Maternal Syndrome Research Articles

Docosahexaenoic and Eicosapentaenoic Acid Supplementation Could Attenuate Negative Effects of Maternal Metabolic Syndrome on Liver Lipid Metabolism and Liver Betacellulin Expression in Male and Female Rat Offspring.

Background/Objectives: This study investigated the effects of maternal metabolic syndrome during pregnancy on hepatic fatty acid metabolism and betacellulin expression in rat offspring. A rat model of maternal metabolic syndrome was created with a high-fructose diet (15% fructose in drinking water for six months). Methods: The females with metabolic syndrome were divided into the CON group, the HF group, which received fructose in drinking water, and the HF-DHA group, which received fructose in water and increased amounts of DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) in the diet (2.5% fish oil in the diet). The male and female offspring were killed at birth and their liver tissue was analyzed for the fatty acid profile and expression of Δ-9-desaturase and betacellulin. Results: When the rat offspring were exposed in utero to maternal fatty acids altered by the high-fructose diet, this resulted in a similarly altered fatty acid profile in the liver, with the most significant changes being Δ-9 desaturation and a dramatic increase in monounsaturated fatty acids. The offspring also showed an overexpression of hepatic betacellulin. Supplementation with DHA and EPA increased the DHA content and normalized the fatty acid composition of oleic acid, saturated fatty acids, linoleic acid and n3-docosapentaenoic acid in the offspring of mothers on a high-fructose diet. In addition, the DHA/EPA supplementation of fructose-fed mothers normalized hepatic Δ-9-desaturase and betacellulin overexpression in the offspring, suggesting that DHA/EPA supplementation affects not only the fatty acid content but also the liver function. Conclusions: The changes observed in this study suggest that DHA/EPA supplementation may modulate the effects of maternal programming on disorders of the lipid metabolism in the offspring.

Maternal autoimmune systemic connective tissue disease and vasculitis and electrocardiographic findings in the offspring.

Maternal autoimmune systemic connective tissue diseases (CTDs) and their related antibodies have been associated with adverse fetal outcomes, including complete heart block. In this study, we assessed the association between maternal CTD or vasculitis and neonatal electrocardiographic (ECG) parameters. Our study population was drawn from the Copenhagen Baby Heart Study (CBHS), a prospective, population-based cohort study open to all neonates born in the Copenhagen area. All CBHS neonates born to mothers with CTD or vasculitis were matched 1:3 to neonates born to mothers without these diseases on sex, gestational age, age and weight at time of examination, and maternal age at delivery. Maternal CTD and vasculitis diagnoses were validated through medical record review. Our primary analyses compared ECG parameters for exposed and unexposed neonates overall. Where numbers allowed, subanalyses were then conducted by specific CTD diagnoses and autoantibody types. Among 17,862 CBHS neonates with an available ECG, 40 neonates of mothers with CTDs or vasculitis (50% males, median age 12 [interquartile range 8-16] days) were matched to unexposed neonates. Overall, no significant differences in heart rate, PR interval, QRS axis, QRS duration, QT/QTc interval, or R- or S-wave amplitudes were found when comparing exposed and unexposed neonates (all p>0.05). Similarly, separate analyses of the 10 neonates with anti-Ro/SSA-positive mothers and their matched comparators revealed no significant between-group differences. However, neonates born to mothers with antiphospholipid syndrome (n=15) had a significantly longer QRS duration (median 56ms vs. 52ms, p=0.02) and corrected QT interval (median QTcBaz 430ms vs. 414ms, p=0.01), compared with matched unexposed neonates. In this population-based study, no significant overall differences in ECG parameters were found between neonates exposed to maternal CTD or vasculitis and unexposed neonates. However, neonates exposed to maternal antiphospholipid syndrome had significantly longer QRS- and QTc intervals than unexposed neonates. The potential clinical implications of these findings are unknown and, combined with the limitations of this study, warrant further investigation in larger cohorts.

Gestational Age at Delivery Is an Independent Predictor of Neonatal Outcome for Maternal HELLP Syndrome.

Hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome is a severe complication of preeclampsia (PE), with a higher incidence rate in people living at high altitudes, such as Tibet area. Maternal HELLP syndrome is associated with an elevated neonatal mortality rate. The purpose of this study was to investigate the predicting factors for neonatal outcomes with maternal HELLP syndrome. We collected 49 PE with HELLP cases and stratified them into the Survival Group (n=28) and Death Group (n=21) based on the neonatal outcomes. We compared the basic characteristics and laboratory indicators using the Student's t-test or the Mann-Whitney U test, followed by univariate and multivariate logistic regression analysis to detect the independent predicting factors for neonatal outcomes. Subsequently, we performed the receiver operating characteristics (ROC) analysis to predict the prognostic power of the variables with a cutoff value. The results indicated that levels of neutrophil-to-lymphocyte ratio (NLR), serum creatinine (Scr), lactic dehydrogenase (LDH), and brain natriuretic peptide (BNP) were significantly elevated, while gestational age (GA) at delivery and alkaline phosphatase (AP) level was significantly decreased in the Death Group. The multivariate regression analysis indicated that only GA at delivery was able to predict the neonatal outcome. The cutoff value was 32.6weeks on the ROC curve, with both 85.7% sensitivity and 85.7% specificity (AUC: 0.927, 95% CI: 0.856-0.998, p<0.001). Thus, it was concluded that GA at delivery less than 32.6weeks was an independent predictor of neonatal death for maternal HELLP syndrome.

ЛЕЧЕНИЕ ХОРИОАНГИОМЫ ПЛАЦЕНТЫ БОЛЬШИХ РАЗМЕРОВ ПУТЕМ ФЕТОСКОПИЧЕСКОЙ ЛАЗЕРНОЙ КОАГУЛЯЦИИ СОСУДОВ

Lacental chorioangioma is the most common nontrophoblastic tumor of the placenta, occurring in 0.41-1.4 % of examined placentas by microscopy. About half of large chorioangiomas can cause fetal complications such as polyhydramnios, fetal anemia, intrauterine growth retardation, heart failure, fetal hydrops and intrauterine fetal death, complications such as hemolytic anemia, thrombocytopenia, disseminated intravascular coagulation, pregnancy-induced hypertension, maternal mirror syndrome, hemoglobinuria and postpartum bleeding. We performed fetoscopic laser coagulation of blood vessels of the large placental chorioangioma at 23 weeks, which prevented the development of fetal heart failure and other serious pregnancy complications.

Maternal polycystic ovary syndrome and Offspring’s Risk of Cardiovascular diseases in Childhood and Young Adulthood

Children born to mothers with polycystic ovary syndrome have a higher prevalence of cardiovascular risk factors and of subclinical cardiovascular disease, but the association between maternal polycystic ovary syndrome and cardiovascular disease in offspring is unclear. We conduct a register-based cohort study of 6 839 703 live singleton births from Denmark (1973–2016) and Sweden (1973–2014) and follow them for up to 48 years. Using Cox regression models, we find that offspring of mothers with polycystic ovary syndrome have a higher risk of overall cardiovascular diseases and of its specific subtypes, independently of comorbidities related to polycystic ovary syndrome. Cousin analyzes suggest that familial confounding does not explain our results. If our findings are replicated by future studies, children of women with polycystic ovary syndrome may benefit from early cardiovascular prevention efforts.

Abstract 364: Pediatric Case of COVID‐Related Serial Large Vessel Occlusions Treated with Repeated Mechanical Thrombectomy

Introduction Infection with the SARS‐CoV‐2 virus, leading to the disease entity Coronavirus disease 2019 (COVID‐19), may be associated with several systemic sequelae, including COVID‐19‐induced hypercoagulability. Such a state may induce thrombus formation and ensuing acute ischemic stroke (AIS) from a large vessel occlusion (LVO). Herein, mechanical thrombectomy (MT) has been shown to be a highly effective therapeutic option for eligible adults with LVO strokes. However, given the relative rarity of AIS due to LVO in pediatric patients, MT as a therapeutic modality is not well defined in this population. Materials/Methods Case report Results The present case is that of an 11‐year‐old male with an extensive contributory medical history presenting twice over a period of 5 months for multiple LVOs. The patient was born with congenital complete heart block, given maternal Sjogren's syndrome, and underwent epicardial pacemaker implantation at 1 month of age, with replacement thereof in 2016. Serial cardiological follow up in the history revealed possible pacemaker‐induced cardiomyopathy with resultant dilated cardiomyopathy necessitating medical management. The patient's first presentation for stroke was in 2/2023 with a classic left middle cerebral artery (L MCA) syndrome constituting a National Institute of Health Stroke Scale (NIHSS) of 16; computed tomography of the head (CTH) findings of L MCA infarction and Alberta Stroke Program Early CT Score (ASPECTS) of 9; and computed tomography angiography (CTA) findings of L M1 occlusion. Intravenous thrombolysis was withheld at this encounter and the patient underwent MT with Thrombolysis in Cerebral Infarction (TICI) 2C reperfusion. Further history revealed COVID‐19 infection one week prior and echocardiogram during admission revealed features of acute systolic heart failure, likely due to COVID‐19 induced myocarditis. The patient experienced significant symptomatic recovery over this hospital stay, being discharged home on warfarin 5mg daily and outpatient follow up. The patient presented again in 7/2023 with initial cortical symptoms and dilated right pupil quickly evolving to unresponsiveness, constituting an NIHSS of 23. Work up revealed an unremarkable CTH but with basilar artery occlusion on CTA. The patient received intravenous thrombolysis with alteplase and was subsequently taken for MT, with TICI 3 reperfusion. Echocardiogram at this admission revealed decreased ejection fraction and a lesion in the anterior free wall of the left ventricle suspicious for thrombus. Evaluation by physical/occupational therapy deemed the patient appropriate for inpatient physical rehabilitation, to where he was subsequently discharged with medical recommendations of aspirin and apixaban, the latter replacing his previous warfarin. Conclusion This is an extremely rare case of a pediatric patient developing recurrent LVO's, likely secondary to COVID infection, undergoing successful MT on both occasions. This case illustrates the potential for MT as a valuable treatment option in pediatric AIS. Despite the controversial aspect of pursuing multiple thrombectomies for treatment, especially given the rarity of AIS due to LVO in the pediatric population, this case provides an example of MT producing a favorable outcome, illustrating potential therapeutic viability.

Naturally acquired microchimerism: clinical, scientific and ethical issues

Microchimerism (MC) is understood as the presence in the body of cells genetically different from the population of the individual, capable of existence and persistence, that is, reproduction and differentiation. This process is associated with the exchange of cellular material between mother and fetus. The consequences of the intrauterine acquisition of maternal MC (MMC) by the fetus are essentially different from the acquisition by the mother of fetal CM (FMC) in the mature state of the organism. Microchimerism has been implicated in the development of autoimmune diseases, but it also helps the body limit a particular disease. Since all these processes take place during the early development of the fetal immune system, the initial response of the immune system is the development of specific tolerance to maternal antigens. MMС can modify immune functions and reactivity through the nongenetic acquisition of cellular and subcellular material. Both FMС and MMС are quite common phenomena, which affects the body of the child and mother, the differentiation and functionality of the host cells. All this allows us to consider foreign cells as a potential target for drugs in the fight against autoimmune diseases or, conversely, stimulation of regeneration processes of damaged tissues. Issues of evolution and prospects for the prevention of various pathological conditions are considered from the standpoint of taking into account maternal and fetal chimerism syndrome.

STK40 inhibits trophoblast fusion by mediating COP1 ubiquitination to degrade P57Kip2

BackgroundThe syncytiotrophoblast (SCT) layer in the placenta serves as a crucial physical barrier separating maternal-fetal circulation, facilitating essential signal and substance exchange between the mother and fetus. Any abnormalities in its formation or function can result in various maternal syndromes, such as preeclampsia. The transition of proliferative villous cytotrophoblasts (VCT) from the mitotic cell cycle to the G0 phase is a prerequisite for VCT differentiation and their fusion into SCT. The imprinting gene P57Kip2, specifically expressed in intermediate VCT capable of fusion, plays a pivotal role in driving this key event. Moreover, aberrant expression of P57Kip2 has been linked to pathological placental conditions and adverse fetal outcomes.MethodsValidation of STK40 interaction with P57Kip2 using rigid molecular simulation docking and co-immunoprecipitation. STK40 expression was modulated by lentivirus in BeWo cells, and the effect of STK40 on trophoblast fusion was assessed by real-time quantitative PCR, western blot, immunofluorescence, and cell viability and proliferation assays. Co-immunoprecipitation, transcriptome sequencing, and western blot were used to determine the potential mechanisms by which STK40 regulates P57Kip2.ResultsIn this study, STK40 has been identified as a novel interacting protein with P57Kip2, and its expression is down-regulated during the fusion process of trophoblast cells. Overexpressing STK40 inhibited cell fusion in BeWo cells while stimulating mitotic cell cycle activity. Further experiments indicated that this effect is attributed to its specific binding to the CDK-binding and the Cyclin-binding domains of P57Kip2, mediating the E3 ubiquitin ligase COP1-mediated ubiquitination and degradation of P57Kip2. Moreover, abnormally high expression of STK40 might significantly contribute to the occurrence of preeclampsia.ConclusionsThis study offers new insights into the role of STK40 in regulating the protein-level homeostasis of P57Kip2 during placental development.

Serum Uric Acid in Women with Preeclampsia and its Relation to Perinatal and Maternal Outcomes

Background and objective: Preeclampsia is a dangerous, progressive condition that is linked to maternal and neonatal death and morbidity. The purpose of this study was to determine the association between serum uric acid levels in preeclampsia with maternal and fetal outcomes. Method: A case-control study was conducted on 300 women delivered at the labour room of Duhok Obstetrics and Gynecology Hospital, from 1st of April 2021 to 1st of April 2022. The study participants were divided into two groups, pregnant women with preeclampsia and normotensive women. The serum uric acid levels of these women were estimated with the impact on fetal and mother outcomes. Results: There was a highly significant association between preeclamptic and normotensive women in relation to mean serum uric acid (5.862 ±1.416) mg/dL and (3.570 ±0.982) mg/dL respectively. A highly significant association was seen between uric acid test levels and maternal eclamptic fit, HELLP syndrome and admission to intensive care unit. A highly significant association also seen with newborn birth weight, APGAR scores and admission to neonatal intensive care unit. Conclusion: The current study demonstrates a significant raise in serum uric acid level in preeclamptic women and associated with adverse perinatal and maternal outcomes.

Abstract P191: Progesterone Supplementation Ameliorates the Maternal Syndrome of Preeclampsia in the Dahl Salt-Sensitive Rats

Introduction: Preeclampsia (PreE) is characterized by new onset hypertension after 20 weeks of gestation. PreE is associated with activated CD4+ T cells, inflammation, autoantibodies to angiotensin II type 1 receptor (AT1-AA) and hypertension. To date, the best treatment remains early delivery of the feto-placental unit. Hypothesis: This study was designed to test the hypothesis that progesterone, in the form of 17-hydroxyprogesterone caproate (17-OHPC), reduces inflammation and blood pressure in the Dahl Salt-Sensitive (Dahl S) rat model of PreE. Methods: A subset of pregnant Sprague-Dawley (SD) and Dahl S rats were injected with 17-OHPC (3.32mg/kg, human dose equivalent) or vehicle (saline) at day 15 (GD15) of gestation. On GD 18, Uterine Artery Resistance Index (UARI) was measured by Doppler Ultrasound and carotid catheters were inserted for mean arterial blood pressure (MAP) measurement on GD19. Circulating and placental populations of CD4+ T cells were quantified by flow cytometry. TNF-alpha and IL-6 were measured by ELISA and AT1-AA were quantified by the chronotropic responses to angiotensin II type 1 receptor-mediated stimulation of cultured neonatal rat cardiomyocytes. Results are reported as means ± standard error means (SEM) and statistically significant when p &lt; 0.05. Results: MAP was 105±5 mmHg in SD+ vehicle rats (n=6), 104±4 in SD+17-OHPC rats (n=6), 136±3 in Dahl S+ saline rats (p &lt;0.05, n=11), which improved to 125±4 in DS+17-OHPC rats (p &lt;0.05, n=7). Pup and Placenta weights were 2.1± 0.1, 0.6 ± 0.1 g in SD+ vehicle rats and reduced to 1.4±0.1 (p&lt;0.05), 0.5±0.1 g in Dahl S +vehicle. UARI was 0.5 ±0.1 in SD+ vehicle rats (n=6) and 0.5 ±0.1 in in SD+17-OHPC (n=6), 0.7±0.1 in Dahl S+ vehicle rats (n=6, p&lt;0.05), which reduced to 0.5±0.1 in Dahl S+17-OHPC (n=7, p&lt;0.05). TNF-alpha and IL-6 levels (n=4-5/group) were 3.0±1.0, 45±11 pg/mL in SD+ vehicle rats, 11.0±1.2, 78±21 in Dahl S+ vehicle rats, which reduced to 4.1±1.6 (p&lt;0.05), 62±12 in Dahl S+17-OHPC. Circulating and placental CD4+ T cells were 9.3±3.7 %, 6.4± 1.6 % gate in SD+ vehicle rats (n=4), 38.9 ±2.9, 33.1±4.3 % gate Dahl S+ Saline rats (n=6), which significantly reduced to 26.3 ± 0.1 %, 3.4±1.2 % gate in DahlS+17-OHPC. AT1-AA were -1 ± 2 ΔBPM (beats per minute) in SD+ vehicle rats, 4 ± 1 in Dahl S+ Saline rats and -0.6±2 Dahl S+17-OHPC rats (n=5, p&lt;0.05). Conclusion: Our findings demonstrate that 17-OHPC ameliorates the maternal syndrome in the Dahl Salt-Sensitive rat model of PreE.

Pathophysiology and pregnancy outcomes of ascites in preeclampsia-a scoping review.

Preeclampsia is a multisystem disorder associated with defective trophoblast invasion, maternal syndrome, and capillary endothelial leak. The presence of ascites/third space fluid accumulation increases the risk of maternal morbidity and mortality. The current criteria/guidelines of preeclampsia do not establish the presence of ascites as a marker of severity or recognize the timing and need for early delivery despite associated complications. Medline and Embase databases were searched to identify relevant literature, reported up to December 2023, regarding the pathophysiology, pregnancy outcome, and management of preeclampsia complicated with ascites. A total of 5 studies on pathophysiology and eight on pregnancy outcomes met the inclusion criteria, with 41 case reports on ascites in preeclampsia. The etiopathogenesis for the development of ascites in preeclampsia includes endothelial damage, capillary hyperpermeability, release of vasoconstrictive agents, reduced intravascular oncotic pressure, and raised intraabdominal pressure. The presence of ascites represents the extreme form of microvascular damage, which also correlates with the raised sFlt-1 levels in this condition. The adverse pregnancy outcomes include increased risk of congestive heart failure, eclampsia, renal failure, disseminated intravascular coagulation, acute respiratory distress syndrome, and maternal death. The presence of ascites in preeclampsia is associated with the deterioration of the maternal condition. Hence, it is indicative of preeclampsia with severe features and requires vigilant monitoring, and prompt delivery may be considered.

O-191 Delayed fetal growth in pregnant women with polycystic ovary syndrome using serial ultrasonographic biometry

Abstract Study question To investigate the effect of maternal polycystic ovary syndrome (PCOS) on intrauterine growth and perinatal outcome of offspring. Summary answer Maternal PCOS might have an adverse impact on fetal growth, represented by serial biometric measurements, and consequently lower the birth weight. What is known already Women with PCOS often have low fertility and high risk of certain pregnancy complications, including miscarriage, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP) and preterm birth (PTB). In addition, the offspring of PCOS mothers are susceptible to short- and long-term health consequences, such as metabolic diseases and neuropsychiatric disorders. And the suboptimal intrauterine environment caused by maternal PCOS condition might be the origin of impaired long-term health of the offspring. Study design, size, duration A total of 1153 pregnant women with pregestational diagnosis of PCOS and 1383 non-PCOS controls were included in the retrospective case-control study for clinical record and ultrasonographic database at women’s hospital, school of medicine, Zhejiang university over a 6-year period. Participants/materials, setting, methods Maternal demographic data, fetal biometric measurements with ultrasound, obstetrical and neonatal outcomes were analyzed. A meta-analysis of birth weight in PCOS offspring in the literature was performed to assess the relationship between the maternal PCOS and neonatal growth. Main results and the role of chance After adjustment for potential confounding variables, we found that biparietal diameter (BPD) and femur length (FL) were notably smaller in fetuses of women with PCOS than controls across the entire gestation. This effect still existed after excluding three major pregnancy complications of PCOS, including GDM, HDP and PTB. Although other fetal biometry including estimated fetal weight and birth weight in PCOS offspring were comparable with controls in our study, the meta-analysis of 22 studies showed that the birth weight in offspring of women with PCOS was lower than controls (WMD -37.813, 95%CL [-69.713, -5.913]), especially for offspring in South America (WMD -84.69, 95%CL [-166.69, -2.68]). Limitations, reasons for caution First, data of other fetal parameters like abdominal and head circumference was scanty. Second, neonatal anthropometric parameters apart from the birth weight were not included. Lastly, we did not have the long-term follow-up results of the offspring to explore the potential effect of delayed fetal biometry in their later life. Wider implications of the findings More attention needs to be paid to the smaller-than-average fetuses in PCOS mothers, and proper management may be needed during and after pregnancy. Further studies are needed to confirm the intrauterine growth pattern of the PCOS offspring and its clinical significance in the neonatal period and beyond. Trial registration number N/A

Severity of depressive and anxious symptoms and its association with birth outcomes among pregnant women during the COVID-19 pandemic: a prospective case-control study

Aim Comparing the anxiety and depression severity and their impact on subsequent birth outcomes in pregnant women before and during Omicron wave in Shanghai in 2022. Methods The depression-anxiety symptoms networks were compared between the pregnant women during the outbreak period (outbreak group; n = 783) and a matched control group of pregnant women before the outbreak (pre-outbreak group; n = 783). The impact of baseline mental state on follow-up pregnancy and neonatal outcomes was also explored by logistic regression. Findings Levels of depression and anxiety between the two groups were not significant different. Network analysis showed that central symptom "trouble relaxing" and bridge symptom "depressed mood" shared by both groups. Different symptom associations in different periods of the pandemic. Total scores and sub-symptom scores of prenatal depressive and anxious severities increased the odds ratios of maternal and neonatal syndromes. The influence of mental state on gestational and neonatal outcomes differed across different pandemic periods. Conclusion The Omicron wave did not have a significant negative impact on the depressive and anxious mood in pregnant women. Targeting central and bridge symptoms intervention may be effective in reducing their adverse effects on co-occurring of anxious and depressive mood and birth outcomes.

Gestational weight gain below recommendations and adverse maternal and child health outcomes for pregnancies with overweight or obesity: a United States cohort study

BackgroundThe current Institute of Medicine (IOM) pregnancy weight gain guidelines were developed using the best available evidence but were limited by substantial knowledge gaps. Some have raised concern that the guidelines for individuals affected by overweight or obesity are too high and contribute to short- and long-term complications for the mother and child. ObjectivesTo determine the association between pregnancy weight gain below the lower limit of the current IOM recommendations and risk of 10 adverse maternal and child health outcomes among individuals with overweight and obesity. MethodsWe used data from a prospective cohort study of United States nulliparae with prepregnancy overweight (n = 955) or obesity (n = 897) followed from the first trimester to 2–7 y postpartum. We used multivariable Poisson regression to relate pregnancy weight gain z-scores with a severity-weighted composite outcome consisting of ≥1 of 10 adverse outcomes (gestational diabetes, preeclampsia, unplanned cesarean delivery, maternal postpartum weight increase >10 kg, maternal postpartum metabolic syndrome, infant death, stillbirth, preterm birth, small-for-gestational age birth, and childhood obesity). ResultsPregnancy weight gain z-scores below, within, and above the IOM-recommended ranges occurred in 5%, 13%, and 80% of pregnancies with overweight and 17%, 13%, and 70% of pregnancies with obesity. There was a positive association between pregnancy weight gain z-scores and all adverse maternal outcomes, childhood obesity, and the composite outcome. Pregnancy weight gain z-scores below the lower limit of the recommended ranges (<6.8 kg for overweight, <5 kg for obesity) were not associated with the severity-weighted composite outcome. For example, compared with the lower limit, adjusted rate ratios (95% confidence interval) for z-scores of −2 standard deviations in pregnancies with overweight (equivalent to 3.6 kg at 40 wk) and obesity (−2.8 kg at 40 wk) were 0.99 (95% confidence interval [CI]: 0.91, 1.06) and 0.97 (95% CI: 0.87, 1.07). ConclusionsThese findings support arguments to decrease the lower limit of recommended weight gain ranges in these prepregnancy body mass index groups.

Characteristics and outcomes of pregnancies among women with phenylketonuria from the NBS Connect registry

Women with phenylketonuria (PKU) should maintain blood phenylalanine (phe) concentration within the recommended range before and during pregnancy to prevent maternal PKU syndrome (MPKUS) in their offspring. Women who gave birth to children with MPKUS symptoms were more likely to report elevated phe concentration before pregnancy, and barriers to accessing components of their dietary management during pregnancy, including blood phe testing, medical food, modified low-protein foods, and healthcare visits with PKU specialists.

Titanium Dioxide Nanoparticles Induce Maternal Preeclampsia-like Syndrome and Adverse Birth Outcomes via Disrupting Placental Function in SD Rats.

The escalating utilization of titanium dioxide nanoparticles (TiO2 NPs) in everyday products has sparked concerns regarding their potential hazards to pregnant females and their offspring. To address these concerns and shed light on their undetermined adverse effects and mechanisms, we established a pregnant rat model to investigate the impacts of TiO2 NPs on both maternal and offspring health and to explore the underlying mechanisms of those impacts. Pregnant rats were orally administered TiO2 NPs at a dose of 5 mg/kg body weight per day from GD5 to GD18 during pregnancy. Maternal body weight, organ weight, and birth outcomes were monitored and recorded. Maternal pathological changes were examined by HE staining and TEM observation. Maternal blood pressure was assessed using a non-invasive blood analyzer, and the urinary protein level was determined using spot urine samples. Our findings revealed that TiO2 NPs triggered various pathological alterations in maternal liver, kidney, and spleen, and induced maternal preeclampsia-like syndrome, as well as leading to growth restriction in the offspring. Further examination unveiled that TiO2 NPs hindered trophoblastic cell invasion into the endometrium via the promotion of autophagy. Consistent hypertension and proteinuria resulted from the destroyed the kidney GBM. In total, an exposure to TiO2 NPs during pregnancy might increase the risk of human preeclampsia through increased maternal arterial pressure and urinary albumin levels, as well as causing fetal growth restriction in the offspring.

Effects of the timing of maternal SARS-CoV-2 infection and vaccination status on placental transfer of antibodies to neonates: A cross-sectional study

ObjectivesTo assess the effects of timing of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination status on placental transfer of antibodies to neonates. MethodsIn this cross-sectional study, chemiluminescence was employed to measure SARS-CoV-2 IgG antibody titers in paired maternal-infant samples from women infected during pregnancy who were vaccinated or unvaccinated. Generalized linear regression assessed factors affecting antibody transfer in infected pregnant women and neonatal titers. ResultsThe group with ≥90 days between infection and delivery showed a higher antibody transfer rate than the <90 days group (β= 0.33, 95%CI: 0.01-0.65). Neonatal IgG titers correlated significantly with maternal titers and with maternal infections more than 90 days before delivery. Among infected pregnant women, those who had received 2 or 3 doses of vaccine before pregnancy had higher neonatal antibody titers than those who were not vaccinated (β = 57.70, 95%CI: 31.33-84.07). ConclusionNeonates born to pregnant women who were vaccinated before infection showed higher antibody titers than neonates of pregnant women who were not vaccinated before infection. The transfer rate is higher in pregnant women with ≥90 days from infection to delivery than in those with <90 days. These findings highlight the importance of timely maternal vaccination to optimize maternal and infant immunity.

Clinically defining the opioid-exposed birthing person and infant as a dyad to support bedside care, surveillance, and research.

An increased incidence of maternal opioid use disorder (OUD) and neonatal abstinence syndrome (NAS) has prompted recommendations supporting a dyadic approach to care for birthing persons and their infants. However, there are no consensus guidelines outlining how the dyad is clinically defined. To examine how the opioid-exposed birthing person-infant dyad has been defined for purposes of data collection and research, a literature review applying the RAND/UCLA Appropriateness Method was conducted. The search yielded 320 abstracts, with 110 articles identified as having a dyadic focus. While no articles included a specific definition for the dyad, 33 (30%) contained a descriptive reference to the birthing person-infant dyad. Thematic analysis revealed eight recurring elements characteristic of the dyad: (1) engagement, (2) communication, (3) bonding, (4) attachment, (5) mutual responsiveness, (6) reciprocity, (7) synchrony, and (8) attunement. Integrating these elements revealed the interactional relationship between the opioid-exposed birthing person and infant as the foundational principle that defines the dyad. This definition shifts the focus of the opioid-exposed dyad from two individual patient populations to an interactional relationship that has broad applicability for clinical use, public health data collection, and research considerations.

Eplerenone Reduces Blood Pressure and Improves Vascular Function in a Mouse Model of Leptin-induced Preeclampsia

Preeclampsia is a hypertensive pregnancy disease that increases the risks for adverse outcomes of pregnancy for both mother and baby, notably by reducing fetal growth in utero. We have shown that mid-late gestation leptin infusion induces preeclampsia characteristics in pregnant mice in inducing hypertension, endothelial dysfunction, and fetal growth restriction, which is ablated in mice with endothelial mineralocorticoid receptor deletion (ECMR). However, there is a lack of preclinical data and rationale for MR antagonism for use in preeclampsia in the existing literature. Therefore, we hypothesized that leptin increases ECMR expression and that MR antagonism decreases hypertension, endothelial dysfunction, and fetal growth restriction in leptin-induced preeclamptic mice. We infused timed-pregnant Balb/C mice with saline (sham) or leptin (LEP, 0.9 mg/kg/day) via s.c. osmotic minipump and administered vehicle or eplerenone (EPL, 200mg/kg/day) in drinking water from gestation day (GD)11-18 (n=7-12). We measured mean arterial blood pressure (BP) via radiotelemetry, vascular function in 2nd order mesenteric arteries by wire myography, and pup/placental weights on GD18. We isolated endothelial cells from placentas of our mice via magnetic cell sorting. Pairwise comparisons were by student’s t test and myography curves analyzed by 2-W ANOVA w/RM. Leptin increased ECMR mRNA expression (3.1±0.32 WT LEP vs 1.1±0.48 WT sham, fold change, *p&lt;0.05) compared to WT sham mice in placenta indicating a direct role for leptin to upregulate ECMR in pregnancy. EPL ablated leptin-induced increases in BP (98±4 LEP/EPL vs 113±3 lep/veh mmHg, *p&lt;0.05), and when treated with EPL leptin did not induce endothelial dysfunction, as assessed as a lack of decrease in vascular relaxation to acetylcholine (p&gt;0.05 LEP/EPL vs sham/EPL). Interestingly, EPL treatment did not prevent leptin from decreasing placental effciency in pregnant mice (7.42±0.17 LEP/veh vs 6.71±0.15 LEP/EPL, pup/placenta weight ratio, p&gt;0.05). Collectively, these data show that leptin infusion from GD11-18 in pregnant mice increases ECMR activation by increasing expression. Furthermore, MR antagonism by eplerenone ablates the maternal hypertension and endothelial dysfunction in leptin-induced preeclampsia mice, however, fetal growth is not restored by eplerenone. Therefore, eplerenone may be a promising therapeutic for the maternal cardiovascular syndrome of preeclampsia patients, however, MR antagonism therapies may need additional agents to improve fetal outcomes. 1R01HL169576, 4R00HL146948. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

USING A MULTI-OMICS LANDSCAPE OF THE MATERNAL-FETAL INTERFACE TO MODEL THE LONGITUDINAL PATHOGENESIS OF EARLY-ONSET PRE-ECLAMPSIA

Objective: Pre-eclampsia (PE) is a syndrome that affects multiple organ systems and is the most severe hypertensive disorder in pregnancy. It frequently leads to preterm delivery, maternal and fetal morbidity and mortality and life-long complications. We currently lack efficient screening tools and early therapies to address PE. Design and method: To identify candidate biomarkers and operative pathways in early onset PE (eoPE, severe PE with onset before week 34), we performed spatio-temporal multi-omics profiling of human eoPE placentae and healthy controls, and validated targets in early gestation in a longitudinal clinical cohort. We used a single-nuclei RNA-sequencing combined with spatial proteo- and transcriptomics and mechanistic in vitro signalling analyses to bridge the gap from late pregnancy disease to early pregnancy pathomechanisms. Results: We discovered a key disruption in villous trophoblast differentiation, which is driven by the increase of transcriptional coactivator p300, that ultimately ends with a senescence-associated secretory phenotype (SASP) of trophoblasts in eoPE. We found a significant increase in the senescence markers in preeclamptic maternal serum in early gestation and late gestation, before the development of clinical symptoms, indicating that the placental syndrome drives systemic maternal syndrome, even before clinical manifestation of eoPE. Conclusions: Our work describes a new disease progression model, starting with dysregulated transition in villous trophoblast differentiation. Our study identifies potential pathophysiology-relevant biomarkers for the early diagnosis of the disease as well as possible targets for interventions, which would be crucial steps toward protecting the mother and child from gestational mortality and morbidity and an increased risk of cardiovascular disease later in life.