Safety of low weight gain or weight loss in pregnancies with class 1, 2, and 3 obesity: a population-based cohort study.

BACKGROUND: There are concerns that current gestational weight gain recommendations for women with obesity are too high and that guidelines should differ on the basis of severity of obesity. In this study we investigated the safety of gestational weight gain below current recommendations or weight loss in pregnancies with obesity, and evaluated whether separate guidelines are needed for different obesity classes. METHODS: In this population-based cohort study, we used electronic medical records from the Stockholm-Gotland Perinatal Cohort study to identify pregnancies with obesity (early pregnancy BMI before 14 weeks' gestation ≥30 kg/m2) among singleton pregnancies that delivered between Jan 1, 2008, and Dec 31, 2015. The pregnancy records were linked with Swedish national health-care register data up to Dec 31, 2019. Gestational weight gain was calculated as the last measured weight before or at delivery minus early pregnancy weight (at <14 weeks' gestation), and standardised for gestational age into z-scores. We used Poisson regression to assess the association of gestational weight gain z-score with a composite outcome of: stillbirth, infant death, large for gestational age and small for gestational age at birth, preterm birth, unplanned caesarean delivery, gestational diabetes, pre-eclampsia, excess postpartum weight retention, and new-onset longer-term maternal cardiometabolic disease after pregnancy, weighted to account for event severity. We calculated rate ratios (RRs) for our composite adverse outcome along the weight gain z-score continuum, compared with a reference of the current lower limit for gestational weight gain recommended by the US Institute of Medicine (IOM; 5 kg at term). RRs were adjusted for confounding factors (maternal age, height, parity, early pregnancy BMI, early pregnancy smoking status, prepregnancy cardiovascular disease or diabetes, education, cohabitation status, and Nordic country of birth). FINDINGS: Our cohort comprised 15 760 pregnancies with obesity, followed up for a median of 7·9 years (IQR 5·8-9·4). 11 667 (74·0%) pregnancies had class 1 obesity, 3160 (20·1%) had class 2 obesity, and 933 (5·9%) had class 3 obesity. Among these pregnancies, 1623 (13·9%), 786 (24·9%), and 310 (33·2%), respectively, had weight gain during pregnancy below the lower limit of the IOM recommendation (5 kg). In pregnancies with class 1 or 2 obesity, gestational weight gain values below the lower limit of the IOM recommendation or weight loss did not increase risk of the adverse composite outcome (eg, at weight gain z-score -2·4, corresponding to 0 kg at 40 weeks: adjusted RR 0·97 [95% CI 0·89-1·06] in obesity class 1 and 0·96 [0·86-1·08] in obesity class 2). In pregnancies with class 3 obesity, weight gain values below the IOM limit or weight loss were associated with reduced risk of the adverse composite outcome (eg, adjusted RR 0·81 [0·71-0·89] at weight gain z-score -2·4, or 0 kg). INTERPRETATION: Our findings support calls to lower or remove the lower limit of current IOM recommendations for pregnant women with obesity, and suggest that separate guidelines for class 3 obesity might be warranted. FUNDING: Karolinska Institutet and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Pregnancy Weight Gain After Gastric Bypass or Sleeve Gastrectomy.

Importance: Pregnancy weight gain may affect the association of bariatric surgery with postsurgery pregnancy outcomes. However, the association of pregnancy weight gain with bariatric surgery is unclear. Objective: To compare pregnancy weight gain among women with a history of bariatric surgery vs those without and to investigate whether pregnancy weight gain differs by surgical procedure, surgery-to-conception interval, and/or surgery-to-conception weight loss. Design, Setting, and Participants: This nationwide, population-based matched cohort study was conducted in Sweden from 2014 to 2021. Singleton pregnancies with a history of bariatric surgery were propensity score matched (1:1) to pregnancies without such a history according to early-pregnancy body mass index (BMI), prepregnancy diabetes, prepregnancy hypertension, maternal age, smoking status, education level, height, country of birth, and delivery year. In addition, post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy. Data analysis was performed from November 2022 to May 2023. Exposure: History of bariatric surgery. Main Outcomes and Measures: Pregnancy weight gain was standardized by gestational age into early-pregnancy BMI-specific z scores. Results: This study included 12 776 pregnancies, of which 6388 had a history of bariatric surgery and 6388 were matched controls. The mean (SD) age was 31.6 (4.9) years for the surgery group and 31.4 (5.2) for the matched controls, with an early-pregnancy mean (SD) BMI of 29.4 (5.2) in both groups. Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls. The differences in pregnancy weight gain z score values between the 2 groups were -0.33 (95% CI, -0.43 to -0.23) for normal weight, -0.33 (95% CI, -0.40 to -0.27) for overweight, -0.21 (95% CI, -0.29 to -0.13) for obese class I, -0.16 (95% CI, -0.29 to -0.03) for obese class II, and -0.08 (95% CI, -0.28 to 0.13) for obese class III. Pregnancy weight gain did not differ by surgical procedure. A shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss was associated with lower pregnancy weight gain. Conclusions and Relevance: In this nationwide matched cohort study, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls with similar early-pregnancy characteristics. Pregnancy weight gain was lower in those with a shorter surgery-to-conception interval or lower surgery-to-conception weight loss, but did not differ by surgical procedure.

Association between SARS-CoV-2 infection and newly diagnosed hypertension during pregnancy: prospective, population based cohort study.

Objective: To study the association between SARS-CoV-2 infection and newly diagnosed hypertension during pregnancy. Design: Prospective, population based cohort study. Setting: All singleton pregnancies after 22 completed gestational weeks registered in the Swedish Pregnancy Register and the Medical Birth Registry of Norway, from 1 March 2020 to 24 May 2022. Participants: 312 456 individuals available for analysis (201 770 in Sweden and 110 686 in Norway), with pregnancies that reached 42 completed gestational weeks by the end of follow-up in the pregnancy registries, excluding individuals with SARS-CoV-2 infection before pregnancy and those with a diagnosis of pre-existing hypertension or onset of hypertension before 20 gestational weeks. Main outcome measures: Newly diagnosed hypertension during pregnancy was defined as a composite outcome of a diagnosis of gestational hypertension, pre-eclampsia, HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome, or eclampsia, from gestational week 20 to one week after delivery. The association between SARS-CoV-2 infection and hypertension during pregnancy was investigated with a stratified Cox proportional hazard model, adjusting for maternal age, body mass index, parity, smoking, region of birth, education, income, coexisting medical conditions, previous hypertension during pregnancy, number of healthcare visits during the past year, and vaccination against SARS-CoV-2. Pre-eclampsia was also analysed as a separate outcome. Results: Of 312 456 individuals available for analysis, 8% (n=24 566) had SARS-CoV-2 infection any time during pregnancy, 6% (n=18 051) had a diagnosis of hypertension during pregnancy, and 3% (9899) had pre-eclampsia. SARS-CoV-2 infection during pregnancy was not associated with an increased risk of hypertension during pregnancy (adjusted hazard ratio 0.99, 95% confidence interval 0.93 to 1.04) or pre-eclampsia (0.98, 0.87 to 1.10). The results were similar for SARS-CoV-2 infection in all gestational trimesters and in different time periods that corresponded to dominance of different variants of the SARS-CoV-2 virus. Conclusions: This population based study did not find any evidence of an association between SARS-CoV-2 infection during pregnancy and an increased risk of hypertension during pregnancy or pre-eclampsia.

Pregnancy Outcomes in Women With Psoriatic Arthritis in Relation to Presence and Timing of Antirheumatic Treatment.

OBJECTIVE: To evaluate pregnancy outcomes in relation to antirheumatic treatment before and during pregnancy, as a proxy of disease severity in pregnant women with psoriatic arthritis (PsA), compared to those without PsA. METHODS: Our study focused on a Swedish nationwide registry-based cohort study that included 921 PsA pregnancies and 9,210 non-PsA pregnancies occurring between 2007 and 2017 (matched 1:10 based on maternal age, year of delivery, and parity). We estimated adjusted odds ratios (ORs) overall, with 95% confidence intervals (95% CIs), and stratified by presence, timing, and type of antirheumatic treatment. Adjustments were made for maternal body mass index, smoking, education level, and country of birth. The outcome of preterm birth was also stratified by parity. RESULTS: Pregnant women with PsA versus those without PsA were more obese, more often smokers, and more frequently had a diagnosis of pregestational hypertension and diabetes mellitus. Increased risks in PsA pregnancies versus non-PsA pregnancies were primarily preterm birth (adjusted OR 1.69 [95% CI 1.27-2.24]) and cesarean delivery (adjusted OR 1.77 [95% CI 1.43-2.20] for elective delivery, and adjusted OR 1.42 [95% CI 1.10-1.84] for emergency delivery). The risks differed according to the presence, timing, and type of antirheumatic treatment, with the most increased risk in PsA pregnancies (versus non-PsA) occurring with antirheumatic treatment during pregnancy (adjusted OR 2.30 [95% CI 1.49-3.56] for preterm birth). The corresponding adjusted OR for preterm birth in women with PsA who were exposed specifically to biologic treatment during pregnancy was 4.49 [95% CI 2.60-7.79]. Risk of preterm birth was primarily increased in first pregnancies. CONCLUSION: Compared to non-PsA pregnancies, risks of preterm birth and cesarean delivery were mostly increased in those exposed to antirheumatic treatment during pregnancy, especially biologic treatments. As parity influences the risk of preterm birth in women with PsA, special attention to first pregnancies is warranted. Women with PsA should receive individualized monitoring during pregnancy.

Long-term risk of anaemia after bariatric surgery: results from the Swedish Obese Subjects study.

BACKGROUND: Nutritional deficiencies, such as iron and vitamin B12 deficiencies, are potential adverse consequences of bariatric surgery. Long-term data on anaemia after bariatric surgery are largely lacking. We aimed to investigate the risk of anaemia, iron and vitamin B12 deficiency anaemia, and vitamin B12 deficiency over 20 years in individuals who had bariatric surgery or received usual obesity care. METHODS: The prospective, controlled Swedish Obese Subjects study recruited people with obesity via recruitment campaigns in the mass media and at primary health-care centres, and was done at 480 primary health-care centres and in 25 surgical departments in Sweden. Eligible participants were aged 37-60 years and had a BMI of either 34 kg/m2 or more (for men) or 38 kg/m2 or more (for women). Participants were excluded if they had undergone previous bariatric surgery or had contraindicating conditions. Two main groups were formed: those who chose bariatric surgery, the type of which was determined by the operating surgeon, and a contemporaneously matched control group, created by use of 18 matching variables, who received usual non-surgical obesity care that ranged from lifestyle advice to no treatment. Haemoglobin concentration was measured during examination visits at baseline and at 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years of follow-up. Anaemia was defined as a haemoglobin concentration of less than 120 g/L for women and 130 g/L for men. The primary, non-specified outcome was the incidence of anaemia, and was assessed in the as-treated population, which comprised only patients who received the actual treatment. The associations between treatment type and anaemia are expressed as unadjusted hazard ratios (HRs) and HRs adjusted for age, sex, BMI, menopausal status, education, diabetes, and hypertension, with 95% CIs. This study is registered in ClinicalTrials.gov, NCT01479452, and is closed to new participants, with follow-up ongoing. FINDINGS: Between Sept 1, 1987, and Jan 31, 2001, 6905 individuals were assessed for eligibility, of whom 5335 were eligible. Of these, we included 2007 patients who chose bariatric surgery (266 in the gastric bypass group, 1365 in the vertical-banded gastroplasty group, and 376 in the gastric banding group) and 2040 matched controls who received usual obesity care. During a maximum of 20 years and a median of 10 years (IQR 3-20) of follow-up, there were 133 anaemia events in the gastric bypass group, 359 in the vertical-banded gastroplasty group, 101 in the gastric banding group, and 261 in the control group. Compared with the control group (13 cases per 1000 person-years, 95% CI 11-14), the incidence of anaemia was higher in the gastric bypass group (64 cases per 1000 person-years, 53-74; HR 5·05, 95% CI 3·94-6·48; p<0·0001), the vertical-banded gastroplasty group (23 cases per 1000 person-years, 21-26; 2·67, 2·25-3·18; p<0·0001), and the gastric banding group (26 per 1000 person-years, 21-31; 2·76, 2·15-3·52; p<0·0001). These associations remained after adjustment. INTERPRETATION: Our findings highlight the increased risk of anaemia after bariatric surgery and the importance of long-term compliance to nutritional supplementation and monitoring to enable prevention and early detection of serious nutritional deficiencies after bariatric surgery. FUNDING: Swedish Research Council, the Swedish state under the agreement between the Swedish Government and the county councils, the Swedish Diabetes Foundation, the Swedish Heart-Lung Foundation, and the Novo Nordisk Foundation.

Gestational weight gain and delivery outcomes: A population-based cohort study.

BACKGROUND: Gestational weight gain is a modifiable factor that could impact maternal and infant health. However, its effect on delivery outcomes is not well established. OBJECTIVES: To investigate the associations between gestational weight gain and delivery outcomes stratified by early-pregnancy body mass index (BMI). METHODS: The study population included singleton livebirths in the Stockholm-Gotland obstetric cohort (January 2008 to October 2014; n = 174 953). The exposure was total gestational weight gain standardised into gestational-age-specific z-scores by using previously defined Swedish pregnancy weight gain-for-gestational age charts. The outcomes included caesarean delivery (overall, elective, and emergency), instrumental vaginal delivery, induction of labour, and postpartum haemorrhage. Confounders included maternal age, maternal height, parity, smoking status, cohabitation status, chronic hypertension, and pre-pregnancy diabetes. Logistic regression models with marginal standardisation were used to estimate risk ratios (RR) with 95% confidence intervals (CI) for each delivery outcome stratified by early-pregnancy BMI. RESULTS: Above average weight gain (z-score ≥ 0.50 SD) increased risks of caesarean delivery (from RR 1.08, 95% CI 1.00, 1.15 to RR 1.45, 95% CI 1.35, 1.55 across BMI groups), induction of labour (from RR 1.14, 95% CI 1.04, 1.23 to RR 1.38, 95% CI 1.25, 1.51 across BMI groups except underweight), and postpartum haemorrhage (from RR 1.13, 95% CI 1.07, 1.19 to RR 1.25, 95% CI 1.09, 1.41 among normal and overweight). Below average weight gain (z-score <-0.50 SD) decreased caesarean delivery risk (from RR 0.77, 95% CI 0.61, 0.93 to RR 0.89, 95% CI 0.84, 0.95 across BMI groups except underweight). CONCLUSIONS: In normal and overweight women, the risks of caesarean delivery, induction of labour, and postpartum haemorrhage increased with gestational weight gain. In obese women, higher gestational weight gain increased risks of caesarean delivery and induction of labour. Low gestational weight gain reduced risk of caesarean delivery in all BMI groups except underweight.

Body mass index in early pregnancy and future risk of severe liver disease: a population-based cohort study.

BACKGROUND: In young men, high body mass index (BMI) has been linked to liver disease later in life, but it is unclear if this also applies to women. AIM: To study the association between BMI early in life and development of liver disease later in life in women. METHODS: We obtained data on early pregnancy BMI from 1 139 458 Swedish women between 1992 and 2015. National registers were used to ascertain incident severe liver disease, defined as cirrhosis, decompensated liver disease (hepatocellular carcinoma, oesophageal varices, hepatorenal syndrome or hepatic encephalopathy) or liver failure. A Cox regression model was used to investigate associations of BMI with incident severe liver disease adjusting for maternal age, calendar year, country of birth, smoking, civil status and education. RESULTS: During an average follow-up of 13.8 years, 774 women developed severe liver disease. Compared to women with a low normal BMI (18.5-22.4), an increased risk of severe liver disease was found in women with BMI between 22.5 and 24.9 kg/m2 (adjusted hazard ratio [aHR] 1.25, 95% CI 1.04-1.50), 25.0 and 29.9 kg/m2 (aHR 1.27, 95% CI 1.05-1.53) and BMI ≥ 30 kg/m2 (aHR 1.77, 95% CI 1.40-2.24). When examining BMI as a continuous variable, the aHR increased by 4% per kg/m2 (95% CI 1.02-1.05). A diagnosis of diabetes was associated with an increased risk of severe liver disease independent of baseline BMI. CONCLUSION: A high BMI early in life in women is associated with a dose-dependent, increased risk for future severe liver disease.

Delivery outcomes in term births after bariatric surgery: Population-based matched cohort study.

BACKGROUND: Obesity increases the risk of adverse delivery outcomes. Whether weight loss induced by bariatric surgery influences these risks remains to be determined. The objective was to investigate the risk of adverse delivery outcomes among post-surgery women compared with women without bariatric surgery history but with similar characteristics. METHODS AND FINDINGS: We identified 801,443 singleton live-born term births (≥37 gestational weeks) in the Swedish Medical Birth Register between 1 January 2006 and 31 December 2013, of which 1,929 were in women with a history of bariatric surgery and a pre-surgery weight available from the Scandinavian Obesity Surgery Registry. For each post-surgery delivery, up to 5 control deliveries were matched by maternal pre-surgery BMI (early-pregnancy BMI used for controls), age, parity, smoking, education, height, country of birth, and delivery year (N post-surgery deliveries:matched controls = 1,431:4,476). The main outcome measures were mode of delivery, induction of labor, post-term pregnancy (≥42 + 0 gestational weeks), epidural analgesia, fetal distress, labor dystocia, peripartum infection, obstetric anal sphincter injury (perineal tear grade III-IV), and postpartum hemorrhage. Among the women with a history of bariatric surgery, the mean pre-surgery BMI was 42.6 kg/m2, the median surgery-to-conception interval was 1.4 years, and the mean BMI loss between surgery and early pregnancy was 13.5 kg/m2 (38 kg). Compared to matched control women, post-surgery women were less likely to have cesarean delivery (18.2% versus 25.0%, risk ratio [RR] 0.70, 95% CI 0.60-0.80), especially emergency cesarean (6.8% versus 15.1%, RR 0.40, 95% CI 0.31-0.51). Post-surgery women also had lower risks of instrumental delivery (5.0% versus 6.5%, RR 0.73, 95% CI 0.53-0.98), induction of labor (23.4% versus 34.0%, RR 0.68, 95% CI 0.59-0.78), post-term pregnancy (4.2% versus 10.3%, RR 0.40, 95% CI 0.30-0.53), obstetric anal sphincter injury (1.5% versus 2.9%, RR 0.46, 95% CI 0.25-0.81), and postpartum hemorrhage (4.6% versus 8.0%, RR 0.58, 95% CI 0.44-0.76). Since this study was not randomized, a limitation is the possibility of selection bias, despite our efforts using careful matching. CONCLUSIONS: Bariatric-surgery-induced weight loss was associated with lower risks for adverse delivery outcomes in term births.

Mediterranean diet and risk of rheumatoid arthritis: a population-based case-control study.

BACKGROUND: The Mediterranean diet has been associated with lower mortality and lower risk of cardiovascular diseases and cancer. Although its components have been analysed in several studies, only one study has specifically investigated the association between Mediterranean diet and risk of rheumatoid arthritis (RA), and reported no association. METHODS: Data on 1721 patients with incident RA (cases) and 3667 controls, matched on age, gender and residential area, from the Swedish epidemiological investigation of RA (EIRA), a population-based case-control study, were analysed using conditional logistic regression. The Mediterranean diet score, ranging from 0 to 9, was calculated from a 124-item food frequency questionnaire. RESULTS: In the EIRA study (median age of participants 53 years), 24.1% of the patients and 28.2% of the controls had high adherence to the Mediterranean diet (a score between 6 and 9). After adjustments for body mass index, educational level, physical activity, use of dietary supplements, energy intake, and smoking, high adherence reduced the odds of developing RA by 21% (OR 0.79; 95% CI 0.65-0.96) as compared to low adherence (a score between 0 and 2). The OR was even lower among men (OR 0.49; 95% CI 0.33-0.73), but no significant association was found among women (OR 0.94; 95% CI 0.74-1.18). An association between high diet score and low risk of RA was observed in rheumatoid factor (RF)-positive (OR 0.69; 95% CI 0.54-0.88), but not RF-negative RA (OR 0.96; 95% CI 0.68-1.34), and in RA characterised by presence of antibodies to citrullinated peptides (ACPA), but not in ACPA-negative RA. CONCLUSIONS: In this large population-based case-control study, the Mediterranean diet score was inversely associated with risk of RA. However, an association was only found among men and only in seropositive RA.

Risk of suicide and non-fatal self-harm after bariatric surgery: results from two matched cohort studies.

BACKGROUND: Bariatric surgery reduces mortality, but might have adverse effects on mental health. We assessed the risk of suicide and self-harm after bariatric surgery compared with non-surgical obesity treatment. METHODS: Suicide and non-fatal self-harm events retrieved from nationwide Swedish registers were examined in two cohorts. The non-randomised, prospective Swedish Obese Subjects (SOS) study compared bariatric surgery (n=2010; 1369 vertical-banded gastroplasty, 376 gastric banding, and 265 gastric bypass) with usual care (n=2037; recruitment 1987-2001). The second cohort consisted of individuals from the Scandinavian Obesity Surgery Registry (SOReg; n=20 256 patients who had gastric bypass) matched to individuals treated with intensive lifestyle modification (n=16 162; intervention 2006-13) on baseline BMI, age, sex, education level, diabetes, cardiovascular disease, history of self-harm, substance misuse, antidepressant use, anxiolytics use, and psychiatric health-care contacts. FINDINGS: During 68 528 person-years (median 18; IQR 14-21) in the SOS study, suicides or non-fatal self-harm events were higher in the surgery group (n=87) than in the control group (n=49; adjusted hazard ratio [aHR] 1·78, 95% CI 1·23-2·57; p=0·0021); of these events, nine and three were suicides, respectively (3·06, 0·79-11·88; p=0·11). In analyses by primary procedure type, increased risk of suicide or non-fatal self-harm was identified for gastric bypass (3·48, 1·65-7·31; p=0·0010), gastric banding (2·43, 1·23-4·82; p=0·011), and vertical-banded gastroplasty (2·25, 1·37-3·71; p=0·0015) compared with controls. Out of nine deaths by suicide in the SOS surgery group, five occurred after gastric bypass (two primary and three converted procedures). During 149 582 person-years (median 3·9; IQR 2·8-5·2), more suicides or non-fatal self-harm events were reported in the SOReg gastric bypass group (n=341) than in the intensive lifestyle group (n=84; aHR 3·16, 2·46-4·06; p<0·0001); of these events, 33 and five were suicides, respectively (5·17, 1·86-14·37; p=0·0017). In SOS, substance misuse during follow-up was recorded in 48% (39/81) of patients treated with surgery and 28% (13/47) of controls with non-fatal self-harm events (p=0·023). Correspondingly, substance misuse during follow-up was recorded in 51% (162/316) of participants in the SOReg gastric bypass group and 29% (23/80) of participants in the intensive lifestyle group with non-fatal self-harm events (p=0·0003). The risk of suicide and self-harm was not associated with poor weight loss outcome. INTERPRETATION: Bariatric surgery was associated with suicide and non-fatal self-harm. However, the absolute risks were low and do not justify a general discouragement of bariatric surgery. The findings indicate a need for thorough preoperative psychiatric history assessment along with provision of information about increased risk of self-harm following surgery. Moreover, the findings call for postoperative surveillance with particular attention to mental health. FUNDING: US National Institutes of Health and Swedish Research Council.

Change in Use of Sleep Medications After Gastric Bypass Surgery or Intensive Lifestyle Treatment in Adults with Obesity.

OBJECTIVE: To examine the change in use of hypnotics and/or sedatives after gastric bypass surgery or intensive lifestyle modification in adults with obesity. METHODS: Adults with obesity who underwent gastric bypass surgery or initiated intensive lifestyle modification between 2007 and 2012 were identified through the Scandinavian Obesity Surgery Registry and a Swedish commercial weight loss database. The two cohorts were matched on BMI, age, sex, education, history of hypnotics and/or sedatives use, and treatment year (surgery n = 20,626; lifestyle n = 11,973; 77% women, mean age 41 years, mean BMI 41 kg/m2 ). The proportion of participants with filled hypnotics and/or sedatives prescriptions was compared yearly for 3 years. RESULTS: In the matched treatment cohorts, 4% had filled prescriptions for hypnotics and/or sedatives during the year before treatment. At 1 year follow-up, following an average weight loss of 37 kg and 18 kg in the surgery and intensive lifestyle cohorts, respectively, this proportion had increased to 7% in the surgery cohort but remained at 4% in the intensive lifestyle cohort (risk ratio 1.7; 95% CI: 1.4-2.1); at 2 years, the proportion had increased to 11% versus 5% (risk ratio 2.0; 95% CI: 1.7-2.4); and at 3 years, it had increased to 14% versus 6% (risk ratio 2.2; 95% CI: 1.9-2.6). CONCLUSIONS: Gastric bypass surgery was associated with increased use of hypnotics and/or sedatives compared with intensive lifestyle modification.

Pregnancy outcome in joint hypermobility syndrome and Ehlers-Danlos syndrome.

INTRODUCTION: An increased risk of preterm birth in women with joint hypermobility syndrome or Ehlers-Danlos syndrome is suspected. MATERIAL AND METHODS: In this nationwide cohort study from 1997 through 2011, women with either joint hypermobility syndrome or Ehlers-Danlos syndrome or both disorders were identified through the Swedish Patient Register, and linked to the Medical Birth Register. Thereby, 314 singleton births to women with joint hypermobility syndrome/Ehlers-Danlos syndrome before delivery were identified. These births were compared with 1 247 864 singleton births to women without a diagnosis of joint hypermobility syndrome/Ehlers-Danlos syndrome. We used logistic regression, adjusted for maternal age, smoking, parity, and year of birth, to calculate adjusted odds ratios for adverse pregnancy outcomes. RESULTS: Maternal joint hypermobility syndrome/Ehlers-Danlos syndrome was not associated with any of our outcomes: preterm birth (adjusted odds ratio = 0.6, 95% confidence interval 0.3-1.2), preterm premature rupture of membranes (adjusted odds ratio = 0.8; 95% confidence interval 0.3-2.2), cesarean section (adjusted odds ratio = 0.9, 95% confidence interval 0.7-1.2), stillbirth (adjusted odds ratio = 1.1, 95% confidence interval 0.2-7.9), low Apgar score (adjusted odds ratio = 1.6, 95% confidence interval 0.7-3.6), small for gestational age (adjusted odds ratio = 0.9, 95% confidence interval 0.4-1.8) or large for gestational age (adjusted odds ratio = 1.2, 95% confidence interval 0.6-2.1). Examining only women with Ehlers-Danlos syndrome (n = 62), we found a higher risk of induction of labor (adjusted odds ratio = 2.6; 95% confidence interval 1.4-4.6) and amniotomy (adjusted odds ratio = 3.8; 95% confidence interval 2.0-7.1). No excess risks for adverse pregnancy outcome were seen in joint hypermobility syndrome. CONCLUSION: Women with joint hypermobility syndrome/Ehlers-Danlos syndrome do not seem to be at increased risk of adverse pregnancy outcome.

The Impact of Small for Gestational Age Births in Early and Late Preeclamptic Pregnancies for Preeclampsia Recurrence: a Cohort Study of Successive Pregnancies in Sweden.

BACKGROUND: Results from uterine artery Doppler investigations suggest that the aetiology of late preeclampsia with fetal growth restriction may be more similar to the aetiology of early preeclampsia than with late preeclampsia without fetal growth restriction. We hypothesised that a small-for-gestational-age (SGA) birth in a late preeclamptic pregnancy may be associated with increased subsequent risk of early preeclampsia. We also studied effects of maternal factors on risks of preeclampsia recurrence. METHODS: In a nation-wide Swedish cohort study of first and second consecutive single births between 1992 and 2012, we identified 22 473 mothers with preeclampsia in their first pregnancy. We calculated relative risks (RR), and 95% confidence intervals (CI), to investigate associations between subtypes of preeclampsia in the first pregnancy and risks of early (<34 weeks) and late (≥34 weeks) preeclampsia in the second pregnancy. RESULTS: In women with a previous late preeclampsia, a co-occurring SGA birth was associated with an increased risk of subsequent early preeclampsia (adjusted RR 2.85, 95% CI 1.93, 4.20), but not of subsequent late preeclampsia. Among women with a previous early preeclampsia, a co-occurring SGA birth was not associated with increased subsequent risks of early or late preeclampsia. Interpregnancy weight gain was associated with increased risks of early and late preeclampsia in the second pregnancy. CONCLUSIONS: Late preeclampsia combined with fetal growth restriction may be regarded as an ischaemic placental disease. Given the high absolute risk of preeclampsia recurrence, preventing weight gain may be especially important in women with previous preeclampsia.

Does disease activity at start of biologic therapy influence work-loss in RA patients?

OBJECTIVE: To compare work-loss in RA patients starting their first biologic with high vs moderate disease activity. METHODS: We identified all RA patients aged 20-63 years in the Swedish Biologics Register who started their first biologic 2007-09 with high disease activity (DAS28 >5.1; n = 868) or moderate disease activity (DAS28 3.2-5.1; n = 854). Work days lost, defined as sick leave and disability pension days from the Swedish Social Insurance Agency, were assessed over 5 years after first bio-start. We estimated between-group mean differences adjusted for age, sex, calendar year, education level, disease duration, comorbidities and work-loss the month before bio-start. RESULTS: During 5 years after anti-TNF start, mean monthly work days lost declined from 16.0 to 9.2 (42%; P < 0.001) in patients with high disease activity at baseline and from 12.0 to 7.2 (40%; P < 0.001) in patients with moderate disease activity, with no between-group difference (adjusted mean difference 0.81; 95% CI - 0.44, 2.05). Accumulated 5-year work-loss was, however, higher in the high activity group (724 vs 548 days; adjusted mean difference 70; 95% CI 20, 120), but after stratification on baseline disability pension status, no differences in accumulated work-loss were detected. CONCLUSION: Substantial work-loss was seen in both patients with high and patients with moderate disease activity at anti-TNF start, with a 5-year decline in mean monthly work days lost by ∼40% in both groups and no between-group difference. Accumulated work-loss over 5 years was higher in the high-activity group, which may be explained by differences in baseline disability pension status.

Does disease activity at the start of biologic therapy influence health care costs in patients with RA?

OBJECTIVE: To investigate whether disease activity at baseline influences health care costs in patients with RA initiating biologic treatment. METHODS: In the Swedish Biologics Register, we identified patients with RA with baseline 28-joint DAS (DAS28) recorded and starting their first biologic in 2007-11 [n = 1638 with moderate disease activity (DAS28 3.2-5.1) and n = 1870 with high disease activity (DAS28 > 5.1)]. Data on inpatient and outpatient care and prescription drugs were retrieved from nationwide registers. Mean cost differences were estimated adjusted for age, sex and costs the year before treatment start. RESULTS: Patients with high (vs moderate) disease activity were older (60 vs 56 years; P < 0.001), but did not differ in sex distribution (75 vs 74% women; P = 0.99) or disease duration (10 vs 10 years; P = 0.13). The year after initiation of biologics, patients with high (vs moderate) baseline disease activity accumulated 9% higher health care costs, but the difference was not statistically significant after adjustment [€19,333 vs €17,810; adjusted difference €870 (95% CI -2, 1742)]. In the subgroup of patients with up to 4 years of follow-up data, decreasing costs were observed over the follow-up time, but no difference was found between patients with high compared with moderate baseline disease activity [€13,704 vs €12,349; adjusted difference 878 (95% CI -364, 2120)]. Irrespective of baseline disease activity, health care costs were approximately three times higher the year after initiation of biologics than the year before due to increased drug costs. CONCLUSION: Over up to 4 years of follow-up, no difference in health care costs was found after adjustment in patients starting their first biologic treatment with high vs moderate baseline disease activity.

Outcomes of pregnancy after bariatric surgery.

BACKGROUND: Maternal obesity is associated with increased risks of gestational diabetes, large-for-gestational-age infants, preterm birth, congenital malformations, and stillbirth. The risks of these outcomes among women who have undergone bariatric surgery are unclear. METHODS: We identified 627,693 singleton pregnancies in the Swedish Medical Birth Register from 2006 through 2011, of which 670 occurred in women who had previously undergone bariatric surgery and for whom presurgery weight was documented. For each pregnancy after bariatric surgery, up to five control pregnancies were matched for the mother's presurgery body-mass index (BMI; we used early-pregnancy BMI in the controls), age, parity, smoking history, educational level, and delivery year. We assessed the risks of gestational diabetes, large-for-gestational-age and small-for-gestational-age infants, preterm birth, stillbirth, neonatal death, and major congenital malformations. RESULTS: Pregnancies after bariatric surgery, as compared with matched control pregnancies, were associated with lower risks of gestational diabetes (1.9% vs. 6.8%; odds ratio, 0.25; 95% confidence interval [CI], 0.13 to 0.47; P<0.001) and large-for-gestational-age infants (8.6% vs. 22.4%; odds ratio, 0.33; 95% CI, 0.24 to 0.44; P<0.001). In contrast, they were associated with a higher risk of small-for-gestational-age infants (15.6% vs. 7.6%; odds ratio, 2.20; 95% CI, 1.64 to 2.95; P<0.001) and shorter gestation (273.0 vs. 277.5 days; mean difference -4.5 days; 95% CI, -2.9 to -6.0; P<0.001), although the risk of preterm birth was not significantly different (10.0% vs. 7.5%; odds ratio, 1.28; 95% CI, 0.92 to 1.78; P=0.15). The risk of stillbirth or neonatal death was 1.7% versus 0.7% (odds ratio, 2.39; 95% CI, 0.98 to 5.85; P=0.06). There was no significant between-group difference in the frequency of congenital malformations. CONCLUSIONS: Bariatric surgery was associated with reduced risks of gestational diabetes and excessive fetal growth, shorter gestation, an increased risk of small-for-gestational-age infants, and possibly increased mortality. (Funded by the Swedish Research Council and others.).