Questions. High risk of diabetes. Amniocentesis. My history

Prediction of type 1 diabetes in groups high risk

T.V. Nikonova, I.I. Dedov, J.I.P. Alekseev, M.N. Boldyreva, O.M. Smirnova, I.V. Dubinkin*.

Endocrinological science Center I (director - academician of RAMS I.I. Dedov) RAMS, I *SSC “Institute of Immunology” I (director - academician of RAMS R.M. Khaitov) M3 RF, Moscow. I

Currently, there is an increase in the incidence of type 1 diabetes throughout the world. This is due to a number of factors, including an increase in the life expectancy of patients with diabetes due to improved diagnostic and medical care, increased fertility and worsening environmental situations. The incidence of diabetes can be reduced by preventive measures, predicting and preventing the development of the disease.

Predisposition to type 1 diabetes is genetically determined. The incidence of type 1 diabetes is controlled by a number of genes: the insulin gene on chromosome 11p15.5 (YOM2), genes on the chromosome \\ts (YOM4), 6ts (YOM5). Highest value of the known genetic markers of type 1 diabetes, they have the genes of the HLA region on chromosome 6p 21.3 (SHOM1); up to 40% of the genetic predisposition to type 1 diabetes is associated with them. No other genetic region determines the risk of developing the disease comparable to HLA.

A high risk of developing type 1 diabetes is determined by allelic variants of the HLA genes: OYAB1*03,*04; OOA1 *0501 ,*0301, OOB1*0201, *0302 . 95% of patients with type 1 diabetes have OT*3 or 011*4 antigens, and from 55 to 60% have both antigens. The OOB1*0602 allele is rare in type 1 diabetes and is considered protective.

Clinical manifestations of diabetes are preceded by latent period, characterized by the presence of islet markers cellular immunity; these markers are associated with progressive destruction.

Thus, for family members with a history of type 1 diabetes, disease prognosis is especially important.

The purpose of this work was to form groups at high risk of developing type 1 diabetes in the Russian population of Moscow residents based on the study of genetic, immunological and metabolic markers of diabetes using a family approach.

Materials and research methods

We examined 26 families in which one of the parents has type 1 diabetes, of which 5 were “nuclear” families (101 people in total). The number of family members surveyed ranged from 3 to 10 people. There were 13 fathers with type 1 diabetes, and 13 mothers with type 1 diabetes. There were no families in which both parents had type 1 diabetes.

37 descendants of patients with type 1 diabetes without clinical manifestations diseases, of which 16 were female, 21 were male. The age of the examined offspring ranged from 5 to 30 years. The distribution of examined offspring by age is presented in Table. 1.

Table 1

Age of examined children (descendants)

Age (years) Number

In families with diabetic mothers, 17 children (8 girls, 9 boys) were examined, in families with diabetic fathers - 20 children (8 girls, 12 boys).

Autoantibodies to (3-cells (ICA) were determined in two ways: 1) on cryosections of the human pancreas of blood group I (0) in an indirect immunofluorescence reaction; 2) in the immunoenzyme test “ISLETTEST” from “Biomerica”. Insulin autoantibodies (IAA) were determined in enzyme immunoassay test"ISLETTEST" from Biomerica. Determination of antibodies to HDK was carried out using standard sets“Diaplets anti-GAD” from Boehringer Mannheim.

The determination of C-peptide was carried out using standard kits from Sorrin (France).

HLA typing of patients with diabetes and their family members was performed for three genes: DRB1, DQA1 and DQB1 using sequence-specific primers using polymerase chain reaction(PCR).

Isolation of DNA from lymphocytes peripheral blood carried out according to the method of R. Higuchi N. Erlich (1989) with some modifications: 0.5 ml of blood taken with EDTA was mixed in 1.5 ml Eppendorf microcentrifuge tubes with 0.5 ml of lysis solution consisting of 0. 32 M sucrose, 10 mM Tris - HC1 pH 7.5, 5 mM MgC12, 1% Triton X-100, centrifuged for 1 min at 10,000 rpm, the supernatant was removed, and the cell nucleus pellets were washed 2 times with the indicated buffer. Subsequent proteolysis was carried out in 50 μl of a buffer solution containing 50 mM KCI, 10 mM Tris-HC1 pH 8.3, 2.5 mM MgCI2, 0.45% NP-40, 0.45% Tween-20 and 250 μg/ml proteinase K at 37°C for 20 minutes. Proteinase K was inactivated by heating in a solid-state thermostat at 95°C for 5 min. The resulting DNA samples were immediately used for typing or stored at -20°C. The DNA concentration determined by

fluorescence with Hoechst 33258 on a DNA fluorimeter (Hoefer, USA) averaged 50-100 μg/ml. Total time DNA extraction procedure lasted 30-40 minutes.

PCR was carried out in a 10 μl reaction mixture containing 1 μl of DNA sample and the following concentrations of the remaining components: 0.2 mM each dNTP (dATP, dCTP, dTTP and dGTP), 67 mM Tris-HCl pH=8.8, 2.5 mM MgC12 , 50 mM NaCl, 0.1 mg/ml gelatin, 1 mM 2-mercaptoethanol, and 1 unit of thermostable DNA polymerase. To prevent changes in the concentrations of the components of the reaction mixture due to the formation of condensate, the reaction mixture was covered with 20 μl of mineral oil (Sigma, USA).

Amplification was carried out on a multichannel thermal cycler "MS2" (JSC DNA-Technology, Moscow).

Typing of the DRB1 locus was carried out in 2 stages. During the 1st round, genomic DNA was amplified in two different tubes; in the 1st tube a pair of primers was used that amplified all known alleles of the DRB1 gene, in the 2nd tube a pair of primers was used that amplified only alleles included in the groups DR3, DR5, DR6, DR8. In both cases temperature regime amplification (for the “MC2” thermal cycler with active regulation) was as follows: 1) 94°C - 1 min.; 2) 94°С - 20 s (7 cycles), 67°С - 2 s; 92“C - 1 s (28 cycles); 65°C - 2 s.

The resulting products were diluted 10 times and used in the 2nd round at the following temperature conditions: 92°C - 1 s (15 cycles); 64°C - 1 s.

Typing of the DQA1 locus was carried out in 2 stages. At the 1st stage, a pair of primers was used, amplifying all specificities of the DQA1 locus; at the 2nd stage, pairs of primers were used, amplifying the specificities *0101, *0102, *0103, *0201, *0301, *0401, *0501, *0601 .

The first stage was carried out according to the program: 94 “C - 1 minute; 94°C - 20 s (7 cycles), 58"C - 5 s; 92"C - 1 s, 5 s (28 cycles), 56"C - 2 s.

The amplification products of the 1st stage were diluted 10 times and used at the 2nd stage: 93“C - 1 s (12 cycles), 62“C - 2 s.

Typing of the DQB1 locus was also carried out in 2 stages; on the 1st, a pair of primers was used that amplified all the specificities of the DQB1 locus, the temperature regime was as follows: 94°C - 1 min.; 94°C - 20 s. (7 cycles); 67°C - 5 s.; 93°C - 1 s (28 cycles); 65HP - 2 s.

At the 2nd stage, primer pairs were used that amplified specificities: *0201, *0301, *0302, *0303, *0304, *0305, *04, *0501, *0502, *0503, *0601, *0602/ 08; The products of the 1st stage were diluted 10 times and amplification was carried out in the following mode: 93°C - 1 s. (12 cycles); 67°C - 2 s.

Identification of amplification products and their length distribution was carried out in ultraviolet light (310 nm) after electrophoresis for 15 min either in 10% PAAG, 29:1 at a voltage of 500 V, or in 3% agarose gel at a voltage of 300 V (in both cases, run was 3-4 cm) and stained with ethidium bromide. Digest of plasmid pUC19 with Msp I restriction enzyme was used as a length marker.

Results and its discussion

It was found that in 26 families of 26 parents with type 1 diabetes, 23 people (88.5%) are carriers of the HLA genotypes associated with type 1 diabetes DRB1 *03- DQA1 *0501 - DQB1 *0201; DRB1 *04-DQAl *0301-DQB 1*0302 or their combinations (Table 2). In 2 patients, the genotype contains the DQB 1*0201 allele, associated with type 1 diabetes; only 1 patient in this group had the DRB1 *01 /01 genotype, which

Distribution of genotypes among parents with type 1 diabetes

01?B 1 4/4 2 E1?B 1 - -

Total 23 (88.5%) Total 3

0I?B1-POAI-ROI haplotypes found in the examined individuals

oigvi oaii rovi

which was not associated with type 1 diabetes in population studies, we did not distinguish subtypes of OK B1 *04, although polymorphism of this locus may affect the risk of developing type 1 diabetes.

When genotyping the direct descendants of patients with type 1 diabetes, it was revealed that out of 37 people, 30 (81%) inherited the genotypes OYAV1*03, 011B1*04 and their combination associated with type 1 diabetes; 3 individuals had alleles associated with type 1 diabetes in their genotype : in 1 - TOA 1*0501, in 2 patients - TOA 1*0201. A total of 4 out of 37 subjects had a neutral genotype in relation to type 1 diabetes.

The distribution of offspring genotypes is shown in Table. 3. A number of studies have noted that fathers with type 1 diabetes are more likely to pass on a genetic predisposition.

susceptibility to diabetes (in particular, HLA-01*4 geno-types) in their children than in their mothers. However, a study in the UK did not confirm a significant effect of parental gender on HLA-dependent predisposition in children. In our work, we also cannot note a similar pattern of transmission of genetic predisposition: 94% of children inherited HLA genotypes associated with type 1 diabetes from sick mothers and 85% from sick fathers.

DM is known to be a multigene, multifactorial disease. As factors external environment, playing the role of a trigger, nutrition is considered - consumption in infancy and early childhood proteins cow's milk. De-

Table 3

Distribution of genotypes among children whose parents have type 1 diabetes

Genotypes associated with type 1 diabetes Number of carriers Genotypes not associated with type 1 diabetes Number of carriers

0!*B 1 4/4 4 01*B 1 1/15 1

Total 30 (81%) Total 7 (19%)

those with newly diagnosed diabetes have elevated levels antibodies to cow's milk protein, p-lactoglobulin and bovine serum albumin compared to healthy siblings, which is regarded as an independent risk factor for the development of diabetes.

In the group of 37 children examined, only 4 were at breastfeeding up to 1 year, 26 people received breast milk up to 1.5-3 months, 4 - up to 6 months, 3 were on formula milk from the first weeks of life. Of the 5 children with positive antibodies to β-cells, 2 were breastfed for up to 6 months, 3 for up to 1.5 - 3 months; then kefir and milk mixtures were obtained. Thus, 89% of the examined children received cow's milk proteins in infancy and early childhood, which can be regarded as a risk factor for the development of diabetes in genetically predisposed individuals.

In the examined families, clinically healthy offspring were assessed for cytoplasmic antibodies, autoantibodies to insulin and HDC. Of the 37 examined, 5 children turned out to be positive for the presence of antibodies to β-cells, while all 5 are carriers of a genetic predisposition to diabetes (Table 4). 3 of them (8%) had antibodies to HDK, 1 - to ACTC, 1 - antibodies to ACTC

Table 4

Genotypes of children positive for antibodies to (3-cells

Genotype Number of antibody positive

and insulin. Thus, 5.4% of children have antibodies to ACTC; 2 children with positive antibodies to HDC are descendants of “nuclear” families. The age of the children at the time of detection of antibodies is indicated in Table. 5. To predict diabetes great importance have ACTC titer levels: the higher the antibody titer, the more likely development of diabetes, the same applies to antibodies to insulin. According to the literature, high levels antibodies to HDK are associated with a slower rate of development of diabetes (10% at 4 years) than low levels(50% at 4 years), possibly because high levels of anti-HDC antibodies indicate “preferential” activation humoral immunity and to a lesser extent on the activation of cell-mediated

Table 5

Age of examined children at the time of detection of antibodies

Age of children examined (years) Number of children positive for antibodies

bathed immunity (type 1 diabetes is mainly caused by cell-mediated destruction of P cells by cytotoxic T lymphocytes). A combination of different antibodies provides the most optimal level of prediction.

Children with low birth weight (less than 2.5 kg) develop diabetes much earlier than children born with normal weight. From the anamnesis data, it is noteworthy that out of 5 children with positive antibodies, 2 were born with a body weight of more than 4 kg, 2 - less than 2.9 kg.

In direct descendants of patients with type 1 diabetes, the basal level of C-peptide was determined; in all of them this indicator was within the normal range (including children with positive antibodies to P-cells); a study of the level of stimulated C-peptide was not carried out.

1. Patients with type 1 diabetes in 88.5% of cases are carriers of the genotypes OYAVROZ, OOA1*0501, BOV1*0201, OYAV1*04, BOA1*0301, EOV1*0302, or their combinations.

2. In children from families where one of the parents has type 1 diabetes, in 89% of cases a genetic predisposition to diabetes is detected (in the presence of one sick parent), while 81% inherit genotypes completely associated with type 1 diabetes, which allows them to be considered group at very high risk of developing diabetes.

3. Among the direct descendants of patients with type 1 diabetes who have genetic predisposition, positive antibodies to GDC were detected in 8% of cases, ACTC - in 5.4% of cases. These children need diagnostic test antibody titers, glycohemoglobin and study of insulin secretion.

*1 iteration

1. Atkinson M.A., McLaren N.K. // N.Engl.J.Med.-l 994 -331. P.l 4281436.

2. Aanstoot H.J., Sigurdsson E., Jaffe M. et al // Diabetologia-1994-37.

3. Baekkeskov S., Aanstoot H.J., Christgan S. et al // Nature-1 990-377.

4. Bain S.C., Rowe B.R., Barnett A.H., Todd J.A. // Diabetes-1994-43(12). P. 1432-1468.

5. B/ng/ey P.J., Christie M.R., Bonifacio E., Bonfanti R., Shattock Mw Fonte M.T., Bottazzo C.F. // Diabetes-1 994-43. P. 1304-1310.

6. Boehn B.O., Manifras B., Seibler J. et al // Diabetes-1991-40. P.1435-1439.

7. Chern M.M., Anderson V.E., Barbosa J. // Diabetes-1982-31. P.l 1 151118.

8. Davies J.L., Kawaguchi Y., Bennett S.T. et al. // Nature-1994-371.

9. Erlich H.A., Rotter J.I., Chang J. et al. // Nature Gen.-1993-3. P.358-364.

10. Hahl J., Simell T., Ilonen J., Knip M., Simmel O. // Diabetologia-1 99841. P.79-85.

11. Harrison L.C., Honeyman M.C., DeAizpurua H.J. et al // Lancet-1993341. P.l 365-1369.

12. Hashimoto L., Habita C., Beresse J.P. et al. // Nature-1994-371. P.161-164.

1 3. Karjalainen J., Martin J.M., Knip M. et al // N.Engl.J.Med.-l 992-327. P.302-303.

14. Khan N., Couper T.T., // Diabetes Care-1994-17. P. 653-656.

15. Landin-OIsson M., Palmer J.P., Lernmark A. et al // Diabetologia-1992-40. P.l068-1 073.

16. Leslie R.D.C., Atkinson M.A., Notkins A.L. // Diabetologia-1999-42. P.3-14.

17. Levy-Marchal C., Dubois F., Neel M., Tichet J., Czernichow P. // Diabetes-1995-44. P.1029-1032.

1 8. Lorenzen T., Pociot F., Hougaard P., Nerup J. // Diabetologia-1994-37. P.321-321.

19. Lorenzen T„ Pociot F., Stilgren L. et al // Diabetologia-1998-41. P.666-673.

20. Nepom G., Erlich H.A. // Ann.Rev.Immunol.-1 991-9. P.493-525.

21. Nerup J., Mandrup-Poulsen T., Molvig J. // Diabetes Metab. Rev.-1987-3. P.779-802.

22. Owerbach D., Gabbay K.H. // Diabetes-1995-44.p.l 32-136.

23. PociotF. U Dan.Med.Bull.-l996-43. P.216-248.

24. Rewers M., Bugawan T.L., Norris J.M., Blair A. et al. // Diabetologia-1996-39. P.807-812.

25. Rei/onen H., Ilonen J., Knip N., Akerblom H. // Diabetes-1 991-40.

26. Saukkonen T., Virtanen S.M., Karppinen M. et al // Diabetologia-1998-41. P.72-78.

27. Schatz D., Krischer J., Horne G. et al. // J. Clin. Invest.-1994-93. P.2403-2407.

28. Spielman R.S., Baker L, Zmijewski C.M. //Ann. Hum. Genet.-1980-44. P. 135-150.

29. Thivolet C., Beaufrere B., Gebuhrer Y., Chatelain P., Orgiazzi J. // Diabetologia-1991-34. P.l86-191.

30. Tillil H., Kobberling J.// Diabetes-1982-36. P.93-99.

31. ToddJ.A. U Proc. Natl. Acad. Sci. USA-1990-377. P.8560-8565.

32. ToddJ.A., Farral M. // Hum.Mol.Gen.-5. P.1443-1448.

33. Tuomilehto J., Zimmet P., Mackay I.R. et al // Lancet-1994-343.

34. Van der Anvera B., Van Waeyenberge C., Schuit F. et al. // Diabetes-1995-44. P.527-530.

35. Walker A., Goodworth A.G. // Diabetes-1980-29. P.1036-1039.

36. Warram J., Krolewski A.S., Gottlieb M., Kahn C.R. // N.Engl.J.Med.-1984-311. P.149-151.

37. Ziegler A.G., Herskowitz R.D., Jackson R.A. et al // Diabetes Care-1990-13. P.762-775.

Hi all! Girls who have been in similar situations, please respond! On May 27th I had my first screening. The ultrasound showed everything was normal. They wrote down the phone number just in case, but I didn’t expect that they might call me back, and then a week later I got a call - come for a referral to the Center for Psychological Surveillance, you are at high risk. I don’t remember myself, I arrived in tears, on weak legs, and took all the papers. Risk 1:53. The next day I went for further examination. The ultrasound specialist looked at both the abdomen and vagina for a very long time, turned on the Doppler several times, and everything seemed to be fine, but he didn’t like DOPPLER METRY OF THE TRISCUPID VALVE: REGURGITATION. I entered the new ultrasound data into the program and the screening results from a week ago, the computer showed a diabetes risk of 1:6. I sent him to a geneticist. After looking at the conclusion, she explained to me that this regurgitation could simply be a feature of the fetus, but coupled with an underestimated PAPP-A indicator - 0.232 MoM, this is a marker of chromosomal abnormalities. Everything else is within normal limits. They suggested undergoing a chorionic villus biopsy. I refused for now, the nurse almost fell out of her chair, like the risk is so high and CA cannot be treated, and if she were me, she wouldn’t even think for a minute. I asked a geneticist about the Panorama analysis (a terribly expensive genetic analysis of maternal blood), she told me that of course you can do it, but it excludes only 5 main CAs and several very rare ones, it cannot completely exclude anomalies, and in my case it is recommended invasion. I’ve already read a ton of articles, questions and the like on this topic, and I just don’t understand what they found so terrible in my analyzes? Regurgitation, as it turned out, is physiological at this stage and goes away by 18-20 weeks (if it doesn’t go away, this indicates a risk of heart defects, for many it goes away after childbirth, and some live with it and doesn’t affect anything. Moreover, the husband has prolapse mintral valve, which was inherited from my mother, maybe this is somehow connected). Hormones may not be indicative at all, because... I’ve been taking it since the beginning of pregnancy, I ate 2 hours before the test (it turns out you can’t eat 4 hours before, they didn’t tell me about it), drank coffee, was nervous and worried about the ultrasound and I’m afraid to donate blood, and Lately chronic fatigue, I’m tired with my older child. And all this affects the results. The geneticist didn’t ask anything of the kind, wasn’t interested, they actually have some kind of conveyor belt there, and it was as if they shoved me there for statistics. But they planted a bit of doubt in me, I cried and was not worried about the year ahead. My husband is trying to persuade me to have a biopsy. I am terribly afraid of the consequences, afraid of losing or harming the child, especially if he is healthy. On the one hand, if everything is fine, I will breathe a sigh of relief and send all the doctors away. On the other hand, if everything is bad, what should you do? Will I be able to terminate the pregnancy, allow my child to be dismembered inside me, especially now that it seems to me that I am beginning to feel him. But another option is whether I can raise a child who needs special approach and a lot of attention, when sometimes you want to run away from your completely healthy daughter... Damn, all these thoughts are eating me up. I don’t know what to do... Just in case, I’ll give you the screening data:

Delivery period: 13 weeks

Heart rate 161 beats/min

Ductus venosus PI 1.160

Chorion/placenta low on the anterior wall

Umbilical cord 3 vessels

Fetal anatomy: everything is determined, everything is normal

b-hCG 1.091 MoM

PAPP-A 0.232 MoM

Uterine artery PI 1,240 MoM

Trisomy 21 1:6

Trisomy 18 1:311

Trisomy 13 1:205

Preeclampsia up to 34 weeks 1:529

Preeclampsia up to 37 weeks 1:524

Oh, girls, I don’t even know where to start. I never thought that I would find myself in such a situation. Two years ago I really wanted to get pregnant, but it didn’t work out. I went through doctors, ultrasounds, hormone tests - in the end they said that I had severe ovarian dysfunction, and there was no talk of pregnancy. I was worried, but not very much. After all, I have three daughters.
For two years I was regularly checked by a gynecologist and had ultrasounds done. The last time was in February 2017. Then they couldn’t even find one of my ovaries, they said that I was almost starting menopause. In March, I was offered a job that I had been waiting for for three years. I was happy - both the salary and the position were good. And in April my period did not come. Well, delay and delay. Moreover, I have a cycle Last year was from 24 to 27 days. On day 29 I couldn’t stand it - I took a test, Two stripes. I couldn’t believe it for a long time, I bought a few more - two strips. Joy and shock (what will I say at work?). I ran to take hCG. He confirmed that she was 4 weeks pregnant. Until 8 weeks I lived in a frenzy. I took the hCG test every week, I was afraid of an ectopic (ultrasound at 5 weeks refuted my worries), I was afraid of a frozen one. At 8 weeks I did another ultrasound, listened to the baby’s heartbeat, everything was normal - I calmed down. And at 12 weeks the first screening. Ultrasound is normal, the blood test came back bad on Thursday, the risk of diabetes is 1:43. On Friday I already saw a geneticist, she insists on a placenta puncture. Made an appointment for July 11th. God, I'm so scared!!! I'm not so much afraid of the procedure as of its result.
In my life, I have never had an abortion, I haven’t had a miscarriage, and what’s more, I haven’t even given birth myself. I just can’t imagine how I can go to IR if everything turns out to be true. I try to control myself, but sometimes it really hits me. I have a feeling that the verdict has already been read out and the ax has already been raised over me.
I didn’t write about the tests. My hCG is 1.158 MoM (37.9 IU), and PAPP is 0.222 MoM (0.837 IU). TVP 1.91 mm, KTR 73.3 mm.
I just ask for prayers and support, I don’t know how to live to see the results. I want to do another ultrasound this week, although everyone says that it is no longer informative at 15 weeks.

RS: Girls, thank you all for your support. I just had another paid ultrasound. The doctor looked at it for a long time and said that according to the ultrasound, she did not see any developmental defects at all, including those that are typical for children with diabetes. I know that ultrasound cannot guarantee 100% absence genetic disorders, but still a little lighter on the soul. I asked about the puncture. The doctor said that the uterus is not in good shape and the cervix is of good length, i.e. there are no contraindications if I still decide to go for a puncture. And yes, I have a boy according to the ultrasound. Now I'll think about the puncture.

Nuria asks:

Hello. I am 25 years old. At 16 weeks of pregnancy, I was tested for AFP 30.70/0.99 mΩ,/ and hCG 64.50/3.00 mΩ/. Please tell me what the numbers mean. What is my probability on SD? My pregnancy is 27-28 weeks. I just found out about the screening results. At this time I was taking Duphaston. Tell me how high the risk is. Thank you.

Based on the data you provided, the risk of your child having genetic pathology Down syndrome is low.

Nuria asks:

Thanks for clarifying. But the center gave me a threshold risk, so I’m very worried. What other data is taken into account to identify the risk of diabetes? TVP - 1.5, DNA - 3.2. Ultrasound at 20 weeks is good. Thanks again.

Most likely, the degree of risk was calculated taking into account increased value HCG, since the rest of the examination indicators you presented are normal.

Natalya asks:

Hello. Help, please. I received the screening result and was upset. They put:
Age-related risk of diabetes 1:371
DM risk value 1:306
AFP 26.04 Mohm 0.86, HCGb 29.74 Mohm 1.87
Fully 35 years old, second pregnancy, screened at 15 weeks 6 days, with a difference - they did an ultrasound, and 2 days later they took blood.
Conclusion - threshold risk.
Tell me everything is bad? Thank you

The risk of genetic pathology can be assessed as slightly above average. There is no reason to panic. The screening only assesses the likelihood of having a child with a genetic pathology.

Natalya asks:

in addition to the previous one.
An ultrasound was done at 16 weeks. TVP 4 mm (I read that they usually measure up to 14 weeks).
at 17.5 weeks, nasal bones 6.3 mm
Apparently, on the basis of TVP, the threshold for SD was set. Should we be afraid? Thank you.

The size of the nasal bone is indeed normal, the thickness of the TVP is measured before the 14th week of pregnancy, with the CTE of the fetus (coccygeal-parietal size) not higher than 84 mm, later than this period or at more high rates KTE results of the conducted research cease to be informative. Therefore, in your case, there is no need to worry. Your threshold risk was not determined based on an analysis of screening and ultrasound results, but based on your age.

Elena asks:

Hello! Please tell me. Results of prenatal screening: 1st trimester risk of trisomy 21 1: 2472; 2nd trimester 1:29 How can this be? Complex risk 1:208 Study results 13 weeks: St. beta hCG 74.53 ng/ml (1.74 MoM) PaPP-A5684.00 Mu|L (1.67 MoM) TVP 1.80 mm (1.05 MoM ) 17 weeks: AFP 32.39 IU/ml (1.16 MoM) hCG 207.00 IU/l (6.44 MoM) 2nd ultrasound will be on September 12 (21 weeks), the first at 12 weeks. 4 days no deviations were found. What actions to take? I am 34 years old and have one fetus.

The results of the second screening showed a sharply increased level of hCG, please clarify whether you took any medications before taking blood for analysis?

Oksana asks:

screening 18 weeks 4 days.
age risk 1:135, risk value 1:322
AFP 51.99 MoM 1.16
HCGb 15.60 MoM 1.61
They set a threshold risk, what to do?
I am 39 years old, second child, ultrasound at 21.3 weeks. without deviations

Dear Oksana, the biochemical screening parameters are completely normal. If according to the results ultrasound diagnostics, there are no deviations - there are also no indications for invasive diagnostics. Usually, in similar situation, at 22 weeks of pregnancy, an expert ultrasound is performed; for this examination, the maximum number of qualified specialist with experience in prenatal diagnostics birth defects development. However, if you trust the qualifications of the specialist who performed the last ultrasound at 21.3 weeks, there is no need to repeat the examination. You can read more about deciphering the results of biochemical screening in the second trimester of pregnancy in our medical information section dedicated to this method diagnostics, with the same name: Screening. .

Natalya asks:

Hello! Please help me understand the results of 1 screening within 10 weeks. I am 41 years old, weight 48 kg. The first birth is coming.
KTR 31mm
TVP up to 2mm
hCGb marker: conc. 100.1 ng/mL, corr. PTO 1.28
PAPP-A marker: conc. 623.9 mU/L, corr. PTO 0.58
They diagnosed a high risk of Down syndrome, age risk 1:70, calculated risk 1:65
As far as I know, the norm limits for PTO are 0.5-2.0. Are my PTO readings not up to standard? Do I have cause for concern? Neither my family nor my husband's congenital pathologies No. I would be very grateful for your answer.

Unfortunately, when determining the risk of chromosomal abnormalities, they are guided not only by IOM indicators, but evaluate the results of all studies in combination. If the risk turns out to be high, it is recommended to consult a geneticist, who, together with the attending gynecologist, can decide on a diagnostic intervention such as amniocentesis. More details on this issue You can get information in the thematic section of our website: Down Syndrome

Find out more on this topic:

Blood test for antibodies - detection of infectious diseases (measles, hepatitis, Helicobacter, tuberculosis, lamblia, treponema, etc.). Blood test for the presence of Rh antibodies during pregnancy.
Blood test for antibodies - types (ELISA, RIA, immunoblotting, serological methods), norm, interpretation of results. Where can I get a blood test for antibodies? Research price.
Biochemical blood test - norms, meaning and interpretation of indicators in men, women and children (by age). Concentration of ions (electrolytes) in the blood: potassium, sodium, chlorine, calcium, magnesium, phosphorus
Biochemical blood test - norms, meaning and interpretation of indicators in men, women and children (by age). Iron metabolism indicators: total iron, transferrin, ferritin, haptoglobin, ceruloplasmin