This thesis reinforce that children born preterm are at risk for long-term impairments. Being able to predict who is at risk, by neonatal neuroimaging or early assessment, remains difficult,... Show moreThis thesis reinforce that children born preterm are at risk for long-term impairments. Being able to predict who is at risk, by neonatal neuroimaging or early assessment, remains difficult, especially in children who have milder forms of brain injury and/or experience milder difficulties at two years of age. Currently, most follow-up assessments use standardized outcome measures that might not show the full extent of a child’s daily functioning. Additional measurements and/or the implementation of qualitative research can be of great additional value. Show less
Bos, M.; Koenders, M.J.M.; Dijkstra, K.L.; Meeren, L.E. van der; Nikkels, P.G.J.; Bloemenkamp, K.W.M.; ... ; Hoorn, M.L.P. van der 2023
Introduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta that is associated with poor reproductive outcomes. The intervillous infiltrate consists... Show moreIntroduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta that is associated with poor reproductive outcomes. The intervillous infiltrate consists mostly of maternal mononuclear cells and fibrin depositions, which are both indicators for the severity of the intervillous infiltrate. The severity of the intervillous infiltrate as well as the clinical outcomes of pregnancy differ between cases. Our objective is to determine the relation between the severity of the intervillous infiltrate and the clinical outcomes of CHI. Methods: Cases of CHI were semi-quantitatively graded based on histopathological severity scores. Hereto, CD68 positive mononuclear cells were quantified, fibrin depositions visualized by both a PTAH stain and an immuo-histochemical staining, and placental dysfunction was assessed via thrombomodulin staining. Results: This study included 36 women with CHI. A higher CD68 score was significantly associated with a lower birthweight. Loss of placental thrombomodulin was associated with lower gestational age, lower birthweight, and a lower placenta weight. The combined severity score based on CD68 and PTAH was significantly associated with fetal growth restriction, and the joint score of CD68 and fibrin was associated with birthweight and placental weight. Discussion: More severe intervillous infiltrates in CHI placentas is associated with a lower birth weight and placental weight. Furthermore, this study proposes thrombomodulin as a possible new severity marker of placental damage. More research is needed to better understand the pathophysiology of CHI. Show less
Jansen, L.; Steggerda, S.; Rijken, M.; Steenis, A. van; Vries, L. de; Peeters-Scholte, C.; ... ; Klink, J. van 2022
Preterm infants are at risk of developing social-emotional and behavioural difficulties. To understand the experiences of their caregivers in day-to-day life, parents (at 2 and 10 years) and... Show morePreterm infants are at risk of developing social-emotional and behavioural difficulties. To understand the experiences of their caregivers in day-to-day life, parents (at 2 and 10 years) and teachers (at 10 years) completed a behavioural questionnaire and answered two open-ended questions addressing their concerns and the most positive aspects regarding their child and/or pupil (born <32 weeks gestation). Their answers were analyzed using thematic content analysis. Parental concerns at two years related equally to themes in the clusters Developmental Milestones, Physical Development and Development in Relation to the Self and Others. At 10 years, both parents and teachers reported mainly within the cluster Development in Relation to the Self and Others, but the underlying themes differed. While parents more often mentioned their child's emotional development, teachers were more concerned about their pupils' difficulties interacting with their peers, due to a lack of social skills. In-depth qualitative analysis of what parents and teachers experience from day-to-day improves our understanding of the social-emotional and behavioural development of children born very preterm, revealing important topics that should be addressed during follow-up. Show less
Background: Internationally recognized guidelines recommend the judicious use of low oxygen (21-30%), titrated to peripheral oxygen saturation targets, for the initiation of re- suscitation of very... Show moreBackground: Internationally recognized guidelines recommend the judicious use of low oxygen (21-30%), titrated to peripheral oxygen saturation targets, for the initiation of re- suscitation of very and extremely preterm infants (<32 weeks' gestation). However, despite more than 10 randomized controlled trials on this question, the ideal initial oxygen concentration for this group of vulnerable infants remains uncertain. Aims: This study aims to assess the effect of various initial oxygen concentrations on (1) all-cause mortality, chronic lung disease, intraventricular hemorrhage, and retinopathy of prematurity; and (2) reaching the prescribed oxygen saturation targets by 5 min after birth, in preterm infants requiring resuscitation. Methods: We will conduct a system- atic review and network meta-analysis using individual participant data. Studies of preterm infants <32 weeks' gestation, randomized to initial oxygen concentration, will be included. We will systematically search medical databases and trial registriesfor eligible studies (published or unpublished). Records will be screened by two independent reviewers, with conflicts resolved by the inclusion of a third reviewer. Identified initial oxygen concentrations will be grouped into the following nodes: low (<= 30%), intermediate (60%), and high (>= 90%) oxygen. A two-step random-effects contrastbased network meta-regression will be calculated to compare and rank different oxygen concentrations. Analyses will be intention-to-treat, with the primary outcome of all-cause mortality. Discussion: This is the first individual participant data network meta-analysis of initial oxygen concentrations for the resuscitation of preterm infants. This novel approach may address long-standing uncertainty regarding optimal oxygen supplementation practice for the resuscitation of preterm infants <32 weeks' gestation. (C) 2022 S. Karger AG, Basel Show less
Visser, S.S.M.; Diemen, W.J.M. van; Kervezee, L.; Hoogen, A. van den; Verschuren, O.; Pillen, S.; ... ; Dudink, J. 2021
Premature birth (before 37 weeks of gestation) has been linked to a variety of adverse neurological outcomes. Sleep problems are associated with decreased neurocognitive functioning, which is... Show morePremature birth (before 37 weeks of gestation) has been linked to a variety of adverse neurological outcomes. Sleep problems are associated with decreased neurocognitive functioning, which is especially common in children born preterm. The exact relationship between prematurity and sleep at school age is unknown. A systematic review is performed with the aim to assess the relationship between prematurity and sleep at school age (5th to 18th year of life), in comparison to sleep of their peers born full-term. Of 347 possibly eligible studies, nine were included. The overall conclusion is that prematurity is associated with earlier bedtimes and a lower sleep quality, in particular more nocturnal awakenings and more non-rapid eye movement stage 2 sleep. Interpretations and limitations of the review are discussed. Moreover, suggestions for future research are brought forward, including the need for a systematic approach with consistent outcome measures in this field of research. A better understanding of the mechanisms that influence sleep in the vulnerable group of children born preterm could help optimize these children's behavioral and intellectual development. (C) 2021 The Author(s). Published by Elsevier Ltd. Show less
Salaets, T.; Aertgeerts, M.; Gie, A.; Vignero, J.; Winter, D. de; Regin, Y.; ... ; Toelen, J. 2020
Background Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth,... Show moreBackground Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits. Methods Pups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms. Results Preterm pups assessed at birth depicted a more rudimentary lung structure (larger alveoli and thicker septations) and a lower expression of surfactant proteins in comparison to term pups. MicroCT and dark field imaging revealed delayed lung aeration in preterm pups, in comparison to term pups. Preterm birth led to smaller pups, with smaller lungs with a lower alveolar surface area on day 7/day 4. Furthermore, preterm birth affected lung function with increased tissue damping, tissue elastance and resistance and decreased dynamic compliance. Expression of vascular endothelial growth factor (VEGFA) was significantly decreased in preterm pups, however in the absence of structural vascular differences. Conclusions Preterm birth affects lung structure and function at birth, but also has persistent effects on the developing lung. This supports the use of a preterm animal model, such as the preterm rabbit, for preclinical research on BPD. Future research that focuses on the identification of pathways that are involved in in-utero lung development and disrupted by pre-term birth, could lead to novel therapeutic strategies for BPD. Show less
Hooper, S.B.; Roberts, C.; Dekker, J.; Pas, A.B. te 2019
The transition from fetal to newborn life involves a complex series of physiological events that commences with lung aeration, which is thought to involve 3 mechanisms. Two mechanisms occur during... Show moreThe transition from fetal to newborn life involves a complex series of physiological events that commences with lung aeration, which is thought to involve 3 mechanisms. Two mechanisms occur during labour, Na+ reabsorption and fetal postural changes, and one occurs after birth due to pressure gradients generated by inspiration. However, only one of these mechanisms, fetal postural changes, involves the loss of liquid from the respiratory system. Both other mechanisms involve liquid being reabsorbed from the airways into lung tissue. While this stimulates an increase in pulmonary blood flow (PBF), in large quantities this liquid can adversely affect postnatal respiratory function. The increase in PBF (i) facilitates the onset of pulmonary gas exchange and (ii) allows pulmonary venous return to take over the role of providing preload for the left ventricle, a role played by umbilical venous return during fetal life. Thus, aerating the lung and increasing PBF before umbilical cord clamping (known as physiological based cord clamping), can avoid the loss of preload and reduction in cardiac output that normally accompanies immediate cord clamping. Show less
Children born small-for-gestational-age (SGA) are at risk for short stature, and cardiovascular disease and type 2 diabetes in later life. There is some preliminary evidence for a similar phenotype... Show moreChildren born small-for-gestational-age (SGA) are at risk for short stature, and cardiovascular disease and type 2 diabetes in later life. There is some preliminary evidence for a similar phenotype in survivors of preterm birth. In contrast to children born SGA, preterm infants born appropriate-for-gestational-age who experienced neonatal growth retardation, resulting in a small size at term, are excluded from growth hormone therapy if they fail to catch up in height subsequently. We tested in 19-year-olds born before 32 gestational weeks from the Project On Preterm and Small-for-gestational-age infants cohort the effect of early growth on the growth pattern and adult metabolic health. Childhood growth and adult height were similar in preterm infants born SGA and those with neonatal growth retardation (weight and/or length at 3 months <-2 SD score). Young adults born preterm had a waist circumference and a waist-to-hip ratio much greater than the population reference mean, especially women. In addition, they showed a tendency towards insulin resistance and a high prevalence of hypertension. These findings were not explained by antenatal glucocorticoid treatment. Carriers of the 23K variant of the R23K polymorphism in the glucocorticoid receptor, associated with a mild glucocorticoid resistance, were less insulin-resistant and showed complete catch-up growth early in infancy and attained height was similar to the population reference mean, whereas stature in non-carriers was on average 0.5 SD below this mean Show less
