Developmental abnormalities due to fetus and placenta, study finds


A recent study shows that abnormal development is controlled by the genetics of the fetus and placenta, rather than the intrauterine environment.

The genetics of the fetus and placenta, and not the intrauterine environment, are what control abnormal development, according to research published in the journal Placenta. The study was conducted by Harvey Kliman, MD, PhD, a research scientist in the department of obstetrics, gynecology & reproductive services at the Yale School of Medicine and colleagues. Kliman also is the director of the Reproductive and Placental Research Unit at Yale School of Medicine.

In an interview with Contemporary OB/GYN®, Kliman said the most important takeaway from the study for providers in practice is that pregnancy losses or complications are rarely the result of actions or behaviors of the mother. “They are almost always the result of intrinsic developmental and biological processes out of the mother’s control. In short: it is not the mother’s fault,” he emphasized.

For the next steps to be taken in this area of research, Kliman said that a better understanding of the specific genetic abnormalities that result in trophoblast inclusions is needed. He added that “it is essential for providers to always make sure the placenta is sent to the pathology department whenever there are any complications or untoward events in the pregnancy, delivery, or related to the newborn.”

Researchers gathered placental data from 48 sets of identical and non-identical twins. Non-identical twins share half of their DNA sequence, while identical twins share the same DNA sequence. Researchers placed placentas into groups by zygosity: monozygotic (MZ), dizygotic (DZ), or unknown zygotic (UZ) to look for trophoblast inclusions (TIs), which are linked with pregnancy loss and aneuploidy, to see if the cause is related to genetics. TIs mark developmental abnormalities, researchers said.1

Kliman and colleagues reported that identical twins had a similar frequency of TIs, while non-identical twins had very different TI counts. The study showed identical twins often had the same quantity of TIs or were within 1 of having identical TI counts. Non-identical twins had TI counts that averaged different by 4 or 5. Researchers said, “MZ twins are concordant for trophoblast inclusions, while DZ twins are not.”1

Researchers reported that the mean difference in total TIs per slide for DZ twins was significantly greater than that for MZ twins.1 They also said that the mean difference in the total TIs per slide for the UZ group was also significantly greater than the total TIs per slide between MZ pairs.1

According to the Centers for Disease Control (CDC), 1 out of 33 children is diagnosed with a birth defect in the United States, and that amounts to 120,000 per year. Mothers often blame themselves for these defects, according to the researchers.

“This work suggests that developmental abnormalities are much more likely to be due to the genetics of the child, and not the mother's fault," Kliman said in a press release.

Inspiration for the study came from lead author Julia Katz, a medical student at Hofstra University who attended Yale as an undergraduate. She and her brother Jesse are non-identical twins. Jesse was born with several congenital abnormalities and was underweight, while Julia was born without these abnormalities. “I had a lot of guilt, growing up, about why my twin had certain conditions that I didn't. I think mothers also tend to blame themselves,” she said in the release.

Katz asked Kliman following a lecture at Yale about the difference between herself and her twin, which led to a discussion about Katz wanting to obtain information on her and her twin’s genetics, including viewing her own placental slide from when she was born.

The discussion motivated Kliman to conduct the study with Katz’s involvement.

"Julia's need to resolve this burden is what propelled our study," Kliman said. "Hopefully, this finding will help many other people, as well."

"This experience has shown me that if you have a question, ask it. And if you don't get an answer, try to answer it yourself," Katz said in the release.


  1. Katz J, Holzer PH, Kliman HJ. Genetics, not the uterine environment, drive the formation of trophoblast inclusions: Insights from a twin study [published online ahead of print, 2021 Apr 18]. Placenta. 2021;S0143-4004(21)00128-4. doi:10.1016/j.placenta.2021.04.010
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