Fetal Growth Research Articles

A Virome and Proteomic Analysis of Placental Microbiota in Pregnancies with and without Fetal Growth Restriction.

Metagenomic research has allowed the identification of numerous viruses present in the human body. Viruses may significantly increase the likelihood of developing intrauterine fetal growth restriction (FGR). The goal of this study was to examine and compare the virome of normal and FGR placentas using proteomic techniques. The study group of 18 women with late FGR was compared with 18 control patients with physiological pregnancy and eutrophic fetus. Proteins from the collected afterbirth placentas were isolated and examined using liquid chromatography linked to a mass spectrometer. In this study, a group of 107 viral proteins were detected compared to 346 in the controls. In total, 41 proteins were common in both groups. In total, 64 proteins occurred only in the study group and indicated the presence of bacterial phages: E. coli, Bacillus, Mediterranenean, Edwardsiella, Propionibacterium, Salmonella, Paenibaciilus and amoebae Mimiviridae, Acanthamoeba polyphaga, Mimivivirus, Pandoravirdae, Miroviridae, Pepper plant virus golden mosaic virus, pol proteins of HIV-1 virus, and proteins of Pandoravirdae, Microviridae, and heat shock proteins of the virus Faustoviridae. Out of 297 proteins found only in the control group, only 2 viral proteins occurred statistically significantly more frequently: 1/hypothetical protein [uncultured Mediterranean phage uvMED] and VP4 [Gokushovirus WZ-2015a]. The detection of certain viral proteins exclusively in the control group suggests that they may play a protective role. Likewise, the proteins identified only in the study group could indicate a potentially pathogenic function. A virome study may be used to identify an early infection, evaluate its progress, and possible association with fetal growth restriction. Utilizing this technology, an individualized patient therapy is forthcoming, e.g., vaccines.

Effects of supportive hemodialysis on the management of a pregnant woman with advanced chronic kidney disease: a case report and literature review

BackgroundPregnancy in women with chronic kidney disease (CKD) is associated with an increased risk of adverse maternal and fetal outcomes, including worsening renal function, hypertension, proteinuria, preeclampsia, preterm delivery, stillbirth, and intrauterine growth restriction. Some pregnant women with CKD may require dialysis after conception. Clinical guidelines provide recommendations for optimal hemodialysis prescription in pregnant women undergoing maintenance hemodialysis for end-stage kidney disease. However, the timing of initiation and optimal doses of hemodialysis for pregnant women with non-dialysis advanced CKD remain uncertain.Case presentationWe describe the case of a 29-year-old woman with a history of CKD for at least 2 years. She was referred to our department with a serum creatinine level of 2.48 mg/dL and an estimated glomerular filtration rate of 20 mL/min/1.73 m2. Because she was found to be pregnant at the initial visit, she was referred to the Department of Obstetrics. At 23 weeks’ gestation, she was admitted due to threatened premature delivery and urinary tract infection, which were managed with ritodrine hydrochloride and antibiotics. Owing to maternal weight loss and asymmetrical fetal growth restriction, daily protein intake was increased from 40 g/day to 60–80 g/day. Additionally, supportive hemodialysis (three times per week) was initiated at 26 weeks’ gestation, and the pre-dialysis blood urea nitrogen (BUN) level was consistently maintained < 40 mg/dL. Consequently, the patient’s weight increased, and fetal growth recovered. Because her blood pressure increased particularly during and after dialysis sessions, dialysis was discontinued at 32 weeks’ gestation. Urinary protein increased to a nephrotic level, and blood pressure was poorly controlled by medication, suggesting the onset of preeclampsia. Thus, a cesarean section was performed at 33 weeks’ gestation, and she delivered a male baby weighing 1449 g. Following childbirth, the patient did not require hemodialysis.ConclusionsSupportive hemodialysis during pregnancy in women with advanced CKD can increase maternal protein intake without elevating BUN levels, leading to improved fetal growth.

Evaluation of fetal growth and birth weight in pregnancies with placenta previa with and without placenta accreta spectrum.

We evaluated fetal growth and birthweight in pregnancies with placenta previa with and without placenta accreta spectrum (PAS). We retrospectively studied pregnant patients with placenta previa with or without PAS diagnosed at 20-37weeks' gestation. Estimated fetal weight (EFW) percentile and fetal growth rate were calculated based on ultrasound at two timepoints: 20-24 and 30-34-weeks' gestation. Fetuses were small (SGA) or large for gestational age (LGA) when EFW or abdominal circumference was <10th or >90th percentile for gestational age, respectively. Fetal growth rate was estimated by subtracting EFW percentiles from the two ultrasounds. Birthweight in grams and percentiles were estimated via Anderson and INTERGROWTH-21 standards adjusted for neonatal sex. EFW percentiles, fetal growth rate, birth weight and birthweight percentiles were compared between patients with placenta previa with and without PAS. We studied 171 patients with and 146 patients without PAS. SGA rates did not differ between groups on first (PAS n=3, no-PAS n=3, p=0.8) or second ultrasound (PAS n=10, no-PAS n=8, p=0.8). LGA rates were similar between groups on first (PAS n=11, no-PAS n=9, p=0.8) and second ultrasound (PAS n=20, no-PAS n=12, p=0.6). The growth rate was higher in fetuses with PAS than placenta previa (1.22±22.3 vs.-4.1±18.1, p=0.07), but not significantly. The birthweight percentile was higher in the PAS than the placenta previa group (74 vs. 67, p=0.01). On multi-linear regression, birthweight percentile remained higher in the PAS group, but not significantly. Placenta previa with or without PAS is not associated with SGA, LGA or lower birthweight.

Obstetric and neonatal outcomes of immune thrombocytopenic purpura in pregnancy and the role of delta hemoglobin index: A case-control study from a tertiary center.

To evaluate the effect of idiopathic thrombocytopenic purpura (ITP) on pregnancies and the role of the delta hemoglobin indices in the evaluation of treatment effectiveness. This case-control study was conducted with 23 ITP and 115 low-risk pregnancies. Obstetric outcomes (fetal growth retardation (FGR), preterm delivery) and neonatal outcomes (weights, APGAR scores, NICU admissions, thrombocytopenia) were recorded. ITP group was subgrouped based on the platelet ratio at the admission for delivery and evaluated the impact of platelet ratios on blood loss amounts at delivery by using delta hemoglobin indices. Eleven patients received treatment during pregnancy. The gestational age at birth and fetal APGAR scores were lower, and the preterm delivery and FGR rates were higher in the ITP group. Four newborns (17.4%) had thrombocytopenia. There were two postpartum hemorrhages. Newborn platelet counts did not correlate with maternal platelet counts. The study showed no difference in delta hemoglobin counts between the ITP and control groups. ITP is associated with an increased risk of maternal and fetal complications. The presented study showed by using the delta hemoglobin indices that, hemorrhagic complications could be prevented with appropriate management. Neonatal thrombocytopenia should be considered for all ITP patients.

Decoding Apelin: Its Role in Metabolic Programming, Fetal Growth, and Gestational Complications.

Placental insufficiency and gestational diabetes, which are both serious pregnancy complications, are linked to altered fetal growth, whether restricted or excessive, and result in metabolic dysfunction, hypoxic/oxidative injury, and adverse perinatal outcomes. Although much research has been carried out in this field, the underlying pathogenetic mechanisms have not as yet been fully elucidated. Particularly because of the role it plays in cardiovascular performance, glucose metabolism, inflammation, and oxidative stress, the adipokine apelin was recently shown to be a potential regulator of fetal growth and metabolic programming. This review investigated the numerous biological actions of apelin in utero and aimed to shed more light on its role in fetal growth and metabolic programming. The expression of the apelinergic system in a number of tissues indicates its involvement in many physiological mechanisms, including angiogenesis, cell proliferation, energy metabolism, inflammation, and oxidative stress. Moreover, it appears that apelin has a major function in disorders such as diabetes mellitus, fetal growth abnormalities, fetal hypoxia, and preeclampsia. We herein describe in detail the regulatory effects exerted by the adipokine apelin on fetal growth and metabolic programming while stressing the necessity for additional research into the therapeutic potential of apelin and its mechanisms of action in pregnancy-related disorders.

Embryonic and Fetal Heart Development Before 12 Weeks of Gestation.

To assess embryonic and fetal cardiac growth and development using transvaginal 2-dimensional sonography before 12 weeks of gestation. Transvaginal scans for first-trimester dating were performed for 131 normal fetuses at 8-11 + 6 weeks of gestation. The basal-apical length (BAL), transverse length (TL), cardiac circumference (ECC), embryonic cardiac area (ECA), global sphericity index (GSI), and cardio-thoracic area ratio (CTAR) were able to be obtained in 105 normal embryos and fetuses. Nomograms for several cardiac parameters including BAL, TL, ECC, ECA, GSI, and CTAR were constructed. BAL, TL, ECC, and ECA increased curvilinearly with advancing gestation (R2 = 0.97406, 0.980396, 0.978359, and 0.920705, respectively, P < .001). GSI (mean, 1.14; SD, 0.10) and CTAR (mean, 15.7%; SD, 3.3%) values were constant at 8-11 + 6 weeks of gestation. There were significant curvilinear correlations between BAL, TL, ECC, and ECA, and crown-rump length (CRL) (R2 = 0.975976, 0.983482, 0.980673, and 0.929936, respectively, P < .001). GSI and CTAR values were not changed with the increase of CRL during this period. Our results provide nomograms for several cardiac parameters which may improve the understanding of embryonic and fetal cardiac growth and development prior to 12 weeks of gestation.

Maternal NO2 exposure and fetal growth restriction: Hypoxia transmission and lncRNAs-proinflammation-mediated abnormal hematopoiesis

Epidemiological studies show a strong correlation between air pollution and fetal growth restriction (FGR), but existing results are controversial due to inherent limitations, such as causality of specific pollutants, developmental origin, and maternal-fetal transmission. To address this controversy, we first conducted a retrospective analysis of 28,796 newborns and revealed that maternal nitrogen dioxide (NO2) exposure during the second trimester was positively associated with FGR, with an adjusted odds ratio of 1.075 (95% confidence interval: 1.020-1.133) per 10 μg/m3 NO2 increase for small for gestational age. Then, by establishing an animal model of prenatal NO2 exposure, we confirmed its adverse effects on embryonic growth and hematopoiesis in the yolk sac and fetal liver, primarily affecting the differentiation of hematopoietic stem and progenitor cells and erythroid maturation. By applying internal exposure analyses coupled with 15N isotope tracing, we found that maternal NO2 inhalation induced acquired methemoglobinemia through its byproducts and placental hypoxia in pregnant mice. Importantly, by combining transcriptional profiling, bioinformatics analysis, and RNA binding protein immunoprecipitation (RIP)/chromatin immunoprecipitation (CHIP), we clarified that placental-fetal hypoxia transmission activated hypoxia-inducible factors, disturbed hematopoiesis through the hypoxia-inducible factor 1β-long noncoding RNAs-CCAAT/enhancer binding protein alpha-proinflammatory signaling pathway, ultimately contributing to FGR progression. These findings provide insights for risk prevention and clinical intervention to promote child well-being in NO2-polluted areas.

Aberrant Number of Vessels in the Umbilical Cord: What Do We Know?

The umbilical cord, comprising three vital blood vessels, serves as the lifeline between mother and fetus. Prenatal care emphasizes detailed ultrasound examinations of the umbilical cord and postnatal inspections of the placenta and cord to preemptively address potential complications. Studies have consistently shown a significant link between a single umbilical artery and unfavorable perinatal consequences, such as mortality and congenital abnormalities. Conversely, the impact of additional vessels remains uncertain. This review is dedicated to enhancing our understanding and refining diagnostic and therapeutic approaches in prenatal healthcare. The objective is to identify knowledge gaps and propose evidence-based solutions to improve care for pregnant women and their unborn babies. The presence of a single umbilical artery in prenatal diagnosis may signify potential risks for fetal anomalies and adverse pregnancy outcomes such as hemodynamic instability, ischemia, and an increased likelihood of intrauterine growth restriction. Additionally, even the presence of supernumerary vessels may be associated with fetal malformations. Serial fetal evaluations are recommended for detecting anomalies and monitoring fetal growth throughout pregnancy. Despite the generally benign nature of isolated SUA and supernumerary vessels, close monitoring and comprehensive prenatal care are essential to ensuring optimal outcomes for both mother and baby.

Maternal and neonatal outcomes of congenital syphilis at a tertiary care center in Turkey; a retrospective observational study

Background Maternal syphilis (MS) can lead to significant maternal morbidity and neonatal morbidity and mortality if inadequately treated. This study is aimed to retrospectively analyse the maternal and neonatal outcomes of pregnant women diagnosed with MS at our clinic. Materials and Methods We accessed the medical records of 64 cases diagnosed with MS between 2020 and 2022 from our hospital database and the perinatology clinic archives in this retrospective observational study. Case distributions by years, sociodemographic characteristics, and maternal and neonatal outcomes were recorded. Results The distribution of MS cases was 16 (25.0%) in 2020, 20 (31.25%) in 2021, and 28 (43.75%) in 2022. The mean age of the patients was 26.4 ± 6.3 years, mean BMI was 23.36 ± 3.14, the smoking rate was 31.25%, and the majority of patients were educated to primary level (37.5%). Most were housewives (43.75%), lived in urban areas (43.75%), and had lower-level incomes (68.75%). In addition, 43.75% received adequate maternal treatment, the caesarean delivery rate was 43.25%, 31.25% had preterm births, and the mean birth weight was 2956.36 + 514.46 g. CS was largely diagnosed during delivery or the postpartum period (43.75%). Fifty percent of patients were in the latent stage, gestational hypertension and preeclampsia were present in four case each (6.25%), and gestational diabetes mellitus in eight (12.5%). Twenty babies (31.25%) were admitted to the neonatal intensive care unit, eight (12.5%) had congenital anomalies, 12 had foetal growth restriction (18.25%), stillbirth was present in four (6.25%) case, and early neonatal death in four (6.25%). Conclusions Delayed diagnosis and inadequate treatment of MS can lead to significant maternal and neonatal morbidity and mortality. Well-planned antenatal care services should be provided for all expectant mothers in order to reduce these adverse outcomes.

Ultrasound Microvessel Imaging of the Human Placenta Demonstrates Altered Vessel Densities in Fetal Growth Restriction With Vascular and Immune Pathologies: A Pilot Case-Control Study.

Fetal growth restriction (FGR) is commonly associated with placental dysfunction, increasing perinatal morbidity and mortality. Visualizing placental vessels in utero would be advantageous for identifying functional FGR cause and determining proper management strategies. We aimed to utilize high-sensitivity ultrasound microvessel imaging (HUMI) for quantifying placental vessel density (VD) in pregnancies diagnosed with FGR. This pilot case-control study enrolled subjects in the third trimester with a diagnosis of FGR (n = 40) and gestational age-matched controls with normal fetal growth (n = 20) at a 2:1 ratio, respectively. The Verasonics Vantage ultrasound system was used to perform HUMI on each participant at one timepoint. Scanning involved randomized singular value decomposition-based clutter filtering to identify the villous tree, followed by step-by-step scanning to acquire 3-dimensional-like data. Mean VD was calculated from three ultrasound measurements per subject. Additional clinical and pathology data were also collected and compared. Sixteen participants were utilized to establish the scanning protocol and 2 met exclusion criteria at delivery. Thus, VD was successfully measured on 42 pregnancies scanned at 35 weeks 5 days on average. In FGR (n = 24), placental VD was significantly reduced compared to controls (P < .01). VD measures were as good at predicting FGR as systolic/diastolic (S/D) ratios (area under the curve 0.86 versus 0.80). In a smaller cohort, VD in placentas with a diagnosis of inflammatory villitis (n = 10) by histology showed an increase in VD compared to those without inflammation (P = .01). Low VD was correlated with increased S/D ratios (P = .03). HUMI is useful for identifying altered placental vascularization in utero for FGR. VD may be a valuable indicator for placental health and could lead to improved risk stratification methods considering underlying biology.

Double umbilical artery converging into a single umbilical artery: A case report.

The normal structure and Doppler parameters of the umbilical cord are closely related to many diseases, including fetal infection, chromosomal abnormalities, hypoxia, and growth and development restrictions. We report a case of bilateral umbilical artery confluence resulting in the formation of a single umbilical artery in the free segment of the fetal umbilical cord, diagnosed at 24 weeks and 4 days gestation. The fetus was born prematurely after premature membrane rupture at 31 weeks and 3 days gestation. The Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test showed positive results for Toxoplasma gondii, rubella virus, and herpes simplex virus IgG antibodies. A 36-year-old woman had vaginal discharge for > 1 hour at 31 weeks + 3 days gestation and came to our obstetrics department for treatment. The pregnant woman sought treatment due to premature membrane rupture and vaginal discharge for > 1 hour. The vaginal discharge was caused by Escherichia coli. After cesarean section, the Toxoplasma, Others, Rubellavirus, Cytomegalovirus, Herpesvirus test revealed positive results for the following: T gondii, rubella virus, and herpes simplex virus IgG antibodies. The patient underwent 2 ultrasound examinations and was diagnosed with umbilical artery malformation (the free segment of the umbilical cord on the fetal side converged into a single umbilical artery), which may have been related to fetal infection. The patient received anti-inflammatory and fetal lung maturation treatment for 2 days before undergoing a cesarean section. The mother and newborn received anti-inflammatory, symptomatic, and supportive treatment and were discharged after 1 week of improvement. After 1 month, 6 months, and 1 year of follow-up after birth, the growth and development of the infant (height and weight) were significantly lower than those of her peers, and her responses to sound and light were slightly delayed. Umbilical artery malformation is extremely rare and may be related to intrauterine parasitic and viral infections. Ultrasound has the advantages of being noninvasive and cost-effective and can be used to dynamically observe umbilical artery structure. An abnormal change in umbilical artery structure found during ultrasound examination can indicate intrauterine infection risk, which provides clinical guidance for further examination of pregnant women, early diagnosis, timely targeted treatment, and fetal prognosis improvement.

Epigenetic programming of obesity in early life through modulation of the kynurenine pathway.

Childhood obesity is a global health concern that has its origins before birth. Although genetics plays a crucial role, increasing evidence suggests that epigenetic modifications during fetal life could also influence its incidence. In this model, during the fetal period, interactions between genetic makeup, intrauterine factors, and environmental conditions, increase the risk of childhood obesity. This is in accordance with the Developmental Origins of Health and Disease (DOHaD) hypothesis, in which specific intrauterine environments can have long-lasting effects on the immune system's essential functions during crucial stages of fetal growth, resulting in permanent changes to the immune function of the offspring. Consequently, dysfunction can consequently make the offspring more prone to inflammatory and immune-related disorders later in life. In this review, we examine how maternal inflammation could influence the risk of childhood obesity. We propose that during pregnancy, modification of the expression of critical genes in metabolic and signaling pathways, such as the kynurenine (Kyn) pathway, occurs due to increased levels of maternal inflammation. We also propose that such expression differences are mediated by epigenetic changes. Furthermore, we also hypothesize that the Kyn pathway produces metabolites that have immunoregulatory effects and may play a crucial role in regulating inflammation during pregnancy. As a result, interventions aimed at improving maternal inflammation may be able to help alleviate the risk of childhood obesity.

The pregnancy-associated secretome in malaria pathogenesis and immunity during gestation

In pregnancy, fetal health, growth and development are dependent on normal placental development. However, the mechanisms that support maternal immune tolerance for the fetus, fetal nourishment, and pregnancy maintenance to term are not fully understood. Placental secretions into the intervillous space play a key role in shaping early placental function. In their entirety, they represent the pregnancy-associated secretome (PAS). PAS alterations have been associated with various complications such as fetal growth restriction, maternal anemia, and preterm birth. Placental malaria (PM), caused by the sequestration of Plasmodium falciparum-infected erythrocytes in the intervillous space, affects PAS composition. In this review, we explore how P. falciparum-induced changes of PAS may contribute to pathogenesis and immune dysregulation during pregnancy, as well as the possibilities of leveraging PAS components as biomarkers for the prevention, diagnosis, and management of PM.

Vitamin D Receptor-Interplay in COVID-19-Negative, -Infected, and -Vaccinated Women during Pregnancy.

Background: The trophoblast is a significant source of vitamin D synthesis during pregnancy, with the literature suggesting its role in fetal growth. We aim to underline a possible mechanism that would explain negative fetal outcomes in COVID-19-positive mothers by examining the relationship between altered placental structure and function and throphoblast cells' vitamin D receptor levels. Methods: The study included 170 placental samples collected from women who gave birth at term without complications, divided into three groups: COVID-19-positive and unvaccinated, COVID-19-negative and vaccinated, and COVID-19-negative and unvaccinated, with exclusion criteria for any other medical complications. Immunohistochemistry (IHC) was performed to detect vitamin D receptor (VDR) expression, and immediate fetal outcomes (weight and Apgar score) were assessed. Results: We found lower gestational age at birth, lower birth weight, and reduced placental VDR (vitamin D receptor) levels in COVID-19-positive women compared to COVID-19-vaccinated and COVID-19-negative women. Conclusions: The presence of the vitamin D receptor in the placenta is related to fetal and placental growth. Its deficiency may contribute to negative fetal outcomes in COVID-19-positive cases.

Trophoblast-specific overexpression of adiponectin receptor 2 causes fetal growth restriction in pregnant mice.

Maternal obesity in pregnancy is strongly associated with complications such as fetal overgrowth and infants of obese mothers have an increased risk to develop obesity, diabetes, and cardiovascular disease later in life. However, the underlying mechanisms are not well established. Circulating levels of adiponectin are low in obese pregnant women and maternal circulating adiponectin is negatively associated with birth weight. We have reported that normalizing maternal adiponectin in obese pregnant mice prevents placental dysfunction, fetal overgrowth, and programming of offspring cardio-metabolic disease. However, the mechanistic link between maternal adiponectin, placental function, and fetal growth remains to be established. We hypothesized that trophoblast-specific overexpression of the adiponectin receptor 2 (Adipor2) in healthy pregnant mice inhibits placental mTORC1 signaling and nutrient transport, resulting in fetal growth restriction. Using lentiviral transduction of blastocysts with a mammalian gene expression lentiviral vector for up-regulation of Adipor2 (Adipor2-OX), we achieved a ~ 3-fold increase in placenta Adipor2 mRNA levels and a 2-fold increase of the ADIPOR2 protein in the trophoblast plasma membrane. Placenta-specific Adipor2-OX increased placental peroxisome proliferator-activated receptor-α phosphorylation, ceramide synthase expression and ceramide concentrations. Furthermore, Adipor2-OX inhibited placental mTORC1 signaling and reduced invivo placental transport of glucose and amino acids. Lastly, Adipor2-OX reduced fetal weight by 11%. These data provide mechanistic evidence that placental Adipor2 signaling directly affects fetal growth. We propose that low circulating adiponectin in maternal obesity causes fetal overgrowth and programs the offspring for cardio-metabolic disease mediated by a direct effect on placental function.

Cardiovascular health of women 10 to 20 years after placenta-related pregnancy diseases considering the possible effect of pentaerythrityl tetranitrate treatment during pregnancy on long-term maternal cardiovascular health (PAVA study).

Women developing preeclampsia (PE) or fetal growth restriction (FGR) during pregnancy are at higher risk for cardiovascular diseases (CVD) later in life. We aimed to analyse cardiovascular health of women 10-20 years after affected pregnancies in comparison to women after uneventful pregnancies. In addition, we assessed a potential long-term effect of the NO-donor pentaerythrityl tetranitrate (PETN). Women 10-20 years after severe PE, including women receiving PETN during pregnancy and matched controls were recruited and assessed for baseline clinical data and cardiovascular function by transthoracic echocardiography, VICORDER and USCOM. SPSS was used for statistical analysis. 53 participants after PE/FGR (13 with former PETN intake) and 51 controls were recruited for follow-up at an average of 14 years after index pregnancies. Compared to controls, women after PE/FGR had a significantly higher incidence of arterial hypertension (13.7% vs. 41.5%, p<0.001), and were more likely to be hypertensive (41.2% vs. 67.30%, p = 0.008). There were no differences in cardiovascular function observed. Affected women with PETN intake during pregnancy showed lower mean values for right atrial area and ventricle in comparison to controls and also to affected women without former medication. In conclusion, our study results confirm that the risk of CVD is increased in women after PE/FGR compared to women after uneventful pregnancies. Contrary to our expectations, no major cardiovascular changes were observed in our cohort 10-20 years post pregnancy. The observed differences found in right heart dimensions were within reference ranges, and should be interpreted with caution.

Comparison of fetal growth patterns from Western India with Intergrowth-21st.

To generate longitudinal fetal growth data in an Indian population and compare it with Intergrowth-21st. Fetal biometry data was collected in a prospective longitudinal observational study (REVAMP: Research Exploring Various Aspects and Mechanisms in Preeclampsia) from 2017 to 2022. Fetal crown-rump length (CRL) was measured at 11-14 weeks gestation, and biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) at 18-22 and 32-35 weeks, and converted into Z-scores using the Intergrowth standard. Generalized Additive Models for Location, Scale and Shape (GAMLSS) models were used to construct fetal growth centile curves compared against Intergrowth centiles. Out of 1096 singleton pregnancies in REVAMP, this analysis included 655 'healthy' pregnancies (uncomplicated by pre-eclampsia, diabetes, pre-term delivery or low birth weight) and a sub-set of 106 'low-risk' pregnancies defined using Intergrowth criteria. The 'healthy' study subjects showed lower mean CRL Z-score [-0.45 SD (95% CI:-0.54,-0.37)] at 11-14 weeks, and BPD Z-score [-1.2 SD (-1.28,-1.11) and -1.17 SD (-1.23,-1.1)] at 18-22 and 32-35 weeks respectively. Mean HC Z-score was comparable to the Intergrowth standard at 18-22 weeks [-0.08 SD (-0.16, 0.02)] but smaller at 32-35 weeks [-0.25 SD (-0.32,-0.19)]. Mean AC Z-score was lower at 18-22 weeks [-0.32 SD (-0.41,-0.23)] but comparable at 32-35 weeks [0.004 SD (-0.07, 0.07)]. FL was comparable to or larger than the Intergrowth standard at both time points [0.05 SD (-0.05, 0.14); 0.82 SD (0.75, 0.89), respectively]. These findings were similar, though measurements were slightly larger, in the 'low-risk' sample. This data from healthy and low-risk pregnant women in urban western India indicates that some fetal dimensions and growth trajectories differ significantly from the Intergrowth-21st. Our data suggest the need for a larger representative study to define a population-specific fetal growth reference for India, for identification of fetal growth restriction.

Phosphodiesterase Inhibitors in Fetal Growth Restriction: Do Not Forget to Consider Fetal Sex and Subcellular Compartmentation.

Fetal growth restriction (FGR) is a common complication of pregnancy, associated with major perinatal mortality and morbidity, and with an increased risk to develop cardiometabolic diseases later in life. There is currently no effective approach to prevent or treat FGR, despite numerous animal and human studies assessing substances likely to improve fetal growth. Phosphodiesterase (PDE) inhibitors appeared as promising drugs to improve FGR management. However, to date, studies have led to somewhat disappointing or controversial results. In this Opinion article, we would like to draw attention to the need to consider the biological sex and the relative reactivity of human umbilical vein and arteries when developing therapeutic interventions to improve human umbilical circulation using PDE inhibitors. Indeed, we suspect that fetal sex, vessel type and the presence of FGR may influence subcellular compartmentation, which could jeopardize beneficial effects of PDE inhibitors.

Ambient temperature exposure and rapid infant weight gain.

Childhood obesity is a major public health concern, and the global rate is rising. Rapid infant weight gain is a risk factor for later overweight. Studies have linked prenatal ambient temperature exposure to fetal growth, and preliminary evidence suggests postnatal exposure may be associated with infant weight gain. Using a population-based historical cohort study including 1100576 infants born 2011-2019, we assessed the relationship between prenatal and one-month postnatal ambient temperature exposure and rapid infant weight gain. We used a hybrid spatiotemporal model to assess temperatures at the family's recorded residence at birth. Repeated weight measurements between birth and 15 months were used to model the outcome using the SuperImposition by Translation and Rotation (SITAR) method. We employed generalized linear models and distributed lag models to estimate the association between prenatal and postnatal exposure and rapid infant weight gain, defined as the upper tertile of the SITAR growth velocity. Overall, higher ambient temperatures were associated with rapid infant weight gain. The cumulative adjusted relative risk for the highest exposure quintile during pregnancy compared with the lowest quintile was 1.33 [95% confidence interval (CI): 1.25, 1.40], and the corresponding association for the first postnatal month was 1.19 (95% CI: 1.15, 1.23). Exposure to high ambient temperature during early and mid-pregnancy, as well as the first postnatal month, was associated with rapid weight gain, while during late pregnancy, exposure to low temperatures was associated with this outcome. Prenatal and postnatal ambient temperatures are associated with rapid infant weight gain.

Methionine supply during mid-gestation modulates the bovine placental mTOR pathway, nutrient transporters, and offspring birth weight in a sex-specific manner.

The mechanistic target of rapamycin (mTOR) predominantly regulates the expression and activity of placental nutrient transporters. The mTOR pathway can be activated by several nutrients, including the essential amino acid methionine. Additionally, previous research in nonruminant animals suggests that mTOR is influenced in a sexually dimorphic manner. In bovine, there is limited understanding of how maternal nutrition and offspring sexual dimorphism affect the placental transfer of nutrients. Thus, we investigated the effects of increasing the supply of dietary methionine to beef cattle heifers during mid-gestation on mTOR signaling, placental nutrient transporters, and fetal growth in male and female offspring. Forty purebred Angus heifers were used in a randomized complete block design experiment. From day 90 to 180 of gestation, heifers received a basal diet with no added methionine (CON, n = 20), or the basal diet plus 8.3g of rumen-protected methionine (MET, n = 20) per animal daily. All animals received a basal diet in the first and third trimesters of gestation. Cotyledonary tissue samples were collected at parturition and utilized to examine the mTOR pathway and nutrient transporters through protein and gene expression analysis. The offspring's body weight was measured at birth. Data were analyzed using a mixed model that included the fixed effect of treatment, offspring sex, their interactions, and the random effect of block. At day 170 of gestation, MET-supplemented heifers showed higher plasma concentrations of methionine and glutamate (P < 0.01) and lower glycine and proline levels (P ≤ 0.01) compared to the CON group. A treatment × sex interaction was observed for calf birth weight (P = 0.03). In heifers that delivered male calves, MET supplementation increased the birth weight of the calves (P < 0.01). However, the dietary treatments had no effect on the birth weight of female calves (P = 0.32). The increase in birth weight of male calves from MET-fed heifers resembles with the upregulation of placental mTOR and phosphorylated mTOR (P ≤ 0.03), as well as the amino acid transporters SLC1A5, SLC7A5, SLC38A6, and SLC38A11, and the glucose transporters SLC2A1 and SLC2A8 (P ≤ 0.05). Our findings suggest that increasing the supply of methionine to beef heifers during mid-gestation can modulate placental nutrient transport and fetal growth in a sex-dependent manner and that these effects are mediated, at least in part, by the mTOR pathway.