Ulrik Schiøler Kesmodel

Introduction: Globally, colposcopy is often performed by non‐experts with no certification or routine use of colposcopic scoring tools. A systematic colposcopic scoring tool, the Swedescore, has been developed to enhance the detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We aimed to compare the diagnostic accuracy of two colposcopy methods (systematic use of the Swedescore versus conventional colposcopy) for detecting CIN2+. Material and Methods: This multicenter, non‐randomized clinical study included women (23–65 years) referred for colposcopy and with a visible transformation zone (type 1 and 2). Colposcopy was performed using the systematic scoring tool, Swedescore, or the conventional method. All women had four cervical biopsies collected. Colposcopists collected lesion‐directed biopsies (target biopsies) from abnormal areas with or without non‐lesion‐directed biopsies (random biopsies) from areas that appeared normal. The gold standard was the most severe diagnosis (CIN2+) based on all four biopsies. The primary outcome was CIN2+. We calculated sensitivity (SN), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence intervals and compared results between the two methods. Results were stratified by age, body mass index (BMI), human papillomavirus (HPV) vaccination status, screening method, index cytology, index HPV type, and colposcopists. Clinical Trial Registration ClinicalTrials.gov NCT05870787. Results: Among 929 women included (Swedescore: 534, conventional: 395), the diagnostic accuracy for the detection of CIN2+ was slightly higher with the Swedescore compared to the conventional method (SN: 84.7% vs. 77.8%, SP: 37.3% vs. 30.9%, PPV: 47.6% vs. 43.9%, NPV: 78.3% vs. 66.7%). Sensitivity for CIN2+ was significantly higher with the Swedescore compared to the conventional method in women ≥50 years (92.9% vs. 62.5%), those with high‐grade cytology (92.4% vs. 83.2%), and when colposcopy was performed by residents (91.8% vs. 70.6%). Regardless of HPV vaccination status and screening method, the Swedescore performed slightly better than the conventional method, although the differences were not statistically significant. Conclusions: Our findings may suggest that, in a non‐expert setting, a systematic colposcopic examination using the Swedescore was associated with a slightly higher diagnostic accuracy for detecting CIN2+ compared to the conventional method. These findings should be interpreted considering baseline imbalances between the two methods.

Introduction: A transabdominal cerclage is inserted to prevent recurrent midtrimester loss and spontaneous preterm birth. The transabdominal cerclage often remains as a permanent foreign body for years. Synthetic materials within the abdomen, cesarean birth, and prior adverse pregnancy outcomes have each been associated with long‐term complications or poorer health‐related quality‐of‐life. However, the long‐term effects of a permanent transabdominal cerclage have not been investigated. We aimed to evaluate patient‐reported late effects and health‐related quality‐of‐life in Danish women who underwent transabdominal cerclage between 2004 and 2025. Material and Methods: In this nationwide cohort study, women with a transabdominal cerclage were matched in a 1:1:1 ratio to two comparison groups: (1)women without transabdominal cerclage who had a cesarean birth, and (2)women without transabdominal cerclage who had a non‐instrumental vaginal birth and no prior cesarean birth. Participants completed validated questionnaires assessing quality‐of‐life, anxiety and depression, bladder discomfort, pelvic pain and sexual health. The primary outcome was the General Health scale in SF‐36. Domain‐ and total scale scores were compared between the groups using multiple linear regression. The study was pre‐registered on clinicaltrials.gov (NCT06875401). Results: Two hundred three women with a transabdominal cerclage, 90 with a cesarean section, and 98 with a vaginal birth participated. The mean General Health score did not differ between groups by a predefined minimally important difference of 10 points. Adjusted mean differences were − 4.0 points (95% CI ‐9.5–1.4) for women with cesarean birth and −0.6 (95% ‐CI‐6.2–4.9) for women with vaginal birth in comparison to the transabdominal cerclage group. Mental health, bladder discomfort, pelvic pain, and sexual health symptom burdens were similar between groups. Response rates were higher in the transabdominal cerclage group, which may have introduced selection bias. Cerclage‐related complications leading to suture removal after completed pregnancies were rare (3/203 women, 1.5%). Quality‐of‐life scores tended to be higher with longer time since cerclage procedure. Conclusions: Permanent transabominal cerclage was not associated with poorer self‐reported general health compared with women without transabominal cerclage, regardless of mode of birth. These findings support that a permanent transabominal cerclage does not appear to have long‐term negative health effects.

Hormonal contraceptive (HC) use is known to be associated with elevated CRP levels. However, evidence on the effect of HC on several circulating inflammatory biomarkers in healthy humans is limited. The aim of this study was to examine the association between hormonal contraceptives and circulating biomarker levels and differential cell counts. A cross‐sectional observational study design with biomarker measurements from 4,160 healthy females was used, coupled with registered HC prescriptions. We compared 752 high and low dose combined oral contraceptive (COC) users, 77 progestin‐only pill users, 417 levonorgestrel intrauterine device users, 65 hormonal therapy users, and 1,523 post‐menopausal women with a control group of 1,326 women below 50 years. Repeated differential cell counts from a different dataset of 16,231 females were analyzed for the effects of HC. Data were analyzed using various regression models. COC use was associated with higher vascular marker levels but lower chemokine levels. We found no association with progestin‐only use. The association with differential cell counts was limited for most HC types. This study emphasizes the widespread impact of HC on the immune and vascular systems and how the impact may differ between HC types. The biomarker associations found could be targets for elucidation in functional studies.

Background/Objectives: Although current research suggests beneficial effects of dietary supplements on female infertility, existing evidence is often inconsistent and of limited certainty. This systematic review and meta-analysis aimed to investigate the effect of dietary supplements on female infertility in terms of endometrial thickness, pregnancy, live birth, and miscarriage compared to placebo (primary objective) and compared to placebo or a no-treatment comparator (secondary objective). Methods: PubMed, Embase, and CENTRAL were searched up to March 2025. Randomized controlled trials assessing the effect of dietary supplements compared to placebo or a no-treatment comparator among infertile women were included. Screening, data extraction, risk of bias, and certainty of evidence assessments were conducted by two independent reviewers. Data was synthesized quantitatively using random effects restricted maximum likelihood models. Results: Twenty placebo-controlled and 20 no-treatment comparator studies were included. Most studies had some concerns in risk of bias. Primary analyses showed an improvement in endometrial thickness following N-acetyl-cysteine supplementation compared to placebo, while no effect was found for supplements on pregnancy-related outcomes. Certainty of evidence of primary analyses was low. Secondary analyses indicated positive differences in endometrial thickness and pregnancy-related outcomes following supplementation with different supplements compared to placebo and no treatment. Conclusions: This review found no high-certainty evidence that dietary supplements improve female infertility outcomes when compared with placebo. Secondary analyses combining placebo and no-treatment comparator studies generated hypotheses for myo-inositol, N-acetyl-cysteine, vitamin D, vitamin E, and ≥3 substance dietary supplements, but these are at higher risk of bias and require confirmation in adequately powered placebo-controlled trials with live birth as the primary outcome.

Context: Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and is associated with type 2 diabetes, which is associated with breast cancer and kidney cancer. However, little is known about the risk of cancer following a GDM diagnosis. Objective: This study aimed to test the hypothesis that a history of GDM associates with increased risk of breast, gynecological, thyroid, and kidney cancer. Methods: National cohort study, based on Danish registry data. The study population included a group of women exposed to GDM in their pregnancy leading to delivery between 2000 and 2019 or 1978 and 1997 and a 1:10 matched nonexposed group, matched on calendar period of delivery, the woman´s age (birth year), and the woman´s registered region of residence at delivery. Poisson regression adjusting for educational level was conducted. Results: Of the 314 742 deliveries included, 28 613 deliveries were in the exposed group and 286 129 in the nonexposed. The median follow-up time was 8.1 years. We found no increased risk of the selected cancers combined [adjusted incidence rate ratio (aIRR) 1.05; 95% confidence interval (CI), 0.94-1.18], breast cancer (aIRR 1.02; 95% CI, 0.89-1.17), gynecological cancer (aIRR 1.00; 95% CI, 0.79-1.26), or thyroid cancer (aIRR 1.26; 95% CI, 0.86-1.82). However, an increased risk of kidney cancer was seen in women with previous GDM compared with women without GDM (aIRR 1.92; 95% CI, 1.10-3.33), although it was a very small absolute risk. Conclusion: No elevated risk was found for the selected cancers combined. Women with previous GDM had an increased risk of kidney cancer, a rare cancer form.

Aim: The incidence of neonatal abstinence syndrome (NAS) has risen, but published data are limited. The aim of this study was to investigate the incidence of NAS and the associated prenatal drug exposure in a Danish population. Methods: We conducted a historical multicentre cohort study of neonates treated for NAS during 2013–2018. The Danish National Patient Register identified 447 neonates with one of four predefined diagnoses. Reviews of the medical records showed that 98 of the neonates were pharmacologically treated for NAS. Results: The incidence of NAS in the 6‐year period was stable at 0.6 per 1000 live births. The majority of neonates treated for NAS were born to mothers treated with analgesic opioids. However, one‐third of the neonates treated for NAS were not exposed to opioids. The most frequent other drugs causing NAS were cannabis, benzodiazepines, antidepressants and psychoactive drugs. Half of the neonates were only exposed to a single drug; 14% were exposed to cannabis and 9% of all neonates treated for NAS were exposed to cannabis as a single drug in addition to tobacco. Conclusion: The incidence of NAS in the 6‐year period was stable. Healthcare professionals should be aware of NAS after prenatal exposure to cannabis.

Introduction: Antenatal corticosteroid treatment (ACS), administered intramuscularly to pregnant women, is recommended as standard care when birth before 34 weeks of gestational age is anticipated. ACS is widely recognized for its ability to reduce neonatal mortality and morbidity, but it may affect maternal mental health due to its neuropsychiatric side effects and its timing during a period of heightened psychological vulnerability. Despite this, the potential association between ACS and maternal postpartum psychiatric disorders remains understudied. This study aimed to examine the possible associations between ACS and maternal postpartum depression and other postpartum psychiatric disorders. Methods: This register‐based cohort study included 165,936 births by 130,235 unique women at seven Danish hospitals between 2003 and 2018. Data on ACS administration, pregnancies, births, postpartum psychiatric disorders, and potential confounders were retrieved from Danish registers. The women were followed 1 year after giving birth for incident psychiatric disorders, and associations with ACS were explored in Cox proportional hazards regression models. The models were clustered by maternal ID and adjusted for sociodemographic, obstetric, and psychiatric covariates to estimate hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). An interaction between gestational age and ACS exposure was included in all models. Results: Women who had been exposed to ACS but gave birth at term or post‐term had significantly higher hazards of postpartum depression, other postpartum psychiatric disorders, and the combined outcome compared with non‐exposed women giving birth at similar gestational ages, with HRs: 1.66 (1.18–2.33), 1.50 (1.03–2.19), and 1.64 (1.24–2.18), respectively. In contrast, associations among women who gave birth preterm were not statistically significant. Conclusion: ACS exposure was associated with increased risks of maternal postpartum psychiatric disorders among women who gave birth term or post‐term, but not among those who gave birth preterm. The increased risks in the term/post‐term group are likely attributable to unmeasured confounding. These findings provide reassurance that ACS is unlikely to substantially increase the risk of postpartum psychiatric disorders among women delivering preterm, but they also highlight the need for attentive follow‐up of women with threatened preterm labor who ultimately give birth at term. Our results also call for improved registration of ACS administration to strengthen future surveillance and drug safety.

Introduction: Adequate treatment of cervical precancer, defined as negative margins and a negative HPV test post‐treatment, is essential for cervical cancer prevention, as inadequate excision of cervical precancer and a positive HPV test are associated with increased risk of recurrence. Here, we aimed to describe trends in the proportion of women receiving adequate treatment in Denmark. Material and Methods: Nationwide historical cohort study including Danish women ≥18 years treated with large loop excision of the transformation zone (LLETZ) from 2013 to 2022. Using the Danish Pathology Register, we collected information on all LLETZ procedures performed due to cervical intraepithelial neoplasia grade 1 or worse (CIN1+). We calculated the proportion of negative margins and negative HPV tests post‐treatment, overall and stratified by histology, age, calendar time, and residing region. Results were mainly reported descriptively. Results: We included 41 128 women (median age: 35 years, interquartile range: 28–44). A total of 20 744 (50.4%) had negative margins, with the lowest proportion in women with CIN3 (47.2%) or adenocarcinoma in situ (38.3%). The proportion of negative margins declined with increasing age, from 54.1% in women aged 18–29 years to 43.6% in women aged ≥50 years. Overall, 62.4% had a negative HPV test, with no major differences observed across histology groups. The proportion of negative HPV tests ranged from 62.8% to 66.9% in women aged 18–49, whereas it was lower in women aged ≥50 years (48.4%). Conclusions: Women aged ≥50 years were less likely to have negative margins and a negative HPV test post‐treatment compared to women aged 18–49. These findings prompt a need to optimize treatment in this group of women to reduce the risk of cervical cancer.

Children with heavy prenatal alcohol exposure may experience increased healthcare needs and access barriers. We aimed to quantify their healthcare utilisation patterns compared to all other Danish children in this nationwide cohort study of children born 1997–2020, followed until Dec 31, 2022. Data was derived from eight national registers. Heavy prenatal alcohol exposure was defined by hospital contacts with 100% alcohol-attributable diagnoses given to mother or child, redeemed prescriptions for drugs to treat alcohol dependence, or enrollment into treatment clinics, one year before or during pregnancy. We estimated age- and sex-specific rates and incidence rate ratios (IRRs) for use of somatic and psychiatric hospitals, and use of general practice (GP), and risk ratio (RR) for participation in the GP-based preventive child health programme. Of 1,457,962 children followed for 17,778,705 person-years, 5898 (0.4%) were heavily prenatal alcohol exposed. Exposed children had higher use of GP and hospitals compared to reference children, particularly notable for psychiatric hospital contacts with IRR for respectively ages 0–5, 6–11 and 12–18 years of 3.55 (2.98–4.24), 2.68 (2.41–2.98), and 2.19 (1.95–2.46); and for planned outpatient contacts 2.01 (1.92–2.10), 1.29 (1.21–1.37), and 1.20 (1.12–1.28). Despite higher healthcare use, participation in the preventive child health programme had a RR of 0.69 (95% CI 0.67–0.72) for exposed compared to reference children. The higher use of hospitals and GP, but lower participation in the child health programme underscores the long-term consequences and societal burden of heavy prenatal alcohol exposure, and leaves a need for awareness and adequate support to ensure health equity.