Gestation Length Research Articles

Reproductive and developmental toxicity evaluation of cannabidiol.

An important data gap in determining a safe level of cannabidiol (CBD) intake for consumer use is determination of CBD's potential to cause reproductive or developmental toxicity. We conducted an OECD Test Guideline 421 GLP-compliant study in rats, with extended postnatal dosing and hormone analysis, where hemp-derived CBD isolate (0, 30, 100, or 300 mg/kg-bw/d) was administered orally. Treatment-related mortality, moribundity, and decreased body weight and food consumption were observed in high-dose F0 adult animals, consistent with severe maternal toxicity. No effects were observed on testosterone concentrations, F0 reproductive performance, or reproductive organs. Hepatocellular hypertrophy in the 100- and 300 mg/kg-bw/day groups correlated with hypertrophy/hyperplasia in the thyroid gland and changes in mean thyroid hormone concentrations in F0 animals. Mean gestation length was unaffected; however, total litter loss for two females and dystocia for two additional females in the high-dose group occurred. Other developmental effects were limited to lower mean pup weights in the 300 mg/kg-bw/d group than those of controls. The following NOAELs were identified for CBD isolate based on this study: 100 mg/kg-bw/d for F0 systemic toxicity and female reproductive toxicity, 300 mg/kg-bw/d for F0 male reproductive toxicity, and 100 mg/kg-bw/d for F1 neonatal and F1 generation toxicity.

Doxycycline hyclate in late-term pregnant mares: pharmacokinetics, diffusion to the fetoplacental unit and safety in the resulting foal

Doxycycline is a second-generation tetracycline with excellent tissue penetration, high-protein-binding, and 5-10-fold higher lipophilic character than tetracycline. It is used to treat difficult-to-identify and atypical pathogens in diseases such as granulocytic anaplasmosis, Potomac fever, Lyme disease, and placentitis caused by Leptospira and nocardioform Actinomycetes. Despite routine use of doxycycline in pregnant mares, there is no data on their pharmacokinetics during pregnancy, transplacental diffusion, or potential toxicity to the fetus and resulting foal. This study aimed to determine the pharmacokinetics of doxycycline in the late-pregnant mare, its diffusion to the fetoplacental unit and its safety in the neonate. The study hypothesizes that doxycycline crosses the equine fetoplacental unit after administration during late-term pregnancy and is safe for the resulting foal. In experiment 1, six mares received a dose of compounded doxycycline hyclate (10mg/kg, p.o.) at 300d of gestation. Doxycycline plasma concentrations were measured with LC-MS/MS at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48h after administration to confirm absorption and pharmacokinetics. The compounded doxycycline used herein was absorbed rapidly, and maximum plasma concentrations were achieved in 0.79h. Pharmacokinetic parameters of the doxycycline were similar to previous studies using commercial canine preparations. In experiment 2, transplacental diffusion and safety to the resulting foal were studied after administration of repeated doses ofdoxycycline to late-term pregnant mares. Seven mares received doxycycline (10mg/kg p.o. q12h) from 320d of gestation until foaling, and six gestationally-age-matched mares served as controls. Once impending signs of imminent parturition were detected coupled with mammary gland secretion pH ≤6.4, foaling was induced with oxytocin (10-units, intramuscularly) to ensure a controlled sampling of fetal fluids. Fetal fluids and foal synovial fluids were harvested at foaling to determine doxycycline concentrations with LC-MS/MS. After parturition, foals had daily clinical examinations, blood chemistry, and complete blood cell counts performed for seven days. Shapiro-Wilk was used to test normal distribution and data were analyzed with ANOVA and Tukey's as post hoc. Mares received doxycycline on average for 15±2d (range 9-23d). No adverse side effects were associated with doxycycline treatment, and complete blood cell count or blood chemistry pre- and post-partum remained within normal reference ranges. Gestation length for doxycycline-treated mares (335±2d) was similar to controls (339±4) (P=0.4). Concentrations of doxycycline were 9-fold higher in the allantoic fluid (73.5±13.9ng/mL) than amniotic fluid (8.3±3.3ng/mL) and 1.5-fold higher in the foal's plasma (35.5±4.3ng/mL than its synovial fluid (23.6±4.3ng/mL). In conclusion, doxycycline was well-absorbed and detectable in fetal fluids, foal plasma, and synovial fluid, and no adverse effects were observed in mares nor their foals.

Placentitis occurrence, treatments, pregnancy outcome and subsequent fertility on a large warmblood stud farm: a retrospective field study

Little is known about the incidence and outcome of high-risk pregnancies including placentitis. Common placentitis treatments combine antibiotics, non-steroidal anti-inflammatory drugs and progestins. However, clinical studies on spontaneous placentitis cases and treatments are missing. Therefore, the aim of this retrospective field study was to describe the occurrence and severity of placentitis, the abortion rate after placentitis diagnosis (based on udder development, combined-thickness-of-uterus-and-placenta and fetal fluid echogenicity) and treatment during pregnancy (2017-2019) on one warmblood stud farm. Furthermore gestational, placental and foal characteristics were analyzed to determine their association with the severity of placentitis, which was scored (Placentitis score (PSc) 1-3; low to high). Pregnancy day of diagnosis (PDD), placentitis treatment and subsequent fertility were recorded as well as the effects of mare's age and status (own pregnancy (OP) or embryo transfer recipient (ER)). Statistical analyses were conducted to analyze potential associations and significant effects on PSc using a Chi-Square test and a generalized linear mixed model. The proportion of pregnancies affected by placentitis was 4.2% (n=177/4192) occurring in 164 mares (3-24 years; Mean±SD= 11.8±5.10). After clinical diagnosis (PDD 256.7±50.4 days) mares were treated with one of nine different treatments (TM 1-9). Abortion occurred in 17/177 (9.6 %) pregnancies diagnosed with placentitis. The remainingplacentitis pregnancies were further characterized by decreased gestational length (330.1±10.04 days), foal birth weight (54.3±7.09 kg), foal height (103.6±4.28 cm) and placental weight (6.3±1.9 kg). Placentitis severity was scored as PSc1 (51.4%), PSc2 (32.8%) and PSc3 (15.8%). PSc was affected by mare's status (P=0.034) with ER mares having increased PSc compared with mares having their own pregnancy. PSc significantly influenced the choice of TM (χ² (16) = 161.4, P<0.0001) and duration of treatment (PSc1: 19.1a ±23.5 days, PSc2: 51.8b ±33.3 days, PSc3: 65.1b ±43.8 days). Mares with PSc1 were most commonly treated with TM1 (Ceftiofur+Flunixin; 37.4%) and TM8 (TrimSulfa+Flunixin; 33.0%). PSc2 mares predominantly received TM2 (Ceftiofur+Flunixin for 7d, followed by TrimSulfa+Altrenogest; 51.7%) and animals showing PSc3 were treated with TM5 (TrimSulfa+Altrenogest+Clenbuterol+Pentoxifylline) and TM3 (Ceftiofur+Flunixin for 7 d, followed by TrimSulfa+Altrenogest+Clenbuterol+Pentoxifylline) (both 28.6%). Overall, at the end of the next season, 61.1% of placentitis mares were pregnant, 32.0% barren, and 6.9% open (n=175). Pregnancy was established in 62/91(68.1%) of mares with PSc1, 31/58(53.4%) with PSc2 and 14/26(53.8%) with PSc3. Most pregnancies were achieved in the first 81/107(75.7%) or second 18/107(16.8%) inseminated cycle. In conclusion, early detection and treatment of placentitis can save high-risk pregnancies in > 90% of cases and mares show a satisfying subsequent fertility.

Longitudinal follow-up of zearalenone and deoxynivalenol mycotoxins in breast milk in the first five months of life

ObjectivesThere is a possibility for exposed lactating mammalians to transfer some contaminants to their milk. This study aimed to determine the levels and changes of Zearalenone (ZEN), Deoxynivalenol (DON) mycotoxins for the first five months in human milk.MethodsVoluntary lactating mothers having infants with gestational length ≥ 37 weeks were enrolled between August 2017 and June 2018 in Şanlıurfa. Mothers and infants with chronic health problems were not included in the study. Human milk samples were taken at three different times; on enrollment (Day 6–10, visit 1), between 4 and 6 weeks postpartum (visit 2), and between 14 and 19 weeks postpartum (visit 3). Mycotoxin levels in human milk were measured utilizing Helica brand commercial kit.ResultsNineteen voluntary mothers and their breastfed infants with three human milk samples completed the study. The mean ages of mothers and infant (± SD) were 27.4 (± 5.4) years and 7.6 (± 0.9) days on enrollment. Median levels of ZEN and DON in human milk samples were 0.39 and 16.7 ng/mL, respectively. None of the cases had a ZEN daily intake higher than 250 ng/kg bw per day. However, three fourth of the cases had DON intake higher than > 1000 ng/kg bw per day. When adjusted for infant weight for age and sex, both ZEN levels and daily intake were decreased progressively from visit 1 to visit 3 (p < 0.001). DON levels and daily intake at visit 2 were found to be significantly lower in samples of visit 3 than that taken in visit 2 (p = 0.004 and p < 0.001, respectively).ConclusionsBreast milk monitoring study revealed that ZEN and DON mycotoxins were present in the mother-infant environment. Contamination levels changed during the lactation period.

Genomic prediction of fertility and calving traits in Holstein cattle based on models including epistatic genetic effects.

The goal of this study was to investigate whether the inclusion of genomic information and epistatic (additive by additive) genetic effects would increase the accuracy of predicting phenotypes adjusted for known environmental effects, reduce prediction bias and minimize the confounding between additive and additive by additive epistatic effects on fertility and calving traits in Holstein cattle. Phenotypic and genotypic records were available for 6090 cows. Eight cow traits were assessed including 56-day nonreturn rate (NRR), number of services (NS), calving to first insemination (CTFS), first insemination to conception (FSTC), gestation length (GL), calving ease (CE), stillbirth (SB) and calf size (CZ). Four scenarios were assessed for their ability to predict adjusted phenotypes, which included: (1) traditional pedigree-based Best Linear Unbiased Prediction (P-BLUP) for additive genetic effects (PA); (2) P-BLUP for additive and epistatic (additive by additive) genetic effects (PAE); (3) genomic BLUP (G-BLUP) for additive genetic effects (GA); and (4) G-BLUP for additive and epistatic genetic effects (GAEn, where n = 1-3 depending on the alternative ways to construct the epistatic genomic matrix used). Constructing epistatic relationship matrix as the Hadamard product of the additive genomic relationship matrix (GAE1), which is the usual method and implicitly assumes a model that fits all pairwise interactions between markers twice and includes the interactions of the markers with themselves (dominance). Two additional constructions of the epistatic genomic relationship matrix were compared to test whether removing the double counting of interactions and the interaction of the markers with themselves (GAE2), and removing double counting of interactions between markers, but including the interaction of the markers with themselves (GAE3) would had an impact on the prediction and estimation error correlation (i.e. confounding) between additive and epistatic genetic effects. Fitting epistatic genetic effects explained up to 5.7% of the variance for NRR (GAE3), 7.7% for NS (GAE1), 11.9% for CTFS (GAE3), 11.1% for FSTC (GAE2), 25.7% for GL (GAE1), 2.3% for CE (GAE1), 14.3% for SB (GAE3) and 15.2% for CZ (GAE1). Despite a substantial proportion of variance being explained by epistatic effects for some traits, the prediction accuracies were similar or lower for GAE models compared with pedigree models and genomic models without epistatic effects. Although the prediction accuracy of direct genomic values did not change significantly between the three variations of the epistatic genetic relationship matrix used, removing the interaction of the markers with themselves reduced the confounding between additive and additive by additive epistatic effects. These results suggest that epistatic genetic effects contribute to the variance of some fertility and calving traits in Holstein cattle. However, the inclusion of epistatic genetic effects in the genomic prediction of these traits is complex and warrant further investigation.

Newborn metabolomic signatures of maternal per- and polyfluoroalkyl substance exposure and reduced length of gestation

Marginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. In the present study, we characterized the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot metabolome among 267 African American dyads in Atlanta, Georgia between 2016 and 2020. Pregnant people with higher serum perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations had increased odds of an early birth. After false discovery rate correction, the effect of prenatal PFAS exposure on reduced length of gestation was associated with 8 metabolomic pathways and 52 metabolites in newborn dried blood spots, which suggested perturbed tissue neogenesis, neuroendocrine function, and redox homeostasis. These mechanisms explain how prenatal PFAS exposure gives rise to the leading cause of infant death in the United States.

Prenatal care and infant outcomes of teenage births: a Project WATCH study

IntroductionInfants of teenage births are known to have increased risk of poor infant outcomes. Adequate prenatal care (PNC) is essential to the overall health of infants and their birthing persons. While teenage births continue to be of concern in rural areas, little is known about the association between inadequate PNC and poor infant outcomes in teenage populations.PurposeTo determine the association between inadequate PNC (< 10 visits) and poor infant outcomes neonatal intensive care unit (NICU) stay, low APGAR score, small for gestational age (SGA) and length of stay (LOS).MethodsThe study used West Virginia (WV) Project WATCH population level data (May 2018-March 2022). Multiple logistic regressions and survival analysis were performed on infant outcomes; NICU stay, APGAR score, infant size, and infant length of stay (LOS) with PNC categories inadequate (< 10 PNC visits) vs adequate (10 or more) adjusting for covariates including maternal race, insurance status, parity, smoking status, substance use status, and diabetes status.ResultsOf births to teenagers, 14% received inadequate PNC. Teens who received inadequate PNC had increased odds of infant admitted to NICU (aOR: 1.84, CI:(1.41, 2.42), p < 0.0001), low 5- minute APGAR score (aOR: 3.26, CI:(2.03,5.22), p < 0.0001), and increased LOS (Est. = -0.33, HR: 0.72, CI:(0.65,0.81), p < 0.0001).ConclusionsResults demonstrated that infants of teenagers who received inadequate PNC are at increased risk of requiring a NICU stay, having a low APGAR score and requiring an increased LOS. PNC is particularly important for these groups as they are at increased risk of poor birth outcomes.

Lameness in Pregnant Sows Alters Placental Stress Response.

Pregnant sows from commercial pig farms may experience painful states, such as lameness, an essential indicator in assessing sow welfare. We investigated the effect of lameness during the last third of pregnancy on reproductive performance and placental glucocorticoid concentrations in sows. Periodic locomotion assessments were carried out on two commercial pig farms using a validated 0-5 scoring system (from 0: normal locomotion; to 5: a downer animal). Sows from both farms (N = 511) were grouped based on their average locomotion scores. On Farm 1, 30 sows were selected and grouped as either Not Lame (NL = 16; X¯ = 0-1) or Lame (L = 14; X¯ > 1). On Farm 2, 39 sows were selected and grouped as either Not Lame (G1 = 12; X¯ = 0-1), Moderately Lame (G2 = 13; X¯ = 1.1-2), or Severely Lame (G3 = 14; X¯ ≥ 2.1). Reproductive data (gestation length, litter weight, average piglet weight, litter size, and the number of piglets born alive/mummified/stillborn) were recorded on both farms. Moreover, on Farm 2, piglet intrauterine growth restriction score and the number of piglets dead during the first week were also recorded, and placenta samples were collected to determine their cortisol/cortisone concentrations. A linear mixed model was used to analyze the data. The proportion of lameness in pregnant sows (N = 511) was >40%, and the gestation length tended to decrease with the presence of lameness (p < 0.1) in both farms. G2 sows had a higher placental cortisol/cortisone ratio than G1 and G3 sows (p < 0.01). In conclusion, lameness was high in the sows assessed, which may decrease sow gestation length and reduce placental efficiency in protecting the offspring from the sows' stress response.

Effects of controlled ovarian stimulation regimens on top-quality blastocyst development and perinatal outcomes with the freeze-all strategy: A retrospective comparative study.

This study aimed to determine the effect of ovarian stimulation regimens on the top-quality blastocyst development rate and perinatal outcomes with the freeze-all strategy. A retrospective comparative cohort analysis of 149 in vitro fertilization (IVF) cycles using the freeze-all strategy was conducted. The IVF cycles were stimulated with either a gonadotropin-releasing hormone antagonist or clomiphene citrate along with gonadotropin based on the patient's serum anti-Müllerian hormone level. Oocyte retrieval, fertilization, and embryo culture were performed following standard procedures. All good-quality blastocysts were cryopreserved and used for frozen-thawed embryo transfer (FET) in subsequent cycles. The fertilization, blastulation, and top-quality blastocyst development rates were calculated. The perinatal outcomes of FET cycles, gestational period, and birth weight were assessed. The main outcome of this study was the top-quality blastocyst development rate, and the secondary outcomes were perinatal parameters (e.g., gestational period and birth weight) between the stimulation regimens. Despite the higher number of usable-quality embryos in the antagonist group, the blastocyst development rate remained comparable (p=0.105). Similarly, perinatal outcomes were comparable in subsequent FET cycles (p=0.538). These findings suggest that the choice between antagonist and clomiphene citrate with gonadotropin as stimulation in controlled ovarian stimulation regimens may not affect the top-quality blastocyst development rate. The IVF outcomes (e.g., clinical pregnancy, miscarriage, and live birth rates) remained unaffected in subsequent FET cycles. Unlike fresh embryo transfer, the birth weight and gestational length were not associated with prior controlled ovarian stimulation regimens when the freeze-all strategy was used.

Maternal pre-conceptional glyphosate exposure impacts the offspring hepatic and ovarian proteome.

Glyphosate (GLY) is an herbicide used for rural and urban weed control. Urinary GLY in women is associated with shortened gestational length yet effects of GLY on offspring due to maternal exposure are unclear. This study tested the hypothesis that maternal chronic pre-conceptional GLY exposure would cause phenotypic and molecular changes in F1 offspring. Female C57BL/6 mice (7-week-old; n = 40) received saline vehicle control (CT; n = 20) or GLY (2 mg/kg; n = 20) daily per os for 10 weeks. At dosing completion, females were housed with unexposed males and divided into Cohort 1 who were euthanized at gestation day 14 (n = 10 per treatment) and Cohort 2 who completed gestation (n = 10 per treatment). F1 female ovarian and liver samples underwent LC-MS/MS and bioinformatic analysis. Maternal exposure did not affect litter (P > .05) sex ratio, or embryonic or neonatal gross phenotypes. In Cohort 2 offspring, no treatment effect on (P > .05) offspring anogenital distance, puberty onset, or ovarian follicular composition was noted. Body weight was increased (P < .05) in male GLY-exposed compared with CT dam offspring. F1 females from GLY-exposed dams had altered (P < .05) abundance of 54 ovarian and 110 hepatic proteins. Pathways altered in the ovary (false discovery rate [FDR] ≤ 0.07) included thermogenesis and phosphatidylinositol-3 kinase-AKT signaling and in liver (FDR ≤ 0.08) included metabolic, glutathione metabolism, oxidative phosphorylation, non-alcoholic fatty liver disease, and thermogenesis. Thus, pre-conceptional GLY exposure affected offspring phenotypic and molecular profiles potentially impacting reproductive health.

Interrogating Components of 2 Diet Quality Indices in Pregnancy using a Supervised Statistical Mixtures Approach

BackgroundThe Healthy Eating Index (HEI)-2015 and Alternative Healthy Eating Index (AHEI)-2010 evaluate diet holistically in pregnancy. However, it remains unclear how individual index components interact to contribute to health. ObjectivesTo evaluate associations of HEI-2015 and AHEI-2010 components with gestational length using traditional and novel statistical methods in a prospective cohort. MethodsPregnant women completed a 3-mo food-frequency questionnaire (FFQ) at median 13 wk gestation to calculate the HEI-2015 or AHEI-2010. Covariate-adjusted linear regression models evaluated associations of HEI-2015 and AHEI-2010 total scores and individual components (one at a time and simultaneously adjusted) with gestational length. Covariate-adjusted weighted quantile sum regression models evaluated 1) associations of HEI-2015 or AHEI-2010 components as mixtures with gestational length and 2) contributions of components to these associations. ResultsEach 10-point increase in HEI-2015 and AHEI-2010 total score was associated with 0.11 (95% CI: −0.05, 0.27) and 0.14 (95% CI: 0.00, 0.28) wk longer gestation, respectively. In individual or simultaneously adjusted HEI-2015 models, higher intakes of seafood/plant proteins, total protein foods, greens/beans, and saturated fats but lower intakes of added sugars and refined grains were associated with longer gestational length. For the AHEI-2010, higher intake of nuts/legumes and lower intake of sugar-sweetened beverages (SSBs)/fruit juice were associated with longer gestational length. Jointly, 10% increases in HEI-2015 or AHEI-2010 mixtures were associated with 0.17 (95% CI: 0.001, 0.34) and 0.18 (95% CI: 0.05, 0.30) wk longer gestational length, respectively. Seafood/plant protein, total protein foods, dairy, greens/beans, and added sugars were the largest contributors to the HEI-2015 mixture. Nuts/legumes, SSBs/fruit juice, sodium, and DHA/EPA were the largest contributors to the AHEI-2010 mixture. Associations were less precise but consistent in women with spontaneous labors. ConclusionsCompared to traditional methods, associations of diet index mixtures with gestational length were more robust and identified unique contributors. Additional studies could consider interrogating these statistical approaches using other dietary indices and health outcomes.

Prolonged stretching of rat uteri causes hypoxia and inhibits contractility via potassium channel TREK1.

During pregnancy, uterine kept quiescence along with uterine overdistention before labor. Prolonged stretching induced uterus myometrial hypoxia, increased TREK1 expression, and relaxed the myometrium, which may contribute to uterine quiescence and atony during pregnancy. The mechanisms underlying pre-labor uterine quiescence and uterine atony during overdistention are unclear. TREK1 (a two-pore domain potassium channel) and hypoxia-inducible factor-1α (HIF-1α) are activated by mechanical stretch, and their expression is upregulated by decreased uterine contractility. HIF-1α is a nuclear factor which regulates numerous target proteins, but whether it regulates TREK1 during the uterine stretch to cause uterine quiescence and/or atony is unclear. We investigated uterine contractility at different gestational stages in rats, as well as in non-pregnant uteri, which were induced by prolonged stretching and hypoxia. We also assessed the effects of incubating the uteri with or without echinomycin or l-methionine. Moreover, we analyzed HIF-1α and TREK1 expression levels in each group, as well as at various gestational stages of pregnant human uteri. We found that contractility was significantly decreased in pregnant uteri when compared with non-pregnant uteri, and this decrease was associated with increases in HIF-1α and TREK1 expression levels. HIF-1α and TREK1 expression levels in human uteri increased with the gestational length. Decreased uterine contractility and increased HIF-1α and TREK1 expression levels were also observed in non-pregnant rat uteri under 8 g of stretching tension or hypoxia. Inhibition of hypoxia with echinomycin restored normal uterine contractility, while HIF-1α and TREK1 protein expression remained reduced. TREK1 inhibition with l-methionine also restored uterine contractility under tension or hypoxia. In conclusion, we demonstrated that prolonged stretching induces myometrial hypoxia, increases TREK1 expression, and relaxes the myometrium, which may contribute to uterine quiescence and atony.

Factors Affecting Gestation Length in Gir Cattle

The present study was planned to understand the factors affecting gestation length in nulliparous and pluriparous Gir cows. A cumulative ten years (2010-2019) full term calving record (n = 1272) of Gir cows were incorporated. The overall mean gestation length of Gir cattle was 283.29 ± 0.16 days. It was shortest in 8th and above parities and longest in 7th parity Gir cows (282.39 and 285.84 days, respectively); with statistically significant (p&lt;0.05) difference. The gestation length remained almost similar from nulliparous to 6th parities cows (ranged from 283.10 to 283.74 days) and the values were more or less close to the overall mean of gestation length. The mean gestation length in cows having female calf was 1.4 days shorter than those with male calf (282.60 vs. 283.99 days). There was period wise significant variation of gestation length in Gir cows (p&lt;0.05). The Gir cattle served during December and March had shortest and longest mean gestation length (282.22 and 284.40 days), respectively; the difference was statistically significant (p&lt;0.05). The mean gestation length across different calving months varied significantly (p&lt;0.05). Season of service and season of birth did not affect gestation length in Gir cattle. The results showed that Gir cows are less affected for gestation length by different factors throughout the year.

Associations between days in the close-up group and milk production, transition cow diseases, reproductive performance, culling, and behavior around calving of Holstein dairy cows

The objective of experiment I was to evaluate the association between days in the close-up group (DINCU) and milk production, early lactation diseases, reproductive performance, and culling. In experiment II behavioral changes associated with DINCU were evaluated using a neck-mounted sensor (Smarttag neck, Nedap Livestock Management, Groenlo, the Netherlands). Cow-lactations of 28,813 animals from 14,155 individual cows of 2 farms in northern Germany and western Slovakia, calving between January 2015 and December 2020, were included in the study. After exclusion of cows with a gestation length <262 and >292 d and cows with >42 DINCU data from 8,794 and 19,598 nulliparous and parous cows, respectively, were available for final statistical analyses. To analyze the association between DINCU and second test-d 305-d mature-equivalent milk projection, linear mixed models were calculated. Binary data (i.e., clinical hypocalcemia, hyperketonemia, retained placenta [RP], acute puerperal metritis [APM], mastitis, left displaced abomasum [LDA], first service pregnancy risk) were analyzed using logistic regression models. To analyze the association between DINCU and culling or death during the first 300 DIM Cox proportional hazards were used. To analyze the association between DINCU and behavior 7 d before to 7 d after calving (i.e., activity, inactivity, eating, ruminating time), linear mixed models were calculated. Nulliparous cows with a short (<10 DINCU) and a long stay (>30 DINCU) in the close-up group had a lower milk production an increased risk for hyperketonemia, RP, and APM compared with nulliparous cows with DINCU between 21 to 28 d. Parous cows with a short (<10 DINCU) and a long stay (>30 DINCU) in the close-up group had a lower milk production, an increased risk for RP and mastitis, a reduced first service pregnancy risk, and an increased culling risk, compared with parous cows with DINCU between 21 to 28 d. Furthermore, the risk for clinical hypocalcemia and LDA was increased in parous cows with >30 DINCU compared with parous cows with <30 DINCU. The risk for APM was increased in parous cows with <10 DINCU compared with parous cows with >10 DINCU. In nulliparous cows no association was found between DINCU and the risk for left displaced abomasum and mastitis. In experiment II, cows with 7 and 35 DINCU had an impaired behavior around calving compared with cows with 14, 21, and 28 DINCU. During the last 7 d before parturition, these cows were more inactive and had a reduced eating and ruminating time. After calving, cows with 7 DINCU spent less time eating. In conclusion, cows with <10 DINCU and cows with >30 DINCU had a lower milk production, a higher risk to incur diseases and an impaired behavior, especially before calving.

89 Influence of Melatonin Supplementation in Pregnant Cattle Consuming Endophyte-Infected Tall Fescue Seed on Offspring Performance

Abstract The objective was to evaluate growth performance and estimates of body composition in offspring of dams that consumed diets containing tall fescue seed with (E+) or without (E-) the toxic endophyte and with or without melatonin during mid-late gestation. Pregnant heifers (n = 57) artificially inseminated with sex-sorted semen (X chromosome-bearing sperm) from a single Angus sire were administered dietary treatments in a 2 x 2 factorial treatment arrangement (E- without melatonin, E-/NM; E- with melatonin, E-/M; E+ without melatonin, E+/NM; or E+ with melatonin, E+/M; melatonin dose: 100 µg/kg of BW) for a 70-day period between May and July starting at 160±13 d of gestation to mimic ergot alkaloid concentrations in a grazing scenario. All diets contained corn gluten and molasses and were fed using SmartFeed Pro (C-Lock Inc.) controlled feeding units between 0900 and2 1200 h daily. Cattle were removed from dietary treatments 39 ± 19 d before calving. Two replicates were housed separately in an open-air barn, each with a 1.2-ha paddock. Prior to and following the 70-d treatment period, all cattle were maintained as a single group free from toxic fescue. Calves were weaned at 226 ± 19 d of age. Gestation length, calf birth weight, 205-day adjusted weaning weight (205-d WW), carcass ultrasonography measures (ribeye area, REA; REA/CWT; percent intramuscular fat, IMF; rib fat thickness, UFAT; rump fat thickness, URUMP), post-weaning weights (recorded every 28 d between weaning and 84 d post-weaning), and post-weaning ADG (between weaning and 84 d post-weaning) were evaluated in offspring (n = 44). Post-weaning calf weights were analyzed using the MIXED procedure of SAS specific for repeated measures with treatment and time as fixed effects and replicate as random. All other variables were analyzed using the MIXED procedure of SAS with treatment as a fixed effect and replicate as random with gestation length as a covariate for birth weight. Gestation length, birth weight, 205-d WW, and post-weaning calf weight were decreased (P &amp;lt; 0.04) in offspring of dams that consumed E+ relative to E- during gestation. Birth weight was increased (P = 0.02) in offspring of dams receiving melatonin relative to those without melatonin during gestation. The 205-d WW and REA were decreased in calves born to E+/NM dams relative to E-/NM, E-/M, and E+/M (P &amp;lt; 0.03). Post-weaning weight tended to be decreased in calves born to E+/NM dams relative to E-/NM, E-/M, and E+/M (P = 0.06). The UFAT tended to be decreased (P = 0.06) in offspring of dams that consumed E+ relative to E- during gestation. There were no other effects of treatment, time or the interaction (P &amp;gt; 0.10). To our knowledge, these preliminary results are the first to evaluate the potential of melatonin as a therapeutic to recover performance losses in offspring born to pregnant cattle consuming toxic fescue.

47 Influence of Melatonin Supplementation in Pregnant Cattle Consuming Endophyte-Infected Tall Fescue Seed on Offspring Performance

Abstract The objective was to evaluate growth performance and estimates of body composition in offspring of dams that consumed diets containing tall fescue seed with (E+) or without (E-) the toxic endophyte and with or without melatonin during mid-late gestation. Pregnant heifers (n = 57) artificially inseminated with sex-sorted semen (X chromosome-bearing sperm) from a single Angus sire were administered dietary treatments in a 2 x 2 factorial treatment arrangement (E- without melatonin, E-/NM; E- with melatonin, E-/M; E+ without melatonin, E+/NM; or E+ with melatonin, E+/M; melatonin dose: 100 µg/kg of BW) for a 70-d period between May and July starting at 160 ± 13 days of gestation to mimic ergot alkaloid concentrations in a grazing scenario. All diets contained corn gluten and molasses and were fed using SmartFeed Pro (C-Lock Inc.) controlled feeding units between 0900 and 1400 h daily. Cattle were removed from dietary treatments 39 ± 19 days before calving. Two replicates were housed separately in an open-air barn, each with a 1.2-ha paddock. before and following the 70-d treatment period, all cattle were maintained as a single group free from toxic fescue. Calves were weaned at 226 ± 19 d of age. Gestation length, calf birth weight, 205-day adjusted weaning weight (205-d WW), carcass ultrasonography measures (ribeye area, REA; REA/CWT; percent intramuscular fat, IMF; rib fat thickness, UFAT; rump fat thickness, URUMP), post-weaning weights (recorded every 28 days between weaning and 84 days post-weaning), and post-weaning ADG (between weaning and 84 days post-weaning) were evaluated in offspring (n = 44). Post-weaning calf weights were analyzed using the MIXED procedure of SAS specific for repeated measures with treatment and time as fixed effects and replicate as random. All other variables were analyzed using the MIXED procedure of SAS with treatment as a fixed effect and replicate as random with gestation length as a covariate for birth weight. Gestation length, birth weight, 205-d WW, and post-weaning calf weight were decreased (P &amp;lt; 0.04) in offspring of dams that consumed E+ relative to E- during gestation. Birth weight was increased (P = 0.02) in offspring of dams receiving melatonin relative to those without melatonin during gestation. The 205-d WW and REA were decreased in calves born to E+/NM dams relative to E-/NM, E-/M, and E+/M (P &amp;lt; 0.03). Post-weaning weight tended to be decreased in calves born to E+/NM dams relative to E-/NM, E-/M, and E+/M (P = 0.06). UFAT tended to be decreased (P = 0.06) in offspring of dams that consumed E+ relative to E- during gestation. There were no other effects of treatment, time or the interaction (P &amp;gt; 0.10). To our knowledge, these preliminary results are the first to evaluate the potential of melatonin as a therapeutic to recover performance losses in offspring born to pregnant cattle consuming toxic fescue.

72 Seminal Plasma Uterine Priming Reduces Offspring Growth and Alters Uterine Artery Indices of Vascular Resistance in Embryo-Recipient Beef Cows

Abstract Uterine priming with seminal plasma has been shown to alter endometrial gene expression as well as uterine cytokines and chemokines. However, the effects of seminal plasma uterine priming on uterine blood flow, fetal and postnatal offspring growth performance have yet to be elucidated. Therefore, we investigated the effects of pooled seminal plasma uterine priming at estrus on embryo crown-rump length, uterine blood flow, and birth weights. Commercial cows (n = 65) were synchronized, evaluated for standing estrus (day 0), and randomly assigned to treatment groups: seminal plasma or control. Seminal plasma treated cows (n = 27) received 0.5 mL of pooled seminal plasma from commercial bulls mismatched from embryo sire placed in their uterine body via artificial insemination rod2 hours after estrus detection (day 0). Control cows (n = 27) were passed through the chute without receiving treatment. On day 7, cows underwent non-surgical embryo transfer and were confirmed pregnant on day 35 via ultrasonography. Final treatment numbers were n = 9 seminal plasma and n = 7 control. On days 35, 40, and 45 embryo crown-rump length was measured via transrectal ultrasonography. On days 140, 180, 200 and 220, uterine artery hemodynamics were measured via Doppler ultrasonography. Birth weights were collected within 24 hours of birth. Data collected over time were analyzed using repeated measures of ANOVA with fixed effects of treatment, day, and their respective interaction. Birth weights and gestation length were analyzed using ANOVA. Embryo sire and dam, side of pregnancy, and fetal sex were included as covariates if P &amp;lt; 0.10. Covariance structure was selected based on lowest AIC and BIC. Embryo crown-rump length was decreased (P = 0.0483) among seminal plasma treated cows compared with controls. Embryo crown-rump length increased (P &amp;lt; 0.0001) by day. Total uterine blood flow increased (P &amp;lt; 0.0001) as gestation proceeded. Ipsilateral resistance index was increased (P = 0.0431) among seminal plasma treated cows compared with controls. Ipsilateral resistance index was increased (P = 0.0107) on day 180 of gestation compared with days 200 and 220 of gestation. Ipsilateral pulsatility index was decreased (P &amp;lt; 0.0001) on day 220 of gestation compared with days 140 and 180 of gestation. Contralateral blood flow was decreased (P = 0.0037) on day 140 of gestation compared with days 180, 200, and 220 of gestation. There were no differences in contralateral uterine artery blood flow, resistance index, or pulsatility index, or gestation length between treatment groups. Birth weights were decreased (P = 0.0102) among calves from seminal plasma treated cows compared with calves from control cows. In summary, seminal plasma uterine priming reduced offspring growth while increasing uterine artery resistance index, which indicates uterine vascular bed anomalies that persisted into the third trimester of pregnancy.

18 Influence of Pregnant Cattle Grazing Endophyte-Infected Tall Fescue on Innate Immune Response of Male Offspring

Abstract The objective was to evaluate the influence of dams grazing endophyte-infected tall, toxic, fescue (E+) during gestation on innate immune response of male offspring to an endotoxin challenge. Crossbred pregnant multiparous cows (n = 36) bred to Red Angus sires were housed in replicated E+ or novel endophyte-infected, non-toxic, fescue (NE+) pastures before breeding and through the length of gestation. After parturition, cows and calves were moved to a common bermudagrass pasture until calves were weaned. From this calf-crop, a subset of post-weaned steers (E+ n = 8; NE+ n = 8) were selected for a lipopolysaccharide (LPS) challenge. Steers (302 ± 36 d of age; 261 ± 62 kg body weight) were fitted with jugular vein catheters &amp;gt;7 h before sampling. Blood was collected every 30 min starting 2 h before (Pre-LPS) and 9 h following (Post-LPS) LPS administration (0.5 µg/kg body weight). Sickness behavior score (SBS), cortisol, and glucose were analyzed every 30 min. Complete blood count (CBC) and rectal temperature (RT) were analyzed hourly. Peak concentration, time at peak concentration, baseline, return to baseline, and area under the curve (AUC) were evaluated for cortisol and glucose. Cortisol and glucose were determined by radioimmunoassay and hexokinase colorimetric assay, respectively. The CBC data were analyzed using a Hemavet hemocytology analyzer. Pre-LPS and Post-LPS cortisol, glucose, SBS, RT, and CBC were analyzed using the MIXED procedure of SAS specific for repeated measures with treatment, time, and the interaction as fixed effects and dam sire breed as a random effect. Peak concentration, time at peak concentration, baseline, return to baseline, and AUC for cortisol and glucose were analyzed using the MIXED procedure of SAS with treatment as a fixed effect and dam sire breed as a random effect. There was a Pre-LPS treatment by time interaction for RT (P &amp;lt; 0.05). Pre-LPS monocyte count was lower in offspring of dams grazing E+ relative to NE+ during gestation (P &amp;lt; 0.05). Pre-LPS hematocrit was increased in offspring of dams grazing E+ relative to NE+ during gestation (P &amp;lt; 0.05). There was a Pre-LPS effect of time on SBS (P &amp;lt; 0.05). As expected, Post-LPS cortisol, glucose, RT, WBC, neutrophil count, lymphocyte count, lymphocyte percentage, eosinophils count, eosinophils percentage, hematocrit percentage, RBC, and platelets changed over time in response to LPS (P &amp;lt; 0.05). Post-LPS lymphocyte count and monocyte percentage were decreased in offspring of dams grazing E+ relative to NE+ during gestation (P &amp;lt; 0.05). Post-LPS eosinophils count, eosinophil percentage, and hematocrit were increased in offspring of dams grazing E+ relative to NE+ during gestation (P &amp;lt; 0.05). There was a Post-LPS treatment by time interaction for monocyte count and neutrophil percentage (P &amp;lt; 0.05). Preliminary results suggest an altered innate immune response of male offspring of dams grazing toxic relative to novel fescue during gestation.

137 Parturition prediction in mares using gestation length, and pH and hardness of preparturient mammary secretions

Due to variability in gestation length, attention is placed on predictive variables of parturition. Previous studies have focused on variables of days in gestation (DIG), and pH or hardness (Hd) of preparturient mammary secretions. Research on the added benefit of using multiple variables simultaneously is limited. We hypothesized that a combination of mammary secretion pH, Hd, and DIG would improve parturition predictions within 24, 48, and 72h of birth. Our objectives were to identify the best combination of variables that provided probability estimates of parturition and to determine optimal cutoff probabilities for predicting parturition. Diagnostic criteria were compared with previously published criteria using samples collected in this study (Table 1). Mammary secretions (n = 1,524) were collected from 36 mares before 135 births from 2014 to 2021. The pH was measured with narrow range (pH 6.0–7.7, 0.3 precision) pH strips, Hd with the Predict-a-Foal Kit (0–5 squares, 0.5 precision), and DIG was calculated based on the last day bred. Backward stepwise selection with mixed logistic regression was used to select the best combination of variables to estimate probability of whether parturition would occur. Bootstrapping with 10,000 replications and data clustered by foal was utilized to improve precision of coefficients used to determine estimated probability. Decision curve analysis (DCA) was utilized to compare the net benefits of each diagnostic criteria. The best combination of variables for prediction within 24h (8 ± 4h)were pH and DIG, while prediction within 48h (32 ± 4h) and 72h (56 ± 4h) added the variable of Hd. Optimal cutoff probabilities that maximized the sensitivity (SN) and specificity (SP) of parturition diagnosis were 13.8, 10.2, and 12.7% for 24, 48, and 72h. The sum of the SN, positive predictive value (PPV), SP, and negative predictive value (NPV) illustrates how the combination is optimized over any single diagnostic criteria (Table 1). The DCA indicates greater net benefit for predictions using the combination over single diagnostic criteria within realistic threshold probabilities. Using a combination of variables to predict if parturition will occur will reduce false positives without increasing false negatives.

Timing of COVID-19 Vaccination and Rates of Severe COVID-19 Infection [ID: 1377384

INTRODUCTION: Optimal timing of COVID-19 vaccination in pregnancy is not established. We sought to characterize the relationship between vaccine timing and severe COVID-19 in pregnancy. METHODS: This was a retrospective cohort study of pregnant patients at a tertiary health system December 15, 2020 to June 16, 2022. Severe COVID-19 infection was defined as requiring inpatient admission and remdesivir with or without monoclonals. We compared the rate of severe COVID-19 during pregnancy between patients who were 1) never vaccinated, or were vaccinated 2) before pregnancy, 3) in the first trimester, 4) in the second trimester, or 5) in the third trimester. Infections are reported per 1,000 person-years under observation to account for differences in follow-up and length of gestation. All analyses are descriptive given small numbers of severe infections. RESULTS: Among 17,540 patients, 13,226 (75.2%) were unvaccinated throughout pregnancy. 1,795 (10.2%) were vaccinated before pregnancy, 566 (3.2%) first trimester, 1,126 (6.4%) second trimester, and 825 (4.7%) third trimester. There were 33 cases of severe COVID (27 among unvaccinated patients). No cases occurred among patients vaccinated in the first or second trimester (0 per 1,000 person-years). There were 2 cases among patients vaccinated in the third trimester (3.4 per 1,000 person-years) and 4 cases among patients vaccinated prior to pregnancy (3.3 per 1,000 person-years). All 4 cases among patients vaccinated before pregnancy occurred during the Omicron wave. CONCLUSION: There were fewer severe COVID-19 cases among patients vaccinated early in pregnancy compared to those vaccinated before pregnancy or in the third trimester, suggesting that optimal timing for boosters may be in the first or second trimester, and delaying to the third trimester may increase maternal morbidity. Larger studies are needed to better characterize the relationship between vaccine timing and severe COVID-19.