Five reasons we are closer to preventing preterm birth

 

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Most pregnant women assume they will deliver a healthy baby at term. However, 8% of women deliver their baby preterm (before 37 weeks of pregnancy). This figure is higher in the developing world and in certain subgroups of women with medical conditions affecting their health or that of their baby.

Impact of preterm birth

Preterm birth can devastate families. Seeing your baby in an intensive care unit, wondering if they will survive, and if so, whether there has been lifelong damage to their vision, hearing, movement or capacity to learn is every parent’s nightmare.

Sadly, in many cases involving early preterm birth (less than 34 weeks of pregnancy), fears are justified. World-wide, preterm birth remains the leading cause of death and disability in children under five years of age (1,2,3,4).

However, recent developments in our understanding of preterm birth now offer hope to families.

This blog briefly covers a few simple interventions that have been proven to lower rates of preterm birth and some other strategies under investigation.

Causes of preterm birth

Nearly half of all preterm births are spontaneous. The other 50% of cases arise due to a need for elective early delivery due to a pregnancy complication. These may include hypertensive disorders, multiple pregnancy, placental bleeding and diabetes.

The greatest hopes to reduce the devastation of preterm birth lies in discovering why so many babies spontaneously deliver early.

New technologies, spontaneous preterm birth and infection

One common link identified in many spontaneous preterm births is infection (3). Our published systematic review identified infection as a common final pathway in many cases of preterm birth and as a causal factor in long term neurological damage in children (3).

Infection leads to preterm birth in a complex way (5).

Bacteria can enter the intra-uterine space directly by ascending from the vagina. They can also access the intra-uterine space by the blood stream or rarely through invasion from a source of infection elsewhere in the abdominal space or by being directly inoculated following an invasive procedure such as an amniocentesis. (5,6).

Early detection and treatment of infection can reduce preterm birth. Meta-analyses of antibiotic administration to women with bacterial vaginosis have found significant decreases in the rate of preterm birth  (7).

However, many bacteria cannot be cultured, so identifying infectious causes of preterm birth can be difficult. However, the use of innovative new technologies is creating new opportunities.Our research group have been employing 16S rRNA gene technology to identify bacterial taxa in the vagina of women with complicated pregnancy. Our recent case reports have identified unusual bacterial taxa such as Acinetobacter, Bacteroides, Hafnia, Campylobacter and Haemophilus as being implicated in extremely preterm, very preterm and preterm births (8-10)

There is hope modern technologies will help unravel the infectious precursors and causes of preterm birth.

Fish oil to prevent preterm birth

Another large research project we have underway is called ORIP (11). This is one of the largest randomised research trials in the world in pregnancy and is designed to reduce early preterm birth using a nutritional supplement called DHA that is found in some fish oils.

Our previous trial DOMINO (12) involving more than 2500 women, found DHA supplements in pregnancy were associated with lower rates of spontaneous early preterm birth. In order to formally determine if DHA can prevent early preterm birth, we have embarked on the ORIP trial. Currently we have recruited over 3000 women into ORIP. Eventually we plan to recruit more than 5500 women to confirm whether DHA supplements are effective.

If you want to read more, we have published a review article on this subject (11).

Immunisation

It is important to also understand that some very simple measures significantly reduce the risk of preterm birth.

The first of these is immunisation against influenza virus infection in pregnancy.

Sadly, many pregnant women are either not offered vaccination, or else decline vaccination (13). These women remain vulnerable to a severe viral infection that can precipitate preterm birth.

QUIT Stopping smoking

Another simple and obvious fix to preterm birth is to quit smoking. Smoking is a leading independent risk factor for preterm birth. It can act as a direct risk, and also indirectly, through damage to the placenta, resulting in poor growth of the baby or bleeding that means babies must be delivered early to avoid death in utero.

All pregnant women who smoke should ask for help to stop smoking. Many services are available to help – just ask.

Cervical length screening and treating with progesterone

Another new strategy to prevent preterm birth is to measure the length of the cervix using ultrasound. This measurement can be easily undertaken when women have their 18-20 week ultrasound of the baby’s anatomy.

If the cervix is shorter than expected, there is an increased risk of preterm birth (14). A number of studies have linked the length of the cervix in mid pregnancy to the risk of preterm birth. For population purposes, women with a cervix of 15mm or less at 18 to 24 weeks gestation, have a 50% chance of having a preterm delivery at less than 33 weeks of gestation (14-17).

Women identified with a short cervix on ultrasound can be offered intervention with progesterone therapy or cerclage to reduce the risk of preterm birth.

The evidence for progesterone therapy is promising. Several trials have reported a reduction in preterm birth in women with a short cervix (14-17). The largest trial was called the PREGNANT trial.  In this trial 30,000 women were screened for cervical length and women with a short cervix were prescribed  vaginal progesterone gel (90 mg). There was a  45% reduction in the rate of early preterm birth (18).

Cervical cerclage has also been reported to be effective in treating women with short cervical length (19,20).Cervical cerclage is a small surgical procedure where a tape is inserted and tied around the cervix to strengthen the cervix and prevent premature dilation.

Summary

Preterm birth is a terrifying reality for many families. However, we now have several promising interventions that can hopefully reduce this devastating outcome. Any woman who has had a preterm baby should seek help early in her next pregnancy in order to take advantage of emerging therapies.

References

1. Lawn, J. E., Cousens, S. & Zupan, J. (2005). 4 million neonatal deaths: When? Where? Why? Lancet 365, 891-900.

2. Goldenberg, R. L., Culhane, J. F., Iams, J. D. & Romero, R. (2008). Preterm birth 1: Epidemiology and causes of preterm birth. Lancet 371, 75-84.

3. Shatrov, J. G., Birch, S. C., Lam, L. T., Quinlivan, J. A., McIntyre, S. & Mendz G. L. (2010). Chorioamnionitis and cerebral palsy. Obstet Gynecol 116, 387-392.

4. Hussein, J., Ugwumadu, A, & Witkin, S. S. (2011). Editor’s choice. Brit J Obst Gynaecol 118, i-ii. doi: 10.1111/j.1471-0528.2010.02829.x

5. Kaakoush NO, Mendz GL, Quinlivan JA. New techniques to characterize the vaginal microbiome in pregnancy. AIMS Microbiology 2016, 2(1);55-68.

6. Romero, R, & Mazor, M. (1988). Infection and preterm labor. Clin Obstet Gynecol 31, 553-584.

7. Smaill. F. (2001). Antibiotics for asymptomatic bacteriuria in pregnancy. Chocrane Database Syst. Rev 2, CD000490.

8. Mendz, G. L., Petersen, R., Quinlivan, J. A. & Kaakoush, N. O. (2014). Potential involvement of Campylobacter curvus and Haemophilus parainfluenzae in preterm birth. Br Med J Case Rep pii, bcr2014205282. doi: 10.1136/bcr-2014-205282.

9. Kaakoush, N. O., Quilivan, J. A. & Mendz, G. L. (2014). Bacteroides and Hafnia Infections associated with chorioamnionitis and preterm birth. J Clin Gynecol Obstet 3, 76-79.

10. Quinlivan, J. A., Kaakoush, N. O. & Mendz, G. L. (2014). Acinetobacter species associated with spontaneous preterm birth and histological chorioamnionitis. Br J Med Med Res 4, 5293-5297.

11. Quinlivan JA, Pakmehr S. Fish Oilsas a Population Based Strategy to Reduce Early Preterm Birth. Reproductive System and Sexual Disorders 2013; 2: 116. http://dx.doi.org/10.4172/2161-038X.1000116

12. Makrides M, Gibson RA, McPhee AJ, Yelland L, Quinlivan J, Ryan P, DOMInO Investigative Team, Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. JAMA: The Journal Of The American Medical Association, 2010 Oct 20; Vol. 304 (15), pp. 1675-83; PMID: 20959577 ISSN: 1538-3598.

13. White SW, Petersen RW, Quinlivan JA. Pandemic (H1N1) 2009 influenza vaccine uptake in pregnant women entering the 2010 influenza season in Western Australia MJA 2010; 193 (7): 405-407

14. Hassan SS, Romero R, Berry SM et al. Patients with an ultrasonographic cervical lengh < or = 15 mm have nearly 50% risk of early spontaneous preterm delivery. Am J Obstet Gynecol 2000; 82(6): 1458-1467

15. Heath VC, Southall TR, Souka AP et al. Cervical length at 23 weeks of gestation: prediction of spontaneous preterm delivery. Ultrasound Obstet Gynecol1998; 12(5),312-317.

16. Grimes D, Berghella V. Cervical length and prediction of preterm delivery. Curr Opin Obstet Gynecol 2007; 19(2): 191-195.

17. Romero R. Vaginal progesterone to reduce the rate of preterm birth and neonatal morbidity: a solution at last. Women’s Health 2011; 7(5): 501-4.

18. Hassan SS, Romero R, Vidyadhari D et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomised, double blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2011; 38(1): 18-31.

19. Bennett P. Preterm Labour. In: Dewhurst’s Textbook of Obstetrics & Gynaecology, Blackwell Publishing, 2008.

20. Alfirevic Z, Owen J, Carreras Moratonas E et al. Vaginal progesterone, cerclage or cervical pessary for preventing preterm birth in asymptomatic singleton pregnant women with history of preterm birth and a sonographic short cervix. Ultrasound Obstet Gynecol 2012 18 sept epub ahead of print. DOI : 10.1002/uog.12300.

 

 

 

 

 

 

 

 

 

 

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