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Chronic placental inflammation is a routinely diagnosed group of placental lesions that reflect immunologic dysfunction of the mother, fetus, or both. Complete placental pathology examinations were performed for all term births at New York Presbyterian- Brooklyn Methodist Hospital from January 2010–August 2016. Diagnoses were blinded except to gestational age. CPI lesions were marked as chronic choriodeciduitis, decidual plasma cells, chronic inflammation of basal plate with anchoring villitis, and chronic villitis. In this cohort of term pregnancies, 257 (11.6 %) males and 218 (9.8 %) females had ≥1 CPI lesions. Chronic villitis was the most common (319 or 14 %), with chronic choriodeciduitis, decidual plasma cells, and chronic inflammation of basal plate with anchoring villitis in 94 (4 %), 69 (3 %) and 170 (8 %), respectively. In males, chronic villitis was associated with lower gestational adjusted birthweight and had no association with placental weight. In females, chronic villitis was associated with lower gestational adjusted birthweight, but the effect became nonsignificant after adjustment for placental weight. In summary, CPI lesions' incidence and association with birth weight vary by sex. Chronic villitis is associated with lower birthweight in females; this effect is completely mediated by placental weight. Chronic villitis showed a weak direct association of chronic villitis in males, but no association with lower placental weight in males. We suggest that differences between our results and previous publications reflect effects of sampling bias. • Chronic placental inflammation is common in low-risk term pregnancies. • Chronic placental inflammation has sex-specific associations with fetal growth restriction. • Chronic villitis is the most common type of chronic placental inflammation in term pregnancies. [ABSTRACT FROM AUTHOR]

Appropriate assessment of fetal growth is essential for safe clinical care. There have been many recent strategies to improve the detection of aberrant fetal growth patterns, one of which has been to optimize fetal growth centile charts. Over recent years there has been ongoing debates regarding the optimal growth chart for clinical usage. Controversy can arise where growth charts have demonstrated wide variance in the proportion of fetuses classified within the extremities of growth. Standards for growth charts need to be evidenced based and validated against pregnancy outcomes to demonstrate clinical utility and widespread usage. They should be supplied by high quality methodological reasoning and ideally evidenced through large prospective multicentre studies. Given the variable terminology to classify growth centile charts, including the variety of charts available, a complete understanding by healthcare professional can be troublesome to achieve. This practical guide aims to provide clarity on this diverse subject. [ABSTRACT FROM AUTHOR]

Bariatric surgery is increasingly performed in women of reproductive age. As bariatric surgery will result in postoperative rapid catabolic weight loss which potentially leads to fetal malnutrition and directly related impaired intra-uterine growth, it is advised to postpone pregnancy for at least 12–18 months after surgery. To investigate the consequences of preconception gastric bypass surgery (pGB) on fetal growth parameters and maternal pregnancy outcome. Maasstad Hospital, The Netherlands, general hospital and Erasmus Medical Center, The Netherlands, university hospital. We included 97 pGB pregnancies (Maasstad hospital) and 440 non-bariatric pregnancies (Rotterdam Periconception cohort, Erasmus Medical Center). Longitudinal second and third trimester fetal growth parameters (head circumference, biparietal diameter, femur length, abdominal circumference, estimated fetal weight) were analyzed using linear mixed models, adjusting for covariates and possible confounders. Fetal growth and birthweight in pGB pregnancies were compared to non-bariatric pregnancies and Dutch reference curves. Maternal pregnancy outcome in the pGB group was compared to non-bariatric pregnancies. All fetal growth parameters of pGB pregnancies were significantly decreased at 20 weeks' gestation (P <.001) and throughout the remaining part of pregnancy (P <.05) compared with non-bariatric pregnancies (crude and adjusted models). In our cohort, gestational weight gain was not significantly associated with birthweight corrected for gestational age. Birthweight was significantly lower in pGB pregnancies (estimate –241 grams [95% CI, –342.7 to –140.0]) with a 2-fold increased risk of small-for-gestational-age (SGA) (adjusted odds ratio 2.053 [95% CI, 1.058 to 3.872]). Compared to the non-bariatric pregnancies, we found no significant differences in maternal pregnancy outcome. PGB is associated with overall reduced fetal growth trajectories and a 2-fold increased risk of SGA, without significant adverse consequences for maternal pregnancy outcome. We recommend close monitoring of fetal growth after pGB. [ABSTRACT FROM AUTHOR]

Newborns resulting from in-vitro fertilisation (IVF) had a significantly (P = 0.002) higher birthweight centile than those resulting from spontaneous conception (SC) but no significant changes were found in ultrasound estimated fetal weight (EFW) centile between 20-22 and 32–34 weeks between the IVF and SC groups. When stratified for the IVF methods used, significant (P = 0.02) fastest in-utero fetal growth (mean increase in centile of 5 between 2nd to 3rd trimester) was observed in the frozen embryo transfer (FET) subgroup compared to SC, and to IVF pregnancies resulting from fresh blastocyst transfer (FBT) or from oocyte donation (OD). Low placentation was significantly (P < 0.001) more common in the IVF group than in the SC group but was not associated with a change in growth pattern suggesting that fetal growth in-utero is independent of placental location but may be influenced by embryo freezing. • Fetal growth in singleton uncomplicated IVF conceptions is similar to spontaneous conceptions. • Frozen embryos are more likely to present with faster fetal growth in-utero. • Fetal growth in-utero is independent of the placenta position inside the uterus. [ABSTRACT FROM AUTHOR]

We determined the impact of gestational diabetes (GDM) and pre-existing diabetes (DM) on birth/placental weight and cord oxygen values with implications for placental efficiency and fetal-placental growth and development. A hospital database was used to obtain birth/placental weight, cord PO 2 and other information on patients delivering between Jan 1, 1990 and Jun 15, 2011 with GA >34 weeks (N = 69,854). Oxygen saturation was calculated from the cord PO 2 and pH data, while fetal O 2 extraction was calculated from the oxygen saturation data. The effect of diabetic status on birth/placental weight and cord oxygen values was examined adjusting for covariates. Birth/placental weights were stepwise decreased in GDM and DM compared to non-diabetics with placentas disproportionally larger indicating decreasing placental efficiency. Umbilical vein oxygen was marginally increased in GDM but decreased in DM attributed to the previously reported hyper-vascularization in diabetic placentas with absorbing surface area of capillaries initially increased, but then constrained by increasing distance from maternal blood within the intervillous space. Umbilical artery oxygen was unchanged in GDM and DM, with fetal O 2 extraction decreased in DM indicating that fetal O 2 delivery must be increased relative to O 2 consumption and likely due to increased umbilical blood flow. Increased villous density/hyper-vascularization in GDM and DM with placentas disproportionately larger and umbilical blood flow increased, are postulated to normalize umbilical artery oxygen despite increased birth weights and growth-related O 2 consumption. These findings have implications for mechanisms signaling fetal-placental growth and development in diabetic pregnancies and differ from that reported with maternal obesity. • Birth/placental wt is decreased in diabetics as a measure of placental efficiency. • UmV O 2 is increased in GDM but decreased in DM as a measure of placental O 2 delivery. • UmA O 2 is unchanged in GDM and DM as a measure of fetal systemic O 2 levels. • Diabetic cord O 2 findings can be attributed to reported differences in placental development. [ABSTRACT FROM AUTHOR]

The primary focus of this study is to elucidate the adverse effect of dried leaf extract of spearmint (SE) on histomorphometry of ovaries and uterus of pregnant albino rats along with weight and crown-rump length (CRL) of their fetuses. Albino rats (n=30) were split into three groups, viz; Group A (Placebo), Group B (0.3g/kg SE) and Group C (0.6g/kg SE). The SE was administered for 30 days through gastric intubation. On 31st day of experiment, a male was introduced for 5-days in each group to make the female rats pregnant. SE was administered till the parturition of the neonates. At parturition, the maternal uteri and ovaries and neonates’ renal and hepatic tissues were histological analyzed along with the blood for progesterone level. Results means were compared by Mann-Whitney test. The body-weights of experimental groups decreased significantly while counter-part of ovaries followed reverse trend. The ovaries showed atrophied antral, graafian-follicle and corpora lutea. The layer thickness of uteri was also decreased. The degenerative changes in the renal and hepatic tissues were observed with decreased weight and crown-rump-length of neonates. In the light of these results, further research work should be carried out to evaluate its other toxic effects on different organs of the body. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Studies of possible implications of the maternal hepatitis C virus (HCV) infection in terms of intrauterine fetal growth restriction (IUGR), preterm birth (PTB), low birth weight (LBW) infants, premature rupture of membranes (PROM), maternal and neonatal mortality are limited and inconclusive. Our study aims to assess the impact of HCV on maternal and neonatal outcomes. MATERIALS AND METHODS: Systematic literature search was done in PubMed, Scopus, and Google Scholar, Cochrane Library, and TRIP databases for all observational studies published from 1st January 1950 to 15th October 2022. The pooled odds ratio (OR) or risk ratio (RR) with a 95% confidence interval (CI) was estimated. STATA version 12.0 software was used for analysis. Heterogeneity among the included articles was evaluated by sensitivity, meta-regression, and publication bias analyses. RESULTS: A total of 14 studies involving 12,451 HCV (+) and 56,42,910 HCV (-) pregnant women were included in our meta-analysis. Maternal HCV during pregnancy was significantly associated with the increased risk of PTB (OR=1.66, 95% CI: 1.59-1.74), IUGR (OR=2.09, 95% CI: 2.04-2.14) and LBW (OR=1.96, 95% CI: 1.63-2.36) as compared to healthy pregnant women. Subgroup analysis based on ethnicity also suggested a strong association between maternal HCV infection and a higher risk of PTB in Asian and Caucasian populations. Maternal (RR=3.44, 95% CI: 1.85-6.41), as well as neonatal (RR=1.54, 95% CI: 1.18-2.02) mortality was significantly higher in HCV (+) cases. CONCLUSIONS: Mothers with HCV infection had a markedly increased probability of PTB and/or IUGR and/or LBW. In clinical practice, standard care of treatment and proper monitoring are needed for the pregnant population with HCV infection. Our findings may provide useful information for selecting appropriate therapy methods for HCV-positive pregnant women. [ABSTRACT FROM AUTHOR]

Introduction: The pathological decrease of fetal growth during gestation can lead to subsequent poor health outcomes for the fetus. This process is commonly controlled by the placenta, the interface between mother and baby during gestation. Sex-specific gene expression has been implicated in placental function, therefore, there is a need to determine if it is important during reduced fetal growth. We therefore aimed to characterise placental gene expression at term to evaluate sex-specific genetic changes that occur in small for gestational age (SGA) infants.Methods: RNA-sequencing of twelve human placental tissue samples collected from pregnancies yielding either term appropriate for gestational age (AGA) or SGA infants identified at delivery. Candidate genes associated with fetal size and fetal sex were identified using differential gene expression and weighted gene co-expression network analyses. Single-cell sequencing data was used for candidate validation and to estimate candidate transcript expression in specific placental cell populations.Results: Differential gene expression and weighted gene co-expression network analyses identified 403 candidate transcripts associated with SGA infants. One hundred and three of these transcripts showed sex-specific expression. . Published placental sequencing datasets were used to validate the key expression results from the twelve placental samples initially studied; the sex-independent transcript expression for genes involved in cell cycle processes in males (7 transcripts) and endoplasmic reticulum stress in females (17 transcripts).Discussion: This study identified the activation of multiple molecular mechanisms involved in the placental response to an adverse environmental stressor. Mechanisms such as disrupted protein synthesis were shared between infant biological sex when comparing AGA to SGA, whilst other pathways such as cell cycle and endoplasmic reticulum stress appear as independent/specific to either males or females when investigating reduced fetal growth. This data suggests that sexual dimorphism is an important consideration when examining placental dysfunction and poor fetal growth. [ABSTRACT FROM AUTHOR]

Background: Some synthetic phenols alter pathways involved in fetal development. Despite their high within-subject temporal variability, earlier studies relied on spot urine samples to assess pregnancy exposure. In this study, we examined associations between prenatal phenol exposure and fetal growth.Methods: We measured concentrations of two bisphenols, four parabens, benzophenone-3, and triclosan in 478 pregnant women in two weekly pools of 21 samples each, collected at 18 and 34 gestational weeks. We used adjusted linear regressions to study associations between phenol concentrations and growth outcomes assessed twice during pregnancy and at birth.Results: Benzophenone-3 was positively associated with all ultrasound growth parameters in at least one time point, in males but not females. In females, butylparaben was negatively associated with third-trimester abdominal circumference and weight at birth. We observed isolated associations for triclosan (negative) and for methylparaben and bisphenol S (positive) and late pregnancy fetal growth.Conclusions: Our results suggest associations between prenatal exposure to phenols and fetal growth. Benzophenone-3 was the exposure most consistently (positively) associated across all growth parameters. [ABSTRACT FROM AUTHOR]

Background: We previously identified associations between trimester-specific NO2 exposures and reduced fetal growth in the Spanish INfancia y Medio Ambiente (INMA) project. Here, we use temporally refined exposure estimates to explore the impact of narrow (weekly) windows of exposure on fetal growth. Methods: We included 1,685 women from INMA with serial ultrasounds at 12, 20, and 34 gestational weeks. We measured biparietal diameter (BPD), femur length, and abdominal circumference (AC) and from them calculated estimated fetal weight (EFW). We calculated z-scores describing trajectories of each parameter during early (0-12 weeks), mid (12-20 weeks), and late (20-34 weeks) pregnancy, based on longitudinal growth curves from mixed-effects models. We estimated weekly NO2 exposures at each woman's residence using land-use regression models. We applied distributed lag nonlinear models to identify sensitive windows of exposure. We present effect estimates as the percentage change in fetal growth per 10 [mu]g/m3 increase in NO2 exposure, and we calculated cumulative effect estimates by aggregating estimates across adjacent lags. Results: We identified weeks 5-12 as a sensitive window for NO2 exposure on late EFW (cumulative [beta] = -3.0%; 95% CI = -4.1%, -1.9%). We identified weeks 6-19 as a sensitive window for late growth in BPD (cumulative [beta] = -2.0%; 95% CI = -2.7%, -1.4%) and weeks 8-13 for AC (cumulative [beta] = -0.68%; 95% CI = -0.97%, -0.40%). We found suggestive evidence that third trimester NO2 exposure is associated with increased AC, BPD, and EFW growth in late pregnancy. Conclusions: Our findings are consistent with the hypothesis that NO2 exposure is associated with alterations in growth of EFW, BPD, and AC dependent on the specific timing of exposure during gestation. [ABSTRACT FROM AUTHOR]

This study reviewed the literature about the diagnosis, antepartum surveillance, and time of delivery of fetuses suspected to be small for gestational age or growth restricted. Several guidelines have been issued by major professional organizations, including the International Society of Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine. The differences in recommendations, in particular about Doppler velocimetry of the ductus venosus and middle cerebral artery, have created confusion among clinicians, and this review has intended to clarify and highlight the available evidence that is pertinent to clinical management. A fetus who is small for gestational age is frequently defined as one with an estimated fetal weight of <10th percentile. This condition has been considered syndromic and has been frequently attributed to fetal growth restriction, a constitutionally small fetus, congenital infections, chromosomal abnormalities, or genetic conditions. Small for gestational age is not synonymous with fetal growth restriction, which is defined by deceleration of fetal growth determined by a change in fetal growth velocity. An abnormal umbilical artery Doppler pulsatility index reflects an increased impedance to flow in the umbilical circulation and is considered to be an indicator of placental disease. The combined finding of an estimated fetal weight of <10th percentile and abnormal umbilical artery Doppler velocimetry has been widely accepted as indicative of fetal growth restriction. Clinical studies have shown that the gestational age at diagnosis can be used to subclassify suspected fetal growth restriction into early and late, depending on whether the condition is diagnosed before or after 32 weeks of gestation. The early type is associated with umbilical artery Doppler abnormalities, whereas the late type is often associated with a low pulsatility index in the middle cerebral artery. A large randomized clinical trial indicated that in the context of early suspected fetal growth restriction, the combination of computerized cardiotocography and fetal ductus venosus Doppler improves outcomes, such that 95% of surviving infants have a normal neurodevelopmental outcome at 2 years of age. A low middle cerebral artery pulsatility index is associated with an adverse perinatal outcome in late fetal growth restriction; however, there is no evidence supporting its use to determine the time of delivery. Nonetheless, an abnormality in middle cerebral artery Doppler could be valuable to increase the surveillance of the fetus at risk. We propose that fetal size, growth rate, uteroplacental Doppler indices, cardiotocography, and maternal conditions (ie, hypertension) according to gestational age are important factors in optimizing the outcome of suspected fetal growth restriction. [ABSTRACT FROM AUTHOR]

Congenital heart defects (CHDs) are the most common birth defect worldwide. The morbidity and mortality associated with these defects is compounded by increased frequency of fetal growth abnormalities. In the Ohia mouse model of hypoplastic left heart syndrome (HLHS), the double homozygous genotype is embryonically lethal at mid-pregnancy; a time in which optimal establishment of the placenta is crucial to fetal survival. We aimed to characterize placental and fetal growth and development in the double heterozygous genotype (Sap130m/+Pcdha9m/+). There was a shift in frequency of fetuses with reduced weight near term in the Sap130m/+Pcdha9m/+ fetuses compared to wildtype, driven by lower fetal weight in male fetuses compared to female. This shift in fetal weight distribution in the Sap130m/+Pcdha9m/+ fetuses was associated with reduced labyrinth region area (P < 0.001) and reduced fetal capillary density (P < 0.001) in the placentas, the latter being significantly lower in male Sap130m/+Pcdha9m/+ placentas compared to female. mRNA expression of several nutrient transporters was also lower in placentas from males compared to placentas from females, irrespective of genotype. Overall, this data shows that whilst the double heterozygous fetuses do not carry heart defects, placental development and function is impaired, particularly in males. Such differences are similar to findings in studies of human placentas and highlights the importance of this mouse model in continuing to understand the developmental links and disruptions to the heart-placenta axis. [ABSTRACT FROM AUTHOR]

Equine-Assisted Therapy (EAT) is gaining popularity. Ultrasound examination is used to decrease the abortion rate in horses. In this study, to monitor fetal well-being throughout the gestation for EAT, we measured fetal heart rate (FHR), fetal eye orbit (FEO), fetal gonad length (FGL), fetal kidney length (FKL), and the combined thickness of the uterus and placenta (CTUP) by ultrasonography in pony mares. Additionally, we measured the plasma progesterone (P4) and estradiol (E2) concentrations in pregnant horses using enzyme immunoassay. The FGL peaked at week 32 and then decreased to term, and a strong correlation (r=0.72, P<0.001) between the FGL and E2 concentration was observed. A strong correlation with gestational age was detected among the FEO (r=0.96, P<0.001), FKL (r=0.85, P<0.001), and CTUP (r=0.96, P<0.001). The P4 concentration peaked at week 10, decreased to low levels (below 5 ng/ml), and peaked before parturition. In conclusion, this study provides information on fetal growth throughout gestation in pony mares for EAT. In addition, it revealed the relationship between ultrasonographic profile and plasma hormone concentrations during gestation. [ABSTRACT FROM AUTHOR]

Background: Fetal growth restriction is commonly defined using small-for-gestational-age (SGA) birth (birthweight <10th percentile) as a proxy, but this approach is problematic because most SGA infants are small but healthy. In this proof-of-concept study, we sought to develop a new approach for identifying fetal growth restriction at birth that combines information on multiple, imperfect measures of fetal growth restriction in a probabilistic manner.Methods: We combined information on birthweight, placental weight, placental malperfusion lesions, maternal disease, and fetal acidemia using latent profile analysis to classify fetal growth in births at the Royal Victoria Hospital in Montreal, Canada, 2001-2009. We examined the clinical characteristics and health outcomes of infants classified as growth-restricted and non-growth-restricted by our model, and among the subgroup of growth-restricted infants who had a birthweight ≥10th percentile (i.e., would have been missed by the conventional SGA proxy).Results: Among 26,077 births, 345 (1.3%) were classified as growth-restricted by our latent profile model. Growth-restricted infants were more likely than non-growth-restricted infants to have an Apgar score <7 (10 vs. 2%), have hypoglycemia at birth (17 vs. 3%), require neonatal intensive care unit admission (NICU, 59 vs. 6%), die in the perinatal period (3.8 vs. 0.2%), and require an emergency cesarean delivery (42 vs. 15%). Risks remained elevated in growth-restricted infants who were not SGA, suggesting our model identified at-risk infants not detected using the SGA proxy.Conclusions: Latent profile analysis is a promising strategy for classifying growth restriction at birth in fetal growth restriction research. [ABSTRACT FROM AUTHOR]

Background: Being born small for gestational age (SGA, <10th percentile) is a risk factor for worse neurodevelopmental outcomes. However, this group is a heterogeneous mix of healthy and growth-restricted babies, and not all will experience poor outcomes. We sought to determine whether fetal growth trajectories can distinguish who will have the worst neurodevelopmental outcomes in childhood among babies born SGA.Methods: The present analysis was conducted in Generation R, a population-based cohort in Rotterdam, the Netherlands (N = 5,487). Using group-based trajectory modeling, we identified fetal growth trajectories for weight among babies born SGA. These were based on standard deviation scores of ultrasound measures from mid-pregnancy and late pregnancy in combination with birth weight. We compared child nonverbal intelligence quotient (IQ) and attention deficit hyperactivity disorder (ADHD) symptoms at age 6 between SGA babies within each growth trajectory to babies born non-SGA.Results: Among SGA individuals (n = 656), we identified three distinct fetal growth trajectories for weight. Children who were consistently small from mid-pregnancy (n = 64) had the lowest IQ (7 points lower compared to non-SGA babies, 95% confidence interval [CI] = -11.0, -3.5) and slightly more ADHD symptoms. Children from the trajectory that started larger but were smaller at birth showed no differences in outcomes compared to children born non-SGA.Conclusions: Among SGA children, those who were smaller beginning in mid-pregnancy exhibited the worst neurodevelopmental outcomes at age 6. Fetal growth trajectories may help identify SGA babies who go on to have poor neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Paternal low-protein diet can alter sperm methylation status, fetal growth and program offspring ill-health, however its impact on the placenta remains poorly defined. Here we examine the influence paternal low-protein diet has on fetal and placental development and the additional impact of supplementary methyl-donors on fetoplacental physiology.Methods: Male C57BL/6J mice were fed a control normal protein diet (NPD; 18% protein), a low-protein diet (LPD; 9% protein) or LPD with methyl-donor supplementation (MD-LPD; choline chloride, betaine, methionine, folic acid, vitamin B12) for a minimum of 8 weeks. Males were mated with 8-11 week old female C57BL/6J mice and fetal and placental tissue collected on embryonic day 17.5.Results: Paternal LPD was associated with increased fetal weights compared to NPD and MD-LPD with 22% fetuses being above the 90th centile for fetal weight. However, LPD and MD-LPD placental weights were reduced when compared to NPD. Placentas from LPD fathers demonstrated a reduced junctional zone area and reduced free-fatty acid content. MD-LPD placentas did not mirror these finding, demonstrating an increased chorion area, a reduction in junctional-specific glycogen staining and reduced placental Dnmt3bexpression, none of which were apparent in either NPD or LPD placentas.Discussion: A sub-optimal paternal diet can influence fetal growth and placental development, and dietary methyl-donor supplementation alters placental morphology and gene expression differentially to that observed with LPD alone. Understanding how paternal diet and micro-nutrient supplementation influence placental development is crucial for determining connections between paternal well-being and future offspring health. [ABSTRACT FROM AUTHOR]

Background: Women can be exposed to a multitude of hardships before and during pregnancy that may affect fetal growth, but previous approaches have not analyzed them jointly as social exposure mixtures.Methods: We evaluated the independent, mutually adjusted, and pairwise joint associations between self-reported hardships and birthweight for gestational age z-scores in the Chemicals in Our Bodies-2 prospective birth cohort (N = 510) using G-computation. We examined financial hardship, food insecurity, job strain, poor neighborhood environment, low community standing, caregiving, high burden of stressful life events, and unplanned pregnancy collected via questionnaire administered in the second trimester of pregnancy. We used propensity scores to ensure our analyses had sufficient data support and estimated absolute differences in outcomes.Results: Food insecurity was most strongly associated with reduced birthweight for gestational age z-scores individually, with an absolute difference of -0.16, 95% confidence interval (CI) -0.45, 0.14. We observed an unexpected increase in z-scores associated with poor perceived neighborhood environment (0.18, 95% CI -0.04, 0.41). Accounting for coexposures resulted in similar findings. The pairwise joint effects were strongest for food insecurity in combination with unplanned pregnancy (-0.45, 95% CI -0.93, 0.02) and stressful life events (-0.42, 95% CI -0.90, 0.05). Poor neighborhood environment in combination with caregiving was associated with an increase in z-scores (0.47, 95% CI -0.01, 0.95).Conclusions: Our results are consistent with the hypothesis that experiencing food insecurity during pregnancy, alone and in combination with stressful life events and unplanned pregnancy, may affect fetal growth. [ABSTRACT FROM AUTHOR]

Background: Fetal growth standards (prescriptive charts derived from low-risk pregnancies) are theoretically better tools to monitor fetal growth than conventional references. We examined how modifying chart inclusion criteria influenced the resulting curves.Methods: We summarized estimated fetal weight (EFW) distributions from a hospital's routine 32-week ultrasound in all nonanomalous singleton fetuses (reference) and in those without maternal-fetal conditions affecting fetal growth (standard). We calculated EFWs for the 3rd, 5th, 10th, and 50th percentiles, and the proportion of fetuses each chart classified as small for gestational age.Results: Of 2309 fetuses in our reference, 690 (30%) met the standard's inclusion criteria. There were no meaningful differences between the EFW distributions of the reference and standard curves (50th percentile: 1989 g reference vs. 1968 g standard; 10th percentile: 1711 g reference vs. 1710 g standard), or the proportion of small for gestational age fetuses (both 9.9%).Conclusions: In our study, there was little practical difference between a fetal growth reference and standard for detecting small infants. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a global health issue with significant short and long-term complications for both mother and baby. There is a strong need to identify an effective therapeutic that can prevent the development of GDM. A better understanding of the pathophysiology of GDM and the relationship between the adipose tissue, the placenta and fetal growth is required. The placenta regulates fetal growth by modulating nutrient transfer of glucose, amino acids and fatty acids. Various factors secreted by the adipose tissue, such as adipokines, adipocytokines and more recently identified extracellular vesicles, can influence inflammation and interact with placental nutrient transport. In this review, the role of the placental nutrient transporters and the adipose-derived factors that can influence their function will be discussed. A better understanding of these factors and their relationship may make a potential target for therapeutic interventions to prevent the development of GDM and its consequences. [ABSTRACT FROM AUTHOR]

Background: Birthweight is a critical predictor of congenital heart disease (CHD) surgical outcomes. Hypoplastic left heart syndrome (HLHS) is cyanotic CHD with known fetal growth restriction and placental abnormalities. Transposition of the great arteries (TGA) is cyanotic CHD with normal fetal growth. Comparison of the placenta in these diagnoses may provide insights on the fetal growth abnormality of CHD.Methods: Clinical data and placental histology from placentas associated with Transposition of the Great Arteries (TGA) were analyzed for gross pathology, morphology, maturity and vascularity and compared to both control and previously analyzed HLHS placentas [1]. RNA was isolated from HLHS, TGA and control placentas and sequenced by Illumina HiSeq.Transcriptome analysis was performed using AltAnalyze. Immunohistochemistry was utilized to assess placental nutrient transporter expression in all three groups.Results: Placental weight was reduced in TGA cases, and demonstrated reduced villous vasculature, immature terminal villi in the parenchyma compared to controls and reflected our previous data from HLHS placentas. However, birth weight was not reduced in TGA cases compared to controls in contrast to the HLHS cohort and birthweight:placental weight ratio was significantly increased in TGA cases but not HLHS compared to control. Transcriptomic and histologic analysis demonstrates reduced cell activity and nutrient transport capability in HLHS but not TGA placentas which appear to increase/maintain these mechanisms.Conclusions: Despite common vascular disturbances in placentas from HLHAs and TGA, these do not account for the disparities in birthweights frequently seen between these CHD subtypes, in contrast our transcriptomic and histologic analyses reveal differentially regulated mechanisms between the subtypes that may explain these disparities. [ABSTRACT FROM AUTHOR]

Introduction: Pregnant women with sickle cell disease (SCD) are at high risk for sickle cell-related complications, obstetrical complications, and perinatal morbidity. Chronic inflammation and the proangiogenic environment associated with SCD have been associated with endothelial damage. It is unknown whether SCD complications could be associated with placental dysfunction or abnormal placental morphology. Moreover, circulating angiogenic factors in pregnant women with SCD are unexplored.Methods: Clinical records, placental and blood samples were collected at term delivery for 21 pregnant patients with SCD and 19 HbAA pregnant controls with adapted to gestational age birth weight newborns. Histological and stereological analyses and scanning electron microscopy (SEM) of the placenta, and PlGF and sFlt1 measurements in blood were performed.Results: In the SCD group, the parenchyma-forming villi of placentas were thinner than in controls, and increased fibrinoid necrosis and an overabundance of syncytial knots were seen. SEM revealed elongated intermediate villous endings with a reduction in the number of terminal villi compared to controls, indicating a significant branching defect in SCD placentas. Finally, SCD patients had an imbalance in the angiogenic ratio of sFlt1/PlGF (p = 0.008) with a drop of PlGF concentrations.Discussion: We evidence for the first time both abnormal placenta morphology and altered sFlt1/PlGF ratio in SCD patients, uncorrelated with maintained placental efficiency and fetal growth. [ABSTRACT FROM AUTHOR]

Pregnancy is a remarkable physiological state, during which the metabolic system of the mother adapts to ensure that nutrients are made available for transfer to the fetus for growth and development. Adaptations of maternal metabolism during pregnancy are influenced by the metabolic and nutritional status of the mother and the production of endocrine factors by the placenta that exert metabolic effects. Insufficient or inappropriate adaptations in maternal metabolism during pregnancy may lead to pregnancy complications with important short- and long-term effects for both the health of the child and mother. This is very evident in gestational diabetes, which is marked by greater glucose intolerance and insulin resistance above that expected of a normal pregnancy. Gestational diabetes is associated with increased fetal weight and/or increased adiposity, higher instrumented delivery rates and greater risks for both mother and child of developing type 2 diabetes in the long-term. However, despite the negative health impacts of such metabolic imbalances during pregnancy, the precise mechanisms responsible for orchestrating these changes remain largely unknown. The present review describes the dynamic pregnancy-specific changes that occur in the metabolic system of the mother during pregnancy. It also discusses findings using surgical, pharmacological, genetic and dietary methods in experimental animals that highlight the role of pathways in maternal tissues that lead to metabolic dysfunction, with a particular focus on gestational diabetes. Finally, it summarises the work largely employing gene targeting and hormone administration in rodents that have illuminated the involvement of placental endocrine function in driving maternal metabolic adaptations. While current animal models may not fully replicate what is observed in humans, these have been instrumental in showing that there is a dynamic interplay between changes in maternal metabolic physiology and the placental production of endocrine factors that govern the availability of nutrients to the growing fetus. However, more work is required to specifically identify the placenta-driven changes in maternal metabolic physiology that ensure the appropriate level of insulin production and action during pregnancy. In doing so, these studies may pave the way to understanding the development of pregnancy complications like gestational diabetes, as well as further our understanding of type-2 diabetes and the control of metabolic physiology more broadly. [ABSTRACT FROM AUTHOR]

Recent revolutionary advances at the intersection of medicine, omics, data sciences, computing, epidemiology, and related technologies inspire us to ponder their impact on health. Their potential impact is particularly germane to the biology of pregnancy and perinatal medicine, where limited improvement in health outcomes for women and children has remained a global challenge. We assembled a group of experts to establish a Pregnancy Think Tank to discuss a broad spectrum of major gestational disorders and adverse pregnancy outcomes that affect maternal-infant lifelong health and should serve as targets for leveraging the many recent advances. This report reflects avenues for future effects that hold great potential in 3 major areas: developmental genomics, including the application of methodologies designed to bridge genotypes, physiology, and diseases, addressing vexing questions in early human development; gestational physiology, from immune tolerance to growth and the timing of parturition; and personalized and population medicine, focusing on amalgamating health record data and deep phenotypes to create broad knowledge that can be integrated into healthcare systems and drive discovery to address pregnancy-related disease and promote general health. We propose a series of questions reflecting development, systems biology, diseases, clinical approaches and tools, and population health, and a call for scientific action. Clearly, transdisciplinary science must advance and accelerate to address adverse pregnancy outcomes. Disciplines not traditionally involved in the reproductive sciences, such as computer science, engineering, mathematics, and pharmacology, should be engaged at the study design phase to optimize the information gathered and to identify and further evaluate potentially actionable therapeutic targets. Information sources should include noninvasive personalized sensors and monitors, alongside instructive "liquid biopsies" for noninvasive pregnancy assessment. Future research should also address the diversity of human cohorts in terms of geography, racial and ethnic distributions, and social and health disparities. Modern technologies, for both data-gathering and data-analyzing, make this possible at a scale that was previously unachievable. Finally, the psychosocial and economic environment in which pregnancy takes place must be considered to promote the health and wellness of communities worldwide. [ABSTRACT FROM AUTHOR]

Introduction: Recently, Delta-like homolog 1 (DLK1) was identified as a potential marker of small-for-gestational-age (SGA; <10th centile) fetuses; mouse studies suggest reduced levels may represent a fetal stress signal. We sought to measure DLK1 in a large independent cohort of maternal blood samples, correlate levels with measures of placental insufficiency and assess whether DLK1 might be placental derived.Methods: The Fetal Longitudinal Assessment of Growth (FLAG) study was a prospective blood collection from 2000 women. We assessed a case-control cohort at 28 and 36 weeks from the first 1000 FLAG women, before validating changes in the entire second 1000. A subgroup of FLAG participants underwent ultrasound examinations, and 137 neonates, body composition assessment (PEAPOD). DLK1 secretion was assessed from human placentas ex vivo.Results: Circulating DLK1 was significantly reduced at 28 and 36 weeks' gestation in women destined to deliver a SGA fetus and associated with birthweight centile (n = 999, p < 0.0001), and placental weight (n = 96, p = 0.0064). Ex vivo, DLK1 was abundantly released from human placenta and significantly reduced under hypoxia (n = 7, p < 0.05). We found no relationship between circulating DLK1 and estimated fetal weight, cerebroplacental ratio, uterine artery or umbilical artery pulsatility index. Nor was there a relationship between DLK1 and neonatal fat or lean mass (n = 137).Conclusion: We confirmed circulating DLK1 is reduced at both 28 and 36 weeks' gestation preceding delivery of a SGA infant, shown that it is not significantly associated with clinical measures of placental insufficiency, and provide new data demonstrating it may be placenta-derived in humans. [ABSTRACT FROM AUTHOR]

Down syndrome is associated with several comorbidities, including intellectual disability, growth restriction, and congenital heart defects. The prevalence of Down syndrome–associated comorbidities is highly variable, and intellectual disability, although fully penetrant, ranges from mild to severe. Understanding the basis of this interindividual variability might identify predictive biomarkers of in utero and postnatal outcomes that could be used as endpoints to test the efficacy of future therapeutic interventions. The main objective of this study was to examine if antenatal interindividual variability exists in mouse models of Down syndrome and whether applying statistical approaches to clinically relevant measurements (ie, the weights of the embryo, placenta, and brain) could define cutoffs that discriminate between subgroups of trisomic embryos. Three commonly used mouse models of Down syndrome (Dp(16)1/Yey, Ts65Dn, and Ts1Cje) and a new model (Ts66Yah) were used in this study. Trisomic and euploid littermate embryos were used from each model with total numbers of 102 for Ts66Yah, 118 for Dp(16)1/Yey, 92 for Ts65Dn, and 126 for Ts1Cje. Placental, embryonic, and brain weights and volumes at embryonic day 18.5 were compared between genotypes in each model. K-mean clustering analysis was applied to embryonic and brain weights to identify severity classes in trisomic embryos, and brain and placental volumetric measurements were compared between genotypes and classes for each strain. In addition, Ts66Yah embryos were examined for malformations because embryonic phenotypes have never been examined in this model. Reduced body and brain weights were present in Ts66Yah, Dp(16)1/Yey, and Ts65Dn embyos. Cluster analysis identified 2 severity classes in trisomic embryos—mild and severe—in all 4 models that were distinguishable using a putative embryonic weight cutoff of <0.5 standard deviation below the mean. Ts66Yah trisomic embryos develop congenital anomalies that are also found in humans with Down syndrome, including congenital heart defects and renal pelvis dilation. Statistical approaches applied to clinically relevant measurements revealed 2 classes of phenotypic severity in trisomic mouse models of Down syndrome. Analysis of severely affected trisomic animals may facilitate the identification of biomarkers and endpoints that can be used to prenatally predict outcomes and the efficacy of treatments. [ABSTRACT FROM AUTHOR]

Sleep disordered breathing is extremely common in pregnancy and is a risk factor for maternal complications. Animal models demonstrate that intermittent hypoxia causes abnormal fetal growth. However, there are conflicting data on the association between maternal sleep disordered breathing and offspring growth in humans. We investigated this association by conducting a systematic review and meta-analysis. Sixty-three manuscripts, and total study population of 67, 671, 110 pregnant women were included. Thirty-one studies used subjective methods to define sleep disordered breathing, 24 applied objective methods and eight used international codes. Using a random effects model, habitual snoring, defined by subjective methods, and obstructive sleep apnea, diagnosed by objective methods, were associated with an increased risk for large for gestational age (OR 1.46; 95%CI 1.02–2.09 and OR 2.19; 95%CI 1.63–2.95, respectively), while obstructive sleep apnea, identified by international codes, was associated with an increased risk for small for gestational age newborns (OR 1.28; 95%CI 1.02–1.60). Our results support that maternal sleep disordered breathing is associated with offspring growth, with differences related to the type of disorder and diagnostic methods used. Future studies should investigate underlying mechanisms and whether treatment of sleep disordered breathing ameliorates the neonatal growth. [ABSTRACT FROM AUTHOR]

Birthweight is an indicator of fetal development and intrauterine conditions and is associated with future health outcomes. Secular birthweight trends prior to the 1970s are mostly unknown. Our aim was to explore secular birthweight trends in Swedish boys from 1950 to 2010. We have collected detailed growth data including birthweight from archived School Health Care records for children born in Gothenburg from 1946 and onwards and established a unique population-based cohort, the Body Mass Index Epidemiology Study (BEST). The birthweight cohort spans six decades (1950–2010) and includes 46,548 boys. The mean birthweight of the complete study cohort was 3580 ± 562 g. Linear regression analysis of the entire period revealed a minimal negative secular trend for birthweight (BETA = −0.4 g/year; p < 0.01). However, three distinct trends appeared during sub-periods: a decrease 1950–80, an increase 1980–2000 and another decrease 2000–2010. We demonstrate that birthweight in boys has undergone periodic decreases and subsequent increases, but the overall trend from the 1950s to the present is stable. [ABSTRACT FROM AUTHOR]

Fetal growth, an important predictor of cardiometabolic diseases in adults, is influenced by maternal and fetal genetic and environmental factors. We investigated the association between maternal lipid genetic risk score (GRS) and fetal growth among 4 US racial–ethnic populations (Whites, Blacks, Hispanics, and Asians). We extracted genotype data for 2008 pregnant women recruited in the National Institute of Child Health and Human Development Fetal Growth Studies—Singleton cohort with up to 6 standardized ultrasound examinations. GRS was calculated using 240 single-nucleotide polymorphisms previously associated with higher total cholesterol (GRS TChol), low-density lipoprotein cholesterol (GRS LDLc), and triglycerides (GRS TG) and lower high-density lipoprotein cholesterol (GRS HDLc). At 40 weeks' gestation, a unit increase in GRS TG was associated with 11.4 g higher fetal weight (95% confidence interval [CI] 2.8–20.0 g) among normal-weight Whites, 26.3 g (95% CI 6.0–46.6 g) among obese Blacks, and 30.8 g (95% CI 6.3–55.3 g) among obese Hispanics. Higher GRS HDLc was associated with increased fetal weight across 36 to 40 weeks among normal-weight Whites and across 13 to 20 weeks among normal-weight Asians, but with decreased fetal weight across 26 to 40 weeks among normal-weight Hispanics. Higher GRS TChol was suggestively associated with increased fetal weight in males and decreased in females. Associations remained consistent after adjustment for serum lipids. Associations between fetal weight and maternal lipid GRS appear to vary by maternal race–ethnic group, obesity status, and offspring sex. Genetic susceptibility to unfavorable lipid profiles contributes to fetal growth differences even among normal-weight women suggesting a potential future application in predicting aberrant fetal growth. • Genetic risk score (GRS) and fetal weight (FW) associations vary by race–ethnicity, body mass index, and fetal sex. • GRS for triglycerides was associated with increased FW in normal-weight Whites and obese Blacks. • GRS for high-density lipoprotein cholesterol increased FW in normal-weight Whites and Asians but decreased in Hispanics. • GRS for total cholesterol was associated with increased FW in males and decreased in females. • Results suggests that the GRS for low-density lipoprotein cholesterol may operate by modulating circulating low-density lipoprotein cholesterol. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the association between fetal congenital heart defects (CHDs) and measures of brain size throughout pregnancy, from the end of the first trimester to birth.Study Design: The cohort consisted of all fetuses scanned in Western Denmark in 2012 and 2013. Anthropometric measures in fetuses with isolated CHDs diagnosed within 12 months after birth were compared with those in the fetuses without CHDs. Z-scores standardized to gestational age were calculated for first trimester biparietal diameter, second trimester head circumference, fetal weight, birthweight, head circumference, and placental weight.Results: We obtained data from 63 349 pregnancies and identified 295 fetuses with isolated CHDs (major n = 145; minor n = 150). The first trimester mean biparietal diameter Z-scores were not different between those with and those without CHDs. The head circumference mean Z-score difference was -0.13 (95% CI, -0.24 to -0.01; P = .03) in the second trimester and -0.22 (95% CI, -0.35 to -0.09; P < .001) at birth. Fetuses with univentricular physiology or tetralogy of Fallot showed the most pronounced compromise in cerebral size.Conclusions: Our results suggest that the brain alterations inducing an increased risk of impaired neurodevelopment in children with CHDs begin during pregnancy. Although fetuses with univentricular physiology or tetralogy of Fallot exhibited the most pronounced compromise in cerebral size, we recommend neurodevelopmental follow-up for all children with CHDs. [ABSTRACT FROM AUTHOR]

Introduction: Numerous studies show that males have increased intrauterine growth compared to females, and that pregnancy complications may further these growth differences, but the regulatory mechanisms underlying these differences remain unknown. We propose that these growth outcomes may be due to sex-specific differences in androgen sensitivity - giving rise to altered growth signalling pathways - mediated by the differential expression of placental androgen receptor (AR) variants.Methods: Placental protein and mRNA were used to identify AR protein variant levels and AR-downstream target gene expression, and were then analysed against neonatal measurements. Dihydrotestosterone (DHT)-induced AR protein variant expression and downstream growth factors were examined in vitro.Results: Four known AR variants (AR-FL, AR-V1, AR-V7, and AR-45), and three unknown proteins (120, 90 and 55 kDa) immunoreactive to the anti-AR antibody were identified in human placentae. Male placentae from controlled asthmatic pregnancies had increased AR-45 and decreased AR-V1 and AR-V7 nuclear expression. Increased nuclear AR-45 expression was associated with increased insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), and IGF-binding protein 5 (IGFBP-5) mRNA expression and normal male growth. AR-45 mRNA and protein did not change in the presence of uncontrolled maternal asthma and associated with an increase in small for gestational (SGA) male fetuses. In vitro DHT stimulation increased AR-45 protein and IGF-1R and IGFBP-5 mRNA expression.Conclusions: Collectively, our data shows altered AR protein expression and downstream signalling targets may contribute to sex-specific fetal growth outcomes in response to an adverse environment, and that AR-45 appears central in mediating these changes. [ABSTRACT FROM AUTHOR]

Background: Observational cohort studies have consistently shown that maternal weight gain in pregnancy is positively associated with fetal size, but it is unknown whether the association is causal. This study investigated the effect of pregnancy weight gain on fetal growth using a sibling comparison design to control for unmeasured confounding by genetic and shared environmental factors.Methods: Our study population included 44,457 infants (21,680 women) with electronic medical records in the Stockholm-Gotland Obstetrical Database, 2008-2014. We standardized pregnancy weight gain into gestational age-specific z-scores. Fetal size was classified as birthweight (gram), and as small- and large-for-gestational-age birth (birthweight <10th or >90th percentiles, respectively). Our sibling comparison analyses used multivariable linear fixed effects models for birthweight and hybrid logistic fixed effects models for small- and large-for-gestational-age birth (SGA and LGA). We repeated analyses using conventional (unmatched) regression models.Results: Sibling comparison analyses showed a clinically meaningful association between weight gain and fetal size (e.g., adjusted difference of +89 g birthweight [95% CI = 82, 95 g]; adjusted risk ratios [aRR] for SGA of 0.80 [95% CI = 0.75, 0.86] per 1 z-score increase in weight gain for a woman of body mass index [BMI] = 25). These findings were consistent across the range of BMI. Estimates were only modestly attenuated compared with conventional approach (+97 g [95% CI = 92, 102 g], aRR for SGA of 0.70 [95% CI = 0.67, 0.73] per 1 z-score increase in weight gain).Conclusion: The positive association between pregnancy weight gain and fetal size we found using a sibling comparison design suggests that this relation has minimal confounding by familial factors that remain constant between pregnancies. [ABSTRACT FROM AUTHOR]

Background and Aims: Intra-uterine metabolic environment predicts newborns' cardiac morphology, metabolism and future health. In adults, gut microbiota composition relates to altered cardiac structure and metabolism. We investigated the relationship between gut microbiota colonization and fetal cardiac growth.Methods and Results: Bacterial composition in meconium samples of 26 healthy, full-term newborns was assessed by 16S rDNA gene sequencing. Its relationship with birth echocardiographic parameters, and the interaction with cord blood levels of inflammatory markers were investigated. Correlative and cluster analysis, linear discriminant analysis effect size and predictive functional analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were applied. Fetal left ventricle growth was related to gut microbiota composition at birth. Specifically, left ventricle posterior wall thickness (LVPW) greater than 4 mm was associated with lower microbiota beta and alpha diversity, depletion (LDA score > 3) of several bacteria at each taxonomic level, including Lactobacillales, and enrichment (LDA score > 5) in Enterobacteriales and Enterobacteriaceae. The latter was significantly related to cord blood gamma-glutamyltransferase levels (r = 0.58, p = 0.0057). Functionally, a thicker LVPW was related to up-regulation of pathways involved in lipopolysaccharide biosynthesis (+50%, p = 0.045 in correlative analysis) and energy metabolism (+12%, p = 0.028), and down-regulation of pathways involved in xenobiotic biodegradation (-21 to -53%, p = 0.0063-0.039), PPAR signaling (-24%, p = 0.021) and cardiac muscle contraction (-100%, p = 0.049).Conclusion: Fetal cardiac growth and gut colonization are associated. Greater neonatal LVPW thickness is related to lower diversity of the gut microbiota community, depletion of bacteria having anti-remodeling effects, and enrichment in bacteria functionally linked to inflammation. [ABSTRACT FROM AUTHOR]

Placental mediated fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. Heparan sulphate proteoglycans (HSPG) are highly expressed in placentae and regulate haemostasis. We hypothesise that altered expression of HSPGs, glypicans (GPC) may contribute to the development of FGR and small-for-gestational-age (SGA). GPC expression was determined in first-trimester chorionic villous samples collected from women with later SGA pregnancies and in placentae from third-trimester FGR and gestation-matched uncomplicated pregnancies. The expression of both GPC1 and GPC3 were significantly reduced in first-trimester SGA as well as in the third-trimester FGR placentae compared to controls. This is the first study to report a relationship between altered placental GPC expression and subsequent development of SGA/FGR. [ABSTRACT FROM AUTHOR]

Appropriate growth charts are essential for fetal surveillance, to confirm that growth is proceeding normally and to identify pregnancies that are at risk. Many stillbirths are avoidable through antenatal detection of the small-for-gestational-age fetus. In the absence of an international consensus on which growth chart to use, it is essential that clinical practice reflects outcome-based evidence. This study investigated the performance of 4 internationally used fetal weight standards and their ability to identify stillbirth risk in different ethnic and maternal size groups of a heterogeneous population. We analyzed routinely collected maternity data from more than 2.2 million pregnancies. Three population-based fetal weight standards (Hadlock, Intergrowth-21st, and World Health Organization) were compared with the customized GROW standard that was adjusted for maternal height, weight, parity, and ethnic origin. Small-for-gestational-age birthweight and stillbirth risk were determined for the 2 largest ethnic groups in our population (British European and South Asian), in 5 body mass index categories, and in 4 maternal size groups with normal body mass index (18.5–25.0 kg/m2). The differences in trend between stillbirth and small-for-gestational-age rates were assessed using the Clogg z test, and differences between stillbirths and body mass index groups were assessed using the chi-square trend test. Stillbirth rates (per 1000) were higher in South Asian pregnancies (5.51) than British-European pregnancies (3.89) (P <.01) and increased in both groups with increasing body mass index (P <.01). Small-for-gestational-age rates were 2 to 3-fold higher for South Asian babies than British European babies according to the population-average standards (Hadlock: 26.2% vs 12.2%; Intergrowth-21st: 12.1% vs 4.9%; World Health Organization: 32.2% vs 16.0%) but were similar by the customized GROW standard (14.0% vs 13.6%). Despite the wide variation, each standard's small-for-gestation-age cases had increased stillbirth risk compared with non–small-for-gestation-age cases, with the magnitude of risk inversely proportional to the rate of cases defined as small for gestational age. All standards had similar stillbirth risk when the small-for-gestation-age rate was fixed at 10% by varying their respective thresholds for defining small for gestational age. When analyzed across body mass index subgroups, the small-for-gestation-age rate according to the GROW standard increased with increasing stillbirth rate, whereas small-for-gestation-age rates according to Hadlock, Intergrowth-21st, and World Health Organization fetal weight standards declined with increasing body mass index, showing a difference in trend (P <.01) to stillbirth rates across body mass index groups. In the normal body mass index subgroup, stillbirth rates showed little variation across maternal size groups; this trend was followed by GROW–based small-for-gestation-age rates, whereas small-for-gestation-age rates defined by each population-average standard declined with increasing maternal size. Comparisons between population-average and customized fetal growth charts require examination of how well each standard identifies pregnancies at risk of adverse outcomes within subgroups of any heterogeneous population. In both ethnic groups studied, increasing maternal body mass index was accompanied by increasing stillbirth risk, and this trend was reflected in more pregnancies being identified as small for gestational age only by the customized standard. In contrast, small-for-gestation-age rates fell according to each population-average standard, thereby hiding the increased stillbirth risk associated with high maternal body mass index. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Periconceptional maternal ultra-processed food (UPF) consumption impairs embryonic growth. Impacts of exposure to UPF on distinct components of fetal growth in late pregnancy are unknown. Objective: To investigate the influence of frequency of UPF consumption during pregnancy on fetal head circumference (HC), abdominal circumference (AC), and femur length (FL). Methods: This study included 417 live-born singleton pregnancies prospectively followed-up since the antenatal period in the MINA-Brazil Study (Maternal and Child Health and Nutrition in Acre, Brazil), with an available ultrasound scan at >24 gestational weeks. Frequency of food groups consumption in the previous month was categorized as no/monthly, weekly, or daily. Ultrasound scans were conducted at 27.8 (SD: 1.7) gestational weeks. HC, AC, and FL z-scores were calculated for gestational age using the INTERGROWTH-21st Project standards. Simultaneous-quantile regression models were fitted at the 10th, 50th, and 90th percentiles of the distribution of each ultrasound parameter according to UPF consumption, with adjustment for potential confounders. Results: Participants were aged on average 24.7 (SD: 6.5) years, 44.8% were primiparous, and 26.9% and 24.9%, respectively, had weekly and daily UPF consumption. Compared to no/monthly intake, daily UPF consumption impaired HC across its distribution, with significant effect sizes varying from -0.24 to -0.40 z-score. Weekly UPF consumption decreased HC at the 90th percentile by -0.39 z-score (95% CI: -0.78, -0.01) and FL at the 50th percentile by -0.32 z-score (95% CI: -0.60, -0.04). No association was noted with AC. Conclusion: Frequency of UPF consumption was negatively associated with skeletal components of fetal growth in late pregnancy. Infant body composition may benefit from healthy food practices since pregnancy. [ABSTRACT FROM AUTHOR]

Highlights • Sleeve gastrectomy alters fetal growth as Roux-en-Y gastric bypass. • Sleeve gastrectomy induces as many maternal deficiencies as gastric bypass. • Decrease in maternal protein intake is associated with fetal growth restriction. • Increase in iron load is associated with fetal growth restriction. Abstract Background There is a lack of evidence on whether sleeve gastrectomy (SG), which induces fewer nutritional deficiencies than Roux-en-Y gastric bypass (RYGB), also affects fetal growth (FG). Objectives To compare neonatal outcomes after RYGB and SG and to assess the impact of maternal nutritional alterations on FG after both procedures. Setting University Hospital, France. Methods Women with singleton pregnancies who had at least 1 nutritional evaluation in our institution between 2004 and 2017 were included. FG was assessed with birth weight (BW) and BW-Z score (adjusted for sex and term), and maternal nutritional deficiencies were defined according to standard and pregnancy-specific norms. Results During the study period 123 pregnancies were included, 77 after RYGB and 46 after SG. Weight loss was higher after RYGB than after SG (45.6 ± 12.4 versus 39.5 ± 13.7 kg, P =.02), but mean weight before pregnancy and weight gain during pregnancy were similar. Mean BW (3026 ± 677 versus 3162 ± 712 g), mean BW Z-score and incidence of small for gestational age (24% versus 19%) were not significantly different after RYGB and SG. Mean number of nutritional deficiencies during the second trimester was similar (2.2 ± 1.5 versus 2.1 ± 1.2 with specific norms), but the affected parameters differed between procedures. Urinary urea (R =.285, P =.04) was positively correlated to BW Z-score after both procedures. In contrast, serum iron parameters were negatively associated to BW Z-score. Conclusion FG restriction occurs after both SG and RYGB. FG after bariatric surgery is positively associated with protein supply and negatively correlated with maternal iron status. [ABSTRACT FROM AUTHOR]

Introduction: Recent data suggest that in addition to glucose, fetal growth is related to maternal triglycerides (TG). To reach the fetus, TG must be hydrolyzed to free fatty acids (FFA) and transported across the placenta, but regulation is uncertain. Placental lipoprotein lipase (pLPL) hydrolyzes TG, both dietary chylomicron TG (CM-TG) and very-low density lipoprotein TG (VLDL-TG), to FFA. This may promote fetal fat accretion by increasing the available FFA pool for placental uptake. We tested the novel hypothesis that pLPL activity, but not maternal adipose tissue LPL activity, is associated with newborn adiposity and higher maternal TG.Methods: Twenty mothers (n = 13 normal-weight; n = 7 obese) were prospectively recruited. Maternal glucose, insulin, TG (total, CM-TG, VLDL-TG), and FFA were measured at 14-16, 26-28, and 36-37 weeks, and adipose tissue LPL was measured at 26-28 weeks. At term delivery, placental villous biopsies were immediately analyzed for pLPL enzymatic activity. Newborn percent body fat (newborn %fat) was assessed by skinfolds.Results: Placental LPL activity was positively correlated with birthweight (r = 0.48;P = 0.03) and newborn %fat (r = 0.59;P = 0.006), further strengthened by correcting for gestational age at delivery (r = 0.75;P = 0.0001), but adipose tissue LPL was not. Maternal TG and BMI were not correlated with pLPL activity. Additionally, pLPL gene expression, while modestly correlated with enzymatic activity (r = 0.53;P < 0.05), was not correlated with newborn adiposity.Discussion: This is the first study to show a positive correlation between pLPL activity and newborn %fat. Placental lipase regulation and the role of pLPL in pregnancies characterized by nutrient excess and fetal overgrowth warrant further investigation. [ABSTRACT FROM AUTHOR]

Spontaneous preterm birth is the endpoint of multiple different pathophysiological pathways. Fetal growth restriction, assessed by serial ultrasonic fetal biometry, has been shown to predict both preterm and early-term spontaneous labor. The soluble fms-like tyrosine kinase-1 to placental growth factor ratio is predictive of early-term spontaneous labor, but its association with spontaneous preterm birth is unclear. This study aimed to determine whether maternal serum levels of soluble fms-like tyrosine kinase-1, placental growth factor, and the soluble fms-like tyrosine kinase-1: placental growth factor ratio at 20 and 28 weeks' gestation, and the rate of change in these biomarkers between 20 and 28 weeks were predictive of risk of spontaneous preterm birth. The biomarkers were measured in maternal serum at 20- and 28-weeks' gestation in women recruited to a prospective cohort of unselected nulliparous women as part of the Pregnancy Outcome Prediction study in Cambridge, United Kingdom. The risk of spontaneous preterm birth was assessed using Cox regression and competing-risks regression. Associations from Cox regression were quantified by the adjusted hazard ratio for a 1 standard deviation higher level of a given biomarker or a 1 standard deviation increase in the marker between 20 and 28 weeks' gestation. A previously identified risk factor, slow femur length growth, was used as an additional predictor of spontaneous preterm birth for the purpose of risk stratification. Of the 3763 participants in the analysis, 95 (2.5%) had spontaneous preterm birth and 54 (1.4%) had medically indicated preterm birth. At 20 weeks' gestation, higher levels of soluble fms-like tyrosine kinase-1 and the soluble fms-like tyrosine kinase-1:placental growth factor ratio were associated with reduced risk of spontaneous preterm birth (adjusted hazard ratio [95% confidence interval], 0.75 [0.61–0.92]; P =.006 and 0.71 [0.59–0.87]; P =.0009, respectively). At 28 weeks' gestation, there was no association between either soluble fms-like tyrosine kinase-1 or placental growth factor and the risk of spontaneous preterm birth, but there was a U-shaped relation with the soluble fms-like tyrosine kinase-1:placental growth factor ratio. However, when the biomarkers were quantified as the rate of increase between 20 and 28 weeks' gestation, there were strong positive associations between spontaneous preterm birth and rate of increase in soluble fms-like tyrosine kinase-1 (1.36 [1.13–1.63]; P =.001) and the soluble fms-like tyrosine kinase-1:placental growth factor ratio (1.50 [1.30–1.73]; P <.0001), and a strong negative association with the rate of increase in placental growth factor (0.71 [0.61–0.82]; P <.0001). Women who were in the highest decile of increase in the soluble fms-like tyrosine kinase-1:placental growth factor ratio and the lowest decile of femur length growth between 20 and 28 weeks' gestation had approximately 9-fold risk of spontaneous preterm birth (9.27 [4.21–20.37]; P <.0001). Competing-risks regression yielded similar results. Changing levels of soluble fms-like tyrosine kinase-1 and placental growth factor are indicative of placental dysfunction and are strongly associated with the risk of spontaneous preterm birth, especially when combined with slower fetal femur length growth. [ABSTRACT FROM AUTHOR]

Sildenafil is a new approach to treat fetal growth restriction (FGR) and preeclampsia. We performed a systematic meta-analysis to evaluate effects of sildenafil. Our search identified 22 animal studies (mouse, rat, rabbit, sheep, and guinea pigs) and 2 human randomized controlled trials. Data were pooled using ratio of means and mean differences with 95% confidence intervals for fetal growth and maternal blood pressure, respectively. Meta-regression analyses were performed for study-related factors that might affect efficacy of sildenafil, including the model used (healthy pregnancy versus FGR/preeclampsia) and route of administration. Dose-response curves with dose per metabolic weight (mg/kg0.75 per 24 hours) were fitted using splines. Our analyses show that sildenafil increases fetal growth during FGR/preeclampsia pregnancy compared with healthy pregnancy (1.10 [1.06-1.13] versus 1.03 [0.99-1.06]; P=0.006). There was no significant effect on fetal growth in the absence of FGR/preeclampsia. Effects were similar among different species and largest after oral and continuous administration. There was a positive relation between dose and fetal growth up to a human equivalent dose of ≈450 mg/d. A significant blood pressure-lowering effect of sildenafil is present during FGR/preeclampsia pregnancy only (-19 [-25 to -13] mm Hg; P<0.01), with the effect size being highly dependent on baseline blood pressure and without effect in the absence of hypertension. This meta-analysis supports that sildenafil improves fetal growth and maternal blood pressure regulation during FGR and preeclampsia pregnancy. The greatest beneficial effects on fetal growth are with dosages greater than those currently used in human studies. [ABSTRACT FROM AUTHOR]

Use of glyburide in gestational diabetes (GDM) has raised concerns about fetal and neonatal side effects, including increased birth weight. Placental nutrient transport is a key determinant of fetal growth, however the effect of glyburide on placental nutrient transporters is largely unknown. We hypothesized that glyburide treatment in GDM pregnancies is associated with increased expression of nutrient transporters in the syncytiotrophoblast plasma membranes. We collected placentas from GDM pregnancies who delivered at term and were treated with either diet modification (n = 15) or glyburide (n = 8). Syncytiotrophoblast microvillous (MVM) and basal (BM) plasma membranes were isolated and expression of glucose (glucose transporter 1; GLUT1), amino acid (sodium-coupled neutral amino acid transporter 2; SNAT2 and L-type amino acid transporter 1; LAT1) and fatty acid (fatty acid translocase; FAT/CD36, fatty acid transporter 2 and 4; FATP2, FATP4) transporters was determined by Western blot. Additionally, we determined GLUT1 expression by confocal microscopy in cultured primary human trophoblasts (PHT) after exposure to glyburide. Birth weight was higher in the glyburide-treated group as compared to diet-treated GDM women (3764 ± 126 g vs. 3386 ± 75 g; p < 0.05). GLUT1 expression was increased in both MVM (+50%; p < 0.01) and BM (+75%; p < 0.01). In contrast, MVM FAT/CD36 (-65%; p = 0.01) and FATP2 (-65%; p = 0.02) protein expression was reduced in mothers treated with glyburide. Glyburide increased membrane expression of GLUT1 in a dose-dependent manner in cultured PHT. This data is the first to show that glyburide increases GLUT1 expression in syncytiotrophoblast MVM and BM in GDM pregnancies, and may promote transplacental glucose delivery contributing to fetal overgrowth. [ABSTRACT FROM AUTHOR]

Introduction: Placental thickness in the second trimester of pregnancy has been associated with risks of placenta-mediated complications of pregnancy. We aimed to estimate the association between first-trimester maximum placental thickness and the subsequent risk of preeclampsia and/or the delivery of small-for-gestational-age (SGA) neonate.Methods: Prospective cohort study of women recruited at 11-14 weeks gestation. Placental thickness was measured at its apparent center and reported in multiple of median (MoM) adjusted for gestational age. Participants were followed until delivery for pregnancy outcomes. Placental measurements of participants who developed preeclampsia and/or delivered SGA neonate (defined as birth weight below 10th percentile) were compared with those who did not using non-parametric statistical analyses.Results: We recruited 991 participants at a mean gestational age of 12.7 ± 0.7 weeks of gestation. SGA (n = 52) was associated with reduced 1st trimester placental thickness (median: 0.89 MoM; interquartile (IQ): 0.75-1.02 vs 0.98 MoM; IQ: 0.84-1.15; p < 0.01). Pregnancies that developed preeclampsia (n = 20) tended to have greater placental thickness (median: 1.10 MoM; IQ: 0.93-1.25 vs 0.97 MoM; IQ: 0.84-1.14; p = 0.06) with values > 1.2 MoM significantly increasing the risk for preeclampsia (relative risk: 3.6; 95%CI: 1.5-8.6, p < 0.01). Pregnancies complicated by both SGA and preeclampsia (n = 5) had similar placental thickness in the first-trimester in comparison with uncomplicated pregnancies (median: 1.03 MoM; IQ: 0.89-1.42 vs 0.98 MoM; IQ: 0.84-1.14; p = 0.33).Conclusion: First-trimester placental thickness diverges in pregnancies at risk of preeclampsia (increased) or SGA (decreased), but remains within normal values in pregnancies at risk of both conditions, suggesting that the underlying pathologies have some opposing effects on early placental growth. The current findings should be validated in a larger cohort. [ABSTRACT FROM AUTHOR]

The article discusses research using ultrasonography to estimate fetal growth curves in the species Tamadua tetradactyla, offering a reference point for normal fetal development and expected parturition dates for the species.

Background Polyunsaturated fatty acids (PUFA) are essential for offspring development, but it is less clear whether pregnancy PUFA status affects growth and adiposity. Methods In 985 mother-offspring pairs from the ongoing Singaporean GUSTO cohort, we analyzed the associations between offspring growth and adiposity outcomes until age 5 years and five PUFAs of interest, measured in maternal plasma at 26–28 weeks’ gestation: linoleic acid (LA), arachidonic acid, α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (DHA). We measured fetal growth by ultrasound (n=924), neonatal body composition (air displacement plethysmography (n=252 at birth, and n=317 at age 10 days), and abdominal magnetic resonance imaging (n=317)), postnatal growth (n=979) and skinfold thicknesses (n=981). Results were presented as regression coefficients for a 5% increase in PUFA levels. Results LA levels were positively associated with birthweight (β (95% CI): 0.04 (0.01, 0.08) kg), body mass index (0.13 (0.02, 0.25) kg/m 2 ), head circumference (0.11 (0.03, 0.19) cm), and neonatal abdominal adipose tissue volume (4.6 (1.3, 7.8) mL for superficial subcutanous tissue, and 1.2 (0.1, 2.4) mL for internal tissue), but not with later outcomes. DHA levels, although not associated with birth outcomes, were related to higher postnatal length/height: 0.63 (0.09, 1.16) cm at 12 months and 1.29 (0.34, 2.24) cm at 5 years. Conclusions LA was positively associated with neonatal body size, and DHA with child height. Maternal PUFA status during pregnancy may influence fetal and child growth and adiposity. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare maternal and fetal exposure to PCBs in pregnant women from a petrochemical and gas area (PGA) and an urban area (UA), by the analyses of serum samples from mother (MS) and cord (CS). After liquid-liquid extracting, samples were analyzed for 12 PCBs congeners by gas chromatography mass spectrometer. Adjusted multiple linear regression models showed the mean levels (μg/L) of total PCBs in the MS and CS samples from the PGA (1.70 ± 0.81 and 1.19 ± 0.43) were significantly higher than those from UA (1.64 ± 0.75 and 1.07 ± 0.38). PCB 44 was predominant in both MS and CS serum samples, and in both PGA (0.80 ± 0.70 and 0.76 ± 0.67) and UA (0.79 ± 0.39 and 0.67 ± 0.34). A negative correlation was found for PCB 52 as one-unit increase in the cord serum levels was associated with 0.024 g decrease in newborn weight. Similarly, one-unit increase in the maternal serum PCB 18 concentrations were associated with 0.09 and 0.086 cm decrease in newborn height and head circumference. The serum levels of PCB 18 and 52 in the mothers who consumed meat and milk at least 1 meal/week were higher than these who consumed meat and milk never or less than 1 meal/month. The findings in this study indicated that higher maternal exposure to PCBs, as result of living in an industrialized area, leads to higher PCBs accumulation in cord blood, which consequently passes to the developing fetus. These events may cause harmful effects on both them in-utero and afterbirth growth and development. [Display omitted] • ΣPCBs in maternal and cord serums from industrial area was higher than urban area. • PCB 18, 44 and 52 were detected in maternal and cord serum samples. • PCB 44 was predominant compound in maternal and cord serum samples. • A negative association was observed for cord serum PCB 52 and birth weight. • Maternal serum PCB18 was inversely related with birth height and head circumference. [ABSTRACT FROM AUTHOR]

Clinicians and researchers use published standards to assess and classify the size and growth of the fetus and newborn infant. Fetal growth is slower on average in Black fetuses as compared with White fetuses, and existing standards differ in whether they are race-specific or not. Here, we apply a health equity lens to the topic of fetal and newborn growth assessment by critically appraising two widely available growth standards. We conclude that using race-based standards is not well-justified and could perpetuate or even worsen inequities in perinatal health outcomes. We therefore recommend that neonatal and perinatal providers remove race from the assessment of fetal and newborn size. [ABSTRACT FROM AUTHOR]

Introduction: Ultrasonic fetal biometry and arterial Doppler flow velocimetry are widely used to assess the risk of pregnancy complications. There is an extensive literature on the relationship between pregnancy outcomes and the size and shape of the placenta. However, ultrasonic fetal biometry and arterial Doppler flow velocimetry have not previously been studied in relation to postnatal placental morphometry in detail. Methods: We conducted a prospective cohort study of nulliparous women in The Rosie Hospital, Cambridge (UK). We studied a group of 2120 women who had complete data on uterine and umbilical Doppler velocimetry and fetal biometry at 20, 28 and 36 weeks' gestational age, digital images of the placenta available, and delivered a liveborn infant at term. Associations were expressed as the difference in the standard deviation (SD) score of the gestational age adjusted ultrasound measurement (z-score) comparing the lowest and highest decile of the given placental morphometric measurement. Results: The lowest decile of placental surface area was associated with 0.87 SD higher uterine artery Doppler mean pulsatility index (PI) at 20 weeks (95% CI: 0.68 to 1.07, P < 0.001). The lowest decile of placental weight was associated with 0.73 SD higher umbilical artery Doppler PI at 36 weeks (95% CI: 0.54 to 0.93, P < 0.001). The lowest decile of both placental weight and placental area were associated with reduced growth velocity of the fetal abdominal circumference between 20 and 36 weeks (both P < 0.001). Conclusion: Placental area and weight are associated with uterine and umbilical blood flow, respectively, and both are associated with fetal growth rate. [ABSTRACT FROM AUTHOR]

• Multiple sclerosis does not seem to adversely affect fetal and neonatal outcomes. • We studied fetoneonatal growth in offsprings of mothers with multiple sclerosis. • Multiple sclerosis in pregnancy does not seem to affect fetal and neonatal growth. • We think that these results represent a very important and reassuring information. Multiple sclerosis does not seem to adversely affect fetal and neonatal outcomes, although some studies reported a possible reduction in mean birth weight and length, and a higher incidence of preterm delivery, mainly in relation to the exposure to disease-modifying drugs (DMDs) during pregnancy. Few data are available on intrauterine fetal growth and postnatal somatic development of newborns from mothers with multiple sclerosis compared to those from healthy women. For these reasons, we decided to investigate fetal growth, neonatal anthropometric parameters, and postnatal somatic development up to 12 months of life in offsprings from MS mothers. This retrospective cohort study included 211 women with multiple sclerosis, and 384 healthy women paired for maternal age and parity as controls. Fetal biometric parameters (biparietal diameter, head circumference, abdominal circumference, and femur length) measured during the third trimester of pregnancy (30–34 weeks' gestation) were retrieved from the computerized database of the Department (EcoPlus*) where the results of ultrasound exams performed in the hospital are stored. Newborn measurements (weight, length and head circumference) at birth were obtained from the hospital's computerized obstetric and neonatal database (Trackare* and Remote* data base); measurements at 6 and 12 months of life were obtained from the regional database (ECWMED*) of family pediatricians of our region. No differences between the two groups were observed for all the fetal parameters considered, expressed as centiles of growth according to gestational age (biparietal diameter: p = 0.40; head circumference: p = 0.40; abdominal circumference: p = 0.32; femur length: p = 0.32). No differences in gestational age at delivery, birthweight, and in the incidence of low birthweight and small for gestational age newborns were observed between the two groups. In the multiple sclerosis group a significantly higher incidence of caesarean section (p = 0.01) and late preterm delivery (at less than 37 weeks'gestation, p = 0.001) were registered. The trends of postnatal growth in weight (F = 0.53; p -value = 0.590) and length (F = 0.44; p -value = 0.645) were superimposable between the two groups. The trends of growth for head circumference showed a slightly, not significantly greater head circumference of infants from mothers with multiple sclerosis at 6 months of life, but the values at twelve months of life in the two groups were similar (F = 0.85; p -value = 0.427). Moreover, the trends of postnatal increase of weight (F = 1.016; p -value = 0.331), length (F = 2.001; p -value = 0.146) and head circumference (F = 1.591; p -value = 0.212) of newborns/infants (from birth to twelve months of life) born to mothers with multiple sclerosis who breastfed, mothers who did not, and in the control group were similar. Multiple sclerosis in pregnancy does not seem to affect fetal growth and postnatal development during the first year of the offspring life. We think that these results represent an important and reassuring information to provide the patients with during preconception counseling. [ABSTRACT FROM AUTHOR]

Introduction Administration of betamethasone to women at risk of preterm delivery is known to be associated with reduced fetal growth via alterations in placental function and possibly direct effects on the fetus. The placental glucocorticoid receptor (GR) is central to this response and recent evidence suggests there are numerous isoforms for GR in term placentae. In this study we have questioned whether GR isoform expression varies in preterm placentae in relation to betamethasone exposure, fetal sex and birthweight. Methods Preterm (24–36 completed weeks of gestation, n = 55) and term placentae (>37 completed weeks of gestation, n = 56) were collected at delivery. Placental GR expression was examined using Western Blot and analysed in relation to gestational age at delivery, fetal sex, birthweight and betamethasone exposure. Data was analysed using non-parametric tests. Results Eight known isoforms of the GR were detected in the preterm placenta and include GRα (94 kDa), GRβ (91 kDa), GRα C (81 kDa) GR P (74 kDa) GR A (65 kDa), GRα D1–3 (50–55 kDa). Expression varied between preterm and term placentae with a greater expression of GRα C in preterm placentae relative to term placentae. The only sex differences in preterm placentae was that GRα D2 expression was higher in males than females. There were no alterations in preterm placental GR expression in association with betamethasone exposure. Discussion GRα C is the isoform involved in glucocorticoid induced apoptosis and suggests that its predominance in preterm placentae may contribute to the pathophysiology of preterm birth. [ABSTRACT FROM AUTHOR]

The article discusses research concerning the potential effect of insulin-like growth factor 2 (IGF2) in cell growth and differentiation factor of muscle and fat tissues in breeding of pigs.