Early and exclusive enteral nutrition in infants born very preterm.

OBJECTIVE: To characterise the effects of early and exclusive enteral nutrition with either maternal or donor milk in infants born very preterm (280/7-326/7 weeks of gestation). DESIGN: Parallel-group, unmasked randomised controlled trial. SETTING: Regional, tertiary neonatal intensive care unit. PARTICIPANTS: 102 infants born very preterm between 2021 and 2022 (51 in each group). INTERVENTION: Infants randomised to the intervention group received 60-80 mL/kg/day within the first 36 hours after birth. Infants randomised to the control group received 20-30 mL/kg/day (standard trophic feeding volumes). MAIN OUTCOME MEASURES: The primary outcome was the number of full enteral feeding days (>150 mL/kg/day) in the first 28 days after birth. Secondary outcomes included growth and body composition at the end of the first two postnatal weeks, and length of hospitalisation. RESULTS: The mean birth weight was 1477 g (SD: 334). Half of the infants were male, and 44% were black. Early and exclusive enteral nutrition increased the number of full enteral feeding days (+2; 0-2 days; p=0.004), the fat-free mass-for-age z-scores at postnatal day 14 (+0.5; 0.1-1.0; p=0.02) and the length-for-age z-scores at the time of hospital discharge (+0.6; 0.2-1.0; p=0.002). Hospitalisation costs differed between groups (mean difference favouring the intervention group: -$28 754; -$647 to -$56 861; p=0.04). CONCLUSIONS: In infants born very preterm, early and exclusive enteral nutrition increases the number of full enteral feeding days. This feeding practice may also improve fat-free mass accretion, increase length and reduce hospitalisation costs. TRIAL REGISTRATION NUMBER: NCT04337710.

A household survey of intrafamily norovirus transmission.

Norovirus (NoV) is a leading cause of epidemic and sporadic gastroenteritis in people of all ages. Humans are the primary source of NoV and household contact is one of the risk factors for NoV transmission. However, the mechanisms underlying person-to-person NoV transmission are poorly understood. Here we conducted a survey to profile the frequency and characteristics of intrafamily NoV transmission. Stool samples were collected every week from three households between 2016 and 2020; the total number of samples was 1105. The detection of NoV and the genotyping were performed by reverse transcription-polymerase chain reaction targeting the capsid region and direct sequencing methods. NoV was detected in 3.4% of all samples. Eight NoV genotypes were identified. The most common genotype was GII.17, followed in order by GII.6, GI.6, GII.4, GI.3, and GI.2/GI.8/GI.9. Most NoV-positive samples were obtained from asymptomatic individuals. The highest number of NoV transmissions was found in household 3 (6 infections), followed by household 2 (2 infections), while household 1 had no NoV transmission, suggesting that asymptomatic NoV carriers play a major role in infection as NoV reservoirs in the households. Further clarification of the mode of infection will contribute to improved understanding and an appropriate prevention.

Early Human Milk Fortification in Infants Born Extremely Preterm: A Randomized Trial.

OBJECTIVES: Enteral nutrition with unfortified human milk during the first 2 postnatal weeks often leads to cumulative protein and energy deficits among preterm infants. Fortified human milk administered soon after birth could increase fat-free mass (FFM) and improve growth in these infants. METHODS: This was a masked, randomized trial. Starting on feeding day 2, extremely preterm infants 28 weeks or younger fed maternal or donor milk were randomized to receive either a diet fortified with a human-based product (intervention group) or a standard, unfortified diet (control group). This practice continued until the feeding day when a standard bovine-based fortifier was ordered. Caregivers were masked. The primary outcome was FFM-for-age z score at 36 weeks of postmenstrual age (PMA). RESULTS: A total of 150 infants were randomized between 2020 and 2022. The mean birth weight was 795±250 g, and the median gestational age was 26 weeks. Eleven infants died during the observation period. The primary outcome was assessed in 105 infants (70%). FFM-for-age z scores did not differ between groups. Length gain velocities from birth to 36 weeks PMA were higher in the intervention group. Declines in head circumference-for-age z score from birth to 36 weeks' PMA were less pronounced in the intervention group. CONCLUSIONS: In infants born extremely preterm, human milk diets fortified soon after birth do not increase FFM accretion at 36 weeks' PMA, but they may increase length gain velocity and reduce declines in head circumference-for-age z scores from birth to 36 weeks' PMA.

Complete genome analyses of G12P[8] rotavirus strains from hospitalized children in Surabaya, Indonesia, 2017-2018.

Rotavirus A (RVA) is a major viral cause of acute gastroenteritis (AGE) worldwide. G12 RVA strains have emerged globally since 2007. There has been no report of the whole genome sequences of G12 RVAs in Indonesia. We performed the complete genome analysis by the next-generation sequencing of five G12 strains from hospitalized children with AGE in Surabaya from 2017 to 2018. All five G12 strains were Wa-like strains (G12-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1) and were clustered into lineage-III of VP7 gene phylogenetic tree. STM430 sample was observed as a mixed-infection between G12 and G1 strains: G12/G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. A phylogenetic tree analysis revealed that all five Indonesian G12 strains (SOEP379, STM371, STM413, STM430, and STM433) were genetically close to each other in all 11 genome segments with 98.0%-100% nucleotide identities, except VP3 and NSP4 of STM430, suggesting that these strains have originated from a similar ancestral G12 RVA. The VP3 and NSP4 genome segments of STM430-G12P[8] were separated phylogenetically from those of the other four G12 strains, probably due to intra-genotype reassortment between the G12 and G1 Wa-like strains. The change from G12P[6] lineage-II in 2007 to G12P[8] lineage-III 2017-2018 suggests the evolution and diversity of G12 RVAs in Indonesia over the past approximately 10 years.

Total Fluid Administration and Weight Loss during the First 2 Weeks in Infants Randomized to Early Enteral Feeding after Extremely Preterm Birth.

BACKGROUND: Randomized trials have not reported the effects of the early progression of feeding volumes on fluid balance and neurodevelopment among infants born extremely preterm (≤28 weeks). METHOD: Fluid, electrolyte, and neurodevelopment data of 60 extremely preterm infants randomly assigned to receive either 1 (early feeding group) or 4 days (late feeding group) of trophic feeding volumes at 20-24 mL/kg/day were analyzed. RESULTS: Infants randomized to the early feeding group received less parenteral fluids, generated lower urine volumes, and had less excessive weight loss during the first 14 days after birth. The 7-point difference in cognitive scores and the 0.5 difference in weight-for-age z-scores favoring the early feeding group did not reach statistical significance. CONCLUSIONS: In extremely preterm infants, early enteral feeding is associated with less total fluid administration and with less excessive weight loss during the first 2 weeks after birth. These short-term effects could have long-lasting benefits.

Viral shedding and the durability of immunoglobulin G antibodies to severe acute respiratory syndrome coronavirus 2.

We followed 45 participants in Surabaya, Indonesia, for 10 months and compared their PCR and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) results. As much as 13 out of 45 participants were IgG seropositive at least once while the remaining 32 stayed IgG seronegative throughout the study. Among 13 seropositive participants, 9 were consecutively seropositive at least twice and were eligible for IgG longevity evaluation. The duration of IgG detection varied from 47 to ≥233 days. We observed intermittent re-positive PCR results suggestive of viral shedding in participants with a longer duration of IgG detection.

Prevalence and Distribution of Rotavirus Genotypes Among Children With Acute Gastroenteritis in Areas Other Than Java Island, Indonesia, 2016-2018.

Group A rotaviruses (RVAs) are the leading cause of acute gastroenteritis, which is often associated with severe symptoms in children under 5 years old. Genetic reassortments and interspecies transmission commonly occur, resulting in a great diversity of RVA circulating in the world. The aim of this study is to determine the prevalence and distribution of RVA genotypes among children in Indonesia over the years 2016-2018 across representative areas of the country. Stool samples were collected from 202 pediatric patients with acute gastroenteritis in three regions of Indonesia (West Nusa Tenggara, South Sumatra, and West Papua) in 2016-2018. Rotavirus G and P genotypes were determined by reverse transcription PCR (RT-PCR) and direct sequencing analysis. The prevalences of RVA in South Sumatra (55.4%) and West Papua (54.0%) were significantly higher than that in East Java (31.7%) as determined in our previous study. The prevalence in West Nusa Tenggara (42.6%) was the lowest among three regions, but higher than that in East Java. Interestingly, equine-like G3 rotavirus strains were found as predominant strains in South Sumatra in 2016 and in West Papua in 2017-2018. Moreover, the equine-like G3 strains in South Sumatra detected in 2016 were completely replaced by human G1 and G2 in 2018. In conclusion, RVA infection in South Sumatra and West Papua was highly endemic. Equine-like G3 strains were also spread to South Sumatra (West Indonesia) and West Papua (East Indonesia), as well as Java Island. Dynamic change in rotavirus genotypes from equine-like G3 to human genotypes was also observed. Continuous monitoring may be warranted in isolated areas in Indonesia.

Seroepidemiological study of SARS-CoV-2 infection in East Java, Indonesia.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic, including Indonesia. However, there are only limited data regarding the precise prevalence of the COVID-19 pandemic in Indonesia. Here, to estimate the magnitude of SARS-CoV-2 infection in East Java, Indonesia, we investigated the prevalence of immunoglobulin G (IgG) antibodies. We enrolled 1,819 individuals from June to December 2020 and observed that the subjects' overall prevalence of IgG antibody to SARS-CoV-2 was 11.4% (207/1,819). The prevalence of anti-SARS-CoV-2 antibodies differed significantly between the job/occupation groups (P = 0.0001). A greater prevalence of IgG was detected in laboratory technicians (who take samples from suspected cases and deal with polymerase chain reaction [PCR] procedures, 22.2%) compared to medical personnel who see and take direct care of patients with COVID-19 (e.g., physicians and nurses, 6.0%), other staff in medical facilities (2.9%), general population (12.1%) and non-COVID-19 patients (14.6%). The highest prevalence among age groups was in the 40-49-year-olds (14.8%), and the lowest prevalence was in the 20-29-year-olds (7.4%). However, the younger population still showed a higher prevalence than generally reported, suggesting greater exposure to the virus but less susceptibility to the disease. A geographical difference was also observed: a higher prevalence in Surabaya (13.1%) than in Jombang (9.9%). In conclusion, the COVID-19 outbreak among asymptomatic populations was characterized by a high prevalence of infection in East Java, Indonesia.

G2P[4] rotavirus outbreak in Belu, East Nusa Tenggara Province, Indonesia, 2018.

Rotavirus is a major cause of acute gastroenteritis (AGE) in children worldwide. However, rotavirus outbreak has rarely been reported in Indonesia. This study aims to identify the causative agent for AGE outbreak among children in Belu, East Nusa Tenggara, Indonesia in 2018. All the samples were negative for bacteria (Salmonella, V. cholera) and Norovirus. Ten out of 11 stool samples were rotavirus-positive by immunochromatography testing. Reverse-transcription polymerase chain reaction (RT-PCR) and phylogenetic analyses revealed that rotavirus G2P[4] was the possible causative agent for the AGE outbreak, although sample size was limited. These findings suggest that the AGE outbreak was caused by rotavirus G2P[4], highlighting the importance of rotavirus surveillance.

Post-vaccinated asymptomatic rotavirus infections: A community profile study of children in Surabaya, Indonesia.

BACKGROUND: Rotavirus gastroenteritis accounts for significant childhood morbidity and mortality worldwide. Vaccination using RotarixTM (GSK) and RotaTeq® (Merck) was introduced due to the tremendous disease burden. The possibility of asymptomatic infections following vaccinations was poorly understood. This study examined rotavirus cases in post-vaccinated children, their clinical manifestations and the genotypes of isolated strains. METHODS: Stool samples of healthy, vaccinated children under 5 years of age in Surabaya were collected monthly for 1 year between January 2016 and February 2017. Episodes of gastroenteritis were reported, and samples were collected. Rotavirus was identified using multiplex reverse transcription Polymerase Chain Reaction (QIAGEN, Inc., Valencia, CA). Clinical manifestations were measured using the Vesikari score. The genotype was analyzed by Applied Biosystems (Foster, CA). RESULTS: A total of 109 stool samples were collected from 30 subjects, of which 22 received Rotarix; 8 RotaTeq. Nine out of 109 samples were collected during diarrhea episodes of 8 subjects. Two asymptomatic rotavirus infections were identified by RT-PCR. The genotypes isolated were G1P[8] and G3P[8]. CONCLUSIONS: Asymptomatic rotavirus infections can occur in post-vaccinated children. Strains identified were homologous to serotypes eliciting gastroenteritis in unvaccinated children of the same community.