Maternal characteristics may be associated with human milk macronutrients but no definite conclusions have been made to date.
This study aimed to determine the relationship of maternal-associated ...factors on the content of macronutrients in human milk for the first six weeks after preterm delivery.
Prospective observational cohort study.
Milk samples were collected from mothers after premature birth between 24 + 0–35 + 6 weeks.
Macronutrients and energy content were analyzed by mid-infrared transmission spectroscopy. Demographic and anthropometric data from mothers were systematically recorded.
A total 1.558 human milk samples from 192 mothers were analyzed.
Colostrum: higher protein (p = 0.001) and lower carbohydrate content (p = 0.003) were present in primiparous compared to multiparous milk. Vaginal birth was associated with increased carbohydrate content (p = 0.021). Fat and energy content in colostrum was not related to any maternal characteristics.
Mature human milk: similarly to colostrum, higher protein content (p = 0.001) and lower carbohydrates content (p = 0.022) were observed in primiparous compared to multiparous milk. The mode of delivery was found to be another factor possibly influencing protein and carbohydrate levels (p = 0.036, p = 0.003, respectively). Pre-pregnancy obesity was associated with increased fat (p = 0.030) and energy content (p = 0.020) in human milk. On the contrary, smoking had a negative relationship to fat and energy content (p = 0.026, p = 0.007, respectively).
Human milk macronutrient concentration after preterm delivery is associated with pre-pregnancy obesity, parity, mode of delivery and smoking. The impact of maternal factors on human milk composition should be taken into account in a strategy of feeding in premature infants.
•Limited data are available on the influence of maternal characteristics on the human milk.•Maternal characteristics are associated with macronutrients and energy of human milk after premature birth.•Primiparous mothers have higher protein and lower carbohydrates content in human milk. than multiparous.•Obese mothers are found to have higher fat and energy content in human milk.•Smoking is negatively associated with milk fat content.
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.
To evaluate the 3-year follow-up results of two children delivered at our institution in 2019 from mothers with a transplanted uterus.
Observational data on pregnancy outcomes, neonatal course, and ...growth trajectory in two children born to mothers after uterus transplantation, including 3-year follow-up and neurodevelopmental status assessed using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III).
Both children were born prematurely via uneventful caesarean sections, to mothers with Mayer-Rokitansky-Küster-Hauser syndrome and a transplanted uterus. An acute caesarean section was performed in one mother because of the onset of regular uterine contractions at 34 weeks and 6 days of pregnancy; in the other mother, an elective caesarean section was performed at 36 weeks and 2 days of gestation. The children were born healthy with no congenital malformations. They had an uneventful postnatal course and showed a normal growth trajectory during 3 years of follow-up. The Bayley-III neurodevelopmental scores of both children were within the normal ranges at ages 2 and 3 years.
Though pregnancy after uterus transplantation is associated with the risk of premature delivery, no abnormalities were observed in the neonatal course and 3-year follow-up results, including the neurodevelopmental status, of two children born prematurely to mothers with a transplanted uterus. This is the first report on neurodevelopmental outcomes in children born after uterus transplantation. More data on children born after this radical procedure of uterine factor infertility treatment are required to support our promising results.
The aim of this study was to assess the applicability of the neonatal sequential organ failure assessment score (nSOFA) within 72 h after delivery as a predictor for mortality and adverse outcome in ...very preterm neonates. Inborn neonates <32 weeks of gestation were evaluated. The nSOFA scores were calculated from medical records in the first 72 h after birth and the peak value was used for analysis. Death or composite morbidity at hospital discharge defined the adverse outcome. Composite morbidity consisted of chronic lung disease, intraventricular haemorrhage ≥grade III, periventricular leukomalacia and necrotizing enterocolitis. Among 423 enrolled infants (median birth weight 1070 g, median gestational age 29 weeks), 27 died and 91 developed composite morbidity. Death or composite morbidity was associated with organ dysfunction as assessed by nSOFA, systemic inflammatory response, and low birthweight. The score >2 was associated with OR 2.5 (CI 1.39−4.64, p = 0.002) for the adverse outcome. Area under the curve of ROC was 0.795 (95% CI = 0.763−0.827). The use of nSOFA seems to be reasonable for predicting mortality and morbidity in very preterm infants. It constitutes a suitable basis to measure the severity of organ dysfunction regardless of the cause.
To evaluate the efficacy of presepsin (P-SEP) as a potential biomarker of early-onset neonatal sepsis (EOS) and compare it to other routinely used markers of inflammation. To establish the cut-off ...values of P-SEP for EOS.
184 newborns were prospectively recruited between January 2018 to December 2020. Newborns >34th gestational week with suspected infection were included up to 72 h after delivery, and divided into three categories (i.e., unlikely, possible, and probable infection) based on risk factors, clinical symptoms and laboratory results. Values of plasma P-SEP were sequentially analyzed.
Median values of P-SEP in newborns with probable infection were significantly higher compared to healthy newborns (
= 0.0000013) and unlikely infection group (
= 0.0000025). The AUC for discriminating the probable infection group from the unlikely infection group was 0.845 (95% Cl: 0.708-0.921). The diagnostic efficacy of P-SEP was highest when used in combination with IL-6 and CRP (0.97; 95% CI: 0.911-0.990). The optimal cut-off value of P-SEP was determined to be 695 ng/L.
P-SEP, when combined with IL-6 and CRP, may be utilized as a negative predictive marker of EOS (NPV 97.2%, 95% CI: 93.3-101), especially in newborns at low to medium risk of infection.
Neonatal systemic inflammatory response and multiple organ dysfunction syndrome are the main postnatal insults influencing mortality and morbidity. Critically ill newborns with high predicted ...mortality are supported by extracorporeal membrane oxygenation (ECMO). Biomarkers of inflammatory response and endothelial injury can be used for early diagnosis and treatment of critical neonatal situations. The aim of our study was to explore plasma proteins and endothelial microvesicles as markers of inflammation and endothelial activation in newborns on ECMO and to compare them with healthy neonates. Thirteen newborns on ECMO and 13 healthy newborns were included in the study. Plasma soluble biomarkers were measured using multiplex immunoassay based on Luminex® xMAP multianalyte profiling platform. The total microvesicle count and plasma level of surface antigen-specific microvesicles were determined by flow cytometry. The plasma concentration of cell-derived microvesicles was measured using annexin-V labeling, and the endothelial origin of microvesicles was determined using lineage-specific antigen labeling of endothelial cell/microvesicle markers (endoglin/CD105, PECAM1/CD31, VEGFR2/CD309, and MadCAM1). Inflammatory markers (procalcitonin, IL-1β, IL-6, and IL-22) were increased in the ECMO group (P<0.01). The assessment of endothelial markers showed higher concentrations of endocan and angiopoietin-2 (P<0.01) in the ECMO group while VEGF in the ECMO group was significantly lower (P<0.01). In the ECMO group, the concentration of annexin-V-positive microvesicles (total microvesicles) and endothelial microvesicles expressing mucosal vascular addressin cell adhesion molecule 1 (MadCAM1) was increased (P=0.05). In summary, we found increased concentrations of soluble inflammatory and endothelial markers in the plasma of critically ill newborns with multiple organ dysfunction. Increased plasma concentrations of microvesicles may reflect the activation or damage of blood cells and vasculature including endothelial cells. The measurement of cell membrane-derived microvesicles may be added to the panel of established inflammatory markers in order to increase the sensitivity and specificity of the diagnostic process in critically ill newborns.
The large, international, randomized controlled NeoPInS trial showed that procalcitonin (PCT)-guided decision making was superior to standard care in reducing the duration of antibiotic therapy and ...hospitalization in neonates suspected of early-onset sepsis (EOS), without increased adverse events. This study aimed to perform a cost-minimization study of the NeoPInS trial, comparing health care costs of standard care and PCT-guided decision making based on the NeoPInS algorithm, and to analyze subgroups based on country, risk category and gestational age.
Data from the NeoPInS trial in neonates born after 34 weeks of gestational age with suspected EOS in the first 72 h of life requiring antibiotic therapy were used. We performed a cost-minimization study of health care costs, comparing standard care to PCT-guided decision making.
In total, 1489 neonates were included in the study, of which 754 were treated according to PCT-guided decision making and 735 received standard care. Mean health care costs of PCT-guided decision making were not significantly different from costs of standard care (€3649 vs. €3616). Considering subgroups, we found a significant reduction in health care costs of PCT-guided decision making for risk category 'infection unlikely' and for gestational age ≥ 37 weeks in the Netherlands, Switzerland and the Czech Republic, and for gestational age < 37 weeks in the Czech Republic.
Health care costs of PCT-guided decision making of term and late-preterm neonates with suspected EOS are not significantly different from costs of standard care. Significant cost reduction was found for risk category 'infection unlikely,' and is affected by both the price of PCT-testing and (prolonged) hospitalization due to SAEs.
Superior Vena Cava (SVC) flow in neonates measured by the standard approach has been validated by different groups around the world. The modified SVC flow measurement technique was recently ...suggested. The aim of our study was to evaluate standard and modified technique of echocardiography SVC flow measurement in a cohort of extremely preterm neonates in the immediate postnatal period.
Prospective, observational cohort study in a level III neonatal center. Infants with birth weight <1,250 g were eligible for enrolment. SVC flow was measured by echocardiography using standard and modified methods at 6, 18 and 36 h of age. Our primary outcome was equivalency (using raw bounds of -20 to +20 mL/kg/min difference between the paired measurements), agreement and correlation between standard and modified methods of the SVC flow measurements.
Thirty-nine infants were enrolled. The mean gestational age of the cohort was 27.4 (SD 2.1) weeks of postmenstrual age, the mean birth weight was 0.95 kg (SD 0.2). The measurements at 6 and 36 h of age were equivalent as defined in the design of the study (
= 0.003 and
= 0.004 respectively; raw bounds -20 to +20 mL/kg/min). At 6 h of age the mean difference (bias) between the measurements was -0.8 mL/kg/min with 95% limits of agreement -65.0 to 63.4 mL/kg/min. At 18 h of age, the mean difference (bias) between the measurements was +9.5 mL/kg/min, with 95% limits of agreement -79.6 to 98.7 mL/kg/min. At 36 h of age the mean difference (bias) between the measurements was -2.2 mL/kg/min with 95% limits of agreement -73.4 to 69.1 mL/kg/min. There was a weak, but statistically significant correlation between the standard and modified method at 6 h of age (
= 0.39,
= 0.04).
Both SVC flow echocardiography measurement techniques yielded clinically equivalent results, however due to wide limits of agreement and poor correlation they do not seem to be interchangeable.
Fetal intracranial hemorrhage represents a rare event with an estimated prevalence of 1:10 000 pregnancies. We report a patient diagnosed prenatally with intracranial hemorrhage and ventriculomegaly ...carrying a novel, previously unreported, likely pathogenic variant in COL4A1. At the gestational age of 27 weeks, dilation of lateral ventricles was detected during a routine prenatal ultrasound scan, confirmed by prenatal MRI at 30 + 3 weeks of gestation. Prenatal examinations included amniocentesis with conventional G‐band karyotyping and arrayCGH, and maternal testing for TORCH and parvovirus B19 infections. Virtual gene panel based on whole‐exome sequencing data was performed postnatally. At the age of 2.5 months, the patient manifested epileptic seizures that remain difficult to control. Postnatal MRI showed partial thalamic fusion and polymicrogyria, in addition to severe enlargement of lateral ventricles, multiple deposits of hemosiderin in cerebral and cerebellar hemispheres, and thin optic nerve and chiasma. Virtual gene panel based on whole‐exome sequencing data led to a detection of a de novo previously unreported in‐frame deletion NM_001845.5:c.4688_4711del in COL4A1 located in the highly conserved NC1 domain initiating collagen helix assembly. The presented case lies one a more severe end of the COL4A1 mutation‐related disease spectrum, manifesting as fetal intracranial bleeding, malformation of cortical development, drug‐resistant epilepsy, and developmental delay.
Objective To determine if low-flow nasal prongs therapy with room air, compared with no treatment, facilitates weaning from nasal continuous positive airway pressure (NCPAP) in very low birth weight ...(VLBW, birth weight <1500 g) infants. Study design VLBW infants who received respiratory support for ≥48 hours and who were stable on NCPAP for 24 hours were eligible for inclusion in this multicenter, randomized controlled trial. On stopping NCPAP, infants were randomized to receive 1 L/min air via nasal prongs or to spontaneous breathing in room air. The primary outcome measure was failure to wean. Secondary outcome measures included length of time to failure and change in heart rate, respiratory rate, oxygen saturation, and respiratory distress score. Results Seventy-eight infants were randomized: 39 to nasal prongs and 39 to spontaneous breathing. The groups were similar at birth and at randomization. Sixteen infants (41%) in the nasal prongs group failed the weaning process compared with 12 infants (31%) in the spontaneous breathing group (OR 1.57, 95% CI 0.56 to 4.43, P = .48). There were no significant differences between the groups in secondary outcomes. Conclusions In this study, we did not demonstrate a benefit of low-flow room air via nasal prongs to wean VLBW infants from NCPAP.