OBJECTIVE:The primary aim of this study was to determine the appropriate gestational age for planned births by elective cesarean section (ECS) or induction of labor (IOL) in relation to no excess risk of neonatal respiratory distress. STUDY DESIGN:Register-based Swedish cohort study including 575,817 singleton live births at 36 weeks or later. Births not eligible for vaginal delivery, preterm premature rupture of membranes and infants with congenital anomalies were excluded. The primary outcome was respiratory distress, and a secondary outcome was Apgar score <7 at five minutes. The risk of outcomes according to onset of birth was calculated for each day from gestational week 36 to 41 and compared with expectant management (EM), defined as births at least one day later. RESULTS:No excess risk of respiratory distress was found for ECS from 40 weeks and for IOL from 38 weeks compared with EM. At 37 weeks, the absolute risk of respiratory distress was 12.4 % for ECS (aRR:5.7; 95 %CI:4.8; 6.5) and 4.0 % for IOL (aRR:1.7; 95 %CI:1.5; 2.0). At 39 weeks, the absolute risk of respiratory distress for ECS was 3.2 % (aRR:1.6; 95 %CI:1.3; 1.8) whereas the risk was reduced for IOL. ECS <38 weeks increased the risk of Apgar <7 compared with EM. CONCLUSION:Regarding neonatal respiratory distress, IOL was safe from 38 weeks and ECS from 40 weeks. At earlier gestational ages, the risk of respiratory distress was significantly higher, which highlights the importance of clear health policies regarding appropriate timing and indications for planned births by ECS and IOL.

ImportanceGestational hypertension, preeclampsia, and eclampsia are established risk factors for stroke and dementia later in life. Whether these pregnancy complications are associated with an increased risk of new-onset neurological disorders within months to years after giving birth is not known.ObjectiveTo explore whether gestational hypertension, preeclampsia, and eclampsia are associated with new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth.Design, Setting, and ParticipantsIn this register-based cohort study, exposures were identified in the Swedish Medical Birth Register from 2005 to 2018. Follow-up was conducted using the National Patient Register, containing diagnoses from specialized inpatient and outpatient care. Follow-up started 42 days after delivery and continued until the first event, death, emigration, or the end of the follow-up period (2019). The risk was calculated with Cox regression analysis and expressed as adjusted hazard ratio (aHR) with a 95% CI. Through the Swedish Medical Birth Register, 659 188 primiparous women with singleton pregnancies between 2005 and 2018 were identified. Women with a diagnosis of chronic hypertension (n = 4271) or a prepregnancy neurological disorder (n = 6532) were excluded. The final study population included 648 385 women. Data analyses were conducted in 2023.ExposuresGestational hypertension, preeclampsia, and eclampsia.Main outcomeThe primary outcome was a composite neurological outcome of migraine, headache, epilepsy, sleep disorder, or mental fatigue.ResultsThe study included 648 385 women with a mean age of 28.5 (SD, 5.0) years at the time of their first pregnancy. Women with gestational hypertension (n = 11 133), preeclampsia (n = 26 797), and eclampsia (n = 625) all had an association with increased risk for a new-onset neurological disorder compared with women with normotensive pregnancies. The aHR for gestational hypertension was 1.27 (95% CI, 1.12-1.45), 1.32 (95% CI, 1.22-1.42) for preeclampsia, and 1.70 (95% CI, 1.16-2.50) for eclampsia. When exploring individual outcomes, women with eclampsia were associated with more than a 5 times increased risk of epilepsy (aHR, 5.31; 95% CI, 2.85-9.89).Conclusion and RelevanceIn this study, gestational hypertension, preeclampsia, and eclampsia were associated with an increased risk of new-onset migraine, headache, epilepsy, sleep disorder, or mental fatigue within months to years after giving birth. Guidelines recommend follow-up after delivery for women with gestational hypertension and preeclampsia for their increased risk of cardiovascular disease. At these visits, caregivers should also pay attention to persisting or new-onset of neurological symptoms, since this group of women appears to be vulnerable to developing or experiencing neurological disorders.

BACKGROUND:Preeclampsia is associated with higher levels of asymmetric (ADMA) and symmetric (SDMA) dimethylarginines. Dimethylarginines are inhibitors of nitric oxide, a uterine smooth muscles relaxant. Women with preeclampsia experience a shorter labor duration compared with normotensive women. However, very little is known about the possible biochemical mechanisms behind these differences. We aimed to investigate if women with preeclampsia had higher levels of arginines (ADMA, SDMA, and l-arginine) at labor than controls and also investigate the association between arginines and labor duration. METHODS:The study was based on data from the Swedish, Uppsala County population-based, prospective cohort BASIC, 2009-2018. Arginines were analyzed by ultra-high-performance liquid chromatography using plasma samples taken at labor from women with preeclampsia (n = 47) and normotensive pregnancy (n = 90). We also analyzed inflammation markers such as C-reactive protein, tumor necrosis factor (TNF)-R1, TNF-R2, and growth differentiation factor (GDF-15). RESULTS:Women with preeclampsia had higher levels of ADMA (P < 0.001), SDMA (P < 0.001), l-arginine (P < 0.001), TNF-R1 (P < 0.001), TNF-R2 (P = 0.03), and GDF-15 (P < 0.01) compared with controls. Furthermore, ADMA and SDMA, not inflammation markers, were negatively correlated to labor duration in preeclampsia. No correlations were observed when comparing arginines and inflammation markers. CONCLUSIONS:Among women with preeclampsia, our novel findings of higher level of arginines, negative correlation of arginines to labor duration, and absence of correlation of arginines to inflammation markers might support the theory that it is not inflammation but arginines which could be associated with shorter labor duration in preeclampsia.

Importance It is unclear whether a higher dose (150-160 mg) or a lower dose (75 mg) of aspirin should be used to prevent preeclampsia. Objectives To compare the risk of preeclampsia and bleeding complications between women using 150 to 160 mg of aspirin and those using 75 mg of aspirin for preeclampsia prevention. Design, Setting, and Participants This nationwide cohort study included 13 828 women giving birth at 22 weeks’ gestation or later in Sweden between January 2017 and December 2020 who used low dose aspirin (75-160 mg) during pregnancy. Data were analyzed from October to November 2023. Exposure The use of 150 to 160 mg or 75 mg of aspirin in pregnancy. Main Outcome and Measures The main outcome was a preeclampsia diagnosis recorded in the maternal birth record at the time of hospital discharge. The main safety outcome was postpartum hemorrhage, defined as bleeding more than 1000 mL after delivery. Relative risks (RRs) and 95% CIs were estimated using a doubly robust inverse probability–weighted regression adjustment model controlling for background characteristics. Results In the total cohort of 13 828 women, the mean (SD) age was 33.0 (5.5) years and 3003 women (21.7%) were nulliparous. Of the women, 4687 (33.9%) were prescribed 150 to 160 mg of aspirin, and 9141 (66.1%) were prescribed 75 mg of aspirin. A total of 10 635 women (76.9%) had at least 2 dispensed prescriptions of low-dose aspirin. Among women using 150 to 160 mg of aspirin, 443 (9.5%) developed preeclampsia compared with 812 (8.9%) of those using 75 mg of aspirin (adjusted RR [aRR], 1.07; 95% CI, 0.93-1.24). Additionally, the risk of postpartum hemorrhage between the groups was similar, with 326 women (6.9%) using 150 to 160 mg of aspirin experiencing a postpartum hemorrhage compared with 581 (6.4%) in the 75-mg group (aRR, 1.08; 95% CI, 0.90-1.30). Conclusions and Relevance In this cohort study of 13 828 women, no difference was found in preeclampsia incidence or bleeding complications between those using 150 to 160 mg of aspirin vs 75 mg of aspirin during pregnancy for preeclampsia prevention. These findings suggest that either dose may be a reasonable choice when using aspirin to prevent preeclampsia. However, large randomized trials investigating aspirin dose in pregnancy are still needed.

Objective Preterm birth (PTB, birth before 37 gestational weeks) is the leading cause of neonatal death and a major challenge for obstetric and neonatal care. About two-thirds of PTBs are spontaneous PTB (sPTB), of which approximately 30% start with preterm premature rupture of membranes (PPROM). The aim of the study was to investigate risk factors and maternal and perinatal outcomes in sPTB with and without PPROM. Study Design This is a national population-based cohort study including all singleton pregnancies in nulliparous women with spontaneous onset of labor and vaginal births (n = 266,968) registered in the Swedish Medical Birth Register 2005 to 2014. sPTB with PPROM (sPTB-PPROM) and sPTB without PPROM were compared regarding risk factors and maternal and perinatal outcomes. Logistic regression was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Adjustments were made for maternal age, body mass index, country of birth, smoking, chronic hypertension, pregestational and gestational diabetes, and gestational length. Results sPTB-PPROM (n = 5,037), compared with sPTB without PPROM (n = 8,426), was more common in women with previous spontaneous abortions, prepregnancy urinary tract infections, chronic hypertension, and gestational diabetes and had a higher risk of postpartum endometritis (aOR: 2.78, 95% CI: 1.55–5.00). Infants born to women with sPTB-PPROM had a lower risk of birth asphyxia (aOR: 0.60, 95% CI: 0.43–0.83), respiratory distress syndrome (aOR: 0.86, 95% CI: 0.70–1.00), retinopathy of prematurity (aOR: 0.93, 95% CI: 0.92–0.94), necrotizing enterocolitis (aOR: 0.95, 95% CI: 0.94–0.96), and higher risk of hypoglycemia (aOR: 1.14, 95% CI: 1.01–1.28), and hyperbilirubinemia (aOR: 1.28, 95% CI: 1.19–1.38) compared with infants born to sPTB without PPROM. Conclusion Our findings of risk factors and distinct differences in adverse outcomes after sPTB-PPROM compared with sPTB without PPROM are of vital importance and might serve as a basis when elaborating programs for the prevention and management of PPROM. Key Points

(Abstracted from BMJ 2024;385:e079014 Obstetric anal sphincter injury (OASI) is a serious complication to vaginal birth, with the primary risk factors being primiparity and instrumental birth. Rates of OASI vary across countries, affecting up to 4% of primiparous women for spontaneous births and 6% to 24% for instrumental births in the United States, Canada, and Europe.

( BJOG . 2023;130(13):1602–1609. doi: 10.1111/1471-0528.17533) The condition known as neonatal hypoxic ischemic encephalopathy (HIE) occurs when a term or near-term infant suffers asphyxiation during or near birth. The resulting signs and symptoms vary and may be classified as mild, moderate, or severe. Historically, infants diagnosed with mild HIE received alternative, and less intensive care given the understanding that outcomes were less severe compared with infants with the moderate or severe HIE diagnosis. However, recent studies have suggested young children (aged 2 to 5) who were diagnosed with mild HIE as infants are more likely to have a disability when compared with similar aged children without an HIE diagnosis. In addition, when examining mild HIE patients at neonatal discharge, abnormal results were found on amplitude-integrated electroencephalography, brain magnetic resonance imaging, and neurological exam. This population-based cohort study used register-based data to further understand how mild HIE relates to severe neurological outcomes, including death up to 6 years after birth.

Abstract Background Metformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy. Methods We utilised data from two population-based cohorts: Scotland (2012–2018) and Sweden (2007–2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model. Results The Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% (n = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66–1.19]; Sweden aRR 1.08 [95% CI 0.86–1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66–1.60]; Sweden aRR 1.00 [95% CI 0.72–1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79–1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73–1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21–0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight < 3rd or < 10th percentiles. Pooling results from both countries, metformin was not associated with adverse neonatal outcomes, including preterm birth (RR 1.00 [95% CI 0.89–1.13]), and birthweight < 10th percentile (RR 0.82 [95% CI 0.60–1.13]) or < 3rd percentile (RR 0.78 [95% CI 0.41–1.48]). Conclusions In this two-country analysis, metformin use in pregnancy among women with diabetes was not associated with an altered risk of developing any hypertensive disorder of pregnancy. In the combined meta-analysis, metformin was not associated with an altered risk of adverse neonatal outcomes.

Objective: This study aims to assess the external validity of the Alcohol Use Disorders Identification Test (AUDIT) in Swedish prenatal care as an indicator for alcohol-addiction disorders, and to characterize women with mismatched information in healthcare registers Design: This study was designed as a National register-based study. Setting: Sweden Participants: The study sample included 739,735 pregnancies over the period 2014–2020. Methods: Prospectively collected prenatal AUDIT screening in the Swedish Pregnancy register was linked to national health databases through individual identification number. The AUDIT score was dichotomized into < 6 points (low-risk use) and ≥ 6 points (hazardous use). Alcohol addiction disorders were defined by a diagnostic code in The Swedish National Patient Register or drugs dispensed for alcohol dependence in the Swedish Prescribed Drug Register. Primary Outcome Measures: The diagnostic properties of AUDIT were assessed based on sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and accuracy (proportion of true positive and true negative) for an AUDIT score of ≥ 6 points for alcohol disorders. Women with mismatched information in the register were characterized and assessed by multinominal logistic regression, using women with matched information in the registers for reference. Results: An alcohol-related disorder was recorded in 3.1%, while 25,770 (3.5%) had an AUDIT point ≥ 6. The diagnostic accuracy of the AUDIT ≥ 6 points for detection of an alcohol related disorder during a year prior to pregnancy was 95.7% (95% confidence interval [CI]: 95.7, 95.8), with a positive LR of 8.03 (95% CI: 7.5, 8.6). The sensitivity for detecting a pre-pregnancy alcohol related disorder was 33.0% (95% CI: 30.9, 35.1). Being young, nulliparous, of low education, and of Swedish origin increased the likelihood of being misclassified with the AUDIT. Prior psychiatric care was associated with false negatives, especially for women with neuropsychiatric disorders (odds ratio [OR]: 10.39, 95% CI: 9.89, 10.90). Conclusions: The accuracy of AUDIT in screening for alcohol disorders at a population-based level was high, but only identified one third of women with alcohol-related disorders when using a cut-off of six points criterion.

INTRODUCTION:Migrant women are a heterogenous group with both higher and lower risk for pregnancy complications and adverse birth outcomes compared with women in the receiving countries. This study aimed to investigate women's use of Swedish healthcare postpartum, in terms of hospital stay >48 h, readmission to hospital, and specialized out-patient clinic visits, in relation to maternal country of birth. MATERIAL AND METHODS:A population-based register study including 278 219 primiparous and 367 776 multiparous women in Sweden (2014-2019) using data from Swedish Pregnancy Register, National Patient Register and Statistics Sweden. Multivariable logistic regression analyses were used to estimate associations between maternal country of birth and outcomes, adjusting for year of birth, maternal age, education, pre-gestational hypertension and diabetes, and healthcare region, presented as crude and adjusted odds ratios (aOR) with 95% confidence interval (CI) with Swedish-born women as reference. RESULTS:Subgroups of migrant women had higher odds of postpartum hospital stays > 48 h, particularly women from Eritrea (primiparous aOR 2.80, CI 2.49-3.15; multiparous aOR 2.78, CI 2.59-2.98), Somalia (primiparous aOR 2.61, CI 2.34-2.92; multiparous aOR 1.87, CI 1.79-1.97), and India (primiparous aOR 2.52, CI 2.14-2.97; multiparous aOR 2.61, CI 2.33-2.93), compared to Swedish-born women. Primiparous women from Afghanistan (aOR 1.32, CI 1.08-1.6), Iraq (aOR 1.30, CI 1.16-1.46), and Iran (aOR 1.23, CI 1.04-1.45) had slightly higher odds of hospital readmission, along with multiparous women from India (aOR 1.34, CI 1.02-1.76) and Somalia (aOR 1.24, CI 1.11-1.38). Specialized out-patient clinic visits were most common in primiparous women from Somalia (aOR 1.47, CI 1.35-1.59), Iran (aOR 1.31, CI 1.22-1.42) and Afghanistan (aOR 1.31, CI 1.18-1.46), and in multiparous women from Iran (aOR 1.30, CI 1.20-1.41) and Iraq (aOR 1.15, CI 1.11-1.20), however less common in women from some other countries. CONCLUSIONS:The use of Swedish health care during the postpartum period varied among women, depending on their country of birth. Women from certain countries had particularly high odds of postpartum hospital stays exceeding 48 h, compared to Swedish-born women, regardless of parity and pre-gestational medical disorders. Further studies are needed to determine whether the individual needs of migrant women are being met during the postpartum period or not.

ObjectiveTo investigate whether perineal wound complications in the first birth, alone or in conjunction with obstetric anal sphincter injury (OASI), is associated with an increased risk of OASI in the second birth.DesignNationwide population-based cohort study.SettingSweden.PopulationWomen (n = 411 317) with first and second singleton vaginal births in Sweden, 2001-2019.MethodsData on diagnostic codes and surgical procedures were retrieved from the Swedish Medical Birth Register and the Swedish Patient Register. A perineal wound complication was defined as wound infection, dehiscence or perineal haematoma within 2 months of childbirth.Main outcome measuresAssociations between wound complications in the first birth and OASI in the second birth were investigated with logistic regression and presented as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs).ResultsIn total, 2619 (0.6%) women had a wound complication in the first birth, and 5318 (1.3%) had an OASI in the second birth. Women with a wound complication but no OASI in the first birth had more than doubled odds of OASI in the second birth (aOR 2.73, 95% CI 2.11-3.53). Women with OASI and a wound complication in the first birth had almost tenfold odds (aOR 9.97, 95% CI 6.53-15.24) of recurrent OASI.ConclusionsPerineal wound complication in the first birth increases the likelihood of OASI in a subsequent birth.

OBJECTIVE:To assess the effect of lateral episiotomy, compared with no episiotomy, on obstetric anal sphincter injury in nulliparous women requiring vacuum extraction. DESIGN:A multicentre, open label, randomised controlled trial. SETTING:Eight hospitals in Sweden, 2017-23. PARTICIPANTS:717 nulliparous women with a single live fetus of 34 gestational weeks or more, requiring vacuum extraction were randomly assigned (1:1) to lateral episiotomy or no episiotomy using sealed opaque envelopes. Randomisation was stratified by study site. INTERVENTION:A standardised lateral episiotomy was performed during the vacuum extraction, at crowning of the fetal head, starting 1-3 cm from the posterior fourchette, at a 60° (45-80°) angle from the midline, and 4 cm (3-5 cm) long. The comparison was no episiotomy unless considered indispensable. MAIN OUTCOME MEASURES:The primary outcome of the episiotomy in vacuum assisted delivery (EVA) trial was obstetric anal sphincter injury, clinically diagnosed by combined visual inspection and digital rectal and vaginal examination. The primary analysis used a modified intention-to-treat population that included all consenting women with attempted or successful vacuum extraction. As a result of an interim analysis at significance level P<0.01, the primary endpoint was tested at 4% significance level with accompanying 96% confidence interval (CI). RESULTS:From 1 July 2017 to 15 February 2023, 717 women were randomly assigned: 354 (49%) to lateral episiotomy and 363 (51%) to no episiotomy. Before vacuum extraction attempt, one woman withdrew consent and 14 had a spontaneous birth, leaving 702 for the primary analysis. In the intervention group, 21 (6%) of 344 women sustained obstetric anal sphincter injury, compared with 47 (13%) of 358 women in the comparison group (P=0.002). The risk difference was -7.0% (96% CI -11.7% to -2.5%). The risk ratio adjusted for site was 0.47 (96% CI 0.23 to 0.97) and unadjusted risk ratio was 0.46 (0.28 to 0.78). No significant differences were noted between groups in postpartum pain, blood loss, neonatal outcomes, or total adverse events, but the intervention group had more wound infections and dehiscence. CONCLUSIONS:Lateral episiotomy can be recommended for nulliparous women requiring vacuum extraction to significantly reduce the risk of obstetric anal sphincter injury. TRIAL REGISTRATION:ClinicalTrials.gov NCT02643108.

Objective: To investigate whether mild neonatal hypoxic ischaemic encephalopathy (HIE) in term born infants is associated with cerebral palsy, epilepsy, mental retardation and death up to 6 years of age.Design: Population-based cohort study.Setting: Sweden, 2009-2015.Population: Live term born infants without congenital malformations or chromosomal abnormalities (n = 505 075).Methods: Birth and health data were retrieved from Swedish national health and quality registers. Mild HIE was identified by diagnosis in either the Swedish Medical Birth Register or the Swedish Neonatal Quality Register. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).Main outcome measures: A composite of the outcomes cerebral palsy, epilepsy, mental retardation and death up to 6 years of age.Results: Median follow-up time was 3.3 years after birth. Of 414 infants diagnosed with mild HIE, 17 were classified according to the composite outcome and incidence rates were 12.6 and 2.9 per 1000 child-years in infants with and without HIE respectively. Infants with mild HIE was four times as likely to be diagnosed with the composite outcome (HR 4.42, 95% CI 2.75-7.12) compared with infants without HIE. When analysed separately, associations were found with cerebral palsy (HR 21.50, 95% CI 9.59-48.19) and death (HR 19.10, 95% CI 7.90-46.21). HRs remained essentially unchanged after adjustment for covariates.Conclusions: Mild neonatal HIE was associated with neurological morbidity and mortality in childhood. Challenges include identifying infants who may develop morbidity and how to prevent adverse outcomes.

Abstract Background In clinical settings and research studies, childbirth experience is often measured using a single-item question about overall experience. Little is known about what women include in this rating, which complicates the design of adequate follow-up, as well as the interpretation of research findings based on ratings of overall childbirth experience. The aim of this study was to examine which known dimensions of childbirth experience women include in the rating on a single-item measure. Methods Ratings of overall childbirth experience on a 10-point numeric rating scale (NRS) from 2953 women with spontaneous or induced onset of labour at two Swedish hospitals were evaluated against the validated Childbirth Experience Questionnaire 2 (CEQ2), completed on one of the first days postpartum. The CEQ2 measures four childbirth experience domains: own capacity, perceived safety, professional support and participation. Internal consistency for CEQ2 was evaluated by calculating Cronbach’s alpha. NRS ratings were explored in relation to CEQ2 using empirical cumulative distribution function graphs, where childbirth experience was defined as negative (NRS ratings 1–4), mixed (NRS ratings 5–6) or positive (NRS ratings 7–10). A multiple linear regression analysis, presented as beta coefficients (B) and 95% confidence intervals (CI), was also performed to explore the relationship between the four domains of the CEQ2 and overall childbirth experience. Results The prevalence of negative childbirth experience was 6.3%. All CEQ2-subscales reached high or acceptable reliability (Cronbach’s alpha = 0.78; 0.81; 0.69 and 0.66, respectively). Regardless of overall childbirth experience, the majority of respondents scored high on the CEQ2 subscale representing professional support. Overall childbirth experience was mainly explained by perceived safety (B = 1.60, CI 1.48–1.73), followed by own capacity (B = 0.65, CI 0.53–0.77) and participation (B = 0.43, CI 0.29–0.56). Conclusions In conclusion, overall childbirth experience rated by a single-item measurement appears to mainly capture experiences of perceived safety, and to a lesser extent own capacity and participation, but appears not to reflect professional support. CEQ2 shows good psychometric properties for use shortly after childbirth, and among women with induced onset of labour, which increases the usability of the instrument.

Objective: To explore descriptions of negative childbirth experience in relation to mode of birth and events during labour. Design: A descriptive study using a convergent mixed methods design. Written responses to open-ended online questions regarding negative childbirth experience were explored using qualitative content analysis. Generated sub-themes were quantified, and stratified on mode of birth and events during labour. Participants and setting: 112 women with low ratings of overall childbirth experience, participating in a randomised controlled trial evaluating internet-based cognitive behavioural therapy in Sweden. Qualitative data were collected before randomisation, three months postpartum. Results: Four sub-themes emerged from the qualitative analysis: Experiencing fear-based emotions, Experiencing physical distress, Being affected by caregivers' and partner's behaviour and Being affected by bad facilities and poor organisation. Only small differences were found when stratifying sub-themes on mode of birth and events during labour. Regardless of mode of birth and events during labour, the childbirth experience was dominated by fearbased emotions. Key conclusions and implications for practice: Mixed-methods analyses demonstrate the challenges in understanding negative childbirth experience in relation to mode of birth and specific events during labour, with results clearly showing the multifaceted nature of this concept. The central role of fear in relation to negative childbirth experience should be considered when designing support during and after labour, to prevent adverse effects of the childbirth experience.

We are grateful for the opportunity to reply to the letter from Drs Norooznezhad and Nabavian regarding our study “Low-dose aspirin use in pregnancy and the risk of preterm birth: a Swedish register-based cohort study.” Preventing preterm birth (PTB) is exceptionally important, and we thank Drs Norooznezhad and Nabavian for their interest in our findings. We agree with Drs Norooznezhad and Nabavian that low-dose aspirin may have additional effects in pregnancy beyond inhibiting cyclooxygenase. The authors described how infectious conditions are associated with PTB and increased production of proinflammatory cytokines, such as interleukin (IL) 1β, IL-6, and tumor necrosis factor-alpha (TNF-α). Furthermore, they provided evidence that aspirin can inhibit nuclear factor kappa B and TNF-α transcription. TNF-α elicits several cellular responses and is involved in both term labor and preterm labor independent of the presence of infection.1Arman B.M. Binder N.K. de Alwis N. Kaitu’u-Lino T.J. Hannan N.J. Repurposing existing drugs as a therapeutic approach for the prevention of preterm birth.Reproduction. 2023; 165: R9-R23Crossref PubMed Scopus (6) Google Scholar Importantly, aspirin has been shown to prevent TNF-α–mediated endothelial cell dysfunction and insufficient trophoblast invasion. The latter is a cause of uteroplacental ischemia,2Kim J. Lee K.S. Kim J.H. et al.Aspirin prevents TNF-α-induced endothelial cell dysfunction by regulating the NF-κB-dependent miR-155/eNOS pathway: role of a miR-155/eNOS axis in preeclampsia.Free Radic Biol Med. 2017; 104: 185-198Crossref PubMed Scopus (106) Google Scholar a common finding in spontaneous PTB.3Kelly R. Holzman C. Senagore P. et al.Placental vascular pathology findings and pathways to preterm delivery.Am J Epidemiol. 2009; 170: 148-158Crossref PubMed Scopus (93) Google Scholar Although the pathophysiology of PTB is not fully understood, it is thought that the onset of labor is accompanied by a transition from an anti-inflammatory state to a proinflammatory state,1Arman B.M. Binder N.K. de Alwis N. Kaitu’u-Lino T.J. Hannan N.J. Repurposing existing drugs as a therapeutic approach for the prevention of preterm birth.Reproduction. 2023; 165: R9-R23Crossref PubMed Scopus (6) Google Scholar and as such, TNF-α and other proinflammatory cytokines may play a key role. Thus, targeting these molecules with anti-inflammatory drugs, such as aspirin, is a promising approach to preventing PTB. Further insights into aspirin’s mode of action may shed light on the pathophysiology of PTB. Low-dose aspirin and prevention of preterm birth: untold story of inflammationAmerican Journal of Obstetrics & GynecologyVol. 229Issue 3PreviewWith much interest, we read the article by Kupka et al,1 regarding the benefits of using low-dose aspirin in the prevention of preterm birth (PTB). The main mechanism of action for aspirin has been suggested to be the inhibition of cyclooxygenase (COX) and, therefore, the production of prostaglandins (PGs).2 However, it seems that this is not the only pathway. Full-Text PDF