Late Pregnancy Research Articles

Association Between Red Blood Cell Distribution Width in Late Pregnancy and the Incidence of Adverse Perinatal Outcomes: A Retrospective Cohort Study

This study aimed to quantify adverse perinatal outcomes (APO), including small/large for gestational age (SGA/LGA) and preterm birth (PTB), in pregnant women with abnormal red cell distribution width (RDW) and explore the related mechanisms. This study included 11,659 pregnant women who delivered in a specialized hospital. At the time of admission, the lipid profiles and whole blood cell counts were assessed, and APO was analyzed. Women with high RDW (>18.5% [the 97.5th percentile]) in late pregnancy had a higher risk of LGA compared with those with low RDW (<12.3% [the 2.5th percentile]), whereas women with low RDW had a higher risk of SGA and PTB, compared with those with high RDW. A 1% increase in RDW was associated with an increased risk of LGA and a decreased risk of SGA and PTB. Consistent associations were observed in sensitivity analysis among pregnant women of non-advanced age, non-obesity, non-pregnancy complications, and non-PTB (for SGA/LGA only). Increased RDW was significantly associated with increased triglycerides and decreased high-density lipoprotein cholesterol (HDL-C). Triglycerides and HDL-C significantly mediated 10.63 and 15.8% of RDW-associated LGA, 9.51% and 9.40 of RDW-associated SGA, and 8.44 and -8.25% of RDW-associated PTB, respectively. Abnormal RDW was associated with an increased risk of APO, and the RDW-associated APO risk could be partially mediated by triglycerides and HDL-C, suggesting that RDW may be a promising APO predictor.

The Association of Antidepressants in Late Pregnancy with Postpartum Hemorrhage: Systematic Review of Controlled Observational Studies.

Introduction: Despite advances in obstetric care, postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Prior reviews of studies published through 2016 suggest an association of antidepressant use during late pregnancy and increased risk of PPH. However, a causal link between prenatal antidepressants and PPH remains controversial. Objectives: This systematic literature review aimed to synthesize the empirical evidence on the association of antidepressant exposure in late pregnancy with the risk of PPH, including studies published before and after 2016. Methods: A systematic literature search was conducted using PubMed, OVID Medline, EMBASE, SCOPUS, PsycINFO, and CINAHL from inception to September 9, 2023. Original, peer-reviewed studies (published in English) that reported on the frequency or risk of PPH in women with evidence of antidepressant use during pregnancy and included at least one control group were included. Results: Twenty studies (eight published after 2016) met inclusion criteria, most of which focused on the risks of PPH associated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). The main findings from the individual studies were mixed, but the majority documented statistically significant associations of PPH with late prenatal exposure, especially for exposures occurring within 30 days of delivery, compared with unexposed deliveries. Fourteen studies addressed underlying antidepressant indications or their correlates. Few studies focused on prenatal antidepressants and the risk of well-defined severe PPH or on antidepressant dose changes and general PPH risk. None examined competing risks of antidepressant discontinuation on mental health outcomes. Conclusions: Late pregnancy exposure to antidepressants may be a minor risk factor for PPH, but it is unclear to what extent reported associations are causal in nature, as opposed to correlational (effects related to nonpharmacological factors including maternal indication). For patients needing antidepressants during pregnancy, current evidence does not favor routinely discontinuing antidepressants specifically to reduce the risk of PPH.

Maternal adiponectin restores cholinergic vasodilation in resistance vessels from adult offspring exposed to maternal obesity in utero.

Maternal obesity increases the risk of cardiovascular and metabolic disease in the offspring both during childhood and adult life. Pregnant women and mice with obesity have lower circulating levels of adiponectin (ADN) compared to lean controls. ADN is an adipokine involved in regulating energy metabolism, vascular function, and placental function. We hypothesized that offspring of obese mice have impaired resistance artery function, which can be prevented by restoration of normal circulating ADN levels in obese dams during late pregnancy. Adult female mice were fed either control or obesogenic diet and mated with control diet-fed males. Control dams received a continuous infusion of phosphate saline buffer (PBS) during late pregnancy whereas obese females received either PBS or ADN. After weaning, offspring were fed a control diet. Mesenteric arteries (MsA) were dissected from adult offspring and mounted in a wire myograph or fixed for histology. MsA responses to vasoconstrictors (phenylephrine and endothelin-1) were not different between infusion groups. However, the vasodilatory responses to acetylcholine were reduced in offspring from obese dams as compared to control-fed dams. ADN supplementation during pregnancy restored the cholinergic vasodilatory responses of resistance vessels in offspring from obese dams. These observations suggest a target during obese pregnancy for the prevention of the long-lasting vascular effects in the offspring.

Biparietal diameter vs crown-rump length as standard parameter for late first-trimester pregnancy dating.

To compare the precision of biparietal diameter (BPD) and crown-rump length (CRL) as predictors of gestational age in the human fetus in the late first and early second trimesters, using a population-based approach. We constructed term and gestational-age prediction curves for first-trimester dating, based on 11 041 pregnancies with 12 260 measurements of CRL and/or BPD from a population-based Norwegian clinical database. We used a population-based approach with local linear quantile regression, combined with a time-to-event strategy that compensates for induced births. Term prediction precision was assessed by estimating and comparing the prediction residual curves using a time-to-event analysis. Individual differences in gestational-age predictions from CRL and BPD were assessed using measurements performed on the same fetus on the same day. A sensitivity analysis was performed to evaluate the effect of not distinguishing between non-spontaneous and spontaneous births. CRL and BPD provided almost identical term prediction precision judged from the residual distribution. In about 51% of examinations, the difference in predicted gestational age was 1 day or less; 24% of examinations had a difference of 2 days, 14% had a difference of 3 days, 7% had a difference of 4 days and only 5% of all examinations had a difference of 5 days or more. Incorrectly removing induced births from the analysis, or treating them as spontaneous, would cause a substantial systematic prediction bias of about 2 days. Based on population data, using comparisons at an individual level, our study found that BPD is as precise as CRL when used for first-trimester dating. BPD has advantages from a clinical point of view, since it is technically less challenging and less time-consuming to measure compared with CRL, and can be measured and assessed throughout the entire pregnancy. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A nomogram for predicting postpartum post-traumatic stress disorder: a prospective cohort study

BackgroundPostpartumpost-traumatic stress disorder (PTSD), as a psychological stress disorder, has long-term and widespread harm. Still, compared with other postpartum psychiatric disorders, postpartum PTSD has received relatively littleattention in China. This study aims to investigate the risk factors of postpartum PTSD and to develop a convenient and rapid nomogram screening tool to help clinical staff identify high-risk pregnant womenin time and take preventative and management measures.MethodsRecruited pregnant women hospitalized for delivery in Qingdao Municipal Hospital and Jinzhou Maternal and Child Health Hospital from November 2022 to October 2023 as convenient samples for the questionnaire survey. Telephone follow-up was conducted 42 days after delivery. After univariate analysis, multicollinearity analysis, and logistic regression analysis, the risk factors of postnatal PTSD were obtained, a prediction model was established, and a nomogram was drawn by R software. G*power3.1.9.7 calculated the effectiveness of the test. The model was validated internally using the Bootstrap approach, and external validation was carried out using a verification group. The accuracy of the model's predictions and its clinical application value were evaluated by the area under the curve, calibration plot, and decision curve analysis.ResultsA total of 602 women were recruited in this study, and the incidence of postpartum PTSD was 11.1% (67/602). Multifactorial logistic regression analysis showed that poor self-assessment of sleep status in late pregnancy (OR = 5.336), cesarean section (OR = 2.825), instrumental delivery (OR = 5.994), having fear of labor (OR = 4.857), and a high score of Five Factors Inventory Neuroticism subscale (OR = 1.244) were independent risk factors for developing postpartum PTSD. A high Quality of Relationship Index score (OR = 0.891) was a protective factor for postpartum PTSD. In the training and validation sets, the nomogram model's area under the ROC curve was 0.928 and 0.907, respectively. The calibration curves showed that the nomogram model was well-fitted, and the Decision Curve Analysis indicated that the nomogram model had good value for clinical application.ConclusionsWith its strong predictive capacity, the prediction model built using postpartum PTSD risk factors can help clinical caregivers identify high-risk pregnant women early on and implement timely preventive intervention strategies.

Pregnancy and lactation associated osteoporotic vertebral fracture: the neurosurgical perspective through a multicentric study.

Pregnancy and lactation-associated osteoporosis is a rare form of osteoporosis occurring during late pregnancy and early lactation, featuring fragility fractures, primarily involving the vertebral bodies and leading to back pain. Its management involves osteoporosis treatment, complicated by potential drug-related dangerous effects on the fetus. Nevertheless, many controversies remain regarding diagnosis, prognosis, and treatment options. Herein, we propose a multicentric case series to provide a comprehensive neurosurgical, gynecological, and endocrinological perspective on the management of pregnancy and lactation-associated osteoporotic vertebral fractures.A multicenter retrospective study was conducted at the Neurosurgical Department of Università degli Studi di Napoli Federico II, the Neurosurgical Unit of Hopitaux Universitaires de Genève, and the Spine and Spinal Cord Surgery Unit of the University Hospital of Udine, collecting data from January 2014 to December 2022. The study has been approved by the ethical committee of each hospital.N = 11 patients with an overall number of 31 fractures were eligible, with a mean age of 36. N = 5 (16%) fractures in 4 patients (36%) developed during pregnancy, and N = 26 (84%) fractures in 7 (64%) patients occurred during lactation. The mean number of fractures per patient was 2,81. In 10 (90%) patients, fractures occurred at the first pregnancy, and 5 (45%) patients had uneventful subsequent pregnancies. The mean clinical signs and symptoms were back pain (92%), followed by loss of height (75%) and kyphosis (4 patients, 35%). One (9,09%) patient underwent in vitro fertilization (IVF), and one patient (9,09%) was receiving hormonal therapy (ethinylestradiol/drosiprenone). 10 out of 11 (90%) patients were treated conservatively, and 6 of them (60%) were managed with an orthosis. One (9,1%) patient underwent surgery for 5-level kyphoplasty. The mean average reduction of pain after one year of follow-up was 6,7 on the visual analogue scale (p-value 0,04).Pregnancy-related osteoporotic vertebral fractures are an emerging issue in developing countries, for which a conservative strategy ensures the best outcomes. The main goal is to improve bone mineral density through calcium and vitamin D supplementation and bone-active drugs as bisphosphonates or teriparatide. Surgery is warranted only in cases of a risk of severe deterioration of neurological functions.

Does Omega-3 supplementation increase profuse postpartum hemorrhage? A hospital-based register study.

Although Omega-3 is thought to have anticoagulative properties, the potential untoward effects of Omega-3 during pregnancy have not been investigated. No previous studies have been made to specifically assess its effect on postpartum hemorrhage (PPH). Our aim was to determine if an association exists between Omega-3 intake during pregnancy and profuse PPH or massive PPH. Data on all deliveries that occurred at Karolinska University Hospital during the years 2007-2011 (n = 41 139) was collected from the medical record of Obstetrix, maternal health and delivery chart system. Women with reported Omega-3 use in early pregnancy were considered exposed and all other as unexposed. Bivariate and adjusted multivariate analysis was performed on main outcomes. Omega-3 use was associated with 25% increased odds of PPH (adjusted odds ratio (aOR) 1.25, 95% confidence interval [CI] (1.06-1.47)) and a more than doubled odds of massive PPH (aOR 2.36, 95% CI 1.26-4.44). In addition, there was a minor increase in the amount of blood loss. Although few, women on low-dose discontinued terminated at 36th week showed no significant association to blood loss measurements. Our observational findings showed 25% higher odds of PPH and two times higher odds of massive PPH in women who reported using Omega-3 in early pregnancy. Our findings give some support to advocate discontinued use of Omega-3 in late pregnancy.

MicroRNA expression profiles in plasma exosomes of late pregnant giant pandas.

MicroRNAs can regulate various biological functions including cell proliferation, differentiation, embryo formation, and implantation. The giant panda exhibits embryonic diapause, with embryo development resuming in late pregnancy. However, the changes in microRNAs during late pregnancy remain poorly understand. After mating, plasma samples were collected on day 40 of early pregnancy (EP; n = 3) and 30 days before delivery of late pregnancy (LP; n = 3). Following microRNAs screening, a total of 120 microRNAs were detected in the plasma exosomes of pregnant pandas. Nine differentially expressed microRNAs (DEmicroRNAs) were identified in LP compared to EP, including three that were upregulated and six that were downregulated. Notably, miR-25b and miR-47 were significantly downregulated in LP group. All DEmicroRNAs were predicted to target a total of 2,675 genes. Pathway enrichment analysis of these target genes revealed significant enrichment in the MAPK and Rap1 signaling pathways, which are closely related to cell proliferation, differentiation, and cell-cell and cell-matrix interactions. Analysis of protein-protein interaction networks showed that most of the hub genes (five out of eight), including Fgfr1, Fgf2, Fgf18, Erbb4, and Kras within the MAPK and Rap1 pathways are associated with the cell proliferation and differentiation. Significantly, Erbb4 was regulated by significantly differentially expressed miRNA-47. We suggest that plasma exosomal microRNAs are involved in cell proliferation and differentiation during embryonic development by regulating key hub genes within MAPK and Rap1 pathways. These findings provided new insights into the development of giant panda embryos.

Associations between prenatal distress, mitochondrial health, and gestational age: findings from two pregnancy studies in the USA and Turkey.

Pregnancy outcomes are influenced by maternal distress but the pathways underlying these effects are still unknown. Mitochondria, crucial for stress adaptation and energy production, may link psychosocial stress to its biological effects, especially during pregnancy when energy demands significantly increase. This study explores two mitochondrial markers-circulating cell-free mitochondrial DNA (cf-mtDNA) and Growth Differentiation Factor-15 (GDF15)-as potential mitochondrial health indicators linking maternal distress to pregnancy outcomes in two longitudinal studies from the USA and Turkey. We analyzed biological, demographic, and psychological data from women in two pregnancy studies: EPI (N=187, USA, Mean age=29.6(SD=6.2) and BABIP (N=198, Turkey, Mean age=32.4(SD=4.0)). Data were collected at multiple time points during the perinatal period, including late 2nd and 3rd trimester, with EPI also including additional data at early 2nd trimester and 4-14 months postpartum. Prenatal maternal psychological distress was measured as perceived stress, anxiety, and depressive symptoms. Plasma cf-mtDNA and GDF15 levels were assessed using qPCR and ELISA, respectively. Statistical analyses included Wilcoxon signed-rank tests, Spearman correlations, and Mann-Whitney tests. Plasma cf-mtDNA levels did not change significantly during pregnancy in either study. Plasma GDF15 levels increased from early to late pregnancy in both studies and significantly decreased postpartum in EPI. Perinatal maternal distress in the late 2 nd and 3 rd trimesters was not associated with cf-mtDNA or GDF15 in either study. Metabolic distress, measured as higher pre-pregnancy BMI, was negatively correlated with GDF15 in the late 2 nd trimester in EPI and showed a similar trend in BABIP. Similarly, higher maternal psychological distress in the early 2 nd trimester were associated with lower cf-mtDNA and a trend for lower GDF15 in EPI. Finally, higher pre-pregnancy BMI and maternal distress in late pregnancy were linked to a smaller decline in GDF15 from late pregnancy to postpartum in EPI, suggesting an interaction between metabolic stress, prenatal distress and post-pregnancy physiological recovery. This study identified distinct patterns of plasma cf-mtDNA and GDF15 levels during the perinatal period across studies from two countries, revealing unique associations between maternal characteristics, prenatal distress, and pregnancy outcomes, suggesting that maternal distress can interact with energy mobilization during pregnancy.

Ambient temperature exposure and rapid infant weight gain.

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

FGFR4 Is Required for Concentric Growth of Cardiac Myocytes during Physiologic Cardiac Hypertrophy.

Fibroblast growth factor (FGF) 23 is a bone-derived hormone that promotes renal phosphate excretion. Serum FGF23 is increased in chronic kidney disease (CKD) and contributes to pathologic cardiac hypertrophy by activating FGF receptor (FGFR) 4 on cardiac myocytes, which might lead to the high cardiovascular mortality in CKD patients. Increases in serum FGF23 levels have also been observed following endurance exercise and in pregnancy, which are scenarios of physiologic cardiac hypertrophy as an adaptive response of the heart to increased demand. To determine whether FGF23/FGFR4 contributes to physiologic cardiac hypertrophy, we studied FGFR4 knockout mice (FGFR4-/-) during late pregnancy. In comparison to virgin littermates, pregnant wild-type and FGFR4-/- mice showed increases in serum FGF23 levels and heart weight; however, the elevation in myocyte area observed in pregnant wild-type mice was abrogated in pregnant FGFR4-/- mice. This outcome was supported by treatments of cultured cardiac myocytes with serum from fed Burmese pythons, another model of physiologic hypertrophy, where the co-treatment with an FGFR4-specific inhibitor abrogated the serum-induced increase in cell area. Interestingly, we found that in pregnant mice, the heart, and not the bone, shows elevated FGF23 expression, and that increases in serum FGF23 are not accompanied by changes in phosphate metabolism. Our study suggests that in physiologic cardiac hypertrophy, the heart produces FGF23 that contributes to hypertrophic growth of cardiac myocytes in a paracrine and FGFR4-dependent manner, and that the kidney does not respond to heart-derived FGF23.

EV-miRNA associated with environmental air pollution exposures in the MADRES cohort

ABSTRACT Air pollution is a hazardous contaminant, exposure to which has substantial consequences for health during critical periods, such as pregnancy. MicroRNA (miRNA) are an epigenetic mechanism that modulates transcriptome responses to the environment and have been found to change in reaction to air pollution exposure. The data are limited regarding extracellular-vesicle (EV) miRNA variation associated with air pollution exposure during pregnancy and in susceptible populations who may be disproportionately exposed. This study aimed to identify EV-miRNA expression associated with ambient, residential exposure to PM2.5, PM10, NO2, O3 and with traffic-related NOx in 461 participants of the MADRES cohort, a low income, predominantly Hispanic pregnancy cohort based in Los Angeles, CA. This study used residence-based modeled air pollution data as well as Nanostring panels for EVmiRNA extracted with Qiagen exoRNeasy kits to evaluate 483 miRNA in plasma in early and late pregnancy. Average air pollution exposures were considered separately for 1-day, 1-week and 8-week windows before blood collection in both early and late pregnancy. This study identified 63 and 66 EV-miRNA significantly associated with PM2.5 and PM10, respectively, and 2 miRNA associated with traffic-related NOX (FDR-adjusted p-value&amp;lt;0.05). Of 103 unique EV-miRNA associated with PM, 92% were associated with lung conditions according to HMDD (Human miRNA Disease Database) evidence. In particular, EV-miRNA previously identified with air pollution exposure also associated with PM2.5 and PM10 in this study were: miR-126, miR-16-5p, miR-187-3p, miR200b-3p, miR486-3p, and miR-582-3p. There were no significant differences in average exposures in early vs late pregnancy. Significant EV-miRNA were only identified in late pregnancy with an eight-week exposure window, suggesting a vulnerable timeframe of exposure, rather than an acute response. These results describe a wide array of EV-miRNA for which expression is affected by PM exposure and may be in part mediating the biological response to ambient air pollution, with potential for health implications in pregnant women and their children.

Growth Differentiation Factor 15 during pregnancy and postpartum as captured in blood, cerebrospinal fluid and placenta: A cohort study on associations with maternal mental health

IntroductionGrowth Differentiation Factor 15 (GDF15) increases substantially during pregnancy and is primarily produced by the placenta. Elevated levels of GDF15 have been associated with mental health problems in non-perinatal populations, higher corticosterone levels, and decreased estrogen receptor activity. However, the role of GDF15 in mental health during the perinatal transition remains unknown. This longitudinal study is the first to evaluate pregnancy levels of GDF15 in cerebrospinal fluid (cGDF15), plasma (pGDF15) and placenta GDF15 mRNA, along with mapping plasma GDF15 (pGDF15) level changes from late pregnancy to early postpartum. Moreover, we aimed to evaluate the association between pregnancy cGDF15 levels and cortisol early postpartum, evaluate the association between pregnancy cGDF15 levels and mental health in pregnancy and postpartum, and evaluate the association between pGDF15 and estrogens and high-sensitivity C-reactive protein (CRP). MethodsWe included data from 95 women scheduled for a planned cesarean section and obtained cerebrospinal fluid (CSF) and plasma levels of GDF15. We quantified GDF15 mRNA levels in placenta biopsies. Estrogens, high-sensitivity CRP, and mental health measures were further collected on the day or one day before the cesarean section. At five weeks postpartum, mental health measures and saliva samples for cortisol analyses were collected. Correlation analyses for GDF15 in CSF, plasma, and placenta mRNA were performed, along with association analyses for pregnancy cGDF15, Cortisol Awakening Response, and mental health outcomes. ResultsWe demonstrated a strong correlation between cGDF15 and pGDF15 (r=0.52; p<0.001) and found that both cGDF15 and pGDF15 correlated with placenta GDF15 mRNA*placental weight (r=0.62, p<0.001 and r=0.44, p=0.008, respectively). During late pregnancy, both estradiol (E2) and estriol (E3) were significantly associated with pGDF15 levels (E2: p=0.002; E3: p(corrected)<0.001). Finally, we found that cGDF15 levels were not associated with self-reported mental well-being or the Cortisol Awakening Response or absolute cortisol at awakening postpartum. ConclusionThis novel study points to the unique hormonal landscape during the perinatal transition and the specific role of GDF15 in pregnancy, which appears uncoupled with perinatal mental health and cortisol outcomes. Our data also strongly imply that the overall amount of circulating GDF15 in late pregnancy is closely related to placenta size.

Maternal loss of 24-hydroxylase causes increased intestinal calcium absorption and hypercalcemia during pregnancy but reduced skeletal resorption during lactation in mice.

Inactivation of 24-hydroxylase (CYP24A1) causes mild hypercalcemia in humans that becomes severe and life-threatening during pregnancy through unclear mechanisms. We studied Cyp24a1 null mice during pregnancy, lactation, and post-weaning. We hypothesized that Cyp24a1 nulls have a much greater increase in calcitriol during pregnancy and lactation, leading to markedly increased intestinal calcium absorption and reduced lactational bone loss. WT and Cyp24a1 null sisters were mated to Cyp24a1+/- males. Timepoints included baseline (BL), late pregnancy (LP), mid-lactation (ML), late lactation (LL), and weekly x4 weeks of post-weaning recovery (R1-4). Assessments included intestinal calcium absorption (IntCaAbs) by gavage of 45Ca, bone mineral content (BMC) by DXA, microCT of femurs, 3-point bending tests of tibias, serum hormones, serum and urine minerals, milk analysis, and intestinal gene expression. At LP, whole body BMC increased equally by ~12% in null and WT. Calcitriol was 2.5-fold higher in nulls vs WT, accompanied by 3-fold increased IntCaAbs, hypercalcemia, hypercalciuria, and 6.5-fold higher FGF23. PTH was suppressed in both. Twenty percent of null dams died during delivery but their serum calcium at LP did not differ from Cyp24a1 nulls that survived. At ML, calcitriol, IntCaAbs, and FGF23 declined in both genotypes but remained higher than BL values in Cyp24a1 nulls. By LL, nulls were still hypercalcemic vs WT, and had lost less mean whole body BMC (11% vs. 21%, P<.02), but by micro-CT there were no differences from WT in cortical or trabecular bone mass. Lactational losses in BMC, cortical thickness, and trabecular number were restored by R4 in both genotypes. In summary, ablation of Cyp24a1 increased IntCaAbs and caused hypercalcemia during pregnancy and lactation, late gestational mortality in some nulls, and reduced lactational BMC loss. Treating women with gestational hypercalcemia from CYP24A1 mutations should focus on reducing calcitriol or IntCaAbs, since increased bone resorption is not the cause.

The intrauterine effects of a maternal winter diet of either kale or fodder beet on measures of calf stature and bone morphology at birth

ABSTRACT Fodder beet and kale are commonly used winter crops in New Zealand dairy and dairy support farm systems. Fodder beet (FB) is known to have lower crude protein, phosphorus and calcium content compared to kale. The intrauterine effects of feeding FB during late pregnancy on bone growth and development in calves requires attention. This study aimed to examine the intrauterine effects of a maternal diet of either kale or FB on measures of calf stature and bone morphology at birth. In winters 2019 and 2020, two herds of pregnant Friesian × Jersey cows were fed either kale (2019, 2020 n = 20) or FB (2019, 2020 n = 20) supplemented with pasture baleage. Calves born from these mobs were euthanised within ten days of birth and a forelimb and section of rib including the costochondral junction were harvested for peripheral quantitative computed tomography and histological analysis. Calves from the FB treatment had reduced bone density and strength compared to calves from the kale treatment (p < .05). The effect of a nutritional deficit on bone morphology at birth emphasises the importance of sufficient nutrition in pre-calving diets. Future research is required to examine the long-term impact of dam undernutrition on calf growth and production.

Hepatic-derived extracellular vesicles in late pregnancy promote mammary gland development by stimulating prolactin receptor-mediated JAK2/STAT5/mTOR signalling

The mammary glands develop rapidly in late pregnancy to prepare adequately for lactation. At this stage the liver is crucial for mammary gland development, and it can achieve distal mammary gland regulation through hepatic factors and hormones. Recently, an increasing number of studies have found that hepatic-derived extracellular vesicles play an essential role in organ-to-organ communication, however, its effect on mammary gland development remains unclear. In this study, we extracted hepatic-derived extracellular vesicles from pregnant (P-hEVs) and non-pregnant mice (NP-hEVs), respectively, and explored their regulatory role on mammary gland development. The results revealed that P-hEVs was able to promote the proliferation and differentiation of HC11 cells. In addition, intraperitoneal injection of P-hEVs into pubertal female mice increased mammary gland weight and promoted mammary gland development. Mechanistically, P-hEVs activated the PI3K/AKT signalling pathway to enhance the proliferation of mammary epithelial cells, and also activated prolactin receptor-mediated JAK2/STAT5/mTOR signalling to promote mammary epithelial cell lactation and the synthesis of milk proteins and milk lipids. Overall, mouse liver during pregnancy can transmit signals to the mammary gland in the form of extracellular vesicles to promote its development and provide for subsequent lactation.

A Longitudinal Observation of Antenatal Milk Expression in Mothers of Infants with Congenital Anomalies.

Background: For mothers of infants with congenital anomalies, antenatal milk expression (AME), known as hand expression during late pregnancy, allows mothers to contribute to their newborn's care through colostrum collection. However, research is limited by self-report of AME adherence and colostrum volume. Objective: This study examined the ability of participants to adhere to a recommended protocol on AME for any removal and measurement of colostrum during late pregnancy. Materials and Methods: A prospective, longitudinal, observational design was used. Our recommended protocol involved hand expression of 5 minutes per breast for a total of 10 minutes for each AME session twice per 24 hours for any colostrum from 37 0/7 weeks gestation until birth. Women received AME education, completed milk logs, and attempted AME. The study team verified all colostrum volumes. Results: Nineteen women (10 nulliparous) participated, with 13 (68%) carrying infants with major organ system defects and 6 (32%) carrying infants with congenital heart defects. Most participants (52.6%) completed more than half but fewer than all AME sessions. Seven participants (36.8%) fully adhered, completing two AME sessions daily until hospital admission. Eighteen participants (94.7%) could remove milk (80-100% of the time). The 24-hour colostrum volume (median 0.35 mL, interquartile range [IQR] 0.065-0.845) and the total colostrum volume (median 3.99 mL, IQR 1.35-6.82) from AME varied. Conclusions: Among a small group of women of infants with congenital anomalies, adherence to a recommended protocol is feasible but varied by AME session frequency. Most women could collect colostrum for future infant feeding.

Lower Socioeconomic Status Predicts Increased Proinflammatory Signaling in Late Pregnancy: Evidence From a Filipino Cohort.

Maternal socioeconomic status (SES) is an important predictor of adverse birth outcomes and postnatal health across global populations. Chronic inflammation is implicated in cardiometabolic disease risk in high-income contexts and is a potential pathway linking maternal adversity to offspring health trajectories. To clarify how socioeconomic inequality shapes pregnancy inflammation in middle-income settings, we investigated SES as a predictor of inflammatory cytokines in late gestation in a sample from the Cebu Longitudinal Health Nutrition Survey in Cebu, Philippines. We used multiple regression to evaluate maternal SES, reflected in household assets, as a predictor of general inflammation (C-reactive protein), inflammatory cytokines (interleukin-6, interleukin-10), and inflammatory balance (n = 407). Inflammatory markers were measured at 29.9 weeks gestation in dried blood spots, and a measure reflecting relative balance of IL6 and IL10 was calculated to capture pro- versus anti-inflammatory skewed immune profiles. Greater household assets significantly predicted lower IL6 concentration (p < 0.001), with a trend toward lower IL6 relative to IL10 (p = 0.084). C-reactive protein and IL10 were not individually related to SES. The inverse relationship between SES and pregnancy inflammation in Cebu is consistent with results from high-income settings. These findings further highlight the influence of socioeconomic conditions on immune regulation during pregnancy. Given the evidence that gestational inflammation impacts offspring fetal growth, our results suggest that social and economic effects on immune function may be an important pathway for the intergenerational transmission of health disparities.

Maternal blood endometase level as a predictive biomarker for hypertensive disorders during pregnancy: a prospective cohort study

Preeclampsia (PE) occurs due to inadequate spiral artery/trophoblast remodeling in early pregnancy. Endometases are involved in the remodeling of spiral arteries and placental trophoblasts. This study aimed to investigate differences in blood endometase levels between pregnant women with hypertensive disorders (PE and gestational hypertension [GHT]) and healthy pregnant women and to evaluate whether plasma endometase values ​​could play a predictive role in PE or GHT diagnosis. A total of 90 pregnant women (n(PE) = 30, n(GHT) = 30, n(healthy pregnant) = 30) who presented at the hospital between December 2023 and May 2024 and were 26–32 years of age and > 20 weeks pregnant were included in the study. The endometase levels in all pregnant women were determined in maternal blood plasma via enzyme-linked immunosorbent assay. The endometase values were recalculated according to albumin values, and corrected endometase (cEndo) values were determined. No significant differences in blood endometase levels were observed between the groups (p > 0.05). The cEndo value was significantly lower in the PE and GHT groups than in the control group (p < 0.05). There was no statistically significant difference in the cEndo values between the PE and GHT groups (p > 0.05). A statistically significant negative linear relationship was detected between cEndo values and mean systolic blood pressure and mean diastolic blood pressure (p < 0.05). The cEndo values in the PE and GHT groups at early (≤ 32 weeks 3 days) and late pregnancy were compared, and no statistically significant difference was detected (p > 0.05). Maternal blood cEndo values may play a successful role in distinguishing hypertensive diseases of pregnancy (PE + GHT) from healthy pregnant women. cEndo does not play an effective role in the differential diagnosis between pregnant women with PE and those with GHT. Studies with larger patient populations are needed.

Differential gene expression in neonatal calf muscle tissues from Hanwoo cows overfed during mid to late pregnancy period

Maternal nutrition significantly influences fetal development and postnatal outcomes. This study investigates the impact of maternal overfeeding during mid to late pregnancy on gene expression in the round and sirloin muscles of Hanwoo neonatal calves. Eight cows were assigned to either a control group receiving standard nutrition (100%) or a treated group receiving overnutrition (150%). After birth, tissue samples from the round and sirloin muscles of neonatal calves were collected and subjected to RNA sequencing to assess differentially expressed genes (DEGs). RNA sequencing identified 43 DEGs in round muscle and 15 in sirloin muscle, involving genes related to myogenesis, adipogenesis, and energy regulation. Key genes, including PPARGC1A, THBS1, CD44, JUND, CNN1, ENAH, and RUNX1, were predominantly downregulated. Gene ontology (GO) enrichment analyses revealed terms associated with muscle development, such as “biological regulation,” “cellular process,” and “response to stimulus.” Protein-protein interaction networks highlighted complex interactions among DEGs. Random Forest analysis identified ARC, SLC1A5, and GNPTAB as influential genes for distinguishing between control and treated groups. Overall, maternal overnutrition during mid-to-late pregnancy results in the downregulation of genes involved in muscle development and energy metabolism in neonatal Hanwoo calves. These findings provide insights into the molecular effects of maternal nutrition on muscle development.