Obstet Gynecol Sci.  2023 Jan;66(1):1-10. 10.5468/ogs.22263.

Prenatal screening for neural tube defects: from maternal serum alpha-fetoprotein to ultrasonography

Affiliations
  • 1Department of Obstetrics and Gynecology, Chung-Ang University College of Medicine, Seoul, Korea
  • 2Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea

Abstract

The two main screening tests during pregnancy are those for chromosomal abnormalities and neural tube defects (NTDs). In particular, for NTDs, measurement of maternal serum alpha-fetoprotein (MSAFP) levels early in the second trimester (15-18 weeks of gestation) has been considered the gold standard screening test for the past 4 decades. However, with remarkable technological advancements and the widespread use of ultrasound during those periods, mid-trimester ultrasonography has gradually replaced the role of measuring MSAFP levels as a screening method for NTDs. This change was initiated more about 10 years ago in some countries, which have issued national guidelines to use mid-trimester ultrasonography instead of measuring MSAFP levels as a prenatal screening method for NTDs. However, no significant changes have occurred in Korea, where second-trimester ultrasonography is routinely performed with high-quality equipment. We aimed to provide information regarding the importance of changing the screening method for NTDs from MSAFP measurement to ultrasonography, and to detail methods of implementing mid-trimester ultrasonography for screening purposes. We also share our experience of operating a prenatal diagnostic program for NTDs without using MSAFP for more than 15 years.

Keyword

Neural tube defects; Alpha-fetoprotein; Ultrasonography

Figure

  • Fig. 1 Indirect brain signs of the fetus affected by open spinal neural tube defects. (A) Abnormal skull shape (lemon sign, arrows) and ventriculomegaly at 18 gestational weeks; (B) abnormal cerebellum (banana sign, arrow) at 19 gestational weeks.

  • Fig. 2 Axial planes of a normal fetal spine at 25 gestational weeks. (A) Axial plane view of the cervical spine; (B) axial plane view of the thoracic spine; (C) axial plane view of the lumbar spine; (D) axial plane view of the sacrum (arrows: pedicles, arrowhead: vertebral body).

  • Fig. 3 Sagittal plane view of the normal spine and conus medullaris (CM) at 22 gestational weeks (arrow: filum terminale, arrowhead: central canal).

  • Fig. 4 Coronal plane views of the lumbosacral spine at 25 gestational weeks. (A) Single line (arrowhead: vertebral body) of ossification; (B) double line (arrows: pedicles) of ossification; (C) triple line of ossification (arrows: pedicles, arrowhead: vertebral body). (D) Three-dimensional image of the fetal spine at 21 gestational weeks.

  • Fig. 5 Ultrasound images of spinal neural tube defects. (A) Protruding cystic mass (arrow) in sagittal plane; (B) indented skin line (arrow) in the sagittal plane; (C) indented skin (arrow) in the coronal plane; (D) ruptured meningomyelocele (arrow) with contour of the lesion (arowheads) in the coronal plane.


Reference

References

1. Driscoll DA, Gross SJ. Screening for fetal aneuploidy and neural tube defects. Genet Med. 2009; 11:818–21.
Article
2. Practice bulletin No. 187: neural tube defects. Obstet Gynecol. 2017; 130:e279–90.
3. Cameron M, Moran P. Prenatal screening and diagnosis of neural tube defects. Prenat Diagn. 2009; 29:402–11.
Article
4. Wilson RD. Prenatal screening, diagnosis, and pregnancy management of fetal neural tube defects. J Obstet Gynaecol Can. 2014; 36:927–39.
5. Cheschier N. ACOG practice bulletin. Neural tube defects. Int J Gynaeco Obstet. 2003; 83:123–33.
6. Norem CT, Schoen EJ, Walton DL, Krieger RC, O’Keefe J, To TT, et al. Routine ultrasonography compared with maternal serum alpha-fetoprotein for neural tube defect screening. Obstet Gynecol. 2005; 106:747–52.
Article
7. Yagel S, Valsky DV. ISUOG practice guidelines (updated): sonographic examination of the fetal central nervous system. Part 1: performance of screening examination and indications for targeted neurosonography. Ultrasound Obstet Gynecol. 2021; 57:173–4.
8. Paladini D, Malinger G, Birnbaum R, Monteagudo A, Pilu G, Salomon LJ, et al. ISUOG practice guidelines (updated): sonographic examination of the fetal central nervous system. Part 2: performance of targeted neurosonography. Ultrasound Obstet Gynecol. 2021; 57:661–71.
9. Douglas Wilson R, Van Mieghem T, Langlois S, Church P. Guideline no. 410: prevention, screening, diagnosis, and pregnancy management for fetal neural tube defects. J Obstet Gynaecol Can. 2021; 43:124–39.
Article
10. Habib ZA. Maternal serum alpha-feto-protein: its value in antenatal diagnosis of genetic disease and in obstetrical-gynaecological care. Acta Obstet Gynecol Scand Suppl. 1977; 61:1–92.
Article
11. Bergstrand CG, Czar B. Demonstration of a new protein fraction in serum from the human fetus. Scand J Clin Lab Invest. 1956; 8:174.
Article
12. Gitlin D, Boesman M. Serum alpha-fetoprotein, albumin, and gamma-G-globulin in the human conceptus. J Clin Invest. 1966; 45:1826–38.
Article
13. Johansson SG, Kjessler B, Sherman MS, Wahlström J. Alpha-fetoprotein (AFP) levels in maternal serum and amniotic fluid in singleton pregnant women in their 10th-25th week post last menstrual period. Acta Obstet Gynecol Scand Suppl. 1977; 69:20–4.
Article
14. Kim CK, Yang YH. Alpha-fetoprotein values in maternal serum and amniotic fluid for prenatal screening of genetic disorders. Yonsei Med J. 1987; 28:218–27.
Article
15. Leighton PC, Kitau MJ, Chard T, Gordon YB, Leek AE. Levels of alpha-fetoprotein in maternal blood as a screening test for fetal neural-tube defect. Lancet. 1975; 2:1012–5.
Article
16. Wald NJ, Cuckle H, Brock JH, Peto R, Polani PE, Woodford FP. Maternal serum-alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Report of U.K. collaborative study on alpha-fetoprotein in relation to neural-tube defects. Lancet. 1977; 1:1323–32.
17. Bradley LA, Palomaki GE, McDowell GA. Technical standards and guidelines: prenatal screening for open neural tube defects. Genet Med. 2005; 7:355–69.
18. Wald N, Cuckle H, Boreham J, Stirrat G. Small biparietal diameter of fetuses with spina bifida: implications for antenatal screening. Br J Obstet Gynaecol. 1980; 87:219–21.
Article
19. Nicolaides KH, Campbell S, Gabbe SG, Guidetti R. Ultrasound screening for spina bifida: cranial and cerebellar signs. Lancet. 1986; 2:72–4.
Article
20. Warder DE. Tethered cord syndrome and occult spinal dysraphism. Neurosurg Focus. 2001; 10:e1.
Article
21. Richards DS, Seeds JW, Katz VL, Lingley LH, Albright SG, Cefalo RC. Elevated maternal serum alpha-fetoprotein with normal ultrasound: is amniocentesis always appropriate? A review of 26,069 screened patients. Obstet Gynecol. 1988; 71:203–7.
22. Puntachai P, Wanapirak C, Sirichotiyakul S, Tongprasert F, Srisupundit K, Luewan S, et al. Associations between pregnancy outcomes and unexplained high and low maternal serum alpha-fetoprotein levels. Arch Gynecol Obstet. 2015; 292:81–5.
Article
23. Gagnon A, Wilson RD. Obstetrical complications associated with abnormal maternal serum markers analytes. J Obstet Gynaecol Can. 2008; 30:918–32.
24. Chandra S, Scott H, Dodds L, Watts C, Blight C, Van den Hof M. Unexplained elevated maternal serum alphafetoprotein and/or human chorionic gonadotropin and the risk of adverse outcomes. Am J Obstet Gynecol. 2003; 189:775–81.
25. Katz VL, Chescheir NC, Cefalo RC. Unexplained elevations of maternal serum alpha-fetoprotein. Obstet Gynecol Surv. 1990; 45:719–26.
Article
26. Hogge WA, Thiagarajah S, Ferguson JE 2nd, Schnatterly PT, Harbert GM Jr. The role of ultrasonography and amniocentesis in the evaluation of pregnancies at risk for neural tube defects. Am J Obstet Gynecol. 1989; 161:520–3.
Article
27. Crane JP, LeFevre ML, Winborn RC, Evans JK, Ewigman BG, Bain RP, et al. A randomized trial of prenatal ultrasonographic screening: impact on the detection, management, and outcome of anomalous fetuses. The RADIUS study group. Am J Obstet Gynecol. 1994; 171:392–9.
28. Grandjean H, Larroque D, Levi S. The performance of routine ultrasonographic screening of pregnancies in the Eurofetus study. Am J Obstet Gynecol. 1999; 181:446–54.
Article
29. Lennon CA, Gray DL. Sensitivity and specificity of ultrasound for the detection of neural tube and ventral wall defects in a high-risk population. Obstet Gynecol. 1999; 94:562–6.
Article
30. Dashe JS, Twickler DM, Santos-Ramos R, McIntire DD, Ramus RM. Alpha-fetoprotein detection of neural tube defects and the impact of standard ultrasound. Am J Obstet Gynecol. 2006; 195:1623–8.
Article
31. Arnautovic A, Splavski B, Boop FA, Arnautovic KI. Pediatric and adult chiari malformation type I surgical series 1965–2013: a review of demographics, operative treatment, and outcomes. J Neurosurg Pediatr. 2015; 15:161–77.
Article
32. Langridge B, Phillips E, Choi D. Chiari malformation type 1: a systematic review of natural history and conservative management. World Neurosurg. 2017; 104:213–19.
Article
33. McLone DG, Knepper PA. The cause of Chiari II malformation: a unified theory. Pediatr Neurosci. 1989; 15:1–12.
Article
34. D’Addario V, Rossi AC, Pinto V, Pintucci A, Di Cagno L. Comparison of six sonographic signs in the prenatal diagnosis of spina bifida. J Perinat Med. 2008; 36:330–4.
35. Kim GJ, Lee ES, Kim DH, Lee SH, Park JD, Park MH. Factors related with intracranial signs in fetuses with open neural tube defect. Obstet Gynecol Sci. 2005; 48:2541–9.
36. Kollias SS, Goldstein RB, Cogen PH, Filly RA. Prenatally detected myelomeningoceles: sonographic accuracy in estimation of the spinal level. Radiology. 1992; 185:109–12.
37. Stephenson SR. Sonographic signs of fetal neural tube and central nervous system defects. J Diagn Med Sonogr. 2003; 19:347–57.
Article
38. Coleman BG, Langer JE, Horii SC. The diagnostic features of spina bifida: the role of ultrasound. Fetal Diagn Ther. 2015; 37:179–96.
Article
39. Fong KW, Toi A, Okun N, Al-Shami E, Menezes RJ. Retrospective review of diagnostic performance of intracranial translucency in detection of open spina bifida at the 11–13-week scan. Ultrasound Obstet Gynecol. 2011; 38:630–4.
Article
40. Mangione R, Dhombres F, Lelong N, Amat S, Atoub F, Friszer S, et al. Screening for fetal spina bifida at the 11–13-week scan using three anatomical features of the posterior brain. Ultrasound Obstet Gynecol. 2013; 42:416–20.
41. Kappou D, Papastefanou I, Pilalis A, Kavalakis I, Kassanos D, Souka AP. Towards detecting open spina bifida in the first trimester: the examination of the posterior brain. Fetal Diagn Ther. 2015; 37:294–300.
Article
42. Williams MA, Hickok DE, Zingheim RW, Luthy DA, Kimelman J, Nyberg DA, et al. Elevated maternal serum alpha-fetoprotein levels and midtrimester placental abnormalities in relation to subsequent adverse pregnancy outcomes. Am J Obstet Gynecol. 1992; 167:1032–7.
Full Text Links
  • OGS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr