Haemoglobinopathies and newborn haemoglobinopathy screening in Germany.

Germany has been an immigration country since the early 1950s. In December 2007, 6.7 million non-German citizens lived in the country. However, the total number of citizens with a migration background is 15–20 million, about 9 million of whom come from countries where sickle cell disease and thalassaemias are frequent. In a country with 82 million inhabitants health authorities are not worried by the presence of probably 1000–1500 sickle cell and 450 transfusion-dependent thalassaemia patients, and therefore no screening or preventive measures have been taken so far on a national scale. There are plans for a pilot project (1 year) to screen all newborns for sickle cell disease in obstetric hospitals in 4–5 cities with more than 20% migrants. Funding and lack of an infrastructure to provide counselling are major problems

The Endothelial Glycocalyx: Physiology and Pathology in Neonates, Infants and Children

The endothelial glycocalyx (EG) as part of the endothelial surface layer (ESL) is an important regulator of vascular function and homeostasis, including permeability, vascular tone, leukocyte recruitment and coagulation. Located at the interface between the endothelium and the blood stream, this highly fragile structure is prone to many disruptive factors such as inflammation and oxidative stress. Shedding of the EG has been described in various acute and chronic diseases characterized by endothelial dysfunction and angiopathy, such as sepsis, trauma, diabetes and cardiovascular disease. Circulating EG components including syndecan-1, hyaluronan and heparan sulfate are being evaluated in animal and clinical studies as diagnostic and prognostic markers in several pathologies, and advances in microscopic techniques have enabled in vivo assessment of the EG. While research regarding the EG in adult physiology and pathology has greatly advanced throughout the last decades, our knowledge of the development of the glycocalyx and its involvement in pathological conditions in the pediatric population is limited. Current evidence suggests that the EG is present early during fetal development and plays a critical role in vessel formation and maturation. Like in adults, EG shedding has been demonstrated in acute inflammatory conditions in infants and children and chronic diseases with childhood-onset. However, the underlying mechanisms and their contribution to disease manifestation and progression still need to be established. In the future, the glycocalyx might serve as a marker to identify pediatric patients at risk for vascular sequelae and as a potential target for early interventions

Effects of Prematurity on the Cutaneous Microcirculatory Network in the First Weeks of Life

Background: Preterm infants are at increased risk for hypertension in adolescence. Microcirculatory dysfunction has been identified as an underlying cause for cardiovascular disease. Our goal was to document the development of the cutaneous microcirculation in preterm infants during the first weeks of life and to compare it to the situation in term infants at birth. Methods: In 20 preterm infants, microcirculatory parameters were obtained prospectively by Sidestream Dark Field (SDF) Imaging at the upper inner arm once a week until discharge or 37 weeks of gestational age. A single microcirculatory measurement was obtained in 30 term infants during the first 3 days of life. Videos were blinded and analyzed with the AVA software. Results: Microcirculatory parameters in preterm infants differ significantly from term infants with a lower vessel surface (VS), a lower percentage of large and medium but higher percentage of small vessels, a higher Functional Vessel Density (FVD), and a higher Microcirculatory Flow Index (MFI). In multivariable linear regression models we could demonstrate a statistically significant association between the dependent microcirculatory variables (VS, diameter distribution, MFI) and gestational age as independent predictor variable while adjusting for postnatal days of life. Looking at the longitudinal follow-up data of preterm infants by means of a multivariable mixed-effects linear regression model adjusting for clinical variables, there is a significant decrease in FVD with increasing postnatal age, however no other significant changes in microcirculatory parameters over time. Accordingly, comparing the microcirculatory parameters of near term former preterm infants with term born neonates, we could still find significant differences with a higher FVD, lower VS and differences in vessel diameters in the former premature group. Conclusion: Infants born prematurely exhibit distinct microcirculatory alterations compared to term neonates with gestational age at birth being associated with microvascular parameters. Interestingly, this premature vascular phenotype persists even close to corrected term age. In view of the known increased cardiovascular risk of former preterm infants, our observations might have important clinical impact. The factors governing the development of the microvascular network in preterm infants and the contribution of microcirculatory changes observed here to vascular pathology in later life need to be further investigated

In adolescence, extreme prematurity is associated with significant changes in the microvasculature, elevated blood pressure and increased carotid intima-media thickness

Objectives: Increased carotid intima-media thickness (cIMT) and loss of capillary density are antecedents of cardiovascular disease in adults. Former preterm infants are at risk for metabolic precursors of vascular disease, but vascular changes have not yet been studied in this population. Patients and methods: In 54 former preterm (birth weigh (BW) 753 +/- 152 g) and 12 term children (BW 3395 +/- 558 g), functional vessel density (FVD) on the forearm and cIMT were obtained at a mean (+/- SD) age of 11.8 +/- 1.5 years. FVD was measured using sidestream dark field imaging before, during and after arterial occlusion, and cIMT using high resolution B-mode ultrasonography. Statistical comparisons were made using the t test, Mann-Whitney U test and the sign test for symmetry, with a two-sided p value as appropriate. Results: The systolic blood pressure of the former preterm children was significantly increased compared to reference values (females 119 +/- 8, z score 1.23; males 118 +/- 11, z score 1.14 mm Hg), as were the cIMT values (0.45 +/- 0.03 mm vs 0.38 +/- 0.04 mm; p<0.001). FVD was significantly higher in former preterm children compared to controls at baseline (mean +/- SD 33.6 +/- 14.5 cm/cm(2) vs 23.0 +/- 7.1 cm/cm(2); p=0.002) with decreased reactivity during arterial occlusion (chi(2) 7.14, p=0.008). Conclusions: Preterm birth is associated with significant permanent alteration in the microcirculation and increased cIMT and systolic blood pressure. It is unknown whether these changes are due to preterm birth and rapid maturation of the skin or to nutritional factors, as previously thought. This is an important area of future research

In adolescence, extreme prematurity is associated with significant changes in the microvasculature, elevated blood pressure and increased carotid intima-media thickness

Objectives: Increased carotid intima-media thickness (cIMT) and loss of capillary density are antecedents of cardiovascular disease in adults. Former preterm infants are at risk for metabolic precursors of vascular disease, but vascular changes have not yet been studied in this population. Patients and methods: In 54 former preterm (birth weigh (BW) 753 +/- 152 g) and 12 term children (BW 3395 +/- 558 g), functional vessel density (FVD) on the forearm and cIMT were obtained at a mean (+/- SD) age of 11.8 +/- 1.5 years. FVD was measured using sidestream dark field imaging before, during and after arterial occlusion, and cIMT using high resolution B-mode ultrasonography. Statistical comparisons were made using the t test, Mann-Whitney U test and the sign test for symmetry, with a two-sided p value as appropriate. Results: The systolic blood pressure of the former preterm children was significantly increased compared to reference values (females 119 +/- 8, z score 1.23; males 118 +/- 11, z score 1.14 mm Hg), as were the cIMT values (0.45 +/- 0.03 mm vs 0.38 +/- 0.04 mm; p<0.001). FVD was significantly higher in former preterm children compared to controls at baseline (mean +/- SD 33.6 +/- 14.5 cm/cm(2) vs 23.0 +/- 7.1 cm/cm(2); p=0.002) with decreased reactivity during arterial occlusion (chi(2) 7.14, p=0.008). Conclusions: Preterm birth is associated with significant permanent alteration in the microcirculation and increased cIMT and systolic blood pressure. It is unknown whether these changes are due to preterm birth and rapid maturation of the skin or to nutritional factors, as previously thought. This is an important area of future research

Loss of Kindlin-1 Causes Skin Atrophy and Lethal Neonatal Intestinal Epithelial Dysfunction

Kindler Syndrome (KS), characterized by transient skin blistering followed by abnormal pigmentation, skin atrophy, and skin cancer, is caused by mutations in the FERMT1 gene. Although a few KS patients have been reported to also develop ulcerative colitis (UC), a causal link to the FERMT1 gene mutation is unknown. The FERMT1 gene product belongs to a family of focal adhesion proteins (Kindlin-1, -2, -3) that bind several β integrin cytoplasmic domains. Here, we show that deleting Kindlin-1 in mice gives rise to skin atrophy and an intestinal epithelial dysfunction with similarities to human UC. This intestinal dysfunction results in perinatal lethality and is triggered by defective intestinal epithelial cell integrin activation, leading to detachment of this barrier followed by a destructive inflammatory response

Noninvasive Ventilation in Preterm Infants: Factors Influencing Weaning Decisions and the Role of the Silverman-Andersen Score

The factors influencing weaning of preterm infants from noninvasive ventilation (NIV) are poorly defined and the weaning decisions are often driven by subjective judgement rather than objective measures. To standardize quantification of respiratory effort, the Silverman-Andersen Score (SAS) was included in our nursing routine. We investigated the factors that steer the weaning process and whether the inclusion of the SAS would lead to more stringent weaning. Following SAS implementation, we prospectively evaluated 33 neonates born <= 32 + 0 weeks gestational age. Age-, weight- and sex-matched infants born before routine SAS evaluation served as historic control. In 173 of 575 patient days, NIV was not weaned despite little respiratory distress (SAS <= 2), mainly due to bradycardias (60% of days without weaning), occurring alone (40%) or in combination with other factors such as apnea/desaturations. In addition, soft factors that are harder to grasp impact on weaning decisions, whereas the SAS overall played a minor role. Consequently, ventilation times did not differ between the groups. In conclusion, NIV weaning is influenced by various factors that override the absence of respiratory distress limiting the predictive value of the SAS. An awareness of the factors that influence weaning decisions is important as prolonged use of NIV has been associated with adverse outcome. Guidelines are necessary to standardize NIV weaning practice

Comparison of neonatal outcomes of small for gestational age and appropriate for gestational age preterm infants born at 28-36 weeks of gestation: a multicentre study in Ethiopia

PurposeThe aim of this study was to assess morbidity and mortality pattern of small for gestational age (SGA) preterm infants in comparison to appropriate for gestational age (AGA) preterm infants of similar gestational age.MethodWe compared neonatal outcomes of 1336, 1:1 matched, singleton SGA and AGA preterm infants based on their gestational age using data from the study 'Causes of Illness and Death of Preterm Infants in Ethiopia (SIP)'. Data were analysed using SPSS V.23. ORs and 95% CIs and chi (2) tests were done, p value of <0.05 was considered statistically significant.ResultThe majority of the infants (1194, 89%) were moderate to late preterm (32-36 weeks of gestation), 763 (57%) were females. Male preterm infants had higher risk of being SGA than female infants (p<0.001). SGA infants had increased risk of hypoglycaemic (OR and 95% CI 1.6 (1.2 to 2.0), necrotising enterocolitis (NEC) 2.3 (1.2 to 4.1), polycythaemia 3.0 (1.6 to 5.4), late-onset neonatal sepsis (LOS) 3.6 (1.1 to 10.9)) and prolonged hospitalisation 2.9 (2.0 to 4.2). The rates of respiratory distress syndrome (RDS), apnoea and mortality were similar in the SGA and AGA groups.ConclusionNeonatal complications such as hypoglycaemic, NEC, LOS, polycythaemia and prolonged hospitalisation are more common in SGA infants, while rates of RDS and mortality are similar in SGA and AGA groups. Early recognition of SGA status, high index of suspicion and screening for complications associated and timely intervention to prevent complications need due consideration

Incidence and associated factors of extrauterine growth restriction (EUGR) in preterm infants, a cross-sectional study in selected NICUs in Ethiopia

BackgroundPreterm infants have high risk of developing growth restriction and long-term complications. Enteral feeding is often delayed in neonatal intensive care units (NICUs) for the fear of feeding intolerance and the associated necrotising enterocolitis, and recent advances in nutritional support are unavailable in low-income countries.ObjectiveThe aim of this study was to assess the incidence and associated factors of extrauterine growth restriction (EUGR) among preterm infants in selected NICUs in Ethiopia.MethodThis was a cross-sectional study involving a subgroup analysis of preterm infants admitted to hospitals, from a multicentre descriptive study of cause of illness and death in preterm infants in Ethiopia, conducted from 2016 to 2018. EUGR was defined as weight at discharge Z-scores <-1.29 for corrected age. Clinical profiles of the infants were analysed for associated factors. SPSS V.23 software was used for analysis with a significance level of 5% and 95% CI.ResultFrom 436 preterm infants included in the analysis, 223 (51%) were male, 224 (51.4%) very low birth weight (VLBW) and 185 (42.4%) small for gestational age (SGA). The mean (SD) of weight for corrected age Z-score at the time of discharge was -2.5 (1.1). The incidence of EUGR was 86.2%. Infants who were SGA, VLBW and longer hospital stay over 21 days had increased risk of growth restriction (p-value<0.01). SGA infants had a 15-fold higher risk of developing EUGR at the time of discharge from hospital than those who were appropriate or large for gestational age (OR (95%CI)=15.2 (4.6 to 50.1).ConclusionThe majority of the infants had EUGR at the time of discharge from the hospital, which indicates suboptimal nutrition. Revision of national guidelines for preterm infants feeding and improvement in clinical practice is highly required