Pregnancy Complications and Risk of Cardiovascular Disease Later in Life: A Nationwide Cohort Study

Background The aim of this study was to investigate the associations between pregnancy complications and cardiovascular mortality and hospitalizations of cardiovascular disease (CVD) after adjustment for major confounding. Methods and Results In a nationwide register‐based cohort study, women with singleton births between 1973 and 2014 were included from the Swedish Medical Birth Register. Outcomes of mortality and hospitalizations of CVD were collected from the Cause of Death Register and the National Inpatient Register. The cohort was followed from the date of the first delivery until death or end of follow‐up, whichever occurred first. The pregnancy complications studied were preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, small for gestational age, and stillbirth. Among the 2 134 239 women (mean age at first pregnancy, 27.0 [SD, 5.1] and mean parity 1.96 [SD, 0.9]), 19.1% (N=407 597) had 1 of the studied pregnancy complications. All pregnancy complications were associated with all‐cause and cardiovascular mortality and hospitalization for CVD (ischemic heart disease, ischemic stroke, and peripheral artery disease) after adjustment for major confounding in a Cox proportional hazard regression model. The adjusted hazard ratio for cardiovascular mortality was 1.84 (95% CI, 1.38–2.44) for preterm birth and 3.14 (95% CI, 1.81–5.44) for stillbirth. Conclusions In this large cohort study, pregnancy complications were associated with all‐cause mortality, cardiovascular mortality, and hospitalizations for CVD, also after adjusting for confounding, including overweight, smoking, and comorbidities. The study highlights that less established pregnancy complications such as preterm birth and stillbirth are also associated with cardiovascular mortality and CVD.

Maternal smoking during pregnancy and type 1 diabetes in the offspring: A nationwide register-based study with family-based designs

Objectives: Maternal smoking during pregnancy is associated with a reduced risk of type 1 diabetes (T1D) in the offspring. We investigated whether this association is consistent with a causal interpretation by accounting for familial (shared genetic and environmental) factors using family-based, quasi-experimental designs. Design: A nationwide, prospective cohort study and a nested case-control study (quasi-experiment) comparing children with T1D to their age-matched siblings (or cousins). Setting: Swedish national registers. Participants: We included 2,995,321 children born in Sweden between 1983 and 2014. Exposure: Information on maternal smoking during pregnancy was retrieved from the Swedish Medical Birth Register. Main outcome measures: Children were followed for a diagnosis of T1D until 2020 through the National Patient, Diabetes and Prescribed Drug Registers. Results: A total of 18,617 children developed T1D, with a median age at diagnosis of 9.4 years. The sibling and cousin comparison design included 14,284 and 7,988 of these children, respectively. Maternal smoking during pregnancy was associated with a 22% lower risk of offspring T1D in the full cohort (hazard ratio: 0.78, 95% confidence interval [CI]: 0.75 to 0.82) in the multivariable-adjusted model. The corresponding odds ratio was 0.78 (95% CI: 0.69 to 0.88) in the sibling and 0.72 (95% CI: 0.66 to 0.79) in the cousin comparison analysis. Conclusions: This nationwide, family-based study provides support for a protective effect of maternal smoking on offspring T1D. Mechanistic studies are needed to elucidate the underlying pathways behind this link.

Relation of maternal birthweight with early pregnancy obesity, gestational diabetes, and offspring macrosomia

This study aimed to investigate how maternal birthweight is related to early pregnancy obesity, gestational diabetes mellitus (GDM), and offspring birthweight. Females born term and singleton in Sweden between 1973 and 1995 (N = 305,893) were studied at their first pregnancy. Information regarding their birthweight, early pregnancy body mass index, and pregnancy complications was retrieved from the Swedish Medical Birth Register, as were data on their mothers and offspring. High maternal birthweights (2–3 standard deviation scores (SDS) and >3 SDS) were associated with greater odds of early pregnancy obesity, odds ratio (OR) 1.52 (95% confidence interval (CI) 1.42–1.63) and OR 2.06 (CI 1.71–2.49), respectively. A low maternal birthweight (<2 SDS) was associated with greater odds of GDM (OR 2.49, CI 2.00–3.12). No association was found between high maternal birthweight and GDM. A maternal birthweight 2–3 SDS was associated with offspring birthweight 2–3 SDS (OR 3.83, CI 3.44–4.26), and >3 SDS (OR 3.55, CI 2.54–4.97). Corresponding ORs for a maternal birthweight >3 SDS were 5.38 (CI 4.12–7.01) and 6.98 (CI 3.57–13.65), respectively. In conclusion, a high maternal birthweight was positively associated with early pregnancy obesity and offspring macrosomia. A low, but not a high maternal birthweight, was associated with GDM.

Is increased size at birth associated with longevity on the population level? – A historical and comparative analysis of regions in Sweden

Increased population longevity could be influenced by early life factors. Some areas have long-lived populations, also in a historical perspective. We aimed to study these factors in Halland, an area with the highest life expectancy in Sweden. We collected archival data on gestational age and birth characteristics from 995 live singleton full-term births at the Halmstad Hospital, Halland, from the period 1936 to 1938 and compared these to 3364 births from three hospitals in nearby Scania for the period 1935–1945. In addition, data were obtained on maternal and offspring characteristics from the national Swedish Medical Birth Register during 1973–2013. The results show that when controlling for background maternal and offspring characteristics, mean birth weight (BW) and mean birth length were higher in Halland than in Scania, but the proportion of low birth weight (LBW) and small for gestational age (SGA) was lower. However, mean BW for Halland did not differ from the rest of Sweden in recent years 2004–2013. We also conducted a mortality follow-up for children born in Scania, which showed that LBW, being born SGA, or short birth length reduced survival. In conclusion, the high mean life expectancy in Halland compared to the rest of Sweden could have been associated with beneficial early life factors influencing birth size in the past. In more recent decades the mean BW of Halland is not different from the national mean. Thus, longevity could be expected to become more equal to the national mean in the future.

Associations of maternal hypertensive disorders during pregnancy with offspring risks of ischemic heart disease and stroke: a Nordic cohort study

Background A substantial body of evidence suggests that children exposed to maternal hypertensive disorders during pregnancy (HDP) have increased risks of preterm birth, fetal growth restriction and several cardiovascular risk factors (e.g., hypertension, obesity, diabetes) later in life. However, the direct evidence on the link between maternal HDP and the risk of severe cardiovascular diseases such as ischemic heart disease (IHD) and stroke in the offspring is very limited. Objective To investigate the associations between maternal HDP and the risk of IHD and stroke in the offspring. Methods We conducted a population-based cohort study by linking several national registers in Sweden and Finland. Live singleton births from the Swedish Medical Birth Register (1973–2014) and the Finnish Medical Birth Register (1987- 2014) were followed for IHD and stroke until 2014 by the national patient and cause of death registers. We performed Cox regression models to examine the association between maternal HDP and its subtypes, i.e., pre-existing chronic hypertension, gestational hypertension, and preeclampsia, and the risk of IHD, and stroke in the offspring while adjusting for relevant maternal and pregnancy-related confounders. We conducted sibling analyses to control for unmeasured shared familial (genetic and/or environmental) risk factors. Results Among the 5,807,122 singletons included in the study, 218,322 (3.76%) children were born to mothers with HDP. During the up to 41 years of follow-up, 2,340 (0.04%) offspring were diagnosed with IHD and 5,360 (0.09%) were diagnosed with stroke. Offspring exposed to maternal HDP had an increased risk of IHD (adjusted hazard ratio (aHR), 1.29; 95% confidence interval (CI), 1.01–1.63), and stroke (aHR,1.33; 95% CI, 1.14–1.56). Significantly increased rates of stroke were also observed in children exposed to the subtypes of maternal HDP: pre-existing chronic hypertension (aHR, 1.64; 95% CI, 1.03–2.60), gestational hypertension (HR, 1.38; 95% CI, 1.08–1.77), and preeclampsia (HR, 1.26; 95% CI, 1.02–1.55). The associations between maternal HDP and offspring's IHD and stroke were independent of preterm birth and small for gestational age at birth. Maternal HDP remained associated with stroke in the offspring (aHR, 1.94; 95% CI, 1.16–3.22), but not with IHD (aHR, 0.89; 95% CI, 0.47–1.67) in the sibling analyses. Conclusion Children to mothers with HDP have increased rates of IHD and stroke from childhood to young adulthood. While the link between maternal HDP and IHD in the offspring seemed to be attributed to confounding by familial factors, the relation between maternal HDP and stroke persisted even when considering such confounding. Persons born to mothers with HDP may benefit from early screening and prevention efforts to reduce the risk of IHD and stroke later in life. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Heart and Lung Foundation

Social inequalities and trends in pre-pregnancy body mass index in Swedish women

Obesity rates in adolescence and young adulthood have increased in Sweden, reflecting global trends. To which extent this occurs across different socioeconomic strata has not been clarified. The aim of the present study was to investigate trends in social inequalities in body mass index (BMI) in young/mid-adulthood Swedish women. We obtained weight and height for all women aged 20–45 years, at their first registered pregnancy (< 12 weeks of gestation) in the Swedish Medical Birth Register 1982–2013 (1,022,330, mean age = 28.8 years), documenting education and county of residence. Trends in mean BMI and in the prevalence of BMI categories between 1982 and 2013 were estimated across education levels and geographical location. Overall, mean BMI increased from 22.7 kg/m2 (SD 3.2) to 24.3 kg/m2 (SD 4.4) between 1982 and 2013. Simultaneously, the prevalence of overweight and obesity (BMI ≥ 25 kg/m2) increased from 18.1 to 33.4% while that of moderate obesity (BMI ≥ 30 to < 35 kg/m2) and severe obesity (BMI ≥ 35 kg/m2) increased markedly from 3.4 and 0.4% to 7.4 and 3.1%, respectively. The prevalence of moderate and severe obesity more than doubled during the study period across all educational levels. In conclusion, BMI and moderate and severe obesity increased markedly among young/mid-adulthood Swedish women regardless of education with a widening gap between those with lower and higher education. These growing social inequalities in BMI are likely to cause a rising divide in serious health problems following early and long-lasting obesity.

Clinical and Biochemical Signs of Polycystic Ovary Syndrome in Young Women Born Preterm

Objective: It has been suggested that adverse early life exposures increase the risk of developing polycystic ovary syndrome (PCOS) in later life. We hypothesized that women born preterm would have more biochemical and clinical signs of PCOS than women born at term. Design: The ESTER Preterm Birth Study participants were born in Northern Finland, and identified from the Northern Finland Birth Cohort and the Finnish Medical Birth Register. Altogether, 74 women born very or moderately preterm (<34 gestational weeks, VMPT), 127 born late preterm (at 34–36 weeks, LPT), and 184 born full term (≥37 weeks, controls) were included in the analysis (mean age 23.2y). Methods: We measured serum total testosterone and sex hormone binding globulin (SHBG) and calculated free androgen index (FAI). PCOS according to the clinical and biochemical signs was defined either as hirsutism and oligoamenorrhea (via questionnaire), or as oligoamenorrhea and elevated testosterone levels (>2.4 nmol/l). Results: Women born VMPT/LPT exhibited 33.0% (8.7, 62.8)/16.4% (-2.0, 38.1) higher testosterone, 28.5% (5.3, 45.9)/24.1% (5.6, 38.9) lower SHBG levels, and 64.6% (19.4, 127.1)/ 42.5% (11.1, 82.9) higher FAI than controls after adjusting for age and recruitment cohort, maternal BMI, smoking, and pregnancy disorders, parental education, history of hypertension, diabetes, myocardial infarction or stroke, and subject’s birth weight SD. Odds ratios for having PCOS were 1.67 (0.44, 6.23)/3.11 (1.26, 7.70). Conclusions: Women born preterm have a more hyperandrogenic hormonal profile, and those born LPT are approximately three times more likely at risk to have PCOS compared to women born at term.

Effect of Grandmaternal Smoking on Body Size and Proportions at Birth

Many long-term adverse effects of smoking during pregnancy are known. Increasingly, adverse effects in the grandchild after grandmaternal smoking during pregnancy are reported. We explored this in a birth cohort of 24,000 grandmother–mother–child triads identified from the Finnish Medical Birth Register in 1991–2016. Multiple logistic regression was used to analyze the association between any smoking during pregnancy by both grandmother and mother, or only grandmother or mother on adverse birth outcomes. No smoking by neither grandmother nor mother was used as the reference. As endpoints, preterm birth, low birth weight, small for gestational age (birth weight, birth length, head circumference), and body proportionality (low ponderal index, high brain-to-body ratio, high head-to-length ratio) were included. Smoking by both grandmother and mother was consistently associated with higher risks than smoking only by the mother. Birth length and weight were especially sensitive to (grand)maternal smoking. In conclusion, the combined effect of grandmaternal and maternal smoking is associated with higher risks than only maternal smoking.

Breastfeeding practice, breastfeeding policy and hospitalisations for infectious diseases in early and later childhood: a register-based study in Uppsala County, Sweden

ObjectiveTo examine the association between breastfeeding practice and hospitalisations for infectious diseases in early and later childhood, in particular, to compare exclusive breast feeding 4–5 months with exclusive breastfeeding 6 months or more. Thereby, provide evidence to inform breastfeeding policy.DesignA register-based cohort study.SettingA cohort was created by combining the Swedish Medical Birth Register, the National Inpatient Register, the Cause of Death Register, the Total Population Register, the Longitudinal integration database for health insurance and labour market studies, with the Uppsala Preventive Child Health Care database.Patients37 825 term and post-term singletons born to women who resided in Uppsala County (Sweden) between 1998 and 2010.Main outcome measuresNumber of hospitalisations for infectious diseases in early (<2 years) and later childhood (2–4 years).ResultsThe risk of hospitalisations for infectious diseases decreased with duration of exclusive breastfeeding until 4 months of age. In early childhood, breast feeding was associated with a decreased risk of enteric and respiratory infections. In comparison with exclusive breast feeding 6 months or more, the strongest association was found between no breastfeeding and enteric infections (adjusted incidence rate ratios, aIRR 3.32 (95% CI 2.14 to 5.14)). In later childhood, breast feeding was associated with a lower risk of respiratory infections. In comparison with children exclusively breastfed 6 months or more, the highest risk was found in children who were not breastfed (aIRR 2.53 (95% CI 1.51 to 4.24)). The risk of hospitalisations for infectious diseases was comparable in children exclusively breastfed 4–5 months and children exclusively breastfed 6 months or more.ConclusionsOur results support breastfeeding guidelines that recommend exclusive breastfeeding for at least 4 months.