Multiple gestation pregnancies from in vitro fertilization are a major contributor to the increase in preterm births. Otherwise, as in all things medical, socio-economic class is important.
Evidence for screening and selective treatment exists for:
Eur J Obstet Gynecol Reprod Biol 2006, PMID 16517046
Cervical incompetence is a cause of recurrent late miscarriages and premature births - can present with chorioamnionitis (chicken/egg?). Cervical length scan may show progressive shortening which suggests impending delivery but no good cut offs; and by the time the probability is high it is usually too late to do cerclage! Cervical length greater than 30 mm has a reasonably high NPV (Iams, Paraskos, Landon, Teteris, & Johnson, 1994). Rate of shortening is also important.
OPPTIMUM trial to assess benefit of prophylactic progesterone eg previous preterm birth or midterm loss, plus positive fibronectin test at 22/40.
Fetal fibronectin is normally absent from vaginal secretions between 24 to 34 weeks. Negative predictive value is good (ie 99%+ with a negative result do not give birth in the subsequent 2 weeks. Positive predictive values are less useful (Peaceman et al, 1997).
Certain work activities, such as prolonged standing and the use of industrial machines, have been linked to early births.
Periodontal diseases - in one case control study (n= 124 pregnant and postpartum mothers), women with periodontal diseases were 7.9 times more likely to have preterm low-birth-weight infants, after controlling for numerous other risk factors.
Smoking cessation, ideally prior to pregnancy or early in pregnancy, may have more potential for reducing preterm and LBW birth than any other single strategy.
Rates of preterm birth are highest among women ages 17 and younger and women 35 and older. Most attention in past years has focused on teenage pregnancies. African Americans have consistently experienced rates of preterm and LBW births that are higher than other racial and ethnic groups. Poverty is a contributor to this elevated rate, but it is not the only reason
Having had a preterm already - in a meta-analysis of eight studies, relative risk of a second preterm infant was moderately increased, between 2.3 and 4.8 (Adams, Elam-Evans, Wilson, & Gilbertz, 1998). But only about 10% of preterm births are to women with previous preterm births
At least 9 RCTs of repeat courses of antenatal steroids. The landmark systematic review concluding benefit of antenatal steroids is the basis of the Cochrane group logo. But the benefit seemed to be limited to doses given 1-7 days prior to delivery, hence earlier practice of repeat courses, before concerns about neuro effects of steroids on fetal brain. But could this window be an artefact? No interaction tests are reported in the studies where subgroups were looked at; equally, dividing subgroups on the basis of an outcome variable (ie the number is not known at time of randomization, only afterwards) often produces misleading results.
Administration of repeat doses of antenatal corticosteroids reduces neonatal morbidity without changing either survival free of major neurosensory disability or body size at 2 years of age (n=1000). N Engl J Med. 2007 Sep 20;357(12):1179-89. [17881750]
Although there is good evidence that infection is a factor in preterm labour (eg increased rates in pyelonephritis and bacterial vaginosis), the benefit of antibiotics for preterm labour is unclear. ORACLE II found an increased risk of cerebral palsy at 7yrs in children of women with intact membranes who received antibiotics, even though there is evidence that infection itself can be a risk factor for cerebral palsy. OR was around 1.9. Not the case for ruptured membranes (ORACLE I), where antibiotics appeared to reduce delivery rates, and composite outcome of death/neuro abnormality/chronic lung disease. Erythromycin is preferred since Co-amoxiclav was associated with increased risk of NEC.
Screening for abnormal vaginal flora does not seem to help. Results for treating bacterial vaginosis are contradictory, and is not recommended by NICE. Use of Erythromycin has been associated with substantial increase in resistance.
So for now, only treat definite infections in pregnancy. But give erythromycin for preterm rupture of membranes.
1995 cohort of extreme preterms (n=138). At discharge from hospital:
At 2 years, of the 24 & 25 weekers:
ie half fine, a quarter severe, a quarter in between
At 6 years, moderate or severe disability seen in:
Other cohort studies show higher rates of psychiatric problems and need for learning support at ages up to at least 9 yrs. And mild CP will present late.
See Ethics. (BMJ)
Preterms at 10 yr are lighter, shorter and have smaller heads. They score less well on motor function and intelligence, and this is related to their size attributes. It is known that growth retarded preterms fare less well if they fail to catch up. In fact, the worst affected tend not to be the growth restricted ones, but the ones who fall through the centiles. This may imply that postnatal nutrition and growth may have a role in improving neurodevelopmental outcome.
Hypothermia associated with mortality! At the Simpson's in Edinburgh they have totally abolished hypothermia associated with resuscitation by using a freezer bag, cutting holes as necessary for access.
Neonatal illness may have negative effects on parent–infant interactions. Optimal school outcome among former preterm children has been shown to be more strongly associated with stability of family composition and level of parental education than with medical complications. (Arch Fet 2004; 89 )
A Cochrane meta-analysis including 20 studies, of which 14 had a randomised controlled design, states positive impact on tube to bottle transition, behaviour (improvement of sleep states, decreased stress behaviour during gavage feeding), and length of hospital stay. But very individualized, poorly standardized, and wide variability between different units in baseline rates. (Arch Fet 2004; 89)
Kangaroo care associated with improved growth and breast feeding rate and reduced nosocomial infections.38 However, most trials have been conducted in developing countries, and the results may not have the same relevance in countries where high technology neonatal care is more widely available. (Arch Fet 2004; 89 )
IUGR in prematurity is associated with increased mortality, necrotizing enterocolitis, need for respiratory support at 28 days of age, and retinopathy. Doesn’t make you tougher, after all. Am J Obstet Gynecol. 2004 Aug;191
Disease seen in babies with high oxygen saturations, but also in those with widely varying saturations. Units that have lower target ranges for saturation have lower incidence. Retina normally starts avascular at 24/40, vessels gradually spread out from centre hence zone of vascularization (1=innermost, 3= temporal margin). First sign of disease is neovascularization; these abnormal extra vessels begin to penetrate out into the vitreous and eventually cause retinal detachment. Zone 3 disease is of minimal impact clinically (peripheral vision only). Once retina has fully vascularized, no further risk of retinopathy. Stage = severity:
Plus disease can co-exist at any stage, and are signs of rapid progression eg tortuosity. Stage3+ is termed threshold disease, and is the point at which treatment should be initiated.
Laser has overtaken cryo - multiple burns to the retina kill cells releasing growth factors (but destroys retina). Historically 40% of treated have poor visual outcome so nowadays tend to treat earlier. Prophylactic patching does not help!
Logistic regression revealed six factors to be significant variables. Birthweight under 1000 g, intraventricular hemorrhage, sepsis (most important), and use of glucocorticoid or dopamine were risk factors associated with higher incidence of ROP. Supplementation of vitamin E was shown to relate to lower incidence of ROP. (n=159, birth weight under 1600g)Am J Perinatol. 2005 Feb;22(2):115-20. Liu PM, Taiwan.
Known as the Barker hypothesis.
Fetal growth in first trimester contributes to low birth weight and preterm birth (research from IVF pregnancies). Since low birth weight is associated with adult illnesses, suggests metabolic programming starts even earlier than thought.
Racial factors affect perinatal mortality – eg S Asians have higher risks.
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