http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, Early Online: 1–6 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.979783
ORIGINAL ARTICLE
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Neurodevelopmental outcomes of premature infants with severe intraventricular hemorrhage _ Erhan Calisici1, Zeynep Eras1, Mehmet Yekta Oncel1, Serife Suna Oguz1, Ismail Kursat Gokce1, and Ugur Dilmen2 1
Division of Neonatology, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey and 2Division of Neonatology, Yıldırım Beyazıt University, Ankara, Turkey Abstract
Keywords
Objective: Our objective was to determine the neurodevelopmental outcome at 18–24 months’ of corrected age (CA) in preterm infants with severe intraventricular hemorrhage (IVH). Methods: This was a retrospective cohort study of all preterm infants who were 537 weeks’ gestation, had Grade 3–4 IVH, were admitted between January 2009 and December 2010 and discharged. The cohort was divided into three groups. Group 1 was defined as infants born with a birth weight (BW) less than 1000 g, group 2 was defined as infants born with a BW between 1000 and 1500 g and group 3 was defined as infants born with a BW between 1501 and 2500 g. Severe IVH was defined as the presence of grade 3–4 IVH on cranial ultrasound. Cranial ultrasound was performed in the first week of life and subsequently at weekly intervals by a radiologist. A comprehensive assessment including hearing, vision, neurological and developmental evaluation with Bayley Scales of Infant Development, Second edition was performed by the experienced researchers at 18–24 months’ CA. Neurodevelopmental impairment (NDI) was defined as at the presence of one or more of the following: cerebral palsy; Mental Developmental Index score lower than 70; Psychomotor Developmental Index score lower than 70; bilateral hearing impairment; or bilateral blindness. Results: From January 2009 to December 2010, a total of 138 infants were diagnosed as severe IVH (grade 3–4). Of them, 74 (71.1%) infants (group 1 ¼ 31, group 2 ¼ 29 and group 3 ¼ 14 infants) completed the follow-up visit and evaluated at 18–24 months’ CA. Median Apgar score (p50.01) and resuscitation at birth (p50.01) were significantly different for groups 1–3. The use of catheterization, need for mechanical ventilation, need for phototherapy, retinopathy of premature and bronchopulmonary dysplasia were significantly higher in group 1 compared to groups 2 and 3 (p50.001, p50.001, p50.01, p50.01 and p ¼ 0.014, respectively). The duration of hospitalization and mortality rates consistent with the degree of prematurity were significantly higher in group 1 compared to groups 2 and 3 (p ¼ 0.03 and p ¼ 0.01). Among the long-term outcomes, the rates of CP and NDI did not differ between the groups (p ¼ 0.68 and p ¼ 0.068). Conclusion: Our results demonstrated that long-term outcomes of preterm infants did not differ between the groups classified according to the BW at two years of age. This has leaded to the conclusion that severe IVH is alone represents a significant risk factor for poor neurodevelopmental outcome in this already high-risk population.
Neurodevelopmental outcome, preterm infants, severe intraventricular hemorrhage
Introduction One of the challenges of modern perinatal care for preterm infants is achieving optimal survival while simultaneously limiting the rate of neurodevelopmental handicap [1]. Highgrade intraventricular hemorrhage (IVH) is a complication, which has been shown to contribute to long-term disabilities associated with preterm birth [1–4]. It appears in 20–25% in very low birthweight infants infants (birth weight [BW]51500 g) [2]. The incidence of IVH increases with Address for correspondence: Erhan Calisici, MD, Division of Neonatology, Zekai Tahir Burak Maternity Teaching Hospital, 06230 Cebeci, Ankara, Turkey. Tel: +90 312 3065270. Fax: +90 312 3094702. E-mail: [email protected]
History Received 2 November 2013 Accepted 20 October 2014 Published online 14 November 2014
decreasing gestational age (GA) and BW, where as it occurs in 31.5, 29.8, 15.8 and 7.2% of infants with BW5750, 751–1000, 1001–1250, 1251–1500 g, respectively [5]. IVH is most commonly encountered within the first 24 hours after birth, and hemorrhages can progress over 48 h or more. By the end of the first postnatal week, 90% of the hemorrhages can be detected at their full extent, and this risk period for IVH is independent of GA [6]. Studies addressing the etiology of IVH have identified numerous environmental and medical risk factors including low GA, low BW, absence of antenatal steroid exposure, antenatal maternal hemorrhage, maternal chorioamnionitis/ infection/inflammation, mode of delivery, prolonged labor, postnatal resuscitation and intubation, gender, severe
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Biblioteka Uniwersytetu Warszawskiego on 12/08/14 For personal use only.
2
E. Calisici et al.
respiratory distress syndrome, delayed surfactant administration, sepsis, patent ductus arteriosus (PDA), recurrent endotracheal suctioning, metabolic acidosis, hypo-hypertension, coagulation abnormalities, rapid volume expansion, hypoxemia, hypercapnia, pneumothorax, seizures, small for GA status, treatment for acidosis and treatment with pressors [7– 13]. For reducing the incidence of IVH, several pharmacological interventions have been proposed, including antenatal steroids, prenatal tocolytic therapy, postnatal administration of low-dose indomethacin and surfactant [14–17]. IVH can be described by the following classification: grade 1 – germinal matrix hemorrhage; grade 2 – intraventricular blood without distension of the ventricular system; grade 3 – blood filling and distending the ventricular system; and grade 4 – parenchymal involvement of hemorrhage, also known as periventricular venous infarction [18,19]. In the newborn period, 5–10% of preterm infants with grade 3–4 IVH suffer seizures and as many as 50% experience posthemorrhagic hydrocephalus (PHH). Finally, mortality is higher in infants with grade 3–4 IVH than in GA-matched subjects without grade 3–4 IVH [18,20]. Grade 3 IVH (without parenchymal involvement) and grade 4 IVH (with parenchymal involvement) are often combined into description of a single entity, usually ‘‘severe’’ IVH, despite different long-term neurodevelopmental outcome. Grades 3–4 IVH are considered major determinants of poor later neurodevelopmental outcomes, including cerebral palsy and subnormal cognitive function [21–23]. PHH and periventricular leukomalacia are two significant sequelae of severe IVH. Many investigators believe that the white matter injury, which accompanies IVH, represents the major cause of the neurodevelopmental impairments (NDIs) suffered by these neonates [24,25]. Accurate prediction of the outcomes of infants with periventricular hemorrhagic infarct PVHI can be relevant to withdrawal of intensive care for critically ill neonates and to design of rehabilitative care [23,24]. Therefore, we undertook a single-center study with a large population of preterm infants with severe IVH to determine the neurodevelopmental outcomes at two years of age.
Methods Study population and design The retrospective cohort study was conducted in the neonatal intensive care unit (NICU) of Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey, between January 2009 and December 2010. The preterm infants (537 weeks gestation) admitted in our NICU and diagnosed as grade 3– 4 IVH were enrolled. Exclusion criteria were congenital viral infections, genetic abnormalities, structural brain malformations and metabolic diseases. IVH was diagnosed by cranial ultrasonography (USG). Perinatal data was collected retrospectively from medical records. Maternal characteristics included maternal age, antenatal steroid therapy, mode of delivery and complications of pregnancy (e.g. gestational diabetes mellitus, preeclampsia and drug usage). Additional birth data included BW, GA, gender, head circumference, resuscitation at birth and Apgar score at five minutes. Neonatal morbidities included length of
J Matern Fetal Neonatal Med, Early Online: 1–6
hospital stay, sepsis, PDA, insert catheterization, thrombocytopenia, hypoglycemia, need for mechanical ventilation, small for gestational age (SGA), need for phototherapy, retinopathy of prematurity (ROP) that required laser therapy and bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks’ postmenstrual age. In the first week of life, cranial USG using Aloka Prosound SSD-5500 (Aloka, Tokyo, Japan) with a cranial 7.5 MHz probe transducer that was interpreted by the initial reader as showing a grade 3 or 4 IVH was copied for repeat interpretation by a single radiologist. This reader assigned a diagnosis on the basis of the criteria documented by Papile et al. [26]. Grade 3 was defined as massive IVH with blood filling 450% of the ventricular volume associated with acute dilatation of this ventricle. Grade 4 was defined as an IVH with an associated ipsilateral parenchymal echo density present. The ventricular width was measured according to the criteria of Levene [27], and post hemorrhagic ventricular dilatation (PHVD) was defined as a measurement 497%. Sonographic examination was repeated subsequently at weekly intervals by a radiologist. The cohort was divided into three groups. Group 1 was defined as infants born with a BW less than 1000 g, group 2 was defined as infants born with a BW between 1000 and 1500 g and group 3 was defined as infants born with a BW between 1501 and 2500 g. The families were asked to return for a comprehensive visit at 18–24 months’ corrected age (CA). The local research ethics committee approved the data collection and evaluation for this study. Written informed consent had been obtained from the infants’ parents. Neurodevelopmental outcome The surviving infants were seen regularly at the outpatient premature follow-up clinic. A comprehensive assessment including hearing, vision, neurological and developmental evaluation was performed by the experienced researchers at 18–24 months’ CA. Measures of neurodevelopmental outcomes included the Bayley Scales of Infant Development, Second Edition (BSID II), Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) with recommended adaptations for visual and auditory impairments [28]. The mean BSID II score is 100 for MDI and PDI, with an SD of 15; a score of less than 70 (42 SDs below the mean) indicates significant delay. Infants who were so severely impaired that testing with the BSID II could not be performed were assigned a MDI and PDI score of 49. Vision impairment was defined as blindness or bilateral field of vision loss. Hearing impairment was defined as hearing aids in one or both ears. CP was defined as appearance in early life of a persistent but not unchanging disorder in tone, movement and posture that was attributable to a nonprogressive disorder of the brain [29]. NDI was defined as at the presence of one or more of the following: cerebral palsy; MDI score lower than 70; PDI score lower than 70; bilateral hearing impairment; or bilateral blindness [11]. Statistical analysis Statistical analysis was performed with SPSS software version 16.0 (SPSS Inc., Chicago, IL), and statistical significance was
Neurodevelopmental outcomes of premature infants with severe IVH
DOI: 10.3109/14767058.2014.979783
set at p50.05. Differences in the groups for all variables were tested with the Student t test, Mann–Whitney test, 2 test, independent samples t test and one-way analysis of variance, as appropriate.
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Biblioteka Uniwersytetu Warszawskiego on 12/08/14 For personal use only.
Results From January 2009 to December 2010, a total of 1850 preterm infants born 537 weeks’ GA were admitted to our level 3 NICU and 138 (7.4%) were diagnosed as severe IVH by cranial USG. Of 138 infants (group 1 ¼ 63, group 2 ¼ 49 and group 3 ¼ 26 infants), 69 were defined as grade 3 and 69 were defined as grade 4 IVH. Thirty-four (24.6%) of these patients died before discharge. A hundred and four (75.4%) were survived, discharged from the NICU and eligible for the follow-up. Of these, 74 (71.1%) infants (group 1 ¼ 31, group 2 ¼ 29 and group 3 ¼ 14 infants) completed the follow-up visit and evaluated at 18–24 months’ CA. The flowchart of the patients was presented in Figure 1. Patient characteristics The median age at first diagnosed as severe IVH by cranial ultrasound was 7.1 d. The mean BW and GA of all patients were 1154 ± 435 g and 28.6 ± 3.3 weeks, respectively. Of 69 infants with grade 3 IVH, 30 infants were in group 1, 23 infants were in group 2 and 16 infants were in group 3. Of 69 infants with grade 4, 33 infants were in group 1, 26 infants in group 2 and 10 infants were in group 3. The distribution of Figure 1. The flowchart of the patients.
patients according to BW groups and IVH type are shown in Figure 2. We compared the maternal and perinatal characteristics of our group of infants with grades 3–4 IVH. We found no significant differences between the three groups except Apgar score and resuscitation at birth. Median Apgar score (p50.01) and resuscitation at birth (p50.01) were significantly different for groups 1–3 in as listed in Table 1. Neonatal morbidities including the rates of sepsis, PDA, thrombocytopenia, hypoglycemia, SGA, PHVD and ventriculoperitoneal shunt (VPS) did not differ between the groups (p ¼ 0.20, p ¼ 0.20, p ¼ 030, p ¼ 0.20, p ¼ 0.40, p ¼ 0.175 and p ¼ 0.585, respectively). On the other hand, insert of catheter, need for mechanical ventilation, need for phototherapy and incidence of incidence of ROP and BPD were significantly higher in group 1 compared to groups 2 and 3 (p50.001, p50.001, p50.01 p50.01 and p ¼ 0.014, respectively). Overall, the mortality rate of the cohort was 24.6%. The length of hospital stay and mortality rates consistent with the degree of prematurity and were significantly higher in group 1 compared to groups 2 and 3 (p ¼ 0.03 and p ¼ 0.01) (Table 2). Neurodevelopmental outcomes Seventy-four (71.1%) infants who survived and completed the follow-up were assessed at 18–24 months’ CA. Of 74 infants, 42 infants had grade 3 IVH and 32 had grade 4 IVH. The
Premature neonates (GA
ORIGINAL ARTICLE
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Biblioteka Uniwersytetu Warszawskiego on 12/08/14 For personal use only.
Neurodevelopmental outcomes of premature infants with severe intraventricular hemorrhage _ Erhan Calisici1, Zeynep Eras1, Mehmet Yekta Oncel1, Serife Suna Oguz1, Ismail Kursat Gokce1, and Ugur Dilmen2 1
Division of Neonatology, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey and 2Division of Neonatology, Yıldırım Beyazıt University, Ankara, Turkey Abstract
Keywords
Objective: Our objective was to determine the neurodevelopmental outcome at 18–24 months’ of corrected age (CA) in preterm infants with severe intraventricular hemorrhage (IVH). Methods: This was a retrospective cohort study of all preterm infants who were 537 weeks’ gestation, had Grade 3–4 IVH, were admitted between January 2009 and December 2010 and discharged. The cohort was divided into three groups. Group 1 was defined as infants born with a birth weight (BW) less than 1000 g, group 2 was defined as infants born with a BW between 1000 and 1500 g and group 3 was defined as infants born with a BW between 1501 and 2500 g. Severe IVH was defined as the presence of grade 3–4 IVH on cranial ultrasound. Cranial ultrasound was performed in the first week of life and subsequently at weekly intervals by a radiologist. A comprehensive assessment including hearing, vision, neurological and developmental evaluation with Bayley Scales of Infant Development, Second edition was performed by the experienced researchers at 18–24 months’ CA. Neurodevelopmental impairment (NDI) was defined as at the presence of one or more of the following: cerebral palsy; Mental Developmental Index score lower than 70; Psychomotor Developmental Index score lower than 70; bilateral hearing impairment; or bilateral blindness. Results: From January 2009 to December 2010, a total of 138 infants were diagnosed as severe IVH (grade 3–4). Of them, 74 (71.1%) infants (group 1 ¼ 31, group 2 ¼ 29 and group 3 ¼ 14 infants) completed the follow-up visit and evaluated at 18–24 months’ CA. Median Apgar score (p50.01) and resuscitation at birth (p50.01) were significantly different for groups 1–3. The use of catheterization, need for mechanical ventilation, need for phototherapy, retinopathy of premature and bronchopulmonary dysplasia were significantly higher in group 1 compared to groups 2 and 3 (p50.001, p50.001, p50.01, p50.01 and p ¼ 0.014, respectively). The duration of hospitalization and mortality rates consistent with the degree of prematurity were significantly higher in group 1 compared to groups 2 and 3 (p ¼ 0.03 and p ¼ 0.01). Among the long-term outcomes, the rates of CP and NDI did not differ between the groups (p ¼ 0.68 and p ¼ 0.068). Conclusion: Our results demonstrated that long-term outcomes of preterm infants did not differ between the groups classified according to the BW at two years of age. This has leaded to the conclusion that severe IVH is alone represents a significant risk factor for poor neurodevelopmental outcome in this already high-risk population.
Neurodevelopmental outcome, preterm infants, severe intraventricular hemorrhage
Introduction One of the challenges of modern perinatal care for preterm infants is achieving optimal survival while simultaneously limiting the rate of neurodevelopmental handicap [1]. Highgrade intraventricular hemorrhage (IVH) is a complication, which has been shown to contribute to long-term disabilities associated with preterm birth [1–4]. It appears in 20–25% in very low birthweight infants infants (birth weight [BW]51500 g) [2]. The incidence of IVH increases with Address for correspondence: Erhan Calisici, MD, Division of Neonatology, Zekai Tahir Burak Maternity Teaching Hospital, 06230 Cebeci, Ankara, Turkey. Tel: +90 312 3065270. Fax: +90 312 3094702. E-mail: [email protected]
History Received 2 November 2013 Accepted 20 October 2014 Published online 14 November 2014
decreasing gestational age (GA) and BW, where as it occurs in 31.5, 29.8, 15.8 and 7.2% of infants with BW5750, 751–1000, 1001–1250, 1251–1500 g, respectively [5]. IVH is most commonly encountered within the first 24 hours after birth, and hemorrhages can progress over 48 h or more. By the end of the first postnatal week, 90% of the hemorrhages can be detected at their full extent, and this risk period for IVH is independent of GA [6]. Studies addressing the etiology of IVH have identified numerous environmental and medical risk factors including low GA, low BW, absence of antenatal steroid exposure, antenatal maternal hemorrhage, maternal chorioamnionitis/ infection/inflammation, mode of delivery, prolonged labor, postnatal resuscitation and intubation, gender, severe
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Biblioteka Uniwersytetu Warszawskiego on 12/08/14 For personal use only.
2
E. Calisici et al.
respiratory distress syndrome, delayed surfactant administration, sepsis, patent ductus arteriosus (PDA), recurrent endotracheal suctioning, metabolic acidosis, hypo-hypertension, coagulation abnormalities, rapid volume expansion, hypoxemia, hypercapnia, pneumothorax, seizures, small for GA status, treatment for acidosis and treatment with pressors [7– 13]. For reducing the incidence of IVH, several pharmacological interventions have been proposed, including antenatal steroids, prenatal tocolytic therapy, postnatal administration of low-dose indomethacin and surfactant [14–17]. IVH can be described by the following classification: grade 1 – germinal matrix hemorrhage; grade 2 – intraventricular blood without distension of the ventricular system; grade 3 – blood filling and distending the ventricular system; and grade 4 – parenchymal involvement of hemorrhage, also known as periventricular venous infarction [18,19]. In the newborn period, 5–10% of preterm infants with grade 3–4 IVH suffer seizures and as many as 50% experience posthemorrhagic hydrocephalus (PHH). Finally, mortality is higher in infants with grade 3–4 IVH than in GA-matched subjects without grade 3–4 IVH [18,20]. Grade 3 IVH (without parenchymal involvement) and grade 4 IVH (with parenchymal involvement) are often combined into description of a single entity, usually ‘‘severe’’ IVH, despite different long-term neurodevelopmental outcome. Grades 3–4 IVH are considered major determinants of poor later neurodevelopmental outcomes, including cerebral palsy and subnormal cognitive function [21–23]. PHH and periventricular leukomalacia are two significant sequelae of severe IVH. Many investigators believe that the white matter injury, which accompanies IVH, represents the major cause of the neurodevelopmental impairments (NDIs) suffered by these neonates [24,25]. Accurate prediction of the outcomes of infants with periventricular hemorrhagic infarct PVHI can be relevant to withdrawal of intensive care for critically ill neonates and to design of rehabilitative care [23,24]. Therefore, we undertook a single-center study with a large population of preterm infants with severe IVH to determine the neurodevelopmental outcomes at two years of age.
Methods Study population and design The retrospective cohort study was conducted in the neonatal intensive care unit (NICU) of Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey, between January 2009 and December 2010. The preterm infants (537 weeks gestation) admitted in our NICU and diagnosed as grade 3– 4 IVH were enrolled. Exclusion criteria were congenital viral infections, genetic abnormalities, structural brain malformations and metabolic diseases. IVH was diagnosed by cranial ultrasonography (USG). Perinatal data was collected retrospectively from medical records. Maternal characteristics included maternal age, antenatal steroid therapy, mode of delivery and complications of pregnancy (e.g. gestational diabetes mellitus, preeclampsia and drug usage). Additional birth data included BW, GA, gender, head circumference, resuscitation at birth and Apgar score at five minutes. Neonatal morbidities included length of
J Matern Fetal Neonatal Med, Early Online: 1–6
hospital stay, sepsis, PDA, insert catheterization, thrombocytopenia, hypoglycemia, need for mechanical ventilation, small for gestational age (SGA), need for phototherapy, retinopathy of prematurity (ROP) that required laser therapy and bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks’ postmenstrual age. In the first week of life, cranial USG using Aloka Prosound SSD-5500 (Aloka, Tokyo, Japan) with a cranial 7.5 MHz probe transducer that was interpreted by the initial reader as showing a grade 3 or 4 IVH was copied for repeat interpretation by a single radiologist. This reader assigned a diagnosis on the basis of the criteria documented by Papile et al. [26]. Grade 3 was defined as massive IVH with blood filling 450% of the ventricular volume associated with acute dilatation of this ventricle. Grade 4 was defined as an IVH with an associated ipsilateral parenchymal echo density present. The ventricular width was measured according to the criteria of Levene [27], and post hemorrhagic ventricular dilatation (PHVD) was defined as a measurement 497%. Sonographic examination was repeated subsequently at weekly intervals by a radiologist. The cohort was divided into three groups. Group 1 was defined as infants born with a BW less than 1000 g, group 2 was defined as infants born with a BW between 1000 and 1500 g and group 3 was defined as infants born with a BW between 1501 and 2500 g. The families were asked to return for a comprehensive visit at 18–24 months’ corrected age (CA). The local research ethics committee approved the data collection and evaluation for this study. Written informed consent had been obtained from the infants’ parents. Neurodevelopmental outcome The surviving infants were seen regularly at the outpatient premature follow-up clinic. A comprehensive assessment including hearing, vision, neurological and developmental evaluation was performed by the experienced researchers at 18–24 months’ CA. Measures of neurodevelopmental outcomes included the Bayley Scales of Infant Development, Second Edition (BSID II), Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) with recommended adaptations for visual and auditory impairments [28]. The mean BSID II score is 100 for MDI and PDI, with an SD of 15; a score of less than 70 (42 SDs below the mean) indicates significant delay. Infants who were so severely impaired that testing with the BSID II could not be performed were assigned a MDI and PDI score of 49. Vision impairment was defined as blindness or bilateral field of vision loss. Hearing impairment was defined as hearing aids in one or both ears. CP was defined as appearance in early life of a persistent but not unchanging disorder in tone, movement and posture that was attributable to a nonprogressive disorder of the brain [29]. NDI was defined as at the presence of one or more of the following: cerebral palsy; MDI score lower than 70; PDI score lower than 70; bilateral hearing impairment; or bilateral blindness [11]. Statistical analysis Statistical analysis was performed with SPSS software version 16.0 (SPSS Inc., Chicago, IL), and statistical significance was
Neurodevelopmental outcomes of premature infants with severe IVH
DOI: 10.3109/14767058.2014.979783
set at p50.05. Differences in the groups for all variables were tested with the Student t test, Mann–Whitney test, 2 test, independent samples t test and one-way analysis of variance, as appropriate.
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by Biblioteka Uniwersytetu Warszawskiego on 12/08/14 For personal use only.
Results From January 2009 to December 2010, a total of 1850 preterm infants born 537 weeks’ GA were admitted to our level 3 NICU and 138 (7.4%) were diagnosed as severe IVH by cranial USG. Of 138 infants (group 1 ¼ 63, group 2 ¼ 49 and group 3 ¼ 26 infants), 69 were defined as grade 3 and 69 were defined as grade 4 IVH. Thirty-four (24.6%) of these patients died before discharge. A hundred and four (75.4%) were survived, discharged from the NICU and eligible for the follow-up. Of these, 74 (71.1%) infants (group 1 ¼ 31, group 2 ¼ 29 and group 3 ¼ 14 infants) completed the follow-up visit and evaluated at 18–24 months’ CA. The flowchart of the patients was presented in Figure 1. Patient characteristics The median age at first diagnosed as severe IVH by cranial ultrasound was 7.1 d. The mean BW and GA of all patients were 1154 ± 435 g and 28.6 ± 3.3 weeks, respectively. Of 69 infants with grade 3 IVH, 30 infants were in group 1, 23 infants were in group 2 and 16 infants were in group 3. Of 69 infants with grade 4, 33 infants were in group 1, 26 infants in group 2 and 10 infants were in group 3. The distribution of Figure 1. The flowchart of the patients.
patients according to BW groups and IVH type are shown in Figure 2. We compared the maternal and perinatal characteristics of our group of infants with grades 3–4 IVH. We found no significant differences between the three groups except Apgar score and resuscitation at birth. Median Apgar score (p50.01) and resuscitation at birth (p50.01) were significantly different for groups 1–3 in as listed in Table 1. Neonatal morbidities including the rates of sepsis, PDA, thrombocytopenia, hypoglycemia, SGA, PHVD and ventriculoperitoneal shunt (VPS) did not differ between the groups (p ¼ 0.20, p ¼ 0.20, p ¼ 030, p ¼ 0.20, p ¼ 0.40, p ¼ 0.175 and p ¼ 0.585, respectively). On the other hand, insert of catheter, need for mechanical ventilation, need for phototherapy and incidence of incidence of ROP and BPD were significantly higher in group 1 compared to groups 2 and 3 (p50.001, p50.001, p50.01 p50.01 and p ¼ 0.014, respectively). Overall, the mortality rate of the cohort was 24.6%. The length of hospital stay and mortality rates consistent with the degree of prematurity and were significantly higher in group 1 compared to groups 2 and 3 (p ¼ 0.03 and p ¼ 0.01) (Table 2). Neurodevelopmental outcomes Seventy-four (71.1%) infants who survived and completed the follow-up were assessed at 18–24 months’ CA. Of 74 infants, 42 infants had grade 3 IVH and 32 had grade 4 IVH. The
Premature neonates (GA
