Reduction of cortical parvalbumin-expressing GABAergic interneurons in a rodent hyperoxia model of preterm birth brain injury with deficits in social behavior and cognition.

The inhibitory GABAergic system in the brain is involved in the etiology of various psychiatric problems, including autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD) and others. These disorders are influenced not only by genetic but also by environmental factors, such as preterm birth, although the underlying mechanisms are not known. In a translational hyperoxia model, exposing mice pups at P5 to 80% oxygen for 48 h to mimic a steep rise of oxygen exposure caused by preterm birth from in utero into room air, we documented a persistent reduction of cortical mature parvalbumin-expressing interneurons until adulthood. Developmental delay of cortical myelin was observed, together with decreased expression of oligodendroglial glial cell-derived neurotrophic factor (GDNF), a factor involved in interneuronal development. Electrophysiological and morphological properties of remaining interneurons were unaffected. Behavioral deficits were observed for social interaction, learning and attention. These results demonstrate that neonatal oxidative stress can lead to decreased interneuron density and to psychiatric symptoms. The obtained cortical myelin deficit and decreased oligodendroglial GDNF expression indicate that an impaired oligodendroglial-interneuronal interplay contributes to interneuronal damage.

Trends in Apgar scores and umbilical artery pH: a population-based cohort study on 10,696,831 live births in Germany, 2008-2022.

Low Apgar scores and low umbilical arterial (UA) blood pH are considered indicators of adverse perinatal events. This study investigated trends of these perinatal health indicators in Germany. Perinatal data on 10,696,831 in-hospital live births from 2008 to 2022 were obtained from quality assurance institutes. Joinpoint regression analysis was used to quantify trends of low Apgar score and UA pH. Additional analyses stratified by mode of delivery were performed on term singletons with cephalic presentation. Robustness against unmeasured confounding was analyzed using the E-value sensitivity analysis. The overall rates of 5-min Apgar scores < 7 and UA pH < 7.10 in liveborn infants were 1.17% and 1.98%, respectively. For low Apgar scores, joinpoint analysis revealed an increase from 2008 to 2011 (annual percent change (APC) 5.19; 95% CI 3.66-9.00) followed by a slower increase from 2011 to 2019 (APC 2.56; 95% CI 2.00-3.03) and a stabilization from 2019 onwards (APC - 0.64; 95% CI - 3.60 to 0.62). The rate of UA blood pH < 7.10 increased significantly between 2011 and 2017 (APC 5.90; 95% CI 5.15-7.42). For term singletons in cephalic presentation, the risk amplification of low Apgar scores was highest after instrumental delivery (risk ratio 1.623, 95% CI 1.509-1.745), whereas those born spontaneous had the highest increase in pH < 7.10 (risk ratio 1.648, 95% CI 1.615-1.682).          Conclusion: Rates of low 5-min Apgar scores and UA pH in liveborn infants increased from 2008 to 2022 in Germany. What is Known: • Low Apgar scores at 5 min after birth and umbilical arterial blood pH are associated with adverse perinatal outcomes. • Prospective collection of Apgar scores and arterial blood pH data allows for nationwide quality assurance. What is New: • The rates of liveborn infants with 5-min Apgar scores < 7 rose from 0.97 to 1.30% and that of umbilical arterial blood pH < 7.10 from 1.55 to 2.30% between 2008-2010 and 2020-2022. • In spontaneously born term singletons in cephalic presentation, the rate of metabolic acidosis with pH < 7.10 and BE < -5 mmol/L in umbilical arterial blood roughly doubled between the periods 2008-2010 and 2020-2022.

No change in mother's own milk provision and breastfeeding rates in preterm infants during the COVID-19 pandemic.

AIM: The aim of the study was to evaluate the duration of mother's own milk (MOM) provision to preterm very low-birth weight (VLBW, <1500 g) infants during the COVID-19 pandemic. We hypothesised that COVID-19 restrictions would reduce the duration of MOM provision. METHODS: This retrospective study compared VLBW infants born at the Berlin university hospital during the pandemic (15 March 2020 to 14 March 2021, n = 108) with infants born in the pre-pandemic year (01 January 2019 to 31 January 2019, n = 121). We calculated the duration of MOM provision and analysed factors associated with its early cessation. RESULTS: During the pandemic, the rate of primiparous mothers increased from 29% to 44% while the distribution of all other parental and infants' characteristics remained similar. There were no differences in the median duration of MOM provision (47 vs. 51 days), feeding type (MOM 67% vs. 65%) and breastfeeding rates at discharge (exclusive, 8% vs. 13%; partial 69% vs. 60%). Cox proportional hazard analysis revealed smoking during pregnancy and parental school education consistently as independent risk factors for early cessation of MOM provision. CONCLUSION: Supply of MOM for VLBW infants can be upheld also during pandemic restrictions.

Bilirubin Exerts Protective Effects on Alveolar Type II Pneumocytes in an In Vitro Model of Oxidative Stress.

Newborn infants face a rapid surge of oxygen and a more protracted rise of unconjugated bilirubin after birth. Bilirubin has a strong antioxidant capacity by scavenging free radicals, but it also exerts direct toxicity. This study investigates whether cultured rat alveolar epithelial cells type II (AEC II) react differently to bilirubin under different oxygen concentrations. The toxic threshold concentration of bilirubin was narrowed down by means of a cell viability test. Subsequent analyses of bilirubin effects under 5% oxygen and 80% oxygen compared to 21% oxygen, as well as pretreatment with bilirubin after 4 h and 24 h of incubation, were performed to determine the induction of apoptosis and the gene expression of associated transcripts of cell death, proliferation, and redox-sensitive transcription factors. Oxidative stress led to an increased rate of cell death and induced transcripts of redox-sensitive signaling pathways. At a non-cytotoxic concentration of 400 nm, bilirubin attenuated oxidative stress-induced responses and possibly mediated cellular antioxidant defense by influencing Nrf2/Hif1α- and NFκB-mediated signaling pathways. In conclusion, the study demonstrates that rat AEC II cells are protected from oxidative stress-induced impairment by low-dose bilirubin.

Fatal congenital copper transport defect caused by a homozygous likely pathogenic variant of SLC31A1.

Known hereditary human diseases featuring impaired copper trafficking across cellular membranes involve ATP7A (Menkes disease, occipital horn disease, X-linked spinal muscular atrophy type 3) and ATP7B (Wilson disease). Herein, we report a newborn infant of consanguineous parents with a homozygous pathogenic variant in a highly conserved sequence of SLC31A1, coding for the copper influx transporter 1, CTR1. This missense variant, c.236T > C, was detected by whole exome sequencing. The infant was born with pulmonary hypoplasia and suffered from severe respiratory distress immediately after birth, necessitating aggressive mechanical ventilation. At 2 weeks of age, multifocal brain hemorrhages were diagnosed by cerebral ultrasound and magnetic resonance imaging, together with increased tortuosity of cerebral arteries. Ensuing seizures were only partly controlled by antiepileptic drugs, and the infant became progressively comatose. Laboratory investigations revealed very low serum concentrations of copper and ceruloplasmin. No hair shaft abnormalities were detected by dermatoscopy or light microscopic analyses of embedded hair shafts obtained at 4 weeks of life. The infant died after redirection of care and elective cessation of invasive mechanical ventilation at 1 month of age. This case adds SLC31A1 to the genes implicated in severe hereditary disorders of copper transport in humans.

Dexmedetomidine Protects Cerebellar Neurons against Hyperoxia-Induced Oxidative Stress and Apoptosis in the Juvenile Rat.

The risk of oxidative stress is unavoidable in preterm infants and increases the risk of neonatal morbidities. Premature infants often require sedation and analgesia, and the commonly used opioids and benzodiazepines are associated with adverse effects. Impairment of cerebellar functions during cognitive development could be a crucial factor in neurodevelopmental disorders of prematurity. Recent studies have focused on dexmedetomidine (DEX), which has been associated with potential neuroprotective properties and is used as an off-label application in neonatal units. Wistar rats (P6) were exposed to 80% hyperoxia for 24 h and received as pretreatment a single dose of DEX (5µg/kg, i.p.). Analyses in the immature rat cerebellum immediately after hyperoxia (P7) and after recovery to room air (P9, P11, and P14) included examinations for cell death and inflammatory and oxidative responses. Acute exposure to high oxygen concentrations caused a significant oxidative stress response, with a return to normal levels by P14. A marked reduction of hyperoxia-mediated damage was demonstrated after DEX pretreatment. DEX produced a much earlier recovery than in controls, confirming a neuroprotective effect of DEX on alterations elicited by oxygen stress on the developing cerebellum.

A unique cerebellar pattern of microglia activation in a mouse model of encephalopathy of prematurity.

Preterm infants often show pathologies of the cerebellum, which are associated with impaired motor performance, lower IQ and poor language skills at school ages. Using a mouse model of inflammation-induced encephalopathy of prematurity driven by systemic administration of pro-inflammatory IL-1ß, we sought to uncover causes of cerebellar damage. In this model, IL-1ß is administered between postnatal day (P) 1 to day 5, a timing equivalent to the last trimester for brain development in humans. Structural MRI analysis revealed that systemic IL-1ß treatment induced specific reductions in gray and white matter volumes of the mouse cerebellar lobules I and II (5% false discovery rate [FDR]) from P15 onwards. Preceding these MRI-detectable cerebellar volume changes, we observed damage to oligodendroglia, with reduced proliferation of OLIG2+ cells at P10 and reduced levels of the myelin proteins myelin basic protein (MBP) and myelin-associated glycoprotein (MAG) at P10 and P15. Increased density of IBA1+ cerebellar microglia were observed both at P5 and P45, with evidence for increased microglial proliferation at P5 and P10. Comparison of the transcriptome of microglia isolated from P5 cerebellums and cerebrums revealed significant enrichment of pro-inflammatory markers in microglia from both regions, but cerebellar microglia displayed a unique type I interferon signaling dysregulation. Collectively, these data suggest that perinatal inflammation driven by systemic IL-1ß leads to specific cerebellar volume deficits, which likely reflect oligodendrocyte pathology downstream of microglial activation. Further studies are now required to confirm the potential of protective strategies aimed at preventing sustained type I interferon signaling driven by cerebellar microglia as an important therapeutic target.

Multi-centre randomised trial of invasive and less invasive surfactant delivery methods showed similar spirometry results at 5-9 years of age.

AIM: We explored whether subnormal forced expiratory volume within 1 s (FEV1 ) at 5-9 years of age was lower in children born preterm who received less invasive surfactant administration (LISA) rather than surfactant via an endotracheal tube. METHODS: The multi-centre, randomised Nonintubated Surfactant Application trial enrolled 211 preterm infants born at 23-26 weeks of gestation from 13 level III neonatal intensive care units from April 2009 to March 2012. They received surfactant via LISA (n = 107) or after conventional endotracheal intubation (n = 104). The follow-up assessments were carried out by a single team blinded to the group assignments. The main outcome was FEV1 < 80% of predicted values. RESULTS: Spirometry was successful in 102/121 children. The other children died or were lost to follow-up. Median FEV1 was 93% (interquartile range 80%-113%) of predicted values in the LISA group and 86% (interquartile range 77-102%) in the control group (p = 0.685). Rates of FEV1 < 80% were 11/57 (19%) and 15/45 (33%), respectively, which was an absolute risk reduction of 14% (95% confidence interval -3.1% to 31.2%, p = 0.235). There were no differences in other outcome measures. CONCLUSION: The proportion of children aged 5-9 years with subnormal FEV1 was not significantly different between the groups.

Plötzlicher Kindstod von zwei Säuglingen in Babytragehilfen.

Sudden unexpected death in infancy (SUDI), previously termed sudden infant death syndrome (SIDS), is the second leading cause of death in infants beyond the neonatal period in Germany, and a major cause of infant mortality in economically well developed countries (OECD Health Statistics, 2019). The risk of SUDI peaks at the age of 2-4 months and then decreases continuously till the end of the first year. A complex multifactorial cause, rather than a single characteristic factor, may cause SUDI within a critical period of infant development (Guntheroth WG et al., Pediatrics 2002; 110: e64-e64). Risk factors include prematurity, male gender, bottle-feeding, prone sleeping position, overheating, as well as exposure to smoke amongst others (Carpenter RG et al., Lancet 2004; 363: 185-191). Thus, health professionals consistently advise and educate parents about avoidable risk factors of SUDI at routine well-baby examinations. Since the advent of SUDI prevention strategies in the 1980s, the incidence has decreased 10fold, from 1,55/1.000 live births in 1991 to 0,15/1000 in 2015. This number seems to have reached a steady state (Statistisches Bundesamt Germany, 2015).

Dosage escalation of antenatal steroids in preterm twin pregnancies does not improve long-term outcome.

OBJECTIVES: To analyze long-term effects of antenatal betamethasone (≤16 mg, =24 mg and >24 mg) in preterm twins on infant and childhood morbidity. METHODS: Retrospective cohort study among 198 preterm twins. Three follow up time points, including a total of 84 outcomes, were evaluated: first neonatal examination after birth and in the neonatal period up to 10 days after birth using data from the clinic charts; examination from the 21st to the 24th month of life and examination from the 60th to the 64th months, using data from copies of the children's examination booklets sent back by the parents. Dosage-dependent and sex-specific long-term effects of antenatal betamethasone treatment on neonatal, infant and early childhood development and morbidity up to 5.3 years of age were analyzed. RESULTS: Dosage escalation of >24 mg was not associated with improved neonatal, infant or early child hood outcome, independent of twin pair structure. In contrast, higher doses >24 mg were significantly linked to increased rates of congenital infections (OR 5.867, 95% CI 1.895-18.167). Male sex as a factor was obvious for lower rates of apnea-bradycardia-syndrome in neonates, higher rates of no free steps after 15 months in infancy and highest rates of motor clumsiness in early childhood. CONCLUSIONS: Betamethasone dosage escalation >24 mg in twins born between 23+5 and 33+6 weeks of gestation did not improve neonatal, infant or early childhood morbidity. In contrast, higher doses >24 mg total dose resulted in significantly higher rates of congenital infections and are not recommended. For males, 24 mg betamethasone appears to be the preferable dose.

The Impact of Prematurity on Morbidity and Mortality in Newborns with Dextro-transposition of the Great Arteries.

Prematurity is a risk factor for adverse outcomes after arterial switch operation in newborns with D-TGA (D-TGA). In this study, we sought to investigate the impact of prematurity on postnatal and perioperative clinical management, morbidity, and mortality during hospitalization in neonates with simple and complex D-TGA who received arterial switch operation (ASO). Monocentric retrospective analysis of 100 newborns with D-TGA. Thirteen infants (13.0%) were born premature. Preterm infants required significantly more frequent mechanical ventilation in the delivery room (69.2% vs. 34.5%, p = 0.030) and during the preoperative course (76.9% vs. 37.9%, p = 0.014). Need for inotropic support (30.8% vs. 8.0%, p = 0.035) and red blood cell transfusions (46.2% vs. 10.3%, p = 0.004) was likewise increased. Preoperative mortality (23.1% vs 0.0%, p = 0.002) was significantly increased in preterm infants, with necrotizing enterocolitis as cause of death in two of three infants. In contrast, mortality during and after surgery did not differ significantly between the two groups. Cardiopulmonary bypass times were similar in both groups (median 275 vs. 263 min, p = 0.322). After ASO, arterial lactate (34.5 vs. 21.5 mg/dL, p = 0.007), duration of mechanical ventilation (median 175 vs. 106 h, p = 0.038), and venous thrombosis (40.0% vs. 4.7%, p = 0.004) were increased in preterm, as compared to term infants. Gestational age (adjusted unit odds ratio 0.383, 95% confidence interval 0.179-0.821, p = 0.014) was independently associated with mortality. Prematurity is associated with increased perioperative morbidity and increased preoperative mortality in D-TGA patients.

[Evaluation of the Endotracheal Tube by Ultrasound in Neonates]. / Ultraschallgestützte Lagekontrolle des Endotrachealtubus bei Neugeborenen.

The reliable evaluation of a correctly placed endotracheal tube is an essential challenge in neonatology. Point-of-care ultrasound is an emerging method to address this concern with the following advantages: less time-consuming, no exposure to radiation, less staff-intensive, and high tolerability by the patients. This article focuses on the evaluation of the clinical application of point-of-care ultrasound to examine the position of the endotracheal tube with regard to visualization, consistency compared to the chest X-ray, and the level of training to obtain sufficient results. We identified nine studies relevant to these questions. The visualization of the endotracheal tube by using point-of-care ultrasound is highly effective. The assessment of a correctly placed endotracheal tube is comparable to the results of a chest X-ray. The technique is suitable for any examiner with previous ultrasound experience. Future applications such as emergency intubations, implementation in the standard care of extremely low birth weight preterm babies, and use in low-resource settings could be promising. This article offers a practical guideline to promote the level of awareness and the clinical application.

Adult Donor Blood Products as Risk Factors for Central Venous Catheter-associated Thromboembolism in Neonates: A Retrospective Case-Control Study.

This study aimed to examine whether the transfusion of donor blood products, abnormal coagulation or inflammation increase the risk of venous thromboembolism (VTE) associated with central venous catheters (CVC) in neonates. A retrospective case-control study including 25 neonates with CVC-associated VTE and tightly matched controls with CVC, but without VTE was performed. The frequency of (i) abnormal coagulation screens, (ii) increased inflammatory marker proteins before catheter insertion, or (iii) catheter-associated blood stream infection did not differ between cases and controls. No difference was found in the number or type of transfusions within the last day before VTE. However, the total number of transfusions in the time period between catheter placement and VTE diagnosis (median 6.5 d) was significantly higher (P<0.001) in cases (44 red blood cell, 61 plasma, and 18 platelet transfusions) compared with an equal median time period of 7 days postcatheter insertion in controls (26/24/11). In conclusion, intensive transfusion treatment (through a peripheral line) after CVC insertion was associated with a higher risk of VTE (odds ratio 7.58; 95% confidence interval, 0.84-68.46), suggesting that transfusion of adult donor blood products into the cellular and plasmatic hemostatic system of the neonate increases the risk for CVC-associated VTE.

Digestive enzyme replacement relieves growth failure in preterm infants with poor exocrine pancreatic function: a retrospective case series.

In orally fed preterm infants, poor weight gain may be linked to low fecal pancreatic elastase-1 (FPE-1) activity, indicative of exocrine pancreatic insufficiency. The objective of this study was the retrospective assessment of the effect of exogenous digestive enzyme replacement by gavage in preterm infants with growth failure and low FPE-1 (<200 µg/g). We analyzed weight gain relative to baseline and caloric intake during 14-day periods before and after institution of digestive enzyme replacement containing 6000 U lipase and 240 U protease kg-1 d-1. Among 46 of 132 preterm infants < 1250g birth weight surviving to at least 14 days in whom FPE-1 was determined, 38 infants had low FPE-1 (< 200 µg/g), and 33 infants received exogenous digestive enzyme replacement. Average daily weight gain significantly increased from 14.4 [range 2.6-22.4] g kg-1 d-1 to 17.4 [8.4-29.0] g kg-1 d-1 (P = 0.001), as did weight gain per kcal, from 0.08 [0.02-0.13] g kcal-1 d-1 to 0.11 [0.05-0.18] g kcal-1 d-1.Conclusion: In preterm infants with signs and symptoms of exocrine pancreatic insufficiency, exogenous digestive enzyme replacement is associated with improved growth. What is Known: • Very preterm infants on full enteral nutrition may display growth failure linked to transient poor exocrine pancreatic function. • Porcine pancreatic enzymes covered with an acid-resistant coating are too large to pass the internal diameter of most gavage tubes used in very preterm infants. What is New: • Administration of a liquid formulation of acid-resistant microbial digestive enzymes in preterm infants with growth failure and low fecal pancreatic elastase-1 values was associated with improved weight gain. • Response to exogenous digestive enzyme replacement was associated with the prior extent of growth failure.

Developmental outcome of extremely preterm infants is improved after less invasive surfactant application: Developmental outcome after LISA.

AIM: The aim of this study was to evaluate neurocognitive outcome at 24 months of corrected age after less invasive surfactant application (LISA) in preterm infants born at 23-26 weeks of gestational age. METHODS: Surviving participants of a LISA trial conducted in 13 German level III neonatal intensive care units were reviewed for assessment of developmental outcome, hearing and vision problems, growth and rehospitalisation days. Maternal depression, breastfeeding rates and socio-economic factors were evaluated as potentially confounding factors. RESULTS: In total, 156/182 infants took part in the study, 78 had received surfactant via LISA and 78 via endotracheal intubation. 22% of LISA infants compared to 42% of intubated infants had a psychomotor development index (PDI) <70 (0.012). A significant difference in mental development index (MDI) was observed in the stratum of more mature infants (25 and 26 weeks of GA). For this group, MDI < 70 was observed in 4% of LISA infants vs 21% of intubated infants (P = 0.008). CONCLUSION: At 24 months of age, the LISA-treated infants scored less often PDI < 70 and had similar results in MDI. Infants born at 25 and 26 weeks treated with LISA had lower rates of severe disability. LISA is safe and may be superior.

Neuroendoscopic surgery in neonates - indication and results over a 10-year practice.

PURPOSE: Neuroendoscopic procedures for treatment of term and preterm newborn infants, such as endoscopic lavage for posthemorrhagic hydrocephalus, are gaining popularity despite sparse data. This single-institution report compiles all neuroendoscopic surgical procedures performed in neonates during a 10-year period. METHODS: Charts and electronic records were reviewed of all consecutive newborns who underwent a neuroendoscopic procedure before reaching a postmenstrual age of 44 weeks between 09/2010 and 09/2020. Available documentation was reviewed regarding the performed neuroendoscopic procedure, course of disease, complications, and all re-operations throughout the first year of life. RESULTS: During the 10-year study period, 116 infants (median gestational age at birth: 29 1/7 weeks) underwent a total of 153 neuroendoscopic procedures (median postmenstrual age at surgery: 35 0/7 weeks). The most common indication at the time of the neuroendoscopic procedures (n = 153) was intraventricular hemorrhage (IVH, n = 119), intraventricular infection (n = 15), congenital malformation (n = 8), isolated 4th ventricle (n = 7), multiloculated hydrocephalus (n = 3), and tumor (n = 1). Thirty-eight of 116 children (32.8%) underwent 43 operative revisions after 153 neuroendoscopic procedure (28.1%). Observed complications requiring surgical revision were secondary infection (n = 11), CSF fistula (n = 9), shunt dysfunction (n = 8), failure of ETV (n = 6), among others. 72 children (62%) of 116 children required permanent CSF diversion via a shunt. The respective shunt rates per diagnosis were 47 of 80 (58.8%) for previously untreated IVH, 11 of 13 (84.6%) for intraventricular infection. Shunt survival rate for the first year of life was 74% for the whole cohort. CONCLUSION: The experience with this large cohort of neonates demonstrates the feasibility of neuroendoscopic technique for the treatment of posthemorrhagic or postinfectious hydrocephalus. Rate and type of complications after neuroendoscopic procedures were within the expected range. Assessing the potential long-term benefits of neuroendoscopic techniques has to await results of ongoing studies.

Reduced rates of infection after myelomeningocele closure associated with standard perioperative antibiotic treatment with ampicillin and gentamicin.

PURPOSE: Postnatal closure of a myelomeningocele (MMC) is a complex procedure with frequent complications following surgery. Bacterial colonization of the placode may cause infection and subsequent complications. The objectives of this study were to determine the preoperative bacterial colonization rates, to assess the antibiotic regimen, and to evaluate the overall postoperative infection rate. METHODS: All consecutive patients undergoing MMC closure in our hospital from January 2010 to January 2020 were evaluated. Epidemiological data, surgical data, complication characteristics, and microbiological results were documented. RESULTS: A total of 45 patients were evaluated; in 41 patients, a wound swab of the placode was performed directly before MMC closure (91%). All patients received a prophylactic antibiotic treatment for a mean of 5.6 ± 2.7 days around the performed MMC closure. In three patients with a wound swab (7.3%), a bacterial colonization could be detected-none of the patients developed a subsequent infection. Overall, 7 other patients developed an infection (15.6%), three local surgical site infections, and four shunt-related infections. After applying a standardized perioperative prophylactic antibiotic treatment with ampicillin and gentamicin, the infection rate was observed to be lower compared with that of a non-standardized treatment (6% vs. 45%; p = 0.019). CONCLUSIONS: In neonates who undergo MMC closure in the first 48 h after birth, the colonization rate of the placode was lower than previously reported. While the data presented cannot proof the benefit of a perioperative antibiotic prophylaxis, as compared with no prophylaxis, infection rates are low with a standardized antibiotic regime comprising ampicillin and gentamicin.

Preoperative Anemia and Outcomes After Corrective Surgery in Neonates With Dextro-Transposition of the Great Arteries.

OBJECTIVES: The authors aimed to assess whether untreated preoperative anemia was associated with increased risk for adverse outcomes after the arterial switch operation in neonates with dextro-transposition of the great arteries (d-TGA). DESIGN: Retrospective cohort study. SETTING: Single cardiac surgery center. PARTICIPANTS: Eighty-two newborns with d-TGA. INTERVENTIONS: The authors categorized the cohort into the following two groups: the infants with preoperative anemia group (defined as a hematocrit <0.40 L/L) and the control group. MEASUREMENTS AND MAIN RESULTS: Preoperative anemia was diagnosed in 21 (25.6%) infants. Anemic infants received intraoperative red blood cell transfusions significantly more often than controls (81.0% v 34.4%, p < 0.001). No differences were observed in the incidence of adverse events, duration of hospitalization (median 27 days v 26 days, p = 0.881), and mortality (0% v 4.9%, p = 0.566). Postnatal hematocrit was the only variable independently associated with preoperative anemia in multivariate logistic regression analysis (unit odds ratio, 0.832; 95% confidence interval, 0.743-0.931; p = 0.001). CONCLUSIONS: Untreated preoperative anemia was not associated with adverse outcomes in neonates undergoing reparative surgery for d-TGA.

Long term alterations of growth after antenatal steroids in preterm twin pregnancies.

OBJECTIVES: To compare the long-term effects of antenatal betamethasone (ANS, ≤16 mg, =24 mg and >24 mg) in twins on infant and childhood growth. METHODS: A retrospective cohort follow up study among 198 twins after ANS including three time points: U1 first neonatal examination after birth and in the neonatal period; U7 examination from the 21st to the 24th month of life and U9 examination from the 60th to the 64th month of life using data from copies of the children's examination booklets. Inclusion criteria are twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to ANS between 23+5 and 33+6 weeks. Outcome measures are dosage-dependent and sex-specific effects of ANS on growth (body weight, body length, head circumference, body mass index and ponderal index) up to 5.3 years. RESULTS: Overall, 99 live-born twin pairs were included. Negative effects of ANS on fetal growth persisted beyond birth, altered infant and childhood growth, independent of possible confounding factors. Overall weight percentile significantly decreased between infancy and early childhood by 18.8%. Birth weight percentiles significantly changed in a dose dependent and sex specific manner, most obviously in female-female and mixed pairs. The ponderal index significantly decreased up to 42.9%, BMI index increased by up to 33.8%. CONCLUSIONS: ANS results in long-term alterations in infant and childhood growth. Changes between infancy and early childhood in ponderal mass index and BMI, independent of dose or twin pair structure, might indicate an ANS associated increased risk for later life disease. SYNOPSIS: First-time report on long-term ANS administration growth effects in twin pregnancies, showing persisting alterations beyond birth in infant and childhood growth up to 5.3 years as potential indicator of later life disease risk.

A Closer Look at a Small Brain: Transnuchal Ultrasound Facilitates High-Resolution Imaging of the Cerebellum in Preterm Infants.

PURPOSE: Very preterm infants are at risk for cerebellar injury and impaired cerebellar growth with adverse neurodevelopmental outcome. Ultrasound through the mastoid fontanel (MF) with a curved-array or sector probe is the most established method for the sonographic examination of the cerebellum. The goal of our study was to examine the validity of transnuchal ultrasound through the foramen occipitale magnum (FOM) with a linear probe for monitoring postnatal cerebellar growth. METHODS: Retrospective analysis of routine ultrasound scans through FOM and MF in 105 preterm infants born between 23 and 36 weeks of gestation with a birthweight of less than 1500 g. RESULTS: Diameters of the cerebellar hemispheres obtained through the two acoustic windows mastoid fontanel and foramen occipitale magnum showed high correlations (r's = 0.981 and 0.983, p's < 0.001). Corrected gestational age was significantly associated with transverse cerebellar diameter (TCD) on the first scan (r = 0.908, p < 0.001) as well as postnatal cerebellar growth (r = 0.920, p < 0.001). Postnatal growth was slightly decreased resulting in cerebellar growth restriction on serial scans. Both associations exceeded the calculated ratio of TCD to head circumference (r = 0.657, p < 0.001) and TCD to biparietal diameter with gestational age (r = 0.705, p < 0.001). CONCLUSION: Transnuchal ultrasound is feasible for examination of the preterm cerebellum and improves image quality compared to scans through the MF with higher resolution at a very short distance. Monitoring cerebellar growth during early postnatal life via transnuchal ultrasound can help to identify children at high risk for neurodevelopmental impairment.