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Introduction: During pregnancy, women rely on a variety of sources to obtain information. However, not all of these sources are equally reliable, and there is the concern that especially online information-seeking may increase pregnancy-related anxiety. This study examines to what extent different sources of pregnancy information are associated with concurrent pregnancy-related anxiety (RQ1) and changes in pregnancy-related anxiety throughout the pregnancy (RQ2).

Methods: This study was integrated into the ongoing Swedish Mom2B study (substudy data collection: December 2022–April 2024), where women complete weekly questionnaires via a research app. Each trimester, they received questions about their use of information sources and pregnancy-related anxiety.

Results: Our sample consisted of 751 pregnant women (273 with at least two waves of data). Using the midwife (β= -0.14, p<0.001; 95% CI: -3.32 – -1.13) or social circle (β= -0.08, p<0.05; 95% CI: -2.83 – -0.07) as a source of pregnancy-and childbirth-related information was associated with lower levels of pregnancy-related anxiety. In contrast, reliance on online sources for information was associated with higher levels of anxiety (β=0.14, p<0.001; 95% CI: 1.52–5.03). Except for (e-)books, which lowered the odds of improving anxiety (OR=0.62, p<0.01; 95% CI: 0.45–0.85), none of the information sources predicted changes in pregnancy-related anxiety over time.

Conclusions: Not all information sources play an equal role in relation to pregnancyrelated anxiety. Interpersonal sources in particular may help mitigate anxiety. However, future research with more nuanced methodologies and shorter measurement intervals could clarify possible causal relationships and refine our understanding of how various information sources affect pregnancy-related anxiety over time.

Background

Peripartum depression is a common but potentially debilitating pregnancy complication. Mobile applications can be used to collect data throughout the pregnancy and postpartum period to improve understanding of early risk indicators.

Aim

This study aimed to improve understanding of why women drop out of a peripartum depression mHealth study, and how we can improve the app design.

Method

Participants who dropped out of the Mom2B study (n = 134) answered closed and open questions on their motives for dropping out of the study, suggestions for improvement, and preferred timeframe of the study. A mix of quantitative and qualitative strategies was used to analyze the responses.

Results

The most common reasons for discontinuation were lack of time, problems with or loss of the pregnancy, the use of other pregnancy applications, surveys being too lengthy, the app draining too much battery, and participants incorrectly believing that their answers were irrelevant for the study. Participants suggested fewer survey moments, more reminders, and a need for more unique content compared to commercially available apps.

Conclusions

Researcher who want to use mHealth designs in peripartum studies need to ensure that their study designs are as time-efficient as possible, remind participants about the study, manage expectations about the study and what is expected of participants throughout the study, design their apps to be attractive in a competitive market, and follow-up with participants who are excluded from the study due to pregnancy complications.

BACKGROUND: In this study, we aimed to characterize the gut microbiome and its potential functioning in 2 populations at 2 time points during pregnancy in relation to mental distress. METHODS: During the second and third trimester, individuals from the United States and Sweden completed the Edinburgh Postnatal Depression Scale and provided fecal samples for whole-genome metagenomics. A total of 832 and 161 samples were sequenced and analyzed from the Swedish cohort and the U.S. cohort, respectively. Multiple characterizations of the microbial community were analyzed in relation to distress measured using the Edinburgh Postnatal Depression Scale. Principal coordinate analysis and distance-based redundancy analysis assessed variation in functional gut-brain modules. For the U.S. cohort, the Trier Social Stress Test was administered 8 weeks postpartum while collecting salivary cortisol. RESULTS: Principal coordinate analysis identified 4 sample clusters based on the gut-brain modules distinguished by functions such as short-chain fatty acid synthesis and cortisol degradation. While with distance-based redundancy analysis, mental distress subtypes did not significantly contribute to variation in gut-brain modules (p = .085 for Sweden, p = .23 for the U.S.), a U.S. sample cluster distinguished by lower cortisol degradation from another cluster with higher gut microbial cortisol degradation abundance had significantly higher odds of being associated with depression (p = .024). The U.S. sample cluster with lower gut microbial cortisol degradation abundance also had significantly higher cortisol levels after a postpartum social stressor. CONCLUSIONS: Further studies are warranted to investigate the potential for the gut microbiome to serve as biomarkers of gut-brain axis health during pregnancy across disparate populations.

Background

Infant neurodevelopment in the first years after birth is determined by multiple factors, including parental care and maternal mental wellbeing. In this study, we aim to assess the impact of persistent maternal depressive symptoms during the first 3 months postpartum on infant neurodevelopment at 6 months.

Methods

Using a longitudinal cohort design, 1253 mother-infant pairs were followed up at 7, 45, and 90 days to assess postpartum depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS); infants were followed up at 6 months to assess neuro-developmental status using the WHO's Infant and Young Child Development (IYCD) tool. A generalized linear regression model was used to assess the association between persistent postpartum depressive symptoms and infant neurodevelopmental delay at 6 months. A generalized linear mixed model (GLMM) with a hospital as a random intercept was used to assess the persistent postpartum depressive symptoms with an IYCD score. Linear regression was used to compare the IYCD scores between exposure groups.

Results

In the study population, 7.5% of mothers had persistent depressive symptoms, and 7.5% of infants had neurodevelopmental delay. Infants born to mothers with persistent depressive symptoms had a higher proportion of neurodevelopmental delay than infants born to women without persistent symptoms (48.6% vs 5.1%; p < 0.001). In the adjusted regression model, infants whose mothers had persistent depressive symptoms at 7, 45, and 90 days had a 5.21-fold increased risk of neurodevelopmental delay (aRR, 5.21; 95% CI, 3.17, 8.55). Mean scores in the motor domain (12.7 vs 15.2; p < 0.001) and language domain (6.4 vs 8.5; p < 0.001) were significant when a mother had persistent depression vs. no depression. Mean scores in the general behavioral domain (5.9 vs 10.4, p < 0.001) and the socio-emotional domain (15.4 vs 17.7; p < 0.001) were significantly different when a mother had persistent depression vs no persistent depression.

Conclusions

Our results suggest that 6-month-old infants are at higher risk for neurodevelopment delays if their mother reports persistent symptoms of depression from 7 to 90 days postpartum. The neurodevelopmental delay can be observed in all functional domains. Preventive intervention to reduce maternal postpartum depression may reduce the impact on infant developmental delay.

Objective 

Diabetes is frequently linked with depression, and both conditions are common complications during pregnancy. However, research findings exploring the relationship between diabetes mellitus in pregnancy (DMP) and perinatal depression (PND) have been inconsistent. Thus, this study seeks to examine the association between DMP and PND in a prospective population-based cohort.

Methods 

Women aged 18 to 48 years (n = 4459) were identified from the Biology, Affect, Stress, Imaging and Cognition study. The diagnosis of DMP was based on International Classification of Diseases code O24 from medical records and was classified as pregestational, gestational, or unspecified diabetes. PND was assessed using psychometric instruments, clinical interviews, and/or register data and categorized into antepartum or postpartum depression. Multivariable logistic regressions were used to study the associations of DMP with antepartum and postpartum depression. The association between DMP and continuous depression scores, antepartum and postpartum, was investigated with multivariable linear regressions.

Results 

Of 4459 pregnancies, 949 women had antepartum depression (21.2%) and 1123 had postpartum depression (25%). DMP had a prevalence of 1.2%. Women with DMP had twofold higher odds for postpartum depression compared with women without DMP. Although no association was observed between DMP and antepartum depression, DMP was associated with higher antepartum depression scores.

Conclusions 

Our study shows an association between DMP and PND, which might be considered a risk factor when screening for high-risk groups.

Introduction Data suggest that micronised progesterone (mP) in menopausal hormone therapy is safer for the breast than synthetic progestins, while protection of the endometrium appears to be less effective. However, comparative randomised trial data are lacking. The objective of the Progesterone Breast Endometrial Safety Study is to investigate breast and endometrial safety of mP versus norethisterone acetate (NETA) in continuous combination with oral oestrogen.

Methods and analysis This multicentre trial, conducted at three University Hospitals in Stockholm and Uppsala, Sweden, consists of two phases: part 1 focuses on breast safety and is designed as a double-blind, randomised controlled trial. 260 postmenopausal women will be randomised to 100 mg mP or 0.5 mg NETA per day in continuous combination with 1 mg oestradiol. The primary objective is to compare the treatments with respect to percentage change in mammographic breast density after 12-month treatment. Secondary outcomes are breast proliferation, endometrial histology and proliferation, bleeding pattern, gut and vaginal microbiome, hormone levels and coagulation and metabolic factors, mood, and health-related quality of life. Part 2 features an open, single-arm design to study endometrial safety of 1-year treatment with mP in continuous combination with oestradiol on endometrial pathology (hyperplasia and cancer). We will treat 260 additional women with 100 mg mP/1 mg oestradiol resulting in an endometrial safety population of 390 women. The total number of participants in part 1 and part 2 will be 520.

Ethics and dissemination The study protocol was approved by the Swedish Ethical Review Authority (2021-03033) on 29 June 2021 with amendment (2023-01480-02, protocol version 3.1) on 14 March 2023. Results of the study will be published in peer-reviewed journals and presented at scientific meetings.

Trial registration number NCT05586724.

Objective To assess the effect of contemporary menopausal hormone therapy on the risk of cardiovascular disease according to the route of administration and combination of hormones.

Design Nationwide register based emulated target trial.

Setting Swedish national registries.

Participants 919 614 women aged 50-58 between 2007 and 2020 without hormone therapy use in the previous two years, identified from the Swedish population.

Interventions 138 nested trials were designed, starting each month from July 2007 until December 2018. Using the prescription registry data for that specific month, women who had not used hormone therapy in the previous two years were assigned to one of eight treatment groups: oral combined continuous, oral combined sequential, oral unopposed oestrogen, oral oestrogen with local progestin, tibolone, transdermal combined, transdermal unopposed oestrogen, or non-initiators of menopausal hormone therapy.

Main outcome measures Hazard ratios with 95% confidence intervals were estimated for venous thromboembolism, as well as for ischaemic heart disease, cerebral infarction, and myocardial infarction separately and as a composite cardiovascular disease outcome. Treatment effects were estimated by contrasting initiators and non-initiators in observational analogues to “intention-to-treat” analyses and continuous users versus never users in “per protocol” analyses.

Results A total of 77 512 women were initiators of any menopausal hormone therapy and 842 102 women were non-initiators. 24 089 women had an event recorded during the follow-up: 10 360 (43.0%) had an ischaemic heart disease event, 4098 (17.0%) had a cerebral infarction event, 4312 (17.9%) had a myocardial infarction event, and 9196 (38.2%) had a venous thromboembolic event. In intention-to-treat analyses, tibolone was associated with an increased risk of cardiovascular disease (hazard ratio 1.52, 95% confidence interval 1.11 to 2.08) compared with non-initiators. Initiators of tibolone or oral oestrogen-progestin therapy had a higher risk of ischaemic heart disease (1.46 (1.00 to 2.14) and 1.21 (1.00 to 1.46), respectively). A higher risk of venous thromboembolism was observed for oral continuous oestrogen-progestin therapy (1.61, 1.35 to 1.92), sequential therapy (2.00, 1.61 to 2.49), and oestrogen-only therapy (1.57, 1.02 to 2.44). Additional results in per protocol analyses showed that use of tibolone was associated with a higher risk of cerebral infarction (1.97, 1.02 to 3.78) and myocardial infarction (1.94, 1.01 to 3.73).

Conclusions Use of oral oestrogen-progestin therapy was associated with an increased risk of heart disease and venous thromboembolism, whereas the use of tibolone was associated with an increased risk of ischaemic heart disease, cerebral infarction, and myocardial infarction but not venous thromboembolism. These findings highlight the diverse effects of different hormone combinations and administration methods on the risk of cardiovascular disease.

The objective of this study was to investigate how placental gene expression differs in two consecutive pregnancies in same sex siblings, and its possible association with the "maternal constraint" hypothesis. Material was gathered from the BASIC study (Biological, Affect, Stress, Imaging, and Cognition in Pregnancy and the Puerperium), a population based prospective study that was started in 2009 in Uppsala. Over 900 specimens of placenta biopsies were collected and out of these 10 women gave birth twice, to the same sex child, and were included in this study. The total RNA was isolated and prepared from frozen villous tissue from the placenta and further analyzed by use of Ion AmpliSeq Human Transcriptome Gene Expression kit. A total of 234 genes differed significantly between the first and second pregnancy placentas, when adjusting for delivery mode, maternal BMI and gestational age. Of special interest was the down-regulated group of genes in the second pregnancy. Exemplified by Pentraxin 3, SRY-Box Transcription Factor 9, and Serum Amyloid A1, which all were associated with biological processes involved in the immune system and inflammation. Further, protein-protein interaction analysis visualized them as hub genes interacting with several of the other differentially expressed genes. How these altered gene expressions affect maternal constraint during pregnancy needs further validation in lager study cohorts and also future validation in functional assays.

BACKGROUND: Preeclampsia complicates 3-5% of all pregnancies and is associated with higher levels of asymmetric (ADMA) and symmetric (SDMA) dimethylarginines. Dimethylarginines are inhibitors of nitric oxide, which is a uterine smooth muscles relaxant. Women with hypertensive disorders experience a shorter labor duration compared to normotensive women. However, very little is known about the possible biochemical mechanisms behind differences in labor duration. In this study 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, between 2009 and 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 CRP, TNF-R1, TNF-R2 and 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 to controls. Further, 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 arigines, negative correlation of arginines to duration of labor 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 duration of labor in preeclampsia.

Problem: Preterm birth (PTB) is a leading cause of infant mortality and morbidity. The pathogenesis of PTB is complex and involves many factors, including socioeconomy, inflammation and infection. Asymmetric dimethylarginine, ADMA and symmetric dimethylarginine, SDMA are involved in labor as inhibitors of nitric oxide, a known relaxant of the uterine smooth muscles. Arginines are scarcely studied in relation to PTB and we aimed to investigate arginines (ADMA, SDMA and L-arginine) in women with spontaneous PTB and term birth.

Methods of the Study: The study was based on data from the population-based, prospective cohort BASIC study conducted in Uppsala County, Sweden, between September 2009 and November 2018. Arginines were analyzed by Ultra-High Performance Liquid Chromatography using plasma samples taken at the onset of labor from women with spontaneous PTB (n = 34) and term birth (n = 45). We also analyzed the inflammation markers CRP, TNF-R1 and TNF-R2 and GDF-15.

Results: Women with spontaneous PTB had higher plasma levels of ADMA (p < 0.001), and L-Arginine (p = 0.03). In addition, inflammation marker, TNF-R1 (p = 0.01) was higher in spontaneous PTB compared to term birth. Further, in spontaneous PTB, no significant correlations could be observed when comparing levels of arginines with inflammation markers, except ADMA versus CRP.

Conclusions: These findings provide novel evidence for the potential involvement of arginines in the pathogenesis of spontaneous PTB and it seems that arginine levels at labor vary independently of several inflammatory markers. Further research is warranted to investigate the potential of arginines as therapeutic targets in the prevention and management of spontaneous PTB.