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.

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.

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.

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.

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.

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.

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.

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.

Anaemia in the first trimester and poor physiological plasma expansion during pregnancy negatively impact foetal weight and newborn anthropometrics: An observational cohort study in Tanzania.

OBJECTIVES: Anaemia during pregnancy is a major health challenge affecting pregnancy outcome worldwide. The objectives of this study were to investigate the impact of severe-moderate anaemia in the first trimester, as well as changes in haemoglobin during pregnancy among non-anaemic women, on foetal weight, placental blood flow and newborn anthropometrics. METHODS: In a prospective cohort study, 346 women residing in rural Tanzania were followed throughout pregnancy with serial ultrasound and newborn anthropometrics assessed within 24 h of delivery. Associations between placental blood flow, foetal weight and newborn anthropometrics with either first trimester severe-moderate anaemia (haemoglobin≤9.5 g/dL) or changes in haemoglobin from the first to the third trimester among non-anaemic women, were assessed by mixed model regression and multiple linear regression, adjusting for maternal and foetal co-variables. Foetal weights and birthweight were converted to z-scores using a population based sex-specific weight reference. RESULTS: Severe-moderate anaemia in the first trimester was associated with significantly reduced foetal weight z-scores (adjusted mean difference (aMD) -0.44 (95% CI -0.81, -0.07)) and newborn anthropometric indices (birth weight z-score aMD -0.55 (-0.9, -0.13), abdominal circumference aMD -11 mm (95% CI -20, -3)). There were no association between first trimester severe-moderate anaemia and placental blood flow. Among women who were non-anaemic in the first trimester, women with the least reduction in haemoglobin (Δ ≥ -0.3 g/dL) delivered significantly smaller newborns (birthweight z-score aMD -0.55 (-0.91, -0.20), abdominal circumference aMD -10 mm (95% CI -17, -3), compared to women with the greatest reduction (Δ haemoglobin ≤ -1.4 g/dL)). CONCLUSIONS: Severe-moderate anaemia in early pregnancy was associated with smaller newborn anthropometrics which was reflected in smaller mean foetal weights in the second and third trimester. Furthermore, among women who were non-anaemic in the first trimester, there was an association between smaller newborn anthropometrics and limited haemoglobin decrease during pregnancy, possibly reflecting insufficient plasma expansion.

Rate of deterioration of umbilical artery Doppler indices in fetuses with severe early-onset fetal growth restriction.

BACKGROUND: Incorporation of umbilical artery Doppler in the surveillance of fetal growth restriction has been shown to reduce the risk of perinatal deaths. Systole/Diastole ratio, Pulsatility Index and Resistance Index are obtained upon Doppler interrogation of the umbilical artery however it is unknown which index predicts more advanced stages of placental deterioration. OBJECTIVE: This study aimed to examine risk factors for the development of absent or reversed end-diastolic velocity and the time intervals of deterioration from normal umbilical artery end-diastolic velocity (indicated by systole/diastole ratio, pulsatility index, or resistance index) to decreased and absent or reversed end-diastolic velocity in fetuses with early-onset severe fetal growth restriction. STUDY DESIGN: This was a retrospective cohort study performed from 2005 to 2020. All singleton pregnancies with severe (estimated fetal weight or abdominal circumference below the third percentile) and early-onset (diagnosed between 20 0/7 and 31 6/7 weeks of gestation) fetal growth restriction were included. Patients with fetal genetic or structural anomalies, suspected congenital infections, absent or reversed end-diastolic velocity at diagnosis, poor pregnancy dating, and absence of follow-up ultrasounds were excluded. Estimated fetal weight, abdominal circumference, and Doppler indices were reviewed longitudinally from diagnosis to delivery. To examine risk factors for absent or reversed end-diastolic velocity, we performed backward stepwise logistic regression and calculated odds ratios with 95% confidence intervals. Kaplan-Meier curves were compared using log-rank tests. RESULTS: A total of 985 patients met the inclusion criteria, and 79 (8%) progressed to absent or reversed end-diastolic velocity. Factors associated with development of absent or reversed end-diastolic velocity included gestational age at diagnosis (adjusted odds ratio, 4.88 [95% confidence interval, 2.55-9.37] at 20 0/7 to 23 6/7 weeks; adjusted odds ratio, 1.56 [95% confidence interval, 0.86-2.82] at 24 0/7 to 27 6/7 weeks compared with 28 0/7 to 31 6/7 weeks) and presence of chronic hypertension (adjusted odds ratio, 2.37 [95% confidence interval, 1.33-4.23]). Rates of progression from diagnosis of fetal growth restriction with normal umbilical artery Doppler to absent or reversed end-diastolic velocity were significant after 4 weeks from diagnosis (5.84% [95% confidence interval, 4.50-7.57]). Regarding the Doppler indices, the progression from normal values to abnormal indices was similar at 1 and 2 weeks. However, the rate of progression from normal to abnormal systole/diastole ratio compared with the rates of progression from normal to abnormal pulsatility index or resistance index was higher at 4 and 6 weeks. Deterioration from abnormal indices to absent or reversed end-diastolic velocity was shorter with abnormal resistance index and pulsatility index when compared with the systole/diastole ratio at 2, 4, and 6 weeks after diagnosis and at 6 weeks, respectively. CONCLUSION: Earlier gestational age at diagnosis and chronic hypertension are considered as risk factors for Doppler deterioration and development of absent or reversed end-diastolic velocity in the umbilical artery. With normal Doppler indices, significant deterioration and progression to absent or reversed end-diastolic velocity is unlikely until 4 weeks after diagnosis. Abnormal systole/diastole ratio seems to appear first. However, abnormal pulsatility index or resistance index was associated with absent or reversed end-diastolic velocity.

Routine third-trimester ultrasound assessment for intrauterine growth restriction.

Intrauterine growth restriction significantly impacts perinatal outcomes. Undetected IUGR escalates the risk of adverse outcomes. Serial symphysis-fundal height measurement, a recommended strategy, is insufficient in detecting abnormal fetal growth. Routine third-trimester ultrasounds significantly improve detection rates compared with this approach, but direct high-quality evidence supporting enhanced perinatal outcomes from routine scanning is lacking. In assessing fetal growth, abdominal circumference alone performs comparably to estimated fetal weight. Hadlock formulas demonstrate accurate fetal weight estimation across diverse gestational ages and settings. When choosing growth charts, prescriptive standards (encompassing healthy pregnancies) should be prioritized over descriptive ones. Customized fetal standards may enhance antenatal IUGR detection, but conclusive high-quality evidence is elusive. Emerging observational data suggest that longitudinal fetal growth assessment could predict adverse outcomes better. However, direct randomized trial evidence supporting this remains insufficient.

Associations of intrauterine exposure to manganese with fetal and early-childhood growth: a prospective prenatal cohort study.

Prenatal manganese (Mn) exposure may be related to poor birth outcomes; however, there are few relevant epidemiological reports on the effects of intrauterine Mn levels on intrauterine fetal and early childhood growth. From 2013 to 2016, 2082 pairs of mothers and infants were recruited in Wuhan, China, who provided an entire set of urine samples during their first, second, and third trimesters. Fetal head circumference (HC), abdominal circumference (AC), femoral length (FL), and estimated fetal weight (EFW) were obtained by ultrasound at the 16, 24, and 31 weeks of pregnancy. When the children were born, 6 months old, 12 months old, and 24 months old, their weight, height, weight-for-height, and BMI were measured. We used generalized linear models, generalized estimated equations, and restricted cubic spline curves (RCS) to investigate the linear and nonlinear relationships between antenatal Mn levels and fetal and early childhood growth. In all fetuses, Mn exposure during the 1st and 2nd gestation was associated with decreased fetal AC, FL, and EFW at 24 weeks (e.g., for each doubling of urinary Mn concentrations during the 1st and 2nd gestation, the SD score of EFW at 24 weeks decreased by - 4.16% (95% CI, - 6.22%, - 2.10%) and - 3.78% (95% CI, - 5.86%, - 1.70%)). Mn concentrations in the highest tertile group of the 1st and 2nd gestation were related to decreased fetus growth parameters compared to the lowest tertile group. For each doubling of the average Mn concentrations during pregnancy, the z-scores of weight, weight-for-height, and BMI at 12 months decreased, with percentage changes of - 2.93% (95% CI, - 5.08%, - 0.79%), - 3.25% (95% CI, - 5.56%, - 0.94%), and - 3.09% (95% CI, - 5.44%, - 0.73%). In the RCS model, we found a reverse U-shaped association between 1st trimester Mn concentration and fetal FL at 16 weeks and HC at 31 weeks in male fetuses and a non-linear association between mean Mn concentration during pregnancy and girls' weight-for-height and BMI at 6 months. Intrauterine exposure to Mn may be related to restricted growth in the fetus and early childhood, especially in fetuses at 24 weeks of gestation and children at 12 months of age. Also, meaningful curvilinear relationships were found in the sex stratification.

Risk factors of more severe hypotension after spinal anesthesia for cesarean section.

BACKGROUND: The aim of this study was to examine the risk factors associated with the use of vasopressors to prevent hypotension that occurs after spinal anesthesia during cesarean section. Although the prophylactic use of vasopressors is already suggested as routine care in many parts of the world, the occurrence of spinal anesthesia-induced hypotension (SAIH) is still common in parturients. METHODS: This retrospective study included parturients receiving elective cesarean deliveries under spinal anesthesia from April 2016 to March 2020. Risk factors related to ephedrine dosage were analyzed using a hurdle model, and risk factors related to SAIH were further analyzed with logistic regression. RESULTS: Five risk factors, namely maternal body mass index (BMI, p < 0.001), baseline systolic blood pressure (SBP, p < 0.001), baseline heart rate (HR, p = 0.047), multiparity ( p = 0.003), and large fetal weight ( p = 0.005) were significantly associated with the requirement for ephedrine. Furthermore, a higher ephedrine dosage was significantly associated with maternal BMI ( p < 0.001), baseline SBP ( p < 0.001), baseline HR ( p < 0.001), multiparity ( p = 0.027), large fetal weight ( p = 0.030), maternal age ( p = 0.009), and twin pregnancies ( p < 0.001). Logistic regression analysis also showed that the same five risk factors-maternal BMI ( p = 0.030), baseline SBP ( p < 0.001), baseline HR ( p < 0.001), multiparity ( p < 0.001), and large fetal weight ( p < 0.001)-were significantly associated with SAIH, even in cases where vasopressors were administered. CONCLUSION: These findings can be useful for clinicians when deciding the dose of prophylactic ephedrine or phenylephrine to prevent SAIH.

A case-control retrospective study for the effect of Shoutai Wan on IVF-ET pregnancy outcome.

It has a long history of preventing and treating disease using traditional Chinese medicine (TCM). In recent years, it has been widely used in adjuvant therapies of in vitro fertilization - embryo transfer (IVF-ET) in China. To observe the effect and safety of Shoutai Wan on pregnancy outcomes after IVF-ET. A total of 352 patients who underwent IVF-ET from July 1, 2020 to June 30, 2021. The participants who only received routine luteal support during clinical pregnancy of FET were defined as the control group, and others who received TCM decoction Shoutai Wan for prevention of miscarriage and routine luteal support were defined as the Chinese medicine protection Shoutai Wan group (St group). This project has been approved by the Ethics Committee of Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine (Approval NO: 2023-0305). The results of this retrospective cohort study revealed that Shoutaiwan combined with luteal support treatment can significantly decreased the miscarriage rate in pregnancy undergoing IVF-FET compared to the group accepted only luteal support treatment (P = .001). Meanwhile, St during pregnancy did not affect fetal birth weight (P = .354), and there was no adverse event in the St group reported, which confirmed the safety of TCM for fetus protection during pregnancy. This study not only provides evidences for the clinical administration of Shoutai Wan in IVF-ET, but also provides a novel direction for basic research into the subsequent innovative application of TCM.

Maternal GLP-1 receptor activation inhibits fetal growth.

Glucagon-like peptide 1 (GLP-1) regulates food intake, insulin production, and metabolism. Our recent study demonstrated that pancreatic α-cells-secreted (intraislet) GLP-1 effectively promotes maternal insulin secretion and metabolic adaptation during pregnancy. However, the role of circulating GLP-1 in maternal energy metabolism remains largely unknown. Our study aims to investigate systemic GLP-1 response to pregnancy and its regulatory effect on fetal growth. Using C57BL/6 mice, we observed a gradual decline in maternal blood GLP-1 concentrations. Subsequent administration of the GLP-1 receptor agonist semaglutide (Sem) to dams in late pregnancy revealed a modest decrease in maternal food intake during initial treatment. At the same time, no significant alterations were observed in maternal body weight or fat mass. Notably, Sem-treated dams exhibited a significant decrease in fetal body weight, which persisted even following the restoration of maternal blood glucose levels. Despite no observable change in placental weight, a marked reduction in the placenta labyrinth area from Sem-treated dams was evident. Our investigation further demonstrated a substantial decrease in the expression levels of various pivotal nutrient transporters within the placenta, including glucose transporter one and sodium-neutral amino acid transporter one, after Sem treatment. In addition, Sem injection led to a notable reduction in the capillary area, number, and surface densities within the labyrinth. These findings underscore the crucial role of modulating circulating GLP-1 levels in maternal adaptation, emphasizing the inhibitory effects of excessive GLP-1 receptor activation on both placental development and fetal growth.NEW & NOTEWORTHY Our study reveals a progressive decline in maternal blood glucagon-like peptide 1 (GLP-1) concentration. GLP-1 receptor agonist injection in late pregnancy significantly reduced fetal body weight, even after restoration of maternal blood glucose concentration. GLP-1 receptor activation significantly reduced the placental labyrinth area, expression of some nutrient transporters, and capillary development. Our study indicates that reducing maternal blood GLP-1 levels is a physiological adaptation process that benefits placental development and fetal growth.

Perinatal outcome of fetuses predicted to be large-for-gestational age on universal third-trimester ultrasound in non-diabetic pregnancy.

OBJECTIVE: To describe the perinatal outcome of fetuses predicted to be large-for-gestational age (LGA) on universal third-trimester ultrasound in non-diabetic pregnancies of women attempting vaginal delivery. METHODS: This was a prospective population-based cohort study of patients from a single tertiary maternity unit in the UK offering universal third-trimester ultrasound and practicing expectant management of suspected LGA until 41-42 weeks. All women with a singleton pregnancy and an estimated due date between January 2014 and September 2019 were included. Women delivering before 37 weeks, those having a planned Cesarean delivery, those with pre-existing or gestational diabetes, those with fetal abnormalities and those who did not undergo a third-trimester scan were excluded from the assessment of perinatal outcome of cases with LGA predicted on ultrasound after implementation of the universal scan period. Association of LGA on universal third-trimester ultrasound screening and perinatal adverse outcome was assessed, with the exposures of interest being estimated fetal weight (EFW) at the 90th -95th , > 95th and > 99th percentile. The reference group was composed of fetuses with EFW at the 30th -70th percentile. Analysis was performed using multivariate logistic regression. The evaluated adverse perinatal outcomes included a composite outcome of admission to neonatal intensive care unit, Apgar score < 7 at 5 min and arterial cord pH < 7.1 (CAO1) and a composite outcome of stillbirth, neonatal death and hypoxic ischemic encephalopathy (CAO2). Secondary maternal outcomes were induction of labor, mode of delivery, postpartum hemorrhage, shoulder dystocia and obstetric anal sphincter injury. RESULTS: Cases with EFW > 95th percentile on universal third-trimester scan were at increased risk of CAO1 (adjusted odds ratio (aOR), 2.18 (95% CI, 1.69-2.80)) and CAO2 (aOR, 2.58 (95% CI, 1.05-6.34)). Cases with EFW at the 90th -95th percentile had a less pronounced increase in the risk of CAO1 (aOR, 1.35 (95% CI, 1.02-1.78)) and were not at increased risk of CAO2. All pregnancies with a fetus predicted to be LGA were at increased risk of all of the evaluated secondary maternal outcomes except for obstetric anal sphincter injury. The risk of adverse maternal outcome was typically higher with increasing EFW. Post-hoc exploration of data suggested that shoulder dystocia had a limited contribution to composite adverse perinatal outcomes in LGA cases (population attributable fraction of 10.8% for CAO1 and 29.1% for CAO2). CONCLUSIONS: Cases with EFW > 95th percentile are at increased risk of severe adverse perinatal outcome, such as death and hypoxic ischemic encephalopathy. These findings should aid antenatal counseling regarding the associated risk and delivery options. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal insular measurements in pregnancy with estimated fetal weight <10th centile and childhood neurodevelopmental outcomes.

BACKGROUND: A growing body of evidence suggests that fetal growth restriction is associated with changes in brain structures as a result of chronic hypoxia. However, less is known about the effects of growth restriction on the fetal insula, particularly in less severely affected late-onset growth-restricted fetuses. OBJECTIVE: This study aimed to (1) compare sonographic insular measurements between fetal-growth restricted, small-for-gestational-age, and appropriate-for-gestational-age control fetuses; and (2) evaluate the association of sonographic insular measurements with perinatal and neurodevelopmental outcomes in fetuses categorized as fetal-growth restricted or small-for-gestational-age. STUDY DESIGN: This was a cohort study of singleton nonanomalous pregnancies with an estimated fetal weight <10th centile. Using data from the last examination before delivery, fetal insular depth, Sylvian fissure depth, hypoechoic insular zone thickness, circumference, and area were measured. All measurements were adjusted for by head circumference. Neurodevelopmental outcomes were evaluated at 2 to 3 years of age using the Bayley-III scales. Kruskal-Wallis H tests were performed to compare insular measurements between groups. Paired t tests were used to compare insular measurements between appropriate-for-gestational-age fetuses and gestational age-matched growth-restricted fetuses. Insular measurements for patients with and without an adverse perinatal outcome were compared using independent-samples t-tests. Spearman correlations were performed to evaluate the relationship of insular measurements to the percentile scores for each of the 5 Bayley-III subscales and to a summative percentile of these subscales. RESULTS: A total of 89 pregnancies were included in the study; 68 of these pregnancies had an estimated fetal weight <10th percentile (fetal-growth restricted: n=39; small-for-gestational-age: n=29). The appropriate-for-gestational-age cohort consisted of 21 pregnancies. The gestational age at measurement was similar between fetal-growth restricted and small-for-gestational-age groups, but lower in the appropriate-for-gestational-age group. Differences between groups were noted in normalized insular depth, Sylvian fissure depth, and hypoechoic insular zone (P<.01). Normalized insular depth and hypoechoic insular zone circumference were larger in the growth-restricted cohort (P<.01). Normalized Sylvian fissure depth was smaller in the growth-restricted cohort (P<.01). There were no significant differences in insular measurements between pregnancies with and without an adverse perinatal outcome. Bayley-III results were available in 32 of the growth-restricted cases. Of all insular measurements, hypoechoic insular zone circumference was inversely correlated with the adaptive behavior Bayley-III score. CONCLUSION: In our cohort, fetuses with estimated fetal weight <10th percentile had smaller Sylvian fissure depths and larger insular depths and hypoechoic insular zone circumferences than normally grown controls. A larger hypoechoic insular zone circumference was substantially correlated with worse neurodevelopmental outcomes in early childhood. We speculate that enlargement of this region may be an indication of accelerated neuronal maturation in growth-restricted fetuses with mild hypoxia.

Fetal Thymus Size at 19-22 Weeks of Gestation: A Possible Marker for the Prediction of Low Birth Weight?

INTRODUCTION: The purpose was to compare thymus size measured during second trimester screening of fetuses who were subsequently small for gestational age at birth (weight below 10th percentile, SGA group) with fetuses with normal birth weight (control group). We hypothesized that measuring the fetal thymic-thoracic ratio (TT-ratio) might help predict low birth weight. METHODS: Using three-vessel view echocardiograms from our archives, we measured the anteroposterior thymus size and the intrathoracic mediastinal diameter to derive TT-ratios in the SGA (n = 105) and control groups (n = 533) between 19+0 and 21+6 weeks of gestation. We analyzed the association between TT-ratio and SGA adjusted to the week of gestation using logistic regression. Finally, we determined the possible TT-ratio cut-off point for discrimination between SGA and control groups by means of receiver operating characteristics (ROC) curve analysis. RESULTS: The TT-ratio was significantly higher in the SGA group than in the control group (p < 0.001). An increase of the TT-ratio by 0.1 was associated with a 3.1-fold increase in the odds of diagnosing SGA. We determined that a possible discrimination cut-off point between SGA and healthy controls was achieved using a TT-ratio of 0.390 (area under the ROC curve 0.695). CONCLUSION: An increased TT-ratio may represent an additional prenatal screening parameter that improves the prediction of birth weight below the 10th percentile. Prospective studies are now needed to evaluate the use of fetal thymus size as predictive parameter for adverse fetal outcome.

Diagnostic performance of 32 vs 36 weeks ultrasound in predicting late-onset fetal growth restriction and small-for-gestational-age neonates: a systematic review and meta-analysis.

OBJECTIVE: Fetal growth restriction is an independent risk factor for fetal death and adverse neonatal outcomes. The main aim of this study was to investigate the diagnostic performance of 32 vs 36 weeks ultrasound of fetal biometry in detecting late-onset fetal growth restriction and predicting small-for-gestational-age neonates. DATA SOURCES: A systematic search was performed to identify relevant studies published until June 2022, using the databases PubMed, Web of Science, and Scopus. STUDY ELIGIBILITY CRITERIA: Cohort studies in low-risk or unselected singleton pregnancies with screening ultrasound performed at ≥32 weeks of gestation were used. METHODS: The estimated fetal weight and abdominal circumference were assessed as index tests for the prediction of small for gestational age (birthweight of <10th percentile) and detecting fetal growth restriction (estimated fetal weight of <10th percentile and/or abdominal circumference of <10th percentile). The quality of the included studies was independently assessed by 2 reviewers using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. For the meta-analysis, hierarchical summary area under the receiver operating characteristic curves were constructed, and quantitative data synthesis was performed using random-effects models. RESULTS: The analysis included 25 studies encompassing 73,981 low-risk pregnancies undergoing third-trimester ultrasound assessment for growth, of which 5380 neonates (7.3%) were small for gestational age at birth. The pooled sensitivities for estimated fetal weight of <10th percentile and abdominal circumference of <10th percentile in predicting small for gestational age were 36% (95% confidence interval, 27%-46%) and 37% (95% confidence interval, 19%-60%), respectively, at 32 weeks ultrasound and 48% (95% confidence interval, 41%-56%) and 50% (95% confidence interval, 25%-74%), respectively, at 36 weeks ultrasound. The pooled specificities for estimated fetal weight of <10th percentile and abdominal circumference of <10th percentile in detecting small for gestational age were 93% (95% confidence interval, 91%-95%) and 95% (95% confidence interval, 85%-98%), respectively, at 32 weeks ultrasound and 93% (95% confidence interval, 91%-95%) and 97% (95% confidence interval, 85%-98%), respectively, at 36 weeks ultrasound. The observed diagnostic odds ratios for an estimated fetal weight of <10th percentile and an abdominal circumference of <10th percentile in detecting small for gestational age were 8.8 (95% confidence interval, 5.4-14.4) and 11.6 (95% confidence interval, 6.2-21.6), respectively, at 32 weeks ultrasound and 13.3 (95% confidence interval, 10.4-16.9) and 36.0 (95% confidence interval, 4.9-260.0), respectively, at 36 weeks ultrasound. The pooled sensitivity, specificity, and diagnostic odds ratio in predicting fetal growth restriction were 71% (95% confidence interval, 52%-85%), 90% (95% confidence interval, 79%-95%), and 25.8 (95% confidence interval, 14.5-45.8), respectively, at 32 weeks ultrasound and 48% (95% confidence interval, 41%-55%), 94% (95% confidence interval, 93%-96%), and 16.9 (95% confidence interval, 10.8-26.6), respectively, at 36 weeks ultrasound. Abdominal circumference of <10th percentile seemed to have comparable sensitivity to estimated fetal weight of <10th percentile in predicting small-for-gestational-age neonates. CONCLUSION: An ultrasound assessment of the fetal biometry at 36 weeks of gestation seemed to have better predictive accuracy for small-for-gestational-age neonates than an ultrasound assessment at 32 weeks of gestation. However, an opposite trend was noted when the outcome was fetal growth restriction. Fetal abdominal circumference had a similar predictive accuracy to that of estimated fetal weight in detecting small-for-gestational-age neonates.