Proteomics-Based Mapping of Bronchopulmonary Dysplasia-Associated Changes in Noninvasively Accessible Oral Secretions.

OBJECTIVE: To determine if oral secretions (OS) can be used as a noninvasively collected body fluid, in lieu of tracheal aspirates (TA), to track respiratory status and predict bronchopulmonary dysplasia (BPD) development in infants born <32 weeks. STUDY DESIGN: This was a retrospective, single center cohort study that included data and convenience samples from week-of-life (WoL) 3 from 2 independent preterm infant cohorts. Using previously banked samples, we applied our sample-sparing, high-throughput proteomics technology to compare OS and TA proteomes in infants born <32 weeks admitted to the Neonatal Intensive Care Unit (NICU) (Cohort 1; n = 23 infants). In a separate similar cohort, we mapped the BPD-associated changes in the OS proteome (Cohort 2; n = 17 infants including 8 with BPD). RESULTS: In samples collected during the first month of life, we identified 607 proteins unique to OS, 327 proteins unique to TA, and 687 overlapping proteins belonging to pathways involved in immune effector processes, neutrophil degranulation, leukocyte mediated immunity, and metabolic processes. Furthermore, we identified 37 OS proteins that showed significantly differential abundance between BPD cases and controls: 13 were associated with metabolic and immune dysregulation, 10 of which (eg, SERPINC1, CSTA, BPI) have been linked to BPD or other prematurity-related lung disease based on blood or TA investigations, but not OS. CONCLUSIONS: OS are a noninvasive, easily accessible alternative to TA and amenable to high-throughput proteomic analysis in preterm newborns. OS samples hold promise to yield actionable biomarkers of BPD development, particularly for prospective categorization and timely tailored treatment of at-risk infants with novel therapies.

Implications of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic on the Epidemiology of Pediatric Respiratory Syncytial Virus Infection.

Respiratory viral infections account for a large percentage of global disease and death. Respiratory syncytial virus is a seasonal virus affecting immunologically vulnerable populations, such as preterm newborns and young infants; however, its epidemiology has changed drastically during the coronavirus disease 2019 pandemic. In this perspective, we discuss the implications of coronavirus disease 2019 on respiratory syncytial virus seasonality patterns and mitigation efforts, as well as the urgent need for vaccination as a preventive tool.

Precision Vaccine Adjuvants for Older Adults: A Scoping Review.

Older adults, defined as those ≥60 years of age, are a growing population vulnerable to infections including severe acute respiratory syndrome coronavirus 2. Although immunization is a key to protecting this population, immunosenescence can impair responses to vaccines. Adjuvants can increase the immunogenicity of vaccine antigens but have not been systematically compared in older adults. We conducted a scoping review to assess the comparative effectiveness of adjuvants in aged populations. Adjuvants AS01, MF59, AS03, and CpG-oligodeoxynucleotide, included in licensed vaccines, are effective in older human adults. A growing menu of investigational adjuvants, such as Matrix-M and CpG plus alum, showed promising results in early phase clinical trials and preclinical studies. Most studies assessed only 1 or 2 adjuvants and no study has directly compared >3 adjuvants among older adults. Enhanced preclinical approaches enabling direct comparison of multiple adjuvants including human in vitro modeling and age-specific animal models may derisk and accelerate vaccine development for older adults.

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

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus. METHODS: We measured spike-specific immunoglobulin G (anti-S IgG) and immunoglobulin A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in 2 academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity. RESULTS: The study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P), and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation. VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (P < .0001), whereas INF mothers had higher BM:serum anti-S IgA ratios compared to VAX mothers (P = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (P < .0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, P = .013), but not infection. CONCLUSIONS: BNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S immunoglobulin, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM immunoglobulin production. Next-generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit.

Immunometabolic approaches to prevent, detect, and treat neonatal sepsis.

The first days of postnatal life are energetically demanding as metabolic functions change dramatically to accommodate drastic environmental and physiologic transitions after birth. It is increasingly appreciated that metabolic pathways are not only crucial for nutrition but also play important roles in regulating inflammation and the host response to infection. Neonatal susceptibility to infection is increased due to a functionally distinct immune response characterized by high reliance on innate immune mechanisms. Interactions between metabolism and the immune response are increasingly recognized, as changes in metabolic pathways drive innate immune cell function and activation and consequently host response to pathogens. Moreover, metabolites, such as acetyl-coenzyme A (acetyl-CoA) and succinate have immunoregulatory properties and serve as cofactors for enzymes involved in epigenetic reprogramming or "training" of innate immune cells after an initial infectious exposure. Highly sensitive metabolomic approaches allow us to define alterations in metabolic signatures as they change during ontogeny and as perturbed by immunization or infection, thereby linking metabolic pathways to immune cell effector functions. Characterizing the ontogeny of immunometabolism will offer new opportunities to prevent, diagnose, and treat neonatal sepsis.

Mast cell activation and autism.

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by varying degrees of dysfunctional communication and social interactions, repetitive and stereotypic behaviors, as well as learning and sensory deficits. Despite the impressive rise in the prevalence of autism during the last two decades, there are few if any clues for its pathogenesis, early detection or treatment. Increasing evidence indicates high brain expression of pro-inflammatory cytokines and the presence of circulating antibodies against brain proteins. A number of papers, mostly based on parental reporting on their children's health problems, suggest that ASD children may present with "allergic-like" problems in the absence of elevated serum IgE and chronic urticaria. These findings suggest non-allergic mast cell activation, probably in response to environmental and stress triggers that could contribute to inflammation. In utero inflammation can lead to preterm labor and has itself been strongly associated with adverse neurodevelopmental outcomes. Premature babies have about four times higher risk of developing ASD and are also more vulnerable to infections, while delayed development of their gut-blood-brain barriers makes exposure to potential neurotoxins likely. Perinatal mast cell activation by infectious, stress-related, environmental or allergic triggers can lead to release of pro-inflammatory and neurotoxic molecules, thus contributing to brain inflammation and ASD pathogenesis, at least in a subgroup of ASD patients. This article is part of a Special Issue entitled: Mast cells in inflammation.

Mast cells and inflammation.

Mast cells are well known for their role in allergic and anaphylactic reactions, as well as their involvement in acquired and innate immunity. Increasing evidence now implicates mast cells in inflammatory diseases where they are activated by non-allergic triggers, such as neuropeptides and cytokines, often exerting synergistic effects as in the case of IL-33 and neurotensin. Mast cells can also release pro-inflammatory mediators selectively without degranulation. In particular, IL-1 induces selective release of IL-6, while corticotropin-releasing hormone secreted under stress induces the release of vascular endothelial growth factor. Many inflammatory diseases involve mast cells in cross-talk with T cells, such as atopic dermatitis, psoriasis and multiple sclerosis, which all worsen by stress. How mast cell differential responses are regulated is still unresolved. Preliminary evidence suggests that mitochondrial function and dynamics control mast cell degranulation, but not selective release. Recent findings also indicate that mast cells have immunomodulatory properties. Understanding selective release of mediators could explain how mast cells participate in numerous diverse biologic processes, and how they exert both immunostimulatory and immunosuppressive actions. Unraveling selective mast cell secretion could also help develop unique mast cell inhibitors with novel therapeutic applications. This article is part of a Special Issue entitled: Mast cells in inflammation.

IL-33 augments substance P-induced VEGF secretion from human mast cells and is increased in psoriatic skin.

The peptide substance P (SP) has been implicated in inflammatory conditions, such as psoriasis, where mast cells and VEGF are increased. A relationship between SP and VEGF has not been well studied, nor has any interaction with the proinflammatory cytokines, especially IL-33. Here we report that SP (0.1-10 microM) induces gene expression and secretion of VEGF from human LAD2 mast cells and human umbilical core blood-derived cultured mast cells (hCBMCs). This effect is significantly increased by coadministration of IL-33 (5-100 ng/mL) in both cell types. The effect of SP on VEGF release is inhibited by treatment with the NK-1 receptor antagonist 733,060. SP rapidly increases cytosolic calcium, and so does IL-33 to a smaller extent; the addition of IL-33 augments the calcium increase. SP-induced VEGF production involves calcium-dependent PKC isoforms, as well as the ERK and JNK MAPKs. Gene expression of IL-33 and histidine decarboxylase (HDC), an indicator of mast cell presence/activation, is significantly increased in affected and unaffected (at least 15 cm away from the lesion) psoriatic skin, as compared with normal control skin. Immunohistochemistry indicates that IL-33 is associated with endothelial cells in both the unaffected and affected sites, but is stronger and also associated with immune cells in the affected site. These results imply that functional interactions among SP, IL-33, and mast cells leading to VEGF release contribute to inflammatory conditions, such as the psoriasis, a nonallergic hyperproliferative skin inflammatory disorder with a neurogenic component.

Mitochondria distinguish granule-stored from de novo synthesized tumor necrosis factor secretion in human mast cells.

BACKGROUND: Mast cells are immune cells derived from hematopoietic precursors that mature in the tissue microenvironment. Mast cells are critical for allergic, immune and inflammatory processes, many of which involve tumor necrosis factor (TNF). These cells uniquely store TNF in their secretory granules. Upon stimulation, mast cells rapidly (30 min) secrete ß-hexosaminidase and granule-stored TNF through degranulation, but also increase TNF mRNA and release de novo synthesized TNF 24 h later. The regulation of these two distinct pathways is poorly understood. METHODS: Human LAD2 leukemic mast cells are stimulated by substance P. TNF secretion and gene expression were measured by ELISA and real-time PCR, and mitochondrial dynamics was observed in live cells under confocal microscopy. Cell energy consumption was measured in terms of oxygen consumption rate. RESULTS: Here, we show that granule-stored TNF is preformed, and its secretion from LAD2 mast cells stimulated by substance P (1) exhibits higher energy consumption and is inhibited by the mitochondrial ATP pump blocker oligomycin, (2) shows rapid increase in intracellular calcium levels, and (3) exhibits reversible mitochondrial translocation, from a perinuclear distribution to the cell surface, as compared to de novo synthesized TNF release induced by lipopolysaccharide. This mitochondrial translocation is confirmed using primary human umbilical cord blood-derived mast cells stimulated by an allergic trigger (IgE/streptavidin). CONCLUSION: Our findings indicate that unique mitochondrial functions distinguish granule-stored from newly synthesized TNF release from human mast cells, thus permitting the versatile involvement of mast cells in different biological processes.

Contribution of stress to asthma worsening through mast cell activation.

OBJECTIVE: To review the available evidence linking stress to asthma and to investigate whether mast cells contribute to the effect of stress through activation by corticotropin-releasing hormone (CRH). DATA SOURCE: The PubMed database was searched for articles (1998-2011) using the keywords anxiety, asthma, exacerbation, inflammation, mast cells, socioeconomic status, stress, violence, and worsening. STUDY SELECTION: Articles were selected based on their relevance to the topic, with emphasis on clinical or epidemiologic data linking stress to asthma and studies that offered possible explanations for how stress may affect asthma. RESULTS: Many articles point to an association between stress (socioeconomic status, interpersonal conflicts, emotional distress, terrorism) and asthma exacerbations but without any distinct pathogenetic mechanism. A few articles have reported reduced circulating cortisol and/or sensitivity to corticosteroids. We propose that mast cells, known to be involved in the pathophysiology of asthma, can be activated by CRH, which is secreted under stress in the lungs, leading to selective release of proinflammatory mediators. This effect may be augmented by neuropeptides or cytokines. CRH also reduces T-regulatory cell production of interleukin 10, which in known to inhibit allergic mast cell activation. CONCLUSION: More studies are required to investigate lung levels of CRH and selective mast cell mediators. Reducing stress and using CRH receptor antagonists and/or mast cell blockers may serve as possible new therapeutic approaches for asthma.

Perinatal stress, brain inflammation and risk of autism-review and proposal.

BACKGROUND: Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by varying deficits in social interactions, communication, and learning, as well as stereotypic behaviors. Despite the significant increase in ASD, there are few if any clues for its pathogenesis, hampering early detection or treatment. Premature babies are also more vulnerable to infections and inflammation leading to neurodevelopmental problems and higher risk of developing ASD. Many autism "susceptibility" genes have been identified, but "environmental" factors appear to play a significant role. Increasing evidence suggests that there are different ASD endophenotypes. DISCUSSION: We review relevant literature suggesting in utero inflammation can lead to preterm labor, while insufficient development of the gut-blood-brain barriers could permit exposure to potential neurotoxins. This risk apparently may increase in parents with "allergic" or autoimmune problems during gestation, or if they had been exposed to stressors. The presence of circulating auto-antibodies against fetal brain proteins in mothers is associated with higher risk of autism and suggests disruption of the blood-brain-barrier (BBB). A number of papers have reported increased brain expression or cerebrospinal fluid (CSF) levels of pro-inflammatory cytokines, especially TNF, which is preformed in mast cells. Recent evidence also indicates increased serum levels of the pro-inflammatory mast cell trigger neurotensin (NT), and of extracellular mitochondrial DNA (mtDNA), which is immunogenic. Gene mutations of phosphatase and tensin homolog (PTEN), the negative regulator of the mammalian target of rapamycin (mTOR), have been linked to higher risk of autism, but also to increased proliferation and function of mast cells. SUMMARY: Premature birth and susceptibility genes may make infants more vulnerable to allergic, environmental, infectious, or stress-related triggers that could stimulate mast cell release of pro-inflammatory and neurotoxic molecules, thus contributing to brain inflammation and ASD pathogenesis, at least in an endophenotype of ASD patients.

Human mast cell degranulation and preformed TNF secretion require mitochondrial translocation to exocytosis sites: relevance to atopic dermatitis.

BACKGROUND: Mast cells derive from hematopoietic cell precursors and participate in tissue allergic, immune, and inflammatory processes. They secrete many mediators, including preformed TNF, in response to allergic, neuropeptide, and environmental triggers. However, regulation of mast cell degranulation is not well understood. OBJECTIVE: We investigated the role of mitochondrial dynamics in degranulation of human cultured mast cells. METHODS: Human umbilical cord blood-derived mast cells (hCBMCs) and Laboratory of Allergic Diseases 2 (LAD2) mast cells were examined by confocal and differential interference contrast microscopy during activation by IgE/antigen and substance P (SP). Mast cells in control and atopic dermatitis (AD) skin were evaluated by transmission electron microscopy. LAD2 cells were pretreated with mitochondrial division inhibitor, a dynamin-related protein 1 (Drp1) inhibitor, and small interfering RNA for Drp1, which is necessary for mitochondrial fission and translocation. Calcineurin and Drp1 gene expression was analyzed in stimulated LAD2 cells and AD skin biopsies. RESULTS: Stimulation of hCBMCs with IgE/antigen or LAD2 cells with SP leads to rapid (30 minutes) secretion of preformed TNF. Degranulation is accompanied by mitochondrial translocation from a perinuclear location to exocytosis sites. Extracellular calcium depletion prevents these effects, indicating calcium requirement. The calcium-dependent calcineurin and Drp1 are activated 30 minutes after SP stimulation. Reduction of Drp1 activity by mitochondrial division inhibitor and decrease of Drp1 expression using small interfering RNA inhibit mitochondrial translocation, degranulation, and TNF secretion. Mitochondrial translocation is also evident by transmission electron microscopy in skin mast cells from AD biopsies, in which gene expression of calcineurin, Drp1, and SP is higher than in normal skin. CONCLUSION: Human mast cell degranulation requires mitochondrial dynamics, also implicated in AD.

A quality improvement initiative to reduce acid-suppressing medication exposure in the NICU.

BACKGROUND: Acid-suppressing medications (ASMs) are commonly prescribed in the neonatal intensive care unit (NICU), in particular among preterm infants, despite well-established adverse effects and little evidence to support efficacy. LOCAL PROBLEM: We sought to develop an initiative to reduce ASM exposure in our predominantly inborn level III NICU. Our specific aim was to reduce the number of nonindicated ASM prescriptions by 50% within a 12-month period. METHODS: Our multidisciplinary team developed an evidence-based guideline defining indications for ASM prescription in a level III NICU. Plan-do-study-act cycles included staff education, formal clinical practice guideline implementation, and implementation of standardized documentation tools in the electronic health record (EHR). Outcome measures were the number of nonindicated and total inpatient prescriptions started per month, duration of ASM prescription, and number of prescriptions continued after NICU discharge. Balancing measures were the number of patients started on thickened feeds and number of patients discharged home on nasogastric tube feeds. We used statistical process control and Pareto charts to assess these measures over a 12-month baseline period, 9-month implementation period, and 19-month post-implementation period spanning September 2017-December 2020. RESULTS: Nonindicated ASM prescriptions decreased from median 3 to 0 per month from the baseline to post-implementation period. Simultaneously, the median number of ASM prescriptions at discharge declined from 2 to 0 per month. The median duration of inpatient prescriptions declined from 23 to 7 days. Rates of patients started on thickened feeds and patients discharged home on nasogastric tube feeds remained stable throughout the study. CONCLUSION: Enactment of an evidence-based guideline was associated with a substantial decline in nonindicated ASM use in our NICU and a decline in duration of exposure to ASM's when prescribed. Our interventions proved effective in altering clinical practice and could be applied to other NICUs with similar patient populations aiming to reduce ASM use.

Bacille Calmette-Guérin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro.

Vaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology enables characterization of mechanisms of action, these tools have yet to be applied to infants, who are at high risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) and TB-unrelated infections via incompletely understood mechanisms. We employ mass-spectrometry-based metabolomics of blood plasma to profile BCG-induced infant responses in Guinea-Bissau in vivo and the US in vitro. BCG-induced lysophosphatidylcholines (LPCs) correlate with both TLR-agonist- and purified protein derivative (PPD, mycobacterial antigen)-induced blood cytokine production in vitro, raising the possibility that LPCs contribute to BCG immunogenicity. Analysis of an independent newborn cohort from The Gambia demonstrates shared vaccine-induced metabolites, such as phospholipids and sphingolipids. BCG-induced changes to the plasma lipidome and LPCs may contribute to its immunogenicity and inform the development of early life vaccines.

The Effects of COVID-19 Hospital Practices on Breastfeeding Initiation and Duration Postdischarge.

Background: Early in the COVID-19 pandemic, many birth hospitals separated SARS-CoV-2-positive mothers from their newborn infants and advised against breastfeeding to decrease postnatal SARS-CoV-2 transmission. Information on how these practices impacted breastfeeding postdischarge is limited. Objectives: In a statewide sample of SARS-CoV-2-positive mothers, we aimed to determine the extent to which (1) mother-infant separation and (2) a lack of breastfeeding initiation in-hospital were associated with breast milk feeding postdischarge. Design/Methods: From 11 birthing hospitals in Massachusetts, we identified 187 women who tested positive for SARS-CoV-2 from 14 days before to 72 hours after delivery (March 1-July 31, 2020) and their newborn infants. We abstracted chart data from the delivery hospitalization on main exposure variables (mother-infant separation, in-hospital breast milk feeding [expressed milk feeding and/or direct breastfeeding]) and from outpatient visits until 30 days postdischarge. We evaluated associations of in-hospital practices with outcomes up to 30 days postdischarge, adjusting for confounders using multivariable logistic and linear regression. Results: Mother-infant separation in-hospital was associated with a shorter duration of any breast milk feeding (regression coefficient estimate -5.29 days, 95% confidence intervals [CI] [-8.89 to -1.69]). Direct breastfeeding in-hospital was associated with higher odds of any breast milk feeding (adjusted odds ratios [AOR] 5.68, 95% CI [1.65-23.63]) and direct breastfeeding (AOR 8.19, 95% CI [2.99-24.91]) postdischarge; results were similar for any breast milk feeding in-hospital. Conclusions: Perinatal hospital care practices implemented early in the COVID-19 pandemic, specifically mother-infant separation and prevention of breast milk feeding initiation, were associated with adverse effects on breast milk feeding outcomes assessed up to 1 month postdischarge.

Human Newborn Monocytes Demonstrate Distinct BCG-Induced Primary and Trained Innate Cytokine Production and Metabolic Activation In Vitro.

Background: Newborns exhibit distinct immune responses and are at high risk of infection. Neonatal immunization with BCG, the live attenuated vaccine against tuberculosis (TB), is associated with broad protection against a range of unrelated pathogens, possibly reflecting vaccine-induced training of innate immune cells ("innate memory"). However, little is known regarding the impact of age on BCG-induced innate responses. Objective: Establish an age-specific human monocyte in vitro training platform to characterize and compare BCG-induced primary and memory cytokine responses and immunometabolic shifts. Design/Methods: Human neonatal and adult CD33-selected monocytes were stimulated for 24h with RPMI (control) or BCG (Danish strain) in 10% autologous serum, washed and cultured for 5 additional days, prior to re-stimulation with the TLR4 agonist LPS for another 24h. Supernatants were collected at Day 1 (D1) to measure primary innate responses and at Day 7 (D7) to assess memory innate responses by ELISA and multiplex cytokine and chemokine assays. Lactate, a signature metabolite increased during trained immunity, was measured by colorimetric assay. Results: Cytokine production by human monocytes differed significantly by age at D1 (primary, BCG 1:750 and 1:100 vol/vol, p<0.0001) and D7 (innate memory response, BCG 1:100 vol/vol, p<0.05). Compared to RPMI control, newborn monocytes demonstrated greater TNF (1:100, 1:10 vol/vol, p<0.01) and IL-12p40 (1:100 vol/vol, p<0.05) production than adult monocytes (1:100, p<0.05). At D7, while BCG-trained adult monocytes, as previously reported, demonstrated enhanced LPS-induced TNF production, BCG-trained newborn monocytes demonstrated tolerization, as evidenced by significantly diminished subsequent LPS-induced TNF (RPMI vs. BCG 1:10, p <0.01), IL-10 and CCL5 production (p<0.05). With the exception of IL-1RA production by newborn monocytes, BCG-induced monocyte production of D1 cytokines/chemokines was inversely correlated with D7 LPS-induced TNF in both age groups (p<0.0001). Compared to BCG-trained adult monocytes, newborn monocytes demonstrated markedly impaired BCG-induced production of lactate, a metabolite implicated in immune training in adults. Conclusions: BCG-induced human monocyte primary- and memory-innate cytokine responses were age-dependent and accompanied by distinct immunometabolic shifts that impact both glycolysis and training. Our results suggest that immune ontogeny may shape innate responses to live attenuated vaccines, suggesting age-specific approaches to leverage innate training for broad protection against infection.

Leveraging the Massachusetts perinatal quality collaborative to address the COVID-19 pandemic among diverse populations.

OBJECTIVE: We leveraged the Massachusetts perinatal quality collaborative (PQC) to address the COVID-19 pandemic. Our goals were to: (1) implement perinatal practices thought to reduce mother-to-infant SARS-CoV-2 transmission while limiting disruption of health-promoting practices and (2) do so without inequities attributable to race/ethnicity, language status, and social vulnerability. METHODS: Main outcomes were cesarean and preterm delivery, rooming-in, and breastfeeding. We examined changes over time overall and according to race/ethnicity, language status, and social vulnerability from 03/20-07/20 at 11 hospitals. RESULTS: Of 255 mothers with SARS-CoV-2, 67% were black or Hispanic and 47% were non-English speaking. Cesarean decreased (49% to 35%), while rooming-in (55% to 86%) and breastfeeding (53% to 72%) increased. These changes did not differ by race/ethnicity, language, or social vulnerability. CONCLUSIONS: Leveraging the Massachusetts PQC led to rapid changes in perinatal care during the COVID-19 crisis in a short time, representing a novel use of statewide PQC structures.

Association of Maternal Perinatal SARS-CoV-2 Infection With Neonatal Outcomes During the COVID-19 Pandemic in Massachusetts.

Importance: The incidence of mother-to-newborn SARS-CoV-2 transmission appears low and may be associated with biological and social factors. However, data are limited on the factors associated with neonatal clinical or viral testing outcomes. Objective: To ascertain the percentage of neonates who were born to mothers with positive SARS-CoV-2 test results during the birth hospitalization, the clinical and sociodemographic factors associated with neonatal test result positivity, and the clinical and virological outcomes for newborns during hospitalization and 30 days after discharge. Design, Setting, and Participants: This multicenter cohort study included 11 academic or community hospitals in Massachusetts and mother-neonate dyads whose delivery and discharge occurred between March 1, 2020, and July 31, 2020. Eligible dyads were identified at each participating hospital through local COVID-19 surveillance and infection control systems. Neonates were born to mothers with positive SARS-CoV-2 test results within 14 days before to 72 hours after delivery, and neonates were followed up for 30 days after birth hospital discharge. Exposures: Hypothesized maternal risk factors in neonatal test result positivity included maternal COVID-19 symptoms, vaginal delivery, rooming-in practice, Black race or Hispanic ethnicity, and zip code-derived social vulnerability index. Delivery indicated by worsening maternal COVID-19 symptoms was hypothesized to increase the risk of adverse neonatal health outcomes. Main Outcomes and Measures: Primary outcomes for neonates were (1) positive SARS-CoV-2 test results, (2) indicators of adverse health, and (3) clinical signs and viral testing. Test result positivity was defined as at least 1 positive result on a specimen obtained by nasopharyngeal swab using a polymerase chain reaction-based method. Clinical and testing data were obtained from electronic medical records of nonroutine health care visits within 30 days after hospital discharge. Results: The cohort included 255 neonates (mean [SD] gestational age at birth, 37.9 [2.6] weeks; 62 [24.3%] with low birth weight or preterm delivery) with 250 mothers (mean [SD] age, 30.4 [6.3] years; 121 [48.4%] were of Hispanic ethnicity). Of the 255 neonates who were born to mothers with SARS-CoV-2 infection, 225 (88.2%) were tested for SARS-CoV-2 and 5 (2.2%) had positive results during the birth hospitalization. High maternal social vulnerability was associated with higher likelihood of neonatal test result positivity (adjusted odds ratio, 4.95; 95% CI, 1.53-16.01; P = .008), adjusted for maternal COVID-19 symptoms, delivery mode, and rooming-in practice. Adverse outcomes during hospitalization were associated with preterm delivery indicated by worsening maternal COVID-19 symptoms. Of the 151 newborns with follow-up data, 28 had nonroutine clinical visits, 7 underwent SARS-CoV-2 testing, and 1 had a positive result. Conclusions and Relevance: The findings emphasize the importance of both biological and social factors in perinatal SARS-CoV-2 infection outcomes. Newborns exposed to SARS-CoV-2 were at risk for both direct and indirect adverse health outcomes, supporting efforts of ongoing surveillance of the virus and long-term follow-up.