Background: Preterm infants are at risk for neurodevelopmental deficits. An association between retinopathy of prematurity (ROP) and impaired cognitive outcome has already been described. However, less is known about the impact of ROP on visual motor integration (VMI), which is a prerequisite not only for fine motor abilities but also for further school skills. Therefore, the aim of this study was to retrospectively investigate the impact of ROP on VMI at preschool age.
Methods: The study was conducted at the Medical University of Vienna, including patients born between January 2009 and December 2014 with a gestational age of less than 30 weeks and/or a birth weight of less than 1,500 g. VMI was determined by Beery-Buktenica Developmental Test of Visual Motor Integration (Beery VMI) at the age of 5 years.
Results: Out of 1,365 patients, 353 met inclusion criteria for this study. Two hundred sixteen of them had no ROP, while 137 had ROP (stage 1: n = 23, stage 2: n = 74, stage 3: n = 40). Mean value of the Beery VMI score was significantly lower in the ROP group compared to the No-ROP group (90 ± 16 vs. 99 ± 14; p < 0.01). By correcting for other important medical conditions, ROP still had a significant impact on Beery VMI score (p < 0.01). Particularly, lower scores were found for stage 2 (p < 0.01) and stage 3 (p < 0.01).
Conclusion: Beery VMI scores were significantly lower in preterm infants with ROP stage 2 and 3 than in infants without ROP. This study shows the negative impact of ROP on VMI skills at preschool age, even after adjustment for key demographic and medical characteristics.
{"title":"Impact of Retinopathy of Prematurity on Visual Motor Integration.","authors":"Daniel Lukas Zimmermann, Hannah Schned, Lukas Unterasinger, Lieselotte Kirchner, Renate Fuiko, Monika Olischar, Katrin Klebermass-Schrehof, Angelika Berger, Manfred Weninger, Vito Giordano","doi":"10.1159/000529594","DOIUrl":"https://doi.org/10.1159/000529594","url":null,"abstract":"<p><strong>Background: </strong>Preterm infants are at risk for neurodevelopmental deficits. An association between retinopathy of prematurity (ROP) and impaired cognitive outcome has already been described. However, less is known about the impact of ROP on visual motor integration (VMI), which is a prerequisite not only for fine motor abilities but also for further school skills. Therefore, the aim of this study was to retrospectively investigate the impact of ROP on VMI at preschool age.</p><p><strong>Methods: </strong>The study was conducted at the Medical University of Vienna, including patients born between January 2009 and December 2014 with a gestational age of less than 30 weeks and/or a birth weight of less than 1,500 g. VMI was determined by Beery-Buktenica Developmental Test of Visual Motor Integration (Beery VMI) at the age of 5 years.</p><p><strong>Results: </strong>Out of 1,365 patients, 353 met inclusion criteria for this study. Two hundred sixteen of them had no ROP, while 137 had ROP (stage 1: n = 23, stage 2: n = 74, stage 3: n = 40). Mean value of the Beery VMI score was significantly lower in the ROP group compared to the No-ROP group (90 ± 16 vs. 99 ± 14; p < 0.01). By correcting for other important medical conditions, ROP still had a significant impact on Beery VMI score (p < 0.01). Particularly, lower scores were found for stage 2 (p < 0.01) and stage 3 (p < 0.01).</p><p><strong>Conclusion: </strong>Beery VMI scores were significantly lower in preterm infants with ROP stage 2 and 3 than in infants without ROP. This study shows the negative impact of ROP on VMI skills at preschool age, even after adjustment for key demographic and medical characteristics.</p>","PeriodicalId":18924,"journal":{"name":"Neonatology","volume":"120 3","pages":"317-324"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10148017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oxygen Saturation Index: A Trigger for Neonatal Transfer?","authors":"Srirupa Hari Gopal, Caraciolo J Fernandes","doi":"10.1159/000529649","DOIUrl":"https://doi.org/10.1159/000529649","url":null,"abstract":"","PeriodicalId":18924,"journal":{"name":"Neonatology","volume":"120 3","pages":"400-401"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9778861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MIRAGE syndrome is characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. This report describes heat stroke and rhabdomyolysis caused by anhidrosis as a symptom of MIRAGE syndrome in a small-for-gestational-age (SGA) female neonate born at 32 weeks of gestation (birth weight, 911 g [-3.8 SD]). She developed severe temperature instability with anhidrosis, growth failure, mild developmental delay, hypothyroidism, and intractable enteropathy. On day 156, her temperature reached 42.0°C; her fever persisted for 2 h with prolonged irritability. Her serum creatine kinase level increased to a peak value of 12,716 (normal range, 43-321) IU/L. The clinical feature was diagnosed as rhabdomyolysis caused by heat stroke, which resulted from physical exertion with anhidrosis. Her SAMD9 variant was c.2945G>A, p. (Arg982His). Neonatologists should be aware of MIRAGE syndrome as a differential diagnosis of SGA with temperature instability.
MIRAGE综合征的特征是骨髓发育不良、感染、生长受限、肾上腺发育不全、生殖器表型和肠病。本文报道了一例孕32周出生的小胎龄(SGA)女婴(出生体重911 g [-3.8 SD])中暑和无汗引起的横纹肌溶解为MIRAGE综合征的症状。她出现了严重的体温不稳定、无汗、生长衰竭、轻度发育迟缓、甲状腺功能减退和顽固性肠病。第156天,她的体温达到42.0℃;她发烧持续了2小时,并伴有长时间的烦躁。血清肌酸激酶升高至峰值12,716(正常范围43-321)IU/L。临床诊断为中暑引起的横纹肌溶解,是由体力消耗和无汗引起的。她的SAMD9变异为c.2945G>A, p. (Arg982His)。新生儿医生应该意识到MIRAGE综合征作为SGA与温度不稳定的鉴别诊断。
{"title":"A Small-for-Gestational-Age Infant with MIRAGE Syndrome Who Developed Heat Stroke and Rhabdomyolysis due to Severe Temperature Instability.","authors":"Kana Saito, Ryota Nakagawa, Satoshi Narumi, Hirofumi Ohashi, Akiko Ishiguro, Kazuhiko Kabe","doi":"10.1159/000529762","DOIUrl":"https://doi.org/10.1159/000529762","url":null,"abstract":"<p><p>MIRAGE syndrome is characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. This report describes heat stroke and rhabdomyolysis caused by anhidrosis as a symptom of MIRAGE syndrome in a small-for-gestational-age (SGA) female neonate born at 32 weeks of gestation (birth weight, 911 g [-3.8 SD]). She developed severe temperature instability with anhidrosis, growth failure, mild developmental delay, hypothyroidism, and intractable enteropathy. On day 156, her temperature reached 42.0°C; her fever persisted for 2 h with prolonged irritability. Her serum creatine kinase level increased to a peak value of 12,716 (normal range, 43-321) IU/L. The clinical feature was diagnosed as rhabdomyolysis caused by heat stroke, which resulted from physical exertion with anhidrosis. Her SAMD9 variant was c.2945G>A, p. (Arg982His). Neonatologists should be aware of MIRAGE syndrome as a differential diagnosis of SGA with temperature instability.</p>","PeriodicalId":18924,"journal":{"name":"Neonatology","volume":"120 3","pages":"390-394"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9790867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Snorri Donaldsson, Elena Palleri, Baldvin Jonsson, Thomas Drevhammar
Objective: Exploratory secondary analysis of the CORSAD trial compared a new resuscitation system (rPAP) to the standard T-piece system. This analysis focused on the subgroup of infants who were not intubated in the delivery room. The aim was to compare the use of noninvasive positive pressure ventilation (PPV), oxygen saturation, and Apgar scores for the two resuscitation systems during the 30-min intervention period.
Methods: This is secondary analysis of CORSAD trial using data from the intervention period in the delivery room. Infants in the original randomized system groups were divided into intubated and nonintubated groups. For nonintubated breathing infants, we compared demographics, the use of PPV, Apgar scores, and oxygen saturation at 5 and 10 min after birth. Generalized linear models were applied to calculate the risk difference and odds ratio with 95% CI between the two groups.
Results: Among nonintubated infants, the use of PPV repeatedly (defined as PPV with at least 1 min of spontaneous breathing between PPV cycles) was less frequent in the rPAP group (26.8% vs. 43.3%, %RD -16.5, 95% CI [-31.7 to -1.1], p 0.04). The use of PPV after 5 min of age was also less common in the rPAP group (23.2% vs. 38.8%, %RD -15.6, 95% CI [-30.7 to -0.8], p 0.04). There were no statistically significant differences in Apgar scores or oxygen saturation levels between the groups.
Conclusion: In the CORSAD trial, less PPV was needed to establish stable breathing in extremely preterm infants using the rPAP compared to using the standard T-piece without significant difference in Apgar scores or oxygenation.
{"title":"Transition of Extremely Preterm Infants from Birth to Stable Breathing: A Secondary Analysis of the CORSAD Trial.","authors":"Snorri Donaldsson, Elena Palleri, Baldvin Jonsson, Thomas Drevhammar","doi":"10.1159/000528754","DOIUrl":"https://doi.org/10.1159/000528754","url":null,"abstract":"<p><strong>Objective: </strong>Exploratory secondary analysis of the CORSAD trial compared a new resuscitation system (rPAP) to the standard T-piece system. This analysis focused on the subgroup of infants who were not intubated in the delivery room. The aim was to compare the use of noninvasive positive pressure ventilation (PPV), oxygen saturation, and Apgar scores for the two resuscitation systems during the 30-min intervention period.</p><p><strong>Methods: </strong>This is secondary analysis of CORSAD trial using data from the intervention period in the delivery room. Infants in the original randomized system groups were divided into intubated and nonintubated groups. For nonintubated breathing infants, we compared demographics, the use of PPV, Apgar scores, and oxygen saturation at 5 and 10 min after birth. Generalized linear models were applied to calculate the risk difference and odds ratio with 95% CI between the two groups.</p><p><strong>Results: </strong>Among nonintubated infants, the use of PPV repeatedly (defined as PPV with at least 1 min of spontaneous breathing between PPV cycles) was less frequent in the rPAP group (26.8% vs. 43.3%, %RD -16.5, 95% CI [-31.7 to -1.1], p 0.04). The use of PPV after 5 min of age was also less common in the rPAP group (23.2% vs. 38.8%, %RD -15.6, 95% CI [-30.7 to -0.8], p 0.04). There were no statistically significant differences in Apgar scores or oxygen saturation levels between the groups.</p><p><strong>Conclusion: </strong>In the CORSAD trial, less PPV was needed to establish stable breathing in extremely preterm infants using the rPAP compared to using the standard T-piece without significant difference in Apgar scores or oxygenation.</p>","PeriodicalId":18924,"journal":{"name":"Neonatology","volume":"120 2","pages":"250-256"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9341255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2023-08-25DOI: 10.1159/000532084
Yasmin Pellkofer, Marlene Hammerl, Elke Griesmaier, Maria Sappler, Elke Ruth Gizewski, Ursula Kiechl-Kohlendorfer, Vera Neubauer
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 was 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 or 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.
{"title":"The Effect of Postnatal Cytomegalovirus Infection on (Micro)structural Cerebral Development in Very Preterm Infants at Term-Equivalent Age.","authors":"Yasmin Pellkofer, Marlene Hammerl, Elke Griesmaier, Maria Sappler, Elke Ruth Gizewski, Ursula Kiechl-Kohlendorfer, Vera Neubauer","doi":"10.1159/000532084","DOIUrl":"10.1159/000532084","url":null,"abstract":"<p><strong>Introduction: </strong>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 was 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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 or in microstructural brain development between both groups. This applied equally to the subgroup of infants <28 gestational weeks.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":18924,"journal":{"name":"Neonatology","volume":" ","pages":"727-735"},"PeriodicalIF":2.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10458704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joseph L Mathew, Navneet Kaur, Jeanne Maria Dsouza
{"title":"Therapeutic Hypothermia for Neonatal Encephalopathy in Low-Resource Settings: Methodological Inaccuracies and Inconsistencies in the Latest Systematic Review.","authors":"Joseph L Mathew, Navneet Kaur, Jeanne Maria Dsouza","doi":"10.1159/000526596","DOIUrl":"https://doi.org/10.1159/000526596","url":null,"abstract":"","PeriodicalId":18924,"journal":{"name":"Neonatology","volume":"120 2","pages":"268-269"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9280348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stephanie Margarete Mueller, Benjamin W Ackermann, Sven Martin, Katrin Seifert, Alina Mohr, Waseem Alali, Ulrich H Thome, Martin Grunwald
Objectives: An increased frequency of intermittent hypoxemia (IH) is associated with a higher risk for poor developmental outcomes, disability, or death in extremely preterm infants. The objective of the prFesent study is to quantify the effect of hands-on medical and parental interventions on the incidence of IH in extremely preterm infants.
Methods: An observational design with intraindividual comparisons was used. Blood oxygen saturation levels (SpO2) and time-lapse video were recorded. Frequency, duration, and time to occurrence of IH (SpO2 <80% for ≥10 s) were compared between nursing and medical care (NMC), health care by parents, skin-to-skin contact (SSC), touch in incubator, physiotherapy, and rest. Each infant was observed for six consecutive 24-h periods. Inclusion criteria were as follows: gestational age ≤28 weeks, birth weight <1500 g, postnatal age 0-6 weeks, gavage feeding, no severe illnesses or invasive procedures, no mechanical ventilation.
Results: The highest proportion of time with IH occurred during NMC (2.49%) and incubator touch (1.32%), the lowest during SSC (0.74%) and health care by parents (0.67%). IH frequency per hour was highest during NMC (2.95, IQR 1.19-4.01) and lowest during SSC (0.88, IQR 0.37-2.32, p < 0.001). While an increase in IH during NMC was expected, the high incidence during incubator touch was surprising. Parental touch in the incubator is intended to be soothing, not stressful.
Conclusions: Future studies need to clarify how preterm infants process touch, which attributes of touch are fundamental trigger mechanisms of IH, and which handling strategies are most effective in lowering the incidence of IH during hands-on medical care.
{"title":"Incidence of Intermittent Hypoxemia Increases during Clinical Care and Parental Touch in Extremely Preterm Infants.","authors":"Stephanie Margarete Mueller, Benjamin W Ackermann, Sven Martin, Katrin Seifert, Alina Mohr, Waseem Alali, Ulrich H Thome, Martin Grunwald","doi":"10.1159/000527725","DOIUrl":"https://doi.org/10.1159/000527725","url":null,"abstract":"<p><strong>Objectives: </strong>An increased frequency of intermittent hypoxemia (IH) is associated with a higher risk for poor developmental outcomes, disability, or death in extremely preterm infants. The objective of the prFesent study is to quantify the effect of hands-on medical and parental interventions on the incidence of IH in extremely preterm infants.</p><p><strong>Methods: </strong>An observational design with intraindividual comparisons was used. Blood oxygen saturation levels (SpO2) and time-lapse video were recorded. Frequency, duration, and time to occurrence of IH (SpO2 <80% for ≥10 s) were compared between nursing and medical care (NMC), health care by parents, skin-to-skin contact (SSC), touch in incubator, physiotherapy, and rest. Each infant was observed for six consecutive 24-h periods. Inclusion criteria were as follows: gestational age ≤28 weeks, birth weight <1500 g, postnatal age 0-6 weeks, gavage feeding, no severe illnesses or invasive procedures, no mechanical ventilation.</p><p><strong>Results: </strong>The highest proportion of time with IH occurred during NMC (2.49%) and incubator touch (1.32%), the lowest during SSC (0.74%) and health care by parents (0.67%). IH frequency per hour was highest during NMC (2.95, IQR 1.19-4.01) and lowest during SSC (0.88, IQR 0.37-2.32, p < 0.001). While an increase in IH during NMC was expected, the high incidence during incubator touch was surprising. Parental touch in the incubator is intended to be soothing, not stressful.</p><p><strong>Conclusions: </strong>Future studies need to clarify how preterm infants process touch, which attributes of touch are fundamental trigger mechanisms of IH, and which handling strategies are most effective in lowering the incidence of IH during hands-on medical care.</p>","PeriodicalId":18924,"journal":{"name":"Neonatology","volume":"120 1","pages":"102-110"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9286468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cornelis Smit, Aline G J Engbers, Samira Samiee-Zafarghandy, Tamara van Donge, Sinno H P Simons, Robert B Flint, Marc Pfister, Catherijne A J Knibbe, John N van den Anker
Introduction: Oral ibuprofen is more effective than intravenous (IV) ibuprofen for closure of a patent ductus arteriosus (PDA). This study explored whether higher concentrations of the biologically active S-enantiomer or increased R- to S-conversion following oral dosing could explain this finding.
Methods: Two datasets containing 370 S- and R-ibuprofen concentrations from 95 neonates with PDA treated with oral (n = 27, 28%) or IV ibuprofen were analyzed using nonlinear mixed effects modeling. Concentration-time profiles in typical neonates were explored and compared in different dosing or R- to S-conversion scenarios.
Results: Postnatal age (PNA), gestational age (GA), and being small for GA impacted S- and R-ibuprofen clearance. Upon oral dosing, S-ibuprofen concentrations were lower compared to IV ibuprofen for a large part of the dosing interval. We could show that R- to S-conversion will not exceed 45%. Exploration of a 30% presystemic R- to S-conversion resulted in a 25-32% increase in S-ibuprofen exposure following oral administration with AUC72h values varying between 700-2,213 mg*h/L (oral) and 531-1,762 (IV) for the standard or 1,704-2,893 (oral) and 1,295-2,271 mg*h/L (IV) for PNA-based dosing.
Discussion: The absence of higher S-ibuprofen concentrations does not support a beneficial concentration-time profile after oral dosing. While a fraction of up to 45% presystemic R- to S-conversion could not be ruled out, the impact of such a low conversion might be only relevant for the standard but not high dosing regimens, considering reported exposure-response targets. Perhaps, the lack of high peak concentrations observed following IV dosing may play a role in the observed effects upon oral dosing.
{"title":"Oral Ibuprofen Is More Effective than Intravenous Ibuprofen for Closure of a Patent Ductus Arteriosus: Can Pharmacokinetic Modeling Help Us to Understand Why?","authors":"Cornelis Smit, Aline G J Engbers, Samira Samiee-Zafarghandy, Tamara van Donge, Sinno H P Simons, Robert B Flint, Marc Pfister, Catherijne A J Knibbe, John N van den Anker","doi":"10.1159/000526210","DOIUrl":"https://doi.org/10.1159/000526210","url":null,"abstract":"<p><strong>Introduction: </strong>Oral ibuprofen is more effective than intravenous (IV) ibuprofen for closure of a patent ductus arteriosus (PDA). This study explored whether higher concentrations of the biologically active S-enantiomer or increased R- to S-conversion following oral dosing could explain this finding.</p><p><strong>Methods: </strong>Two datasets containing 370 S- and R-ibuprofen concentrations from 95 neonates with PDA treated with oral (n = 27, 28%) or IV ibuprofen were analyzed using nonlinear mixed effects modeling. Concentration-time profiles in typical neonates were explored and compared in different dosing or R- to S-conversion scenarios.</p><p><strong>Results: </strong>Postnatal age (PNA), gestational age (GA), and being small for GA impacted S- and R-ibuprofen clearance. Upon oral dosing, S-ibuprofen concentrations were lower compared to IV ibuprofen for a large part of the dosing interval. We could show that R- to S-conversion will not exceed 45%. Exploration of a 30% presystemic R- to S-conversion resulted in a 25-32% increase in S-ibuprofen exposure following oral administration with AUC72h values varying between 700-2,213 mg*h/L (oral) and 531-1,762 (IV) for the standard or 1,704-2,893 (oral) and 1,295-2,271 mg*h/L (IV) for PNA-based dosing.</p><p><strong>Discussion: </strong>The absence of higher S-ibuprofen concentrations does not support a beneficial concentration-time profile after oral dosing. While a fraction of up to 45% presystemic R- to S-conversion could not be ruled out, the impact of such a low conversion might be only relevant for the standard but not high dosing regimens, considering reported exposure-response targets. Perhaps, the lack of high peak concentrations observed following IV dosing may play a role in the observed effects upon oral dosing.</p>","PeriodicalId":18924,"journal":{"name":"Neonatology","volume":"120 1","pages":"81-89"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9287522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abandoning undesired newborn infants was a Roman form of family limitation. They were exposed or given to foster mothers. Christianization alleviated their lot when in 374 CE, Emperor Valentinian's law provided some protection. The Milan Foundling Hospital was established in 787 CE. When the Carolingian Empire fell apart during the 10th century, monastic networks (the Holy Spirit Order and Daughters of Charity) took over social support for the poor, the sick, and the insane. Foundling hospitals proliferated in Italy between the 13th and 15th centuries, in France during the 16th and 17th, and in Germany and Austria in the 18th century. Metropolitan hospices admitted thousands of infants each year. Most were not "found" exposed but were admitted anonymously via a revolving box or registered in an open office. Soon after admission, they were transported for foster care to wet nurses in villages. Sick infants, especially those suspected of suffering from syphilis, were denied the breast, and artificial feeding was tried with little success. Official death statistics were falsified by relating infant deaths not to admissions but to the total number of children cared for. Over 60% died during their first year of life, mostly from pre-admission problems such as malformation, hypothermia, and disease; from poor hygiene in overcrowded wards; and from artificial feeding. Although not intended for that purpose, the hospices became medical research institutions when in late 18th century, physicians and surgeons were employed by maternity and foundling hospitals.
{"title":"Exposed and Abandoned. Origins of the Foundling Hospital.","authors":"Michael Obladen","doi":"10.1159/000527837","DOIUrl":"https://doi.org/10.1159/000527837","url":null,"abstract":"<p><p>Abandoning undesired newborn infants was a Roman form of family limitation. They were exposed or given to foster mothers. Christianization alleviated their lot when in 374 CE, Emperor Valentinian's law provided some protection. The Milan Foundling Hospital was established in 787 CE. When the Carolingian Empire fell apart during the 10th century, monastic networks (the Holy Spirit Order and Daughters of Charity) took over social support for the poor, the sick, and the insane. Foundling hospitals proliferated in Italy between the 13th and 15th centuries, in France during the 16th and 17th, and in Germany and Austria in the 18th century. Metropolitan hospices admitted thousands of infants each year. Most were not \"found\" exposed but were admitted anonymously via a revolving box or registered in an open office. Soon after admission, they were transported for foster care to wet nurses in villages. Sick infants, especially those suspected of suffering from syphilis, were denied the breast, and artificial feeding was tried with little success. Official death statistics were falsified by relating infant deaths not to admissions but to the total number of children cared for. Over 60% died during their first year of life, mostly from pre-admission problems such as malformation, hypothermia, and disease; from poor hygiene in overcrowded wards; and from artificial feeding. Although not intended for that purpose, the hospices became medical research institutions when in late 18th century, physicians and surgeons were employed by maternity and foundling hospitals.</p>","PeriodicalId":18924,"journal":{"name":"Neonatology","volume":"120 1","pages":"134-141"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9340308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}