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Preterm Birth: Vitamin D and Membrane Microfractures

​​Preterm births are a major problem to neonatal health world wide. Being born before 37 weeks of gestation is considered the second largest cause of death in children under five years of age, with about a million baby’s dying each year of direct complications due to preterm birth. It is estimated that in 2010 almost 15 million baby’s were born preterm, which boils down to 11,1% of all live births in that year. Two recent studies put the spotlight on some of the factors that might play a role.

Vitamin D

One factor frequently associated with preterm birth is the vitamin D status of the mother. Research suggests an inverse relation: the lower the concentration of calcifediol (also known as 25(OH)D) in the woman’s blood, the higher the risk of a preterm birth. A recent study, carried out at the Medical University of South Carolina (MUSC) in Charleston, seems to confirm previous studies that indicate an association between vitamin D status and preterm birth (PTB).

Previous research pointed towards a positive influence on the preterm birth rate of a calcifediol level of 40 ng/ml or more. In one of the studies, women with those calcifediol levels were found to have a 59% lower risk of PTB than women with a level of 20 ng/ml or less. In recent years, this lead the MUSC to adopt a gradually expanding policy of testing pregnant women’s vitamin D status, providing education on vitamin D and promoting the use of supplements.

​​In their recent study, the MUSC aimed to see whether the results of the previous studies could be replicated. In short, they could. Even when taking into account some factors with regard to socioeconomic status, the results looked remarkably similar. Of the somewhat over 1000 women included in the study, those with calcifediol levels of 40 ng/ml or more were on the whole found to have a 62% lower risk of giving birth prematurely when compared to those whose calcifediol level was 20 or lower. More or less similar percentages were found among the different ethnic groups included in the study. For women who had previously had a preterm labour, those with a level of 40 or more had 80% less risk of a recurrent preterm birth, as opposed to the group with a level of 20 or less.

As with any study, there were some limitations to this one. Nevertheless, it does point towards the importance of monitoring and, if necessary, enhancing the Vitamin D status of pregnant women. This is in line with a recently updated NICE guideline on the use of vitamin D supplements.

Amniochorionic Membranes

Considering that an estimated one-third of all preterm births is caused by Preterm Premature Rupture of Membranes (PPROM), it is no surprise that researchers show an interest in amniochorionic membranes and the role they play in gestation and parturition. In a recent study, researchers have reported on their exploration of methods and techniques to compare the structural changes in amniochorionic membranes of term and preterm births. Innovative microscopic and 3D imaging techniques were applied to study the structural characteristics of the membranes. This lead to the finding that “microfractures”, structural defects in amniochorionic membranes, are “likely developed due to structural alteration created by biochemical and cellular levels changes”.

​​Amniochorionic membranes grow and expand due to fetal growth. This, the researchers think, leads to the development of microfractures, which involves a kind of local inflammation that triggers a restoration mechanism to reseal and remodel the membrane. They suggest that under certain conditions or circumstances this restoration mechanism can fail, which leads to a premature rupture. Factors involved may be the number of fractures or certain pathologies.

The researchers discovered that there was an increase in the number of microfractures in both membranes that were exposed to oxidative stress in vitro and in preterm premature ruptured membranes (a possible explanation for the latter being that pPROM is associated with “increased oxidative stress”). Risk factors that are thought to contribute to oxidative stress are infection, poor nutrition, high BMI and behavioral risk.

At Midwife Without Borders, we’re looking forward to seeing the results of the follow up studies in this highly interesting field. These will be looking into the impact of other risk factors contributing to oxidative stress as well as pathological factors, and the part they might play in forming microfractures, and the remodeling or breakdown of the membranes.

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Blencowe, H. et al. (2012). National, regional and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 379(9832): 2162-72. DOI: 10.1016/S0140-6736(12)60820-4

Blencowe, H. et al. (2013). Born Too Soon Preterm Birth Action Group. Born too soon: the global epidemiology of 15 million preterm births. Reprod. Health. 10(Suppl 1): S2. DOI: 10.1186/1742-4755-10-S1-S2

Centers for Disease Control (s.d.). Preterm Birth. See:

McDonnel, S. et al. (2017). Maternal 25(OH)D concentrations ≥40 ng/mL associated with 60% lower preterm birth risk among general obstetrical patients at an urban medical center. DOI: 10.1371/journal.pone.0180483

National Institute for Health and Care Excellence (2017). Vitamin D: supplement use in specific population groups. See:

Richardson, L. et al. (2017). Discovery and Characterization of Human Amniochorionic Membrane Microfractures. The American Journal of Pathology. DOI: 10.1016/j.ajpath.2017.08.019

Photo credits

Photo 1: CCBY Sarah Hopkins, Flickr, see:

Photo 2: CCBY Alenta Getman, Flickr, see:

Photo 3: By drsuparna -, CC BY-SA 2.0,

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