Patient characteristics.

ObjectivesTo examine spatial effects in neonatal care, we conducted a retrospective cohort study to investigate the geographical distribution of antimicrobial exposure among very preterm and very low birth weight infants in Japan.Study designWe utilized a nationwide claims database in Japan to extract prescriptions of injectable antimicrobials for 41,423 very preterm and very low birth weight infants admitted within the first two days of life from April 2010 to March 2021. We identified frequently prescribed antimicrobials, revealed early neonatal exposure and neonatal exposure to each antimicrobial agent by 47 prefectures in Japan, and evaluated their spatial autocorrelation using global and local Moran’s I statistics. We then scrutinized regional disparities in antimicrobial drug prescriptions.ResultsThe top 10 antimicrobials prescribed to very preterm and very low birth weight infants in Japan were ampicillin, amikacin, gentamicin, cefotaxime, fluconazole, ampicillin combination, micafungin, cefmetazole, cefazolin, and vancomycin. We identified northern cold spots for fluconazole exposure and southern hot spots for ampicillin, amikacin, gentamicin, and cefmetazole exposure. Geographical heterogeneity in the selection of antibacterial and antimycotic agents was observed.ConclusionOur study revealed the geographical distribution of antimicrobial exposure among very preterm and very low birth weight infants in Japan, thus disclosing its spatial effects. Further research addressing the spatial effects of neonatal care is needed to understand how drug exposure affects the outcomes of preterm infants.</div

Local indicators of spatial association cluster plots of early neonatal exposure and neonatal exposure to the top 10 frequently used antimicrobial agents.

Local indicators of spatial association cluster plots of early neonatal exposure and neonatal exposure to the top 10 frequently used antimicrobial agents.</p

Flowchart showing initial patient eligibility and exclusion because of early discharge.

Flowchart showing initial patient eligibility and exclusion because of early discharge.</p

STROBE statement—checklist of items that should be included in reports of observational studies.

STROBE statement—checklist of items that should be included in reports of observational studies.</p

Early neonatal and neonatal exposure and the global Moran’s <i>I</i> statistics for each antimicrobial agent, tallied at the fifth level of the anatomical therapeutic chemical classification.

Early neonatal and neonatal exposure and the global Moran’s I statistics for each antimicrobial agent, tallied at the fifth level of the anatomical therapeutic chemical classification.</p

Geographical distribution of early neonatal exposure and neonatal exposure to each antibiotic agent, tallied at the fifth level of the anatomical therapeutic chemical classification.

Geographical distribution of early neonatal exposure and neonatal exposure to each antibiotic agent, tallied at the fifth level of the anatomical therapeutic chemical classification.</p

Geographical distribution of early neonatal exposure and neonatal exposure to each antibiotic agent, tallied at the fourth level of the anatomical therapeutic chemical classification.

Geographical distribution of early neonatal exposure and neonatal exposure to each antibiotic agent, tallied at the fourth level of the anatomical therapeutic chemical classification.</p

Heatmaps of regional diversity in drug administration stratified by gestational age and birth weight.

(A) Early and late neonatal episodes of antibacterial administration per 1,000 infants. (B) Drug selection rates on the first day of early neonatal courses of antibacterial administration (days 0–6). (C) Drug selection rates on the first day of late neonatal courses of antibacterial administration (days 7–27). (D) Early neonatal antimycotic drug exposure (days 0–6). We omitted the selection rate and exposure for categories with few cases, such as infants with a gestational age of 22 to 23 weeks and birth weight of 1,000 to 1,499 g and infants with a gestational age of 28 to 31 weeks and birth weight less than 500 g, because of concerns regarding high variance. (PDF)</p

Visualization of the eight regions of Japan and spatial weight matrix assigned to the 47 prefectures.

Visualization of the eight regions of Japan and spatial weight matrix assigned to the 47 prefectures.</p

Early neonatal and neonatal exposure and the global Moran’s <i>I</i> statistics for each antimicrobial agent, tallied at the fourth level of the anatomical therapeutic chemical classification.

Early neonatal and neonatal exposure and the global Moran’s I statistics for each antimicrobial agent, tallied at the fourth level of the anatomical therapeutic chemical classification.</p