10th Postgraduate Course for Training in Reproductive Medicine and Reproductive Biology

Preterm delivery

J-C Schellenberg

Preterm delivery is an important cause of perinatal mortality. In highly developed countries, it has become the single most important health problem in obstetrics since other factors associated with perinatal morbidity and mortality have decreased and maternal mortality has become a rarity. A similar development is likely to occur in less developed countries as their medical infrastructure develops. The chances of survival of preterm infants are strikingly different between geographical regions. In many developing countries, infants of less than 2000 g, (corresponding to about 32 weeks of gestation in a normally grown fetus) have little chance of survival. In contrast, survival in developed countries of infants born at 32 weeks is similar to that of infants born at term, with a survival rate of around 50% for infants born at 25 weeks. Similar survival rates for preterm infants who are cared for in specialised neonatal intensive care units have been reported in developing countries, but as such facilities are sparse they have little influence on overall neonatal outcome. It follows from these, and similar observations, that transfer (if possible: in utero) of preterm infants to specialised obstetric and neonatal units is crucial for a good outcome. Gestational age at birth and ready access to a specialised centre are the two most important factors affecting neonatal mortality and morbidity, whereas glucocorticoid therapy to advance lung maturation, antibiotics to combat infection, and avoidance of hypoxia during labour are other preeminent factors.

An abundant body of literature exists on the topic of preterm labour and delivery. This is a brief overview of the topic, focused on the problems currently existing in developed countries, and accompanied by a number of classic references, and some recent ones that allude to current controversies.

Preterm birth (i.e. delivery before 37 completed weeks of gestation) is a major public health problem. At least 80% of infants without major malformations who die within the first few weeks after birth are born preterm. The incidence of preterm birth has remained constant at around 5% in most countries where statistics are kept. In North America, this incidence, including spontaneous and iatrogenic preterm birth, has increased and is currently over 11% in the USA. Although a decrease in the incidence of preterm birth has been reported in France (from 7.9% in 1972 for singleton livebirths to 4.0% in 1988-1989) and in Finland (from 9.1 % for all preterm births in 1966 to 4.8% in 1985-1986), the absolute numbers of preterm infants remain high and the problem is by no means resolved. A substantial increase in the survival rates of preterm infants has been achieved in all countries with an advanced medical system, due to the creation of specialised neonatal and obstetric centres and improved access to such centres. In contrast, the incidence of severe handicap in infants born at a very low gestational age has remained constant for at least 10 years. This has resulted in a growing number of severely handicapped survivors. Thus, the limits of the effectiveness of neonatal intensive care seem to have been reached, at least in regard to the prevention of severe handicap in very preterm infants. Undoubtedly, therefore, the prevention of preterm delivery remains an absolute priority. Severe handicap, such as cerebral palsy, mental retardation and blindness, occurs in approximately 10% of infants born with a birth weight of less than 1000 g. It has been estimated that at least 10% of all preterm infants have neurological sequelae of a lesser or greater extent. The financial costs for intensive neonatal care are high and the financial and social burdens for handicapped survivors are heavy. Giving birth to a preterm baby and living through the period of neonatal intensive care puts tremendous emotional pressure on the parents, with divorce a possible consequence. Finally, preterm infants requiring intensive neonatal care have to undergo a substantial number of unpleasant invasive procedures.

The aetiology of preterm labour is unknown in the majority of cases. No method to prevent preterm labour and birth has unequivocally been proven effective. The lack of an effective preventive therapy is not amazing in view of incomplete understanding of the biology of preterm and, even, of term labour. Preterm labour and delivery are exceptional in animals, which precludes the use of animal models to study spontaneous preterm birth. Research on preterm labour in women is limited by practical and ethical considerations. Hence, a combined effort by researchers in the area of normal animal parturition, normal human parturition, and preterm labour is indispensable to further our understanding of preterm labour. Knowledge of the basic mechanisms of parturition will be indispensable for the development of methods so sorely needed to prevent preterm delivery. An improved knowledge of organ development is important to establish whether infants born preterm are different at the time of birth from those that remain in utero. This could provide an indication of the aetiology of preterm birth, and of whether it should be prevented in all cases by therapy that will hopefully be available in the future. Developmental studies on preterm infants are also important to establish the consequences of preterm birth, how sequelae can be prevented or minimised, and how social integration of these children is best achieved when such complications exist.

Recommended reading:
  1. Battin M, Ling EW, Whitfield MF, et al. Has the outcome for extremely low gestational age (ELGA) infants improved following recent advances in neonatal intensive care? Am J Perinatol 1998 Aug;15(8):469-77.
  2. Breart G, Blondel B, Tuppin P, et al. Did preterm deliveries continue to decrease in France in the 1980s? Paediatr Perinat Epidemiol 1995 July;9(3):296-306.
  3. Carey JC, Blackwelder WC, Nugent RP, et al. Antepartum cultures for Ureaplasma urealyticum are not useful in predicting pregnancy outcome. Am J Obstet Gynecol 1991;164(3):728-33.
  4. Carey JC, Klebanoff MA, Hauth JC, et al. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. N Engl J Med 2000; 342:534-40.
  5. Chien PFW, Ogston S, Owen P. The diagnostic accuracy of cervico-vaginal fetal fibronectin in predicting perterm delivery: an overview. Br J Obstet Gynaecol 1997;104:436-44.
  6. Creasy RK, Iams, JD. Preterm labor and delivery. In: Creasy RK, Resnik R, editors. Maternal-fetal medicine: principles and practice. 4th ed. Philadelphia: Saunders, 1999.
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  36. The Canadian Preterm Labor Investigators Group. Treatment of preterm labour with the beta-adrenergic agonist ritodrine. N Engl J Med 1992;327:308.12.
 
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