INTRODUCTION

Preterm labor is defined as regular contractions of the uterus resulting in changes in the cervix ( cervical
dilatation >2cm and more than 80% effacement) that start before 37 weeks of pregnancy. Birth that occurs
between 20 weeks of pregnancy and 37 weeks of pregnancy, is called preterm birth.

Prematurity represents incomplete development of various organs of the body, that causes increased infant
mortality and also has a risk of long term morbidity. It is the most common cause of infant death and is the
leading cause of long-term disability in children.4

In 2018, preterm birth affected 1 of every 10 infants born in the United States. Preterm birth rates decreased
from 2007 to 2014, and CDC research shows that this decline is due, in part, to declines in the number of births
to teens and young mothers. However, the preterm birth rate rose for the fourth straight year in 2018.
Additionally, racial and ethnic differences in preterm birth rates remain. In 2018, the rate of preterm birth
among African-American women (14%) was about 50 percent higher than the rate of preterm birth among white
women (9%).

According to WHO, every year about 15 million babies are born prematurely around the world and that is more
than one in 10 of all babies born globally. Almost 1 million children die each year due to complications of
preterm birth (2013). Across 184 countries, the rate of preterm birth ranges from 5% to 18% of babies born.
More than 60% of preterm births occur in Africa and South Asia, but preterm birth is truly a global problem. In
the lower-income countries, on average, 12% of babies are born too early compared with 9% in higher-income
countries. Within countries, poorer families are at higher risk. In India, out of 27 million babies born every year
(2010 data), 3.5 million babies born are premature, Ranking NO. 1 as per WHO.
Newborn deaths account for 40 percent of all deaths among children under five years of age. Preterm birth is the
world’s number one cause of newborn deaths, and the second leading cause of all child deaths under five, after
pneumonia.
Many of the preterm babies who survive suffer from various disabilities like cerebral palsy, sensory deficits,
learning disabilities and respiratory illnesses. The morbidity associated with preterm birth often extends to later
life, resulting in physical, psychological and economic stress to the individual and the family. Late-preterm
infants typically have better health outcomes than those born earlier, but they are still three times more likely to
die in the first year of life than are full-term infants.

About 24,000 infants a year and 80 percent of infants born before 27 weeks of gestation will develop respiratory
distress syndrome (RDS). RDS is associated with surfactant deficiency. The incidence of RDS increases with
decreasing gestational age and is higher among white infants than African American infants at each week of
gestation. Although respiratory distress is less common in infants born at 33 to 36 weeks of gestation and is rare
in full-term infants, it can be severe, with a 5 percent mortality rate.

The chronic lung disease (CLD) that sometimes follows RDS in preterm infants is also called
bronchopulmonary dysplasia (BPD), that results from inflammation, injury, and scarring of the airways and the
alveoli. It is associated with growth, health, and neurodevelopmental problems during childhood

Necrotizing enterocolitis (NEC) is an acute injury of the small or large intestines that causes inflammation and
injury to the bowel lining and that primarily affects preterm infants.

Preterm infants have immature immune systems that are inefficient at fighting off the bacteria, viruses, and
other organisms that can cause infections. The most serious manifestations of infections with these agents
commonly seen in preterm infants include pneumonia, sepsis, meningitis, and urinary tract infections. As many
as 65 percent of infants with birth weights of less than 1,000 grams have at least one infection during their initial
hospitalization.

Neonates contract these infections at birth from their mothers or after birth through their immature skin, lungs,
or GI tract, which lack fully developed immunoprotective functions. They have difficulty confining infections to
where they arise and forming abscesses, so sepsis frequently develops. Septic infants are generally critically ill,
and infection can spread to other parts of the body (resulting in, for example, meningitis, an infection of the
membranes that surround the brain). In addition to intravenous antibiotics, septic infants often require support
for other organ systems that break down (e.g., respiratory and blood pressure support). Neonates with birth
weights of less than 1,000 gram and infections have been found to have poorer head growth, more cognitive
impairment, and higher rates of cerebral palsy than those who did not have infections as neonates

Incomplete formation of the CNS makes neonates vulnerable to CNS injury, especially if the infant was born
preterm. Injury to the CNS can occur during pregnancy, labor, delivery, the transition to extrauterine life, or a
subsequent illness or exposure. Many etiologies of preterm delivery (e.g., infection and maternal illness)
contribute to fetal CNS injury.

Respiratory distress syndrome (RDS) is one of the major causes of early neonatal morbidity and mortality
especially in developing countries1. Antenatal administration of corticosteroids for women at risk for preterm
birth is the main line to improve fetal lung surfactant production and enhance the fetal lung maturity2. Besides
that, they reduce the incidence of intraventricular hemorrhage, necrotizing enterocolitis and overall neonatal
mortality in preterm infants3.

Dexamethasone is generally safe during pregnancy. Unlike betamethasone, some studies reported reduction in
fetal body movements, fetal breathing movements and heart rate variation after administration4,5. Repeated
courses of steroids have been associated with increased risk of fetal growth restriction6. Therefore, assessment
of fetal hemodynamic status after corticosteroid administration by Doppler is essential.
Indications of Dexamethasone: 1. True preterm labour 2. Following conditions that lead to imminent delivery: •
Antepartum haemorrhage • Preterm premature rupture of membrane • Severe pre-eclampsia

Contraindicatins Of Dexamethasone: Frank chorioamnionitis is an absolute contraindication for using antenatal

corticosteroids. Following signs and symptoms in the mother suggests Frank amnionitis: 1. History of fever and
lower abdominal pain 2. On examination: Foul smelling vaginal discharge, tachychardia and uterine tenderness
3. Fetal tachycardia

Maternal diabetes, pre-eclampsia and hypertension are NOT contraindications for using injection corticosteroid
in pregnant women. Dexamethasone can be administered if otherwise indicated with a careful watch on blood
sugar and blood pressure [If chorioamnionitis is suspected, consider delivering the baby].

Maternal antenatal corticosteroids are one of the most effective obstetric interventions to reduce neonatal
morbidity and mortality in premature babies. The most recent Cochrane review of this treatment, a meta-
analysis of 21 randomised trials including 4269 women, reported that neonatal respiratory distress syndrome
occurred in 17.3% of the group receiving corticosteroids compared with 26% of the control group and that
neonatal mortality was 10.1% in the corticosteroid group compared with 14.8% in the control group.2 This and
other benefits have led to a focus on ensuring that corticosteroids are administered promptly.
Last year the World Health Organization (WHO) and the UK National Institute for Health and Care Excellence
(NICE) published guidelines on preterm labour and birth. Both documents recommend the administration of
antenatal corticosteroids to women at risk of early delivery.

WHO recommends giving corticosteroids from 24 to 34 weeks’ gestation, while NICE recommends that
clinicians consider steroids at 24-25 weeks but offer corticosteroids from 26 weeks to 33 weeks. Both agree the
maximum benefit occurs from 24 hours to 7 days after initial administration.3 4 We know that compared with a
single course, multiple courses of corticosteroids do not alter risk of death or disability at age 5
years.5 However, evidence suggests that multiple courses may adversely affect in utero growth, with possible
harms such as obesity and increased cardiovascular risk manifesting in adult life.6
Timing of the administration of corticosteroids is crucial, with the key phrase being “at risk of preterm
delivery.”
Diagnosis of preterm labour was prioritised by NICE for health economic analysis, and the apparent reliance on
these results to determine who should receive corticosteroids has been questioned. The complex economic
modelling has resulted in a policy of treating all at less than 30 weeks’ gestation if clinical assessment alone
suggests the woman is in preterm labour. At gestations of 30 or more weeks, NICE recommends transvaginal
ultrasonography to measure cervical length. If that’s not available, cervicovaginal fetal fibronectin
concentrations could be measured to determine likelihood of birth within 48 hours.
Relative side effects: Antenatal corticosteroid administration for enhancing fetal lung maturity can be expected
to induce negative maternal and fetal side-effects. Maternal short-term effects after multiple courses of
corticosteroids are an increase of infections and a higher incidence of endometritis and chorionamnionitis in
patients with premature rupture of membranes. A single dose of corticosteroid induces an increase in the count
of maternal white blood cells and metabolic effects such as the augmentation of amino acid concentration and of
fasting glucose levels in maternal plasma. Negative fetal effects of antenatal corticosteroids are a reduction of
fetal body and breathing movements and a reduction of fetal heart rate variation, without any changes in
Doppler waveform patterns of fetoplacental vessels. It has been suggested that a multiple course of
corticosteroids antenatally might induce negative effects on fetal intrauterine growth and on neonatal birth
weight. In addition, multiple courses are associated with an increased risk of early-onset neonatal sepsis.

In 2006 systematic review of RCT comparing antenatal steroids vs placebo, Treatment with antenatal
corticosteroids is associated with an

 overall reduction in neonatal death (relative risk (RR) 0.69, 95% confidence interval (CI) 0.58 to 0.81,
18 studies, 3956 infants),
 reduction in RDS (RR 0.66, 95% CI 0.59 to 0.73, 21 studies, 4038 infants),
 reduction in cerebroventricular haemorrhage (RR 0.54, 95% CI 0.43 to 0.69, 13 studies, 2872 infants),
 reduction in necrotising enterocolitis (RR 0.46, 95% CI 0.29 to 0.74, eight studies, 1675 infants),
 reduction in respiratory support, intensive care admissions (RR 0.80, 95% CI 0.65 to 0.99, two studies,
277 infants)
 reduction in systemic infections in the first 48 hours of life (RR 0.56, 95% CI 0.38 to 0.85, five studies,
1319 infants).

Long-term morbidity: Corticosteroid therapy was associated with a trend towards a

 reduction in the number of children treated for cerebral palsy in childhood (RR 0.60, 95% CI 0.34–
1.03; 5 studies, 904 children),
 reduction in developmental delay (RR 0.49, 95% CI 0.24–1.00; 2 studies, 518 children).

Differences between groups for visual and hearing impairment, neurodevelopmental delay, intellectual
impairment and behavioural or learning difficulties were not statistically significant in children or adults,
although the relative risks were all in favour of a reduction.

Single Rescue Course

Although the initial data (43) suggested the benefit of corticosteroids may decrease after 7 days, the duration of
corticosteroid benefit remains controversial (44). A multicenter randomized trial of a single rescue course was
performed in 437 patients without preterm PROM who had completed a single course of antenatal
corticosteroids before 30 0/7 weeks of gestation and at least 14 days before inclusion, and were judged to have a
recurring threat of preterm birth within 7 days before 33 0/7 weeks of gestation (45). The investigators found a
significant reduction in respiratory distress syndrome, the need for surfactant, and composite morbidity for those
giving birth before 34 0/7 weeks of gestation and for the overall cohort. No increase in newborn complications
or intrauterine growth restriction was identified, although the power to evaluate these individual outcomes was
low. There was no difference in bronchopulmonary dysplasia, and long-term outcome developmental data are
not available for these patients. The 2015 Crowther Cochrane meta-analysis (10 trials, 4,733 women and 5,700
infants) included trials with a repeat course of corticosteroids as early as 7 days from initial course. The results
of the meta-analysis showed reduction in RDS and there was noted an associated small reduction in size at birth,
but no significant adverse outcomes. Therefore, a single repeat course of antenatal corticosteroids should be
considered in women who are less than 34 0/7 weeks of gestation who are at risk of preterm delivery within 7
days, and whose prior course of antenatal corticosteroids was administered more than 14 days previously (45).
Rescue course corticosteroids could be provided as early as 7 days from the prior dose, if indicated by the
clinical scenario, given the Cochrane meta-analysis results (11, 46). Whether to administer a rescue course of
corticosteroids with PROM is controversial, and there is insufficient evidence to make a recommendation for or
against