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RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

Nowadays, infectious diseases are decreasing, the rate of genetic, metabolic and cardiovascular diseases is increasing. In Vietnam, besides being affected by environmental agents that cause genetic abnormalities, we are also affected by Agent Orange/dioxin [10].

1. INTRODUCTION

Nowadays, infectious diseases are decreasing, the rate of genetic, metabolic and cardiovascular diseases is increasing. In Vietnam, besides being affected by environmental agents that cause genetic abnormalities, we are also affected by Agent Orange/dioxin [10].

During the war, Thanh Khe - Da Nang and Bien Hoa were exposed to Agent Orange/dioxin because they were stored and transported at the airport. Some authors show that: Thanh Khe and Bien Hoa are places with higher rates of DTBS and abnormal pregnancy rates than other places [1], [5], [9], using folic acid, screening, prenatal diagnosis can reduce embryo abnormalities [2], [3], [6], [7], [8].

The question here is what is the current situation of birth defects and genetic diseases in Thanh Khe - Da Nang and Bien Hoa areas?, what measures to prevent birth defects should be carried out?. To answer the above questions, we conduct this study with the aim of:

- Analysis of the characteristics of birth defects, pregnancy abnormalities in people exposed to and at risk of exposure to Agent Orange in Thanh Khe and Bien Hoa.

- Evaluate the effectiveness of measures of screening, prenatal diagnosis, genetic counseling for those exposed and at risk of Agent Orange exposure to prevent birth defects in Thanh Khe and Bien Hoa.

- Propose a model of screening, prenatal diagnosis, and genetic counseling for those exposed and at risk of Agent Orange exposure.

Biên Hòa

2. RESEARCH SUBJECTS AND METHODS

2.1. Place and time of study

- The study was conducted in wards located around the airport and on the way rainwater flows from the airport to the sea: in Thanh Khe there are 4 wards: Chinh Gian, Thac Gian, An Khe and Hoa Khe, in Bien Hoa - Dong Nai are 5 wards: Trung Dung, Tan Phong, Tan Tien, Thong Nhat and Tan Mai.

- The study was conducted from 2013 to December 2015.

2.2. Research methods and subbjects

Research method: is an intervention method with comparison before and after.

- Using folic acid to prevent birth defects and pregnancy abnormalities: we apply it to women who intend to get pregnant in Thanh Khe and Bien Hoa.

- To determine the rate of birth defects, pregnancy abnormalities before and after the intervention: survey 1500/1 local women of reproductive age who have been pregnant.

- Conduct prenatal screening: In Thanh Khe double test and fetal ultrasound for 500 pregnant women, triple test for 277 women, in Bien Hoa, double test and fetal ultrasound for 564 pregnant women, triple test for 288 pregnant women.

- Prenatal diagnosis and counseling for high- risk pregnant women: Subjects are pregnant women who have high- risk pregnant women when STIs or have had children with birth defects.

In Thanh Khe we provide counseling for 128 pregnant women, in Bien Hoa 103 pregnant women.

- Proposing a model of screening, prenatal screening, and reproductive counseling for those exposed and at risk of Agent Orange/dioxin exposure

3. RESEARCH RESULTS AND DISCUSSION

3.1. Using folic acid to prevent pregnancy abnormalities

Table 1. Use folic acid.

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

The results in the table above show that most of the pregnant women used folic acid (98.29% in Bien Hoa, 97.34% in Thanh Khe - Da Nang).

Figure 1. Rate and form of folic acid used

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

The results in the chart above show that the percentage of pregnant women using folic acid in combination form in Bien Hoa is 82.24%, in Thanh Khe is 85.88%. The percentage of pregnant women using folic acid alone was less than in Bien Hoa 19.16%, in Thanh Khe 36.22%. There are some pregnant women who take both folic acid alone and combination pills that contain folic acid.

Table 2. Percentage of child birth defects according to the mother's history of folic acid use during pregnancy.

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

Regarding the effectiveness of folic acid use, we found in Bien Hoa, the rate of birth defects in the group of mothers who did not use folic acid during pregnancy was higher than in the group of mothers who used folic acid (p<0.01). the group of mothers who used folic acid during pregnancy had only 0.32 times chance giving birth to a baby with defects compared did not use it (95% ci: 0.16 - 0.64). in thanh khe, due small number studies, 10 children were counted, so obtained results cannot accurately reflect relationship between mother's and children. however, analysis situation bien hoa, if women take acid, risk having has been reduced.< />>

3.2. Status of prenatal screening

Table 3. Percentage of women with prenatal screening

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

The results in the table above show that most pregnant women have fetal ultrasound (99.52% in Thanh Khe, 99.79% in Bien Hoa). However, the percentage of pregnant women with STIs by maternal serum test is still small, doing double test in both localities is only 38.66%, doing triple test is even lower, only 20.68%.

Table 4. Abnormalities on ultrasound

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

The results in the table above show that: The abnormal rate detected by ultrasound is low, the most common abnormalities are vascular plexus cysts, high nuchal translucency, nasal abnormalities (short nasal bone, thick anterior nasal bone).), cardiac abnormalities.

Table 5. Double test results in Thanh Khe - Da Nang and Bien Hoa

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

The above table shows: the detection rate of high- risk pregnant women mainly from HTM, common for 2 localities is 10.24%. The rate of high- risk pregnant women by maternal age in 2 localities is 8.36. The rate of high- risk pregnant women according to ultrasound was 1.32%.

Table 6. Triple test results in Thanh Khe - Da Nang and Bien Hoa

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

The results in the table above show that: for both localities, the detection rate of NNC mainly from HTM test is 11.15%. The rate of high- risk pregnant women by maternal age is 11.15%. The rate of high- risk pregnant women with neural tube defects is 2.30%. The rate of high- risk pregnant women trisomy 18 was 1.59%.

Thus, the percentage of pregnant women who have had an STI using an IVF is still low. This result shows that the care and monitoring of pregnancy needs to be done much better, especially in those who live in an environment with the impact of bad agents.

The rate of detection of high- risk pregnant women mainly from HTM laboratory, for 2 localities with double test is 10.24%, with triple test is 11.15%. The rate of high- risk pregnant women by maternal age common for the 2 localities with pregnant women doing double test is 8.36%, with pregnant women doing triple test is 11.15%. The rate of high- risk pregnant women according to ultrasound in the first 3 months is 1.32%.

Regarding fetal ultrasound, most pregnant women have fetal ultrasound >3 times. However, there are still a few that do not monitor fetal growth with ultrasound. At the same time, there are pregnant women who have fetal ultrasound but the ultrasounds are only in 1 trimester.

3.3. Prenatal diagnosis

Table 7. Results of chromosomal analysis from amniotic cells

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

The results in the table above show:

In Thanh Khe: analyzing amniotic cells of 258 pregnant women, the abnormal rate detected by amniotic cell chromosomal analysis was 6.25%.

In Bien Hoa: analyzing amniotic cells of 103 pregnant women, the abnormal rate detected through chromosomal analysis of amniotic cells was 3.88%.

3.4. Maternity abnormalities and birth defects before and after intervention

Table 8. Miscarriage situation in Thanh Khe - Da Nang

Tim

The results in the table above show that: the rate of miscarriage and the rate of mothers with STIs in Thanh Khe in 2015 were lower than in 2013, the difference was statistically significant with p<0.01 and<0.05.< />>

Table 9. Miscarriage situation in Bien Hoa

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

The results in the table above show that: the rate of miscarriage and the rate of mothers with ST in Bien Hoa in 2015 were lower than in 2013, the difference was statistically significant with p<0.001 and<0.01.< />>

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

Figure 2. TCL situation and the percentage of mothers with stillbirth

in Thanh Khe - Da Nang

The results in the chart above show that the rate of stillbirth and the percentage of pregnant women with stillbirth in Thanh Khe - Da Nang in 2013 and 2015 are similar, p>0.05.

Table 10. Stillbirth situation and percentage of mothers

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

The results in the table above show that the stillbirth rate and the stillbirth rate in Bien Hoa in 2015 were lower than 2013, the difference with p<0.05.< />>

Table 11. Situation of birth defects in Bien Hoa and Thanh Khe

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

The results in the table above show that the rate of birth defects in Thanh Khe - Da Nang and in Bien Hoa in 2015 was lower than 2013, with p<0.05.< />>

The rate of congenital malformations in Thanh Khe and Bien Hoa in 2015 was lower than 2013. In 3 years, 29 cases of chromosomal abnormalities and 1 heart defect were detected, if this type of number is in newborn babies. then it accounts for more than a quarter of the number of children with disabilities that may appear (according to the 2013 survey). Therefore, it can be seen that prenatal screening and diagnosis using folic acid has reduced birth defects.

Comparing with the surveys in 2001, 2013 and 2015 [4] we find:

Table 12. Maternity abnormalities in Thanh Khe, Bien Hoa, Phu Cat in 2001, 2012, 2013, 2015.

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

Comparing at different times, the results in the above table show that: in Thanh Khe: the rate of pregnancy abnormalities has gradually decreased, the difference between the time points is p<0.05 and<0.01; in bien hoa: the rate of pregnancy abnormalities 2015 was lower than 2013 with p<0.001; phu cat: 2012 2001 p<0.001.< />>

The declining rate of pregnancy abnormalities is a good sign, possibly because the impact of environmental pollution, including Agent Orange/dioxin, has decreased, or the reproductive health care measures have improved such as the Folic acid use has gradually become popular…

Table 13. Identify risk factors for exposure and pregnancy abnormalities.

RESEARCH AND APPLICATION OF METHODS OF ANTENATAL SCREENING, DIAGNOSIS, AND GENETIC COUNSELING TO PREVENT REPRODUCTIVE ABNORMALITIES IN THANH KHE - DA NANG AND BIEN HOA

The results in the table above show that: in Thanh Khe there is no association between exposure to Agent Orange/dioxin with pregnancy abnormalities, in Bien Hoa there is a relationship between exposure to Agent Orange/dioxin with pregnancy abnormalities: OR=3.19 (1.45-6.89).

3.5. Building a model of genetic counseling for subjects at high risk of pregnancy abnormalities

In hot areas such as Thanh Khe and Bien Hoa, to a certain extent, measures similar to high- risk pregnant women s are needed, so in these places attention should be paid:

- It is necessary to prevent the whole community, such as: increasing the use of foods rich in antioxidants and rich in folic acid.

- This region has a higher rate of pregnancy abnormalities and birth defects than other places, it should be noted that the dose of folic acid for people with high- risk pregnant women is 4-5mg/day. For those with high- risk pregnant women, taking a higher dose of folic acid should use a single form, and at the same time take more B vitamins.

With the above noted characteristics, the model of restricting birth defects and pregnancy abnormalities for subjects suffering the consequences of Agent Orange/dioxin is as follows:

- Women who want to become pregnant should have counseling before 3 months, should take folic acid, vitamin B group 2-3 months before pregnancy, the first 3 months of pregnancy.

- Pregnancy ultrasound in the first 3 months, 2nd trimester, Double test, Triple test

+ If the risk is low, continue to follow up with ultrasound.

+ If high- risk pregnant women, it is necessary to diagnose before birth and then receive genetic counseling to prevent abnormalities for subsequent individuals.

4. CONCLUSION

4.1. Effective use of folic acid

The rate of pregnant women taking folic acid in Thanh Khe in 2013 was 95.88% in 2015 was 97.34%; in Bien Hoa in 2013 was 84.19%, in 2015 it was 98.29%.

Folic acid is inversely related to birth defects: OR = 0.32 (95% CI: 0.16 - 0.64).

4.2. Effectiveness of screening, prenatal diagnosis, genetic counseling in Thanh Khe and Bien Hoa

* Prenatal screening

- In Thanh Khe: Pregnant women with double test is 36.90%, triple test is 19.73%.

- In Bien Hoa: Pregnant women double test is 40.23%, triple test is 21.61%.

* Efficiency of fetal ultrasound: The rate of pregnant women having fetal ultrasound in Thanh Khe is 99.52%, in Bien Hoa is 99.79%, detecting abnormal pregnancy is 1.43%, in Bien Hoa is 0. 78%

* Prenatal diagnosis efficiency: In Thanh Khe: The detection rate of chromosomal abnormalities in Thanh Khe is 6.25%, in Bien Hoa is 3.88%.

4.3. Characteristics of birth defects, pregnancy abnormalities in Thanh Khe and Bien Hoa

- In Thanh Khe: In 2013, the rate of pregnancy abnormalities was 5.32%, miscarriage, stillbirth was 5.38%, birth defects was 2.40%. In 2015: the rate of pregnancy abnormalities was 2.84%, Miscarriage, stillbirth was 2.24%, Birth defects was 0.29%.

- In Bien Hoa: In 2013, the rate of pregnancy abnormalities was 9.40%, miscarriage, stillbirth was 7.45%, birth defects was 3.40%. In 2015: the rate of pregnancy abnormalities was 4.07%, Miscarriage, stillbirth was 3.07%, Birth defects were 0.34%.

- In Thanh Khe and Bien Hoa: pregnancy abnormalities in 2015 is lower than 2013.

Relationship between pregnancy abnormalities and Agent Orange/dioxin exposure: In Bien Hoa: there is a relationship between Agent Orange/dioxin contamination with pregnancy abnormalities: in 2013 there was OR=3.19 (95% CI: 1.45-6.89), in 2015: OR = 5.67 (95 % CI: 2.24 - 13.12). In Thanh Khe: no association was found between exposure to Agent Orange/dioxin and pregnancy abnormalities.

4.4. Limited model Maternity abnormalities in Thanh Khe - Da Nang and Bien Hoa

In hot areas, it should be noted, the dose of folic acid for people with high- risk pregnant women is 4-5mg/day, it should be used even before pregnancy.

Models for limiting pregnancy abnormalities and birth defects for hot areas need:

- Eat foods rich in folic acid and antioxidants.

- Take oral folic acid before and during the first trimester of pregnancy.

- Prenatal screening.

- Fetal ultrasound to measure KS and detect malformations.

- Prenatal diagnosis and genetic counseling.

REFERENCES

Trinh Van Bao, Tran Duc Phan, Nguyen Ngoc Hung et al. (2004), State-level project “Building a model of genetic counseling for families affected by chemical warfare agents”.

Bannink F., Larok R., Kirabira P., Bauwens L., Van Hove G. (2015), Prevention of spina bifida: folic acid intake during pregnancy in Gulu district, northern Uganda. Pan. Afr. Med. J. 30: 20 - 29.

Cueto H. T., Riis A. H., Hatch E. E., Wise L. A., Rothman K. J., Sørensen H. T., Mikkelsen E. M. (2015), Folic acid supplement use and menstrual cycle characteristics: a cross-sectional study of Danishpregnancy planners. Ann. Epidemiol. 25(10): 723-729.

Truong Quang Dat, Tran Duc Phan, Ngo Van Toan (2013), Rate of birth defects and some related factors in Phu Cat district - Binh Dinh. Journal of Practical Medicine,10 (884), 82 - 86.

Hoang Dinh Cau et al (1998), Some charateristics of birth defects caused by dioxin (Agent Orange). Viet Nam Medical journal, 3, 222, 1 - 23.

Dovev M.N., Vaknin Z., Keidar R., Reish O., Meltzer Y., Maymon R. (2014), Prenatal diagnosis of triploidy: the experience of Assaf-Harofe Medical Center. Harefuah. 153(9): 518 - 521.

Drury S., Williams H., Trump N., Boustred C., GOSGene, Lench N., Scott R.H., Chitty L.S. (2015). Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities. Prenat. Diagn. 35(10): 1010 - 1017.

Hasegawa J., Nakamura M., Sekizawa A. (2015), How do the trends in the prenatal diagnosis of aneuploidy change after a non-invasive prenataltest becomes available? A Japanese single center study. J. Med. Ultrason. 42(2): 195 - 198.

Le Bach Quang, Doan Huy Hau, Pham Ngoc Dinh, Nguyen Phu Khang (2002), Research on clinical epidemiology, congenital malformations and pregnancy abnormalities in the community living in areas contaminated with Agent Orange/dioxin. Vietnam - US scientific conference on the effects of Agent Orange/dioxin on human health and the environment, pp. 178 - 186.

Stellman J. M., Stellman S. D. Christian R., Weber T. Tomasallo C. (2003), The extent and pattern of usage of Agent Orange and other herbicides in Vietnam. Nature 422 (6933): 681 - 687.

Tran Duc Phan, Luong Thi Lan Anh, Hoang Thi Ngoc Lan, Hoang Thu Lan, Duong Hong Chuong, Tran Danh Cuong, Pham Ba Nha

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