Procalcitonin (PCT) levels are elevated early after birth in newborn infants; however, the physiological features and reference of serum PCT concentrations have not been fully studied in preterm infants. The aims of the current study were to establish an age-specific percentile-based reference curve of serum PCT concentrations in preterm infants and determine the features. The PCT concentration peaked in infants at 1 day old and decreased thereafter. At 1 day old, serum PCT concentrations in preterm infants <34 weeks’ gestational age were higher than those in late preterm infants between 34 and 36 weeks’ gestational age or term infants ≥37 weeks’ gestational age. Although the 50-percentile value in late preterm and term infants reached the adult normal level (0.1 ng/mL) at 5 days old, it did not in preterm infants. It took 9 weeks for preterm infants to reach it. Serum PCT concentrations at onset in late-onset infected preterm infants were over the 95-percentile value. We showed that the physiological feature in preterm infants was significantly different from that in late preterm infants, even in those <37 weeks’ gestational age. To detect late-onset bacterial infection and sepsis, an age-specific percentile-based reference curve may be useful in preterm infants.

Few therapeutic methods exist for preventing preterm birth (PTB), or delivery before completing 37 weeks of gestation. In the US, progesterone (P4) supplementation is the only FDA-approved drug for use in preventing recurrent spontaneous PTB. However, P4 has limited effectiveness, working in only approximately one-third of cases. Computational drug repositioning leverages data on existing drugs to discover novel therapeutic uses. We used a rank-based pattern-matching strategy to compare the differential gene expression signature for PTB to differential gene expression drug profiles in the Connectivity Map database and assigned a reversal score to each PTB-drug pair. Eighty-three drugs, including P4, had significantly reversed differential gene expression compared with that found for PTB. Many of these compounds have been evaluated in the context of pregnancy, with 13 belonging to pregnancy category A or B — indicating no known risk in human pregnancy. We focused our validation efforts on lansoprazole, a proton-pump inhibitor, which has a strong reversal score and a good safety profile. We tested lansoprazole in an animal inflammation model using LPS, which showed a significant increase in fetal viability compared with LPS treatment alone. These promising results demonstrate the effectiveness of the computational drug repositioning pipeline to identify compounds that could be effective in preventing PTB.

Although earlier studies have shown that antiviral treatment regimens using valganciclovir (VGCV) improved hearing function in some infants with congenital cytomegalovirus (CMV) infection; its efficacy on the severity of hearing dysfunction is unclear. We conducted a prospective study among 26 infants with congenital CMV infections from 2009 to 2018. Oral VGCV (32 mg/kg/day) was administered for 6 weeks (November 2009 to June 2015; n = 20) or 6 months (July 2015 to March 2018, n = 6). Hearing function was evaluated by measuring the auditory brainstem response before VGCV treatment and at 6 months. Hearing dysfunction, defined as a V-wave threshold >40 dB, was categorized into: most severe, ≥91 dB; severe, 61–90 dB; and moderate, 41–60 dB. Hearing improvement was defined as a decrease of ≥20 dB from the pretreatment V-wave threshold. Of 52 ears in 26 infants with congenital CMV infection, 29 (56%) had hearing dysfunction, and of 29 ears, 16 (55%) improved after VGCV treatment. Although, 16 (84%) of 19 ears with moderate or severe hearing dysfunction improved after treatment (p < 0.001), 10 ears with the most severe form did not. In conclusion, VGCV treatment is effective in improving moderate and severe hearing dysfunction in infants with congenital CMV infection.