Reducing the Burden of Prematurity – The Obstetric Perspective

Introduction: ‘Preterm or Premature Birth’ is defined as birth occurring before completion of 37 weeks or 259 days since the first day of the last menstrual period of the mother. Every year, an estimated 15 million babies (more than one in ten births) are born preterm worldwide, and this number is rising. In Sri Lanka, approximately 24,500 babies are born prematurely each year. Efforts by obstetricians and neonatologists have led to significant advances in reducing preterm birth and improving outcomes.


INTRODUCTION DEFINITION AND PREVALENCE
'Preterm or Premature Birth' is defined as birth occurring before completion of 37 weeks or 259 days since the first day of the last menstrual period of the mother. 1 Every year, an estimated 15 million babies (more than one in ten births) are born preterm worldwide, and this number is rising. 2 In Sri Lanka, approximately 24,500 babies are born prematurely each year. 3 Efforts by obstetricians and neonatologists have led to significant advances in reducing preterm birth and improving outcomes.

THE BURDEN OF PRETERM BIRTH
Prematurity has been the leading cause of neonatal mortality worldwide for at least a decade and has now become the second leading cause of childhood mortality up to five years of age. Prolonging pregnancies even for a few weeks significantly reduces risks for the new-born, since gestational age is the essential determinant of most perinatal outcomes. 6 The pathophysiological mechanisms that underlie preterm labour are poorly understood but it is suggested that a host of multiple factors trigger the pathogenic processes leading to a final common pathway for the initiation of uterine contractions that will lead to SPB. 6 Unmodifiable risk factors for SPB include a shortened cervix less than 25mm before 28weeks (Risk rate is 6.19 for the length of 26mm or less) and a history of preterm delivery (1.5 to 2 fold risk of subsequent preterm delivery There is not a single or combined screening method for preterm birth with high sensitivity which will truly identify the women at risk for preterm birth while also with high specificity to prevent unnecessary interventions and high treatment costs.

RISK FACTORS, PREDICTORS AND OUTCOMES
The maternal history, health condition, and socio-demographic factors need to be taken into consideration. The measurement of cervical length is the most cost-effective method that is used in clinical practice. Bedside tests have also been developed for detecting markers like foetal fibronectin, insulin-like growth factor binding protein-1 (IGFBP-1), interleukin-6, and placental alpha-macroglobulin-1.
The major clinical outcomes that are important to preterm infants are survival and normal long-term neurodevelopment. (Figure 1)

PREVENTION OF PRETERM BIRTH
Interventions aimed at preventing preterm birth can be classified as primary, secondary, or tertiary prevention. Primary prevention involves the provision of interventions before and between pregnancies which enhance the mother's health and reduce risks of her or the baby succumbing to preventable adverse pregnancy conditions. 6 The main aim of primary prevention is to identify and improve women's health or pregnancy outcomes through various interventions.
The main aim of secondary prevention involves interventions directed towards early detection of pregnant women at risk of preterm labour and helping them to prolong their pregnancy to term.
Tertiary prevention mainly aims to minimize complications of prematurity.
Antenatal therapies with insufficient evidence of benefit include screening and treatment of asymptomatic women for lower genital tract infection, treatment for periodontal disease, bed rest and relaxation or stress reduction.

PRECONCEPTION CARE
The

ANTENATAL CARE
Enhanced antenatal care for the prevention of PTB focuses on the management of pregnancies with potential risk. The mother should be educated regarding early warning signs, possible complications of the pregnancy, healthy behaviour, and the necessity of regular antenatal care visits.
Health care providers must be competent in identifying pregnancies with a higher risk for PTB and the requirement for multidisciplinary care.

REDUCING MULTIPLE PREGNANCIES
The rate of PTB is about 10% in twin pregnancies

CERVICAL PESSARY
The main aim of inserting a pessary is to produce a more acute cervical angle relative to the uterus,

EVALUATION OF PATIENTS WITH PRETERM LABOUR
Preterm labour is diagnosed when a mother with less than 37 completed weeks of the gestational period has regular uterine contractions that are followed by progressive cervical dilation and effacement. It is essential to determine if the patient is in true labour or if the delivery is imminent.
Less than 10% of women with a clinical diagnosis of preterm labour will deliver within seven days of initial presentation 17 .
A distinction between the clinical presentation of both preterm labour (PTL) and preterm pre-   there is a concern regarding an increased risk of cerebral palsy. According to the RCOG guidelines 'Antenatal corticosteroid use reduces neonatal death within the first 24 hours and therefore should still be given even if delivery is expected within this time' 21 as a rescue therapy.

ANTENATAL CORTICOSTEROID THERAPY
Betamethasone 12 mg given intramuscularly in two doses or dexamethasone 6 mg given intramuscularly in four doses are the steroids of choice to enhance lung maturation 21 .

RESCUE CERVICAL CERCLAGE
In a study conducted in women with prolapse of the amniotic sac during live pregnancies between the 17+0 and 26+0 weeks of gestation, the following results were noted. With emergency cerclage, the pregnancy was prolonged by 41 days with an outcome of 72% live births as opposed to the pregnancy prolongation of 3 days and only 25% of live births resulting with the conservative therapy (including bed rest, tocolysis, and antibiotics) 22 .
It is recommended to consider rescue cerclage for women between 16 and 27+6 weeks of pregnancy with a dilated cervix and exposed, unruptured

ANTIBIOTICS
Preterm labour is associated with intrauterine bacterial infection and it is more evident before 32weeks of gestation. Several reviews and metaanalyses conducted to determine the effectiveness of the use of prophylactic antibiotics found out that there was no benefit of its use especially, with intact membranes. It is further suggested that babies exposed to antenatal Co-amoxiclav had an increased risk of cerebral palsy 12 .

ANTENATAL AND INTRAPARTUM FOETAL MONITORING
The monitoring options for a patient in established P-PROM include foetal heart rate monitoring, foetal scalp electrodes, and foetal scalp blood sampling.
It is recommended to offer women in established preterm labour (but with no other risk factors), a choice of foetal heart rate monitoring using either cardiotocography using external ultrasound or by intermittent auscultation. If it is not possible to monitor foetal heart rate using the above methods it is advisable to discuss with the women between 34 and 36+6 weeks of pregnancy, the possible use of a foetal scalp electrode. The possibility of using foetal scalp blood sampling between 34 and 36+6 weeks of pregnancy can be considered if the benefits are likely to outweigh the potential risks 13 .

PRACTICE POINTS AND RECOMMENDATIONS
Preterm birth is a health issue with a significant burden due to the high rate of neonatal morbidity and mortality associated with prematurity. Gestational age of delivery is the main determining factor of the foetal outcome hence prolonging pregnancies even for a few weeks reduces risks for the newborn.
The risk of recurrence of preterm birth mainly depends on the associated specific condition which necessitated the previous early delivery.
There is not a single or combined screening method with high sensitivity and specificity for early identification of preterm birth.
Primary prevention initiated during the period of preconception is the most effective step in reducing the incidence of preterm labour.
The risk of PTB is inversely related to the length of the cervix. Natural progesterone decreases the risk by 50%, in singleton pregnancies with a short cervix with statistically significant reduction in the risk of respiratory distress syndrome, low birth weight, and fewer admissions to the neonatal intensive care unit.
The risk estimation for preterm delivery can be improved by ransvaginal cervical length assessment combine with the detection of fetal fibronectin in the cervicovaginal secretions.
Vaginal progesterone and cervical cerclage are equally effective for the prevention of preterm labour in women with singleton pregnancies. However, there is no adequate evidence that progesterone is effective in preventing preterm deliveries in multiple pregnancies. Therefore, further research is needed to clarify this association.
Antenatal corticosteroids (either B etamethasone or Dexamethasone) and Magnesium sulphate due to their associated reduction in neonatal mortality and morbidity, play a major role in the treatment of preterm labour.