The mediating effects of parenting self-efficacy between readiness for hospital discharge and post-discharge coping difficulty among mothers of preterm infants.

Post-discharge coping difficulty presents a significant challenge for mothers of preterm infants. The readiness for hospital discharge and parenting self-efficacy are crucial factors influencing post-discharge coping difficulty. However, the pathways through which these factors impact post-discharge coping difficulty remain unclear. This study aims to investigate the impact of readiness for hospital discharge on post-discharge coping difficulty and the mediating role of parenting self-efficacy among mothers of preterm infants. A prospective study involving 462 mothers of preterm infants from six tertiary hospitals in Shandong Province was conducted. Mothers were evaluated on the day of discharge (using the Baseline characteristics and Readiness for Hospital Discharge Scale) and three weeks post-discharge (utilizing the Parenting Sense of Competence Scale-Efficacy subscale and Post-Discharge Coping Difficulty Scale). Structural equation modeling was employed to analyze the mediating effect. The results of this study revealed that readiness for hospital discharge significantly decreased post-discharge coping difficulty (ß = - 0.533, P < 0.001), and parenting self-efficacy also significantly reduced post-discharge coping difficulty (ß = - 0.419, P < 0.001). Furthermore, parenting self-efficacy partially mediated the relationship between readiness for hospital discharge and post-discharge coping difficulty, accounting for 25.35% of the total effect. Mothers reported a moderate level of post-discharge coping difficulty. In assisting mothers of premature infants to alleviate post-discharge coping difficulty, nurses could implement strategies focused on enhancing readiness for hospital discharge and parenting self-efficacy.

Trends in transport injuries burden and risk factors among children under 14 years old in China: 1990-2019.

BACKGROUND: Transport injuries (TI) remains one of leading causes of death in children in China. This study aimed to analyze the temporal trend of disease burden and associated risk factors of TI among children aged 0-14 years in China, utilizing data from 1990 to 2019. METHODS: We retrieved data of disease burden and risk factors of TI among children aged 0-14 year in China from 1990 to 2019 from the Global Burden of Disease (GBD) dataset. We estimated incidence rate, death rate, and disability adjusted life years (DALYs) rate with a 95% uncertainty interval (95% UI), stratified by age, sex, and all type-road users. Trends in disease burden with annual percentage changes (APC) and average annual percent change (AAPC) were performed by Joinpoint regression model. RESULTS: The incidence rate (AAPC = 1.18%, P < 0.001) of TI among children aged 0-14 years showed an increasing trend, whereas mortality rate (AAPC = -3.87%, P < 0.001) and DALYs rate (AAPC = -3.83%, P < 0.001) decreased annually. Notably, boys experienced a higher increase in incidence (1.30%) compared to girls (1.06%), but a faster decrease in mortality and DALYs rate (-3.90% vs. -3.82%, -3.88% vs. -3.79%, respectively) (Pall < 0.001). Declines in death rates and DALYs rates were observed across all age groups (Pall < 0.001), while remained the highest among children aged 0-4 in 2019. Among different road-type users, cyclist road injuries were identified as the primary cause of TI (182.3 cases per 100,000) while pedestrians were the group with the highest mortality (2.9 cases per 100,000) and DALYs rate (243 cases per 100,000) in 2019. Besides, alcohol use was a significant risk factors for TI, while low temperature appeared to be a protective factor. CONCLUSION: Future efforts must prioritize raising awareness among children and their guardians to mitigate the disease burden of TI in children. It's critical to enhance preventive interventions for boys, children aged 0-4 and vulnerable road users such as pedestrians and cyclists in future.

Epidemiological characteristics and clinical antibiotic resistance analysis of Ureaplasma urealyticum infection among women and children in southwest China.

BACKGROUND: The aim of this study was to investigate the epidemiological characteristics and antibiotic resistance patterns of Ureaplasma urealyticum (UU) infection among women and children in southwest China. METHODS: A total of 8,934 specimens, including urogenital swabs and throat swabs were analyzed in this study. All samples were tested using RNA-based Simultaneous Amplification and Testing (SAT) methods. Culture and drug susceptibility tests were performed on UU positive patients. RESULTS: Among the 8,934 patients, the overall positive rate for UU was 47.92%, with a higher prevalence observed among women of reproductive age and neonates. The majority of UU positive outpatients were women of reproductive age (88.03%), while the majority of UU positive inpatients were neonates (93.99%). Overall, hospitalization rates due to UU infection were significantly higher in neonates than in women. Further analysis among neonatal inpatients revealed a higher incidence of preterm birth and low birth weight in UU positive inpatients (52.75% and 3.65%, respectively) than in UU negative inpatients (44.64% and 2.89%, respectively), especially in very preterm and extremely preterm neonates. Moreover, the incidence rate of bronchopulmonary dysplasia (BPD) among hospitalized neonatal patients was significantly higher in the UU positive group (6.89%) than in the UU negative group (4.18%). The drug susceptibility tests of UU in the neonatology, gynecology and obstetrics departments exhibited consistent sensitivity patterns to antibiotics, with high sensitivity to tetracyclines and macrolides, and low sensitivity to fluoroquinolones. Notably, UU samples collected from the neonatology department exhibited significantly higher sensitivity to azithromycin and erythromycin (93.8% and 92.9%, respectively) than those collected from the gynecology and obstetrics departments. CONCLUSIONS: This study enhances our understanding of the current epidemiological characteristics and antibiotic resistance patterns of UU infection among women and children in southwest China. These findings can aid in the development of more effective intervention, prevention and treatment strategies for UU infection.

The disease burden and its distribution characteristics of clonorchiasis in Guangdong Province, Southern China.

BACKGROUND: Clonorchiasis has significant socioeconomic importance in endemic areas; however, studies investigating the disease burden in specific sub-regions are lacking. This study aims to address the gap by quantifying the current disease burden caused by clonorchiasis in Guangdong province and assessing its distribution characteristics. METHODS: Comprehensive measures, including prevalence rates, disability-adjusted life years (DALYs), and direct medical costs, were used to assess the disease burden of clonorchiasis. To estimate the prevalence rate, the number of infections was divided by the examined population, based on the annual surveillance data on clonorchiasis cases during 2016-2021. The calculation of DALYs was based on the epidemiological parameters according to the definition issued by the World Health Organization. Cost data of clonorchiasis were utilized to quantify the direct medical costs. The distribution characteristics of disease burden were assessed through comparisons of groups of population defined by geographic area, time, and characteristics of people. RESULTS: In 2021, clonorchiasis posed a significant disease burden in Guangdong Province. The prevalence rate was found to be 4.25% [95% CI (4.02%, 4.49%)], with an associated burden of DALYs of 406,802.29 [95% CI (329,275.33, 49,215,163.78)] person-years. The per-case direct medical costs of patients with clonorchiasis were estimated to be CNY 7907.2 (SD = 5154.4). Notably, while the prevalence rate and DALYs showed a steady decrease from 2016 to 2020, there was a rising trend in 2021. Spatial clustering of clonorchiasis cases and DALYs was also observed, particularly along the Pearl River and Han River. This suggests a concentration of the disease in these regions. Furthermore, significant differences in prevalence rates were found among various demographic groups, including sex, age, occupation, and education level. Additionally, patients with longer hospital stays were more likely to incur higher direct medical costs. CONCLUSIONS: The burden of clonorchiasis in Guangdong Province remains high, despite significant progress achieved through the implementation of the prevention and control programs. It is suggested that measures should be taken based on the distribution characteristics to maximize the effectiveness of prevention and control, with a primary focus on key populations and areas.

[Prevention of Spontaneous Premature Birth With Cervical Pessary: A Single-Center Prospective Cohort Study]. / å®«é¢ˆæ‰˜é¢„é˜²è‡ªå‘æ€§æ—©äº§çš„å•ä¸­å¿ƒå‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

Objective: To study and compare the clinical effects of cervical pessary and progesterone for preventing preterm birth in singleton pregnant women with a short cervical length (CL). Methods: This study was a prospective cohort study. A total of 148 pregnant women with CL≤25 mm, as determined by ultrasound examination performed before 28 weeks of pregnancy, were included in the study. All subjects were admitted to West China Second Hospital, Sichuan University between August 2020 and December 2022. According to their treatment plans, the pregnant women were divided into a cervical pessary group (n=55) and a progesterone group (n=93). Spontaneous preterm birth before 37 weeks of pregnancy was defined as the main outcome index. Preterm birth (abortion) or spontaneous preterm birth (abortion) before 37, 34, 32, 30, and 28 weeks of pregnancy, mean extended gestational age, neonatal morbidity, and neonatal mortality were the secondary outcome indicators. The pregnancy outcomes and the neonatal outcomes of the two groups were compared and statistically analyzed. Results: There was no statistically significant difference in the incidence of preterm birth (including iatrogenic preterm birth, spontaneous preterm birth, and abortion) before 37, 34, 32, 30, and 28 weeks between the cervical pessary group and the progesterone group. When iatrogenic preterm birth was excluded, the incidence of spontaneous preterm birth before 37 weeks was lower in the cervical pessary group (23.6%) than that in the progesterone group (41.9%), with the difference between the two groups being statistically significant (P=0.024). There was no statistically significant difference in the incidence of spontaneous preterm birth (including miscarriage) before 34, 32, 30, and 28 weeks. There was no statistically significant difference in the incidence of neonatal morbidity, the rate of transfer to the neonatal care unit after birth, and the neonatal mortality rate between the two groups. Multivariate logistic analysis showed that treatment with cervical pessary was a protective factor for spontaneous preterm birth before 37 weeks compared to progesterone therapy. Conclusion: Using cervical pessary to prevent spontaneous preterm birth in singleton pregnant women with a short cervical length in the second trimester can significantly reduce the incidence of spontaneous preterm birth before 37 weeks.

The association of Chinese and American antenatal care utilization indices with birth outcomes.

Objective: Few comparisons have been implemented between different prenatal care utilization indices and their effects on adverse outcomes. This study investigated the appropriateness of Chinese antenatal care (ANC) regulations and compared Chinese and American adequacy of prenatal care utilization (APNCU) scores. Methods: From 2010 to 2022, the medical records of 60,114 pregnant women were collected from the electronic medical record system (EMRS) in Zhoushan, China. ANC utilization was measured using the APNCU score and five times antenatal care (ANC5). Birth weight outcomes, including small for gestational age (SGA) and large for gestational age (LGA), low birth weight (LBW), macrosomia, birth weight, and preterm birth (PTB), were utilized as outcomes. Multinomial, linear, and logistic regression were used to analyze the association of ANC5 and APNCU with outcomes, respectively. Crossover analysis was implemented to compare the interaction between ANC5 and APNCU on the outcomes. Results: Women who received inadequate prenatal care had increased odds for PTB (ANC5: odds ratio (OR) = 1.12, 95% confidence interval (95%CI) = 1.03-1.21; APNCU: OR = 1.18, 95%CI: 1.07-1.29), delivering SGA infants (ANC5: OR = 1.13, 95%CI = 1.07-1.21; APNCU: OR = 1.11, 95%CI = 1.03-1.20). Crossover analysis revealed that inadequate prenatal care in APNCU only was significantly associated with an increased risk of PTB (OR = 1.48, 95%CI: 1.26-1.73). Conclusion: Women with inadequate prenatal care in ANC5 or APNCU were more likely to suffer from adverse birth outcomes, including PTB, birth weight loss, SGA, and LBW. It indicated that adequate prenatal care is necessary for pregnant women. However, there were interactions between ANC5 and APNCU on PTB, with inadequate prenatal care use by APNCU showing the highest risk of PTB. This indicates that APNCU would be a better tool for evaluating prenatal care use.

Global burden of vaccine-associated rheumatic diseases and their related vaccines, 1967-2023: A comprehensive analysis of the international pharmacovigilance database.

Vaccine-associated rheumatic diseases are rare but one of the most feared adverse drug reactions (ADRs). However, this topic has been investigated less with large-scale data in the literature. With the rapid progress in the development and approval of vaccines during the pandemic, public concerns regarding their safety have been raised. To assess the global and regional burden, long-term trends, and potential risk factors of vaccines-associated six types of rheumatic diseases (ankylosing spondylitis [AS], polymyalgia rheumatica [PMR], rheumatoid arthritis [RA], Sjögren's syndrome, Systemic lupus erythematosus [SLE], Systemic scleroderma), this study conducted disproportionality analysis based on the reports from the World Health Organization International Pharmacovigilance Database documented between 1967 and 2023 (n for total reports = 131 255 418) across 156 countries and territories. We estimated the reporting odds ratio (ROR) and information component (IC) to determine the disproportionality signal for rheumatic diseases. Of 198 046 reports of all-cause rheumatic diseases, 14 703 reports of vaccine-associated rheumatic diseases were identified. While the reporting counts have gradually increased over time globally, we observed a dramatic increase in reporting counts after 2020, potentially due to a large portion of reports of COVID-19 mRNA vaccine-associated rheumatic diseases. The disproportionality signal for rheumatic diseases was most pronounced in HBV vaccines (ROR, 4.11; IC025, 1.90), followed by COVID-19 mRNA (ROR, 2.79; IC025, 1.25), anthrax (ROR, 2.52; IC025, 0.76), papillomavirus (ROR, 2.16; IC025, 0.95), encephalitis (ROR, 2.01; IC025, 0.58), typhoid (ROR, 1.91; IC025, 0.44), influenza (ROR, 1.49; IC025, 0.46), and HAV vaccines (ROR, 1.41; IC025, 0.20). From age- and sex-specific perspective, young females and old males are likely to have vaccine-associated rheumatic disease reports. Furthermore, overall vaccines showed a disproportionality signal for PMR (IC025, 3.13) and Sjögren's syndrome (IC025, 0.70), systemic scleroderma (IC025, 0.64), specifically while the COVID-19 mRNA vaccines are associated with all six types of diseases. Although multiple vaccines are associated with rheumatic disease reports, healthcare providers should be aware of the potential of autoimmune manifestations following vaccination, particularly the COVID-19 mRNA and HBV vaccines, and take into account for risk factors associated with these ADRs. Most ADRs exhibited an average time to onset of 11 days, underscoring the significance of monitoring and timely management by clinicians.

[Excess deaths in Argentina during the COVID-19 pandemic: analysis of mortality between 2020 and 2022]. / Exceso de muertes en Argentina durante la pandemia por COVID-19: análisis de la mortalidad entre 2020 y 2022.

Reports of excess mortality during the COVID-19 pandemic in Argentina have been partial and fragmented so far. This study aimed to quantify excess deaths and explore their demographic, temporal, and geographic distribution during the period 2020-2022. Using data from 1 192 963 death records from vital statistics and population projections, expected mortality was estimated using regression models. Excess death was calculated as the difference between observed and expected mortality. An excess of 160 676 deaths (95% CI 146 861 to 174 491) was estimated, representing a rate of 116.9 (95% CI 115.5 to 118.3) additional deaths per 100 000 personyears. Significant heterogeneity was found among the different argentine provinces. The results indicate an uneven impact of the pandemic, with higher excess mortality rates in some regions and more vulnerable age groups. These patterns suggest the need for differentiated strategies of healthcare response and support to the most vulnerable populations in scenarios of new epidemics.

Los reportes del exceso de mortalidad durante la pandemia por COVID-19 en Argentina han sido parciales y fragmentados hasta el momento. Este estudio se propuso cuantificar el exceso de muertes y explorar su distribución demográfica, temporal y geográfica durante el periodo 2020-2022. Utilizando datos de 1 192 963 registros de muertes de estadísticas vitales y proyecciones poblacionales, se estimó la mortalidad esperada mediante modelos de regresión. El exceso de muertes se calculó como la diferencia entre la mortalidad observada y la esperada. Se estimó un exceso de 160 676 muertes (IC 95% 146 861 a 174 491), representando una tasa de 116.9 muertes (IC 95% 115.5 a 118.3) adicionales por cada 100 000 personas-año. Se verificó una significativa heterogeneidad entre las distintas provincias argentinas. Los resultados indican un impacto desigual de la pandemia, con mayores tasas de exceso de mortalidad en algunas regiones y grupos de edad más vulnerables. Estos patrones sugieren la necesidad de estrategias diferenciadas de respuesta sanitaria y apoyo a las poblaciones más vulnerables en escenarios de nuevas epidemias.

Predictors of early child development for screening pregnant women most in need of support in Brazil.

Background: Home visiting programmes can support child development and reduce inequalities, but failure to identify the most vulnerable families can undermine such efforts. We examined whether there are strong predictors of poor child development that could be used to screen pregnant women in primary health care settings to target early interventions in a Brazilian population. Considering selected predictors, we assessed coverage and focus of a large-scale home visiting programme named Primeira Infância Melhor (PIM). Methods: We undertook a prospective cohort study on 3603 children whom we followed from gestation to age four years. We then used 27 potential socioeconomic, psychosocial, and clinical risk factors measurable during pregnancy to predict child development, which was assessed by the Battelle Developmental Inventory (BDI) at the age of four years. We compared the results from a Bonferroni-adjusted conditional inference tree with exploratory linear regression and principal component analysis (PCA), and we conducted external validation using data from a second cohort from the same population. Lastly, we assessed PIM coverage and focus by linking 2015 cohort data with PIM databases. Results: The decision tree analyses identified maternal schooling as the most important variable for predicting BDI, followed by paternal schooling. Based on these variables, a group of 214 children who had the lowest mean BDI (BDI = -0.48; 95% confidence interval (CI) = -0.63, -0.33) was defined by mothers with ≤5 years and fathers with ≤4 years of schooling. Maternal and paternal schooling were also the strongest predictors in the exploratory analysis using regression and PCA, showing linear associations with the outcome. However, their capacity to explain outcome variance was low, with an adjusted R2 of 5.3% and an area under the receiver operating characteristic curve of 0.62 (95% CI = 0.60, 0.64). External validation showed consistent results. We also provided an online screening tool using parental schooling data to support programme's targeting. PIM coverage during pregnancy was low, but the focus was adequate, especially among families with longer enrolment, indicating families most in need received higher dosage. Conclusions: Information on maternal and paternal schooling can improve the focus of home visiting programmes if used for initial population-level screening of pregnant women in Brazil. However, enrolment decisions require complementary information on parental resources and direct interactions with families to jointly decide on inclusion.

Global burden, risk factor analysis, and prediction study of leukaemia from 1990 to 2030.

Background: Leukaemia is a devastating disease with an incidence that progressively increases with advancing age. The World Health Organization has designated 2021-30 as the decade of healthy ageing, highlighting the need to address age-related diseases. We estimated the disease burden of leukaemia and forecasted it by 2030. Methods: Based on the Global Burden of Disease 2019 database, we systematically analysed the geographical distribution of leukaemia and its subtypes. We used Joinpoint regression and Bayesian age-period-cohort models to evaluate incidence and mortality trends from 1990 to 2019 and projections through 2030. We analysed five leukaemia subtypes and the impact of age, gender, and social development. Decomposition analysis revealed the effects of disease burden on ageing and population growth. We used frontier analysis to illustrate the potential of each country to reduce its burden based on its development levels. Results: Globally, the absolute numbers of leukaemia incidence and mortality have increased, while the age-standardised rates (ASRs) have shown a decreasing trend. The disease burden was more pronounced in men, the elderly, and regions with a high socio-demographic index (SDI), where ageing and population growth played varying roles across subtypes. From 2000 to 2006, disease burdens were most effectively controlled. Global ASRs of incidence might stabilise, while ASRs of death are expected to decrease until 2030. Frontier analysis showed that middle and high-middle SDI countries have the most improvement potential. Smoking and high body mass index were the main risk factors for leukaemia-related mortality and disability-adjusted life years. Conclusions: The absolute number of leukaemia cases has increased worldwide, but there has been a sharp decline in ASRs over the past decade, primarily driven by population growth and ageing. Countries with middle and high-middle SDI urgently need to take action to address this challenge.

Effects of Rotavirus Vaccination Coverage among Infants on Hospital Admission for Gastroenteritis across All Age Groups, Japan, 2011-2019.

We assessed the effect of rotavirus vaccination coverage on the number of inpatients with gastroenteritis of all ages in Japan. We identified patients admitted with all-cause gastroenteritis during 2011-2019 using data from the Diagnosis Procedure Combination system in Japan. We used generalized estimating equations with a Poisson distribution, using hospital codes as a cluster variable to estimate the impact of rotavirus vaccination coverage by prefecture on monthly numbers of inpatients with all-cause gastroenteritis. We analyzed 294,108 hospitalizations across 569 hospitals. Higher rotavirus vaccination coverage was associated with reduced gastroenteritis hospitalizations compared with the reference category of vaccination coverage <40% (e.g., for coverage >80%, adjusted incidence rate ratio was 0.87 [95% CI 0.83-0.90]). Our results show that achieving higher rotavirus vaccination coverage among infants could benefit the entire population by reducing overall hospitalizations for gastroenteritis for all age groups.

Induced abortion after advent of fetal sex detection technology and child sex at birth.

BACKGROUND: National level Sex Ratio at Birth (SRB) is normal in Bangladesh despite its patriarchal social structures, strong son preference, and low fertility level, widely recognized as preconditions for Gender-Biased Sex Selection (GBSS). To better understand this anomaly, we examine the trend in SRB in a sub-district in Bangladesh and assess the impact of the introduction of fetal sex-detection technology and the history of induced abortion on child sex using longitudinal data. METHODS: We have used secondary data collected routinely by icddr, b's Matlab Health and Demographic Surveillance System (HDSS) between 1982 and 2018. All births occurring during this period (N = 206,390) were included in the analyses. We calculated the SRB and used multivariate logistic regression analyses to assess the likelihood of birth of a male child before and after the introduction of ultrasonogram in Matlab. RESULTS: Overall, SRB was within the natural limit (106) during 1982-2018 in Matlab. SRB among women with a history of induced abortion was 109.3 before the introduction of ultrasonography in 2001 and 113.5 - after 2001. Women's history of induced abortion prior to introduction of ultrasonogram (1982-2000) increased the likelihood of birth of a male child 1.06 times (AOR 1.06; 95% CI- 1.01-1.11). In the period after, however, this likelihood was 1.08 (AOR 1.08; 95% CI- 1.02-1.15). CONCLUSIONS: In a context with normal SRB, it was found to be skewed among women who had induced abortion. SRB was relatively more skewed among such women after the advent of ultrasonogram compared to a period without ultrasonogram. Moreover, induced abortion after introduction of fetal sex determination technology increased the likelihood of birth of a male child. These findings suggest the plausibility of GBSS in a sub-group. Further research is needed, particularly in regions with skewed SRB to examine whether GBSS is indeed a threat to Bangladesh.

Proportion of confluent B-Lines predicts respiratory support in term infants shortly after birth.

OBJECTIVE: To develop and evaluate the predictive value of a simplified lung ultrasound (LUS) method for forecasting respiratory support in term infants. METHODS: This observational, prospective, diagnostic accuracy study was conducted in a tertiary academic hospital between June and December 2023. A total of 361 neonates underwent LUS examination within 1 h of birth. The proportion of each LUS sign was utilized to predict their respiratory outcomes and compared with the LUS score model. After identifying the best predictive LUS sign, simplified models were created based on different scan regions. The optimal simplified model was selected by comparing its accuracy with both the full model and the LUS score model. RESULTS: After three days of follow-up, 91 infants required respiratory support, while 270 remained healthy. The proportion of confluent B-lines demonstrated high predictive accuracy for respiratory support, with an area under the curve (AUC) of 89.1% (95% confidence interval [CI]: 84.5-93.7%). The optimal simplified model involved scanning the R/L 1-4 region, yielding an AUC of 87.5% (95% CI: 82.6-92.3%). Both the full model and the optimal simplified model exhibited higher predictive accuracy compared to the LUS score model. The optimal cut-off value for the simplified model was determined to be 15.9%, with a sensitivity of 76.9% and specificity of 91.9%. CONCLUSIONS: The proportion of confluent B-lines in LUS can effectively predict the need for respiratory support in term infants shortly after birth and offers greater reliability than the LUS score model.

Unravelling the evolutionary dynamics of antibiotic resistance genes in the infant gut microbiota during the first four months of life.

BACKGROUND: Alongside microbiota development, the evolution of the resistome is crucial in understanding the early-life acquisition and persistence of Antibiotic Resistance Genes (ARGs). Therefore, the aim of this study is to provide a comprehensive view of the evolution and dynamics of the neonatal resistome from 7 days to 4 months of age using a high-throughput qPCR platform. METHODS: In the initial phase, a massive screening of 384 ARGs using a high-throughput qPCR in pooled healthy mother-infant pairs feces from the MAMI cohort was carried out to identify the most abundant and prevalent ARGs in infants and in mothers. This pre-analysis allowed for later targeted profiling in a large number of infants in a longitudinal manner during the first 4 months of life. 16S rRNA V3-V4 amplicon sequencing was performed to asses microbial composition longitudinally. Potential factors influencing the microbiota and ARGs in this period were also considered, such as mode of birth and breastfeeding type. RESULTS: Following the massive screening, the top 45 abundant ARGs and mobile genetic elements were identified and studied in 72 infants during their first months of life (7 days, 1, 2, and 4 months). These genes were associated with resistance to aminoglycosides, beta-lactams and tetracyclines, among others, as well as integrons, and other mobile genetic elements. Changes in both ARG composition and quantity were observed during the first 4 months of life: most ARGs abundance increased over time, but mobile genetic elements decreased significantly. Further exploration of modulating factors highlighted the effect on ARG composition of specific microbial genus, and the impact of mode of birth at 7 days and 4 months. The influence of infant formula feeding was observed at 4-month-old infants, who exhibited a distinctive resistome composition. CONCLUSIONS: This study illustrates the ARG evolution and dynamics in the infant gut by use of a targeted, high-throughput, quantitative PCR-based method. An increase in antibiotic resistance over the first months of life were observed with a fundamental role of delivery mode in shaping resistance profiles. Further, we highlighted the influence of feeding methods on the resistome development. These findings offer pivotal insights into dynamics of and factors influencing early-life resistome, with potential avenues for intervention strategies.

Lost in translation: Cesarean antibiotics and the infant microbiome.

In this issue of Cell Host & Microbe, Sinha et al. describe their randomized trial assessing whether antibiotics given for maternal benefit prior to Cesarean disrupted the infants' microbiomes. Despite pre-incision antibiotics reaching the neonate, there was no meaningful alteration to the infant microbiome-especially when compared with breastmilk feeding.

Isoniazid preventive therapy during infancy does not adversely affect growth among HIV-exposed uninfected children: Secondary analysis of data from a randomized controlled trial.

BACKGROUND: Isoniazid preventive therapy (IPT) decreases risk of tuberculosis (TB) disease; impact on long-term infant growth is unknown. In a recent randomized trial (RCT), we assessed IPT effects on infant growth without known TB exposure. METHODS: The infant TB Infection Prevention Study (iTIPS) trial was a non-blinded RCT among HIV-exposed uninfected (HEU) infants in Kenya. Inclusion criteria included age 6-10 weeks, birthweight ≥2.5 kg, and gestation ≥37 weeks. Infants in the IPT arm received 10 mg/kg isoniazid daily for 12 months, while the control trial received no intervention; post-trial observational follow-up continued through 24 months of age. We used intent-to-treat linear mixed-effects models to compare growth rates (weight-for-age z-score [WAZ] and height-for-age z-score [HAZ]) between trial arms. RESULTS: Among 298 infants, 150 were randomized to IPT, 47.6% were females, median birthweight was 3.4 kg (interquartile range [IQR] 3.0-3.7), and 98.3% were breastfed. During the 12-month intervention period and 12-month post-RCT follow-up, WAZ and HAZ declined significantly in all children, with more HAZ decline in male infants. There were no growth differences between trial arms, including in sex-stratified analyses. In longitudinal linear analysis, mean WAZ (ß = 0.04 [95% CI:-0.14, 0.22]), HAZ (ß = 0.14 [95% CI:-0.06, 0.34]), and WHZ [ß = -0.07 [95% CI:-0.26, 0.11]) z-scores were similar between arms as were WAZ and HAZ growth trajectories. Infants randomized to IPT had higher monthly WHZ increase (ß to 24 months 0.02 [95% CI:0.01, 0.04]) than the no-IPT arm. CONCLUSION: IPT administered to HEU infants did not significantly impact growth outcomes in the first two years of life.

Integrated-omics analysis with explainable deep networks on pathobiology of infant bronchiolitis.

Bronchiolitis is the leading cause of infant hospitalization. However, the molecular networks driving bronchiolitis pathobiology remain unknown. Integrative molecular networks, including the transcriptome and metabolome, can identify functional and regulatory pathways contributing to disease severity. Here, we integrated nasopharyngeal transcriptome and metabolome data of 397 infants hospitalized with bronchiolitis in a 17-center prospective cohort study. Using an explainable deep network model, we identified an omics-cluster comprising 401 transcripts and 38 metabolites that distinguishes bronchiolitis severity (test-set AUC, 0.828). This omics-cluster derived a molecular network, where innate immunity-related metabolites (e.g., ceramides) centralized and were characterized by toll-like receptor (TLR) and NF-κB signaling pathways (both FDR < 0.001). The network analyses identified eight modules and 50 existing drug candidates for repurposing, including prostaglandin I2 analogs (e.g., iloprost), which promote anti-inflammatory effects through TLR signaling. Our approach facilitates not only the identification of molecular networks underlying infant bronchiolitis but the development of pioneering treatment strategies.