AFJOG

GUIDELINES 5. If the pregnancy is in the first trimester, with a singleton fetus without obvious abnormalities, the options for screening should be discussed, including first trimester biochemistry screening (PAPP-A and free β HCG), first trimester combination screening by a practitioner accredited with the Fetal Medicine Foundation (FMF-cFTS) and NIPT. First trimester biochemistry screening is widely available at a cost of R1000 and has an acceptable detection rate in younger and older patients for an acceptable screen positive rate (table 1). 4 The gestational age has to be determined accurately by a crown rump length measurement prior to first trimester biochemistry screening. The sensitivity of FMF-cFTS is superior to other forms of combined or biochemical screening, with good test performance in younger and older patients (table 1). 4 An up-to-date list of FMF accredited practitioners can be found at https://fetalmedicine.org/lists/map/certified/NT. For practical, logistical and financial reasons FMF-cFTS might not be available, feasible or affordable for all patients. Combination screening with first trimester αlpha has a similar screen positive rate as FMF-cFTS, but a lower detection rate overall, and especially for patients younger than 35 (table 1). 4 Measuring the nuchal translucency without FMF accreditation can expose the practitioner to unnecessary medicolegal risk because of a higher risk of false negative findings. NIPT is the most sensitive and specific screening test for common fetal aneuploidies, 8, 9 but remains expensive (R4500 to R6800 per test). Although currently many patients may not have the personal financial means or medical aid cover to fund NIPT, all patients who opt for screening for trisomies, regardless of maternal age or baseline risk should be made aware of the availability of NIPT, and make their own decision. 10 First trimester biochemistry screening will probably be the first (or only) choice of many patients. Table 1. Detection rate and screenpositive rate of high risk results (> 1:300 infirst trimester; >1:270 in second trimester) αlpha software first trimester FMF combined first trimester screening αlpha software second trimester biochemistry screeening biochemistry screening combined screening Screen positive rate Overall 12 (11.3-12.2) 3.5 (3.4-3.7) 3.7 (3.5-3.9) 7.7 (7.5-7.8) Maternal age < 35 years 6.9 (6.6-7.3) 1.7 (1.6-1.8) 2.4 (2.2-2.6) 3.7 (3.6-3.9) Maternal age ≥ 35 years 35 (33.9-36.8) 12 (10.9-12.0) 7.2 (6.7-7.7) 28 (27.1-28.6) Detection rate for high-risk result Overall 94 (69.7to>99.9) 79 (67.2–87.5) 94 (87.3-97.5) 75 (61.0–84.5) Maternal age < 35 years 75 (28.9-96.6) 54 (35.5-71.3) 87 (71.6-94.6) 42 (23.1-63.8) Maternal age ≥ 35 years 100 (71.8-100.0) 97 (84.6->99.9) 98 (90.7->99.9) 94 (78.8-99.3) Numbers reflect percentages (95% confidence intervals in brackets) Simplified from reference (4) 6. If the risk for common autosomal trisomies based on first trimester biochemistry screening is between 1:2 and 1:300 (“high risk”), the patient should be referred timeously for further screening: (before 14 weeks) for FMF-cFTS screening if possible or otherwise NIPT. First trimester FMF-cFTS has a lower screen positive rate than biochemistry-only screening and offers more accurate triage into high, intermediate and low risk. 4 If cFTS-FMF is not possible, NIPT should be offered as a superior screening test. Parents should also be given the choice to opt for invasive testing, although this should not be first choice recommendation. 7. All patients who opt for NIPT should have both pre-test and post-test genetic counselling. A list of genetic counsellors can be found at https://sashg. org/genetic_services/. A patient’s spouse or partner should be included in the counselling where appropriate. There are different types of NIPT based on counting, single nucleotide polymorphism (SNP) or single gene technology. NIPT should be requested from a reputable laboratory that provides the fetal DNA fraction (and preferably other quality metrics). 11 In Rhesus negative patients or patients with Rhesus, Kell or Duffy iso-immunization, preference should be given to single-gene NIPT which can also determine the fetal Rh D, C, c, E, e, Kell or Fya antigen status. 13 “All chromosomes NIPT” can provide information on the chromosomal status for all chromosomes and segmental deletions and duplications bigger than 7Mb. The use of “all chromosomes NIPT” is still debatable because of the risks of false positives, and should not be used without detailed prior genetic counselling. Screening for sex chromosome abnormalities should also not be done routinely. 10 If NIPT demonstrates a high risk for aneuploidy, genetic counselling and confirmatory invasive testing should be offered. Pregnancy termination should not be offered without a confirmatory test. 11 NIPT cannot be performed on triplet and higher order multiple pregnancies, and results should be interpreted with caution in pregnancies complicated with vanishing twins. 8. Discuss the possibility, risks and diagnostic advantage of invasive testing. If a patient opts for invasive testing, she should receive thorough pre- and posttest genetic counselling. Counselling should include the discussion of risks and complications of invasive testing. Practitioners performing less than 100 invasive procedures annually have higher fetal loss rates 14 and it would be misleading to quote a miscarriage rate (such as 1:200) derived from centers where practitioners perform more procedures. The discussion should also include other benefits of invasive testing, including as the use of more detailed tests such as chromosomal micro-array 15 or whole exome sequencing. 16 9. If a multiple pregnancy is present, refer the patient for combination first trimester screening with an extended NT scan to a maternal fetal medicine specialist accredited with the FMF (Fetal Medicine Foundation) (Extended FMF screening). In a multiple pregnancy, biochemical screening reflects the risk of the pregnancy rather than the individual fetus. African Journal of Obstetrics and Gynaecology | Volume 1 | Issue 2 | 2023 | 27