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Evidence Library · The baseline

Four out of five major birth defects have no known cause

In 5,504 major birth defects, a definite cause could be assigned in 20.2%. The remaining 79.8% had no identifiable cause at all.

This is the most important fact in this whole stage, and almost nobody is told it.

The Utah study did something unusual. It did not just count birth defects; it tried to assign a cause to each one. Its finding, word for word:

Definite cause was assigned in 20.2% (n=1114) of cases: chromosomal or genetic conditions accounted for 94.4% (n=1052), teratogens for 4.1% (n=46, mostly poorly controlled pregestational diabetes), and twinning for 1.4% (n=16, conjoined or acardiac). The 79.8% (n=4390) remaining were classified as unknown etiology; of these 88.2% (n=3874) were isolated birth defects.

Nearly four in five major birth defects, in a modern US population, had no identifiable cause. Not chromosomal. Not a single gene. Not a drug, an exposure or an infection. Nothing.

Three things follow, and they matter more than any test result in this stage.

Most birth defects are not screened for. A blood test that looks at chromosome numbers is looking at a slice of a slice.

Most birth defects are not preventable. Not by diet, not by supplements, not by doing everything right.

Most birth defects are nobody's fault. Least of all yours.

Two numbers, side by sideMajor birth defects of all kinds occur at roughly 300 per 10,000 live births (CDC, about 3%). The three conditions the standard blood test is principally sold on occur at these rates, from US surveillance across 13 programs for 2016 to 2020, adjusted for maternal race and ethnicity:

Trisomy 21, 15.55 per 10,000 (about 1 in 643). Trisomy 18, 3.00 per 10,000 (about 1 in 3,336). Trisomy 13, 1.44 per 10,000 (about 1 in 6,967).

Those two sets of figures come from different sources with different definitions of what counts as a birth defect. They should be read as a gap in scale, not turned into a ratio or a percentage. The point is visible without arithmetic.
Age changes the odds, and by a lotFrom the same surveillance, trisomy 21 at birth by maternal age, per 10,000 live births: 6.42 at ages 20 to 24, 7.70 at 25 to 29, 12.36 at 30 to 34, 38.98 at 35 to 39, and 120.74 at 40 and over.

The same blood test, run on the same machine, gives very different odds after a positive result in a 24-year-old and a 41-year-old. That is the whole story of the next few topics.
Say this out loud"If something is found, will we be able to say what caused it?"

"Is there anything I could have done differently? I would like a straight answer."
Where this comes from:
467. Centers for Disease Control and Prevention. About birth defects. Atlanta (GA): CDC.
469. Feldkamp ML, Carey JC, Byrne JLB, Krikov S, Botto LD. Etiology and clinical presentation of birth defects: population based study. BMJ. 2017;357:j2249.
471. Stallings EB, Isenburg JL, Rutkowski RE, Kirby RS, Nembhard WN, Sandidge T, et al. National population-based estimates for major birth defects, 2016-2020. Birth Defects Res. 2024;116(1):e2301.

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