Selective chromosome analysis in couples with two or more miscarriages: case-control study

TLDR

The study aimed to determine which maternal age and family‑history factors modify the likelihood that couples with two or more miscarriages carry a chromosomal abnormality. A nested case‑control study was conducted across six Dutch genetics centres, comparing 279 carrier couples with 428 non‑carrier controls to identify independent predictors of carrier status. Four predictors—maternal age at the second miscarriage, ≥3 prior miscarriages, ≥2 miscarriages in a sibling, and ≥2 miscarriages in a parent—raised carrier‑status probability from 0.5 % to 10.2 %, suggesting that targeted chromosome testing could reduce unnecessary analyses and costs.

Abstract

<h3>Abstract</h3> <b>Objective</b> To identify additional factors, such as maternal age or factors related to previous reproductive outcome or family history, and the corresponding probability of carrying a chromosome abnormality in couples with two or more miscarriages. <b>Design</b> Nested case-control study. <b>Setting</b> Six centres for clinical genetics in the Netherlands. <b>Participants</b> Couples referred for chromosome analysis after two or more miscarriages in 1992-2000; 279 carrier couples were marked as cases, and 428 non-carrier couples served as controls. <b>Main outcome measures</b> Independent factors influencing the probability of carrier status and the corresponding probability of carrier status. <b>Results</b> Four factors influencing the probability of carrier status could be identified: maternal age at second miscarriage, a history of three or more miscarriages, a history of two or more miscarriages in a brother or sister of either partner, and a history of two or more miscarriages in the parents of either partner. The calculated probability of carrier status in couples referred for chromosome analysis after two or more miscarriages varied between 0.5% and 10.2%. <b>Conclusions</b> The probability of carrier status in couples with two or more miscarriages is modified by additional factors. Selective chromosome analysis would result in a more appropriate referral policy, could decrease the annual number of chromosome analyses, and could therefore lower the costs.