Background To determine the frequency of pregnancy complications and their association with the risk of cardiovascular outcomes in women with structural heart disease (SHD).Methods This nationwide registry-based cohort study included women in Sweden with SHD (pulmonary arterial hypertension, congenital heart disease or acquired valvular heart disease) with singleton births registered in the national Medical Birth Register (MBR) between 1973 and 2014. Exposures were pregnancy complications; pre-eclampsia/gestational hypertension (PE/gHT), preterm birth and small for gestational age (SGA) collected from MBR. The outcomes were cardiovascular mortality and hospitalisations defined from the Cause of Death Register and the National Patient Register. Cox regression models were performed with time-dependent covariates, to determine the possible association of pregnancy complications for cardiovascular outcomes.Results Among the total of 2 134 239 women included in the MBR, 2554 women with 5568 singleton births were affected by SHD. Women without SHD (N=2 131 685) were used as a reference group. PE/gHT affected 5.8% of pregnancies, preterm birth 9.7% and SGA 2.8%. Preterm birth (adjusted HR, aHR 1.91 (95% CI 1.38 to 2.64)) was associated with an increased risk of maternal all-cause mortality. PE/gHT (aHR 1.64 (95% CI 1.18 to 2.29)) and preterm birth (aHR 1.56 (95% CI 1.19 to 2.04)) were associated with an increased risk of hospitalisations for atherosclerotic CVD.Conclusions Pregnancy complications were frequent in women with SHD. With a median follow-up time of 22 years, preterm birth was associated with a higher risk of cardiovascular mortality, and PE/gHT and preterm birth were associated with cardiovascular morbidity. In women with SHD, pregnancy complications may provide additional information for the risk assessment of future cardiovascular outcomes.

Abstract 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.

While there is evidence that being born large-for-gestational-age (LGA) is associated with an increased risk of obesity later in life, the data are conflicting. Thus, we aimed to examine the associations between proportionality at birth and later obesity risk in adulthood. This was a retrospective study using data recorded in the Swedish Birth Register. Anthropometry in adulthood was assessed in 195,936 pregnant women at 10–12 weeks of gestation. All women were born at term (37–41 weeks of gestation). LGA was defined as birth weight and/or length ≥2.0 SDS. Women were separated into four groups: appropriate-for-gestational-age according to both weight and length (AGA – reference group; n = 183,662), LGA by weight only (n = 4,026), LGA by length only (n = 5,465), and LGA by both weight and length (n = 2,783). Women born LGA based on length, weight, or both had BMI 0.12, 1.16, and 1.08 kg/m 2 greater than women born AGA, respectively. The adjusted relative risk (aRR) of obesity was 1.50 times higher for those born LGA by weight and 1.51 times for LGA by both weight and height. Length at birth was not associated with obesity risk. Similarly, women born LGA by ponderal index had BMI 1.0 kg/m 2 greater and an aRR of obesity 1.39 times higher than those born AGA. Swedish women born LGA by weight or ponderal index had an increased risk of obesity in adulthood, irrespective of their birth length. Thus, increased risk of adult obesity seems to be identifiable from birth weight and ignoring proportionality.

Today we lack knowledge if size at birth and gestational age interact regarding postnatal growth pattern in children born at 32 gestational weeks or later. This population-based cohort study comprised 41,669 children born in gestational weeks 32–40 in Uppsala County, Sweden, between 2000 and 2015. We applied a generalized least squares model including anthropometric measurements at 1.5, 3, 4 and 5 years. We calculated estimated mean height, weight and BMI for children born in week 32 + 0, 35 + 0 or 40 + 0 with birthweight 50th percentile (standardized appropriate for gestational age, sAGA) or 3rd percentile (standardized small for gestational age, sSGA). Compared with children born sAGA at gestational week 40 + 0, those born sAGA week 32 + 0 or 35 + 0 had comparable estimated mean height, weight and BMI after 3 years of age. Making the same comparison, those born sSGA week 32 + 0 or 35 + 0 were shorter and lighter with lower estimated mean BMI throughout the whole follow-up period. Our findings suggest that being born SGA and moderate preterm is associated with short stature and low BMI during the first five years of life. The association seemed stronger the shorter gestational age at birth.

We assessed anthropometry in 22,421 adult daughters in association with their mothers’ tobacco smoking early in pregnancy (at their first antenatal visit) in Sweden, particularly their risk of short stature and obesity. Adult daughters were grouped by maternal smoking levels during pregnancy: Non-smokers (58.5%), Light smokers (24.1%; smoked 1–9 cigarettes/day), and Heavier smokers (17.4%; smoked ≥10 cigarettes/day). Anthropometry was recorded on the adult daughters at approximately 26.0 years of age. Obesity was defined as BMI ≥30 kg/m2, and short stature as height more than two standard deviations below the population mean. Daughters whose mothers were Light and Heavier smokers in early pregnancy were 0.8 cm and 1.0 cm shorter, 2.3 kg and 2.6 kg heavier, and had BMI 0.84 kg/m2 and 1.15 kg/m2 greater, respectively, than daughters of Non-smokers. The adjusted relative risk of short stature was 55% higher in women born to smokers, irrespectively of smoking levels. Maternal smoking had a dose-dependent association with obesity risk, with offspring of Heavier smokers 61% and of Light smokers 37% more likely to be obese than the daughters of Non-smokers. In conclusion, maternal smoking in pregnancy was associated with an increased risk of short stature and obesity in their adult daughters.

Background Maternal smoking impairs fetal growth; however, if postnatal growth differs between children born small for gestational age (SGA) with smoking and non-smoking mother is unknown. Methods Cohort-study of term born children born appropriate for gestational age with non-smoking mother (AGA-NS, n = 30,561), SGA (birthweight <10 th percentile) with smoking mother (SGA-S, n = 171) or SGA with non-smoking mother (SGA-NS, n = 1761). Means of height and weight measurements, collected at birth, 1.5, 3, 4, and 5 years, were compared using a generalized linear mixed effect model. Relative risks of short stature (<10 th percentile) were expressed as adjusted risk ratios (aRR). Results At birth, children born SGA-S were shorter than SGA-NS, but they did not differ in weight. At 1.5 years, SGA-S had reached the same height as SGA-NS. At 5 years, SGA-S were 1.1 cm taller and 1.2 kg heavier than SGA-NS. Compared with AGA-NS, SGA-S did not have increased risk of short stature at 1.5 or 5 years, while SGA-NS had increased risk of short stature at both ages; aRRs 3.0 (95% CI 2.6;3.4) and 2.3 (95% CI 2.0;2.7), respectively. Conclusions Children born SGA-S have a more rapid catch-up growth than SGA-NS. This may have consequences for metabolic and cardiovascular health in children with smoking mothers.

Background-While there is some evidence of elevated blood pressure later in life in preterm survivors, data on adult women are still lacking. Thus, we assessed the associations between preterm birth and blood pressure in young adult women. Methods and Results-We studied 5232 young adult women who volunteered for military service in Sweden between 1990 and 2007. Anthropometric and clinic blood pressure data were collected during the medical examination at the time of conscription. There was a progressive decline in systolic and diastolic blood pressures, as well as in mean arterial pressure, with increasing gestational age. Women born preterm had an adjusted increase in systolic blood pressure of 3.8 mm Hg (95% CI, 2.5-5.1; P<0.0001) and mean arterial pressure of 1.9 mm Hg (95% CI, 0.9-2.8; P 0.0001) compared with young women born at term. Rates of systolic hypertension were also considerably higher in young women born preterm (14.0% versus 8.1%, P<0.0001), as were rates of isolated systolic hypertension. The adjusted relative risk of systolic hypertension in women born preterm was 1.72 (95% CI, 1.26-2.34; P<0.001) that of women born at term or post-term, but there was no significant difference in the risk of diastolic hypertension (adjusted relative risk, 1.60; 95% CI, 0.49-5.20). Conclusions-Young adult women born preterm display elevated systolic blood pressure and an increased risk of hypertension compared with peers born at term or post-term.

Aim This study investigated how maternal birth weight was related to offspring birth weight, as well as to risk of obesity in pregnancy and gestational diabetes.Methods The cohort (N= 305 893) comp ...

Background Preeclampsia is associated with low birth weight, both because of increased risks of preterm and of small-for-gestational-age (SGA) births. Low birth weight is associated with accelerated childhood height gain and cardiovascular diseases later in life. The aim was to investigate if prenatal exposure to preeclampsia is associated with accelerated childhood height gain, also after adjustments for SGA-status and gestational age at birth. Methods In a cohort of children prenatally exposed to preeclampsia (n = 865) or unexposed (n = 22,898) we estimated height gain between birth and five years of age. The mean difference in height gain between exposed and unexposed children was calculated and adjustments were done with linear regression models. Results Children exposed to preeclampsia were on average born shorter than unexposed. Exposed children grew on average two cm more than unexposed from birth to five years of age. After adjustments for maternal characteristics including socioeconomic factors, height, body mass index (BMI) and diabetes, as well as for parents smoking habits, infant’s breastfeeding and childhood obesity, the difference was 1.6 cm (95% CI 1.3–1.9 cm). Further adjustment for SGA birth only slightly attenuated this estimate, but adjustment for gestational age at birth decreased the estimate to 0.5 cm (95% CI 0.1–0.7 cm). Conclusion Prenatal exposure to preeclampsia is associated with accelerated height gain in early childhood. The association seemed independent on SGA-status, but partly related to shorter gestational age at birth.

BACKGROUNDThere is an established association between adverse events during perinatal life and chronic hypertension in adult life. However, disadvantageous conditions often co-exist in the same pregnancy. We investigated single and joint perinatal exposure to preeclampsia, being born small for gestational age (SGA) or preterm and subsequent risk of chronic hypertension.METHODSThe study population consisted of 731 008 primiparous women from Norway and Sweden registered in the Medical Birth Registers, both as infants and as first time mothers between 1967-2009 (Norway) and 1973-2010 (Sweden). Risk of chronic hypertension in early pregnancy was calculated in women with perinatal exposures to preeclampsia, born SGA or preterm by log-binominal regression analysis, and adjusted for maternal age and level of education in the first generation.RESULTSThe rate of chronic hypertension was 0.4%. Risk of chronic hypertension was associated with single perinatal exposure to preeclampsia, being born SGA or preterm with adjusted relative risk (95% confidence interval, CI) of 2.2 (95% CI 1.8, 2.7), 1.1 (95% CI 1.0, 1.3), and 1.3 (95% CI 1.0, 1.5) respectively. The risks increased after joint exposures, with an almost fourfold risk increase after perinatal exposure to preeclampsia and preterm birth. Additional adjustment for BMI and smoking in the second generation in a subset of the cohort only had a minor impact on the results.CONCLUSIONSPerinatal exposure to preeclampsia, being born SGA or preterm is independently associated with increased risk of chronic hypertension. The highest risk was seen after exposure to preeclampsia, especially if combined with SGA or preterm birth.

We examined whether being born preterm was associated with changes in adult anthropometry in women. We assessed data on 201,382 women (born in 1973-1988) from the Swedish Birth Register. The mean age was 26.0 years. Of the women in our cohort, 663 were born very preterm (< 32 weeks of gestation), 8,247 were born moderately preterm (at least 32 weeks but < 37 weeks), and 192,472 were born at term (37-41 weeks). Subgroup analyses were carried out among siblings and also after adjustment for maternal anthropometric data. Statistical tests were 2-sided. Decreasing gestational age was associated with lower height (-1.1 mm per week of gestation; P < 0.0001), so that women who were born very preterm were on average 12 mm shorter than women who were born moderately preterm (P < 0.0001) and 17 mm shorter than women born at term (P < 0.0001). Compared with women who were born at term, those who were born very preterm had 2.9 times higher odds of short stature (< 155.4 cm), and those born moderately preterm had 1.43 times higher odds. Subgroup analyses showed no differences between women born moderately preterm and those born at term but accentuated differences from women born very preterm. Among siblings (n = 2,388), very preterm women were 23 mm shorter than those born at term (P = 0.003), with a 20-mm difference observed in subgroup analyses (n = 27,395) that were adjusted for maternal stature (P < 0.001). A shorter final height was associated with decreasing gestational age, and this association was particularly marked in women born very preterm.

Several studies have demonstrated that mothers with intellectual disability (ID) have a higher prevalence of mental health illness, lower socio-economic status, and a higher risk of alcohol and drug use compared to mothers without ID. The children of mothers with ID are over-represented in child protection and legal proceedings but are generally a less studied group than the mothers. The aim of this study was to investigate if children born to mothers with ID had an increased risk of being diagnosed with mental illness, injuries, and violence compared with children of mothers without ID. The study comprised a population-based cohort of children born in Sweden between 1999 and 2005. Data were collected from the Medical Birth Register and linked with two other national registers; ICD-10 codes were used for medical diagnoses, including ID. The children were followed from birth to seven years of age. In total, 478,577 children were included, of whom 2749 were born to mothers with ID. Children of mothers with ID were at a greater risk of having mental health problems (adjusted odds ratio (OR)=2.02; 95% confidence interval (CI)=1.74–2.35) and ID (OR=4.14; CI=2.95–5.82) in early childhood. They had an increased risk for injuries due to falls (OR=1.15; Cl 1.04–1.27). The largest risk related to trauma was violence and child abuse (OR=3.11; CI=1.89–5.12). In conclusion, children of mothers with ID had an increased risk for injuries, violence, and child abuse. We therefore suggest that parents with ID should receive evidence based support so that their children receive the best care and protection.

Aim: To assess the relationship between severity of small for gestational age (SGA) and the risk of poor school performance, and to investigate whether adult stature modifies this risk. Methods: 1,088,980 Swedish children born at term between 1973 and 1988 were categorized into severe SGA (less than –3 standard deviations (SD) of expected birth weight), moderate SGA (–2.01 to –3 SD), mild SGA (–1.01 to –2 SD), and appropriate for gestational age (–1 to 0.99 SD). The risk of poor school performance at the time of graduation from compulsory school (grades <10th percentile) was calculated using unconditional logistic regression models and adjusted for socio-economic factors. In a sub-analysis, we stratified boys by adult stature, and adjusted for maternal but not paternal height. Results: All SGA groups were significantly associated with an increased risk of poor school performance, with adjusted odds ratios and 95% confidence intervals ranging from 1.85 (1.65–2.07) for severe SGA to 1.25 (1.22–1.28) for mild SGA. In the sub-analysis, all birth weight groups were associated with an increased risk of poor school performance among boys with short stature compared to those with non-short stature. Conclusion: Mild SGA is associated with a significantly increased risk of poor school performance, and the risk increases with severity of SGA. Further, this risk diminishes after adequate catch-up growth.

BACKGROUND:There is increasing evidence that lower maternal stature is associated with shorter gestational length in the offspring. We examined the association between maternal height and the likelihood of delivering preterm babies in a large and homogeneous cohort of Swedish women.METHODS:This study covers antenatal data from the Swedish Medical Birth Register on 192,432 women (aged 26.0 years on average) born at term, from singleton pregnancies, and of Nordic ethnicity. Continuous associations between women's heights and the likelihood of preterm birth in the offspring were evaluated. Stratified analyses were also carried out, separating women into different height categories.RESULTS:Every cm decrease in maternal stature was associated with 0.2 days shortening of gestational age in the offspring (p<0.0001) and increasing odds of having a child born preterm (OR 1.03), very preterm (OR 1.03), or extremely preterm (OR 1.04). Besides, odds of all categories of preterm birth were highest among the shortest women but lowest among the tallest mothers. Specifically, women of short stature (≤155 cm or ≤-2.0 SDS below the population mean) had greater odds of having preterm (OR 1.65) or very preterm (OR 1.47) infants than women of average stature (-0.5 to 0.5 SDS). When compared to women of tall stature (≥179 cm), mothers of short stature had even greater odds of giving birth to preterm (OR 2.07) or very preterm (OR 2.16) infants.CONCLUSIONS:Among Swedish women, decreasing height was associated with a progressive increase in the odds of having an infant born preterm. Maternal short stature is a likely contributing factor to idiopathic preterm births worldwide, possibly due to maternal anatomical constraints.

Background: There is increasing evidence that post-term birth (≥42 weeks of gestation) is associated with adverse long-term outcomes. We assessed whether women born post-term displayed increased risk of overweight and obesity in adulthood. Methods: Data were collected at first antenatal visit (~10–12 weeks of gestation) on singleton Swedish women aged ≥18 years in 1991–2009 (mean age 26.1 years), who were born post-term (n=27,153) or at term (37–41 weeks of gestation; n=184,245). Study outcomes were evaluated for continuous associations with gestational age. Stratified analyses were carried out comparing women born post-term or at term. Analyses were also run with a 2-week buffer between groups to account for possible errors in gestational age estimation, comparing women born very postterm (≥43 weeks of gestation; n=5,761) to those born within a narrower term window (38–40 weeks of gestation; n=130,110). Results: Increasing gestational age was associated with greater adult weight and BMI. Stratified analyses showed that women born post-term were 0.5 kg heavier and had BMI 0.2 kg/m2 greater than those born at term. Differences were more marked between women born very post-term (≥43 weeks) versus a narrower term group (38–40 weeks): 1.0 kg and 0.3 kg/m2. The adjusted relative risks of overweight/obesity and obesity in women born very post-term were 1.13 and 1.12 times higher, respectively, than in those born at term Conclusions: Post-term birth is associated with greater BMI and increased odds of overweight and obesity in adulthood, particularly among women born ≥43 weeks of gestation.

BACKGROUNDThere is increasing evidence that post-term birth (≥42 weeks of gestation) is associated with adverse long-term outcomes. We assessed whether women born post-term displayed increased risk of overweight and obesity in adulthood.METHODSData were collected at first antenatal visit (~10-12 weeks of gestation) on singleton Swedish women aged ≥18 years in 1991-2009 (mean age 26.1 years), who were born post-term (n = 27 153) or at term (37-41 weeks of gestation; n = 184 245). Study outcomes were evaluated for continuous associations with gestational age. Stratified analyses were carried out comparing women born post-term or at term. Analyses were also run with a 2-week buffer between groups to account for possible errors in gestational age estimation, comparing women born very post-term (≥43 weeks of gestation; n = 5761) to those born within a narrower term window (38-40 weeks of gestation; n = 130 110).RESULTSIncreasing gestational age was associated with greater adult weight and body mass index (BMI). Stratified analyses showed that women born post-term were 0.5 kg heavier and had BMI 0.2 kg/m(2) greater than those born at term. Differences were more marked between women born very post-term (≥43 weeks) vs. a narrower term group (38-40 weeks): 1.0 kg and 0.3 kg/m(2) . The adjusted relative risks of overweight/obesity and obesity in women born very post-term were 1.13 and 1.12 times higher, respectively, than in those born at term.CONCLUSIONSPost-term birth is associated with greater BMI and increased risk of overweight and obesity in adulthood, particularly among women born ≥43 weeks of gestation.

Background A number of large studies have shown phenotypic differences between first-borns and later-borns among adult men. In this study, we aimed to assess whether birth order was associated with height and BMI in a large cohort of Swedish women.Methods Information was obtained from antenatal clinic records from the Swedish National Birth Register over 20 years (1991-2009). Maternal anthropometric data early in pregnancy (at approximately 10-12 weeks of gestation) were analysed on 13 406 pairs of sisters who were either first-born or second-born (n=26 812).Results Early in pregnancy, first-born women were of BMI that was 0.57 kg/m(2) (2.4%) greater than their second-born sisters (p<0.0001). In addition, first-borns had greater odds of being overweight (OR 1.29; p<0.0001) or obese (OR 1.40; p<0.0001) than second-borns. First-borns were also negligibly taller (+1.2 mm) than their second-born sisters. Of note, there was a considerable increase in BMI over the 18-year period covered by this study, with an increment of 0.11 kg/m(2) per year (p<0.0001).Conclusions Our study corroborates other large studies on men, and the steady reduction in family size may contribute to the observed increase in adult BMI worldwide.

We examined changes in obesity rates in two generations of Swedish women entering pregnancy, and assessed the effects of maternal body mass index (BMI) on the risk of overweight or obesity among adult daughters. This study covered an intergenerational retrospective cohort of 26,561 Swedish mothers and their 26,561 first-born daughters. There was a 4-fold increase in obesity rates, which rose from 3.1% among women entering pregnancy in 1982-1988 to 12.3% among their daughters in 2000-2008 (p < 0.0001) when entering pregnancy. The greater the maternal BMI, the greater the odds of overweight and/or obesity among daughters. Underweight mothers had half the odds of having an overweight or obese daughter in comparison to mothers of normal BMI (p < 0.0001). In contrast, the odds ratio of obese mothers having obese daughters was 3.94 (p < 0.0001). This study showed a strong association between maternal obesity and the risk of obesity among their first-born daughters. In addition, we observed a considerable increase in obesity rates across generations in mother-daughter pairs of Swedish women entering pregnancy. Thus, it is important to have preventative strategies in place to halt the worsening intergenerational cycle of obesity.

BACKGROUND:An increased risk of poor school performance for children born preterm has been shown in many studies, but whether this increase is attributable to preterm birth per se or to other factors associated with preterm birth has not been resolved. METHODS:We used data from the Swedish Medical Birth Register, the Longitudinal Integration Database for Sickness Insurance and Labor Market Study, the Swedish Multigeneration Register, and the National School Register to link records comprising the Swedish birth cohorts from 1974 through 1991. Linear regression was used to assess the association between gestational duration and school performance, both with and without controlling for parental and socioeconomic factors. In a restricted analysis, we compared siblings only with each other. RESULTS:Preterm birth was strongly and negatively correlated with school performance. The distribution of school grades for children born at 31-33 weeks was on average 3.85 (95% confidence interval = -4.36 to -3.35) centiles lower than for children born at 40 weeks. For births at 22-24 weeks, the corresponding figure was -23.15 (-30.32 to -15.97). When taking confounders into account, the association remained. When restricting the analysis to siblings, however, the association between school performance and preterm birth after week 30 vanished completely, whereas it remained, less pronounced, for preterm birth before 30 weeks of gestation. CONCLUSIONS:Our study suggests that the association between school performance and preterm birth after 30 gestational weeks is attributable to factors other than preterm birth per se.

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