Maternal Body Weight Research Articles

Impact of Mid and Late-gestation Toll-like Receptor 7 Stimulation on Development and Anxiety-like Behavior in Offspring

Maternal immune activation (MIA) can occur during pregnancy due to exposure to infectious diseases or other inflammatory conditions. MIA is a risk factor for various psychiatric disorders, such as major depressive disorder, as well as cardiac disorders in the offspring. Resiquimod (R-848), a toll-like receptor (TLR) 7 agonist, induces systemic inflammatory responses and mimics responses to viral infections. Previous studies have shown that MIA with a TLR 4 agonist lipopolysaccharide or the viral mimic, TLR 3 agonist polyinosinic:polycytidylic acid produces neuropsychiatric effects in the offspring. The current project investigates the degree to which mid and late-gestation MIA with R-848 impacts offspring development and anxiety-like behavior. Pregnant rat dams received vehicle (phosphate-buffered saline) or R-848 (1 mg/kg, s.c.) injections on gestation day (GD) 14 (mid-gestation) or GD18 (late gestation). Maternal body weight as well as offspring body weight, developmental milestones, and anxiety-like behavior were assessed. Although all dams gained weight throughout pregnancy, the R-848 dams from both injection days displayed pronounced weight fluctuations post-injection, with a trend toward attenuated weight gain in dams injected in late gestation. On postnatal day 21 (PND21), the R-848 dams injected on GD14 had significantly lower body weights (p=0.007) compared to the vehicle dams, whereas the body weights of the R-848 dams injected on GD18 did not differ significantly from the vehicles. Litter size, male-to-female ratio, and birth weight were also not affected by R-848. Semi-weekly offspring weights were not statistically different between any experimental groups by sex during any measured week in the mid-gestation-exposed cohort, but both male and female R-848-exposed offspring in the late-gestation exposure cohort displayed significantly decreased body weights at week 7 (males, p=0.0282 and females, p=0.0009). Eye opening, an important developmental milestone, was not different between the vehicle and R-848 pups regardless of the timing of exposure. Open field testing in the mid-gestation-exposed adult offspring revealed no significant locomotion differences or differences in time spent in the center zone. Open field testing in the late-gestation-exposed adult offspring also revealed no locomotion differences, however, the R-848-exposed female offspring spent markedly less time in the center zone than all other groups. These findings suggest that late gestation R-848 exposure results in attenuated maternal weight gain as well as increased anxiety-like behaviors in female offspring. Future exploration of pre-pubertal stages and assessments of autonomic regulation in offspring exposed to R-848 in late gestation will provide further insight into the long-term consequences of immune activation during pregnancy. NIH U54 MH118919. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Prenatal physical exercise and Zika virus infection have no effect on maternal behavior

Some of the worst effects associated with the Zika virus infection during gestation include microcephaly, and central nervous system damage. Pregnancy-related physical exercise is recognized to improve both the mother's and her unborn child's health. It is widely known that male newborns of late-pregnancy mother infection tend to exhibit more depressive and anxious behaviors as they age. However, nothing is known about how the Zika virus could affect a mother's behavior in the first few days after giving birth. The objective of this study was to evaluate if 4 weeks of moderate-intensity swimming during pregnancy prevents negative outcomes of prenatal Zika infection in the behavior of the dams. Dams were randomly selected and divided into three groups: Mock (n= 8) - untrained group, intraperitoneally injected with saline; Zika (n = 8) - untrained group, intraperitoneally injected with Zika; and Zika/swim (n = 8) - trained group, intraperitoneally injected with Zika. The swimming sessions were initiated before mating, which occurred between the 5th and 7th day of the 1st week of the swimming training, according to the estrous cycle and lasted until the parturition date. Prenatal Zika virus infection did not change maternal body weight or maternal behavior significantly independently of performing or not physical exercise.

Fetal protective effect of Indonesian propolis from Apis mellifera against rifampicin-pyrazinamide induced impaired pregnancy in BALB/c mice.

Anti-tuberculosis drugs rifampicin and pyrazinamide combination in pregnancy can cause morphological, visceral and skeletal damage. Several studies showed that propolis improves pregnancy outcomes. This study aims to determine the fetal protective effect of propolis in BALB/c mice given the anti-tuberculosis drug combination rifampicin and pyrazinamide. A total of 21 pregnant mice were randomly divided into three groups: the normal group (N)was given distilled water as a vehicle, the positive control group (RP) were given rifampicin 15 mg/kg BW, pyrazinamide 35 mg/kg BW and the treatment group (IP) were given rifampicin 15 mg/kg BB, pyrazinamide 35 mg/kg BW and propolis 400 mg/kg BW. The treatment was given during the period of organogenesis, from day 6 to day 15. Laparotomy was performed on the 18th day of pregnancy. Maternal and fetal body weight, fetal length, number of fetuses, and skeletal defects of fetuses were used as parameters to identify the teratogenic effect. All data were analyzed using the ANOVA. All groups significantly differed between maternal and fetal body weights (p<0.05). The administration of rifampicin-pyrazinamide and propolis during pregnancy did not significantly affect the number of fetuses (p>0.05). The administration of propolis protects the fetus from skeletal abnormalities. While in the RP and IP groups, we can find resorption sites and haemorrhagic. This study may suggest the protective effects of propolis against rifampicin pyrazinamide-induced impaired pregnancy.

The Effect of N-Carbamylglutamate Supplementation during the Last Third of Gestation on the Growth and Development of Fetuses Born to Nutrient-Restricted Twin-Bearing Ewes.

N-carbamylglutamate (NCG) is postulated to improve fetal growth in nutrient-restricted gestations when supplemented from day 35 to 110 of gestation, but the effects of supplementation from 100 days of gestation to birth have not been evaluated. The aim of this study was to evaluate the effect of oral NCG supplementation from 100 days of gestation (dga) to term in naturally nutrient-restricted grazing twin-bearing ewes, on the maternal body weight (BW), body condition score (BCS), placental morphology, fetal body and organ weights and blood biochemistry and antioxidant status in the ewe and fetuses. Eighteen twin-bearing ewes maintained under grazing management were randomly allocated to either a treatment group (NCG; n = 10), orally dosed once daily with 60 mg/kg of NCG from day 100 until 140 dga, or an unsupplemented control group (CON; n = 8). At 140 dga, blood gases, redox status, maternal and fetal plasma and fetal biometrics were obtained after caesarian section. The serum concentration of NCG was increased 15-fold in the NCG ewes compared to the CON. No major effects on dam or fetal body weight nor on blood biochemistry or antioxidant parameters were observed. These results indicate that NCG supplementation in mid-to-late gestation to grazing ewes was unable to rescue the negative production effects of severe natural nutritional restriction on both the dam and fetuses.

THE TERATOGENIC EFFECT OF DIETHYLENE GLYCOL (DEG) ON FETUS MORPHOLOGY IN WHITE MICE (MUS MUSCULUS L.)

Objective: Diethylene glycol is listed in the Inventory of Cosmetic Ingredients as a solvent, viscosity controller, and fragrance. Most of diethylene glycol's toxicity is caused by ingesting the contaminated product. This study aims to determine the effect of a teratogen caused by diethylene glycol on mice fetuses.&#x0D; Methods: In this study, 20 mice were used, which were divided into four groups. Diethylene glycol was given with three variations of doses 1662.5, 3325, and 6650 mg/kgBW during the organogenesis period, day 6-15. The effects of teratogens observed were maternal body weight, fetal body weight, and number of fetuses, which were analyzed using one-way ANOVA, as well as morphological and skeletal abnormalities, which were analyzed descriptively.&#x0D; Results: Based on the results of the study, there was a significant difference in the body weight of the mice given diethylene glycol and the control group (p&lt;0.05). There was no significant difference in body weight and the number of fetuses in the control and treatment groups (p&gt;0.05). On the results of fixation of Bouins' solution, defects in the form of hemorrhage, resorption sites, and slow growth were found. At the same time, the results of the fixation of alizarin red solution found defects in the sternal, nasal, caudal, metacarpal, metatarsal, and phalanges bones.&#x0D; Conclusion: The conclusion based on the research is that diethylene glycol has the potential to provide teratogenic effects on mouse fetuses.

How does gestational weight gain influence short- and long-term postpartum weight retention? An updated systematic review and meta-analysis.

This systematic review and meta-analysis provide an update of an earlier meta-analysis examining the impact of gestational weight gain (GWG) on postpartum weight retention (PPWR). Thirty-four observational studies were included, and results from 18 studies were combined in meta-analyses. We found that women with excessive GWG retained an additional 2.98 kg (95% CI: 0.59, 5.37 kg, I2 = 91%) at 0.5years, 1.89 kg (95% CI: 0.90, 2.88 kg, I2 = 61%) at > 0.5-1year and 2.89 kg (95% CI: 1.74, 4.04 kg, I 2 =0%) at 2-4years, compared to women who met the National Academy of Medicine GWG recommendations. Moreover, synthesis of confounder-adjusted regression coefficients showed that each 1kg increase of GWG corresponded to 0.62 kg (95% CI: 0.22, 1.02 kg, I2 = 96%) additional PPWR at 6-9months, 0.48 kg (95% CI: 0.14, 0.81 kg, I2 = 93%) at 1-3years, and 0.31 kg (95% CI: -0.24, 0.86 kg, I2 = 89%) at 5-7years postpartum. Findings suggest that higher GWG contributes to increased maternal body weight in the short- and long-term after childbirth, independent of prepregnancy body mass index. The heterogeneity of reported data and methodological differences across studies complicate the ability to synthesize data and interpret findings.

Maternal GLP-1 receptor activation inhibits fetal growth.

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

Rate of body weight gain during early gestation in F0 beef heifers has effects that extend multigenerationally to the F2 fetuses.

Our aim was to investigate the effects of maternal (F0) body weight (BW) gain during the first 84 d of gestation on body composition, ovarian reserve, and hormonal and metabolic parameters of breeding-age F1 heifers, as well as the BW and morphometry of F2 fetuses. The study also evaluated the effect of maternal BW gain (F0) on the mRNA relative abundance of the small intestine of both F1 heifers and F2 fetuses. Crossbred Angus heifers (F0; n = 100) were managed to gain 0.20kg/d (low gain [LG], n = 50) or 0.75kg/d (moderate gain [MG], n = 50) for the first 84 d of gestation. Subsequently, F0 dams were managed on a common forage-based diet for the rest of gestation until the weaning of the F1 offspring. At 15 mo of age, a subset of F1 heifers was randomly selected for the current experiment (n = 8 LG and n = 8 MG). Heifers were bred via artificial insemination (AI; day 0), then harvested on day 84 of gestation. On days -10, 42, and 84, BW was recorded, and blood was collected and analyzed for concentrations of glucose, non-esterified fatty acids, progesterone, insulin, and insulin-like growth factor-1. The weight of F1 carcasses, organs, gravid uteri, and F2 fetuses and organs were recorded at harvest. Visible follicles were counted on F1 ovaries at harvest, and histology was used to count microscopic follicles. Liver and jejunal samples from F1 heifers were collected to measure tissue oxygen consumption and jejunal samples from F1 heifers and F2 fetuses were collected for mRNA relative abundance analysis. BW of F1 heifers from MG dams tended to be 12kg greater (P = 0.06) than for F1 heifers from LG dams. Concentrations of glucose were greater (P = 0.03) in F1 heifers from the MG group, with no differences in other blood metabolites or follicular populations (P ≥ 0.16). Interestingly, mammary glands were heavier (P = 0.05), and placentas and body depth tended to be heavier and greater, respectively (P ≤ 0.10), for F2 fetuses from F0 LG heifers. Oxygen consumption in the liver and jejunum, as well as mRNA relative abundance in the jejunum of F1 heifers, were not affected by F0 rate of gain (P ≥ 0.16). However, the NDUFC1, SDHA, UQCR1, and PPARG genes were upregulated (P ≤ 0.05) in the jejunum of F2 fetuses from the LG group. In conclusion, BW gain of F0 heifers during early gestation exerts subtle effects on pre-breeding BW and blood metabolites in F1 offspring, with impacts present in F2 placenta, mammary gland, and intestine.

Fetal programming effect of rumen-protected methionine on primiparous Angus × Simmental offspring's performance and skeletal muscle gene expression.

Primiparous Angus × Simmental dams (n = 22) with an average body weight (BW) of 449 ± 32kg of BW were divided based on two nutritional treatments: control (CTRL) and rumen-protected methionine (RPM). The control group received bermudagrass hay, corn gluten, and soybean hulls pellets supplementation (base diet); whereas the RPM group received the base diet in addition to 0.07% of DM of RPM at a fixed rate during the last trimester of gestation and the first ~80d of lactation, in which calves (n = 17) were early weaned. Only male calves were included in this study. After weaning, calves born to RPM dams also received RPM from weaning (day 1) to day 100. Blood sampling and skeletal muscle biopsies for subsequent quantitative polymerase chain reaction (PCR) analysis were conducted on days 1, 25, 50, and 100 on calves. Quantitative PCR data were analyzed using GLIMMIX, and blood metabolites concentrations, BW, and body condition score (BCS) were analyzed using the MIXED procedure of SAS. There was no difference in maternal BW and BCS between treatments. Glucose and blood metabolites that served as biomarkers for liver health (e.g., aspartate transaminase, albumin, alkaline phosphatase, and alanine transaminase) were in the normal levels for all calves (P > 0.40). Calves in the RPM group had a greater expression of adipogenic genes (e.g., PPARG, LPL, and CEBPD) at day 100 compared with CTRL (P < 0.01). In addition, DNA methylation (DNMT1) and oxidative stress-related genes (SOD2 and NOS3) in the RPM group were upregulated at day 100 compared with CTRL (P < 0.01). These results may suggest that calves born to primiparous dams exposed to RPM supplementation are more prone to develop greater adipose tissue than CTRL calves. Furthermore, RPM supplementation may improve methylation processes, as shown by the upregulation of DNMT1. The results shown in our study aim at expanding the knowledge on fetal programming and early-life growth and development of beef cattle under supplementation with RPM.

One-carbon metabolite supplementation increases vitamin B12, folate, and methionine cycle metabolites in beef heifers and fetuses in an energy dependent manner at day 63 of gestation.

One-carbon metabolites (OCM) are metabolites and cofactors which include folate, vitamin B12, methionine, and choline that support methylation reactions. The objectives of this study were to investigate the effects of moderate changes in maternal body weight gain in combination with OCM supplementation during the first 63 d of gestation in beef cattle on (1) B12 and folate concentrations in maternal serum (2) folate cycle intermediates in maternal and fetal liver, allantoic fluid (ALF), and amniotic fluid (AMF) and (3) metabolites involved in one-carbon metabolism and related metabolic pathways in maternal and fetal liver. Heifers were either intake restricted (RES) and fed to lose 0.23 kg/d, or fed to gain 0.60 kg/d (CON). Supplemented (+ OCM) heifers were given B12 and folate injections weekly and fed rumen-protected methionine and choline daily, while non-supplemented (-OCM) heifers were given weekly saline injections. These two treatments were combined in a 2 × 2 factorial arrangement resulting in 4 treatments: CON-OCM, CON + OCM, RES-OCM, and RES + OCM. Samples of maternal serum, maternal and fetal liver, ALF, and AMF were collected at slaughter on day 63 of gestation. Restricted maternal nutrition most notably increased (./ ≤ 0.05) the concentration of vitamin B12 in maternal serum, 5,10-methylenetetrahydrofolate and 5,10-methenyltetrahydrofolate in maternal liver, and cystathionine in the fetal liver; conversely, maternal restriction decreased (P = 0.05) 5,10-methylenetetrahydrofolate concentration in fetal liver. Supplementing OCM increased (P ≤ 0.05) the concentrations of maternal serum B12, folate, and folate intermediates, ALF and AMF 5-methyltetrahydrofolate concentration, and altered (P ≤ 0.02) other maternal liver intermediates including S-adenosylmethionine, dimethylglycine, cystathionine Glutathione reduced, glutathione oxidized, taurine, serine, sarcosine, and pyridoxine. These data demonstrate that OCM supplementation was effective at increasing maternal OCM status. Furthermore, these data are similar to previously published literature where restricted maternal nutrition also affected maternal OCM status. Altering OCM status in both the dam and fetus could impact fetal developmental outcomes and production efficiencies. Lastly, these data demonstrate that fetal metabolite abundance is highly regulated, although the changes required to maintain homeostasis may program altered metabolism postnatally.

Reproductive toxicity of JJH201501 in rats: Perinatal study

AbstractIntroductionIn this study, JJH201501 was examined for reproductive toxicity during the perinatal period to support its safety as a novel serotonergic agent (5‐HT) antidepressant. Pregnant Sprague–Dawley rats (F0, n = 24/group) were continuously exposed to 0 (control), 6, 18, and 60 mg/kg body weight/day of JJH201501 by intragastric administration from gestation day 15 to lactation day 21.MethodsDuring this period, maternal toxicity was evaluated based on clinical signs, body weight, feed intake, delivery condition, litter parameters, and necropsy, with body weight, sex ratios, malformation incidence, physical, and neurodevelopmental assessments conducted on all offspring rats. Ten pups (male:female 1:1) from each dam within each dose group on postnatal day 4 (PND4) were randomly selected. One pair was evaluated for behavior evaluations (F1a) after PND35, one for reproduction performance (F1b) after 10 weeks, and three for organ weight and deformities (F1c) on PND35. After successful mating, F1b male rats were weighed and dissected to assess reproductive organ weight and sperm motility. Pregnant F1b rats were weighed and monitored for food intake twice weekly until laparotomy on GD14, which recorded live/dead fetuses, resorptions, implantations, corpora lutea, and uterine weight. Some statistical differences were found between the JJH‐treated and control groups in maternal weight, food consumption, and F1 body weight and water maze performance.ResultsAutopsy results showed that JJH201501 had a low cardiac index effect in F0, with no significant histopathological changes detected. Only one F1 offspring died in the high‐dose group throughout the experiment. Due to the lack of dose‐dependent effects and the consistent growth pattern of these alterations, the study findings do not suggest any toxicological significance for the observed results.ConclusionIn conclusion, the no‐observed‐adverse‐effect level of JJH201501 for perinatal rats is about 60 mg/kg b.w./day.

Demand and Requirements for a Digital Healthcare System to Manage Gestational Diabetes in Patients and Healthcare Professionals: A Cross-sectional Survey.

This study aimed to assess the current status of gestational diabetes mellitus (GDM) diagnosis and management, and the demand for a digital healthcare system, in order to develop an optimal digital-based management model for GDM. An anonymous online survey was conducted targeting pregnant/postpartum women (Group W), internal medicine physicians (Group P), and obstetricians (group O) from September 6, 2022 to December 31, 2022. The survey assessed the women's knowledge of GDM and gathered information about healthcare professionals' (HCPs) current GDM management practices. All groups were asked about their acceptance of and demands for a digital healthcare system for GDM. Statistical comparisons between groups were conducted using the chi-square test or Fisher's exact test where appropriate. A total of 168 participants were in Group W, 185 in Group P, and 256 in Group O. Participants from all groups recognized the need for a digital healthcare system for GDM (Group W: 95.8%, Group P: 85.9%, Group O: 60%). However, HCPs showed less willingness to integrate these systems into their clinics than pregnant/postpartum women. Essential features identified were recording blood glucose levels and insulin, along with automatic data linkage from self-monitoring devices. Group W showed a higher preference for lab test access, search functionality, and fetal weight assessment than groups P and O (all P < .0001), while Groups P and O had a greater preference for recording insulin and maternal body weight compared to Group W (P = .0141 and .0023, respectively). Both pregnant/postpartum women and HCPs acknowledged the benefits of utilizing a digital healthcare system for managing GDM. However, there were differences in perspectives among these groups.

FTO and MC4R polymorphisms, and selected pre-, peri- and postnatal factors as determinants of body mass index and fatness in children: a thorough analysis of the associations

BackgroundOverweight and obesity among children have become significant global health concerns. Previous studies have highlighted the potential role of genetic factors, particularly polymorphisms in the FTO and MC4R genes, as well as environmental factors in the development of childhood obesity. This study aimed to investigate the relationships between genetic, socioeconomic and perinatal factors, adverse childhood events (ACEs), and lifestyle, and their impact on overweight, obesity and body composition parameters in children. Additionally, we explored potential interactions between genetic factors and ACEs.MethodsFour hundred fifty-six children aged 6–12 years participated in our study. Information on the socioeconomic status, perinatal factors, ACEs and lifestyle of the children was collected with a questionnaire completed by their parents/guardians. We examined the children’s body weight and conducted an electrical bioimpedance analysis. Overweight and obesity were diagnosed based on the International Obesity Task Force and McCarthy criteria. We genotyped two selected polymorphisms in the FTO and MC4R genes using the TaqMan SNP allelic discrimination method.ResultsHigher BMI (Body Mass Index) z scores were related to higher paternal BMI and lower maternal age at the child’s birth. Higher FMI (Fat Mass Index) z scores were associated with higher paternal BMI, increased gestational weight, lower maternal education and the presence of the FTO risk allele. Higher FatM (fat mass in kg) z scores were linked to lower maternal education, lower maternal age at the child’s birth, higher maternal body weight gain, paternal BMI and the presence of the FTO risk allele. Moreover, interaction effects were observed on BMI z scores between ACE and FTO AA, and on FMI z scores and FatM z scored between ACE and MC4R CC.ConclusionsThe contribution of environmental factors is more strongly related to changes in body composition than genetic ones. Additionally, the presence of the risk allele combined with unfavourable environmental factors like ACEs leads to visible interaction effects, resulting in increased BMI z scores and FMI z scores in children.

Long-lasting developmental effects in rat offspring after maternal exposure to acetamiprid in the drinking water during gestation.

Neonicotinoids (NNTs) are a class of insecticides proposed to be safe for pest control in urban, suburban, and agricultural applications. However, little is known about their developmental effects after repeated low-dose exposures during gestation. Here, we tested a dose considered subthreshold for maternal toxicity in rats (6 mg/kg/day) by assessing several morphological, biochemical, and neurobehavioral features in preterm fetuses and developing pups after maternal administration of the NTT acetamiprid (ACP) dissolved in the drinking water during gestational days (GD) 2-19. The exploratory evaluation included monitoring maternal body weight gain, fetal viability, body weight and sex ratio, cephalic length, neonatal body weight and sex ratio, metabolic enzymes in the placenta, maternal blood and fetal liver, and anogenital distance and surface righting response during infancy. We also used the circling training test to study the integrity of the associative-spatial-motor response in adolescence. Results showed no consistent findings indicating maternal, reproductive or developmental toxicity. However, we found ACP effects on maternal body weight gain, placental butyrylcholinesterase activity, and neurobehavioral responses, suggestive of a mild toxic action. Thus, our study showed a trend for developmental susceptibility at a dose so far considered subtoxic. Although the ACP concentration in environmental samples of surface water and groundwater has been mostly reported to be much lower than that used in our study, our results suggest that the ACP point of departure used in current guidelines aimed to prevent developmental effects may need to be verified by complementary sensitive multiple-endpoint testing in the offspring.

Prenatal fluoride exposure, offspring visual acuity and autonomic nervous system function in 6-month-old infants

BackgroundPrenatal fluoride exposure can have adverse effects on children’s development; however, associations with visual and cardiac autonomic nervous system functioning are unknown. We examined associations between prenatal fluoride exposure and visual acuity and heart rate variability (HRV) in 6-month-old infants. MethodsWe used data from Canadian mother-infant pairs participating in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort. We estimated prenatal fluoride exposure using: i) fluoride concentration in drinking water (mg/L), ii) maternal urinary fluoride adjusted for specific gravity (MUFSG; mg/L) and averaged across pregnancy, and iii) maternal fluoride intake (µg/kg/day) from consumption of water, tea, and coffee, adjusted for maternal body weight (kg). We used multivariable linear regression to examine associations between each measure of fluoride exposure and Teller Acuity Card visual acuity scores (n = 435) and assessed HRV (n = 400) using two measures: root mean square of successive differences (RMSSD) and the standard deviation of N-N intervals (SDNN) measured at 6-months of age. ResultsMedian (IQR) values for water fluoride, MUFSG, and daily fluoride intake were 0.20 (IQR: 0.13–0.56) mg/L; 0.44 (0.28–0.70) mg/L and 4.82 (2.58–10.83) µg/kg/day, respectively. After adjustment for confounding variables, water fluoride concentration was associated with poorer infant visual acuity (B = -1.51; 95 % CI: −2.14,-0.88) and HRV as indicated by lower RMSSD (B = -1.60; 95 % CI: −2.74,-0.46) but not SDNN. Maternal fluoride intake was also associated with poorer visual acuity (B = -0.82; 95 % CI: −1.35,-0.29) and lower RMSSD (B = -1.22; 95 % CI: −2.15,-0.30). No significant associations were observed between MUFSG and visual acuity or HRV. ConclusionFluoride in drinking water was associated with reduced visual acuity and alterations in cardiac autonomic function in infancy, adding to the growing body of evidence suggesting fluoride's developmental neurotoxicity.

Maternal Body Mass Index Trends and Weight Gain in Singleton Pregnancies at the Time of Fetal Anatomic Survey: Changes in the Last Decade and New Trends in the Modern Era.

(1) Background: the worldwide impact of overweight and obesity is rising, increasingly resembling an epidemic (a price we have to pay for our new way of living). (2) Methods: our study aims to evaluate the temporal trends and patterns of singleton pregnant women's BMI (body mass index) in our region during a 12-year time frame between 2010 and 2021. (3) Results: We noticed a statistically significant difference between the BMIs of nulliparous and multiparous women and a significantly increased pregestational BMI in women with previous ART (assisted reproductive technology) procedures. Smoking pregnant women had a higher second trimester weight gain, regardless of parity. Women with folic acid supplementation alone had a higher BMI than those with folic acid and multivitamin intake. The weight of both nulliparous and multiparous women with chronic hypertension was statistically significantly higher in all three timeframes. Global weight gain did not reveal any statistically significant changes concerning women with pregestational diabetes, regardless of parity and the pregnancy trimester. (4) Conclusions: our article describes the trends in obesity and overweight in our middle-income country, in which this pathology is continuously growing, negatively influencing our reproductive-aged women and future generations.

PSI-21 The Role of N-Carbamylglutamate Supplementation During Last Third of Gestation in Nutrient Restricted Twin-Bearing Ewes

Abstract Nutrient restriction in sheep during pregnancy normally occurs in Patagonia with negative effects on ewe body condition (BCS) and reproductive performance. N-carbamylglutamate (NCG), an analogue of N-acetylglutamate, is postulated to improve urea recycling, nitrogen utilization and antioxidant capacity in ruminants. The objective of this study was to evaluate the effect of oral NCG supplementation in naturally nutrient restricted grazing twin-bearing ewes, on maternal body weight (BW) and body condition score (BCS), serum biochemical indexes and antioxidant capacity in mid-late gestation. Ten twin-bearing ewes were orally dosed once-daily with 60 mg/kg BW NCG in a water carrier from 100 to 140 days of gestation (dg) and were compared with unsupplemented controls (CON; n = 8). Maternal BW, and BCS were recorded every 10 days, from 100 to 140 dg. Blood samples were collected at the same time points to evaluate plasma metabolites (NEFA, urea, total protein, albumin, globulin, Ca, P, Mg, Cholesterol, ASAT, CK, GGT, GLDH, total bilirubin and triglycerides), antioxidant status [malondialdehyde (MDA)], and total antioxidant capacity (TAC). Ewes were managed as a single mob in a paddock with natural pasture (3.3% CP, 1.9 Mcal/kg ME), supplemented with alfalfa hay (600 g· ewe-1· /day-1; 13% CP and ME 2.2 Mcal/kg ME) from 130 dg, with a stocking rate of 0.9 ewes per hectare and a dry matter availability of 525 kg per hectare, representative of Patagonian prairie conditions. The effect of treatment on ewe BW, BCS and plasma metabolites were analyzed using REML analysis in R using lme4 R package with time (dg) and treatment (and their interaction) as fixed effects and animal as the random effect. Ewe BW increased (P &amp;lt; 0.0001) and BCS decreased (P = 0.005) with advancing gestation, but there was no effect of treatment. There was a tendency for a treatment effect (P = 0.07) on plasma urea with ~10% less concentrations in NCG than CON ewes at 130 dg (P = 0.08) and 140 dg (P = 0.04). There was a treatment by time interaction for total bilirubin (P = 0.005), phosphorus (P = 0.02), and a similar trend for albumin (P = 0.09). Ewes supplemented with NCG had~10% lower concentrations of bilirubin at 100 (P = 0.01) and 120 dg (P = 0.04), less concentrations of phosphorus (P = 0.003) and albumin (P = 0.02) at 140 dg compared with CON ewes. No other effects of treatment on blood metabolites or antioxidant status or capacity were observed. Collectively these results suggest that supplementation of nutritionally restricted ewes with 60 mg/kg BW from 100 to 140 dg did not influence BW or LWT but may have some effects on liver function, protein metabolism, urea recycling, feed intake and/or feed efficiency which warrant further investigation.*Funded by FONDECYT Project N°1221042; AgResearch Strategic Science Investment Fund.

Results of Preclinical Animal Studies to Evaluate the Effect of Iptacopan on Pregnancy-Related Outcomes

Introduction: Iptacopan is a first-in-class, oral, selective inhibitor of factor B, a key component of the complement system alternative pathway. Inhibition of the complement system represents a potential mechanism for treatment of several complement-driven diseases including paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Here, we report results from the preclinical GLP toxicology studies of iptacopan on embryo-fetal development in rats and rabbits and pre- and postnatal development in rats. Methods: In the definitive embryo-fetal development studies,iptacopan was dosed orally via gavage to pregnant rats at 0, 100, 300, and 1000 mg/kg/day (N=24/group) and to pregnant rabbits at doses of 0, 100, 250, and 450 mg/kg/day (N=20/group) during the period of organogenesis (Gestation Day [GD] 6 to 17 and GD7 to 20, respectively). The progress and outcome of pregnancy were evaluated and fetuses were examined for external, visceral, and skeletal abnormalities. In a pre- and postnatal developmental toxicity study in pregnant rats, iptacopan was dosed orally via gavage at 0, 100, 300, and 1000 mg/kg/day (N=22/group) from GD6 to Lactation Day (LD) 21. The untreated offspring were allowed to mature and the effects on development, behavior, and reproductive performance were assessed. Results: In the rat embryo-fetal development study, maternal administration of iptacopan resulted in no adverse clinical observations, no effects on maternal body weights, and no adverse fetal findings. Non-adverse fetal variations of delayed ossification were observed in the skull. Two fetuses in one out of 22 litters at 1000 mg/kg/day had benign cysts on the left side of the parietal region of the head, with no impact on skeletal (skull), CNS (brain), or any other head-based structure. The no observed adverse effect level (NOAEL) for maternal toxicity and embryo-fetal development was 1000 mg/kg/day. In the definitive rabbit embryo-fetal development study, administration of iptacopan caused reduced maternal body weight gain and food consumption at 450 mg/kg/day. There were no treatment-related fetal malformations or variations. The NOAEL was 250 mg/kg/day for maternal toxicity and 450 mg/kg/day for embryo-fetal development. In the pre- and postnatal development study, no adverse findings were observed in the mated female rats during gestation, parturition, and lactation and there were no adverse effects on development of their offspring, including survival, physical development, behavior, and reproductive performance. The NOAEL for maternal (F0 generation) toxicity, maternal performance, and development of the F1 generation offspring was the highest dose of 1000 mg/kg/day. NOAEL and estimated AUC-based safety margins based on total plasma concentrations for all mentioned studies are shown in the Table. Conclusion: In nonclinical reproductive toxicity studies conducted in pregnant rats and rabbits, iptacopan was found to be generally safe with no teratogenic effects in the rat and rabbit. Estimated AUC-based safety margins were &amp;gt;5-fold for all developmental findings compared to exposure at the clinical dose of 200 mg twice daily. While these preclinical data do not provide definitive conclusions or guidance on the use of iptacopan in pregnant women, they do provide reassurance that there is no overt preclinical signal of embryo-fetal toxicity.

Neonatal-Maternal Bodyweight Ratio at Birth: An Indicator for First-Week Survival Prognosis in Canine Newborns.

Objectives. In dogs, neonatal bodyweight (NBW) varies at birth. Size-specific reference values for NBW are essential to correctly manage newborns. The present study aimed to define a new tool to evaluate NBW that could be routinely applied in canine neonatology, promptly identifying puppies requiring more care. Methods. The records of 89 litters were retrospectively evaluated. Data were grouped according to maternal bodyweight (MBW) in five categories: toy (≤5 kg), small (5.1-9.9 kg), medium (10-24.9 kg), large (25-39.9 kg), and giant (≥40 kg) dogs. At birth, the NBW of 412 puppies, alongside their litter size (LS) and gender (G), were recorded. Neonatal mortality within the first week was considered. The influence of MBW, LS, and G on NBW and the effect of NBW on the 1-week outcome were evaluated using ANOVA (p < 0.05). The ratio between NBW and MBW expressed as a percentage (N-MBW%), was assessed for each puppy. Through Receiver-Operating Characteristic (ROC) curves, N-MBW% thresholds between puppies alive or dead at one week of age were calculated in each group. Results. The LS was different among groups, except for small vs. medium dogs. In small litters, N-MBW% was lower in medium-, large- and giant-sized dogs than in toy and small dogs. In medium and large litters, N-MBW% differed among the five groups. Male and female N-MBW% differed among the five groups. Only in large and giant sizes did LS affect N-MBW%, which was lower in a large LS. The N-MBW% was higher in healthy puppies than in those who died within one week. The ROC-derived N-MBW% thresholds were as follows: 4.5% in toy-, 3.2% in small-, 1.5% in medium-, 1.2% in large-, and 1% in giant dogs. Clinical significance. The ROC-derived N-MBW% thresholds can be used to cautiously identify puppies at increased risk for one-week mortality and may be helpful in clinical practice, representing a suitable parameter to give a prognosis on 1-week survival immediately at birth.

221 Assessment of Modern Gilts and Sows Body Weight (BW) Throughout Gestation and how Different Gilt BW at Breeding Impact the Energy Requirement for Maintenance at Each Parity

Abstract In addition to reproductive traits, growth, robustness, and carcass traits also contribute to the selection index of maternal lines, resulting in leaner and faster-growing modern genotype females. As a consequence, today’s gilts achieve heavier BW at a similar breeding age and remain heavier throughout their lifetime. Larger and heavier females are expected to have increased energy requirements for maintenance (MEm). Our objective was to describe the BW change of females across gestation according to the parity category and assess the impacts of the increasing average BW of gilts at breeding on the MEm requirement throughout their productive life. Two datasets were used to estimate gilt and sow BW:1) 1,903 PIC Camborough gilts were weighed at breeding and at d 112 of each gestation from parity 0-3; 2) 1,150 PIC Camborough gilts and sows (ranging from parity 0-12) were weighed at d 4 and d 112 within one gestation (Thomas et al., 2018). Average maternal BW gain observed between each cycle were +31, +28, +19, -7, +6, +5, and +11kg for parities 1, 2, 3, 4, 5, 6, and 7+, respectively. Growth of females throughout each stage of gestation was estimated assuming that 30% of the BW gain occurred until d 60, and 70% from d 61-112. A quadratic equation was fit to describe the BW change as a function of the day of gestation for each parity category (Table 1). An equation to estimate the maternal net gain in each cycle (Gain, kg = 0.5357 ′ parity2 – 8.8929 ′ parity + 35.857) was used to determine the BW of the female at weaning based on gilt BW at breeding. Different gilt BW at breeding (144, 155, and 166 kg) were simulated to estimate the estimated sow BW and their MEm at each parity category across gestation. The MEm was calculated according to NRC (2012) model, and a feeding level of 5.9 Mcal of ME/d was assumed. When gilt BW at breeding is 144 kg, it is estimated that only parity 4+ females would be fed below maintenance from d 90-112 of gestation (Figure 1). Increasing average gilt BW at breeding to 155 kg would result in P5+ sows fed below maintenance throughout gestation, P4 sows fed below maintenance from d 30 of gestation, and P2 and P3 sows fed below maintenance from d 9 0 to 112. At 166kg of gilt BW at breeding, P4+ females would be fed below maintenance throughout gestation, P2 and P3 sows would be fed below maintenance in mid and late gestation, and P1 sows would be fed below maintenance in late gestation. In summary, increased growth rates in maternal lines may result in heavier gilts at breeding who become heavier sows in subsequent parities, leading to increased energy intake during gestation to meet the maintenance demand.