Utilization of Antenatal Corticosteroids on premature babies of 27-34 weeks of gestational age born at ***** during 2003-2004

Introduction
ANS is a corticosteroid treatment given intramuscular to the pregnant mother at risk of premature delivery.

This corticosteroid will cross blood placental barrier and act upon premature lungs of fetus and help enhancing its maturity.

 Premature newborns of 27-34 weeks gestation are at high risk of developing respiratory distress syndrome (RDS) due to lack of surfactant in their premature lung also called Hyaline membrane disease. (HMD)

 Surfactant is a natural substance produced by pneumocytes II In the lungs.

It is a heterogenous mixture of lipids and proteins. Dipamitoyl phosphatidyl choline is the main component of the surfactant.

It spreads in the lung tissue- air interface preventing alveolar collapse during expiration, to open easily at next inspiration.

 Hyaline Membrane Distress (HMD) occurs due to inadequate production of pulmonary surfactant in premature lung and is seen if labour occurs before 32-34 weeks of pregnancy.

The alveolar wall collapses during expiration and each inspiration will require considerable effort.

This situation rapidly leads to fatigue, decreased respiratory effort, Hypoxia, cynosis, acidosis and eventually death, if not corrected by immediate treatment.

 The steroids given IM to mothers passes across blood placental barrier and act upon the pneumocytes type II of lung, inducing production of surfactant and these help in preventing the HMD.

Steroids used are usually Betamethasone or Dexamethasone.

 Antenatal Corticosteroid apart from reducing RDS (HMD) also reduce intraventricular hemorrhage and neonatal mortality.

Indication of Antenatal corticosteroid:

1. Indicated to all women pregnant of 24 to 34 weeks at risk of premature delivery within 7 days followed.

2. The women of 34-36 weeks can also be given ANS in certain critical condition e.g. elective c.s for these clinical cases in 7 days following the ANC , e.g. gestational Diabetes mellitus, PIH, Placenta praevia

Contra indication of Antenatal corticosteroid :

woman suffering from systemic infection including T.B Caution is advised if suspected chorioamnionitis is diagnosed.

Dosage & Route of administration:

Treatment of choice: 2 doses of Betamethasone 12mg given IM 24 hrs apart. 2nd line of treatment: -4 doses of dexamethasone 6mg given IM 12 hrs apart -2 doses of 12 mg given IM 12 to 24 hrs apart.

 Betamethasone is not available in public service in M********. Most extensively used regimen used in M*********: 2 doses of Dexamethasone 12mg IM 12 to 24 hrs apart Most recently some doctors are using single dose of ANS in view of side effect of ANS.

The optimacy of treatment:

The optimal treatment- delivery interval for administration of ANS is more than 24 hrs but fewer than 7 days after start of treatment.

History of ANS Therapy

Benefits are well known since 1972. Liggins and Howic were the first who described the benefit of ANS in 1972. Controlled trial of Betamethasone therapy was carried out in 282 mothers with threatened premature delivery before 37 weeks. There was no death with HMD or IVH in infants of mother who had received Betamethasone at least 24 hrs before delivery.

Justification for study on ANS

Mortality Rate : Infantile Mortality rate per 1000 live births Perinatal per 1000 total births Early neonatal per 1000 live births Late neonatal pour 1000 live births 1973 1998 2001 2004

63.3 56.5 22.8 7

19.4 23.5 12 2.5

13.9 19.9 7.7 2.5

14.0 16.5 7.5 2.8

In M*********, in years 70s after independence day, IMR was very high due to very high neonatal and perinatal rates.

After the integration of MCH (Maternal & Child Health) programme, antenatal service improved at primary health centre ** and became easily accessible to all & hence mortality rates started decreasing.

Comparison between African countries in 2000

African Countries Perinatal Mortality Rates 217 81 33 22.1 Early neonatal Mortality Rates 27 38 15 8.8 Late neonatal mortality Rates 36 48 21 3.6

B******** C******** S******** M*******

Comparison with developed countries & R****** Island in 2000

Developed countries Taux de mortalit prinatal pour 1000 naissances totales Taux de mortalit neonatal prcoce pour 1000 naissances vivantes 3 2 3 Taux de mortalit neonatal tardive pour 1000 naissances vivantes 3 3 3

Australia France England

6 7 8

USA
R****** M******

7
14 22.1

4
3 8.8

5
4 3.6

 For further improvement, NICU services started in M*******.

At **********, in 1999 At *********, in 2001 But the services are very costly & big economic burden on Government. ANS therapy decreases the risk of HMD, hence decrease the need of NICU treatment & hence the cost of treatment.

Objective of Study
To describe the utilization of ANS in pregnancies of 27-34 weeks with high risk of premature deliveries.

Describe the outcome of premature babies in 3 groups according to ANS: With no ANS treatment With ANS incomplete or suboptimal treatment With complete & optimal ANS therapy

Methodology
It is a retrospective descriptive observational study on premature babies of 27-34 weeks born at ***** Hospital during Jan 2003 to Dec 2004. Though we know that best technique for this study would be the randomised clinical trial, but it was not possible due to existing circumstances and ethical reasons.

Total premature babies born alive during 2003-2004 =421 Selected for study=112 Criteria of inclusion: Babies of gestational age 27-34 weeks born at ******* only including inutero transfer Criteria of exclusion: Premature babies with congenital malformation, infant of diabetic mother, multiple pregnancies

 Subdivided our population of study in 3 groups: Group of babies with suboptimal ANS therapy (no=29) Group of babies with optimal ANS therapy (no=49) Group of babies with no ANS (no=34) Group suboptimal whose mothers had Incomplete course of ANS with short interval between therapy and delivery, i.e. less than 24 hrs. Group optimal whose mothers had complete course of ANS at least 24 hrs before delivery

Grading of prematurity
Extreme premature: G.A of 26-32 weeks no=5 Severe premature: 28-31 weeks no=55 Mild premature: 32-34 weeks no=52

Criteria of diagnosis of severity of RDS

According to clinical conditions Chest X Ray Need of treatment Mild RDS X Ray chest result, need of O2 less than 30% fiO2, NO need of surfactant & less tachypnia Severe RDS X Ray result, severe tachypnia, need of O2 more than 30% even with respiratory Support, need of surfactant

Results
Percentage of antenatal corticotherapy
Type de CAN Sub optimal Treatment
Optimal Treatment

No. of pregnancies
29
49

%
25.9%
43.8%

NO ANS

34

30%

Total

112

100%

About 30% of the eligible women couldnt get ANS.

Main reason: Very rapid delivery of baby; i.e. within 24 hrs of hospitalization 26/34 (76.4%) delivered rapidly

Incidence of severe RDS (HMD)

NUMBER OF CASES
30

25

HMD
20

Mild
15

Severe
NIL

10

SUBOPTIMAL

OPTIMAL CORTICOTHERAPY

NIL

44% (13 / 29 ) in group sub optimal treatment 41.1% (14 / 34 ) in NO ANS group 10.2% (5 / 49 ) in group optimal

On comparison among 3 different groups:

Significant difference between optimal & sub
optimal group (P=0.0012)
Significant difference between optimal & NO ANS (P=0.0023) No difference between group sub optimal & group NO ANS.

Utilization of surfactant on Premature babies in different groups

Type of ANS Therapy No. of babies given surfactant %

Sub optimal ANS treatment Optimal ANS Treatment

n=29 11

37.9%

n=49 4

8.16%

No ANS group

n=34 11

32.4%

Need for artificial ventilation

Artificial Ventilation Sub optimal group Optimal group NO ANS group Total

Yes

23 (79.3%)

25 (51.0%)

30 (89.0%)

78 (69.6%)

No

6 (20.7%)

24 (49%)

4 (11%)

34 (30.4%)

Total

29 (100%)

49 (100%)

34 (100%)

112 (100%)

 It is costly when we use surfactant & ventilation. Optimal ANS will help in decreasing the cost of treatment.

Duration of stay in NICU

Groupe of ANS Minimum Sub optimal 0 Stay in NICU (days) Mean 11.4 Median 6 Maximum 61

Optimal

9.6

10

53

NO ANS

13.3

10

72

No significant difference in duration of stay in NICU (P-value=0.476)

Total stay in hospital

Type of ANS
Minimum Sub Optimal 2

Total stay in hospital (days)

Mean 18.8 Median 16 Maximum 96

optimal

20.7

17

53

NO ANS

20.9

18

72

No significant difference among the 3 groups (P value=0.89)

2 principle reasons for no significant difference in duration of stay among the 3 groups:

Very high rates of nosocomial infections in our units Slow weight gain

Morbidity No significant difference among the 3 groups in occurrence of: 1. Patent ductus arteriosus 2. Intra ventricular hemorrhage 3. Broncho pulmonary dysplasia

This result is due to small size of our sample.

Mortality
No significant difference among the 3 groups in results of mortality Reason: 1. Nosocomial infections are the main cause of neonatal mortality 2. Short duration of study It suggests to do study on long duration and compile more datas.

Recommendations
We propose more aggressive campaign of
sensiblisation and education of pregnant women about regular follow up of antenatal clinics, its advantage.
Informing these mothers of the signs and symptoms of complication of pregnancy which provoked premature labour.

Recommendations
Informing doctors conducting ANC at LHC (most often generalists) about:
o problems of premature labour o Antenatal steroid protocol so that they can always start treatment without delaying as dexamethasone is easily available at LHC.

Recommendations
We recommend to start use Betamethasone as drug of choice due to:
o simplicity of application & better patient compliance o superiority on Dexamethasone- decreased risk of cystic peri ventricular leucomalacia among premature infant born at 24th to 31 week G.A

Conclusion
It is very important to give ANS at right time with right doses to achieve maximum effect. In future, a randomised clinical trial should be done between single dose therapy and conventional treatment so that we can establish better protocol without increasing any harm to baby or mother.