INTRODUCTION:

Each year, 15million (1 in 10) neonates are born as pre-term (before completing 37 weeks of gestation)^1,2,3 globally. Pre-term birth is a risk factor in at least 50% of all neonatal deaths and is the 2^nd most common cause for death among children under the age of 5⁴. In India, out of 2.6 crore live births each year, 35 lakh babies are born pre-term and 3.03 lakh (approximately 10%) babies die due to complications (neonatal jaundice, intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), sepsis etc.) of pre-term births^5,6. Respiratory distress syndrome (RDS) is one of the most common causes of death among them^7,8. Antenatal corticosteroids (ACS) (betamethasone and dexamethasone) are used therapeutically to prevent RDS in PNs and are administered to women who are at risk of preterm delivery (24^0-7weeks to 36^1-6weeks of gestation).The World Health Organization (WHO), American College of Obstetricians and Gynecologist (ACOG), Royal College of Obstetricians and Gynecologist (RCOG) list both dexamethasone or betamethasone as an effective drug for preventing complications in pre-terms. (Using either a dosage of 24mg of dexamethasone (4 doses of 6 mg 12hours apart IM) or 24 mg of betamethasone (2 doses of 12mg 24 hours apart IM))⁹. ACS induces the production of type 1 and type 2 pneumocytes that lead to structural and biochemical changes that improve both lung mechanics and gas exchange^10-12. Intramuscular injection of both betamethasone and dexamethasone are effective in preventing RDS but some studies suggest greater risk of maternal sepsis¹³.

Even though evidence for the use of betamethasone is available in hand but there is limited information on the effectiveness of this practice in developing countries¹⁴. Hence this study aims to assess the effectiveness of single& double dose of antenatal betamethasone in PNs.

METERIALS AND METHODS:

This is six months (October 2018 to March 2019) prospective observational multi-centered study conducted at Gynecology and Obstetrics, Neonatal departments of two teaching hospitals in South India. The study was approved by the Institutional Ethics Committee (IEC/NOV/18/07) of the hospital. This study is the part of previously published article named ‘Antenatal use of corticosteroid to prevent respiratory distress syndrome in preterm babies’. Informed consents were taken from their legally representative guardian. All infants born alive between 24-36^1-6weeks of gestation were included in the study. Presences of any confirmed or suspected congenital or genetic anomaly, out born neonates, maternal data are not available were excluded in the study.

The selected newborns were classified into 3 groups:

· No dose–Neonate’s mothers, who had not been exposed to antenatal betamethasone.

· Single dose–Neonate’s mothers, who had been exposed to single dose of antenatal betamethasone. (one dose of 12 mg betamethasone)

· Double dose–Neonate’s mothers, who had been exposed to double dose of ANC. (Two doses of 12 mg betamethasone, 24 hours apart)

Statistical analysis:

Data’s were entered into Microsoft Excel 2016 datasheet and was analysed using software SPSS 20 Version. Association of betamethasone in prevention of RDS in PNs was done by Chi Square test. Independent T-test was used to compare the mean difference between two groups. In all the tests, the level of significance was set at 0.05.

RESULTS:

During the period of study, eighty-five neonates were born as pre-term. Of these, data were not available for mothers of fifteen cases (mothers’ data were missing). Among seventy neonates, 28 (40%) belonged to no dose group, 25(35.75%) in single dose group and 17(24.2%) in double dose group. The mean gestational age at administration was 32 weeks. Out of seventy neonates, neonates of 42 mothers have been exposed to antenatal betamethasone in which 23 developed RDS (49%) whereas in 28 whom had not been exposed to antenatal betamethasone, twenty-four developed RDS (83%). This difference was statistically significant (P= 0.009) (Table 1). In the study population, twenty-five were exposed to single dose of betamethasone out of which 15 (60%) developed RDS whereas 28 were not exposed and of these, twenty-four (85.71%) developed RDS. This difference was not statistically significant (P = 0.060) (Table 2(a)). Comparison of double dose with no dose of betamethasone administration was also done. Seventeen were exposed to double dose of betamethasone out of which 8 developed RDS (47.1% v/s 85.71%) which was statistically significant (P= 0.008) (Table 2(b)). Neonatal complications in preterm babies were compared among the three groups; only RDS (P=0.015) and NNHB (P=0.004) were found to be significant. (Table 3). The comparison of neonatal complications among the groups were done and found that only RDS was significant (P=0.006) (Table 4).

Table 1: Association of betamethasone in prevention of RDS in preterm babies

Corticosteroid used	RDS developed		Total	P Value
Corticosteroid used	YES	NO	Total	P Value
YES	23	19	42	0.009
NO	24	4	28	0.009
Total	47	23	70

(RDS-Respiratory Distress Syndrome)

Table 2(a): Comparison of Single dose and no dose of antenatal betamethasone.

	RDS		Total	P Value
	Yes	No	Total	P Value
Single dose	15	10	25	0.060
No steroids	24	4	28
Total	39	14	53

(RDS- Respiratory Distress Syndrome)

Table 2(b): Comparison of double dose and no dose of antenatal betamethasone.

	RDS		Total	P Value
	Yes	No	Total	P Value
Double dose	8	9	17	0.008
No dose	24	4	28	0.008
Total	32	13	45

(RDS- Respiratory Distress Syndrome)

Table 3: Evaluation of difference in neonatal complications among three groups.

Single dose (n=25)

Double dose (n=17)

No dose (n=28)

P value

RDS

Yes

0.015

NNHB

Yes

0.004

TTNB

Yes

0.153

HMD

Yes

0.572

NEC

Yes

0.825

Neonatal sepsis

Yes

0.683

(RDS- Respiratory Distress Syndrome, NNHB- Neonatal Hyperbilirubinemia, TTNB- Transient Tachyapnea of New Born, HMB- Hyaline Membrane Disease, NEC- Necrotising Enterocolitis)

Table 4: Evaluation of difference in neonatal complications among no dose and double dose betamethasone

	Doubl edose (n=42) n (%)	No dose (n=28) n (%)	P value
RDS	23 (54.76)	24 (85.71)	0.009
NNHB	14(33.3)	13 (46.4)	0.109
TTNB	5 (11.9)	3(10.7)	0.878
HMD	5(11.9)	5 (17.85)	0.486
NEC	3 (7.142)	1(3.57)	0.645
Neonatal sepsis	3 (7.142)	4 (14.28)	0.426

(RDS- Respiratory Distress Syndrome, NNHB- Neonatal Hyperbilirubinemia, TTNB- Transient Tachyapnea of New Born, HMB- Hyaline Membrane Disease, NEC- Necrotising Enterocolitis)

DISCUSSION:

During this study period, 249 neonates were born in two different hospitals. Out of these, eighty-five neonates were born as pre-term. This data is consistent with those published earlier, where the trend of pre-term births is increasing^7,9,15. Elderly primigravida, parity, multiple pregnancies, assisted reproductive technologies and scheduled caesarean deliveries are the major cause for pre-term birth^15-19. During this study period, elderly primigravida mothers were not seen and assisted reproductive technologies were not used. However, 67.14% of caesarean deliveries, 77.14% parity and 4.28% of multiple pregnancies were observed. These results indicate that all these factors are interrelated.

Evidence suggests that, betamethasone can improve the foetal lung maturity thereby preventing RDS in PNs. In this study, 42(60%) received betamethasone antenatally and NICU admission rates were found to be higher for those neonates (28, 40%) whose mothers did not receive betamethasone. The Child Health Division, Ministry of health and family welfare, Government of India, Spanish and US Association of Obstetricians and Gynecologists recommends ANC administration to those who are at the risk of pre-term delivery in order to reduce the incidence of RDS, Intra Ventricular Haemorrhage (IVH), Necrotising Enterocolitis (NEC) and/or neonatal death^20,21.

RDS is the most common complication associated with pre-term birth. Our study showed, 47(67.14%) of PNs who developed RDS, this higher incidence of RDS could be due to delayed or abnormality in the foetal lung fluid clearance. Some studies proposed that, due to low in number or inactive Na⁺transport across the alveolar epithelium may lead to abnormality in foetal lung fluid clearance. Similarly, in this study, the incidence of RDS was higher in neonates whose mothers (85.71%) did not receive betamethasone group than those who (54.7%) received betamethasone-received group (Table1)²².

Apart from RDS, other complications such as neonatal hyperbilirubinemia (NNHB 38%), NEC (5.7%), neonatal sepsis (NS 10%), transient tachypnea of new-born (TTNB 11.4%) and hyaline membrane disease (HMD 14.2%) were observed. Use of ANC in gestational women would be an effective strategy to reduce the length of stays (LOS) and utilization of resources in NICU^[23] (premature neonatal care requires expensive technology^[24]) because there is a significant difference in the need of respiratory support (oxygen therapy 52% in betamethasone exposed group and 78% in betamethasone unexposed group), fluid therapy and phototherapy (50% in exposed and 57.14% in unexposed group) among betamethasone received and not received PNs.

There are studies that do not support the effects of antenatal betamethasone in pre-term women^[25,26]. Gyamfi-Bannerman et al showed that there is no association between antenatal betamethasone exposure and a decrease in respiratory morbidity in PNs. The main limitation of their study was dose and time of drug administration which were unknown, as the effect of corticosteroids decreases with passage of time²⁷.

Most expected adverse effect of betamethasone is likely increase in the risk of perinatal infections and this could lead to immaturity of the immune systems of PNs^[28]. Our study showed less association between antenatal betamethasone administration and induction of neonatal sepsis, (7.1% in exposed group and 14.2% in unexposed group) and hence the study showed the usage of ANC did not increase the risk of infection in PNs.

CONCLUSION:

In our study, the morbidity of PNs and incidence of RDS were lower in those mothers who had been exposed to double dose (two dose of 12 mg betamethasone 24 hours apart) of betamethasone than single dose of betamethasone (one dose of 12 mg). Limitation of our study is that, we did not observe the effects of betamethasone for a longer period. If an absence of adverse effects for a long-term follow-up is confirmed, antenatal betamethasone can be used safely to prevent RDS in PNs. Safe and Effective use of betamethasone could reduce the morbidity, LOS, socio economic burden, mortality and may help in better utilization of resources.

ACKNOWLEDGEMENT:

We would like to thank PK Das Institute of Medical Science and Valluvanad Hospital for allowing us to do this work in the respective departments.

REFERENCE:

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Received on 05.03.2021 Modified on 12.05.2021

Research J. Pharm.and Tech 2022; 15(4):1533-1536.

DOI: 10.52711/0974-360X.2022.00255

Even though evidence for the use of betamethasone is available in hand but there is limited information on the effectiveness of this practice in developing countries14. Hence this study aims to assess the effectiveness of single& double dose of antenatal betamethasone in PNs.

METERIALS AND METHODS:

RESULTS:

Table 1: Association of betamethasone in prevention of RDS in preterm babies

Corticosteroid used

RDS developed

Total

P Value

YES

NO

YES

23

19

42

0.009

NO

24

4

28

Total

47

23

70

(RDS-Respiratory Distress Syndrome)

Table 2(a): Comparison of Single dose and no dose of antenatal betamethasone.

(RDS- Respiratory Distress Syndrome)

Table 2(b): Comparison of double dose and no dose of antenatal betamethasone.

(RDS- Respiratory Distress Syndrome)

(RDS- Respiratory Distress Syndrome, NNHB- Neonatal Hyperbilirubinemia, TTNB- Transient Tachyapnea of New Born, HMB- Hyaline Membrane Disease, NEC- Necrotising Enterocolitis)

(RDS- Respiratory Distress Syndrome, NNHB- Neonatal Hyperbilirubinemia, TTNB- Transient Tachyapnea of New Born, HMB- Hyaline Membrane Disease, NEC- Necrotising Enterocolitis)

CONCLUSION:

ACKNOWLEDGEMENT:

Even though evidence for the use of betamethasone is available in hand but there is limited information on the effectiveness of this practice in developing countries¹⁴. Hence this study aims to assess the effectiveness of single& double dose of antenatal betamethasone in PNs.