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Older Maternal Age Tied to Lower Risk of Fetal Anomalies

— NEW ORLEANS -- Women 35 and older seemed to have a lower risk for major congenital abnormalities compared with younger women, researchers reported here.

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NEW ORLEANS -- Women 35 and older seemed to have a lower risk for major congenital abnormalities compared with younger women, researchers reported here.

Advanced maternal age (≥35) was associated with a lower risk for major fetal anomalies, in the absence of aneuploidy, when compared with women under age 35 (1.7% versus 2.6%, adjusted odds ratio 0.59, 95% CI 0.52-0.66, P<0.001), according to, of Washington University School of Medicine in St. Louis, and colleagues.

Action Points

  • This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

"Everyone, including my co-authors, were a little surprised at the findings," Goetzinger told 51˶ at the annual meeting of the Society of Maternal-Fetal Medicine where the study results were presented.

"There's nothing magic that happens at age 35. The risk of chromosomal abnormalities, like Down syndrome, goes up, but the 35 cutoff was based on older data," Goetzinger said.

However, she cautioned that "this is an initial finding and it should be confirmed in future studies."

Goetzinger noted that there are very few studies in medical literature that look at whether there is an increased risk for major congenital anomalies in the absence of chromosomal malformation. And many of the studies out there have conflicting results.

For example, the risk of having a miscarriage with amniocentesis was roughly the same as having a child with Down syndrome, but that newer data shows the risk of miscarriage to be much lower.

"But we're still kind of stuck on this age 35," Goetzinger said.

Her group looked at the routine second trimester ultrasound screenings of 76,156 euploid fetuses over the course of 18 years at Washington University Physicians, and the data were split into younger than 35 and 35 and older.

Overall, 2.4% (1,804) of those screened had a major anomaly. But contrary to previous beliefs, only 1.7% of women of advanced maternal age had a fetus with a major anomaly compared with 2.6% of younger women (aOR 0.59, 95% CI 0.52-0.66, P<0.001).

After adjustments for alcohol use, gestational diabetes, pre-gestational diabetes, African-American race, tobacco use, and parity for abdominal wall defect only, the advanced maternal age mothers were less likely to have the following major fetal anomalies compared with women under 35:

  • Central nervous system: 0.4% versus 0.7% (aOR 0.49, 95% CI 0.38-0.62, P<0.001)
  • Renal: 0.2% versus 0.3% (aOR 0.49, 95% CI 0.38-0.62, P<0.001)
  • Abdominal wall defect: 0.1% versus 0.3% (aOR 0.23, 95% CI 0.13-0.40, P<0.001)

Cardiac anomalies were equal between groups (0.4% versus 0.4%, P=0.56).

Goetzinger said it was possible that with advancing egg age/advancing maternal age, fertilization events that were going to result in a baby with a major malformation may end up as a failed pregnancy or early miscarriage, and those pregnancy events that are going to result in a normal baby progressing.

"Survival of the fittest," Goetzinger said.

"These findings may suggest that the "all or nothing" phenomenon plays a more robust role in embryonic development with advancing oocyte age, with anatomically normal fetuses being more likely to survive," her group explained.

Goetzinger also suggested in her presentation that women of advanced maternal age may pay greater attention to healthy behaviors (prenatal vitamins, diet, exercise) and abstain from unhealthy behaviors compared with younger women.

Study limitations included the retrospective design, data from a referral population, lack of paternal age, and rare outcomes, making it difficult to pin down the exact cause or reason for the findings, Goetzinger stated.

She pointed out that genetic testing will allow for a greater understanding of other genetic abnormalities as opposed to the classic risks that have been talked about for years.

"I don't want to downplay the risks of genetic abnormalities and other maternal risks of pregnancy with advancing ages, but I would urge my peers to counsel their patients that the [odds] of having a normal child is higher [than previously thought]," she said.

For the next step, Goetzinger said her group intends to look at the data more in depth with regard to age groups and specific anomalies instead of organ systems in general.

Disclosures

Goetzinger and co-authors did not report conflicts of interest.

Primary Source

Society for Maternal-Fetal Medicine

Goetzinger KR, et al "Advanced maternal age and the risk of major congenital anomalies: survival of the fittest?" SMFM 2014; Abstract 34.