Search

Accidental exposure to high-dose radiation while pregnant has shown significant negative effects on the developing fetus. One fetal organ which has been studied is the placenta. The placenta performs all essential functions for fetal development, including nutrition, respiration, waste excretion, endocrine communication, and immunological functions. Improper placental development can lead to complications during pregnancy, as well as the occurrence of intrauterine growth-restricted (IUGR) offspring. IUGR is one of the leading indicators of fetal programming, classified as an improper uterine environment leading to the predisposition of diseases within the offspring. With numerous studies examining fetal programming, there remains a significant gap in understanding the placenta's role in irradiation-induced fetal programming. This review aims to synthesize current knowledge on how irradiation affects placental function to guide future research directions. This review provides a comprehensive overview of placental biology, including its development, structure, and function, and summarizes the placenta's role in fetal programming, with a focus on the impact of radiation on placental biology. Taken together, this review demonstrates that fetal radiation exposure causes placental degradation and immune function dysregulation. Given the placenta's crucial role in fetal development, understanding its impact on irradiation-induced IUGR is essential. [ABSTRACT FROM AUTHOR]

Controllable growth of copper nanostructures has attracted great interest due to their academic and commercial values. As compared to nanostructures, micro/nanoscale composite structures with more surface area available for high-efficiency heat transfer are preferable. Here, we report growth restriction of copper nanocones at the groove's bottom and adjacent regions of finned heat sinks as groove width is below 0.4 mm and groove depth is above 3 mm, which is ascribed to hydrogen bubbles' blockage. This finding will trigger more thinking about how to grow metal nanostructures in confined microenvironments, which are the matter basis for developing high-performance chip coolers. [ABSTRACT FROM AUTHOR]

• Obesity is a major public health issue in pregnancy. • There is a direct correlation between the severity of obesity and perinatal morbidity. • Gestational weight gain is a key parameter to address during pregnancy. • The IOM recommendations appear too permissive, and new standards should be proposed. In 2009, the Institute of Medicine (IOM) issued recommendations for gestational weight gain (GWG) based on body mass index (BMI). Several studies have challenged those recommendations for women with obesity, considering them too liberal and advising more limited weight gain – or even weight loss – during pregnancy to improve maternal and neonatal outcomes. Our aim was to study how gestational weight gain in women with obesity impacted maternal and fetal complications in the Belgian population. We did this by comparing the results from two groups of patients with obesity: those who met the 2009 IOM standards and those who satisfied the stricter recommendations suggested by other authors. This is a retrospective cohort study using data collected at the Centre d'Epidémiologie Périnatale (CEpiP) from obese (BMI ≥ 30 kg/m2) pregnant women with live singleton deliveries between 2010 and 2019 in Wallonia-Brussels Federation (n = 65,314). Compared to obese patients whose GWG satisfied the IOM standards, those with GWG meeting the stricter recommendations had lower rates of gestational hypertension (7.1 % vs. 10.1 %; p = 0.0059), cesarean section (22.1 % vs. 26.3 %; p = 0.0074), and macrosomia (12.0 % vs. 17.7 %; p < 0.0001). There was no significant difference in the rate of preterm delivery (6.9 % vs 5.8 %; p = 0.12) or small-for-gestational-age births (7.2 % vs. 6.2 %; p = 0.16). Gestational weight gain below that currently recommended by the IOM appears beneficial to the health of mothers with obesity and their children. These data, from our population, further challenge the standards proposed since 2009. [ABSTRACT FROM AUTHOR]

Introduction: Early life growth restriction significantly increases the risk of adulthood physical inactivity and thereby chronic disease incidence. Improvements in motor skill acquisition could result in greater physical activity engagement in the growth-restricted population, thus reducing chronic disease risk. The purpose of this study was to implement an early life motor training intervention to improve physical activity engagement in control and growth-restricted mice. Methods: Mice were growth restricted in early life utilizing a validated nutritive model or remained fully nourished in early life as a control. All mice were tested throughout early life for various components of motor skill acquisition. On postnatal day 10,mice were randomly assigned to engage in an early life motor skill intervention daily until postnatal day 21 or remained as a sedentary control. All mice were given access to an in-cage running wheel from postnatal days 45-70. Results: Growth-restricted group (PGR) mice had impaired trunk and postural control, coordination/vestibular development, and hindlimb strength in early life compared with control mice. There were no differences in wheel running behavior between the trained and sedentary mice, although control mice ran at a faster average speed compared with PGR mice. Control female mice ran more than PGR female mice during the week 2 dark cycle. Conclusions: Early life growth restriction reduced motor skill attainment throughout early life, which may be associated with reduced ability to engage in physical activity in adulthood. The early life motor skill intervention did not elicit changes in body weight or physical activity engagement in control or PGR mice, indicating that a more intense/different intervention specifically targeting skeletal muscle may be necessary to counteract the detrimental effects of early life growth restriction. [ABSTRACT FROM AUTHOR]

Abstract Background To evaluate the effects of local radiotherapy (RT) on growth, we evaluated the chronological growth profiles and vertebral features of children with high-risk neuroblastoma. Methods Thirty-eight children who received local photon or proton beam therapy to the abdomen or retroperitoneum between January 2014 and September 2019 were included. Simple radiography of the thoracolumbar spine was performed before and every year after RT. The height and vertical length of the irradiated vertebral bodies (VBs) compared with the unirradiated VBs (vertebral body ratio, VBR) were analyzed using the linear mixed model. Shape feature analysis was performed to compare the irradiated and unirradiated vertebrae. Results The follow-up was a median of 53.5 months (range, 21–81 months) after RT. A decline in height z-scores was mainly found in the early phase after treatment. In the linear mixed model with height, the initial height (fixed, p

Abstract Postnatal growth restriction (PGR) can increase the risk of cardiovascular disease (CVD) potentially due to impairments in oxidative phosphorylation (OxPhos) within cardiomyocyte mitochondria. The purpose of this investigation was to determine if PGR impairs cardiac metabolism, specifically OxPhos. FVB (Friend Virus B‐type) mice were fed a normal‐protein (NP: 20% protein), or low‐protein (LP: 8% protein) isocaloric diet 2 weeks before mating. LP dams produce ∼20% less milk, and pups nursed by LP dams experience reduced growth into adulthood as compared to pups nursed by NP dams. At birth (PN1), pups born to dams fed the NP diet were transferred to LP dams (PGR group) or a different NP dam (control group: CON). At weaning (PN21), all mice were fed the NP diet. At PN22 and PN80, mitochondria were isolated for respirometry (oxygen consumption rate, JO2) and fluorimetry (reactive oxygen species emission, JH2O2) analysis measured as baseline respiration (LEAK) and with saturating ADP (OxPhos). Western blotting at PN22 and PN80 determined protein abundance of uncoupling protein 3, peroxiredoxin‐6, voltage‐dependent anion channel and adenine nucleotide translocator 1 to provide further insight into mitochondrial function. ANOVAs with the main effects of diet, sex and age with α‐level of 0.05 was set a priori. Overall, PGR (7.8 ± 1.1) had significant (P = 0.01) reductions in respiratory control in complex I when compared to CON (8.9 ± 1.0). In general, our results show that PGR led to higher electron leakage in the form of free radical production and reactive oxygen species emission. No significant diet effects were found in protein abundance. The observed reduced respiratory control and increased ROS emission in PGR mice may increase risk for CVD in mice.

Background: To evaluate the effects of local radiotherapy (RT) on growth, we evaluated the chronological growth profiles and vertebral features of children with high-risk neuroblastoma. Methods: Thirty-eight children who received local photon or proton beam therapy to the abdomen or retroperitoneum between January 2014 and September 2019 were included. Simple radiography of the thoracolumbar spine was performed before and every year after RT. The height and vertical length of the irradiated vertebral bodies (VBs) compared with the unirradiated VBs (vertebral body ratio, VBR) were analyzed using the linear mixed model. Shape feature analysis was performed to compare the irradiated and unirradiated vertebrae. Results: The follow-up was a median of 53.5 months (range, 21–81 months) after RT. A decline in height z-scores was mainly found in the early phase after treatment. In the linear mixed model with height, the initial height (fixed, p < 0.001), sex (time interaction, p = 0.008), endocrine dysfunction (time interaction, 0.019), and age at diagnosis (fixed and time interaction, both p = 0.002) were significant. Unlike the trend in height, the change in VBR (ΔVBR) decreased gradually (p < 0.001). The ΔVBR in the group that received more than 30 Gy decreased more than in the group that received smaller doses. In the shape feature analysis, the irradiated VBs changed to a more irregular surface that were neither round nor rectangular. Conclusion: The irradiated VBs in children were gradually restricted compared to the unirradiated VBs in long-term follow-up, and higher RT doses were significantly affected. Radiation-induced irregular features of VBs were observed. [ABSTRACT FROM AUTHOR]

Objective Delta-like homolog 1 (DLK1) is a growth factor that is reduced in maternal sera in pregnancies with small for gestational age neonates. We sought to determine if DLK1 is associated with stillbirth (SB), with and without placental insufficiency. Study Design A nested case-control study was performed using maternal sera from a multicenter case-control study of SB and live birth (LB). SB and LB were stratified as placental insufficiency cases (small for gestational age <5% or circulatory lesions on placental histopathology) or normal placenta controls (appropriate for gestational age and no circulatory lesions). Enzyme-linked immunosorbent assay (ELISA) was used to measure DLK1. The mean difference in DLK1 was compared on the log scale in an adjusted linear regression model with pairwise differences, stratified by term/preterm deliveries among DLK1 results in the quantifiable range. In exploratory analysis, geometric means were compared among all data and the proportion of "low DLK1" (less than the median value for gestational age) was compared between groups and modeled using linear and logistic regression, respectively. Results Overall, 234 SB and 234 LB were analyzed; 246 DLK1 values were quantifiable within the standard curve. Pairwise comparisons of case and control DLK1 geometric means showed no significant differences between groups. In exploratory analysis of all data, adjusted analysis revealed a significant difference for the LB comparison only (SB: 71.9 vs. 99.1 pg/mL, p = 0.097; LB: 37.6 vs. 98.1 pg/mL, p = 0.005). In exploratory analysis of "low DLK1," there was a significant difference between the odds ratio of having "low DLK1" between preterm cases and controls for both SB and LB. There were no significant differences in geometric means nor "low DLK1" between SB and LB. Conclusion In exploratory analysis, more placental insufficiency cases in preterm SB and LB had "low DLK1." However, low DLK1 levels were not associated with SB. Key Points Maternally circulating DLK1 is correlated with placental insufficiency. Maternally circulating DLK1 is not correlated with SB. DLK1 is a promising marker for placental insufficiency. [ABSTRACT FROM AUTHOR]

Objectives: First, to evaluate the predictive performance for preterm growth‐related neonatal morbidity of a high soluble fms‐like tyrosine kinase‐1 (sFlt‐1)/placental growth factor (PlGF) ratio or low PlGF at midgestation and, second, to compare the performance of a high sFlt‐1/PlGF ratio or low PlGF with that of the competing‐risks model for small‐for‐gestational age (SGA), utilizing a combination of maternal risk factors, sonographic estimated fetal weight and uterine artery pulsatility index. Methods: This was a prospective observational study in women attending for a routine hospital visit at 19–24 weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, carrying out an ultrasound scan and measuring serum PlGF and sFlt‐1. The primary outcome was delivery < 32 and < 37 weeks' gestation of a SGA neonate with birth weight < 10th or < 3rd percentile, combined with neonatal unit (NNU) admission for ≥ 48 h or a composite of major neonatal morbidity. The detection rates in screening by PlGF < 10th percentile, sFlt‐1/PlGF ratio > 90th percentile and the competing‐risks model for SGA were estimated and then compared using McNemar's test. Results: In the study population of 40 241 women, prediction of preterm growth‐related neonatal morbidity provided by the competing‐risks model for SGA was superior to that of screening by low PlGF concentration or high sFlt‐1/PlGF ratio. For example, at a screen‐positive rate of 10.0%, as defined by the sFlt‐1/PlGF ratio > 90th percentile, the competing‐risks model predicted 70.1% (95% CI, 61.0–79.2%) of SGA < 10th percentile and 76.9% (95% CI, 67.6–86.3%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered < 32 weeks' gestation. The respective values for SGA with major neonatal morbidity were 73.8% (95% CI, 64.4–83.2%) and 77.9% (95% CI, 68.0–87.8%). These were significantly higher than the respective values of 35.1% (95% CI, 25.6–44.6%), 35.9% (95% CI, 25.3–46.5%), 38.1% (95% CI, 27.7–48.5%) and 39.7% (95% CI, 28.1–51.3%) achieved by the application of the sFlt‐1/PlGF ratio > 90th percentile (all P < 0.0001). Conclusion: At midgestation, the prediction of growth‐related neonatal morbidity by the competing‐risks model for SGA is superior to that of a high sFlt‐1/PlGF ratio or low PlGF. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

The sFlt-1/PlGF ratio is a biomarker used in the prediction, diagnosis and management of hypertensive disorders of pregnancy. In preeclampsia, there is an imbalance between angiogenic and anti-angiogenic factors, leading to decreased levels of PlGF and to increased levels of sFlt-1. An elevated sFlt-1/PlGF ratio is associated with an increased risk of developing preeclampsia within the subsequent four weeks. The aim of this article was to review the recent evidence regarding the utility of sFlt-1/PlGF ratio in fetal growth restriction, stillbirth and preterm birth. Although the clinical utility of sFlt-1, PlGF and the sFlt-1/PlGF ratio is high, and it has been known to be valuable in pregnancies complicated by preeclampsia, further research with a higher number of cases needs to be done in order to implement the biomarkers in guidelines for other issues such as fetal growth restriction, stillbirth and other adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To explore the contribution of maternal and fetal parameters in predicting the time interval between diagnosis and development of adverse events leading to delivery in singleton pregnancies complicated with fetal microsomia. Methods: Prospective study on singleton pregnancies referred to a tertiary center because of suspicion of fetal smallness in the third trimester. The study cohort included cases with fetal abdominal circumference (AC) ≤ 10th centile or estimated fetal weight ≤ 10th centile or umbilical artery pulsatitlity index ≥ 90th centile. Development of pre-eclampsia, fetal demise, and fetal deterioration diagnosed by fetal Doppler studies or fetal heart rate monitoring and leading to delivery were considered as adverse events. Maternal demographics, obstetric history, blood pressure, serum PLGF, and fetal Doppler studies were explored as predictors of the time interval between the first visit to the clinic and the diagnosis of complications. Results: In 59 women, the median incubation period from presentation to the clinic to an adverse event was 6, 2 weeks, whereas half of the pregnancies (52.5%) did not develop any adverse event. PLGF was the strongest predictor of adverse events. Both PLGF in raw values and PLGF MOM had equally good predictive ability (AUC 0.82 and 0.78 respectively). Optimal cut-off points were 177.7 pg/ml for PLGF raw values (sensitivity 83% and specificity 66.7%) and 0.277 MoM (sensitivity 76% and specificity 86.7%). On multiple Cox regression analysis, maternal systolic blood pressure, PLGF, fetal increased umbilical artery PI, and reduced CP ratio were independently associated with adverse events. Half of the pregnancies with low PLGF and only one in ten with high PLGF were delivered within two weeks after the initial visit. Conclusion: Half of the pregnancies carrying a small fetus in the third trimester will not develop maternal or fetal complications. PLGF is a strong predictor of adverse events that can be used to customize antenatal care. [ABSTRACT FROM AUTHOR]

Postnatal growth restriction (PGR) can increase the risk of cardiovascular disease (CVD) potentially due to impairments in oxidative phosphorylation (OxPhos) within cardiomyocyte mitochondria. The purpose of this investigation was to determine if PGR impairs cardiac metabolism, specifically OxPhos. FVB (Friend Virus B‐type) mice were fed a normal‐protein (NP: 20% protein), or low‐protein (LP: 8% protein) isocaloric diet 2 weeks before mating. LP dams produce ∼20% less milk, and pups nursed by LP dams experience reduced growth into adulthood as compared to pups nursed by NP dams. At birth (PN1), pups born to dams fed the NP diet were transferred to LP dams (PGR group) or a different NP dam (control group: CON). At weaning (PN21), all mice were fed the NP diet. At PN22 and PN80, mitochondria were isolated for respirometry (oxygen consumption rate, JO2${J_{{{\mathrm{O}}_{\mathrm{2}}}}}$) and fluorimetry (reactive oxygen species emission, JH2O2${J_{{{\mathrm{H}}_{\mathrm{2}}}{{\mathrm{O}}_{\mathrm{2}}}}}$) analysis measured as baseline respiration (LEAK) and with saturating ADP (OxPhos). Western blotting at PN22 and PN80 determined protein abundance of uncoupling protein 3, peroxiredoxin‐6, voltage‐dependent anion channel and adenine nucleotide translocator 1 to provide further insight into mitochondrial function. ANOVAs with the main effects of diet, sex and age with α‐level of 0.05 was set a priori. Overall, PGR (7.8 ± 1.1) had significant (P = 0.01) reductions in respiratory control in complex I when compared to CON (8.9 ± 1.0). In general, our results show that PGR led to higher electron leakage in the form of free radical production and reactive oxygen species emission. No significant diet effects were found in protein abundance. The observed reduced respiratory control and increased ROS emission in PGR mice may increase risk for CVD in mice. What is the central question of this study?Postnatal growth restriction (PGR) in early life is associated with cardiovascular disease: what are the mechanisms with regard to oxidative phosphorylation (OxPhos)?What is the main finding and its importance?PGR during development reduces cardiac metabolism through impairments in OxPhos. Our results show the PGR heart has higher electron leakage in the form of free radical production and reactive oxygen species emission. These findings are associated with an increased risk for cardiovascular disease in adulthood. Simply put, a brief period of growth restriction in early life has long‐lasting effects on cardiac metabolism in adulthood. [ABSTRACT FROM AUTHOR]

Objectives: First, to describe the distribution of biomarkers of impaired placentation in small‐for‐gestational‐age (SGA) pregnancies with neonatal morbidity; second, to examine the predictive performance for growth‐related neonatal morbidity of a high soluble fms‐like tyrosine kinase‐1 (sFlt‐1)/placental growth factor (PlGF) ratio or low PlGF; and, third, to compare the performance of a high sFlt‐1/PlGF ratio or low PlGF with that of the competing‐risks model for SGA in predicting growth‐related neonatal morbidity. Methods: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, an ultrasound scan and measurement of serum PlGF and sFlt‐1. The primary outcome was delivery within 4 weeks after assessment and at < 42 weeks' gestation of a SGA neonate with birth weight < 10th or < 3rd percentile, combined with neonatal unit (NNU) admission for ≥ 48 h or a composite of major neonatal morbidity. The detection rates in screening by PlGF < 10th percentile, sFlt‐1/PlGF ratio > 90th percentile, sFlt‐1/PlGF ratio > 38 and the competing‐risks model for SGA, using combinations of maternal risk factors and Z‐scores of estimated fetal weight (EFW) with multiples of the median values of uterine artery pulsatility index, PlGF and sFlt‐1, were estimated. The detection rates by the different methods of screening were compared using McNemar's test. Results: In the study population of 29 035 women, prediction of growth‐related neonatal morbidity at term provided by the competing‐risks model was superior to that of screening by low PlGF concentration or a high sFlt‐1/PlGF concentration ratio. For example, at a screen‐positive rate (SPR) of 13.1%, as defined by the sFlt‐1/PlGF ratio > 38, the competing‐risks model using maternal risk factors and EFW predicted 77.5% (95% CI, 71.7–83.3%) of SGA < 10th percentile and 89.3% (95% CI, 83.7–94.8%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for SGA with major neonatal morbidity were 71.4% (95% CI, 56.5–86.4%) and 90.0% (95% CI, 76.9–100%). These were significantly higher than the respective values of 41.0% (95% CI, 34.2–47.8%) (P < 0.0001), 48.8% (95% CI, 39.9–57.7%) (P < 0.0001), 37.1% (95% CI, 21.1–53.2%) (P = 0.003) and 55.0% (95% CI, 33.2–76.8%) (P = 0.035) achieved by the application of the sFlt‐1/PlGF ratio > 38. At a SPR of 10.0%, as defined by PlGF < 10th percentile, the competing‐risks model using maternal factors and EFW predicted 71.5% (95% CI, 65.2–77.8%) of SGA < 10th percentile and 84.3% (95% CI, 77.8–90.8%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for SGA with major neonatal morbidity were 68.6% (95% CI, 53.1–83.9%) and 85.0% (95% CI, 69.4–100%). These were significantly higher than the respective values of 36.5% (95% CI, 29.8–43.2%) (P < 0.0001), 46.3% (95% CI, 37.4–55.2%) (P < 0.0001), 37.1% (95% CI, 21.1–53.2%) (P = 0.003) and 55.0% (95% CI, 33.2–76.8%) (P = 0.021) achieved by the application of PlGF < 10th percentile. Conclusion: At 36 weeks' gestation, the prediction of growth‐related neonatal morbidity by the competing‐risks model for SGA, using maternal risk factors and EFW, is superior to that of a high sFlt‐1/PlGF ratio or low PlGF. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Assessing fetal growth constitutes a fundamental aim within the realm of prenatal care. Impaired prenatal growth increases the risk of perinatal mortality, morbidity, and poor newborn outcomes. Growth restriction increases the risk of premature birth problems, as well as the risk of poor neurodevelopmental outcomes and future non-communicable disorders such as hypertension and metabolic syndrome as adults. The objective of this systematic review is to accumulate current literature evidence to assess the patterns of serum adipokine levels among women with growth-restricted fetuses and assess their potential alterations in those high-risk pregnancies. Methods: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception until 31 March 2023. All observational studies reporting serum adipokine values among women with appropriately grown and growth-restricted fetuses were held eligible. Results: The current systematic review encompassed a total of 20 studies, incorporating a patient population of 1850 individuals. Maternal blood leptin emerged as the adipokine most investigated, as evidenced by 13 studies encompassing a collective sample size of 1081 patients, all of which explored its potential correlation with intrauterine growth restriction. Elevated levels of leptin were detected in fetuses with intrauterine growth restriction, although the observed difference did not reach statistical significance. Furthermore, regarding adiponectin, the meta-analysis conducted indicated that there were not any statistically significant differences observed in the mean values of adiponectin. The available data on the remaining three adipokines were extremely limited, making it difficult for any solid conclusions to be extracted. Conclusions: Though limited and inconsistent, the existing data suggest that fetal growth restriction is not linked to leptin, adiponectin, visfatin, resistin, or RBP4. More substantial prospective studies are needed to comprehend the importance of established and novel adipokines. [ABSTRACT FROM AUTHOR]

Objectives: To compare perinatal outcomes in growth restricted Fetuses based on normal and abnormal umbilical artery doppler studies. Study Design: Prospective Cohort Study. Place and Duration of Study: This Study was conducted in Civil Hospital Karachi. Duration of the study was 6 months, from 24 November 2018 to 25 May 2019. Materials and Methods: 232 growth restricted Fetuses were divided into two equal groups, 116 with normal umbilical artery doppler studies (Group A) and 116 with abnormal umbilical artery doppler studies (Group B). Inclusion criteria were pregnant patients with age 20-35 years and excluding malformations. Doppler assessment used 3-5 MHz probe (GE PRO-V, USA) for umbilical artery and vein, noting absent/reversed flow.Follow-up included delivery, neonatal assessment, and mortality recording. Results: The mean age in our study was 28.92 ± 5.71 years, while gestational age was 33.97 ± 2.58 years. The normal umbilical artery doppler group experienced a 14.66% rate of premature deliveries compared to 52.59% in the abnormal group (p-value: 0.0001). NICU admissions were reported at 26.72% in the normal umbilical artery doppler group and notably higher at 76.72% in the abnormal group (p-value: 0.0001). A striking observation was the threefold increase in perinatal deaths within the abnormal umbilical artery doppler group (18.10%) as opposed to the normal group (7.76%) (p-value: 0.024). Conclusion: Adverse perinatal outcomes were associated with abnormal umbilical artery Doppler in Fetuses with growth restriction. Timely preventive measures should be taken to reduce perinatal morbidity and mortality.

PLAGL1 is one of a group of imprinted genes, whose altered expression causes imprinting disorders impacting growth, development, metabolism, and behavior. PLAGL1 over‐expression causes transient neonatal diabetes mellitus (TNDM type 1) and, based on murine models, under‐expression would be expected to cause growth restriction. However, only some reported individuals with upd(6)mat have growth restriction, giving rise to uncertainty about the role of PLAGL1 in human growth. Here we report three individuals investigated for growth restriction, two with upd(6)mat and one with a mosaic deletion of the paternally‐inherited allele of PLAGL1. These cases add to evidence of its involvement in pre‐ and early post‐natal human growth. [ABSTRACT FROM AUTHOR]

Objective: Cleft lip and palate are the most common congenital anomalies of the head and neck region. According to studies, 13.5% of children under 5 years of age were reported to be underweight. When compared with the global data, this ratio was found to be higher in patients with isolated cleft lip, isolated cleft palate, and cleft lip with cleft palate. This study aimed to evaluate the frequency of malnutrition in isolated Veau type 1 and type 2 cleft palate in an institutional patient group. Material and Methods: Patients with isolated Veau type 1 and type 2 cleft palate who were operated between November 2019 and February 2022 were included in the study. The age (month), height (centimeters), and weight (kilograms) of the patients were noted one day before the surgery, and Z scores were calculated for malnutrition assessment. Result: A total of 40 patients were included in this study. The mean age of the patients was 16.82±2.73 months (7-48 months). Fourteen patients were male whereas 26 patients were female. Malnutrition was not observed in nine patients. Eight patients had chronic mild malnutrition, 5 patients had chronic moderate malnutrition and 13 patients had chronic severe malnutrition. In addition, chronic mild obesity was observed in two patients, chronic moderate obesity was observed in two patients, and chronic severe obesity was observed in one patient. In total, malnutrition was observed in 65% of the patients. Conclusion: One of the most important problems in patients with cleft palate is feeding. Inadequate nutrition predisposes to malnutrition in the preoperative period. To prevent this situation, the patients should be referred for prompt professional nutritionist care and early follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Growth restriction (GR) reduces ribosome abundance and skeletal muscle mass in mice. A reduction in skeletal muscle mass increases the risk of frailty and is associated with high morbidity and mortality rates. As eccentric type exercise increases muscle mass, this investigation aimed to determine if eccentric loading of skeletal muscle via downhill running (DHR) increased muscle mass in GR mice. Methods: Mice were growth-restricted either gestational undernutrition (GUN, n = 8 litters), postnatal undernutrition (PUN, n = 8 litters), or were not restricted (CON, n = 8 litters) via a validated cross-fostering nutritive model. On postnatal day (PN) 21, allmice were weaned to a healthy diet, isolating the period of GR to early life as seen in humans. At PN45,mice were assigned to either aDHR (CON, n = 4 litters;GUN, n = 4 litters; PUN, n = 4 litters) or sedentary (SED: CON, n = 4 litters;GUN, n = 4 litters; PUN, n = 4 litters) group. Downhill running (16% decline: 18 m·min--1) was performed in 30-min bouts, three times per week, for 12 wk on a rodent treadmill. At PN129, the quadriceps femoris was dissected and evaluated for mass, myofiber size and type, and molecular markers of growth. Results: Following training, CON-DHR mice having larger cells than CON-SED, GUN-SED, PUN-SED, and PUN-DHR mice (P < 0.05). The PUN group (as compared with CON) had reduced body mass (P < 0.001), upstream binding factor abundance (P = 0.012), phosphor-mTOR (P < 0.001), and quadriceps mass (P = 0.02). The GUN and PUN groups had increased MuRF1 abundance (P < 0.001) compared with CON (P < 0.001). Conclusions: The blunted response to training suggests GR mice may have anabolic resistance when exposed to eccentric type exercise. [ABSTRACT FROM AUTHOR]

Twin gestations are associated with increased risk of pregnancy complications. However, high-quality evidence regarding the management of twin pregnancies is limited, often resulting in inconsistencies in the recommendations of various national and international professional societies. In addition, some recommendations related to the management of twin gestations are often missing from the clinical guidelines dedicated to twin pregnancies and are instead included in the practice guidelines on specific pregnancy complications (eg, preterm birth) of the same professional society. This can make it challenging for care providers to easily identify and compare recommendations for the management of twin pregnancies. This study aimed to identify, summarize, and compare the recommendations of selected professional societies from high-income countries on the management of twin pregnancies, highlighting areas of both consensus and controversy. We reviewed clinical practice guidelines of selected major professional societies that were either specific to twin pregnancies or were focused on pregnancy complications or aspects of antenatal care that may be relevant for twin pregnancies. We decided a priori to include clinical guidelines from 7 high-income countries (United States, Canada, United Kingdom, France, Germany, and Australia and New Zealand grouped together) and from 2 international societies (International Society of Ultrasound in Obstetrics and Gynecology and the International Federation of Gynecology and Obstetrics). We identified recommendations regarding the following care areas: first-trimester care, antenatal surveillance, preterm birth and other pregnancy complications (preeclampsia, fetal growth restriction, and gestational diabetes mellitus), and timing and mode of delivery. We identified 28 guidelines published by 11 professional societies from the 7 countries and 2 international societies. Thirteen of these guidelines focus on twin pregnancies, whereas the other 16 focus on specific pregnancy complications predominantly in singletons but also include some recommendations for twin pregnancies. Most of the guidelines are recent, with 15 of the 29 guidelines published over the past 3 years. We identified considerable disagreement among guidelines, primarily in 4 key areas: screening and prevention of preterm birth, using aspirin to prevent preeclampsia, defining fetal growth restriction, and the timing of delivery. In addition, there is limited guidance on several important areas, including the implications of the "vanishing twin" phenomenon, technical aspects and risks of invasive procedures, nutrition and weight gain, physical and sexual activity, the optimal growth chart to be used in twin pregnancies, the diagnosis and management of gestational diabetes mellitus, and intrapartum care.This consolidation of key recommendations across several clinical practice guidelines can assist healthcare providers in accessing and comparing recommendations on the management of twin pregnancies and identifies high-priority areas for future research based on either continued disagreement among societies or limited current evidence to guide care. [ABSTRACT FROM AUTHOR]

Grain refinement in Al-Si alloys is crucial for enhancing material castability and mechanical properties. Industrial practice involves adding inoculants, composed of TiB2 particles coated with metastable Al3Ti via adsorption, to the melt. This introduces essential free titanium for metastable phase formation and subsequent growth restriction. The superstoichiometric grain refiner Al-5Ti-1B, with 2.2 wt.% free titanium, is applied for this purpose. A peritectic reaction forms α-aluminium from this layer. However, when silicon content exceeds 3.5 wt.%, grain coarsening occurs due to silicon's detrimental effect. This study quantified silicon poisoning in an Al-10Si alloy using stoichiometric and superstoichiometric grain refiners through ASTM-standardized TP1 tests. Adding 0.02 wt.% tantalum acted as an antidote to the τ1 phase, resulting in a finer microstructure. This was attributed to the formation of a Ta-rich layer on TiB2 particles, which causes α-aluminium formation via a peritectic reaction without generating ternary phases with Ti or Si. Correlating to the increasing particle size curves from the TP1 tests, phases were collected in the filter cake with the help of a PoDFA apparatus. These could be examined more closely on the SEM and identified as needle- or plate-shaped. By using an EDS unit, the phases found were assigned to the poisoning phase and further investigated. After the addition of tantalum, a solubility of tantalum could be detected in former poisoning phases. In combination with the gradients of the grain size, it can thus be assumed that tantalum is both an antidote for silicon poisoning in the Al-Si-Ti system and can itself have a grain-refining effect in this system. [ABSTRACT FROM AUTHOR]

The gene RARRES3 uses an unexpected strategy to eliminate the parasite Toxoplasma gondii from human cells.

Most pregnancy complications originate with early placentation. MicroRNAs (miRNAs) may play an important role in placentation and function as biomarkers of future pregnancy complications. We summarized from the literature all first trimester circulating miRNAs associated with pregnancy complications of placental origin and further identified the miRNAs which have the most evidence as potential early biomarkers for pregnancy complications. We conducted a systematic review following PRISMA reporting guidelines (PROSPERO CRD42020183421). We identified all first trimester serum or plasma miRNAs associated with a pregnancy complication of placental origin (preeclampsia, intrauterine growth restriction (IUGR), gestational hypertension, preterm delivery) and the number of times those miRNAs were identified, as a measure of replication. Twenty-one studies examined 118 unique miRNAs, and 87 were associated with at least one pregnancy complication; preeclampsia was the most common. Seven miRNAs were significantly associated with a pregnancy complication in at least two studies: miR-125b, miR-518b, miR-628-3p, miR-365a-3p, miR-520h, miR-374a-5p, miR-191-5p. Few miRNAs were associated with more than one pregnancy complication: miR-518b and miR-520h with preeclampsia and gestational hypertension, miR-374a-5p and miR-191-5p with preterm birth and preeclampsia. Our systematic review suggests seven miRNAs as potential biomarkers of pregnancy complications. These complications are thought to originate with early placental defects and these miRNAs may also be biomarkers of placental pathology. First-trimester biomarkers of pregnancy complications can facilitate early detection and interventions.

Objective: Monochorionic (MC) triplet pregnancies are extremely rare and information on these pregnancies and their complications is limited. We aimed to investigate the risk of early and late pregnancy complications, perinatal outcome and the timing and methods of fetal intervention in these pregnancies. Methods: This was a multicenter retrospective cohort study of MC triamniotic (TA) triplet pregnancies managed in 21 participating centers around the world from 2007 onwards. Data on maternal age, mode of conception, diagnosis of major fetal structural anomalies or aneuploidy, gestational age (GA) at diagnosis of anomalies, twin‐to‐twin transfusion syndrome (TTTS), twin anemia–polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence and or selective fetal growth restriction (sFGR) were retrieved from patient records. Data on antenatal interventions were collected, including data on selective fetal reduction (three to two or three to one), laser surgery and any other active fetal intervention (including amniodrainage). Data on perinatal outcome were collected, including numbers of live birth, intrauterine demise, neonatal death, perinatal death and termination of fetus or pregnancy (TOP). Neonatal data such as GA at birth, birth weight, admission to neonatal intensive care unit and neonatal morbidity were also collected. Perinatal outcomes were assessed according to whether the pregnancy was managed expectantly or underwent fetal intervention. Results: Of an initial cohort of 174 MCTA triplet pregnancies, 11 underwent early TOP, three had an early miscarriage, six were lost to follow‐up and one was ongoing at the time of writing. Thus, the study cohort included 153 pregnancies, of which the majority (92.8%) were managed expectantly. The incidence of pregnancy affected by one or more fetal structural abnormality was 13.7% (21/153) and that of TRAP sequence was 5.2% (8/153). The most common antenatal complication related to chorionicity was TTTS, which affected just over one quarter (27.6%; 42/152, after removing a pregnancy with TOP < 24 weeks for fetal anomalies) of the pregnancies, followed by sFGR (16.4%; 25/152), while TAPS (spontaneous or post TTTS with or without laser treatment) occurred in only 4.6% (7/152) of pregnancies. No monochorionicity‐related antenatal complication was recorded in 49.3% (75/152) of pregnancies. Survival was apparently associated largely with the development of these complications: there was at least one survivor beyond the neonatal period in 85.1% (57/67) of pregnancies without antenatal complications, in 100% (25/25) of those complicated by sFGR and in 47.6% (20/42) of those complicated by TTTS. The overall rate of preterm birth prior to 28 weeks was 14.5% (18/124) and that prior to 32 weeks' gestation was 49.2% (61/124). Conclusion: Monochorionicity‐related complications, which can impact adversely perinatal outcome, occur in almost half of MCTA triplet pregnancies, creating a challenge with regard to counseling, surveillance and management. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

We aimed to investigate whether maternal serum kisspeptin levels are associated with late-onset FGR and contribute to adverse perinatal outcomes. In this case-control study, a total of 90 pregnant women admitted to the perinatology clinic were enrolled. Forty-five of them were diagnosed with FGR and 45 women with healthy pregnancies formed the control group. Maternal serum levels of kisspeptin 1 were compared. Median kisspeptin1 serum levels were higher in the group of patients with FGR according to gestational age than in the control group [79.4(3.9–230.2) pg/mL vs. 39.8(0.4–188.3) pg/mL; p = 0.001]. The optimal cut-off value for kisspeptin1 was 30.32 pg/mL, with a positive predictive value of 64.6% (95% CI; 0.54–0.86), negative predictive value of 87.5% (95% CI; 0.44–0.72), positive likelihood ratio 1.75 (95% CI; 1.31–2.32), negative likelihood ratio 0.14 (95% CI; 0.04–0.44). Kisspeptin1 differed significantly in late-onset FGR compared with the control group. This difference from the control group can be used to estimate late-onset FGR. • Late-onset fetal growth retardation is diagnosed at 32 weeks. • Diagnosis and prediction are difficult. • The optimal cut-off value for kisspeptin1 in the third trimester was 30.32 pg/mL. [ABSTRACT FROM AUTHOR]

Introduction: Artificial placenta therapy (APT) is an experimental life support system to improve outcomes for extremely preterm infants (EPI) less than 1,000 g by obviating the need for pulmonary gas exchange. There are presently no long-term survival data for EPI supported with APT. To address this, we aimed to maintain 95d-GA (GA; term-150d) sheep fetuses for up to 2 weeks using our APT system. Methods: Pregnant ewes (n = 6) carrying singleton fetuses underwent surgical delivery at 95d GA. Fetuses were adapted to APT and maintained for up to 2 weeks with constant monitoring of key physiological parameters and extensive timecourse blood and urine sampling, and ultrasound assessments. Six age-matched in-utero fetuses served as controls. Data were tested for group differences with ANOVA. Results: Six APT Group fetuses (100%) were adapted to APT successfully. The mean BW at the initiation of APT was 656 ± 42 g. Mean survival was 250 ± 72 h (Max 336 h) with systemic circulation and key physiological parameters maintained mostly within normal ranges. APT fetuses had active movements and urine output constantly exceeded infusion volume over the experiment. At delivery, there were no differences in BW (with edema in three APT group animals), brain weight, or femur length between APT and in-utero Control animals. Organ weights and humerus lengths were significantly reduced in the APT group (p < 0.05). Albumin, IGF-1, and phosphorus were significantly decreased in the APT group (p < 0.05). No cases of positive blood culture were detected. Conclusion: We report the longest use of APT to maintain extremely preterm fetuses to date. Fetal systemic circulation was maintained without infection, butgrowth was abnormal. This achievement suggests a need to focus not only on cardiovascular stability and health but also on the optimization of fetal growth and organ development. This new challenge will need to be overcome prior to the clinical translation of this technology. [ABSTRACT FROM AUTHOR]

Objectives: Fetal human cytomegalovirus (HCMV) infection might be involved in fetal growth restriction (FGR). Maternal serostatus and the prevalence of congenital HCMV infection are affected by various factors, such as socioeconomic status and ethnicity. Therefore, the prevalence of congenital HCMV-related FGR should be examined in each region. Methods: Seventy-eight cases of FGR with delivery between January 2012 and January 2017 at Fujita Health University Hospital were studied. Twenty-one non-FGR cases were also included as a control group. Placental sections obtained from the FGR and control cases were immunostained with two primary antibodies for detecting immediate early antigens. Results: Nineteen placental samples from FGR cases with another etiology were excluded. Finally, 59 placental samples from FGR cases of unknown etiology were included in the pathological analysis. Four of 59 (6.8%) placental samples were positive for HCMV antigen. All four positive cases were stained with the M0854 antibody, and there were no positive case with the MAB810R antibody. Neither maternal nor infantile clinical features were different between the HCMV-positive and -negative FGR cases. A pathological examination showed a hematoma in three of four cases and infarction in two of four cases. Conclusions: HCMV antigen was detected in 6.8% of placental samples obtained from FGR cases without an obvious etiology. No remarkable maternal or neonatal clinical features discriminated HCMV-related FGR from FGR due to other causes. Vasculitis and inflammation might play important roles in the pathogenesis of HCMV-related FGR.

Objective: To identify predictors of adverse perinatal outcomes in pregnancies with fetal growth restriction (FGR) using a combination of maternal clinical factors and simple ultrasound parameters and develop a risk‐scoring model for predicting adverse perinatal outcomes. Methods: A retrospective study of 370 non‐anomalous singleton pregnancies with FGR was conducted. Multivariate logistic regression analysis was used to identify factors associated with adverse perinatal outcomes; P < 0.05 was considered statistically significant. The discriminative ability was measured with the area under the receiver operating characteristic curve (AUC). A weighted score for each predictor was calculated. Results: Adverse perinatal outcomes occurred in 165/370 (44.6%) cases. There were eight predictive factors, including a history of pregnancy‐induced hypertension (PIH) (score = 1), chronic hypertension (score = 3), PIH (score = 2), maternal weight gain less than 8 kg (score = 1), early‐onset FGR (score = 1), estimated fetal weight less than 5th percentile (score = 2), amniotic fluid index less than 5 cm (score = 3), and abnormal umbilical artery Doppler (score = 2), with total scores ranging from 0 to 15. AUC for the eight‐item predictive model was 0.799 (95% confidence interval 0.753–0.845). Conclusion: A combination of maternal clinical factors and simple ultrasound parameters showed acceptable predictive performance for adverse perinatal outcomes in FGR. Synopsis: A combination of maternal clinical factors and simple ultrasound parameters has acceptable predictive performance for adverse perinatal outcomes in fetal growth restriction. [ABSTRACT FROM AUTHOR]

Background. This study aims to describe the omphalocele, hypospadias, bifid scrotum and micropenis association characteristics, along with the care, prenatal diagnosis strategies and postnatal outcomes. We also present a case with this unusual association of malformations in a fetus with a normal male karyotype. Methodology. For this study, we present a case with detailed imaging and follow-up investigations before and after birth. Also, we searched the literature regarding the management of this complex malformation, and we present the review results. Results. According to literature, the following syndromes were linked to the spectrum of omphalocele-hypospadias: trisomy 13, trisomy 18, trisomy 21, 45X, 47XXY and 47XXX, Beckwith-Wiedemann syndrome, and 2q22.1q22.3 deletion. According to our complex investigations, the omphalocele, bifid scrotum, hypospadias and micropenis, in the case of our patient, were isolated, despite literature findings. In the absence of associated major structural or genetic abnormalities, the management was conservative, with a good outcome. Conclusions. Structural anomalies can often appear alone, spontaneously or in association with other structural anomalies as part of syndromes. According to the detailed prenatal and postnatal evaluation, micropenis-hypospadias and omphalocele associations were isolated in our case, despite the literature findings. Fetal growth and well-being should be monitored, as intrauterine fetal growth restriction may occur. [ABSTRACT FROM AUTHOR]

Objective This study aimed to evaluate the association of induction method on delivery mode in pregnancies complicated by oligohydramnios with and without fetal growth restriction (FGR). Study Design This was a secondary analysis of a National Institutes of Health funded retrospective cohort study of singleton deliveries at a tertiary-care hospital between 2002 and 2013 with diabetes, mild hypertension, and/or FGR. Chart abstraction was performed by trained research nurses. Patients with a diagnosis of fetal oligohydramnios with and without FGR were identified. Our analytic cohort was further stratified into three groups per initial induction agent: prostaglandins (PGEs) alone, PGE plus mechanical ripening, or oxytocin only. Primary outcome was mode of delivery. Secondary outcomes included indications for cesarean delivery and neonatal morbidity. Results Out of 4,929 patients in the original database, 546 subjects with fetal oligohydramnios were identified; of these, 270 were induced and included for analysis. Outcomes were compared between 171 patients who had fetuses with isolated oligohydramnios and 99 patients who had fetuses with oligohydramnios and FGR. There were no significant differences in demographic characteristics between the groups. Patients with fetuses with isolated oligohydramnios had similar rates of spontaneous vaginal delivery (SVD) when PGEs were used (n = 44/79, 55.7% PGE alone, n = 44/76, 57.9% PGE with mechanical ripening) and when they were not used (n = 5/13, 38.5% oxytocin alone; p = 0.43). Similarly, the majority of patients in both cohorts underwent SVD regardless of induction method (n = 30/44, 68.2% PGE alone, n = 30/44, 68.2% PGE with mechanical ripening, and n = 6/10, 60% oxytocin alone; p = 0.90). There was no significant difference in composite neonatal morbidity. Conclusion In patients with fetuses with oligohydramnios with and without FGR, most patients delivered by SVD regardless of induction method. In this population, PGE use was associated with a high chance of SVD in patients with fetuses with suspected placental insufficiency regardless of the presence of absence of FGR. Key Points The majority of fetuses with oligohydramnios with or without FGR deliver vaginally. The use of prostaglandins did not increase rates of cesarean for fetal distress in oligohydramnios. Prostaglandin use did not increase rate of neonatal intensive care unit admission among pregnancies with oligohydramnios. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure (PAE) causes growth restriction that worsens in the first year of life. However, the roles of postnatal nutrition in fetal alcohol growth restriction and the impact of postnatal alcohol exposure via breastmilk on growth remain unknown. We aimed to compare infant feeding practices during the first 6.5 months of life between heavy drinkers and abstainers/light drinkers, to examine whether these practices play confounding roles in fetal alcohol growth restriction, and to determine the impact of postnatal alcohol exposure via breastmilk on growth. Eighty-seven heavy-drinking pregnant women and 71 abstainers/light drinkers (controls) were recruited prenatally from antenatal clinics in Cape Town, South Africa. Demographic background and alcohol, cigarette, marijuana, and methamphetamine use during pregnancy were assessed pre- and postnatally. Infant feeding practices were assessed at 6.5 months postpartum using the USDA Infant Feeding Questionnaire. Infant weight, length, and head circumference were measured at 2 weeks, 6.5 and 12 months, and 5 years. Neither prenatal nor postnatal alcohol consumption was related to the duration of breastfeeding, exclusive breastfeeding, exclusive formula, or mixed feeding. Complementary feeding practices were remarkably similar between exposure groups. PAE was related to all postnatal anthropometry measures at all age points, independent of infant feeding practices. Postnatal alcohol exposure via breastmilk was unrelated to any anthropometry outcome after control for PAE. In conclusion, fetal alcohol-related postnatal growth restriction was not attributable to differences in postnatal infant feeding practices or postnatal alcohol exposure and is thus likely a direct teratogenic effect of PAE. [ABSTRACT FROM AUTHOR]

Objective: To identify the estimated fetal weight (EFW) formula and threshold for the optimal prediction of fetal growth restriction (FGR) at 26–34 weeks' in fetuses with gastroschisis. Methods: Late second and third trimester ultrasound data were used to calculate the EFW utilizing eight different formulas: Hadlock I‐IV, Honarvar, Shepard, Siemer, and Warsof. EFW and birth weight percentiles were assigned from US population growth curves. FGR and small for gestational age (SGA) were defined as EFW and birth weight less than the tenth percentile for gestational age; Receiver operating characteristic (ROC) curves were used to compare formula performance for FGR diagnosis at 26–34 weeks' to identify an SGA birth weight. Results: There were 170 newborns with gastroschisis; 46 (27%) were SGA. The mean gestational age at the time of ultrasound was 30.8 ± 1.7 weeks. The mean gestational age at birth was 36.3 ± 1.7 weeks. ROC curve analysis found the Hadlock III formula had the largest area under the curve (AUC) of 0.813 closely followed by Hadlock IV (AUC = 0.811) and Hadlock II (AUC = 0.808) for diagnosis of FGR correlating to neonatal SGA diagnosis. Hadlock II, Hadlock III, and Hadlock IV had the highest diagnostic accuracies when compared to the other EFW formulas. Conclusions: The Hadlock II, Hadlock III, and Hadlock IV formulas have comparable predictive performance in the optimal identification of FGR in fetuses with gastroschisis at 26–34 weeks'. A threshold of an EFW less than the 25.2th percentile is suggested. Access the CME test here and search by article title. [ABSTRACT FROM AUTHOR]

Introduction: Pregnancies conceived through assisted reproductive techniques (ARTs) are on the rise worldwide and have been associated with a higher risk of placental-related disease in the third trimester. Methods: A cohort was created of singleton pregnancies after assisted reproduction, admitted at our institution for delivery, between January 2020 and August 2022. Fetal growth velocity from the second trimester to delivery was compared against a gestational-age-matched group of pregnancies spontaneously conceived according to the origin of the selected oocyte (i.e., autologous vs. donated). Results: 125 singleton pregnancies conceived through ART were compared to 315 singleton spontaneous conceptions. Overall, after adjusting for possible confounders, multivariate analysis demonstrated that ART pregnancies had a significantly lower estimated fetal weight (EFW) z-velocity from the second trimester to delivery (adjusted mean difference = −0.002; p = 0.035) and a higher frequency of EFW z-velocity in the lowest decile (adjusted OR = 2.32 [95% CI, 1.15–4.68]). Also, when ART pregnancies were compared according to the type of oocyte, those conceived with donated oocytes showed a significantly lower EFW z-velocity from the second trimester to delivery (adjusted mean difference = −0.008; p = 0.001) and a higher frequency of EFW z-velocity in the lowest decile (adjusted OR = 5.33 [95% CI, 1.34–21.5]). Conclusions: Pregnancies achieved through ART exhibit a pattern of lower growth velocity across the third trimester, especially those conceived with donated oocytes. The former represents a sub-group at the highest risk of placental dysfunction that may warrant closer follow-up. [ABSTRACT FROM AUTHOR]

Objective: To assess the feasibility of using ductus venosus Doppler (DVD) to time delivery in early‐onset fetal growth restriction (FGR) and pre‐eclampsia in a resource‐constrained setting. Methods: This was a prospective, observational study of pregnancies affected by early‐onset FGR and pre‐eclampsia. Patient characteristics, risk factors, ultrasound findings, and pregnancy outcomes were entered into a data collection tool. The association of these variables with perinatal and maternal outcomes were determined using binary logistic regression analysis. Results: The study had 61 participants. Most patients were delivered at 29–31+6 weeks of pregnancy (67%). Neonates with an estimated fetal weight on ultrasound of less than 800 g had the highest incidence of perinatal mortality (63%). There was a near six‐fold increase in risk of major neonatal morbidity in patients with abnormal DVD (odds ratio 5.9, 95% confidence interval [CI] 1.8–19.0). Absent flow in the DVD a‐wave carried a higher risk of perinatal mortality (OR 23.8, 95% CI 1.7–334.8); 22% of patients with an abnormal DVD a‐wave experienced placental abruption. Conclusion: Having an abnormal DVD in the background of pre‐eclampsia was related to increased perinatal morbidity and mortality, with increased risk of placental abruption. Synopsis: Awaiting late ductus venosus Doppler changes in patients with pre‐eclampsia and early‐onset fetal growth restriction results in adverse outcomes in a resource‐limited setting. [ABSTRACT FROM AUTHOR]

BACKGROUND: Gastroschisis and omphalocele are the 2 most common congenital fetal abdominal wall defects. Both malformations are commonly associated with small-for-gestational-age neonates. However, the extent and causes of growth restriction remain controversial in both gastroschisis and omphalocele without associated malformations or aneuploidy. OBJECTIVE: This study aimed to examine the role of the placenta and the birthweight–to–placental weight ratio in fetuses with abdominal wall defects. STUDY DESIGN: This study included all cases of abdominal wall defects examined at our hospital between January 2001 and December 2020, retrieving the data from the hospital's software. Fetuses with any other combined congenital anomalies, known chromosomal abnormalities, or lost to follow-up were excluded. Overall, 28 singleton pregnancies with gastroschisis and 24 singleton pregnancies with omphalocele met the inclusion criteria. Patient characteristics and pregnancy outcomes were reviewed. The primary outcome was to investigate the association between birthweight and placental weight in pregnancies with abdominal wall defects as measured after delivery. To correct for gestational age and to compare total placental weights, ratios between the observed and expected birthweights for the given gestational age in singletons were calculated. The scaling exponent β was compared with the reference value of 0.75. Statistical analysis was performed using GraphPad Prism (version 8.2.1; GraphPad Software, San Diego, CA) and IBM SPSS Statistics. A P value of

Tobacco use in pregnant women remains prevalent with an estimated prevalence of 8.1 % in the European region. In whatever form it is partaken, tobacco use is associated with significant short- and long-term consequences for both the mother and the progeny thus making the habit an important obstetric and public health concern. It is recommended that an active intervention policy should be adopted by healthcare providers to promote preconception smoking cessation and provide services for counselling with behavioural modification support, and the provision of smoking cessation pharmaceutical services. Women who continue to smoke should have closer antenatal surveillance throughout the whole of pregnancy. [ABSTRACT FROM AUTHOR]

It is generally accepted that intrauterine growth restriction (IUGR) increases morbidity and mortality among very preterm neonates. However, evidence is hampered by the widespread practice of using the terms small for gestational age (SGA) and IUGR as synonyms. We conducted a systematic review of studies reporting on the association between IUGR/SGA and patent ductus arteriosus (PDA). PubMed/MEDLINE and EMBASE databases were searched. Of 993 studies reviewed, 47 (50,790 infants) were included. Studies were combined using a random effects model and sources of heterogeneity were determined by subgroup and meta-regression analyses. Meta-analysis of all included studies showed a significantly reduced risk of PDA in the SGA/IUGR group with an odds ratio (OR) of 0.82, and a 95% confidence interval (CI) of 0.70 to 0.96 (p = 0.015). Of the 47 studies, only 7 used a definition for growth restriction that went beyond birth weight (BW) for gestational age (GA). When pooled, meta-analysis could not demonstrate a significant effect size (OR 1.31, 95% CI 0.75 to 2.27, p = 0.343). Moreover, the significantly reduced risk of PDA was found in the 25 studies defining SGA as BW

Objectives: Does cigarette smoking impact the embryonic growth rate in the first trimester? Methods: This is a retrospective multicentre observational study of 2912 pregnancies. Women who presented to the early pregnancy and perinatal ultrasound units between 2010 and 2019 were included in the study. The data collected included the following: smoking status, the crown–rump length (CRL) of the pregnancy at the first ultrasound that showed an embryonic heart rate, the gestation in days and the CRL at another ultrasound up to the nuchal translucency scan and the gestation in days. Additional demographic data included the following: age, weight, height, parity and mode of delivery. Of the 2912, complete smoking and demographic data were available for 657 pregnancies. One hundred and thirty‐seven (26.3%) were smokers, and 520 (73.7%) were not. The rate of change of smokers vs non‐smokers between two CRLs and two different days of gestation was calculated. The Wilcoxon rank sum test with continuity correction was used for statistical analysis. Results: This gives a value of W = 31,940 and a P‐value = 0.06. There is a slight shift in location for the smokers; however, it is not statistically significant. The insignificance may be due to the general large variance in growth rate. Conclusion: The impact of cigarette smoking on embryonic growth rate detected by CRL in the first trimester is statistically insignificant. [ABSTRACT FROM AUTHOR]

Background: Fetal growth restriction (FGR) is an obstetric complication associated with adverse perinatal outcomes. Doppler ultrasound can improve perinatal outcomes through monitoring at‐risk fetuses and helping time delivery. Aim: To investigate the prognostic value of different Doppler ultrasound measurements for adverse perinatal outcomes. Materials: Individual participant data. Methods: We performed a pooled analysis on individual participant data. We compared six prognostic models using multilevel logistic regression, where each subsequent model added a new variable to a base model that included maternal characteristics. Estimated fetal weight (EFW) and four Doppler ultrasound measurements were added in turn: umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI), cerebroplacental ratio (CPR), and mean uterine artery pulsatility index (mUtA PI). The primary outcome was a composite adverse perinatal outcome, defined as perinatal mortality, emergency caesarean delivery for fetal distress, or neonatal admission. Discriminative ability was quantified with area under the curve (AUC). Results: Three data sets (N = 3284) were included. Overall, the model that included EFW and UA PI improved AUC from 0.650 (95% CI 0.624–0.676) to 0.673 (95% CI 0.646–0.700). Adding more ultrasound measurements did not improve further the discriminative ability. In subgroup analysis, the addition of EFW and UA PI improved AUC in both preterm (AUC from 0.711 to 0.795) and small for gestational age pregnancies (AUC from 0.729 to 0.770), but they did not improve the models in term delivery or normal growth subgroups. Conclusions: Umbilical artery pulsatility index added prognostic value for adverse perinatal outcomes to the already available information, but the combination of other Doppler ultrasound measurements (MCA PI, CPR or UtA PI) did not improve further prognostic performance. [ABSTRACT FROM AUTHOR]

To explore the association between abnormal uterine artery Dopplers (combined PI > 2.5) - with normal PAPP-A - and adverse obstetric/neonatal outcomes. This was a retrospective cohort study of 800 patients between 1 March 2019 − 23 November 2021 in a tertiary UK hospital, where it is routine to measure uterine artery Dopplers of all pregnancies during their anomaly scans. 400 nulliparous women/birthing people with complete data were included. 400 nulliparous controls scanned in the same time frame (1.5 years) with normal PAPP-A and uterine artery Dopplers were matched for age and BMI. Outcomes included: mode of birth, postpartum complications, birth weight/centile, Apgar score, gestational age at delivery, neonatal unit admission, and clinical neonatal hypoglycemia. Multivariable analysis was used. Compared to controls, pregnancies with abnormal uterine artery Dopplers and normal PAPP-A were at increased risk of induction (46.5% vs 35.5%, p =.042), cesarean section (46.0% vs 38.0%, p =.002), emergency cesarean section (35.0% vs 26.5%, p =.009), and pre-eclampsia 5.8% vs 2.5%, p =.021). Their babies were more likely to be admitted to the neonatal unit – mostly for prematurity (15.3% vs 6.3%, p =.0004), hypoglycemia (4.0% vs 1.0%, p =.007), be small for gestational age (26.5% vs 11.5%, p =.0001), had intrauterine growth restriction (10.8% vs 1.3%, p =.0001), and be born prematurely (10.0% vs 3.5%, p =.002). Routine measurement of uterine artery Dopplers increased the detection rate of small for gestational age fetuses by 15.1%. Over half of the babies admitted with neonatal hypoglycemia in pregnancies with abnormal uterine artery Dopplers had an unexplained cause. Pregnancies with abnormal uterine Dopplers are not only at increased risk of pre-eclampsia and small for gestational age fetuses/intrauterine growth restriction, but are also at increased risk of emergency cesarean section and adverse neonatal outcomes. The increased incidence of neonatal hypoglycemia is likely driven to some degree by prematurity and placental complications, but possibly also by undiagnosed glucose dysmetabolism. This may warrant routine measurement of uterine artery Dopplers in all pregnancies (regardless of risk), where feasible, to aid antenatal management and counseling. What are the novel findings of this work? Pregnancies with abnormal uterine artery Dopplers at the time of the anomaly scan and normal PAPP-A are at increased risk of having pre-eclampsia, small for gestational age fetuses, emergency cesarean, neonatal unit admission (including but not limited to prematurity), and neonatal hypoglycemia. What are the clinical implications of this work? Due to the significantly increased risk of adverse maternal and neonatal outcomes in first time mothers with increased uterine artery Dopplers despite normal PAPP-A, ultrasound assessment of placental function should be offered to all during their anomaly scans, subject to resources, to aid antenatal management and counseling. Further research is needed into undiagnosed diabetes. [ABSTRACT FROM AUTHOR]

Heart disease is the leading cause of death in humans and evidence suggests early life growth-restriction increases heart disease risk in adulthood. Therefore, this study sought to investigate the effects of low birth weight (LBW) and postnatal restricted nutrition (RN) on cardiac function in neonatal pigs. We hypothesized that LBW and RN would reduce cardiac function in pigs but this effect would be reversed with refeeding. To investigate this hypothesis, pigs born weighing <1.5 kg were assigned LBW, and pigs born >1.5 kg were assigned normal birth weight (NBW). Half the LBW and NBW pigs underwent ~25% total nutrient restriction via intermittent suckling (assigned RN) for the first 4 wk post-farrowing. The other half of piglets were allowed unrestricted suckling access to the sow (assigned NN). At 28 d of age (weaning), pigs were weaned and provided ad libitum access to a standard diet. Echocardiographic, vascular ultrasound, and blood pressure (BP) measurements were performed on day 28 and again on day 56 to assess cardiovascular structure and function. A full factorial three-way ANOVA (NN vs. RN, LBW vs. NBW, male vs. female) was performed. Key findings include reduced diastolic BP (P = 0.0401) and passive ventricular filling (P = 0.0062) in RN pigs at 28 d but this was reversed after refeeding. LBW piglets have reduced cardiac output index (P = 0.0037) and diastolic and systolic wall thickness (P = 0.0293 and P = 0.0472) at 56 d. Therefore, cardiac dysfunction from RN is recovered with adequate refeeding while LBW programs irreversible cardiac dysfunction despite proper refeeding in neonatal pigs. [ABSTRACT FROM AUTHOR]

Most pregnancy complications originate with early placentation. MicroRNAs (miRNAs) may play an important role in placentation and function as biomarkers of future pregnancy complications. We summarized from the literature all first trimester circulating miRNAs associated with pregnancy complications of placental origin and further identified the miRNAs which have the most evidence as potential early biomarkers for pregnancy complications. We conducted a systematic review following PRISMA reporting guidelines (PROSPERO CRD42020183421). We identified all first trimester serum or plasma miRNAs associated with a pregnancy complication of placental origin (preeclampsia, intrauterine growth restriction (IUGR), gestational hypertension, preterm delivery) and the number of times those miRNAs were identified, as a measure of replication. Twenty-one studies examined 118 unique miRNAs, and 87 were associated with at least one pregnancy complication; preeclampsia was the most common. Seven miRNAs were significantly associated with a pregnancy complication in at least two studies: miR-125b, miR-518b, miR-628-3p, miR-365a-3p, miR-520h, miR-374a-5p, miR-191-5p. Few miRNAs were associated with more than one pregnancy complication: miR-518b and miR-520h with preeclampsia and gestational hypertension, miR-374a-5p and miR-191-5p with preterm birth and preeclampsia. Our systematic review suggests seven miRNAs as potential biomarkers of pregnancy complications. These complications are thought to originate with early placental defects and these miRNAs may also be biomarkers of placental pathology. First-trimester biomarkers of pregnancy complications can facilitate early detection and interventions. [ABSTRACT FROM AUTHOR]

Background Fetal Growth restriction (FGR) is the pathological failure of a fetus to reach its biologically determined growth potential. Detection of FGR fetuses is a universally agreed key objective of antenatal care. Antenatal detection of FGR has undeniable benefits, juggling between intensive fetal surveillance and optimized timing of delivery; it reduces adverse perinatal outcomes by up to four-fold. However, FGR is still widely underdiagnosed. We aimed to identify the prevalence of FGR diagnosis in our wards and study the impact of the 2013 published French guidelines on the detection rate of FGR. The secondary objective aimed to highlight the factors of suboptimal screening in the population of non-diagnosed FGR fetuses and emphasize the screening method that led to antenatal diagnosis of FGR. Materials and methods We conducted a retrospective study at a single tertiary maternity center in Lyon-France, the Femme Mère Enfant Hospital, including the exhaustive population of FGR born after 24 + 0 weeks of gestation from 1 January 2011 to 31 December 2017. FGR was defined combining the neonatal and antenatal consensus-based definitions for early and late FGR in absence of congenital anomalies, excluding small for gestational age fetuses. For all FGR fetuses, we compared the antenatal detection rate of FGR during 2011–2013 to 2015–2017, since the French guidelines were published in December 2013. When FGR fetuses underwent an antenatal diagnosis of FGR, we retrospectively collected the characteristics that led to the diagnosis. When fetuses were not diagnosed as FGR, we retrospectively reviewed the implementation of the recommended screening method, enabling to evaluate whether screening was optimal or not. Statistical analysis was performed in July 2018, and statistical significance was regarded as a p-value <.05. Results Over the seven-year period, and among 31,052 newborns, 1020 (3.3%) infants were identified as FGR and met the inclusion criteria. The detection rate of FGR was similar before and after publication of the French Guidelines related to FGR in 2013. Indeed, 50.8% (201/395) FGR were diagnosed between 2011 and 2013 versus 52.6% (245/465) between 2015 and 2017 (p = .59). In the population of non-diagnosed FGR infants, screening was suboptimal in 80%. Symphysis-fundal height (SFH) was not measured in 10.7%, with no difference before and after 2014 (7.3 versus 11.8% p = .11). Ultrasound examination for fetal biometry had not been prescribed in spite of abnormal SFH in 47.7% of undiagnosed FGR infants. Diagnosis has been missed in 11.5% of infants because of misinterpretation of the estimated fetal weight’s centile. Conclusion FGR is widely underdiagnosed. However, the limited performances can partially be explained by the regular misuse of screening method in clinical practice. Despite the systematic third trimester ultrasound screening, the detection rate of FGR was similar to the one reported in the medical literature. The timing of routine third trimester ultrasound in low-risk women may be rethought. [ABSTRACT FROM AUTHOR]

Purpose of Review: Synthesize the clinical, epidemiological, and preclinical evidence for antenatal programming of hypertension and critically appraise paradigms and paradoxes to improve translation. Recent Findings: Clinical and epidemiological studies persistently demonstrate that antenatal factors contribute to programmed hypertension under the developmental origins of health and disease framework, including lower birth weight, preterm birth, and fetal growth restriction. Preclinical mechanisms include preeclampsia, maternal diabetes, maternal undernutrition, and antenatal corticosteroid exposure. However, clinical and epidemiological studies to date have largely failed to adequately identify, discuss, and mitigate many sources and types of bias in part due to heterogeneous study designs and incomplete adherence to scientific rigor. These limitations have led to incomplete and biased paradigms as well as persistent paradoxes that have significantly limited translation into clinical and population health interventions. Summary: Improved understanding of these paradigms and paradoxes will allow us to substantially move the field forward. [ABSTRACT FROM AUTHOR]

Abstract Background Wolf-Hirschhorn syndrome (WHS) is a well-defined disorder, whose core phenotype encompasses growth restriction, facial gestalt, intellectual disability and seizures. Nevertheless, great phenotypic variability exists due to the variable extent of the responsible 4p deletion. In addition, exome sequencing analyses, recently identified two genes, namely NSD2 and NELFA, whose loss-of-function variants contribute to a clinical spectrum consistent with atypical or partial WHS. The observation of patients exhibiting clinical features resembling WHS, with only mild developmental delay and without the typical dysmorphic features, carrying microdeletions sparing NSD2, has lead to the hypothesis that NSD2 is responsible for the intellectual disability and the facial gestalt of WHS. While presenting some of the typical findings of WHS (intellectual disability, facial gestalt, microcephaly, growth restriction and congenital heart defects), NSD2-deleted children tend to display a milder spectrum of skeletal abnormalities, usually consisting of clinodactyly, and do not exhibit seizures. We describe the clinical picture of a child with WHS due to a de novo mutation of NSD2 and discuss the clinical and diagnostic implications. Case presentation A 6-year-old boy was evaluated for a history of intrauterine growth restriction, low birth weight, neonatal hypotonia, and psychomotor delay. No episodes of seizure were reported. At physical examination, he displayed marphanoid habitus, muscle hypotrophy and facial dysmorphisms consisting in high frontal hairline, upslanting palpebral fissures and full lips with bifid ugula. Cryptorchidism, shawl scrotum, mild clinodactyly of the right little finger and bilateral syndactyly of the II and III toes with sandal gap were also noted. The radiographic essay demonstrated delayed bone age and echocardiography showed mild mitral prolapse. Whole genome sequencing analysis revealed a heterozygous de novo variant of NSD2 (c.2523delG). Conclusions Full WHS phenotype likely arises from the cumulative effect of the combined haploinsufficiency of several causative genes mapping within the 4p16.3 region, as a contiguous genes syndrome, with slightly different phenotypes depending on the specific genes involved in the deletion. When evaluating children with pictures resembling WHS, in absence of seizures, clinicians should consider this differential diagnosis.

Abstract Genes associated with specific neurocognitive phenotypes in Williams–Beuren syndrome are still controversially discussed. This study identified nine patients with atypical deletions out of 111 patients with Williams–Beuren syndrome; these deletions included seven smaller deletions and two larger deletions. One patient had normal neurodevelopment with a deletion of genes on the distal side of the Williams–Beuren syndrome chromosomal region, including GTF2I and GTF2IRD1. However, another patient retained these genes but showed neurodevelopmental abnormalities. By comparing the genotypes and phenotypes of patients with typical and atypical deletions and previous reports in the literature, we hypothesize that the BAZ1B, FZD9, and STX1A genes may play an important role in the neurodevelopment of patients with WBS.