ABSTRACT Objective To investigate whether periconceptual use of progesterone is associated with an altered risk of new‐onset hypertensive disorders of pregnancy (gestational hypertension, preeclampsia, or superimposed preeclampsia). Design Population‐based cohort study using statewide pregnancy and birth data from Victoria, Australia, linked with hospital and medication prescribing data. Setting Victoria, Australia (2009–2020). Population Nulliparous women who gave birth between 2009 and 2020 in Victoria, Australia. Women with missing delivery dates, medicine dispensation dates, or who were exposed to progesterone in the second or third trimester were excluded. Methods We compared nulliparous women exposed to progesterone in the periconceptual period (6 weeks preconception until the end of the first trimester) with those not exposed to progesterone. Inverse probability‐weighted regression adjustment was used to control for confounding factors and investigate the effect of progesterone on the risk of preeclampsia (including superimposed preeclampsia) and gestational hypertension. Main Outcome Measures Development of preeclampsia or gestational hypertension. Results Among 386 475 pregnancies, 5657 (1.5%) women used progesterone in the periconceptual period. Progesterone use was associated with a statistically significant reduction in the risk of any new onset hypertensive disorders of pregnancy (adjusted risk ratio [aRR] 0.81 [95% confidence interval [CI] 0.67, 0.98]; adjusted risk difference [aRD] −1.72% [95% CI −3.21%, −0.24%]). Investigating type of hypertension, we found progesterone use was associated with a 1.69% absolute reduced risk of gestational hypertension (aRR 0.60 [95% CI 0.43, 0.83]; aRD −1.69% [95% CI −2.52%, −0.86%]) but no significant change was observed for preeclampsia (aRR 0.97 [95% CI 0.75, 1.25]; aRD −0.13% [95% CI −1.49%, 1.23%]). Restricting our analyses to pregnancies conceived via assisted reproductive technology only, we found similar results, with a statistically significant reduction in the risk of gestational hypertension (aRR 0.80 [95% CI 0.67, 0.95]; aRD −1.02% [95% CI −1.73%, −0.30%]) but not preeclampsia (aRR 0.96 [95% CI 0.83, 1.11]; aRD −0.25% [95% CI −1.23%, 0.72%]). Conclusions Among 386 475 nulliparous women, we found periconceptual progesterone use to be associated with a statistically significant reduction in the risk of gestational hypertension, but not preeclampsia. However, these findings are unlikely to be clinically meaningful.
ABSTRACT Background Adenomyosis is a prevalent gynaecological disorder whose pathogenesis remains incompletely understood. Congenital Müllerian anomalies provide an informative in vivo model, since obstructive and non‐obstructive variants impose spatially defined alterations of intrauterine pressure, myometrial architecture, and contractility. Objectives To characterise adenomyosis localisation across Müllerian anomaly subtypes, assess concomitant endometriosis prevalence, and examine their topographic concordance with sites of uterine obstruction. Search Strategy PubMed/MEDLINE, Embase and Scopus were searched from inception to October 2025 using MeSH/Emtree and free‐text terms for adenomyosis and congenital Müllerian anomalies, without date restrictions. Selection Criteria Original case reports, case series, and observational studies in English explicitly describing the diagnostic modalities used for both conditions. Data Collection and Analysis Two reviewers independently screened and extracted data; methodological quality was assessed with the Joanna Briggs Institute tools. Data were synthesised descriptively by malformation subtype, with case‐by‐case laterality analysis where individual patient‐level data were available. Main Results Forty‐two studies (135 patients) were included. Unicornuate uterus predominated (102/135, 75.6%). Among patients with directly reported localisation and a non‐communicating functional rudimentary horn, adenomyosis involved the rudimentary horn in 10/12 cases (83.3%). In Robert's uterus, adenomyosis was ipsilateral to the blind hemicavity in 3/3 evaluable cases (100%). In Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome, adenomyosis occurred in remnants lacking functional endometrium in 10/15 patients (66.7%). Concomitant endometriosis (43/134 evaluable patients, 32.1%) was most frequent in obstructive anomalies (Herlyn‐Werner‐Wunderlich syndrome (HWW) 3/5, 60.0%; Robert's uterus 2/4, 50.0%) and least frequent in septate uterus (0/2, 0%) and MRKH (2/15, 13.3%), localising ipsilateral to the obstruction in 9/10 (90.0%) reported obstructive cases. Conclusions Adenomyosis preferentially involved structurally abnormal or obstructed uterine compartments. The endometriosis gradient was compatible with impaired menstrual efflux as a shared mechanical determinant. These findings derive from a low‐quality evidence base and should therefore be regarded as hypothesis‐generating. Prospective confirmation is required, although these findings may support increased clinical awareness in women with Müllerian anomalies, particularly obstructive variants.
ABSTRACT Objectives To investigate the relationship between the first trimester gut microbiome and small vulnerable newborns (SVN). Setting Rural low‐ and middle‐income country: Bangladesh. Population 213 women were enrolled during the first trimester of pregnancy as part of the NICHD Global Network for Women's and Children's Health registry, Bangladesh. Methods Observational study of the maternal gut microbiome and birth outcomes. Blood and stool samples were collected at enrollment. Birth outcomes were recorded within 72 h of delivery. Random forest machine learning models trained on microbiome data were used to predict SVN or first‐trimester maternal features of interest. Hold out sets were used to test model accuracy. Main Outcome Measures SVN (born preterm, low birth weight, or small for gestational age). Results The birth outcome SVN ( n = 106) was discriminated from non‐SVN ( n = 107) using a microbiome‐trained random forest model (AUC = 0.653, 95% CI 0.518–0.789). The microbiome also predicted the inflammatory markers plasma alpha‐1‐acid glycoprotein and faecal calprotectin (AUC = 0.742, 95% CI: 0.616–0.868 and AUC = 0.793, 95% CI: 0.680–0.905, respectively), while micronutrient concentrations, anaemia, C‐reactive protein and the presence of atypical Enteropathogenic E. coli were not reliably predicted. Higher alpha‐1‐acid glycoprotein was significantly associated with SVN (aOR = 1.98; 95% CI: 1.04–3.85) whereas calprotectin was not. Conclusions In this prospective cohort, first‐trimester maternal gut microbiome composition showed modest discrimination for SVN and a marker of systemic inflammation. These findings support further investigation of early pregnancy microbiome–inflammation pathways in fetal growth restriction and preterm birth.
ABSTRACT Objective To develop an operational, systems‐oriented framework for analysing sustainable maternal healthcare utilisation, grounded in Nigerian evidence and intended for contextual adaptation and testing. Design Conceptual framework study using narrative synthesis, structured comparative evidence synthesis and independent face and content appraisal. Setting Nigeria, with consideration of applicability to other maternal healthcare settings. Population or Sample Purposively selected peer‐reviewed Nigerian maternal healthcare studies; three independent external appraisers comprising two maternal‐health researchers and one healthcare professional. Methods We synthesised empirical evidence into linked domains and hypothesised relationships, compared it with established maternal‐health and health‐systems frameworks and challenged it against additional Nigerian studies. Appraisers assessed relevance, clarity, completeness, cross‐domain plausibility, and practical utility. Main Outcome Measures Conceptual coherence, domain relevance, completeness, explanatory plausibility, practical utility, and candidate indicators of sustainable maternal healthcare utilisation; no patient‐level clinical outcomes were measured. Results We specified six linked domains: policy and governance, health‐system capacity, community engagement, equity, quality of care, and monitoring, evaluation and learning. Governance provides structural conditions; capacity, quality and community engagement interact; equity modifies pathways; and monitoring supports feedback and adaptation. External appraisal offered qualified support and identified boundaries requiring refinement. Conclusions The framework offers a testable systems structure for diagnosing interacting barriers and guiding context‐appropriate indicators and multilevel interventions. Prospective testing is needed to establish construct validity, responsiveness and transferability.
