Perspective of Indonesian Pediatricians on the Role of PrebioticSupplemented Formula towards Immunity, Growth and Development in Preterm Infants: A Preliminary Data

ABSTRACT Background: Immature immune system in preterm infants is associated with gut dysbiosis and poses significant health risks to their growth and development. Current guidelines for managing preterm infants focuses solely on macro- and micronutrients, whereas preterm infants’ gastrointestinal system requires optimalization to support nutrient absorption. Studies on the positive impacts of prebiotics as supplements have been conducted, but has not been implemented in Indonesia. Indonesian pediatricians’ perspective on these findings needs to be assessed. Objectives: To describe the perspectives of Indonesian pediatricians on the role of gut microbiota balance in supporting immunity, growth, and development of preterm infants, and the role of breastmilk and prebiotic-supplemented formula in optimizing gut microbiota balance. Methods: A cross-sectional study was conducted on 114 Indonesian pediatricians using a previously-validated and previously-used questionnaire on the role of gut microbiota balance on preterm infants, as well as the role of breastmilk and prebiotic-supplemented formula in optimizing gut microbiota balance. Results: Most respondents agreed that gut microbiota balance supports immunity, growth, and development of preterm infants. Respondents also agreed that breastmilk contains nutrients that support gut microbiota balance and when breastmilk becomes unavailable, prebiotic-supplemented formula can be given as substitute. Conclusions: Indonesian pediatricians considered gut microbiota balance to be important for immunity, growth, and development of preterm infants, and breastmilk to be the most ideal source of nutrition for preterm infants in optimizing gut microbiota balance. When breastmilk is unavailable, prebiotic-supplemented formula can be considered as an alternative.

Preterm Birth and Inflammation

Half of all preterm births are caused or triggered by an inflammation at fetal-maternal interface. The sustained inflammation that preterm neonates are exposed is generated by maternal chorioamnionitis, premature rupture of membranes. This inflammation will facilitate the preterm labor, but also plays an important role in development of disease like: bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, intraventricular hemorrhage and periventricular leukomalacia. Preterm neonates have immature immune system. The fragile co-regulation between immune defense mechanisms and immunosuppression (tolerance) is often disturbed at this category of patients. They are at high risk of sepsis due to this imbalance between the defense and suppression mechanisms but also several injuries can contribute to the onset or perpetuation of sustained inflammation. They experience altered antigen exposure in contact with hospital-specific germs, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia. This is more significant at extremely preterm infants less than 28 weeks of gestation as they have not developed adaptation processes to tolerate maternal and self-antigens.

REVIEW ARTICLE ABOUT PERINATALAND NEONATAL MANAGEMENT FOR THE PREVENTION AND CONTROL OF THE 2019 NOVEL CORONAVIRUS INFECTION

An epidemic of new coronavirus 2019 (COVID-19) has emerged in China since December 2019. WHO declared it as a pandemic on March 2020 as it has spread worldwide. Several cases among neonate were observed with rst reported 36 hours after birth. Due to the possibility of the infection and the immature immune system of the neonate there should be preventive and control measures at Neonatal Intensive Care Units. According to WHO guideline and other published articles in COVID-19 in infants and neonate a technical working group including community physician and Pediatricians has put measures for clinical management, prevention and control of COVID-19 in neonates.

Ionizable lipid nanoparticles for in utero mRNA delivery

Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)–mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, and intestines with higher efficiency and safety compared to benchmark delivery systems, DLin-MC3-DMA and jetPEI. We demonstrate that LNPs can deliver mRNAs to induce hepatic production of therapeutic secreted proteins. These LNPs may provide a platform for in utero mRNA delivery for protein replacement and gene editing.

Inguinal abscess in twin infants

Inguinal abscess is uncommon in infants and children. Majority of cases in the infantile period is primary and they present as leg or groin swelling, limitation of limb movement and pain. The source of microorganism is from the haematogenous spread of normal flora of the skin due to immature immune system. Ultrasound is the investigation of choice which confirms the diagnosis and delineates the areas of collection. Antibiotic alone is insufficient in most cases and drainage is required. Delayed treatment and inadequate drainage carry a high risk of mortality and sequelae due to damage to the underlying joint. We present 2 cases of primary inguinal abscess in twin infants who presented at 1 month and 2 months of age correspondingly, in whom early diagnosis and management lead to quick recovery.

The Determinants of the Human Milk Metabolome and Its Role in Infant Health

Human milk is needed for optimal growth as it satisfies both the nutritional and biological needs of an infant. The established relationship between breastfeeding and an infant’s health is attributable to the nutritional and non-nutritional, functional components of human milk including metabolites such as the lipids, amino acids, biogenic amines and carbohydrates. These components have diverse roles, including protecting the infant against infections and guiding the development of the infant’s immature immune system. In this review, we provide an in-depth and updated insight into the immune modulatory and anti-infective role of human milk metabolites and their effects on infant health and development. We also review the literature on potential determinants of the human milk metabolome, including maternal infectious diseases such as human immunodeficiency virus and mastitis.

Age of first infection across a range of parasite taxa in a wild mammalian population

Newborn mammals have an immature immune system that cannot sufficiently protect them against infectious diseases. However, variation in the effectiveness of maternal immunity against different parasites may couple with temporal trends in parasite exposure to influence disparities in the timing of infection risk. Determining the relationship between age and infection risk is critical in identifying the portion of a host population that contributes to parasite dynamics, as well as the parasites that regulate host recruitment. However, there are no data directly identifying timing of first infection among parasites in wildlife. Here, we took advantage of a longitudinal dataset, tracking infection status by viruses, bacteria, protists and gastro-intestinal worms in a herd of African buffalo ( Syncerus caffer ) to ask: how does age of first infection differ among parasite taxa? We found distinct differences in the age of first infection among parasites that aligned with the mode of transmission and parasite taxonomy. Specifically, we found that tick-borne and environmentally transmitted protists were acquired earlier than directly transmitted bacteria and viruses. These results emphasize the importance of understanding infection risk in juveniles, especially in host species where juveniles are purported to sustain parasite persistence and/or where mortality rates of juveniles influence population dynamics.

Sialylated Oligosaccharides and Glycoconjugates of Human Milk. The Impact on Infant and Newborn Protection, Development and Well-Being

Human milk not only has nutritional value, but also provides a wide range of biologically active molecules, which are adapted to meet the needs of newborns and infants. Mother’s milk is a source of sialylated oligosaccharides and glycans that are attached to proteins and lipids, whose concentrations and composition are unique. Sialylated human milk glycoconjugates and oligosaccharides enrich the newborn immature immune system and are crucial for their proper development and well-being. Some of the milk sialylated oligosaccharide structures can locally exert biologically active effects in the newborn’s and infant’s gut. Sialylated molecules of human milk can be recognized and bound by sialic acid-dependent pathogens and inhibit their adhesion to the epithelial cells of newborns and infants. A small amount of intact sialylated oligosaccharides can be absorbed from the intestine and remain in the newborn’s circulation in concentrations high enough to modulate the immunological system at the cellular level and facilitate proper brain development during infancy. Conclusion: The review summarizes the current state of knowledge on sialylated human milk oligosaccharides and glycoconjugates, discusses the significance of sialylated structures of human milk in newborn protection and development, and presents the advantages of human milk over infant formula.

Animal model investigation suggests betamethasone alters the pharmacokinetics of amikacin

Corticosteroids, such as betamethasone, are sometimes administered to women who are at risk of pre-term delivery. These corticosteroids cross the placenta to the fetus and decrease respiratory distress syndrome in preterm newborns. Preterm newborns are often susceptible to infections partly due to their immature immune system. Amikacin is one of the aminoglycosides used in the treatment of newborn infections. There is, however, a dearth of information on the effect of prenatal corticosteroids on the disposition of aminoglycosides administered to newborns days later. We evaluated the effect of pre-administration of betamethasone on the disposition of amikacin, 72 h after last dose of betamethasone, using an animal model. The pharmacokinetic parameters of rats administered betamethasone followed by amikacin vis-a-vis rats administered saline followed by amikacin were as follows: Cmax; 16.6 μmol L-1 vs. 31.4 μmol L-1, AUC0→8; 26.8 μmol h L-1 vs. 153.5 μmol h L-1, Ke; 0.26 h-1 vs. 0.18 h-1, and t1/2; 2.6 h vs. 3.9 h, respectively. About a 1.5-fold increase in the elimination of amikacin was observed in the Sprague-Dawley rats pre-treated with betamethasone compared with those pre-treated with saline. This ultimately led to differences in the other pharmacokinetic parameters amongst the two groups of rats. Although an animal model investigation showed some level of interaction, a follow-up study in preterm newborns where possible interaction of the two drugs is studied later than Day 1, is recommended.

INFANT’S SKIN AND CARE NEEDS WITH SPECIAL CONSIDERATION TO FORMULATION ADDITIVES

Infancy is the time of adaptation from intrauterine life to the rather dry and cold, environment. Infant skin is more sensitive due to the immature immune system, hence, effortlessly prone to complications. Children from different age groups face diverse skin problems such as cradle cap, infant eczema, diaper rash, prickly heat, and many more. During early infancy, the products such as mild cleansers and lotions are used, and later, massage oils, creams, lotions, soaps, bubble bath, and other products are utilized for another few years, as a part of routine care. The preterm infants are more prone to skin damage and percutaneous toxicity from topically applied products. The ingredients incorporated in infant care products require special attention while choosing a product for them. Topical application of any such product requires thorough screening for potentially harmful ingredients before its exposure to the infant’s skin. Products used for infants should be safe and restricted of fragrance, coloring agents, parabens, plant oils, extracts, and other obnoxious ingredients. The literature is flooded with the list of safer excipients that can be utilized for the development of skin care products for infants and children.