Genetic distance and ancestry proportion modify the association between maternal genetic risk score of type 2 diabetes and fetal growth.

BACKGROUND: Maternal genetic risk of type 2 diabetes (T2D) has been associated with fetal growth, but the influence of genetic ancestry is not yet fully understood. We aimed to investigate the influence of genetic distance (GD) and genetic ancestry proportion (GAP) on the association of maternal genetic risk score of T2D (GRST2D) with fetal weight and birthweight. METHODS: Multi-ancestral pregnant women (n = 1,837) from the NICHD Fetal Growth Studies - Singletons cohort were included in the current analyses. Fetal weight (in grams, g) was estimated from ultrasound measurements of fetal biometry, and birthweight (g) was measured at delivery. GRST2D was calculated using T2D-associated variants identified in the latest trans-ancestral genome-wide association study and was categorized into quartiles. GD and GAP were estimated using genotype data of four reference populations. GD was categorized into closest, middle, and farthest tertiles, and GAP was categorized as highest, medium, and lowest. Linear regression analyses were performed to test the association of GRST2D with fetal weight and birthweight, adjusted for covariates, in each GD and GAP category. RESULTS: Among women with the closest GD from African and Amerindigenous ancestries, the fourth and third GRST2D quartile was significantly associated with 5.18 to 7.48 g (weeks 17-20) and 6.83 to 25.44 g (weeks 19-27) larger fetal weight compared to the first quartile, respectively. Among women with middle GD from European ancestry, the fourth GRST2D quartile was significantly associated with 5.73 to 21.21 g (weeks 18-26) larger fetal weight. Furthermore, among women with middle GD from European and African ancestries, the fourth and second GRST2D quartiles were significantly associated with 117.04 g (95% CI = 23.88-210.20, p = 0.014) and 95.05 g (95% CI = 4.73-185.36, p = 0.039) larger birthweight compared to the first quartile, respectively. The absence of significant association among women with the closest GD from East Asian ancestry was complemented by a positive significant association among women with the highest East Asian GAP. CONCLUSIONS: The association between maternal GRST2D and fetal growth began in early-second trimester and was influenced by GD and GAP. The results suggest the use of genetic GD and GAP could improve the generalizability of GRS.

Application of ultrasonographic human estimated foetal weight formulas to cynomolgus monkeys (Macaca fascicularis) at 129-132 days of gestation: A comparative study of estimated and actual birthweight.

BACKGROUND: Cynomolgus monkeys (Macaca fascicularis) are essential in biomedical research, including reproductive studies. However, the application of human estimated foetal weight (EFW) formulas using ultrasonography (USG) in these non-human primates is not well established. OBJECTIVES: This study aims to evaluate the applicability of human EFW formulas for estimating foetal weight in cynomolgus monkeys at approximately 130 days of gestation. METHODS: Our study involved nine pregnant cynomolgus monkeys. We measured foetal parameters, including biparietal diameter, head circumference, abdominal circumference and femur length using USG. The EFW was calculated using 11 human EFW formulas. The actual birthweight (ABW) was recorded following Cesarean section, the day after the EFW calculation. For comparing EFW and ABW, we employed statistical methods such as mean absolute percentage error (APE) and Bland-Altman analysis. RESULTS: The ABW ranged between 200.36 and 291.33 g. Among the 11 formulas, the Combs formula showed the lowest APE (4.3%) and highest correlation with ABW (p < 0.001). Notably, EFW and ABW differences for the Combs formula were ≤5% in 66.7% and ≤10% in 100% of cases. The Bland-Altman analysis supported these results, showing that all cases fell within the limits of agreement. CONCLUSIONS: The Combs formula is applicable for estimating the weight of cynomolgus monkey fetuses with USG at approximately 130 days of gestation. Our observations suggest that the Combs formula can be applied in the prenatal care and biomedical research of this species.

[Association between prenatal exposure to PM2.5 and fetal growth: a prospective cohort study].

Objective: To investigate the association of exposure to PM2.5 and its constituents during pregnancy and fetal growth and to further identify critical windows of exposure for fetal growth. Methods: We included 4 089 mother-child pairs from the Jiangsu Birth Cohort Study between January 2016 and October 2019. Data of general characteristics, clinical information, daily average PM2.5 exposure, and its constituents during pregnancy were collected. Fetal growth parameters, including head circumference (HC), abdominal circumference (AC), and femur length (FL), were measured by ultrasound after 20 weeks of gestation, and then estimated fetal weight (EFW) was calculated. Generalized linear mixed models were adopted to examine the associations of prenatal exposure to PM2.5 and its constituents with fetal growth. Distributed lag nonlinear models were used to identify critical exposure windows for each outcome. Results: A 10 µg/m3 increase in PM2.5 exposure during pregnancy was associated with a decrease of 0.025 (ß=-0.025, 95%CI: -0.048- -0.001) in HC Z-score, 0.026 (ß=-0.026, 95%CI: -0.049- -0.003) in AC Z-score, and 0.028 (ß=-0.028, 95%CI:-0.052--0.004) in EFW Z-score, along with an increased risk of 8.5% (RR=1.085, 95%CI: 1.010-1.165) and 13.5% (RR=1.135, 95%CI: 1.016-1.268) for undergrowth of HC and EFW, respectively. Regarding PM2.5 constituents, prenatal exposure to black carbon, organic matter, nitrate, sulfate (SO42-) and ammonium consistently correlated with decreased HC Z-score. SO42- exposure was also associated with decreased FL Z-scores. In addition, we found that gestational weeks 2-5 were critical windows for HC, weeks 4-13 and 19-40 for AC, weeks 4-13 and 23-37 for FL, and weeks 4-12 and 20-40 for EFW. Conclusions: Our findings demonstrated that exposure to PM2.5 and its constituents during pregnancy could adversely affect fetal growth and the critical windows for different fetal growth parameters are not completely consistent.

Association between Doppler assessment and secondary cesarean delivery for intrapartum fetal compromise in small-for-gestational-age fetuses.

PURPOSE: To elucidate the association between arterial and venous Doppler ultrasound parameters and the risk of secondary cesarean delivery for intrapartum fetal compromise (IFC) and neonatal acidosis in small-for-gestational-age (SGA) fetuses. METHODS: This single-center, prospective, blinded, cohort study included singleton pregnancies with an estimated fetal weight (EFW) < 10th centile above 36 gestational weeks. Upon study inclusion, all women underwent Doppler ultrasound, including umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, fetal aortic isthmus (AoI) PI, umbilical vein blood flow (UVBF), and modified myocardial performance index (mod-MPI). Primary outcome was defined as secondary cesarean section due to IFC. RESULTS: In total, 87 SGA pregnancies were included, 16% of which required a cesarean section for IFC. Those fetuses revealed lower UVBF corrected for abdominal circumference (AC) (5.2 (4.5-6.3) vs 7.2 (5.5-8.3), p = 0.001). There was no difference when comparing AoI PI, UA PI, ACM PI, or mod-MPI. No association was found for neonatal acidosis. After multivariate logistic regression, UVBF/AC remained independently associated with cesarean section due to IFC (aOR 0.61 [0.37; 0.91], p = 0.03) and yielded an area under the curve (AUC) of 0.78 (95% CI, 0.67-0.89). A cut-off value set at the 50th centile of UVBF/AC reached a sensitivity of 86% and specificity of 58% for the occurrence of cesarean section due to IFC (OR 8.1; 95% CI, 1.7-37.8, p = 0.003). CONCLUSION: Low levels of umbilical vein blood flow (UVBF/AC) were associated with an increased risk among SGA fetuses to be delivered by cesarean section for IFC.

Reduced uterine perfusion pressure as a model for preeclampsia and fetal growth restriction in murine: a systematic review and meta-analysis.

The reduced uterine perfusion pressure (RUPP) model is frequently used to study preeclampsia and fetal growth restriction. An improved understanding of influential factors might improve reproducibility and reduce animal use considering the variability in RUPP phenotype. We performed a systematic review and meta-analysis by searching Medline and Embase (until 28 March, 2023) for RUPP studies in murine. Primary outcomes included maternal blood pressure (BP) or proteinuria, fetal weight or crown-rump length, fetal reabsorptions, or antiangiogenic factors. We aimed to identify influential factors by meta-regression analysis. We included 155 studies. Our meta-analysis showed that the RUPP procedure results in significantly higher BP (MD = 24.1 mmHg; [22.6; 25.7]; n = 148), proteinuria (SMD = 2.3; [0.9; 3.8]; n = 28), fetal reabsorptions (MD = 50.4%; [45.5; 55.2]; n = 42), circulating soluble FMS-like tyrosine kinase-1 (sFlt-1) (SMD = 2.6; [1.7; 3.4]; n = 34), and lower fetal weight (MD = -0.4 g; [-0.47; -0.34]; n = 113. The heterogeneity (variability between studies) in primary outcomes appeared ≥90%. Our meta-regression identified influential factors in the method and time point of BP measurement, randomization in fetal weight, and type of control group in sFlt-1. The RUPP is a robust model considering the evident differences in maternal and fetal outcomes. The high heterogeneity reflects the observed variability in phenotype. Because of underreporting, we observed reporting bias and a high risk of bias. We recommend standardizing study design by optimal time point and method chosen for readout measures to limit the variability. This contributes to improved reproducibility and thereby eventually improves the translational value of the RUPP model.

Exposure to fine particulate matter 2.5 from wood combustion smoke causes vascular changes in placenta and reduce fetal size.

During gestation, maternal blood flow to the umbilical cord and placenta increases, facilitating efficient nutrient absorption, waste elimination, and effective gas exchange for the developing fetus. However, the effects of exposure to wood smoke during this period on these processes are unknown. We hypothesize that exposure to PM2.5, primarily sourced from wood combustion for home heating, affects placental vascular morphophysiology and fetal size. We used exposure chambers that received either filtered or unfiltered air. Female rats were exposed to PM2.5 during pre-gestational and/or gestational stages. Twenty-one days post-fertilization, placentas were collected via cesarean section. In these placentas, oxygen diffusion capacity was measured, and the expression of angiogenic factors was analyzed using qPCR and immunohistochemistry. In groups exposed to PM2.5 during pre-gestational and/or gestational stages, a decrease in fetal weight, crown-rump length, theoretical and specific diffusion capacity, and an increase in HIF-1α expression were observed. In groups exposed exclusively to PM2.5 during the pre-gestational stage, there was an increase in the expression of placental genes Flt-1, Kdr, and PIGF. Additionally, in the placental labyrinth region, the expression of angiogenic factors was elevated. Changes in angiogenesis and angiogenic factors reflect adaptations to hypoxia, impacting fetal growth and oxygen supply. In conclusion, this study demonstrates that exposure to PM2.5, emitted from wood smoke, in both pre-gestational and gestational stages, affects fetal development and placental health. This underscores the importance of addressing air pollution in areas with high levels of wood smoke, which poses a significant health risk to pregnant women and their fetuses.

Maternal choline supplementation mitigates premature foetal weight gain induced by an obesogenic diet, potentially linked to increased amniotic fluid leptin levels in rats.

Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11-17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects.

Estimating fetal weight in gastroschisis: A 10 year audit of outcomes at the National Maternity Hospital.

OBJECTIVE: To identify whether conventional methods of estimating fetal growth (Hadlock's formula), which relies heavily on abdominal circumference measurements, are accurate in fetuses with gastroschisis. METHODS: A retrospective cohort study was performed between the period January 1, 2011 and December 31, 2021 in a tertiary referral maternity hospital identifying all pregnancies with a diagnosis of gastroschisis. Projected fetal weight was obtained using the formula (EFW [Hadlock's formula] + 185 g × [X/7]) where X was the number of days to delivery. RESULTS: During the study period 41 cases were identified. The median maternal age was 25. The median BMI was 25 and 63% were primiparous women (n = 26). Median gestation at diagnosis was 21 weeks. Median gestation at delivery was 36 weeks. A total of 4.8% of mothers had a history of drug use (n = 2). The rate of maternal tobacco use was 21.9% (n = 9). A total of 4.8% of fetuses had additional congenital anomalies including amniotic band syndrome and myelomeningocele (n = 2). Estimated fetal weight (EFW) and birth weight data were available for 34 cases. A Wilcoxon signed-rank test showed projected EFW using Hadlock's formula did not result in a statistically significant different birth weight (Z = -1.3, P = 0.169). Median projected weight and actual birth weight were 2241.35 and 2415 g respectively. Median difference was 0.64 g (95% CI: -148 to -28.5). CONCLUSION: Our data showed accuracy using standard formulae for EFW in fetuses with gastroschisis.

Reference Values for Placental Weight and Placental:Fetal Weight Ratio in a Swedish Population.

INTRODUCTION: There is important clinical information from placental weight and its ratio to the fetal weight. The aim with this study was to establish reference values for the placental weight and the placental:fetal weight ratio for gestational weeks 13-43 in a Swedish population. MATERIALS AND METHODS: Cases were retrospectively collected from the database used at the Pathology Department at Karolinska University Hospital and information about the placental weight, fetal weight, and gestational age was retrieved. Conditions, which could affect the placental- or fetal weight were excluded. Thereafter percentile curves were calculated for the placental weight and the placental:fetal weight ratio for gestational weeks. RESULTS: A total of 730 cases were included and percentile curves for the placental weight for gestational week 13-43 and placental:fetal weight ratio for gestational week 18-43 are presented. CONCLUSIONS: Reference values for post fixation placental weight and its ratio to fetal weight for a Swedish population are presented. The reference values are lower than the current reference values used in our institution, and this will be of importance when interpreting findings after placental examination.

A simulation study to assess the potential benefits of MRI-based fetal weight estimation as a second-line test for suspected macrosomia.

OBJECTIVE: To simulate the outcomes of Boulvain's trial by using magnetic resonance imaging (MRI) for estimated fetal weight (EFW) as a second-line confirmatory imaging. STUDY DESIGN: Data derived from the Boulvain's trial and the study PREMACRO (PREdict MACROsomia) were used to simulate a 1000-patient trial. Boulvain's trial compared induction of labor (IOL) to expectant management in suspected macrosomia, whereas PREMACRO study compared the performance of ultrasound-EFW (US-EFW) and MRI-EFW in the prediction of birthweight. The primary outcome was the incidence of significant shoulder dystocia (SD). Cesarean delivery (CD), hyperbilirubinemia (HB), and IOL at < 39 weeks of gestation (WG) were selected as secondary outcomes. A subgroup analysis of the Boulvain's trial was performed to estimate the incidence of the primary and secondary outcomes in the true positive and false positive groups for the two study arms. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) for the prediction of macrosomia by MRI-EFW at 36 WG were calculated, and a decision tree was constructed for each outcome. RESULTS: The PPV of US-EFW for the prediction of macrosomia in the PREMACRO trial was 56.3 %. MRI-EFW was superior to US-EFW as a predictive tool resulting in lower rates of induction for false-positive cases. Repeating Boulvain's trial using MRI-EFW as a second-line test would result in similar rates of SD (relative risk [RR]:0.36), CD (RR:0.84), and neonatal HB (RR:2.6), as in the original trial. Increasing the sensitivity and specificity of MRI-EFW resulted in a similar relative risk for SD as in Boulvain's trial, but with reduced rates of IOL < 39 WG, and improved the RR of CD in favor of IOL. We found an inverse relationship between IOL rate and incidence of SD for both US-EFW and MRI-EFW, although overall rates of IOL, CD, and neonatal HB would be lower with MRI-derived estimates of fetal weight. CONCLUSION: The superior accuracy of MRI-EFW over US-EFW for the diagnosis of macrosomia could result in lower rates of IOL without compromising the relative advantages of the intervention but fails to demonstrate a significant benefit to justify a replication of the original trial using MRI-EFW as a second-line test.

Obesogenic diet in pregnancy disrupts placental iron handling and ferroptosis and stress signalling in association with fetal growth alterations.

Obesity and gestational diabetes (GDM) impact fetal growth during pregnancy. Iron is an essential micronutrient needed for energy-intense feto-placental development, but if mis-handled can lead to oxidative stress and ferroptosis (iron-dependent cell death). In a mouse model showing maternal obesity and glucose intolerance, we investigated the association of materno-fetal iron handling and placental ferroptosis, oxidative damage and stress signalling activation with fetal growth. Female mice were fed a standard chow or high fat, high sugar (HFHS) diet during pregnancy and outcomes were measured at day (d)16 or d19 of pregnancy. In HFHS-fed mice, maternal hepcidin was reduced and iron status maintained (tissue iron levels) at both d16 and d19. However, fetal weight, placental iron transfer capacity, iron deposition, TFR1 expression and ERK2-mediated signalling were reduced and oxidative damage-related lipofuscin accumulation in the placenta was increased in HFHS-fed mice. At d19, whilst TFR1 remained decreased, fetal weight was normal and placental weight, iron content and iron transporter genes (Dmt1, Zip14, and Fpn1) were reduced in HFHS-fed mice. Furthermore, there was stress kinase activation (increased phosphorylated p38MAPK, total ERK and JNK) in the placenta from HFHS-fed mice at d19. In summary, a maternal HFHS diet during pregnancy impacts fetal growth trajectory in association with changes in placental iron handling, ferroptosis and stress signalling. Downregulation of placental iron transporters in HFHS mice may protect the fetus from excessive oxidative iron. These findings suggest a role for alterations in placental iron homeostasis in determining perinatal outcomes of pregnancies associated with GDM and/or maternal obesity.

Expression of Placental Lipid Transporters in Pregnancies Complicated by Gestational and Type 1 Diabetes Mellitus.

The objective of the study was to assess the expression of proteins responsible for placental lipid transport in term pregnancies complicated by well-controlled gestational (GDM) and type 1 diabetes mellitus (PGDM). A total of 80 placental samples were obtained from patients diagnosed with PGDM (n = 20), GDM treated with diet (GDMG1, n = 20), GDM treated with diet and insulin (GDMG2, n = 20), and a non-diabetic control group (n = 20). Umbilical and uterine artery blood flows were assessed by means of ultrasound in the period prior to delivery and computer-assisted quantitative morphometry of immunostained placental sections was performed to determine the expression of selected proteins. The morphometric analysis performed for the vascular density-matched placental samples demonstrated a significant increase in the expression of fatty acid translocase (CD36), fatty acid binding proteins (FABP1, FABP4 and FABP5), as well as a decrease in the expression of endothelial lipase (EL) and fatty acid transport protein (FATP4) in the PGDM-complicated pregnancies as compared to the GDMG1 and control groups (p < 0.05). No significant differences with regard to the placental expression of lipoprotein lipase (LPL) and FATP6 protein between GDM/PGDM and non-diabetic patients were noted. Maternal pre-pregnancy weight, body mass index, placental weight as well as the expression of LPL and FABP4 were selected by the linear regression model as the strongest contributors to the fetal birth weight. To conclude, in placentas derived from pregnancies complicated by well-controlled PGDM, the expression of several lipid transporters, including EL, CD36, FATP4, FABP1, FABP4 and FABP5, is altered. Nonetheless, only LPL and FABP4 were significant predictors of the fetal birth weight.

Effect of maternal serum albumin level on birthweight and gestational age: an analysis of 39200 singleton newborns.

Background: Serum albumin plays a pivotal role in regulating plasma oncotic pressure and modulating fluid distribution among various body compartments. Previous research examining the association between maternal serum albumin levels and fetal growth yielded limited and inconclusive findings. Therefore, the specific influence of serum albumin on fetal growth remains poorly understood and warrants further investigation. Methods: A retrospective study involved 39200 women who had a singleton live birth at a tertiary-care academic medical center during the period from January 2017 to December 2020. Women were categorized into four groups according to the quartile of albumin concentration during early pregnancy: Q1 group, ≤41.0 g/L; Q2 group, 41.1-42.6 g/L; Q3 group, 42.7-44.3 g/L and Q4 group, >44.3 g/L. The main outcome measures were mid-term estimated fetal weight, birthweight and gestational age. Multivariate linear and logistic regression analysis were performed to detect the independent effect of maternal serum albumin level on fetal growth after adjusting for important confounding variables. Results: In the crude analysis, a significant inverse correlation was found between early pregnancy maternal serum albumin levels and fetal growth status, including mid-term ultrasound measurements, mid-term estimated fetal weight, birthweight, and gestational age. After adjustment for a number of confounding factors, mid-term estimated fetal weight, birthweight, and birth height decreased significantly with increasing albumin levels. Compared to the Q2 group, the Q4 group had higher rates of preterm birth (aOR, 1.16; 95% CI, 1.01-1.34), small-for-gestational-age (aOR, 1.27; 95% CI, 1.11-1.45) and low birthweight (aOR, 1.41; 95% CI, 1.18-1.69), and lower rate of large-for-gestational-age (aOR, 0.85; 95% CI, 0.78-0.94). Moreover, to achieve the optimal neonatal outcome, women with higher early pregnancy albumin levels required a greater reduction in albumin levels in later pregnancy stages. Conclusions: A higher maternal serum albumin level during early pregnancy was associated with poor fetal growth, with the detrimental effects becoming apparent as early as the mid-gestation period. These findings provided vital information for clinicians to predict fetal growth status and identify cases with a high risk of adverse neonatal outcomes early on.

To know or not to know: Effect of third-trimester sonographic fetal weight estimation on outcomes of large-for-gestational age neonates.

OBJECTIVE: The aim of the present study was to evaluate the impact of late third-trimester sonographic estimation of large for gestational age fetuses on pregnancy management and selected fetal and maternal adverse outcomes. METHODS: A retrospective cohort study was conducted in a tertiary, university-affiliated medical center between 2015 and 2019. All singleton large-for-gestational-age neonates born during this period were included. The cohort was divided into two groups: neonates for whom fetal weight was estimated on late third trimester (<14 days before delivery) sonography and neonates with no recent fetal weight estimation. The groups were compared for pregnancy management strategies, rates of labor induction, cesarean deliveries, and maternal and neonatal outcomes. RESULTS: A total of 1712 neonates were included in the study, among whom 791 (46.2%) had a late third-trimester fetal weight estimation (study group) and 921 (53.8%) did not (control group). Compared to the control group, the study group was characterized by higher rates of maternal primiparity (24.20% vs 19.20%, P = 0.013), higher maternal body mass index (26.0 ± 6.2 kg/m2 vs 24.7 ± 4.5 kg/m2, P = 0.002), more inductions of labor (29.84% vs 16.40%, P < 0.001) and cesarean deliveries (31.0% vs 19.97%, P < 0.001). There were no clinical differences in neonatal birth weight (4041 ± 256 g vs 3984 264 g, P < 0.001) and no significant differences between other neonatal outcomes, as rates of admission to the neonatal intensive care unit, jaundice, hypoglycemia, and shoulder dystocia. CONCLUSION: Late third-trimester sonographic fetal weight estimation is associated with a higher rate of labor induction and planned and intrapartum cesarean deliveries. In this retrospective cohort study, those interventions did not lead to reduction in maternal or neonatal adverse outcomes.

Impact of adenomyosis on pregnancy outcomes: a retrospective consecutive cohort study.

OBJECTIVE: This retrospective study explored the potential connection between adenomyosis and pregnancy outcomes. PATIENTS AND METHODS: A study included data from a total of 1,208 pregnancies. The adenomyosis group included 334 pregnant women with adenomyosis, and women in the control group (n=874) had uncomplicated pregnancies. Data on pregnancy complications and maternal and neonatal outcomes were compared. RESULTS: The incidence of gestational hypertension, gestational diabetes, and placenta previa was higher in the adenomyosis group compared to the control group (p<0.05). Adenomyosis was linked to a higher risk of postpartum hemorrhage (1,000-1,500 ml) but a lower risk of premature rupture of membranes (PROM) (p<0.05). Diagnosis of adenomyosis correlated with increased incidence of low fetal weight (20.3% vs. 21.3%, p<0.05) and a low APGAR score at 1 min (p<0.05). CONCLUSIONS: Adenomyosis correlated with a higher incidence of gestational hypertension, placenta previa, and gestational diabetes. At the same time, adenomyosis correlated with a significantly lower incidence of PROM compared to uncomplicated pregnancy. There was a significant increase in the incidence of postpartum hemorrhage and a higher risk of low fetal weight and lower APGAR score at 1 min in pregnancies with adenomyosis.

Artificial intelligence assistance for fetal development: evaluation of an automated software for biometry measurements in the mid-trimester.

BACKGROUND: This study presents CUPID, an advanced automated measurement software based on Artificial Intelligence (AI), designed to evaluate nine fetal biometric parameters in the mid-trimester. Our primary objective was to assess and compare the CUPID performance of experienced senior and junior radiologists. MATERIALS AND METHODS: This prospective cross-sectional study was conducted at Shenzhen University General Hospital between September 2022 and June 2023, and focused on mid-trimester fetuses. All ultrasound images of the six standard planes, that enabled the evaluation of nine biometric measurements, were included to compare the performance of CUPID through subjective and objective assessments. RESULTS: There were 642 fetuses with a mean (±SD) age of 22 ± 2.82 weeks at enrollment. In the subjective quality assessment, out of 642 images representing nine biometric measurements, 617-635 images (90.65-96.11%) of CUPID caliper placements were determined to be accurately placed and did not require any adjustments. Whereas, for the junior category, 447-691 images (69.63-92.06%) were determined to be accurately placed and did not require any adjustments. In the objective measurement indicators, across all nine biometric parameters and estimated fetal weight (EFW), the intra-class correlation coefficients (ICC) (0.843-0.990) and Pearson correlation coefficients (PCC) (0.765-0.978) between the senior radiologist and CUPID reflected good reliability compared with the ICC (0.306-0.937) and PCC (0.566-0.947) between the senior and junior radiologists. Additionally, the mean absolute error (MAE), percentage error (PE), and average error in days of gestation were lower between the senior and CUPID compared to the difference between the senior and junior radiologists. The specific differences are as follows: MAE (0.36-2.53 mm, 14.67 g) compared to (0.64- 8.13 mm, 38.05 g), PE (0.94-9.38%) compared to (1.58-16.04%), and average error in days (3.99-7.92 days) compared to (4.35-11.06 days). In the time-consuming task, CUPID only takes 0.05-0.07 s to measure nine biometric parameters, while senior and junior radiologists require 4.79-11.68 s and 4.95-13.44 s, respectively. CONCLUSIONS: CUPID has proven to be highly accurate and efficient software for automatically measuring fetal biometry, gestational age, and fetal weight, providing a precise and fast tool for assessing fetal growth and development.

The rhizomes of Atractylodes macrocephala Koidz improve gastrointestinal health and pregnancy outcomes in pregnant mice via modulating intestinal barrier and water-fluid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Baizhu (BZ) is the dried rhizome of Atractylodes macrocephala Koidz (Compositae), which invigorates the spleen, improves vital energy, stabilizes the fetus, and is widely used for treating spleen deficiency syndrome. However, the impact of BZ on gastrointestinal function during pregnancy remains unexplored. AIM OF THE STUDY: This study elucidated the ameliorative effects of BZ on gastrointestinal health and pregnancy outcomes in pregnant mice with spleen deficiency diarrhea (SDD). METHODS: To simulate an irregular human diet and overconsumption of cold and bitter foods leading to SDD, a model of pregnant mice with SDD was established using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, general indicators and diarrhea-related parameters were measured. Gastric and intestinal motility (small intestinal propulsion and gastric emptying rates) were evaluated. Serum motilin (MTL), ghrelin, growth hormone (GH), gastrin (Gas), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), chorionic gonadotropin ß (ß-CG), progesterone (P), and estradiol (E2) were quantified using an enzyme-linked immunosorbent assay. Pathological changes were examined by hematoxylin and eosin staining (H&E) and alcian blue periodic acid Schiff staining (AB-PAS). Immunohistochemistry and immunofluorescence were used to measure the expression levels of the intestinal barrier and water metabolism-related proteins in colonic tissues. The pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, small size, average fetal weight, and body length of fetal mice were calculated. RESULTS: The results showed that BZ significantly improved general indicators and diarrhea in pregnant mice with SDD, increased gastric emptying rate and small intestinal propulsion rate, elevated the levels of gastrointestinal hormones (AMS, ghrelin, GH, and Gas) in the serum, and reduced lipid levels (TC and LDL-c). It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin, claudin-1, ZO-1, AQP3, AQP4, and AQP8 in colonic tissues, downregulating the mRNA and protein expression levels of claudin-2, thereby alleviating intestinal barrier damage and regulating the balance of water and fluid metabolism. BZ also held the levels of pregnancy hormones (ß-CG, P, and E2) in the serum of pregnant mice with SDD. Moreover, it increased the pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, litter size, average fetal weight, and body length of fetal mice. These findings indicate that BZ can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.

Fetal growth after fresh and frozen embryo transfer and natural conception: A population-based register study.

OBJECTIVE: To investigate fetal growth trajectories and risks of small and large for gestational age (SGA and LGA), and macrosomia in pregnancies after fresh and frozen embryo transfer (ET), and natural conception (NC). DESIGN: Longitudinal population-based cohort study. SETTING: Swedish national registers. POPULATION: A total of 196 008 singleton pregnancies between 2013 and 2017. METHODS: Of all singleton pregnancies resulting in live births in the Swedish Pregnancy Register, 10 970 fresh ET, 6520 frozen ET, and 178 518 NC pregnancies with ultrasound data were included. A general least squares model was used to examine the effect of fresh or frozen ET on fetal growth while adjusting for confounders. MAIN OUTCOME MEASURES: Fetal growth velocity. SGA, LGA and macrosomia. RESULTS: At 120 days, fetal weights were lower in fresh ET pregnancies compared with NC pregnancies. Thereafter fresh ET as well as FET fetuses had higher fetal weights than NC fetuses, with no differences between themselves until the second trimester. From 210 days, FET fetuses were heavier than fresh ET fetuses, whereas fresh ET fetuses had lower fetal weights than NC fetuses from 245 days. After fresh ET, SGA was more frequent, whereas LGA and macrosomia were less frequent, than after FET. CONCLUSIONS: This study gives new insights into the differences in fetal growth dynamics between fresh and frozen ET and NC pregnancies. Clinically relevant differences in proportions of SGA, LGA and macrosomia were observed.

Assessment of fetal growth trajectory identifies infants at high risk of perinatal mortality.

OBJECTIVE: To analyze perinatal risks associated with three distinct scenarios of fetal growth trajectory in the latter half of pregnancy compared with a reference group. METHODS: This cohort study included women with a singleton pregnancy that delivered between 32 + 0 and 41 + 6 weeks' gestation and had two or more ultrasound scans, at least 4 weeks apart, from 18 + 0 weeks. We evaluated three different scenarios of fetal growth against a reference group, which comprised appropriate-for-gestational-age fetuses with appropriate forward-growth trajectory. The comparator growth trajectories were categorized as: Group 1, small-for-gestational-age (SGA) fetuses (estimated fetal weight (EFW) or abdominal circumference (AC) persistently < 10th centile) with appropriate forward growth; Group 2, fetuses with decreased growth trajectory (decrease of ≥ 50 centiles) and EFW or AC ≥ 10th centile (i.e. non-SGA) at their final ultrasound scan; and Group 3, fetuses with decreased growth trajectory and EFW or AC < 10th centile (i.e. SGA) at their final scan. The primary outcome was overall perinatal mortality (stillbirth or neonatal death). Secondary outcomes included stillbirth, delivery of a SGA infant, preterm birth, emergency Cesarean section for non-reassuring fetal status and composite severe neonatal morbidity. Associations were analyzed using logistic regression. RESULTS: The final study cohort comprised 5319 pregnancies. Compared to the reference group, the adjusted odds of perinatal mortality were increased significantly in Group 2 (adjusted odds ratio (aOR), 4.00 (95% CI, 1.36-11.22)) and Group 3 (aOR, 7.71 (95% CI, 2.39-24.91)). Only Group 3 had increased odds of stillbirth (aOR, 5.69 (95% CI, 1.55-20.93)). In contrast, infants in Group 1 did not have significantly increased odds of demise. The odds of a SGA infant at birth were increased in all three groups compared with the reference group, but was highest in Group 1 (aOR, 111.86 (95% CI, 62.58-199.95)) and Group 3 (aOR, 40.63 (95% CI, 29.01-56.92)). In both groups, more than 80% of infants were born SGA and nearly half had a birth weight < 3rd centile. Likewise, the odds of preterm birth were increased in all three groups compared with the reference group, being highest in Group 3, with an aOR of 4.27 (95% CI, 3.23-5.64). Lastly, the odds of composite severe neonatal morbidity were increased in Groups 1 and 3, whereas the odds of emergency Cesarean section for non-reassuring fetal status were increased only in Group 3. CONCLUSION: Assessing the fetal growth trajectory in the latter half of pregnancy can help identify infants at increased risk of perinatal mortality and birth weight < 3rd centile for gestation. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Neonatal Outcomes among Fetuses with an Abdominal Circumference <3rd %ile and Estimated Fetal Weight 3rd to 9th %ile Compared to Fetuses with an EFW <3rd %ile.

OBJECTIVE: Fetal growth restriction (FGR) is defined as an estimated fetal weight (EFW) or abdominal circumference (AC) <10th percentile (%ile) for gestational age (GA). An EFW <3rd %ile for GA is considered severe FGR (sFGR). It remains unknown if fetuses with isolated AC <3rd %ile should be considered sFGR. Our primary objective was to assess composite neonatal outcomes in fetuses with an AC <3rd %ile and overall EFW 3rd to 9th %ile compared with those with an EFW <3rd %ile. STUDY DESIGN: This retrospective cohort study was undertaken at a tertiary academic center from January 2016 to December 2021. Inclusion criteria were singleton fetuses with an EFW <3rd %ile (Group 1) or AC <3rd %ile with EFW 3rd to 9th %ile (Group 2) at 28 weeks' gestation or greater. Exclusion criteria were multiple gestations, presence of a major fetal anomaly, resolution of FGR, genetic syndrome, or infection. Composite neonatal outcome was defined by any of the following: neonatal intensive care unit admission >48 hours, necrotizing enterocolitis, sepsis, respiratory distress syndrome, mechanical ventilation, retinopathy of prematurity, seizures, intraventricular hemorrhage, stillbirth, or death before discharge. Small for gestational age (SGA) was defined as birth weight <10th %ile for GA. RESULTS: A total of 743 patients fulfilled our study criteria, with 489 in Group 1 and 254 in Group 2. The composite neonatal outcome occurred in 281 (57.5%) neonates in Group 1 and 53 (20.9%) in Group 2 (p < 0.01). The rates of SGA at birth were 94.9 and 75.6% for Group 1 and Group 2, respectively (OR 5.99, 95% confidence interval 3.65-9.82). CONCLUSION: Although AC <3rd %ile with EFW 3rd to 9th %ile is associated with a lower frequency of SGA and neonatal morbidity than EFW <3 %ile, fetuses with AC <3 %ile still exhibited moderate rates of these adverse perinatal outcomes. Consideration should be given to inclusion of an AC <3rd %ile with EFW 3rd to 9th %ile as a criterion for sFGR. However, prospective studies comparing delivery at 37 versus 38 to 39 weeks' gestation are needed to ensure improved outcomes before widespread adaptation in clinical practice. KEY POINTS: · The composite neonatal outcome occurred in 57.5% of fetuses with an overall EFW <3rd %ile and 20.9% of fetuses with an AC <3rd %ile but EFW 3rd to 9th %ile.. · Both groups demonstrated a high positive predictive value for SGA birth weight.. · Consideration should be given to inclusion of an AC <3rd %ile as a criterion for sFGR..