Introduction There are conflicting data on the association between postnatal cytomegalovirus (CMV) infection and growth and cognitive outcome in very preterm infants. The aim of the current study was to systematically evaluate the effect of postnatal CMV infection on growth and cognitive outcome in an unselected, contemporary cohort of very preterm infants. Methods Infants <32 gestational weeks (2011-2018) were screened for postnatal CMV infection. We compared head circumference, weight and length from birth to three months corrected age, mental development at 12 and 24 months corrected age (Bayley Scales of Infant (Toddler) Development II/III) and intelligence quotient at five years (Kaufman Assessment Battery for Children-II, Wechsler Preschool and Primary Scale of Intelligence-III or Snijders-Oomen Non-verbal Intelligence Test) between infants with and without postnatal CMV infection.Results The final study cohort consisted of 431 infants with a median gestational age of 29.9 (23.7-31.9) weeks. Of these, 20 (4.6%) infants had a postnatal CMV infection. Median ∆ z scores from birth to the corrected age of three months for head circumference, weight and length did not differ between infants with and without postnatal CMV infection. Continuous and categorized parameters of cognitive development did not differ between the two groups. A subgroup analysis of infants <28 gestational weeks showed similar results.Conclusion We did not observe a negative effect of postnatal CMV infection on growth or cognitive development of very preterm infants. These findings should be taken into account when discussing the use of raw mother's milk in the feeding of preterm infants.

Introduction There are conflicting data on the association between postnatal cytomegalovirus (CMV) infection and growth and cognitive outcome in very preterm infants. The aim of the current study was to systematically evaluate the effect of postnatal CMV infection on growth and cognitive outcome in an unselected, contemporary cohort of very preterm infants. Methods Infants <32 gestational weeks (2011-2018) were screened for postnatal CMV infection. We compared head circumference, weight and length from birth to three months corrected age, mental development at 12 and 24 months corrected age (Bayley Scales of Infant (Toddler) Development II/III) and intelligence quotient at five years (Kaufman Assessment Battery for Children-II, Wechsler Preschool and Primary Scale of Intelligence-III or Snijders-Oomen Non-verbal Intelligence Test) between infants with and without postnatal CMV infection.Results The final study cohort consisted of 431 infants with a median gestational age of 29.9 (23.7-31.9) weeks. Of these, 20 (4.6%) infants had a postnatal CMV infection. Median ∆ z scores from birth to the corrected age of three months for head circumference, weight and length did not differ between infants with and without postnatal CMV infection. Continuous and categorized parameters of cognitive development did not differ between the two groups. A subgroup analysis of infants <28 gestational weeks showed similar results.Conclusion We did not observe a negative effect of postnatal CMV infection on growth or cognitive development of very preterm infants. These findings should be taken into account when discussing the use of raw mother's milk in the feeding of preterm infants.

Introduction: Neurological consequences of preterm infants born to mothers with gestational diabetes mellitus (GDM) are unclear. In this pilot study, we investigated the effect of GDM on brain activity in very preterm infants. Methods: Preterm infants <32 gestational weeks of mothers with GDM compared to gestational age- and sex-matched controls born between 2011 and 2018 were included. Amplitude-integrated electroencephalography (aEEG) was assessed for total maturation and individual component scores according to Burdjalov and colleagues, the dominating visual background, and the presence of sleep-wake cycles per hour in the first 72 h of life and weekly at days 7, 14, 21, and 28. Results: We included 47 infants of mothers with GDM and 94 control infants. Both the aEEG total maturation score and its individual component scores, as well as the percentage of continuous background pattern, increased equally during the first 4 weeks after birth in both groups. GDM-exposed infants showed a slightly but significantly higher number of sleep-wake cycles per hour. Conclusion: We found normal maturation of brain activity in the first 4 weeks after birth in very preterm infants born to mothers with GDM, not differing from a very preterm control group. The higher number of sleep-wake cycles per hour in GDM-exposed infants could indicate transiently enhanced maturation. Further studies on brain activity and brain development in very preterm infants of mothers with GDM are needed to validate our results.

Introduction: Neurological consequences of preterm infants born to mothers with gestational diabetes mellitus (GDM) are unclear. In this pilot study, we investigated the effect of GDM on brain activity in very preterm infants. Methods: Preterm infants <32 gestational weeks of mothers with GDM compared to gestational age- and sex-matched controls born between 2011 and 2018 were included. Amplitude-integrated electroencephalography (aEEG) was assessed for total maturation and individual component scores according to Burdjalov and colleagues, the dominating visual background, and the presence of sleep-wake cycles per hour in the first 72 h of life and weekly at days 7, 14, 21, and 28. Results: We included 47 infants of mothers with GDM and 94 control infants. Both the aEEG total maturation score and its individual component scores, as well as the percentage of continuous background pattern, increased equally during the first 4 weeks after birth in both groups. GDM-exposed infants showed a slightly but significantly higher number of sleep-wake cycles per hour. Conclusion: We found normal maturation of brain activity in the first 4 weeks after birth in very preterm infants born to mothers with GDM, not differing from a very preterm control group. The higher number of sleep-wake cycles per hour in GDM-exposed infants could indicate transiently enhanced maturation. Further studies on brain activity and brain development in very preterm infants of mothers with GDM are needed to validate our results.

Introduction: Preterm infants are at risk for impairment in brain maturation at term equivalent age (TEA). Diffusion tensor imaging (DTI) is a powerful magnetic resonance imaging (MRI) technique, quantitatively reflecting microstructural brain development of white matter regions with parameters such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Amplitude-integrated electroencephalography (aEEG) assesses electrocortical activity and brain function. Methods: Aim of this study was to investigate a possible correlation between functional and microstructural brain maturation using neonatal aEEG and DTI-MRI at TEA. The study was conducted as a retrospective single center study in 446 infants born below 32 gestational weeks. Spearman rank´s correlation coefficients were calculated between aEEG (total maturation score) and FA/ADC value. To compare aEEG and DTI-MRI to neurodevelopmental outcome at 24 months of corrected age, we performed a multivariate linear regression analysis. Results: Analysis showed an all-time significant correlation between total maturation score and FA/ADC values of the corpus callosum at TEA with the strongest correlation at day 2, day 3, week 3 and week 4. After including perinatal variables in the model, this correlation remained highly significant at day 2 and 3. When comparing the association of aEEG and DTI-MRI to outcome, both the total maturation score at day 2, day 3 and FA/ADC of the splenium of the corpus callosum showed a significant correlation. Conclusion: This study indicates that early monitoring of functional brain maturation may predict later assessment of microstructural brain development of corpus callosum in preterm infants with a relation to neurodevelopmental outcome.

Introduction: There are some data indicating a negative impact of postnatal cytomegalovirus (CMV) infection on long-term neurodevelopmental outcome of preterm infants. So far, there is only little knowledge about a cerebral imaging correlate of these neurodevelopmental alterations induced by postnatal CMV infection in preterm infants. The aim of the current study is to investigate the effect of postnatal CMV infection on the incidence of brain injury and on microstructural brain maturation in very preterm infants at term-equivalent age. Methods: Infants <32 gestational weeks (02/2011- 11/2018) received cerebral MRI including axial diffusion-weighted images at term-equivalent age. All infants were screened for CMV infection using urine/saliva samples, and infection was regarded as acquired postnatal if a sample became positive >5 postnatal days. We compared brain injury as well as fractional anisotropy and apparent diffusion coefficient in 14 defined cerebral regions between infants with and without postnatal CMV infection. Results: 401 infants were eligible, of whom 18 (4.5%) infants had a postnatal CMV infection. There were no significant differences in rates of brain injury, nor in microstructural brain development between both groups. This applied equally to the subgroup of infants <28 gestational weeks. Conclusion: Although infants with postnatal CMV infection were born more immature and more frequently suffered from complications related to immaturity, we neither observed a higher rate of preterm brain injury nor disadvantageous alterations in microstructural brain maturation at term-equivalent age.

Introduction: There are some data indicating a negative impact of postnatal cytomegalovirus (CMV) infection on long-term neurodevelopmental outcome of preterm infants. So far, there is only little knowledge about a cerebral imaging correlate of these neurodevelopmental alterations induced by postnatal CMV infection in preterm infants. The aim of the current study is to investigate the effect of postnatal CMV infection on the incidence of brain injury and on microstructural brain maturation in very preterm infants at term-equivalent age. Methods: Infants <32 gestational weeks (02/2011- 11/2018) received cerebral MRI including axial diffusion-weighted images at term-equivalent age. All infants were screened for CMV infection using urine/saliva samples, and infection was regarded as acquired postnatal if a sample became positive >5 postnatal days. We compared brain injury as well as fractional anisotropy and apparent diffusion coefficient in 14 defined cerebral regions between infants with and without postnatal CMV infection. Results: 401 infants were eligible, of whom 18 (4.5%) infants had a postnatal CMV infection. There were no significant differences in rates of brain injury, nor in microstructural brain development between both groups. This applied equally to the subgroup of infants <28 gestational weeks. Conclusion: Although infants with postnatal CMV infection were born more immature and more frequently suffered from complications related to immaturity, we neither observed a higher rate of preterm brain injury nor disadvantageous alterations in microstructural brain maturation at term-equivalent age.

Introduction: Preterm infants are at risk for impairment in brain maturation at term equivalent age (TEA). Diffusion tensor imaging (DTI) is a powerful magnetic resonance imaging (MRI) technique, quantitatively reflecting microstructural brain development of white matter regions with parameters such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Amplitude-integrated electroencephalography (aEEG) assesses electrocortical activity and brain function. Methods: Aim of this study was to investigate a possible correlation between functional and microstructural brain maturation using neonatal aEEG and DTI-MRI at TEA. The study was conducted as a retrospective single center study in 446 infants born below 32 gestational weeks. Spearman rank´s correlation coefficients were calculated between aEEG (total maturation score) and FA/ADC value. To compare aEEG and DTI-MRI to neurodevelopmental outcome at 24 months of corrected age, we performed a multivariate linear regression analysis. Results: Analysis showed an all-time significant correlation between total maturation score and FA/ADC values of the corpus callosum at TEA with the strongest correlation at day 2, day 3, week 3 and week 4. After including perinatal variables in the model, this correlation remained highly significant at day 2 and 3. When comparing the association of aEEG and DTI-MRI to outcome, both the total maturation score at day 2, day 3 and FA/ADC of the splenium of the corpus callosum showed a significant correlation. Conclusion: This study indicates that early monitoring of functional brain maturation may predict later assessment of microstructural brain development of corpus callosum in preterm infants with a relation to neurodevelopmental outcome.

Introduction: Prophylactic low-dose paracetamol administration is used to induce closure of the ductus arteriosus. Effects on the neurological outcome in preterm infants remain unknown. We compared microstructural brain development in very preterm infants with and without exposure to prophylactic paracetamol by using MR-based diffusion tensor imaging. Materials and Methods: Infants aged <32 gestational weeks born between October 2014 and December 2018 received prophylactic paracetamol (10 mg/kg intravenously every 8 h until echocardiography after at least 72 h) and form the paracetamol group; infants born between February 2011 and September 2014 form the control group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at term-equivalent age were measured in 14 defined cerebral regions and compared between the groups. Results: Included in the study were 340 infants, of whom 217 received prophylactic paracetamol, and 123 formed the control group. The paracetamol group showed significantly higher FA values and lower ADC values in the splenium of the corpus callosum, as well as higher FA values in the pons bilaterally, the left middle cerebellar peduncle, the right occipital white matter, and the right posterior limb of the internal capsule (p ≤ 0.02). Conclusion: The perceived safety of prenatal paracetamol exposure has been questioned in recent years. We found no impairment on microstructural maturation processes in the brain of preterm infants at term-equivalent age following early paracetamol administration. The clinical relevance of these imaging findings has to be determined in long-term follow-up studies on neurodevelopmental outcome.

Introduction: Prophylactic low-dose paracetamol administration is used to induce closure of the ductus arteriosus. Effects on the neurological outcome in preterm infants remain unknown. We compared microstructural brain development in very preterm infants with and without exposure to prophylactic paracetamol by using MR-based diffusion tensor imaging. Materials and Methods: Infants aged <32 gestational weeks born between October 2014 and December 2018 received prophylactic paracetamol (10 mg/kg intravenously every 8 h until echocardiography after at least 72 h) and form the paracetamol group; infants born between February 2011 and September 2014 form the control group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) at term-equivalent age were measured in 14 defined cerebral regions and compared between the groups. Results: Included in the study were 340 infants, of whom 217 received prophylactic paracetamol, and 123 formed the control group. The paracetamol group showed significantly higher FA values and lower ADC values in the splenium of the corpus callosum, as well as higher FA values in the pons bilaterally, the left middle cerebellar peduncle, the right occipital white matter, and the right posterior limb of the internal capsule (p ≤ 0.02). Conclusion: The perceived safety of prenatal paracetamol exposure has been questioned in recent years. We found no impairment on microstructural maturation processes in the brain of preterm infants at term-equivalent age following early paracetamol administration. The clinical relevance of these imaging findings has to be determined in long-term follow-up studies on neurodevelopmental outcome.