Associations between low Apgar scores and mortality by race in the United States: A cohort study of 6,809,653 infants

BackgroundApgar scores measure newborn health and are strongly associated with infant outcomes, but their performance has largely been determined in primarily white populations. Given the majority of the global population is not white, we aim to assess whether the association between low Apgar score and mortality in infants varies across racial groups.Methods and findingsPopulation-based cohort study using 2016 to 2017 United States National Vital Statistics System data. The study included singleton infants born between 37⁺⁰ and 44⁺⁶ weeks to mothers over 15 years, without congenital abnormalities. We looked at 3 different mortality outcomes: (1) early neonatal mortality; (2) overall neonatal mortality; and (3) infant mortality. We used logistic regression to assess the association between Apgar score (categorized as low, intermediate, and normal) and each mortality outcome, and adjusted for gestational age, sex, maternal BMI, education, age, previous number of live births, and smoking status, and stratified these models by maternal race group (as self-reported on birth certificates). The cohort consisted of 6,809,653 infants (52.8% non-Hispanic white, 23.7% Hispanic, 13.8% non-Hispanic black, 6.6% non-Hispanic Asian, and 3.1% non-Hispanic other). A total of 6,728,829 (98.8%) infants had normal scores, 63,467 (0.9%) had intermediate scores, and 17,357 (0.3%) had low Apgar scores. Compared to infants with normal scores, low-scoring infants had increased odds of infant mortality. There was strong evidence that this association varied by race (p < 0.001) with adjusted odds ratios (AORs) of 54.4 (95% confidence interval [CI] 49.9 to 59.4) in non-Hispanic white, 70.02 (95% CI 60.8 to 80.7) in Hispanic, 23.3 (95% CI 20.3 to 26.8) in non-Hispanic black, 100.4 (95% CI 74.5 to 135.4) in non-Hispanic Asian, and 26.8 (95% CI 19.8 to 36.3) in non-Hispanic other infants. The main limitation was missing data for some variables, due to using routinely collected data.ConclusionsThe association between Apgar scores and mortality varies across racial groups. Low Apgar scores are associated with mortality across racial groups captured by United States (US) records, but are worse at discriminating infants at risk of mortality for black and non-Hispanic non-Asian infants than for white infants. Apgar scores are useful clinical indicators and epidemiological tools; caution is required regarding racial differences in their applicability.

Emma Gillette and co-authors assess the associations between low Apgar scores and mortality in infants by race in the United States.     

Pharmacological profile of a novel carbacyclin derivative with high metabolic stability and oral activity in the rat

A novel carbacyclin derivative (16S)-13,14-dehydro-16,20-dimethyl-3-oxa-18,18,19,19-tetradehydro- 6a- carbaprostaglandin-I2 (3-oxa-analogue) has been synthesized in order to find chemically and metabolically stable prostacyclin-mimetics with a potency equal or even superior to PGI2. The 3-oxa-analogue was found to be stabilized against beta-oxidation, a main metabolic degradation step also for chemically stable PGI2-analogues. The compound is orally available and displays a long duration of 4.5-48 h of antiaggregatory and hypotensive action. The 3-oxa-analogue inhibits ADP-induced platelet aggregation with an IC50 of 3.0 nM. Following intravenous application the 3-oxa-analogue lowers diastolic blood pressure in a dose dependent manner, the ED20 being 0.1-0.2 micrograms/kg after injection and less than or equal to 0.05 micrograms/kg/min after infusion respectively. In vivo platelet aggregation is inhibited after i.v. infusion of the 3-oxa-analogue with an IC50 of 0.037 micrograms/kg/min. As compared to Iloprost, the 3-oxa-analogue is 5-12 fold more potent with respect to in vivo hypotensive and anti-aggregatory effects. The results of the present studies indicate that the 3-oxa-analogue has a pharmacological profile comparable to prostacyclin (PGI2) and Iloprost. Due to the fact that the 3-oxa-analogue is chemically and metabolically stable, long term oral treatment can be achieved in clinical conditions in which PGI2 and Iloprost have already been shown to be therapeutically useful principles.     

Specific transport of S-nitrosocysteine in human red blood cells: Implications for formation of S-nitrosothiols and transport of NO bioactivity within the vasculature

The transport of various S-nitrosothiols, NO and NO donors in human red blood cells (RBC) and the formation of erythrocytic S-nitrosoglutathione were investigated. Of the NO species tested only S-nitrosocysteine was found to form S-nitrosoglutathione in the RBC cytosol. L-Serine, L-cysteine and L-lysine inhibited formation of S-nitrosoglutathione. Incubation of RBC pre-incubated with S-[15N]nitroso-L-cysteine with native plasma or platelet-rich plasma led to formation of S-[15N]nitrosoalbumin and inhibited platelet aggregation, respectively. The specific transporter system of S-nitroso-L-cysteine in the RBC membrane may have implications for formation of S-nitrosoalbumin and S-nitrosohemoglobin and for transport of NO bioactivity within the vasculature.     

The Duisburg birth cohort study: influence of the prenatal exposure to PCDD/Fs and dioxin-like PCBs on thyroid hormone status in newborns and neurodevelopment of infants until the age of 24 months

Prenatal exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) can affect neurobehavioral development of infants and children. This effect may be mediated through disruption of thyroid hormone homeostasis. However, epidemiological studies reveal no consistent influence of PCDD/Fs and PCBs on thyroid status and neurodevelopment at environmental background levels. The effects may resolve with time of further decreasing exposure to these compounds. The aim of this study was to find out if there are still effects related to prenatal PCDD/F and PCB observable at the meanwhile decreased levels of exposure by using the same methods which have been applied in similar studies during the last 10 years in Europe. The birth cohort study was initiated in the year 2000 in the industrialized city of Duisburg, Germany. 232 healthy mother-infant pairs were recruited between 2000 and 2002. Dioxins, dioxin-like PCBs and six indicator PCBs were analyzed in maternal blood during pregnancy and in maternal milk following extraction and sample clean-up by HRGC/HRMS. Thyroid stimulating hormone (TSH), total thyroxine (T4), total triiodothyronine (T3), free thyroxine (FT4) and free triiodothyronine (FT3) were measured in serum samples of the pregnant women and in cord serum samples by chemiluminescent immunometric assay. Neurological examinations were performed at ages 2 weeks and 18 months using the neurological optimality score (NOS), mental and motor development were assessed using the Bayley Scales of Infant Development (BSID) at ages 12 and 24 months. Multiple linear regression analysis was used to describe the association of PCDD/F and PCB in maternal blood or milk with the outcome measurements after adjustment for confounding. Blood levels (n=182) of WHO 2005 toxic equivalents (TEQ) (PCDD/F+PCB) were in the range of 3.8-58.4 pg/glipid base (median: 19.3 pg/glipid base). The corresponding data for human milk (n=149) were 2.6-52.4 pg/glipid base (median: 19.7 pg/glipid base). Multiple regression analysis showed no decrease of thyroid hormones related to WHO 2005 TEQ in blood and milk of mothers and their newborns. Furthermore, no associations between exposure and neurological and developmental measures were observed. This study supports the view that the current decreased exposure to PCDD/Fs and PCBs does not impair thyroid function of newborns and neurodevelopment of infants until the age of 24 months.     

Modulated receptor interactions in bacterial transmembrane signaling

Bacteria can detect and respond to a remarkably diverse set of environmental conditions. This ability enables motile species to integrate stimuli, to compare current surroundings with those of the recent past, and to adjust swimming behavior to move up gradients of attractants and avoid repellents. Many of the molecular details involved in the bacterial chemotaxis system have been elucidated. Several models have been proposed recently to explain how cells process external information through a patch of highly interactive transmembrane receptors and transduce this information to other components in the cytoplasm that, in turn, function to regulate motility.     

The Biophysical Properties of Basal Lamina Gels Depend on the Biochemical Composition of the Gel

The migration of cells within a three-dimensional extracellular matrix (ECM) depends sensitively on the biochemical and biophysical properties of the matrix. An example for a biological ECM is given by reconstituted basal lamina gels purified from the Engelbreth-Holm-Swarm sarcoma of mice. Here, we compare four different commercial variants of this ECM, which have all been purified according to the same protocol. Nevertheless, in those gels, we detect strong differences in the migration behavior of leukocyte cells as well as in the Brownian motion of nanoparticles. We show that these differences correlate with the mechanical properties and the microarchitecture of the gels which in turn arise from small variations in their biochemical composition.     

Dissimilarity in the reductive unfolding pathways of two ribonuclease homologues

Using DTT(red) as the reducing agent, the kinetics of the reductive unfolding of onconase, a frog ribonuclease, has been examined. An intermediate containing three disulfides, Ir, that is formed rapidly in the reductive pathway, is more resistant to further reduction than the parent molecule, indicating that the remaining disulfides in onconase are less accessible to DTT(red). Disulfide-bond mapping of Ir indicated that it is a single species lacking the (30-75) disulfide bond. The reductive unfolding pattern of onconase is consistent with an analysis of the exposed surface area of the cysteine sulfur atoms in the (30-75) disulfide bond, which reveals that these atoms are about four- and sevenfold, respectively, more exposed than those in the next two maximally exposed disulfides. By contrast, in the reductive unfolding of the homologue, RNase A, there are two intermediates, arising from the reduction of the (40-95) and (65-72) disulfide bonds, which takes place in parallel, and on a much longer time-scale, compared to the initial reduction of onconase; this behavior is consistent with the almost equally exposed surface areas of the cysteine sulfur atoms that form the (40-95) and (65-72) disulfide bonds in RNase A and the fourfold more exposed cysteine sulfur atoms of the (30-75) disulfide bond in onconase. Analysis and in silico mutation of the residues around the (40-95) disulfide bond in RNase A, which is analogous to the (30-75) disulfide bond of onconase, reveal that the side-chain of tyrosine 92 of RNase A, a highly conserved residue among mammalian pancreatic ribonucleases, lies atop the (40-95) disulfide bond, resulting in a shielding of the corresponding sulfur atoms from the solvent; such burial of the (30-75) sulfur atoms is absent from onconase, due to the replacement of Tyr92 by Arg73, which is situated away from the (30-75) disulfide bond and into the solvent, resulting in the large exposed surface-area of the cysteine sulfur atoms forming this bond. Removal of Tyr92 from RNase A resulted in the relatively rapid reduction of the mutant to form a single intermediate (des [40-95] Y92A), i.e. it resulted in an onconase-like reductive unfolding behavior. The reduction of the P93A mutant of RNase A proceeds through a single intermediate, the des [40-95] P93A species, as in onconase. Although mutation of Pro93 to Ala does not increase the exposed surface area of the (40-95) cysteine sulfur atoms, structural analysis of the mutant reveals that there is greater flexibility in the (40-95) disulfide bond compared to the (65-72) disulfide bond that may make the (40-95) disulfide bond much easier to expose, consistent with the reductive unfolding pathway and kinetics of P93A. Mutation of Tyr92 to Phe92 in RNase A has no effect on its reductive unfolding pathway, suggesting that the hydrogen bond between the hydroxyl group of Tyr92 and the carbonyl group of Lys37 has no impact on the local unfolding free energy required to expose the (40-95) disulfide bond. Thus, these data shed light on the differences between the reductive unfolding pathways of the two homologous proteins and provide a structural basis for the origin of this difference.     

Fine-scale genetic pattern and evidence for sex-biased dispersal in the túngara frog, Physalaemus pustulosus

Túngara frogs (Physalaemus pustulosus) are a model system for sexual selection and communication. Population dynamics and gene flow are of major interest in this species because they influence speciation processes and microevolution, and could consequently provide a deeper understanding of the evolutionary processes involved in mate recognition. Although earlier studies have documented genetic variation across the species' range, attempts to investigate dispersal on a local level have been limited to mark-recapture studies. These behavioural studies indicated high mobility at a scale of several hundred metres. In this study we used seven highly polymorphic microsatellite loci to investigate fine-scaled genetic variation in the túngara frog. We analysed the influence of geographical distance on observed genetic patterns, examined the influence of a river on gene flow, and tested for sex-biased dispersal. Data for 668 individuals from 17 populations ranging in distance from 0.26 to 11.8 km revealed significant levels of genetic differentiation among populations. Genetic differentiation was significantly correlated with geographic distance. A river acted as an efficient barrier to gene flow. Several tests of sex-biased dispersal were conducted. Most of them showed no difference between the sexes, but variance of Assignment Indices exhibited a statistically significant male bias in dispersal.