PREMATURITY-PREVENTION-PROGRAM

Institute of Perinatal Medicine, Berlin, Germany

We began our activities to reduce the rate of prematures 33 years ago [Saling 1972], but our successes [Giffei & Saling 1974] were only transiently satisfying. The program could not be maintained for long periods because it was too expensive for practical use. 15 years ago, we changed to another policy and developed a new ‘Prematurity-Prevention-Program’ which is based on the most frequent cause of prematurity, namely, as mentioned in "Abortion and prematurity", the ascension infection genesis. Some reports on this program have already been published [Saling 1991, Saling et al. 1991, Saling 1992a, Saling 1992b,Saling 1993]. Its practical introduction into our clinical routine and later in general practitioners’ offices by colleagues in the area has led to a considerable decrease in the number of very small, low-birth-weight infants. However, in spite of achieving a reduction rate of about 40% in our department and 50% in co-operation with practitioners, we had to admit that the practical employment of the program and the consequent application of preventive measures started at a relatively late stage in the entire prematurity pathogenetic process. Therefore, in 1993 we additionally developed another supporting new concept, namely an active co-operation of the pregnant patient herself in our so called Self-Care-Program [Saling et al. 1995a and 1995b]. Our present program is the combination of these two important parts. This solution appears to be quite different from conventional measures; it is a relatively simple, economical and more easily achieved way to attain considerable success in reducing the rate of very small and extremely small prematures.

Diagnostic Measures

Risk factors

Risk factors (Table 3) can be divided into anamnestic risk factors (mainly previous premature births or stillbirths), and events in the current pregnancy.

Table 3: Risk factors for prematurity

Anamnestic risk factors

One or more premature births or stillbirths
Two or more pregnancy terminations
Prior cervical conization
Prior vaginal infections
After infertility treatment

In the present pregnancy

Low social status
Younger than 18 or older than 35
Multiples (twins, triplets, etc)
Polyhydramnios
Certain pressure situations (professional or private, physical or emotional)
Smoking, regular alcohol consumption, or use of other drugs
Parodontitis

Screening for infections

Each time when a pregnant patient consults her physician, attention should also be paid to disturbances of the vaginal milieu or to manifest infections. Besides medical history and physical examination (vaginal discharge, redness, ...), especially measurement of the pH value should be performed. An increased pH value normally indicates a so-called ‘dysbiosis’, a Bacterial Vaginosis, or – less frequently – another infection.

It is also important to notice, that some vaginal infections are normally not associated with increased pH values. This concerns Candida species, Chlamydia trachomatis, Neisseria gonorrhoeae, and B-Streptococci.

Systemic infections and urinary tract infections can also lead to prematurity. Therefore we should always look for symptoms and signs of these infections (see also ”Ascending Infections”, and Table 2).

Measurement of pH value

The most important step during routine diagnosis in our Prematurity-Prevention-Program is to measure the pH value in the vagina. A high level of acidity in the vaginal milieu does not guarantee completely secure protection against ascending infections, but it is certainly very effective.

According to our investigations in an undisturbed course of pregnancy the pH-value at the introitus vaginae (at a depth of approximately 2-3 cm) is regarded as normal

4.2 when measured with pH-meter

4.4 when measured with indicator paper.

In order to achieve uniformity, we recommend that measurements on principle be made in the lower area of the vagina. The higher in the vagina measured, that is the nearer to the cervical canal, according to our examinations, the higher are the pH values [Riedewald et al. 1992]. In the cervical canal itself, for example when measured in the external os, almost neutral pH conditions at 6.5 are to be found in women with an undisturbed course of pregnancy.

A simple way of measuring the pH is to use a small, portable pH-meter.

The indicator strips are introduced into the area of the introitus vaginae with the finger either before or after the vaginal examination and compared with the corresponding color scale.
We made by far the best experiences, when using ”Spezialindikator pH 4.0-7.0”; art-no. 1.09542 by Merck, Darmstadt (Germany), because reading is here especially easy and reliable.

Stage 1: Anamnestic risk

In the first, very early stage, a potentially increased risk is found in cases with poor medical history, such as one or more previous late spontaneous abortions or very premature labor. The best prophylactic countermeasure is, to perform an operative Early Total Cervix Occlusion at about 12 gestational weeks to create a barrier against ascension of organisms.

Stage 2: Disturbance of vaginal milieu

The second early stage of increased risk is a disturbance of the vaginal milieu which mostly can be detected by simple pH-measurement at the introitus. In such a case of so-called ‘dysbiosis’ simple substitution with a Lactobacillus acidophilus preparation for about 7 days is recommended. Especially effective are Lactobacillus strains, that produce H2O2. For instance, the German preparations Döderlein Med® and Gynoflor® contain only H2O2 producing Lactobacilli (Novartis Consumer Health GmbH, personal communication, 6. September 2004 resp. Organon GmbH, personal communication, 25. August 2004). Because Lactobacillus therapy normally takes 2-8 days, until the pH values normalize, additional local acidifying therapy might be indicated (e.g. lactic acid in the morning, and Lactobacillus preparation in the evening). However, currently there is no scientific proof that this additional measure reduces the rate of prematurity.

Both stages 1 and 2 allow the best chances for success in prevention of prematurity.

Stage 3: Infection

The third, also relatively early stage of increased risk includes cases without symptoms of premature labor, but in which vaginal infection has been confirmed, such as Bacterial Vaginosis, Chlamydia infection of the cervical canal or urethra, infections of the lower egg-pole (which can be detected by our egg-pole lavage), or significant bacteriuria. In such cases, we recommend:

in case of Bacterial Vaginosis: local therapy with Octenidine hydrochloride, Metronidazole or Clindamycin
when there is evidence of Chlamydia in the cervix or urethra: pregnant patients should get systemic therapy with Erythromycine succinate
other infections (including significant bacteriuria > 100 000/ml): specific systemic antibiotic therapy

In some countries, some colleagues are hesitant to apply antibiotics in pregnancy. Therefore we want to stress, that pregnancy is not an obstacle for a necessary local or systemic therapy against microorganisms.

The patients should have the recommended amount of physical rest, as well as use of psychological relaxing measures to try to improve their immunological status. The chances of success are still acceptable.

Stage 4: Symptoms of threatened prematurity

This most advanced stage is found when symptoms of prematurity such as apparent premature uterine contractions and/or critical cervical findings are present. If organisms can be identified, or laboratory parameters such as C-reactive protein (CRP) are positive, systemic antibiotic therapy (e.g. with Clindamycin, or better according to the antibiogram, if available) is the method of choice. In most of these cases, admittance to hospital is recommended. In the last stage, the therapeutic measures are increasingly unsuccessful.

In both stages an additional ”after treatment” with L. acidophilus preparations may be indicated because most of the therapeutic measures concerned also disturb the vaginal milieu which can be confirmed by increased vaginal pH values.

In this context, it should be emphasized that our Prematurity-Prevention-Program contains, above all, measures most suitable for the prevention of premature rupture of the membranes, as ascending infection is the most frequent cause of this event.