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ABSTRACT Objective Design Setting Sample Methods Main Outcome Measures Results Conclusions To investigate longitudinal trends in fetal and offspring cardiovascular adaptation in fetal growth restriction (FGR).Prospective longitudinal study.Fetal Medicine Unit.Thirty‐five FGR pregnancies and 37 healthy controls assessed as term fetuses (mean age 37 ± 1 weeks) and again in infancy (mean age 8 ± 2 months).Conventional echocardiographic techniques, tissue Doppler imaging and speckle tracking echocardiography.Left ventricular (LV) and right ventricular (RV) geometry and function. Echocardiographic parameters were normalised by ventricular size adjusting for differences in body weight between groups.Compared to healthy controls, late FGR fetuses showed significant alterations in cardiac geometry with more globular LV chamber (LV sphericity index, 0.56 vs. 0.52), increase in biventricular global longitudinal systolic contractility (MAPSE, 0.29 vs. 0.25 mm; TAPSE, 0.42 vs. 0.37 mm) and elevated cardiac output (combined CO: 592 vs. 497 mL/min/kg, p < 0.01 for all). Indices of LV diastolic function in FGR fetuses were significantly impaired with myocardial diastolic velocities (LV A', 0.30 vs. 0.26 cm/s; IVS E', 0.19 vs. 0.16 cm/s) and LV torsion (1.2 vs. 3.5 deg./cm, p < 0.01 for all). At postnatal assessment, FGR offspring revealed persistently increased SAPSE (0.27 vs. 0.24 mm), LV longitudinal strain (−19.0 vs. −16.0%), reduced LV torsion (1.6 vs. 2.1 deg./cm) and elevated CO (791 vs. 574 mL/min/kg, p < 0.01 for all).Perinatal cardiac remodelling and myocardial dysfunction in late FGR fetuses is most likely due to chronic placental hypoxaemia. Persistent changes in cardiac geometry and function in FGR offspring may reflect fetal cardiovascular maladaptation that could predispose to long‐term cardiovascular complications in later life. [ABSTRACT FROM AUTHOR]

Poor placental angiogenesis is associated with several pregnancy complications including fetal growth restriction (FGR), which causes low birth weight (LBW) babies to have a high risk of growth disorders and metabolic disorders in adulthood. Recent research using syncytin knock-out mice showed significant disruption in the growth of placental vascularization. Syncytin-1 which encoded by ERVW-1 gene, is proposed to have a role in placental angiogenesis, but its relationship with other proangiogenic factors such as vascular endothelial growth factor (VEGF) in the placenta of LBW babies has not yet been determined. By knowing the mechanisms of FGR, more proactive preventive and therapeutic measures can be taken in the future. This study aimed to determine the expression of ERVW-1 , proangiogenic gene VEGF and its receptor (FLT-1), and hypoxia inducible factor-1 (HIF-1) in LBW placentas, and investigate the relationship between these genes' expression in the placenta of LBW babies. Total RNA was extracted from placental tissue. Total RNA is used as a cDNA synthesis template, followed by qRT-PCR. Correlations of ERVW-1, VEGF, FLT-1 and HIF-1 genes' expression were analyzed by linear regression. The age and body mass index of mothers with LBW and normal birth weight (NBW) babies were not significantly different. ERVW-1 expression in LBW placentas was lower than in NBW placentas, but VEGF, FLT-1 and HIF-1 expressions were higher. ERVW-1 was negatively correlated with HIF-1 and VEGF. Low expression of ERVW-1 in the placenta of LBW babies may result in impaired placental angiogenesis and possibly lead to hypoxia. • Lower expression of ERVW-1 was found in the placenta of Low Birth Weight babies. • Low ERVW-1 expression leads to hypoxia, as indicated by high HIF-1 expression. • Hypoxic conditions are compensated by upregulation of VEGF and its receptor, FLT-1. [ABSTRACT FROM AUTHOR]

Fetal growth restriction and underlying placental insufficiency are associated with increased oxidative stress. Current diagnostics fail to identify all growth restricted fetuses and newborns, due to focus on small size. This scoping review aims to summarize the available evidence on usefulness of cord blood oxidative stress biomarkers for identification of growth restricted newborns in need of monitoring and support because of associated health risks. MEDLINE and EMBASE were searched from inception to May 2024. Studies were included if oxidative stress biomarkers were measured in cord blood collected immediately after delivery in newborns suspected to be growth restricted. Biomarkers were categorized based on the origin and/or biological function and their interrelationships. Oxidative stress was determined for each individual biomarker and category. Literature search identified 78 studies on 39 different biomarkers, with a total of 2707 newborns with suspected growth restriction, and 4568 controls. Total oxidant/antioxidant status, catalase, glutathione, ischemia-modified albumin, and nucleated red blood cells were most consistently associated with suspected growth restriction. Reactive oxygen species/reactive nitrogen species, factors in their production, antioxidant enzymes, non-enzymatic antioxidants, and products of oxidative stress were not consistently associated. This review collates the evidence of associations between cord blood oxidative stress biomarkers and growth restriction. Total oxidant/antioxidant status, catalase, glutathione, ischemia-modified albumin, and nucleated red blood cells could potentially be candidates for developing a cord blood diagnostic tool for future clinical use. • Oxidative stress cord blood biomarkers useful to identify growth restricted newborns. • (Anti)oxidant status, CAT, GSH, IMA, NRBC most associated with growth restriction. • Offering possibilities for development of cord blood diagnostic tool for clinical use. [ABSTRACT FROM AUTHOR]

A high frequency of single nucleotide somatic mutations in the placenta has been recently described, but its relationship to placental dysfunction is unknown. We performed a pilot case-control study using paired fetal, maternal, and placental samples collected from healthy live birth controls (n = 10), live births with fetal growth restriction (FGR) due to placental insufficiency (n = 7), and stillbirths with FGR and placental insufficiency (n = 11). We quantified single nucleotide and structural somatic variants using bulk whole genome sequencing (30-60X coverage) in four biopsies from each placenta. We also assessed their association with clinical and histological evidence of placental dysfunction. Seventeen pregnancies had sufficiently high-quality placental, fetal, and maternal DNA for analysis. Each placenta had a median of 473 variants (range 111–870), with 95 % arising in just one biopsy within each placenta. In controls, live births with FGR, and stillbirths, the median variant counts per placenta were 514 (IQR 381–779), 582 (450–735), and 338 (245–441), respectively. After adjusting for depth of sequencing coverage and gestational age at birth, the somatic mutation burden was similar between groups (FGR live births vs. controls, adjusted diff. 59, 95 % CI -218 to +336; stillbirths vs controls, adjusted diff. −34, −351 to +419), and with no association with placental dysfunction (p = 0.7). We confirmed the high prevalence of somatic mutation in the human placenta and conclude that the placenta is highly clonal. We were not able to identify any relationship between somatic mutation burden and clinical or histologic placental insufficiency. • Somatic mutation is highly prevalent in the human placenta. • 95 % of comatic variants were present in just one of four biopsies in each placenta. • Somatic mutation estimates were driven by sequencing depth and gestational age. • Two variant calling algorithms yield very different somatic variation estimates. • We found no association between somatic variant burden and clinical outcome. [ABSTRACT FROM AUTHOR]

The congenital condition gastroschisis is associated with delayed villous development and placental malperfusion, suggesting placental involvement. This study uses RNA sequencing to compare the placental transcriptome in pregnancies with and without gastroschisis. 180 coding genes were differentially expressed, mapping to multiple gene ontology pathways. Altered placental gene expression may represent fetal signalling to the placenta, and these changes could contribute to the pathogenesis of gastroschisis and associated morbidities, including fetal growth restriction. • Gastroschisis is a congenital condition where the infant's intestines extend outside the abdomen. • Developmental and vascular defects are associated with Gastroschisis. • Gastroschisis associated changes in the placental transcriptome were observed. • These changes may reflect altered fetal to placental signalling. [ABSTRACT FROM AUTHOR]

Dexamethasone is frequently prescribed for preterm infants to wean from respiratory support and/or to facilitate extubation. This pre-/postintervention prospective study ascertained the impact on clinical (respiratory support) and echocardiographic parameters after dexamethasone therapy in preterm fetal growth restriction (FGR) infants compared with appropriate for gestational age (AGA) infants. Echocardiography was performed within 24 h before the start and after completion of 10-day therapy. Parameters assessed included those reflecting pulmonary vascular resistance and right ventricular output. Seventeen FGR infants (birth gestation and birth weight, 25.2 ± 1.1 wk and 497 ± 92 g, respectively) were compared with 22 AGA infants (gestation and birth weight, 24.5 ± 0.8 and 663 ± 100 g, respectively). Baseline respiratory severity score (mean airway pressure × fractional inspired oxygen) was comparable between the groups, (median [interquartile range] FGR, 10 [6, 13] vs. AGA, 8 ± 2.8, P = 0.08). Pre-dexamethasone parameters of pulmonary vascular resistance (FGR, 0.19 ± 0.03 vs. AGA, 0.2 ± 0.03, P = 0.16) and right ventricular output (FGR, 171 ± 20 vs. 174 ± 17 mL/kg/min, P = 0.6) were statistically comparable. At post-dexamethasone assessments, the decrease in the respiratory severity score was significantly greater in AGA infants (median [interquartile range] FGR, 10 [6, 13] to 9 [2.6, 13.5], P = 0.009 vs. AGA, 8 ± 2.8 to 3 ± 1, P < 0.0001). Improvement in measures of pulmonary vascular resistance (ratio of time to peak velocity to right ventricular ejection time) was greater in AGA infants (FGR, 0.19 ± 0.03 to 0.2 ± 0.03, P = 0.13 vs. AGA 0.2 ± 0.03 to 0.25 ± 0.03, P < 0.0001). The improvement in right ventricular output was significantly greater in AGA infants (171 ± 20 to 190 ± 21, P = 0.014 vs. 174 ± 17 to 203 ± 22, P < 0.0001). This highlights differential cardiorespiratory responsiveness to dexamethasone in extremely preterm FGR infants, which may reflect the in utero maladaptive state. NEW & NOTEWORTHY: Dexamethasone (DEX) is frequently used in preterm infants dependent on ventilator support. Differences in vascular structure and function that may have developed prenatally arising from the chronic intrauterine hypoxemia in FGR infants may adversely affect responsiveness. The clinical efficacy of DEX was significantly less in FGR (birth weight < 10th centile) infants, compared with appropriate for gestational age (AGA) infants. Echocardiography showed significantly less improvement in pulmonary vascular resistance in FGR, compared with AGA infants. [ABSTRACT FROM AUTHOR]

Fetal hypoxia due to placental dysfunction is the hallmark of fetal growth restriction (FGR). Preferential perfusion of the brain (brain-sparing effect), as a part of physiological placental cardiovascular compensatory mechanisms to hypoxia, in FGR was reported. Therefore, the correlation between vascular endothelial growth factor A (VEGF-A) protein expression in the FGR placentas and newborns' early neurological outcome was examined. This study included 50 women with FGR complicated pregnancies and 30 uneventful pregnancies. Fetal hemodynamic parameters, neonatal acid–base status after delivery, placental pathohistology and VEGF-A expression were followed. Early neonatal morphological brain evaluation by ultrasound and functional evaluation of neurological status by Amiel – Tison Neurological Assessment at Term (ATNAT) were performed. VEGF-A protein expression level was significantly higher in the FGR placentas than normal term placentas (Fisher–Freeman–Halton's test, p≤0.001). No statistically significant correlation between placental VEGF-A expression and different prenatal and postnatal parameters was noticed. Whereas the alteration of an early neurological status assessed by ATNAT was found in 58 % of FGR newborns, morphological brain changes evaluated by UZV was noticed in 48 % of cases. No association between the level of placental VEGF-A expression and the early neurological deficits was found. As far as we know this is the first study of a possible connection between VEGF-A protein expression in the FGR placentas and neonates' early neurological outcomes. The lack of correlation between the FGR placental VEGF-A expression and neonates' neurological outcome could indicate that optimal early neurodevelopment may take place due to compensatory mechanism not related to placental VEGF-A expression. [ABSTRACT FROM AUTHOR]

Objectives: Small for gestational age (SGA) singletons are at increased risk for neurodevelopmental abnormalities. Scarce data exist regarding the long-term implications of SGA in twins. We opted to study the association between SGA of one twin and long-term neurologic related morbidity in dichorionic diamniotic twins. Study design: A population-based retrospective cohort study including consecutive dichorionic diamniotic twins, born between the years 1991 and 2021 at a tertiary medical center was conducted. Total and subtypes of neurologic related pediatric hospitalizations among SGA versus non-SGA twins were compared. A Kaplan–Meier survival curve was used to compare the cumulative neurologic morbidity incidence, and a Cox proportional hazards model was constructed to adjust for confounders. Results: The study population included 4222 newborns; 180 (4.3%) were SGA. Rate of long-term neurologic related hospitalizations was comparable between the two groups (8.7 vs. 8.0%, p = 0.755; Kaplan–Meier survival curve Log-rank p = 0.652). Using a Cox proportional hazards model, controlling for gender and birth order, no association was found between SGA and the risk for subsequent neurologic pediatric morbidity of the offspring (Adjusted HR = 1.0, 95% CI 0.6–1.8, p = 0.973). Conclusions: SGA is not associated with an increased risk for long-term pediatric neurologic morbidity in dichorionic diamniotic twins. [ABSTRACT FROM AUTHOR]

Purpose: Fetal movements are crucial indicators of fetal well-being, with reduced fetal movements (RFM) suggesting potential fetal compromise. Fetal growth restriction (FGR), often linked to placental insufficiency, is a major cause of perinatal morbidity and mortality. This study aimed to investigate the neonatal, labor, and placental outcomes of FGR pregnancies with and without RFM at term. Methods: In this retrospective study, data from all term, singleton deliveries with FGR and concomitant RFM were obtained and compared to an equal control group of FGR without RFM. Maternal characteristics, pregnancy and neonatal outcomes, and placental histology were compared. The primary outcome was a composite of adverse neonatal outcomes. A multivariable regression analysis was performed to identify independent associations with adverse neonatal outcomes. Results: During the study period, 250 FGR neonates with concomitant RFM and an equal control group were identified. The groups did not differ in maternal demographics aside from significantly higher rates of maternal smoking in the RFM group (p < 0.001). Polyhydramnios and oligohydramnios (p = 0.032 and p = 0.007, respectively) and meconium-stained amniotic fluid (p < 0.001) were more prevalent in the FGR+RFM group. Additionally, the RFM group showed higher rates of adverse neonatal outcomes despite having larger neonates (p = 0.047 and p < 0.001, respectively). No significant differences were observed in placental findings. Logistic regression identified RFM as an independent predictor of adverse neonatal outcomes (aOR 2.45, 95% CI 1.27–4.73, p = 0.008). Conclusion: Reduced fetal movements are significant and independent predictors of worse neonatal outcomes in FGR pregnancies, suggesting an additional acute insult on top of underlying placental insufficiency. [ABSTRACT FROM AUTHOR]

Prediction of fetal growth restriction (FGR) and small of gestational age (SGA) infants by using various ultrasound cardiac parameters in a logistic regression model. In this retrospective study we obtained standardized ultrasound images of 357 fetuses between the 20th and 39th week of gestation, 99 of these fetuses were between the 3rd and 10th growth percentile, 61 smaller than 3rd percentile and 197- appropriate for gestational age over the 10th percentile (control group). Several cardiac parameters were studied. The cardiothoracic ratio and sphericity of the ventricles was calculated. A binary logistic regression model was developed for prediction of growth restriction using the cardiac and biometric parameters. There were noticeable differences between the control and study group in the sphericity of the right ventricle (p = 0.000), left and right longitudinal ventricle length (pright = 0.000, pleft = 0.000), left ventricle transverse length (p = 0.000), heart diameter (p = 0.002), heart circumference (p = 0.000), heart area (p = 0.000), and thoracic diameter limited by the ribs (p = 0.002). There was no difference of the cardiothoracic ratio between groups. The logistic regression model achieved a prediction rate of 79.4 % with a sensitivity of 74.5 % and specificity of 83.2 %. The heart of growth restricted infants is characterized by a more globular right ventricle, shorter ventricle length and smaller thorax diameter. These parameters could improve prediction of FGR and SGA. [ABSTRACT FROM AUTHOR]

• MVFI can display the real-time perfusion status of fetal microvessels, including blood flow velocity, volume, and other related parameters. This technology is a non-invasive method that can be used to evaluate the blood flow situation in the fetal cranial region. • Growth restricted fetuses have lower biparietal diameter, head circumference, abdominal circumference, and femur length than normal fetuses, and their microvascular index and peak systolic velocity of internal arteries are also lower than normal fetuses. • The larger the microvascular index and peak systolic velocity of the internal artery, the more severe the fetal growth restriction. The study conducted retrospective analysis design, aiming to explore the use of Microvascular Imaging Technique (MVFI) to assess fetal cerebral microcirculation and analyze the relationship between Microvascular Index (MVI) and fetal growth and development. 100 pregnant women who met the criteria for fetal growth restriction (FGR) provided in the Expert Consensus on Fetal Growth Restriction (2019 Edition) and underwent routine prenatal examinations at the Obstetrics and Gynecology Department of Peking University Third Hospital from January 2021 to June 2023 were selected as the study subjects. A normal fetus with a fetal weight less than 10 % can be classified as FGR, Pregnant women with fetal umbilical artery (UA) systolic and diastolic (S/D) values ≥3 were included in the observation group, while 200 pregnant women with normal fetuses were selected as the control group during the same period. The fetuses' change in both groups were measured using color Doppler ultrasound, including bi-parietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). The cerebral microcirculation of the fetuses in both groups was evaluated using MVFI, and the MVI values were compared. The clinical characteristics of FGR fetuses with umbilical artery S/D ratio ≥ 3 were summarized, and the correlation between fetal cerebral microvascular status and fetal growth and development was analyzed using Pearson correlation analysis. The outcomes told that the BPD, HC, AC, and FL values of the fetuses in the control group were lower the other's value (P < 0.05), and the MVI and peak systolic velocity of the middle cerebral artery (MCA-PSV) values were also lower in the control group (P < 0.05). Pearson correlation analysis revealed a positive correlation between fetal growth and development and MVI and MCA-PSV values in FGR fetuses. In conclusion, MVFI can monitor and quantitatively analyze fetal intracranial microcirculation, visualize slow blood flow in microvascular structures, and this study provides preliminary evidence of the close relationship between fetal cerebral microcirculation and intrauterine growth and development. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Military aviation poses unique occupational risks, including exposures to intermittent hypoxia, high gravitational force, and toxic materials, in addition to circadian disruption, cosmic radiation, and ergonomic stressors also present in commercial flight. We sought to investigate whether a military aviation officer's career is associated with adverse maternal or fetal health outcomes. METHODS: We conducted a retrospective cohort study of female aviation and nonaviation officers in the Military Health System from October 2002 to December 2019. Exposure was identified as assignment of an aviation occupation code. Maternal and fetal health outcomes were identified by International Classification of Diseases codes from medical records. Regression analysis was used to estimate adjusted relative risks (aRR). RESULTS: I ncluded in the study were 25,929 active-duty female officers, with 46,323 recorded pregnancies and 32,853 recorded deliveries; 2131 pregnancies were diagnosed in aviation officers. Pregnant aviation officers had a decreased risk of composite adverse pregnancy outcomes [aRR 0.82 (0.73-0.92)], including gestational diabetes [aRR 0.69 (0.57-0.85)] and gestational hypertension [aRR 0.84 (0.71-0.99)]. Pregnant aviation officers had a decreased risk of depression prior to delivery [aRR 0.43 (0.35-0.53)] and hyperemesis gravidarum [aRR 0.74 (0.57-0.96)], but an increased risk of placental complications [aRR 1.15 (1.02-1.30)] and fetal growth restriction [aRR 1.36 (1.16-1.60)]. DISCUSSION: Pregnant military aviation officers have an increased risk of placental complications and fetal growth restriction in spite of a lower risk of gestational diabetes and gestational hypertension. Further research is needed to determine how flight-related occupations impact pregnancy. [ABSTRACT FROM AUTHOR]

Customized birthweight centiles have improved the detection of small for gestational age (SGA) and large for gestational age (LGA) babies compared to existing population standards. This study used perinatal registry data to derive coefficients for developing customized growth charts for Qatar.The PEARL registry data on women delivering in Qatar (2017–2018) was used to develop a multivariable linear regression model predicting optimal birthweight. Physiological variables included gestational age, maternal height, weight, ethnicity, parity, and sex of the baby. Pathological variables such as hypertension, preexisting and gestational diabetes and smoking were calculated and excluded to derive the optimal weight at term.The regression model found a term optimal birthweight of 3,235 g for a Qatari nationality mother with median height (159 cm), booking weight (72 kg), parity (1) and gestation at birth (276 days) at the end of an uncomplicated pregnancy. Constitutional coefficients significantly affecting birthweight were gestational age, height, weight, and parity. The main pathological factors were preexisting diabetes (increase by +175.7 g) and smoking (decrease by −190.9 g). The SGA and LGA rates in the entire cohort after applying the population-specific customized centiles were 11.1 and 12.2 %, respectively (contrasting with the Hadlock standard: SGA-26.3 % and LGA-1.8 %, and Fenton standard: SGA-12.9 % and LGA-4.0 %).Constitutional and pathological variations in fetal growth and birthweight apply in the maternity population in Qatar and have been quantified to allow the generation of customised charts for better identification of pregnancies with abnormal growth. Currently in-use population standards may misdiagnose many SGA and LGA babies. [ABSTRACT FROM AUTHOR]

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.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.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 %.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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate obstetric and perinatal outcomes among small for gestational age (SGA) infants born to patients diagnosed with Gestational diabetes mellitus (GDM). Materials and methods: A multicenter retrospective cohort study between 2005 and 2021. The perinatal outcomes of SGA infants born to patients with singleton pregnancy and GDM were compared to SGA infants born to patients without GDM. The primary outcome was a composite adverse neonatal outcome. Infants with known structural/genetic abnormalities or infections were excluded. A univariate analysis was conducted followed by a multivariate analysis (adjusted odds ratio [95% confidence interval]). Results: During the study period, 11,662 patients with SGA infants met the inclusion and exclusion criteria. Of these, 417 (3.6%) SGA infants were born to patients with GDM, while 11,245 (96.4%) were born to patients without GDM. Overall, the composite adverse neonatal outcome was worse in the GDM group (53.7% vs 17.4%, p < 0.01). Specifically, adverse neonatal outcomes such as a 5 min Apgar score < 7, meconium aspiration, seizures, and hypoglycemia were independently associated with GDM among SGA infants. In addition, patients with GDM and SGA infants had higher rates of overall and spontaneous preterm birth, unplanned cesarean, and postpartum hemorrhage. In a multivariate logistic regression assessing the association between GDM and neonatal outcomes, GDM was found to be independently associated with the composite adverse neonatal outcome (aOR 4.26 [3.43–5.3]), 5 min Apgar score < 7 (aOR 2 [1.16–3.47]), meconium aspiration (aOR 4.62 [1.76–12.13]), seizures (aOR 2.85 [1.51–5.37]) and hypoglycemia (aOR 16.16 [12.79–20.41]). Conclusions: Our study demonstrates that GDM is an independent risk factor for adverse neonatal outcomes among SGA infants. This finding underscores the imperative for tailored monitoring and management strategies in those pregnancies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the indications for maternal TORCH (Toxoplasma gondii, rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV)) serology, with a focus on the yield in isolated fetal growth restriction (FGR). Materials and Methods: A retrospective review of antenatal TORCH testing between January 2014 and December 2018 was carried out at two hospitals in Melbourne, Australia. TORCH testing ordered for pregnancy losses and stillbirth was excluded. Results: Medical records of 718 pregnancies were reviewed, representing 760 fetuses. Isolated FGR was the indication for TORCH screening in 71.2% of pregnancies. Screens ordered for isolated FGR were positive in 7.4% (95% CI 5.5–10.0%). There were 49 positive maternal immunoglobulin M (CMV = 34, Toxoplasma = 15). Two acute maternal infections during pregnancy were diagnosed (CMV = 1, Toxoplasma = 1), with both screens ordered to assess symptomatic maternal illness. There was one neonatal CMV infection, born to a woman with symptomatic primary CMV. No maternal or neonatal rubella or HSV infections were identified. We found a diagnostic yield of TORCH screening for isolated FGR of 0.0% (95% CI 0.00–0.8%). An estimated AUD$64 269.75 was expended on maternal TORCH screens in this study. Conclusion: Maternal TORCH testing for isolated FGR is of no diagnostic yield and should be abandoned. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) is a common outcome in human suboptimal gestation and is related to prenatal origins of cardiovascular dysfunction in offspring. Despite this, therapy of human translational potential has not been identified. Using human umbilical and placental vessels and the chicken embryo model, we combined cellular, molecular, and functional studies to determine whether N‐acetylcysteine (NAC) and hydrogen sulphide (H2S) protect cardiovascular function in growth‐restricted unborn offspring. In human umbilical and placental arteries from control or FGR pregnancy and in vessels from near‐term chicken embryos incubated under normoxic or hypoxic conditions, we determined the expression of the H2S gene CTH (i.e. cystathionine γ‐lyase) (via quantitative PCR), the production of H2S (enzymatic activity), the DNA methylation profile (pyrosequencing) and vasodilator reactivity (wire myography) in the presence and absence of NAC treatment. The data show that FGR and hypoxia increased CTH expression in the embryonic/fetal vasculature in both species. NAC treatment increased aortic CTH expression and H2S production and enhanced third‐order femoral artery dilator responses to the H2S donor sodium hydrosulphide in chicken embryos. NAC treatment also restored impaired endothelial relaxation in human third‐to‐fourth order chorionic arteries from FGR pregnancies and in third‐order femoral arteries from hypoxic chicken embryos. This NAC‐induced protection against endothelial dysfunction in hypoxic chicken embryos was mediated via nitric oxide independent mechanisms. Both developmental hypoxia and NAC promoted vascular changes in CTH DNA and NOS3 methylation patterns in chicken embryos. Combined, therefore, the data support that the effects of NAC and H2S offer a powerful mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. Key points: Gestation complicated by chronic fetal hypoxia and fetal growth restriction (FGR) increases a prenatal origin of cardiovascular disease in offspring, increasing interest in antenatal therapy to prevent against a fetal origin of cardiovascular dysfunction.We investigated the effects between N‐acetylcysteine (NAC) and hydrogen sulphide (H2S) in the vasculature in FGR human pregnancy and in chronically hypoxic chicken embryos.Combining cellular, molecular, epigenetic and functional studies, we show that the vascular expression and synthesis of H2S is enhanced in hypoxic and FGR unborn offspring in both species and this acts to protect their vasculature.Therefore, the NAC/H2S pathway offers a powerful therapeutic mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. [ABSTRACT FROM AUTHOR]

Fetal growth restriction (FGR) occurs in 8% of human pregnancies, and the growth restricted newborn is at a greater risk of developing heart disease in later adult life. In sheep, experimental restriction of placental growth (PR) from conception results in FGR, a decrease in cardiomyocyte endowment and an upregulation of pathological hypertrophic signalling in the fetal heart in late gestation. However, there is no change in the expression of markers of cellular proliferation nor in the level of cardiomyocyte apoptosis in the heart of the PR fetus in late gestation. This suggests that FGR arises early in gestation and programs a decrease in cardiomyocyte endowment in early, rather than late, gestation. Here, control and PR fetal sheep were humanely killed at 55 days' gestation (term, 150 days). Fetal body and heart weight were lower in PR compared with control fetuses and there was evidence of sparing of fetal brain growth. While there was no change in the proportion of cardiomyocytes that were proliferating in the early gestation PR heart, there was an increase in measures of apoptosis, and markers of autophagy and pathological hypertrophy in the PR fetal heart. These changes in early gestation highlight that FGR is associated with evidence of early cell death and compensatory hypertrophic responses of cardiomyocytes in the fetal heart. The data suggest that early placental restriction results in a decrease in the pool of proliferative cardiomyocytes in early gestation, which would limit cardiomyocyte endowment in the heart of the PR fetus in late gestation. Key points: Placental restriction leading to fetal growth restriction (FGR) and chronic fetal hypoxaemia in sheep results in a decrease in cardiomyocyte endowment in late gestation.FGR did not change cardiomyocyte proliferation during early gestation but did result in increased apoptosis and markers of autophagy in the fetal heart, which may result in the decreased endowment of cardiomyocytes observed in late gestation.FGR in early gestation also results in increased hypoxia inducible factor signalling in the fetal heart, which in turn may result in the altered expression of epigenetic regulators, increased expression of insulin‐like growth factor 2 and cardiomyocyte hypertrophy during late gestation and after birth. [ABSTRACT FROM AUTHOR]

Objective: In this study, we examined the HOXA1 expression in the placentas of women diagnosed with fetal growth restriction (IUGR) by immunoexpression and in silico analysis. Methods: Placenta samples from 40 control (healthy) and 40 pregnant women diagnosed with IUGR were included in the study. The samples were fixed in zinc-formal and embedded in paraffin. Demographic information of the patients was recorded. Sections taken from paraffin blocks were analyzed by Hematoxylin-Eosin and HOXA1 immunostaining. The protein-protein interaction network of HOXA1 was constructed using the STRING database and analyzed with Cytoscape. The route description was made with the DAVID web tool. Results: In histopathological examination, intense fibrin accumulation, structural degeneration of placental components, congestion, dilatation and increased syncytial nodes were observed in the IUGR group compared to the control group. HOXA1 gene expression was significantly increased in the IUGR group. The HOXA1 PPI network contained 201 nodes and 3876 edges. MCODE analysis identified 8 modules, the highest scoring module was related to the “Systemic lupus erythematosus”, “Alcoholism” and “Neutrophil extracellular trap formation” pathways. Conclusion: With immunoexpression and in silico analysis, we showed HOXA1 is a player of immune pathways, tissue development, and placental regulation, suggesting potential research avenues in understanding IUGR mechanisms. [ABSTRACT FROM AUTHOR]

Abstract—Fetal growth restriction is a complication of pregnancy that is defined as the inability of the fetus to realize its genetically determined growth potential. Despite the high social and medical significance of this problem the exact pathogenesis of fetal growth restriction is not known. Therefore, the analysis of the molecular genetics mechanisms of this pathology within the framework of approaches using modern high-performance technologies of next generation sequencing is of undoubted interest. In this review we focused on the analysis of data obtained in studies of the genetics component of fetal growth restriction. The authors of these studies used next generation sequencing technologies and carried out whole transcriptome profiling. The results of the gene expression genome-wide analysis in placental tissue allow us to identify 1430 differentially expressed genes between fetal growth restriction and normal pregnancy, of which only 1% were found in at least two studies. These differentially expressed genes are involved in the Wnt/β-catenin signaling pathway, which plays an important role in cell migration, neural pattern formation and organogenesis during embryonic development. Common genes are associated with both obstetric and gynecological diseases, as well as with various somatic conditions from the groups of neurodegenerative, cardiovascular diseases and mental disorders, which probably reflects their involvement in the development of postnatal consequences of fetal growth restriction. The results of our work do not only point to potential molecular mechanisms and key genes underlying fetal growth restriction, but also indicate the important role of gene–gene communications in this pathology: about 30% of all identified differentially expressed genes products interact with each other within the same gene network. In general, genome-wide RNA sequencing combined with the analysis of protein–protein interactions represents a promising direction in research in the development and functioning of the placenta, as well as the identification of genetic mechanisms of placental insufficiency diseases, including fetal growth restriction. [ABSTRACT FROM AUTHOR]

Problem: Preeclampsia (PE) and fetal growth restriction (FGR) are often associated with maternal inflammation and an increased risk of cardiovascular and metabolic disease in the affected mothers. The mechanism responsible for this increased risk of subsequent disease may involve reprogramming of innate immune cells, characterized by epigenetic modifications. Method of Study: Circulating monocytes from women with PE, FGR, or uncomplicated pregnancies (control) were isolated before labor. Cytokine release from monocytes following exposure to lipopolysaccharide (LPS) and the presence of lysine 4‐trimethylated histone 3 (H3K4me3) within TNF promoter sequences were evaluated. Single‐cell transcriptomic profiles of circulating monocytes from women with PE or uncomplicated pregnancies were assessed. Results: Monocytes from women with PE or FGR exhibited increased IL‐10 secretion and decreased IL‐1β and GM‐CSF secretion in response to LPS. While TNFα secretion was not significantly different in cultures of control monocytes versus those from complicated pregnancies with or without LPS exposure, monocytes from complicated pregnancies had significantly decreased levels of H3K4me3 associated with TNF promoter sequences. Cluster quantification and pathway analysis of differentially expressed genes revealed an increased proportion of anti‐inflammatory myeloid cells and a lower proportion of inflammatory non‐classical monocytes among the circulating monocyte population in women with PE. Conclusions: Monocytes from women with PE and FGR exhibit an immune tolerance phenotype before initiation of labor. Further investigation is required to determine whether this tolerogenic phenotype persists after the affected pregnancy and contributes to increased risk of subsequent disease. [ABSTRACT FROM AUTHOR]

• The diagnosis of fetal growth restriction (FGR) due to uteroplacental insufficiency improves perinatal outcome. • Using angiogenic markers to diagnose small for gestational age fetuses can enhance the current diagnostic FGR consensus. • Further studies are needed to integrate angiogenic markers into ultrasound parameters currently used for FGR diagnosis. The identification of fetal growth restriction (FGR) due to uteroplacental insufficiency is important to improve perinatal outcomes. To distinguish FGR from small for gestational age (SGA), FGR consensus definition is currently based on biometry and/or additional biophysical parameters. This study aims to verify if this definition might be modified by including circulating angiogenic factors. This historical cohort study included singleton pregnancies with SGA fetuses after 20 weeks. All patients underwent detailed ultrasound and measurements of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) at first assessment. ISUOG criteria for FGR were applied. Total PlGF was calculated using free PlGF, sFlt-1 and a receptor pharmacology model, and multiple of the median (MoM) values for sFlt-1, free PlGF, total PlGF and sFlt-1/PlGF ratio were calculated to adjust for gestational age. 72 pregnancies with SGA were first evaluated at median (IQR) of 28+5 (26+2 –31+3) weeks' gestation, and 51 fetuses (70.8 %) satisfied the FGR consensus definition. Pregnancies with FGR showed significantly lower levels of free and total PlGF MoM (0.12, 95 % IQR: 0.07–0.36 vs 0.32, 95 % IQR: 0.20–0.53, p = 0.008) and 0.26, 95 % CI: 0.16–0.55 vs 0.43, 95 % IQR: 0.23–0.53, p = 0.028) respectively; and higher sFlt-1 MoM (4.62, 95 % IQR: 1.80–7.30 vs 1.74, 95 % IQR:1.11–3.61, p = 0.014) than pregnancies not classified as FGR. Free and total PlGF MoM correlated significantly with gestational age at delivery (r = 0.776, p < 0.001 and r = 0.707, p < 0.001, respectively). sFlt-1 MoM and sFlt-1/PlGF ratio MoM also correlated with gestational age at delivery (r = -0.681, p < 0.001 and r = -0.823, p < 0.001). Six cases identified as FGR at first ultrasound were not confirmed at birth showing significantly higher levels of free PlGF MoM (0.77, 95 % IQR: 0.27–3.07 vs 0.17, 95 % IQR: 0.08–0.43, p = 0.022). These findings show that total as well as free PlGF levels are lower in pregnancies affected with placental growth restriction. Angiogenic biomarkers might improve the differentiation between placental growth restriction and constitutional smallness. Further studies are needed to determine how to integrate them into the current definitions of FGR. [ABSTRACT FROM AUTHOR]

Objective：To study the diagnostic efficacy of thromboelastography combined with ultrasound quantitative parameters on fetal growth restriction (FGR). Methods：A total of 50 cases of pregnant women with FGR admitted to Zhengzhou Maternal and Child Health Hospital from July 2021 to May 2023 were collected as the FGR group, and 50 pregnant women with normal fetal development in the same period and age group were selected as controls (the control group). The thromboelastogram indicators［maximum amplitude (MA), Angle, coagulation time (K), coagulation response time (R)］, umbilical and middle cerebral artery resistance index (RI), pulsation index (PI), end⁃systolic/end⁃diastolic peak value (S/D), cerebroplacental rate (CPR), weight, and abdominal circumference were compared between the two groups. Binary correlation and partial correlation analyses were performed to explore the correlation of thromboelastogram and ultrasound quantitative parameters with weight or abdominal circumference. The receiver operating characteristic (ROC) curve was performed to analyze the diagnostic value of thromboelastogram, ultrasound quantitative parameters, and the combined diagnosis of FGR. Results：Second-trimester, late-pregnancy, and before delivery the value of R and K were lower in the FGR group than in the control group, while the value of Angle and MA were higher (P < 0.05). The value of Umbilical artery S/D, umbilical artery PI, and umbilical artery RI in the FGR group were higher than those in the control group during the second⁃trimester, late-pregnancy, and before delivery, while the value of middle cerebral artery S/D, middle cerebral artery PI, middle cerebral artery RI, and CRP were lower than those in the control group (P < 0.05). The weight and abdominal circumference of the FGR group were lower than those of the control group in the second⁃trimester, late-pregnancy, and before delivery (P < 0.05). The binary correlation analysis showed that the thromboelastography and ultrasound quantitative parameters before delivery were more strongly correlated with both body weight and abdominal circumference (P < 0.05). Partial correlation analysis indicated that the value of R, K, middle cerebral artery RI, and CRP were positively correlated with body weight and abdominal circumference before delivery, while the value of Angle, MA, umbilical artery S/D, umbilical artery PI and umbilical artery RI remained negatively correlated with body weight and abdominal circumference (P < 0.05). The combined diagnosis of FGR by using thromboelastography and ultrasound quantitative parameters before delivery had a higher area under curve (AUC) than each single index (P < 0.05). Conclusion：The quantitative detection of thromboelastography combined with ultrasound in pregnant women with FGR can effectively monitor changes in coagulation function and fetal hemodynamics at different stages of pregnancy, which has a high value in the diagnosis of FGR. [ABSTRACT FROM AUTHOR]

Objectives: Fetuses with late‐onset growth restriction (FGR) have a higher risk of suboptimal neurocognitive performance after birth. Previous studies have reported that impaired brain and cortical development can start in utero. The primary aim of this study was to report midline structure growth and cortical development in fetuses with late‐onset FGR according to its severity; the secondary aim was to elucidate whether the severity of FGR, as defined by the presence of abnormal Doppler findings, plays a role in affecting brain growth and maturation. Methods: This was a prospective observational study that included fetuses with late‐onset FGR (defined according to the Delphi FGR criteria) undergoing neurosonography between 32 and 34 weeks' gestation. Midline structure (corpus callosum (CC) and cerebellar vermis (CV)) length and cortical development, including the depth of the Sylvian (SF), parieto‐occipital (POF) and calcarine (CF) fissures, were compared between late‐onset FGR, small‐for‐gestational‐age (SGA) and appropriate‐for‐gestational‐age (AGA) fetuses. Subgroup analysis according to the severity of FGR (normal vs abnormal fetal Doppler) was also performed. Univariate analysis was used to analyze the data. Results: A total of 52 late‐onset FGR fetuses with normal Doppler findings, 60 late‐onset FGR fetuses with abnormal Doppler findings, 64 SGA fetuses and 100 AGA fetuses were included in the analysis. When comparing AGA controls with SGA fetuses, late‐onset FGR fetuses with normal Doppler findings and late‐onset FGR fetuses with abnormal Doppler findings, there was a progressive and significant reduction in the absolute values of the following parameters: CC length (median (interquartile range (IQR)), 43.5 (28.9–56.1) mm vs 41.9 (27.8–51.8) mm vs 38.5 (29.1–50.5) mm vs 31.7 (23.8–40.2) mm; K = 26.68; P < 0.0001), SF depth (median (IQR), 14.5 (10.7–16.8) mm vs 12.7 (9.8–15.1) mm vs 11.9 (9.1–13.4) mm vs 8.3 (6.7–10.3) mm; K = 75.82; P < 0.0001), POF depth (median (IQR), 8.6 (6.3–11.1) mm vs 8.1 (5.6–10.4) mm vs 7.8 (6.1–9.3) mm vs 6.6 (4.2–8.0) mm; K = 45.06; P < 0.0001) and CF depth (median (IQR), 9.3 (6.7–11.5) mm vs 8.2 (5.7–10.7) mm vs 7.7 (5.2–9.4) mm vs 6.3 (4.5–7.2) mm; K = 46.14; P < 0.0001). Absolute CV length was significantly higher in AGA fetuses compared with all other groups, although the same progressive pattern was not noted (median (IQR), 24.9 (17.6–29.2) mm vs 21.6 (15.2–26.1) mm vs 19.1 (13.8–25.9) mm vs 21.0 (13.5–25.8) mm; K = 16.72; P = 0.0008). When the neurosonographic variables were corrected for fetal head circumference, a significant difference in the CC length and SF, POF and CF depths, but not CV length, was observed only in late‐onset FGR fetuses with abnormal Doppler findings when compared with AGA and SGA fetuses. Conclusions: Fetuses with late‐onset FGR had shorter CC length and delayed cortical development when compared with AGA fetuses. After controlling for fetal head circumference, these differences remained significant only in late‐onset FGR fetuses with abnormal Doppler. These findings support the existence of a link between brain development and impaired placental function. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: This systematic review explores the level of oxidative stress (OS) markers during pregnancy and their correlation with complications. Unlike previous studies, it refrains from directly investigating the role of OS but instead synthesises data on the levels of these markers and their implications for various pregnancy-related complications such as preeclampsia, intrauterine growth restrictions, preterm premature rupture of membranes, preterm labour, gestational diabetes mellitus and miscarriages. Method: Study Design: Utilizing a systematic review approach, we conducted a comprehensive search across databases, including MEDLINE, CINAHL (EBSCOhost), ScienceDirect, Web of Science, and SCOPUS. Our search encompassed all publication years in English. Results: After evaluating 54,173 records, 45 studies with a low risk of bias were selected for inclusion. This systematic review has underscored the importance of these markers in both physiological and pathological pregnancy states such as preeclampsia, intrauterine growth restrictions, preterm premature rupture of membranes, preterm labour, gestational diabetes mellitus and miscarriages. Conclusion: This systematic review provides valuable insights into the role of OS in pregnancy and their connection to complications. These selected studies delved deeply into OS markers during pregnancy and their implications for associated complications. The comprehensive findings highlighted the significance of OS markers in both normal and pathological pregnancy conditions, paving the way for further research in this field. [ABSTRACT FROM AUTHOR]

Pregnancy is a complex and challenging process associated with physiological changes whose objective is to adapt the maternal organism to the increasing energetic requirements due to embryo and fetal development. A failed adaptation to these demands may lead to pregnancy complications that threaten the health of both mothers and their offspring. Since mitochondria are the main organelle responsible for energy generation in the form of ATP, the adequate state of these organelles seems crucial for proper pregnancy development and healthy pregnancy outcomes. The homeostasis of these organelles depends on several aspects, including their content, biogenesis, energy production, oxidative stress, dynamics, and signaling functions, such as apoptosis, which can be modified in relation to diseases during pregnancy. The etiology of pregnancy disorders like preeclampsia, fetal growth restriction, and gestational diabetes mellitus is not yet well understood. Nevertheless, insufficient placental perfusion and oxygen transfer are characteristic of many of them, being associated with alterations in the previously cited different aspects of mitochondrial homeostasis. Therefore, and due to the capacity of these multifactorial organelles to respond to physiological and pathophysiological stimuli, it is of great importance to gather the currently available scientific information regarding the relationship between main pregnancy complications and mitochondrial alterations. According to this, the present review is intended to show clear insight into the possible implications of mitochondria in these disorders, thus providing relevant information for further investigation in relation to the investigation and management of pregnancy diseases. [ABSTRACT FROM AUTHOR]

Background: Small for gestational age (SGA) fetuses are at risk for perinatal adverse outcomes. Fetal body composition reflects the fetal nutrition status and hold promise as potential prognostic indicator. MRI quantification of fetal anthropometrics may enhance SGA risk stratification. Hypothesis: Smaller, leaner fetuses are malnourished and will experience unfavorable outcomes. Study Type: Prospective. Population: 40 SGA fetuses, 26 (61.9%) females: 10/40 (25%) had obstetric interventions due to non‐reassuring fetal status (NRFS), and 17/40 (42.5%) experienced adverse neonatal events (CANO). Participants underwent MRI between gestational ages 30 + 2 and 37 + 2. Field Strength/Sequence: 3‐T, True Fast Imaging with Steady State Free Precession (TruFISP) and T1‐weighted two‐point Dixon (T1W Dixon) sequences. Assessment: Total body volume (TBV), fat signal fraction (FSF), and the fat‐to‐body volumes ratio (FBVR) were extracted from TruFISP and T1W Dixon images, and computed from automatic fetal body and subcutaneous fat segmentations by deep learning. Subjects were followed until hospital discharge, and obstetric interventions and neonatal adverse events were recorded. Statistical Tests: Univariate and multivariate logistic regressions for the association between TBV, FBVR, and FSF and interventions for NRFS and CANO. Fisher's exact test was used to measure the association between sonographic FGR criteria and perinatal outcomes. Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated. A P‐value <0.05 was considered statistically significant. Results: FBVR (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.2–0.76) and FSF (OR 0.95, CI 0.91–0.99) were linked with NRFS interventions. Furthermore, TBV (OR 0.69, CI 0.56–0.86) and FSF (OR 0.96, CI 0.93–0.99) were linked to CANO. The FBVR sensitivity/specificity for obstetric interventions was 85.7%/87.5%, and the TBV sensitivity/specificity for CANO was 82.35%/86.4%. The sonographic criteria sensitivity/specificity for obstetric interventions was 100%/33.3% and insignificant for CANO (P = 0.145). Data Conclusion: Reduced TBV and FBVR may be associated with higher rates of obstetric interventions for NRFS and CANO. Evidence Level: 2 Technical Efficacy: Stage 5 [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions The IMPACT BCN trial—a parallel‐group randomized clinical trial where 1221 pregnant women at high risk for small‐for‐gestational age (SGA) newborns were randomly allocated at 19‐ to 23‐week gestation into three groups: Mediterranean diet, Mindfulness‐based Stress reduction or non‐intervention—has demonstrated a positive effect of Mediterranean diet and Stress reduction in the prevention of SGA. However, the mechanism of action of these interventions remains still unclear. The aim of this study is to investigate the effect of Mediterranean diet and Stress reduction on placental volume and perfusion.Participants in the Mediterranean diet group received monthly individual and group educational sessions, and free provision of extra‐virgin olive oil and walnuts. Women in the Stress reduction group underwent an 8‐week Stress reduction program adapted for pregnancy, consisting of weekly 2.5‐h and one full‐day sessions. Non‐intervention group was based on usual care. Placental volume and perfusion were assessed in a subgroup of randomly selected women (n = 165) using magnetic resonance (MR) at 36‐week gestation. Small placental volume was defined as MR estimated volume <10th centile. Perfusion was assessed by intravoxel incoherent motion.While mean MR placental volume was similar among the study groups, both interventions were associated with a lower prevalence of small placental volume (3.9% Mediterranean diet and 5% stress reduction vs. 17% non‐intervention; p = 0.03 and p = 0.04, respectively). Logistic regression showed that small placental volume was significantly associated with higher risk of SGA in both study groups (OR 7.48 [1.99–28.09] in Mediterranean diet and 20.44 [5.13–81.4] in Stress reduction). Mediation analysis showed that the effect of Mediterranean diet on SGA can be decomposed by a direct effect and an indirect effect (56.6%) mediated by a small placental volume. Similarly, the effect of Stress reduction on SGA is partially mediated (45.3%) by a small placental volume. Results on placental intravoxel incoherent motion perfusion fraction and diffusion coefficient were similar among the study groups.Structured interventions during pregnancy based on Mediterranean diet or Stress reduction are associated with a lower proportion of small placentas, which is consistent with the previously observed beneficial effects of these interventions on fetal growth. [ABSTRACT FROM AUTHOR]

Objective Oligohydramnios (defined as amniotic fluid volume < 5 cm or deepest vertical pocket < 2 cm) is regarded as an ominous finding on prenatal ultrasound. Amniotic fluid, however, is not static, and to date, there have been no studies comparing perinatal outcomes in patients who are diagnosed with oligohydramnios that resolves and those who have persistent oligohydramnios. Study Design This is a secondary analysis of a National Institutes of Health–funded retrospective cohort study of singleton gestations delivered at a tertiary care hospital between 2002 and 2013 with mild hypertensive disorders and/or fetal growth restriction (FGR). Maternal characteristics, delivery, and neonatal information were abstracted by trained research nurses. Patients with a diagnosis of oligohydramnios were identified, and those with resolved versus persistent oligohydramnios at the time of delivery were compared. The primary outcome was a composite of neonatal resuscitation at delivery: administration of oxygen, bag–mask ventilation, continuous positive airway pressure, intubation, chest compression, or cardiac medication administration. Secondary outcomes included FGR, timing, and mode of delivery. Results Of 527 women meeting study criteria, 42 had oligohydramnios that resolved prior to delivery, whereas 485 had persistent oligohydramnios. There were no significant differences in patient demographics between groups. The gestational age at diagnosis was significantly lower for patients with resolved versus persistent oligohydramnios (median: 33.0 [interquartile range, IQR: 29.1–35.9] vs. 38.0 [IQR: 36.4–39.3], p < 0.001). There was not a substantial difference in rate of neonatal resuscitation (41 vs. 32%, p = 0.31). Patients with resolved oligohydramnios were more likely to have developed FGR than those with persistent oligohydramnios (55 vs. 36%, p < 0.02). There were no significant differences for gestational age at delivery, birth weight, or neonatal intensive care unit admission. Conclusion Patients whose oligohydramnios resolved were diagnosed earlier yet had similar rates of neonatal resuscitation but higher rates of FGR than those who had persistent oligohydramnios. Key Points When diagnosed earlier in pregnancy, oligohydramnios was more likely to resolve prenatally. Patients who were diagnosed with oligohydramnios earlier in pregnancy had higher rates of FGR. There were no differences in the rates of the composite outcome of need for neonatal resuscitation when comparing those with resolved versus those with persistent oligohydramnios. No differences in composite neonatal morbidity were noted between those with resolved versus persistent oligohydramnios. [ABSTRACT FROM AUTHOR]

Maternal Zika virus (ZIKV) infection during pregnancy has been associated with severe intrauterine growth restriction (IUGR), placental damage, metabolism disturbances, and newborn neurological abnormalities. Here, we investigated the impact of maternal ZIKV infection on placental nutrient transporters and nutrient‐sensitive pathways. Immunocompetent (C57BL/6) mice were injected with Low (103 PFU‐ZIKVPE243) or High (5 × 107 PFU‐ZIKVPE243) ZIKV titers at gestational day (GD) 12.5, and tissue was collected at GD18.5 (term). Fetal–placental growth was impaired in male fetuses, which exhibited higher placental expression of the ZIKV infective marker, eukaryotic translation initiation factor 2 (eIF2α), but lower levels of phospho‐eIF2α. There were no differences in fetal–placental growth in female fetuses, which exhibited no significant alterations in placental ZIKV infective markers. Furthermore, ZIKV promoted increased expression of glucose transporter type 1 (Slc2a1/Glut1) and decreased levels of glucose‐6‐phosphate in female placentae, with no differences in amino acid transport potential. In contrast, ZIKV did not impact glucose transporters in male placentae but downregulated sodium‐coupled neutral amino acid 2 (Snat2) transporter expression. We also observed sex‐dependent differences in the hexosamine biosynthesis pathway (HBP) and O‐GlcNAcylation in ZIKV‐infected pregnancies, showing that ZIKV can disturb placental nutrient sensing. Our findings highlight molecular alterations in the placenta caused by maternal ZIKV infection, shedding light on nutrient transport, sensing, and availability. Our results also suggest that female and male placentae employ distinct coping mechanisms in response to ZIKV‐induced metabolic changes, providing insights into therapeutic approaches for congenital Zika syndrome. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To investigate the association between infant mortality and birth weight using estimated fetal weight (EFW) versus birth‐weight charts, by gestational age (GA).This nationwide population‐based study used data from the Finnish Medical Birth Register from 2006 to 2016 on non‐malformed singleton live births at 24–41+6 weeks of gestation (N = 563 630). The outcome was death in the first year of life. Mortality risks by birth‐weight z score, defined as a continuous variable using Maršál's EFW and Sankilampi's birth‐weight charts, were assessed using generalized additive models by GA (24–27+6, 28–31+6, 32–36+6, 37–38+6, 39–41+6 weeks). We calculated z score thresholds associated with a two‐ and three‐fold increased risk of infant death compared with newborns with a birth weight between 0 and 0.675 standard deviations.The z score thresholds (with corresponding centiles in parentheses) associated with a two‐fold increase in infant mortality were: −3.43 (<0.1) at 24–27+6 weeks, −3.46 (<0.1) at 28–31+6 weeks, −1.29 (9.9) at 32–36+6 weeks, −1.18 (11.9) at 37–38+6 weeks, and − 1.34 (9.0) at 39–41+6 weeks according to the EFW chart. These values were − 2.43 (0.8), −2.62 (0.4), −1.34 (9.0), −1.37 (8.5), and − 1.43 (7.6) according to the birth‐weight chart.The association between birth weight and infant mortality varies by GA whichever chart is used, suggesting that different thresholds for the screening of growth anomalies could be used across GA to identify high‐risk newborns. [ABSTRACT FROM AUTHOR]

Placental macrophages, which include maternal decidual macrophages and fetal Hofbauer cells, display a high degree of phenotypical and functional plasticity. This provides these macrophages with a key role in immunologically driven events in pregnancy like host defense, establishing and maintaining maternalfetal tolerance. Moreover, placental macrophages have an important role in placental development, including implantation of the conceptus and remodeling of the intrauterine vasculature. To facilitate these processes, it is crucial that placental macrophages adapt accordingly to the needs of each phase of pregnancy. Dysregulated functionalities of placental macrophages are related to placental malfunctioning and have been associated with several adverse pregnancy outcomes. Although fetal growth restriction is specifically associated with placental insufficiency, knowledge on the role of macrophages in fetal growth restriction remains limited. This review provides an overview of the distinct functionalities of decidual macrophages and Hofbauer cells in each trimester of a healthy pregnancy and aims to elucidate the mechanisms by which placental macrophages could be involved in the pathogenesis of fetal growth restriction. Additionally, potential immune targeted therapies for fetal growth restriction are discussed. [ABSTRACT FROM AUTHOR]

Nutrient sensing and adaptation in the placenta are essential for pregnancy viability and proper fetal growth. Our recent study demonstrated that the placenta adapts to nutrient insufficiency through mechanistic target of rapamycin (mTOR) inhibition-mediated trophoblast differentiation toward syncytiotrophoblasts (STBs), a highly specialized multinucleated trophoblast subtype mediating extensive maternal-fetal interactions. However, the underlying mechanism remains elusive. Here, we unravel the indispensable role of the mTORC1 downstream transcriptional factor TFEB in STB formation both in vitro and in vivo. TFEB deficiency significantly impaired STB differentiation in human trophoblasts and placenta organoids. Consistently, systemic or trophoblast-specific deletion of Tfeb compromised STB formation and placental vascular construction, leading to severe embryonic lethality. Mechanistically, TFEB conferred direct transcriptional activation of the fusogen ERVFRD-1 in human trophoblasts and thereby promoted STB formation, independent of its canonical function as a master regulator of the autophagy-lysosomal pathway. Moreover, we demonstrated that TFEB directed the trophoblast syncytialization response driven by mTOR complex 1 (mTORC1) signaling. TFEB expression positively correlated with the reinforced trophoblast syncytialization in human fetal growth-restricted placentas exhibiting suppressed mTORC1 activity. Our findings substantiate that the TFEB-fusogen axis ensures proper STB formation during placenta development and under nutrient stress, shedding light on TFEB as a mechanistic link between nutrient-sensing machinery and trophoblast differentiation. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies. Methods: This is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used. Results: 466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks. Conclusion: A high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended. [ABSTRACT FROM AUTHOR]

Introduction: To determine a cut-off value for systemic immune-inflammation index (SII) (neutrophil × platelet/lymphocyte) in the prediction of fetal growth restriction (FGR). Materials and methods: This case–control study was conducted retrospectively at the Obstetrics-Gynecology and Perinatology Clinics of Etlik Zubeyde Hanim Women's Health Education and Training Hospital. Singleton pregnant women with late-onset FGR who were followed up in outpatient clinics or hospitalized and whose pregnancy resulted at our hospital were included in the study group (group I). Healthy early and full-term singleton pregnant women with spontaneous labor who were followed up in the same hospital and whose pregnancy resulted at the same hospital were included in the control group (group II). Receiver-operating characteristic curves were used to assess the performance of SII value in predicting FGR. Results: We recruited 79 cases (pregnant with late-onset fetal growth restriction) and 79 controls (healthy pregnant), matched for age, body mass index, and parity. ΔSII was statistically significantly higher in the pregnant with late-onset FGR compared with healthy pregnant (123 vs − 65; p = 0.039). The values in ROC curves with the best balance of sensitivity/specificity were > 152 109/L (49% sensitivity, 70% specificity) and > 586 109/L (27% sensitivity, 90% specificity) for late-onset FGR. Discussion: Higher ΔSII levels in maternal blood indicate an inflammatory process causing FGR. The cut-off value for ΔSII (> 586 109/L) at 90% specificity can be used as a screening test. In the presence of ΔSII levels > 586 109/L (27% sensitivity and 90% specificity), the physicians should be more cautious about risk for FGR. Therefore, pregnant women at risk for FGR should be checked more frequently and monitored closely. However, further studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to compare maternal and neonatal outcomes when the diagnosis of FGR was based on isolated abdominal circumference < 10th percentile for gestational age (GA) (iAC group) versus overall estimated fetal weight < 10th percentile (EFW group). Methods: This was a retrospective cohort study of singleton gestations who underwent growth ultrasounds and delivered at a single health system from 1/1/19–9/4/20. The study group was comprised of patients with AC < 10th percentile and EFW ≥ than the 10th percentile (iAC group). The control group included patients with overall EFW < 10th percentile (EFW group). Outcomes evaluated included GA at delivery, mode of delivery, fetal and neonatal outcomes. Data was analyzed using Mann Whitney U, X2, and Fisher exact tests with significance defined as p < 0.05. Results: 635 women met the inclusion criteria, 259 women in the iAC group and 376 women in the EFW group. The iAC group was noted to have a later GA at diagnosis and delivery. iAC was associated with lower rates of preterm birth (PTB), NICU admission, SGA at delivery and umbilical artery cord gas < 7.0. Conclusion: Using iAC as a definition of FGR increased the number of FGR cases by 1.69-fold over EFW criteria alone. However, obstetrical and neonatal outcomes for the iAC group appear to be significantly better than those in the EFW group, with low rates of PTB, NICU admission, and umbilical artery cord gas < 7.0. [ABSTRACT FROM AUTHOR]

Abnormal fetal growth, i.e., intrauterine growth restriction (IUGR) or fetal growth restriction (FGR) and fetal overgrowth, is associated with increased perinatal morbidity and mortality and is strongly linked to the development of metabolic and cardiovascular disease in childhood and later in life. Emerging evidence suggests that changes in placental amino acid transport may contribute to abnormal fetal growth. This review is focused on amino acid transport in the human placenta, however, relevant animal models will be discussed to add mechanistic insights. At least 25 distinct amino acid transporters with different characteristics and substrate preferences have been identified in the human placenta. Of these, System A, transporting neutral nonessential amino acids, and System L, mediating the transport of essential amino acids, have been studied in some detail. Importantly, decreased placental Systems A and L transporter activity is strongly associated with IUGR and increased placental activity of these two amino acid transporters has been linked to fetal overgrowth in human pregnancy. An array of factors in the maternal circulation, including insulin, IGF‐1, and adiponectin, and placental signaling pathways such as mTOR, have been identified as key regulators of placental Systems A and L. Studies using trophoblast‐specific gene targeting in mice have provided compelling evidence that changes in placental Systems A and L are mechanistically linked to altered fetal growth. It is possible that targeting specific placental amino acid transporters or their upstream regulators represents a novel intervention to alleviate the short‐ and long‐term consequences of abnormal fetal growth in the future. [ABSTRACT FROM AUTHOR]

Objective Design Setting Population Methods Main Outcome Measures Results Conclusions To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies.Cross‐sectional survey.International.Clinicians involved in the management of MCDA twin pregnancies with sFGR.A structured, self‐administered survey.Clinical practices and attitudes to diagnostic criteria and management strategies.Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter‐twin EFW discordance of >25% for the diagnosis of sFGR. For early‐onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early‐onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early‐onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early‐onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide.There is significant variation in clinician practices and attitudes towards the management of early‐onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high‐level evidence to guide management. [ABSTRACT FROM AUTHOR]

Objective: To assess the association of the umbilicocerebral ratio (UCR) with adverse perinatal outcome in late preterm small‐for‐gestational age (SGA) fetuses and to investigate the effect on perinatal outcomes of immediate delivery. Design: Multicentre cohort study with nested randomised controlled trial (RCT). Setting: Nineteen secondary and tertiary care centres. Population: Singleton SGA pregnancies (estimated fetal weight [EFW] or fetal abdominal circumference [FAC] <10th centile) from 32 to 36+6 weeks. Methods: Women were classified: (1) RCT‐eligible: abnormal UCR twice consecutive and EFW below the 3rd centile at/or below 35 weeks or below the 10th centile at 36 weeks; (2) abnormal UCR once or intermittent; (3) never abnormal UCR. Consenting RCT‐eligible patients were randomised for immediate delivery from 34 weeks or expectant management until 37 weeks. Main outcome measures: A composite adverse perinatal outcome (CAPO), defined as perinatal death, birth asphyxia or major neonatal morbidity. Results: The cohort consisted of 690 women. The study was halted prematurely for low RCT‐inclusion rates (n = 40). In the RCT‐eligible group, gestational age at delivery, birthweight and birthweight multiple of the median (MoM) (0.66, 95% confidence interval [CI] 0.59–0.72) were significantly lower and the CAPO (n = 50, 44%, p < 0.05) was more frequent. Among patients randomised for immediate delivery there was a near‐significant lower birthweight (p = 0.05) and higher CAPO (p = 0.07). EFW MoM, pre‐eclampsia, gestational hypertension and Doppler classification were independently associated with the CAPO (area under the curve 0.71, 95% CI 0.67–0.76). Conclusions: Perinatal risk was effectively identified by low EFW MoM and UCR. Early delivery of SGA fetuses with an abnormal UCR at 34–36 weeks should only be performed in the context of clinical trials. [ABSTRACT FROM AUTHOR]

Objective: To assess the utility of placental growth factor (PlGF) levels and the soluble fms‐like tyrosine kinase‐1/placental growth factor (sFlt‐1/PlGF) ratio to predict preterm birth (PTB) for infants with fetal growth restriction (FGR) and those appropriate for gestational age (AGA). Design: Prospective, observational cohort study. Setting: Tertiary maternity hospital in Australia. Population: There were 320 singleton pregnancies: 141 (44.1%) AGA, 83 (25.9%) early FGR (<32+0 weeks) and 109 (30.0%) late FGR (≥32+0 weeks). Methods: Maternal serum PlGF and sFlt‐1/PlGF ratio were measured at 4‐weekly intervals from recruitment to delivery. Low maternal PlGF levels and elevated sFlt‐1/PlGF ratio were defined as <100 ng/L and >5.78 if <28 weeks and >38 if ≥28 weeks respectively. Cox proportional hazards models were used. The analysis period was defined as the time from the first measurement of PlGF and sFlt‐1/PlGF ratio to the time of birth or censoring. Main outcome measures: The primary study outcome was overall PTB. The relative risks (RR) of birth within 1, 2 and 3 weeks and for medically indicated and spontaneous PTB were also ascertained. Results: The early FGR cohort had lower median PlGF levels (54 versus 229 ng/L, p < 0.001) and higher median sFlt‐1 levels (2774 ng/L versus 2096 ng/L, p < 0.001) and sFlt‐1/PlGF ratio higher (35 versus 10, p < 0.001). Both PlGF <100 ng/L and elevated sFlt‐1/PlGF ratio were strongly predictive for PTB as well as PTB within 1, 2 and 3 weeks of diagnosis. For both FGR and AGA groups, PlGF <100 ng/L or raised sFlt‐1/PlGF ratio were strongly associated with increased risk for medically indicated PTB. The highest RR was seen in the FGR cohort when PlGF was <100 ng/L (RR 35.20, 95% CI 11.48–175.46). Conclusions: Low maternal PlGF levels and elevated sFlt‐1/PlGF ratio are potentially useful to predict PTB in both FGR and AGA pregnancies. [ABSTRACT FROM AUTHOR]

Objective: To compare obstetric outcomes between women with β‐thalassemia/hemoglobin E (β‐thal/HbE) disease and those of low‐risk pregnancies, and also between the two subgroups, β‐thal0/HbE and β‐thal+/HbE disease. Methods: A retrospective cohort study was undertaken on pregnant women with β‐thal/HbE disease and low‐risk pregnancies, which were randomly selected with a case‐to‐control ratio of 1:10. Results: Pregnancies with β‐thal/HbE disease were identified in 0.19% of 59 152 pregnancies, including 104 women in the study group and 1040 women in the control group. The mean gestational age and mean birth weight were significantly lower in the study group. The prevalence of fetal growth restriction, preterm birth and low birth weight were significantly increased in the study group based on both univariate and multivariate analysis. The impacts were more striking in the β‐thal0/HbE subgroup than in the β‐thal+/HbE subgroup. The cesarean rate was significantly higher in the study group. No maternal death or serious complication was found in this cohort. Conclusion: Based on this cohort, the largest ever published, β‐thal/HbE disease is significantly associated with increased incidence of fetal growth restriction, preterm birth and low birth weight. The impacts were more pronounced in the β‐thal0/HbE subgroup. Pregnancy may be relatively safer for women with β‐thal/HbE disease. Synopsis: β‐thal/HbE disease is associated with increased incidence of risk of fetal growth restriction and preterm birth. The adverse impact appears to be more pronounced with β‐thal0/HbE disease. [ABSTRACT FROM AUTHOR]

Background: Prematurity is considered to be the leading cause of death in children under 5 years of age, with one child dying every 2 s. Smoking is known to be one of the factors associated with prematurity, with both immediate and late consequences. However, it is difficult to obtain concrete data on the relationship between smoking and spontaneous preterm birth. Objective: The aim of this study was to evaluate the influence of active and passive smoking on spontaneous preterm birth. Methods: This was a multicenter, cross‐sectional complementary study that included data on preterm births in 20 maternity hospitals in Brazil between 2011 and 2012. The relationship between smoking category (people who smoke [PWS]; people who smoke indirectly [PWSI]; and people who do not smoke [PWDNS]) and sociodemographic characteristics, birth, and neonatal data was assessed. Statistical analysis was performed using frequencies, percentages, the χ2 test, and stepwise comparisons, with a significance level of 5%. Results: The original study included 5295 pregnant participants and their preterm infants. There were 1491 spontaneous preterm births (SPBs); 1191 preterm rupture of membranes; 1468 therapeutic preterm births; and 1146 term births. The proportion of women who were PWS during pregnancy was 13.5%, and 31.6% were PWSI. Pregnant individuals who smoked and who smoked indirectly had a higher incidence of SPBs (61.2%) compared with PWDNS (48.4%; P < 0.0001); however, multivariate analysis did not confirm causality. Conclusions: This study did not confirm that smoking during pregnancy increases the risk of SPB. PWSI also did not have an increased incidence of spontaneous preterm birth or adverse neonatal outcomes. Synopsis: Active and passive smoking during pregnancy are associated with, but do not directly cause, spontaneous preterm birth.. [ABSTRACT FROM AUTHOR]