Incident Cardiovascular Disease in Women With Type 1 or Type 2 Diabetes Following a Hypertensive Disorder of Pregnancy.

BACKGROUND: The extent to which a history of hypertensive disorders of pregnancy is associated with incident cardiovascular disease also among women with diabetes is unknown. METHODS: In this nationwide register-based cohort study, parous women aged 18 to 69 years with a first delivery in the Swedish Medical Birth Register, regardless of diabetic status at that time, and a subsequent clinical visit in the Swedish National Diabetes Register were included. Time to first cardiovascular disease event (myocardial infarction, stroke, or heart failure) before age 70 years by hypertensive disorders of pregnancy history was separately analyzed by diabetes type using Cox regression models that included conventional risk factors. RESULTS: In total, 1748 (18.9%) of 9230 women with type 1 and 5904 (10.6%) of 55 773 women with type 2 diabetes had their first delivery complicated by a hypertensive disorder of pregnancy. Median time (25-75th percentile) between first delivery and start of follow-up was 3.3 (1.4-13.0) years for women with type 1 and 29.8 (22.4-35.6) years for women with type 2 diabetes. In modeling, the risk for any cardiovascular disease event among women with a history of hypertensive disorders of pregnancy was generally 10% to 20% higher, with main models estimating hazard ratios to 1.20 (95% CI, 0.99-1.47) for women with type 1 and 1.15 (95% CI, 1.02-1.29) for women with type 2 diabetes. CONCLUSIONS: In women with diabetes, a history of hypertensive disorders of pregnancy was associated with an increased risk of incident cardiovascular disease and should be considered as a risk enhancer.

Exposure to per- and polyfluoroalkyl substances in early pregnancy and risk of cerebral palsy in children.

BACKGROUND: Most cerebral palsy (CP) cases have an unexplained etiology, but a role for environmental exposures has been suggested. One purported environmental risk factor is exposure to endocrine-disrupting pollutants specifically per- and polyfluoroalkyl substances (PFAS). OBJECTIVES: We investigated the association between prenatal PFAS exposures and CP in Swedish children. METHODS: In this case-control study, 322 CP cases, 343 population controls, and 258 preterm controls were identified from a birth registry in combination with a CP follow-up program from 1995 to 2014 and linked to a biobank which contains serum samples from week 10-14 of pregnancy. Maternal serum concentrations of four PFAS compounds: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonate (PFOS) were analyzed using liquid chromatography-tandem-mass-spectrometry. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for CP and each PFAS in quartiles and as continuous variables controlling for various sociodemographic and lifestyle factors. RESULTS: In crude and adjusted analyses, we did not find consistent evidence of associations between serum PFHxS, PFOA, PFNA, PFOS and concentrations in early pregnancy and CP, except in preterm infants. The ORs comparing the highest PFAS quartiles to the lowest were 1.05 (95 % CI: 0.63-1.76), 0.96 (95 % CI: 0.55-1.68), 0.71 (95 % CI: 0.41-1.25), and 1.17 (95 % CI: 0.61-2.26), for PFHxS, PFOA, PFNA, and PFOS, respectively. Some positive associations were observed for preterm infants, but the results were imprecise. Similar patterns were observed in analyses treating PFAS as continuous variables. CONCLUSIONS: In this study, we found little evidence that early pregnancy prenatal exposure to PFHxS, PFOA, PFNA, or PFOS increases the risk of CP. However, some positive associations were observed for preterm cases and warrant further investigation.

Infertility, pregnancy loss and assisted reproduction in women with asthma: a population-based cohort study.

STUDY QUESTION: Is the chance of childbirth, and risk of infertility, pregnancy loss and need for assisted reproduction different for women with asthma compared to women without asthma? SUMMARY ANSWER: Women with asthma had comparable chances of giving birth compared to the reference population, however, their risk of both infertility and pregnancy loss, as well their need for medically assisted reproduction, was higher. WHAT IS KNOWN ALREADY: Reproductive dysfunction has been reported among women with asthma, including longer time to pregnancy, increased risk of pregnancy loss and a higher need of medically assisted reproduction, but their risk of clinical infertility is unknown. STUDY DESIGN, SIZE, DURATION: This longitudinal register-based cohort study included all women with a healthcare visit for delivery, infertility, pregnancy loss or induced abortion in the southernmost county in Sweden, over the last 20 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using the Skåne Healthcare Register, we identified all women aged 15-45 between 1998 and 2019, who received a diagnosis of asthma before their first reproductive outcome (n = 6445). Chance of childbirth and risk of infertility, pregnancy loss and assisted reproduction were compared to a healthcare seeking population of women without any asthma (n = 200 248), using modified Poisson regressions. MAIN RESULTS AND THE ROLE OF CHANCE: The chance of childbirth was not different between women with asthma versus those without, adjusted risk ratio (aRR) = 1.02, 95% CI: 1.01-1.03. The risk of seeking care for infertility was increased, aRR = 1.29, 95% CI: 1.21-1.39, and women with asthma more often needed assisted reproduction aRR = 1.34 95% CI: 1.18-1.52. The risk of suffering a pregnancy loss was higher, aRR = 1.21, 95% CI: 1.15-1.28, and induced abortions were more common, aRR = 1.15, 95% CI: 1.11-1.20, among women with asthma. LIMITATIONS, REASONS FOR CAUTION: The study was an observational study based on healthcare visits and lacked detailed anthropometric data, thus residual confounding cannot be excluded. Only women with a healthcare visit for a reproductive outcome were included, which cannot be translated into pregnancy intention. A misclassification, presumed to be non-differential, may arise from an incorrect or missing diagnosis of asthma or female infertility, biasing the results towards the null. WIDER IMPLICATIONS OF THE FINDINGS: This study points towards reproductive dysfunction associated with asthma, specifically in regards to the ability to maintain a pregnancy and the risk of needing medically assisted reproduction following clinical infertility, but reassuringly the chance of subsequently giving birth was not lower for these women. STUDY FUNDING/COMPETING INTEREST(S): This article is part of the ReproUnion collaborative study, co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne and Ferring Pharmaceuticals. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Influence of Socio-Economic Factors and Region of Birth on the Risk of Preeclampsia in Sweden.

OBJECTIVES: To investigate the association between socio-economic factors and the risk of preeclampsia in Sweden, specifically investigating if this relationship is confounded by maternal region of birth. STUDY DESIGN: All singleton births between 1999 and 2009 in an ethnically diverse area in southern Sweden, totaling 46,618 pregnancies, were included in this study. The data on maternal pregnancy outcomes were retrieved from a regional birth register and socio-economic variables from Statistics Sweden. The risk ratios for preeclampsia were calculated for educational level and household disposable income, adjusting for maternal region of birth, maternal age, body mass index, parity, and smoking. RESULTS: Low income levels were associated with a higher risk for preeclampsia, adjusted risk ratio (aRR) = 1.25 (95% confidence interval [CI]: 0.99, 1.59) and aRR = 1.36 (95% CI: 1.10, 1.68) for the two lowest quintiles, respectively, compared to the highest. There was an educational gradient in preeclampsia risk, although not all categories reached statistical significance: aRR = 1.16, (95% CI: 0.89-1.50) for low educational attainment and aRR = 1.23 (95% CI: 1.08, 1.41) for intermediate educational attainment compared to women with highest education. The socio-economic gradient remained after adjusting for region of birth. There was a lower risk for preeclampsia for women born in Asia, aRR = 0.60 (95% CI: 0.47, 0.75), regardless of socio-economic position. CONCLUSION: An increased risk for preeclampsia was seen for women with measures of lower socio-economic position, even in a universal, government-funded healthcare setting. The relationship was not explained by region of birth, indicating that the excess risk is not due to ethnically differential genetic pre-disposition but rather due to modifiable factors.

Fertility outcomes in women with pre-existing type 2 diabetes-a prospective cohort study.

OBJECTIVE: To study childbirth and the risk of miscarriage and infertility among women who have received a diagnosis of type 2 diabetes before the start of their reproductive journey. DESIGN: Register-based cohort study using the Skåne Healthcare Register SETTING: All healthcare visits for the whole population of the southernmost region in Sweden over the past 20 years PATIENT(S): All women who were aged 18-45 years between January 1, 1998 and December 31, 2019 and who received a clinical diagnosis of type 2 diabetes before their first childbirth, miscarriage, or infertility diagnosis (n = 230) were compared with a healthcare-seeking population of women without any type of diabetes, matched for calendar year and age (n = 179,434). INTERVENTION(S): None MAIN OUTCOME MEASURE(S): Childbirth, miscarriage, and infertility diagnosis RESULT(S): The birthrate was lower among women with type 2 diabetes (62.6% vs. 83.8%), and they were less likely to give birth (crude risk ratio [RR] = 0.73, 95% confidence interval [CI]: 0.66-0.81). They had a higher risk of experiencing a miscarriage (RR = 1.88, 95% CI: 1.50-2.36). The risk of infertility was increased (RR = 3.44, 95% CI: 2.88-4.10) as was the risk of having infertility and not giving birth (RR = 4.47, 95% CI: 3.44-5.82). All results remained the same after adjustment for polycystic ovary syndrome and obesity. CONCLUSION(S): Women with type 2 diabetes with onset before their reproductive journey were more often childless compared with women without diabetes and had a higher risk of experiencing both miscarriage and infertility. This patient group may be in need of targeted information regarding potential fertility issues as part of their clinical treatment.

Exposure to psychosocial work strain and changes in smoking behavior during pregnancy - a longitudinal study within the Danish National Birth Cohort.

Objective Knowledge of the relationship between psychosocial strain in the work environment and smoking during pregnancy is scarce. This study aimed to examine the association between psychosocial job strain and change in smoking behavior during pregnancy. Methods The cohort included 65 645 pregnancies from the Danish National Birth Cohort (1996-2002), where pregnant women were interviewed on job factors and lifestyle during the first and third trimesters. Smoking was categorized into non-, non-daily, and daily smoking at each interview. Psychosocial job strain was categorized into four groups based on the concept of Karasek's demand-control model: low strain (reference), passive, active and high strain. Associations between psychosocial strain and change in smoking status between the first and second interviews were analyzed by multinomial logistic regression, separately for each smoking category at first interview. Results Non-smoking women exposed to high strain work were more likely to become daily smokers [adjusted odds ratio (OR adj) 1.41, (95% confidence interval (CI) 1.08-1.83)] compared to non-smoking women exposed to low strain work. Non-smoking women exposed to passive work were more likely to become both non-daily and daily smokers [OR adj1.59 (95% CI 1.21-2.08) and OR adj1.32 (95% CI 1.03-1.70), respectively]. Daily smoking women exposed to high strain work were less likely to decrease their smoking [OR adj0.57 (95% CI 0.32-0.99)] compared to daily smoking women exposed to low strain work. Conclusions Psychosocial strain influenced the women's smoking behavior during pregnancy, especially in job types with low control.

Cotinine Validation of Self-Reported Smoking During Pregnancy in the Swedish Medical Birth Register.

INTRODUCTION: Self-reported data on smoking during pregnancy from the Medical Birth Register of Sweden (MBR) are widely used. However, underreporting of such behavior may occur, leading to biases. It is of importance to validate the smoking data in the MBR. The main objective was to investigate the agreement between self-reported smoking data from the MBR and cotinine levels in maternal serum among women from the general population in the region of Skåne, Sweden. We also estimated the transfer of cotinine from mother to fetus. METHODS: From a cohort used previously to investigate the relationship between intrauterine environmental exposures and offspring neuropsychiatric outcomes, there were 204 control children retrieved from the MBR with data on maternal smoking in early pregnancy registered. Data on maternal and umbilical cord cotinine at delivery were available for these children from a regional biobank. RESULTS: There was a high agreement between cotinine levels and MBR smoking data (κ = 0.82) and a high correlation between cotinine levels in maternal and umbilical cord serum (r s = 0.90, P < .001). Of the self-reported nonsmokers, 95% (95% confidence interval: 89% to 97%) were classified as nonsmokers after cotinine measurements. CONCLUSION: In these data, we found that the agreement between mothers' self-reported smoking habits during pregnancy and their levels of serum cotinine was high, as was the transfer of cotinine from mother to fetus. This indicates that birth register data on pregnancy smoking in Sweden could be considered a valid measure.

Maternal Smoking during Pregnancy and Daughters' Preeclampsia Risk.

BACKGROUND: An obstetrical paradox is that maternal smoking is protective for the development of preeclampsia. However, there are no prior studies investigating the risk of preeclampsia in women who were exposed to tobacco smoking during their own fetal period. We aimed to study the subsequent risk of preeclampsia in women who were exposed to tobacco smoke in utero, using a national population-based register. METHODS: Data were obtained from the Medical Birth Register of Sweden for women who were born in 1982 (smoking data first recorded) or after, who had given birth to at least one child; 153 885 pregnancies were included. RESULTS: The associations between intrauterine smoking exposure (three categories: non-smokers, 1-9 cigarettes/day [moderate exposure], and >9 cigarettes/day [heavy exposure]) and subsequent preeclampsia (n = 5721) were assessed using logistic regressions. In models adjusted for maternal age, parity and own smoking, the odds ratios (OR) for preeclampsia were 1.06 [95% CI: 0.99,1.13 for moderate intrauterine exposure, and 1.18, [95% CI: 1.10,1.27] for heavy exposure. Estimates were slightly strengthened in non-smoking women who experienced heavy intrauterine exposure (adjusted OR 1.24 [95% CI: 1.14,1.34]). Results were no longer statistically significant after adjustment for the woman's own BMI, gestational age and birthweight Z-scores. CONCLUSION: These data revealed some evidence of a possible weak positive association between intrauterine smoking exposure and the risk of subsequent preeclampsia, however, results were not significant over all manifestations of preeclampsia and confounder adjustment. The increased risk might be mediated through exposed women's own BMI or birthweight.

Levels of perfluoroalkyl substances and risk of coronary heart disease: Findings from a population-based longitudinal study.

BACKGROUND: Cross-sectional studies have shown an association between exposure to perfluoroalkyl substances (PFASs) and coronary heart disease (CHD). These findings need to be evaluated in longitudinal settings. OBJECTIVES: To investigate the risk of CHD in relation to PFAS levels in a longitudinal setting among Swedish rural residents. METHODS: In a population-based prospective cohort of male farmers and rural residents recruited in 1990-1991, all men who received a CHD diagnosis between 1992 and 2009 were identified from national registers (n=253). For each CHD case, one control, matched for age, was chosen randomly from the cohort. For all cases and controls, levels of eight PFASs at baseline were measured in stored blood samples. In addition, for a subsample, PFAS levels were also measured in serum samples collected at a follow-up in 2002-2003. RESULTS: There were no statistically significant associations between levels of seven of the eight PFASs at baseline and risk for developing CHD. There was a significant association between perfluoroheptanoic acid (PFHpA) and CHD (OR=2.72; 95% CI: 1.52, 4.84) for the 3rd quartile and (OR=2.45; 95% CI: 1.40, 4.29) for the 4th quartile compared to the lowest quartile. Changes in levels of PFCs between baseline and follow-up did not differ systematically between cases and controls. CONCLUSIONS: This longitudinal study does not lend support to the previously reported cross-sectional relationship between PFAS levels and CHD risk. We found a significant association with PFHpA, but this could be a chance finding, considering its chemical resemblance to other PFASs.

Maternal smoking during pregnancy and offspring type 1 diabetes mellitus risk: accounting for HLA haplotype.

The main objective of this study was to investigate the risk of type 1 diabetes mellitus (T1D) in children exposed to tobacco smoking in utero, also taking genetic predisposition as expressed by HLA haplotype into account. In Skåne, the southernmost county of Sweden, all children born 1999-2005 who developed T1D were registered, resulting in 344 cases. For each child with T1D, three control children, matched for HLA haplotype and birthyear, were selected. Information on prenatal smoking exposure was retrieved from a regional birth register. Conditional logistic regressions were used to evaluate T1D risk following prenatal smoking exposure. In these data, maternal smoking in early pregnancy was associated with a higher risk of her child developing T1D [odds ratio (OR) 2.83; 95% confidence interval (CI) 1.67-4.80 for 1-9 cigarettes/day, and OR 3.91; 95% CI 1.22-12.51 for >9 cigarettes/day]. Results remained through all adjustments and sensitivity analyses. When genetic predisposition in terms of HLA haplotype was taken into account, we found that children exposed to smoking during fetal life were at higher risk of developing T1D in childhood.

Influence of maternal and paternal birthweight on offspring birthweight - a population-based intergenerational study.

BACKGROUND: The correlation between infant birthweight and parental birthweight has received substantial interest. However, fewer studies including the birthweight of the father have had access to large sets of population-based data. The objective of this study is to examine the influence of maternal and paternal birthweight on the birthweight of the offspring in the context of other birthweight determinants, with a special focus on the contribution of paternal birthweight. METHODS: The data used were retrieved from the Swedish Population Register, Medical Birth Register and Multi-Generation Register. Full-term, singleton births were included and linked through personal ID numbers given to every resident at birth, forming 137 538 mother-father-child units with valid birthweights. The analyses were made through linear regression models. RESULTS: The positive association for both maternal and paternal birthweight remained after introducing other determinants in the model, yielding a difference in offspring birthweight by 164 g [95% confidence interval 159, 170] and 149 g [95% confidence interval 145, 154] for every 1000 g rise in birthweight of the mother and father respectively. Maternal birthweight explained 6% of the variance in birthweight, whereas paternal birthweight explained 3%. There was no difference when analyses were stratified according to gender. CONCLUSION: These results suggest that maternal and paternal birthweight remain relevant for infant birthweight, even after consideration of other determinants of birthweight.