The prevalence of intraventricular hemorrhage and its related risk factors among preterm neonates

Introduction

Regardless of gestational age, low birth weight infants are born weighing less than 2.5 kg, and preterm infants are born at less than 37 weeks gestational age. For newborns and children under five, preterm birth is the primary cause of mortality and morbidity.¹ The survival rate of preterm infants has increased dramatically in the last 20 years due to advancements in neonatal perinatal services. This progress is a result of increased prenatal steroid use, surfactant therapy, better respiratory and nutritional management, and other advancements in prenatal, perinatal, and neonatal care.² The high morbidities of these preterm infants, which are linked to a higher incidence of adverse neurodevelopmental outcomes, continue to be a serious concern despite this improvement. Intraventricular hemorrhage (IVH) is one of the main morbidities that seriously impairs mental retardation, cerebral palsy, and immediate mortality.²

In preterm infants, the overall incidence of IVH is approximately 36%, and the incidence rises with decreasing gestational age and birth weight.^3,4 It affects roughly 52% of preterm infants born at less than 28 weeks’ gestation and 45% of extremely preterm infants weighing less than 750 g at birth.^4,5 Ninety percent of IVH cases happen within three days of birth, and fifty percent happen within one day following birth.^4,6 The Papile system divides IVH into four grades, which is helpful in assessing the phenomenon and predicting the outcome during the neonatal period as well as during the follow-up period.⁷ The following are known risk factors for IVH: birth weight, asphyxia, hypoxia, infection, coagulation dysfunction, twins, intrauterine infection, mechanical ventilation, respiratory distress syndrome requiring surfactant treatment, placenta abnormalities such as placenta abruption.⁸ The overall mortality risk was comparable for infants with (4–7%) and without (10%) IVH of grade one, and it was significantly higher for infants with higher IVH values, specifically 8–10% for grade two, 18% for grade three, and approximately 40% for grade four.^9,10

The survival rate of extremely preterm infants has increased due to advancements in neonatal intensive care, which has consequently increased the number of infants at high risk of developing IVH.¹¹ In order to determine the prevalence, related risk factors, and short-term consequences of intraventricular hemorrhage (IVH) among preterm neonates at King Fahd University Hospital in Khobar, Saudi Arabia, this study was conducted.

Methods

Results

This study reviewed two hundred and one preterm infants. As described in ( Table 1), 50.7% were males. Regarding maternal characteristics, 51.2% had a gestational age of 29 weeks or less. The most common method of delivery was caesarean (63.2%). Half of the mothers had a maternal age of over 30 years. Birth patterns were mostly singleton (77.6%).

( Table 2) shows the medical characteristics of the comorbidities of the patients. About 87.1% were diagnosed with septicemia, and 14.9% had NEC. The incidence of IVH was 41.8%, with grade 1 being the most common reported (41.7%). BPD, CHD, hydrocephalus, RDS, seizure, PRBC, IUGR, jaundice, and PROM were seen in 16.9%, 38.3%, 3.5%, 88.1%, 6.5%, 48.3%, 14.9%, 62.7%, and 15.4%, respectively. ROP was 37.3%, with stage 1 being the most frequent (45.3%). DM, PIH, pre-eclampsia, hypothyroidism, IVF, chorioamnionitis, consanguinity, UTI, pneumothorax, pulmonary hemorrhage, and pulmonary hypertension were seen in 9.5%, 11.4%, 12.9%, 2%, 14.4%, 3%, 49.8%, 33.3%, 3%, 4.5%, and 6.5%, respectively. Regarding patient treatment and management, nearly all (95.5%) received antenatal steroids, while 7% received steroids during the postnatal period (7%). Surfactants were administered to 60.7% of the patients of them, 41.8% received a single dose. In addition, nearly half (44.3%) used oxygen for more than 28 days.

In ( Table 3) the incidence of IVH was significantly more common among patients with a birth weight of 1200 g or less (p=0.001), those who were born by NVD method (p=0.007), increasing duration of oxygen used (p<0.001), septicemia (p=0.003), CHD (p<0.001), RDS (p=0.002), seizure (p=0.008), PRBC (p<0.001), jaundice (p<0.001), ROP (p<0.001), and consanguinity (p<0.001).

A multivariate regression analysis was subsequently performed in ( Table 4) to determine the significant independent predictors of IVH. Based on the results, it was found that patients with CHD were predicted to increase the risk of having IVH by at least 4.27 times higher (AOR=4.272; 95% CI=1.987 – 9.183; p<0.001). Patients with seizures were at increased risk of having IVH by almost 5.5 times higher (AOR=5.496; 95% CI=1.208 – 24.996; p=0.027). Also, patients who had ROP were at increased risk of having IVH by at least 3.2-fold higher (AOR=3.158; 95% CI = 1.057 – 9.349; p=0.039). No significant effects were observed between the incidence of IVH in relation to birth weight, mode of delivery, O2 duration, follow-up, surfactant used, septicemia, RDS, PRBC, jaundice, and consanguinity after adjustment to a regression model (p>0.05).

Discussion

This study explores the incidence of IVH among preterm infants born between 01 January 2016 and 01 January 2023 at King Fahad Hospital of The University, Khobar, Saudi Arabia. The results showed that among the 207 preterm infants collected, 84 of them had IVH, and the overall incidence was 41.8%. IVH grade mainly was mild (grade 1 + grade 2: 76.2%), and only 20.3% were classified as severe (grade 3 + grade 4). This is strikingly similar to that of Maduray et al. (2019).¹² Study documented an IVH prevalence of 67% and 44.3% detected among VLBW and LBW infants. Consistent with these reports, Sisenda et al. (2022)¹³ indicated that the one-year prevalence of IVH among preterm neonates was 33.8%, mainly mild (67.6%) followed by severe (32.4%). According to the systematic review of Siffel et al. (2021),¹⁴ the worldwide incidence of IVH grade 3/4 ranges between 5% and 52%. Considering population-based studies, the rate of IVH grade 3/4 was between 6% and 22%. Lower IVH grades, however, were rarely documented, but they evolved between 5% and 19%.

Based on our univariate analysis, low birth weight is a predictor of IVH among preterm infants; however, this did not remain significant in a multivariate regression model (p=0.972). Further, we found a higher prevalence of IVH among those who were born through NVD, have over 28 days of O2 use, those who have required follow-ups, and those with septicemia, NEC, RDS, PRBC, jaundice, PROM, and consanguinity. However, we did not find an association between IVH in terms of gender, maternal age, multiple births, birth patterns, and gestational age (p>0.05). This contradicted the reports of a study done in South Africa, suggesting that birth weight and gestational were significantly associated with IVH.¹³ In Nigeria, lower gestational age (<32 weeks gestation), low Apgar scores, need for respiratory support, lower social class, outborn status of neonates, and blood transfusion were recognized as predictors of IVH.¹⁵ Consistent with these reports, a study published in Canada also recognized weight and small birth gestation as risk factors for IVH. Other important predictors identified in the study were insufficiency of antenatal corticosteroids, chorioamnionitis, Apgar score, RDS, prolonged intubation, early-onset sepsis, hypercapnia, pCO2 fluctuations, inhaled nitric oxide, inotropes or normal saline boluses, bicarbonate/THAM therapy opioids infusions, and metabolic derangements.¹⁶

In our multivariate regression estimates, only CHD, seizure, and ROP remained significant and were determined to be the independent risk factors for IVH. In Portugal, multivariate regression estimates that the significant risk factors for Germinal Matrix Hemorrhage (GMH)-IVH include resuscitation exposure in the delivery room, visual impairment, and gross motor and locomotor dysfunction.¹⁷ In Poland, multivariate analysis suggested that the more risk factors present, the greater the risk of severe IVH degrees, particularly in children born before 32 weeks of gestation and without AST and born with asphyxia and hypotension and with acidosis. In addition, grade 3 and 4 IVH were linked to increased mortality in preterm infants.^12,13,18

IVH, particularly those severe ones, is a serious condition that develops between the perinatal and postnatal periods. Identifying the occurrence of IVH is a criterion for its antecedents and then applying preventive actions.¹⁹ In our study, antennal steroids were the most prominent treatment being administered to patients. However, steroid use was not identified as a predictive factor for IVH (p=0.122). This did not coincide with the study done in Kenya,¹³ suggesting that the use of antennal steroids was associated with decreasing IVH risk. A previous study done in Poland supported these reports.²⁰ Incomplete or no antenatal steroid therapy could lead to the progression of IVH. Hence, steroid therapy should be considered to be given to women at risk of premature delivery. The implication of IVH magnifies the need to conduct a regional periodical analysis concerning its incidence, causes, and impacts to enhance local treatment outcomes by recognizing courses of action.²⁰

Conclusion

There was a high incidence of IVH among preterm infants during the last 7 years. Patients with CHD, seizure, and ROP were the most susceptible to IVH as compared to other preterm infants. Hence, continuous monitoring is vital among these groups of patients, and finding new therapeutic strategies aimed at reducing the serious consequences of IVH is warranted. The factors identified in this study can be considered clinically relevant and subjected to further investigation. Screening and early detection of brain injury among high-risk neonates are crucial to facilitate necessary treatment and management associated with adverse chronic neurodevelopmental outcomes.

Ethics and consent

This research project was approved by institutional review board of King Fahd Hospital of the University (May 26, 2024) [Certificate# REC-2024-NOV-ETHICS405]. Participants’ information was kept confidential and anonymous. Informed consent was not required since the study will be retrospective.

Pre-print citation

AlGhamdi M, Alnaim A, Al Ghadeer H, Aldajani A, Alabdulqader M, Alarbash A, Alkhamis A, AlBassam L, AlQahtani F, Abdulghani D, Al Noaim K, Alahmari A, Alhejji M, Alamer E, Aldandan H. The Prevalence Of Intraventricular Hemorrhage And Its Related Risk Factors Among Preterm Neonates. Figshare [Preprint]. 2025 [cited 2025 MAY 6]. Available from: https://doi.org/10.6084/m9.figshare.28731242.