Pregnancy-specific dietary guidelines for Americans are not met: Findings from a pilot study.

Objective: To assess maternal dietary intake during pregnancy and adherence to the 2020-2025 pregnancy-specific Dietary Guidelines for Americans (DGA). Methods: This was a retrospective observational study. The study population consisted of women who gave birth to term infants (>37 weeks of gestation). Participants were given the Dietary Screener Questionnaire (DSQ) after birth and asked to recall their dietary intake in the last month of pregnancy. Participants' estimated dietary intakes were then compared to the 2020-2025 DGA which includes specific recommendations for pregnant women. Results: Out of 51 women who completed the DSQ, none consumed the recommended amounts of all surveyed dietary factors. Specifically, only one woman (2%) met the recommended intake of fruits, 11 women (22%) met the recommended intake of calcium, 25 women (49%) exceeded the recommended upper limit for added sugar intake, and none of the women (0%) met the intake of vegetables, whole grains, dairy and fiber. Conclusion: Women in our study did not adhere to the pregnancy-specific DGA recommendations in the last month of pregnancy. Our findings underscore the need to increase maternal nutritional awareness and education to improve adherence to the DGA.

The preterm human milk microbiota fluctuates by postpartum week and is characterized by gestational age and maternal BMI.

IMPORTANCE: Despite a growing recognition that the type of nutrition received by preterm infants influences their intestinal microbiome and health outcomes, the microbiota of mother's own milk (MOM), pasteurized donor human milk (PDHM), and infant formula remain poorly characterized. In our study, we found that the structure of microbial communities, bacterial diversity, and relative abundances of specific genera were significantly different between MOM, PDHM, and formula. Additionally, our results suggest that the microbiota of MOM changes as a function of time and maternal factors. Lastly, we identified three lactotypes within MOM that have distinct microbial compositions and described the maternal factors associated with them. These findings set the stage for future research aimed at advancing our knowledge of the microbiota of preterm infant nutrition and the specific influence it may have on health outcomes.

Long-term dysbiosis and fluctuations of gut microbiome in antibiotic treated preterm infants.

Postnatal acquisition of the microbiome is critical to infant health. In preterm infants, empiric use of antibiotics is common, with significant health consequences. To understand the influence of antibiotics on acquisition of the microbiome over time, we longitudinally profiled microbial 16S rRNA in the stool of 79 preterm infants during their hospitalization in the intensive care unit and compared antibiotic treated and untreated infants. Despite similar clinical presentation, antibiotic treated infants had strong deviations in the content, diversity, and most dramatically, temporal stability of their microbiome. Dysbiosis and fluctuations of microbiome content persisted long after antibiotic exposure, up to hospital discharge. Microbiome diversity was dominated by a few common bacteria consistent among all infants. Our findings may inform clinical practice related to antibiotic use and targeted microbial interventions aimed at overcoming the adverse influence of antibiotics on the microbiome of preterm infants at specific developmental time points.

A Scoping Review of Neonatal Opioid Withdrawal and the Infant Gut Microbiome: Does Human Milk Optimize Infant Outcomes?

BACKGROUND: While a growing body of literature has established the role of human milk as a mechanism of protection in the formation of the infant gut microbiome, it remains unclear the extent to which this association exists for infants with neonatal opioid withdrawal syndrome. PURPOSE: The purpose of this scoping review was to describe the current state of the literature regarding the influence of human milk on infant gut microbiota in infants with neonatal opioid withdrawal syndrome. DATA SOURCES: CINAHL, PubMed, and Scopus databases were searched for original studies published from January 2009 through February 2022. Additionally, unpublished studies across relevant trial registries, conference proceedings, websites, and organizations were reviewed for possible inclusion. A total of 1610 articles met selection criteria through database and register searches and 20 through manual reference searches. STUDY SELECTION: Inclusion criteria were primary research studies, written in English, published between 2009 and 2022, including a sample of infants with neonatal opioid withdrawal syndrome/neonatal abstinence syndrome, and focusing on the relationship between the receipt of human milk and the infant gut microbiome. DATA EXTRACTION: Two authors independently conducted title/abstract and full-text review until there was consensus of study selection. RESULTS: No studies satisfied the inclusion criteria, which resulted in an empty review. IMPLICATIONS FOR PRACTICE AND RESEARCH: Findings from this study document the paucity of data exploring the associations between human milk, the infant gut microbiome, and subsequent neonatal opioid withdrawal syndrome. Further, these results highlight the timely importance of prioritizing this area of scientific inquiry.

Effective Use of Extended Dwell Peripheral Intravenous Catheters in Neonatal Intensive Care Patients.

BACKGROUND: Implementing innovative approaches to vascular access can be challenging in the newborn intensive care unit (NICU). PURPOSE: The purpose of this project was to describe the implementation of extended dwell peripheral intravenous (EPIV) catheters, a vascular access device not widely used in the NICU. The implementation involved (1) designing clinical criteria for EPIV catheter use, (2) education of vascular access NICU nurses, and (3) comparing clinical outcomes between vascular access devices (ie, PIV and EPIV catheters). METHODS: We developed evidence-based clinical criteria guiding the use of vascular access devices. We then developed an educational plan for NICU nurses focused on vascular access. Finally, we collected and compared demographic characteristics and clinical data on catheter type and placement attempts, dwell time, and clinical complications associated with each catheter. RESULTS: EPIV catheters were implemented according to evidence-based criteria by a vascular access NICU nursing team. Fifteen percent of PIV catheter placements required 3 or more attempts compared with just 1% of EPIV catheter placement attempts. EPIV catheters had a longer median dwell time (3.5 vs 1 day) and fewer complications than PIV catheters (P < .001). IMPLICATIONS FOR PRACTICE AND RESEARCH: Implementation of an evidence-based approach to vascular access by a team of NICU nurses may improve clinical outcomes. EPIV catheters may be an appropriate alternative device to PIV catheters due to fewer placement attempts, longer dwell times, and overall fewer complications during use. Future vascular access research in the NICU may include a greater focus on innovative placement strategies, optimal maintenance and infection control, and prevention of complications.

Human milk pH is associated with fortification, postpartum day, and maternal dietary intake in preterm mother-infant dyads.

OBJECTIVE: To compare pH of human milk types (mother's own milk (MOM), pasteurized donor human milk (PDHM), fortified MOM, and fortified PDHM) fed to preterm infants. STUDY DESIGN: This observational study consisted of 63 mother-infant dyads < 34 weeks gestation. Human milk samples (n = 245), along with maternal factors, were collected for pH analysis. pH of MOM was analyzed over the course of lactation accounting for fortification status, postpartum day, and storage conditions. RESULTS: Mean pH of MOM was slightly acidic at 6.60 ± 0.28, which was significantly higher (p < 0.05) than other milk types. pH of MOM varied by fortification, postpartum day, and maternal vegetable/fiber intake. There was a significant interaction between fortification status and postpartum day; pH of MOM decreased over time, while pH of fortified MOM increased over time. CONCLUSION: pH of human milk varied by type. pH of MOM was significantly associated with fortification status, postpartum day, and maternal vegetable/fiber intake.

Intestinal Inflammation is Significantly Associated With Length Faltering in Preterm Infants at Neonatal Intensive Care Unit Discharge.

OBJECTIVE: The aim of the study was to assess intestinal inflammatory measures, urinary intestinal fatty acid-binding protein (IFABP), and fecal calprotectin (FC) by gestational age (GA) and postmenstrual age (PMA) and determine the association between intestinal inflammation and growth in preterm infants from birth to hospital discharge. We hypothesized that intestinal inflammation is associated with adverse growth in preterm infants. METHODS: We assayed repeated measures of IFABP and FC in 72 hospitalized preterm infants (<34 weeks' gestation). We calculated weight and length z scores at birth and discharge using the Fenton growth reference. Associations between mean IFABP or FC, growth z scores at discharge, and growth faltering (weight or length z score difference <-0.8 from birth to discharge) were assessed using mixed linear and logistic regression models, adjusted for intrafamilial correlation and potential confounders: GA, sex, birth z score, race/ethnicity, and maternal age. RESULTS: Mean IFABP was greater among infants born at earlier GA and decreased with increasing PMA. Mean FC did not vary by GA or PMA. Higher mean IFABP and FC were associated with lower discharge growth z scores and greater likelihood of growth faltering significant only for mean IFABP and discharge length z score (ß = -0.353, 95% confidence interval [CI]: -0.704 to -0.002) and mean IFABP and length faltering (odds ratio [OR] 1.99, P = 0.018). CONCLUSIONS: Intestinal inflammation, measured by IFABP, was associated with lower length z scores and length faltering at discharge. Interventions to prevent intestinal inflammation may improve linear growth among preterm infants.

Integrating longitudinal clinical and microbiome data to predict growth faltering in preterm infants.

Preterm birth affects more than 10% of all births worldwide. Such infants are much more prone to Growth Faltering (GF), an issue that has been unsolved despite the implementation of numerous interventions aimed at optimizing preterm infant nutrition. To improve the ability for early prediction of GF risk for preterm infants we collected a comprehensive, large, and unique clinical and microbiome dataset from 3 different sites in the US and the UK. We use and extend machine learning methods for GF prediction from clinical data. We next extend graphical models to integrate time series clinical and microbiome data. A model that integrates clinical and microbiome data improves on the ability to predict GF when compared to models using clinical data only. Information on a small subset of the taxa is enough to help improve model accuracy and to predict interventions that can improve outcome. We show that a hierarchical classifier that only uses a subset of the taxa for a subset of the infants is both the most accurate and cost-effective method for GF prediction. Further analysis of the best classifiers enables the prediction of interventions that can improve outcome.

Elevated Intestinal Inflammation in Preterm Infants With Signs and Symptoms of Gastroesophageal Reflux Disease.

OBJECTIVES: Reflux is common in infancy; however, persistent signs and symptoms of gastrointestinal distress are often attributed to gastroesophageal reflux disease (GERD). In this pilot study, we aimed to characterize associations between signs and symptoms of suspected GERD and noninvasive markers of intestinal inflammation in preterm infants. METHODS: We reviewed Electronic Medical Record (EMR) data to identify clinical signs and symptoms among case patients (n = 16). Controls (n = 16) were matched on gestational age. Univariate and multivariate regression analyses were used to compare fecal calprotectin and urinary intestinal fatty acid binding protein (I-FABP) levels between cases and controls. RESULTS: We found no differences in baseline characteristics between cases and controls. In the multivariate regression analysis controlling for the proportion of mother's milk, cases had higher fecal calprotectin levels than controls, with no differences in I-FABP levels between cases and controls. CONCLUSION: Our findings suggest that preterm infants with signs and symptoms of GERD have higher levels of intestinal inflammation as indicated by fecal calprotectin compared to their controls. Further studies are needed to evaluate the role of intestinal inflammation in signs and symptoms of gastrointestinal distress and whether fecal calprotectin might have predictive value in diagnosing GERD.

Patient characteristics associated with SARS-CoV-2 infection in parturients admitted for labour and delivery in Massachusetts during the spring 2020 surge: A prospective cohort study.

BACKGROUND: While studies from large cities affected by coronavirus disease 2019 (COVID-19) have reported on the prevalence of SARS-CoV-2 in the context of universal testing during admission for delivery, the patient demographic, social and clinical factors associated with SARS-CoV-2 infection in pregnant women are not fully understood. OBJECTIVE: To evaluate the epidemiological factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in women admitted for labour and delivery, in the context of universal screening at four Boston-area hospitals. METHODS: In this prospective cohort study, we reviewed the health records of all women admitted for labour and delivery at four hospitals from the largest health system in Massachusetts between 19 April 2020 and 27 June 2020. We calculated the risk of SARS-CoV-2 infection, including asymptomatic infection. We calculated associations between SARS-CoV-2 infection and demographic and clinical characteristics. RESULTS: A total of 93 patients (3.2%, 95% confidence interval 2.5, 3.8) tested positive for SARS-CoV-2 infection on admission for labour and delivery out of 2945 patients included in the analysis; 80 (86.0%) of the patients who tested positive were asymptomatic at the time of testing. Factors associated with SARS-CoV-2 infection included the following: younger age, obesity, African American or Hispanic race/ethnicity, residence in heavily affected communities (as measured in cases reported per capita), presence of a household member with known SARS-CoV-2 infection, non-health care essential worker occupation and MassHealth or Medicaid insurance compared to commercial insurance. 93.8% of patients testing positive for SARS-CoV-2 on admission had one or more identifiable factors associated with disease acquisition. CONCLUSIONS: In this large sample of deliveries during the height of the surge in infections during the spring of 2020, SARS-CoV-2 infection was largely concentrated in patients with distinct demographic characteristics, those largely from disadvantaged communities. Racial disparities seen in pregnancy persist with respect to SARS-CoV-2 infection.

Bioactive Factors in Human Breast Milk Attenuate Intestinal Inflammation during Early Life.

Human breast milk is well known as the ideal source of nutrition during early life, ensuring optimal growth during infancy and early childhood. Breast milk is also the source of many unique and dynamic bioactive components that play a key role in the development of the immune system. These bioactive components include essential microbes, human milk oligosaccharides (HMOs), immunoglobulins, lactoferrin and dietary polyunsaturated fatty acids. These factors all interact with intestinal commensal bacteria and/or immune cells, playing a critical role in establishment of the intestinal microbiome and ultimately influencing intestinal inflammation and gut health during early life. Exposure to breast milk has been associated with a decreased incidence and severity of necrotizing enterocolitis (NEC), a devastating disease characterized by overwhelming intestinal inflammation and high morbidity among preterm infants. For this reason, breast milk is considered a protective factor against NEC and aberrant intestinal inflammation common in preterm infants. In this review, we will describe the key microbial, immunological, and metabolic components of breast milk that have been shown to play a role in the mechanisms of intestinal inflammation and/or NEC prevention.

Donor Milk Policies for Level 1 Newborn Care: A Descriptive Analysis.

Background and Objectives: Providing pasteurized donor human milk (DHM) to healthy newborns is an emerging practice. The content of hospital policies that govern this practice is unknown. Materials and Methods: We collected policies from 15 Northeast U.S. hospitals through (1) a 2017 survey on DHM use and (2) an e-mail listserv of levels 1 and 2 newborn care staff maintained by a regional milk bank. Two authors reviewed each policy and identified how they addressed three predetermined themes: who is eligible to receive DHM, how DHM is used and described, and how lactation is supported. Responses were compared, discussed, and reconciled. Level 1 newborn care was defined as basic care for healthy newborns ≥35 weeks' gestation. Results: Thirteen of 15 policies stated criteria for DHM eligibility, most commonly as a bridge until mother's supply comes in (73%) or for infant medical conditions (67%). All required consent for DHM. Most did not limit number of days infants could receive DHM (60%). Nine specified that DHM be discarded 24 hours after thaw, whereas five recommended discarding at 48 hours. Although many (53%) policies endorsed human milk as the preferred diet for newborns, only 27% specifically endorsed DHM as the preferred supplementation type. Parent education (73%) was emphasized, but few (27%) discussed the importance of establishing mother's milk supply. Conclusions: Many DHM policies address eligibility criteria for receiving DHM and show how to provide DHM, but few address how to support lactation while DHM is provided, which may be crucial for optimizing long-term breastfeeding outcomes.

Author Correction: A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip.

In the version of this Article originally published, the authors mistakenly cited Fig. 5d in the sentence beginning 'Importantly, the microbiome cultured in these primary Intestine Chips...'; the correct citation is Supplementary Table 2. This has now been amended.

A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip.

The diverse bacterial populations that comprise the commensal microbiome of the human intestine play a central role in health and disease. A method that sustains complex microbial communities in direct contact with living human intestinal cells and their overlying mucus layer in vitro would thus enable the investigation of host-microbiome interactions. Here, we show the extended coculture of living human intestinal epithelium with stable communities of aerobic and anaerobic human gut microbiota, using a microfluidic intestine-on-a-chip that permits the control and real-time assessment of physiologically relevant oxygen gradients. When compared to aerobic coculture conditions, the establishment of a transluminal hypoxia gradient in the chip increased intestinal barrier function and sustained a physiologically relevant level of microbial diversity, consisting of over 200 unique operational taxonomic units from 11 different genera and an abundance of obligate anaerobic bacteria, with ratios of Firmicutes and Bacteroidetes similar to those observed in human faeces. The intestine-on-a-chip may serve as a discovery tool for the development of microbiome-related therapeutics, probiotics and nutraceuticals.

Changing the paradigm of defining, detecting, and diagnosing NEC: Perspectives on Bell's stages and biomarkers for NEC.

Better means to diagnose and define necrotizing enterocolitis are needed to guide clinical practice and research. Adequacy of Bell's staging system for clinical practice and clarity of cases used in NEC clinical datasets has been a topic of controversy for some time. This article provides reasons why a better global definition for NEC is needed and offers a simple alternative bedside definition for preterm NEC called the "Two out of Three" rule. Some argue that biomarkers may fill knowledge gaps and provide greater precision in defining relevant features of a clinical disease like NEC. NEC biomarkers include markers of inflammation, intestinal dysfunction, hematologic changes, and clinical features. Development and reporting of NEC biomarkers should be guided by the FDA's BEST Consensus resource, "Biomarkers, EndpointS, & other Tools" and consistently report metrics so that studies can be compared and results pooled. Current practice in the NICU would be enhanced by clinical tools that effectively inform the clinical team that a baby is at increasing risk of NEC. Ideally, these tools will incorporate both clinical information about the baby as well as molecular signals that are indicative of NEC. While meaningful biomarkers for NEC and clinical tools exist, translation into practice is mediocre.

Prevalence and Trends in Donor Milk Use in the Well-Baby Nursery: A Survey of Northeast United States Birth Hospitals.

BACKGROUND AND OBJECTIVES: Pasteurized donor human milk ("donor milk") is an alternative to formula for supplementation of breastfed infants. We conducted a survey to determine (1) prevalence, trends, and hospital-level correlates of donor milk use for healthy newborns in the northeast United States and (2) clinician knowledge and opinions regarding this practice. METHODS: We conducted parallel surveys of clinicians (88% nurse and/or lactation consultant) at (1) all birth hospitals in Massachusetts (MA) and (2) all birth hospitals served by a northeast United States milk bank. We asked about hospital use of donor milk for newborns ≥35 weeks' gestation and receiving Level I care in well nursery, hospital-related factors we hypothesized would be associated with this practice, and clinician knowledge and opinions about donor milk use. RESULTS: 35/46 (76%) of MA birth hospitals and 51/69 (74%) of hospitals served by the milk bank responded; 71 unique hospitals were included. Twenty-nine percent of MA birth hospitals and 43% of hospitals served by the milk bank reported using donor milk for healthy newborns. Hospitals that used donor milk for healthy newborns had higher exclusive breastfeeding at hospital discharge than hospitals that did not (77% versus 56%, p = 0.02). Eighty-three percent of respondents agreed or strongly agreed that using donor milk is an effective way to increase the hospital's exclusive breastfeeding rate. CONCLUSIONS: Many northeast United States birth hospitals currently use donor milk for healthy newborns. This practice is associated with higher exclusive breastfeeding at hospital discharge. Relationships with breastfeeding after discharge and related outcomes are unknown.

Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a catastrophic disease of preterm infants, and microbial dysbiosis has been implicated in its pathogenesis. Studies evaluating the microbiome in NEC and preterm infants lack power and have reported inconsistent results. METHODS AND RESULTS: Our objectives were to perform a systematic review and meta-analyses of stool microbiome profiles in preterm infants to discern and describe microbial dysbiosis prior to the onset of NEC and to explore heterogeneity among studies. We searched MEDLINE, PubMed, CINAHL, and conference abstracts from the proceedings of Pediatric Academic Societies and reference lists of relevant identified articles in April 2016. Studies comparing the intestinal microbiome in preterm infants who developed NEC to those of controls, using culture-independent molecular techniques and reported α and ß-diversity metrics, and microbial profiles were included. In addition, 16S ribosomal ribonucleic acid (rRNA) sequence data with clinical meta-data were requested from the authors of included studies or searched in public data repositories. We reprocessed the 16S rRNA sequence data through a uniform analysis pipeline, which were then synthesized by meta-analysis. We included 14 studies in this review, and data from eight studies were available for quantitative synthesis (106 NEC cases, 278 controls, 2944 samples). The age of NEC onset was at a mean ± SD of 30.1 ± 2.4 weeks post-conception (n = 61). Fecal microbiome from preterm infants with NEC had increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes prior to NEC onset. Alpha- or beta-diversity indices in preterm infants with NEC were not consistently different from controls, but we found differences in taxonomic profiles related to antibiotic exposure, formula feeding, and mode of delivery. Exploring heterogeneity revealed differences in microbial profiles by study and the target region of the 16S rRNA gene (V1-V3 or V3-V5). CONCLUSIONS: Microbial dysbiosis preceding NEC in preterm infants is characterized by increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes. Microbiome optimization may provide a novel strategy for preventing NEC.

Influence of maternal breast milk ingestion on acquisition of the intestinal microbiome in preterm infants.

BACKGROUND: The initial acquisition and early development of the intestinal microbiome during infancy are important to human health across the lifespan. Mode of birth, antibiotic administration, environment of care, and nutrition have all been shown to play a role in the assembly of the intestinal microbiome during early life. For preterm infants, who are disproportionately at risk of inflammatory intestinal disease (i.e., necrotizing enterocolitis), a unique set of clinical factors influence the establishment of the microbiome. The purpose of this study was to establish the influence of nutritional exposures on the intestinal microbiome in a cohort of preterm infants early in life. RESULTS: Principal component analysis of 199 samples from 30 preterm infants (<32 weeks) over the first 60 days following birth showed that the intestinal microbiome was influenced by postnatal time (p < 0.001, R 2 = 0.13), birth weight (p < 0.001, R 2 = 0.08), and nutrition (p < 0.001, R 2 = 0.21). Infants who were fed breast milk had a greater initial bacterial diversity and a more gradual acquisition of diversity compared to infants who were fed infant formula. The microbiome of infants fed breast milk were more similar regardless of birth weight (p = 0.049), in contrast to the microbiome of infants fed infant formula, which clustered differently based on birth weight (p < 0.001). By adjusting for differences in gut maturity, an ordered succession of microbial phylotypes was observed in breast milk-fed infants, which appeared to be disrupted in those fed infant formula. Supplementation with pasteurized donor human milk was partially successful in promoting a microbiome more similar to breast milk-fed infants and moderating rapid increases in bacterial diversity. CONCLUSIONS: The preterm infant intestinal microbiome is influenced by postnatal time, birth weight, gestational age, and nutrition. Feeding with breast milk appears to mask the influence of birth weight, suggesting a protective effect against gut immaturity in the preterm infant. These findings suggest not only a microbial mechanism underpinning the body of evidence showing that breast milk promotes intestinal health in the preterm infant but also a dynamic interplay of host and dietary factors that facilitate the colonization of and enrichment for specific microbes during establishment of the preterm infant microbiota.