Neonatal Serum Research Articles

Target analysis and suspect screening of per- and polyfluoroalkyl substances in paired samples of maternal serum, umbilical cord serum, and placenta near fluorochemical plants in Fuxin, China

The levels of legacy per- and polyfluoroalkyl substances (PFASs) have been growing in the environmental matrices and blood of residents living around the fluorochemical industrial park (FIP) in Fuxin of China over the past decade. Although some recent studies have reported occurrence of novel PFAS alternatives in biotic and abiotic matrices near fluorochemical facilities worldwide, little is known about novel PFAS congeners in maternal sera, umbilical cord sera, and placentas from the female residents close to the FIP and their related health risks. In this study, 50 paired samples of maternal and cord serum as well as placenta were derived from Fuxin pregnant women at delivery, and 21 target analytes of legacy PFASs in all the samples were analyzed via high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS), revealing that PFBS, PFBA, and PFOA were the dominant PFAS contaminants observed in the whole samples. Based upon the suspect screening through high-resolution mass spectrometry (HRMS), 49 novel PFASs assigned to 11 classes were further identified in the Fuxin samples, of which, 20 novel congeners in 4 classes were reported in human blood and placentas for the first time. Moreover, the coefficients for mother-placenta transfer (Rm/p), placenta-newborn transfer (Rp/n), and mother-newborn transfer (Rm/n) of legacy PFASs could be calculated with median values of 1.7, 1.1, and 2.0, respectively, and Rm/p, Rp/n, and Rm/n for each novel PFAS identified were also estimated with the median values of 0.9, 1.2, and 0.8 individually. Accordingly, novel PFASs contributed 90% of all the legacy and novel PFASs in maternal sera and even occupied 96% of the whole PFASs in both placentas and cord sera. In addition, significant associations were determined among the neonate birth outcomes and serum concentrations of thyroid hormone, sex hormone, and glucocorticoid, together with the levels of certain legacy and novel PFASs in cord sera.

Associations of prenatal exposure to perfluoroalkyl substances with preterm birth: A family-based birth cohort study

Studies have investigated associations between maternal exposure to PFAS and preterm birth, but the impact of paternal and overall family exposure to PFAS mixtures on preterm birth remains unknown. To address this knowledge gap, a total of 355 preterm births and 481 controls were selected for a family-based birth cohort study in a coastal area of China, between 2016 and 2018. Seven PFAS, including perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), were quantified in maternal, paternal and neonatal sera. Preterm birth was defined as live delivery at <37 completed gestational weeks. Bayesian kernel machine regression (BKMR) model was used to inspect the combined effect of family PFAS mixtures. Latent class analysis was used to identify family-level PFAS exposure profiles. Multiple linear regression analysis showed higher odds of preterm birth in association with higher maternal PFBA (OR = 1.16, 95%CI:1.09, 1.25), PFOA (OR = 1.51, 95%CI:1.27, 1.80), PFOS (OR = 2.07, 95%CI:1.70, 2.52) and PFNA (OR = 1.36, 95%CI: 1.01, 1.83), and neonatal PFBA (OR = 1.16, 95%CI:1.05,1.29), PFHxA (OR = 1.46, 95%CI:1.32, 1.62), PFHxS (OR = 1.15, 95%CI:1.05, 1.26) and PFNA (OR = 1.30, 95%CI:1.09,1.56). The associations were reversed between individual paternal PFAS exposures and preterm birth. At the family level, higher PFAS mixture concentration was associated with higher odds of preterm birth. In particular, higher PFNA and PFDA exposure was associated with greater preterm birth risk (OR = 2.55, 95%CI:1.45, 4.50). The PFAS-preterm association was modified by family-level seafood consumption. Our results suggest that higher family-level PFNA and PFDA exposure was associated with greater preterm birth risk, although the results for individual paternal, maternal and neonatal PFAS exposures were contradictory. If replicated in other coastal areas, these findings highlight a need to focus on the family triad and to consider seafood consumption when assessing the reproductive toxicity of PFAS exposure.

The Blood Immune Cell Count, Immunoglobulin, Inflammatory Factor, and Milk Trace Element in Transition Cows and Calves Were Altered by Increasing the Dietary n-3 or n-6 Polyunsaturated Fatty Acid Levels.

Transition dairy cows experience sudden changes in both metabolic and immune functions, which lead to many diseases in postpartum cows. Therefore, it is crucial to monitor and guarantee the nutritional and healthy status of transition cows. The objective of this study was to determine the effect of diet enriched in n-3 or n-6 polyunsaturated fatty acid (PUFA) on colostrum composition and blood immune index of multiparous Holstein cows and neonatal calves during the transition period. Forty-five multiparous Holstein dairy cows at 240 days of pregnancy were randomly assigned to receive 1 of 3 isoenergetic and isoprotein diets: 1) CON, hydrogenated fatty acid (control), 1% of hydrogenated fatty acid [diet dry matter (DM) basis] during prepartum and postpartum, respectively; 2) HN3, 3.5% of extruding flaxseed (diet DM basis, n-3 PUFA source); 3) HN6, 8% of extruding soybeans (diet DM basis, C18:2n-6 PUFA source). Diets containing n-3 and n-6 PUFA sources decreased colostrum immunoglobulin G (IgG) concentration but did not significantly change the colostrum IgG yield compared with those with CON. The commercial milk yield (from 14 to 28 days after calving) was higher in the HN3 and HN6 than that in the CON. Furthermore, the n-3 PUFA source increased neutrophil cell counts in blood during the prepartum period and increased neutrophil percentage during the postpartum period when compared with those with control treatment. Diets containing supplemental n-3 PUFA decreased the serum concentration of interleukin (IL)-1β in maternal cows compared with those in control and n-6 PUFA during prepartum and postpartum. In addition, the neonatal calf serum concentration of tumor necrosis factor (TNF) was decreased in HN3 compared with that in the HN6 treatment. The diet with the n-3 PUFA source could potentially increase the capacity of neutrophils to defend against pathogens in maternal cows by increasing the neutrophil numbers and percentage during the transition period. Meanwhile, the diet with n-3 PUFA source could decrease the pro-inflammatary cytokine IL-1β of maternal cows during the transition period and decline the content of pro-inflammatary cytokine TNF of neonatal calves. It suggested that the highest milk production in n-3 PUFA treatment may partially be due to these beneficial alterations.

NT-proBNP Concentrations in the Umbilical Cord and Serum of Term Neonates: A Systematic Review and Meta-Analysis.

The detection of NT-proBNP levels both in umbilical cord blood (UCB) samples and in serum samples collected from healthy term neonates during the neonatal period. A systematic review of relevant literature in accordance with PRISMA guidelines was conducted. For quality appraisal, the potential risk of bias was assessed using the BIOCROSS evaluation tool. The random-effects and fixed-effects models were used to calculate weighted mean differences with a corresponding 95% confidence interval. A total of forty (40) studies met the inclusion criteria for the systematic review. After further examination, eighteen (18) studies (1738 participants) from the UCB sample group and fourteen (14) studies (393 participants) from the serum sample group were selected to perform a meta-analysis. Using the fixed-effects model, the mean intervals of NT-proBNP in UCB and serum samples were 492 pg/mL (95% CI: 480–503 pg/mL) and 1341 pg/mL (95% CI: 1286–1397 pg/mL), respectively. A higher concentration of ΝΤ-proBNP was observed in the serum sample group compared to the UCB samples (p < 0.001). We present the intervals of NT-proBNP in UCB and in the serum of healthy term neonates. The determination of the potential effect of perinatal factors on the biomarker’s reference range was also aimed.

Comparison of Vitamin E Isoforms Among Plasma, Breast Milk, and Dietary Intake Measure of Mother-Infant Dyads

ObjectivesVitamin E is a fat-soluble nutrient with four isoforms: α-, β-, δ-, and γ-tocopherol. These isoforms differentially modulate inflammation and are related to important perinatal outcomes such as preterm delivery and Apgar scores. Understanding the dietary consumption of these isoforms and their respective prevalence in biological samples is an important component to optimize nutritional recommendations. The purpose of this study is to compare tocopherol isoform proportions among maternal, cord, and neonatal plasma; maternal breast milk; and maternal dietary intake.MethodsSamples of maternal breast milk and maternal, cord, and neonatal plasma were obtained within 1 month following delivery for maternal-infant dyads (N = 17) from the neonatal intensive care unit. Maternal dietary intake was assessed using the Harvard Willett Food Frequency Questionnaire. Relative proportions of α-, δ-, and γ-tocopherol in each sample type were measured and median tocopherol concentrations were compared using Kruskal-Wallis tests. A p-value < 0.05 was statistically significant.ResultsTotal tocopherol concentrations were significantly different across sample groups (P < 0.001). Concentrations were highest in maternal serum, followed by neonatal serum, maternal breast milk, and umbilical cord serum. In all samples, α-tocopherol had the highest relative proportion, followed by γ- and δ-tocopherol, respectively. Compared to all biological samples, the dietary intake proportion of γ-tocopherol was significantly higher (P < 0.001), while the proportion of α-tocopherol was significantly lower (p = 0.04).ConclusionsWe observed significant differences in tocopherol concentrations across related biological samples, with maternal plasma containing the highest concentration and umbilical cord plasma the lowest. Mothers also consumed significantly higher percentages of γ-tocopherol than those found in both their plasma and breast milk. This suggests that proportions of individual tocopherol isoforms are influenced by factors other than dietary intake. Additional research should explore these associations in a larger cohort and analyze the effects of supplementation on tocopherol concentrations.Funding SourcesUNMC Pediatrics Department; Child Health Research Institute.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection Versus Vaccination in Pregnancy: Implications for Maternal and Infant Immunity.

BackgroundSARS-CoV-2 infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus.MethodsWe measured Spike-specific immunoglobulin G (anti-S IgG) and A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in two academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity.ResultsThe study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P) and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation (VAX-L). VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (p < .0001), while INF mothers had higher BM: serum anti-S IgA ratios compared to VAX mothers (p = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (p < 0.0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, p = 0.013), but not infection.ConclusionsBNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S Ig, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM Ig production. Next generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit.

Metabolomics Applied to Cord Serum in Preeclampsia Newborns: Implications for Neonatal Outcomes.

Preeclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality. However, it is still uncertain how PE affects neonate metabolism. We conducted an untargeted metabolomics analysis of cord blood to explore the metabolic changes in PE neonates. Umbilical cord serum samples from neonates with preeclampsia (n = 29) and non-preeclampsia (non-PE) (n = 32) pregnancies were analyzed using the UHPLC-QE-MS metabolomic platform. Different metabolites were screened, and pathway analysis was conducted. A subgroup analysis was performed among PE neonates to compare the metabolome between appropriate-for-gestational-age infants (n = 21) and small-for-gestational-age (SGA) infants (n = 8). A total of 159 different metabolites were detected in PE and non-PE neonates. Creatinine, N4-acetylcytidine, sphingomyelin (D18:1/16:0), pseudouridine, uric acid, and indolelactic acid were the most significant differential metabolites in the cord serum of PE neonates. Differential metabolite levels were elevated in PE neonates and were involved in the following metabolic pathways: glycine, serine, and threonine metabolism; sphingolipid, glyoxylate, and dicarboxylate metabolism; and arginine biosynthesis. In PE neonates, SGA neonates showed increased levels of hexacosanoyl carnitine and decreased abundance of 3-hydroxybutyric acid and 3-sulfinoalanine. Taurine-related metabolism and ketone body-related pathways were mainly affected. Based on the UHPLC-QE-MS metabolomics analysis, we identified the metabolic profiles of PE and SGA neonates. The abundance of metabolites related to certain amino acid, sphingolipid, and energy metabolism increased in the umbilical cord serum of PE neonates.

Does the delivery mode affect post-birth neonatal serum C-reactive protein levels? A causal effect analysis.

AimTo determine if the delivery mode has a causal effect on neonatal serum C‐reactive protein (CRP) levels. If such a causal effect exists, we aim to quantify its magnitude.MethodsWe investigated the causal effect of the delivery mode on serum CRP levels 6–8 h after delivery, with appropriate statistical tools for retrospective studies, combining classical and machine‐learning methods. The statistical inference is followed by sensitivity analysis to quantify the magnitude of unobserved bias required in order to alter the study's conclusion.ResultsThis retrospective study reviewed laboratory records of neonates after birth who underwent blood tests due to suspected sepsis. A total of 440 newborns were included, 324 of which underwent a vaginal delivery, 59 an urgent caesarean delivery, and 57 an elective caesarean delivery. Our results revealed that serum CRP values following elective caesarean deliveries were 50% less than those following a vaginal delivery (P = 0.030; −0.907; 95% CI [−1.545, −0.268] in log‐CRP units). No significant effect was found for urgent caesarean deliveries compared to vaginal deliveries (P = 0.887). Those results were strengthened by (1) a sensitivity magnitude of 1.6 to unobserved bias and (2) non‐significant effects when analysis is repeated on blood collected 12–24 h after birth.ConclusionCRP concentrations in neonatal blood during the first 6–8 h of life are higher following vaginal deliveries compared to elective caesarean deliveries. Further studies with the intent of improving EONS detection should include information on the delivery mode.

410 Mild Maternal Undernutrition Results in a Premature Neonatal Leptin Surge and Resistance in Male Offspring to a High Fat Diet

OBJECTIVES/GOALS: Maternal undernutrition, a form of malnutrition, can alter neonatal leptin signaling and result in metabolic dysfunction in adulthood. We developed a mild undernutrition model to relate more to societys nutritional challenges and to test the hypothesis that a shift in the neonatal leptin surge would result in sex-specific metabolic changes. METHODS/STUDY POPULATION: We studied pups from undernourished dams which were calorically restricted by 20% (CR20) from embryonic day 15 until postnatal day (PND) 21. We tested 216 offspring from 11 Fed dams and 13 undernourished dams (CR20), detecting a leptin surge in control fed progeny at PND11. At 3 months of age, offspring from 3 dams per maternal nutrient status were either exposed to a 45% high fat diet (HFD) or control diet (10% fat) for 16 weeks. Anterior pituitary hormones were analyzed in the pituitary and serum of neonates and adults. To determine the mechanism of the phenotype observed in male adult offspring on the HFD, single cell RNA sequencing was used to analyze the pituitary, fat and liver. RESULTS/ANTICIPATED RESULTS: Offspring of CR20 dams had an early leptin surge peaking at PND8 and GH levels at PND1 were higher in CR20 progeny. Weights of both male and female CR20 offspring were lower and body lengths were shorter than controls. As adults, Fed mice from both sexes had increased weight gain with HFD. However, although CR20 females gained weight on the HFD, male progeny from CR20 dams did not gain weight on the HFD and appeared protected from impact. We found sex-specific changes in pituitary Gh, Ghrhr, and Ghsr mRNA levels. Single cell RNA sequencing of pituitary, fat and liver of male offspring showed significant regulation of transcripts in fat of male offspring from Fed dams that was not found in CR20 males when compared to control fed mice. DISCUSSION/SIGNIFICANCE: Mild undernutrition causes a prematurely high leptin surge and sex-specific growth responses to a HFD, including resistance to a HFD in underfed males. Transcript analysis in fat of males resistant to HFD induced obesity may reveal mechanisms that provide protection against HFD induced weight gain.

Hypermagnesemia in preterm neonates exposed to antenatal magnesium sulfate.

One of the possible adverse outcomes of magnesium sulfate (MgSO4) administration for preterm fetal neuroprotection is hypermagnesemia in the newborn. The objectives of this study were to evaluate the association between antenatal MgSO4 administration for neuroprotection and neonatal serum magnesium levels in the first days of life. A single-center retrospective case-control study was conducted on preterm neonates born in our institution between January 2017 and December 2019. Prenatal, perinatal, and postnatal parameters were recorded, and demographic information was collected. Comparative analysis between the group of neonates exposed to antenatal MgSO4 and the control group was performed. A total of 98 patients were enrolled in the study, 49 of them were exposed to antenatal MgSO4 for neuroprotection. The serum magnesium levels in the 5 first days of life were higher in the case group, and higher than the normal range of serum magnesium levels (>2.4 mg/dL), with a statistical significance. The number of days needed to normalize serum magnesium levels was higher in the case group compared to the control group (median of 7 days [1-8] versus 2 days [1-5]). Our findings show that antenatal administration of MgSO4 is associated with high serum magnesium levels in neonates. This group of patients needs close electrolyte monitoring during the first days of life. Parenteral nutrition supplemented with magnesium should only be considered after evaluation of serum magnesium levels.

Elevated serum lead levels in neonates born to mothers suffering from opiate use disorder.

This study was performed to investigate lead levels in neonates born to the mothers suffering from opiate use disorder (OUD) and the association of lead levels with the Apgar score. The present cross-sectional study included 56neonates who were referred to the neonatal ward of Amir-Al Momenin Hospital, Zabol. The neonates were divided into two groups: the neonates whose mothers suffered OUD and the control group. Data were collected using aresearcher-prepared questionnaire, and blood lead level was determined using the atomic absorption method. Data were statistically analyzed. In all, 56neonates (28from OUD mothers and 28from the control mothers) were included in this study. Among the women with OUD, 16 (57%) used inhaled opium, while12 (43%) consumed opium orally. There was asignificant difference regarding Apgar score (9.76 ± 2.11 versus. 7.11 ± 4.21; p = 0.02) and the neonate's blood lead level (2.33 ± 1.3 µg/dl versus 7.33 ± 5.9 µg/dl) between the control and OUD groups (p < 0.001). The odds ratio of abnormally elevated blood lead level rose with increasing duration of maternal opiate disorder for opiate usage durations of 3to 5years (adjusted odds ratio [OR] 42.82, 95% confidence interval [CI] 3.27-561, p = 0.004) and > 5years (adjusted OR 45.5, 95% CI 2.97-698, p = 0.006). The results of this study suggested asignificant relationship between maternal opium consumption during pregnancy and neonatal serum lead levels, as well as decreased neonatal Apgar score.

The relationship between Vitamin A and Vitamin E levels and neonatal morbidities.

In the neonatal period, diseases such as respiratory distress syndrome, necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, patent ductus arteriosus hypoxic-ischemic encephalopathy, and hyperbilirubinemia are frequently seen, despite being differently affected by the gestational age. This study aims to examine the relationship between morbidities in the neonatal period and serum vitamin A and vitamin E levels. In this prospective cohort study, patients who were treated and followed up in the Neonatal Intensive Care Unit between August 2020 and September 2021 were evaluated. 381 patients, 202 male (53%) and 179 female (47%), were included in the study. The mean birth weight was 2642.13±835.91 g (minimum 480 g, maximum 4285 g) and the mean gestational week was 35.3±3.8 (minimum 24 weeks, maximum 42 weeks). The weight of 332 patients (87.2%) was above 1500 g in whom there was a significant increase in respiratory distress, hypoxic-ischemic encephalopathy, and hyperbilirubinemia correlated with a decrease in the vitamin E levels (p=0.001, 0.02, and 0.001, respectively). In infants over 32 weeks of age, there was a significant increase in respiratory distress, hypoxic-ischemic encephalopathy, and hyperbilirubinemia correlated with a decrease in the vitamin E levels (p=0.001, 0.02, and 0.001, respectively). No significant relationship was found between vitamin A levels and neonatal morbidities regardless of the birth weight or gestational age. We believe that our study may provide convenience to pediatricians and neonatologists in terms of the relationship between vitamin A and E levels and neonatal morbidities in neonates.

The Effect of Gestational Age at BNT162b2 mRNA Vaccination on Maternal and Neonatal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Levels.

BackgroundCOVID-19 during pregnancy and early infancy can result in severe disease. Evaluating the effect of gestational age at the time of SARS-CoV-2 vaccination on maternal antibody levels and transplacental antibody transfer has important implications for maternal care and vaccination strategies.MethodsMaternal and cord blood sera were collected from mother/newborn dyads (n=402), following term delivery after antenatal two-dose SARS-CoV-2 BNT162b2 mRNA vaccination. SARS-CoV-2 spike protein (S) and receptor binding domain (RBD)-specific IgG levels were evaluated in the samples collected.ResultsMedian anti-S and anti-RBD-specific IgG levels in maternal sera at the time of delivery were lowest following 1 st trimester vaccination (n=90) (anti-S IgG: 76 AU/mL, anti-RBD-specific IgG: 478 AU/mL), intermediate in those vaccinated in the 2 nd trimester (n=124) (anti-S IgG: 126 AU/mL, anti-RBD-specific IgG: 1263 AU/mL), and highest after 3 rd trimester vaccination (n=188) (anti-S IgG: 240 AU/mL, anti-RBD-specific IgG: 5855 AU/mL). Antibody levels in neonatal sera followed a similar pattern and were lowest following antenatal vaccination in the 1 st trimester (anti-S IgG: 126 AU/mL, anti-RBD-specific IgG: 1140 AU/mL). In a subgroup of parturients vaccinated in the 1 st trimester (n=30), a third booster dose was associated with significantly higher maternal and neonatal antibody levels.ConclusionsThese results suggest a considerable antibody waning throughout pregnancy in those vaccinated at early gestation. The observed boosting effect of a third vaccine dose, hints to its potential benefit in those who completed the two-dose vaccine series at early pregnancy or prior to conception. The impact of antenatal immunization timing on SARS-CoV-2 transplacental antibody transfer may influence neonatal seroprotection.

Serum Vitamin A Levels as a Novel Predictor for Respiratory Distress Syndrome in Neonates: Is It Beneficial?

Neonatal Respiratory Distress Syndrome (RDS) is a dangerous disease in neonates and is accompanied by neonatal complications and death. The aim of this study was the early determination of neonatal serum vitamin A levels as a possible novel predictor for neonatal RDS. A case-control study with the identification number TCTR20210206001, was performed on 100 neonates who were admitted to the Neonatal Intensive Care Unit (NICU) of Tanta University Hospital (TUH) suffering from RDS (patient group) and 100 healthy neonates (control group). Estimation of serum vitamin A (retinol) was made for all neonates of this study within the first four hours after birth before any nutrition or therapies. The results showed no significant difference between serums retinol (RT) levels in grade 1 & 2 RDS neonates (patient group) and the serum RT levels in the control group, while there was a significant difference between serums retinol levels in grade 3 & 4 RDS neonates (patient group) and the serum retinol levels in the control group where the P-value was 0.006 and 0.002 respectively. Serum vitamin A levels in neonates were found to be decreased in RDS neonates and could be used as a predictor for the development and severity of RDS. It is recommended to carry out routine estimation of serum vitamin A levels in neonates as a novel predictor for neonatal RDS.

Is a Little Enough? Paucity of Immune Proteins in Serum of Precocial Neonates of a Marine Carnivoran—the Atlantic Grey Seal

Mammalian mothers usually provide their offspring with large quantities of immunoglobulins (antibodies) for circulation in blood, either trans-placentally before birth, via colostrum briefly thereafter, or, less commonly, from milk. Neonates of true, phocid seals, however, are peculiarly impoverished in serum immunoglobulins, the levels of which slowly increase but do not reach adult levels by the time of weaning. We investigated whether grey seal (Halichoerus grypus) neonates compensate through an elevation or rapid maturation in levels of serum innate immune factors, namely acute phase and complement proteins. Instead, their sera contained remarkably low levels of acute phase proteins (including C-reactive protein, haptoglobin, hemopexin, ceruloplasmin, orosomucoid), compared to their mothers, that barely increased to adult levels by weaning. For complement, there was a strong demarcation between the early activation and amplification cascade components (present at normal adult levels in pups) and the late lytic membrane attack complex and regulatory proteins (consistently at low relative levels). Phocid neonates therefore differ dramatically from land Carnivorans, such as dogs and cats, in early life immune protection. That neonatal phocids survive this apparent vulnerability to infections between birth and weaning prompts questions as to what other mechanisms protect them, and the adaptive value of their seeming vulnerability.

Maternal oral supplementation with citrulline increases plasma citrulline but not arginine in pregnant Merino ewes and neonatal lambs

Context Arginine supplementation can counter the negative effects of fetal growth restriction in ewes bearing multiple lambs by increasing birth weight and brown adipose fat stores in lambs; however ruminal degradation limits its bioavailability and necessitates ruminal protection. The arginine precursor citrulline increases circulating arginine after a single oral dose without ruminal protection, and bolus intravenous infusion of citrulline increases maternal and fetal circulating arginine for at least 4 h post infusion. Responses to oral and chronic citrulline have not, however, been evaluated in neonatal lambs. Aims This experiment sought to determine whether orally fed citrulline would increase circulating plasma concentrations of citrulline and arginine in pregnant Merino ewes. Methods Pregnant Merino ewes were fed citrulline (CIT, 8 g/day, n = 9) or no supplement (CON, n = 9) from Day 125 of gestation (DG 125) until parturition. Ewe (DG 125) and neonatal lamb serum (&lt;2 h old) was analysed for circulating plasma citrulline and arginine concentrations. Key results Circulating concentrations of citrulline were higher in CIT than CON ewes 4 h post feeding at DG 125, and in CIT compared to CON neonatal lambs. Despite higher citrulline concentrations, supplementation did not increase maternal or neonatal circulating arginine concentrations. Conclusions Maternal supplementation with this dose of citrulline was not effective in increasing circulating levels of arginine. Implications Further studies may be merited in pregnant sheep to determine whether higher doses of oral citrulline can increase arginine availability during gestation.

Reference Intervals of Serum TSH from Mixed Distributions Using Truncation Points and the Kolmogorov-Smirnov Distance.

Serum TSH reference intervals (RIs) are methodology, population, and age specific. However, the ethical and practical challenges restrict the establishment of pediatric RIs using conventional approaches and advocates the use of indirect data mining-based algorithms. This study was carried out to estimate the reference interval of neonatal serum TSH in Pakistani population using an indirect approach. A data mining of serum TSH results of neonates (≤ 1 month of age) from 2013 - 2018 was done. Two subgroups on the basis of age from birth to 5 days and 6 - 30 days were assessed. The German study group's pre-validated indirect algorithm 'KOSMIC' was utilized for the statistical analysis. A total of non-duplicate 82,299 neonatal serum TSH tests were retrieved over a period of 6 years, including 88% (n = 70,788) aged 0 - 5 days and 12% (n = 11,511) ranging from 6 days to 1 month. The estimated RIs for the first age partition was 0.7 (90% CI 0.6 - 0.8) to 15.5 (90% CI 12.9 - 16.2) and for the second group 0.7 (90% CI 0.5 - 0.9) to 7.8 (90% CI 6.1 - 9.9) µIU/mL. This study revealed age related trends in serum TSH. The study advocates the need for population specific RIs owing to the significant variations noted on comparison with previously published literature. Precise RIs become vital particularly when serum TSH is undertaken as a confirmatory test for presumptive positive results on newborn screening for congenital hypothyroidism.

Prevalence of vitamin A and vitamin D deficiency in hospitalized neonates in Xi'an, China.

To investigate the prevalence of vitamin A and vitamin D deficiency and the associated factors in hospitalized neonates in Xi'an, China. A total of 524 hospitalized neonates were collected in this study. Serum vitamin A and D concentrations were detected in neonates within two weeks of birth. Serum vitamin A and D concentrations of hospitalized neonates were 0.55±0.21 μmol/L and 42.0±20.6 nmol/L, respectively. They were greater in full-term neonates than in preterm neonates, greater in rural neonates than in urban, and greater in single than in twin (all p<0.001). The prevalence of vitamin A and D deficiency were 14.9% and 33.0%, the prevalence of marginal vitamin A deficiency was 64.7%, and vitamin D insufficiency was 35.1%. Neonatal serum vitamin A and D concentrations were all positively correlated with birth weight and gestational age. Neonatal serum vitamin D concentration was also positively correlated with maternal serum vitamin D concentration. Additionally, neonatal vitamin A concentration was positively correlated with neonatal serum vitamin D concentration. Vitamin A and vitamin D statuses are compromised in hospitalized neonates in Xi'an, especially in premature neonates, low birth weight neonates, twins, and those born in urban areas. Individualized supplementation with vitamin A and vitamin D in neonates should be a clinical consideration.

Association Between Maternal and Neonatal Serum Vitamin D Levels and the Incidence of Early-Onset Sepsis

Background: Early-onset neonatal sepsis (EOS) is a systemic infection that occurs within the first week of life. Objectives: This study investigated the association of serum vitamin D levels in pregnant women and their neonates with the prevalence of EOS. Methods: This case-control study was performed among 50 term/late pre-term neonates admitted to our NICU due to EOS, alongside 50 healthy neonates matched for gestational age range and sex. Maternal and neonatal serum vitamin D levels were measured. The criteria for diagnosing EOS included any/combination of: respiratory, cardiovascular, hemodynamic, neurological, gastrointestinal, body temperature, or metabolic signs. For sepsis cases, CBC, CRP, blood type, blood culture, chest X ray, and in some cases, and CSF analysis and culture were tested. Mothers’ clinical history was collected. Results: Each group included 30 (60%) male and 20 (40%) female neonates. Birth weight averages were 2772 ± 667 and 3215 ± 349 grams in the case and control groups, respectively (P &lt; 0.001). The mean serum vitamin D levels were 49.75 ± 25.53 and 56.41 ± 18.17 nmol/L in the case and control groups, respectively. The control group mothers had a significantly higher vitamin D level (68.24 nmol/L versus 55.01 in mothers of sepsis cases, p = 0.005) and showed a correlation with the vitamin D levels of their neonates (R = 0.731, P &lt; 0.001), while the data failed to show a correlation between vitamin D level in mothers and their neonates in the sepsis group (R = 0.241, P = 0.115). C-section delivery was more prevalent among the sepsis cases (P &lt; 0.001). Conclusions: Early-onset neonatal sepsis is associated with vitamin D deficiency in neonates and their mothers, low birth weight, and being delivered by C-section.

Bacterial DNA detection in very preterm infants assessed for risk of early onset sepsis

The aim of this study is to evaluate the diagnostic ability of multiplex real-time polymerase chain reaction (PCR) in very preterm infants assessed for risk of early onset neonatal sepsis (EOS). Prospective observational cohort study. Blood samples of preterm neonates≤32weeks of gestation were evaluated by commercial multiplex real-time PCR within 2h after delivery. The definition of EOS was based on positive blood culture and clinical signs of infection or negative blood culture, clinical signs of infection and abnormal neonatal blood count and serum biomarkers. Among 82 subjects analyzed in the study, 15 had clinical or confirmed EOS. PCR was positive in four of these infants (including the only one with a positive blood culture), as well as in 15 of the 67 infants without sepsis (sensitivity 27%, specificity 78%). Out of 19 PCR positive subjects, Escherichia coli was detected in 12 infants (63%). Statistically significant association was found between vaginal E.coli colonization of the mother and E.coli PCR positivity of the neonate (p=0.001). No relationship was found between neonatal E.coli swab results and assessment findings of bacterial DNA in neonatal blood stream. Multiplex real-time PCR had insufficient diagnostic capability for EOS in high risk very preterm infants. The study revealed no significant association between PCR results and the diagnosis of clinical EOS. Correlation between maternal vaginal swab results and positive PCR in the newborn needs further investigation to fully understand the role of bacterial DNA analysis in preterm infants.