|Year : 2019 | Volume
| Issue : 3 | Page : 298-304
Factors associated with intraventricular hemorrhage among preterm neonates in Aminu Kano teaching hospital
CC Egwu1, WN Ogala2, ZL Farouk3, AM Tabari4, AH Dambatta4
1 Department of Paediatrics, Aminu Kano Teaching Hospital, Kano, Nigeria
2 Department of Paediatrics, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State, Nigeria
3 Department of Paediatrics, Bayero University Kano, Aminu Kano Teaching Hospital, Kano, Nigeria
4 Department of Radiology, Bayero University Kano, Aminu Kano Teaching Hospital, Kano, Nigeria
|Date of Acceptance||28-Sep-2018|
|Date of Web Publication||6-Mar-2019|
Dr. C C Egwu
Department of Paediatrics, Aminu Kano Teaching Hospital, PMB 3452, Zaria Road, Kano
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Intraventricular hemorrhage (IVH) is a severe complication among preterm neonates which can result in hydrocephalus, cerebral palsy, behavioural disorders, learning disabilities, or death. It is important to identify the factors associated with IVH in order to prevent these neurological consequences and reduce the resultant burden of neurological disease. Aim: To determine the factors associated with IVH among preterm neonates. Design: The study was prospective cross-sectional in design. Subjects and Methods: Ninety-nine preterm neonates who were < 37 completed weeks of gestation were recruited consecutively from the Special Care Baby Unit of a Tertiary Hospital. Transfontanelle ultrasonography was used to detect IVH and the factors associated with IVH were classified into: neonatal, maternal (prenatal), and clinical factors. Data were analyzed using SPSS version 16.0 for windows. Chi-squared test and Fisher's exact probability test were used as appropriate. The level of significance was set at P < 0.05. The association between these factors and IVH was evaluated by univariate and multivariate logistic regression analyses. Results: Among the 99 preterm neonates studied, 36 (36.4%) of them were between 28 and 31 weeks of gestation, whereas 63 (63.6%) were between 32 and 36 weeks of gestation. In univariate analysis, the factors found to be associated with IVH were lower gestational age <32 weeks gestation, low Apgar score of <3 in 1 and 5 min, respectively, outborn status of neonates, lower social class, need for respiratory support, and blood transfusion. However, the lower gestational age (odds ratio [OR]: 10.9, 95% confidence interval [CI]:1.95–61.04) and respiratory support (continuous positive airway pressure (CPAP)) [OR: 52.24; CI: 3.40–721.84] were retained as significant predictors of IVH in the multivariate logistic regression model. Conclusion: The lower gestational age and respiratory support (CPAP) are independent predictors for IVH. Prevention of preterm delivery and improvement in interventions of neonatal care (CPAP) are necessary to prevent the risk for IVH especially in the early preterm neonates.
Keywords: Intraventricular hemorrhage, neonate, preterm, risk factors, transfontanelle ultrasonography
|How to cite this article:|
Egwu C C, Ogala W N, Farouk Z L, Tabari A M, Dambatta A H. Factors associated with intraventricular hemorrhage among preterm neonates in Aminu Kano teaching hospital. Niger J Clin Pract 2019;22:298-304
|How to cite this URL:|
Egwu C C, Ogala W N, Farouk Z L, Tabari A M, Dambatta A H. Factors associated with intraventricular hemorrhage among preterm neonates in Aminu Kano teaching hospital. Niger J Clin Pract [serial online] 2019 [cited 2019 Sep 17];22:298-304. Available from: http://www.njcponline.com/text.asp?2019/22/3/298/253444
| Introduction|| |
Intraventricular hemorrhage (IVH) is an important neurological complication in preterm neonates. A preterm neonate is a live birth delivered before 37 completed weeks of gestation following the onset of the last menstrual period., The prevalence of IVH reported from studies in different countries ranges from 15% to 100% among preterm neonates with very low birth weights.,,,,, It is important to identify IVH as early as possible because of its high rate of mortality , as well as the associated neurodevelopmental sequelae such as cerebral palsy, learning disability, epilepsy, and other disturbances of psychomotor development in affected neonates.,
A number of factors, such as low gestational age and birthweight, vaginal delivery, low Apgar scores, male gender, outborn status, respiratory distress, postnatal resuscitation and intubation, metabolic acidosis, sepsis, and premature rupture of membranes (PROM) among others, have been implicated in the development of IVH in neonates.,,,,, The peculiarities of the cerebral microvasculature in preterm neonates favor the onset of IVH because of the presence of marked capillary fragility, especially in relation to the germinal matrix vessels.,,, These capillaries are susceptible to ischemic lesions promoting breakage and subsequent bleeding.,,, Identifying the risk factors and underlying mechanism for IVH allows for the development of strategies to reduce its prevalence, consequent mortality, and associated neurodevelopmental problems.,,
This study was carried out to identify the factors associated with IVH as early identification of these risk factors will also allow for preventive measures to be put in place. The majority of studies on IVH in Nigeria were carried out in the southern part of the country.,, However, Northwestern Nigeria, in particular, has a high burden of preterm delivery  and lower access to tertiary health facilities and skilled manpower , resulting in higher neonatal mortality rates , compared with the South. There is, therefore, the need to improve anticipatory care for IVH by studying the associated factors in this part of the country.
| Materials and Methods|| |
The study was hospital-based, prospective and cross-sectional in design and was conducted between February and November 2014.
The study population included neonates delivered before 37 completed weeks of gestation and admitted at the Special Care Baby Unit (SCBU) of the hospital.
- Preterm neonates (those delivered before 37 completed weeks) who were admitted at the SCBU of the hospital within the first 1 week of life
- Those whose parents/caregivers consented to the study.
- Preterm neonates who had congenital anomalies of the central nervous system such as neural tube defects.
Ethical approval for the study was obtained from the Research and Ethics Committee of the hospital. A written informed consent to enroll the patient into the study was obtained from the parent(s) or the accompanying caregiver(s) of each neonate.
Sample Size and Sampling Method
The minimum sample size of the study was calculated using the formula.
where n = minimum sample size; z = standard normal deviate corresponding to 95% confidence level (1.96); p = prevalence of IVH in preterm neonates, which is 30% in Ilorin.
q = (1 − p), the proportion of the population without the condition
d = the desired precision is equal to 10%.
n = 81
Adding an attrition rate of 20%, a total of 99 preterm neonates were recruited for the study.
By convenient sampling method, consecutive preterm neonates who fulfilled the inclusion criteria were enrolled. Questionnaires were administered to parents or caregivers to obtain relevant data pertaining to the factors associated with IVH such as attendance at antenatal care, place, and mode of delivery. Partographs and antenatal cards were used to retrieve other information such as pregnancy-induced hypertension, maternal use of steroids, time of rupture of membranes, gestational age at delivery, Apgar scores, and the need for postnatal resuscitation or endotracheal intubation for those neonates delivered at the hospital. For outborn neonates of unbooked mothers without partographs or antenatal cards, some information such as the Apgar scores could not be obtained. The neonates were assigned a socioeconomic class based on Olusanya's classification. A detailed physical examination was conducted at presentation with emphasis on the birthweight (taken within the first hour of life),, sex, and age at presentation. The gestational age was assessed using the New Ballards Score  which is reliable up to the first 7 days of life, while the Lubchenco Chart  was used to obtain the weight-for-gestational age classification. The neonates were examined for clinical features such as pallor, apnea, cyanosis, seizures, bulging anterior fontanel, respiratory distress, abnormal posture or tone, and weak and rapid pulses.
All the neonates had the packed cell volume (PCV) done at enrollment and serial PCV was done according to the standard protocol of the unit which is every alternate day for the first week of life, then once in the second week of life.
Before commencement of the study, the researcher who performed the transfontanelle ultrasound scans had a 3 months intensive training on the principles and practice of cranial ultrasonography, specifically for identifying IVH. Transfontanelle ultrasonography was conducted on each enrolled infant by the researcher with the assistance of a Consultant Radiologist using the Mindray R model DP8500 (Shenzhen, China) ultrasound scanner (manufactured in 2009) coupled with 3.5–5 MHz curvilinear and 7.5 MHz linear transducers. For inborn neonates, serial scans were performed as follows; within 24 h of postnatal life, between 24 and 72 h, within 4–7 days of life, and between 8 and 14 days of postnatal life. The outborn neonates who presented after 24 h of life had the remaining scans appropriate for their age based on the study protocol. Each preterm neonate had at least one cranial ultrasound scan. All the neonates had cranial ultrasound scan in both coronal and sagittal sections. The anterior fontanel which is the widest and least variable acoustic window was used.
The findings were classified as either “Normal” or “IVH.” If there was IVH, then it was graded according to Papille et al. into Grade 1: subependymal hemorrhage; Grade II: IVH without ventricular dilatation; Grade III: IVH with ventricular dilatation; Grade IV: IVH with parenchymal extension.
The neonates who had IVH were treated based on the existing protocol of the unit. For the purpose of this study, each baby was followed up till they were discharged or died. Those who had or required specific interventions such as blood transfusion, intubation, or respiratory support (continuous positive airway pressure (CPAP)) were noted or resuscitated before they had the cranial ultrasound scan.
Statistical analysis was conducted using the statistical software package SPSS V.16.0 (Chicago, IL, USA) and the results were presented in figures and tables as appropriate. Quantitative variables were summarized using means and standard deviations, whereas qualitative variables were summarized using frequencies and percentages. Proportions were compared using Chi-squared test and Fisher's exact probability test was used where figures were small. The level of significance was set at P < 0.05. The factors associated with IVH were classified into: neonatal, maternal, and clinical course. These factors were compared between groups with IVH and those without IVH. Those variables that achieved significance in univariate analysis were subsequently entered into multivariate logistic regression analysis to determine the predictors of IVH. The odds ratio (OR) was determined with 95% confidence interval (CI). Many different multivariate logistic regression analysis models were developed using various combinations of these variables based on the consideration of multicollinearity, cofounders, and model stability (based on the number of subjects per cell) until the final model was selected. The OR was determined with 95% CI.
| Results|| |
Ninety-nine preterm neonates with a mean gestational age of 32 (±2 SD) weeks were studied. The mean birthweight of the inborn neonates was 1473 (±422 SD) grams. There were 41 (41.4%) males and 58 (58.6%) females with male to female ratio of 1:1.4. Fifty-five (55.6%) preterm neonates were delivered in the hospital, while 44 (44.4%) were outborn neonates. Seventy-nine (79.8%) neonates presented in the first 24 h of postnatal life, 13 (13.1%) presented between 24 and 72 h, while 7 neonates presented between 4 and 7 days of postnatal life. The majority of neonates were of Hausa-Fulani ethnicity and a little over half of them 51 (51.5%) had parents from lower socioeconomic class [Table 1].
|Table 1: The neonatal risk factors associated with IVH among the studied neonates|
Click here to view
The overall prevalence of IVH was 16.2% (16/99). IVH was detected in 12 (33.3%) neonates between 28 and 31 weeks gestation, while 4 (6.3%) cases were seen among neonates between 32 and 36 weeks of gestation. Five cases of IVH (31.3%) were observed within 24 h of postnatal life, 9 (56.2%) were detected in neonates between 48 and 72 h, while 2 (12.5%) cases were observed between 4 and 7 days of postnatal life.
In univariate analysis, the factors associated with IVH were: place of birth, social class, gestational age, Apgar scores in the first and fifth minute of life, need for respiratory support and blood transfusion [Table 1], [Table 2], [Table 3]. For the multivariate logistic regression analysis, the two Apgar scores were not included because some categories of them had cells with small numbers giving rise to very unstable results and affecting the precision of parameter estimates for most covariates in the model. Therefore, at the multivariate logistic regression model, the lower gestational age (OR: 10.9, 95% CI: 1.95–61.04) and respiratory support (CPAP) (OR: 52.24; CI: 3.40–721.84) were retained as significant predictors of IVH. The early preterm neonates between 28 and 31 weeks of gestation were 11 times at risk for developing IVH [Table 4].
|Table 2: The prenatal risk factors associated with IVH among the studied neonates|
Click here to view
|Table 3: The clinical features/course associated with IVH among the studied neonat|
Click here to view
| Discussion|| |
We have investigated the associated factors for IVH among preterm neonates. The result of this study may also be applied to other settings with high neonatal mortality contributed majorly by prematurity.,
There was an inverse relationship between the gestational age and IVH in this study. This is in agreement with the works of Sandler et al. and Kadri et al., but is in contrast to the observations by Ajayi and Nzeh  who did not report any association between the gestational age of the neonates and IVH. The findings of this study can be explained by the relative immaturity of the early preterm neonates and the consequent fragility of their periventricular blood vessels within the germinal matrix., These tiny blood vessels lack vascular support and are prone to rupture., The lack of association between the gestational age and IVH in the Ilorin study may be because of biases inherent in the natural selection process.
A low Apgar Score of ≤3 in 1 and 5 min was found to be significantly associated with an abnormal scan in this study. This is in accord with the work of Koksal et al. who reported a similar finding. Kpodapanahandeh et al. also observed that the prevalence of IVH in very low birthweight neonates was highly associated with a low 5 min Apgar score at birth. The infants with lower Apgar scores were more subjected to an increased number of interventions such as positive pressure ventilation, endotracheal intubation, and chest compression that possibly resulted in wide fluctuation in cerebral pressure increasing their risk for IVH.
This study found interventions used in neonatal care, such as the need for CPAP and blood transfusion, to be significantly associated with IVH. This finding is also supported by the work of other authors. These interventions influence a change in cerebral circulation and cerebral venous pressure resulting in IVH. Rapid volume expansion with blood products results in rapid increase in cerebral blood flow and this can cause injury to the fragile germinal matrix blood vessels.
IVH was more prevalent in the outborn infants in this study. This agrees with the findings of Koksal et al. The delivery of a preterm neonate in a center specialized in high risk deliveries results in a decrease in IVH as better monitoring, manpower, and skill are ensured. The majority of the preterm neonates in this study were from the lower socioeconomic background and this is similar to the reports of Shankaran et al. Poverty and illiteracy are associated with poor maternal nutrition and anemia which are known risk factors for preterm delivery. They are also major factors that affect the health seeking behavior of individuals.
We did not find any association between the birthweight of neonates and IVH. This result remained so even after including 24 outborn neonates who presented within the first 24 h of life, based on the recommendations of Noel-Weiss et al. This observation may be related to the few numbers of neonates with very low birthweight. In addition, the gestational age is a better index of maturity of a neonate than the birthweight. There was no significant association between the development of IVH and the birthweights for gestational age class, gender of neonate, maternal PROM, need for intubation, chest compression or positive pressure ventilation, and IVH. This study did not confirm the protective role of antenatal corticosteroids and maternal tocolysis (MgSO4) as reported by Adegoke et al. and Khodapanahandeh et al., respectively. This finding could be ascribed to the low rate of deliveries with antenatal steroids and maternal tocolysis. The presence of seizures and pallor were significantly associated with IVH and this is similar to the findings by Kadri et al. The significant predictors for IVH were the lower gestational age and respiratory support (CPAP).
| Conclusion|| |
A lower gestational age and respiratory support (CPAP) are significant predictors for IVH. Prevention of preterm delivery and improvement in interventions of neonatal care (CPAP) are necessary to prevent the risk for IVH especially in the early preterm neonates.
Limitations of the study
The inability to assess other objective measures of asphyxia such as hypoxia, acidosis, and hypercapnia was because of the unavailability of arterial blood gas as well as microanalysis for bleeding disorders. The birthweight and Apgar scores of some outborn neonates could not be obtained. We also acknowledge that reverse causation, being a potential limitation for cross-sectional studies, could have also been a limitation in this study.
The authors' sincere appreciation goes to entire staff of the SCBU for their support and cooperation throughout the study.
Financial support and sponsorship
Conflict of interest
There are no conflicts of interest.
| References|| |
Lee JY, Kim HS, Jung E, Kim ES, Shim GH, Lee HJ. Risk factors for periventricular-intraventricular haemorrhage in premature infants. Korean Med J Sci 2010;25:418-24.
Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Reqvejo JH, et al
. The worldwide incidence of preterm birth; A systematic review of maternal mortality and morbidity. Bull World Health Organ 2010;88:31-8.
Iyoke CA, Lawani OL, Ezugwu EC, Ilechukwu G, Nkwo PO, Mba SG, et al
. Prevalence and perinatal mortality associated with preterm births in a tertiary medical centre in South East Nigeria. Int J Women Health 2014;6:881-8.
Sandler DL, Cooper PA, Bolton KD, Bental RY, Simchowitz ID. Periventricular- intraventricular haemorrhage in low-birth-weight infants in Baragwanath hospital. S Afr Med J 1994;84:26-9.
Ajayi O, Nzeh DA. Intraventricular haemorrhage and periventricular leukomalacia in Nigerian infants of very low birth weight. West Afr J Med 2003;22:164-6.
Koksal N, Baytan B, Bayran Y, Nacarkucuk E. Risk factors for intraventricular haemorrhage in very low birth weight infants. Indian J Paediatr 2002;69:561-4.
Adegoke SA, Olugbemiga AO, Bankole KP, Tinuade OA. Intraventricular hemorrhage in newborns weighing <1500 g: Epidemiology and short term clinical outcome in a resource poor setting. Ann Trop Med Public Health [serial online] 2014;7:48-54.
Larroque B, Marret S, Ancel PY, Arnaud C, Marppeau L, Supernaut K, et al
. White matter damage and intraventricular haemorrhage in very preterm infants: The EPIPAGE study. J Paediatr 2003;143:477-8.
Boo NY, Ong LC, Lye MS, Wong KP, Mastura MM. Periventricular haemorrhage in very low birth weight Malaysian neonates. J Trop Paediatr 1993;39:224-8.
Linder N, Haskin O, Levit O, Klinger G. Risk factors for intraventricular haemorrhage in very low birth weight premature infants: A retrospective case control study. Paediatrics 2003;111:590-5.
Guzzetta F, Shackelford GD, Volpe S, Perlman JM, Volpe JJ. Periventricular intraparenchymal echodensities in the premature newborn: Critical determinant of neurologic outcome. Paediatrics 1986;78:995-1006.
Mancini Mc, Barbosa NE, Banwart D, Silveira S, Guerpelli JL, Leone CR. Intraventricular hemorrhage in very low birthweight infants: Associated risk factors and outcome in the neonatal period. Rev Hosp Clin Fac Med Sao Paulo 1999;54:151-4.
Kadri H, Mawla AA, Kazah J. The incidence, timing and predisposing factors of germinal matrix and intraventricular haemorrhage (GMH/IVH) in preterm neonates. Childs Nerv Syst 2006;22:1086-90.
Whitelaw A. Core Concepts: Intraventricular haemorrhage. Neoreviews 2011;12:94-101.
Judy S, Dietch R. Periventricular intraventricular haemorrhage. Neonatal Netw 1993;12:7-16.
Ballabh P. Intraventricular haemorrhage in premature infants: Mechanism of disease. Pediatr Res 2010;67:1-8.
Osborn DA, Evans N, Kluckow M. Hemodynamic and antecedent risk factors for early and late periventricular/intraventricular hemorrhage in premature infants. Pediatrics 2003;112:33-9.
Vural M, Yilmaz I, IIikan B, Erginoz E, Perk Y. Intraventricular hemorrhage in preterm newborn: Risk factors and results from a University Hospital in Instanbul, 8 years after. Pediatr 2007;49:341-4.
Adefuloju A, Yusuf A, John I, Soyebi K, Fajolu I. Association between germinal matrix haemorrhage and perinatal risk factors in preterm neonates in a Southwestern Nigerian Hospital. JAMMR 2018;25:1-11.
Adekunle A, Kofoworola S, Ireti F. Ultrasonographic pattern of intraventricular haemorrhage in preterm neonates in Lagos. West Afr J Ultrasound 2016;17:10-7.
Omole-Ohonsi A, Attah RA. Risk factors for preterm deliveries at Aminu Kano Teaching Hospital, Kano, Nigeria. SAJMS 2012;1:3-10.
Adewuyi EO, Auta A, Khanal V, Bamidele OD, Akuoko CP, Adefemi K, et al
. Prevalence and factors associated with underutilization of antenatal care services in Nigeria: A comparative study of rural and urban residences based on 2013 Nigeria Demographic and Health Survey. Available from: http://doi.org?10.1371/journal.pone. 0197324
. [Last accessed on 2018 Aug 15].
Ononokpono DN, Odimegwu CO. Determinants of maternal health utilization in Nigeria: Multilevel approach. Pan Afr Med J 2014;17(Suppl 1):2.
Muktar-Yola M, Iliyasu Z. A review of neonatal mortality in Aminu Kano Teaching Hospital, Northern Nigeria. Trop Doct 2007;37:130-2.
Oyedeji CO. Sample size estimation. In: Oyedeji CO, editor. Health Research Methods for Developing Country Scientist. Ibadan: Codat Publication; 1992. p. 59-63.
Olusanya O, Okpere EE, Ezimokhai M. The importance of social class in voluntary fertility control in a developing country. W Afr Med J. 1985;4:205-11.
Guha DK. Basic perinatal-neonatal nomenclature. In: Saili A, Bhat S, Shenoi A, editors. Guha Neonatology- Principles and Practice. 3rd
ed. New Delhi: Jaypee Brothers Ltd; 2005. p. 54.
Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL, Lipp R. New Ballards score, expanded to include extremely premature infants. J Pediatr 1991;119:417-23.
Sasidharan K, Dutta S, Narang A. Validity of new ballards score until 7th
day of post-natal life in moderately preterm neonates. Arch Dis Child Fetal Neonatal Ed2009;94:F39-44.
Battaglia FC, Lubchenco LO. A practical classification of newborn infants by weight and gestational age. J Pediatr 1967;71:159-63.
Papille LA, Burnstein J, Burnstein R, Koffler H. Incidence and evolution of subependymal and intraventricular haemorrhage: A study of infants with birth weights less than 1500 grams. J Paediatr 1978;92:529-34.
Lawn JE, Cousen S, Zupan J. Lancet neonatal survival steering team, 4 million neonatal deaths: When? Where? Why? Lancet 2005;365:891-900.
Khodapanahandeh F, Khosravi N, Larijani T. Risk factors for intraventricular haemorrhage in very low birth weight infants. Iran J Pediatr 2007;17:101-7.
Shankaran S, Lin A, Maller-Kasselman J, Zhang H, O'Shea TM, Bada HS, et al
. Maternal race, demography and healthcare disparities impact risk for intraventricular haemorrhage in preterm neonates. J. Pediatr 2014;165:1005-11.
Noel-Weiss J, Woodend AK, Peterson WE, Gibb W, Groll DL. An observational study of the associations among maternal fluids during parturition, neonatal output, and breastfed newborn weight loss. Int Breastfeed J 2011;6:9.
Kim KR, Jung SW, Kim DW. Risk factors associated with germinal matrix intraventricular haemorrhage in preterm neonates. J Korean Neurosurg Soc 2014;56:334-7.
[Table 1], [Table 2], [Table 3], [Table 4]