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Keywords:

  • Antibiotics;
  • infectious disease;
  • preterm;
  • tocolytics

Abstract

  1. Top of page
  2. Abstract
  3. Preterm birth in ‘third world’ countries
  4. Preterm birth in developing countries
  5. Preterm birth in developed countries
  6. Tocolysis
  7. The role of inflammation
  8. Preventative measures
  9. References

The major burden of preterm birth is in the developing world, where most of the increasing death and morbidity is secondary to infectious diseases such as malaria, HIV, tuberculosis, bacterial vaginosis and intestinal parasites. In some developing countries, the growth of medical care has outstripped the growth of preventive public health, with an associated increase in iatrogenic preterm births. In developed countries, more than one-third of preterm births are medically indicated because of conditions such as fulminating pre-eclampsia or severe intrauterine growth restriction. Neither of these conditions is currently preventable. One in five preterm births is associated with multiple pregnancy, and these have been greatly increased by assisted reproduction techniques. The use of tocolytics has proved disappointing perhaps because inflammation rather than spontaneous uterine activity is increasingly recognised as the final common pathway. Inappropriate antibiotics used late in pregnancy are ineffective and may have adverse effects. Currently, the most promising interventions are public health related and include reducing the transmission of communicable diseases, improvements in the management of diabetes and reduction in harmful behaviours such as smoking and drug abuse.


Preterm birth in ‘third world’ countries

  1. Top of page
  2. Abstract
  3. Preterm birth in ‘third world’ countries
  4. Preterm birth in developing countries
  5. Preterm birth in developed countries
  6. Tocolysis
  7. The role of inflammation
  8. Preventative measures
  9. References

The major burden of preterm birth is in the developing world, where most of the death and morbidity is secondary to infectious diseases such as malaria, HIV, tuberculosis, bacterial vaginosis and intestinal parasites.1 Unfortunately, there has been little progress over the past 50 years in developing cost-effective approaches for the prevention and treatment of these conditions, and in some places, their effect is increasing. In Africa, in the 50 years up to 1990, average longevity had increased from approximately 45 years to almost 60 years. In the past 10 years, there has been a precipitous fall so that life expectancy is now 45 years or less in many African countries, such as South Africa, Kenya and Uganda, and less than 40 years in Botswana and Zimbabwe. The most common infections responsible for this decline, malaria, HIV and tuberculosis, are also potent causes of preterm birth and are also threatening the hard-won gains in public health in other parts of the world.

Preterm birth in developing countries

  1. Top of page
  2. Abstract
  3. Preterm birth in ‘third world’ countries
  4. Preterm birth in developing countries
  5. Preterm birth in developed countries
  6. Tocolysis
  7. The role of inflammation
  8. Preventative measures
  9. References

The growth of the medical care industry in many developing countries has had paradoxical effects on preterm birth, so that the highest rates of preterm birth are seen in the most affluent areas, associated with high caesarean section rates.2,3 This is reminiscent of the pattern of maternal mortality in the UK in the first 30 years of the 19th century. At that time, maternal mortality was highest in the upper social classes, who could afford to have their births attended by doctors. To justify their payment, doctors were more likely to intervene in labour, increasing the mortality due to haemorrhage and puerperal sepsis. In 2005, Barros et al.4 have reported an eight-fold rise in caesarean section rates in Brazil over the past 20 years, associated with a three-fold rise in the incidence of preterm birth.

Preterm birth in developed countries

  1. Top of page
  2. Abstract
  3. Preterm birth in ‘third world’ countries
  4. Preterm birth in developing countries
  5. Preterm birth in developed countries
  6. Tocolysis
  7. The role of inflammation
  8. Preventative measures
  9. References

Preterm birth rates are rising in many developed countries, such as Denmark,5 probably due to the incidence of multiple pregnancy associated with assisted reproduction techniques6 (one in five preterm births is associated with multiple pregnancy7) and increases in iatrogenic preterm birth encouraged by improvements in neonatal care and neonatal mortality rates. In developed countries, the causes of spontaneous preterm labour are many and varied (Table 1), such that it is unlikely that a single preventive measure will be effective. More than one-third of preterm births are medically indicated, and delivery is by induction of labour or elective caesarean section (Figure 1) for conditions such as fulminating pre-eclampsia (Figure 2) or severe intrauterine growth restriction. Neither of these conditions is currently treatable, although amelioration using interventions such as low-dose aspirin reduces the risk of early-onset pre-eclampsia by 15%.8 Antepartum haemorrhage (APH) is associated with one in five early preterm births (Figure 3), and since little is known about its aetiology, preventive strategies are elusive.

Table 1.  Causes of preterm birth
Spontaneous preterm birth (70%)
Infection/inflammation
Preterm prelabour rupture of membranes
Multiple pregnancy
Cervical weakness
APH
Stress
Nutrient deficiency
Social
Iatrogenic preterm birth (30%)
Hypertension
Diabetes
APH
Intrauterine growth restriction
Nonreassuring fetal heart rate pattern
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Figure 1. The role of iatrogenic delivery in preterm birth (North West Thames database 1988–2000 inclusive, n = 517 381). US, ultrasound; LMP, last menstrual period.

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Figure 2. The role of hypertensive disease in preterm birth (North West Thames database 1988–2000 inclusive, n = 517 381). US, ultrasound; LMP, last menstrual period.

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Figure 3. The role of APH in preterm birth (North West Thames database 1988–2000 inclusive, n = 517 381). US, ultrasound; LMP, last menstrual period.

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Tocolysis

  1. Top of page
  2. Abstract
  3. Preterm birth in ‘third world’ countries
  4. Preterm birth in developing countries
  5. Preterm birth in developed countries
  6. Tocolysis
  7. The role of inflammation
  8. Preventative measures
  9. References

Tocolysis (the abolition of uterine contractions by pharmacological means) is only applicable in about 10% of cases of spontaneous preterm labour.9 Almost half the cases of spontaneous preterm labour occur after 34 completed weeks of gestation, during which few would advocate tocolysis. Of those who deliver earlier, about one-third have ruptured membranes, following which tocolysis is relatively contraindicated, a further one-third have medical indications for delivery, and in the remainder, there are often contraindications to intervention, such as APH and nonreassuring fetal heart rate pattern on the cardiotocograph.

Even in cases of spontaneous preterm labour where their use is appropriate, the use of tocolytics has proved disappointing perhaps because inflammation rather than spontaneous uterine activity is increasingly recognised as the major aetiological factor. In the majority of randomised controlled trials, 75% of women not given tocolytics fail to deliver within 48 hours and, as many as 40% of those treated with placebo reach term. This reflects the difficulty in diagnosing spontaneous preterm labour. Excluding the placebo effect, tocolysis probably decreases the proportion of women delivering within 48 hours by less than 15%, and those reaching term by less than 10%. Meta-analysis of the randomised trials of tocolysis has failed to show any overall improvement in perinatal outcome associated with their use. This has led the Royal College of Obstetricians and Gynaecologists in the UK to state in their ‘Greentop guidelines’ that ‘… it is reasonable not to use tocolytic drugs, as there is no clear evidence that they improve outcome’. It must be acknowledged, however, that trials of sufficient size to exclude a worthwhile benefit have never been performed, and given current regulatory contraints, it is unlikely that they will be.

The role of inflammation

  1. Top of page
  2. Abstract
  3. Preterm birth in ‘third world’ countries
  4. Preterm birth in developing countries
  5. Preterm birth in developed countries
  6. Tocolysis
  7. The role of inflammation
  8. Preventative measures
  9. References

Due to the increasing recognition of the role of inflammation in the aetiology of spontaneous preterm labour, many workers continue to investigate the potential for antibiotic treatment to reduce its incidence. The use of the wrong antibiotics (those inactive against organisms likely to be present) in inappropriate women (those at risk of preterm birth for reasons other than diagnosed infection of abnormal flora) too late in pregnancy (beyond 22 weeks’ gestation) may cause more harm than good.10–12 Unfortunately, the identification of the right antibiotics in appropriate women has proven equally elusive. Most cases of spontaneous preterm labour are probably not due to a simple process of infection by one bacterium, but a complex interaction between a variety of organisms and the host, resulting in cytokine release. This is illustrated by increasing evidence that periodontal disease is a major inflammatory precursor to spontaneous preterm labour and may be implicated in up to 50% of cases.13 Perhaps, dentists can succeed in reducing the incidence of preterm birth where obstetricians have failed.

Preventative measures

  1. Top of page
  2. Abstract
  3. Preterm birth in ‘third world’ countries
  4. Preterm birth in developing countries
  5. Preterm birth in developed countries
  6. Tocolysis
  7. The role of inflammation
  8. Preventative measures
  9. References

At present, the most promising interventions to reduce the incidence of preterm birth lie in the area of regulating medical practice and public health initiatives. It seems likely that there will be further restrictions placed on the replacement of multiple embryos in in vitro fertilisation, and there is growing pressure on obstetricians to avoid early iatrogenic delivery when prolonging pregnancy is a reasonable option. Moves to control or even reverse the growing epidemic of obesity and diabetes could also have a significant impact. Finally, encouraging women not to delay childbearing unnecessarily, to optimise their health prior to pregnancy and to avoid smoking and drug abuse during pregnancy would almost certainly be cost-effective with respect to preventing preterm birth.

References

  1. Top of page
  2. Abstract
  3. Preterm birth in ‘third world’ countries
  4. Preterm birth in developing countries
  5. Preterm birth in developed countries
  6. Tocolysis
  7. The role of inflammation
  8. Preventative measures
  9. References