Analysis of noise levels in the neonatal intensive care unit: the impact of clinical microsystems.

Reorganization of neonatal intensive care by introducing clinical microsystems may help to allocate nursing time more appropriately to the needs of patients. However, there is concern that cohorting infants according to acuity may enhance noise levels. This single-center study investigated the impact of reorganization of neonatal intensive care unit by implementing clinical microsystems in a Level III NICU on environmental noise. This prospective study measured 24-h noise levels over a period of 6 months during pre- and post-implementation of microsystems cohorting infants of similar acuity. Comparative analyses of the mixed acuity (i.e., before) and the cohorting (i.e., after) model were performed by creating daily profiles from continuous noise level measurements and calculating the length of exposure to predefined noise levels. Compared to baseline daytime measurements, noise levels were 3-6 dBA higher during physician handover. Noise levels were 2-3 dBA lower on weekends and 3-4 dBA lower at night, independent of the organizational model. The introduction of clinical microsystems slightly increased average noise levels for high-acuity pods (A and B) but produced a much more substantial decrease for low-acuity pods (E), leading to an overall reduction in unit-wide noise levels.    Conclusion: Our data show that noise levels are more driven by human behavior than by technical devices. Implementation of microsystems may help to reduce noise exposure in the lower acuity pods in a NICU. What is Known: • Excessive noise levels can lead to adverse effects on the health and development of premature infants and other critically ill newborns. • The reorganization of the neonatal intensive care unit following the clinical microsystems principles might improve quality of care but also affect noise exposure of staff and patients. What is New: • The transition from a mixed -acuity to cohorting model is associated with an overall reduction in noise levels, particularly in low-acuity pods requiring less nursing care. • Nevertheless, baseline noise levels in both models exceeded the standard permissible limits.

Less is more: Antibiotics at the beginning of life.

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.

Availability of Safe and Effective Therapeutic Options to Pregnant and Lactating Individuals Following the United States Food and Drug Administration Pregnancy and Lactation Labeling Rule.

OBJECTIVE: To explore the extent and type of pregnancy and lactation data of newly approved prescription drugs and assess whether the presented recommendations are data-driven, as required by the US Food and Drug Administration Pregnancy and Lactation Labeling Rule implemented in 2015. STUDY DESIGN: In this descriptive analysis, we reviewed pregnancy and lactation data of all new molecular entities approved between 2001 and 2020 in their most updated labeling. Information was collected regarding the pregnancy and lactation risk statements, the source of pregnancy and lactation data, and the design and methods of pregnancy and lactation studies in the labeling. RESULTS: Of the 422 new molecular entities, the key advisory statement for use of 133 (32%) drugs in pregnancy and 194 (46%) drugs in lactation were classified as "against use." Less than 2% of all drugs had a key advisory statement that supported their use during pregnancy or lactation. The sources of data regarding use in pregnancy were studies in human and animals in 46 (11%) and 348 (82%) drugs, respectively. For use during lactation, data included studies in human and animals in 23 (5%) and 251 (59%) drugs, respectively. The key advisory recommendation was consistent with the available human information in 4 (8%) drugs in pregnancy and 3 (13%) drugs in lactation. Prescription drug labeling contains limited data to support informed decision-making for the use of prescription drugs during pregnancy/lactation. Close collaboration among stakeholders is required to enhance the availability of data in this population.

Cannabis use during lactation may alter the composition of human breast milk.

BACKGROUND: Cannabis is often used by women to manage symptoms of morning sickness during pregnancy, and postpartum stress and anxiety. While exclusive breastfeeding has been recommended for the first 6 months of an infant's life, the presence of cannabinoids in the milk of cannabis users complicates this recommendation. The objective of this study was to investigate the effect of maternal cannabis use on changes in the levels of macronutrients and bioactive factors in breast milk. METHODS: Milk was collected from women who were 6-8 weeks postpartum and were either using cannabis post-delivery, had used cannabis during pregnancy, or were non-users. Levels of cannabinoids, macronutrients, lactose, and SIgA were assessed in the milk of all subjects. RESULTS: THC was detected in the milk of women who reported cannabis use during lactation (n = 13, median: 22 ng/mL). Carboxy-THC, 11-hydroxy-THC, CBD, and CBN were also detected in the milk of women who used cannabis postpartum. Relative to non-users (n = 17), lactose levels were higher and SIgA levels were significantly lower in the milk of subjects who used cannabis during lactation (n = 14). CONCLUSIONS: The presence of cannabinoids, along with altered lactose and SIgA levels in the milk of cannabis users, may have implications for infant health. IMPACT: Metabolites of cannabis are found in breast milk and can accumulate in higher concentrations with ongoing consumption, which is concerning for potential exposure among infants born to mothers who consume cannabis. This work reports that lactose levels are increased and SIgA levels are decreased in the breast milk of cannabis users, relative to the milk of non-users. Change in levels of lactose and SIgA in the milk of cannabis users may have significant implications on infant health, which must be investigated in the future to better inform mothers.

Prevalence and Implications of Low Reticulocyte-Hemoglobin Levels among Extreme Preterm Neonates: A Single-Center Retrospective Study.

This retrospective cohort study aims to determine the epidemiology of iron deficiency among extreme preterm neonates and the association of iron-deficient status during the NICU stay with neurodevelopmental outcomes at 18−24 months. Neonates ≤29 weeks gestational age (GA) born between June 2016 and December 2019, who received routine iron supplementation were enrolled. Iron deficiency was defined as reticulocyte−hemoglobin (Ret-Hb) levels ≤ 29 pg at 36 weeks corrected age. A subcohort of neonates completed standardized developmental assessment at 18−24 months corrected age. Significant neurodevelopmental impairment (sNDI) was defined as either Bayley Scales of Infant Development score < 70 or cerebral palsy or blindness or hearing aided. Among a cohort of 215 neonates [GA 25.8 (1.7) weeks, birthweight 885 (232) g], prevalence of iron deficiency was 55%, 21%, 26%, and 13%, in neonates <24 weeks, 24−25 + 6 weeks, 26−27 + 6 weeks, and ≥ 28 weeks GA, respectively. Male sex and receipt of corticosteroid therapy were associated with iron-deficiency. In the subcohort analysis (n = 69), there was no statistically significant association between Ret-Hb levels at 36 weeks corrected age and the risk of sNDI [OR 0.99 (95% CI 0.85−1.2)]. Male infants and those who received postnatal corticosteroids are likely to have iron-limited erythropoiesis at corrected term despite routine iron-supplementation; however, low Ret-Hb levels during the neonatal period were not associated with significant neurological disability in early childhood.

Analysis of Antibiotic Exposure and Early-Onset Neonatal Sepsis in Europe, North America, and Australia.

Importance: Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure. Objective: To compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries. Design, Setting, and Participants: This is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022. Exposures: Exposure to antibiotics started in the first postnatal week. Main Outcomes and Measures: The main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality. Results: A total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered. Conclusions and Relevance: The findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life.

Novel strategy to personalise use of ibuprofen for closure of patent ductus arteriosus in preterm neonates.

OBJECTIVE: Exploration of a novel therapeutic drug monitoring (TDM) strategy to personalise use of ibuprofen for closure of patent ductus arteriosus (PDA) in preterm neonates. DESIGN: Prospective, single-centre, open-label, pharmacokinetics study in preterm neonates. SETTING: Neonatal intensive care unit at McMaster Children's Hospital. PATIENTS: Neonates with a gestational age ≤28+6 weeks treated with oral ibuprofen for closure of a PDA. METHODS: Population pharmacokinetic parameters, concentration-time profiles and exposure metrics were obtained using pharmacometric modelling and simulation. MAIN OUTCOME MEASURE: Association between ibuprofen plasma concentrations measured at various sampling time points on the first day of treatment and attainment of the target exposure over the first 3 days of treatment (AUC0-72h >900 mg·hour/L). RESULTS: Twenty-three preterm neonates (median birth weight 780 g and gestational age 25.9 weeks) were included, yielding 155 plasma ibuprofen plasma samples. Starting from 8 hours' postdose on the first day, a strong correlation between ibuprofen concentrations and AUC0-72h was observed. At 8 hours after the first dose, an ibuprofen concentration >20.5 mg/L was associated with a 90% probability of reaching the target exposure. CONCLUSION: We designed a novel and practical TDM strategy and have shown that the chance of reaching the target exposure (AUC0-72h >900 mg·hour/L) can be predicted with a single sample collection on the first day of treatment. This newly acquired knowledge can be leveraged to personalise ibuprofen dosing regimens and improve the efficacy of ibuprofen use for pharmacological closure of a PDA.

Investigating Noise Exposure to Newborn Infants From Respiratory Support: Methodological Considerations.

Background and objective Excessive noise in the neonatal intensive care unit (NICU) may lead to serious long-term effects on hearing and sensory development in newborns. As such, the maximum allowed noise level is 45 A-weighted decibels (dBA). Studies regarding noise exposure to ventilated preterm infants show inconsistent results; however, these studies also vary considerably in their methodology in terms of noise ascertainment. We hypothesized that the study methodology can significantly influence data quality when measuring noise levels. In this study, we aimed to investigate whether the variations in ventilator noise levels in NICUs could be a result of methodological differences in study designs. Methods A ventilator circuit was set up using nasal continuous positive airway pressure (nCPAP) and high-frequency (HF) modes with nasal prongs. Noise levels were measured using a commercially calibrated noise meter. Three different scenarios were tested: (1) measurements were taken at different angles (0° to 180°), with 180° facing the end of the nasal prongs, without a mannequin, with the membrane/orifice of the noise meter placed 2 mm laterally from the prongs; (2) noise levels were measured at 180° at distances of 0-20 mm from the nasal prongs; (3) measurements were taken in the oral cavity of a life-size intubation mannequin of a newborn baby. Results Overall, the noise levels produced at different settings varied significantly, ranging from 45.7 dB to 82.2 dB. The average environmental background noise was 44.4 dB. Noise levels typically increased as the angle increased, with the highest noise level recorded at 180° for both HF and nCPAP modes, at 58.4 dB and 58.2 dB, respectively. Noise levels recorded at HF were slightly higher than nCPAP values. Furthermore, with regard to distance, the highest mean value, 82.2 dB, was recorded with the noise meter approximately 3 mm from the nasal prongs, and the lowest mean value, 47.6 dB, was recorded at ~20 mm. During trials with the mannequin, the lowest value, 50.1 dB, was recorded at the entrance of the mouth with slightly higher values being recorded within the oral cavity. Conclusion The results indicate that small changes in experimental settings, such as positioning and distance from the nasal prongs, can greatly influence noise levels, particularly above the recommended levels for neonates. These differences may be attributed to wind-generated noise. In summary, some study results are potentially influenced more by the study design than the device type or ventilator setting. We recommend further research and detailed reporting in the NICU to gain deeper insights into the topic.

Individualized Target Fortification of Breast Milk: Optimizing Macronutrient Content Using Different Fortifiers and Approaches.

Background: Native breast milk composition displays significant inter- and intra-individual variation which persists after standard fortification with fixed doses and challenges target fortification. This study aims to analyze the macronutrient composition of different commercially available fortifiers and the effect of different fortification strategies on nutritional intake of preterm infants. Methods: In 103 preterm infants, native breast milk samples were collected from 24-h feeding batches (n = 3,338) and fat, protein and carbohydrate contents were analyzed. Nutrient content was compared for breast milk that had undergone either (i) standard fortification, (ii) targeted fortification, (iii) selective batching according to breast milk composition, or (iv) partial lyophilization. For (i) eight commercially available standard fortifiers were tested. Targeted fortification (ii) involved the addition of single component modulars of either protein, fat or carbohydrates to standard fortified breast milk. Using a mathematical growth model, the combined effect of protein, fat and carbohydrate intake on growth was assessed. The best composition of standard fortifiers as the initial step for target fortification was explored assuming three clinical scenarios for milk analysis. Results: Macronutrient content was highly variable between native breast milk samples, and this variation was still present after standard fortification, however at elevated macronutrient levels. Standard fortification, breast milk batching, as well as partial lyophilization of human milk resulted in deficient and imbalanced enteral intakes in a significant proportion of infants. Target fortification reduced this variation in a, respectively, higher percentage of samples. The effect size was dependent on the number of measurements per week. The optimum composition of standard fortifiers was dependent on the clinical scenario (measurement frequency) for target fortification. Conclusions: To provide precise and accurate intakes of macronutrients, breast milk should be target fortified. Standard fortified breast milk can result in excess above recommended intakes of some macronutrients which limits the efficiency of target fortification. Standard fortifiers with improved composition are needed for target fortification.

Completeness of reporting of quality improvement studies in neonatology is inadequate: a systematic literature survey.

INTRODUCTION: Quality improvement (QI) is a growing field of inquiry in healthcare, but the reporting quality of QI studies in neonatology remains unclear. We conducted a systematic survey of the literature to assess the reporting quality of QI studies and factors associated with reporting quality. METHODS: We searched Medline for publications of QI studies from 2016 to 16 April 2020. Pairs of reviewers independently screened citations and assessed reporting quality using a 31-item modified Standards for Quality Improvement Reporting Excellence, 2nd edition (SQUIRE 2.0) checklist. We reported the number (percentage) of studies that reported each item and their corresponding 95% CIs. We used Poisson regression to explore factors associated with reporting quality, namely, journal endorsement of SQUIRE 2.0, declaration of funding sources, year of publication and number of authors. The results were reported as incidence rate ratio (IRR) and 95% CI. RESULTS: Of 1921 citations, 336 were eligible; among them, we randomly selected 100 articles to assess reporting quality. The mean (standard deviation) number of SQUIRE 2.0 items adhered to was 22.0 (4.5). Percentage of articles reporting each item varied from 26% to 100%. Journal endorsement of SQUIRE 2.0 (IRR=1.11, 95% CI 1.02 to 1.21, p=0.015), declaration of funding sources and increasing number of authors were significantly associated with better reporting. CONCLUSIONS: Reporting quality of QI studies in neonatology is inadequate. Endorsing the SQUIRE 2.0 guideline is a step that journals can implement to enhance the completeness of reporting.

Capturing the diversity of the human milk microbiota through culture-enriched molecular profiling: a feasibility study.

Previous human milk studies have confirmed the existence of a highly diverse bacterial community using culture-independent and targeted culture-dependent techniques. However, culture-enriched molecular profiling of milk microbiota has not been done. Additionally, the impact of storage conditions and milk fractionation on microbiota composition is not understood. In this feasibility study, we optimized and applied culture-enriched molecular profiling to study culturable milk microbiota in eight milk samples collected from mothers of infants admitted to a neonatal intensive care unit. Fresh samples were immediately plated or stored at -80°C for 2 weeks (short-term frozen). Long-term samples were stored at -20°C for >6 months. Samples were cultured using 10 different culture media and incubated both aerobically and anaerobically. We successfully isolated major milk bacteria, including Streptococcus, Staphylococcus and Bifidobacterium, from fresh milk samples, but were unable to culture any bacteria from the long-term frozen samples. Short-term freezing shifted the composition of viable milk bacteria from the original composition in fresh samples. Nevertheless, the inter-individual variability of milk microbiota composition was observed even after short-term storage. There was no major difference in the overall milk microbiota composition between milk fractions in this feasibility study. This is among the first studies on culture-enriched molecular profiling of the milk microbiota demonstrating the effect of storage and fractionation on milk microbiota composition.

Individualized target fortification of breast milk with protein, carbohydrates, and fat for preterm infants: A double-blind randomized controlled trial.

BACKGROUND & AIMS: In preterm infants, natural variation of breast milk composition makes it difficult to achieve recommended macronutrient intakes with standard fortification. Evidence suggests that nutritional deficiency induces poor postnatal growth. This study investigates impacts of target fortification on preterm growth and metabolism by adjusting breast milk macronutrients. METHODS: This study was conducted as a single-centre, double-blind, randomized controlled trial for infants <30 gestational weeks. The control group received standard fortification and the intervention group received standard plus target fortification adding modular protein, lipids, and carbohydrates. Breast milk content was measured 3x/week using a validated near-infrared bedside spectrometer (NIRS). Modulars were added to achieve recommended values. To assess total nutrient intake, all 2810 native breast milk samples were analyzed - protein and fat using bedside-NIRS, lactose using tandem mass spectrometry (UPLC-MS/MS). Body composition was measured using air displacement plethysmography. Primary outcome was weight gain during the first 21 days of intervention. RESULTS: Baseline characteristics, morbidities, and total fluid intake were not different between groups (intervention n = 52, control n = 51). The intervention group infants had higher macronutrient intakes, weight gain (21.2 ± 2.5 vs 19.3 ± 2.4 g/kg/d, mean difference: 1.9 g/kg/d, 95% CI: 0.9 - 2.9), and body weight. Infants in the intervention group from mothers with below-average breast milk protein content showed greatest impact on weight at 36 weeks (2580 ± 280 g vs 2210 ± 300 g), length, head circumference, fat, and fat-free mass. Also, feeding intolerance was less frequent, blood urea was higher, and triglycerides were lower. CONCLUSIONS: This study provides evidence that target fortification of breast milk with low macronutrient content enhances the quality of nutrition and growth and is feasible in clinical routine.

A Pumpless Microfluidic Neonatal Lung Assist Device for Support of Preterm Neonates in Respiratory Distress.

Premature neonates suffer from respiratory morbidity as their lungs are immature, and current supportive treatment such as mechanical ventilation or extracorporeal membrane oxygenation causes iatrogenic injuries. A non-invasive and biomimetic concept known as the "artificial placenta" (AP) would be beneficial to overcome complications associated with the current respiratory support of preterm infants. Here, a pumpless oxygenator connected to the systemic circulation supports the lung function to relieve respiratory distress. In this paper, the first successful operation of a microfluidic, artificial placenta type neonatal lung assist device (LAD) on a newborn piglet model, which is the closest representation of preterm human infants, is demonstrated. This LAD has high oxygenation capability in both pure oxygen and room air as the sweep gas. The respiratory distress that the newborn piglet is put under during experimentation, repeatedly and over a significant duration of time, is able to be relieved. These findings indicate that this LAD has a potential application as a biomimetic artificial placenta to support the respiratory needs of preterm neonates.

Efficiency of budesonide delivery via a mesh nebulizer in an in-vitro neonatal ventilator model.

OBJECTIVE: To determine the delivery efficiency of budesonide aerosol via a mesh nebulizer in a neonatal ventilator model. DESIGN/METHOD: In an in-vitro ventilated neonatal model, budesonide suspension was administered using a mesh nebulizer. A collection filter was placed distal to the endotracheal tube and budesonide captured by the filter was measured using UV spectroscopy. The ventilator was, in turn, either on high frequency or conventional ventilation mode and the nebulizer was placed either proximal (close to the endotracheal tube) or distal (between the wet side of humidifier and the inspiratory circuit). Each combination (nebulizer position and ventilation mode) to assess budesonide delivery was tested five times. RESULTS: Overall delivery of budesonide to the distal end of the endotracheal tube a small percentage of the total dose administered. The deposition with conventional ventilation was 2.12% (±1.06) and 1.26% (±0.27), with proximal and distal placement of the nebulizer, respectively. With high-frequency ventilation, the deposition percentages were 1.82% (±0.82) and 1.69% (±0.23), with proximal and distal nebulizer placement, respectively. CONCLUSION: Only a small percentage of administered budesonide is delivered to the distal endotracheal tube, irrespective of ventilation mode, and nebulizer placement.

Milk analysis using milk analyzers in a standardized setting (MAMAS) study: A multicentre quality initiative.

BACKGROUND: Human milk analyzers are increasingly used to rapidly measure the macronutrient content in breast milk for individual target fortification, to reduce the risk of postnatal growth restriction. However, many milk analyzers are used without calibration, validation or quality assurance. AIMS: To investigate measurement quality between different human milk analyzers, to test whether accuracy and precision of devices can be improved by establishing individual calibration curves, and to assess long-term stability of measurements, following good clinical laboratory practice (GCLP). METHODS: Sets of identical breast milk samples were sent to 13 participating centres in North America and Europe, for a total of 15 devices. The study included 3 sets of samples: A) initial assessment of the device's performance consisting of 10 calibration samples with random replicates; B) long term stability and quality control consisting of 2 batches of samples to be measured every time before the device is used, over 6 months; C) ring trial consisting of 2 samples to be measured monthly. The devices tested were Unity SpectraStar (n = 5) and MIRIS Human Milk Analyzer (n = 10). RESULTS: There are significant variations in accuracy and precision between different milk analyzers' fat, protein and lactose measurements. However, the accuracy of measurements can be improved by establishing individual correction algorithms. Repeated measurements are more robust when coming from a larger batch volume. Long term stability also varies between devices. CONCLUSION: The variations in measurements between devices are clinically significant and would impact both daily dietary prescriptions, and the outcomes of clinical studies assessing the effect of targeted adjustment of nutrient intake in preterm babies. This study shows that it is crucial to follow GCLP when using milk analyzers to ensure proper measurement of macronutrients, similar to what is required of other medical devices.

Summer Season and Recommended Vitamin D Intake Support Adequate Vitamin D Status throughout Pregnancy in Healthy Canadian Women and Their Newborns.

BACKGROUND: Vitamin D deficiency in pregnancy is reported as a prevalent public health problem. OBJECTIVES: We aimed to evaluate, in pregnant Canadian women, 1) vitamin D intake, 2) maternal and cord serum 25-hydroxycholecalciferol [25(OH)D] and maternal 1,25-dihydroxycholecalciferol [1,25(OH)2D], and 3) factors associated with maternal serum 25(OH)D. METHODS: Women (n = 187; mean prepregnancy BMI 24.4 kg/m2, mean age 31 y) recruited to the Be Healthy in Pregnancy study provided fasting blood samples and nutrient intake at 12-17 (early) and 36-38 (late) weeks of gestation, and cord blood. Vitamin D intakes (Nutritionist Pro™) and serum 25(OH)D and 1,25(OH)2D concentrations (LC-tandem MS) were measured. RESULTS: Vitamin D intake was comparable in early and late pregnancy [median (IQR) = 586 (459, 859) compared with 689 (544, 974) IU/d; P = 0.83], with 71% consumed as supplements. Serum 25(OH)D was significantly higher in late pregnancy (mean ± SD: 103.1 ± 29.3 nmol/L) than in early pregnancy (82.5 ± 22.5 nmol/L; P < 0.001) and no vitamin D deficiency (<30 nmol/L) occurred. Serum 1,25(OH)2D concentrations were significantly higher in late pregnancy (101.1 ± 26.9 pmol/L) than in early pregnancy (82.2 ± 19.2 pmol/L, P < 0.001, n = 84). Cord serum 25(OH)D concentrations averaged 55% of maternal concentrations. In adjusted multivariate analyses, maternal vitamin D status in early pregnancy was positively associated with summer season (est.ß: 13.07; 95% CI: 5.46, 20.69; P < 0.001) and supplement intake (est.ß: 0.01; 95% CI: 0.00, 0.01; P < 0.001); and in late pregnancy with summer season (est.ß: 24.4; 95% CI: 15.6, 33.2; P < 0.001), nonmilk dairy intake (est.ß: 0.17; 95% CI: 0.02, 0.32; P = 0.029), and supplement intake (est.ß: 0.01; 95% CI: 0.00, 0.01; P = 0.04). CONCLUSIONS: Summer season and recommended vitamin D intakes supported adequate vitamin D status throughout pregnancy and in cord blood at >50 nmol/L in healthy Canadian pregnant women. This trial was registered at clinicaltrials.gov as NCT01693510.

An ultra-thin, all PDMS-based microfluidic lung assist device with high oxygenation capacity.

Preterm neonates with immature lungs require a lung assist device (LAD) to maintain oxygen saturation at normal levels. Over the last decade, microfluidic blood oxygenators have attracted considerable interest due to their ability to incorporate unique biomimetic design and to oxygenate in a physiologically relevant manner. Polydimethylsiloxane (PDMS) has become the main material choice for these kinds of devices due to its high gas permeability. However, fabrication of large area ultrathin microfluidic devices that can oxygenate sufficient blood volumes at clinically relevant flow rates, entirely made of PDMS, have been difficult to achieve primarily due to failure associated with stiction of thin PDMS membranes to each other at undesired locations during assembly. Here, we demonstrate the use of a modified fabrication process to produce large area ultrathin oxygenators entirely made of PDMS and robust enough to withstand the hydraulic conditions that are encountered physiologically. We also demonstrate that a LAD assembled from these ultrathin double-sided microfluidic blood oxygenators can increase the oxygen saturation level by 30% at a flow rate of 30 ml/min and a pressure drop of 21 mm Hg in room air which is adequate for 1 kg preterm neonates. In addition, we demonstrated that our LAD could withstand high blood flow rate of 150 ml/min and increase oxygen saturation by 26.7% in enriched oxygen environment which is the highest gas exchange reported so far by any microfluidic-based blood oxygenators. Such performance makes this LAD suitable to provide support to 1 kg neonate suffering from respiratory distress syndrome.