Temporal trends in adverse pregnancy outcomes in axial spondyloarthritis in Sweden : a cohort study

Background: Evidence on the risks associated with pregnancy and childbirth in women with axial spondyloarthritis is scarce and conflicting, with more research needed to guide policy and clinical practice. We aimed to assess the risks of adverse pregnancy outcomes in a large cohort of women with axial spondyloarthritis, and to investigate how outcomes varied over time and in relation to anti-rheumatic treatment. Methods: In this register-based cohort study, we included births in Sweden between April 1, 2007, and Dec 31, 2020, to women with axial spondyloarthritis and general population comparators, matched 1:10 on year of delivery, maternal age, and parity. Our main data source was the Medical Birth Register (MBR), which includes over 98% of births in Sweden and prospectively collects data on antenatal care, delivery, and foetal outcomes. The information in MBR was linked to other registers, including the National Patient Register, the Prescribed Drug Register, and registers with demographic data. Our main outcomes were the relative risks of adverse pregnancy outcomes, analysed using modified Poisson regression. We also studied how the frequency of certain adverse outcomes, as well as disease-modifying antirheumatic drug (DMARD) and non-steroidal anti-inflammatory drug treatments, changed over the study period by linear regression and loess plots. Findings: Between April 1, 2007, and Dec 31, 2020, 1580 births in women with axial spondyloarthritis recorded in MBR fulfilled the inclusion criteria and were matched with 15 792 comparator births. Among the 1580 births in women with axial spondyloarthritis, we found increased risks of preterm birth (risk ratio 1.43, 95% CI 1.13-1.80), pre-eclampsia (1.44, 1.08-1.92), elective caesarean delivery (1.59, 1.37-1.84), and serious infant infection (1.29, 1.05-1.59) compared with births in general population comparators. The risks of preterm birth, infant infection, and caesarean delivery decreased by around 0.5 percentage points annually during the study period, while the use of tumour necrosis factor inhibitors during pregnancy increased. Interpretation: In view of remaining concerns regarding safety of the use of biological DMARDs during pregnancy, we saw a reassuring trend in which pregnancy outcomes improved over time in the axial spondyloarthritis group, concurrent with increased use of biological DMARDs. If the current rate of improvement is maintained, women with axial spondyloarthritis treated in accordance with clinical guidelines might eventually not be at an increased risk of adverse pregnancy outcomes.NoneAccepte

Cesarean delivery, preterm birth and risk of food allergy : nationwide Swedish cohort study of over 1 million children

Background & Objectives: Little is known about early life risk factors for food allergy in children. We examined the association between perinatal characteristics and future risk of food allergy in offspring. Methods: This nationwide Swedish cohort study of 1,086,378 children born in Sweden in 2001-2012 used prospectively recorded data from health care registers. Using Cox regression, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between perinatal characteristics (e.g. caesarean delivery, preterm birth) and food allergy as defined by diagnoses in the National Patient Register, adjusting for infant sex and maternal factors (age at delivery, country of birth, parity, smoking, body mass index and asthma/pulmonary disease). Results: During the 13-year follow-up, 26,732 children (2.5%) were diagnosed with food allergy. Food allergy was positively associated with caesarean delivery (HR=1.21; 95%CI=1.18-1.25), large for gestational age (HR=1.15; 95%CI=1.10-1.19) and low 5-minute Apgar score (HR=1.22, 95CI=1.10-1.36) but negatively associated with very preterm birth (<32 weeks of gestation: HR=0.74; 95%CI=0.56-0.98). No association was found between food allergy and moderately preterm birth, low birth weight or small for gestational age. Risk estimates were similar when the outcome was restricted to two records of diagnosed food allergy. In 1,000 children undergoing caesarean delivery, an extra 5 developed food allergy compared with the reference group, suggesting that 17% of food allergy in children born with caesarean delivery can be explained by this exposure (attributable fraction). Conclusions: Caesarean delivery was associated with increased risk of food allergy, whereas very preterm birth with decreased risk.NoneAccepte

Prolonged second stage of labor is associated with low Apgar score

There is no consensus on the effects of a prolonged second stage of labor on neonatal outcomes. In this large Swedish population-based cohort study, our objective was to investigate prolonged second stage and risk of low Apgar score at 5 minutes. All nulliparous women (n= 32 796) delivering a live born singleton infant in cephalic presentation at ≥37 completed weeks after spontaneous onset of labor between 2008 and 2012 in the counties of Stockholm and Gotland were included. Data were obtained from computerized records. Exposure was time from fully retracted cervix until delivery. Logistic regression analyses were used to estimate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI). Adjustments were made for maternal age, height, BMI, smoking, sex, gestational age, sex-specific birth weight for gestational age and head circumference. Epidural analgesia was included in a second model. The primary outcome measure was Apgar score at 5 minutes <7 and <4. We found that the overall rates of 5 minute Apgar score <7 and <4 were 7.0 and 1.3 per 1000 births, respectively. Compared to women with <1 hour from retracted cervix to birth, adjusted ORs of Apgar score <7 at 5 minutes generally increased with length of second stage of labor: 1-<2 hours: OR 1.78 (95% CI 1.19-2.66); 2- <3 hours: OR 1.66 (1.05-2.62); 3-<4 hours: OR 2.08 (1.29-3.35); and ≥4 hours: OR 2.71 (1.67-4.40). We conclude that prolonged second stage of labor is associated with an increased risk of low 5 minute Apgar score.The study was funded by the Swedish Research Council (No. 2008-423-57440-63, OS, http://www.vr.se/inenglish/researchfunding) and grants provided by the Stockholm County Council (ALFproject, OS, SC, http://www.forskningsstod.sll.se/Ansokan/start.asp).Manuscrip

The incidence of first stroke in and around pregnancy: A population-based cohort study from Sweden

Introduction: Research has suggested that delivery is associated with an increased risk of stroke in women; however, there is a lack of contemporary estimates on the incidence of stroke in and after pregnancy compared with the baseline risk in women of childbearing age in Sweden. Patients and methods: All women aged 15–49 years with live births/stillbirths in 1992–2011 were identified from the Swedish Medical Birth Registry linked with the National Patient Registry. First stroke during the study period was identified. Incidence rates per 100,000 person-years and adjusted incidence rate ratios (IRRs) were calculated for antepartum, peripartum and early and late postpartum periods, compared with all other available follow-up time (time before pregnancy and after postpartum) using Poisson regression adjusted for maternal age, education attainment and calendar time. Results: Of 1,124,541 women, 3094 had a first incident stroke (331 occurred during pregnancy or first 12 weeks postpartum), about half having ischaemic stroke. The incidence was 15.0 per 100,000 person-years (95% confidence interval 14.5–15.6) in non-pregnant time. The incidence was lower antepartum (7.3/100,000 person-years, 6.0–8.9; adjusted IRR = 0.7, 0.5–0.8) but higher peripartum (314.4/100,000 person-years, 247.5–399.5; adjusted IRR = 27.3, 21.4–34.9) and early postpartum (64.0/100,000 person-years, 54.1–75.7; adjusted IRR = 5.5, 4.6–6.6). The increased risk in peripartum was more evident for intracerebral haemorrhage than other types of stroke. Conclusion: Overall risk of stroke was low in women of childbearing age, but stroke risk peaks in the peripartum and early postpartum periods. Future work should address factors that contribute to this increased risk in order to develop approaches to attenuate risk

Duration of second stage of labour at term and pushing time : risk factors for postpartum haemorrhage

BACKGROUND: Prolonged labour is associated with increased risk of postpartum haemorrhage (PPH), but the role of active pushing time and the relation with management during labour remains poorly understood. METHODS: A population-based cohort study from electronic medical record data in the Stockholm-Gotland Region, Sweden. We included 57 267 primiparous women with singleton, term gestation, livebirths delivered vaginally in cephalic presentation in 2008-14. We performed multivariable Poisson regression to estimate the association between length of second stage, pushing time, and PPH (estimated blood loss >500 mL during delivery), adjusting for maternal, delivery, and fetal characteristics as potential confounders. RESULTS: The incidence of PPH was 28.9%. The risk of PPH increased with each passing hour of second stage: compared with a second stage <1 h, the adjusted relative risk (RR) for PPH were for 1 to <2 h 1.10 (95% confidence interval (CI) 1.07, 1.14); for 2 to <3 h 1.15 (95% CI 1.10, 1.20); for 3 to <4 h 1.28 (95% CI 1.22, 1.33); and for ≥4 h 1.40 (95% CI 1.33, 1.46). PPH also increased with pushing time exceeding 30 min. Compared to pushing time between 15 and 29 min, the RR for PPH were for <15 min 0.98 (95% CI 0.94, 1.03); for 30-44 min 1.08 (95% CI 1.04, 1.12); for 45-59 min 1.11 (95% CI 1.06, 1.16); and for ≥60 min 1.20 (95% CI 1.15, 1.25). CONCLUSIONS: Increased length of second stage and pushing time during labour are both associated with increased risk of PPH.Swedish Research Council, 2013-2429Stockholm County Council (ALF project), 20130156Accepte

Development and validation of risk prediction model for venous thromboembolism in postpartum women: multinational cohort study

Objective: To develop and validate a risk prediction model for venous thromboembolism in the first six weeks after delivery (early postpartum). Design: Cohort study. Setting: Records from England based Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and data from Sweden based registry. Participants: All pregnant women registered with CPRD-HES linked data between 1997 and 2014 and Swedish medical birth registry between 2005 and 2011 with postpartum follow-up. Main outcome measure: Multivariable logistic regression analysis was used to develop a risk prediction model for postpartum venous thromboembolism based on the English data, which was externally validated in the Swedish data. Results: 433 353 deliveries were identified in the English cohort and 662 387 in the Swedish cohort. The absolute rate of venous thromboembolism was 7.2 per 10 000 deliveries in the English cohort and 7.9 per 10 000 in the Swedish cohort. Emergency caesarean delivery, stillbirth, varicose veins, pre-eclampsia/eclampsia, postpartum infection, and comorbidities were the strongest predictors of venous thromboembolism in the final multivariable model. Discrimination of the model was similar in both cohorts, with a C statistic above 0.70, with excellent calibration of observed and predicted risks. The model identified more venous thromboembolism events than the existing national English (sensitivity 68% v 63%) and Swedish guidelines (30% v 21%) at similar thresholds. Conclusion: A new prediction model that quantifies absolute risk of postpartum venous thromboembolism has been developed and externally validated. It is based on clinical variables that are available in many developed countries at the point of delivery and could serve as the basis for real time decisions on obstetric thromboprophylaxis

The linked survival prospects of siblings : evidence for the Indian states

This paper reports an analysis of micro-data for India that shows a high correlation in infant mortality among siblings. In 13 of 15 states, we identify a causal effect of infant death on the risk of infant death of the subsequent sibling (a scarring effect), after controlling for mother-level heterogeneity. The scarring effects are large, the only other covariate with a similarly large effect being mother’s (secondary or higher) education. The two states in which evidence of scarring is weak are Punjab, the richest, and Kerala, the socially most progressive. The size of the scarring effect depends upon the sex of the previous child in three states, in a direction consistent with son-preference. Evidence of scarring implies that policies targeted at reducing infant mortality will have social multiplier effects by helping avoid the death of subsequent siblings. Comparison of other covariate effects across the states offers some interesting new insights

Evaluation of birth by cesarean delivery and development of early-onset colorectal cancer

IMPORTANCE: The incidence of early-onset colorectal cancer (CRC), diagnosed younger than 50 years of age, has increased worldwide. Gut dysbiosis throughout the life course is hypothesized as a leading mechanism, yet epidemiologic data are limited. OBJECTIVE: To prospectively examine the association between birth by cesarean delivery and early-onset CRC among offspring. DESIGN, SETTING, AND PARTICIPANTS: In this population-based, nationwide case-control study in Sweden, adults diagnosed with CRC between 18 and 49 years of age from 1991 to 2017 were identified through the Epidemiology Strengthened by Histopathology Reports in Sweden (ESPRESSO) cohort. Up to 5 general population control individuals without CRC were matched with each case on age, sex, calendar year, and county of residence. Pathology-confirmed end points were linked with the Swedish Medical Birth Register and other national registers. Analyses were conducted from March 2022 through March 2023. EXPOSURE: Birth by cesarean delivery. MAIN OUTCOMES AND MEASURES: The primary outcome was development of early-onset CRC in the overall population and by sex. RESULTS: We identified 564 case patients with incident early-onset CRC (mean [SD] age, 32.9 [6.2] years; 284 [50.4%] male) and 2180 matched controls (mean [SD] age, 32.7 [6.3] years; 1104 [50.6%] male). Compared with vaginal delivery, birth by cesarean delivery was not associated with early-onset CRC in the overall population (adjusted odds ratio [aOR], 1.28; 95% CI, 0.91-1.79) after multivariable adjustment for matching and maternal and pregnancy-related factors. A positive association was found for females (aOR, 1.62; 95% CI, 1.01-2.60), but there was no association for males (aOR, 1.05; 95% CI, 0.64-1.72). CONCLUSIONS AND RELEVANCE: In this nationwide, population-based case-control study, birth by cesarean delivery was not associated with early-onset CRC compared with birth by vaginal delivery in the overall population in Sweden. However, females born by cesarean delivery had greater odds of early-onset CRC compared with individuals born through vaginal delivery. This finding suggests that early-life gut dysbiosis may contribute to early-onset CRC in females