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Study Question: What is the cost-effectiveness of elective single embryo transfer (eSET) versus double embryo transfer (DET) strategies from a societal perspective, when applying a time horizon of 1, 5 and 18 years?Summary Answer: From a short-term perspective (1 year) it is cost-effective to replace DET with single embryo transfer; however when intermediate- (5 years) and long-term (18 years) costs and consequences are incorporated, DET becomes the most cost-effective strategy, given a ceiling ratio of €20 000 per quality-adjusted life years (QALY) gained.What Is Already Known: According to previous cost-effectiveness research into embryo transfer strategies, DET is considered cost-effective if society is willing to pay around €20 000 for an extra live birth. However, interpretation of those studies is complicated, as those studies fail to incorporate long-term costs and outcomes and used live birth as a measure of effectiveness instead of QALYs. With this outcome, both multiple and singletons were valued as one live birth, whereas costs of all children of a multiple were incorporated.Study Design, Size, Duration: A Markov model (cycle length: 1 year; time horizon: 1, 5 and 18 years) was developed comparing a maximum of: (i) three cycles of eSET in all patients; (ii) four cycles of eSET in all patients; (iii) five cycles of eSET in all patients; (iv) three cycles of standard treatment policy (STP), i.e. eSET in women <38 years with a good quality embryo, and DET in all other women; and (v) three cycles of DET in all patients.Participants/materials, Setting, Methods: Expected life years (LYs), child QALYs and costs were estimated for all comparators. Input parameters were derived from a retrospective cohort study, in which hospital resource data were collected (n=580) and a parental questionnaire was sent out (431 respondents). Probabilistic sensitivity analysis (5000 iterations) was performed.Main Results and the Role Of Chance: With a time horizon of 18 years, DETx3 is most effective (0.54 live births, 10.2 LYs and 9.8 QALYs) and expensive (€37 871) per couple starting IVF. Three cycles of eSET are least effective (0.43 live births, 7.1 LYs and 6.8 QALYs) and expensive (€25 563). We assumed that society is willing to pay €20 000 per QALY gained. With a time horizon of 1 year, eSETx3 was the most cost-effective embryo transfer strategy with a probability of being cost-effective of 99.9%. With a time horizon of 5 or 18 years, DETx3 was most cost-effective, with probabilities of being cost-effective of 77.3 and 93.2%, respectively.Limitations, Reasons For Caution: This is the first study to use QALYs generated by the children in the economic evaluation of embryo transfer strategies. There remains some disagreement on whether QALYs generated by new life should be used in economic evaluations of fertility treatment. A further limitation is that treatment ends when it results in live birth and that only child QALYs were considered as measure of effectiveness. The results for the time horizon of 18 years might be less solid, as the data beyond the age of 8 years are based on extrapolation.Wider Implications Of the Findings: The current Markov model indicates that when child QALYs are used as measure of outcome it is not cost-effective on the long term to replace DET with single embryo transfer strategies. However, for a balanced approach, a family-planning perspective would be preferable, including additional treatment cycles for couples who wish to have another child. Furthermore, the analysis should be extended to include QALYs of family members.Study Funding/competing Interests: This study was supported by a research grant (grant number 80-82310-98-09094) from the Netherlands Organization for Health Research and Development (ZonMw). There are no conflicts of interest in connection with this article.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

In neonates, bolus feeding is associated with greater rates of intestinal growth than is continuous feeding. We tested whether the concentrations and secretion rates of trophic gut peptides are higher in bolus-fed than in continuously fed piglets. Five 21-d-old piglets were surgically implanted with gastric, arterial and portal catheters and a portal blood flow probe. At postnatal d 30 and 31, pigs received an equal amount of primed continuous or bolus feeding of a cow's milk formula in a randomized, crossover design. During a 6-h period, portal blood flow and arterial and portal concentrations of glucagon-like peptide-2 (GLP-2), peptide YY (PYY) and gastric inhibitory polypeptide (GIP) were measured. All hormone levels were significantly increased within 1 h of the start of the experiment, independent of the feeding modality. There were no differences between bolus and continuous feeding in either the arterial concentrations or secretion rates of GLP-2, PYY and GIP. In both treatment groups, the increases in the plasma concentrations of GLP-2 and GIP after feeding were substantially greater than those for PYY. We conclude that the production or circulating concentrations of GLP-2, PYY and GIP are not significantly different in bolus- and primed continuously fed piglets. [ABSTRACT FROM AUTHOR]

The period of growth and development between birth and weaning is crucial for the long-term well-being of the organism. Protein deposition is very rapid, is achieved with a high nutritional efficiency, and is accompanied by marked differences in the growth rates of individual tissues and a series of maturational processes. These important aspects of development occur while the neonate is consuming a single and highly-specific food source, milk. Surprisingly, although there is a clear relationship between the nutrient density of milk and the growth rate of its recipient, this relationship does not apply to the overall amino acid composition of mixed milk proteins. Some amino acids, notably glycine and arginine, are supplied in milk in quantities that are much less than the needs of the neonate. The milk-fed neonate is therefore capable of carrying out a tightly-regulated transfer of N from amino acids in excess to those that are deficient. The rapid growth of the neonate is supported by a high rate of tissue protein synthesis. This process appears to be activated by the consumption of the first meals of colostrum. Recent research has identified that skeletal muscle and the brain are specifically responsive to an unidentified factor in colostrum. Following the initial anabolic response the rate of protein synthesis in some tissues, notably muscle, falls from birth to weaning. This decrease reflects a progressively smaller anabolic response to nutrient intake, which not only involves an overall fall in the capacity for protein synthesis, but also in responses to insulin and amino acids. The study of growth and protein metabolism, and their regulation in the neonate is not only important for pediatrics, but may provide important pointers to more general aspects of regulation that could be applied to the nutrition of the mature animal. [ABSTRACT FROM AUTHOR]

A letter to the editor describing a method to study the role of dietary threonine in intestinal MUC2 synthesis and to determine the fractional synthetic rate of small intestinal MUC2 in human neonates as a parameter for intestinal barrier function, is presented.

Background: Assessing Quality of Life (QoL) of persons with profound intellectual and multiple disabilities (PIMD) is challenging, yet QoL plays an important role in medical decision-making processes concerning persons with PIMD. The perspectives of parents of children with PIMD on the assessment of their QoL have not been studied., Aim: To explore the perspectives of parents on the assessment of QoL of their children., Methods: We conducted a qualitative study, forming three focus groups with 22 parents of children with PIMD to explore their views on what is necessary to assess QoL of their children and subsequently, who is best suited to assess QoL., Results: Parents describe a long-term relationship of the assessor with family (child and parents), with trust as an important aspect, as a requirement to assess QoL. Parents consider family members, preferably the parents themselves as the best assessors of QoL, followed by siblings. Professional caregivers, mostly mentioned by name, are considered the next alternative. Most parents thought that physicians do not know the child well enough to assess their QoL., Conclusions: In conclusion, the parents of children with PIMD in our study consider trust and a long-term relationship essential for assessing QoL., Competing Interests: Disclosure statement The authors declare that they have no conflicts of interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Maternal stress in the postpartum period affects not only the mother, but also her newborn child who is at increased risk for a wide range of disorders later in life. The mechanisms underlying transmission of maternal stress to the child remain elusive. Human milk (HM) is a potential candidate and is an important source of fatty acid (FA), which are crucial for child (neuro)development. This study aims to investigate whether maternal psychological and biological stress influences HM FA composition over the first month postpartum., Methods: The Amsterdam Mother's Milk study is a prospective cohort study. We included lactating women who delivered at term with a large range of stress levels: a high stress (HS) group, women whose child was hospitalized for a minimum of 2 days (n=23) and a control (CTL) group, women who gave birth to a healthy child (n=73). HM was collected three times a day at postpartum days 10, 17 and 24. Perceived psychological stress was measured using multiple validated questionnaires, while biological stress measures were based on cortisol in hair, saliva and HM. HM FAs were analyzed by gas-chromatography and compared between groups., Results: Maternal perceived stress scores were significantly higher in the HS group (p < 0.01), whereas cortisol measurements did not differ between groups. The absolute concentrations of total FA in HM (p=0.023), including the total amount of poly unsaturated fatty acids (PUFAs) (p=0.022) and omega-6 PUFAs (p=0.018), were lower in the HS group compared to the CTL group. Relative values of FAs did not differ between groups., Conclusion: Maternal stress in the first month postpartum was associated with overall lower levels of FA in HM. This possibly indicates a route of transmission of maternal stress signals to the infant. Future research should investigate if these stress-induced changes in HM FAs have consequences for child development., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Gastrointestinal viral infections are a major global cause of disease and mortality in infants. Cytotoxic CD8 + T cells are critical to achieve viral control. However, studies investigating the development of CD8 + T cell immunity in human tissues early in life are lacking. Here, we investigated the maturation of the CD8 + T cell compartment in human fetal, infant and adult intestinal tissues. CD8 + T cells exhibiting a memory phenotype were already detected in fetal intestines and increased after birth. Infant intestines preferentially harbored effector CCR7 - CD45RA - CD127 - KLRG1 +/- CD8 + T cells compared to tissue-resident memory CD69 + CD103 + CD8 + T cells detected in adults. Functional cytotoxic capacity, including cytokine and granzyme B production of infant intestinal effector CD8 + T cells was, however, markedly reduced compared to adult intestinal CD8 + T cells. This was in line with the high expression of the inhibitory molecule PD-1 by infant intestinal effector CD8 + T cells. Taken together, we demonstrate that intestinal CD8 + T cell responses are induced early in human development, however exhibit a reduced functionality. The impaired CD8 + T cell functionality early in life contributes to tolerance during foreign antigen exposure after birth, however functions as an immune correlate for the increased susceptibility to gastrointestinal viral infections in infancy.

The aim of this study was to determine the potential impact of the Pediatric Emergency Care Applied Research Network (PECARN) rules on the CT rate in a large paediatric minor traumatic head injury (MTHI) cohort and compare this with current national Dutch guidelines. This was a planned sub-study of a prospective multicentre observational study that enrolled 1006 children younger than 18 years with MTHI. We calculated the number of recommended CT scans and described trauma-related CT scan abnormalities. The PECARN rules recommended a significantly lower percentage of CT scans in all age categories, namely 101/357 (28.3%) versus 164/357 (45.9%) (p < 0.001) in patients under 2 years of age and 148/623 (23.8%) versus 394/623 (63.2%) (p < 0,001) versus in patients 2 years and older.Conclusion: The projected CT rate can significantly be reduced if the PECARN rules are applied. We therefore advocate that the PECARN guidelines are also implemented in The Netherlands. What is Known: • To guide clinicians whether to perform a CT scan in children with a minor traumatic head injury (MTHI) clinical decision rules has been developed. • The overall CT scan rate in adherence with the Dutch MTHI guidelines is 44%. What is New: • The projected CT rate can significantly be reduced in a Dutch cohort of MTHI if the PECARN rules are applied. • The Dutch national guidelines for MTHI can safely be replaced by the PECARN rules.

Background & Aims: Maternal obesity at conception is considered a major predictor of offspring obesity. This could by driven at least in part by an altered placental fat transfer. However, the pathophysiological mechanisms involved are not fully understood. We investigated the in vivo materno-fetal transfer of fatty acids (FAs) in obese pregnant women using stable isotopes., Methods: Ten obese and ten normo-weight pregnant women (control) received orally a bolus of 13 C-labeled FAs 12 h before elective caesarean section: oleic acid ( 13 C-OA), linoleic acid ( 13 C-LA) and docosahexaenoic acid ( 13 C-DHA). Maternal blood samples were collected at -12 (basal), -8, -4, -2, 0 h relative to the time of cesarean section. At the time of birth, arterial and venous cord bloods as well as placental tissue were collected. FAs composition was determined by gas-liquid chromatography and isotopic enrichment by gas chromatography-combustion-isotope ratio mass spectrometry., Results: Maternal plasma insulin and placental weight tended to higher values in obese pregnant women although they did not present serum hyperlipidemia. Higher concentrations of 13 C-LA and 13 C-DHA were found in non-esterified FAs fraction in maternal plasma of obese mothers. The ratio of placental uptake for 13 C-LA and 13 C-DHA was lower in obese women compared to normal weight pointing toward a limited capacity of FA placental transfer, especially of essential FAs. Maternal insulin was associated to this lower placenta/maternal plasma ratio for both 13 C-LA (R = -0.563, P = 0.012) and 13 C-DHA (R = -0.478, P = 0.033). In addition, the ratio cord/maternal plasma of 13 C-LA was significantly lower in obese women compared to controls., Conclusions: In conclusion, obese mothers without hyperlipidemia showed a reduced materno-fetal transfer of polyunsaturated FAs which could affect fetal development. This affect dietary recommendation for obese pregnant women., Trial Registry Number: ISRCTN69794527., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Persons with Profound Intellectual and Multiple Disabilities (PIMD) are supported by professional caregivers for a large part of their lives. However, the perspectives of professional caregivers on good or poor Quality of Live (QoL) of persons with PIMD have hardly been explored. To explore the perspective of professional caregivers on QoL of persons with PIMD, we performed a qualitative study, conducting semi-structured interviews with eleven professional caregivers and thematically analysed them. In the interviews, these professional caregivers described examples of good and poor QoL. Good QoL was mostly described in emotional terms such as happiness, pleasure and enjoying things. Poor QoL was mostly described in physical terms such as pain, sickness and shortage of breath. The capability of persons with PIMD to influence the environment was described as an element of good QoL. Furthermore, these professional caregivers described how they assessed QoL. They 'sensed' QoL, they tested it (trial and error) and discussed QoL of persons with PIMD with colleagues. Participants emphasized the dependency of persons with PIMD on professional caregivers. Furthermore, these professional caregivers described feelings of failure and powerlessness if they could not assess or fulfil the needs of persons with PIMD. We conclude that these professional caregivers use their (tacit) knowledge to understand QoL of persons with PIMD. The relationship between QoL of persons with PIMD and professional caregivers needs more investigation, because of its consequences both for the persons with PIMD and the professional caregivers., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Preterm infants are at risk for impaired bone mineralization and growth in length later in life due to inadequate nutritional intake in the early postnatal period., Objective: To investigate whether increased nutritional supplementation of calcium, phosphate and protein in Very Low Birth Weight (VLBW) infants during the first 14days after birth was associated with improvement in length and bone development until 9-10years of age., Design: Observational follow-up study of VLBW infants (birth weight<1500g or gestational age<32weeks) born in two consecutive years (eligible infants: 2004 n: 63 and 2005: n: 66). Cohort 2005 received higher intake of calcium, phosphate and protein with parenteral nutrition compared to Cohort 2004. Anthropometric data were collected during standard follow-up visits until five years, and additionally at 9-10years of age including measurements of bone mineral content, bone mineral density of the whole body and lumbar spine determined by dual-energy X-ray absorptiometry. Long-term growth trajectories of both cohorts were evaluated separately for participants born appropriate (AGA) and small for gestational age (SGA), stratified by gender. Multivariate linear regression was used to examine the effect of nutritional intake and clinical covariates on length and bone mineralization., Results: Both cohorts achieved a catch-up in length to SDS within the normal range by 6months (length SDS: estimated mean (95% confidence interval (CI): 6months: Cohort 2004: -0.7 (-1.1, -0.3) Cohort 2005: -0.5 (-0.8, -0.2)). Bone mineral content and density were within the normal range and not different between the cohorts. SGA children achieved a catch-up in length at 5years with bone mineralization comparable to AGA children. Only for girls birth weight was significantly associated with length SDS (per gram: β 0.001; 95% CI (0.000, 0.003); p=0.03) There was no evidence of an association between early nutritional intake and bone mineralization., Conclusion: Children born as appropriate or small for gestational age preterm infants are able to catch up in length after the postnatal period, and achieve a normal length and bone mineralization at age nine-ten years. An improvement of calcium and phosphate intake during the first 14days after birth was not associated with improvement in length and bone development., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)