Computer Vision for Identification of Increased Fetal Heart Variability in Cardiotocogram.

INTRODUCTION: Increased fetal heart rate variability (IFHRV), defined as fetal heart rate (FHR) baseline amplitude changes of >25 beats per minute with a duration of ≥1 min, is an early sign of intrapartum fetal hypoxia. This study evaluated the level of agreement of machine learning (ML) algorithms-based recognition of IFHRV patterns with expert analysis. METHODS: Cardiotocographic recordings and cardiotocograms from 4,988 singleton term childbirths were evaluated independently by two expert obstetricians blinded to the outcomes. Continuous FHR monitoring with computer vision analysis was compared with visual analysis by the expert obstetricians. FHR signals were graphically processed and measured by the computer vision model labeled SALKA. RESULTS: In visual analysis, IFHRV pattern occurred in 582 cardiotocograms (11.7%). Compared with visual analysis, SALKA recognized IFHRV patterns with an average Cohen's kappa coefficient of 0.981 (95% CI: 0.972-0.993). The sensitivity of SALKA was 0.981, the positive predictive rate was 0.822 (95% CI: 0.774-0.903), and the false-negative rate was 0.01 (95% CI: 0.00-0.02). The agreement between visual analysis and SALKA in identification of IFHRV was almost perfect (0.993) in cases (N = 146) with neonatal acidemia (i.e., umbilical artery pH <7.10). CONCLUSIONS: Computer vision analysis by SALKA is a novel ML technique that, with high sensitivity and specificity, identifies IFHRV features in intrapartum cardiotocograms. SALKA recognizes potential early signs of fetal distress close to those of expert obstetricians, particularly in cases of neonatal acidemia.

Intrapartum cardiotocography with simultaneous maternal heart rate registration improves neonatal outcome.

BACKGROUND: Intrapartum cardiotocographic monitoring of fetal heart rate by abdominal external ultrasound transducer without simultaneous maternal heart rate recording has been associated with increased risk of early neonatal death and other asphyxia-related neonatal outcomes. It is unclear, however, whether this increase in risk is independently associated with fetal surveillance method or is attributable to other factors. OBJECTIVE: This study aimed to compare different fetal surveillance methods and their association with adverse short- and long-term fetal and neonatal outcomes in a large retrospective cohort of spontaneous term deliveries. STUDY DESIGN: Fetal heart rate and maternal heart rate patterns were recorded by cardiotocography during labor in spontaneous term singleton cephalic vaginal deliveries in the Hospital District of Helsinki and Uusimaa, Finland between October 1, 2005, and September 30, 2023. According to the method of cardiotocography monitoring at birth, the cohort was divided into the following 3 groups: women with ultrasound transducer, women with both ultrasound transducer and maternal heart rate transducer, and women with internal fetal scalp electrode. Umbilical artery pH and base excess values, low 1- and 5-minute Apgar scores, need for intubation and resuscitation, neonatal intensive care unit admission for asphyxia, neonatal encephalopathy, and early neonatal death were used as outcome variables. RESULTS: Among the 213,798 deliveries that met the inclusion criteria, the monitoring type was external ultrasound transducer in 81,559 (38.1%), both external ultrasound transducer and maternal heart rate recording in 62,268 (29.1%), and fetal scalp electrode in 69,971 (32.7%) cases, respectively. The rates of both neonatal encephalopathy (odds ratio, 1.48; 95% confidence interval, 1.08-2.02) and severe acidemia (umbilical artery pH <7.00 and/or umbilical artery base excess ≤-12.0 mmol/L) (odds ratio, 2.03; 95% confidence interval, 1.65-2.50) were higher in fetuses of women with ultrasound transducer alone compared with those of women with concurrent external fetal and maternal heart rate recording. Monitoring with ultrasound transducer alone was also associated with increased risk of neonatal intubation for resuscitation (odds ratio, 1.22; 95% confidence interval, 1.03-1.44). A greater risk of severe neonatal acidemia was observed both in the ultrasound transducer (odds ratio, 2.78; 95% confidence interval, 2.23-3.48) and concurrent ultrasound transducer and maternal heart rate recording (odds ratio, 1.37; 95% confidence interval, 1.05-1.78) groups compared with those monitored with fetal scalp electrodes. No difference in risk of neonatal encephalopathy was found between newborns monitored with concurrent ultrasound transducer and maternal heart rate recording and those monitored with fetal scalp electrodes. CONCLUSION: The use of external ultrasound transducer monitoring of fetal heart rate without simultaneous maternal heart rate recording is associated with higher rates of neonatal encephalopathy and severe neonatal acidemia. We suggest that either external fetal heart rate monitoring with concurrent maternal heart rate recording or internal fetal scalp electrode be used routinely as a fetal surveillance tool in term deliveries.

Low-grade inflammation from prenatal period to age 6-8 years in a Vitamin D trial.

BACKGROUND: Low-grade systemic inflammation measured as high sensitivity C-reactive protein (hs-CRP) has been associated with non-communicable disease risk. We assessed whether prenatal inflammation and early-childhood vitamin D are associated with inflammation until age 6-8. METHODS: We analyzed blood hs-CRP and 25-hydroxy vitamin D [25(OH)D] in pregnancy, at birth from umbilical cord blood (UCB), from offspring at ages 1, 2, and 6-8 years in the Vitamin D Intervention in Infants (VIDI) study. VIDI was a randomized-controlled trial of vitamin D supplementation of 10 µg/day or 30 µg/day from age 2 weeks until 2 years in 975 infants recruited in 2013-14, with follow-up at age 6-8 in 2019-21 (n = 283). RESULTS: Pregnancy hs-CRP was associated with UCB hs-CRP (r = 0.18, p < 0.001) but not independently with childhood hs-CRP (Estimate [95% CI] 0.04 [<-0.00, 0.09]). Higher UCB hs-CRP was associated independently with higher hs-CRP until 6-8 years (0.20 [0.12, 0.29]). Infant vitamin D dose had no effect on longitudinal hs-CRP (6-8 years, 0.11 [-0.04, 0.25]). Childhood 25(OH)D were associated positively with hs-CRP until age 6-8 (0.01 [>0.00, 0.01]). CONCLUSION: Our results indicate that in children, inflammation, assessed by hs-CRP, persists from birth until 6-8 years. We observed positive associations between 25(OH)D and hs-CRP in vitamin D-sufficient children. IMPACT: High sensitivity C-reactive protein (hs-CRP) concentrations tract from birth to age 8 years Our novel finding suggests a long-lasting pro-inflammatory phenotype in the child Higher vitamin D concentration - but not dose - is associated with higher childhood hs-CRP Chronic disease risk related to inflammation may in part originate from the prenatal period or early childhood Further studies are needed to investigate the effects of inflammation on long-term clinical health outcomes.

Body composition in adults born preterm with very low birth weight.

BACKGROUND: Studies on body composition in preterm very low birth weight (VLBW < 1500 g) survivors are inconsistent and trajectories later in life unknown. We assessed body composition and its change from young to mid-adulthood in VLBW adults. METHODS: We studied 137 VLBW adults and 158 term-born controls from two birth cohorts in Finland and Norway at mean age 36 years. Body composition was assessed by 8-polar bioelectrical impedance. We compared results with dual-energy x-ray absorptiometry measurements at 24 years. RESULTS: In mid-adulthood, VLBW women and men were shorter than controls. Fat percentage (mean difference in women 1.1%; 95% CI, -1.5% to 3.5%, men 0.8%; -2.0% to 3.6%) and BMI were similar. VLBW women had 2.9 (0.9 to 4.8) kg and VLBW men 5.3 (2.7 to 8.1) kg lower lean body mass than controls, mostly attributable to shorter height. Between young and mid-adulthood, both groups gained fat and lean body mass (p for interaction VLBW x age>0.3). CONCLUSION: Compared with term-born controls, VLBW adults had similar body fat percentage but lower lean body mass, largely explained by their shorter height. This could contribute to lower insulin sensitivity and muscular fitness previously found in VLBW survivors and predispose to functional limitations with increasing age. IMPACT: In mid-adulthood, individuals born preterm with very low birth weight had similar body fat percentage but lower lean body mass than those born at term. This was largely explained by their shorter height. First study to report longitudinal assessments of body size and composition from young to mid-adulthood in very low birth weight adults. Lower lean body mass in very low birth weight adults could contribute to lower insulin sensitivity and muscular fitness and lead to earlier functional limitations with increasing age.

Time of Delivery Contributes to Mortality and Morbidity in Preterm Infants.

INTRODUCTION: Knowledge about the time of birth and its impact on premature infants is essential when planning perinatal and neonatal care and resource allocation. We studied the time of birth and its contribution to early death and morbidity in preterm infants. METHODS: We explored the time and mode of birth of infants with birthweight of <1,500 g and gestational age of <32+0/7 weeks. Additionally, we divided the infants into three groups stratified by their time of birth, i.e., during office hours, evening, and nighttime and assessed associations between these groups and mortality and morbidity. RESULTS: The study comprised 1,610 infants of whom 156 (10%) died during their stay in neonatal intensive care unit. The highest number of deliveries occurred on Fridays (21%, n = 341/1,610), primarily due to high number of cesarean sections. Deliveries peaked on workdays at 10 a.m. and 2:00 p.m. Mortality was lowest among infants born on Fridays (6%, n = 21/341) and highest on Mondays (13%, n = 28/218). Intraventricular hemorrhage (IVH) (odds ratio [OR]: 1.50, 95% CI: 1.10-2.03, p = 0.010) and necrotizing enterocolitis (NEC) (OR: 2.11, 95% CI: 1.13-3.91, p = 0.019) were more common among infants born at nighttime. These associations attenuated after adjustment for covariates. CONCLUSION: Deliveries of premature infants peaked on Fridays. Mortality was lower among those born on Fridays, compared with Mondays. Many low-risk deliveries on Fridays may decrease, and the tendency to postpone high-risk deliveries to Mondays, increase the proportional risk of mortality. Indication of higher risk of IVH and NEC among infants born during nighttime may be due to different patient population.

Variation in the fibroblast growth factor 23 (FGF23) gene associates with serum FGF23 and bone strength in infants.

Introduction: The effects of genetic variation in fibroblast growth factor 23 (FGF23) are unclear. This study explores the associations of single-nucleotide polymorphisms (SNPs) of FGF23 with phosphate and vitamin D metabolism and bone strength in early childhood. Methods: The study is part of the vitamin D intervention in infant (VIDI) trial (2013-2016), in which healthy term infants born to mothers of Northern European origin received vitamin D3 supplementation of 10 or 30 µg/day from 2 weeks to 24 months of age (ClinicalTrials.gov NCT01723852). Intact and C-terminal FGF23 (cFGF23), 25-hydroxyvitamin D (25-OHD), parathyroid hormone, phosphate, and peripheral quantitative computed tomography (pQCT)-derived bone strength parameters were analyzed at 12 and 24 months. The study included 622 VIDI participants with genotyping data on FGF23 SNPs rs7955866, rs11063112, and rs13312770. Results: Rs7955866 minor allele homozygotes had lowest cFGF23 at both time-points (mixed model for repeated measurements, pvariant = 0.009). Minor alleles of rs11063112 were associated with a greater age-related decrease in phosphate concentration (pinteraction = 0.038) from 12 to 24 months. Heterozygotes of rs13312770 had the greatest total bone mineral content (total BMC), cross-sectional area (total CSA), and polar moment of inertia (PMI) at 24 months (ANOVA p = 0.005, 0.037, and 0.036, respectively). Rs13312770 minor alleles were associated with a greater increase of total BMC, but a smaller increase of total CSA and PMI, during follow-up (pinteraction <0.001, 0.043, and 0.012, respectively). Genotype of FGF23 did not modify 25-OHD. Conclusion: The study finds that genetic variation in FGF23 modifies cFGF23, phosphate, and pQCT-derived bone strength parameters from 12 to 24 months of age. These findings potentially promote an understanding of the regulation of FGF23 and its role in bone metabolism and temporal changes thereof during early childhood.

Very low birthweight infants receive less enteral feeding than what is prescribed.

AIM: Feeding a very low birthweight (VLBW, <1500 g) infant is challenging. Our aims were to study how prescribed enteral feeding is implemented in VLBW infants and to identify factors associating with slow enteral feeding progression. METHODS: Our retrospective cohort included 516 VLBW infants born before 32 weeks of gestation during 2005-2013 and admitted to Children's Hospital, Helsinki, Finland, for at least the two first weeks of life. Nutritional data were collected from birth until the age of 14-28 days, depending on the length of stay. RESULTS: We found that enteral feeding progressed slower than recommended and implementation differed from the prescriptions, especially during the parenteral nutrition phase (milk intake 10-20 mL/kg/day): 71% [40-100], median [IQR], of the prescribed enteral milk was administered. The full prescribed amount was less likely administered if a higher volume of gastric residual was aspirated or if the infant did not pass stool during the same day. Longer opiate use, patent ductus arteriosus, respiratory distress syndrome and slower passage of the first meconium associated with slower enteral feeding progression. CONCLUSION: Enteral feeding of a VLBW infant is often not administered as prescribed, which possibly plays a significant role in the slow progression of enteral feeding.

Effect of Vitamin D3 Supplementation in the First 2 Years of Life on Psychiatric Symptoms at Ages 6 to 8 Years: A Randomized Clinical Trial.

Importance: Vitamin D is associated with neurodevelopment, but causality, critical windows, and potentials for modification remain unknown. Objective: To determine the impact of high-dose (1200 IU) vs standard-dose (400 IU) vitamin D3 supplementation during the first 2 years on psychiatric symptoms at ages 6 to 8 years and whether the impact is different in children with lower vs higher maternal vitamin D3 levels; lower vs higher levels were defined as 25-hydroxyvitamin D (25[OH]D) less than 30 ng/mL vs 30 ng/mL or greater. Design, Setting, and Participants: This study was a long-term follow-up of the double-blind randomized clinical trial (RCT) Vitamin D Intervention in Infants (VIDI) conducted at a single center in Helsinki, Finland, at 60 degrees north latitude. Recruitment for VIDI took place in 2013 to 2014. Follow-up data for secondary data analysis were collected 2020 to 2021. VIDI originally included 987 term-born infants; 546 of these individuals participated in the follow-up at ages 6 to 8 years, among whom 346 individuals had data on parent-reported psychiatric symptoms. Data were analyzed from June 2022 to March 2023. Interventions: There were 169 infants randomized to receive 400-IU and 177 infants randomized to receive 1200-IU oral vitamin D3 supplementation daily from ages 2 weeks to 24 months. Main Outcomes and Measures: Primary outcomes were internalizing, externalizing, and total problems scores, with clinically significant problems defined as T scores of 64 or greater in the Child Behavior Checklist questionnaire. Results: Among 346 participants (164 females [47.4%]; mean [SD] age, 7.1 [0.4] years), the vitamin D3 dose was 400 IU for 169 participants and 1200 IU for 177 participants. Clinically significant internalizing problems occurred in 10 participants in the 1200-IU group (5.6% prevalence) compared with 20 participants (11.8%) in the 400-IU group (odds ratio, 0.40; 95% CI, 0.17-0.94; P = .04) after adjustment for sex, birth season, maternal depressive symptoms at birth, and parental single status at follow-up. In a post hoc subgroup analysis, 48 children in the 400-IU group with maternal 25(OH)D concentrations less than 30 ng/mL had higher internalizing problems scores compared with children in the 1200-IU group, including 44 children with maternal 25(OH)D concentrations below 30 ng/mL (adjusted mean difference, 0.49; 95% CI, 0.09-0.89; P = .02) and 91 children with maternal concentrations above 30 ng/mL (adjusted mean difference, 0.37; 95% CI, 0.03-0.72; P = .04). Groups did not differ in externalizing or total problems. Conclusions and Relevance: This randomized clinical trial found that higher-than-standard vitamin D3 supplementation in the first 2 years decreased risk of internalizing problems at ages 6 to 8 years. Trial Registration: ClinicalTrials.gov Identifiers: NCT01723852 (VIDI) and NCT04302987 (VIDI2).

Alkaline Phosphatase and Hyperphosphatasemia in Vitamin D Trial in Healthy Infants and Toddlers.

CONTEXT: Childhood hyperphosphatasemia is usually transient and may be associated with infections. It remains less well known how hyperphosphatasemia is related to growth and bone mineralization. OBJECTIVE: We explored alkaline phosphatase (ALP) concentrations and prevalence of hyperphosphatasemia, and their association with vitamin D, growth, infections, and bone parameters in healthy children. METHODS: The study was a secondary analysis of a vitamin D intervention trial. Participants received vitamin D3 10 or 30 µg daily from age 2 weeks to 2 years. Children with data on ALP at 12 and/or 24 months (n = 813, girls 51.9%) were included. Anthropometrics and bone parameters were measured at 12 and 24 months. Infections were recorded prospectively by the parents. RESULTS: Boys had higher ALP than girls at 12 months (median [IQR] 287 [241-345] U/L vs 266 [218-341] U/L; P = .02). At 24 months concentrations were lower than at 12 months (240 [202-284]; P < .001) but without sex difference. The prevalence of hyperphosphatasemia (ALP > 1000 U/L) at 12 months was 5.3% and at 24 months 0.6%. Body size, growth rate, and bone mineral content associated positively with ALP, while vitamin D intervention had no effect. Infants with hyperphosphatasemia were smaller than infants with ALP ≤ 1000 U/L. Hyperphosphatasemia was not associated with previous infections. CONCLUSION: Approximately 5% of infants had hyperphosphatasemia at 12 months, but <1% at 24 months. ALP concentrations and hyperphosphatasemia were associated with sex, anthropometry, and bone mineralization. Infections did not contribute to hyperphosphatasemia.

High Concentration of Protein Oxidation Biomarker O-Tyr/Phe Predicts Better Outcome in Childhood Bacterial Meningitis.

Neuronal damage in bacterial meningitis (BM) partly stems from the host´s inflammatory response and induced oxidative stress (OS). We studied the association of cerebrospinal fluid (CSF) biomarkers indicating oxidative damage to proteins with course of illness and outcome in childhood BM in Angola. Ortho-tyrosine/phenylalanine (o-Tyr/Phe), 3-chlorotyrosine/para-tyrosine (3Cl-Tyr/p-Tyr), and 3-nitrotyrosine/para-tyrosine (3NO2-Tyr/p-Tyr) concentration ratios were measured in 79 BM admission CSF samples, employing liquid chromatography coupled to tandem mass spectrometry. Besides death, disease outcomes were registered on Day 7 of treatment and one month after discharge (control visit). The outcome was graded according to the modified Glasgow Outcome Scale (GOS), which considers neurological and audiological sequelae. Children with a o-Tyr/Phe ratio below the median were more likely to present focal convulsions and secondary fever during recovery and suboptimal outcome (GOS < 5) on Day 7 and at control visit (odds ratio (OR) 2.85; 95% CI 1.14-7.14 and OR 5.23; 95% CI 1.66-16.52, respectively). Their most common sequela was ataxia on Day 7 and at control visit (OR 8.55; 95% CI 2.27-32.22 and OR 5.83; 95% CI 1.12-30.4, respectively). The association of a higher admission CSF o-Tyr/Phe ratio with a better course and outcome for pediatric BM points to a beneficial effect of OS.

Effects of a 2-Year Early Childhood Vitamin D3 Intervention on Tooth Enamel and Oral Health at Age 6-7 Years.

INTRODUCTION: The aim of the study was to compare the effects of a 30 µg/day versus 10 µg/day vitamin D supplementation, given during the two first years of life, on oral health at the age of six to 7 years. METHODS: In 2013-2016, we conducted a randomized, double-blinded, clinical trial from age 2 weeks to 2 years of daily vitamin D3 supplementation (10 vs. 30 µg), including 975 healthy infants. For the present follow-up study at age 6-7 years, a sample of 123 children underwent oral examination by investigators blinded to the intervention group. Tooth enamel defect and caries findings, oral rinse active matrix metalloproteinase-8 levels, and tooth eruption were recorded. The intervention groups were compared with χ2 and Mann-Whitney U tests. Associations of the oral health outcomes were evaluated with correlation analysis and logistic regression. RESULTS: Of the children (median age 7.4 years, 51% boys), 56% belonged to the 30 µg intervention group. Developmental defect of enamel (DDE) was found in 39% of the children in the 10 µg intervention group and in 53% of the 30 µg group (p = 0.104). In total, 94% of children were vitamin D sufficient (25[OH]D ≥50 nmol/L) and 88% had caries-free teeth. No associations were found between vitamin D intervention group in infancy and oral health or the presence of DDE. CONCLUSION: Daily supplementation with 10 µg vitamin D3 in the Northern Hemisphere seems adequate in healthy children younger than 2 years in ensuring good oral health at early school age.

Prenatal maternal and cord blood vitamin D concentrations and negative affectivity in infancy.

Higher maternal vitamin D concentration during pregnancy is associated with better child mental health. Negative affectivity, an early-emerging temperamental trait, indicates an increased risk of psychopathology. We investigated if maternal early/mid-pregnancy 25-hydroxyvitamin D (25(OH)D) and neonatal cord blood 25(OH)D concentrations are associated with Negative affectivity in infancy. We studied term-born infants from the vitamin D Intervention in Infants study (VIDI, n = 777, follow-up rate 80%, Finland), and the Generation R Study (n = 1505, follow-up rate 40%, Netherlands). We measured maternal serum 25(OH)D at 6-27 weeks (VIDI) or 18-25 weeks (Generation R) of pregnancy, and cord blood 25(OH)D at birth (both cohorts). Caregivers rated infant Negative affectivity at 11.7 months (VIDI) or 6.5 months (Generation R) using the Revised Infant Behavior Questionnaire. Using linear regression, we tested associations between 25(OH)D and Negative affectivity adjusted for infant age, sex, season of 25(OH)D measurement, maternal age, education, smoking, and body-mass-index. Per 10 nmol/l increase in maternal early/mid-pregnancy 25(OH)D, infant Negative affectivity decreased by 0.02 standard deviations (95% confidence interval [CI] - 0.06, - 0.004) in VIDI, and 0.03 standard deviations (95% CI - 0.03, - 0.01) in Generation R. Cord blood 25(OH)D was associated with Negative affectivity in Generation R (- 0.03, 95% CI - 0.05, - 0.01), but not VIDI (0.00, 95% CI - 0.02, 0.02). Lower maternal 25(OH)D concentrations were consistently associated with higher infant Negative affectivity, while associations between cord blood 25(OH)D concentrations and Negative affectivity were less clear. Maternal vitamin D status during early- and mid-pregnancy may be linked with early-emerging differences in offspring behavior.

Supplemental Oxygen Treats Periodic Breathing without Effects on Sleep in Late-Preterm Infants.

BACKGROUND: The effect of supplemental oxygen on sleep has not been studied in preterm infants. METHODS: We studied 18 stable late-preterm infants with observed periodic breathing at a median gestational age of 36 weeks. Polysomnography was performed on room air and on 25% oxygen-enriched ambient air. RESULTS: Supplemental oxygen did not affect sleep stage distribution, sleep efficiency, the frequency of sleep stage transitions, the appearance of rapid-eye movement (REM) sleep periods, or the high number of spontaneous arousals. The percentage in periodic breathing out of total sleep time decreased from 10% (interquartile range [IQR] 5-9%) on room air to 1% (IQR 0-3%) (p < 0.001) on supplemental oxygen. Also, the number of central apneas decreased from 48 (IQR 32-68) to 23 (IRQ 15-32) per hour (p < 0.001), and the number of oxygen desaturations of a minimum 3% from 38 (IQR 29-74) to 10 (IQR 5-24) per hour (p < 0.001). On room air in non-REM sleep, the median end-tidal carbon dioxide values were systematically lower during periodic breathing at 5.1 (IQR 4.6-6.4) kPa than during stable breathing at 5.5 (4.9-5.9) kPa (p < 0.0001). CONCLUSIONS: In late-preterm infants, supplemental oxygen effectively reduces periodic breathing and the number of oxygen desaturations while having no significant effect on sleep. The results support the importance of carotid body over-reactivity on the genesis of periodic breathing in preterm infants.

Transplantation of maternal intestinal flora to the newborn after elective cesarean section (SECFLOR): study protocol for a double blinded randomized controlled trial.

BACKGROUND: A complication of elective cesarean section (CS) delivery is its interference with the normal intestinal colonization of the infant, affecting the immune and metabolic signaling in early life- a process that has been associated with long-term morbidity, such as allergy and diabetes. We evaluate, in CS-delivered infants, whether the normal intestinal microbiome and its early life development can be restored by immediate postnatal transfer of maternal fecal microbiota (FMT) to the newborn, and how this procedure influences the maturation of the immune system. METHODS: Sixty healthy mothers with planned elective CS are recruited and screened thoroughly for infections. A maternal fecal sample is taken prior to delivery and processed according to a transplantation protocol. After double blinded randomization, half of the newborns will receive a diluted aliquot of their own mother's stool orally administered in breast milk during the first feeding while the other half will be similarly treated with a placebo. The infants are clinically followed, and fecal samples are gathered weekly until the age of 4 weeks, then at the ages of 8 weeks, 3, 6, 12 and 24 months. The parents fill in questionnaires until the age of 24 months. Blood samples are taken at the age of 2-3 days and 3, 6, 12 and 24 months to assess development of major immune cell populations and plasma proteins throughout the first years of life. DISCUSSION: This is the first study to assess long-time effects on the intestinal microbiome and the development of immune system of a maternal fecal transplant given to term infants born by CS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04173208 , registration date 21.11.2019.

Collagen X Biomarker (CXM), Linear Growth, and Bone Development in a Vitamin D Intervention Study in Infants.

Collagen X biomarker (CXM) is suggested to be a biomarker of linear growth velocity. However, early childhood data are limited. This study examines the relationship of CXM to the linear growth rate and bone development, including the possible modifying effects of vitamin D supplementation. We analyzed a cohort of 276 term-born children participating in the Vitamin D Intervention in Infants (VIDI) study. Infants received 10 µg/d (group-10) or 30 µg/d (group-30) vitamin D3 supplementation for the first 2 years of life. CXM and length were measured at 12 and 24 months of age. Tibial bone mineral content (BMC), volumetric bone mineral density (vBMD), cross-sectional area (CSA), polar moment of inertia (PMI), and periosteal circumference (PsC) were measured using peripheral quantitative computed tomography (pQCT) at 12 and 24 months. We calculated linear growth as length velocity (cm/year) and the growth rate in length (SD unit). The mean (SD) CXM values were 40.2 (17.4) ng/mL at 12 months and 38.1 (12.0) ng/mL at 24 months of age (p = 0.12). CXM associated with linear growth during the 2-year follow-up (p = 0.041) but not with bone (p = 0.53). Infants in group-30 in the highest tertile of CXM exhibited an accelerated mean growth rate in length compared with the intermediate tertile (mean difference [95% CI] -0.50 [-0.98, -0.01] SD unit, p = 0.044) but not in the group-10 (p = 0.062) at 12 months. Linear association of CXM and growth rate until 12 months was weak, but at 24 months CXM associated with both length velocity (B for 1 increment of √CXM [95% CI] 0.32 [0.12, 0.52] cm/yr, p = 0.002) and growth rate in length (0.20 [0.08, 0.32] SD unit, p = 0.002). To conclude, CXM may not reliably reflect linear growth from birth to 12 months of age, but its correlation with growth velocity improves during the second year of life. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).