Growth Restriction Research Articles

Intrauterine growth-restricted pregnant rats, from placental ischemic dams, display preeclamptic-like symptoms: A new rat model of preeclampsia.

Preeclampsia (PE) is characterized by de novo hypertension (HTN) and is often associated with intrauterine growth restriction (IUGR). Hallmarks of PE are placental ischemia, decreased nitric oxide (NO) bioavailability, oxidative stress (OS), and organ damage in the kidneys and brain. This study aims to characterize a new model of PE using pregnant IUGR rats from hypertensive placental ischemic dams. It is hypothesized that pregnant IUGR rats from hypertensive placental ischemic dams will have elevated blood pressure (BP), OS, and organ damage. In this study, pregnant rats are divided into two groups: normal pregnant (NP) and hypertensive placental ischemic dams (RUPP). Offspring from NP and RUPP dams were mated at 10 weeks of age to generate pregnant IUGR (IUGR Preg) and pregnant control (CON Preg) rats. BP and other markers of PE were evaluated during late gestation. Pregnant IUGR rats had elevated BP and systemic OS. The maternal body weight of pregnant IUGR rats and their pups' weights were decreased, while the brains were enlarged with elevated OS. In summary, pregnant IUGR rats, born from hypertensive placental ischemic dams, have HTN and increased systemic and brain OS, with larger brain sizes and smaller pups. Furthermore, this study shows that pregnant IUGR rats exhibit a preeclamptic-like phenotype, suggesting a new epigenetic model of PE.

Fetal ezrin expression affects macrophages and regulatory T cells in mouse placental decidua

Ezrin is a cross-linker protein between membrane proteins and cytosolic actin, abundantly expressed in the placenta among the ERM protein family. Ezrin gene knockout mice exhibit fetal growth restriction after gestational day (GD) 15.5. This study aimed to clarify the effect of ezrin on immune cells that influence fetal growth and immune tolerance. Ezrin heterozygous knockout (Ez+/-) mice were interbred, and the gene expressions and immune cell distributions in the placentas of wild-type (Ez+/+) and ezrin knockout (Ez-/-) fetuses were analyzed. IL-6 expression in the placenta of Ez-/- fetuses was significantly higher than in Ez+/+ fetuses at GD 15.5. The mRNA expression of IL-6 in the uterine decidua attached to Ez-/- fetuses was higher compared to that attached to Ez+/+ fetuses but not in the junctional zone and labyrinth. Classical M1 and M2 macrophages in the decidua were analyzed by flow cytometry using CD86 and CD206 as markers. M1 macrophages increased in the decidua attached to Ez-/- mice compared to Ez+/+ mice, while M2 macrophages did not increase. CD4-positive T cells showed a reduction in the decidua attached to Ez-/- fetuses. Further analysis involved the subcutaneous administration of tacrolimus in pregnant Ez+/- mice from GD 8.5 to GD 15.5, which prevented the decrease in fetal body weight and decidual CD4-positive T cells in Ez-/- mice at GD 15.5. These results suggest that impaired expression of fetoplacental-derived ezrin induces inflammatory conditions in the uterine decidua through M1 polarization of macrophages, increased IL-6, and decreased CD4-positive T cells, including Treg cells.

COMPARISON OF PLGF LEVELS, AMONG SMALL FOR GESTATIONAL AGE AND APPROPRIATE FOR GESTATIONAL AGE MOTHERS

Objective. Early detection of small for gestational age fetuses can prevent infant morbidity and mortality. The objective of this study was to compare the levels of Placental Growth Factor among small for gestational age with appropriate for gestational age mothers and to identify the predictive value of PlGF in detecting pregnancies with Intra uterine growth retardation in local population. Design. Quasi experimental (comparative cross-sectional) study. Place & duration of study. Gynecological department of Ayub Medical complex, Abbottabad from August 2021 to January 2022. Methodology. The studied population included total 68 mothers in last trimester with 34 in each group, i.e. appropriate for gestational age and small for gestational age. Fetal size was estimated either by clinical examination (symphysis fundal height) or estimated fetal weight by ultrasound examination. Sociodemographic along with reproductive history were recorded and blood samples analyzed for PlGF difference in both groups. Results. The median age of mothers was 32.5 years. The PlGF in small for gestational age was observed in the below normal concentration (mean value = 126.7 pg/mL) while it was observed in normal ranges in appropriate for gestational age mothers (mean value = 24.2 pg/ml) with P-value (<0.001). Conclusion. Mothers with small for gestational age were having significantly lower placental growth factor levels compared to mothers with appropriate for gestational age.

Congenital Syphilis in the United States: A Narrative Review.

Congenital syphilis (CS) continues to pose a significant global challenge. There has been a marked increase in reported cases in the US, with 102.5 cases per 100,000 live births in 2022 compared to 11.6 cases per 100,000 live births in 2014. CS can lead to a range of severe complications, including premature birth, intrauterine growth restriction, miscarriage, perinatal death, stillbirth, and postnatal complications that may persist into later life. Maternal/parental factors such as age, race/ethnicity, occupation, income level, access to healthcare services, and incarceration have been linked to higher rates of CS. Additionally, pregnant individuals who engage in high-risk behaviors such as sex work, having multiple sexual partners, or substance use are at a higher risk of exposure and subsequent infection. Routine screening for syphilis during pregnancy is crucial for its detection, timely management, and prevention of CS. The asymptomatic nature of the latent stage of syphilis further underscores the importance of prenatal syphilis screening. Studies in various countries have shown that early or first antenatal care visit screening for CS is cost-effective. This review article critically evaluates the current knowledge of CS in the US, including its prevalence, social determinants of health, prevention efforts, challenges, the significance of screening, and the call to action to address the rising trend.

COVID-19 and Its Potential Impact on Children Born to Mothers Infected During Pregnancy: A Comprehensive Review

Pregnancy is a vulnerable period of time during which pregnant people are prone to infections like COVID-19, which can increase risks for both the mother and fetus. These infections may lead to complications such as preterm birth, developmental delays, and congenital abnormalities. While COVID-19 poses additional risks like placental dysfunction and neonatal infections, studies on long-term effects remain limited. Ongoing research and monitoring are essential to understand and mitigate potential cognitive and developmental challenges in children born to mothers infected with COVID-19. This review aims to guide clinicians in managing these risks throughout childhood. Maternal COVID-19 infection during pregnancy can have significant implications for fetal development, even if the newborn is not infected at birth. The release of inflammatory cytokines may cross the placental barrier, potentially disrupting fetal brain development and increasing the risk of long-term cognitive and behavioral issues, such as ADHD or autism. Placental dysfunction, caused by inflammation or thrombosis, can lead to intrauterine growth restriction (IUGR), preterm birth, or hypoxia, affecting both neurological and respiratory health in newborns. Furthermore, a compromised fetal immune system can increase susceptibility to autoimmune conditions and infections. The early diagnosis and management of infections during pregnancy are crucial in mitigating risks to both the mother and fetus. Swift intervention can prevent complications like preterm birth and long-term developmental challenges, ensuring better health outcomes for both the mother and child. Long-term monitoring of children born to mothers infected with COVID-19 is necessary to understand the full extent of the virus’s impact. This review evaluates the long-term systemic effects of maternal COVID-19 infection during pregnancy on fetuses, newborns, and children, focusing beyond vertical transmission. It highlights the broader impacts on fetal development, offering insights to help clinicians manage potential issues that may arise later in life.

Associations of Maternal Nutritional Status and Supplementation with Fetal, Newborn, and Infant Outcomes in Low-Income and Middle-Income Settings: An Overview of Reviews

Background/Objectives: Despite advances in maternal nutritional knowledge, the effect of maternal diet, micronutrient status and undernutrition, and the effect of maternal supplementation on fetal, neonatal and infant outcomes still have gaps in the literature. This overview of reviews is intended to assess the available information on these issues and identify the main maternal nutritional factors associated with offspring outcomes in low- and middle-income countries as possible targets for public health interventions. Methods: The literature search was performed in Medline (PubMed) and Cochrane Library datasets in June 2024. Pre-specified outcomes in offspring were pooled using standard meta-analytical methods. Results: We found consistent evidence on the impact of maternal undernutrition indicated by low body mass index (BMI), mid-upper arm circumference (MUAC), and stature, but not of individual micronutrient status, on intrauterine-growth retardation, preterm birth, low birth weight, and small for gestational age, with research showing a possible effect of maternal undernutrition in later child nutritional status. Studies on micronutrient supplementation showed possible beneficial effects of iron, vitamin D, and multiple micronutrients on birthweight and/or decreasing small for gestational age, as well as a possible effect of calcium on preterm birth reduction. Interventions showing more consistent beneficial outcomes were balanced protein-energy and lipid base supplements, which demonstrated improved weight in newborns from supplemented mothers and a decreased risk of adverse neonatal outcomes. Conclusions: Further research is needed to identify the benefits and risks of maternal individual micronutrient supplementation on neonatal and further child outcomes.

Association between Gestational Bisphenol A Exposure and Maternofoetal Outcomes: A Cohort Study in a Single Tertiary Hospital in Klang Valley

A growing body of literature has documented the adverse effects of bisphenol A (BPA) exposure on pregnancy and birth outcomes. Regardless, how gestational BPA exposure affects mother-newborn pairs in Malaysia is yet to be explored. Hence, this study aimed to investigate urinary BPA levels of pregnant women living in Klang Valley and their associations with adverse obstetric and birth outcomes. This cross-sectional study involved pregnant women in their third trimester attending antenatal clinic in Hospital Al Sultan Abdullah (HASA), UiTM Puncak Alam, who planned to have their delivery in HASA. Information on maternal age, parity, education, household income, gestational age, and obstetric complications, such as Gestational Diabetes Mellitus (GDM), preeclampsia, preterm labour, and foetal growth restriction (FGR) were collected. Maternal urine samples were also obtained and evaluated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, the neonatal outcomes including mode of delivery, gestational age, birth weight and need for NICU admission were documented. Our LC-MS/MS analysis showed that BPA was present in all the urine samples, with levels varying from 4.42 to 30.86 ng/mL. The median level was 15.96 ng/mL. Urinary BPA level has no significant correlation with gestational hypertension (GHTN), preterm labour and low birth weight babies. Babies who need NICU admission were born to mothers who exhibited significantly different urinary BPA levels compared to those whose babies were not admitted (p=0.049). Finding from this study suggestive of further investigation on level of gestational urinary BPA with NICU admission, ideally with a larger sample size to validate these results.

The effect of incretin hormone GLP-1 on the phenotypic profile of mononuclear cells in fetal growth restriction

The effect of incretin hormone GLP-1 on the phenotypic profile of mononuclear cells in fetal growth restriction

Pregestational neural network prediction of fetal growth restriction or small-for-gestational-age fetus with subsequent intensive care of the newborn

Pregestational neural network prediction of fetal growth restriction or small-for-gestational-age fetus with subsequent intensive care of the newborn

Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient mouse placentas

Background During pregnancy, the placenta is an extremely important organ as it secretes its own hormones, e.g. insulin-like growth factor 1 (IGF-1), to ensure proper intrauterine fetal growth and development. Ethanol, an addictive and widely used drug, has numerous adverse effects during pregnancy, including fetal growth restriction (FGR). To date, the molecular mechanisms by which ethanol triggers its toxic effects during pregnancy, particularly in the placenta, are not entirely known. For this reason, a murine model of partial IGF-1 deficiency was used to determine ethanol alterations in placental morphology and aspartyl/asparaginyl β-hydroxylase (AAH) expression. Methods Wild type (WT, Igf1 +/+) and heterozygous (HZ, Igf1 +/-) female mice were given 10% ethanol in water during 14 days as an acclimation period and throughout pregnancy. WT and HZ female mice given water were used as controls. At gestational day 19, pregnant dams were sacrificed, placentas were collected and genotyped for subsequent studies. Results IGF-1 deficiency and ethanol consumption during pregnancy altered placental morphology, and decreased placental efficiency and AAH expression in placentas from all genotypes. No differences were found in Igf1, Igf2, Igf1r and Igf2r mRNA expression in placentas from all groups. Conclusions IGF-1 deficiency and ethanol consumption throughout gestation altered placental development, suggesting the crucial role of IGF-1 in the establishment of an adequate intrauterine environment that allows fetal growth. However, more studies are needed to study the precise mechanism to stablish the relation between both insults.

Cellular and Molecular Pathophysiology of Gestational Diabetes

Gestational diabetes (GD) is a metabolic disorder characterized by glucose intolerance during pregnancy, significantly impacting maternal and fetal health. Its global prevalence is approximately 14%, with risk factors including obesity, family history of diabetes, advanced maternal age, and ethnicity, which are linked to cellular and molecular disruptions in glucose regulation and insulin resistance. GD is associated with short- and long-term complications for both the mother and the newborn. For mothers, GD increases the risk of developing type 2 diabetes, cardiovascular diseases, and metabolic syndrome. In the offspring, exposure to GD in utero predisposes them to obesity, glucose intolerance, and metabolic disorders later in life. This review aims to elucidate the complex cellular and molecular mechanisms underlying GD to inform the development of effective therapeutic strategies. A systematic review was conducted using medical subject headings (MeSH) terms related to GD’s cellular and molecular pathophysiology. Inclusion criteria encompassed original studies, systematic reviews, and meta-analyses focusing on GD’s impact on maternal and fetal health, adhering to PRISMA guidelines. Data extraction captured study characteristics, maternal and fetal outcomes, key findings, and conclusions. GD disrupts insulin signaling pathways, leading to impaired glucose uptake and insulin resistance. Mitochondrial dysfunction reduces ATP production and increases reactive oxygen species, exacerbating oxidative stress. Hormonal influences, chronic inflammation, and dysregulation of the mammalian target of rapamycin (mTOR) pathway further impair insulin signaling. Gut microbiota alterations, gene expression, and epigenetic modifications play significant roles in GD. Ferroptosis and placental dysfunction primarily contribute to intrauterine growth restriction. Conversely, fetal macrosomia arises from maternal hyperglycemia and subsequent fetal hyperinsulinemia, resulting in excessive fetal growth. The chronic inflammatory state and oxidative stress associated with GD exacerbate these complications, creating a hostile intrauterine environment. GD’s complex pathophysiology involves multiple disruptions in insulin signaling, mitochondrial function, inflammation, and oxidative stress. Effective management requires early detection, preventive strategies, and international collaboration to standardize care and improve outcomes for mothers and babies.

Diagnosis of arcuate uterus using three-dimensional transvaginal ultrasound and investigation of its association withperinatal complications.

Arcuate uterus does not impact the success of infertility treatments, but there is no consensus on whether it influences perinatal outcomes. The objective of the present study was to investigate whether minor congenital uterine anomalies such as an arcuate uterus contribute to perinatal complications. This was a retrospective cohort study at a single institution. The study included 1097 deliveries after 22 weeks of gestation. Transvaginal ultrasound, with three-dimensional functionality, assessed uterine morphology based on American Society for Reproductive Medicine criteria. We compared maternal backgrounds and perinatal complications between arcuate uterus and normal uterus groups. Statistical analyses, including multivariate analysis, aimed to identify independent risk factors. A total of 69 patients (7.5%) with diagnosed arcuate uterus were included. Maternal background factors showed no significant differences between groups. In perinatal complications, an arcuate uterus was associated with a significantly higher incidence of preterm delivery (13% versus 4.7%, P = 0.01), preterm premature rupture of membranes (7.2% versus 1.6%, P = 0.01), fetal growth restriction (FGR; 16% versus 6.7%, P = 0.01), and abnormal placental cord insertion (33% versus 7.6%, P < 0.01). After multivariate analysis, arcuate uterus emerged as an independent risk factor for preterm delivery (adjusted odds ratio [aOR], 4.0 [95% confidence interval (CI), 1.6-9.9], P < 0.01), FGR (aOR, 2.6 [95% CI, 1.2-5.6], P = 0.02), and abnormal placental cord insertion (aOR, 6.0 [95% CI, 3.4-10.6], P < 0.01). Arcuate uterus stands as an independent risk factor for preterm delivery, FGR, and abnormal placental cord insertion. The findings emphasize the importance of recognizing even minor uterine morphological abnormalities in assessing and managing perinatal complications.

Expanded Fetal Growth Restriction Definition Identifies High Proportion of Umbilical Artery Doppler Anomalies.

Fetal growth restriction (FGR) increases the risk for perinatal morbidity and mortality. The Society for Maternal-Fetal Medicine expanded the definition of FGR to independently include abdominal circumference (AC) < 10th percentile for gestational age (GA), regardless of estimated fetal weight (EFW). While studies have shown increased detection of small for GA neonates with expanded definition, no studies have evaluated the likelihood of abnormal umbilical artery Dopplers (UAD) detection with expanded definition. The objective of this study was to compare the likelihood of identifying UAD abnormalities in fetuses with normal EFW and restricted AC versus those by EFW alone. Single-institution retrospective cohort study of fetal growth ultrasounds meeting criteria for FGR either by EFW < 10th percentile or AC < 10th percentile with normal EFW. Those with FGR by AC alone were compared with those with FGR by EFW. Primary outcome was prevalence of UAD abnormalities, including elevated systolic/diastolic ratio, and absent and/or reversed end diastolic velocity. Receiver operator characteristic curves were generated to compare predictive value of UAD abnormalities by FGR definition. A total of 619 scans met criteria for FGR between November 2020 and June 2021, with 441 (71%) meeting definition by EFW and 178 (29%) by AC criteria alone. Baseline characteristics were similar between groups. FGR by AC alone was identified earlier (30.4 ± 3.3 vs. 35.4 ± 3.0 weeks' gestation, p < 0.001) with higher proportion identified before 32 weeks (70 vs. 11%, p < 0.001). Proportion of abnormal UAD were similar between groups (15 vs. 15%, adjusted odds ratio: 1.12, 95% confidence interval: 0.61-2.23). Use of EFW alone would have failed to identify 29% of abnormal UAD. A combined definition of FGR had the highest detection of abnormal UAD (area under curve: 0.78 vs. AC alone 0.73 vs. EFW alone 0.69). A definition of FGR that considers both EFW and AC improves detection of abnormal UAD. · Fetuses with restricted AC are equally likely to exhibit abnormal UAD indices compared with those that meet criteria by EFW.. · Earlier GA of FGR detection and improved detection of abnormal UAD with expanded growth definition.. · Expanded definition of FGR significantly improves detection of abnormal UAD as compared with those diagnosed with EFW criteria alone.. · Expanded growth restriction definition improves Doppler identification..

Preliminary data on short-term outcomes within the cardio-obstetrics registry

Abstract Background Pregnancy leads to physiological changes within the cardiovascular system such as increased plasma volume and cardiac output or hypercoagulability. These changes can be challenging for women with pre-existing cardiovascular disease with higher risks of complications. The guidelines of the European Society of Cardiology recommend treating high-risk patients in specialized centres by an interdisciplinary pregnancy heart team. In a team-based approach, the Pregnancy Heart Team was founded at our university hospital, in order to establish specific structures of communication and responsibility. Methods A prospective registry of all patients treated by the Pregnancy Heart Team between November 2022 and March 2024 was established. Patients consisted of women with pre-existing cardiovascular disease undergoing pregnancy as well as women who developed pregnancy-associated cardiovascular disease. Patients were evaluated throughout pregnancy by lab work and echocardiography during each trimester as well as in the postpartum period. Results In total 39 women (mean age 34±5 years) were prospectively included in the registry. 17 patients (43.5%) were classified as mWHO ≥ III. 17 patients (43.5 %) with pre-existing (pregnancy-associated) cardiovascular disease were managed throughout pregnancy and delivery. 9 patients (18.4 %) developed pregnancy-associated cardiovascular diseases such as peripartum cardiomyopathy or spontaneous coronary artery dissection. Preliminary data shows that mean left-ventricular ejection fraction remained stable during pregnancy with a non-significant trend towards lower values postpartum. Cardiac biomarkers such as high-sensitivity troponin T and NT-pro-BNP showed a non-significant trend towards increased values in the third trimester and postpartum. Adverse maternal outcomes occurred in 14 patients (35.9 %), including preterm premature rupture of membranes (12.2%), gestational hypertension (7.6%), gestational diabetes (5.1%), preeclampsia/eclampsia (7.6%) and delivery-associated complications (10.2%). Fetal complications included macrosomia (10.2%) or intrauterine growth retardation (5.1%). Discussion These preliminary data of a real-world patient collectivedemonstrate that a significant number of patients experienced adverse pregnancy outcomes which was associated with a trend towards increased cardiac biomarkers throughout pregnancy and postpartum. As recent studies have shown, interpretation of standard parameters such as cardiac biomarkers is not fully understood during pregnancy, especially in women with pre-existing cardiovascular disease. Our data may aid to understand prognostic implications of cardiac biomarkers during pregnancy.

The Significance of the Myocardial Performance Index and Fetal Doppler Abnormalities in Growth-Restricted Fetuses: A Systematic Review of the Literature

Introduction: This review aims to investigate the clinical implications of using the myocardial performance index (MPI), obtained through tissue Doppler imaging (TDI) and spectral Doppler, in assessing fetal cardiac function in growth-restricted fetuses. It explores the MPI’s potential in predicting adverse perinatal outcomes and its utility when combined with conventional pulsed-wave Doppler assessments for enhanced fetal well-being evaluations. Material and Methods: A systematic search of PubMed and Google Scholar databases spanning from 2004 to 2023 was conducted to identify pertinent articles on the MPI’s clinical application in managing growth-restricted fetuses. Inclusion criteria followed the Fetal Medicine Barcelona definition of fetal growth restriction (FGR) to mitigate study group heterogeneity. The research sources were PubMed and Google Scholar databases, and the review was conducted without any specific clinical or laboratory setting. Only articles meeting the inclusion criteria for FGR, as per the Fetal Medicine Barcelona definition, were considered. Six studies meeting these criteria were included in the review. The review analyzed the correlation between MPI values and conventional Doppler parameters, investigating the progression of myocardial function impairment and its association with the risk of fetal demise. The primary outcome measures included the relationship between MPI values, fetal well-being, and the potential for prenatal cardiac dysfunction in growth-restricted fetuses. Results: The findings indicate that as conventional Doppler parameters deteriorate, MPI values increase, suggesting progressive myocardial dysfunction. The MPI may cross the 95th percentile before abnormal flow in the ductus venosus and aortic isthmus, highlighting the potential for diastolic dysfunction preceding hypoxia in growth-restricted fetuses. Elevated MPI levels were observed in both growth-restricted and small-for-gestational-age (SGA) fetuses, indicating prenatal cardiac impairment. The strong association between an abnormal MPI and perinatal mortality has been shown for early FGR. Conclusions: MPI alterations appear to precede abnormal Doppler parameters in early- and late- onset FGR, potentially indicating diastolic dysfunction preceding hypoxia. Additionally, the MPI correlates with the risk of fetal demise. However, larger studies are needed to establish its sensitivity and specificity. Furthermore, the significance of prenatal cardiac impairment in some SGA fetuses raises questions about its potential impact on perinatal outcomes and cardiovascular programming.

Echocardiographic findings in newborns with inadequate intrauterine growth during pregnancy

Abstract Background Infants born small for gestational age (SGA) or diagnosed with fetal growth restriction (FGR) are at increased risk of neonatal mortality as well as cardiovascular disease later in life. Previous studies based on smaller cohorts (n&amp;lt;200) of newborns with SGA and FGR (n&amp;lt;200) have demonstrated structural and morphological alterations in the heart compared to infants born appropriate for gestational age (AGA). However, to our knowledge no previous study has systematically investigated the effect of SGA and FGR on echocardiographic parameters in the infant heart. Purpose To investigate whether echocardiographic parameters differ among infants born SGA or with FGR, in comparison to infants born AGA. Methods This study is a population-based cohort study of infants (n&amp;gt;25,000) offering postnatal cardiac examination including transthoracic echocardiography (TTE) between 2016-2018. We compared left ventricular (LV) TTE parameters in infants born SGA (birthweight ≥3rd and &amp;lt;10th percentile, n=2,106) and with FGR (birthweight &amp;lt;3rd percentile, n=972) with infants born AGA (birthweight ≥10th and &amp;lt;90th percentile, n=20,468) using a multiple linear regression analysis. We have investigated LV volumes, systolic function, diastolic function, and LV structure. All analyses were adjusted for sex, gestational age at birth, weight, length, and age at cardiac examination. Results Infants born SGA had higher heart rates compared with infants born AGA. Both infants born SGA and infants with FGR had significantly smaller LV dimensions including septal and posterior wall thicknesses (IVSd and LVPWd), and LV internal diameters (LVIDd and LVIDs). Infants born SGA had smaller end-diastolic and end-systolic volumes compared with infants born AGA (Table 1). Infants born SGA or with FGR had significantly higher mitral valve early peak velocities, compared with infants born AGA, and infants born SGA showed increased mitral valve atrial peak velocities indicating altered diastolic function (Table 1). Conclusion Infants born with inadequate intrauterine growth had smaller LV dimensions compared with infants born AGA, even when adjusting for infant size and age. Infants born SGA and with FGR both exhibited altered diastolic function. Longitudinal studies of children with inadequate intrauterine growth are needed to determine the impact on adult cardiac health.

The mechanism of paclitaxel induced damage on placental trophoblast cells

ObjectiveChemotherapy during pregnancy has a certain risk of causing a series of complications, such as miscarriage, premature birth, or fetal growth restriction, although the relationship between these complications and chemotherapy is currently unclear. This experiment focuses on the possible damage mechanism of the chemotherapeutic drug paclitaxel on placental trophoblast cells, and explores whether chemotherapy can affect pregnancy outcomes by directly damaging placental tissue.MethodsThis study explored the mechanism of paclitaxel induced damage on placental trophoblast cell lines JEG-3 and BEWO through immunofluorescence staining, Western blot experiments, cell flow cytometry, Seahorese cell metabolism experiments, and mouse modeling verification.ResultsThe experiment found that paclitaxel could induce JEG-3 and BEWO cells to produce reactive oxygen species (ROS), and elevate the ratio of Bax/Bcl-2 expression. Besides, paclitaxel mediated the reduction of mitochondrial membrane potential in JEG-3 and BEWO cells, causing damage and leading to mitochondrial autophagy and the occurrence of unfolded protein response. Paclitaxel inhibited the glycolysis rate of JEG-3 and BEWO cells, and leaded to impaired mitochondrial function, including decreased basal respiratory values, decreased respiratory reserve capacity, and proton leakage. In pregnant mice with tumor modeling, paclitaxel could cause DNA damage in placental tissue cells, and might lead to apoptosis of chemotherapy mice placental tissue cells and impairment of normal physiological functions.ConclusionPaclitaxel may directly or indirectly affect the normal physiological functions of placental trophoblast cells, including energy metabolism and protein synthesis dysfunction, which may be related to the adverse pregnancy outcomes caused by paclitaxel chemotherapy.

Electrocardiographic findings in newborns with inadequate intrauterine growth during pregnancy

Abstract Background Infants born small for gestational age (SGA) or following fetal growth restriction (FGR) have an increased risk of neonatal mortality as well as cardiovascular disease later in life. Prenatal electrocardiograms (ECGs) in fetuses with FGR exhibit QT prolongation. However, neonatal alterations in the conduction system in infants born SGA or with FGR has not previously been assessed in a large cohort of infants. Purpose To investigate potential variations in electrocardiographic parameters between infants born SGA or diagnosed with FGR, in comparison to infants born appropriate for gestational age (AGA). Methods This study was based on data from a population-based cohort study of infants (n&amp;gt;25,000) with prenatal inclusion and postnatal cardiac examination including eight-lead ECG between 2016-2018. We conducted a multiple linear regression analysis to compare ECG parameters among infants with FGR (birthweight &amp;lt;3rd percentile, n=544) and SGA (birthweight ≥3rd and &amp;lt;10th percentile, n=1,384) to infants born AGA (birthweight ≥10th percentile and &amp;lt;90th percentile, n=14,076). Parameters of interest included: heart rate (HR), uncorrected and corrected (Bazzet and Fridericia) QT intervals, QRS duration, PR interval, QRS axis, maximum amplitudes of the R- and S-waves in V1 and V6. All analyses were adjusted for infant sex, gestational age at birth, and weight, length, and age at ECG examination. Results Infants born SGA or with FGR had higher HR and consequently shorter uncorrected QT intervals compared with infants born AGA (Table 1). Infants with FGR had significantly shorter corrected (Fridericias) QT intervals. Infants born SGA had smaller amplitudes of both the R- and S-wave in V6, and significantly larger amplitude of the S-wave in V1, compared with infants born AGA (Table 1). Conclusion ECGs from infants born SGA and infants with FGR differed from infants born AGA, including higher HRs and shorter uncorrected QT-intervals even after adjustments for infant size and age at the examination. Furthermore, we saw infants born SGA had reduced amplitudes of the S and R wave in the lateral lead (V6), and an increased amplitude of the S-wave in V1, compared with infants born AGA. Follow-up examinations of these infants could determine whether these alterations persist beyond the neonatal period, and to fully understand their implications of the cardiac function later in life.

Analysis of the role of low molecular weight heparin in preeclampsia and fetal growth restriction syndrome: A systematic review

Introduction: preeclampsia is defined as hypertension during pregnancy and this increase in blood pressure can lead to serious and unwanted decompensations for both the mother and the fetus. It has been shown that among the factors that lead to maternal death, PE ranks third, not being surpassed only by hemorrhages and thrombosis.Objective: to determine the role of low molecular weight heparin in preeclampsia and fetal growth restriction syndrome.Method: a systematic review of the literature was carried out addressing the analysis of the efficacy and safety of low molecular weight heparin in the treatment of preeclampsia. The articles were searched in the following databases such as Pubmed, Elsevier in the following languages: English, Spanish and Portuguese, from the last 20 years.Results: 16 studies that met the inclusion criteria were included and 25,261 pregnant women were analyzed.Conclusion: the analysis carried out shows that the efficacy of using LMWH in preeclampsia and fetal growth restriction syndrome can be an option in the treatment and prevention, however a great heterogeneity was detected in the results of the trials, which does not yet allow its use in medical practice

Miro2 sulfhydration by CBS/H2S promotes human trophoblast invasion and migration via regulating mitochondria dynamics

Insufficient cytotrophoblast (CTB) migration and invasion into the maternal myometrium leads to pregnancy related complications like Intra-uterus Growth Restriction (IUGR), and pre-eclampsia (PE). We previously found that hydrogen sulfide (H2S) enhanced CTB migration without knowing the mechanism(s) and the pathophysiological significance. By studying human samples and cell line, we found that H2S levels were lower in PE patients’ plasma; H2S synthetic enzyme cystathionine β-synthetase (CBS) was reduced in PE extravillious invasive trophoblasts. GYY4137 (H2S donor, 1 µM) promoted CBS/H2S translocation onto mitochondria, preserved mitochondria functions, enhanced cell invasion and migration. CBS knockdown hindered the above functions which were rescued by GYY4137, indicating the vital roles of CBS/H2S signal. Disturbance of mitochondria dynamics inhibited cell invasion and migration. The 185 and 504 cysteines of Mitochondrial Rho GTPase 2 (Miro2C185/C504) were highly sulfhydrated by H2S. Knockdown Miro2 or double mutation of Miro2C185/C504 to serine fragmented mitochondria, and inhibited cell invasion and migration which can’t be rescued by H2S. The present study showed that human cytotrophoblast receives low dose H2S regulation; CBS/H2S sustained mitochondria functions via Miro2C185/C504 sulfhydration to enhance cytotrophoblast mobility. These findings established a new regulatory pathway for cytotrophoblast functions, and provided new targets for IUGR and PE.