Maternal factors associated with labor dystocia in low-risk nulliparous women. A systematic review and meta-analysis

Objective: To identify maternal factors associated with labor dystocia in low-risk nulliparous women. Methods: MEDLINE, Embase, ClinicalTrials.gov, Cochrane, and CINAHL were searched for intervention studies and observational studies published from January 2000 to January 2022. Low-risk was defined as nulliparous women with a singleton, cephalic birth in spontaneous labor at term. Labor dystocia was defined by national or international criteria or treatment. Countries were restricted to OECD members. Two authors independently screened 11,374 titles and abstracts, extracted data, and assessed risk of bias using the Newcastle-Ottawa Scale. Results were presented narratively and by meta-analysis when compatible. Results: Seven cohort studies were included. Overall, the certainty of the evidence was moderate. Three studies found that higher maternal age was associated with an increased frequency of labor dystocia (relative risk 1.68; 95% CI 1.43–1.98). Further three studies found that higher maternal BMI was associated with increased frequency of labor dystocia (relative risk 1.20; 95% CI 1.01–1.43). Maternal short stature, fear of childbirth, and high caffeine intake were also associated with an increased frequency of labor dystocia, while maternal physical activity was associated with a decreased frequency. Conclusion: Maternal factors associated with an increased frequency of labor dystocia were mainly maternal age, physical characteristics, and fear of childbirth. Maternal physical activity was associated with a decreased frequency. Intervention studies targeting these maternal factors would need to be initiated before or early in pregnancy to test the causality of the identified factors and labor dystocia.</p

Association between migraine, migraine subtype, and adverse pregnancy outcomes:A systematic review and meta-analysis

Introduction: Migraine is one of the most prevalent conditions worldwide. This systematic review aimed to evaluate the association between migraine, its subtypes, and adverse pregnancy outcomes. Material and Methods: Eligible cohort and retrospective case–control studies were included from PubMed and Embase databases from their inception to May 2024. Adverse pregnancy outcomes of interest were preeclampsia, preterm birth, low birthweight, small for gestational age, and placental abruption. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analyses of the outcomes with their odds ratios (ORs) and adjusted ORs (aOR), including a 95% confidence interval (CI), were performed using RevMan. Outcomes were pooled using random effects models, with separate analyses for cohort and retrospective case–control studies. The protocol was registered with PROSPERO (no. CRD42023404759). Results: This meta-analysis included 19 studies (11 cohort and 8 retrospective case–control) encompassing 1 420 690 deliveries. Significant associations were observed between migraine and increased risk of preeclampsia (cohort: aOR 1.28 [95% CI: 1.11–1.47], I2 = 0%), (retrospective case–control: aOR 3.4 [95% CI: 1.81–6.4], I2 = 83%) and preterm birth (cohort: aOR 1.30 [95% CI: 1.17–1.44], I2 = 11%). The meta-analyses of adjusted data on low birthweight and small for gestational age were inconsistent with respect to statistical significance (cohort: aOR 1.27 [95% CI: 0.89–1.82], I2 = 36% and cohort: aOR 1.07 [95% CI: 1.03–1.12], I2 = 0%, respectively). In addition, migraine without aura (MO) (cohort: OR 1.62 [95% CI: 1.30–2.01], I2 = 0%; retrospective case–control: aOR 4.91 [95% CI: 2.78–8.67], I2 = 0%) and migraine with aura (MA) (cohort: OR 2.06 [95% CI: 1–4.27], I2 = 29%) were significantly associated with the risk of preeclampsia. Similarly, MO (cohort: OR 1.28 [95% CI: 1.11–1.49], I2 = 0%) and MA (cohort: OR 1.25 [95% CI: 1.07–1.47], I2 = 0%) were associated with preterm birth risk. Conclusions: Pregnant women with migraines have a higher risk of preeclampsia and preterm birth compared with those without migraines. Migraine could be associated with an increased risk of low birth weight and small for gestational age. Sub-analyses indicate an elevated risk of preeclampsia and preterm birth across migraine subtypes. Notably, no previous meta-analyses have differentiated between migraine subtypes. Additional studies are needed to strengthen these findings.</p

Paracetamol use prior to and in early pregnancy:Prevalence and patterns among women with and without chronic medical diseases

Aims: Paracetamol is commonly consumed by pregnant women, even though recent data have questioned its safety. Having chronic medical diseases (CMDs) may influence the prevalence of use during pregnancy. We aimed to assess the prevalence and patterns of use 3 months prior to pregnancy and in the first trimester among women with and without CMDs and the potential influence of CMDs on frequent use in the first trimester. Methods: We used patient-reported data from the Copenhagen Pregnancy Cohort from 1 October 2013 to 23 May 2019 with information on CMDs and paracetamol use. Prevalence and patterns of use were assessed descriptively and by multivariable logistic regression models. Results: We included 24 019 pregnancies. Use of paracetamol prior to and in early pregnancy was significantly higher among women with CMDs compared to women without (40.7% vs. 35.8% and 9.1% vs. 5.1%, respectively). Women with CMDs were 2.7 times more likely to have a frequent intake compared to women without [aOR 2.69 (95% CI 2.05–3.32)]. Migraine, rheumatoid arthritis and mental disease were associated with a higher use of paracetamol [aOR 4.39 (3.20–6.02), aOR 4.32 (2.41–7.72) and aOR 2.74 (1.67–4.49), respectively]. Conclusions: Women with CMDs had a higher paracetamol use before and during pregnancy than women without CMDs. Women with migraine, rheumatoid arthritis and mental disease showed the highest risk of frequent use. This study highlights the importance of discussing pain relief in pregnancy and evaluating the influence of maternal CMDs when assessing adverse effects of paracetamol use during pregnancy.</p

First-trimester prediction of preterm prelabour rupture of membranes incorporating cervical length measurement

Objectives: To examine early pregnancy risk factors for preterm prelabour rupture of membranes (PPROM) and develop a predictive model. Study design: Retrospective analysis of a cohort of mixed-risk singleton pregnancies screened in the first and second trimesters in three Danish tertiary fetal medicine centres, including a cervical length measurement at 11–14 weeks, at 19–21 weeks and at 23–24 weeks of gestation. Univariable and multivariable logistic regression analyses were employed to identify predictive maternal characteristics, biochemical and sonographic factors. Receiver operating characteristic (ROC) curve analysis was used to determine predictors for the most accurate model. Results: Of 3477 screened women, 77 (2.2%) had PPROM. Maternal factors predictive of PPROM in univariable analysis were nulliparity (OR 2.0 (95% CI 1.2–3.3)), PAPP-A < 0.5 MoM (OR 2.6 (1.1–6.2)), previous preterm birth (OR 4.2 (1.9–8.9)), previous cervical conization (OR 3.6 (2.0–6.4)) and cervical length ≤ 25 mm on transvaginal imaging (first-trimester OR 15.9 (4.3–59.3)). These factors all remained statistically significant in a multivariable adjusted model with an AUC of 0.72 in the most discriminatory first-trimester model. The detection rate using this model would be approximately 30% at a false-positive rate of 10%. Potential predictors such as bleeding in early pregnancy and pre-existing diabetes mellitus affected very few cases and could not be formally assessed. Conclusions: Several maternal characteristics, placental biochemical and sonographic features are predictive of PPROM with moderate discrimination. Larger numbers are required to validate this algorithm and additional biomarkers, not currently used for first-trimester screening, may improve model performance

First-trimester screening for pre-eclampsia

Pre-eclampsia is a common and serious pregnancy complication. This review describes that low-dose acetylsalicylic acid can reduce the risk of preterm pre-eclampsia in high-risk pregnant women if treatment is started before the 16th week of pregnancy. A new screening algorithm can already, in the first trimester of pregnancy, predict an individual woman’s risk of developing pre-eclampsia by combining a series of biophysical and biochemical markers with maternal risk factors. The screening has been validated internationally and in Denmark. In 2025, a national implementation project will be initiated to evaluate the effectiveness of a change in screening strategy in Denmark

Project Half Double: results of phase 1 and phase 2 - June 2019

The purpose of this report in a series of reports from Project Half Double is to present the final overall results from phase 1 and phase 2 of Project Half Double as well as to describe the nine pilot projects from phase 2 in detail

Is smoking heaviness causally associated with alcohol use? A Mendelian randomization study in four European cohorts

BACKGROUND: Observational studies have shown that tobacco and alcohol use co-occur, but it is not clear whether this relationship is causal. METHODS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK Biobank, we used observational methods to test the hypothesis that smoking heaviness increases alcohol consumption. Mendelian randomization (MR) analyses were then used to test the causal relationship between smoking heaviness and alcohol consumption using 55 967 smokers from four European studies [ALSPAC, The Nord-Trøndelag Health Study (HUNT), the Copenhagen General Population Study (CGPS) and UK Biobank]. MR analyses used rs1051730/rs16969968 as a genetic proxy for smoking heaviness. RESULTS: Observational results provided evidence of an association between cigarettes per day and weekly alcohol consumption (increase in units of alcohol per additional cigarette smoked per day = 0.10, 95% confidence interval (CI) 0.05 to 0.15, P ≤ 0.001 in ALSPAC; and 0.48, 95% CI 0.45 to 0.52, P ≤ 0.001 in UK Biobank). However, there was little evidence for an association between rs1051730/rs16969968 and units of alcohol consumed per week across ALSPAC, HUNT, CGPS and UK Biobank (standard deviation increase in units of alcohol per additional copy of the risk allele = –0.004, 95% CI –0.023 to 0.016, P=0.708, I² = 51.9%). We had 99% and 88% power to detect a change of 0.03 and 0.02 standard deviation units of alcohol per additional copy of the risk allele, respectively. CONCLUSIONS: Previously reported associations between smoking and alcohol are unlikely to be causal, and may be the result of confounding and/or reverse causation. This has implications for public health research and intervention research

Exploring the Role of Cardiac Troponin-Specific Autoantibodies:Prolonged Cardiac Troponin Elimination, Reduced Clearance, and Variable Interference across 5 Commercial Assays

Background High-sensitivity cardiac troponin (hs-cTn) assays are prone to negative and positive interferences caused by endogenous cardiac troponin-specific autoantibodies (cTnAAbs). Large macrotroponin complexes formed of cardiac troponin (cTn) and cTnAAbs may result in falsely elevated hs-cTn results. This is potentially due to reduced clearance of macrotroponin, but direct evidence is still lacking. In this study, we investigated the possible effects of cTnAAbs on the elimination of cTn. Methods Twenty patients with ST-elevation myocardial infarction (MI) underwent plasmapheresis within 24 h after revascularization to harvest plasma with a high cTn concentration. After clinical recovery, patients returned to the hospital for autologous plasma re-transfusion. Following re-transfusion, blood samples were collected at fixed time points and analyzed with 5 commercial hs-cTn assays. The presence of cTnAAbs in the samples and the epitope specificity of cTnAAbs were investigated with in-house immunoassays. Results Altogether, 2 out of 20 patients (10%) were cTnAAb-positive. With 4 commercial hs-cTn assays, cTnAAb-positive patients mainly showed longer elimination half-lives and slower cTn clearances than most cTnAAb-negative patients. One hs-cTn assay was prone to negative cTnAAb interference but correspondingly less prone to positive macrotroponin interference. The central part of cardiac troponin I (cTnI) was predominantly affected by cTnAAbs. Conclusions Endogenous cTnAAbs were for the first time shown to prolong the elimination half-life and reduce the clearance of cTn in the circulation. Additionally, the extent of analytical interference from cTnAAbs and their reactivity to macrotroponin varies among commercial hs-cTn assays, an important consideration for laboratories to ensure accurate diagnosis of MI.</p

Impact of age on cardiac troponin concentration among healthy individuals

Background: The 99th percentile of cardiac troponin (cTn) among healthy individuals is the diagnostic cutoff for myocardial infarction. This study investigates the effect of age on the 99th percentile of cTn among healthy individuals. Methods: We sampled healthy Danish blood donors, screened using hemoglobin A1c, N-terminal pro-brain natriuretic peptide, and creatinine. The cTn assays investigated were Siemens Atellica and Dimension Vista hs-cTnI, Abbott hs-cTnI, Vitros hs-cTnI, and Roche hs-cTnT. The 99th percentiles were calculated using the non-parametric method and modeled using quantile regressions adjusted for sex and creatinine concentration. Results: We included 2287 participants, excluding 118 due to a history of heart disease, insufficient plasma, or biomarker screening, leaving 2169 participants with a median age of 58 years (IQR 49–69 years), and 1152 (53 %) were female. Concentrations increased with age for all assays (p &lt; 0.001). Only the 99th percentile of hs-cTnT was significantly associated with age (0.42 ng/L increase/year, p &lt; 0.001); for participants &gt;70 years, the 99th percentile was 36.8 ng/L (90 % CI 33.8–40.7 ng/L), with 22.2 % above the manufacturer's 99th percentile. The difference in the 99th percentile between age groups was less clear for cTnI, except for the Vitros assay: &lt;50 years 6.5 ng/L (90 % CI 5.0–26.9 ng/L) vs &gt;70 years 17.3 ng/L (90 % CI 9.7–33.2 ng/L). Conclusions: Age was associated with increased cTn concentrations for all assays. The correlation was strongest for hs-cTnT, where the 99th percentile for participants &gt;70 years was more than double compared to those &lt;50 years, with over 20 % exceeding the manufacturer's 99th percentile. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05336435.</p