Obstetric anal sphincter injury in the second birth after perineal wound complication in the first birth: A nationwide register cohort study.

OBJECTIVE: To investigate whether perineal wound complications in the first birth, alone or in conjunction with obstetric anal sphincter injury (OASI), is associated with an increased risk of OASI in the second birth. DESIGN: Nationwide population-based cohort study. SETTING: Sweden. POPULATION: Women (n = 411 317) with first and second singleton vaginal births in Sweden, 2001-2019. METHODS: Data on diagnostic codes and surgical procedures were retrieved from the Swedish Medical Birth Register and the Swedish Patient Register. A perineal wound complication was defined as wound infection, dehiscence or perineal haematoma within 2 months of childbirth. MAIN OUTCOME MEASURES: Associations between wound complications in the first birth and OASI in the second birth were investigated with logistic regression and presented as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs). RESULTS: In total, 2619 (0.6%) women had a wound complication in the first birth, and 5318 (1.3%) had an OASI in the second birth. Women with a wound complication but no OASI in the first birth had more than doubled odds of OASI in the second birth (aOR 2.73, 95% CI 2.11-3.53). Women with OASI and a wound complication in the first birth had almost tenfold odds (aOR 9.97, 95% CI 6.53-15.24) of recurrent OASI. CONCLUSIONS: Perineal wound complication in the first birth increases the likelihood of OASI in a subsequent birth.

Breastfeeding in primiparous women with congenital heart disease - a register study.

BACKGROUND: The number of pregnant women with congenital heart disease (CHD) is rising, and the disease poses increased risks of cardiovascular and obstetric complications during pregnancy, potentially impacting breastfeeding success. This study aimed to investigate breastfeeding in primiparous women with CHD compared to primiparous women without CHD, and to examine potential hindering factors for breastfeeding in women with CHD. METHODS: The data were gathered between 2014 and 2019 and obtained by merging the Swedish Congenital Heart Disease Register (SWEDCON) with the Swedish Pregnancy Register. Primiparous women ≥ 18 years of age with CHD (n = 578) were matched by age and municipality to 3049 women without CHD, giving birth after 22 gestational weeks. Multivariable logistic regression analysis was used to identify factors associated with non-breastfeeding in women with CHD. RESULTS: Fewer women with CHD breastfed than women without CHD two days (94% vs. 97%, p = 0.001) and four weeks after birth (84% vs. 89%, p = 0.006). When all women were analysed, having CHD was associated with non-breastfeeding at both two days and four weeks after birth. For women with CHD, body mass index (BMI) ≥ 30 (OR 3.1; 95% CI 1.4, 7.3), preterm birth (OR 6.4; 95% CI 2.1, 19.0), self-reported history of psychiatric illness (OR 2.4; 95% CI 1.2, 5.1), small for gestational age (OR 4.2; 95% CI 1.4, 12.2), and New York Heart Association Stages of Heart Failure class II - III (OR 6.0; 95% CI 1.4, 26.7) were associated with non-breastfeeding two days after birth. Four weeks after birth, factors associated with non-breastfeeding were BMI ≥ 30 (OR 4.3; 95% CI 2.1, 9.0), self-reported history of psychiatric illness (OR 2.2; 95% CI 1.2, 4.2), and preterm birth (OR 8.9; 95% CI 2.8, 27.9). CONCLUSIONS: The study shows that most women with CHD breastfeed, however, at a slightly lower proportion compared to women without CHD. In addition, factors related to the heart disease were not associated with non-breastfeeding four weeks after birth. Since preterm birth, BMI ≥ 30, and psychiatric illness are associated with non-breastfeeding, healthcare professionals should provide greater support to women with CHD having these conditions.

Time to childbirth and assisted reproductive treatment in women with congenital heart disease.

OBJECTIVE: To investigate the time to first childbirth and to compare the prevalence of assisted reproductive treatment (ART) in women with congenital heart disease (CHD) compared with women without CHD. METHODS: All women in the national register for CHD who had a registered first childbirth in the Swedish Pregnancy Register between 2014 and 2019 were identified. These individuals (cases) were matched by birth year and municipality to women without CHD (controls) in a 1:5 ratio. The time from the 18th birthday to the first childbirth and the prevalence of ART was compared between cases and controls. RESULTS: 830 first childbirths in cases were identified and compared with 4137 controls. Cases were slightly older at the time for first childbirth (28.9 vs 28.5 years, p=0.04) and ART was more common (6.1% vs 4.0%, p<0.01) compared with controls. There were no differences in ART when stratifying for the complexity of CHD. For all women, higher age was associated with ART treatment (OR 1.24, 95% CI 1.20 to 1.28). CONCLUSIONS: Women with and without CHD who gave birth to a first child did so at similar ages. ART was more common in women with CHD, but disease severity did not influence the need for ART. Age was an important risk factor for ART also in women with CHD and should be considered in consultations with these patients.

Biomarkers associated with cardiovascular disease in women with spontaneous preterm birth: A case-control study.

INTRODUCTION: Women with spontaneous preterm birth have an increased risk of cardiovascular disease later in life. Studies suggest potential pathophysiological mechanisms in common, but whether these could be identified by measurement of soluble circulating protein biomarkers in women with spontaneous preterm birth is unknown. The aim of this study was to determine if protein biomarkers associated with cardiovascular disease distinguish women with spontaneous preterm birth from healthy controls, both at pregnancy and at follow up. MATERIAL AND METHODS: Study participants were identified in the population-based Uppsala biobank of pregnant women in Sweden, where plasma samples were collected in mid-pregnancy. In a first screening phase, we identified participants who subsequently experienced spontaneous preterm birth (<37 weeks) in the index pregnancy (N = 13) and controls (N = 6). In these samples, differences in protein expression were examined by comparative mass spectrometry. In a second validation phase, we invited 100 cases with previous spontaneous preterm birth in the index pregnancy and 100 controls (matched for age, body mass index, and year of delivery) from the same source population, to a follow-up visit 4-15 years after pregnancy. At follow up, we collected plasma samples and data on cardiovascular risk factors. We measured concentrations of selected biomarkers identified in the screening phase, as well as lipid profiles in samples both from pregnancy (biobank) and follow up. CLINICALTRIALS: gov registration NCT05693285. RESULTS: In the screening phase, fibrinogen, cadherin-5, complement C5, factor XII, plasma kallikrein, apolipoprotein M, and vitamin D-binding protein differed significantly at pregnancy. In the validation phase, 65 women agreed to participate (35 cases and 30 controls), with a median follow-up time of 11.8 years since pregnancy. The concentration of fibrinogen (p = 0.02) and triglycerides (p = 0.03) were slightly higher in cases compared with matched controls at follow up. CONCLUSIONS: Compared with women without preterm birth, those with spontaneous preterm birth had slightly higher concentrations of fibrinogen, both at mid-pregnancy and a decade after pregnancy. Additionally, we found slightly higher concentration of triglycerides at follow up in women with previous spontaneous preterm birth. The relevance of this finding is uncertain but might indicate potential pathophysiological mechanisms in common between spontaneous preterm birth and cardiovascular disease.

Novel Associations Between Mid-Pregnancy Cardiovascular Biomarkers and Preeclampsia: An Explorative Nested Case-Control Study.

Prediction of women at high risk of preeclampsia is important for prevention and increased surveillance of the disease. Current prediction models need improvement, particularly with regard to late-onset preeclampsia. Preeclampsia shares pathophysiological entities with cardiovascular disease; thus, cardiovascular biomarkers may contribute to improving prediction models. In this nested case-control study, we explored the predictive importance of mid-pregnancy cardiovascular biomarkers for subsequent preeclampsia. We included healthy women with singleton pregnancies who had donated blood in mid-pregnancy (~ 18 weeks' gestation). Cases were women with subsequent preeclampsia (n = 296, 10% of whom had early-onset preeclampsia [< 34 weeks]). Controls were women who had healthy pregnancies (n = 333). We collected data on maternal, pregnancy, and infant characteristics from medical records. We used the Olink cardiovascular II panel immunoassay to measure 92 biomarkers in the mid-pregnancy plasma samples. The Boruta algorithm was used to determine the predictive importance of the investigated biomarkers and first-trimester pregnancy characteristics for the development of preeclampsia. The following biomarkers had confirmed associations with early-onset preeclampsia (in descending order of importance): placental growth factor (PlGF), matrix metalloproteinase (MMP-12), lectin-like oxidized LDL receptor 1, carcinoembryonic antigen-related cell adhesion molecule 8, serine protease 27, pro-interleukin-16, and poly (ADP-ribose) polymerase 1. The biomarkers that were associated with late-onset preeclampsia were BNP, MMP-12, alpha-L-iduronidase (IDUA), PlGF, low-affinity immunoglobulin gamma Fc region receptor II-b, and T cell surface glycoprotein. Our results suggest that MMP-12 is a promising novel preeclampsia biomarker. Moreover, BNP and IDUA may be of value in enhancing prediction of late-onset preeclampsia.

Combined maternal central adiposity measures in relation to infant birth size.

Improvement of prenatal identification of large-for-gestational-age (LGA) infants could lower the risk for adverse outcomes. Therefore, we sought to evaluate the association of a combination of maternal waist circumference (WC) and abdominal fat depths with infant birth size. A cohort study including 1240 women was performed between 2015 and 2018 at Uppsala University Hospital, Sweden. Maternal WC was measured at the first antenatal visit, and visceral (VF) and subcutaneous (SCF) fat depths by ultrasound at the second-trimester anomaly scan. Waist circumference, VF, and SCF were categorized as low or high (cut-offs WC ≥ 88 cm, VF ≥ 54 mm, SCF ≥ 21 mm). Outcomes were birth weight standard deviation score (BWSDS) and LGA (BWSDS > 90th and > 97th percentile). Secondary outcome was small-for-gestational-age (SGA, BWSDS < 10th and < 3rd percentile). Univariate analysis of variance and logistic regression analyses were performed adjusted for maternal weight, height, parity, smoking, country of birth, pregestational diabetes, and chronic hypertension. For both high and low WC, high VF was positively associated with BWSDS and LGA. There was no association with SGA. The results did not demonstrate any value of the combination of WC and fat depth measures in predicting infant birth size but suggested VF as a marker for large infants.

Self-rated health in primiparous women with congenital heart disease before, during and after pregnancy - A register study.

Background. Poor maternal self-rated health in healthy women is associated with adverse neonatal outcomes, but knowledge about self-rated health in pregnant women with congenital heart disease (CHD) is sparse. This study, therefore, investigated self-rated health before, during, and after pregnancy in women with CHD and factors associated with poor self-rated health. Methods. The Swedish national registers for CHD and pregnancy were merged and searched for primiparous women with data on self-rated health; 600 primiparous women with CHD and 3062 women in matched controls. Analysis was performed using descriptive statistics, chi-square test and logistic regression. Results. Women with CHD equally often rated their health as poor as the controls before (15.5% vs. 15.8%, p = .88), during (29.8% vs. 26.8% p = .13), and after pregnancy (18.8% vs. 17.6% p = .46). None of the factors related to heart disease were associated with poor self-rated health. Instead, factors associated with poor self-rated health during pregnancy in women with CHD were ≤12 years of education (OR 1.7, 95%CI 1.2-2.4) and self-reported history of psychiatric illness (OR 12.6, 95%CI 1.4-3.4). After pregnancy, solely self-reported history of psychiatric illness (OR 5.2, 95%CI 1.1-3.0) was associated with poor self-rated health. Conclusion. Women with CHD reported poor self-rated health comparable to controls before, during, and after pregnancy, and factors related to heart disease were not associated with poor self-rated health. Knowledge about self-rated health may guide professionals in reproductive counselling for women with CHD. Further research is required on how pregnancy affects self-rated health for the group in a long-term perspective.

Pregnancy outcomes for women with myasthenia gravis and their newborns: A nationwide register-based cohort study.

BACKGROUND AND PURPOSE: Few large-scale studies examine whether maternal myasthenia gravis (MG) is a risk factor for complications during pregnancy and childbirth. This study evaluated whether maternal MG is associated with an increased risk of adverse pregnancy, delivery, and neonatal outcomes. METHODS: We conducted a nationwide Swedish register-based cohort study of women who gave birth to singleton infants (≥22 gestational weeks) during 1987-2019. Exposed women were diagnosed with MG before or during the index pregnancy (N = 443). Unexposed women comprised 4249 women without a diagnosis of MG, matched for age, parity, hospital, and year of childbirth. The risks of adverse pregnancy, delivery, and neonatal outcomes for women with MG were estimated using regression modeling and presented as adjusted odds ratios (aOR). RESULTS: There was no increased risk of pregnancy complications in women with MG. Women with MG had a spontaneous onset of labor less often than women without MG (69.8% vs. 79.5%; aOR 0.59; p < 0.001) as well as higher labor induction rates and elective cesarean section deliveries (16.0% vs. 12.3%, aOR 1.42; p = 0.02 and 12.0% vs. 8.1%, aOR 1.59; p = 0.009). Infants of women with MG were born on average 2 days earlier (p = 0.002); however, these infants did not have a higher risk of having low APGAR, being small for gestational age, or having a congenital malformation. CONCLUSION: This first nationwide study of pregnancy in women with MG in Sweden demonstrates reassuring results overall, suggesting generally safe pregnancy outcomes for women with MG and their infants.

Severe Perineal Lacerations in First Delivery: Association with Subsequent Reproductive Outcomes.

Background: Severe perineal lacerations (SPLs), common worldwide, are associated with short- and long-term complications: pelvic floor disorders, fecal incontinence, fistula, and profound psychological impacts. Limited research suggests that experiencing SPL may influence future reproductive intentions, but research on outcomes is lacking. Methods: We analyzed the effect of experiencing SPL during a first delivery among a large cohort of Swedish births between 1992 and 2013. We used linear and multinomial logistic regression to estimate the associations between SPL and four reproductive outcomes: subsequent total birth number, probability of a second birth, interpregnancy interval (IPI), and subsequent scheduled cesarean birth. Results: Among 947,035 singleton live-born first-births, we found that experiencing SPL was associated with slightly fewer overall births in fully adjusted models (a decrease of -0.020 births; 95% confidence interval [CI]: -0.028 to -0.012), but no difference in the probability of a second birth (risk ratio [RR]: 1.00; 95% CI: 0.99 to 1.00) or IPI. Scheduled cesarean was increased in births after SPL (adjusted RR: 4.57; 95% CI: 4.42 to 4.73). A secondary comparison of SPL to severe postpartum hemorrhage suggests that some of these observed differences may be related to experiencing any severe outcome, and some specifically to perineum disruption. Conclusion: This study provides a deeper understanding of the long-term impacts of SPL, which may be useful in informing best clinical practices for supporting women who have experienced SPL.

Polycystic ovary syndrome and risk of pre-eclampsia: A national register-based cohort study.

OBJECTIVE: To explore whether the association between polycystic ovary syndrome (PCOS) and pre-eclampsia depends on treated clinical hyperandrogenism and whether PCOS is associated with different subtypes of pre-eclampsia. DESIGN: Nationwide register-based cohort study. SETTING: Sweden. POPULATION: Nulliparous women with PCOS (n = 22 947) and non-PCOS controls (n = 115 272) giving singleton birth at ≥22 gestational weeks during 1997-2015. Treated clinical hyperandrogenism was defined as filled prescriptions of anti-androgenic drugs during 2005-2017 (n = 2301 among PCOS women). METHODS: The risk of pre-eclampsia was estimated with conditional logistic regression, expressed as adjusted odds ratio (OR) with 95% confidence interval (CI). Adjustments were performed individually for confounders and predictors. MAIN OUTCOME MEASURES: Overall pre-eclampsia. Early/late (delivery <34/≥34 weeks) pre-eclampsia. Pre-eclampsia with or without a small-for-gestational-age (SGA) infant. RESULTS: Compared with controls, women with PCOS had a 29% increased risk of pre-eclampsia (predictor adjusted OR 1.29, 95% CI 1.20-1.39), with similar risk estimates for PCOS women with and without treated clinical hyperandrogenism. The association between PCOS and early pre-eclampsia seemed stronger than its association with late pre-eclampsia (predictor adjusted OR 1.64 (95% CI 1.33-2.02) and 1.26 (95% CI 1.17-1.37). Additionally, the association seemed slightly stronger between PCOS and pre-eclampsia in women with an SGA infant than without. CONCLUSIONS: Women with PCOS face an increased risk for pre-eclampsia, especially early pre-eclampsia and pre-eclampsia with an SGA infant. We were unable to determine on the basis of available data, whether hyperandrogenism is associated with pre-eclampsia.

Maternal early mid-pregnancy adiponectin in relation to infant birth weight and the likelihood of being born large-for-gestational-age.

This study aimed to evaluate the association of maternal adiponectin with infant birth size in 1349 pregnant women at Uppsala University Hospital, Sweden. The mean age of the women was 31.0 years, and 40.9% were nulliparous. Maternal early mid-pregnancy adiponectin was measured in microgram/mL. Linear regression models were performed to evaluate the association between adiponectin and infant birth weight. Logistic regression models were used to evaluate adiponectin in relation to the odds of giving birth to an infant large-for-gestational-age (LGA, infant birth weight standard deviation score > 90th percentile). Adjustments were made for early pregnancy BMI and diabetes mellitus. Prior adjustments, adiponectin was inversely associated with infant birth weight (ß - 17.1, 95% confidence interval (CI) - 26.8 to - 7.4 g, P < 0.001), and one microgram/mL increase in adiponectin was associated with a 9% decrease in the odds of giving birth to an LGA infant (odds ratio 0.91, CI 0.85-0.97, P = 0.006). The associations did not withstand in the adjusted models. We found a significant interaction between adiponectin and infant sex on birth size. This interaction was driven by an inverse association between maternal adiponectin and birth size in female infants, whereas no such association was found in males.

Comparing the results from a Swedish pregnancy cohort using data from three automated placental growth factor immunoassay platforms intended for first-trimester preeclampsia prediction.

INTRODUCTION: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy. MATERIAL AND METHODS: First-trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific. RESULTS: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGFRoche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGFPerkinElmer = 0.673 (95% CI 0.618-0.729) * PlGFThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGFRoche = 1.809 (95% CI 1.694-1.923) * PlGFPerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGFRoche = 1.237 (95% CI 1.113-1.361) * PlGFThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGFThermoFisher = 1.485 (95% CI 1.363-1.607) * PlGFPerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGFThermoFisher = 0.808 (95% CI 0.726-0.891) * PlGFRoche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4). CONCLUSION: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia.

Latent phase duration and associated outcomes: a contemporary, population-based observational study.

BACKGROUND: Little is known about the latent phase of labor, including whether its duration influences subsequent labor processes or birth outcomes. OBJECTIVE: This study aimed to describe the duration of the latent phase of labor from self-report of the onset of painful contractions to a cervical dilation of 5 cm in a large, Swedish population and evaluate the association between the duration of the latent phase of labor and perinatal processes and outcomes that occurred during the active phase of labor, second stage of labor, birth and immediately after delivery, stratified by parity. STUDY DESIGN: This was a population-based cohort study of 67,267 pregnancies with deliveries between 2008 and 2020 in the Stockholm-Gotland Regions, Sweden. Nulliparous and parous women without a history of cesarean delivery in spontaneous labor with a term (≥37 weeks of gestation), singleton, live, and vertex fetus without major malformations were included. Imputation was used if the notation of the end of the latent phase of labor (ie, cervical dilation of 5 cm) was missing in the partograph. Multivariable logistic regression was used to estimate the association with adjusted odds ratios and 95% confidence intervals, controlling for potential covariates. RESULTS: Including the time from painful contraction onset to a cervical dilation of 5 cm, the median durations of the latent phase of labor were 16.0 (interquartile range, 10.0-26.6) hours for nulliparous women and 9.4 (interquartile range, 5.9-15.3) hours for multiparous women. The durations of the latent phase of labor beyond the median were associated with increased odds of labor dystocia diagnosis during the first stage active phase or second stage of labor and interventions commonly associated with dystocia (amniotomy, oxytocin augmentation, epidural, and cesarean delivery). The duration of the latent phase of labor of ≥90th percentile vs less than the median in nulliparous women demonstrated an increased risk of adverse neonatal outcomes (Apgar score of <7 at 5 minutes and neonatal intensive care unit admission), chorioamnionitis, and fetal occiput posterior. In multiparous women, longer duration of the latent phase of labor was associated with an increased risk of neonatal intensive care unit admission and chorioamnionitis but was not associated with an Apgar score of <7 at 5 minutes. The duration of the latent phase of labor was not associated with additional markers of maternal risk. CONCLUSION: The duration of the latent phase of labor in nulliparous women was longer than that of multiparous women at each point of distribution. A longer duration of the latent phase of labor was associated with more frequent dystocia diagnoses and related interventions during the first stage active phase or second stage of labor, including cesarean delivery, nulliparous fetal occiput posterior position, chorioamnionitis, and markers of neonatal morbidity. More research is needed to identify potential mediating paths between the duration of the latent phase of labor and neonatal morbidity.

Outcomes in children after mild neonatal hypoxic ischaemic encephalopathy: A population-based cohort study.

OBJECTIVE: To investigate whether mild neonatal hypoxic ischaemic encephalopathy (HIE) in term born infants is associated with cerebral palsy, epilepsy, mental retardation and death up to 6 years of age. DESIGN: Population-based cohort study. SETTING: Sweden, 2009-2015. POPULATION: Live term born infants without congenital malformations or chromosomal abnormalities (n = 505 075). METHODS: Birth and health data were retrieved from Swedish national health and quality registers. Mild HIE was identified by diagnosis in either the Swedish Medical Birth Register or the Swedish Neonatal Quality Register. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: A composite of the outcomes cerebral palsy, epilepsy, mental retardation and death up to 6 years of age. RESULTS: Median follow-up time was 3.3 years after birth. Of 414 infants diagnosed with mild HIE, 17 were classified according to the composite outcome and incidence rates were 12.6 and 2.9 per 1000 child-years in infants with and without HIE respectively. Infants with mild HIE was four times as likely to be diagnosed with the composite outcome (HR 4.42, 95% CI 2.75-7.12) compared with infants without HIE. When analysed separately, associations were found with cerebral palsy (HR 21.50, 95% CI 9.59-48.19) and death (HR 19.10, 95% CI 7.90-46.21). HRs remained essentially unchanged after adjustment for covariates. CONCLUSIONS: Mild neonatal HIE was associated with neurological morbidity and mortality in childhood. Challenges include identifying infants who may develop morbidity and how to prevent adverse outcomes.

Study protocol: The cross-sectional Uppsala weight gain in pregnancy study (VIGA study).

Background: More than two in five Swedish women are overweight or obese when becoming pregnant. Maternal overweight or obesity and excessive pregnancy weight gain are associated with several adverse pregnancy outcomes. The underlying mechanisms that link maternal adiposity, diet, exercise, pregnancy weight gain with pregnancy outcome are incompletely understood. Methods: We describe the design for a cross-sectional study of pregnant women at Uppsala University Hospital, Sweden. All participants delivered by elective cesarean section before the onset of labor. At inclusion, participants answered two questionnaires concerning their dietary and exercise habits. Fasting maternal blood samples (buffy coat, plasma, serum) were collected. During the cesarean section, biopsies of maternal subcutaneous and visceral adipose tissues were obtained. Placental tissue was collected after delivery. All biological samples were processed as soon as possible, frozen on dry ice, and stored at -70 °C. Pregnancy outcomes and supplementary maternal characteristics were collected from medical records. Results: In total, 143 women were included in the study. Of these women, 33.6% were primiparous, 46.2% had a pre-pregnancy body mass index (BMI) over 25 kg/m2, and 11.2% of the offspring were born large for gestational age (LGA). Complete collection, that is both questionnaires and all types of biological samples, was obtained from 81.1% of the participants. Conclusions: This study is expected to provide a resource for exploration of the associations between maternal weight, diet, exercise, pregnancy weight gain, and pregnancy outcome. Results from this study will be published in peer-reviewed, international scientific journals. This study was approved by the Regional Ethics Review Board in Uppsala (approval no 2014/353) and with an amendment by the Swedish Ethical Review Authority (approval no 2020-05844).

Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography.

Importance: Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown. Objective: To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening. Design, Setting, and Participants: Cross-sectional study of a population-based cohort of women in Sweden (n = 10 528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected. Exposures: Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures. Main Outcomes and Measures: Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100. Results: A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk. Conclusions and Relevance: Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.

Pre-pregnancy participation and performance in world's largest cross-country ski race as a proxy for physical exercise and fitness, and perinatal outcomes: Prospective registry-based cohort study.

OBJECTIVE: Investigate associations between pre-pregnancy participation and performance in a demanding cross-country ski race (proxy for exercise volume and fitness) and perinatal outcomes. Pre-registered protocol: osf.io/aywg2. DESIGN: Prospective cohort study. SETTING: Based on entire overlap between the Vasaloppet registry and the population-based Swedish Pregnancy Register. SAMPLE: All female Vasaloppet participants 1991-2017 with subsequent singleton delivery (skiers), and age- and county-matched non-skiers. METHODS: We calculated odds ratios (ORs) for non-skiers versus skiers (model 1) and, among skiers, by performance (model 2), in Bayesian logistic regressions adjusted for socio-demographics, lifestyle factors, and comorbidities. We repeated calculations adjusting for early pregnancy body mass index (potential mediator) and explored robustness (selection/exposure settings; multiple comparisons correction). MAIN OUTCOME MEASURES: Twenty-nine important perinatal outcomes, predefined based on existing expert consensus. RESULTS: Non-skiers (n = 194 384) versus skiers (n = 15 377) (and slower versus faster performance, not shown) consistently had higher odds of gestational diabetes mellitus (GDM) (OR 1.70, 95% highest density interval: 1.40-2.09), excessive gestational weight gain (GWG) (1.28, 1.22-1.38), psychiatric morbidity (1.60, 1.49-1.72), any caesarean section (CS) (1.34, 1.28-1.40), elective CS (1.39, 1.29-1.49), and large-for-gestational-age babies (>90th percentile, 1.11, 1.04-1.18); lower odds of inadequate GWG (0.83, 0.79-0.88); and no associations with fetal/neonatal complications (e.g. preterm birth [1.09, 0.98-1.20], small for gestational age [SGA] [1.23, 1.05-1.45]). Adjustment for body mass index attenuated associations with excessive (1.20, 1.14-1.30) and inadequate GWG (0.87, 0.83-0.92) and large for gestational age (1.07, 1.00-1.13). CONCLUSION: Non-skiers compared with skiers, and slower versus faster performance, consistently displayed higher odds of GDM, excessive GWG, psychiatric morbidity, CS and large-for-gestational-age babies; and lower odds of inadequate GWG, after adjustment for socio-demographic and lifestyle factors and comorbidities. There were no associations with fetal/neonatal complications.

Brain Vascular Dysfunction in Mothers and Their Children Exposed to Preeclampsia.

Preeclampsia is a maternal syndrome characterized by the new onset of hypertension and proteinuria after 20 weeks of gestation associated with multisystemic complications, including brain alterations. Indeed, brain complications associated with preeclampsia are the leading direct causes of fetal and maternal morbidity and mortality, especially in low- and middle-income countries. In addition to the well-recognized long-term adverse cardiovascular effects of preeclampsia, women who have had preeclampsia have higher risk of stroke, dementia, intracerebral white matter lesions, epilepsy, and perhaps also cognitive decline postpartum. Furthermore, increasing evidence has also associated preeclampsia with similar cognitive and cerebral disorders in the offspring. However, the mechanistic links between these associations remain unresolved. This article summarizes the current knowledge about the cerebrovascular complications elicited by preeclampsia and the potential pathophysiological mechanisms involved, emphasizing the impaired brain vascular function in the mother and their offspring.