Miscarriage is really common. About 10-20% of known conceptions miscarry; the real rate is probably higher, perhaps as high as 50%, as many women miscarry without even knowing they’re pregnant, usually in the first three weeks of pregnancy. The most common causes of miscarriage have to do with mutations in the fetus, especially chromosomal abnormalities. So reducing the risk of miscarriage is an overlapping project with increasing fertility, and also with increasing the chance of having a healthy baby without birth defects. All of these things roughly correlate.
So, what increases the risk of miscarriage?
- Antiphospholipid syndrome. This is an autoimmune disorder affecting 1-5% of the healthy population, in which the body attacks certain proteins binding to cell membranes, causing a high risk of blood clots.This causes miscarriage in 90% of pregnancies. (Blood clots are Bad News in pregnancy; in general, anything associated with excessive clotting increases the risk of the most common Bad Things like miscarriage, low-birth-weight fetuses, and preeclampsia.) Antiphospholipid syndrome is more common in people with lupus (15-25% of SLE patients also have APS) and it has a strong genetic component. APS can be treated with blood thinners such as aspirin, warfarin, and/or heparin. These triple the probability of conception in women with APS and a history of miscarriage.
- Maternal and paternal age. The risk really starts to go up around age 35 or so; e.g. couples where both the mother and father are age 35-40 have a risk of miscarriage 3.87x baseline.
- Maternal folate deficiency. High homocysteine levels and low folate levels were associated with a 3.6x and 2.1x increase, respectively, in the risk of miscarriage. These are signs of a folic acid deficiency and can be prevented by taking a folic acid supplement. MTHFR polymorphisms (C677T and A1298C) are associated with a 14.2x risk of miscarriage; MTHFR is the enzyme that breaks down folate. That is, if you can’t process folate properly, you’re also at risk of miscarriage. This suggests (though there’s not direct evidence of this) that pregnant women with MTHFR mutations should be taking L-Methylfolate instead of regular folic acid, since L-Methylfolate is one step downstream in metabolism from folate; if you can’t methylate folate yourself, it may make sense to consume it “pre-methylated.”
- Excessive maternal exercise. Heavy exercise during pregnancy increases risk of miscarriage. Women who exercised >300 min/week (e.g. a daily six-mile run) while pregnant had a risk of miscarriage 3.29x as high as women who didn’t exercise at all.
- Maternal prothrombic genes. Mutations in maternal blood clotting genes (FVL or FIIG20210A) cause a 3.19x increase in the risk of miscarriage in white women. (These mutations are rare in nonwhite women.) This is part of the same pattern of “blood clots are bad for you.” In particular, prothrombotic genes are a risk factor for recurrent miscarriages.
In terms of what you can do to prevent miscarriages, the big ones are:
- have kids by your mid-thirties
- take your folate supplements (or perhaps L-methylfolate if you’re an MTHFR mutant)
- don’t overdo the high-impact exercise
Smoking, drinking, and caffeine all increase the risk of miscarriage, but you don’t get big effect sizes until you’re looking at really high consumption; you have to drink 8 cups of coffee a day to get up to a 1.84x risk of miscarriage , smoke 20 cigarettes a day to get up to 1.6x risk, and drink 21+ drinks a week to get up to 1.82x risk. (Emily Oster, in Expecting Better, notes that there’s a confounding effect for coffee: pregnant women who are nauseous are less likely to miscarry, and nausea makes coffee less appealing.)
There’s a dose-response relationship for all these substances, of course, and alcohol and tobacco are unhealthy for lots of additional reasons. (As we’ll see later, smoking increases the risk of birth complications.)
Likewise in the smallish effect size category is being underweight; maternal BMI < 18.5 causes a 1.72x increase in miscarriage rates.
So, arguably, women trying to avoid miscarriage should also:
- avoid caffeine, tobacco, and alcohol
- get up to a healthy weight
Preemptively taking aspirin if you don’t have APS does not reduce the risk of miscarriage. A fair number of the genetic causes of recurrent miscarriage seem to be genuinely outside your control, at least for now.
Gezer, Sefer. “Antiphospholipid syndrome.” Disease-a-month 49.12 (2003): 696-741.
de La Rochebrochard, Elise, and Patrick Thonneau. “Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study.” Human Reproduction 17.6 (2002): 1649-1656.
Nelen, Willianne LDM, et al. “Homocysteine and folate levels as risk factors for recurrent early pregnancy loss.” Obstetrics & Gynecology 95.4 (2000): 519-524.
Rymol, Lars, et al. “Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated alleles in spontaneously aborted embryos.” European Journal of Human Genetics 10 (2002): 113-118.
Madsen, M., et al. “Leisure time physical exercise during pregnancy and the risk of miscarriage: a study within the Danish National Birth Cohort.” BJOG: An International Journal of Obstetrics & Gynaecology 114.11 (2007): 1419-1426.
Lissalde‐Lavigne, G., et al. “IN FOCUS: Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case–control ‘NOHA first’study.” Journal of Thrombosis and Haemostasis 3.10 (2005): 2178-2184.
Feodor Nilsson, S., et al. “Risk factors for miscarriage from a prevention perspective: a nationwide follow‐up study.” BJOG: An International Journal of Obstetrics & Gynaecology 121.11 (2014): 1375-1385.
Armstrong, Ben G., Alison D. McDonald, and Margaret Sloan. “Cigarette, alcohol, and coffee consumption and spontaneous abortion.” American Journal of Public Health 82.1 (1992): 85-87.
Maconochie, N., et al. “Risk factors for first trimester miscarriage—results from a UK‐population‐based case–control study.” BJOG: An International Journal of Obstetrics & Gynaecology 114.2 (2007): 170-186.
Rai, R., et al. “Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies).” Bmj 314.7076 (1997): 253.
Rai, Raj, et al. “Recurrent miscarriage—an aspirin a day?.” Human reproduction 15.10 (2000): 2220-2223.
Nisio, M., L. W. Peters, and S. Middeldorp. “Aspirin or anticoagulants for the treatment of recurrent miscarriage in women without antiphospholipid syndrome.” The Cochrane Library (2005).