Preterm birth and premature rupture of the membranes

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SYLLABUS

Preterm birth and premature rupture of the membranes

(Basic level)

Premature birth is an unsolved obstetric problem worldwide, which affects both developed and less developed countries. In the United States of America, for example, it ranges between 12%, while in underdeveloped countries, due to the lack of adequate data, it is often difficult to assess the problem in its entirety. (1)

According to WHO data, around 15 million preterm births occur worldwide each year, about 10% of all births. About 1 million children die each year due to complications caused by premature birth. The main cause of death under 5 years of age can also be traced back to complications caused by premature birth. (2)

Another problem is that the chances of survival of premature babies are far from the same in different parts of the world. In underdeveloped countries, about half of newborns born before 32 weeks die, while in developed countries the survival rate is almost 100%.
What are the most important causes of preterm birth?

  • Medically related factors: previous premature birth, premature rupture of membranes in the history, short cervix, intrauterine infection, sexually transmitted infections: Chlamydia, Gonorrhea. (3)
  • Maternal diseases: high blood pressure, diabetes, twin pregnancy, too low or too high body weight, less than 18 months between pregnancies. (4)
  • Maternal age: younger women under 17 and older women over 35.
  • Incorrect lifestyle: smoking (including second hand smoke), alcohol, drugs, short period
between pregnancies (less than 18 months between pregnancies). (5)

  • Environmental factors: air pollution, consumption of polluted water.
  • Social factors: poverty, poor social conditions. (6)

The weight of different risk factors is not the same. The most important are the presence
of prior premature birth in the medical history and premature rupture of membranes, which is responsible for 1/3-1/4 of preterm births. (5)

What are the main risk factors in an ongoing pregnancy?

In the case of an ongoing pregnancy, the most important risk factors are previous vaginal bleeding, twin pregnancy, polyhydramnios, pregnancy created with IVF techniques, short cervix.

The main cause of prior vaginal bleeding is threatened miscarriage and placenta previa, which are obvious risk factors. Another important factor is the length of the cervix.

Premature rupture of membranes affects about 3-5% of pregnancies and is the cause of about 30% of premature births. Preterm pre-labor rupture of the membranes – PPROM most often has an infectious cause. If someone has a history of preterm pre-labor rupture of the membranes - PPROM, they are more likely to have a recurrence in the next pregnancy. (7,8)

What is the diagnosis of threatened preterm labor?

Symptoms of threatened preterm birth are bleeding, the appearance of uterine contractions, or premature rupture of the membranes. When these symptoms appear, the risk of preterm birth is already quite high. There is a natural need to find ways to screen out cases where there is an increased risk of preterm birth before these symptoms appear. One such method is to monitor the length of the cervix.

Although routine screening of cervical length for all pregnant women is not recommended, in practice many do it. As for the limit of cervical length below which there is an increased risk of preterm birth, there is no consensus. The most accepted limit at 24 weeks gestational age is 25mm (10th percentile). (9)

The Fetal Medicine Foundation recommends routine cervical length ultrasound screening in pregnant women with a history of preterm birth. (10) (grade 1A)

What laboratory methods are used in the diagnosis of preterm birth?

  • Fetal fibronectin determination: alone or in combination with cervical length  measurement. Fetal fibronectin can be found in cervicovaginal secretions up to 22 weeks. If present between 24 and 33 weeks, it draws attention to the increased risk of preterm birth. Recommended limit values: less than 10 ng/ml and greater than 200 ng/ml). So, with a value below 10 ng/ml, the risk of preterm birth is unlikely, while above 200 ng/ml, the risk of preterm birth is high.
  • Determination of insulin-like growth factor-binding protein-1 (IGFBP-1). With a value of <10 g/l (negative Actim Partus Test), asymptomatic pregnant women have a low risk of preterm birth.

Other tests used to predict preterm birth are: placental alpha microglobulin-1 test (PAMG-1) and phosphorylated insulin-like growth factor-binding protein-1. (IGFBP-1)

For now, none of the tests achieves the desired accuracy, which is why their application and distribution are limited.

What are the symptoms of premature rupture of membranes?

Premature rupture of membranes before 37 weeks of gestation, premature rupture of membranes after 37 weeks of gestation, before the onset of labor. The pathology of premature rupture of membranes is most often obvious when the clear leakage of amniotic fluid is visible. If the leakage is not clear, the leakage can be detected with sterile speculum placed in the vagina. If this is not clear either, then the pH determination from the vaginal discharge (alkaline) or the drawing of a fern leaf of the drying secretion will help. An ultrasound examination can detect an obvious decrease in the amount of amniotic fluid. According to the RCOG 73 guideline, PAMG-1 and IGFBP-1 determination may be useful in dubious cases. (11) If the presence of rupture of the membranes is confirmed, the gestational age, the intrauterine position of the fetus and the fetal status diagnosis should be determined. Look for signs of infection, premature placental abruption, and fetal distress. A vaginal bacteriological examination should be performed with particular attention to the detection of Group B Streptococcus.

A cardiotocography examination is also recommended, which shows signs of possible fetal distress and possible uterine activity. Termination of pregnancy is justified in the case of existing severe infection, premature placental abruption and symptoms of fetal distress.

What is the treatment of preterm birth?

Unfortunately, we still do not have an optimal treatment procedure in this case. This is due to the fact that the treatment method is mainly influenced by the gestational age and the presence of possible complications, such as chorioamnionitis 15-25%, premature placental abruption 2-5%, onset of premature labor, etc.

The probability of premature rupture of membranes before fetal viability is reached is about 1%. In such cases, fetuses have very little chance of survival. This rate is about 17% and the rate of serious complications is very high (bronchopulmonary dysplasia 50% and intrauterine retardation 36%, which usually starts about 2 weeks after the rupture). (12) Pulmonary dysplasia is usually caused by a very small amount of residual amniotic fluid left after preterm pre-labor rupture of the membranes PPROM. In these cases, only the conservative procedure (expectative management) is recommended, even if there is a high chance of intraamniotic infection, endometritis, premature placental abruption, and placental disruptions disorders after delivery.

Neither corticosteroid prophylaxis, nor tocolysis, nor magnesium sulfate treatment is recommended before fetal viability is achieved. Only antibiotic prophylaxis is recommended, which should also be directed against possible Group B streptococcal infection. (13)

After 24 weeks of gestation, the fetus's chances of survival are higher, but since lung maturation is only completed at approximately 33 weeks, breathing support is necessary for the vast majority of fetuses born. As a result, it is a generally accepted principle that, in favorable cases, one should try to prolong the pregnancy, preferably until the lung maturation is completed, after which the waiting position is no longer justified.

This was refuted by a study published in 2016 (PPROMT trial), which concluded that despite the fact that, theoretically, the process of lung maturation is completed by 33 weeks of pregnancy, the adaptation of the fetuses after birth improves and the morbidity indicators decrease with the application of the waiting position in case of. (14) Thus, the benefits from the waiting position outweigh the risks and in the absence of signs of infection or other complications that would require artificial induction of labor or immediate termination of the pregnancy, it is recommended to use the waiting position below 37 weeks of gestation (expectantly management).

What to do in case of threatened preterm birth and premature rupture of membranes?

Hospital referral, continuous search for signs of infection, premature placental abruption, umbilical cord compression, fetal distress. Follow-up of fetal growth with periodic ultrasound control. As far as the fetal condition assessment after preterm pre-labor rupture of the membranes - PPROM is concerned, there is no uniformly accepted position on exactly what parameters should be followed and at what intervals.

What are the contradictions related to the treatment of threatened premature birth and premature rupture of membranes?

  • The question of tocolysis: prophylactic tocolysis before 34 weeks of gestation prolongs pregnancy by a few days, but increases the risk of chorioamnionitis. In the case of preterm labor, tocolysis no longer has a demonstrable benefit and is therefore not recommended. (13). Although tocolysis generally prolongs the duration of pregnancy by an average of 73 hours, there are studies that show that this is not associated with better rates of fetal morbidity. (Evidence Level 1+, 11, 15, 16)
  • Corticosteroid prophylaxis: is not recommended before 24 weeks of gestation. Its use between 24-25 weeks is beneficial (Evidence Level B), while between 25 and 33 weeks of gestation the benefits are clear (Evidence Level A). According to the latest research, the benefits are clear even between 33-35 weeks. (10) (Evidence Level A)
  • Administration of magnesium sulfate: There are several studies showing that magnesium sulfate at 24-32 weeks of gestation is beneficial in preventing neurological damage. (11,13,17) (Evidence Level A)
  • Antibiotic prophylaxis: Antibiotic prophylaxis reduces the chance of infection, thus indirectly contributing to the prolongation of pregnancy. According to a Cochrane meta-analysis, the use of antibiotics significantly reduces the chance of chorioamnionitis, and also the risk of preterm delivery within seven days. (18)

The most frequently used scheme: intravenous ampicillin (4x2g) and erythromycin (4x250mg) for 7 days, then orally administered amoxicillin or erythromycin. The chance of neonatal necrotizing enterocolitis increases after amoxicillin-clavulanic acid combinations.

Group B Streptococcus infection is not an indication for the immediate initiation of labor,
here too expectantly management is possible, but in such cases, antibiotic prophylaxis is recommended even intrapartum to prevent vertical spread. (11,13) (Evidence Level A). Antibiotic prophylaxis is not justified for pre-planned caesarean section with intact membranes. If you have received antibiotic prophylactic treatment at least 4 hours before delivery and the fetus is in good condition, it does not require any further special attention.

  • Women with preterm rupture of membranes - PROM who have a cervical cerclage

If it is decided to the cerclage remains in place, antibiotic treatment for longer than 7 days is not recommended.

  • Amnioinfusion: The routine use of amnioinfusion in PPROM is not recommended, despite

the fact that there are publications that emphasize the advantages of the method, but the number of these studies is still small. The advantages of the method include the improvement of the umbilical cord flow values ​​and the reduction of the number of variable decelerations during labor.

After 37 weeks of gestation, the initiation of labor is clearly recommended. At this
gestational age, both oxytocin infusion and prostaglandin cervical ripening are effective, but infectious complications are rarer with oxytocin infusion.

What are the options for preventing premature birth?

If a previous pregnancy ended in premature birth, or preterm rupture of membranes was also present, the risk of recurrence during a subsequent pregnancy is very high. If little time passes between consecutive pregnancies, this risk is greater. One possible preventive measure is progesterone therapy used between 16-24 weeks of pregnancy. For pregnant women whose previous pregnancy was complicated by preterm rupture of membranes, if the length of the cervix is ​​less than 2.5 cm before 24 weeks, prophylactic cerclage surgery is recommended. (13,19)

If someone had a Group B Streptococcus infection during the previous pregnancy, the risk of recurrence is 50%, therefore antibiotic prophylaxis is recommended. (20)

What are the social aspects of preterm birth?

Caring for a premature baby requires longer hospital care, which increases the associated costs. In the USA, the average cost of care for a healthy newborn is $4,389, while the average cost for a premature baby is $54,194. In addition to the higher costs, the more important thing is that many complications appear in premature babies, which are associated with higher mortality, or do not allow the individual to live a full life later, or may require additional care until the end of life. The birth of a premature baby can also disrupt relationships within the family: postpartum recovery can be made difficult by the stress of premature birth, lack of sleep, feelings of guilt or self-blame, anger or fear about the child's future, the guilt caused by the neglected children left at home due to prolonged hospital care, the loss of the dream of the perfect child and family.

To draw attention to the importance of premature birth, since 2011, UNICEF has declared November 17 as the World Prematurity Day

Bibliography

1. https://apps.who.int/iris/bitstream/handle/10665/363697/9789240058262-eng.pdf
2. http://www.who.int/mediacentre/factsheets/fs363/en/
3. Preterm Birth - MN Dept. of Health
https://www.health.state.mn.us/people/womeninfants/prematurity/index.html
4. Belayneh Hamdela Jena, Gashaw Andargie Biks, Yigzaw Kebede Gete, Kassahun Alemu Gelaye: Incidence of preterm premature rupture of membranes and its association with inter-pregnancy interval: a prospective cohort study, Scientific Reports volume 12(1):5714 (2022) Published: 05 April 2022, https://doi.org/10.1038/s41598-022-09743-3.
5. Deirdre J. Murphy: Epidemiology and environmental factors in preterm labour, Best Practice &Research Clinical Obstetrics & Gynaecology Vol 21(5): 773-89, 2007 Oct.
6. John W. Snelgrove, Kellie E. Murphy: Preterm birth and social inequality: assessing the effects of material and psychosocial disadvantage in a UK birth cohort, Acta Obstetrica et Gynecologica Scandinavica 94(7): 766–775, 2015 July, https://doi.org/10.1111/aogs.12648.
7. Mercer B M, Goldenberg R L, Moawad A H, Meis P J, Iams J D, Das A F, et al.: The preterm prediction study: effect of gestational age and cause of preterm birth on subsequent obstetric outcome. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, Am J Obstet. Gynecol. 181(5 Pt 1):1216–21, 1999 Nov, doi: 10.1016/s0002-9378(99)70111-0.
8. Asrat T, Lewis D F, Garite T J, Major C A, Nageotte M P, Towers C V, et al.: Rate of recurrence of preterm premature rupture of membranes in consecutive pregnancies, Am J Obstet. Gynecol., 165(4 Pt 1):1111–5, 1991 Oct, doi: 10.1016/0002-9378(91)90481-6.
9. V. Berghella, M. Palacio, A. Ness, Z. Alfirevic, K. H. Nicolaides, G. Saccone: Cervical length screening for prevention of preterm birth in singleton pregnancy with threatened preterm labor: systematic review and meta-analysis of randomized controlled trials using individual patient-level data, Ultrasound Obstet. Gynecol., 49(3):322–329, 2017 Mar., doi: 10.1002/uog.17388.
10. Jennifer McIntosh, Helen Feltovich, V. Berghella, T. Manuck: The role of routine cervical length screening in selected high -and low- risk women for preterm birth, Am J Obstet. Gynecol., 215(3):B 2-7, 2016 Sept., https://doi.org/10.1016/j.ajog.2016.04.02.
11. RCOG Green-top Guideline No. 73, Care of Women Presenting with Suspected Preterm Prelabour Rupture of Membranes from 24+0 Weeks of Gestation, AJ Thomson, on behalf of the Royal College of Obstetricians and Gynecologists, published: 17 June 2019 https://doi.org/10.1111/1471-0528.15803.
12. H.M Tanir, T Sener, N Tekin, A Aksit, N Ardic:  Preterm premature rupture of membranes and neonatal outcome prior to 34 weeks of gestation, International Journal of Gynecology &
Obstetrics, 82(2):167-72, 2003 Aug, doi: 10.1016/s0020-7292(03)00125-5.
13. ACOG Practice Bulletin No. 188: Prelabor rupture of membranes, Obstet. Gynecol., 131(1): e1-e14, 2018 Jan, doi: 10.1097/AOG.0000000000002455. (2018), pp. e1-e14.
14. Jonathan M Morris, Christine L Roberts, Jennifer R Bowen , Jillian A Patterson , Diana M Bond , Charles S Algert , Jim G Thornton , Caroline A Crowther ; PPROMT Collaboration: Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial, Randomized Controlled Trial Lancet, 387(10017):444-52, 2016 Jan 30, doi: 10.1016/S0140-6736(15)00724-2. Epub 2015 Nov 10.
15. Nijman T A J, van Vliet E O G, Naaktgeboren C A, Oude RK, de Lange T S, Bax C J, et al.: Nifedipine versus placebo in the treatment of preterm prelabor rupture of membranes: a randomised controlled trial. Assessment of perinatal outcome by use of tocolysis in early labor – APOSTEL IV trial, Eur. J Obstet. Gynecol. Reprod. Biol., 205:79–84, 2016 Oct, 31., doi: 10.1016/j.ejogrb.2016.08.024.
16. Lorthe E, Goffinet F, Marret S, Vayssiere C, Flamant C, Quere M, et al.: Tocolysis after preterm premature rupture of membranes and neonatal outcome: a propensity-score analysis, Am J Obstet. Gynecol., 217(2):212. e1-212.e12, 2017 Aug., doi: 10.1016/j.ajog.2017.04.015.
17. Doyle LW, Crowther CA, Middleton P, Marret S, Rouse D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, Cochrane Database of Systematic Reviews, 21;(1):CD004661, 2009 Jan., doi: 10.1002/14651858.CD004661.pub3.
18. Kenyon S, Boulvain M, Neilson JP: Antibiotics for preterm rupture of membranes. Cochrane Database of Systematic Reviews 2010, Issue 8. Art. No.: CD001058. DOI: 10.1002/14651858.CD001058.pub2.
19. Vincenzo Berghella, Timothy J Rafael, Jeff M Szychowski, Orion A Rust, John Owen J: Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth: a meta-analysis. Obstet. Gynecol. 117(3):663–67, 2011 Mar. doi: 10.1097/AOG.0b013e31820ca847.
20. RCOG Green-top Guideline No. 36, Prevention of Early-onset Group B Streptococcal Disease, on behalf of the Royal College of Obstetricians and Gynecologists, published: 13 September 2017, https://doi.org/10.1111/1471-0528.14821.



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