Increased nuchal translucency linked to progesterone therapy

1. Women receiving progesterone therapy in the first trimester were more likely to have fetuses with increased nuchal translucency at 11-14 weeks gestation.

2. Formulation, dosage and route of administration of progesterone were not associated with significant differences in NT.

Evidence Rating Level: 2 (Good)  

Study Rundown: Nuchal translucency (NT) is a biomarker used in pregnancy in conjunction with maternal beta human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels to screen for Down syndrome. NT uses ultrasound to measure the thickness of the translucent space at the posterior fetal neck at 10-14 weeks. The combination of NT, β-hCG and PAPP-A is able to detect 85% of fetuses with Down syndrome, with a false positive rate of 5% and is superior to the use of NT alone.

While evidence supporting the use of progesterone therapy is limited to women using assisted reproductive technology (ART) and those with a history of or at high risk for preterm birth, it remains common practice to also use progesterone to prevent miscarriage and treat threatened abortion. Prior work suggests progesterone may influence vascular smooth muscle relaxation and alter placental blood flow. In the present work, authors found that progesterone therapy was associated with increased NT levels. This finding represents the first clinical evidence that exogenous progesterone may directly affect the developing fetus.

Limitations of the study include observational design, which precludes the authors’ assumption of causality between progesterone therapy and increased NT, and exclusion of women with chronic health issues, limiting the generalizability of the study results. Findings call for exploration of the implied associations herein, with particular attention paid to determining whether progesterone-related increases in NT are also associated with an increased risk of Down syndrome in offspring.

Click to read the study in AJOG

Relevant Reading: Ultrasound screening for fetal major abnormalities at 11-14 weeks

In-Depth [prospective cohort study]: This study evaluated NT at 11-14 weeks gestation among 1090 women receiving progesterone therapy for ART, prevention of miscarriage and treatment of threatened abortion, and 2626 women not receiving progesterone treatment. The primary outcome of interest was NT.

Nuchal translucency was higher among women in the progesterone treatment group (p<0.05). A similar relationship was observed among women at low risk for aneuploidy and other fetal abnormalities, defined as women with NT < 2.5mm (p < 0.05). Formulation, dosage and route of administration of progesterone were not associated with significant differences in NT.

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