Measures Following Abnormal Non-Invasive Prenatal Testing (NIPT) for Trisomies 13, 18, and 21

A Retrospective Cohort Study Using Billing Data of the Barmer Health Insurance Company

Since German health insurers have been covering non-invasive prenatal testing (NIPT) for trisomies 13, 18, and 21 for all pregnant women, billing data have become available that show that the test is accessed by one out of every two pregnant women (1). The hoped-for reduction in invasive prenatal diagnostic procedures was not achieved; rather, rates even rose by 0.1–0.25/1000 women, contrary to the long-term trend (1).

According to the guideline, an abnormal result of NIPT has to be further investigated to exclude false positive results (2). Data from the health insurers enable follow-up of the measures taken after a positive NIPT result. This study analyzes whether in a scenario of an abnormal finding, invasive or non-invasive diagnostic testing was carried out and whether the current pregnancy was prematurely terminated.

Methods

This retrospective cohort study is based on billing data from the BARMER Health Insurance Company (proportion of the population: ca 10%). We analyzed the age of the pregnant women and information according to maternity benefit as well as quarterly diagnoses (according to ICD-10GM) and daily outpatient (according to fee schedule item [EBM] in the uniform assessment scale [GOP]) and inpatient medical procedures (according to the German coding system for operations and procedures, OPS).

The study population consisted of women receiving medical antenatal care (EBM-GOP 01770) with NIPT (EBM-GOP 01970) between 1 July 2022 and 31 December 2023. We excluded pregnant women whose insurance period was incomplete or who were abroad for the duration.

The identified end points were continued pregnancy (further antenatal care items EBM-GOP 01770 between the 90th and 180th day after NIPT), termination of pregnancy (EBM-GOP 0190 [4–6]; OPS: 5–69 [0.1], 5–751) and miscarriage (confirmed incident events, ICD-10 O0 [2–5]). After identifying a consultation in response to a positive NIPT result (EBM-GOP 01790), we determined the billing frequency for invasive diagnostic testing (amniocentesis, EBM-GOP 01781 or OPS 1–852, or chorionic villus sampling, EBM-GOP 01787 or OPS 1–473) and supplementary first trimester sonographic screening for congenital anomalies (FTS), EBM-GOP 01773).

Results

In the observation period we identified 31 568 completed invasive prenatal diagnostic tests and 26 022 completely observable pregnancies. Among these, counseling was billed for in 224 pregnancies (0.9%) after a positive NIPT. In 115 of these pregnant women (51%), invasive prenatal diagnostic testing was billed for (34 underwent chorionic villus sampling [CVS] and 83 had an amniocentesis [ACT]).

Of the 224 pregnant women with abnormal NIPT results, supplementary first trimester sonographic anomaly screening was billed for, in 98 cases in the recommended combination with ACT or CVS. In 48 pregnant women (21%) none of the named diagnostic procedures was carried out in spite of billed-for counseling after positive NIPT results. In 10 of these 48 pregnant women (21%), the data indicated a pregnancy termination. In these cases, the pregnancy was therefore terminated without obtaining clarification by invasive diagnostic testing and/or structured sonographic anomaly screening. The Table shows the outcome for all pregnancies after NIPT.

Table

Comparison of subsequent prenatal diagnostic testing and pregnancy outcomes after billed NIPT without*1 and with abnormal result*2

The Figure shows the observed numbers of counseling sessions after abnormal NIPT results relative to the age-related expected numbers of abnormal tests (expected-to-observed ratio) on the basis of the known incidence rates for trisomies (3).

Figure

Counseling after positive non-invasive prenatal testing (NIPT) depending on the age of the pregnant woman, Expected-to-observed ratio (E/O ratio)as a ratio of expected cases of trisomy 13, 18, or 21 and counseling sessions after positive result of non-inva sive prenatal testing

Discussion

The inclusion of NIPT in the catalogue of services covered by the statutory health insurers enables analyses of what happens subsequent to counseling after a positive test result. In only half of cases receiving counseling after an abnormal NIPT the diagnosis was confirmed by ACT or CVS, and in only 98 of 224 cases (44%) by the technically indicated combination with sonographic FTS. About one in every five pregnant women did not undergo invasive diagnostic testing after counseling for an abnormal NIPT result, but in at least 10 of 48 cases, the pregnancy was terminated. This falls seriously short of the required technical standard: “The indication for terminating a pregnancy must not be based on positive NIPT findings” (2, 5). If the NIPT result is abnormal, national and international guidelines also stipulate non-invasive structured sonographic anomaly screening, which was, however, billed for in only 163 of the affected pregnant women (73%).

If the fetal sono-anatomy is unremarkable, an ACT should be performed instead of a CVS, since the maternal blood contains free DNA of placental origin, which corresponds to the results of a CVS with genetic characterization of placental cells, including possible mosaicism (confined placental mosaicism ]CPM]) and other abnormalities. Only amniotic fluid can be used to diagnose the actual fetal karyotype (5). In spite of this, invasive testing was done contrary to the recommendation in 34 out of 224 women (15%).

In pregnant women younger than 40 years of age, the number of counseling sessions after positive NIPT was notably higher than would have been expected on the basis of the (age related) probability for the presence of trisomies. The reason may be the probability of error of 5% (alpha error) that NIPT screening is based on, which is notably greater than the lower prevalence of fetal aneuploidy in young pregnant women (4).

Limitations

We did not access actual test results, only the billed-for counseling and treatment services. Unclear test results and miscoding cannot be ruled out. Similarly, services that had not been billed for were not included in the analysis (for example, continuing ultrasonography or pregnancy termination after a counseling procedure without reimbursement). The strength of our analysis is the large sample without reimbursement that is representative for Germany.

Conclusion

The unintended consequences of the decision of the Joint Federal Committee (G-BA) of 19 August 2021, for NIPT screening costs to be covered by health insurers, as shown in this article seem to make it an urgent requirement to clarify this regulation.

Dagmar Hertle, Danny Wende, Ekkehard Schleußner

BARMER Institut für Gesundheitssystemforschung, Wuppertal (Hertle, Wende)

Klinik für Geburtsmedizin, Universitätsklinikum Jena (Schleußner)

[e-mail]

Conflict of interest statement

The authors declare that no conflict of interest exists.

Manuscript received on 26 October 2025, revised version accepted on 23 February 2026.

Translated from the original German by Birte Twisselmann, PhD.

Cite this as:
Hertle D, Wende D, Schleussner E: Measures following abnormal non-invasive prenatal testing (NIPT) for trisomies 13, 18, and 21: A retrospective cohort study using billing data of the BARMER Health Insurance Company. Dtsch Arztebl Int 2026; 123: 248–9. DOI: 10.3238/arztebl.m2026.0036

References

1. Hertle D, Wende D: Initial data on a non-invasive prenatal test (NIPT) for trisomies 13, 18, and 21: A retrospective cohort study based on billing ­records of the BARMER health insurance carrier. Dtsch Arztebl Int 2025; 122: 283–284

2. von Kaisenberg C, Kozlowski P, Kagan KO, Hoopmann M, Heling KS, Chaoui R,Klaritsch P, Pertl B, Burkhardt T, Tercanli S, Frenzel J, Mundlos C: AWMF 085–002 S2e LL First trimester diagnosis and therapy @ 11–13+6 weeks of gestation. https://register.awmf.org/de/leitlinien/detail/085-002 (last accessed on4 March 2026 )

3. G-BA: Bluttest auf Trisomien—Der nicht invasive Pränaltaltest (NIPT) auf Trisomie 13, 18 und 21: Eine Versicherteninformation. www.g-ba.de/downloads/83-691-715/2021-11-09_G-BA_Versicherteninformation_NIPT_bf.pdf (last accessed on 9 September 2024).(last accessed on 9 September 2024).

4. IQWiG: Nicht invasive Pränataldiagnostik (NIPD) zur Bestimmung des ­Risikos autosomaler Trisomien 13, 18 und 21 bei ­Risikoschwangerschaften: Bericht Nr. 623. Abschlussbericht 2018 .

5. DEGUM-Empfehlung: Wegweiser auffälliger NIPT? www.degum.de/fileadmin/user_upload/NIPT-Wegweiser-auffaelliger-NIPT_v2023-02-28.pdf (last accessed on 4 March 2026).