposed group (n = 2,255, 4.33%) (OR: 1.18, 95% CI: 1.05-1.33, p = 0.005). The adjusted OR (aOR) was 1.14 (95% CI: 1.00-1.30, p = 0.047). There was a higher overall prevalence of CAs, particularly chromosomal abnormalities (0.52% vs. 0.21%), in the GDM-exposed group (OR: 2.49, 95% Cl: 1.69-3.66, p < 0.001). The aOR was 1.93 (95% Cl: 1.25-2.99, p = 0.003)., Conclusions: Offspring exposed to GDM have a higher prevalence of major CAs. Of note, risk factors other than GDM, such as older maternal age and a higher pre-pregnancy BMI, diminished the between group differences in the prevalence of major CAs. Nevertheless, our findings suggest that offspring exposed to maternal GDM are more likely to be diagnosed with a chromosomal abnormality, independent of maternal age, parity, pre-pregnancy BMI, and smoking., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach., Methods: We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool., Discussion: Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial., Trial Identifiers: Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018-004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.

Background: To determine the risk of cesarean delivery after labor induction among patients with prior placenta-mediated pregnancy complications (pre-eclampsia, late pregnancy loss, placental abruption or intrauterine growth restriction)., Methods: The AFFIRM database includes patient level data from 9 randomized controlled trials that evaluated the role of LMWH versus no LMWH during pregnancy to prevent recurrent placenta-mediated pregnancy complications. The primary outcome of this sub-study was the proportion of women who had an unplanned cesarean delivery after induction of labor compared to after spontaneous labor., Results: There were 512 patients from 7 randomized trials included in our sub-study. There was no difference in the risk of cesarean delivery between women with labor induction (21/148, 14.2%) and spontaneous labor (79/364, 21.7%) (odds ratio (OR) 0.60, 95% CI, 0.35-1.01; p = 0.052). Among 274 women who used LMWH prophylaxis during pregnancy, the risk of cesarean delivery was lower among those that underwent labor induction (9.8%) compared to spontaneous labor (22.4%) (OR 0.38, 95% CI, 0.17-0.84; p = 0.01)., Conclusions: The risk of cesarean delivery is not increased after labor induction among a higher risk patient population with prior pregnancy complications. Our results suggest that women who receive LMWH during pregnancy might benefit from labor induction.

Background: Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and birth of a small-for-gestational-age (SGA) neonate. These complications are leading causes of maternal, fetal, and neonatal morbidity and mortality in high-income countries. Affected women are at high risk of recurrence in subsequent pregnancies; however, effective strategies to prevent recurrence are absent. Findings from our previous study-level meta-analysis suggested that low-molecular-weight heparin reduced the risk of recurrent placenta-mediated pregnancy complications. However, we identified significant heterogeneity in the results, possibly due to trial design or inclusion criteria. To identify which patients benefit from, and which outcomes are prevented by, low-molecular-weight heparin, we did an individual patient data meta-analysis., Methods: We did a systematic review in May, 2013, which identified eight eligible randomised trials done between 2000 and 2013 of low-molecular-weight heparin to prevent recurrent placenta-mediated pregnancy complications. We excluded studies on the basis of the wrong population, the study being ongoing, inability to confirm eligibility of participants, intervention stopped too early, and no response from the principal investigator. We requested individual patient data from the study authors for eligible women (women pregnant at the time of the study with a history of previous pregnancy that had been complicated by one or more of the following: pre-eclampsia, placental abruption, birth of an SGA neonate [<10th percentile], pregnancy loss after 16 weeks' gestation, or two losses after 12 weeks' gestation) and recoded, combined, and analysed the data for our meta-analysis. The primary outcome was a composite of early-onset (<34 weeks) or severe pre-eclampsia, birth of an SGA neonate (<5th percentile), late pregnancy loss (≥20 weeks' gestation), or placental abruption leading to delivery, assessed on an intention-to-treat basis. We assessed risk of bias with the Cochrane Risk of Bias tool. This study is registered with PROSPERO, number CRD42013006249., Findings: We analysed data from 963 eligible women in eight trials: 480 randomly assigned to low-molecular-weight heparin and 483 randomly assigned to no low-molecular-weight heparin. Overall, the risk of bias was not substantial enough to affect decisions regarding trial inclusion. Participants were mostly white (795/905; 88%) with a mean age of 30·9 years (SD 5·0) and 403/963 (42%) had thrombophilia. In the primary analysis, low-molecular-weight heparin did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications (low-molecular-weight heparin 62/444 [14%] versus no low-molecular-weight heparin 95/443 (22%) absolute difference -8%, 95% CI -17·3 to 1·4, p=0·09; relative risk 0·64, 95% CI 0·36-1·11, p=0·11). We noted significant heterogeneity between single-centre and multicentre trials. In subgroup analyses, low-molecular-weight heparin in multicentre trials reduced the primary outcome in women with previous abruption (p=0·006) but not in any of the other subgroups of previous complications., Interpretation: Low-molecular-weight heparin does not seem to reduce the risk of recurrent placenta-mediated pregnancy complications in at-risk women. However, some decreases in event rates might have been too small for the power of our study to explore., Funding: Canadian Institutes of Health Research., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, An individual patient data meta-analysis oF low-molecular-weight heparin For prevention of placenta-medIated pRegnancy coMplications., Methods/design: We conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy., Discussion: The goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and exploration of which complications are specifically prevented by low-molecular-weight heparin., Systematic Review Registration: PROSPERO (International Prospective Registry of Systematic Reviews) 23 December 2013, CRD42013006249.

Background: Earlier studies on the association between oral inflammation and preterm birth limited the inflammation source to periodontal disease. This might have caused an underestimation of the total inflammatory burden from the oral cavity., Methods: We conducted a postpartum cross-sectional study of 328 Finnish women with singleton births, of whom 77 had preterm births and 251 had full-term births. Gingival bleeding on probing, probing depth, and the presence of dental calculus and mouth ulcers were recorded; the oral inflammatory burden index (OIBI) was constructed based on these clinical findings. A data-driven oral inflammation score (OIS) was also created by stochastically combining the same parameters assessed independently. We used the t, Mann-Whitney, and chi(2) tests for univariate analyses and multivariate logistic regression methods to examine the association between OIBI/OIS and preterm birth. The confounders adjusted for were age, smoking (past, present, and never), diabetes (type 1, type 2, and gestational), primiparity, antimicrobial treatment as a proxy for systemic infection, infertility treatment, and weight gain during pregnancy., Results: OIBI was significantly associated with preterm birth after adjusting for confounding factors (odds ratio [OR], 1.85; 95% confidence interval [CI]: 1.10 to 3.10; P = 0.02). Without adjusting for weight gain, OIS was significantly associated with preterm birth (OR, 1.97; 95% CI: 1.09 to 3.57; P = 0.03); however, this association became non-significant after adding weight gain to the model., Conclusion: The combined effects of multiple oral infections were significantly associated with preterm birth.

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.

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.

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.

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]

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]

Pre-eclampsia is a hypertensive disorder associated with proteinuria appearing during the second half of pregnancy. It is also a state of increased insulin resistance and sympathetic overactivity. The most common lipid abnormalities are hypertriglyceridemia and increased circulating free fatty acids, which can precede the onset of the disease. The other abnormalities include low HDL-C (especially HDL-2-C) and a relatively high small density LDL-C level. These lipid/lipoprotein abnormalities may enhance endothelial dysfunction, which is the major pathogenetic factor of pre-eclampsia. These lipid/lipoprotein abnormalities may enhance endothelial dysfunction during pre-eclamptic pregnancy by increased free fatty acids and oxidative stress, by the blunting of nitric oxide-dependent tone and by impairing the prostacyclin:thromboxane ratio. These abnormalities resolve after delivery, but may 'return' if the woman becomes insulin resistant de novo with weight gain and/or loses ovarian estrogen production. [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]

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]

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: 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]