Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management.

Background: Growth of preterm infants is monitored using fetal charts despite individual trajectories being downshifted postnatally by adaptational processes. The study aims to compare different approaches to create individualized postnatal trajectories.Methods: Three approaches to achieve growth similar to healthy term infants at 42+0/7 weeks postmenstrual age (PMA) on World Health Organization growth standards (WHOGS) (target weight) were tested by comparing trajectories obtained by: 1) following birth percentiles (Birth‐Weight‐Percentile Approach); 2) following percentiles achieved at day of life 21 (Postnatal‐Percentile Approach); 3) using day‐specific fetal median growth velocities starting at day of life 21 (Fetal‐Median‐Growth Approach [FMGA]). The primary outcome was delta weight (ΔW), defined as difference between target weight (WHOGS) at 42+0/7 weeks and weight predicted by trajectories. The secondary outcome was ΔW vs %fat mass in a cohort of 20 disease‐free surviving very low‐birth‐weight infants.Results: Birth‐Weight‐Percentile and Postnatal‐Percentile Approach showed high ΔW; FMGA alone reduced ΔW. Introducing a factor to FMGA to reflect the transition to extrauterine conditions (Growth‐Velocity Approach [GVA]) minimized ΔW. GVA merged with target and best normalized for body composition related to ΔW.Conclusions: GVA provides an evidence‐based approach for individualized growth trajectories. GVA is based on physiologic data and that healthy preterm infants adjust their postnatal trajectory below their birth percentile. GVA may reflect a biologic principle because it matches consistently with WHOGS at 42+0/7 weeks for all preterm infants from 24 to 34 weeks. This concept could become a bedside tool to aid clinicians in monitoring growth, guiding nutrition, and minimizing chronic adult disease risks as a consequence of unguided, inappropriate growth.

Target fortification (TFO) reduces natural macronutrient variation in breast milk (BM). Daily BM analysis for TFO increases neonatal intensive care unit work load by 10–15 min/patient/day and may not be feasible in all nurseries. The variation of macronutrient intake when BM analysis is done for various schedules was studied. In an observational study, we analyzed 21 subsequent samples of native 24-h BM batches, which had been prepared for 10 healthy infants (gestational age 26.1 ± 1.3 weeks, birth weight: 890 ± 210 g). Levels of protein and fat (validated near-infrared milk analyzer), as well as lactose (UPLC-MS/MS) generated the database for modelling TFO to meet recommendations of European Society for Paediatric Gastroenterology Hepatology and Nutrition. Intake of macronutrients and energy were calculated for different schedules of BM measurements for TFO (n = 1/week; n = 2/week; n = 3/week; n = 5/week; n = 7/week) and compared to native and fixed dose fortified BM. Day-to-day variation of macronutrients (protein 20%, carbohydrate 13%, fat 17%, energy 10%) decreased as the frequency of milk analysis increased and was almost zero for protein and carbohydrate with daily measurements. Measurements two/week led to mean macronutrient intake within a range of ±5% of targeted levels. A reduced schedule for macronutrient measurement may increase the practical use of TFO. To what extent the day-to-day variation affects growth while mean intake is stable needs to be studied.

Preterm neonates suffering from respiratory distress syndrome require assistive support in the form of mechanical ventilation or extracorporeal membrane oxygenation, which may lead to long-term complications or even death. Here, we describe a high performance artificial placenta type microfluidic oxygenator, termed as a double-sided single oxygenator unit (dsSOU), which combines microwire stainless-steel mesh reinforced gas permeable membranes on both sides of a microchannel network, thereby significantly reducing the diffusional resistance to oxygen uptake as compared to the previous single-sided oxygenator designs. The new oxygenator is designed to be operated in a pumpless manner, perfused solely due to the arterio-venous pressure difference in a neonate and oxygenate blood through exposure directly to ambient atmosphere without any air or oxygen pumping. The best performing dsSOUs showed up to ∼343% improvement in oxygen transfer compared to a single-sided SOU (ssSOU) with the same height. Later, the dsSOUs were optimized and integrated to build a lung assist device (LAD) that could support the oxygenation needs for a 1–2 kg neonate under clinically relevant conditions for the artificial placenta, namely, flow rates ranging from 10 to 60 ml/min and a pressure drop of 10–60 mmHg. The LAD provided an oxygen uptake of 0.78–2.86 ml/min, which corresponded to the increase in oxygen saturation from 57 ± 1% to 93%–100%, under pure oxygen environment. This microfluidic lung assist device combines elegant design with new microfabrication methods to develop a pumpless, microfluidic blood oxygenator that is capable of supporting 30% of the oxygen needs of a pre-term neonate.

Acute kidney injury (AKI) is often observed in critically ill patients and is associated with high morbidity and mortality. Non-recovery from AKI has a negative impact on the prognosis of affected patients and early risk stratification seems key to improve clinical outcomes. We analyzed metabolites of a conserved key inflammatory pathway (i.e. tryptophan degradation pathway) in serial urine samples of patients with AKI. One hundred twelve ICU patients with AKI were included in a prospective observational analysis. After exclusion criteria, 92 patients were eligible for analysis. Serial urine samples were collected and tryptophan levels including key tryptophan metabolites were measured using tandem mass spectrometry. Sixty-seven patients recovered in the first 7 days of AKI (early recovery, ER) whereas n = 25 had late−/non-recovery (LNR). Urinary concentrations of tryptophan, kynurenine, 3-OH anthranillic acid, serotonine, and kynurenine/tryptophan were significantly lower in LNR patients. In contrast, creatinine normalized excretion of kynurenic acid (KynA) was substantially increased in LNR patients (7.59 ± 6.81 vs. 3.19 ± 3.44 (ER) μmol/mmol, p < 0.005). High urinary KynA excretion was associated with higher RIFLE class, longer AKI duration, increased need for RRT, and 30-day mortality. Logistic regression revealed KynA as the single most important predictor of renal recovery on days 1 and 2 of AKI. Increased urinary levels of kynurenic acid, a key inflammatory metabolite of the tryprophan degradation pathway, are associated with adverse renal and clinical outcomes in critically ill patients with AKI. Urinary KynA may serve as an early risk stratificator in respective patients with AKI.