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Abstract Maternal obesity increases the risk of childhood obesity and programs the offspring to develop metabolic syndrome later in their life. Palmitate is the predominant saturated free fatty acid (FFA) that is transported across the placenta to the fetus. We have recently shown that saturated FFA in the maternal circulation as a result of increased adipose tissue lipolysis in third trimester of pregnancy induces trophoblast lipoapoptosis. Here, we hypothesized that palmitate induces integrated stress response by activating mitogen-activated protein kinases (MAPKs), endoplasmic reticulum (ER) stress and granular stress and lipoapoptosis in trophoblasts. Choriocarcinoma-derived third-trimester placental trophoblast-like cells (JEG-3 and JAR) referred as trophoblasts were exposed to various concentrations of palmitate (PA). Apoptosis was assessed by nuclear morphological changes and caspase 3/7 activity. Immunoblot and immunofluorescence analysis was performed to measure the activation of MAPKs, ER stress and granular stress response pathways. Trophoblasts exposed to pathophysiological concentrations of PA showed a concentration-dependent increase in trophoblast lipoapoptosis. PA induces a caspase-dependent trophoblast lipoapoptosis. Further, PA induces MAPK activation (JNK and ERK) via phosphorylation, and activation of ER stress as evidenced by an increased phosphorylation eIF2α & IRE1α. PA also induces the activation of stress granules formation. Two pro-apoptotic transcriptional mediators of PA-induced trophoblast lipoapoptosis, CHOP and FoxO3 have increased nuclear translocation. Mechanistically, PA-induced JNK is critical for trophoblast lipoapoptosis. However, PA-induced activation of ERK and stress granule formation were shown to be cell survival signals to combat subcellular stress due to PA exposure. In conclusion, PA induces the activation of integrated stress responses, among which small molecule inhibition of JNK demonstrated that activation of JNK is critical for PA-induced trophoblast lipoapoptosis and small molecule activation of stress granule formation significantly prevents PA-induced trophoblast lipoapoptosis.

ObjectiveThe gastrointestinal microbiome in preterm infants exhibits significant influence on optimal outcomes-with dysbiosis shown to substantially increase the risk of the life-threatening necrotizing enterocolitis. Iron is a vital nutrient especially during the perinatal window of rapid hemoglobin production, tissue growth, and foundational neurodevelopment. However, excess colonic iron exhibits potent oxidation capacity and alters the gut microbiome-potentially facilitating the proliferation of pathological bacterial strains. Breastfed preterm infants routinely receive iron supplementation starting 14 days after delivery and are highly vulnerable to morbidities associated with gastrointestinal dysbiosis. Therefore, we set out to determine if routine iron supplementation alters the preterm gut microbiome.MethodsAfter IRB approval, we collected stool specimens from 14 infants born ResultsWe observed no significant differences in either phyla or key genera relative abundance between pre- and post-iron timepoints. We observed notable shifts in infant microbiome composition based on season of delivery.ConclusionThough no obvious indication of iron-induced dysbiosis was observed in this unique study in the setting of prematurity, further investigation in a larger sample is warranted to fully understand iron's impact on the gastrointestinal milieu.

Although there are many recognized health benefits for the consumption of omega-3 (n-3) long-chain polyunsaturated fatty acids (LCPUFA), intake in the United States remains below recommended amounts. This analysis was designed to provide an updated assessment of fish and n-3 LCPUFA intake (eicosapentaenoic (EPA), docosahexaenoic acid (DHA), and EPA+DHA) in the United States adult population, based on education, income, and race/ethnicity, using data from the 2003-2014 National Health and Nutrition Examination Survey (NHANES) (n = 44,585). Over this survey period, participants with less education and lower income had significantly lower n-3 LCPUFA intakes and fish intakes (p < 0.001 for all between group comparisons). N-3 LCPUFA intake differed significantly according to ethnicity (p < 0.001), with the highest intake of n-3 LCPUFA and fish in individuals in the "Other" category (including Asian Americans). Supplement use increased EPA + DHA intake, but only 7.4% of individuals consistently took supplements. Overall, n-3 LCPUFA intake in this study population was low, but our findings indicate that individuals with lower educational attainment and income are at even higher risk of lower n-3 LCPUFA and fish intake.

Omega-3 fatty acids are important to pregnancy and neonatal development and health. One mechanism by which omega-3 fatty acids exert their protective effects is through serving as substrates for the generation of specialized pro-resolving lipid mediators (SPM) that potently limit and resolve inflammatory processes. We recently identified that SPM levels are increased in maternal blood at delivery as compared to umbilical cord blood, suggesting the placenta as a potential site of action for maternal SPM. To explore this hypothesis, we obtained human placental samples and stained for the SPM resolvin D2 (RvD2) receptor GPR18 via immunohistochemistry. In so doing, we identified GPR18 expression in placental vascular smooth muscle and extravillous trophoblasts of the placental tissues. Using in vitro culturing, we confirmed expression of GPR18 in these cell types and further identified that stimulation with RvD2 led to significantly altered responsiveness (cytoskeletal changes and pro-inflammatory cytokine production) to lipopolysaccharide inflammatory stimulation in human umbilical artery smooth muscle cells and placental trophoblasts. Taken together, these findings establish a role for SPM actions in human placental tissue.

Background/Objectives: Identifying nutritional interventions in extremely low-birth-weight (ELBW) infants (<1000 g) that are associated with favorable clinical outcomes is important. Delayed enteral feeding initiation (>3 days) has been associated with increased odds of developing morbidity. Therefore, the aim of this study is to evaluate the relationship between hour of life at enteral feeding initiation and associated clinical outcomes. Methods: An IRB-approved retrospective chart review evaluated ELBW infants. Birth acuity was evaluated using CRIB II scoring and incidence of various morbidities (bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and spontaneous intestinal perforation (SIP)) and mortality was assessed after adjustment. p < 0.05 was statistically significant. Results: A total of 27/61 (44.3%) initiated enteral feeding <12 h of life. CRIB II scores were lower in infants with earlier enteral feeding initiation. There were no statistical differences in NEC, SIP, or death between categories of hour of life at enteral feeding initiation. After adjusting for CRIB II scores, enteral feeding initiation ≥12 h of life was associated with more days receiving oxygen >21% inspired air (β = 32.7; p = 0.040), approximately 7-fold higher odds of developing moderate/severe BPD (95% CI 1.2.8–38.28; p = 0.025), and 9-fold higher odds of being discharged home while receiving oxygen therapy (95% CI 1.03–79.81; p = 0.047). Conclusions: Timing of enteral feeding initiation may be delayed in ELBW infants with higher clinical acuity, yet later initiation by hour of life is associated with worsened clinical respiratory outcomes. Early initiation within the first 12 h of life is feasible and was not associated with gastrointestinal morbidity in this single-center cohort of ELBW infants. [ABSTRACT FROM AUTHOR]

Despite the importance of n-3 fatty acids for health, intakes remain below recommended levels. The objective of this study was to provide an updated assessment of fish and n-3 fatty acid intake (i.e., eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and EPA+DHA) in the United States using the 2003⁻2014 National Health and Nutrition Examination Survey (NHANES) data (n = 45,347)). Over this survey period, toddlers, children, and adolescents (aged 1⁻19) had significantly lower n-3 fatty acid intake (p < 0.001) compared to adults and seniors, which remained significant after adjusting for caloric intake. Females demonstrated lower n-3 fatty acid intake than males (p < 0.001), with adult and senior women having significantly lower intakes compared to men in the same age categories (p < 0.001) after adjustment for energy intake. Women also consumed less fish than men (5.8 versus 6.1 servings/month, p < 0.001). The estimated intakes of n-3 fatty acids in pregnant women did not differ from non-pregnant women (p = 0.6 for EPA+DHA), although pregnant women reported consuming less high n-3 fatty acid-containing fish than non-pregnant women (1.8 versus 2.6 servings/month, p < 0.001). Our findings indicate that subgroups of the population may be at higher risk of n-3 fatty acid intakes below recommended levels.

Omega (n)-3 fatty acids are vital to neonatal maturation, and recent investigations reveal n-3 fatty acids serve as substrates for the biosynthesis of specialized pro-resolving lipid mediators (SPM) that have anti-inflammatory and immune-stimulating effects. The role SPM play in the protection against negative maternal-fetal health outcomes is unclear, and there are no current biomarkers of n-3 fatty acid sufficiency. We sought to ascertain the relationships between n-3 fatty acid intake, SPM levels, and maternal-fetal health outcomes. We obtained n-3 fatty acid intake information from 136 mothers admitted for delivery using a food frequency questionnaire and measured docosahexaenoic acid (DHA)-derived SPMs resolvin D1 (RvD1) and RvD2 in maternal and cord plasma. We found significantly elevated SPM in maternal versus cord plasma, and increased SPM levels were associated with at-risk outcomes. We also identified that increased DHA intake was associated with elevated maternal plasma RvD1 (p = 0.03; R² = 0.18) and RvD2 (p = 0.04; R² = 0.20) in the setting of neonatal intensive care unit (NICU) admission. These findings indicate that increased n-3 fatty acid intake may provide increased substrate for the production of SPM during high-risk pregnancy/delivery conditions, and that increased maternal plasma SPM could serve as a biomarker for negative neonatal outcomes.

Abstract Background Previous studies suggest higher rates of caesarean section among women who identify as racial/ethnic minorities. The objective of this study was to understand factors contributing to differences in caesarean rates across racial and ethnic groups. Methods Data was collected from 2005 to 2014 Nebraska birth records on nulliparous, singleton births occurring on or after 37 weeks gestation (n = 87,908). Risk ratios (RR) and 95% confidence intervals (CI) for caesarean were calculated for different racial and ethnic categories, adjusting for maternal age, marital status, county of residence, education, insurance status, pre-pregnancy BMI, and smoking status. Fairlie decomposition technique was utilized to quantify the contribution of individual variables to the observed differences in caesarean. Results In the adjusted analysis, relative to non-Hispanic (NH) White race, both Asian-NH (RR 1.21, 95% CI 1.14, 1.28) and Black-NH races (RR 1.13, 95% CI 1.08, 1.19) were associated with a significantly higher risk for caesarean. The decomposition analysis showed that among the variables assessed, maternal age, education, and pre-pregnancy BMI contributed the most to the observed differences in caesarean rates across racial/ethnic groups. Conclusion This analysis quantified the effect of social and demographic factors on racial differences in caesarean delivery, which may guide public health interventions aimed towards reducing racial disparities in caesarean rates. Interventions targeted towards modifying maternal characteristics, such as reducing pre-pregnancy BMI or increasing maternal education, may narrow the gap in caesarean rates across racial and ethnic groups. Future studies should determine the contribution of physician characteristics, hospital characteristics, and structural determinants of health towards racial disparities in caesarean rates.

α-tocopherol is a vitamin E isoform with potent antioxidant activity, while the γ-tocopherol isoform of vitamin E exerts more pro-inflammatory effects. In maternal–fetal environments, increased plasma α-tocopherol concentrations are associated with positive birth outcomes, while higher γ-tocopherol concentrations are linked with negative pregnancy outcomes. However, little is known about tocopherol concentrations in placental tissue and their role in modulating placental oxidative stress, a process that is implicated in many complications of pregnancy. The objectives of this research are to evaluate the concentrations of α- and γ-tocopherol in placental tissue and assess relationships with maternal and umbilical cord plasma concentrations. A total of 82 mother–infant dyads were enrolled at the time of delivery, and maternal and umbilical cord blood samples and placenta samples were collected. α- and γ-tocopherol concentrations in these samples were analyzed by high-performance liquid chromatography (HPLC). γ-tocopherol concentrations demonstrated significant, positive correlations among all sample types (p-values < 0.001). Placental tissue had a significantly lower ratio of α:γ-tocopherol concentrations when compared to maternal plasma and umbilical cord plasma (2.9 vs. 9.9 vs. 13.2, respectively; p < 0.001). Additional research should explore possible mechanisms for tocopherol storage and transfer in placental tissue and assess relationships between placental tocopherol concentrations and measures of maternal–fetal oxidative stress and clinical outcomes of pregnancy.

Having a common framework for early action to cope with complex disasters can make it easier for authorities and other stakeholders, including populations at risk, to understand the full spectrum of secondary and tertiary effects and thus where to focus preparedness efforts, and how best to provide more targeted warnings and response services. Meteorological and hydrological services world-wide have developed and implemented Multi-Hazard Early Warning Systems (MHEWS) for weather and climate related hazards that are now being expanded and transitioned towards Multi-Hazard Impact-based Early Warning Systems (MHIEWS). While it is still early days it is becoming clear that there are useful lessons from this approach in the COVID-19 global pandemic, and some valuable insight to be gained in risk communication, risk analysis and monitoring methodologies and approaches. The ability to understand and respond effectively to warnings through appropriate behaviours and actions is central to resilient societies and communities. By avoiding physical, societal and economic harm to the greatest extent possible, recovery from a hazard is likely to be faster, less costly and more complete. MHIEWS can be a common approach for all hazards and therefore more likely to become a trusted tool that everyone can understand and use as a basic element of their national disaster risk management system. The interconnectedness of hazards and their impacts is a strong motivator for a common approach. One of the lessons from the COVID-19 pandemic and extreme weather events is the need to understand the vulnerability of individuals, communities and societies so as to provide reliable, targeted guidance and warnings and the willingness and capacity to prepare for a reasonable worst-case scenario based on informed long-term planning. Meteorology and hydrology are making good progress in this direction and the process can be readily applied to health and other sectors.

Normal pregnancy relies on inflammation for implantation, placentation, and parturition, but uncontrolled inflammation can lead to poor maternal and infant outcomes. Maternal diet is one modifiable factor that can impact inflammation. Omega-3 and -6 fatty acids obtained through the diet are metabolized into bioactive compounds that effect inflammation. Recent evidence has shown that the downstream products of omega-3 and -6 fatty acids may influence physiology during pregnancy. In this review, the current knowledge relating to omega-3 and omega-6 metabolites during pregnancy will be summarized.

This study seeks to quantify and rank the contribution of selected factors to the observed racial/ethnic disparities in low-birth-weight births (LBWBs) and preterm births (PTBs). Based on vital statistics data on births to primiparous women and characteristics of mothers in the State of Nebraska during the period of 2005 to 2014 (n = 93,375), unadjusted and adjusted odds ratios were estimated to examine the association between selected variables and the odds of having LBWBs or PTBs. Fairlie decomposition analysis was performed to quantify the contribution of each selected factor to racial/ethnic differences in LBWB and PTB rates. The prevalence of PTBs was 9.1% among non-Hispanic White (NHW) women, as compared to 12.8% among non-Hispanic Black (NHB) women and 10.6% among Hispanic women. The corresponding prevalence of LBWBs in the three groups were 5.9%, 11.9%, and 7.2%, respectively. The higher educational attainment among NHW women, relative to NHB women accounted for 10% of the observed difference in LBWB rate between the two groups. Health insurance coverage was the second most important factor accounting for the observed disparities in birth outcomes. Addressing socioeconomic disadvantages in NHB and Hispanic women would be important for them to narrow their gaps with NHW women in LBWB and PTB prevalence. More research is needed to identify key factors leading to the disparities in birth outcomes between NHW and NHB women.

Low levels of vitamin D in maternal and cord blood have been associated with neonatal sepsis. This study assessed the association of vitamin D metabolites (25(OH)D, 3-epi-25(OH)D3, and 24,25(OH)2D3) levels in maternal and cord blood with newborn sepsis evaluation in Nigerian mother–infant dyads. Maternal and cord blood from 534 mothers and 536 newborns were processed using liquid chromatography-tandem mass spectrometry. Spearman correlation was used to compare continuous variables, Mann–Whitney for dichotomous variables, and Kruskal–Wallis for two or more groups. High cord percent 3-epi-25(OH)D3 levels were positively associated with newborn evaluation for sepsis (p = 0.036), while maternal and cord 25(OH)D and 24,25(OH)2D3 levels were not. Being employed was positively associated with maternal and newborn 3-epi-25(OH)D3 concentrations (p = 0.007 and p = 0.005, respectively). The maternal 3-epi-25(OH)D3 and percent 3-epi-25(OH)D3 were positively associated with vaginal delivery (p = 0.013 and p = 0.012, respectively). Having a weight-for-age Z-score ≤ −2 was positively associated with newborn percent 3-epi-25(OH)D3 levels (p = 0.004), while a weight-for-length Z-score ≤ −3 was positively associated with maternal and newborn percent 3-epi-25(OH)D3 levels (p = 0.044 and p = 0.022, respectively). Our study highlights the need to further investigate the biological role of 3-epi-25(OH)D3 and its clinical significance in fetal growth and newborn outcome. [ABSTRACT FROM AUTHOR]

IntroductionObesity during pregnancy increases the risk for maternal complications like gestational diabetes, preeclampsia, and maternal inflammation. Maternal obesity also increases the risk of childhood obesity, intrauterine growth restriction (IUGR) and diabetes to the offspring. Increased circulating free fatty acids (FFAs) in obesity due to adipose tissue lipolysis induces lipoapoptosis to hepatocytes, cholangiocytes, and pancreatic-β-cells. During the third trimester of human pregnancy, there is an increase in maternal lipolysis and release of FFAs into the circulation. It is currently unknown if increased FFAs during gestation as a result of maternal obesity cause placental cell lipoapoptosis. Increased exposure of FFAs during maternal obesity has been shown to result in placental lipotoxicity. The objective of the present study is to determine saturated FFA-induced trophoblast lipoapoptosis and also to test the protective role of monounsaturated fatty acids against FFA-induced trophoblast lipoapoptosis using in vitro cell culture model. Here, we hypothesize that saturated FFAs induce placental trophoblast lipoapoptosis, which was prevented by monounsaturated fatty acids.MethodsBiochemical and structural markers of apoptosis by characteristic nuclear morphological changes with DAPI staining, and caspase 3/7 activity was assessed. Cleaved PARP and cleaved caspase 3 were examined by western blot analysis.ResultsTreatment of trophoblast cell lines, JEG-3 and JAR cells with palmitate (PA) or stearate (SA) induces trophoblast lipoapoptosis as evidenced by a significant increase in apoptotic nuclear morphological changes and caspase 3/7 activity. We observed that saturated FFAs caused a concentration-dependent increase in placental trophoblast lipoapoptosis. We also observed that monounsaturated fatty acids like palmitoleate and oleate mitigates placental trophoblast lipoapoptosis caused due to PA exposure.ConclusionWe show that saturated FFAs induce trophoblast lipoapoptosis. Co-treatment of monounsaturated fatty acids like palmitoleate and oleate protects against FFA-induced trophoblast lipoapoptosis.

Introduction . Respiratory distress (RD) contributes to common causes of neonatal mortality. Bubble continuous positive airway pressure (bCPAP) is a safe, low-cost therapy for RD; however, adoption of bCPAP programs remains challenging. Aim . To increase the percentage of neonates with RD treated with bCPAP from 2% to 25% by January 2019. Methods . In the newborn unit (NBU) at the Nakuru County and Referral Hospital in Kenya, a pre-initiative (pre) period (March 2016 to December 2017) and a post-initiative (post) period (January 2018 to December 2018) were defined. Tests of change included organization of infrastructure, staff trainings, development of a nurse educator role, and treatment protocols. Clinical and outcome data were abstracted from all available medical records. Results . A total of 405 infants were included in the pre group, with 2% bCPAP use. A total of 1157 infants were included in the post group, with 100 (17.6%) treated with bCPAP. bCPAP use increased during the post period. Rates of RD (49.9% pre, 49.0% post, P = .64) and mortality (30.9% pre, 29.1% post, P = .35) were similar. Neonates treated with bCPAP had lower mean birth weight and a higher risk of death (relative risk = 1.41, 95% confidence interval = 1.21-1.65) compared with those not treated with bCPAP. Conclusion . It was possible to build capacity for the use of bCPAP to treat neonates in this low-resource setting. Gaps in the delivery bCPAP remain, and the current capacity in the PGH NBU allows for application of bCPAP to smaller, likely, sicker neonates.

One of the most important predictors of preterm births (PTBs) or low-birth-weight births (LBWBs) is whether a mother has had a history of these birth outcomes. This study examined how different characterizations of birth history (e.g., any previous incidence of PTBs or LBWBs, immediate previous birth that was preterm or of low birth weight, and number of previous PTBs or LBWBs) were associated with PTBs or LBWBs. Based on birth records (n = 98,776) reported to the vital statistics electronic registration system in Nebraska from 2005 to 2014, mothers with a history of PTBs or LBWBs were more likely to have recurrences of these outcomes than those who did not have any history of PTBs or LBWBs. The adjusted odds ratios for recurrent PTBs ranged from 2.82 (95% CI: 2.62, 3.04) to 5.54 (95% CI: 4.67, 6.57) depending on how previous incidence of PTBs or LBWBs were characterized. The corresponding adjusted odds ratio for LBWBs ranged from 1.58 (95% CI: 1.43, 1.74) to 6.75 (95% CI: 4.96, 9.17). Relative to other measures used to characterize birth history, the use of number of previous PTBs or LBWBs allows for identifying mothers most vulnerable to recurrences of these birth outcomes. To help identify mothers at risk for future PTBs or LBWBs, it is beneficial to develop state-wide surveillance of reoccurrences for adverse birth outcomes which is feasible by integrating all separated birth records for the same mother using vital statistics data. Keywords: Preterm birth, Low birthweight, Birth history, Recurrence, Vital statistics

Abstract Background The point prevalence of Clostridium difficile stool shedding in hospitalized infants from two neonatal intensive care units (NICUs) was examined utilizing standard clinical testing compared with duplex PCR to identify toxigenic and non-toxigenic C. difficile strains. Methods All infants from the two NICUs affiliated with a single academic medical center were eligible for inclusion. Stool collection was blinded to patient characteristics and occurred during a one week period at each NICU and repeated with a second weeklong collection 6 months later to increase sample size. Stools were tested for C. difficile using EIA (GDH/toxin A/B) with samples testing +/+ or +/− subsequently evaluated by Loop-Mediated Isothermal Amplification (LAMP) and by duplex PCR amplification of tcdB and tpi (housekeeping) genes. Cytotoxicity assays were performed on all samples positive for C. difficile by any modality. Results Eighty-four stools were collected from unique infants for evaluation. EIA results showed 6+/+ [7.1%], 7 +/− [8.3%], and 71 −/− [84.5%] samples. All 6 EIA +/+ were confirmed as toxigenic C. difficile by LAMP; 6/7 EIA +/− were negative by LAMP with one identified as invalid. Duplex PCR concurred with LAMP in all 6 stools positive for toxigenic C. difficile. PCR identified 2 EIA −/− stools positive for tpi, indicating shedding of non-toxigenic C. difficile. Cytotoxicity assay was positive in 4/6 duplex PCR positive samples and negative for all stools that were EIA +/− but negative by molecular testing. Conclusions C. difficile blinded point prevalence in infants from two NICUs was 7.1% by molecular methods; and lower than expected based on historical incidence estimates. In house duplex PCR had excellent concordance with clinically available LAMP and EIA tests, and added detection of non-toxigenic C. difficile strain shedding. Evolving NICU care practices may be influencing the composition of infant gut microbiota and reducing the point prevalence of C. difficile shedding in NICU patient stools.

Carotenoids are antioxidant nutrients with the potential to provide protection against oxidative stress. Plasma carotenoid concentrations are lower in newborn infants compared to their mothers; however, limited information is available regarding how concentrations differ by gestational age. The objective of this research is to assess maternal and umbilical cord plasma carotenoid concentrations and maternal-umbilical cord plasma ratios across five groups of birth gestational age. Mother-infant dyads were enrolled at delivery for collection of maternal and umbilical cord blood. Plasma carotenoids were analyzed by HPLC and LC-MS/MS. Birth gestational age was categorized into five groups, and the Kruskal–Wallis test compared carotenoid concentrations and maternal-umbilical cord plasma ratios between these groups. A p-value of < 0.05 was considered statistically significant. 370 mother-infant dyads were included, with most infants delivered at early term (20.3%) or term (64.6%). Though maternal plasma concentrations increased with birth gestational age, we observed less variability in umbilical cord plasma concentrations, thus the maternal-umbilical cord plasma ratio also increased with birth CGA groups for lutein + zeaxanthin (p = 0.008), β-cryptoxanthin (p = 0.027), α-carotene (p = 0.030); β-carotene approached significance (p = 0.056). Additional research is needed to determine if carotenoid concentrations were physiologic to varying gestational ages or if they were impacted by factors associated with preterm birth.

Zika virus (ZIKV) infection in pregnancy is associated with the development of microcephaly, intrauterine growth restriction, and ocular damage in the fetus. ZIKV infection of the placenta plays a crucial role in the vertical transmission from the maternal circulation to the fetus. Our previous study suggested that ZIKV induces endoplasmic reticulum (ER) stress and apoptosis of placental trophoblasts. Here, we showed that palmitoleate, an omega-7 monounsaturated fatty acid, prevents ZIKV-induced ER stress and apoptosis in placental trophoblasts. Human trophoblast cell lines (JEG-3 and JAR) and normal immortalized trophoblasts (HTR-8) were used. We observed that ZIKV infection of the trophoblasts resulted in apoptosis and treatment of palmitoleate to ZIKV-infected cells significantly prevented apoptosis. However, palmitate (saturated fatty acid) did not offer protection from ZIKV-induced ER stress and apoptosis. We also observed that the Zika viral RNA copies were decreased, and the cell viability improved in ZIKV-infected cells treated with palmitoleate as compared to the infected cells without palmitoleate treatment. Further, palmitoleate was shown to protect against ZIKV-induced upregulation of ER stress markers, C/EBP homologous protein and X-box binding protein-1 splicing in placental trophoblasts. In conclusion, our studies suggest that palmitoleate protects placental trophoblasts against ZIKV-induced ER stress and apoptosis.

Background: QuPath is an open-source digital image analyzer notable for its user-friendly design, cross-platform compatibility, and customizable functionality. Since it was first released in 2016, at least 624 publications have reported its use, and it has been applied in a wide spectrum of settings. However, there are currently limited reports of its use in placental tissue. Here, we present the use of QuPath to quantify staining of G-protein coupled receptor 18 (GPR18), the receptor for the pro-resolving lipid mediator Resolvin D2, in placental tissue. Methods: Whole slide images of vascular smooth muscle (VSM) and extravillous trophoblast (EVT) cells stained for GPR18 were annotated for areas of interest. Visual scoring was performed on these images by trained and in-training pathologists, while QuPath scoring was performed with the methodology described herein. Results: Bland–Altman analyses showed that, for the VSM category, the two methods were comparable across all staining levels. For EVT cells, the high-intensity staining level was comparable across methods, but the medium and low staining levels were not comparable. Conclusions: Digital image analysis programs offer great potential to revolutionize pathology practice and research by increasing accuracy and decreasing the time and cost of analysis. Careful study is needed to optimize this methodology further.

Retinol (vitamin A) is essential, so the objective of this Institutional Review Board approved study is to evaluate retinol placental concentration, intrauterine transfer, and neonatal status at time of term delivery between cases of maternal retinol adequacy, insufficiency, and deficiency in a United States population. Birth information and biological samples were collected for mother–infant dyads (n = 260). Maternal and umbilical cord blood retinol concentrations (n = 260) were analyzed by HPLC and categorized: deficient (≤0.7 umol/L), insufficient (>0.7–1.05 umol/L), adequate (>1.05 umol/L). Intrauterine transfer rate was calculated: (umbilical cord blood retinol concentration/maternal retinol concentration) × 100. Non-parametric statistics used include Spearman’s correlations, Mann–Whitney U, and Kruskal–Wallis tests. p-values n = 73) differed between adequate vs. deficient mothers (median 0.13 vs. 0.10 μg/g; p = 0.003). Umbilical cord blood concentrations were similar between deficient, insufficient, and adequate mothers (0.61 vs. 0.55 vs. 0.57 μmol/L; p = 0.35). Intrauterine transfer increased with maternal deficiency (103.4%) and insufficiency (61.2%) compared to adequacy (43.1%), p < 0.0001. Results indicate that intrauterine transfer rate is augmented in cases of maternal retinol inadequacy, leading to similar concentrations in umbilical cord blood at term delivery.

Background: Growth is essential for very low birth weight infants, but is compromised in those receiving dexamethasone, especially when given as a consecutive 10-day treatment course to wean ventilatory support. The purpose of this review is to analyze growth outcomes of enteral nutrition practices for infants born < 1,500 grams who received at least one consecutive 10-day treatment course during hospitalization compared to untreated peers. Methods: An IRB-approved retrospective chart review compared 17 dexamethasone-treated study infants vs. 34 untreated controls born < 1,500 grams. Wilcoxon rank sum test and Fisher’s exact test compared continuous data and associations of categorical variables. Multiple regression analyzed predictors for growth outcomes when adjusting for birth gestational age. P-value < 0.05 was considered statistically significant. Results: Treated infants were born younger (25+4 vs. 27+6 weeks gestational age [GA]) with smaller anthropometric measurements (p < 0.05). Growth from birth to 36 weeks GA approached significance (15.1 grams/kg/day study vs. 16.65 grams/kg/day control [p = 0.07]). Treated infants were discharged at similar weight percentiles as untreated infants (p = 0.7). Head growth percentiles were well-maintained for all infants (treated: median 12th% birth, 21st% discharge; untreated: 29th% birth, 43rd% discharge). Treated infants had lower length measurements at 36 weeks GA (p = 0.011) and discharge (p = 0.095). Treated infants received more nutrition, median 131 vs. 119 calories/kg/day (p = 0.0005), 4.4 vs. 4.1 grams protein/kg/day (p = 0.0004). Average nutrition delivery during dexamethasone treatment was 138 calories/kg/day, 4.5 grams protein/kg/day. There were no differences in highest blood glucose (p = 0.071), BUN (p = 0.053), or alkaline phosphatase (p = 0.17) between groups. Conclusions: Infants receiving at least one consecutive 10-day treatment course with dexamethasone during hospitalization experienced altered growth by 36 weeks GA, but comparable growth to non-treated infants for weight and head circumference can be achieved by discharge by optimizing enteral nutrition before, during, and after dexamethasone treatment. Future studies are needed to assess if this leads to improved developmental outcomes.