Impending Premature Birth: Drug Therapy

Therapeutic target

The goal is either to prolong (extend) the pregnancy as far as possible in time, since the daily increase in maturity means a reduction in morbidity (disease incidence) and mortality (death rate), or, in the case of appropriate pathology such as marked placental insufficiency, induce lung maturity by administration of glucocorticoids and transfer the pregnant woman to a perinatal center (facility for the care of premature infants and newborns), thus giving the child a greater chance of survival or a life without handicap.

Therapy, general

Under risk-benefit considerations, drug tocolysis is recommended from 24+0 weeks’ gestation (SSW) to 34+0 SSW. Before 24+0 SSW, the children usually have no chance of survival; after 34+0 SSW, the children’s chances of survival are so good that prolonging the pregnancy with tocolysis, since it is risky, no longer benefits the child and can be problematic for the mother. See also under “Further therapy.” Drug therapy (basic considerations)

  • The duration of tocolysis (labor inhibition) should be as short as possible.
  • Tokolysis > 48 h should be the exception and individually justified.
  • Oral tocolysis with betamimetics is ineffective and therefore obsolete.
  • In Germany, only two tocolytics are approved for therapy: The betamimetic fenoterol and the oxytocin antagonist atosiban.
  • According to current knowledge, there is no first-choice tocolytic (labor inhibitor). The drug should be selected under individual considerations (side effects, contraindications/counterindications, efficacy, effectiveness, special situation, off-label situation).

Indications for therapy

  • Preterm labor: spontaneous, regular contractions (> 4/20 min) and.
  • Concurrent shortening of functional cervical length and/or.
  • Opening of the cervix

Sonographic cervix length measurement

Cervical length
≥ 30 mm 15-30 mm < 15 mm
Biochemical test*
Negative Positive
Low risk: no treatment Low risk: no treatment Increased risk: hospital admission, tocolysis Increased risk: inpatient admission, tocolysis

* Fetal fibronectin (fFN; see under Laboratory Diagnostics)Contraindications to therapy.

  • Amniotic infection syndrome (English : amniotic infection syndrome, abbreviated as AIS; infection of the egg cavity, placenta, membranes, and possibly the fetus/unborn child during pregnancy or delivery with risk of sepsis (blood poisoning) to the child).
  • Malformations of the child incompatible with life.
  • Child indication for termination of pregnancy
  • Maternal indication for termination of pregnancy

Active ingredients

  • In Germany, only fenoterol and atosiban are approved for tocolysis.
  • Indomethacin and nifedipine are the most effective tocolytics in terms of prolonging pregnancy by 48 hours. They have the fewest side effects and a good neonatal outcome, meaning that the medication does well for the newborn.
  • In preterm birth <32 SSW, i.v. magnesium administration can achieve fetal neuroprotection in terms of reducing infantile cerebral palsies.

Pulmonary maturation induction with glucocorticoids

Prenatal application of glucocorticoids (synonym: antenatal corticosteroid therapy, ACT) between 24+0 SSW and 33+6 SSW to induce (initiate) lung maturity, i.e., forcing intraalveolar surfactant synthesis, is the most effective therapy for prophylaxis of fetal respiratory distress syndrome. It also reduces intraventricular cerebral hemorrhage, the incidence of necrotizing enterocolitis (NEC; intestinal disease feared as a complication in the treatment of very small premature infants with a birth weight less than 1. 500 g) and thus perinatal mortality (number of infant deaths in the perinatal period/deaths and deaths up to the 7th day after birth).In the case of neonatal intensive care maximum therapy and threatened premature birth < 24 SSW, steroid administration can also be given from 22+0 SSW if requested by the parents.Prenatal administration of steroids from the 34th to the end of the 36th week of gestation reduced the incidence of respiratory complications by 20% in a randomized clinical trial. Therapy was associated with an increased rate of neonatal hypoglycemia that did not result in serious outcomes. Extension of prenatal steroid therapy until the end of the 36th gestational week is certainly worth discussing. Further references

  • A cohort study of nearly 30,000 extreme preterm infants demonstrates that lung maturation induction with glucocorticoids improved survival even when birth occurred between 22 and 23 gestational weeks (weeks of gestation). CONCLUSION: Glucocorticoids should be given prenatally if there is an expected threat of preterm birth from the 22nd week of gestation.
  • A population-based, retrospective cohort study was able to show that premature infants whose mothers had received glucocorticoids to mature fetal lung function were significantly more likely to suffer from mental disorders and behavioral problems than infants who had not been exposed.Conclusion: only infants who are actually born prematurely derive any benefit from therapy. This means that the selection for therapy must be made carefully to exclude unnecessary mistreatment.

Antibiotic therapy

Vaginal infections (vaginal infections) are the most important causes of preterm labor and premature rupture of membranes. Therefore, the administration of antibiotics has long been discussed as a primary therapy. Meta-analyses confirm that the application in cases of premature rupture of membranes is useful from the point of view of preventing premature birth and reducing fetal morbidity (incidence of illness) and mortality (death rate). In cases of threatened preterm birth without premature rupture of the membranes, the maternal infection rate can be reduced, but the pregnancy cannot be prolonged and fetal morbidity and mortality can be reduced. For this reason, routine application of antibiotics for preterm labor is not currently recommended. Asymptomatic bacteriuria: Antibiotic therapy for asymptomatic bacteriuria is also an important measure to reduce the number of preterm births.

Agents for tocolysis (main indication)

  • Betamimetics
  • Calcium antagonists
  • Magnesium
  • Nitrates (nitro compounds)
  • Oxytocin receptor antagonists
  • Prostaglandin synthesis inhibitors antiphlogistic and antipyretic analgesics (analgesics; non-steroidal anti-inflammatory drugs (NSAID), non-steroidal anti-inflammatory drugs) and non-steroidal anti-inflammatory drugs (NSAIDs), respectively.

Antibiotic therapy for premature rupture of membranes

There are currently no universal recommendations on the procedure (approach), especially regarding the choice of antibiotics and the duration of application (application varies from two doses to 10 days of therapy. Many do intravenous therapy for two days followed by oral therapy for five days). Meta-analyses have clearly demonstrated that there is a significant reduction in amniotic infection syndrome, as well as maternal and infant infectious morbidity.

Supplements (dietary supplements; vital substances)

Appropriate dietary supplements should contain the following vital substances:

* Prevention

Note: The listed vital substances are not a substitute for drug therapy. Dietary supplements are intended to supplement the general diet in the particular life situation.