This is one of the first studies of IVH in LBW neonates in a LIC in sub-Saharan Africa and the first in east Africa. We found that more than a third of neonates born weighing ≤2000g had any IVH and 15% had high grade IVH. The majority of IVH had occurred by day 7. Vaginal delivery, GA <32 weeks, resuscitation in the NNU and being SGA (<10th centile) increased the odds of having an IVH.
Incidence and severity and timing of IVH
Our findings show a higher prevalence of IVH amongst low birthweight neonates than in some of the few studies available from LICs in sub-Saharan Africa, although the numbers are comparable to one higher quality study from Zambia. This prospective study of neonates in Zambia weighing <1500g found an IVH prevalence of 34.2% comparable to our finding of 38.7% in the same group(10). In this study, neonates were only scanned up to day 7 however, and this study showed 9.8% of IVH occurred after day 7, which may explain the small difference in overall prevalence between the two studies. In contrast, two studies from Nigeria found lower rates of IVH than this study. One looked prospectively at 87 neonates weighing <1500g and found a 24.1% prevalence of IVH(9). This lower rate may be because each infant was only scanned once within the first week (range 60 hours to 7 days), therefore it is likely that some IVH will have occurred after the single scan, thus lowering the apparent prevalence. The second Nigerian study examined 93 neonates weighing <1500g and found 29.7% had IVH, 7.5% of which were high grade(11). This is likely to be an underestimation for multiple reasons including that 73 of 196 eligible neonates were not scanned as they died within 72 hours of birth which may have resulted in many IVHs being missed. No studies in LICs in sub-Saharan Africa have examined IVH in neonates weighing 1500-2000g. This data showing that in this subgroup, almost one in three have IVH and one in 10 have high grade IVH, are therefore the first in this area.
On analysis by gestation, in neonates of 28-31 weeks GA we found rates of IVH of 31.6%, comparable with findings from another Nigerian study of 33.3%(12). However, in the 32-42 week GA group we found much higher rates (34.2%) than in their 32-36 week group (6.3%). Of note, this study had much lower rates of SGA neonates than ours (21.8% vs 42.5%) which may contribute to this difference, although the relationship of SGA with IVH varies between studies(24,25). Additionally, this study took place in a tertiary teaching hospital and although the resource availability is unclear, endotracheal intubation is mentioned which is suggestive of a higher resource environment than that in which our study was undertaken.
Overall and in all subgroups of weight and gestation for any IVH and high grade IVH, our rates of IVH are higher than those reported in HICs. The difference is smallest in the <1500g and <28 week gestation groups and largest in babies weighing >1500g or >37 weeks, suggesting in our setting it could be the higher weight and later gestation babies that could benefit most from modification of risk factors(13–16,26).
Our results show that 34% of all IVH had occurred on day 1, 58.5% by day 3 and 90.2% by day 7. In the Zambian study, 68.7% of IVH had occurred by 72 hours of age, however as they only scanned up to day 7 this may be an overestimation of the total proportion(10). Evidence from HICs shows that approximately 50% of IVHs occur in the first 24 hours after birth and almost all by 72 hours(27). Our data suggests that IVH in our setting happens later than in HICs, but with almost all occurring by day 7. This could be due to different aetiologies for IVH in our settings, with more influence from postnatal risk factors due to the availability of neonatal care.
Risk factors
Our results show that neonates with GA of <32 weeks had increased odds of having both mild and severe IVH, in keeping with other studies from HICs and LICs(9,10,12,13,18,28). Birthweight was not shown to be associated with IVH, which is contrary to most findings from HICs but in keeping with some studies in Africa(5,11,12,17). This lack of association of weight with IVH is likely due to the high prevalence of SGA neonates (42.5%) giving a higher GA than expected for birthweight, thus comparatively reducing risk of IVH.
Vaginal delivery was associated with increased odds of having any IVH when compared with Caesarean delivery. It was not shown to be associated with low grade IVH, however the sample was too small to determine the relationship with high grade IVH when adjusted for GA, sex and weight. Whilst vaginal delivery is a recognised risk factor for high grade IVH in HICs, this finding has not been replicated in studies from LICs in sub-Saharan Africa(9,10,12,29,30). This may be related to the timing and indication for Caesarean differing.
Resuscitation in the NNU was associated with an increased probability of any IVH and high grade IVH. The need for resuscitation at birth is a known risk factor for IVH however this was not demonstrated in our results(31). This is likely in part due to poor documentation of perinatal resuscitation events and limited accessibility to adequate neonatal resuscitation. We found that the prevalence of cerebellar haemorrhage (1.7%) and cPVL (2.4%) were comparable with expected rates from HICs; there are no comparable data currently available from LICs in Africa(32).
We found that SGA neonates had increased odds of having low grade IVH. The few comparable studies in LICs in sub-Sharan Africa found no association with SGA and IVH, and in HICs the relationship of SGA with IVH varies between studies(11,12,24,25). Our study had both a larger sample size and much higher rates of SGA than other African studies which may explain why we identified an association where they did not(11,12). Additionally, it is recognised that low grade IVH can be difficult to detect using cUS, so it is possible that some low grade IVHs were not identified in these studies(33). Many known risk factors for SGA are present in our population, including maternal malnutrition, infections and PET and their prevalence and relationship with IVH in this setting is an area of future interest(34).
Whilst no relationship between exposure to 1 or 2 doses of antenatal steroids and IVH was shown, of the 6 neonates who received 2 doses of antenatal steroids, none had IVH. These findings were not statistically significant, potentially due to the small sample size. Antenatal corticosteroids are protective against IVH in HICs, however current evidence suggests that in LICs antenatal steroids can increase the risk of neonatal death(14,35,36). Although it is possible that the low rates of steroid exposure in our study (only 47%) may have contributed to the high rates of IVH, further data on the impact of antenatal steroids on IVH and other preterm complications are needed; use of antenatal steroids in this setting remains controversial and needs further exploration.
We did not find IVH to be an independent predictor of survival. There is little evidence on survival after IVH in LICs, but in this cohort there was a much lower mortality in neonates with IVH than in Nigerian neonates with IVH weighing <1500g (41.7% vs 66.7%)(9). This is likely due to the relatively high standard of care at our centre, resulting in decreased preterm mortality, following implementation of a two-tiered hospital-based neonatal care package and bCPAP(19).
Outcomes at 28 days
Strengths and limitations
Strengths of this study included that the cUS were performed by well-trained investigators and that the image analysis was undertaken prospectively and independently by 2 blinded, experienced, senior clinicians. Outcomes are known for a high proportion of participants (115/120, 95.8%) and 71/81 (87.7%) babies alive at day 28 underwent a day 28 cUS.
Limitations include that reliable capture of obstetric and perinatal data including resuscitation at birth was challenging due to inconsistent documentation, patients being transferred from other facilities without documentation and home deliveries. Additionally, 26 neonates died very early, before recruitment. These may have been the most premature and unwell and have had IVH contributing to their early death and therefore the occurrence of IVH, particularly severe IVH may be underestimated. This could also cause an underestimation in the mortality associated with IVH. Furthermore, 10/81 surviving neonates (12.3%) were unable to attend for day 28 scans so it is possible that some findings such as cPVL were underestimated. Assessing potential risk factors for IVH was a secondary analysis and therefore the sample size may have been too small to determine relationships for some risk factors. Additionally, clinical data was collected retrospectively from the medical notes.