Neural tube defects in Pondicherry
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《美国医学杂志》
Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, India
Abstract
OBJECTIVE: This study was carried out to identify the trend and the frequency of neural tube defects from July 1998 to June 2004. METHODS: A total of 310 babies were born with neural tube defects with the overall frequency of 5.7/1000 births compared to 2.3/1000 births observed earlier in our hospital. RESULTS: The most common defect was spina bifida (54.8%) followed by anencephaly (31.6%), and encephalocele (11.6%). More neural tube defects were observed in female and low birth weight babies, still births and unbooked mothers. Neural tube defect was significantly higher among babies born to parents of consanguineous marriage (p<0.01). Associated congenital defects were observed in thirty nine (12.6%) cases. CONCLUSION : The rise in the frequency of NTDS may indicate the current trend of NTDs in Southern India. A further prospective study is desired to measure the effectiveness of regular folic acid supplementation in bringing down this frequency.
Keywords: Neural tube defects; Consanguinity; Associated defects
Neural Tube Defects (NTDs) are the most common of the central nervous system malformations and the burden of the disease is very high in low socioeconomic countries like India. The incidence of NTDs varies from 0.5 to 11 per 1000 births in different parts of India.[1], [2] Previous studies reported higher incidence from northern part of India (3.9-10/1000)[3], [4] compared to other parts (0.5-2.64/1000)[1] with an exception from Davangere,[5] Karnataka. There is not enough data on the trend and the frequency of neural tube defects in Southern India. Hence, the present study was aimed to ascertain the trend, frequency and maternal-child characteristics of NTDs in a Pondicherry hospital.
Materials and Methods
This study included all births in this hospital between July 1998 and June 2004. All babies with NTDs were enrolled for evaluation during the study period. The information collected were: age of the mother, parity, antenatal care, family history, parental consanguinity, drug ingestion, and infections during antenatal period. Other details included mode of delivery, birth weight, sex and gestational age of the babies, type of neural tube defect, chromosomal anomalies and associated malformation. The Wilcoxon rank test and Chi-square test were used for statistical analysis. Further a comparison was made regarding the trend of NTDs during current period with a previously published data on congenital malformation from this hospital.[6]
Results
There were 54738 births during the study period. A total of 310 babies were born with NTDs with the overall frequency of 5.7 per 1000 births. The trend of NTDs during the study period compared to previously published data from our hospital is shown in Figure1. The male: female ratio was 0.6:1. Among the total cases 56.4% were still-births. Prematurity was noted among 44.5% babies with NTDs and 74.1% were low birth weight babies. Of the preterm babies, sixty nine percent of cases were very low birth weight (<1.5 kg). There is no significant change in the annual frequency of NTDs during the study period by using the Wilcoxon rank test (p>0.05). There was no significant difference in different months of the year (p>0.1). In the present study, spina bifida was the most common type of neural tube defect (54.8%) followed by anencephaly (31.6%), encephalocele (11.6%), and craniorachischisis (0.6%). table1 Two hundred and seventy-five babies (88.7%) had single defect and remaining had combined defects. There were no NTDs observed among the siblings of the cases. Of the maternal characteristics hydramnios was noted in forty- two (13.5%) mothers of babies born with NTDs. table2 shows maternal and child characteristics observed among the babies born to mothers with and without neural tube defects. Among them 17 (40.4%) were anencephaly babies. Only ninety-two (29.7%) were booked mothers, the remaining were unbooked (70.3%). Among the other maternal characteristics, ages between 21-30 years, teenage pregnancies and advanced age (>30 years) constitute 80%, 14%, 6% of babies with NTDs respectively. One hundred and twenty-six (40.6%) babies with NTDs were born to primi mothers. Forty-three percent babies were born to consanguineous parents. The frequency of NTDs among consanguineous parents were 10.3/1000 births compared to 4.2/1000 births among non-consanguineous parents (p<0.01) table3.
Discussion
In general, there is variation in the frequency of neural tube defects among various ethnic groups, races and geographic locations. In the present study, the overall frequency of NTDs was 5.7/ 1000 births compared to 2.3/1000 births during 1989-92[6] Figure1. The increasing frequency of NTDs in our hospital was probably due to large number of babies (70.3%) born to unbooked mothers. A high frequency of maternal malnutrition and low socioeconomic status could also be responsible for the increase in the frequency of NTDs in the present study. Sharma et al[3] and Airede[7] have observed no difference in the frequency among different socioeconomic status. Antenatal screening and selective termination of severely affected fetus in the earlier trimester is not being done in the present setup. In the western countries, overall decline in NTDs rates were observed as early as 1980's.[8] The decline was attributed to better prenatal care, wide spread maternal screening for NTDs and termination of affected pregnancies.[9]
The frequency of neural tube defect in the present study is 5.7/ 1000 births comparable to previous study by Agarwal et al.[10] A wide range of frequency has been quoted from different parts of India and it was 3.9/1000 in Lucknow[3], 7/1000 in East Delhi[11] and 11.4/1000 births in Davangere.[5] The reasons for the wide geographical variation of frequency are exactly not known because the etiology of NTDs is mostly multifactorial and genetic predisposition may contribute to this geographic variation.[9] There was no seasonal variation in the occurrence of NTDs. Previous studies also made similar observations.[7], [12]
The prevalence of NTDs among consanguineous and non-consanguineous marriage was 16.3-20.6/1000 and 5.9-8.4/1000 couples respectively.[1] In the present study, frequency of NTDs among consanguineous marriage was 10.3/1000 births against 4.2/1000 births among non- consanguineous marriage. Kulkarni et al reported a similar observation.[2] Various authors have attributed the higher frequency of NTDs to consanguinity.[2], [13], [14] However, studies have also reported lower frequency of NTDs with high consanguinity rate.[15], [16] Airede[7] has observed no consanguinity in his study and explained the possible genetic association without influence of parental consanguinity. The role of consanguinity in the frequency NTDs warrants further study.
Recent studies have reported various environmental causes in association with NTDs such as latex allergy[17] and hyperthermia in early pregnancy.[18] Sharma and Gulati have reported three times increase in the frequency of NTDs with an epidemic of dengue virus infection[19]. There was no epidemic illness and exposure to specific agents observed during the study period.
Anencephaly was the most common neural tube defects observed in Western countries and in some Indian studies.[4], [7], [20] But, spina bifida (54.8%) was the commonest malformation followed by anencephaly (31.6%) and encephalocele (11.6%) in the present study. A similar pattern of neural tube defects was observed in Nigeria[7].
Associated congenital defects were observed in thirty- nine (12.6%) cases. Airede[7] reported congenital defects in all of his 42 (100%) cases. The lower frequency of associated anomalies in the present series is probably due to genetic variation among the study population and fewer autopsies performed in the present cases. Associated malformations observed in the present cases include cleft lip and palate (5.5%), gastrointestinal anomalies (1.9%), polycystic kidney (1.3%), congenital dislocation of hip (1.3%), Meckel Gruber syndrome (1%), ocular malformations (0.6%), polydactyly (0.6%) and ectopia vesicae (0.3%). Seventy cases (22.6%) had hydrocephalus in the present study. Congenital talipes equinovarus (CTEV) is the most common skeletal defect observed in various studies[5], [8] and it was noted in thirty one (10%) of the present cases. The reported frequency of CTEV varied from 7 to 40 percent depending on the method of diagnosis[21]. However, CTEV is often the complication of NTDs.
The causes of NTDs and their rise and fall remain elusive. Establishment of an effective primary prevention of NTDs will have significant impact in the reduction of socio-economical burden of the family and the country. Randomized controlled studies raised the hope of primary prevention of NTDs by administration of periconceptional folic acid supplementation.[22], [23] In the present study, majority of mothers were unbooked and did not receive regular folic acid and iron supplementation. The rise in the frequency of NTDs in the present study may indicate the current trend of NTDs in Southern India. A further prospective study is needed to measure the effectiveness of regular folic acid supplementation in bringing down the frequency of NTDs in the present setup.
References
1. Agarwal SS. Neural tube defect. A preventable congenital malformation. Indian Pediatr 1999; 36: 643-648.
2. Kulkarni ML, Mathew MA, Ramachandran B. High incidence of neural tube defects in South India. Lancet 1987; 1260.
3. Sharma AK, Upreti M, Kamboj M, Mehra P, Das K, Misra A et al. Incidence of neural tube defects of Lucknow over a 10 year period from 1982-1991. Indian J Med Res 1994; 99: 223-226.
4. Kalra A, Kalra K, Sharma V, Singh M, Dayal RS. Congenital malformations. Indian Pediatr 1984; 21: 945-950.
5. Kulkarni ML, Mathew MA, Reddy V. The range of neural tube defects in southern India. Arch Dis Child 1989; 64: 201-204.
6. Bhat BV, Babu L. Congenital malformations at birth - A prospective study from south India. Indian J Pediatr 1998; 65: 873-881.
7. Airede KI. Neural tube defects in the middle belt of Nigeria. J Trop Pediatr 1992; 38: 27-30.
8. Windham GC, Edmonds LD. Current trends in the incidence of neural tube defects. Pediatrics 1982; 70: 333-337.
9. Seller MJ. Unanswered questions on neural tube defects. British Medical Journal 1987; 294: 1-2.
10. Agarwal SS, Singh U, Singh PS, Singh SS, Das V, Sharma A et al. Prevalence and spectrum of congenital malformations in a prospective study at a teaching hospital. Indian J Med Res 1991; 94: 413-419.
11. Sood MN, Agarwal N, Verma S, Bhargava SK. Neural tubal defects in an east Delhi hospital. Indian J Pediatr 1991; 58: 363-365.
12. Dowd MJ, Connolly K, Ryan A. Neural tube defects in rural Ireland. Arch Dis Child 1987; 62: 297-298.
13. Stevenson AC, Johston HA, Steward MIP, Golding DR. Congenital malformations-a report of a study of series of consecutive births in 24 centers. Bull WHO 1966; 34(suppl):1-127.
14. Naderi S. Congenital abnormalities in newborns of consanguineous and non-consanguineous parents. Obstet Gynecol 1979; 53: 195-199.
15. Sharma PD. The incidence of major congenital malformations in Mysore. Indian J Pediatr 1970; 37: 618-619.
16. Lakshminarayana P. Evaluation of Genetic and Environmental Factors in Pregnancy loss and malformed fetus. Final Report DST No. SP/SO/B-38-91, Department of Science and Technology New Delhi, 1998.
17. Szepfalusi Z, Seidl R, Bernert G, Dietrich W, Spitzauer S, Urbanek R. Latex sensitization in spina bifida appears disease-associated. J Pediatr 1999; 134: 344-348.
18. Edwards MJ, Shiota K, Smith MSR, Walsh DA. Hyperthermia and birth defects. Reprod Toxicol 1995; 9: 411-425.
19. Sharma JB, Gulati N. Potential relationship between dengue fever and neural tube defects in a northern district of India. Int J Gynaecol Obstet 1992; 39: 291-295.
20. Botto LA, Moore CA, Khoury MJ, Erickson JD. Neural tube defects. New Eng J Med 1999; 341: 1509-1519.
21. Alasdair-Hunter GW. Neural tube defects in eastern Ontario and Western Quebec. Demography and family data. Am J Med Genet 1984; 19: 45-63.
22. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991; 338: 131-137.
23. Czeizel AE, Dudαs I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992; 327: 1832-1835.(Mahadevan B, Bhat B Vishn)
Abstract
OBJECTIVE: This study was carried out to identify the trend and the frequency of neural tube defects from July 1998 to June 2004. METHODS: A total of 310 babies were born with neural tube defects with the overall frequency of 5.7/1000 births compared to 2.3/1000 births observed earlier in our hospital. RESULTS: The most common defect was spina bifida (54.8%) followed by anencephaly (31.6%), and encephalocele (11.6%). More neural tube defects were observed in female and low birth weight babies, still births and unbooked mothers. Neural tube defect was significantly higher among babies born to parents of consanguineous marriage (p<0.01). Associated congenital defects were observed in thirty nine (12.6%) cases. CONCLUSION : The rise in the frequency of NTDS may indicate the current trend of NTDs in Southern India. A further prospective study is desired to measure the effectiveness of regular folic acid supplementation in bringing down this frequency.
Keywords: Neural tube defects; Consanguinity; Associated defects
Neural Tube Defects (NTDs) are the most common of the central nervous system malformations and the burden of the disease is very high in low socioeconomic countries like India. The incidence of NTDs varies from 0.5 to 11 per 1000 births in different parts of India.[1], [2] Previous studies reported higher incidence from northern part of India (3.9-10/1000)[3], [4] compared to other parts (0.5-2.64/1000)[1] with an exception from Davangere,[5] Karnataka. There is not enough data on the trend and the frequency of neural tube defects in Southern India. Hence, the present study was aimed to ascertain the trend, frequency and maternal-child characteristics of NTDs in a Pondicherry hospital.
Materials and Methods
This study included all births in this hospital between July 1998 and June 2004. All babies with NTDs were enrolled for evaluation during the study period. The information collected were: age of the mother, parity, antenatal care, family history, parental consanguinity, drug ingestion, and infections during antenatal period. Other details included mode of delivery, birth weight, sex and gestational age of the babies, type of neural tube defect, chromosomal anomalies and associated malformation. The Wilcoxon rank test and Chi-square test were used for statistical analysis. Further a comparison was made regarding the trend of NTDs during current period with a previously published data on congenital malformation from this hospital.[6]
Results
There were 54738 births during the study period. A total of 310 babies were born with NTDs with the overall frequency of 5.7 per 1000 births. The trend of NTDs during the study period compared to previously published data from our hospital is shown in Figure1. The male: female ratio was 0.6:1. Among the total cases 56.4% were still-births. Prematurity was noted among 44.5% babies with NTDs and 74.1% were low birth weight babies. Of the preterm babies, sixty nine percent of cases were very low birth weight (<1.5 kg). There is no significant change in the annual frequency of NTDs during the study period by using the Wilcoxon rank test (p>0.05). There was no significant difference in different months of the year (p>0.1). In the present study, spina bifida was the most common type of neural tube defect (54.8%) followed by anencephaly (31.6%), encephalocele (11.6%), and craniorachischisis (0.6%). table1 Two hundred and seventy-five babies (88.7%) had single defect and remaining had combined defects. There were no NTDs observed among the siblings of the cases. Of the maternal characteristics hydramnios was noted in forty- two (13.5%) mothers of babies born with NTDs. table2 shows maternal and child characteristics observed among the babies born to mothers with and without neural tube defects. Among them 17 (40.4%) were anencephaly babies. Only ninety-two (29.7%) were booked mothers, the remaining were unbooked (70.3%). Among the other maternal characteristics, ages between 21-30 years, teenage pregnancies and advanced age (>30 years) constitute 80%, 14%, 6% of babies with NTDs respectively. One hundred and twenty-six (40.6%) babies with NTDs were born to primi mothers. Forty-three percent babies were born to consanguineous parents. The frequency of NTDs among consanguineous parents were 10.3/1000 births compared to 4.2/1000 births among non-consanguineous parents (p<0.01) table3.
Discussion
In general, there is variation in the frequency of neural tube defects among various ethnic groups, races and geographic locations. In the present study, the overall frequency of NTDs was 5.7/ 1000 births compared to 2.3/1000 births during 1989-92[6] Figure1. The increasing frequency of NTDs in our hospital was probably due to large number of babies (70.3%) born to unbooked mothers. A high frequency of maternal malnutrition and low socioeconomic status could also be responsible for the increase in the frequency of NTDs in the present study. Sharma et al[3] and Airede[7] have observed no difference in the frequency among different socioeconomic status. Antenatal screening and selective termination of severely affected fetus in the earlier trimester is not being done in the present setup. In the western countries, overall decline in NTDs rates were observed as early as 1980's.[8] The decline was attributed to better prenatal care, wide spread maternal screening for NTDs and termination of affected pregnancies.[9]
The frequency of neural tube defect in the present study is 5.7/ 1000 births comparable to previous study by Agarwal et al.[10] A wide range of frequency has been quoted from different parts of India and it was 3.9/1000 in Lucknow[3], 7/1000 in East Delhi[11] and 11.4/1000 births in Davangere.[5] The reasons for the wide geographical variation of frequency are exactly not known because the etiology of NTDs is mostly multifactorial and genetic predisposition may contribute to this geographic variation.[9] There was no seasonal variation in the occurrence of NTDs. Previous studies also made similar observations.[7], [12]
The prevalence of NTDs among consanguineous and non-consanguineous marriage was 16.3-20.6/1000 and 5.9-8.4/1000 couples respectively.[1] In the present study, frequency of NTDs among consanguineous marriage was 10.3/1000 births against 4.2/1000 births among non- consanguineous marriage. Kulkarni et al reported a similar observation.[2] Various authors have attributed the higher frequency of NTDs to consanguinity.[2], [13], [14] However, studies have also reported lower frequency of NTDs with high consanguinity rate.[15], [16] Airede[7] has observed no consanguinity in his study and explained the possible genetic association without influence of parental consanguinity. The role of consanguinity in the frequency NTDs warrants further study.
Recent studies have reported various environmental causes in association with NTDs such as latex allergy[17] and hyperthermia in early pregnancy.[18] Sharma and Gulati have reported three times increase in the frequency of NTDs with an epidemic of dengue virus infection[19]. There was no epidemic illness and exposure to specific agents observed during the study period.
Anencephaly was the most common neural tube defects observed in Western countries and in some Indian studies.[4], [7], [20] But, spina bifida (54.8%) was the commonest malformation followed by anencephaly (31.6%) and encephalocele (11.6%) in the present study. A similar pattern of neural tube defects was observed in Nigeria[7].
Associated congenital defects were observed in thirty- nine (12.6%) cases. Airede[7] reported congenital defects in all of his 42 (100%) cases. The lower frequency of associated anomalies in the present series is probably due to genetic variation among the study population and fewer autopsies performed in the present cases. Associated malformations observed in the present cases include cleft lip and palate (5.5%), gastrointestinal anomalies (1.9%), polycystic kidney (1.3%), congenital dislocation of hip (1.3%), Meckel Gruber syndrome (1%), ocular malformations (0.6%), polydactyly (0.6%) and ectopia vesicae (0.3%). Seventy cases (22.6%) had hydrocephalus in the present study. Congenital talipes equinovarus (CTEV) is the most common skeletal defect observed in various studies[5], [8] and it was noted in thirty one (10%) of the present cases. The reported frequency of CTEV varied from 7 to 40 percent depending on the method of diagnosis[21]. However, CTEV is often the complication of NTDs.
The causes of NTDs and their rise and fall remain elusive. Establishment of an effective primary prevention of NTDs will have significant impact in the reduction of socio-economical burden of the family and the country. Randomized controlled studies raised the hope of primary prevention of NTDs by administration of periconceptional folic acid supplementation.[22], [23] In the present study, majority of mothers were unbooked and did not receive regular folic acid and iron supplementation. The rise in the frequency of NTDs in the present study may indicate the current trend of NTDs in Southern India. A further prospective study is needed to measure the effectiveness of regular folic acid supplementation in bringing down the frequency of NTDs in the present setup.
References
1. Agarwal SS. Neural tube defect. A preventable congenital malformation. Indian Pediatr 1999; 36: 643-648.
2. Kulkarni ML, Mathew MA, Ramachandran B. High incidence of neural tube defects in South India. Lancet 1987; 1260.
3. Sharma AK, Upreti M, Kamboj M, Mehra P, Das K, Misra A et al. Incidence of neural tube defects of Lucknow over a 10 year period from 1982-1991. Indian J Med Res 1994; 99: 223-226.
4. Kalra A, Kalra K, Sharma V, Singh M, Dayal RS. Congenital malformations. Indian Pediatr 1984; 21: 945-950.
5. Kulkarni ML, Mathew MA, Reddy V. The range of neural tube defects in southern India. Arch Dis Child 1989; 64: 201-204.
6. Bhat BV, Babu L. Congenital malformations at birth - A prospective study from south India. Indian J Pediatr 1998; 65: 873-881.
7. Airede KI. Neural tube defects in the middle belt of Nigeria. J Trop Pediatr 1992; 38: 27-30.
8. Windham GC, Edmonds LD. Current trends in the incidence of neural tube defects. Pediatrics 1982; 70: 333-337.
9. Seller MJ. Unanswered questions on neural tube defects. British Medical Journal 1987; 294: 1-2.
10. Agarwal SS, Singh U, Singh PS, Singh SS, Das V, Sharma A et al. Prevalence and spectrum of congenital malformations in a prospective study at a teaching hospital. Indian J Med Res 1991; 94: 413-419.
11. Sood MN, Agarwal N, Verma S, Bhargava SK. Neural tubal defects in an east Delhi hospital. Indian J Pediatr 1991; 58: 363-365.
12. Dowd MJ, Connolly K, Ryan A. Neural tube defects in rural Ireland. Arch Dis Child 1987; 62: 297-298.
13. Stevenson AC, Johston HA, Steward MIP, Golding DR. Congenital malformations-a report of a study of series of consecutive births in 24 centers. Bull WHO 1966; 34(suppl):1-127.
14. Naderi S. Congenital abnormalities in newborns of consanguineous and non-consanguineous parents. Obstet Gynecol 1979; 53: 195-199.
15. Sharma PD. The incidence of major congenital malformations in Mysore. Indian J Pediatr 1970; 37: 618-619.
16. Lakshminarayana P. Evaluation of Genetic and Environmental Factors in Pregnancy loss and malformed fetus. Final Report DST No. SP/SO/B-38-91, Department of Science and Technology New Delhi, 1998.
17. Szepfalusi Z, Seidl R, Bernert G, Dietrich W, Spitzauer S, Urbanek R. Latex sensitization in spina bifida appears disease-associated. J Pediatr 1999; 134: 344-348.
18. Edwards MJ, Shiota K, Smith MSR, Walsh DA. Hyperthermia and birth defects. Reprod Toxicol 1995; 9: 411-425.
19. Sharma JB, Gulati N. Potential relationship between dengue fever and neural tube defects in a northern district of India. Int J Gynaecol Obstet 1992; 39: 291-295.
20. Botto LA, Moore CA, Khoury MJ, Erickson JD. Neural tube defects. New Eng J Med 1999; 341: 1509-1519.
21. Alasdair-Hunter GW. Neural tube defects in eastern Ontario and Western Quebec. Demography and family data. Am J Med Genet 1984; 19: 45-63.
22. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991; 338: 131-137.
23. Czeizel AE, Dudαs I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992; 327: 1832-1835.(Mahadevan B, Bhat B Vishn)