Feasibility of bedside portable MRI in neonates and children during ECLS.

Magnetic resonance imaging (MRI) is the preferred neuroimaging technique in pediatric patients. However, in neonates and instable pediatric patients accessibility to MRI is often not feasible due to instability of patients and equipment not being feasible for MRI. Low-field MRI has been shown to be a feasible neuroimaging tool in pediatric patients. We present the first four patients receiving bedside high-quality MRI during ECLS treatment. We show that it is safe and feasible to perform bedside MRI in this patient population. This opens the route to additional treatment decisions and may guide optimized treatment in these patients.

Biodynamic lighting conditions preserve nocturnal melatonin production in pregnant women during hospitalization: A randomized prospective pilot study.

Background and purpose: Maternal circadian rhythms are important for maintaining maternal and fetal homeostasis. The maternal circadian system coordinates the internal clock of the fetus with environmental lighting conditions via the melatonin signal. The intensity and wavelength of daylight influence nocturnal melatonin production. This study aims to evaluate the effect of environmental lighting conditions on melatonin production in pregnant women with reduced mobility during hospitalization. Methods: We installed a human-centric lighting system with biodynamic effects (BDL, biodynamic lighting) in the patient rooms. The pregnant women in the patient rooms with standard indoor conditions served as a control group. The illuminance (lux) and dose of effective circadian irradiation (Hec) were recorded every 10 seconds by light dosimeters (Lucerne University, Switzerland) attached to the patients` clothing. Results: We analyzed the illuminance status of 47 pregnant women with a median (IQR) gestational age of 29.9 (25.4-32.3) weeks of gestation. The median illuminance in the control group was significantly lower (p<0.05) than in the BDL group in the morning and afternoon from day 1 to 5. BDL patients had a significantly higher effective circadian irradiation in the morning. The effective circadian irradiation showed a significant daily rhythm only in the BDL group. The BDL group had a significantly higher melatonin production on day 3 (p=0.006) and day 5 (p=0.012) than the control group median (IQR) nocturnal 6-Sulfatoxymelatonin excretion 15840 (10140-22160) ng/12h vs. 6141 (2080-11328) ng/12h on day 3 and 18780 (11320-23562) ng/12h vs. 6380 (3500-17600) ng/12h on day 5). Conclusion: We have demonstrated that dramatically altered lighting conditions of hospitalized pregnant women may be optimized by installing biodynamic lighting systems in the patient rooms resulting in the maintenance of nocturnal melatonin production in pregnant women.

The fetal gastrointestinal tract is exposed to melatonin and superoxide dismutase rich amniotic fluid throughout prenatal development.

Amniotic fluid (AF) is the first fluid to enter the gastrointestinal tract. Preterm birth is leading to a sudden interruption of AF swallowing. Understanding the composition of amniotic fluid is crucial to implement strategies preventing intestinal injury in preterm infants. We hypothesized that the fetal gastrointestinal tract (GIT) is exposed to melatonin and antioxidant enzymes via amniotic fluid throughout prenatal development. Amniotic fluid samples from 76 pregnant women with a median (range) gestational age of 38.0 (14.3-40.1) weeks have been collected. Immediately after birth blood samples were collected from the umbilical vein (n = 53). Median (Interquartile range) melatonin concentration was 30.5 pg/ml (12.7-118.3) and superoxide dismutase 1 (SOD1) concentration was 84 ng/ml (59-123). Extracellular glutathione peroxidase concentration was either not detectable or exceptionally low. We found a positive correlation between melatonin concentration in amniotic fluid and gestational age (Spearman's correlation coefficient, r = 0.570, p<0.001), while SOD1 concentration in amniotic fluid was inversely correlated with gestational age (r = -0.246, p = 0.032). Compared to serum samples, melatonin concentration was statistically significantly higher in amniotic fluid (p<0.001). Our results indicate that the fetal gastrointestinal system is continuously exposed to melatonin and SOD1 via the amniotic fluid throughout prenatal development.

Human Milk Oligosaccharides Are Present in Amniotic Fluid and Show Specific Patterns Dependent on Gestational Age.

(1) Background: Human milk oligosaccharides (HMOs) are already found in maternal circulation in early pregnancy, changing with gestational age. HMOs are also present in cord blood and amniotic fluid (AF). We aimed to assess HMO profiles in AF over the course of gestation. (2) Methods: AF was collected during diagnostic amniocentesis, fetal surgery, or C-section from 77 women with a gestational age of ranging from 14.3 to 40.9 weeks. Samples were analysed using high performance liquid chromatography with fluorescence detection. (3) Results: We found lactose and up to 16 HMO structures in all AF samples investigated, starting at 14 weeks of gestation. Overall, 3'-sialyllactose (3'SL) and 2'-fucosyllactose (2'FL) were the most abundant HMOs. Individual and total HMO concentrations were significantly positively correlated with gestational age. HMO composition also changed between early, mid- and late pregnancy, with relative concentrations of 3'SL significantly decreasing (44%, 25%, 24%) and 2'FL increasing (7%, 13%, 21%), respectively. (4) Conclusion: Our study shows that HMOs are already present in AF early in pregnancy. This demonstrates extensive contact of the fetus with a broad variety of HMOs, suggesting roles for HMOs in fetal tissue development during the time course of pregnancy.

DMBT1 amount in amniotic fluid depends on gestational age.

OBJECTIVE: Amniotic fluid is a mixture containing many different proteins as immunomodulatory peptides and growth factors. The glycoprotein Deleted in Malignant Brain Tumors 1 (DMBT1) is participated in innate immunity, angiogenesis and epithelial differentiation. We analyzed the DMBT1 concentration in amniotic fluid during gestation. METHODS: DMBT1 concentration was quantified by ELISA. Amniotic fluid samples were collected from preterm and term neonates. Effects of maternal or neonatal parameters were analyzed. To evaluate the source of DMBT1 we examined RNA of fetal tissue in relation to DMBT1 expression. RESULTS: The median DMBT1 concentration in amniotic fluid was 54.4 ng/ml. Amniotic fluid obtained <28 weeks of gestation revealed significantly lower DMBT1 concentrations compared to ≥28 weeks. We found a positive correlation between DMBT1 concentration and gestational age (p = .026). The fetal DMBT1 expression was pronounced in the gastrointestinal tract. CONCLUSIONS: The results showed that DMBT1 concentrations in amniotic fluid correlate with the gestational age during gestation and that the fetal gastrointestinal tract is a potential source of DMBT1. BRIEF RATIONALE: Amniotic fluid contains not only nutrients, but also many immunomodulatory peptides and growth factors. Deleted in Malignant Brain Tumors 1 (DMBT1) is an innate immunity protein with functions in epithelial differentiation and angiogenesis. The aim of this research was to study the DMBT1 content and the factors affecting its concentration in amniotic fluid during gestation. In summary, the results obtained in this study showed that DMBT1 is a component of amniotic fluid and that DMBT1 concentrations in amniotic fluid correlate with gestational age. In addition to this, the fetal gastrointestinal tract is a potential source of DMBT1 detected in amniotic fluid.

TBK1 and TNFRSF13B mutations and an autoinflammatory disease in a child with lethal COVID-19.

Among children, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are typically mild. Here, we describe the case of a 3.5-year-old girl with an unusually severe presentation of coronavirus disease (COVID-19). The child had an autoinflammatory disorder of unknown etiology, which had been treated using prednisolone and methotrexate, and her parents were half cousins of Turkish descent. After 5 days of nonspecific viral infection symptoms, tonic-clonic seizures occurred followed by acute cardiac insufficiency, multi-organ insufficiency, and ultimate death. Trio exome sequencing identified a homozygous splice-variant in the gene TBK1, and a homozygous missense variant in the gene TNFRSF13B. Heterozygous deleterious variants in the TBK1 gene have been associated with severe COVID-19, and the variant in the TNFRSF13B gene has been associated with common variable immunodeficiency (CVID). We suggest that the identified variants, the autoinflammatory disorder and its treatment, or a combination of these factors probably predisposed to lethal COVID-19 in the present case.

COVID-19-Associated Cerebral White Matter Injury in a Newborn Infant With Afebrile Seizure.

Coronavirus disease 2019 (COVID-19) symptoms in newborn infants are incompletely described. We present the first case of neuroradiologic abnormality associated with COVID-19 in a newborn infant with afebrile seizure. This case underlines the possible neurologic involvement of severe acute respiratory syndrome coronavirus 2 in this age group.

Association of serum periostin levels with clinical features in children with asthma.

BACKGROUND: The aim of this study was to investigate the association of serum periostin levels with clinical features in children with asthma. METHODS: Children with physician-diagnosed asthma who attended regularly to an outpatient pediatric allergy and asthma center were enrolled in the study along with control subjects. Asthma severity and control status of the patients were evaluated according to the recent GINA guidelines. RESULTS: A total of 158 children (125 with asthma and 33 age- and sex-matched control subjects) with a median age of 10.2 years (range 5.9-17.0) were enrolled. Asthma severity was mild in 41 (32.8%), moderate in 63 (50.4%), and severe in 21 (16.8%) children. Children with asthma had significantly higher periostin levels than controls (53.1 ± 13.1 vs 43.0 ± 11.2 ng/mL, P < .001). The mean serum periostin levels in children with severe asthma (63.8 ± 10.8) were significantly higher than in children with moderate asthma (53.3 ± 12.7) and mild asthma (47.4 ± 11.1) (P < .001). Results of multivariable logistic regression analysis demonstrated an association between serum periostin levels and asthma severity in children (OR, 1.10; 95% CI, 1.04-1.15, P < .001). When analyzed for the best cut-off value with the highest combined sensitivity and specificity, a cut-off value of 52 ng/mL for serum periostin level was obtained with sensitivity, specificity, PPV, and NPV of 100%, 50%, 29%, and 100%, respectively. CONCLUSION: Although serum periostin levels are higher in children with asthma, its diagnostic role in identifying children with severe asthma is limited.

Neurological outcome at 24 months corrected age of prematurely born infants after preterm premature rupture of membranes (PPROM) of at least 7 days: a two-center experience in Germany.

Objective: Preterm premature rupture of membranes (PPROM) is a risk factor for chorioamnionitis (CA) and injury to the fetal brain. However, prolongation of gestation prevents morbidity and decreases complications of prematurity. The current investigation is to define risk factors for the adverse neurological outcome from the influence of PPROM of at least 7 days.Methods: A case-control study included three groups of preterm infants born at the University Hospitals Bonn and Essen, Germany. The first group consisted of infants with PPROM of at least 7 days and no chorioamnionitis (CA) (PPROM group), the second included preterm infants with CA (CA group), and the third group consisted of infants without PPROM and CA (control group). The outcome was assessed using Bayley Scales of Infant Development at a corrected age of 24 months. Each group consisted of 20 corresponding infants with an identical birth weight and gestational age at birth.Results: There was no significant difference between the mental development index (MDI) and psychomotor development index (PDI) scores (mean ± SD): the MDI score was 101 ± 14 in the PPROM group, 98 ± 12 in the CA group and 96 ± 17 in the control group; the PDI score 96 ± 10, 89 ± 16, and 90 ± 17, respectively. Multiple regression analysis revealed no significant influence of PPROM and CA on neurological outcome.Conclusions: PPROM of at least 7 days has no influence on neurodevelopmental outcome at a corrected age of 24 months when birth is initiated in the case of beginning CA.

Congenital diaphragmatic hernia in a case of Cat eye syndrome.

Our findings extend the phenotypic spectrum of Cat eye syndrome, a disorder with wide clinical variability. The potentially life-threatening complications of congenital diaphragmatic hernia should be considered in genetic counseling and prenatal diagnostic.

Circulating microRNAs are associated with Pulmonary Hypertension and Development of Chronic Lung Disease in Congenital Diaphragmatic Hernia.

Pulmonary hypertension (PH) contributes to high mortality in congenital diaphragmatic hernia (CDH). A better understanding of the regulatory mechanisms underlying the pathology in CDH might allow the identification of prognostic biomarkers and potential therapeutic targets. We report the results from an expression profiling of circulating microRNAs (miRNAs) in direct post-pulmonary blood flow of 18 CDH newborns. Seven miRNAs differentially expressed in children that either died or developed chronic lung disease (CLD) up to 28 days after birth, compared to those who survived without developing CLD during this period, were identified. Target gene and pathway analyses indicate that these miRNAs functions include regulation of the cell cycle, inflammation and morphogenesis, by targeting molecules responsive to growth factors, cytokines and cellular stressors. Furthermore, we identified hub molecules by constructing a protein-protein interaction network of shared targets, and ranked the relative importance of the identified miRNAs. Our results suggest that dysregulations in miRNAs let-7b-5p, -7c-5p, miR-1307-3p, -185-3p, -8084, -331-3p and -210-3p may be detrimental for the development and function of the lungs and pulmonary vasculature, compromise cardiac function and contribute to the development of CLD in CDH. Further investigation of the biomarker and therapeutic potential of these circulating miRNAs is encouraged.

Perinatal risk factors for asthma in children with allergic rhinitis and grass pollen sensitization.

BACKGROUND: Results of epidemiologic studies have determined several risk factors for asthma in school-age children. OBJECTIVE: To examine whether parental and perinatal risk factors, along with infantile feeding patterns, were associated with asthma in children with grass pollen allergy and allergic rhinitis. METHODS: We retrospectively analyzed the data of our cohort, which consisted of children with allergic rhinitis. Only children with grass pollen sensitization were enrolled. A detailed questionnaire regarding demographic features and perinatal events was given to the parents. RESULTS: A total of 293 children (200 boys [68.3%]; with median age, 10.2 years [interquartile range {IQR}, 7.4-13.0 years]) were included. A total of 109 children (37.2%) had accompanying asthma. The median age of onset of rhinitis symptoms was earlier (5.3 years [IQR, 4.0-8.0 years] versus 7.0 years [IQR, 5.0-10.0 years]; p = 0.001), histories of prematurity (16.7 versus 6.5%; p = 0.006), preeclampsia (5.5 versus 0%; p = 0.001), neonatal intensive care unit admission (15.1 versus 6.0%; p = 0.01), phototherapy (17.9 versus 7.1%; p = 0.004), early formula feeding (58.7 versus 41.2%; p = 0.006), and parental asthma (25.0 versus 11.4%; p = 0.002) were more frequent in children with asthma. Multivariate logistic regression analysis revealed prematurity (odds ratio [OR] 2.78 [95% confidence interval [CI],1.24-6.24]; p = 0.013), history of formula feeding (OR 1.81 [95% CI, 1.09-3.01]; p = 0.022), and parental asthma (OR 2.37 [95% CI, 1.22-4.63]; p = 0.011) were associated with asthma in school-age children with grass pollen-induced allergic rhinitis. CONCLUSION: Close monitoring of patients with these risk factors may help with an earlier diagnosis of asthma and prompt initiation of therapeutic interventions in children with allergic rhinitis and who were sensitized to grass pollen.

Effect of Remote Ischemic Preconditioning on Intestinal Ischemia-Reperfusion Injury in Adults Undergoing On-Pump CABG Surgery: A Randomized Controlled Pilot Trial.

OBJECTIVE: Cardiopulmonary bypass (CPB) surgery commonly threatens the heart and remote organs with ischemia-reperfusion injury. Transient episodes of ischemia to nonvital tissue, known as remote ischemic preconditioning (RIPC), is thought to help local and remote vital organs to withstand subsequent ischemic insults. DESIGN: Prospective, randomized, double-blinded control trial. SETTING: Tertiary referral academic teaching hospital. PARTICIPANTS: Thirty patients undergoing elective CPB surgery INTERVENTION: RIPC was achieved via three 5-minute cycles of upper limb ischemia using a blood pressure cuff or control (sham cuff). MEASUREMENTS AND MAIN RESULTS: Primary outcome was the occurrence of intestinal injury, as measured by an increase in intestinal fatty acid binding protein (I-FABP). Secondary outcomes included incidence of gastrointestinal complications and duration of intensive care unit (ICU) stay. RIPC did not affect serum IFABP levels at the end of surgery and on the first postoperative day (p = 0.697 and p = 0.461, respectively). For all patients, mean I-FABP levels significantly increased at the end of surgery and decreased to under baseline levels on the first postoperative day (from a mean [± standard deviation] baseline value of 764 ± 492 pg/mL to 2,002 ± 974 pg/mL and decreased to 568 ± 319 pg/mL, p < 0.001). All patients remained clinically absent of gastrointestinal complications until hospital discharge. Duration of ICU stay was not correlated with I-FABP levels at the end of surgery. Neither duration of CPB nor duration of aortic clamping significantly correlated with postoperative I-FABP levels. CONCLUSIONS: These findings suggest that RIPC does not affect intestinal injury in patients undergoing CPB surgery. In patients undergoing cardiac surgery, intestinal injury appears to be moderate and transient without any clinical relevant complication.

Esophageal Atresia with or without Tracheoesophageal Fistula (EA/TEF): Association of Different EA/TEF Subtypes with Specific Co-occurring Congenital Anomalies and Implications for Diagnostic Workup.

BACKGROUND: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) represents the most common developmental malformation of the upper digestive tract. It is classified into six subtypes according to the classification of Vogt, depending on anatomical variation of this malformation. Around 50% of the patients with EA/TEF present additional anomalies, which often influence, next to the EA/TEF subtype, the overall prognosis of EA/TEF newborns. Here, we investigated the association of the different EA/TEF subtypes with co-occurring congenital anomalies in EA/TEF patients and demonstrate their implications for postnatal diagnostic workup. MATERIALS AND METHODS: We investigated 333 patients of a large German multicenter study born between 1980 and 2012. After evaluation of all available clinical records, 235 patients were included in our analysis. We compared our results with existing data. RESULTS: The highest risk for co-occurring anomalies was seen in patients with most common Vogt 3b (p = 0.024), especially for additional gastrointestinal anomalies (p = 0.04). Co-occurring anomalies of the skin were significantly more common in patients with subtype Vogt 2 (p = 0.024). A significant correlation was observed for an impaired neurodevelopmental outcome and EA/TEF Vogt 3a (p = 0.041). Patients with EA/TEF showed a higher risk to present with any additional congenital anomaly compared with the general population (p < 0.001). CONCLUSION: Our results warrant thorough clinical workup for gastrointestinal anomalies especially in patients with Vogt 3b. Moreover, it might be necessary to focus on a thorough aftercare for neurocognitive development in patients with Vogt 3a. The here presented observations need to be confirmed by future studies.

An examination of the factors affecting intestinal wall integrity in newborns at birth.

BACKGROUND: An understanding of the factors that influence intestinal wall integrity during the transition from fetal to neonatal life is important to elucidate and minimize potential contributions to the development of intestinal pathologies in vulnerable newborns. OBJECTIVE: To assess the factors affecting intestinal wall integrity of late preterm and term newborns at birth. METHODS: The concentrations of serum intestinal fatty acid-binding protein (I-FABP) as biomarker of intestinal wall injury, superoxide dismutase (SOD), and glutathione peroxidase (Gpx) as parameters of oxidative stress, and blood gas analyses were measured in the arterial cord blood of 80 newborns, delivered by spontaneous vaginal delivery (labor group) or elective cesarean delivery (non-labor group). RESULTS: Compared with the non-labor group, I-FABP, SOD, and Gpx levels were significantly higher in the labor group. I-FABP concentration was inversely correlated with pH and BE and positively correlated with SOD and Gpx concentrations, second stage of labor duration, and active pushing time. CONCLUSIONS: This study demonstrates that oxidative stress at birth and prolonged second stage of labor may lead to the intestinal injury, which is reflected in increased serum concentration of I-FABP.

Characteristics of feeding tube dependency with respect to food aversive behaviour and growth.

The use of feeding tubes in pediatric medical procedures and management has dramatically increased over the last three decades. With this increase, the prevalence of Feeding Tube Dependency (FTD) - a reliance on enteral feeding following medical recovery due to lack of oral intake of nutrition, despite being able to eat- has increased too. It has been suggested, that cases with FTD show avoidant feeding behaviours such as food refusal, gagging or swallowing resistance, but evidence for this hypothesis is scarce. In a German population of 146 cases requesting feeding tube dependency treatment between 2005 and 2008 the frequency of occurrence of avoidant behaviour in FTD cases has been evaluated and was correlated to growth. The study includes children under 50 months of age being tube fed for at least three months. Parents received the Anamnestic Questionnaire for Feeding Disorder and Tube Weaning (AFT), which evaluates nutritional supply, tube feeding, feeding disorder symptoms, medical diagnosis, growth and psychosocial variables. The study group was comprised of 101 children (50 male, 51 female), with a median age of 15 months (IQR: 10-26.5) and a median tube feeding duration of 13 months (IQR: 8-27). The most prevalent medical diagnoses were congenital malformations (n = 51) and prematurity (n = 27). Parents reported daily symptoms of food aversion through all age groups, like food refusal 2 (IQR: 1-3), gagging 1 (IQR: 0-3), vomiting 1 (0.1-2) and total symptoms 6 (5-11). Vomiting was negatively correlated with weight and length percentile and head circumference. Cases with FTD show frequent and persistent food avoidant behaviors, which may be explain the need for specific psychological treatment during transitioning from tube dependency to oral eating.

Effect of remote ischemic preconditioning on the melatonin and antioxidative status: a pilot study in patients undergoing cardiac surgery.

BACKGROUND: Remote ischemic preconditioning (RIPC), a phenomenon in which a transient ischemia applied to a nonvital tissue protects another organ or tissue from subsequent lethal ischemic injury, is reported to protect the myocardium to withstand a subsequent prolonged ischemic event in patients undergoing cardiac surgery with cardiopulmonary bypass. It remains unclear whether oxidative stress and endogenous antioxidant enzymes play a role in the mechanistic pathways of RIPC. The aim of the present study was to evaluate the effects of RIPC on oxidative stress and extracellular concentrations of melatonin, extracellular superoxide dismutase (eSOD) and extracellular glutathione peroxidase (eGPx) in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Thirty-two patients were randomly assigned to receive either RIPC (N.=15) or sham-RIPC (N.=17). Blood samples were collected immediately before and after RIPC and at the end of surgery. Melatonin levels were determined by radioimmunoassay. Plasma concentrations of eSOD, eGPx and 8-hydroxydeoxyguanosine (8-OhdG) as a marker of DNA oxidative stress were measured via ELISA. RESULTS: We found that RIPC compared to Sham-RIPC independently predicted higher melatonin concentrations at the end of surgery. However, it had no effect on eSOD, eGPx, and DNA oxidative stress. eSOD levels significantly increased during CPB time, while systemic eGPx levels decreased. High baseline melatonin concentration independently predicted lower 8-OHdG levels at the end of surgery. CONCLUSIONS: Our results suggest that extracellular antioxidative enzymes such as eSOD and eGPx as well as oxidative stress levels in the perioperative period do not play a predominant role in the mechanistic pathways of RIPC. RIPC modulates systemic melatonin concentrations but does not affect eSOD, eGPx and oxidative stress levels.

Evaluation of two commercially available ELISA kits for the determination of melatonin concentrations in amniotic fluid throughout pregnancy.

Background The aim of the present study is to evaluate the utility of extraction versus non-extraction-based commercial melatonin ELISA kits for determining the melatonin concentration in amniotic fluid obtained in early and late pregnancy. Methods Pregnancy duration less than 28 weeks was defined as early and from 28 weeks until delivery as late gestation. Nine samples were obtained in early and 18 in late pregnancy. Two commercially available melatonin ELISA kits (melatonin ELISA RE54021, including methanol-based extraction and direct saliva melatonin ELISA RE 54041, not including an extraction step, both from IBL-International, Germany) were used to determine melatonin concentrations in amniotic fluid. Results The mean melatonin concentration in ELISAs assayed by the non-extraction was significantly lower than those assayed after extraction. Subgroup analysis showed that there was no significant difference between melatonin concentration measured by non-extraction versus extraction ELISA in early pregnancy (11.2 ± 7.4 vs. 12.2 ± 7.7, respectively, P = 0.463) but that the mean melatonin concentration in late pregnancy was significantly lower when assayed by non-extraction ELISA than when assayed by extraction ELISA (14.8 ± 9.3 vs. 145.1 ± 179.3, respectively; P < 0.001). Agreement between both measurements in late pregnancy was rather poor (r2 = 0.271, P = 0.022), as opposed to the good correlation found in early pregnancy (r2 = 0.929, P < 0.001). Conclusions The present study revealed that a melatonin assay without an extraction step, such as direct saliva ELISA, does not seem to be a valid method to determine the melatonin concentration of amniotic fluid, especially in late gestation.

Melatonin Concentrations and Antioxidative Capacity of Human Breast Milk According to Gestational Age and the Time of Day.

BACKGROUND: While changes in the composition of breast milk throughout the lactation period are well known, little is known about the antioxidative capacity of breast milk and its regulation as a function of time of day. OBJECTIVE: The aim of this study was to evaluate the antioxidative capacity in breast milk and its regulation by time of day. METHODS: Melatonin, superoxide dismutase (SOD), glutathione peroxidase 3 (Gpx3) concentrations, and the total antioxidative capacity (TAOC) were analyzed in 105 breast milk samples and 12 maternal serum samples from 21 healthy nursing mothers. RESULTS: Comparison between daytime breast milk (collected from 1000-2200 h) and nighttime breast milk (collected from 2200-1000 h) revealed significantly higher concentrations of melatonin and Gpx3 in nighttime milk (melatonin: 1.5 pg/mL [1.0-2.1] day vs 7.3 pg/mL [3.8-13.6] night, median [quartiles], with an estimated mean night-to-day ratio of 5.2 [3.9, 7.1], P < .001; Gpx3: 1436 ng/mL [765-2060] day vs 1800 ng/mL [1242-2297] night, night-to-day difference 192.1 [0.6, 383.7], P = .049). Subgroup analysis showed that melatonin had a circadian rhythm in both preterm and term milk, with a significantly higher nighttime concentration ( P < .001), while antioxidant enzymes had a circadian rhythm only in preterm milk, with a significantly higher nighttime concentration for Gpx3 and a significant higher daytime concentration for SOD and TAOC ( P = .041 and P = .049, respectively). We found no significant correlation between the concentration of melatonin and the concentration of SOD, Gpx3, or TAOC. Moreover, there were no significant correlations observed between gestational age and the concentration of melatonin and antioxidant enzymes. CONCLUSION: Because of its higher melatonin and Gpx3 content, future research is needed to determine if preterm nighttime milk ought to be the first choice in the feeding of high-risk preterm infants.