Utilization of Antenatal Corticosteroids on premature babies of weeks of gestational age born at SSRNH during Dr S. Burahee Tutor: Dr (Miss) Soobadar

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 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 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 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. 2 nd 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 Mauritius. Most extensively used regimen used in Mauritius: 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 Liggins and Howic were the first who described the benefit of ANS in 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 In Mauritius, in years 70’s 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 Early neonatal Mortality Rates Late neonatal mortality Rates Botswana Central Africa South Africa Mauritius

Comparison with developed countries & Reunion Island in 2000 Developed countries Taux de mortalité périnatal pour 1000 naissances totales Taux de mortalité neonatal précoce pour 1000 naissances vivantes Taux de mortalité neonatal tardive pour 1000 naissances vivantes Australia633 France723 England833 USA745 Réunion1434 Mauritius

For further improvement, NICU services started in Mauritius. At Victoria Hospital, in 1999 At SSRN Hospital, 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.

To describe the utilization of ANS in pregnancies of 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 Objective of Study

Methodology It is a retrospective descriptive observational study on premature babies of weeks born at SSRN Hospital during Jan 2003 to Dec 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 =421 Selected for study=112 Criteria of inclusion: Babies of gestational age weeks born at SSRNH 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 weeks no=5 Severe premature: weeks no=55 Mild premature: 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 O 2 less than 30% fiO 2, NO need of surfactant & less tachypnia Severe RDS X Ray result, severe tachypnia, need of O 2 more than 30% even with respiratory Support, need of surfactant

Results Percentage of antenatal corticotherapy Type de CAN No. of pregnancies% Sub optimal Treatment % Optimal Treatment % NO ANS 3430% Total %

About 30% of the eligible women couldn’t 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) SUBOPTIMALOPTIMALNIL CORTICOTHERAPY NUMBER OF CASES Mild Severe NIL HMD 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 n= % Optimal ANS Treatment n= % No ANS group n= %

Need for artificial ventilation Artificial Ventilation Sub optimal group Optimal groupNO ANS group Total Yes23 (79.3%) 25 (51.0%) 30 (89.0%) 78 (69.6%) No6 (20.7%) 24 (49%) 4 (11%) 34 (30.4%) Total29 (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 Stay in NICU (days) MinimumMeanMedianMaximum Sub optimal Optimal NO ANS No significant difference in duration of stay in NICU (P-value=0.476)

Total stay in hospital Type of ANSTotal stay in hospital (days) MinimumMeanMedianMaximum Sub Optimal optimal NO ANS 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 oAntenatal 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 24 th 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.