Gestation Time Research Articles

#3512 GLOMERULOPATHIES DURING PREGNANCY: A TEN-YEAR SINGLE CENTER EXPERIENCE

Abstract Background and Aims Literature regarding pregnancy management and outcomes in women with glomerulopathies is still sparse. Specific guidelines for each glomerulopathy are still lacking which impairs a more homogeneous approach. The authors describe the multidisciplinary approach and the outcomes of pregnant women with primary and genetic glomerulopathies. Method Retrospective observational study in which the authors reviewed maternal, obstetric and perinatal outcomes in pregnant women with primary and genetic glomerulopathies surveilled at our nephro-obstetric clinic from 2011 to 2021. Results We evaluated 23 gestations in 20 patients (two pregnancies still ongoing). Mean age was 32.4±5.4 years (18-41), 17 women were caucasian, 3 black African, 10/23 nulliparous and 5/20 had chronic hypertension. Mean baseline SCr was 0.8±0.3mg/dl (0.5-1.8) and proteinuria was 1360±2199.6 mg/day (150-8615), with 13/6/2 patients being on CKD stage 1/2/3, before pregnancy, respectively (unknown in 2 patients). The most frequent CKD etiologies were IgA nephropathy (6/20), Focal Segmental Glomerulosclerosis (FSGS; 3/20) and Membranous nephropathy (2/20). Exposure to teratogenic therapy during the 1st trimester occurred in 5/23 gestations with a mean exposure of 7.0±3.6 weeks. De novo proteinuria and worsening proteinuria occurred in 3/23 and 16/23 patients, respectively, with full blown nephrotic syndrome in 4/23 patients. Renal function deteriorated in one patient (CKD G3). Kidney biopsy was performed in 1/20 and 3/20 patients during and post pregnancy, revealing IgA Nephropathy (2/20, 1 with superimposed FSGS), C3 glomerulonephritis (1/20) and FSGS (1/20). Genetic diagnosis was done during/post pregnancy in 3/1 patients. Aspirin and LMWH were started in 17/23 and 4/23 gestations, respectively. Immunosuppression consisted of cyclosporin or tacrolimus with or without low dose prednisolone in 6/23 patients with partial and complete remission in all patients. De novo and worsening hypertension occurred in 2/23 and 3/23 gestations, during the 3rd trimester. Preeclampsia developed in 1 patient at 32 weeks. Fetus malformation (trisomy 21) and severe nephrotic syndrome led to pregnancy termination during the 1st trimester in two pregnancies. Cesarean delivery was performed in 5 gestations mainly due to pelvic position. Mean gestation time was 38.9±2 weeks. There was one preterm delivery due to preeclampsia. Mean birth weight was 3076.6±630.7 mg (1500-3850), with 3 newborns having low birth weight (<2500g). Apgar scores at 1/5/10 minutes were 9/10/10, respectively. Neonatal intensive care was needed in 1 newborn. Conclusion In our series, glomerulopathies with proteinuria or nephrotic syndrome were not associated with poor renal and perinatal outcome, with only one patient developing PE and renal function deterioration, probably associated to with CKD stage 3. In patients with nephrotic syndrome, immunosuppression with calcineurin inhibitor and low dose prednisone was associated with complete or partial remission in all patients.

#5009 GESTATIONAL COUNSELING DURING PREGNANCY IN PATIENTS WITH KIDNEY DISEASE: EXPERIENCE OF A MULTIDISCIPLINARY TEAM

Abstract Background and Aims Chronic kidney disease increases morbidity and mortality in pregnancy, being more prone to complications. Because it confers a risk to the fetus, this group of patients should be evaluated by a multidisciplinary unit, including nephrologists, rheumatologists, and obstetricians. Our study's objective is to describe the clinical/analytical characteristics of patients with kidney disease (KD), assessed in a multidisciplinary consultation, to inform them of the risks and to be able to prepare them to reach pregnancy optimally. At the same time, detect patients with increased risk of complications and perform close follow-ups during pregnancy and postpartum. Method Demographic, clinical, analytical, and obstetric variables were collected in a retrospective study that included women with kidney disease (inflammatory/autoimmune) between May 2020 to March 2022. In our hospital, the hereditary kidney disease unit offers reproductive advice to its patients, which was not considered in this study. Results A total of 24 patients with a median age of 35 years (18-39) were evaluated, classifying them into two independent groups: 1-pre-pregnancy (N=12) and 2-during pregnancy (N=12) and postpartum (N=10). All patients from group 1 have kidney disease (100%). Lupus nephropathy (LN) was the most frequent (64%), followed by minimal change disease (17%) and IgA nephropathy (9%). Maternal-fetal risks were evaluated according to clinical and analytical parameters (age, blood pressure, renal function, proteinuria, and disease activity, among others). 17% of patients had a history of high blood pressure. Treatment modification was made in 25%. Renal biopsy was performed in 4/7 LN patients, and pregnancy was not recommended for one of them (class III LN). In group 2, 14% of the patients presented onset KD (one patient presented de novo nephrotic syndrome and another one, an atypical hemolytic uremic syndrome in the immediate postpartum), the rest of them had previous KD: IgA Nephropathy (25%), and minimal change disease (17%), were the most frequent. 8% of the patients had a history of high blood pressure, 25% of them received ACE/ARBs that were discontinued. There were no cases of preeclampsia/eclampsia. The average gestation time was 38.5 weeks, 6.7% <37 weeks, and none <34 weeks. All newborns weigh greater than 2.5 Kg (mean birth weight 3.42 Kg). There were three inductions (two due to diabetes and one due to an altered topographic record). One peri-gestational complication (premature rupture of membranes) and one perinatal complication (respiratory distress) were observed. No other recorded/evidenced complications. Conclusion The gestational counselling and monitoring during pregnancy provide adequate support for patients with KD, being able to carry out a "guided" pregnancy with fewer complications. The strategies of our unit include modification of pre-conception treatment, activity control of underlying pathologies, and monitoring of kidney disease during pregnancy to reduce the risk of miscarriages, premature births, and low birth weight, among other complications.

Does Prediction of Neonatal Mortality by the Observed/Expected Lung-To-Head Ratio Change during Pregnancy in Fetuses with Left Congenital Diaphragmatic Hernia?

Introduction: The aim of this study was to evaluate prediction of neonatal mortality in fetuses with isolated left congenital diaphragmatic hernia (CDH) when the observed/expected lung-to-head ratio (O/E LHR) was estimated at two different gestational time points during pregnancy. Methods: Forty-four (44) fetuses with isolated left CDH were included. O/E LHR was estimated at the time of referral (first scan) and before delivery (last scan). The main outcome was neonatal death due to respiratory complications. Results: There were 10/44 (22.7%) perinatal deaths. The areas under (AU) the ROC curves were: first scan, 0.76, best O/E LHR cut-off 35.5% with 76% sensitivity and 70% specificity; last scan, AU-ROC 0.79, best O/E LHR cut-off 35.2%, with 79.0% sensitivity and 80% specificity. Considering an O/E LHR cut-off ≤35% to define high-risk fetuses at any examination, prediction for perinatal mortality showed: 80% sensitivity, 73.5% specificity, 47.1% positive and 92.6% negative predictive values, and 3.02 (95% CI 1.59–5.73) positive and 0.27 (95% CI 0.08–0.96) negative likelihood ratios. Prediction was similar in the two evaluations as 16/21 (76.2%) of fetuses considered at risk had an O/E LHR ≤35% in the two examinations; in the remaining 5 cases, two were identified only in the first and three only in the last scan. Conclusion: The O/E LHR is a good predictor of perinatal death in fetuses with left isolated CDH. Approximately 80% of fetuses at risk of perinatal death can be identified with an O/E LHR ≤35%, and 90% of them will have similar O/E LHR values at the first and at the last ultrasound examinations prior to delivery. In general, 88.6% of all CDH fetuses have a similar severity classification based on the O/E LHR at the first diagnostic ultrasound or at the ultrasound examination prior to delivery.

Metabolic changes in obese pregnant mares

Pregnancy in mares is associated with insulin dysregulation (Fowden et al. Equine Veterinary Journal. 1984; 16(4), 239-246), which is exacerbated by obesity (Pardié et al. International Congress on Animal Reproduction. June 2022; p204, W71). We studied the effect of body condition score (BCS) on metabolic variables in Criollo pregnant mares. Criollo pregnant mares (n=41) were categorized according to their BCS (scale 1-9, Henneke et al. Equine Veterinary Journal. 1983; 15(4), 371-372) as obese (7 to 9 BCS, n=26) or normal BCS (<7, n=15). Animals were grouped into three gestational periods; between 3 and 5 months (mo) of gestation (period I), 8 and 9 mo (period II) and the last mo of gestation (period III), BCS was determined and serum was obtained for biochemistry determination in every period. Biochemistry variables were determined by spectrophotometer, insulin by immunoradiometric assay and all variables were analyzed by ANOVA using a mixed procedure including BCS group, observation (time of gestation) and their interaction. The cut off value used was P<0.05. Glucose concentration was affected by gestation (P<0.0001), BCS (P=0.017) and their interaction (P=0.0005). Glucose concentrations were greater in obese than normal weight mares (82.3±2.7 vs 72.0±2.1 mg/dL, P=0.0046). Insulin concentration was affected by gestation (P<0.01) and BCS effect trended towards significance and its concentrations tended to be greater in obese comparedto normal mares (15.4±1.3 vs 11.2±1.7 mUI/L, P=0.065). Cholesterol concentrations were markedly affected by the gestational period (P=0.0006), tended to be affected by the BCS, but their interaction was not significant. Cholesterol increased during gestation from period I to II (80.1±1.8 vs 93±3.1 mg/dL, P=0.0009) remaining stable thereafter. Obese mares tended to have greater cholesterol concentrations than normal weight mares (92±3 vs 86.8±2.3 mg/dL). Triglycerides concentrations were not affected by any fixed effect. Urea concentration was affected both by gestation (P=0.02) and BCS (P=0.0004), but their interaction was not significant. The urea concentration increased during gestation from period I to II (49.3±1 vs 53.2±1.5 mg/dL, P=0.03). Urea concentration was higher in the normal weight group (55.5±1.1 vs 48±1.4 mg/dL, P<0.05). Creatinine concentrations were affected by gestation (P<0.001) and BCS (P<0.02), but the interaction between them was not significant. The creatinine concentration increased during gestation from periods I to II (P=0.0002) with the most significant increase between periods II and III (P=0.04). Creatinine concentrations were greater in the obese group (1.31±0.04 vs 1.12±0.02 mg/dL), P<0.05. This study shows that there is are metabolic adaptations during gestation, and even though this may be physiological, it could be altered by the degree of body reserves in obese mares.

The potential role of Fibrillin 2 in equine placental and fetal development

Energy adaption in pregnant dams is a vital process to appropriately supply the energy requirements to the fetus through the placenta (Yu et al. EMBO Reports (2020); Fowden et al. Equine vet. J. (1984) 16 (4), 239-246). The placenta is a transient organ with a crucial role in the survival and development of the fetus by providing nutrients, removing waste, and secreting hormones and growth factors. To understand the dynamics of the genes responsible for placental function, we recently investigated the equine placental DNA methylome. Chorioallantois (CA) samples were collected from healthy pregnant mares at different gestational time points (4, 6, and 10 months; n=3 for each time point). DNA was extracted and RRBS (Reduced Representation Bisulfate Sequencing) was performed. We then combined the methylome data with available transcriptomic profiles of the same samples to better detail the placental gene expression dynamics. Based on the reverse relationship between methylation and gene expression, we identified 18 genes with higher expression and lower methylation at 4 months compared to the other time points, including Fibrillin 2 (FBN2). Given the known high expression pattern of FBN2 in the human placenta, especially during early pregnancy in cytotrophoblasts, we decided to further detail its potential role in equine placental development. FBN2 encodes a peptide hormone called placensin that is secreted by trophoblasts and increases cAMP-PKA signaling. In humans, placensin increases gluconeogenesis and glucoserelease which stimulate cAMP release and PKA activity in maternal circulation and therefore, acts as a placental gluconeogenic hormone that increases in serum as pregnancy advances and the insulin resistance level increases. The changes in the glucose level and insulin resistance have also been documented in horses, however, the underlying mechanism has not yet been identified (Fowden et al. Equine vet. J. (1984) 16 (4), 239-246; George et al. Am J Vet Res 2011; 72:666–674). Our preliminary data suggests a possible involvement of FBN2 in gluconeogenesis in mares given its expression pattern. Since maternal glucose is the main source of energy for the fetus, any alteration in maternal glucose and insulin could have an effect on fetal development, which has been described in other species such as sheep (Yu et al. EMBO Reports (2020)). Further detailing the expression dynamics of FBN2 in placenta and placensin in maternal blood could aid elucidation of the mechanisms for glucose homeostasis in pregnant mares. Then, such analyses may be expanded to the additional genes showing similar expression dynamics to further highlight their potential role in placental development. This project was supported by the Center for Equine Health with funds provided by the State of California satellite wagering fund and contributions by private donors.

Gestational diabetes mellitus and time in active labor: A population-based cohort study.

Women with gestational diabetes mellitus (GDM) have higher rates of adverse perinatal outcomes compared with women without GDM, including an increased risk for having labor induced and for cesarean section. The findings from previous studies analyzing duration of labor in women with GDM are contradictory. The aim of the study was to evaluate the impact of GDM on time in spontaneous and induced active labor. This was a population-based cohort study including 247 524 primiparous women who gave birth to a singleton fetus with cephalic presentation, ≥34+0 (completed gestational weeks + additional days) between January 2014 and May 2020 in Sweden. Data was obtained from the Swedish Pregnancy Register. Time in active labor was compared between women with GDM and without GDM with a spontaneous labor onset or induction of labor using Kaplan Meier survival analysis and Cox regression analysis. Women with GDM had significantly longer time in active labor, both with a spontaneous onset and induction of labor compared to women without GDM. Women with GDM had a decreased chance of vaginal delivery at a certain time-point compared to women without GDM, with adjusted hazard ratio of 0.92 (0.88-0.96) and 0.83 (0.76-0.90) for those with spontaneous onset and induction of labor, respectively. Women with GDM had increased risk for time in active labor ≥12 h both in spontaneous labor onset (adjusted odds ratio 1.14 [1.04-1.25]) and in induction of labor (adjusted odds ratio 1.55 [1.28-1.87]). Women with GDM seem to spend a longer time in active labor, both in spontaneous and induced active labor compared to women without GDM. To be able to individualize care intrapartum, there is a need for more studies demonstrating the impact of hyperglycemia during pregnancy on outcomes during childbirth.

In utero delivery of miRNA induces epigenetic alterations and corrects pulmonary pathology in congenital diaphragmatic hernia

Structural fetal diseases, such as congenital diaphragmatic hernia (CDH) can be diagnosed prenatally. Neonates with CDH are healthy in utero as gas exchange is managed by the placenta, but impaired lung function results in critical illness from the time a baby takes its first breath. MicroRNA (miR) 200b and its downstream targets in the TGF-β pathway are critically involved in lung branching morphogenesis. Here, we characterize the expression of miR200b and the TGF-β pathway at different gestational times using a rat model of CDH. Fetal rats with CDH are deficient in miR200b at gestational day 18. We demonstrate that novel polymeric nanoparticles loaded with miR200b, delivered in utero via vitelline vein injection to fetal rats with CDH results in changes in the TGF-β pathway as measured by qRT-PCR; these epigenetic changes improve lung size and lung morphology, and lead to favorable pulmonary vascular remodeling on histology. This is the first demonstration of in utero epigenetic therapy to improve lung growth and development in a pre-clinical model. With refinement, this technique could be applied to fetal cases of CDH or other forms of impaired lung development in a minimally invasive fashion.

Neutralizing Antibody Responses to Messenger RNA Coronavirus Disease 2019 Vaccines Versus Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Pregnant Women and Vaccine-Induced Antibody Transfer to Infants.

Early coronavirus disease 2019 (COVID-19) vaccine trials excluded pregnant women, resulting in limited data about immunogenicity and maternal-fetal antibody transfer, particularly by gestational timing of vaccination. In this multicenter observational immunogenicity study, pregnant and nonpregnant women receiving COVID-19 vaccines were prospectively enrolled. Participants had sera collected before vaccination, at 14-28 days after each vaccine dose, at delivery (umbilical cord and peripheral), and from their infants at 3 and 6 months. Geometric mean titers (GMTs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ID50 neutralizing antibody (nAb) against D614G-like viruses were compared by participant characteristics. Overall, 23 nonpregnant and 85 pregnant participants (trimester of first vaccine dose: 10 first, 47 second, 28 third) were enrolled. Ninety-three percent (76/82 with blood samples) of pregnant participants had detectable SARS-CoV-2 nAb after 2 vaccine doses, but GMTs (95% confidence intervals) were lower in pregnant participants than nonpregnant participants (1722 [1136-2612] vs 4419 [2012-9703]; P = .04). By 3 and 6 months, 28% and 74% of infants, respectively, of vaccinated participants had no detectable nAb to D614G-like viruses. Among the 71 pregnant participants without detectable nAb before vaccination, cord blood GMTs at delivery were 5-fold higher among participants vaccinated during the third versus first trimester, and cord blood nAb titers appeared inversely correlated with weeks since first vaccine dose (R2 = 0.06, P = .06). Though most pregnant women develop nAb after 2 doses of mRNA COVID-19 vaccines, this analysis suggests that infant protection from maternal vaccination varies by gestational timing of vaccination and wanes. Additional prevention strategies such as caregiver vaccination may warrant consideration to optimize infant protection.

Platelet-derived factors dysregulate placental sphingosine-1-phosphate receptor 2 in human trophoblasts

Research questionSphingosine-1-phosphate (S1P) is an essential and bioactive sphingolipid with various functions, which acts through five different G-protein-coupled receptors (S1PR1–5). What is the localization of S1PR1–S1PR3 in the human placenta and what is the effect of different flow rates, various oxygen concentrations and platelet-derived factors on the expression profile of S1PR in trophoblasts? DesignExpression dynamics of placental S1PR1–S1PR3 were determined in human first trimester (n = 10), pre-term (n = 9) and term (n = 10) cases. Furthermore, the study investigated the expression of these receptors in different primary cell types isolated from human placenta, verified the findings with publicly available single-cell RNA-Seq data from first trimester and immunostaining of human first trimester and term placentas. The study also tested whether the placental S1PR subtypes are dysregulated in differentiated BeWo cells under different flow rates, different oxygen concentrations or in the presence of platelet-derived factors. ResultsQuantitative polymerase chain reaction revealed that S1PR2 is the predominant placental S1PR in the first trimester and reduces towards term (P < 0.0001). S1PR1 and S1PR3 increased from first trimester towards term (P < 0.0001). S1PR1 was localized in endothelial cells, whereas S1PR2 and S1PR3 were predominantly found in villous trophoblasts. Furthermore, S1PR2 was found to be significantly down-regulated in BeWo cells when co-incubated with platelet-derived factors (P = 0.0055). ConclusionThis study suggests that the placental S1PR repertoire is differentially expressed across gestation. S1PR2 expression in villous trophoblasts is negatively influenced by platelet-derived factors, which could contribute to down-regulation of placental S1PR2 over time of gestation as platelet presence and activation in the intervillous space increases from the middle of the first trimester onwards.

Preeclampsia Prevention by Timed Birth at Term

Most preeclampsia occurs at term. There are no effective preventative strategies. We aimed to identify the optimal preeclampsia screening and timing of birth strategy for prevention of term preeclampsia. This secondary analysis was of data from a prospective nonintervention cohort study of singleton pregnancies delivering at ≥24 weeks, without major anomalies, at 2 United Kingdom maternity hospitals. At routine visits at 11 to 13 weeks' (57 131 pregnancies screened, 1138 term preeclampsia developed) or 35 to 36 weeks' gestation (29 035 pregnancies screened, 619 term preeclampsia), with patient-specific preeclampsia risks determined by: United Kingdom National Institute for Health and Care Excellence guidance, and the Fetal Medicine Foundation competing-risks model. For each screening strategy, timing of birth for term preeclampsia prevention was evaluated at gestational time points that were fixed (37, 38, 39, 40 weeks) or dependent on preeclampsia risk by the competing-risks model at 35 to 36 weeks. Main outcomes were proportion of term preeclampsia prevented, and number-needed-to-deliver to prevent one term preeclampsia case. The proportion of term preeclampsia prevented was the highest, and number-needed-to-deliver lowest, for preeclampsia screening at 35 to 36 (rather than 11-13) weeks. For delivery at 37 weeks, fewer cases of preeclampsia were prevented for National Institute for Health and Care Excellence (28.8%) than the competing-risks model (59.8%), and the number-needed-to-deliver was higher (16.4 versus 6.9, respectively). The risk-stratified approach (at 35-36 weeks) had similar preeclampsia prevention (by 57.2%) and number-needed-to-deliver (8.4), but fewer women would be induced at 37 weeks (1.2% versus 8.8%). Risk-stratified timing of birth at term may more than halve the risk of term preeclampsia.

Maternal urinary bisphenols and phthalates in relation to estimated fetal weight across mid to late pregnancy

BackgroundBisphenols and phthalates are high production volume chemicals used as additives in a variety of plastic consumer products leading to near ubiquitous human exposure. These chemicals have established endocrine disrupting properties and have been linked to a range of adverse reproductive and developmental outcomes. Here, we investigated exposure in relation to fetal growth. MethodsParticipants included 855 mother-fetal pairs enrolled in the population-based New York University Children’s Health and Environment Study (NYU CHES). Bisphenols and phthalates were measured in maternal urine collected repeatedly during pregnancy. Analyses included 15 phthalate metabolites and 2 bisphenols that were detected in 50 % of participants or more. Fetal biometry data were extracted from electronic ultrasonography records and estimated fetal weight (EFW) was predicted for all fetuses at 20, 30, and 36 weeks gestation. We used quantile regression adjusted for covariates to model exposure-outcome relations across percentiles of fetal weight at each gestational timepoint. We examined sex differences using stratified models. ResultsFew statistically significant associations were observed across chemicals, gestational time periods, percentiles, and sexes. However, within gestational timepoints, we found that among females, the molar sums of the phthalates DiNP and DnOP were generally associated with decreases in EFW among smaller babies and increases in EFW among larger babies. Among males, the opposite trend was observed. However, confidence intervals were generally wide at the tails of the distribution. ConclusionIn this sample, exposure to bisphenols and phthalates was associated with small sex-specific shifts in fetal growth; however, few associations were observed at the median of fetal weight and confidence intervals in the tails were wide. Findings were strongest for DiNP and DnOP, which are increasingly used as replacements for DEHP, supporting the need for future research on these contaminants.

Even periconceptional alcohol consumption can have long-term consequences on heart health in the offspring.

Even periconceptional alcohol consumption can have long-term consequences on heart health in the offspring.

Moderate maternal nutrient reduction in pregnancy alters fatty acid oxidation and RNA splicing in the nonhuman primate fetal liver.

Fetal liver tissue collected from a nonhuman primate (NHP) baboon model of maternal nutrient reduction (MNR) at four gestational time points (90, 120, 140, and 165 days gestation [dG], term in the baboon is ∼185 dG) was used to quantify MNR effects on the fetal liver transcriptome. 28 transcripts demonstrated different expression patterns between MNR and control livers during the second half of gestation, a developmental period when the fetus undergoes rapid weight gain and fat accumulation. Differentially expressed transcripts were enriched for fatty acid oxidation and RNA splicing-related pathways. Increased RNA splicing activity in MNR was reflected in greater abundances of transcript splice variant isoforms in the MNR group. It can be hypothesized that the increase in splice variants is deployed in an effort to adapt to the poor in utero environment and ensure near-normal development and energy metabolism. This study is the first to study developmental programming across four critical gestational stages during primate fetal liver development and reveals a potentially novel cellular response mechanism mediating fetal programming in response to MNR.

Direct Effects of Mifepristone on Mice Embryogenesis: An In Vitro Evaluation by Single-Embryo RNA Sequencing Analysis

The clinical use of mifepristone for medical abortions has been established in 1987 in France and since 2000 in the United States. Mifepristone has a limited medical period that lasts <9 weeks of gestation, and the incidence of mifepristone treatment failure increases with gestation time. Mifepristone functions as an antagonist for progesterone and glucocorticoid receptors. Studies have confirmed that mifepristone treatments can directly contribute to endometrium disability by interfering with the endometrial receptivity of the embryo, thus causing decidual endometrial degeneration. However, whether mifepristone efficacy directly affects embryo survival and growth is still an open question. Some women choose to continue their pregnancy after mifepristone treatment fails, and some women express regret and seek medically unapproved mifepristone antagonization with high doses of progesterone. These unapproved treatments raise the potential risk of embryonic fatality and developmental anomalies. Accordingly, in the present study, we collected mouse blastocysts ex vivo and treated implanted blastocysts with mifepristone for 24 h. The embryos were further cultured to day 8 in vitro to finish their growth in the early somite stage, and the embryos were then collected for RNA sequencing (control n = 3, mifepristone n = 3). When we performed a gene set enrichment analysis, our data indicated that mifepristone treatment considerably altered the cellular pathways of embryos in terms of viability, proliferation, and development. The data indicated that mifepristone was involved in hallmark gene sets of protein secretion, mTORC1, fatty acid metabolism, IL-2-STAT5 signaling, adipogenesis, peroxisome, glycolysis, E2F targets, and heme metabolism. The data further revealed that mifepristone interfered with normal embryonic development. In sum, our data suggest that continuing a pregnancy after mifepristone treatment fails is inappropriate and infeasible. The results of our study reveal a high risk of fetus fatality and developmental problems when pregnancies are continued after mifepristone treatment fails.

Abstract P245: Early Pregnancy Exposure to Per- And Polyfluoroalkyl Substances and Thyroid Function Throughout Gestation: A Longitudinal Study

Introduction: Thyroid function during pregnancy is pivotal for both maternal and fetal health. Data on environmental determinants of thyroid function in pregnancy are yet limited. We prospectively investigated associations of early pregnancy per- and polyfluoroalkyl substances (PFAS), known environmental endocrine disruptors, with thyroid function longitudinally measured throughout pregnancy. Hypothesis: Early pregnancy PFAS exposure adversely affects thyroid function. Methods: Within the NICHD Fetal Growth Studies-Singleton Cohort, we enrolled 2,802 pregnant women at gestational weeks (gw) 10-14 and measured concentrations of 9 PFAS (NMeFOSAA, PFDA, PFDoDA, PFDS, PFHpA, PFHxS, PFNA, PFOA, PFOS, PFOSA, PFUnDA) in plasma samples collected at enrollment. In a subsample of 321 pregnant women, we determined thyroid markers (fT3, fT4, TSH) at gw 10-14, 15-26, 23-31, 33-39. Associations were assessed with multivariable regressions per standard deviation increase in ln-transformed PFAS (ng/ml), adjusting for age, body mass index, diet, lifestyle and socio-economic factors, and plasma lipids. Results: Plasma PFAS in early pregnancy were associated with markers of thyroid function throughout pregnancy. The associations varied by gestational age. Higher levels of several PFAS were associated with lower TSH and higher fT3 and fT4 levels at gw 10-14. Adjusted beta coefficients [95%CI] with TSH (mIU/L) were: -1.13 [-2.30, 0.05] for PFOS, -3.15 [-4.45, -1.86] for PFDA, -1.75 [-2.95, -0.55] for NMeFOSAA, -1.68 [-3.00, -0.37] for PFNA, -1.29 [-2.62, 0.03] for PFDoDA, -2.07 [-3.30, -0.83] for PFOA, but 1.11 [0.12, 2.09] for PFHxS. Most of these associations were attenuated to non-significant or changed the direction of the association in later pregnancy (for instance, PFOS-TSH association at gw 10-14: -1.13 [-2.30, 0.05], gw 15-26: 0.98 [0.18, 1.78], gw 23-31: 1.31 [0.50, 2.13], PFDA-TSH association at gw 10-14: -3.15 [-4.45, -1.86], at gw 23-31: 1.13 [0.16, 2.11]). Consistent and positive associations across pregnancy were observed for PFOA-fT3 (at gw 10-14: 0.48 [0.05, 0.91], gw 15-26: 0.41 [0.04, 0.78], gw 23-31: 0.42 [0.02, 0.80] pmol/L) and PFHxS-fT4 (at gw 10-14: 0.12 [0.02, 0.21], gw 15-26: 0.67 [0.54, 0.81], gw 23-31: 0.22 [0.12, 0.33], gw 33-39: 0.14 [0.02, 0.26] ng/dL). Conclusions: Plasma levels of selected PFAS congeners in early pregnancy are significantly associated with thyroid markers in pregnancy. The associations varied by gestational timing. These findings indicate a potential environmental impact on thyroid function. In perspective, multiple assessments of PFAS and thyroid markers throughout pregnancy might be necessary and relevant for conducting gestational age-specific interventional trials.

Risk for stillbirth among pregnant individuals with SARS-CoV-2 infection varied by gestational age

Despite prior research findings on higher risks of stillbirth among pregnant individuals with SARS-CoV-2 infection, it is unclear whether the gestational timing of viral infection modulates the risk for stillbirth. This study aims to examine the association between the timing of SARS-CoV-2 infection during pregnancy and the risk of stillbirth. This is a retrospective cohort study that used multilevel logistic regression analyses of nationwide Electronic Health Records in the United States. Data were from 75 healthcare systems and institutes across 50 states. A total of 191,403 pregnancies among 190,738 individuals of reproductive ages (15-49) who had childbirth between March 1, 2020 and May 31, 2021 were identified and included. The main outcome is stillbirth occurred at or after 20 weeks of gestation. Exposures are the timing of SARS-CoV-2 infection: early pregnancy (< 20 weeks), mid-pregnancy (21-27 weeks), the 3rd trimester (28-43 weeks), any time before delivery, and never infected (reference). We identified 2,342 (1.3%) pregnancies with COVID-19 in early-pregnancy, 2,075 (1.2%) in mid-pregnancy, and 12,697 (6.9%) in the 3rd trimester. After adjusting for the maternal and clinical characteristics, increased odds of stillbirth were observed among pregnant individuals with SARS-CoV-2 infection only in early pregnancy (OR=1.75, 95% CI, 1.25-2.46) or mid-pregnancy (OR=2.09, 95% CI, 1.49-2.93), compared to pregnant individuals never infected. Older age, Black race, hypertension, acute respiratory distress syndrome or acute respiratory failure, and placental abruption were found to be consistently associated with stillbirth across different trimesters. The increased risk of stillbirth is associated with COVID-19 only when pregnant individuals were infected during early and mid-pregnancy, not any time before the delivery or during the 3rd trimester, suggesting the potential vulnerability of the fetus to the SARS-CoV-2 infection in early pregnancies. Our findings underscore the importance of proactive COVID-19 prevention and timely medical intervention for individuals infected with SARS-CoV-2 during early and mid-pregnancy.

Evaluation of physiological and morphological parameters for early prediction of prenatal litter size in goats.

The aim of the present study was to evaluate the physiological and morphological parameters of pregnant does for early prediction of prenatal litter size. In total, 33 does were screened using ultrasonography and further categorized into three groups based on does bearing twins (n = 12), a single fetus (n = 12), or non-pregnant does (n = 9). The rectal temperature °F (RT) and respiration rate (RR) as physiological parameters, while abdominal girth in cm (AG) and udder circumference in cm (UC) as morphological parameters were recorded at different gestation times, i.e. 118, 125, 132 and 140 days. In addition to this, age (years) and weight at service (kg) were also used. The statistical analyses included analysis of variance (ANOVA) and linear discriminant analysis (LDA). The results indicated that groups had significant (P < 0.05) differences among morphological parameters at each gestation time, with higher AG and UC in does bearing twins followed by a single fetus and non-pregnant does. However, both physiological parameters were non-significantly (P > 0.05) associated with litter size groups. It was also revealed that the studied parameters showed increasing trends over gestation time in single and twin fetus categories, but they were on par among non-pregnant does. The results of the LDA revealed that estimated function based on age, weight at service, RR, RT, AG and UC had greater (ranging from 75.00 to 91.70%) accuracy, sensitivity and specificity at different gestation times. It was concluded that using an estimated function, future pregnant does may be identified in advance for single or twin litter size, with greater accuracy.

Integrins and ligands, are correlated at pig placental interface during pregnancy?

In the present work, we emphasize the studies about integrins and their receptors in pig placental interface at different times of gestation. Uterine placental interface (n=24) of 17-, 30-, 60- and 70-days gestation (dg) and non-pregnant uterus (n=4) of crossbred sows were used. The presence of αvβ3 and α5β1 integrins, and their ligands fibronectin (FN), and osteopontin (OPN) were detected by immunohistochemistry, and the immunolabelled area percentage (IAP) and the optical density (OD) were determined. The integrins and its ligands analyzed have presented peaks of expression in early and mid-gestation, both in IAP and the OD area decreasing at 70 dg. These temporal changes showed us that the molecules studied in this work participate in embryo/feto-maternal attachment, variably. Besides, we found a significant correlation both in the intensity and in the extension of immunostaining for trophoblastic FN and endometrial αvβ3, and trophoblastic OPN and endometrial α5β1, throughout the entire pig pregnancy. At late gestation, take place a notable placental remodelation with subsequent removal or renewal of folds at the uterine-placental interface that results in the loss of focal adhesions. The decrease of the expression of some integrins and their ligands in late gestation, particularly at 70 dg, would demonstrate that there would be other adhesion molecules and other ligands that could be participating in the establishment of the maternal-fetal interface.

Prenatal diagnosis at different gestational times and clinical features of choledochal cysts: a single tertiary center report.

This study aimed to evaluate the effect of prenatal diagnosis at different gestational times on the clinical features of patients with choledochal cysts (CDCs). Medical records of patients with prenatally diagnosed CDCs admitted to our hospital (April 2013-April 2018) were retrospectively reviewed. The clinical characteristics and pathological CDC features were analyzed. Two hundred eighteen cases were included. Patients were divided into two groups. Group 1 and group 2 had a prenatal diagnosis at ≤ 27weeks of gestation (second trimester of gestation, n = 157) and > 27weeks (third trimester of gestation, n = 61), respectively. The incidence of jaundice and the TBIL, IBIL and GGT levels were higher in Group 1 (P = 0.021, P = 0.029, P = 0.042, P = 0.007, respectively). The maximum cyst diameter at the time of surgery was larger in Group 1 (P = 0.015). An association study showed that the time of prenatal diagnosis was negatively correlated with the maximum cyst diameter both postnatally (r = -0.223, P = 0.001) and at the time of surgery (r = -0.268, P < 0.001). Unlike patients diagnosed at a late prenatal age, patients diagnosed at an early prenatal age tend to present clinical symptoms (jaundice, manifested as high indirect bilirubin), hepatic function damage, and large cysts at the time of surgery.

Making Up for Lost (Gestational) Time?

Making Up for Lost (Gestational) Time?