Early versus late caffeine and/or non-steroidal anti-inflammatory drugs (NSAIDS) for prevention of intermittent hypoxia-induced neuroinflammation in the neonatal rat.

Preterm infants often experience frequent intermittent hypoxia (IH) episodes which are associated with neuroinflammation. We tested the hypotheses that early caffeine and/or non-steroidal inflammatory drugs (NSAIDs) confer superior therapeutic benefits for protection against IH-induced neuroinflammation than late treatment. Newborn rats were exposed to IH or hyperoxia (50% O2) from birth (P0) to P14. For early treatment, the pups were administered: 1) daily caffeine (Caff) citrate (Cafcit, 20 mg/kg IP loading on P0, followed by 5 mg/kg from P1-P14); 2) ketorolac (Keto) topical ocular solution in both eyes from P0 to P14; 3) ibuprofen (Ibu, Neoprofen, 10 mg/kg loading dose on P0 followed by 5 mg/kg/day on P1 and P2); 4) Caff+Keto co-treatment; 5) Caff+Ibu co-treatment; or 6) equivalent volume saline (Sal). On P14, animals were placed in room air (RA) with no further treatment until P21. For late treatment, pups were exposed from P0 to P14, then placed in RA during which they received similar treatments from P15-P21 (Sal, Caff, and/or Keto), or P15-P17 (Ibu). RA controls were similarly treated. At P21, whole brains were assessed for histopathology, apoptosis, myelination, and biomarkers of inflammation. IH caused significant brain injury and hemorrhage, inflammation, reduced myelination, and apoptosis. Early treatment with Caff alone or in combination with NSAIDs conferred better neuroprotection against IH-induced damage than late treatment. Early postnatal treatment during a critical time of brain development, may be preferable for the prevention of IH-induced brain injury in preterm infants.

Factors Influencing Neonatal Gut Microbiome and Health with a Focus on Necrotizing Enterocolitis.

Maturational changes in the gut start in utero and rapidly progress after birth, with some functions becoming fully developed several months or years post birth including the acquisition of a full gut microbiome, which is made up of trillions of bacteria of thousands of species. Many factors influence the normal development of the neonatal and infantile microbiome, resulting in dysbiosis, which is associated with various interventions used for neonatal morbidities and survival. Extremely low gestational age neonates (<28 weeks' gestation) frequently experience recurring arterial oxygen desaturations, or apneas, during the first few weeks of life. Apnea, or the cessation of breathing lasting 15-20 s or more, occurs due to immature respiratory control and is commonly associated with intermittent hypoxia (IH). Chronic IH induces oxygen radical diseases of the neonate, including necrotizing enterocolitis (NEC), the most common and devastating gastrointestinal disease in preterm infants. NEC is associated with an immature intestinal structure and function and involves dysbiosis of the gut microbiome, inflammation, and necrosis of the intestinal mucosal layer. This review describes the factors that influence the neonatal gut microbiome and dysbiosis, which predispose preterm infants to NEC. Current and future management and therapies, including the avoidance of dysbiosis, the use of a human milk diet, probiotics, prebiotics, synbiotics, restricted antibiotics, and fecal transplantation, for the prevention of NEC and the promotion of a healthy gut microbiome are also reviewed. Interventions directed at boosting endogenous and/or exogenous antioxidant supplementation may not only help with prevention, but may also lessen the severity or shorten the course of the disease.

Quality Improvement Project to Improve Hand Hygiene Compliance in a Level III Neonatal Intensive Care Unit.

This quality improvement project aimed to improve hand hygiene (HH) compliance in a Level III Neonatal Intensive Care Unit. The project was conducted over three Plan-Do-Study-Act (PDSA) cycles, with each cycle lasting two months. The interventions included healthcare worker (HCW) education on HH, repetition of education, and immediate feedback to HCWs. Compliance data were collected through covert observations of HCWs in the NICU. The overall compliance rate increased from 31.56% at baseline to 46.64% after the third PDSA cycle. The HH compliance was noted to be relatively low after touching patient care surroundings, at entry and exit from the NICU main unit, before wearing gloves and after removing gloves, at baseline and throughout the three PDSA cycles. HCW education alone did not result in significant improvements, highlighting the need for additional interventions. The study underscores the importance of involving NICU leadership and providing immediate feedback to promote HH compliance. Further efforts should focus on addressing the false sense of security associated with glove usage among HCWs, individual rewards and involving the healthcare staff in the shared goal of increasing HH compliance. Consideration of workload metrics and their impact on compliance could steer future interventions.

The Effect of Breastfeeding in the First Hour and Rooming-In of Low-Income, Multi-Ethnic Mothers on In-Hospital, One and Three Month High Breastfeeding Intensity.

Despite the known benefits of exclusive breastfeeding, the value of Baby-Friendly Hospital Interventions in increasing breastfeeding rates has been challenged, particularly the interventions of breastfeeding in the first hour of life and rooming-in. This study aimed to measure the association of breastfeeding in the first hour of life and rooming-in with high breastfeeding intensity of low-income, multi-ethnic mothers intending to breastfeed. A prospective, longitudinal cohort study was performed on 149 postpartum mothers who intended to breastfeed their infants. Structured interviews were performed at birth and one and three months. Breastfeeding intensity was defined as the percentage of all feedings that were breast milk, and high breastfeeding intensity was defined as a breastfeeding intensity >80%. The data were analyzed by chi-square, t-test, binary logistic regression analysis, and multivariate logistic regression analysis. Breastfeeding in the first hour was associated with increased high breastfeeding intensity in the hospital (AOR = 11.6, 95% CI = 4.7-28.6) and at one month (AOR = 3.6, 95% CI = 1.6-7.7), but not at three months. Rooming-in was associated with increased high breastfeeding intensity in the hospital (AOR 9.3, 95% CI = 3.6-23.7) and at one month (AOR = 2.4 (1.1-5.3) and three months (AOR 2.7, 95% CI 1.2-6.3). Breastfeeding in the first hour and rooming-in are associated with increasing breastfeeding and should be incorporated into practice.

Impact of Donor Human Milk in an Urban NICU Population.

The American Academy of Pediatrics recommends the use of donor human milk in infants when mother's own milk is not available. Our objective was to analyze whether the use of donor human milk in preterm, very-low-birth-weight (VLBW, <1500 g) infants affected the rates of necrotizing enterocolitis, duration of parenteral nutrition (PN), growth, culture-positive sepsis, length of hospital stay, and mortality in an urban NICU population with low exclusive breast-feeding rates. A retrospective cohort study was conducted comparing two 2-year epochs of VLBW neonates before and after the introduction of donor breast milk in our neonatal intensive care unit (NICU). With the introduction of donor human milk, there was a significant reduction in the rate of necrotizing enterocolitis (NEC) (5% vs. 13%; p = 0.04) and less severe NEC as defined by Stage III based on the Modified Bell Staging Criteria (10% to 3%; p = 0.04). In the donor milk era, there was earlier initiation of enteral feeding (2.69 days vs. 3.84; p = 0.006) and a more rapid return to birthweight (9.5 days. 10.9 days; p = 0.006). In this study, a change in practice to the use of donor breast milk in a population with low rates of human milk provision was associated with earlier initiation of enteral feeding, faster return to birth weight, and a reduced incidence of NEC.

Evidence Base for 2022 Updated Recommendations for a Safe Infant Sleeping Environment to Reduce the Risk of Sleep-Related Infant Deaths.

Every year in the United States, approximately 3500 infants die of sleep-related infant deaths, including sudden infant death syndrome (SIDS) (International Statistical Classification of Diseases and Related Health Problems 10th Revision [ICD-10] R95), ill-defined deaths (ICD-10 R99), and accidental suffocation and strangulation in bed (ICD-10 W75). After a substantial decline in sleep-related deaths in the 1990s, the overall death rate attributable to sleep-related infant deaths have remained stagnant since 2000, and disparities persist. The triple risk model proposes that SIDS occurs when an infant with intrinsic vulnerability (often manifested by impaired arousal, cardiorespiratory, and/or autonomic responses) undergoes an exogenous trigger event (eg, exposure to an unsafe sleeping environment) during a critical developmental period. The American Academy of Pediatrics recommends a safe sleep environment to reduce the risk of all sleep-related deaths. This includes supine positioning; use of a firm, noninclined sleep surface; room sharing without bed sharing; and avoidance of soft bedding and overheating. Additional recommendations for SIDS risk reduction include human milk feeding; avoidance of exposure to nicotine, alcohol, marijuana, opioids, and illicit drugs; routine immunization; and use of a pacifier. New recommendations are presented regarding noninclined sleep surfaces, short-term emergency sleep locations, use of cardboard boxes as a sleep location, bed sharing, substance use, home cardiorespiratory monitors, and tummy time. In addition, additional information to assist parents, physicians, and nonphysician clinicians in assessing the risk of specific bed-sharing situations is included. The recommendations and strength of evidence for each recommendation are published in the accompanying policy statement, which is included in this issue.

Sleep-Related Infant Deaths: Updated 2022 Recommendations for Reducing Infant Deaths in the Sleep Environment.

Each year in the United States, ∼3500 infants die of sleep-related infant deaths, including sudden infant death syndrome (SIDS) (International Classification of Diseases, 10th Revision [ICD-10] R95), ill-defined deaths (ICD-10 R99), and accidental suffocation and strangulation in bed (ICD-10 W75). After a substantial decline in sleep-related deaths in the 1990s, the overall death rate attributable to sleep-related infant deaths has remained stagnant since 2000, and disparities persist. The triple risk model proposes that SIDS occurs when an infant with intrinsic vulnerability (often manifested by impaired arousal, cardiorespiratory, and/or autonomic responses) undergoes an exogenous trigger event (eg, exposure to an unsafe sleeping environment) during a critical developmental period. The American Academy of Pediatrics recommends a safe sleep environment to reduce the risk of all sleep-related deaths. This includes supine positioning; use of a firm, noninclined sleep surface; room sharing without bed sharing; and avoidance of soft bedding and overheating. Additional recommendations for SIDS risk reduction include human milk feeding; avoidance of exposure to nicotine, alcohol, marijuana, opioids, and illicit drugs; routine immunization; and use of a pacifier. New recommendations are presented regarding noninclined sleep surfaces, short-term emergency sleep locations, use of cardboard boxes as a sleep location, bed sharing, substance use, home cardiorespiratory monitors, and tummy time. Additional information to assist parents, physicians, and nonphysician clinicians in assessing the risk of specific bed-sharing situations is also included. The recommendations and strength of evidence for each recommendation are included in this policy statement. The rationale for these recommendations is discussed in detail in the accompanying technical report.

Neonatal Resuscitation in Low Volume Hospital Settings.

The vast majority of term newborns will begin breathing and make a successful transition to extrauterine life, whereas a small percentage of infants will require some intervention immediately after birth by a skilled provider [...].

Vitamin K and the Newborn Infant.

Intramuscular administration of vitamin K for prevention of vitamin K deficiency bleeding (VKDB) has been a standard of care since the American Academy of Pediatrics recommended it in 1961. Despite the success of prevention of VKDB with vitamin K administration, the incidence of VKDB appears to be on the rise. This increase in incidence of VKDB is attributable to parental refusal as well as lowered efficacy of alternate methods of administration. The aim of this statement is to discuss the current knowledge of prevention of VKDB with respect to the term and preterm infant and address parental concerns regarding vitamin K administration.

Pharmacodynamic Effects of Standard versus High Caffeine Doses in the Developing Brain of Neonatal Rats Exposed to Intermittent Hypoxia.

(1) Background: Caffeine citrate, at standard doses, is effective for reducing the incidence of apnea of prematurity (AOP) and may confer neuroprotection and decrease neonatal morbidities in extremely low gestational age neonates (ELGANs) requiring oxygen therapy. We tested the hypothesis that high-dose caffeine (HiC) has no adverse effects on the neonatal brain. (2) Methods: Newborn rat pups were randomized to room air (RA), hyperoxia (Hx) or neonatal intermittent hypoxia (IH), from birth (P0) to P14 during which they received intraperitoneal injections of LoC (20 mg/kg on P0; 5 mg/kg/day on P1-P14), HiC (80 mg/kg; 20 mg/kg), or equivalent volume saline. Blood gases, histopathology, myelin and neuronal integrity, and adenosine receptor reactivity were assessed. (3) Results: Caffeine treatment in Hx influenced blood gases more than treatment in neonatal IH. Exposure to neonatal IH resulted in hemorrhage and higher brain width, particularly in layer 2 of the cerebral cortex. Both caffeine doses increased brain width in RA, but layer 2 was increased only with HiC. HiC decreased oxidative stress more effectively than LoC, and both doses reduced apoptosis biomarkers. In RA, both caffeine doses improved myelination, but the effect was abolished in Hx and neonatal IH. Similarly, both doses inhibited adenosine 1A receptor in all oxygen environments, but adenosine 2A receptor was inhibited only in RA and Hx. (4) Conclusions: Caffeine, even at high doses, when administered in normoxia, can confer neuroprotection, evidenced by reductions in oxidative stress, hypermyelination, and increased Golgi bodies. However, varying oxygen environments, such as Hx or neonatal IH, may alter and modify pharmacodynamic actions of caffeine and may even override the benefits caffeine.

Impact of evolving practices on SARS-CoV-2 positive mothers and their newborns in the largest public healthcare system in America.

OBJECTIVE: The impact of evolving guidelines and clinical practices on SARS-CoV-2-positive dyads across New York City Health and Hospitals during the early peak of COVID-19. DESIGN: A retrospective cohort study of positive-positive (P/P), positive-negative (P/N), and positive-untested (P/U) dyads delivered from March 1 to May 9, 2020. Wilcoxon rank sum, Chi-squared, and Fisher exact tests were used to analyze demographics, clinical variables, and system-wide management practices. RESULT: A total of 2598 mothers delivered. 23.8% (286/1198) of mothers tested for SARS-CoV-2 were positive. 89.7% (260/290) newborns of SARS-CoV-2-positive mothers were tested and 11 were positive. Positive-positive newborns were more likely to be breastfed (81%), be admitted to NICU, and have longer length of stay (7.5 days) than P/N and P/U newborns. CONCLUSION: Our study shows that varied testing, feeding, and isolation practices resulted in favorable short-term outcomes for SARS-CoV-2-positive mothers and their newborns. High-risk populations can be safely and effectively treated in resource-limited environments.

Routine Neuroimaging of the Preterm Brain.

Neuroimaging of the preterm infant is a common assessment performed in the NICU. Timely and focused studies can be used for diagnostic, therapeutic, and prognostic information. However, significant variability exists among neonatal units as to which modalities are used and when imaging studies are obtained. Appropriate timing and selection of neuroimaging studies can help identify neonates with brain injury who may require therapeutic intervention or who may be at risk for neurodevelopmental impairment. This clinical report reviews the different modalities of imaging broadly available to the clinician. Evidence-based indications for each modality, optimal timing of examinations, and prognostic value are discussed.

Factors Influencing Paternal Attachment Among Preterm Infants in an Urban Neonatal Intensive Care Unit.

The aim of this study is to elucidate factors that may influence paternal attachment to preterm infants in an urban hospital setting. Fathers of preterm infants admitted to a level III neonatal intensive care unit (NICU) were eligible for this study. The Paternal Postnatal Attachment Scale (PPAS) is a questionnaire that invokes paternal attachment in five domains: patience, tolerance, pleasure, affection and pride. Clinical and demographic data were collected along with the PPAS to identify factors influencing paternal attachment. Infants studied were 28.1 ± 3.3 weeks gestational age with a birth weight of 1,070 ± 70 grams. Paternal age was 29.2 ± 6.6 years. Infants of fathers who scored in the lowest quartile of attachment were significantly smaller (756 ± 17 grams vs 1,210 ± 76 grams, p = 0.03) and more immature (26.4 ± 1.9 weeks vs 28.8 ± 3.5 weeks, p = 0.04) than infants of fathers with higher attachment scores. Subscores of patience and tolerance (p = 0.05) and pleasure in interaction (p = 0.01) were also significantly lower although there was no significant difference in subscores of affection and pride (p = 0.36). There were no significant differences between attachment scores for paternal age, educational level, marital status, number of children or breastfeeding status. Paternal attachment scores appear to be dependent on infant factors, such as birth weight and gestational age, rather than paternal or demographic factors.

Breastfeeding Intensity and Exclusivity of Early Term Infants at Birth and 1 Month.

Objective: To examine breastfeeding exclusivity and intensity of early term (ET) infants, born at 37-38 weeks, and term infants, born at 39-41 weeks, during the postpartum hospitalization and the first month of life. Materials and Methods: This was a prospective cohort study of 358 mothers of ET and term infants during the first 72 hours after birth and at 1 month of age. Logistic analysis was used to calculate unadjusted and adjusted odds ratios (aORs) and control for confounding variables. Results: ET infants had significantly lower breastfeeding in the first hour (aOR = 0.43, 95% confidence interval [CI] = 0.21-0.87), lower exclusive breastfeeding in the hospital and at 1 month (aOR = 0.46, 95% CI = 0.27-0.71 and aOR = 0.40, 95% CI = 0.22-0.71), and lower rates of high breastfeeding intensity in the hospital and at 1 month (aOR = 0.39, 95% CI = 0.22-0.71 and aOR = 0.33, 95% CI = 0.15-0.72), after controlling for confounding variables. ET infants had more emergency room (ER) visits in the first month (OR = 7.6, 95% CI = 1.01-60.6), and all ET infants who had ER visits were exclusively breastfed. Conclusions: ET infants had lower breastfeeding in the hospital and at 1 month. They should be regarded as a group at risk for breastfeeding challenges and infant morbidity.

Attitudes towards Donor Breast Milk in an Inner City Population.

Objective. The purpose of our study was to identify attitudes towards donor breast milk in our population and identify barriers to its acceptance. Methods. The study sample was comprised of a convenience sample of 174 postpartum women. A questionnaire consisting of demographic information and 12 questions relating to attitudes and understanding of donor breast milk was administered. Results. Among the mothers surveyed, 34% were aware of the use of donor breast milk and donor milk banks. 62% of mothers preferred the use of formula compared to donor breast milk if they were unable to provide their own breast milk. Educational level did play a role with 64% of mothers with education beyond high school believing that donor breast milk was beneficial for newborns as opposed to 46% with a high school education or less (p=0.02). US born mothers were more likely to have heard about donor breast milk (47% versus 29%, p=0.025) than foreign born mothers although they were less likely to believe it was a better option for feeding than formula (22.7% versus 43%, p=.016). Mothers with infants in the NICU were more likely than mothers of well babies to accept milk from a milk bank rather than a relative or friend (81% versus 39%, p≤0.001). Conclusion. Although the beneficial effects of donor breast milk are well established in the scientific community, there remains a lack of awareness and a major discrepancy in the understanding and acceptance of it within our community. Education on the benefits of mother's own milk as well as donor breast milk and milk banks is an important public health initiative needed to increase acceptance of human milk as the optimal form of nutrition in infants.