Unraveling the Mfn2-Warburg effect nexus: a therapeutic strategy to combat pulmonary arterial hypertension arising from catch-up growth after IUGR.

BACKGROUND: The interplay between intrauterine and early postnatal environments has been associated with an increased risk of cardiovascular diseases in adulthood, including pulmonary arterial hypertension (PAH). While emerging evidence highlights the crucial role of mitochondrial pathology in PAH, the specific mechanisms driving fetal-originated PAH remain elusive. METHODS AND RESULTS: To elucidate the role of mitochondrial dynamics in the pathogenesis of fetal-originated PAH, we established a rat model of postnatal catch-up growth following intrauterine growth restriction (IUGR) to induce pulmonary arterial hypertension (PAH). RNA-seq analysis of pulmonary artery samples from the rats revealed dysregulated mitochondrial metabolic genes and pathways associated with increased pulmonary arterial pressure and pulmonary arterial remodeling in the RC group (postnatal catch-up growth following IUGR). In vitro experiments using pulmonary arterial smooth muscle cells (PASMCs) from the RC group demonstrated elevated proliferation, migration, and impaired mitochondrial functions. Notably, reduced expression of Mitofusion 2 (Mfn2), a mitochondrial outer membrane protein involved in mitochondrial fusion, was observed in the RC group. Reconstitution of Mfn2 resulted in enhanced mitochondrial fusion and improved mitochondrial functions in PASMCs of RC group, effectively reversing the Warburg effect. Importantly, Mfn2 reconstitution alleviated the PAH phenotype in the RC group rats. CONCLUSIONS: Imbalanced mitochondrial dynamics, characterized by reduced Mfn2 expression, plays a critical role in the development of fetal-originated PAH following postnatal catch-up growth after IUGR. Mfn2 emerges as a promising therapeutic strategy for managing IUGR-catch-up growth induced PAH.

Expression and significance of CEMIP and CYP11B2 in serum in women with foetal growth restriction.

BACKGROUND: Foetal growth restriction (FGR) occurs when a foetus fails to reach its growth potential. This observational study assessed the expression and significance of cell migration-including protein (CEMIP) and aldosterone synthase (CYP11B2) in the serum of pregnant women with FGR. METHODS: 40 singleton FGR-suffered pregnant women, as well as 40 normal singleton pregnant women, were enrolled. The expression of CEMIP and CYP11B2 in serum was detected in early pregnancy. The correlations between parameters were evaluated. The predictive variables for FGR were determined. The diagnostic value of CEMIP and CYP11B2 for FGR was analysed. RESULTS: CEMIP and CYP11B2 mRNA expression in the serum of pregnant women with FGR decreased (both P < 0.001). CEMIP (95%CI: 0.802-0.921, P < 0.001) and CYP11B2 (95%CI: 0.795-0.907, P < 0.001) mRNA expression in serum and soluble fms like tyrosine kinase-1 (sFLT1)/placental growth factor (PlGF) ratio (95%CI: 0.866-0.974, P < 0.001) were independent predictors of FGR, and CEMIP (r = -0.578, P = 0.001) and CYP11B2 (r = -0.602, P < 0.001) mRNA expression in serum were negatively correlated with sFLT1/PlGF ratio. CEMIP (AUC = 0.741) and CYP11B2 (AUC = 0.764) mRNA expression in serum had good diagnostic value for FGR. CONCLUSION: The expression of CEMIP and CYP11B2 is reduced in the serum of pregnant women with FGR and may become new diagnostic markers for FGR.

Foetal growth restriction is the inability of the foetus to reach its growth potential in the uterus due to various factors. This study aimed to investigate the expression and significance of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction. In our study, we found that the expression of cell migration-including protein and aldosterone synthase in serum of pregnant women with foetal growth restriction were decreased. Cell migration-including protein and aldosterone synthase expression was negatively correlated with soluble fms like tyrosine kinase-1/placental growth factor ratio. In addition, the study also found that cell migration-including protein and aldosterone synthase expression in serum had good diagnostic value for foetal growth restriction.

The Impact of Fetal Growth Restriction on Prenatal 2D Ultrasound and Doppler Study of the Fetal Adrenal Gland.

Background: Uteroplacental insufficiency in fetuses with growth restriction (FGR) leads to chronic hypoxia and stress, predominantly affecting the adrenal glands. However, the mechanisms of impact remain unclear. Objectives: This study is aimed at comparing the Doppler indices of the adrenal artery and the adrenal gland sizes between FGR and those with normal growth. Materials and Methods: A multicenter, cross-sectional study was conducted from February to December 2023. We compared 34 FGR to 34 with normal growth in terms of inferior adrenal artery (IAA) Doppler indices and adrenal gland volumes. Results: The IAA peak systolic velocity (PSV) in the FGR group was 14.9 ± 2.9 cm/s compared to 13.5 ± 2.0 cm/s in the normal group, with a mean difference of 1.4 cm/s (95% confidence interval [CI]: 0.27-2.65; p value = 0.017). There were no significant differences between groups in terms of IAA pulsatility index (PI), resistance index (RI), or systolic/diastolic (S/D), with p values of 0.438, 0.441, and 0.658, respectively. The volumes of the corrected whole adrenal gland and the corrected neocortex were significantly larger in the FGR group, with p values of 0.031 and 0.020, respectively. Conclusion: Both increased IAA PSV and enlarged volumes of the corrected whole adrenal gland and neocortex were found in fetuses with FGR, suggesting significant adrenal gland adaptation in response to chronic intrauterine stress.

Effect of melatonin as a therapeutic strategy against intrauterine growth restriction: a mini-review of current state.

Intrauterine growth restriction (IUGR) or intrauterine growth retardation is a condition that the fetus does not grow as expected. And the biometric profile does not match with the age of fetus. This condition is associated with increased mortality and morbidity of the neonates along with increased risk of cardiovascular, lung, and central nervous system damage. Despite close monitoring of high-risk mothers and the development of new therapeutic approaches, the optimal outcome has not been achieved yet that it indicates the importance of investigations on new therapeutic approaches. Melatonin (MLT) is a neurohormone mainly produced by the pineal gland and has a wide range of effects on different organs due to the broad dispersion of its receptors. Moreover, melatonin is produced by the placenta and also its receptors have been found on the surface of this organ. Not only studies showed the importance of this neurohormone on growth and development of fetus but also they proved its highly anti-oxidant properties. As in IUGR the oxidative stress and inflammation increased melatonin could counteract these changes and improved organ's function. In this study, we found that use of MLT could be a good clinical approach for the treatment of IUGR as its high anti-oxidant activity and vasodilation could dampen the mechanisms lead to the IUGR development.

Amniotic-umbilical-to-cerebral ratio, a Doppler index for estimating adverse perinatal outcomes in fetal growth restriction.

OBJECTIVE: To evaluate amniotic fluid volume with Doppler parameters and its association with composite adverse perinatal outcomes (CAPOs) in fetal growth restriction (FGR). MATERIALS AND METHODS: This study was conducted prospectively in a tertiary referral center between 2023 and 2024 on pregnant women diagnosed with early- and late-onset FGR. Fetal ultrasonographic measurements, including deepest vertical pocket (DVP) for amniotic fluid, and Doppler parameters including uterine artery (UtA) systolic/diastolic (S/D) and pulsatility index (PI), middle cerebral artery (MCA) S/D and PI, and umbilical artery (UA) S/D and PI, were conducted following fetal biometry. The cerebroplacental ratio (CPR), cerebral ratio, cerebro-placental-uterine ratio (CPUR), and amniotic-umbilical-to-cerebral ratio (AUCR) were all calculated. Pregnant women diagnosed with FGR were planned to give birth after 37 weeks' gestation, unless a pregnancy complication requiring earlier delivery occurred. We assessed perinatal outcomes subsequent to delivery, with CAPOs defined as the presence of at least one adverse outcome: 5th minute APGAR score <7, respiratory distress syndrome (RDS), umbilical cord blood pH <7.2, and neonatal intensive care unit (NICU) admission. RESULTS: The study included 132 participants, divided into early- (n = 32) and late-onset FGR (n = 100) groups. AUCR was significantly lower in fetuses with late-onset FGR who experienced CAPOs. Multivariate analysis showed gestational age at birth and birth weight were significant predictors of CAPOs in early-onset FGR, while gestational age, birth weight, and AUCR were significant predictors in late-onset FGR. CPR, UCR, and CPUR did not show significance in predicting CAPOs in both early- and late-onset FGR on multivariate analysis. CONCLUSIONS: AUCR is a potential reliable marker for predicting adverse perinatal outcomes in late-onset FGR.

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction - A prospective study.

INTRODUCTION: The aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. METHODS: This was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. RESULTS: There were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). CONCLUSION: MVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

Pulse Pressure as a Hemodynamic Parameter in Preeclampsia with Severe Features Accompanied by Fetal Growth Restriction.

Background: Modern management of preeclampsia can be optimized by tailoring the targeted treatment of hypertension to an individual's hemodynamic profile. Growing evidence suggests different phenotypes of preeclampsia, including those with a hyperdynamic profile and those complicated by uteroplacental insufficiency. Fetal growth restriction (FGR) is believed to be a result of uteroplacental insufficiency. There is a paucity of research examining the characteristics of patients with severe preeclampsia who do and who do not develop FGR. We aimed to elucidate which hemodynamic parameters differed between these two groups. Methods: All patients admitted to a single referral center with severe preeclampsia were identified. Patients were included if they had a live birth at 23 weeks of gestation or higher. Multiple gestations and pregnancies complicated by fetal congenital anomalies and/or HELLP syndrome were excluded. FGR was defined as a sonographic estimation of fetal weight (EFW) < 10th percentile or abdominal circumference (AC) < 10th percentile. Results: There were 76% significantly lower odds of overall pulse pressure upon admission for those with severe preeclampsia comorbid with FGR (aOR = 0.24, 95% CI = 0.07-0.83). Advanced gestational age on admission was associated with lower odds of severely abnormal labs and severely elevated diastolic blood pressure in preeclampsia also complicated by FGR. Conclusions: Subtypes of preeclampsia with and without FGR may be hemodynamically evaluated by assessing pulse pressure on admission.

Prevention of Pregnancy Complications Using a Multimodal Lifestyle, Screening, and Medical Model.

Prevention of pregnancy complications related to the "great obstetrical syndromes" (preeclampsia, fetal growth restriction, spontaneous preterm labor, and stillbirth) is a global research and clinical management priority. These syndromes share many common pathophysiological mechanisms that may contribute to altered placental development and function. The resulting adverse pregnancy outcomes are associated with increased maternal and perinatal morbidity and mortality and increased post-partum risk of cardiometabolic disease. Maternal nutritional and environmental factors are known to play a significant role in altering bidirectional communication between fetal-derived trophoblast cells and maternal decidual cells and contribute to abnormal placentation. As a result, lifestyle-based interventions have increasingly been recommended before, during, and after pregnancy, in order to reduce maternal and perinatal morbidity and mortality and decrease long-term risk. Antenatal screening strategies have been developed following extensive studies in diverse populations. Multivariate preeclampsia screening using a combination of maternal, biophysical, and serum biochemical markers is recommended at 11-14 weeks' gestation and can be performed at the same time as the first-trimester ultrasound and blood tests. Women identified as high-risk can be offered prophylactic low dose aspirin and monitored with angiogenic factor assessment from 22 weeks' gestation, in combination with clinical assessment, serum biochemistry, and ultrasound. Lifestyle factors can be reassessed during counseling related to antenatal screening interventions. The integration of lifestyle interventions, pregnancy screening, and medical management represents a conceptual advance in pregnancy care that has the potential to significantly reduce pregnancy complications and associated later life cardiometabolic adverse outcomes.

The Relationship between Placental Shear Wave Elastography and Fetal Weight-A Prospective Study.

Background/Objectives: The utility of shear wave elastography (SWE) as an adjunct to ultrasound biometry and Doppler velocimetry for the examination of placental dysfunction and suboptimal fetal growth is unclear. To date, limited data exist correlating the mechanical properties of placentae with fetal growth. This study aimed to investigate the relationship between placental shear wave velocity (SWV) and ultrasound estimated fetal weight (EFW), and to ascertain if placental SWV is a suitable proxy measure of placental function in the surveillance of small-for-gestational-age (SGA) pregnancies. Methods: This prospective, observational cohort study compared the difference in placental SWV between SGA and appropriate-for-gestational-age (AGA) pregnancies. There were 221 women with singleton pregnancies in the study cohort-136 (61.5%) AGA and 85 (38.5%) SGA. Fetal biometry, Doppler velocimetry, the deepest vertical pocket of amniotic fluid, and mean SWV were measured at 2-4-weekly intervals from recruitment to birth. Results: There was no difference in mean placental SWV in SGA pregnancies compared to AGA pregnancies, nor was there any relationship to EFW. Conclusions: Although other studies have shown some correlation between increased placental stiffness and SGA pregnancies, our investigation did not support this. The mechanical properties of placental tissue in SGA pregnancies do not result in placental SWVs that are apparently different from those of AGA controls. As this study did not differentiate between constitutionally or pathologically small fetuses, further studies in growth-restricted cohorts would be of benefit.

Placental Element Content Assessed via Synchrotron-Based X-ray Fluorescence Microscopy Identifies Low Molybdenum Concentrations in Foetal Growth Restriction, Postdate Delivery and Stillbirth.

Placental health and foetal development are dependent upon element homeostasis. Analytical techniques such as mass spectroscopy can provide quantitative data on element concentrations in placental tissue but do not show spatial distribution or co-localisation of elements that may affect placental function. The present study used synchrotron-based X-ray fluorescence microscopy to elucidate element content and distribution in healthy and pathological placental tissue. The X-ray fluorescence microscopy (XFM) beamline at the Australian Synchrotron was used to image trace metal content of 19 placental sections from healthy term (n = 5, 37-39 weeks), foetal growth-restricted (n = 3, <32 weeks, birth weight <3rd centile), postdate (n = 7, >41 completed weeks), and stillbirth-complicated pregnancies (n = 4, 37-40 weeks). Samples were cryo-sectioned and freeze-dried. The concentration and distribution of fourteen elements were detected in all samples: arsenic, bromine, calcium, chlorine, copper, iron, molybdenum, phosphorous, potassium, rubidium, selenium, strontium, sulphur, and zinc. The elements zinc, calcium, phosphorous, and strontium were significantly increased in stillbirth placental tissue in comparison to healthy-term controls. Strontium, zinc, and calcium were found to co-localise in stillbirth tissue samples, and calcium and strontium concentrations were correlated in all placental groups. Molybdenum was significantly decreased in stillbirth, foetal growth-restricted, and postdate placental tissue in comparison to healthy-term samples (p < 0.0001). Synchrotron-based XFM reveals elemental distribution within biological samples such as the placenta, allowing for the co-localisation of metal deposits that may have a pathological role. Our pilot study further indicates low concentrations of placental molybdenum in pregnancies complicated by foetal growth restriction, postdate delivery, and stillbirth.

Does Catch-Up Growth Come with a Cognitive Cost? Cognitive Outcome and Growth Patterns in Growth Discordant Identical Twins.

OBJECTIVE: To determine whether it is the magnitude of early postnatal catch-up growth (CUG) in response to fetal growth restriction (FGR) or the FGR itself that negatively impacts cognitive outcome in a model of monochorionic twins discordant for fetal growth. STUDY DESIGN: This analysis is part of the LEMON study, a cohort study including all monochorionic twins with selective FGR aged 3 through 17 years. Growth measurements as documented by our primary care system were collected retrospectively. An age-appropriate neurodevelopmental test was performed generating a full-scale IQ (FSIQ). CUG at 2 years was calculated as (weight [kg] at 2 years-birth weight [kg]). We used a multivariable regression model investigating the association between FSIQ (outcome) and birth weight zscore, gestational age at birth and CUG at 2 years (predictors). Generalized estimating equations accounted for the fact that observations between cotwins are not independent. RESULTS: Median age at follow-up of the 46 included twin pairs was 11 (IQR 8-13) years. Birth weight z score and gestational age at birth were significantly associated with FSIQ, with ß-coefficients of 5.897 (95% CI 3.382-8.411), and 2.589 (95% CI 1.227-3.951), respectively (P < .0001). Adjusted for birth weight z score and gestational age, CUG in the first 2 years after birth was not significantly associated with FSIQ (ß-coefficient 0.108 [95% CI -1.373 to 1.590], P = .886). CONCLUSIONS: Our results, combining detailed growth measurements and neurodevelopmental follow-up in a discordant identical twin model, demonstrate that FGR itself rather than early postnatal CUG has negative consequences for cognitive development.

Impact on neonatal morbidity of moderate to severe early foetal growth restriction defined by doppler criteria: multicentre study.

INTRODUCTION: In recent years, there has been a change in the conceptualization of foetal growth restriction (FGR), which has gone from being defined solely based on weight criteria to being defined and staged based on Doppler criteria. The aim of our study was to evaluate neonatal risk in a cohort of neonates with moderate to severe early-onset FGR defined by Doppler criteria. POPULATION AND METHODS: We conducted a multicentre prospective cohort study in a cohort of neonates with early-onset foetal growth restriction and abnormal Doppler findings and a control cohort without Doppler abnormalities matched for sex and gestational age. RESULTS: A total of 105 patients (50 cases, 55 controls) were included. We found a higher frequency of respiratory morbidity in the FGR group, with an increased need of surfactant (30% vs. 27.3%; OR, 5.3 [95% CI, 1.1-26.7]), an increased need for supplemental oxygen (66% vs. 49.1%; OR, 5.6 [95% CI, 1.5-20.5]), and a decreased survival without bronchopulmonary dysplasia (70 vs. 87.3%; OR, 0.16 [95% CI, 0.03-0.99]). Patients with FGR required a longer length of stay and more days of parenteral nutrition and had a higher incidence of haematological abnormalities such as neutropenia and thrombopenia. The lactate level at birth was higher in the severe FGR subgroup (6.12 vs. 2.4 mg/dL; P = .02). CONCLUSION: The diagnosis of early-onset moderate to severe FGR defined by Doppler criteria carries a greater risk of respiratory, nutritional and haematological morbidity, independently of weight and gestational age. These patients, therefore, should be considered at increased risk compared to constitutionally small for gestational age preterm infants or preterm infants without FGR.

Prenatal Diagnosis of Fetuses with 4q35 Deletion: Case Series and Review of the Literature.

INTRODUCTION: 4q35 deletion is a rare chromosomal syndrome with a wide range of phenotypes, which can be challenging to detect through prenatal ultrasound. This study aimed to summarize the fetal phenotypes of patients with 4q35 deletion. CASE PRESENTATION: The study included four fetuses with 4q35 deletion, with detailed records of prenatal ultrasound and genetic testing results. These cases included following phenotypes, fetal growth restriction (FGR) (2/4), cystic hygroma (2/4), single umbilical artery (1/4), and fused kidney (1/4). One case was terminated, while the other three were born and showed no obvious abnormalities at the 1-year follow-up. Previous reports have described the fetal phenotype of 4q35 deletion in 6 patients from five families, with prenatal phenotypes including FGR (2/6), cardiac structural abnormalities (1/6), brain ventriculomegaly (1/6), oligohydramnios (1/6), and multicystic dysplastic kidneys (1/6). CONCLUSION: Overall, the phenotypes of fetuses with 4q35 deletion are diverse, with FGR potentially being a significant phenotype in these cases.

Utilizing Repetitive Serial Placental Ultrasounds for Diagnosing a Massive Subchorionic Thrombohematoma: Insights Into Soluble FMS-Like Tyrosine Kinase-1/Placental Growth Factor (sFlt-1/PlGF) Trends.

The patient, a 34-year-old primigravida with no prior medical history, presented at 23 + 0 weeks with gestational hypertension and fetal growth restriction (FGR). Ultrasound examination showed a placental mass, and subsequent repeated ultrasound scans revealed changes in the mass' echogenicity, raising suspicion of a massive subchorionic thrombohematoma (MST). While the blood pressure was mildly elevated without proteinuria and organ dysfunctions, serum soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratios showed significantly elevated values. A cesarean section was performed at 29 + 2 weeks due to the nonreassuring fetal status. The female infant, with Apgar scores of 1/1 at one/five minutes and an umbilical artery pH of 7.16, remained unresponsive and died seven hours postdelivery. Pathology examination revealed a massive hematoma in the subchorionic space, measuring 22 mm thick, directly beneath the umbilical cord attachment. This case underscores the importance of repetitive placental ultrasound in MST diagnosis and suggests the potential utility of sFlt-1/PlGF ratios in predicting adverse outcomes.

Confined placental mosaicism with trisomy 13 complicated by severe preeclampsia: A case report and literature review.

A 31-year-old primiparous woman underwent non-invasive prenatal testing. The result was trisomy 13 (T13) positive. The chromosome 13 t-statistics (Z-score) was significantly high. The result of amniocentesis was normal karyotype (46,XX). Detailed ultrasound showed no fetal structural abnormalities. We suspected T13 confined placental mosaicism (CPM) and observed the course naturally. From the late second trimester, severe fetal growth restriction manifested followed by proteinuria and hypertension, diagnosing her with preeclampsia (PE). At 35 + 5 weeks, emergent cesarean section was required, yielding a 1480 g female infant. We sampled five locations of chorionic villi in the placenta. T13 cells dominated cells with normal karyotypes in all parts and the rate of trisomic cells ranged from 57% to 96%, which were generally high rate. None developed PE in reported T13 CPM cases and this is the first case of PE. The dominancy of T13 cells can be associated with PE development.

Relative uteroplacental insufficiency of labor.

Relative uteroplacental insufficiency of labor (RUPI-L) is a clinical condition that refers to alterations in the fetal oxygen "demand-supply" equation caused by the onset of regular uterine activity. The term RUPI-L indicates a condition of "relative" uteroplacental insufficiency which is relative to a specific stressful circumstance, such as the onset of regular uterine activity. RUPI-L may be more prevalent in fetuses in which the ratio between the fetal oxygen supply and demand is already slightly reduced, such as in cases of subclinical placental insufficiency, post-term pregnancies, gestational diabetes, and other similar conditions. Prior to the onset of regular uterine activity, fetuses with a RUPI-L may present with normal features on the cardiotocography. However, with the onset of uterine contractions, these fetuses start to manifest abnormal fetal heart rate patterns which reflect the attempt to maintain adequate perfusion to essential central organs during episodes of transient reduction in oxygenation. If labor is allowed to continue without an appropriate intervention, progressively more frequent, and stronger uterine contractions may result in a rapid deterioration of the fetal oxygenation leading to hypoxia and acidosis. In this Commentary, we introduce the term relative uteroplacental insufficiency of labor and highlight the pathophysiology, as well as the common features observed in the fetal heart rate tracing and clinical implications.

Correlation of Zinc and Copper Levels In Mothers and Cord Blood of Neonates With Prematurity and Intrauterine Growth Pattern.

Background Trace elements like zinc and copper are indispensable for human growth and development, exerting significant influence on a multitude of physiological processes. Acting as pivotal components for transcription factors and catalytic cofactors for enzymes, these elements play essential roles in cellular differentiation and maturation Objective The objective of this study was to study serum zinc and copper levels in mothers and neonates in relation to prematurity and intrauterine growth retardation (IUGR). Methods This was a cross-sectional study that included 100 mothers who met the inclusion criteria. Maternal history was recorded, and gestational age was estimated using the New Ballard scoring system. Maternal and cord blood samples were taken for zinc and copper analysis. Results The comparison of maternal copper and zinc levels between term and preterm neonates revealed a statistically significant difference with both trace elements found in less concentration in preterm when compared to the term patients (p= 0.03 for Zinc; 0.0001 for copper). We also report a statistically significant difference in maternal and cord blood copper and zinc levels in cases with IUGR compared to normal neonates. Conclusion The findings show that maternal zinc and copper levels are critical for the intrauterine growth of the fetus and for appropriate gestational age.

Advanced magnetic resonance imaging in human placenta: insights into fetal growth restriction and congenital heart disease.

Placental function plays a crucial role in fetal development, as it serves as the primary interface for delivery of nutrients and oxygen from the mother to fetus. Magnetic resonance imaging (MRI) has significantly improved our ability to visualize and understand the placenta's complex structure and function. This review provides an up-to-date examination of the most common and novel placental MRI techniques. It will also discuss the clinical applications of MRI in diagnosing and monitoring placental insufficiency, as well as its implications for fetal growth restriction (FGR) and congenital heart disease (CHD). Ongoing research using multi-parametric MRI techniques aims to develop novel biomarkers and uncover the relationships between placental parameters and pre-onset diseased states, ultimately contributing to better maternal and fetal health outcomes, which is essential to better guide clinical judgement.

Does atenolol use during pregnancy cause small for gestational age neonates? A meta-analysis.

OBJECTIVES: Atenolol is a commonly used beta bloscker in non-pregnant women. Many providers are hesitant in prescribing atenolol in pregnancy because of a possible association with poor fetal growth. We aimed to assess the association between atenolol and the occurrence of small for gestational age neonates compared to other beta blockers, as described in the existing literature. METHODS: We used the meta-analytic method to generate a forest plot for risk ratios (RR) of small for gestational age in patients who used atenolol vs. other beta blockers. Statistical heterogeneity was assessed with the I2 statistic. RESULTS: Two studies were included, with a resultant RR of 1.94 [95 % confidence interval (CI) 1.60; 2.35]. A study by Duan et al. in 2018 noted the following rate of small for gestational age for each beta blocker use: 112/638 atenolol, 590/3,357 labetalol, 35/324 metoprolol, and 50/489 propranolol. A study by Tanaka et al. in 2016 noted the following rate of small for gestational age: 8/22 for propranolol, 2/12 for metoprolol, 2/6 for atenolol, 0/5 for bisoprolol. Heterogeneity (I2) was 0 %. CONCLUSIONS: Our results suggested an elevated risk of small for gestational age associated with atenolol use in comparison to other beta blockers, specifically labetalol, propranolol, bisoprolol, and metoprolol.

Activity restriction and risk of adverse pregnancy outcomes.

BACKGROUND: Activity restriction is a common recommendation given to patients during pregnancy for various indications, despite lack of definitive data showing improvements in pregnancy outcomes. OBJECTIVE: To determine if activity restriction (AR) in pregnancy is associated with decreased odds of adverse pregnancy outcomes (APOs). STUDY DESIGN: Secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) prospective cohort. Nulliparous singletons were followed at 8 sites from October 2010 - September 2013. Demographic and clinical data were collected at 4 timepoints, and participants were surveyed about AR recommendations at 22w0d-29w6d and delivery. We excluded participants missing data on AR and age. Participants were grouped according to history of AR, and APOs included: gestational hypertension (gHTN), preeclampsia/eclampsia, preterm birth (PTB), and small for gestational age (SGA) neonate. Associations between AR and APOs were examined using uni- and multivariable logistic regression models adjusting for a priori identified APO risk factors. RESULTS: Of 10,038 nuMoM2b participants, 9,312 met inclusion criteria and 1,386 (14.9%) were recommended AR; participants identifying as Black [aOR 0.81 (95% CI 0.68-0.98)] or Hispanic [aOR 0.73 (95% CI 0.61-0.87)] were less likely to be placed on AR when compared to those identifying as White. Overall, 3,197 (34.3%) experienced at least one APO [717 (51.7%) of participants with AR compared to 2,480 (31.3%) participants without AR]. After adjustment for baseline differences, the AR group had increased odds of gHTN [aOR 1.61 (95% CI 1.35-1.92)], preeclampsia/eclampsia [aOR 2.52 (95% CI 2.06-3.09)] and iatrogenic and spontaneous PTB [aOR 2.98 (95% CI 2.41-3.69)], but not delivery of an SGA neonate. CONCLUSION: AR in pregnancy was independently associated with increased odds of hypertensive disorders of pregnancy and PTB, but future prospective work is needed to determine potential causality. Further, participants identifying as Black or Hispanic were significantly less likely to be recommended AR compared to those identifying as White. While AR is not an evidence-based practice, these findings suggest bias may impact which patients receive advice to limit activity in pregnancy.