What triggers Preterm Birth and Miscarriages?

By Katherine Bethell 

Pregnancy is a complicated process, the vasculature system of a mother changes completely to support the growth of a foetus, with labor being equally complicated and dangerous. This means it poses a high risk to both the mother and baby’s life. There are several different things that may go wrong throughout the nine months of pregnancy and the process of labor. The high proportion of lost pregnancies due to miscarriage or preterm birth may be due to a variety of problems which will be explored in this article.

Miscarriage is defined as the spontaneous loss of the foetus before 20 weeks of gestation, the majority of miscarriages will occur before 10 weeks (Branch et al., 2010). 

Early miscarriages tend to be due to chromosomal abnormalities in the gametes which results in a non-viable foetus that is then lost. Chromosomal aneuploidy also explains why older women, usually aged over 35 years, find it more difficult to get pregnant because older oocytes appear to have a greater risk of aneuploidy that will result in an early miscarriage (Branch et al., 2010). Another potential cause of miscarriages is the anatomical shape of uterus and reproductive system of the female, congenital uterine malformations were detected in approximately 15% of women who suffered recurrent miscarriage. Anatomy is important and may result in a miscarriage because of vascular insufficiency, if the foetus is not receiving enough nutrients and oxygen through maternal blood the pregnancy is unlikely to continue and a miscarriage may happen (Garrido-Gimenez C. and Alijotas-Reig J., 2015). 

Both miscarriage and preterm birth can be caused by an infection in the reproductive tract. Genital tract infections will allow microorganism to colonise the upper reproductive tract where they will be recognised by toll-like receptors, pro-inflammatory pathways are then activated which involve the release of pro-inflammatory cytokines and chemokines. Usually these molecules, are protective and stimulate an immune response but in this case, they may stimulate the uterus to contract and remodel extracellular matrices causing cervical softening and labor or miscarriage if it occurs before 20 weeks of gestation (Nadeau H et al., 2015)(Giakoumelou S. et al., 2016). 

Preterm birth is defined as the birth of a baby before 37 weeks of pregnancy. Over 15 million babies are born prematurely every year, approximately occurring 1 in every 10 pregnancies. Preterm birth is the leading cause of infant mortality (death of children under the age of five) as it can lead to children having severe respiratory disorders, as the lungs are not properly developed before birth, and some neurological disorders (Sykes L. et al., 2015). 

Two thirds of preterm births occur spontaneously without a proven scientific cause. As mentioned earlier birth whether at term or earlier relies on the activation of inflammatory pathways within the reproductive tract; an inflammatory cascade produces molecules which results in a softened cervix, contractions and the rupturing of chorioamniotic membranes, also known as waters breaking, allowing for birth to occur (Sykes L. et al., 2015). Currently, research is being conducted to try and find a conclusive cause to preterm birth. One of the potential causes which a lot of research is being conducted in at the moment is the link between the vaginal microbiome and preterm birth. 16S ribosomal RNA sequencing has found an association between bacterial vaginosis and preterm birth; bacterial vaginosis is a disorder characterised by the reproductive tract being heavily populated by anaerobic bacteria rather than the health-promoting lactobacillus species which usually colonise the vagina. A non-optimal vaginal microbiota appears to act as a predictor of preterm birth, although the mechanism behind how bacteria can activate the pro-inflammatory and pro-labor pathways remains unknown (Fettweis J. et al., 2019). 

Sometimes a birth is induced before 37 weeks of pregnancy, and is called a medically indicated preterm birth, this occurs is there is a risk to either the mother or baby and a preterm delivery would improve the outcome for both parties involves. The birth may occur through early labor induction or caesarean delivery. Serious medical conditions associated with the pregnancy which cause risk of life are the main reason for a medically indicated birth, for example pre-eclampsia, placental abruption and intrauterine growth restriction can put both the mothers and baby’s life at risk; in circumstances such as these it is better for a preterm birth to occur before it is too late (Ananth C and Vintzileos A.  2007). Autoimmune diseases, such as systemic lupus  erythematosus, may result in a medically indicated preterm birth also as the chronic inflammation and immune dysregulation associated with autoimmune diseases can increase the risk of activation of pro-inflammatory pathways in the reproductive tract which leads to preterm birth; hence it may be safer if patients chose to have a medically induce preterm birth before spontaneously starting labor in a less controlled environment (Kolstad K. et al., 2017). 

Two of the major risks associated with pregnancy are miscarriage and preterm birth as both pose significant dangers to both mother and baby. In this article the multiple causes of both disorders were explored, however more research needs to be conducted as there remains several unknowns within the field. 

References:

Branch D, Gibson M, Silver R. 2010. Recurrent Miscarriage. The New England Journal of Medicine. 363: 1740-1747. Available from: DOI:10.1056/NEJMcp1005330

Garrido-Gimenez C, Alijotas-Reig J. 2015. Recurrent Miscarriage: Causes, Evaluation and Management. British Medical Journal. 91(1073):151-162. Available from: DOI: 10.1136/postgradmedj-2014-132672

Nadeau H, Subramaniam A, Andrews W. 2016. Infection and Preterm Birth. Seminars I Fetal and Neonatal Medicine. 21(2): 100-105. Available from: DOI: 10.1016/j.siny.2015.12.008

Giakoumelou S, Wheelhouse N, Cuschieri K, Entrrican G, Howie S, Horne A. 2016. The Role of Infection in Miscarriage. Human Reproduction Update. 22(1): 116-133. Available from: DOI: 10.1093/humupd/dmv041

Sykes L, Thomson K, Boyce E, Lee Y, Rasheed Z, MacIntyre D et al. 2015. Sulfasalazine augments a pro-inflammatory response in interleukin-1β- stimulated amniocytes and myocytes. Immunology. 146(4): 630-644. Available from: DOI: 10.1111/imm.12534

Fettweis J, Serrano M, Buck G. 2019. The Vaginal Microbiome and Preterm Birth. Nature Medicine. 25: 1012-1021. Available from: DOI: 10.1038/s41591-019-0450-2

Ananth C, Vintzileos A. 2008/ Medically Indicated Preterm Birth: Recognising the importance of the problem. Clinics in Perinatology. 35(1): 53-67. Available from: DOI: 10.1016/j.clp.2007.11.001

Kolstad K, Mayo J, Chung L, Chaichian Y, Kelly V, Druzin M t al. 2017. Preterm Birth phenotypes in Women with Autoimmune Diseases. Arthritis Rheumatol. 69 (supp l10). Available from:  https://acrabstracts.org/abstract/preterm-birth-phenotypes-in-women-with-autoimmune-diseases/. Accessed March 15, 2021.

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