Choline supplementation for preterm infants: metabolism of four Deuterium-labeled choline compounds.

BACKGROUND: Supply of choline is not guaranteed in current preterm infant nutrition. Choline serves in parenchyma formation by membrane phosphatidylcholine (PC), plasma transport of poly-unsaturated fatty acids (PUFA) via PC, and methylation processes via betaine. PUFA-PC concentrations are high in brain, liver and lung, and deficiency may result in developmental disorders. We compared different deuterated (D9-) choline components for kinetics of D9-choline, D9-betaine and D9-PC. METHODS: Prospective study (1/2021-12/2021) in 32 enterally fed preterm infants (28 0/7-32 0/7 weeks gestation). Patients were randomized to receive enterally a single dose of 2.7 mg/kg D9-choline-equivalent as D9-choline chloride, D9-phosphoryl-choline, D9-glycerophosphorylcholine (D9-GPC) or D9-1-palmitoyl-2-oleoyl-PC(D9-POPC), followed by blood sampling at 1 + 24 h or 12 + 60 h after administration. Plasma concentrations were analyzed by tandem mass spectrometry. Results are expressed as median (25th/75th percentile). RESULTS: At 1 h, plasma D9-choline was 1.8 (0.9/2.2) µmol/L, 1.3 (0.9/1.5) µmol/L and 1.2 (0.7/1.4) µmol/L for D9-choline chloride, D9-GPC and D9-phosphoryl-choline, respectively. D9-POPC did not result in plasma D9-choline. Plasma D9-betaine was maximal at 12 h, with lowest concentrations after D9-POPC. Maximum plasma D9-PC values at 12 h were the highest after D9-POPC (14.4 (9.1/18.9) µmol/L), compared to the other components (D9-choline chloride: 8.1 [5.6/9.9] µmol/L; D9-GPC: 8.4 (6.2/10.3) µmol/L; D9-phosphoryl-choline: 9.8 (8.6/14.5) µmol/L). Predominance of D9-PC comprising linoleic, rather than oleic acid, indicated fatty-acyl remodeling of administered D9-POPC prior to systemic delivery. CONCLUSION: D9-Choline chloride, D9-GPC and D9-phosphoryl-choline equally increased plasma D9-choline and D9-betaine. D9-POPC shifted metabolism from D9-betaine to D9-PC. Combined supplementation of GPC and (PO) PC may be best suited to optimize choline supply in preterm infants. Due to fatty acid remodeling of (PO) PC during its assimilation, PUFA co-supplementation with (PO) PC may increase PUFA-delivery to critical organs. This study was registered (22.01.2020) at the Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020502. STUDY REGISTRATION: This study was registered at the Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020502.

Different choline supplement metabolism in adults using deuterium labelling.

BACKGROUND: Choline deficiency leads to pathologies particularly of the liver, brain and lung. Adequate supply is important for preterm infants and patients with cystic fibrosis. We analysed the assimilation of four different enterally administered deuterium-labelled (D9-) choline supplements in adults. METHODS: Prospective randomised cross-over study (11/2020-1/2022) in six healthy men, receiving four single doses of 2.7 mg/kg D9-choline equivalent each in the form of D9-choline chloride, D9-phosphorylcholine, D9-alpha-glycerophosphocholine (D9-GPC) or D9-1-palmitoyl-2-oleoyl-glycero-3-phosphoryl-choline (D9-POPC), in randomised order 6 weeks apart. Plasma was obtained at baseline (t = - 0.1 h) and at 0.5 h to 7d after intake. Concentrations of D9-choline and its D9-labelled metabolites were analysed by tandem mass spectrometry. Results are shown as median and interquartile range. RESULTS: Maximum D9-choline and D9-betaine concentrations were reached latest after D9-POPC administration versus other components. D9-POPC and D9-phosphorylcholine resulted in lower D9-trimethylamine (D9-TMAO) formation. The AUCs (0-7d) of plasma D9-PC concentration showed highest values after administration of D9-POPC. D9-POPC appeared in plasma after fatty acid remodelling, predominantly as D9-1-palmitoyl-2-linoleyl-PC (D9-PLPC), confirming cleavage to 1-palmitoyl-lyso-D9-PC and re-acylation with linoleic acid as the most prominent alimentary unsaturated fatty acid. CONCLUSION: There was a delayed increase in plasma D9-choline and D9-betaine after D9-POPC administration, with no differences in AUC over time. D9-POPC resulted in a higher AUC of D9-PC and virtually absent D9-TMAO levels. D9-POPC is remodelled according to enterocytic fatty acid availability. D9-POPC seems best suited as choline supplement to increase plasma PC concentrations, with PC as a carrier of choline and targeted fatty acid supply as required by organs. This study was registered at Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020498, 22.01.2020. STUDY REGISTRATION: This study was registered at Deutsches Register Klinischer Studien (DRKS) (German Register for Clinical Studies), DRKS00020498.

Fetal Profile Markers for the Detection of Robin Sequence in Fetuses with Retrognathia.

OBJECTIVE: To determine whether the prefrontal space ratio (PSFR), inferior facial (IFA) and maxilla-nasion-mandible angle (MNM), and the fetal profile line (FPL) are helpful in identifying fetuses with Robin sequence (RS) in cases with isolated retrognathia, and thus better predict the likelihood of immediate need for postnatal respiratory support. METHODS: This was a retrospective matched case-control study of fetuses/infants with isolated retrognathia with or without RS receiving pre- and postnatal treatment at the University Hospital of Tübingen, Germany between 2008 and 2020. The PFSR, IFA, MNM, and FPL were measured in affected and normal fetuses according to standardized protocols. Cases were stratified into isolated retrognathia and RS. RESULTS: 21 (n=7 isolated retrognathia, n=14 RS) affected fetuses and 252 normal fetuses were included. Their median gestational age at ultrasound examination was 23.6 and 24.1 weeks, respectively. In fetuses with isolated retrognathia and RS, the PSFR, IFA, and FPL were significantly different from the normal population. At a false-positive rate of 5%, the detection rate was 76.2% for the PFSR, 85.7% for the IFA, and 90.5% for both parameters combined. However, all parameters failed to distinguish between isolated retrognathia and RS. CONCLUSION: PSFR and IFA are simple markers for identifying retrognathia prenatally. However, they are not helpful for the detection of RS in fetuses with isolated retrognathia. Therefore, delivery should take place in a center experienced with RS and potentially life-threatening airway obstruction immediately after birth.

Isolated cytokine-enriched pericardial effusion: A likely key feature for Aymé-Gripp syndrome.

Aymé-Gripp syndrome is a multisystemic disorder caused by a heterozygous variation in the MAF gene (OMIM*177075). Key features are congenital cataracts, sensorineural hearing loss, and a characteristic facial appearance. In a proportion of individuals, pericardial effusion or pericarditis has been reported as part of the phenotypic spectrum. In the present case, a large persistent cytokine-enriched pericardial effusion was the main pre- and postnatal symptom that led to the clinical and later molecular diagnosis of Aymé-Gripp syndrome. In the postnatal course, the typical Aymé-Gripp syndrome-associated features bilateral cataracts and hearing loss were diagnosed. We propose that activating dominant variants in the cytokine-modulating transcription factor c-MAF causes cytokine-enriched pericardial effusions possibly representing a key feature of Aymé-Gripp syndrome.

Neurocognitive development in isolated Robin sequence treated with the Tuebingen palatal plate.

OBJECTIVES: We aimed to determine the neurocognitive development of cleft palate patients with and without Robin sequence (RS). MATERIALS AND METHODS: Children with isolated RS with cleft palate and children with cleft palate only (CPO) were contacted at the age of 5-6 years. All RS children had undergone initial polygraphic sleep study (PG) with a mixed-obstructive apnea index (MOAI) of ≥ 3/h and were consequently treated with the Tuebingen palatal plate. A standardized clinical examination as well as a neuropediatric and neuropsychological examination included the Wechsler Pre-school and Primary Scale of Intelligence (WPPSI-III), Kaufman Assessment Battery for Children (K-ABC), and an assessment of developmental milestones. RESULTS: In total, 44 children (22RS, 22CPO) were included. RS children were younger at study (70.5 ± 7.3 and 75.2 ± 7.5 months; P = .035). Both groups achieved the evaluated milestones within the normed time frame. WPPSI-III and K-ABC results showed no group differences. Mean values for Verbal IQ (101.8 ± 11.1 vs. 97.1 ± 15.7), Performance IQ (102.9 ± 12.1 vs. 99.6 ± 14.5), Processing Speed Quotient (98.9 ± 15.6 vs. 94.5 ± 15.7), Full-Scale IQ (103.2 ± 12.1 vs. 98.4 ± 15.3), and Sequential Processing Scale (102.1 ± 13.1 vs. 94.2 ± 17.3) were within the reference range (IQ 85-115) for RS and CPO children, respectively, indicating average performance of both groups. CONCLUSION: No neurocognitive, physical, or mental impairments were detected suggesting that RS children having upper airway obstruction (UAO) treated early and effectively may use their potential for an age-appropriate neurocognitive development. CLINICAL RELEVANCE: Tuebingen palatal plate treatment successfully releases UAO. Thus, isolated RS does not necessarily result in developmental delay or an impaired neurocognitive outcome. TRIAL REGISTRATION: Deutsches Register Klinischer Studien, DRKS00006831, https://www.drks.de/drks_web/.

Universal Cell Free DNA or Contingent Screening for Trisomy 21: Does It Make a Difference? A Comparative Study with Real Data.

OBJECTIVE: The aim of the objective was to compare the detection rate for trisomy 21 of universal cell free DNA (cfDNA) screening with contingent screening. METHODS: Retrospective study was carried out at 3 German centers. The study included euploid and trisomy 21 pregnancies where cfDNA and first trimester (FT) screening assessment was carried out. The FT risk for trisomy 21 was computed based on combined screening and stratified into the following classes: high risk ≥1:10, intermediate risk 1:11-1,000, low risk ≤1,001. For universal cfDNA screening, the cfDNA test results were examined. For the contingent screening model, the result of the cfDNA test was taken into account in case of an intermediate FT risk. Different strategies combining maternal age, nuchal translucency, nasal bone, beta-hCG, and PAPP-A were evaluated. Screen positivity was defined as either a high risk after FT screening or a cfDNA test indicating a high-risk result. An inconclusive cfDNA test was also considered as screen positive. RESULTS: The search of the database identified 2,255 euploid and 163 affected pregnancies. All affected fetuses were identified by universal cfDNA screening. 1.3% of the euploid fetuses were classified as screen positive due to final inconclusive cfDNA test result. The detection and false-positive rate of a contingent approach that is based on combined screening and cfDNA screening in the intermediate group would be 98.4% and 0.7%, respectively. With this approach, cfDNA screening would be necessary in only about 27% of all pregnancies. CONCLUSION: This study demonstrates that a contingent approach provides similar detection rates for trisomy 21 as universal cfDNA screening, by a reduction of 73% the number of cfDNA tests.

Intraoral scanning of neonates and infants with craniofacial disorders: feasibility, scanning duration, and clinical experience.

OBJECTIVE: The aim of this study was to evaluate intraoral scanning (IOS) in infants, neonates, and small children with craniofacial anomalies for its feasibility, scanning duration, and success rate. Impression taking in vulnerable patients can be potentially life-threatening, with the risk of airway obstruction and aspiration of impression material. The advantage of increasingly digitalized dentistry is demonstrated. MATERIALS AND METHODS: IOS was captured with the Trios 3® (3Shape, Copenhagen, Denmark) intraoral scanner. The underlying disorders were divided into cleft lip and palate (CLP), Trisomy 21 (T21), Robin Sequence (RS), Treacher Collins syndrome (TC), and isolated mandibular retrognathia (MR). Scan data were analysed by scanning duration, number of images, possible correlations of these factors with the different craniofacial disorders, patient age, and relationship between first and subsequent scans. Clinical experiences with the repeated digital impressions are described. RESULTS: Patient data of 141 scans in 83 patients were analysed within an 11-month period. Patients had a median age of 137 days. Median scanning duration was 138 seconds, resulting in a median of 352 images. There was a statistically significant difference in scanning duration (P = 0.001) between infants and neonates. IOS took longest in patients with CLP (537 seconds) and shortest in T21 patients (21 seconds), although there was no statistically significant difference between aetiologies. There was no statistically significant difference between first and subsequent scans in scanning duration. In four cases the IOS had to be repeated, and one patient ultimately required conventional impression taking (all CLP patients; success rate 94%). No severe adverse events occurred. CONCLUSION: IOS is a fast, safe, and feasible procedure for neonates, small children, and infants with craniofacial malformations. One special challenge for both technician and user was identified in patients with CLP, though implementing this new approach of digital impression taking was otherwise found to be highly successful in everyday clinical routine.

Enteral feeding advancement and growth until 5 years in extremely preterm infants.

BACKGROUND: In-utero weight gain can be achieved in very preterm infants through rapid advancement of enteral feeds without increasing risk of necrotizing enterocolitis. There are concerns, however, that such rapid weight gain may lead to an increased childhood adiposity risk, although long-term data are sparse. DESIGN: This retrospective observational study included two well-characterized cohorts comprising 145 infants born at < 28 weeks or with < 1000 g birth weight. We investigated associations between advancing enteral feeding volumes in daily increments of 15-20 ml/kg (Cohort 1, n = 84, born in 2006/2007) vs. 25-30 ml/kg (Cohort 2, n = 61, born in 2010) and growth up to 5 years of age. RESULTS: There was no significant difference in anthropometric parameters post discharge to 5 years between both cohorts. Standard deviation score (SDS) weight and SDS BMI at the age of 5 years remained lower than in the reference population. SDS weight decreased from discharge to about 10-12 months postnatal age and returned to birth values by age 5 years. There was a catch-up for SDS length/height from discharge to 5 years; SDS head circumference decreased from birth to 5 years. Multiple regression analyses revealed that for all anthropometric parameters SDS at birth was the most important predictor for SDS at 5 years. Early parenteral protein intake may be another important factor, at least for head growth. CONCLUSIONS: Growth was similar in both cohorts without benefit from more accelerated feeding advancement in cohort 2. In both cohorts, early enteral nutrition was associated with in-hospital weight gain as in utero, a drop in weight SDS post discharge and catch-up to birth SDS until age 5 years, remaining below the reference population. Length showed catch-up form discharge to 5 years, whereas head circumference progressively deviated from the reference population. Increased parenteral protein supplementation may be needed to accompany early enteral feeding advancements.

Body composition in term offspring after maternal gestational diabetes does not predict postnatal hypoglycemia.

BACKGROUND: Offspring of mothers with gestational diabetes mellitus (GDM) have an increased risk of neonatal complications like birth trauma due to macrosomia or postnatal hypoglycemia, as well as long-term metabolic sequelae. Neonatal body composition may be a sensitive marker of metabolic effects on the fetus caused by suboptimal glycemic control during pregnancy. OBJECTIVE: To determine body composition in offspring of mothers with GDM compared to a reference cohort of healthy term neonates and to assess whether increased body fat would be associated with postnatal hypoglycemia. METHODS: This prospective, observational, cross-sectional study included 311 full-term, singleton infants born between June 2014 and July 2015. Body composition was measured within 96 h of birth using air displacement plethysmography. Results are indicated as median (1st Quartile - 3rd Quartile). RESULTS: Of 311 infants, 40 (12.9%) were born to mothers with GDM. Birth weight standard deviation scores (SDS) (0.24 vs. - 0.07, p = 0.04), fat mass (370 g vs. 333 g, p = 0.02) as well as fat mass/total body mass (BF%; 11.4% vs. 10.8%, p = 0.03) were significantly higher in infants following maternal GDM than in controls. In GDM offspring, anthropometric parameters, fat mass or BF% did not differ between infants with or without postnatal hypoglycemia. In this cohort, SDS for birth weight, fat mass, fat free mass, BF% or postnatal hypoglycemia were not associated with maternal blood glucose levels measured at an oral glucose tolerance test. CONCLUSIONS: SDS for birth weight, neonatal fat mass, and BF% were significantly higher in newborns following maternal GDM. In these infants born to mothers with GDM, body composition did not differ between those with or without postnatal hypoglycemia.

An innovative method for manufacturing the Tuebingen palatal plate for infants with Robin sequence.

BACKGROUND: Robin sequence (RS) is characterized by mandibular micro- and retrognathia, glossoptosis, upper airway obstruction and optionally a cleft palate. With an incidence of 1:8000, it belongs to the so-called rare diseases; 30-50% of patients have RS as part of a syndrome. A comparatively well-studied treatment option is the Tuebingen Palatal Plate (TPP), which has proven effective in both, isolated and syndromic RS, but often requires multiple endoscopies for perfect fit and effectiveness. We report on a new method for fitting the TPP with only one session of nasopharyngeal endoscopy resulting in the plate being finished in one day. METHODS AND RESULTS: First, a prototype is produced, consisting of a traditional acrylic palatal part and a velar extension made of thermoplastic resin, usually measuring 10x40mm. Using polymerization, a scale is added to the posterior part of the extension to help with determining its optimal length during endoscopic evaluation. The extension is pre-bent in the dental laboratory to achieve an approximate shape. During endoscopy, the prototype can be adjusted to the infant's anatomy: first, the angulation is customized by controlled heating, bending and cooling of the thermoplastic spur. Second, the length of the spur is adapted by grinding its tip. Then the prototype is returned to the dental laboratory for completion; the final plate can be delivered to the patient on the same day. It acts by shifting the tongue into a more anterior position, thereby opening the airway and releasing upper airway obstruction, as well as by acting as a functional orthodontic appliance that stimulates mandibular growth through exerting pressure on the base of the tongue. CONCLUSIONS: With the thermoplastic spur presented here, a TPP can be produced within one day, requiring only one endoscopy. This approach may facilitate fabricating the TPP.

Pregnancy following kidney transplantation - impact on mother and graft function and focus on childrens' longitudinal development.

BACKGROUND: Pregnancy after kidney transplantation has been considered as high risk for maternal and fetal complications. After careful patient selection successful pregnancies are described. Little is known about fetal outcomes and data is particularly scarce on childrens´ early development up to two years when born to kidney/-pancreas transplant recipients. Here, we analyzed maternal and fetal risk and evaluated graft function during pregnancy in transplanted women. We aimed to identify factors affecting the outcomes of mothers and their grafts during pregnancy and of children up to 2 years after delivery/ birth. METHODS: All consecutive pregnancies in kidney/ kidney-pancreas recipients with live-born children from 2002 to 2016 were evaluated in two transplant centers (Charité Berlin/ University Tuebingen). All data was gathered from medical records. Impact of pregnancy on obstetrical risks, graft function and fetal development was evaluated. Additionally, for the first time development of children, including physical examination and assessment of neurological function were evaluated at 12 and 24 months. RESULTS: Thirty-two pregnancies in 28 patients with a median duration of 34 gestational weeks (range, 24-38) were analyzed. 13 patients (46.4%) developed deterioration of kidney graft function > 10 ml/min during pregnancy. In majority, caesarean section was performed (75%). Twenty-five (78.1%) children were born prematurely, thereof (16%) < 28 weeks. Almost 70% had low birth weights (LBW) (< 2.500 g); median birth weight was 2.030 g. General health and physical constitution of children were unremarkable with normal development in 94% at 12 and 24 months of corrected age, respectively. CONCLUSION: Despite the high rate of preterm birth and LBW, development up to two years was age-appropriate in this cohort. Due to low absolute numbers, increasing efforts in centralized counseling, diagnostics and committed specialist support are required. Decisive treatment of these high-risk patients in specialized units leading to better performance of these patients (mother/ fetus) is deemed superior. In order to confirm this, prospective studies on neonatal and pediatric outcomes with a standard-of-care comparator arm will be conducted.

Neonatal body composition by air displacement plethysmography in healthy term singletons: a systematic review.

BACKGROUND: There is increasing evidence that intrauterine environment and, consequently, growth in utero have both immediate and far-reaching consequences for health. Neonatal body composition might be a more sensitive marker of intrauterine environment and neonatal adiposity than birth weight and could serve as a predictor for non-communicable diseases later in life. METHODS: To perform a systematic literature review on neonatal body composition determined by air displacement plethysmography in healthy infants. The systematic review was performed using the search terms "air displacement plethysmography", "infant" and "newborn" in Pubmed. Data are displayed as mean (Standard deviation). RESULTS: Fourteen studies (including n = 6231 infants) using air displacement plethysmography fulfilled inclusion criteria for meta-analysis. In these, weighted mean body fat percentage was 10.0 (4.1) % and weighted mean fat free mass was 2883 (356) g in healthy term infants. Female infants had a higher body fat percentage (11.1 (4.1) % vs. 9.6 (4.0) %) and lower fat free mass (2827 (316) g vs. 2979 (344) g). In the Caucasian subpopulation (n = 2202 infants) mean body fat percentage was 10.8 (4.1), whereas data for reference values of other ethnic groups are still sparse. CONCLUSIONS: Body composition varies depending on gender and ethnicity. These aggregated data may serve as reference for body composition in healthy, term, singletons at least for the Caucasian subpopulation.

Neonatal body composition: crossectional study in healthy term singletons in Germany.

BACKGROUND: During pregnancy, a variety of factors can influence fetal growth and development. Intrauterine growth may impact on later life and health. Neonatal body composition may be a more sensitive marker for the intrauterine environment than established anthropometric parameters at birth. METHODS: To study neonatal body composition determined by air displacement plethysmography in healthy, term singletons as national reference data, and to establish factors impacting on neonatal body composition in this population. This prospective cross-sectional observational study included 271 healthy, full-term, singletons born between June 2014 and July 2015. Body composition was measured within 96 h of birth using air displacement plethysmography. RESULTS: Median (Q1, Q2) fat mass / total body mass (BF%) in German singletons was 10.8% (7.7-13.4) and fat free mass (FFM) 2843 g (2606-3099). Female infants had significantly increased BF% compared to male infants (11.2% (8.7-14.0) vs. 9.6% (7.2-12.1)). On multiple regression analysis, BF% and fat mass increased with female gender, maternal pre-pregnancy body mass index, non-smoking mother and parity, whereas FFM increased with male gender and increasing gestational age at birth. Gestational weight gain category, birth mode, and postnatal age at measurement were not associated with BF%, FFM or fat mass. CONCLUSIONS: We generated BF% and FFM centiles for healthy, term, singletons born in Germany; these are similar to those found in other European countries. Infant body composition at birth was associated with modifiable (pre-pregnancy body mass index, smoking), and given factors (gender, gestational age at birth, parity).

Prospective cohort study on facial profile changes in infants with Robin sequence and healthy controls.

BACKGROUND: Various conservative and surgical approaches exist to treat Robin sequence (RS), but their effects on facial profile and mandibular catch-up growth are unclear. A functional treatment concept, used in our centre for 25 years, includes an individualized palatal plate with a velo-pharyngeal extension and intensive feeding training. METHODS: We performed a prospective study to objectively describe facial profiles in infants with RS treated with the above concept. Infants with isolated RS were admitted to our tertiary perinatal and national referral centre for craniofacial malformations between May 2018 and Nov 2019. Infants with RS received 3D-photographs during clinically indicated visits. Healthy controls were recruited from Dec 2018 to Sep 2019 and received 3D-photographs every 3 months. The digitally measured jaw index (JI), defined as alveolar overjet (O) x maxillary arch (U)/mandibular arch (L), and the soft tissue reference points A'-point, Nasion', B'-point angle (ANB'), describing the relative position of maxilla to mandible, were evaluated. Linear mixed models were used to examine time trajectories in JI and ANB'. RESULTS: A total of 207 3D images, obtained in 19 infants with RS and 32 controls, were analysed. JI and ANB' decreased over time in both groups [for JI - 0.18 (95% CI - 0.25 to - 0.10); for ANB': - 0.40° per month [(95% CI - 0.48 to - 0.32)]] but remained lower in controls [for JI - 2.5 (95% CI - 3.2 to - 1.8); for ANB'-1.7° (95% CI - 2.4 to - 1.0)]. Also, the ANB' model showed a significant effect of the interaction term diagnosis x age. CONCLUSIONS: Based on longitudinal 3D images, we describe changes in objective parameters of facial profile in infants with and without RS during the first year of life. Our findings indicate catch-up growth in infants treated for RS. Video Abstract.

Evidence and Perspectives for Choline Supplementation during Parenteral Nutrition-A Narrative Review.

Choline is an essential nutrient, with high requirements during fetal and postnatal growth. Tissue concentrations of total choline are tightly regulated, requiring an increase in its pool size proportional to growth. Phosphatidylcholine and sphingomyelin, containing a choline headgroup, are constitutive membrane phospholipids, accounting for >85% of total choline, indicating that choline requirements are particularly high during growth. Daily phosphatidylcholine secretion via bile for lipid digestion and very low-density lipoproteins for plasma transport of arachidonic and docosahexaenoic acid to other organs exceed 50% of its hepatic pool. Moreover, phosphatidylcholine is required for converting pro-apoptotic ceramides to sphingomyelin, while choline is the source of betaine as a methyl donor for creatine synthesis, DNA methylation/repair and kidney function. Interrupted choline supply, as during current total parenteral nutrition (TPN), causes a rapid drop in plasma choline concentration and accumulating deficit. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) defined choline as critical to all infants requiring TPN, claiming its inclusion in parenteral feeding regimes. We performed a systematic literature search in Pubmed with the terms "choline" and "parenteral nutrition", resulting in 47 relevant publications. Their results, together with cross-references, are discussed. While studies on parenteral choline administration in neonates and older children are lacking, preclinical and observational studies, as well as small randomized controlled trials in adults, suggest choline deficiency as a major contributor to acute and chronic TPN-associated liver disease, and the safety and efficacy of parenteral choline administration for its prevention. Hence, we call for choline formulations suitable to be added to TPN solutions and clinical trials to study their efficacy, particularly in growing children including preterm infants.

Early feeding of fortified breast milk and in-hospital-growth in very premature infants: a retrospective cohort analysis.

BACKGROUND: Fortified human milk may not meet all nutritional needs of very preterm infants. Early transition from complementary parenteral nutrition to full enteral feeds might further impair in-hospital growth. We aimed to investigate the impact of the cumulative intake of fortified human milk on early postnatal growth in a cohort of very low birth weight infants after early transition to full enteral feeds. METHODS: Retrospective single-centre observational study. Data are presented as median (interquartile range). RESULTS: N = 206 very preterm infants were analysed (gestational age at birth 27.6 (25.6-29.6) weeks, birth weight 915 (668-1170) g). Full enteral feeds were established at postnatal day 8 (6-10) and adequate postnatal growth was achieved (difference in standard deviation score for weight from birth to discharge -0.105(-0.603 - -0.323)). Standard deviation score for weight from birth to day 28 decreased more in infants with a cumulative human milk intake > 75% of all enteral feeds (-0.64(-1.08 - -0.34)) compared to those with < 25% human milk intake (-0.41(-0.7 - -0.17); p = 0.017). At discharge, a trend towards poorer weight gain with higher proportions of human milk intake persisted. In contrast, we observed no significant difference for head circumference growth. CONCLUSIONS: Our current standardized fortification of human milk may not adequately support early postnatal growth.

Study protocol for a multicenter, multinational, observational registry of epidemiology, treatment and outcome of patients with Robin sequence.

BACKGROUND: Robin sequence (RS) is a congenital condition characterized by micrognathia, glossoptosis and upper airway obstruction. Diagnosis and treatment are characterized by heterogeneity, resulting in a lack of uniformly collected data. METHODS: We have set up a prospective, observational, multicenter, multinational registry aimed at obtaining routine clinical data from RS patients receiving different treatment approaches and enabling an assessment of outcomes obtained through different therapeutic approaches. Patient enrolment has started in January 2022. Disease characteristics, adverse events and complications depending on the different diagnostic and treatment approaches and their effects on neurocognition, growth, speech development and hearing outcome are evaluated using routine clinical data. In addition to characterizing the patient population and comparing outcomes achieved with different treatment approaches, the registry will evolve to focus on endpoints such as quality of life and long-term developmental status. DISCUSSION: This registry will provide data on different treatment approaches collected during routine care with diverse framework conditions and will allow assessing diagnostic and therapeutic outcomes of children with RS. These data, urgently demanded by the scientific community, may contribute to refining and personalizing existing therapeutic approaches and increase knowledge about the long-term outcome of children born with this rare condition. TRIAL REGISTRATION: DRKS00025365.