Late abortions and preterm births – general information
Erich Saling M.D. FRCOG, Jürgen Lüthje M.D., Monika Schreiber M.D.
The rate of preterm babies (< 37+0 gestational weeks) in Germany has increased from 7.1 % in 2001 to 9.4 % in 2009, and e. g. in the USA from 10.6 % in 1990 to 12.8 % in 2006 (Martin et al. 2009).
One of the most urgent tasks for modern obstetrics is to reduce the rate of very preterm babies (< 32+0 gestational weeks), and those with a very low birth weight (< 1500 g). These infants form the group of newborns with the highest mortality and morbidity.
Mortality and Morbidity
Although in industrial countries neonatologists have achieved enormous success in keeping extremely preterm infants alive, mortality increases rapidly with decreasing birth weight. The immediate and long-term sequelae of prematurity are also alarming – something which is sometimes neglected when just measuring the “successes” of modern intensive care by mortality rates. Table 1 summarizes complications caused by prematurity or low birth weight.
Table 1: Specific published complications caused by prematurity or low birth weight
The psychological and physical burden which often exists for the families concerned is another important factor which underlines the urgent necessity for effective prevention of preterm births.
The enormously high costs of intensive care and of follow-up care should be an urgent inducement to make even more efforts to reduce the number of very small newborns, if possible.
After a calculation by Künzel (1997), based on the well-organized German Perinatal Studies, the costs of care of all babies born at less than 32 gestational weeks (about 8000 per year) were about 300 million EUR, and the costs for those born between 32 and 36 gestational weeks (about 47 000 per year) were about 430 million EUR, amounting to 730 million EUR. Additionally, the costs of clinical management of mothers with threatened prematurity were about 360 million EUR, totaling more than 1 billion EUR per year. These calculations do not even include the costs of long-term care of children and adults, who are impaired due to prematurity.
Lewit et al. (1995) estimated that in the USA each year the costs of medical care, child care and education for the 3.5–4 million children aged 0–15 years, who had been born with low birth weight, were between $ 5.5 billion and $ 6 billion more than they would have been if those children had been born with normal birth weight.
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Causes of late abortions and prematurity
Late abortions and, in particular, very preterm births should be considered together, because their etiology is often the same.
A number of reasons are known to cause late abortions and preterm births. Lockwood and Kuczynski  divided most of the known causes into four pathogenetic processes:
The various patho-mechanisms initially follow different pathways, merge later on and cause changes in the cervix, leading to preterm contractions and/or premature rupture of the membranes and finally to preterm birth.
As far as effective preventive measures are concerned, most of the avoidable causes, particularly before 32 gestational weeks, are to be found among patients with ascending genital infections, and the diagnostic and therapeutic strategies in this direction are of definitive importance.
As far as other, less frequent causes are concerned, both the possibility of treatment being available and also the chances of success are clearly lower than in the infection group. Furthermore, some problems are directly related to the causes resulting from genital infection.
We want to emphasize, that smoking and abuse of other drugs (especially alcohol) are important avoidable causes of prematurity and low birth weight. The physician should inform any pregnant woman about the risks of the above mentioned and should encourage her to discontinue smoking, consuming alcohol or drug taking.
The first convincing and direct confirmation of the ascension infection genesis was found at the beginning of the 1980s when the operative Early Total Cervix Occlusion (ETCO) was introduced for patients with recurrent late abortions [Saling 1981]. This creates a complete barrier within the ascension area, and leads to remarkably good results.
Profound biochemical studies later performed by Romero et al  brought us immensely forward in understanding the mechanisms by which infections lead to preterm birth. Another pioneering step which underlines how important it is to improve prevention of infections is the concept of the “Fetal inflammatory response syndrome” [Gomez et al. 1998]. It explains that fetal inflammation is linked to the onset of labor, and that the multisystemic involvement in this condition can lead to fetal injury such as brain damage, which predisposes the subsequent development of cerebral palsy.
In the meantime, association between infections and prematurity has been proved by many studies. If early diagnosed, infections can often be treated effectively. Besides ascending genital infections, for instance due to Chlamydia trachomatis, other infections must be considered, especially urinary tract infections.
Infections with Candida alone do not normally increase the risk of preterm birth. Chlamydia infections are associated with a risk of preterm birth, that is as high as the risk associated with bacterial vaginosis. Some authors also report a similarly high risk for infection with Trichomonas, but Trichomonas is often associated with Bacterial Vaginosis. However, Chlamydia and Trichomonas infections are not as prevalent as Bacterial Vaginosis.
Table 2 shows several urogenital infections and their impact on pregnancy and morbidity of infants and mothers.
Table 2: Urogenital infections and associated complications in pregnancy [Martius 1998]
Stress and Immune System
Concerning efforts to prevent preterm births, many publications and recommendations have been reviewed in the literature. Most of them, for example by Papiernik , are based on the fact that socio-economical factors such as low social status, psychological and physical stresses are important reasons and causes for preterm birth. Some successes have been achieved with programs based on these aspects, particularly in model studies. However, the main obstacle preventing a consistent reduction in the number of very-low-birth-weight infants on a broad scale concerns the amount of expense involved. Considerable organizational and personal expenses are necessary to realize such projects, and these resources are hardly available to such an extent in all countries.
Another interesting aspect is that, as far as the cellular and humoral parameters of the immune system are concerned, concrete signs of impairments of the immune status could be found in women with prematurity symptoms [Brandt-Niebelschütz et. al 1995]. In pregnant women with symptoms of threatened prematurity, significantly lower levels of lymphocytes, T-lymphocytes and T-helper cells were measured than in women who had a normal course of pregnancy. The T4/T8 ratio was also clearly reduced in those cases where later preterm birth actually occurred; it was particularly low at 1.1 compared to 1.6 in cases with uncomplicated pregnancies. In the group of pregnant women with preterm labor, the rate of those who found their situation ‘very stressful’ amounted to 65 % and in the group whose course of pregnancy was normal, the rate was 26 %. We assume that ascending infections are probably enhanced by such impairments of the immune system.
Furthermore, we conclude that those pregnant women living in critical socio-economical environments and who, therefore, are more likely to have impaired immunity, can be helped effectively through exposure to appropriate information and preventive medical measures initiated early in pregnancy. Early intervention by the Prematurity-Prevention-Program and – as part of it – by our Self-Care-Program for pregnant women is more realistic and consequently more successful in reducing preterm births than the complicated and necessarily expensive intensive measures given by social services or later in pregnancy when prematurity symptoms are evident.
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The Protective Lactobacillus System
Role of lactobacilli
The human vagina possesses a bio-system which under normal conditions provides a balance between physiologic lactobacilli and pathogenic bacterial flora, and so ensures a good protection against the spreading of pathogens, including their ascension to the uterine cavity. The importance of lactobacilli for the normal vaginal milieu was first described by Döderlein .
In an article of particular interest to us, Gregor Reid  describes the role of lactobacilli in urogenital tract infections.
The following main functions of lactobacilli are known (Fig. 1):
1. They produce acids, mainly lactic acid.
2. They produce hydrogene peroxide (H2O2), which releases oxygen and has a disinfecting effect. These factors, combined with
3. Bacteriocines inhibit the growth of pathogens which are always present in the vagina.
4. They produce biosurfactants, which cover the surface of the vaginal wall, thereby inhibiting the adhesion of pathogens
5. They produce coaggregation molecules which block the spread of pathogens.
Not every Lactobacillus strain produces all the factors mentioned above. That’s the reason why some strains are more effective against specific infections than others. For instance, women with H2O2-producing lactobacilli have a lower risk of suffering from Bacterial Vaginosis, than women whose lactobacilli don’t produce H2O2 [Hillier et. al 1992a]. Unfortunately, there are also some microorganisms, the growth of which is not or only marginally inhibited by lactobacilli (e. g. Streptococci and Candida).
However, we can assume that lactobacilli are the main regulating factor of the vaginal milieu. Vaginal pH measurement gives us insight – like peering through a keyhole – into this protective bio-system. Vaginal pH measurement was already used by Döderlein, in order to distinguish pathological from normal vaginal fluid [Döderlein 1892].
Importance of pH measurement
The importance of Lactobacilli and measurement of vaginal pH is illustrated for instance by the following facts:
Ernest et al.  found out, that the risk of premature rupture of the membranes before 37+0 gestational weeks (gw) is three times higher when the vaginal pH is repeatedly above 4.5, compared to pregnant patients with pH ≤ 4.5.
From a retrospective evaluation carried out by one of our co-workers it reveals that: The earlier in pregnancy the examined children were born, the more frequently the mothers had an increased vaginal pH, when admitted to hospital. All 15 mothers (100 %) of children with a gestational age lower than 32+0 gw had increased pH values, as far as preterm babies between 32+0 gw and 36+6 gw were concerned, the rate was still about 60 %; when born mature only 43.5 % were affected [Schumacher 1999]. It follows, that ascending infections very frequently play a role concerning very preterm births, and that in many of these cases threatening prematurity can be detected by measurement of increased pH values.
In a prospective study, Hengst et. al (1992) was able to show the practical importance of measuring the vaginal pH, which we recommend in routine prenatal care for the prevention of preterm births. In a cohort of pregnant women with so far normal course of pregnancy, who had an increased pH values of > 4.5 and who had received no therapy for acidification, the proportion of preterm births amounted to 15.1 %. On the other hand, the proportion was only 2.0 % when an acidifying therapy with Lactobacillus preparations had been applied.
In another earlier evaluation, we also found results concerning how many pregnant patients had normal vaginal pH values and how many had pathological (≥ 4.7). In 67 % of all the 695 evaluated cases, normal pH values were present; in 33 %, the values were increased twice or more, and 7 % of these were permanently increased [Saling et al. 1995].
It is of particular interest to examine the success rate in normalizing the pH, in cases with increased vaginal pH values, by using Lactobacillus therapy. Success was achieved in 83 % of 75 such patients, and this is really an unexpectedly good result. The therapy was carried out for 5 ± 3 days to achieve this success (Saling et al. 1995).
Normal flora – disturbed milieu – infection
According to some published data, we assume that the main reason for the good results of our Prematurity-Prevention-Program is not the early detection of existing infections, but the early detection of their precursors, namely disturbances of the vaginal milieu:
Hillier et al. [1992b] diagnosed an intermediate pattern between normal flora and Bacterial Vaginosis – see also Schröder  – in 16 % of the pregnant women examined, while 22 % of the women suffered from Bacterial Vaginosis, and 61 % had a normal flora. Of the women with such a transitional stage in the 2nd trimester, in the 3rd trimester in about 1/3 the findings were the same, in about 1/3 the findings were normal, and about 1/3 developed a Bacterial Vaginosis.
Hay et al.  found in a study an increased risk for loss of pregnancy, when just an intermediate pattern was present.
Viehweg et al.  reported, that an increasing pH value during the course of pregnancy leads to an increased risk of preterm birth, even when the pH value stays within the normal range.
In the literature, there are controversial results concerning the success of treatment of Bacterial Vaginosis, and its effects on pregnancy outcome. However, there may have been little success, when screening, diagnose, and treatment took place rather late in the course of pregnancy, or when the diagnosis was incorrect, and there was probably a so-called “Aerobic Vaginitis” (which is associated with aerobic microorganisms, mainly group B streptococci and E. coli) rather than a Bacterial Vaginosis [Donders et al. 2002].
We assume, that the main reason for those different results is the following:
Up to now no studies have been published, where vaginal acidity was checked by pH-measurement so early in pregnancy, and at such short intervals (allowing early treatment), like is the case for the pregnant women, who participate in our Self-Care-Program.
We have first results which indicate, that already disturbances of the vaginal milieu can be detected by pH-measurement at regular intervals, before Bacterial Vaginosis develops [Saling/Schreiber 2005]. In 24 pregnant patients, who visited their doctor because they had themselves measured an increased vaginal pH value, 33 diagnoses were made:
46 % of the patients were told, that they only had a disturbance of the vaginal milieu, and not yet a Bacterial Vaginosis.
A Bacterial Vaginosis was diagnosed only in 4 %.
Candida were diagnosed in 33 %, Chlamydia in 8 %, and other bacteria in 8 %, too.
Although we received these data from the patients, and not directly from their physicians – and thus they should be interpreted with caution – there is no reason to question the results on principle.
Self-Care-Program for pregnant women to prevent prematurity
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Further literature about preterm births and their prevention