Second Half Of Gestation Research Articles

Safety and feasibility pilot study of continuous low-dose maternal supplemental oxygen in fetal single ventricle heart disease.

Fetuses with single ventricle physiology (SVP) exhibit reductions in fetal cerebral oxygenation, with associated delays in fetal brain growth and neurodevelopmental outcomes. Maternal supplemental oxygen (MSO) has been proposed to improve fetal brain growth, but current evidence on dosing, candidacy and outcomes is limited. In this pilot study, we evaluated the safety and feasibility of continuous low-dose MSO in the setting of SVP. This single-center, open-label, pilot phase-1 safety and feasibility clinical trial included 25 pregnant individuals with a diagnosis of fetal SVP. Participants self-administered continuous MSO using medical-grade oxygen concentrators for up to 24 h per day from the second half of gestation until delivery. The primary aim was the evaluation of the safety profile and feasibility of MSO. A secondary preliminary analysis was performed to assess the impact of MSO on the fetal circulation using echocardiography and late-gestation cardiovascular magnetic resonance imaging. Early outcomes were assessed, including perinatal growth and preoperative brain injury, and neurodevelopmental outcomes were assessed at 18 months using the Bayley Scales of Infant and Toddler Development 3rd edition, and compared with those of a contemporary fetal SVP cohort (n = 217) that received the normal standard of care (SOC). Among the 25 participants, the median maternal age at conception was 35 years, and fetal SVP diagnoses included 16 with right ventricle dominant, eight with left ventricle dominant and one with indeterminate ventricular morphology. Participants started the trial at approximately 29 + 2 weeks' gestation and self-administered MSO for a median of 16.1 h per day for 63 days, accumulating a median of 1029 h of oxygen intake from enrolment until delivery. The only treatment-associated adverse events were nasal complications that were resolved typically by attaching a humidifier unit to the oxygen concentrator. No premature closure of the ductus arteriosus or unexpected fetal demise was observed. In the secondary analysis, MSO was not associated with any changes in fetal growth, middle cerebral artery pulsatility index, cerebroplacental ratio or head-circumference-to-abdominal-circumference ratio Z-scores over gestation compared with SOC. Although MSO was associated with changes in umbilical artery pulsatility index Z-score over the study period compared with SOC (P = 0.02), this was probably due to initial baseline differences in placental resistance. At late-gestation cardiovascular magnetic resonance imaging, MSO was not associated with an increase in fetal cerebral oxygen delivery. Similarly, no differences were observed in neonatal outcomes, including preoperative brain weight Z-score and brain injury, mortality by 18 months of age and neurodevelopmental outcomes at 18 months of age. This pilot phase-1 clinical trial indicates that low-dose MSO therapy is safe and well tolerated in pregnancies diagnosed with fetal SVP. However, our protocol was not associated with an increase in fetal cerebral oxygen delivery or improvements in early neurological or neurodevelopmental outcomes. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Estrogen promotes fetal skeletal muscle mitochondrial distribution and ATP synthase activity important for insulin sensitivity in offspring

PurposeWe previously showed that offspring delivered to baboons in which levels of estradiol (E2) were suppressed during the second half of gestation exhibit insulin resistance. Mitochondria are essential for the production of ATP as the main source of energy for intracellular metabolic pathways, and skeletal muscle of type 2 diabetics exhibit mitochondrial abnormalities. Mitochondria express estrogen receptor β and E2 enhances mitochondrial function in adults. Therefore, the current study ascertained whether exposure of the fetus to E2 is essential for mitochondrial development.MethodsLevels of ATP synthase and citrate synthase and the morphology of mitochondria were determined in fetal skeletal muscle obtained near term from baboons untreated or treated daily with the aromatase inhibitor letrozole or letrozole plus E2.ResultsSpecific activity and amount of ATP synthase were 2-fold lower (P < 0.05) in mitochondria from skeletal muscle of E2 suppressed letrozole-treated fetuses and restored to normal by treatment with letrozole plus E2. Immunocytochemistry showed that in contrast to the punctate formation of mitochondria in myocytes of untreated and letrozole plus E2 treated animals, mitochondria appeared to be diffuse in myocytes of estrogen-suppressed fetuses. However, citrate synthase activity and levels of proteins that control mitochondrial fission/fusion were similar in estrogen replete and suppressed animals.ConclusionWe suggest that estrogen is essential for fetal skeletal muscle mitochondrial development and thus glucose homeostasis in adulthood.

Plasma relaxin, estrogens and progestogens concentration in coldblooded and hot-blood mares in the second half of gestation

Monitoring estrogens, progestogens, and relaxin plasma concentration can be important for determining pregnancies at risk of failure in mares. However, significant breed-related differences in values of reproductive hormones are known, and data concerning coldblooded (CB) mares are missing. The aim of the study was to determine and compare serum relaxin, estrone sulphate (E1S), estradiol-17β (E2), and progestogens concentration in pregnant CB and hot-blood (HB) mares during the second half of gestation. Blood samples obtained from 94 healthy mares in the second half of gestation with known mating dates were analyzed. Samples were collected from 36 CB mares aged from 3 to 16 years and 58 HB mares aged from 4 to 17 years. The hormone concentrations were measured using immunoenzymatic equine species-specific commercial kits. The serum relaxin concentration was almost three times lower in CB, whereas E1S and E2 almost twice as low, as compared to HB mares (P < 0.05). In conclusion, the extremely low concentration of relaxin in CB mares could be one reason for the increased amounts of difficult parturition requiring veterinary intervention noted in these breeds.

Histomorphological development study of the heart ventricles of local Awassi sheep during the first and second half of gestation

Histomorphological development study of the heart ventricles of local Awassi sheep during the first and second half of gestation

Ergot alkaloid consumption alters serotonin receptor-induced vasoactivity in ovine umbilical vasculature.

Consumption of ergot alkaloids during the second half of gestation has been shown to decrease umbilical artery vasoactivity resulting in decreased birth weights. Negative vascular effects of ergot alkaloids are mediated predominantly through serotonergic and adrenergic receptors in other tissues. Vasoactivity of serotonin (5-HT) receptors 5-HT2A and 5-HT1B/1D in umbilical artery and vein from ewes receiving endophyte-infected seed (E + 1.77mg ergovaline/hd/d) or a control total mixed ration (CON; 0mg ergovaline/hd/d) tall fescue seed at d-110 and d-133 of gestation was evaluated. Gravid reproduction tracts were collected from ewes. Two-mm sections of umbilical artery and vein were exposed to increasing concentrations of a 5-HT1B/1D agonist and 5-HT2A agonist. The 5-HT1B/1D agonist did not stimulate a contractile response in artery or vein or either gestation time point. 5-HT2A agonist caused large responses in artery with greatest occurring at d-110 and decreasing in magnitude as days of gestation increased (p < 0.05). On d-110 and 133 of gestation, arteries from CON ewes had greater contractile response than arteries collected from E+ ewes (p < 0.05). Veins responded to increasing concentrations of the 5-HT2A agonist. Maximal d-110 vein response was greater than d-133 when exposed to 5-HT2A agonist (p < 0.05). Unlike the artery, veins from E+ ewes had greater d-133 contractile response than CON (p < 0.05). Vascular contractions of umbilical artery and vein are induced by 5-HT2A receptor activity and not 5-HT1B/1D. Umbilical artery 5-HT2A receptor activity was more sensitive to seed treatment and could be responsible for ergot alkaloid-induced intra-uterine growth restriction.

Calorie restriction during gestation impacts maternal and offspring fecal microbiome in mice.

Maternal undernutrition is the most common cause of fetal growth restriction (FGR) worldwide. FGR increases morbidity and mortality during infancy, as well as contributes to adult-onset diseases including obesity and type 2 diabetes. The role of the maternal or offspring microbiome in growth outcomes following FGR is not well understood. FGR was induced by 30% maternal calorie restriction (CR) during the second half of gestation in C57BL/6 mice. Pup weights were obtained on day of life 0, 1, and 7 and ages 3, 4 and 16 weeks. Fecal pellets were collected from pregnant dams at gestational day 18.5 and from offspring at ages 3 and 4 weeks of age. Bacterial genomic DNA was used for amplification of the V4 variable region of the 16S rRNA gene. Multivariable associations between maternal CR and taxonomic abundance were assessed using the MaAsLin2 package. Associations between microbial taxa and offspring outcomes were performed using distance-based redundancy analysis and Pearson correlations. FGR pups weighed about 20% less than controls. Beta but not alpha diversity differed between control and CR dam microbiomes. CR dams had lower relative abundance of Turicibacter, Flexispira, and Rikenella, and increased relative abundance of Parabacteroides and Prevotella. Control and FGR offspring microbiota differed by beta diversity at ages 3 and 4 weeks. At 3 weeks, FGR offspring had decreased relative abundance of Akkermansia and Sutterella and increased relative abundance of Anaerostipes and Paraprevotella. At 4 weeks, FGR animals had decreased relative abundance of Allobaculum, Sutterella, Bifidobacterium, and Lactobacillus, among others, and increased relative abundance of Turcibacter, Dorea, and Roseburia. Maternal Helicobacter abundance was positively associated with offspring weight. Akkermansia abundance at age 3 and 4 weeks was negatively associated with adult weight. We demonstrate gut microbial dysbiosis in pregnant dams and offspring at two timepoints following maternal calorie restriction. Additional research is needed to test for functional roles of the microbiome in offspring growth outcomes.

Effects of maternal calcium propionate supplementation on offspring productivity and meat metabolomic profile in sheep.

This study determined the effect of dietary calcium propionate (CaPr) as a source of energy supplementation during the First Half of Gestation (FMG), the Second Half of Gestation (SMG), and during All Gestation (AG), on offspring post-weaning growth performance, meat quality, and meat metabolomic profile. Thirty-one pregnant ewes were assigned to one of four treatments: a) supplementation of 30 gd-1 of CaPr during the first half of gestation (day 1 to day 75, n = 8) (FMG); b) supplementation of 30 gd-1 of CaPr during the second half of gestation (day 76 to day 150, n = 8) (SMG); c) supplementation of 30 gd-1 of CaPr during all gestation (AG, n = 8); d) no CaPr supplementation (control; CS, n = 7). The ewes were ad libitum fed a basal diet based on oat hay and corn silage. Ewes were distributed in a completely randomized unbalanced design to four treatments. The FMG group had lower (P ≤ 0.05) birth weight and weaning weight than the CS group. However, the average daily gain was similar across all treatments. Empty body weight and FMG had lower values (P ≤ 0.05) than the other groups. Both FMG and AG had lower hot carcass weight (P ≤ 0.05) compared to CS, while CaPr treatments resulted in reduced hot carcass yield (P ≤ 0.05). Meat color and texture were similar among treatments. A principal component analysis between gestation stages showed a trend for separating CS and FMG from SMG and AG, and that was explained by 93.7% of the data variability (PC1 = 87.9% and PC2 = 5.8%). Regarding meat metabolomic profile, 23 compounds were positively correlated between all treatments. Only 2 were negatively correlated (eicosane and naphthalene 1,2,3); but tetradecanoic acid, hexadecane, undecane 5-methyl, (-)-alpha, hexadecenoic acid, octadecanoic acid, and octadecane had a highly significant correlation (P ≤ 0.05). Overall, dam supplementation with CaPr during different periods of gestation provoked changes in meat metabolites related to the biosynthesis of fatty acids in lambs without negative changes in lamb's growth performance and carcass quality.

411 Awardee Talk: Fetal Programming and Molecular Characterization of the Skeletal Muscle Development in Ruminants

Abstract Three experiments were developed aiming to investigate the effects of maternal nutrition on the skeletal muscle development and metabolism of the offspring. The first study was designed to evaluate the protein restriction during mid-gestation on the skeletal muscle growth of beef cattle offspring. Our results revealed that maternal protein restriction at this stage of gestation caused a decreased number of muscle fibers in the offspring. The second and third studies aimed to elucidate the effects of maternal feed restriction during different stages of gestation on the transcriptome and proteome profile in the skeletal muscle of the newborn. In these experiments, pregnant goats were feed-restricted (at 50% maintenance requirements) either during the first or second half of gestation. Transcriptome analysis revealed that feed restriction at first half of gestation upregulated genes involved with the maintenance of satellite cells, and fatty acid oxidation in skeletal muscle of the newborn. On the other hand, restriction at the second half of gestation upregulated genes related with the balance of glucose metabolism, in addition to protective mechanisms against the oxidative stress in the skeletal muscle of the newborn. Through the proteomic analysis, we observed enriched biological processes (BP) and signaling pathways (SP) related with the energy-investment phase of glycolysis, in addition to the increase in the usage of glycogen and fatty acids storages in the skeletal muscle of the newborn due to feed restriction at the first half of gestation. We also observed that when feed restriction occurs at second half of gestation there is an enrichment in BP and SP associated with the energy-generation phase of glycolysis, and an enhancement in the biosynthesis of glutamine in skeletal muscle of the newborns. Overall, the results of these studies bring insights that help to develop nutritional strategies during early life development aiming to improve postnatal performance.

Safety of the Administration of an Inactivated PCV2a/PCV2b/Mycoplasma Hyopneumoniae Vaccine to Pregnant and Lactating Sows and Gilts.

Porcine Circovirus type 2 (PCV2) vaccination of gilts during acclimation has become a routine practice in commercial pig farms to homogenize herd immunity to PCV2 and reduce the impact of diseases associated with PCV2 infection, namely reproductive, respiratory, systemic, and other PCV2-associated diseases. The periodic mass vaccination of sows, with the same objectives, is also common. To ensure mass vaccination is an appropriate health management tool, demonstrating that the vaccine is safe in different sow/gilt physiological stages is necessary. The objective of the present studies was to evaluate safety of a PCV2a/PCV2b/Mycoplasma hyopneumoniae (PCV2a2bMHP) killed vaccine in sows and gilts during gestation and lactation, under controlled experimental pen conditions, and during gestation, mimicking mass vaccination, under field conditions. Safety was assessed by monitoring for immediate adverse reactions after vaccination, rectal temperatures after vaccination (controlled experimental pen studies only), local and systemic reactions, and reproductive performance (studies conducted during pregnancy) or lactation performance (studies conducted during lactation). In total, 416 sows/gilts were enrolled, and more than 4000 piglets were observed during their first week of life, under field conditions. In both controlled experimental and field studies, no immediate anaphylactic type reactions were observed after vaccination and the incidence of adverse events, such as depression or decreased appetite, was acceptable for what is expected in a swine herd. In the studies conducted during gestation, vaccination did not significantly increase rectal temperature of the vaccinated animals. Sow reproductive outcomes were not affected by vaccination. The farrowing rate of animals participating in the field study was higher than the historic averages of the farms. In the laboratory studies conducted during the first and second half of gestation, no differences in reproductive outcome were observed between vaccinated and non-vaccinated animals. However, sows vaccinated during lactation experienced a transient hyperthermia which did not affect milk production since the piglets' average daily weight gain was not affected. The previously described results confirm that the administration of a PCV2a2bMHP vaccine was safe in the tested conditions. All the anticipated benefits of sow and gilt PCV2 vaccination, such as homogenization of PCV2 antibody titers or reduction in PCV2 circulation in the herd, would not be masked by potential adverse events due to herd vaccination. In conclusion, the administration of a PCV2a2bMHP vaccine to sows and gilts during different stages of gestation and during lactation is safe.

Effect of supplementing rumen-protected fat during the second half of gestation on maternal performance and metabolism in ewes during pregnancy and subsequent lactation

This study aimed to evaluate the effects of supplementing ewes' diet with calcium salts of soybean oil (CSSO) during the second half of gestation on their nutritional, metabolic, and physiological parameters. Additionally, it also aimed to assess the their offspring's sex effect and its interaction with rumen-protected fat. To achieve this, 30 multiparous hair ewes pregnant from a single fetus and weighing 44.1 ± 6.9 kg were randomly divided into two feeding regimens at 75 days of gestation: (1) Control (CON; n = 16), which received a basal diet that met the basic nutritional requirements of ewes gestating a single fetus, and (2) CSSO (n = 14), which received the basal diet plus calcium salts of soybean oil at a level of 1.5 g per kg of body weight (5 % inclusion based on dry matter). The ewes and their offspring were kept together after birth, and lambs were weaned once they reached 20 kg of body weight. Results showed that CSSO ewes were heavier during late gestation and had higher body weight at lactation than CON ewes (P ≤ 0.05). However, CSSO ewes showed an earlier decline in dry matter intake during late gestation (P ≤ 0.05). CSSO ewes also had greater apparent total tract digestibility of ether extract (P < 0.01) and tended to have lower fat milk concentration by approximately 17 % (P = 0.08). In terms of gene expression, CSSO ewes had greater CPT2 expression and ACACA mRNA levels in the subcutaneous adipose tissue (P = 0.08 and P = 0.04, respectively). ACACA mRNA expressions in the maternal liver tissue were also greater (P ≤ 0.01) for CSSO ewes gestating female offspring. However, liver mRNA expressions of IGF1, PC, PCK1, GK, and PPARy were similar between feeding regimens (P > 0.05). Lambs from CSSO ewes were born 0.57 kg heavier than those from CON ewes (P = 0.01) and tended to be weaned at an younger age (P = 0.06). Additionally, CSSO lambs had greater MyoG expression than CON lambs (P = 0.05). In summary, the supplementation of ewes' diet with CSSO during the second half of gestation shows promise as a technology to enhance fetal development, as well as improve long-term maternal and offspring performance.

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.

Vascular nitrosative stress in hypertension induced by fetal undernutrition in rats

Fetal undernutrition predisposes to hypertension development. Since nitric oxide (NO) is a key factor in blood pressure control, we aimed to investigate the role of NO alterations in hypertension induced by fetal undernutrition in rats. Male and female offspring from dams exposed to undernutrition during the second half of gestation (MUN) were studied at 21 days (normotensive) and 6 months of age (hypertension developed only in males). In aorta, we analyzed total and phosphorylated endothelial NO synthase (eNOS, p-eNOS), 3-nitrotyrosine (3-NT), and Nrf2 (Western blot). In plasma we assessed l-arginine, asymmetric and symmetric dimethylarginine (ADMA, SDMA; LC–MS/MS), nitrates (NOx, Griess reaction), carbonyl groups, and lipid peroxidation (spectrophotometry). In iliac arteries, we studied superoxide anion production (DHE staining, confocal microscopy) and vasodilatation to acetylcholine (isometric tension). Twenty-one-day-old MUN offspring did not show alterations in vascular e-NOS or 3NT expression, plasma l-Arg/ADMA ratio, or NOx. Compared to control group, 6-month-old MUN rats showed increased aortic expression of p-eNOS/eNOS and 3-NT, being Nrf2 expression lower, elevated plasma l-arginine/ADMA, NOx and carbonyl levels, increased iliac artery DHE staining and reduced acetylcholine-mediated relaxations. These alterations in MUN rats were sex-dependent, affecting males. However, females showed some signs of endothelial dysfunction. We conclude that increased NO production in the context of a pro-oxidative environment, leads to vascular nitrosative damage and dysfunction, which can participate in hypertension development in MUN males. Females show a better adaptation, but signs of endothelial dysfunction, which can explain hypertension in ageing.

Cellular immunity in sows in various physiological periods in a norm and in case of postpartum pathology

The relevance of this study is due to the need to assess the functioning of the cellular component of the immune system in dynamics in sows before insemination, during periods of gestation and lactation in the norm and in the event of postpartum pathology.The purpose of the research is to study cellular immunity in sows in different physiological conditions. The article presents the results of a study of cellular immunity in sows before insemination, during periods of gestation and lactation in normal and postpartum pathology in an industrial pigbreeding complex. Cellular immunity indicators were determined in the blood: T- and Blymphocytes, theophylline-resistant (Ttfr), theophylline-sensitive (Ttfh) lymphocytes and their ratio (Ttfr/Ttfh) in accordance with the "Methodological recommendations for assessing and correcting the immune status of animals" .Statistical processing of the obtained data was carried out using the program Statistica v6.1, reliability assessment - Student's test. It has been established that before insemination, diseased animals have reduced cellular adaptive immunity compared to clinically healthy sows. With the onset of gestation (37-39 days), sows of both groups showed suppression of cellular immunity, which is necessary to ensure the tolerance of the mother's body to fetal alloantigens, the normal course of pregnancy and fetal development, which was more significant in diseased animals. In the second half of gestation (78-80 days), the marked increase in cellular adaptive immunity in sows of both groups is associated with the effect of antigens of the administered vaccines, which was more pronounced in clinically healthy animals. During lactation, the cellular immune response to the administered vaccines in diseased sows was also less significant.

Assessment of fetal left atrial volume and function using anovel left atrial volume tracking method.

Several fetal cardiovascular structural defects may alter the hemodynamics of the cardiac chambers resulting in changes in chamber sizes. Quantitative measurements of the sizes of cardiac chambers can augment the diagnostic power of fetal echocardiography. Using a new left atrial volume tracking (LAVT) method, time-left atrial volume curves (TLAVCs) can be automatically obtained. The goal of this study was to examine whether this method can be used to evaluate left atrial volume (LAV) and provide reference values for LAV and indices of left atrial function in normal human fetuses. Two hundred and four normal human fetuses were enrolled. Using LAVT, the maximal left atrial volume (LAVmax) and minimal left atrial volume (LAVmin) were measured from TLAVCs. Left atrial ejection fraction (EF) was calculated. The maximal left atrial area (LAAmax) and minimal left atrial area (LAAmin) were measured using manual method tracing. Between 21 and 40 weeks, mean LAVmax increased from 0.27 ml to 4.15 ml, and mean LAVmin increased from 0.13 ml to 2.26 ml, respectively, while the EF remained stable at around 0.43. From 21 to 40 weeks, mean LAAmax increased from 0.61 cm2 to 2.64 cm2, and mean LAAmin increased from 0.34 cm2 to 1.53 cm2. This study establishes reference values for fetal LAV during the second half of gestation. The LAVT method appears to be feasible in estimating fetal LAV and shows potential for assessing left atrial function.

Back pain and assessment of ankylosing spondylitis activity during gestation: symptoms reflecting exacerbation of the disease and pregnancy

Objective: to study the dynamics of back pain severity and the frequency of its individual components, characterizing the inflammatory and mechanical rhythm, on the background of gestation in women with ankylosing spondylitis (AS) and compare them with manifestations of dorsopathy in healthy pregnant women; to determine the information value of BASDAI during pregnancy, i.e. to identify its components with the optimal sensitivity and specificity ratio for assessing AS activity during gestation.Patients and methods. The main group consisted of 49 pregnant women with AS who met the modified New York criteria of 1984. The average age of patients was 31.7±4.9 years, the average duration of the disease was 134.4±85.8 months. BASDAI for trimesters of pregnancy was: 2.3 [1.2; 4.4], 2.8 [1.4; 4.2] and 2.2 [1.6; 4.0]. The control group included 51 pregnant women with back pain associated with gestation, without rheumatic diseases. The average age was 28.0±4.4 years. The intensity of back pain was assessed on a numerical rating scale. ROC-analysis was performed with calculation of the area under the curve (AUC) of each component of BASDAI in each pregnancy trimester.Results and discussion. More than 80% of pregnant women with AS experienced back pain, while the intensity of general back pain did not differ from that in the control group. Night back pain with improvement on awakening in the main group was present in 70%, 58% and 68.8% of women, respectively, in the I-III trimesters; its intensity was 3 [1; 5], 3.5 [3; 6] and 3.4 [2; 5] respectively; the frequency and severity of night pain were higher than in the control group. The number of women with improvement after exercise in the II and III trimesters did not differ in both groups. In the second half of pregnancy, 40% of AS patients noted improvement during rest, 52.1% – increased pain after exercise; the frequency of mechanical rhythm pain elements remained lower than in the control group. The AUC value for BASDAI in the first trimester was 0.74; AUC of all BASDAI components was &gt;0.5. In the II and III trimesters, the AUC values for fatigue and back pain were 0.8.Conclusion. During pregnancy the vast majority of women with AS experience back pain, the nature of which changes in the second half of gestation. Night pain that improves on awakening reflects AS activity and is not related to pregnancy. The BASDAI components of severity and duration of morning stiffness have the highest classification value during pregnancy.

Hypertension arising after 20 weeks of gestation: gestational hypertension or masked chronic hypertension?

The objectives of this study were 1-to evaluate the prevalence of masked chronic hypertension in pregnant women classified as gestational hypertension 2-to compare the risks of developing preeclampsia in true gestational hypertension vs those women classified as having gestational hypertension but who had had masked hypertension in the first half of pregnancy. We conducted a cohort study in consecutive high-risk pregnancies who were evaluated before 20 weeks of gestation. Women who developed gestational hypertension (normotension in the office before 20 weeks of gestation and office BP ≥ 140/90 mmHg and/or antihypertensive treatment in the second half of gestation) were divided, according to an ABPM performed before 20 weeks of pregnancy, in two subgroups: subgroup 1-if their ABPM was normal, and subgroup 2-if they had masked chronic hypertension. Risks for preeclampsia (PE) were estimated and compared with normotensive women. Before 20 weeks of gestation, 227 women were evaluated (age 32 ± 6 years, median gestation age 15 weeks); 67 had chronic hypertension (29.5%). Of the remaining 160, 39 developed gestational hypertension (16 in subgroup 1 and 23 insubgroup 2. Compared with normotensive pregnant women, subgroup 1 of women with gestational hypertension did not increase the risk of developing PE (OR = 0.76, 95% CI = 0.16-6.65). Conversely, subgroup 2 of gestational hypertension increased the risk of PE more than 4 times (0R = 4.47 CI = 1.16-12.63). Risk estimation did not change substantially after the adjustment for multiple possible confounders. In conclusion, the59% of women initially diagnosed as gestational hypertensive according to current recommendations had masked chronic hypertension and a very high risk of developing PE.

296 Ergot Alkaloid Consumption Alters Serotonin Receptor-Induced Vasoactivity in Ovine Umbilical Vasculature

Abstract Consumption of ergot alkaloids during the second half of gestation have been shown to decrease umbilical artery vasoactivity resulting in lighter birth weights. The objective was to evaluate vasoactivity of serotonin (5HT) receptors 5HT2A and 5HT1B/1D in umbilical artery and vein from ewes receiving endophyte-infected (E+ 1.77 mg ergovaline/animal/day) or endophyte-free (E-; 0 mg ergovaline/animal/day) tall fescue seed at d-85 (n=4), 110 (n=4 E+; n=4 E-), 135 (n =4 E+; n=4 E-) of gestation. Suffolk ewes began receiving seed treatments on d-86 of gestation. Umbilical artery and vein were collected from ewes at slaughter. Two-mm blood vessel cross sections were mounted in multi-myographs containing Krebs-Henseleit buffer and exposed to increasing concentrations of rizatriptan benzoate (5HT1B/1D agonist) and TCB-2 (5HT2A agonist). Data were analyzed as a split-plot with mixed models of SAS. The 5HT1B/1D agonist did not stimulate a contractile response in either vessel for any gestation time point evaluated. The 5HT2A agonist caused contractile responses in umbilical artery with the greatest occurring at d-85 and decreasing in magnitude as days of gestation increased (P&amp;lt; 0.05). On d-110 and 133 of gestation, umbilical arteries from ewes receiving E- seed had a greater contractile response than those arteries collected from ewes receiving the E+ treatment (P&amp;lt; 0.05). Umbilical veins also responded to increasing concentrations of 5HT2A agonist and maximal response was not different between d-85 and 110 of gestation, but both were greater than d-133. Unlike the artery, umbilical veins from ewes receiving E+ seed had greater contractile response than E- at d-133 (P&amp;lt; 0.05). These results demonstrate that ovine vascular smooth muscle contractions of the umbilical artery and vein are induced by 5HT2A receptor activity and not 5HT1B/1D. Umbilical artery 5HT2A receptor activity responded to seed treatment differently than umbilical vein and could be the source of ergot alkaloid-induced intra-uterine growth restriction.

Maternal Left Ventricular Function in Uncomplicated Twin Pregnancies: A Speckle-Tracking Imaging Longitudinal Study.

Objective: The knowledge of maternal cardiovascular hemodynamic adaptation in twin pregnancies is incomplete. We aimed to longitudinally investigate maternal left ventricular (LV) function in uncomplicated twin pregnancies. Methods: 30 healthy and uncomplicated twin pregnant women and 30 controls with normal singleton pregnancies were prospectively enrolled to undergo transthoracic echocardiography at 10–15 week’s gestation (w) (T1), 19–26 w (T2) and 30–38 w (T3). LV dimensions and volumes, as well as LV ejection fraction (LVEF), mass (LVM) and diastolic parameters (at transmitral pulsed wave Doppler and mitral annular plane tissue Doppler), were calculated. Speckle-tracking imaging was also applied to evaluate LV global longitudinal (GLS), radial and circumferential 2D strains. Results: During twin pregnancy, maternal LV dimensions, volumes and LVM had an increasing trend from T1 to T3, similar to singletons, while LVEF remained stable. There was LV remodeling/hypertrophy in 50% of women at T2 and T3 in both groups. Diastolic function had a worsening trend from T1 to T3 with no differences between twins and singletons, except for higher LV filling pressure (i.e., E/E′) at T2 in twins. Two-dimensional strains did not vary during gestation in either group, except for a linear trend to increase (i.e., worsen) GLS in singletons. Radial and circumferential 2D strains were impaired in about half of the women at each trimester, while GLS was altered in one-fourth/one-third of them in both groups. Conclusion: Maternal LV geometry, dimensions and function are significantly impaired during twin pregnancies, in particular in the second half of gestation, with no significant differences compared to singletons.

Sex-specific effects of maternal weight loss on offspring cardiometabolic outcomes in the obese preeclamptic-like mouse model, BPH/5.

Preeclampsia (PE) is a hypertensive disorder that impacts 2–8% of pregnant women worldwide. It is characterized by new onset hypertension during the second half of gestation and is a leading cause of maternal and fetal morbidity/mortality. Maternal obesity increases the risk of PE and is a key predictor of childhood obesity and potentially offspring cardiometabolic complications in a sex‐dependent manner. The influence of the maternal obesogenic environment, with superimposed PE, on offspring development into adulthood is unknown. Obese BPH/5 mice spontaneously exhibit late‐gestational hypertension, fetal demise and growth restriction, and excessive gestational weight gain. BPH/5 females have improved pregnancy outcomes when maternal weight loss via pair‐feeding is imposed beginning at conception. We hypothesized that phenotypic differences between female and male BPH/5 offspring can be influenced by pair feeding BPH/5 dams during pregnancy. BPH/5 pair‐fed dams have improved litter sizes and increased fetal body weights. BPH/5 offspring born to ad libitum dams have similar sex ratios, body weights, and fecal microbiome as well as increased blood pressure that is reduced in the dam pair‐fed offspring. Both BPH/5 male and female offspring born to pair‐fed dams have a reduction in adiposity and an altered gut microbiome, while only female offspring born to pair‐fed dams have decreased circulating leptin and white adipose tissue inflammatory cytokines. These sexually dimorphic results suggest that reduction in the maternal obesogenic environment in early pregnancy may play a greater role in female BPH/5 sex‐dependent cardiometabolic outcomes than males. Reprograming females may mitigate the transgenerational progression of cardiometabolic disease.

Estrogen promotes fetal skeletal muscle myofiber development important for insulin sensitivity in offspring.

Using our nonhuman primate baboon model, we showed that offspring born to mothers deprived of estrogen during the second half of gestation exhibited insulin resistance and a deficit in first phase insulin release. Although insulin resistance was not due to an impairment of fetal or offspring growth, nor to an alteration in adipose or hepatic sensitivity to insulin, skeletal muscle microvacularization critical for delivery of nutrients/insulin was significantly reduced in fetuses and offspring deprived of estrogen in utero. Skeletal muscle myofiber maturation occurs in utero and estrogen modulates myofiber growth in adults. Therefore, the current study determined whether fetal skeletal muscle development was altered in baboons in which estradiol levels were suppressed/restored during the second half of gestation by maternal treatment with letrozole ± estradiol benzoate. In estrogen-suppressed animals, fetal skeletal muscle fascicles were structurally less organized, smaller, and comprised of slow type I and fast type II fibers, the size, but not the number of which were smaller than in untreated baboons. Moreover, the proportion of non-muscle fiber tissue was greater and that of muscle fibers lower in estrogen-deprived fetuses. Thus, the maintenance of fetal body weight in estrogen-deprived animals was maintained at the expense of muscle fibers and likely reflected increased deposition of non-muscle proteins. Importantly, fetal skeletal muscle development, including fascicle organization, myofiber size and composition was normal in baboons treated with letrozole and estradiol benzoate. Collectively, these and our previous findings support our proposal that exposure of the fetus to estrogen is important for fetal skeletal muscle development and glucose homeostasis in adulthood.