Preconception carrier screening
The anchor question: does this person or couple carry a recessive or X-linked condition they could pass on, and will they know before a pregnancy rather than during one? ACMG recommends offering a tier-3 panel to everyone who is pregnant or planning a pregnancy, and prefers preconception screening to prenatal.1
Who this cohort covers
Adults and couples planning a pregnancy, and patients early in a pregnancy until obstetric care takes it over. People screened years ago on a smaller panel, and anyone with a new reproductive partner, since screening should be readdressed when the partner changes.1 Carriers already known from a relative's diagnosis. It also covers the carrier's own health, because some carrier results matter to the carrier: an FMR1 premutation carries a 20% risk of primary ovarian insufficiency in women and a later risk of FXTAS,2 women who carry an X-linked condition may have symptoms of it,1 and CFTR heterozygotes may be at increased risk of respiratory problems and pancreatitis.3
Couple-based screening finds couples who had no reason to suspect anything. In Australia's Mackenzie's Mission, 9,107 couples were screened for at least 1,281 genes; 175 (1.9%) were newly identified as having an increased chance of an affected child, 76.6% of those couples used or planned a reproductive intervention, and 98.9% of participants found screening acceptable.4 Ancestry-based screening misses a good share of this. In a model of 346,790 screened individuals, the guideline panels of the time found 6% of the affected pregnancies an expanded panel found in East Asian couples, and 87% in African or African American couples.5
ACOG accepts ethnic-specific, panethnic and expanded strategies as long as a practice offers one consistently to every patient.6 ACMG and NSGC favor a single panel for everyone over ancestry-based selection.1 7 We follow ACMG: one tier-3 panel, offered to everyone, before conception when we can.
Care map
| Role | Year 1, Establish | Year 2, Treat | Year 3, Sustain |
|---|---|---|---|
| Anchor | Ask about pregnancy plans at routine visits and offer screening before conception; any patient may decline.1 8 Three-generation pedigree, consanguinity, ancestry, known carriers in the family. One standard offer for every patient.6 | After a positive result: partner testing, then genetic counseling if both partners carry.8 Write down the reproductive plan the couple chooses. | Readdress screening with a new partner.1 Follow the carrier's own health where the result calls for it. |
| Genetics | A tier-3 panel: conditions with a carrier frequency of 1 in 200 or higher, 97 autosomal recessive and 16 X-linked genes on the ACMG list.1 Confirm the panel includes FMR1 repeat sizing and SMN1 copy number, which take dedicated assays.2 9 Confirm it calls HBA1 and HBA2 deletions, since most alpha-thalassemia is deletional and the locus is technically complex.1 Tier 4 when the couple is consanguineous (second cousins or closer) or the family history calls for it;1 consanguineous couples received about 10-fold more increased-risk reports in Mackenzie's Mission.9 | Partner testing after a positive result, or both partners screened together from the start.1 8 Residual risk is never zero; counsel both partners on it.1 6 | Cascade: carriers are encouraged to tell relatives, who may carry the same variant.8 |
| Specialists | Genetic counseling before testing when there is a family history of a genetic condition or concern for one.6 | For an at-risk couple: genetic counseling,8 then reproductive endocrinology for IVF with preimplantation testing or maternal-fetal medicine for prenatal diagnosis, as the couple chooses.10 | FMR1 premutation carriers: gynecology or reproductive endocrinology to talk through ovarian function and family-planning timing, given the 20% risk of primary ovarian insufficiency in women.2 |
| Diagnostics | Screen couples from populations with a high carrier rate for the alpha-thalassemia two-gene deletion before or early in pregnancy.12 | Prenatal diagnosis or preimplantation testing where the couple chooses it.10 | |
| Therapies | IVF with preimplantation genetic testing where chosen.10 | ||
| Behavioral health and nutrition | Pretest counseling on what a positive result would mean, and the option to decline.8 | An increased-chance result raises anxiety. In Mackenzie's Mission it eased toward baseline over three to five years, with low decision regret and low decisional conflict.4 11 Offer support early. | As needed. |
| Community | Patient organizations for the condition, for at-risk couples who want them. | A family letter carriers can send to relatives. |
Visit one
The map above is the evidence. This is what to do with the patient in the room. Each line comes from the Year 1 column and carries the same citations.
| Ask | Pregnancy plans and timing. Any prior carrier screening: which lab, which panel, which year. Three-generation pedigree: intellectual disability, early childhood deaths, known carriers, and early menopause in female relatives, which can flag an FMR1 premutation.2 Consanguinity. Ancestry. Whether the partner can be tested. |
| Examine | Nothing on examination changes the panel; the history does the work. |
| Order | A tier-3 panel for the patient, or for both partners together.1 Confirm FMR1 repeat sizing and SMN1 copy number are included.2 9 Tier 4 for consanguinity or a relevant family history.1 For couples from populations with a high alpha-thalassemia carrier rate, screen before or early in pregnancy and confirm the panel calls HBA1 and HBA2 deletions.1 12 |
| Refer | Genetic counseling before testing when the family history is positive,6 and for every couple who both carry.8 Where: the counselor, esoteric assays and specialist rosters. |
| Tell the patient | Screening is optional.8 A carrier result in one partner matters for a pregnancy when the other partner carries the same condition, or when the condition is X-linked. A negative result lowers the chance of being a carrier but never to zero.1 Some carrier results matter for the carrier's own health.1 2 Relatives may carry the same variant.8 |
| Document | Lab, panel name, gene count and date; each partner's result; the residual-risk statement; the reproductive plan; the cascade plan; and a note to readdress screening with a new partner.1 |
Roster for this cohort
Drawn from the counselor roster (preconception and prenatal genetic counselors who take cash-pay visits), the esoteric assays roster (carrier-screening labs that publish a cash price, cover the ACMG tier-3 list and run FMR1 and SMN1 assays), the specialist roster (maternal-fetal medicine, reproductive endocrinology) and the clinical expertise roster (variant interpretation when a partner's result comes back uncertain). Forming; members propose and vet entries in the cohort's Slack channel.
Readings
- Gregg AR, et al. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the ACMG. Genet Med. 2021. The tier system and the gene list.
- ACOG Committee Opinions 690 and 691 (2017), and the NSGC practice guideline on expanded carrier screening (reference 7).
- GeneReviews: FMR1 Disorders (updated 2024), Spinal Muscular Atrophy (updated 2026), Cystic Fibrosis (updated 2026), Alpha-Thalassemia (updated 2026). University of Washington.
References
- Gregg AR, Aarabi M, Klugman S, et al. Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(10):1793-1806. doi:10.1038/s41436-021-01203-z
- Hunter JE, Berry-Kravis E, Hipp H, Todd PK. FMR1 disorders. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 1993-2026. Updated 2024 May 16. NBK1384
- Savant A, Bojanowski CM, Upadia J. Cystic fibrosis. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 1993-2026. Updated 2026 Oct 1. NBK1250
- Kirk EP, Delatycki MB, Archibald AD, et al. Nationwide, couple-based genetic carrier screening. N Engl J Med. 2024;391(20):1877-1889. doi:10.1056/NEJMoa2314768
- Haque IS, Lazarin GA, Kang HP, et al. Modeled fetal risk of genetic diseases identified by expanded carrier screening. JAMA. 2016;316(7):734-742. doi:10.1001/jama.2016.11139
- American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 690 summary: carrier screening in the age of genomic medicine. Obstet Gynecol. 2017;129(3):595-596. doi:10.1097/AOG.0000000000001947
- Sagaser KG, Malinowski J, Westerfield L, et al. Expanded carrier screening for reproductive risk assessment: an evidence-based practice guideline from the National Society of Genetic Counselors. J Genet Couns. 2023;32(3):540-557. doi:10.1002/jgc4.1676
- American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 691: carrier screening for genetic conditions. Obstet Gynecol. 2017;129(3):e41-e55. doi:10.1097/AOG.0000000000001952
- Cliffe CC, Allcock RJN, Laing NG, et al. Laboratory considerations for reproductive genetic carrier screening: experiences from Mackenzie's Mission. J Mol Diagn. 2026;28(10):732-747. doi:10.1016/j.jmoldx.2026.06.009
- Ghiossi CE, Goldberg JD, Haque IS, Lazarin GA, Wong KK. Clinical utility of expanded carrier screening: reproductive behaviors of at-risk couples. J Genet Couns. 2018;27(3):616-625. doi:10.1007/s10897-017-0160-1
- Tutty E, Archibald AD, Dawson-McClaren BJ, et al. Psychosocial outcomes of reproductive genetic carrier screening up to five years post-result. Eur J Hum Genet. Published online 2026 Jun 26. doi:10.1038/s41431-026-02167-x
- Tamary H, Greenberg-Kushnir N, Dgany O. Alpha-thalassemia. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 1993-2026. Updated 2026 Apr 23. NBK1435
References retrieved from PubMed and NCBI Bookshelf on 2026-10-30. Care maps are peer-authored clinical frameworks for network members, not individualized medical advice, and are reviewed at each yearly cycle.