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.

What is the best long-term treatment modality for immature permanent teeth with pulp necrosis and apical periodontitis?

PURPOSE: To evaluate and assess the current knowledge about apexification and regenerative techniques as a meaningful treatment modality and to map the scientific evidence for the efficacy of both methods for the management of traumatised immature teeth with pulp necrosis and apical periodontitis. METHODS: This systematic review searched five databases: PubMed, Web of Science, Cochrane Library, Ovid (Medline), and Embase. Published articles written in English were considered for inclusion. The following keywords were used: Regenerative endodontic treatment OR regenerat* OR revital* OR endodontic regeneration OR regenerative endodontics OR pulp revascularization OR revasculari* OR 'traumatized immature teeth'. Only peer-reviewed studies with a study size of at least 20 cases followed up for 24 months were included. Eligibility assessment was performed independently in a blinded manner by three reviewers and disagreements were resolved by consensus. Subgroup analyses were performed on three clinical outcomes: survival, success, and continued root development. RESULTS: Seven full texts out of 1359 citations were included and conventional content analysis was performed. Most of the identified citations were case reports and case series. CONCLUSIONS: In the present systematic review, the qualitative analysis revealed that both regenerative and apexification techniques had equal rates of success and survival and proved to be effective in the treatment of immature necrotic permanent teeth. Endodontic regenerative techniques appear to be superior to apexification techniques in terms of stimulation of root maturation, i.e. root wall thickening and root lengthening. Knowledge gaps were identified regarding the treatment and follow-up protocols for both techniques.

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.

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.

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.

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.

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.

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.

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 hypertensive disease and risk of dementia and cardiovascular disease in women aged 65 years or older: a cohort study.

OBJECTIVE: The primary aim was to study pregnancy hypertensive disease and subsequent risk of dementia. The second aim was to study if the increased risks of cardiovascular disease (CVD) and stroke after pregnancy hypertensive disease persist in an elderly population. DESIGN: Cohort study. SETTING: Sweden. POPULATION OR SAMPLE: 3232 women 65 years or older (mean 71 years) at inclusion. METHODS: Cox proportional hazards regression analyses were used to calculate risks of dementia, CVD and/or stroke for women exposed to pregnancy hypertensive disease. Exposure data were collected from an interview at inclusion during the years 1998-2002. Outcome data were collected from the National Patient Register and Cause of Death Register from the year of inclusion until the end of 2010. Age at inclusion was set as a time-dependent variable, and adjustments were made for body mass index, education and smoking. MAIN OUTCOME MEASURES: Dementia, CVD, stroke. RESULTS: During the years of follow-up, 7.6% of the women exposed to pregnancy hypertensive disease received a diagnosis of dementia, compared with 7.4% among unexposed women (HR 1.19; 95% CI 0.79 to 1.73). The corresponding rates for CVD were 22.9% for exposed women and 19.0% for unexposed women (HR 1.29; 95% CI 1.02 to 1.61), and for stroke 13.4% for exposed women and 10.7% for unexposed women (HR 1.36; 95% CI 1.00 to 1.81). CONCLUSIONS: There was no increased risk of dementia after self-reported pregnancy hypertensive disease in our cohort. We found that the previously reported increased risk of CVD and stroke after pregnancy hypertensive disease persists in an older population.

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.

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.

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.

In vivo ³¹P-MR spectroscopy in normal pregnancy, early and late preeclampsia: a study of placental metabolism.

INTRODUCTION: Preeclampsia affects about 3% of pregnancies and the placenta is believed to play a major role in its pathophysiology. Lately, the role of the placenta has been hypothesised to be more pronounced in preeclampsia of early (<34 weeks) rather than late (≥ 34 weeks) onset. (31)P Magnetic Resonance Spectroscopy (MRS) enables non-invasive, in vivo studies of placental metabolism. Our aim was to study placental energy and membrane metabolism in women with normal pregnancies and those with early and late onset preeclampsia. METHODS: The study population included fourteen women with preeclampsia (five with early onset and nine with late onset preeclampsia) and sixteen women with normal pregnancy (seven with early and nine with late pregnancy). All women underwent a (31)P-MRS examination of the placenta. RESULTS: The phosphodiester (PDE) spectral intensity fraction of the total (31)P signal and the phosphodiester/phosphomonoester (PDE/PME) spectral intensity ratio was higher in early onset preeclampsia than in early normal pregnancy (p = 0.03 and p = 0.02). In normal pregnancy the PDE spectral intensity fraction and the PDE/PME spectral intensity ratio increased with increasing gestational age (p = 0.006 and p = 0.001). DISCUSSION: Since PDE and PME are related to cell membrane degradation and formation, respectively, our findings indicate increased cell degradation and maybe also decreased cell proliferation in early onset preeclampsia compared to early normal pregnancy, and with increasing gestational age in normal pregnancy. CONCLUSIONS: Our findings could be explained by increased apoptosis due to ischaemia in early onset preeclampsia and also increased apoptosis with increasing gestational age in normal pregnancy.

Placental perfusion in normal pregnancy and early and late preeclampsia: a magnetic resonance imaging study.

OBJECTIVE: Our primary aim was to investigate if women with early or late preeclampsia have different placental perfusion compared with normal pregnancies. A secondary aim was to investigate if placental perfusion changes with increasing gestational age in normal pregnancy. METHODS: The study population included thirteen women with preeclampsia (five with early and eight with late preeclampsia) and nineteen women with normal pregnancy (ten with early and nine with late pregnancy). Early was defined as <34 weeks and late as ≥ 34 weeks gestation. All women underwent a magnetic resonance imaging (MRI) examination including a diffusion weighted sequence at 1.5 T. The perfusion fraction was calculated. RESULTS: Women with early preeclampsia had a smaller placental perfusion fraction (p = 0.001) and women with late preeclampsia had a larger placental perfusion fraction (p = 0.011), compared to women with normal pregnancies at the corresponding gestational age. The placental perfusion fraction decreased with increasing gestational age in normal pregnancies (p = 0.001). CONCLUSION: Both early and late preeclampsia differ in placental perfusion from normal pregnant women. Observed differences are however in the opposite direction, suggesting differences in pathophysiology. Placental perfusion decreases with increasing gestational age in normal pregnancy.

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.

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.