Investigating the influence of perinatal fluoxetine exposure on murine gut microbial communities during pregnancy and lactation.

Selective Serotonin Reuptake Inhibitor (SSRI) therapy is common among perinatal populations for the treatment of mood disorders. Medications can affect diversity and composition of the gut microbiome, which plays a key role in modulating health. While previous studies have examined the effects of antidepressant exposure on the maternal gut microbiome, whether SSRI exposure affects the offspring gut microbiome is unknown. We investigated the effects of maternal fluoxetine exposure on the gut microbiome of maternal and offspring mice during pregnancy and lactation (embryonic day 10-lactation day 21; E10-L21). Stool samples collected on E17, L11, L15, and L21 were examined using 16S rRNA sequencing. Our results suggest that maternal fluoxetine exposure may result in decreased alpha diversity of the offspring gut microbiome in early life. Furthermore, we observed several genera-specific differences in the gut microbiome based on treatment, specifically of Turicibacter, Parasutterella, and Romboutsia. These findings support our understanding of gut health, as dysbiotic development of the gut microbiome has been associated with local and systemic health problems including gastrointestinal morbidities and interrupted growth patterns in infants. Future research should pursue study in human populations and those at high risk for gut microbial dysbiosis and intestinal injury.

Selective serotonin reuptake inhibitors during pregnancy and lactation: A scoping review of effects on the maternal and infant gut microbiome.

Perinatal mood disorders are a tremendous burden to childbearing families and treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants is increasingly common. Exposure to SSRIs may affect serotonin signaling and ultimately, microbes that live in the gut. Health of the gut microbiome during pregnancy, lactation, and early infancy is critical, yet there is limited evidence to describe the relationship between SSRI exposure and gut microbiome status in this population. The purpose of this Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-compliant scoping review is to assess evidence and describe key concepts regarding whether SSRI exposure affects the maternal and infant gut microbiome. Sources were collected from PubMed, Web of Science, and Scopus databases, and an additional gray literature search was performed. Our search criteria returned only three sources, two rodent models and one human subjects research study. Results suggest that fluoxetine (SSRI) exposure may affect maternal gut microbiome dynamics during pregnancy and lactation. There were no available sources to describe the relationship between perinatal SSRI exposure and the infant gut microbiome. There is a significant gap in the literature regarding whether SSRI antidepressants affect the maternal and infant gut microbiome. Future studies are required to better understand how SSRI antidepressant exposure affects perinatal health.

Developmental fluoxetine exposure affects adolescent and adult bone depending on the dose and period of exposure in mice.

At the end of gestation, fetal skeleton rapidly accumulates calcium, and bone development continues in offspring postnatally. To accommodate, maternal skeletal physiology is modulated in a serotonin-dependent manner. Selective serotonin reuptake inhibitors (SSRIs) are generally considered safe for treatment of major depressive disorder, postpartum depression, and other psychiatric illnesses during the peripartum period, but because serotonin affects bone remodeling, SSRIs are associated with decreased bone mass across all ages and sexes, and the impact of SSRIs during fetal and postnatal development has not been fully investigated. In the present study, our aim was to examine developmental fluoxetine exposure on offspring skeleton and to assess varying degrees of impact depending on dose and window of exposure in short-term and long-term contexts. We established that a low dose of lactational fluoxetine exposure caused a greater degree of insult to offspring bone than either a low dose during fetal and postpartum development or a high dose during lactation only in mice. We further discovered lasting impacts of developmental fluoxetine exposure, especially during lactation only, on adult bone and body composition. Herein, we provide evidence fluoxetine exposure during early development may have detrimental effects on the skeleton of offspring at weaning and into adulthood.

Sociodemographic Factors and Intestinal Microbiome Development in Preterm, Very Low Birth Weight Infants.

OBJECTIVE: Preterm very low birth weight (VLBW) infants are at risk for intestinal morbidities and dysbiotic development of the intestinal microbiome. Despite the influence of sociodemographic factors on premature infant health outcomes, whether they shape the intestinal microbiome early in life is not clear. The objective was to explore the associations between race, sex, and socioeconomic status and the intestinal microbiome of VLBW infants during the first 4 weeks of life. STUDY DESIGN: This was a secondary analysis of data from an ongoing randomized trial of 79 infants ≤30 weeks' gestation and ≤1,500 g. Stool samples were collected at week 1 through week 4, frozen to -80°C and analyzed by 16S rRNA sequencing of the V4 region using Illumina MiSeq. Reads were analyzed to measure α and ß diversity as well as relative abundance of bacteria in the intestinal microbiome. RESULTS: Of the 79 infants, 63 had at least one sample available. Twenty-three (37%) of infants were African American, 30 (48%) were male, and 44 (71%) had Medicaid insurance. There were no statistically significant (<0.05) differences in α diversity or ß diversity, and the differential abundance analysis suggests limited patterns of distinction in the intestinal microbiome between non-African American and African American infants, male and female infants, and infants with maternal private or Medicaid insurance. CONCLUSION: Our results suggest race, sex, and socioeconomic status shape colonization of specific microorganisms to a limited extent. Future studies should confirm these findings and determine clinical relevance through further study of differentially abundant microorganisms and additional factors contributing to colonization patterns. KEY POINTS: · Diversity of the gut microbiome was similar between infants of varying race, sex, and socioeconomic status.. · We observed sociodemographic-linked differences in colonization of individual taxa.. · Further study is required to confirm these results and the clinical relevance of these findings..

Neonatal Feeding Tube Colonization and the Potential Effect on Infant Health: A Review.

Background: Infants in the neonatal intensive care unit (NICU) often require feeding tubes (FT) for weeks to months. Because FTs are in near constant contact with human milk and/or formula, rapid and extensive bacterial growth is possible. Due to their immature immunologic and gastrointestinal (GI) systems, infants may be at significant health risk due to FT colonization. In adults, length of time FTs remain in place (dwell time) affects the degree of colonization and biofilm formation which is important in infants whose tubes remain in place up to 30 days. Objective: The purpose of this review was to describe and summarize the evidence regarding FT bacterial colonization in infants and identify gaps needing further investigation. Methods: Medline, CINAHL, and Embase databases were searched for clinical and/or laboratory-based observational and randomized controlled studies investigating the presence of bacteria in neonatal FTs. Results: This review of 10 studies found evidence that neonatal FTs may contain high quantities of potentially pathogenic and antibiotic resistant bacteria and longer dwell times may increase the bacterial load. Furthermore, evidence suggests FT colonization may be nosocomial in origin and contribute to adverse infant health. Feeding tubes are an unrecognized source of bacterial colonization which may increase morbidity in premature infants and thus the presence of bacteria in FTs is an important area of investigation in the nutritional care of vulnerable infants in the NICU. Implications: Further appropriately powered studies which are clinically based, use appropriate analyses, and control for potential covariates are necessary to make clinical recommendations.

Exploring Social and Demographic Factors as Determinants of Intestinal Inflammation in Very Low Birth-Weight Infants.

BACKGROUND: Very low birth-weight (VLBW) infants are disproportionately affected by inflammatory morbidities including necrotizing enterocolitis. Despite the influence of social and demographic factors on infant health outcomes, their relationship with intestinal inflammation is unknown. PURPOSE: To explore the influence of maternal race, maternal socioeconomic status, and infant sex on intestinal inflammation in VLBW infants. METHODS: This was a secondary analysis of existing data from a randomized controlled trial of 143 infants 32 weeks' gestation or less and weighing 1250 g or less. In the previous study, fecal calprotectin and S100A12 values were collected at weeks 3 and 6. The infant sample was determined on the basis of the availability of these results, which served as intestinal inflammation biomarkers for the present study. General linear mixed models assessed the relationship between biomarkers and social and demographic factors. Gestational age, antibiotic exposure, mother's own milk feeding, acuity, and week of sample collection were used as control variables. FINDINGS/RESULTS: The sample included 124 infants. Fifty-two infants (42%) were African American, 86 (69%) had Medicaid coverage, and 65 (53%) were male. Fecal calprotectin levels were higher in African American infants (P = .02) and infants with private insurance coverage (P = .009); no difference was found between sexes. There was no association between S100A12 levels and infant sex, maternal race, or socioeconomic status. IMPLICATIONS FOR PRACTICE AND RESEARCH: Consideration of social and demographic factors may be important when caring for VLBW infants. Further exploration of factors contributing to associations between social or demographic factors and intestinal inflammation is needed.

Feeding Strategies in Preterm Very Low Birth-Weight Infants: State-of-the-Science Review.

BACKGROUND: Providing enteral feeds to preterm very low birth-weight (VLBW) infants is critical to optimize nutrition, enhance growth, and reduce complications. Protocols guiding feeding practices can improve outcomes, but significant variation exists between institutions, which may limit their utility. To be most effective, protocols should be based on the best available evidence. PURPOSE: To examine the state of the science on several key components of feeding protocols for VLBW infants. SEARCH STRATEGY: The authors searched PubMed, CINAHL, and EMBASE databases for terms related to feeding VLBW infants less than 32 weeks' gestational age, including initiation of feedings, rate of feeding advancement, timing of human milk (HM) fortification, and feeding during blood transfusions, when diagnosed with a patent ductus arteriosus (PDA) and during medical treatment of PDA closure. RESULTS: Initiation of feeds within the first 3 days of life and advancement by 30 mL/kg/d may decrease time to attain full feeds without increasing complications. Insufficient evidence guides optimal timing of HM fortification, as well as feeding infants undergoing blood transfusions, infants diagnosed with a PDA, and infants receiving medical treatment of PDA closure. IMPLICATIONS FOR PRACTICE: Integration of existing research regarding feeding initiation and advancement into feeding protocols may improve outcomes. Infants at highest risk of feeding-related complications may benefit from a personalized feeding approach. IMPLICATIONS FOR RESEARCH: Additional research is needed to provide evidence concerning the optimal timing of HM fortification and feeding strategies for infants undergoing blood transfusions and those diagnosed with a PDA or receiving medical treatment of PDA closure to incorporate into evidence-based feeding protocols.

Determinants of the Very Low-Birth-Weight Infant's Intestinal Microbiome: A Systematic Review.

The intestinal microbiome is the genetic material from microorganisms residing in the intestinal tract. Very low-birth-weight infants (VLBW; birth weight ≤1500 g) are a physiologically compromised population undergoing a unique period of initial intestinal microbiome establishment. Evidence supports a connection between the intestinal microbiome and gastrointestinal illness that disproportionately affects VLBW infants. Necrotizing enterocolitis, an inflammatory and often necrotic condition of the intestine, and late-onset sepsis, a bloodstream infection occurring after 3 days of life, are thought to be associated with delayed or abnormal intestinal microbiome development. Here, we review the determinants, or factors, that influence the VLBW infant's intestinal microbiome and discuss clinical implications. PubMed, Web of Science, EMBASE, and CINAHL were systematically searched for publications addressing factors with the potential to affect the intestinal microbiome of VLBW infants. Results indicate that infant's age and weight, mode of delivery, antibiotic exposure, medication use, feeding regime, environment, and perinatal-/infant-associated factors may be important determinants of the microbiome in this vulnerable population. Clinicians have opportunities to support positive development of the VLBW infant's intestinal microbiome through antibiotic stewardship, support of human milk feeding, and hygienic care practices.