Infant gut strain persistence is associated with maternal origin, phylogeny, and traits including surface adhesion and iron acquisition.

Gut microbiome succession affects infant development. However, it remains unclear what factors promote persistence of initial bacterial colonizers in the developing gut. Here, we perform strain-resolved analyses to compare gut colonization of preterm and full-term infants throughout the first year of life and evaluate associations between strain persistence and strain origin as well as genetic potential. Analysis of fecal metagenomes collected from 13 full-term and 9 preterm infants reveals that infants' initially distinct microbiomes converge by age 1 year. Approximately 11% of early colonizers, primarily Bacteroides and Bifidobacterium, persist during the first year of life, and those are more prevalent in full-term, compared with preterm infants. Examination of 17 mother-infant pairs reveals maternal gut strains are significantly more likely to persist in the infant gut than other strains. Enrichment in genes for surface adhesion, iron acquisition, and carbohydrate degradation may explain persistence of some strains through the first year of life.

Genetic and behavioral adaptation of Candida parapsilosis to the microbiome of hospitalized infants revealed by in situ genomics, transcriptomics, and proteomics.

BACKGROUND: Candida parapsilosis is a common cause of invasive candidiasis, especially in newborn infants, and infections have been increasing over the past two decades. C. parapsilosis has been primarily studied in pure culture, leaving gaps in understanding of its function in a microbiome context. RESULTS: Here, we compare five unique C. parapsilosis genomes assembled from premature infant fecal samples, three of which are newly reconstructed, and analyze their genome structure, population diversity, and in situ activity relative to reference strains in pure culture. All five genomes contain hotspots of single nucleotide variants, some of which are shared by strains from multiple hospitals. A subset of environmental and hospital-derived genomes share variants within these hotspots suggesting derivation of that region from a common ancestor. Four of the newly reconstructed C. parapsilosis genomes have 4 to 16 copies of the gene RTA3, which encodes a lipid translocase and is implicated in antifungal resistance, potentially indicating adaptation to hospital antifungal use. Time course metatranscriptomics and metaproteomics on fecal samples from a premature infant with a C. parapsilosis blood infection revealed highly variable in situ expression patterns that are distinct from those of similar strains in pure cultures. For example, biofilm formation genes were relatively less expressed in situ, whereas genes linked to oxygen utilization were more highly expressed, indicative of growth in a relatively aerobic environment. In gut microbiome samples, C. parapsilosis co-existed with Enterococcus faecalis that shifted in relative abundance over time, accompanied by changes in bacterial and fungal gene expression and proteome composition. CONCLUSIONS: The results reveal potentially medically relevant differences in Candida function in gut vs. laboratory environments, and constrain evolutionary processes that could contribute to hospital strain persistence and transfer into premature infant microbiomes. Video abstract.

Combined analysis of microbial metagenomic and metatranscriptomic sequencing data to assess in situ physiological conditions in the premature infant gut.

Microbes alter their transcriptomic profiles in response to the environment. The physiological conditions experienced by a microbial community can thus be inferred using meta-transcriptomic sequencing by comparing transcription levels of specifically chosen genes. However, this analysis requires accurate reference genomes to identify the specific genes from which RNA reads originate. In addition, such an analysis should avoid biases in transcript counts related to differences in organism abundance. In this study we describe an approach to address these difficulties. Sample-specific meta-genomic assembled genomes (MAGs) were used as reference genomes to accurately identify the origin of RNA reads, and transcript ratios of genes with opposite transcription responses were compared to eliminate biases related to differences in organismal abundance, an approach hereafter named the "diametric ratio" method. We used this approach to probe the environmental conditions experienced by Escherichia spp. in the gut of 4 premature infants, 2 of whom developed necrotizing enterocolitis (NEC), a severe inflammatory intestinal disease. We analyzed twenty fecal samples taken from four premature infants (4-6 time points from each infant), and found significantly higher diametric ratios of genes associated with low oxygen levels in samples of infants later diagnosed with NEC than in samples without NEC. We also show this method can be used for examining other physiological conditions, such as exposure to nitric oxide and osmotic pressure. These study results should be treated with caution, due to the presence of confounding factors that might also distinguish between NEC and control infants. Nevertheless, together with benchmarking analyses, we show here that the diametric ratio approach can be applied for evaluating the physiological conditions experienced by microbes in situ. Results from similar studies can be further applied for designing diagnostic methods to detect NEC in its early developmental stages.

Necrotizing enterocolitis is preceded by increased gut bacterial replication, Klebsiella, and fimbriae-encoding bacteria.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease that occurs primarily in premature infants. We performed genome-resolved metagenomic analysis of 1163 fecal samples from premature infants to identify microbial features predictive of NEC. Features considered include genes, bacterial strain types, eukaryotes, bacteriophages, plasmids, and growth rates. A machine learning classifier found that samples collected before NEC diagnosis harbored significantly more Klebsiella, bacteria encoding fimbriae, and bacteria encoding secondary metabolite gene clusters related to quorum sensing and bacteriocin production. Notably, replication rates of all bacteria, especially Enterobacteriaceae, were significantly higher 2 days before NEC diagnosis. The findings uncover biomarkers that could lead to early detection of NEC and targets for microbiome-based therapeutics.

Maternal IgA protects against the development of necrotizing enterocolitis in preterm infants.

Neonates are protected from colonizing bacteria by antibodies secreted into maternal milk. Necrotizing enterocolitis (NEC) is a disease of neonatal preterm infants with high morbidity and mortality that is associated with intestinal inflammation driven by the microbiota1-3. The incidence of NEC is substantially lower in infants fed with maternal milk, although the mechanisms that underlie this benefit are not clear4-6. Here we show that maternal immunoglobulin A (IgA) is an important factor for protection against NEC. Analysis of IgA binding to fecal bacteria from preterm infants indicated that maternal milk was the predominant source of IgA in the first month of life and that a relative decrease in IgA-bound bacteria is associated with the development of NEC. Sequencing of IgA-bound and unbound bacteria revealed that before the onset of disease, NEC was associated with increasing domination by Enterobacteriaceae in the IgA-unbound fraction of the microbiota. Furthermore, we confirmed that IgA is critical for preventing NEC in a mouse model, in which pups that are reared by IgA-deficient mothers are susceptible to disease despite exposure to maternal milk. Our findings show that maternal IgA shapes the host-microbiota relationship of preterm neonates and that IgA in maternal milk is a critical and necessary factor for the prevention of NEC.

Genome-resolved metagenomics of eukaryotic populations during early colonization of premature infants and in hospital rooms.

BACKGROUND: Fungal infections are a significant cause of mortality and morbidity in hospitalized preterm infants, yet little is known about eukaryotic colonization of infants and of the neonatal intensive care unit as a possible source of colonizing strains. This is partly because microbiome studies often utilize bacterial 16S rRNA marker gene sequencing, a technique that is blind to eukaryotic organisms. Knowledge gaps exist regarding the phylogeny and microdiversity of eukaryotes that colonize hospitalized infants, as well as potential reservoirs of eukaryotes in the hospital room built environment. RESULTS: Genome-resolved analysis of 1174 time-series fecal metagenomes from 161 premature infants revealed fungal colonization of 10 infants. Relative abundance levels reached as high as 97% and were significantly higher in the first weeks of life (p = 0.004). When fungal colonization occurred, multiple species were present more often than expected by random chance (p = 0.008). Twenty-four metagenomic samples were analyzed from hospital rooms of six different infants. Compared to floor and surface samples, hospital sinks hosted diverse and highly variable communities containing genomically novel species, including from Diptera (fly) and Rhabditida (worm) for which genomes were assembled. With the exception of Diptera and two other organisms, zygosity of the newly assembled diploid eukaryote genomes was low. Interestingly, Malassezia and Candida species were present in both room and infant gut samples. CONCLUSIONS: Increased levels of fungal co-colonization may reflect synergistic interactions or differences in infant susceptibility to fungal colonization. Discovery of eukaryotic organisms that have not been sequenced previously highlights the benefit of genome-resolved analyses, and low zygosity of assembled genomes could reflect inbreeding or strong selection imposed by room conditions.

The developing premature infant gut microbiome is a major factor shaping the microbiome of neonatal intensive care unit rooms.

BACKGROUND: The neonatal intensive care unit (NICU) contains a unique cohort of patients with underdeveloped immune systems and nascent microbiome communities. Patients often spend several months in the same room, and it has been previously shown that the gut microbiomes of these infants often resemble the microbes found in the NICU. Little is known, however, about the identity, persistence, and absolute abundance of NICU room-associated bacteria over long stretches of time. Here, we couple droplet digital PCR (ddPCR), 16S rRNA gene surveys, and recently published metagenomics data from infant gut samples to infer the extent to which the NICU microbiome is shaped by its room occupants. RESULTS: Over 2832 swabs, wipes, and air samples were collected from 16 private-style NICU rooms housing very low birth weight (< 1500 g), premature (< 31 weeks' gestation) infants. For each infant, room samples were collected daily, Monday through Friday, for 1 month. The first samples from the first infant and the last samples from the last infant were collected 383 days apart. Twenty-two NICU locations spanning room surfaces, hands, electronics, sink basins, and air were collected. Results point to an incredibly simple room community where 5-10 taxa, mostly skin-associated, account for over 50% of the amplicon reads. Biomass estimates reveal four to five orders of magnitude difference between the least to the most dense microbial communities, air, and sink basins, respectively. Biomass trends from bioaerosol samples and petri dish dust collectors suggest occupancy to be a main driver of suspended biological particles within the NICU. Using a machine learning algorithm to classify the origin of room samples, we show that each room has a unique microbial fingerprint. Several important taxa driving this model were dominant gut colonizers of infants housed within each room. CONCLUSIONS: Despite regular cleaning of hospital surfaces, bacterial biomass was detectable at varying densities. A room-specific microbiome signature was detected, suggesting microbes seeding NICU surfaces are sourced from reservoirs within the room and that these reservoirs contain actively dividing cells. Collectively, the data suggests that hospitalized infants, in combination with their caregivers, shape the microbiome of NICU rooms.

Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles.

During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context.IMPORTANCE Humans are colonized by microbes at birth, a process that is important to health and development. However, much remains to be known about the fine-scale microbial dynamics that occur during the colonization period. We conducted a genome-resolved study of microbial community composition, replication rates, and proteomes during the first 3 months of life of both healthy and sick premature infants. Infants were found to be colonized by similar microbes, but each underwent a distinct colonization trajectory. Interestingly, related microbes colonizing different infants were found to have distinct proteomes, indicating that microbiome function is not only driven by which organisms are present, but also largely depends on microbial responses to the unique set of physiological conditions in the infant gut.

Randomized Clinical Trial of Standard- Versus High-Calorie Formula for Methadone-Exposed Infants: A Feasibility Study.

BACKGROUND: Newborns who are prenatally exposed to methadone are at risk for neonatal abstinence syndrome and the associated excess weight loss and poor weight gain. This pilot feasibility study aimed to evaluate early caloric enhancement on weight patterns among infants born to women receiving methadone maintenance therapy while pregnant. METHODS: In this double-blind pilot feasibility study, we randomly assigned infants with fetal methadone exposure to 24 or 20 kcal/oz formula from days 3 to 21. Randomization was stratified by any breastfeeding, sex of the infant, and gestational age. Eligible infants were ≥35 weeks' gestation and weighed ≥2200 g. Outcomes were days to weight nadir, maximum percent weight loss, days to birth weight, percentage weight change per day, and feasibility. RESULTS: A total of 49 infants were randomly assigned (22 to standard- and 27 to high-calorie formula); groups had comparable demographic characteristics. Main outcomes comparing standard- to high-calorie formula groups were not significant (days to weight nadir, 5.0 vs 4.4 days; P = .20; maximum percent weight loss, -9.4% vs -8.6%; P = .15; days to birth weight, 14.7 vs 13.6 days; P = .07); however, in longitudinal analyses (days 4 to 21), the high-calorie group had a higher percent weight gained per day compared with the standard-calorie group (P <.001). There were high levels of protocol adherence, and no adverse effects were observed. CONCLUSIONS: Study findings suggest that early initiation of high-calorie formula for infants with prenatal methadone exposure may be beneficial for weight gain; evaluation in a larger study is warranted.

Strain-resolved analysis of hospital rooms and infants reveals overlap between the human and room microbiome.

Preterm infants exhibit different microbiome colonization patterns relative to full-term infants, and it is speculated that the hospital room environment may contribute to infant microbiome development. Here, we present a genome-resolved metagenomic study of microbial genotypes from the gastrointestinal tracts of infants and from the neonatal intensive care unit (NICU) room environment. Some strains detected in hospitalized infants also occur in sinks and on surfaces, and belong to species such as Staphylococcus epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa, and Klebsiella pneumoniae, which are frequently implicated in nosocomial infection and preterm infant gut colonization. Of the 15 K. pneumoniae strains detected in the study, four were detected in both infant gut and room samples. Time series experiments showed that nearly all strains associated with infant gut colonization can be detected in the room after, and often before, detection in the gut. Thus, we conclude that a component of premature infant gut colonization is the cycle of microbial exchange between the room and the occupant.

Red blood cell transfusion in premature infants leads to worse necrotizing enterocolitis outcomes.

BACKGROUND: Necrotizing enterocolitis (NEC) is a severe intestinal disease of premature infants with high mortality. Studies suggest a causative relationship between red blood cell (RBC) transfusion and NEC; however, whether RBC transfusion leads to worse outcomes in NEC is unknown. We sought to determine whether RBC transfusion was associated with an increased risk of surgical NEC and mortality. METHODS: In this retrospective study, 115 patients were enrolled with NEC Bell's stage 2A or greater from 2010-2015. Patients were classified based on the timing of RBC transfusion before NEC: ≤72 h, >72 h, and no transfusion. Variables including gestational age (GA), birth weight (BW), feedings, and hematocrit levels were analyzed. Outcomes were surgical intervention for NEC following RBC transfusion and mortality. RESULTS: Twenty-three (20%) infants developed NEC ≤ 72 h after RBC transfusion, 16 (69.6%) required surgery with a mortality rate of 21.7% (n = 5). Seventeen (15%) infants developed NEC > 72 h after RBC transfusion, 12 (70.6%) required surgery with a mortality rate of 23.5% (n = 4). 75 (65%) patients developed NEC without RBC transfusion, 17 (22.7%) required surgery with a mortality rate of 4% (n = 3). Lower GA and BW were significantly associated with RBC transfusion and the need for surgical intervention. RBC transfusion ≤72 h before NEC was associated with surgical NEC (pairwise adjusted P < 0.001) and mortality (pairwise adjusted P = 0.048). However, multivariable logistic regression analysis revealed RBC transfusion is not an independent risk factor for surgical NEC. CONCLUSIONS: Infants of lower GA and BW were more likely to receive an RBC transfusion before NEC, which was significantly associated with surgical intervention and an increasing risk of mortality. Judicious use of transfusions in premature infants may improve NEC outcomes.

Identical bacterial populations colonize premature infant gut, skin, and oral microbiomes and exhibit different in situ growth rates.

The initial microbiome impacts the health and future development of premature infants. Methodological limitations have led to gaps in our understanding of the habitat range and subpopulation complexity of founding strains, as well as how different body sites support microbial growth. Here, we used metagenomics to reconstruct genomes of strains that colonized the skin, mouth, and gut of two hospitalized premature infants during the first month of life. Seven bacterial populations, considered to be identical given whole-genome average nucleotide identity of >99.9%, colonized multiple body sites, yet none were shared between infants. Gut-associated Citrobacter koseri genomes harbored 47 polymorphic sites that we used to define 10 subpopulations, one of which appeared in the gut after 1 wk but did not spread to other body sites. Differential genome coverage was used to measure bacterial population replication rates in situ. In all cases where the same bacterial population was detected in multiple body sites, replication rates were faster in mouth and skin compared to the gut. The ability of identical strains to colonize multiple body sites underscores the habit flexibility of initial colonists, whereas differences in microbial replication rates between body sites suggest differences in host control and/or resource availability. Population genomic analyses revealed microdiversity within bacterial populations, implying initial inoculation by multiple individual cells with distinct genotypes. Overall, however, the overlap of strains across body sites implies that the premature infant microbiome can exhibit very low microbial diversity.

Evidence for persistent and shared bacterial strains against a background of largely unique gut colonization in hospitalized premature infants.

The potentially critical stage of initial gut colonization in premature infants occurs in the hospital environment, where infants are exposed to a variety of hospital-associated bacteria. Because few studies of microbial communities are strain-resolved, we know little about the extent to which specific strains persist in the hospital environment and disperse among infants. To study this, we compared 304 near-complete genomes reconstructed from fecal samples of 21 infants hospitalized in the same intensive care unit in two cohorts, over 3 years apart. The genomes represent 159 distinct bacterial strains, only 14 of which occurred in multiple infants. Enterococcus faecalis and Staphylococcus epidermidis, common infant gut colonists, exhibit diversity comparable to that of reference strains, inline with introduction of strains from infant-specific sources rather than a hospital strain pool. Unlike other infants, a pair of sibling infants shared multiple strains, even after extensive antibiotic administration, suggesting overlapping strain-sources and/or genetic selection drive microbiota similarities. Interestingly, however, five strains were detected in infants hospitalized three years apart. Three of these were also detected in multiple infants in the same year. This finding of a few widely dispersed and persistent bacterial colonizers despite overall low potential for strain dispersal among infants has implications for understanding and directing healthy colonization.

Concentrations and Sources of Airborne Particles in a Neonatal Intensive Care Unit.

Premature infants in neonatal intensive care units (NICUs) have underdeveloped immune systems, making them susceptible to adverse health consequences from air pollutant exposure. Little is known about the sources of indoor airborne particles that contribute to the exposure of premature infants in the NICU environment. In this study, we monitored the spatial and temporal variations of airborne particulate matter concentrations along with other indoor environmental parameters and human occupancy. The experiments were conducted over one year in a private-style NICU. The NICU was served by a central heating, ventilation and air-conditioning (HVAC) system equipped with an economizer and a high-efficiency particle filtration system. The following parameters were measured continuously during weekdays with 1-min resolution: particles larger than 0.3 µm resolved into 6 size groups, CO2 level, dry-bulb temperature and relative humidity, and presence or absence of occupants. Altogether, over sixteen periods of a few weeks each, measurements were conducted in rooms occupied with premature infants. In parallel, a second monitoring station was operated in a nearby hallway or at the local nurses' station. The monitoring data suggest a strong link between indoor particle concentrations and human occupancy. Detected particle peaks from occupancy were clearly discernible among larger particles and imperceptible for submicron (0.3-1 µm) particles. The mean indoor particle mass concentrations averaged across the size range 0.3-10 µm during occupied periods was 1.9 µg/m(3), approximately 2.5 times the concentration during unoccupied periods (0.8 µg/m(3)). Contributions of within-room emissions to total PM10 mass in the baby rooms averaged 37-81%. Near-room indoor emissions and outdoor sources contributed 18-59% and 1-5%, respectively. Airborne particle levels in the size range 1-10 µm showed strong dependence on human activities, indicating the importance of indoor-generated particles for infant's exposure to airborne particulate matter in the NICU.

Gut bacteria are rarely shared by co-hospitalized premature infants, regardless of necrotizing enterocolitis development.

Premature infants are highly vulnerable to aberrant gastrointestinal tract colonization, a process that may lead to diseases like necrotizing enterocolitis. Thus, spread of potential pathogens among hospitalized infants is of great concern. Here, we reconstructed hundreds of high-quality genomes of microorganisms that colonized co-hospitalized premature infants, assessed their metabolic potential, and tracked them over time to evaluate bacterial strain dispersal among infants. We compared microbial communities in infants who did and did not develop necrotizing enterocolitis. Surprisingly, while potentially pathogenic bacteria of the same species colonized many infants, our genome-resolved analysis revealed that strains colonizing each baby were typically distinct. In particular, no strain was common to all infants who developed necrotizing enterocolitis. The paucity of shared gut colonizers suggests the existence of significant barriers to the spread of bacteria among infants. Importantly, we demonstrate that strain-resolved comprehensive community analysis can be accomplished on potentially medically relevant time scales.

Mucosa-associated bacterial diversity in necrotizing enterocolitis.

BACKGROUND: Previous studies of infant fecal samples have failed to clarify the role of gut bacteria in the pathogenesis of NEC. We sought to characterize bacterial communities within intestinal tissue resected from infants with and without NEC. METHODS: 26 intestinal samples were resected from 19 infants, including 16 NEC samples and 10 non-NEC samples. Bacterial 16S rRNA gene sequences were amplified and sequenced. Analysis allowed for taxonomic identification, and quantitative PCR was used to quantify the bacterial load within samples. RESULTS: NEC samples generally contained an increased total burden of bacteria. NEC and non-NEC sample sets were both marked by high inter-individual variability and an abundance of opportunistic pathogens. There was no statistically significant distinction between the composition of NEC and non-NEC microbial communities. K-means clustering enabled us to identify several stable clusters, including clusters of NEC and midgut volvulus samples enriched with Clostridium and Bacteroides. Another cluster containing both NEC and non-NEC samples was marked by an abundance of Enterobacteriaceae and decreased diversity among NEC samples. CONCLUSIONS: The results indicate that NEC is a disease without a uniform pattern of microbial colonization, but that NEC is associated with an abundance of strict anaerobes and a decrease in community diversity.

Microbes in the neonatal intensive care unit resemble those found in the gut of premature infants.

BACKGROUND: The source inoculum of gastrointestinal tract (GIT) microbes is largely influenced by delivery mode in full-term infants, but these influences may be decoupled in very low birth weight (VLBW, <1,500 g) neonates via conventional broad-spectrum antibiotic treatment. We hypothesize the built environment (BE), specifically room surfaces frequently touched by humans, is a predominant source of colonizing microbes in the gut of premature VLBW infants. Here, we present the first matched fecal-BE time series analysis of two preterm VLBW neonates housed in a neonatal intensive care unit (NICU) over the first month of life. RESULTS: Fresh fecal samples were collected every 3 days and metagenomes sequenced on an Illumina HiSeq2000 device. For each fecal sample, approximately 33 swabs were collected from each NICU room from 6 specified areas: sink, feeding and intubation tubing, hands of healthcare providers and parents, general surfaces, and nurse station electronics (keyboard, mouse, and cell phone). Swabs were processed using a recently developed 'expectation maximization iterative reconstruction of genes from the environment' (EMIRGE) amplicon pipeline in which full-length 16S rRNA amplicons were sheared and sequenced using an Illumina platform, and short reads reassembled into full-length genes. Over 24,000 full-length 16S rRNA sequences were produced, generating an average of approximately 12,000 operational taxonomic units (OTUs) (clustered at 97% nucleotide identity) per room-infant pair. Dominant gut taxa, including Staphylococcus epidermidis, Klebsiella pneumoniae, Bacteroides fragilis, and Escherichia coli, were widely distributed throughout the room environment with many gut colonizers detected in more than half of samples. Reconstructed genomes from infant gut colonizers revealed a suite of genes that confer resistance to antibiotics (for example, tetracycline, fluoroquinolone, and aminoglycoside) and sterilizing agents, which likely offer a competitive advantage in the NICU environment. CONCLUSIONS: We have developed a high-throughput culture-independent approach that integrates room surveys based on full-length 16S rRNA gene sequences with metagenomic analysis of fecal samples collected from infants in the room. The approach enabled identification of discrete ICU reservoirs of microbes that also colonized the infant gut and provided evidence for the presence of certain organisms in the room prior to their detection in the gut.

The moderating effects of stress and rumination on depressive symptoms in women and men.

Although there is an abundance of research linking stress and rumination to depression in women, little is known with respect to the role stress plays in the relationship between rumination and depression. Moreover, the role of stress in the rumination-depression relationship has not been previously investigated separately in women. In the present study, 301 undergraduate women and 109 undergraduate men were administered a questionnaire battery to assess their degrees of stress, depressive symptoms and ruminative tendencies. Individually, both stress and rumination scores were found to account for a large proportion of variance in depressive symptom scores. The interaction of stress and rumination also accounted for a significant proportion of this variance, suggesting a significant moderating effect of stress on the rumination-depressive symptom relationship in women and men. Furthermore, women and men with the highest degrees of stress demonstrated the strongest rumination-depressive symptom relationship. However, low-stress women and low-stress men demonstrated divergent patterns of relationships. The alternative model of rumination as a moderator of the stress-depression relationship likewise supported divergent relationships between low-rumination women and low-rumination men in the relationship between stress and depression. The implications of these findings regarding vulnerability to depressive symptoms are discussed.

Blood transfusion alters the superior mesenteric artery blood flow velocity response to feeding in premature infants.

Packed red blood cell transfusion may increase the risk of necrotizing enterocolitis in premature infants. We hypothesize that the postprandial increase in mesenteric blood flow velocity (MBFV) would not be altered by a blood transfusion in premature infants. Infants born at 25 to 32 weeks and feeding at least 60 mL/kg/d who required a transfusion were randomized within each of two weight strata to feed or not feed during the transfusion. Mean, peak systolic, and end diastolic Doppler MBFV was measured 30 minutes before and after feedings at baseline (anemic) and with the first feeding posttransfusion. Twenty-two infants (27.3 +/- 2.3 weeks' gestational age; hemoglobin [HgB] 9.3 +/- 1.3 g/dL) were studied on day of life 3 to 71 (mean 31.2 days) and a corrected gestational age of 31.8 +/- 2.9 weeks. In the entire cohort, the peak systolic ( P = 0.02) and the mean ( P = 0.01) MBFV increased in response to feeding in the anemic but not the transfused state. On subgroup analysis, only anemic infants > 1250 g ( N = 12, HgB 8.6 +/- 0.9 g/dL) had an increase in peak systolic ( P = 0.04) and mean ( P = 0.006) MBFV with feeding. In conclusion, the MBFV increases in response to feeding in anemic preterm infants > 1250 g. We speculate that the lack of response to feeding in the immediate posttransfusion state may contribute to the development of transfusion-associated necrotizing enterocolitis.

Variability in cerebral oxygen delivery is reduced in premature neonates exposed to chorioamnionitis.

Premature infants exposed to chorioamnionitis are at increased risk for periventricular leukomalacia (PVL) and intraventricular hemorrhage (IVH), lesions that may result from inflammation and/or fluctuations in cerebral blood flow. The effect of chorioamnionitis on near-infrared spectroscopy (NIRS) measures of cerebral oxygen delivery has not been evaluated previously. Forty-nine infants born at 25-31 6/7 wk gestation underwent NIRS examination on d 1, 2, 3, and 7 of life. Variability in NIRS tracings was analyzed by partitioning each tracing into three components: long-term, intermediate, and short-term variability; the latter two components were analyzed. Chorioamnionitis-exposed infants manifest reduced intermediate variability in cerebral oxygenated and deoxygenated Hb but not total Hb. Infants with severe IVH/PVL had the lowest intermediate variability on d 1. Short-term variability was similar between chorioamnionitis-exposed and unexposed infants, and between infants with versus without severe IVH or PVL. We conclude that intermediate-term variability in NIRS cerebral oxygen delivery is reduced in chorioamnionitis-exposed infants. We speculate that intermediate variability represents the important time frame for evaluating the pathogenesis of perinatal brain injury. Further studies are needed to determine how these findings relate to cerebral blood flow autoregulation and oxygen utilization in premature infants.