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Preeclampsia (PE) is a heterogeneous disease for which the current clinical classification system is based on the presence or absence of specific clinical features. PE-associated placentas also show heterogeneous findings on pathologic examination, suggesting that further subclassification is possible. We combined clinical, pathologic, immunohistochemical, and transcriptomic profiling of placentas to develop integrated signatures for multiple subclasses of PE. In total, 303 PE and 1388 nonhypertensive control placentas were included. We found that maternal vascular malperfusion (MVM) in the placenta was associated with preterm PE with severe features and with small-for-gestational-age neonates. Interestingly, PE placentas with either MVM or no histologic pattern of injury showed a linear decrease in proliferative (p63+) cytotrophoblast per villous area with increasing gestational age, similar to placentas obtained from the nonhypertensive patient cohort; however, PE placentas with fetal vascular malperfusion or villitis of unknown etiology lost this phenotype. This is mainly because of cases of fetal vascular malperfusion in placentas of patients with preterm PE and villitis of unknown etiology in placentas of patients with term PE, which are associated with a decrease or increase, respectively, in the cytotrophoblast per villous area. Finally, a transcriptomic analysis identified pathways associated with hypoxia, inflammation, and reduced cell proliferation in PE-MVM placentas and further subclassified this group into extravillous trophoblast-high and extravillous trophoblast-low PE, confirmed using an immunohistochemical analysis of trophoblast lineage-specific markers. Our findings suggest that within specific histopathologic patterns of placental injury, PE can be subclassified based on specific cellular and molecular defects, allowing the identification of pathways that may be targeted for diagnostic and therapeutic purposes.

Several adverse maternal outcomes have been linked to the excessive consumption of caffeine during pregnancy. Tea is an important source of caffeine. Hypertensive disorders of pregnancy (HDP) are common pregnancy complications with unfavorable maternal and fetal complications. This study aimed to investigate the relationship between antenatal tea drinking and HDP using a meta-analysis of available evidence. We systematically retrieved eligible studies before computing the pooled odds ratio (OR) and 95% confidence interval (CI) of HDP for women who reported the highest versus the lowest frequencies of antenatal tea drinking. We used the I2 statistic to measure heterogeneity across studies and the test for funnel plot asymmetry to evaluate publication bias. The results showed that the highest frequencies of antenatal tea drinking were associated with increased odds of HDP (pooled OR = 1.16, 95% CI: 1.01, 1.33). We identified no signs of heterogeneity across studies (I2 = 0.0% and p-heterogeneity = 0.498) or publication bias (z = 0.791 and p-publication bias = 0.429). When the outcome was limited to (pre-)eclampsia, the association became statistically non-significant (pooled OR = 1.28, 95% CI: 0.86, 1.89, I2 = 0.0%, and p-heterogeneity = 0.751). In conclusion, our results indicated that the highest frequency of antenatal tea drinking was positively associated with HDP. Pregnant women should be advised against excessive tea consumption. Still, future prospective cohort studies, considering the effects of different tea types and caffeine content, are needed to confirm our conclusions.

Objective To investigate the characteristics of thyroid function and its influencing factors in preterm infants born to mothers with preeclampsia. Methods A total of 222 preterm infants, who were admitted to the neonatal intensive care unit of our hospital from January to December 2019, were enrolled, and according to the presence or absence of preeclampsia in the mother, they were divided into experimental group with 120 infants and control group with 102 infants. Basic clinical data were collected from the preterm infants and their mothers, as well as the results of thyroid function test using peripheral venous blood of preterm infants at 10-14 d after birth. The Student’s t-test, a one-way analysis of variance, and the multiple stepwise regression analysis were used to investigate the influencing factors for thyroid function in preterm infants. Results There was no significant difference in maternal thyroid function between the two groups (P>0.05). The experimental group had a significantly higher se-rum level of thyroid stimulating hormone (TSH) than the control group (t=-2.76,P

Abstract Background Pre-term birth, the leading cause of neonatal mortality, has been associated with maternal periodontal disease and the presence of oral pathogens in the placenta. However, the mechanisms that underpin this link are not known. This investigation aimed to identify the origins of placental microbiota and to interrogate the association between parturition complications and immune recognition of placental microbial motifs. Video Abstract Methods Saliva, plaque, serum, and placenta were collected during 130 full-term (FT), pre-term (PT), or pre-term complicated by pre-eclampsia (PTPE) deliveries and subjected to whole-genome shotgun sequencing. Real-time quantitative PCR was used to measure toll-like receptors (TLR) 1–10 expression in placental samples. Source tracking was employed to trace the origins of the placental microbiota. Results We discovered 10,007 functionally annotated genes representing 420 taxa in the placenta that could not be attributed to contamination. Placental microbial composition was the biggest discriminator of pregnancy complications, outweighing hypertension, BMI, smoking, and maternal age. A machine-learning algorithm trained on this microbial dataset predicted PTPE and PT with error rates of 4.05% and 8.6% (taxonomy) and 6.21% and 7.38% (function). Logistic regression revealed 32% higher odds of parturition complication (95% CI 2.8%, 81%) for every IQR increase in the Shannon diversity index after adjusting for maternal smoking status, maternal age, and gravida. We also discovered distinct expression patterns of TLRs that detect RNA- and DNA-containing antigens in the three groups, with significant upregulation of TLR9, and concomitant downregulation of TLR7 in PTPE and PT groups, and dense correlation networks between microbial genes and these TLRs. 70–82% of placental microbiota were traced to serum and thence to the salivary and subgingival microbiomes. The oral and serum microbiomes of PTPE and PT groups displayed significant enrichment of genes encoding iron transport, exosome, adhesion, quorum sensing, lipopolysaccharide, biofilm, and steroid degradation. Conclusions Within the limits of cross-sectional analysis, we find evidence to suggest that oral bacteria might translocate to the placenta via serum and trigger immune signaling pathways capable of inducing placental vascular pathology. This might explain, in part, the higher incidence of obstetric syndromes in women with periodontal disease.

Hypertensive disorders of pregnancy (HDP) represent a substantial risk to maternal and fetal health. Emerging evidence suggests an association between testosterone and pre-eclampsia (PE), potentially mediated through androgen receptors (AR). Nevertheless, the mechanism driving this association is yet to be elucidated. On the other hand, reports of transgender men’s pregnancies offer a limited and insightful opportunity to understand the role of high androgen levels in the development of HDP. In this sense, a literature review was performed from a little over 2 decades (1998–2022) to address the association of testosterone levels with the development of HDP. Furthermore, this review addresses the case of transgender men for the first time. The main in vitro outcomes reveal placenta samples with greater AR mRNA expression. Moreover, ex vivo studies show that testosterone-induced vasorelaxation impairment promotes hypertension. Epidemiological data point to greater testosterone levels in blood samples during PE. Studies with transgender men allow us to infer that exogenous testosterone administration can be considered a risk factor for PE and that the administration of testosterone does not affect fetal development. Overall, all studies analyzed suggested that high testosterone levels are associated with PE.

Abstract Background: Pre-eclampsia (PE) is a multiorgan disorder that affects 2–5% of all pregnant women. Present recommendations for when to start aspirin in high-risk women are after 11 wk of gestation. Objective: We present a protocol to investigate the effectiveness of aspirin use from early pregnancy, which is a randomized controlled trial to assess whether prescribed low-dose aspirin from early pregnancy reduces the prevalence of early and late-onset PE. Additionally, to compare the effectiveness of aspirin administration before and after 11 wk in reducing the occurrence of PE? Materials and Methods: All pregnancies at risk of PE, according to demographic and midwifery history, who are referred to the Maternal-Fetal Clinic of Tehran University hospital, Tehran, Iran were invited to take part in the trial. The outcomes of pregnancy and newborns will be gathered and analyzed. The first registration for the pilot study was in January 2023, and the participants were recognized as high-risk for PE. In addition, enrollment in the main study will begin as of October 2023.

Abstract Hypertensive disorders of pregnancy (HDP) are associated with an increased risk of cardiovascular disorders, with recent evidence linking pre‐eclampsia with vascular dementia. We examined associations of HDP with cognitive performance measured in midlife, in a prospective cohort study, the Avon Longitudinal Study of Parents and Children. Six cognitive function domains were measured 20 years after pregnancy at a mean age of 51 years. The cognition tests were repeated at clinics in the following two years. Cognitive function domains measured were immediate and delayed verbal episodic memory, working memory, processing speed, verbal intelligence, and verbal fluency. Exposures were pre‐eclampsia, gestational hypertension (GH), and a combined category of any HDP, all compared to normotensive pregnancy. Of 3393 pregnancies included in the analysis, GH was experienced by 417 (12.3%) and pre‐eclampsia by 57 (1.7%). GH was associated with lower verbal episodic memory, in the delayed logic memory test (‐0.16 SDs; 95% CI ‐0.30, ‐0.03; p = .015) and there was weak evidence of an association with the immediate logic memory test (‐0.13 SDs; ‐0.27, 0.001; p = .058). However, we did not see steeper declines by age for women with GH and there was no evidence of associations with other cognitive domains or for pre‐eclampsia with any domains. Results were not substantially changed after controlling for midlife blood pressure. Our findings suggest that a history of GH is associated with slightly reduced episodic memory 20 years after pregnancy, but we found no evidence of a quicker age‐related decline compared to women with normotensive pregnancies.

Background: Antiphospholipid Syndrome (APS) is a systemic autoimmune thrombophilic condition characterized by obstetric manifestations, including pregnancy loss, preeclampsia and fetal growth restriction. Early diagnosis and management are key to improve maternal and neonatal outcomes. Objective: The aim of this study is to assess the perinatal outcomes in APS, the development of various adverse pregnancy outcomes (APO), and their association with specific antibody profiles. Material methods: This observational study was carried out on booked cases of singleton pregnancy and diagnosed cases of primary APS in our High-Risk Pregnancy (HRP) clinic from January 2018 to December 2022 after approval from institutional ethics committee. Forty-three confirmed cases of primary APS were enrolled and started on low-dose aspirin and low-molecular-weight heparin (LMWH) as per the patient's body weight after confirmation of fetal heart activity radiologically until 36 weeks of gestation as a standard of care. Results: Forty patients (93 %) had obstetric APS, and three patients (7 %) had thrombotic APS. During the course of the current pregnancy, adverse pregnancy outcomes (APO) developed in 12 (30 %) out of 40 cases of obstetric APS and in all 3 patients with thrombotic APS. Preeclampsia was seen in 11 (25.5 %), FGR in 12 (27.9 %), and preterm birth in 7 (16.2 %) cases. Patients with an antibody profile showing the presence of Anti-β2 GP-I positivity and ACL positivity had fewer APOs (20 % and 29 %) in comparison to patients with a LA and triple positive antibody profile (55 % and 50 %). Conclusion: Treatment of pregnant women with APS causes significant improvement in the live birth rate. The late pregnancy complications like preeclampsia, FGR, and premature birth, occurring despite treatment still remains a challenge and emphasizes the need for stringent antepartum surveillance and timely delivery.

ABSTRACTObjective This study was designed to investigate the effects of hypertensive disorders of pregnancy (HDP) on the complications in very low birth weight (VLBW) neonates.Methods We retrospectively included VLBW neonates (

ABSTRACTObjectives To assess the ability of the USCOM® (USCOM), using measurements of cardiac output (CO) and systemic vascular resistance (SVR), to predict the development of pre-eclampsia (PE) and severe PE in hypertensive pregnancies.Study design Prospective cohort study of women in the second or third trimester recruited at a tertiary center in Sydney, Australia. Demographic data and hemodynamic measurements using the USCOM were taken for all study participants at recruitment. Pregnancy outcome, including development of PE and severe PE, was tracked. Data were analyzed using ANOVA testing, pair-wise comparison testing, and Student’s t-testing.Results Recruitment included 65 normotensive controls, 34 women with chronic hypertension (CH), 51 with gestational hypertension (GH), and 21 with PE. Significantly higher weight, body surface area, and blood pressure measurements were found in the hypertensive, compared with the normotensive control and pregnancies. There were no observed differences in USCOM-measured CO, cardiac index, SVR, or systemic vascular resistance index between hypertensive women who did versus did not develop PE or severe PE in later pregnancy. Analysis of the CH and GH subgroups, as well as only unmedicated hypertensive women (n = 24), also showed no significant difference in hemodynamic parameters between those who did or did not develop PE or severe PE.Conclusions Our group was unable to successfully predict the onset of PE or severe PE based on hemodynamic parameters measured with the USCOM. It is possible this relates to the high proportion of women on antihypertensive medication at recruitment.

BACKGROUND: Pregnant veterans with post-traumatic stress disorder (PTSD) are at increased risk for spontaneous preterm birth, yet the underlying reasons are unclear. We examined factors associated with spontaneous preterm birth among pregnant veterans with active PTSD. METHODS: This was an observational study of births from administrative databases reimbursed by the Veterans Health Association (VA) between 2005 and 2015. Singleton livebirths among veterans with active PTSD within 12 months prior to childbirth were included. The primary outcome was spontaneous preterm birth. Maternal demographics, psychiatric history, and pregnancy complications were evaluated as exposures. Covariates significant on bivariate analysis, as well as age and race/ethnicity as a social construct, were included in multivariable logistic regression to identify factors associated with spontaneous preterm birth. Additional analyses stratified significant covariates by the presence of active concurrent depression and explored interactions between antidepressant use and preeclampsia. RESULTS: Of 3,242 eligible births to veterans with active PTSD, 249 (7.7%) were spontaneous preterm births. The majority of veterans with active PTSD (79.1%) received some type of mental health treatment, and active concurrent depression was prevalent (61.4%). Preeclampsia/eclampsia (adjusted odds ratio [aOR] 3.30, 95% confidence interval [CI] 1.67-6.54) and ≥6 antidepressant medication dispensations within 12 months prior to childbirth (aOR 1.89, 95% CI 1.29-2.77) were associated with spontaneous preterm birth. No evidence of interaction was seen between antidepressant use and preeclampsia on spontaneous preterm birth (p=0.39). Findings were similar when stratified by active concurrent depression. CONCLUSION: Among veterans with active PTSD, preeclampsia/eclampsia and ≥6 antidepressant dispensations were associated with spontaneous preterm birth. While the results do not imply that people should discontinue needed antidepressants during pregnancy in veterans with PTSD, research into these factors might inform preterm birth prevention strategies for this high-risk population.

BackgroundGrowing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on specific Hb thresholds to define anemia and high Hb as well as how cutoffs may vary by anemia etiology and timing of assessment.MethodsWe conducted an updated systematic review (using PubMed and Cochrane Review) on low (

BackgroundThe objective of this study was to (1) qualitatively identify the perceived determinants of physical activity among women who have experienced severe preeclampsia, and (2) examine whether these determinants are consistent with the overarching processes outlined in the integrated behavior change (IBC) model, a novel model that describes physical activity as being a result of motivational, volitional, and automatic processes.MethodsPatients (n = 35) of the Follow-Up PreEClampsia (FUPEC) Outpatient Clinic, Erasmus MC, the Netherlands, participated in an anonymous online survey. The main outcomes under study were their perceived determinants of physical activity. Responses were analyzed using thematic analysis.ResultsThirteen themes emerged from the analysis. Six themes corresponded with motivational processes (future health, perceived ability, attitude, future reward or regret, physical appearance, and doing it for others), two with volitional processes (scheduling and planning), and two with automatic processes (affect and stress). Three themes were classified as environmental factors (time constraint, social support, and physical environment).ConclusionsA range of facilitating and hindering factors were described by women with prior severe preeclampsia as the determinants of their physical activity. These factors corresponded well with the overarching motivational, volitional, and automatic processes described in the IBC model. In addition, motivational and environmental factors beyond the IBC model were described. Addressing these perceived determinants could enhance the efficacy of physical activity interventions in this population.Tweetable abstractMotivational, volitional, automatic, and environmental factors drive physical activity in women with prior severe preeclampsia.

Background Aim Methods Results Conclusion Pacific Islander (PI) women in Australia have an increased risk of gestational diabetes (GDM); however, their perinatal outcomes are poorly understood.The aim was to determine the maternal characteristics and perinatal outcomes of PI women with and without GDM compared to Australian/European (AE)–born women.A retrospective analysis of perinatal outcomes of singleton deliveries >20 weeks’ gestation between 1 January 2011 and 31 December 2020 was conducted at a tertiary provider (Melbourne, Australia). Antenatal details and birth outcomes were extracted from the Birth Outcome Systems database. t‐Tests and χ2, univariate and multivariable logistic regression analyses assessed the relationship between ethnicity and outcomes.Of 52,795 consecutive births, 24,860 AE women (13.3% with GDM) and 1207 PI‐born women (20.1% with GDM) were compared. PI women had significantly greater pre‐pregnancy body mass index (BMI) and significantly lower rates of smoking and nulliparity. PI women with GDM had higher rates of pre‐eclampsia (P < 0.001), large‐for‐gestational age (LGA) neonates (P = 0.037) and neonatal hypoglycaemia (P = 0.017) but lower rates of small‐for‐gestational age neonates (P = 0.034). Neonatal intensive care unit (NICU)/special care nursery requirements did not increase. After having adjusted for covariates, PI women's risk of LGA neonates (adjusted odds ratio (aOR): 1.06, 95% confidence interval (CI): 0.86–1.31) was attenuated; however, risk of pre‐eclampsia (aOR: 1.49, 95% CI: 1.01–2.21) and neonatal hypoglycaemia (aOR: 1.40, 95% CI: 1.01–1.96) still increased. They were less likely to require a primary caesarean section (aOR: 0.86, 95% CI: 0.73–0.99).PI women have higher BMI and GDM rates, contributing to an increased likelihood of adverse perinatal outcomes. BMI is a modifiable risk factor that could be addressed prenatally. [ABSTRACT FROM AUTHOR]