Risk of pre-eclampsia after gastric bypass: a matched cohort study.

OBJECTIVE: To investigate whether gastric bypass before pregnancy is associated with reduced risk of pre-eclampsia. DESIGN: Nationwide matched cohort study. SETTING: Swedish national health care. POPULATION: A total of 843 667 singleton pregnancies without pre-pregnancy hypertension were identified in the Swedish Medical Birth Register between 2007 and 2014, of which 2930 had a history of gastric bypass and a pre-surgery weight available from the Scandinavian Obesity Surgery Registry. Two matched control groups (pre-surgery and early-pregnancy body mass index [BMI]) were propensity score matched separately for nulliparous and parous births, to post-gastric bypass pregnancies (npre-surgery-BMI = 2634:2634/nearly-pregnancy-BMI = 2766:2766) on pre-surgery/early-pregnancy BMI, diabetes status (pre-surgery/pre-conception), maternal age, early-pregnancy smoking status, educational level, height, country of birth, delivery year and history of pre-eclampsia. MAIN OUTCOME MEASURES: Pre-eclampsia categorised into any, preterm onset (<37+0 weeks) and term onset (≥37+0 weeks). RESULTS: In post-gastric bypass pregnancies, mean pre-surgery BMI was 42.9 kg/m2 and mean BMI loss between surgery and early pregnancy was 14.0 kg/m2 (39 kg). Post-gastric bypass pregnancies had lower risk of pre-eclampsia compared with pre-surgery BMI-matched controls (1.7 versus 9.7 per 100 pregnancies; hazard ratio [HR] 0.21, 95% CI 0.15-0.28) and early-pregnancy BMI-matched controls (1.9 versus 5.0 per 100 pregnancies; HR 0.44, 95% CI 0.33-0.60). Although relative risks for pre-eclampsia for post-gastric bypass pregnancies versus pre-surgery matched controls was similar, absolute risk differences (RD) were significantly greater for nulliparous women (RD -13.6 per 100 pregnancies, 95% CI -16.1 to -11.2) versus parous women (RD -4.4 per 100 pregnancies, 95% CI -5.7 to -3.1). CONCLUSION: We found that gastric bypass was associated with lower risk of pre-eclampsia, with the largest absolute risk reduction among nulliparous women. TWEETABLE ABSTRACT: In this large study including two comparison groups matched for pre-surgery or early-pregnancy BMI, gastric bypass was associated with lower risk of pre-eclampsia.

Polycystic ovary syndrome and risk of stillbirth: a nationwide register-based study.

OBJECTIVE: To investigate whether polycystic ovary syndrome (PCOS) is associated with increased risk of stillbirth and whether any such association is linked to PCOS with a severe hyperandrogenic profile. DESIGN: Nationwide register-based cohort study. SETTING: Sweden. POPULATION: The cohort consisted of women giving birth to singleton infants in 1997-2015. All women with a diagnosis of PCOS in the period 1997-2017 and a randomly selected reference group of women without PCOS diagnosis were included. PCOS with a severe hyperandrogenic profile was defined as a PCOS diagnosis with at least two dispensations of prescribed anti-androgens during 2005-2017. METHODS: The risk of stillbirth in women with PCOS was estimated through multiple logistic regression, using women without PCOS as a reference. Risks were expressed as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs), adjusted for maternal age, parity, body mass index, type-1 diabetes, educational level and country of birth. MAIN OUTCOME MEASURES: Stillbirth, at ≥22 weeks of gestation in 2008-2015 and at ≥28 weeks of gestation in 1997-2007. RESULTS: Compared with women without PCOS (n = 241 750), women with PCOS (n = 41 851) had a 50% increased risk of stillbirth (aOR 1.50, 95% CI 1.28-1.77). The incidence of stillbirth in women with PCOS was particularly increased at term. Women with PCOS and a severe hyperandrogenic profile (n = 13 713) did not have a stronger association with stillbirth than women with PCOS who did not have such a profile. CONCLUSIONS: PCOS is associated with stillbirth and should be considered as a possible risk factor in antenatal care. Further research is warranted to investigate possible causal mechanisms. TWEETABLE ABSTRACT: Women with PCOS have increased risk of stillbirth, and the incidence is particularly increased at term.

SSRI use during pregnancy and risk for postpartum haemorrhage: a national register-based cohort study in Sweden.

OBJECTIVE: Evaluate whether selective serotonin reuptake inhibitor (SSRI) use during pregnancy, as well as prior or current untreated psychiatric illness is associated with postpartum haemorrhage (PPH). DESIGN: National register-based cohort study based on data from the Swedish Pregnancy Register. SETTING: Sweden, nationwide coverage. POPULATION: A total of 31 159 pregnant women with singleton deliveries after gestational week 22+0 between January 2013 and July 2017. METHODS: Pregnant women with self-reported SSRI use at any time point during pregnancy were compared with non-SSRI-treated women with prior or current psychiatric illness, as well as wiith healthy women with no psychiatric illness or reporting SSRI use. MAIN OUTCOME MEASURES: Postpartum haemorrhage defined as blood loss >1000 ml during the first 2 hours postpartum reported by the delivering midwife or obstetrician. RESULTS: Postpartum haemorrhage prevalence was 7.0% among healthy women, 7.6% among women with prior or current psychiatric illness and 9.1% among women treated with SSRI. The unadjusted odds for PPH among women with prior or current psychiatric illness and women on SSRI treatment were increased by 9 and 34%, respectively, compared with healthy unmedicated women without a history of psychiatric illness (odds ratio [OR] 1.09, 95% CI 1.04-1.14 and OR 1.34, 95% CI 1.24-1.44, respectively). The estimates remained unchanged after adjustment for several confounders (such as maternal age, body mass index [BMI], parity, prior caesarean section, smoking, occupation and country of birth) and potential covariates (such as delivery mode, polyhydramnion, preterm delivery, labour dystocia and infant birthweight >4000 g). CONCLUSIONS: Higher risk for PPH was observed both among women treated with SSRI during pregnancy and among women with prior or current psychiatric illness. TWEETABLE ABSTRACT: SSRI use at any point during pregnancy and prior or current history of psychiatric illness was associated with an increased likelihood for PPH.

Association of maternal attention deficit hyperactivity disorder and preterm birth: a cohort study.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) affects 3-7% of women of childbearing age. Whether ADHD is associated with an increased risk of preterm birth is unclear. DESIGN: National register-based cohort study. SETTING: Sweden. POPULATION: Nulliparous women giving birth to singleton infants 2007-2014 (n = 377 381). METHODS: Women were considered to have ADHD if they had been dispensed at least one prescription for ADHD medication, i.e. a central nervous system stimulant or non-stimulant drugs for ADHD, prior to, during or after pregnancy (2005-2014). Women with ADHD were compared with women without ADHD in regard to prevalence, severity and mode of onset of preterm birth. Logistic regression models were used, estimating adjusted odds ratios (aOR) with 95% confidence intervals (CI). Adjustments were made for maternal age and country of birth (model 1), and in addition for body mass index (BMI), education, alcohol or substance use disorders, and pre-gestational medical and psychiatric co-morbidity (model 2). MAIN OUTCOME MEASURES: Preterm birth (<37 weeks). RESULTS: During the study period, 6327 (1.7%) women gave birth and had ADHD according to our definition. These women had a higher rate of preterm birth compared with women without ADHD (7.3 versus 5.8%, aOR model 2: 1.17; 95% CI 1.05-1.30). ADHD was particularly associated with very (<32 weeks) preterm births, and associations were seen with both spontaneous and medically indicated onsets. CONCLUSIONS: Women with ADHD (i.e. who had been dispensed ADHD medication at any time in 2005-2014) had an increased risk of preterm birth. TWEETABLE ABSTRACT: Women with ADHD have a higher risk of preterm birth but most of it is due to modifiable risk factors.

Interpregnancy weight change and recurrence of gestational diabetes mellitus: a population-based cohort study.

OBJECTIVE: To estimate recurrence risk of gestational diabetes mellitus (GDM) by interpregnancy weight change. DESIGN: Population-based cohort study. SETTING AND POPULATION: Data from the Swedish (1992-2010) and the Norwegian (2006-2014) Medical Birth Registries on 2763 women with GDM in first pregnancy, registered with their first two singleton births and available information on height and weight. METHODS: Interpregnancy weight change (BMI in second pregnancy minus BMI in first pregnancy) was categorised in six groups by BMI units. Relative risks (RRs) of GDM recurrence were obtained by general linear models for the binary family and adjusted for confounders. Analyses were stratified by BMI in first pregnancy (<25 and ≥25 kg/m2 ). MAIN OUTCOME MEASURE: GDM in second pregnancy. RESULTS: Among overweight/obese women (BMI ≥25), recurrence risk of GDM decreased in women who reduced their BMI by 1-2 units (relative risk [RR] 0.80, 95% CI 0.65-0.99) and >2 units (RR 0.72, 95% CI 0.59-0.89) and increased if BMI increased by ≥4 units (RR 1.26, 95% CI 1.05-1.51) compared wth women with stable BMI (-1 to 1 units). In normal weight women (BMI <25), risk of GDM recurrence increased if BMI increased by 2-4 units (RR 1.32, 95% CI 1.08-1.60) and ≥4 units (RR 1.61, 95% CI 1.28-2.02) compared with women with stable BMI. CONCLUSION: Interpregnancy weight loss reduced risk of GDM recurrence in overweight/obese women. Weight gain between pregnancies increased recurrence risk for GDM in both normal and overweight/obese women. Our findings highlight the importance of weight management in the interconception window in women with a history of GDM. TWEETABLE ABSTRACT: Interpregnancy weight loss reduces recurrence of gestational diabetes mellitus in overweight/obese women.

Prenatal exposures and birth indices, and subsequent risk of polycystic ovary syndrome: a national registry-based cohort study.

OBJECTIVE: To study the associations between prenatal exposures and risk of developing polycystic ovary syndrome (PCOS). DESIGN: National registry-based cohort study. SETTING: Sweden. POPULATION: Girls born in Sweden during the years 1982-1995 (n = 681 123). METHODS: The girls were followed until the year 2010 for a diagnosis of PCOS. We estimated the associations between maternal body mass index (BMI), smoking, and size at birth with the risk of developing a PCOS diagnosis. Risks were calculated by adjusted hazard ratio (aHR) and 95% confidence intervals (95% CIs). MAIN OUTCOME MEASURES: A diagnosis of PCOS at 15 years of age or later. RESULTS: During the follow-up period 3738 girls were diagnosed with PCOS (0.54%). Girls with mothers who were overweight or obese had 1.5-2.0 times higher risk of PCOS (aHR 1.52, 95% CI 1.36-1.70; aHR 1.97, 95% CI 1.61-2.41, respectively), compared with girls born to mothers of normal weight. The risk of PCOS was increased if the mother smoked during pregnancy (1-9 cigarettes/day, aHR 1.31, 95% CI 1.18-1.47; ≥10 cigarettes/day, aHR 1.44, 95% CI 1.27-1.64). Being born small for gestational age (SGA) was associated with a later diagnosis of PCOS in crude estimates, but the association was not significant after adjusting for maternal factors. CONCLUSIONS: Maternal smoking and increased BMI appear to increase the risk of PCOS in offspring. The association between SGA and the development of PCOS appears to be mediated by maternal factors. TWEETABLE ABSTRACT: Smoking during pregnancy and high maternal BMI are associated with PCOS diagnosis in the offspring.

Elevated diastolic blood pressure until mid-gestation is associated with preeclampsia and small-for-gestational-age birth: a population-based register study.

BACKGROUND: Gestational hemodynamic adaptations, including lowered blood pressure (BP) until mid-gestation, might benefit placental function. We hypothesized that elevated BP from early to mid-gestation increases risks of preeclampsia and small-for-gestational-age birth (SGA), especially in women who also deliver preterm (< 37 weeks). METHODS: In 64,490 healthy primiparous women, the change in systolic and diastolic BP from early to mid-gestation was categorized into lowered (≥ 0 mmHg decreased), and elevated (≥ 1 mmHg increase). Women with chronic hypertension, chronic renal disease, pre-gestational diabetes and systemic lupus erythematosus were excluded. Risks of preeclampsia and SGA birth were estimated by logistic regression, presented with adjusted odds ratio (aOR) and 95% confidence intervals (CI). Further, the effect of BP change in combination with stage 1 hypertension (systolic BP 130-139 mmHg or diastolic BP 80-89 mmHg) in early gestation was estimated. RESULTS: Compared to women with lowered diastolic BP from early to mid-gestation, those with elevated diastolic BP had increased risks of preeclampsia (aOR: 1.8 [1.6-2.0]) and SGA birth (aOR: 1.3 [1.2-1.5]). The risk estimates were higher for preeclampsia and SGA when combined with preterm birth (aORs: 2.2 [1.8-2.8] and 2.3 [1.8-3.0], respectively). The highest rate of preeclampsia (9.9%) was seen in women with stage 1 hypertension in early gestation and a diastolic BP that was elevated until mid-gestation. This was three times the risk, compared to women with normal BP in early gestation and a diastolic BP that was decreased until mid-gestation. The association between elevated systolic BP from early to mid-gestation and preeclampsia was weak, and no significant association was found between changes in systolic BP and SGA births. CONCLUSION: Elevated diastolic BP from early to mid-gestation was associated with increased risks of preeclampsia and SGA, especially for women also delivering preterm. The results may imply that the diastolic BP starts to increase around mid-gestation in women later developing placental dysfunction disorders.

The inherited risk of retained placenta: a population based cohort study.

OBJECTIVE: To investigate whether retained placenta in the first generation is associated with an increased risk of retained placenta in the second generation. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: Using linked generational data from the Swedish Medical Birth Register 1973-2012, we identified 494 000 second-generation births with information on the birth of the mother (first-generation index birth). For 292 897 of these births there was information also on the birth of the father. METHODS: Risk of retained placenta in the second generation was calculated as adjusted odds ratios (aOR) by unconditional logistic regression with 95% confidence intervals (95% CI) according to whether retained placenta occurred in a first generation birth or not. MAIN OUTCOME: Retained placenta in the second generation. RESULTS: The risk of retained placenta in a second-generation birth was increased if retained placenta had occurred at the mother's own birth (aOR 1.66, 95% CI 1.52-1.82), at the birth of one of her siblings (aOR 1.58, 95% CI 1.43-1.76) or both (aOR 2.75, 95% CI 2.18-3.46). The risk was slightly increased if retained placenta had occurred at the birth of the father (aOR 1.23, 95% CI 1.07-1.41). For preterm births in both generations, the risk of retained placenta in the second generation was increased six-fold if retained placenta had occurred at the mother's birth (OR 6.55, 95% CI 2.68-16.02). CONCLUSION: There is an intergenerational recurrence of retained placenta on the maternal and most likely also on the paternal side. The recurrence risk seems strongest in preterm pregnancies. TWEETABLE ABSTRACT: A population-based cohort study suggests that there is an intergenerational recurrence of retained placenta.

Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia.

OBJECTIVE: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease later in life. In cases with PE there is a substantial increase in levels of the antiangiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased levels of the proangiogenic factor placental growth factor (PlGF). Elevated levels of sFlt-1 are also found in individuals with cardiovascular disease. The aims of this study were to assess levels of sFlt-1, PlGF and the sFlt-1/PlGF ratio and their correlation with signs of arterial aging by measuring the common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE. METHODS: Serum sFlt-1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22-MHz) ultrasonography in 55 women at PE diagnosis and in 64 women with normal pregnancy at a similar gestational age, with reassessment at 1 year postpartum. RESULTS: During pregnancy, higher levels of sFlt-1, lower levels of PlGF, a thicker intima, a thinner media and a higher I/M ratio of the CCA were found in women with PE vs controls (all P < 0.0001). Further, sFlt-1 and the sFlt-1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all P < 0.0001). At 1 year postpartum, levels of sFlt-1 and the sFlt-1/PlGF ratio had decreased in both groups; however, their levels in the PE group were still higher than in the controls (P = 0.001 and < 0.0001, respectively). Levels of sFlt-1 and the sFlt-1/PlGF ratio remained positively correlated with intima thickness and I/M ratio at 1 year postpartum. CONCLUSIONS: Higher sFlt-1 levels and sFlt-1/PlGF ratio in women with PE were positively associated with signs of arterial aging during pregnancy. At 1 year postpartum, sFlt-1 levels and the sFlt-1/PlGF ratio were still higher in the PE group and were associated with the degree of arterial aging. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Prolonged second stage of labour, maternal infectious disease, urinary retention and other complications in the early postpartum period.

OBJECTIVE: To study the association between duration of second stage of labour and risks of maternal complications (infection, urinary retention, haematoma or ruptured sutures) in the early postpartum period. DESIGN: Population-based cohort study. SETTING AND SAMPLE: We included 72 593 mothers with singleton vaginal deliveries at ≥37 weeks of gestation in cephalic presentation, using the obstetric database from the Stockholm-Gotland region in Sweden, 2008-12. METHODS: Logistic regression analysis. Odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated and adjustments were made for maternal age, body mass index, height, smoking, cohabitation, gestational age, labour induction, epidural analgesia and oxytocin augmentation. RESULTS: Rates of any complication varied by parity from 7.3% in parous women with previous caesarean section, 4.8% in primiparas and 1.7% in parous women with no previous caesarean section. Compared with a second stage <1 hour, the adjusted ORs for any complication (95% CI) in primiparas were for 1 to <2 hours 1.28 (1.11-1.47); 2 to <3 hours 1.54 (1.32-1.79), 3 to <4 hours 1.63 (1.38-1.93) and ≥4 hours 2.08 (1.74-2.49). The corresponding adjusted ORs for parous women without previous caesarean were 2.27 (1.78-2.90), 2.97 (2.09-4.22), 3.65 (2.25-5.94) and 3.16 (1.44-6.94), respectively. The adjusted ORs for women with previous caesarean were for 1 to <2 hours 1.62 (1.13-2.32); 2 to <3 hours 1.56 (1.00-2.43), 3 to <4 hours 2.42 (1.52-3.87), and ≥4 hours 2.31 (1.25-4.24). CONCLUSIONS: Risks of maternal complications in the postpartum period increase with duration of second stage of labour also after accounting for maternal, pregnancy and delivery characteristics. Special attention has to be given to parous women with previous caesarean deliveries.

Maternal tobacco use and extremely premature birth - a population-based cohort study.

OBJECTIVE: To study the associations of maternal tobacco use (smoking or use of snuff) and risk of extremely preterm birth, and if tobacco cessation before antenatal booking influences this risk. To study the association between tobacco use and spontaneous or medically indicated onset of delivery. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: All live singleton births, registered in the Swedish Medical Birth Register, 1999-2012. METHODS: Odds ratios (OR) with 95% confidence intervals (CI) were calculated using multiple logistic regression analysis. MAIN OUTCOME MEASURES: Extremely preterm birth (<28 weeks of gestation), very preterm birth (28-31 weeks), moderately preterm birth (32-36 weeks). RESULTS: Maternal snuff use (OR 1.58; 95% CI: 1.14-2.21) and smoking (OR 1.61; 95% CI: 1.39-1.87 and OR 1.91; 95% CI: 1.53-2.39 for moderate and heavy smoking, respectively) were associated with an increased risk of extremely preterm birth. When cessation of tobacco use was obtained there was no increased risk of preterm birth. Snuff use was associated with a twofold risk increase of medically indicated extremely preterm birth, whereas smoking was associated with increased risks of both medically indicated and spontaneous extremely preterm birth. CONCLUSIONS: Snuff use and smoking in pregnancy were associated with increased risks of extremely preterm birth. Women who stopped using tobacco before the antenatal booking had no increased risk. These findings indicate that nicotine, the common substance in cigarettes and snuff, is involved in the mechanisms behind preterm birth. The use of nicotine should be minimized in pregnancy. TWEETABLE ABSTRACT: Tobacco use increases risk of extremely preterm birth. Cessation is preventive. Avoid nicotine in pregnancy.

Pregnancy and perinatal outcomes in women with polycystic ovary syndrome and twin births: a population-based cohort study.

OBJECTIVE: To investigate pregnancy and perinatal outcomes in twin births among women with and without polycystic ovary syndrome (PCOS) diagnosis. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: We identified 20,965 women with twin births between 1995 and 2009 of whom 226 had a PCOS diagnosis through linkage between the Swedish Medical Birth Register and the Swedish National Patient Register. METHODS: Calculating risk ratios (RR) with 95% confidence intervals (CI) using a log-binomial regression model and hazard ratios (HR) with 95% CI for preterm birth. MAIN OUTCOME MEASURES: Preterm birth, low birthweight, caesarean section, pre-eclampsia, Apgar score <7 at 5 minutes and perinatal mortality. RESULTS: PCOS diagnosis in twin pregnancy was associated with increased risk of preterm delivery (51% versus 43%, RR 1.18 [95% CI 1.03-1.37]), particularly spontaneous preterm delivery (37% versus 28%; RR 1.30 [95% CI 1.09-1.55]) and very preterm birth (<32 weeks) (14% versus 8%, RR 1.62 [95% CI 1.10-2.37]). Twins of PCOS mothers had more often low birthweight (48% versus 39%, adjusted RR 1.40 [95% CI 1.09-1.80]). This difference disappeared when adjusting for gestational age. No risk difference was found for caesarean section, pre-eclampsia, low 5-minute Apgar score or perinatal mortality. CONCLUSIONS: The risk of preterm delivery in twin pregnancies is increased by having a PCOS diagnosis. This should be considered in risk estimation and antenatal follow-up of twin pregnancies.

Magnetic resonance imaging-estimated placental perfusion in fetal growth assessment.

OBJECTIVE: To evaluate in-vivo placental perfusion fraction, estimated by magnetic resonance imaging (MRI), as a marker of placental function. METHODS: A study population of 35 pregnant women, of whom 13 had pre-eclampsia (PE), were examined at 22-40 weeks' gestation. Within a 24-h period, each woman underwent an MRI diffusion-weighted sequence (from which we calculated the placental perfusion fraction), venous blood sampling and an ultrasound examination including estimation of fetal weight, amniotic fluid index and Doppler velocity measurements. The perfusion fractions in pregnancies with and without fetal growth restriction were compared and correlations between the perfusion fraction and ultrasound estimates and plasma markers were estimated using linear regression. The associations between the placental perfusion fraction and ultrasound estimates were modified by the presence of PE (P < 0.05) and therefore we included an interaction term between PE and covariates in the models. RESULTS: The median placental perfusion fractions in pregnancies with and without fetal growth restriction were 21% and 32%, respectively (P = 0.005). The correlations between placental perfusion fraction and ultrasound estimates and plasma markers were highly significant (P = 0.002 and P = 0.0001, respectively). The highest coefficient of determination (R(2) = 0.56) for placental perfusion fraction was found for a model that included pulsatility index in the ductus venosus, plasma level of soluble fms-like tyrosine kinase-1, estimated fetal weight and presence of PE. CONCLUSION: The placental perfusion fraction has the potential to contribute to the clinical assessment of cases with placental insufficiency.

Loss of a close family member the year before or during pregnancy and the risk of placental abruption: a cohort study from Denmark and Sweden.

BACKGROUND: Maternal stress during pregnancy is associated with a modestly increased risk of fetal growth restriction and pre-eclampsia. Since placental abruption shares similar pathophysiological mechanisms and risk factors with fetal growth restriction and pre-eclampsia, we hypothesized that maternal stress may be implicated in abruption risk. We investigated the association between maternal bereavement during pregnancy and placental abruption. METHOD: We studied singleton births in Denmark (1978-2008) and Sweden (1973-2006) (n = 5,103,272). In nationwide registries, we obtained data on death of women's close family members (older children, siblings, parents, and partners), abruption and potential confounders. RESULTS: A total of 30,312 (6/1000) pregnancies in the cohort were diagnosed with placental abruption. Among normotensive women, death of a child the year before or during pregnancy was associated with a 54% increased odds of abruption [95% confidence interval (CI) 1.30-1.82]; the increased odds were restricted to women who lost a child the year before or during the first trimester in pregnancy. In the group with chronic hypertension, death of a child the year before or in the first trimester of pregnancy was associated with eight-fold increased odds of abruption (odds ratio 8.17, 95% CI 3.17-21.10). Death of other relatives was not associated with abruption risk. CONCLUSIONS: Loss of a child the year before or in the first trimester of pregnancy was associated with an increased risk of abruption, especially among women with chronic hypertension. Studies are needed to investigate the effect of less severe, but more frequent, sources of stress on placental abruption risk.

Retained placenta is associated with pre-eclampsia, stillbirth, giving birth to a small-for-gestational-age infant, and spontaneous preterm birth: a national register-based study.

OBJECTIVE: To evaluate whether defective placentation disorders, i.e. pre-eclampsia, stillbirth, small for gestational age (SGA), and spontaneous preterm birth, are associated with risk of retained placenta. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: Primiparous women in Sweden with singleton vaginal deliveries between 1997 and 2009 at 32-41 weeks of gestation (n = 386,607), without placental abruption or infants with congenital malformations. METHODS: Risks were calculated as odds ratios (ORs) by unconditional logistic regression with 95% confidence intervals (95% CIs) after adjustments for maternal, delivery, and infant characteristics. MAIN OUTCOME MEASURE: Retained placenta, defined by the presence of both a diagnostic code (of retained placenta) and a procedure code (for the manual removal of the placenta). RESULTS: The overall rate of retained placenta was 2.17%. The risk of retained placenta was increased for women with pre-eclampsia (adjusted OR, aOR, 1.37, 95% CI 1.21-1.54), stillbirth (aOR 1.71, 95% CI 1.28-2.29), SGA birth (aOR 1.47, 95% CI 1.28-1.70), and spontaneous preterm birth (32-34 weeks of gestation, aOR 2.35, 95% CI 1.97-2.81; 35-36 weeks of gestation, aOR 1.55, 95% CI 1.37-1.75). The risk was further increased for women with preterm pre-eclampsia (aOR 1.69, 95% CI 1.25-2.28) and preterm SGA birth (aOR 2.19, 95% CI 1.42-3.38). There was no association between preterm stillbirth (aOR 1.10, 95% CI 0.63-1.92) and retained placenta, but the exposed group comprised only 15 cases. CONCLUSIONS: Defective placentation disorders are associated with an increased risk of retained placenta. Whether these relationships indicate a common pathophysiology remains to be investigated.

Risk of retained placenta in women previously delivered by caesarean section: a population-based cohort study.

OBJECTIVE: To evaluate whether women with a caesarean section at their first delivery have an increased risk of retained placenta at their second delivery. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: All women with their first and second singleton deliveries in Sweden during the years 1994-2006 (n = 258,608). Women with caesarean section or placental abruption in their second pregnancy were not included in the study population. METHODS: The risk of retained placenta at second delivery was estimated for women with a first delivery by caesarean section (n = 19,458), using women with a first vaginal delivery as reference (n = 239,150). Risks were calculated as odds ratios by unconditional logistic regression analysis with 95% confidence intervals (95%) after adjustments for maternal, delivery, and infant characteristics. MAIN OUTCOME MEASURES: Retained placenta with normal (≤1000 ml) and heavy (>1000 ml) bleeding. RESULTS: The overall rate of retained placenta was 2.07%. In women with a previous caesarean section and in women with previous vaginal delivery, the corresponding rates were 3.44% and 1.96%, respectively. Compared with women with a previous vaginal delivery, women with a previous caesarean section had an increased risk of retained placenta (adjusted OR 1.45; 95% CI 1.32-1.59), and the association was more pronounced for retained placenta with heavy bleeding (adjusted OR 1.61; 95% CI 1.44-1.79). CONCLUSIONS: Our report shows an increased risk for retained placenta in women previously delivered by caesarean section, a finding that should be considered in discussions of mode of delivery.

Thicknesses of individual layers of artery wall indicate increased cardiovascular risk in severe pre-eclampsia.

OBJECTIVE: To assess whether thicknesses of the intima and media in the common carotid artery (CCA) and the intima/media ratio (I/M) indicate an increased cardiovascular risk in non-pregnant women with a history of previous severe pre-eclampsia. METHODS: Thicknesses of the CCA intima and media layers were measured using non-invasive high-frequency (22 MHz) ultrasound in 42 women with a history of severe pre-eclampsia and 44 women with previous normal pregnancy. RESULTS: Women with a history of severe pre-eclampsia had a thicker CCA intima and a higher I/M than had women with previous normal pregnancy, also after adjustment for mean arterial pressure, body mass index and CCA intima-media thickness (IMT) (all P < 0.0001). CCA-IMT did not differ significantly between groups. In receiver-operating characteristics curve analysis, intima thickness and I/M clearly discriminated between women with and those without previous pre-eclampsia (area under the receiver-operating characteristics curve (AUC), 0.98 and 0.93), whereas CCA-IMT did not (AUC, 0.52). CONCLUSIONS: CCA individual intima and media thicknesses as well as I/M, but not CCA-IMT, reflect the known increased long-term cardiovascular risk of pre-eclampsia. Estimation of individual CCA layers using high-frequency ultrasound appears preferable to measuring CCA-IMT for investigating arterial effects and the increased cardiovascular risk in women with a history of severe pre-eclampsia.

Changes in snuff and smoking habits in Swedish pregnant women and risk for small for gestational age births.

OBJECTIVE: To examine associations between antenatal exposure to Swedish oral moist snuff (which includes essentially only nicotine) and to smoking and risks of small-for-gestational-age (SGA) births and to compare risks among women who stopped or continued using snuff or smoking during pregnancy. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: All live singleton births in Sweden 1999-2010. METHODS: Odds ratios (OR) with 95% confidence intervals (CI) were calculated using multiple logistic regression analysis. MAIN OUTCOME MEASURES: SGA birth, also stratified into preterm (≤36 weeks of gestation) and term (≥37 weeks of gestation) SGA births. RESULTS: Compared with non-tobacco users in early pregnancy, snuff users and above all smokers in early pregnancy had increased risks of SGA births: adjusted ORs (95% CI) were 1.26 (1.09-1.46) and 2.55 (2.43-2.67), respectively). Snuff use had, if anything, a stronger association with preterm SGA than term SGA, whereas the opposite was true for smoking. Compared with non-tobacco users, women who stopped using snuff before their first visit to antenatal care had no increased risks of preterm or term SGA, and women who stopped using snuff later during pregnancy had no increased risk of term SGA. Smoking cessation early in pregnancy was associated with a larger reduction in risk than smoking cessation later in pregnancy. CONCLUSIONS: As both smoking and snuff use influence risk of SGA, both nicotine but above all tobacco combustion products are involved in the mechanisms by which maternal smoking increases the risk of SGA.

Hyperemesis gravidarum and risks of placental dysfunction disorders: a population-based cohort study.

OBJECTIVE: To study whether pregnancies complicated by hyperemesis gravidarum in the first (<12 weeks) or second (12-21 weeks) trimester are associated with placental dysfunction disorders. DESIGN: Population-based cohort study. SETTING: Sweden. POPULATION: All pregnancies in the Swedish Medical Birth Register estimated to have started on 1 January 1997 or later and ended in a single birth on 31 December 2009 or earlier (n = 1 156 050). METHODS: Odds ratios with 95% confidence intervals were estimated for placental dysfunction disorders in women with an inpatient diagnosis of hyperemesis gravidarum, using women without inpatient diagnosis of hyperemesis gravidarum as reference. Risks were adjusted for maternal age, parity, body mass index, height, smoking, cohabitation with the infant's father, infant's sex, mother's country of birth, education, presence of hyperthyreosis, pregestational diabetes mellitus, chronic hypertension and year of infant birth. MAIN OUTCOME MEASURES: Placental dysfunction disorders, i.e. pre-eclampsia, placental abruption, stillbirth and small for gestational age (SGA). RESULTS: Women with hyperemesis gravidarum in the first trimester had only a slightly increased risk of pre-eclampsia. Women with hyperemesis gravidarum with first admission in the second trimester had a more than doubled risk of preterm (<37 weeks) pre-eclampsia, a threefold increased risk of placental abruption and a 39% increased risk of an SGA birth (adjusted odds ratios [95% confidence intervals] were: 2.09 [1.38-3.16], 3.07 [1.88-5.00] and 1.39 [1.06-1.83], respectively). CONCLUSIONS: There is an association between hyperemesis gravidarum and placental dysfunction disorders, which is especially strong for women with hyperemesis gravidarum in the second trimester.

High birth weight and obesity--a vicious circle across generations.

OBJECTIVES: Rates of high birth weight infants, overweight and obese children and adults are increasing. The associations between birth weight and adult weight may have consequences for the obesity epidemic across generations. We examined the association between mothers' birth weight for gestational age and adult body mass index (BMI) and these factors' joint effect on risk of having a large-for-gestational-age (LGA) offspring (>+2 s.d. above the mean). DESIGN: A cohort of 162 676 mothers and their first-born offspring with birth information recorded on mothers and offspring in the nation-wide Swedish Medical Birth Register 1973-2006. RESULTS: Compared with mothers with appropriate birth weight for gestational age (AGA; -1 to +1 s.d.), mothers born LGA had increased risks of overweight (BMI 25.0-29.9; odds ratio (OR), 1.50; 95% CI 1.39-1.61), obesity class I (BMI 30.0-34.9; OR 1.77; 95% CI 1.59-1.98), obesity class II (BMI 35.0-39.9; OR 2.77; 95% CI 2.37-3.24) and obesity class III (BMI ≥40.0; OR 2.04; 95% CI 1.49-2.80). In each stratum of mother's birth weight for gestational age, risk of having an LGA offspring increased with mother's BMI. The risk of an LGA offspring was highest among women with a high (≥30) BMI who also had a high birth weight for gestational age (>+1 s.d.). In these groups, the ORs for LGA offspring ranged from 5 to 14 when compared with mothers born AGA with normal BMI (≤24.9). However, the strongest increase in risk by BMI was seen among mothers born SGA: the OR of having an LGA offspring was 13 times as high among SGA mothers with BMI ≥35.0 compared with the OR among SGA mothers with normal BMI (ORs=4.61 and 0.35, respectively). CONCLUSIONS: Prenatal conditions are important for the obesity epidemic. Prevention of LGA births may contribute to curtail the intergenerational vicious cycle of obesity.