Recruitment
The study was conducted between February 2018 and May 2019. Recruitment was stopped
when desired sample size was achieved.
During the period of study, a total of 150 pregnant women were randomized for the study. Out of these women, 5 women carried their pregnancies to term, 4 withdrew consent, 2 were discharged home and subsequently lost to follow up and 1 had intrauterine fetal death. The remaining 138 pregnant women were included in the study. Among these women, there were 6 sets of twins and a set of triplets. This gave a total number of 146 neonates in the study. Of these neonates, 48 were exposed to antenatal placebo. 49 were exposed to antenatal betamethasone and 49 were exposed to antenatal dexamethasone.
DISCUSSION
MAIN FINDINGS
The incidence of respiratory distress syndrome among late preterm neonates in the placebo group, betamethasone group and dexamethasone group were 2.1%, 0% and 2% respectively. The incidence of respiratory distress varies with race.(4) Low incidence of respiratory distress syndrome have been reported among blacks.(4) and may explain the low incidence of respiratory distress in our study coupled with the fact that compared to other categories of preterm births, its incidence is lower in late preterm neonates. There was no significant difference between the group exposed to placebo versus antenatal betamethasone (p= 0.98, RR 1.0, CI 0.09-11.55), the group exposed to placebo versus antenatal dexamethasone (p=0.98, RR=1.0, CI 0.06-16.87) and the group exposed to antenatal betamethasone versus antenatal dexamethasone (p=0.31, RR=0.5, CI 0.09-2.42). This is similar to the findings of Porto et al(10) where he reported low incidence of respiratory distress among late preterm neonates exposed to antenatal betamethasone and those exposed to placebo (1.4% and 0.8% respectively) with no significant difference in the incidence of respiratory distress between the 2 groups( p=0.54, RR 1.90). However, this is not consistent with the findings of Balci et al(11) who reported an incidence of 16% among late preterm neonates that did not receive antenatal steroids and incidence of 4% among those that received betamethasone and the difference between the two groups was statistically significant(p=0.046, OR 0.21). The fact that Balci et al(11) found a significant difference in the incidence of respiratory distress in their study may be due to the fact that they did an open label trial which may have introduced some bias unlike our study and that by Porto et al(10) which were both randomized double blinded. Though a similar double blind randomized controlled trial by Gyamfi-Bannerman et al(12) found a statistically significant higher incidence of primary outcome in the late preterm neonates in the control group, the primary outcome was a neonatal composite of treatment including the use of CPAP or high flow nasal cannula at least for 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygen, or mechanical ventilation or stillbirth or neonatal death rather than respiratory distress alone. This may account for the difference in findings.
The incidence of transient tachypnoea of the newborn was also low in this study with one neonate (2.1%) in the group exposed to placebo developing the outcome (Tables 2 and 3). Our finding of low incidence in transient tachypnoea was not consistent with other reports. Gyamfi-Bannerman et al(12) reported an incidence of transient tachypnoea of the newborn among late preterm neonates exposed to antenatal betamethasone 6.7% and 9.9% in those exposed placebo (9.9%) (p=0.002, RR 0.68 CI 0.53-0.87). A higher incidence was reported by Porto et al(10) where 24% of late preterm neonates exposed to antenatal betamethasone and 22% of those exposed to placebo developed transient tachypnoea. However, there was no significant difference between the groups. The low incidence of transient tachypnoea of the newborn in our study is in keeping with the low incidence of respiratory distress syndrome noted in the study.
This study showed a statistically significant reduction in the need for neonatal resuscitation at birth among the neonates exposed to antenatal betamethasone compared to those exposed to placebo (p <0.001, RR 7.0, CI 2.49-19.46) and also the neonates exposed to antenatal dexamethasone compared to those exposed to placebo (p=0.010, RR 4.0, CI 1.86-26.03). This means that neonates born to women who received placebo were 7 times more likely to need neonatal resuscitation at birth compared to neonates born to women who received betamethasone and 4 times more likely to need resuscitation at birth compared to neonates born to women who received dexamethasone. The use of betamethasone was associated with a 40% decrease in need for resuscitation at birth compared to the use of dexamethasone though this was not statistically significant (p=0.461).
A logistic regression analysis was done to determine the relationship between the need for resuscitation at birth and the study group of the women while adjusting for 1- and 5-minutes APGAR score that was significantly higher in the betamethasone group when compared to the placebo group. The result showed that after adjusting for 1- and 5-minute APGAR score there was a significant reduction in the likelihood of need for neonatal resuscitation by about 85% (ExpB=0.157, p=0.005) when betamethasone was used compared to placebo.
Other studies have also reported decrease in the need for neonatal resuscitation at birth in women exposed to antenatal corticosteroids when compared with women exposed to placebo.(11),(12). This finding is of significance especially in our environment where many deliveries are conducted in the absence of skilled birth attendants that can adequately offer neonatal resuscitation at birth.
The need for admission into SCBU was highest among the placebo group (12.5%), followed by the betamethasone group (8.2%) and least in the dexamethasone group (4.1%). However, the differences observed were not statistically significant (Tables 2, 3 and 4).
Apnoea was not reported in any of the study or control group. This may be because continuous electronic recording of vital signs of the neonates was not done in our study and apneic episodes are short in duration. This has been observed in other studies where a lack of correlation between nurses’ records with continuous electronically recorded events have been demonstrated (13),(14). In a randomized controlled trial on the use of betamethasone for women at risk for late preterm delivery, apnoea was reported to occur in 2.3% of the group that had betamethasone and in 2.6% of the control group with no significant difference between the two groups (p=0.57).(12) Other studies on the use of antenatal corticosteroids in late preterm neonates did not report on apnoea. (10),(11)
The neonates exposed to antenatal dexamethasone had the highest incidence of hypoglycemia (14.3%), followed by those exposed to antenatal betamethasone (8.2%). The neonates exposed to placebo had the lowest incidence of hypoglycemia (4.2%). However, the differences were not statistically significant (Tables 2 ,3 and 4). Conflicting reports exist in the literature with regards to incidence of hypoglycemia in neonates following exposure to antenatal corticosteroids. While some authors(12),(15) reported increase in the rate of hypoglycemia among infants exposed to antenatal corticosteroids, others did not(6). A systematic review and meta-analysis of randomized controlled trials on the use of antenatal corticosteroids in near term and term fetuses also showed an increased risk of neonatal hypoglycemia in women who received antenatal corticosteroids at more than 34 weeks gestation.(15) However, no adverse effects were reported in all the trials. This inconsistency may be due to the fact that neonatal hypoglycemia is a common late term neonatal complication irrespective of the use of antenatal corticosteroids within the period.(16)
Incidence of neonatal and maternal sepsis were low and the differences between the groups were not statistically significant. (Tables 2, 3 and 4). This is consistent with existing literature.(12)
STRENGTHS AND LIMITATIONS
The major strength of this study is the fact that it was a double blind randomized controlled trial and both dexamethasone and betamethasone were used as antenatal corticosteroids. However, it was conducted in a single center which is a limitation.
CONCLUSION
This study found that the use of antenatal corticosteroids in late preterm delivery did not have any significant effect on incidence of respiratory distress syndrome and other neonatal morbidity but significantly reduced the need neonatal resuscitation at birth.
RECOMMENDATIONS
In view of the findings in this study we recommend the use of antenatal corticosteroids in women at risk of preterm delivery with the aim of reducing the need for neonatal resuscitation at birth.
However, there is still the need for more trials on the effect of use of antenatal corticosteroids in late preterm deliveries with the aim of preventing neonatal morbidity and minimizing side effects on both mother and neonates.
ACKNOWLEDGEMENT
We would like to acknowledge the staff of the labour ward and the special care baby unit of Ahmadu Bello University Teaching Hospital for their support during the period of the study.
DISCLOSURE OF INTEREST
The authors declare no conflict of interest. The authors do not have any financial, personal, political, intellectual or religious affiliations/relationships with any institution or organization that may have influenced the research.
CONTRIBUTION TO AUTHORSHIP
AY was involved in the concept, design, definition of intellectual content, literature search, data acquisition, data analysis, statistical analysis, manuscript preparation, manuscript editing and manuscript review. HUS and IA were involved in the definition of intellectual content, data acquisition, manuscript editing and review. BBL was involved in data analysis, statistical analysis, manuscript editing and manuscript review.
DETAILS OF ETHICAL APPROVAL
Ethical approval to conduct the study was sought from the Health Research and Ethics Committee of Ahmadu Bello University Teaching Hospital Shika. The application was reviewed by the committee and permission to conduct the study was given on 07/08/2017 with reference number ABUTHZ/HREC/Y3/2017 (NHREC/10/12/2015; D-U-N-S-No 954524802; ABUTH/HREC/CL/05/). The initial permission to conduct the study expired on 07/08/2018 before the desired sample size was achieved. Permission for extension of study period to 07/08/2018 was granted after due process.
FUNDING
Funding was received from Institution Based Research funds of the Tertiary Education Trust Fund of Nigeria. The funding is part of funding for professional development and not for commercial or other purposes.
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