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Renato Cocchi M.D., Ph.D. (Sociology) Italian Journal of Intellective Impairment 10 (2): 115-20 (1997) Paper presented during the 6th World Down Syndrome Congress, Madrid October 1997 A poster on first 360 cases was presented during the 8th Congress of I.A.S.S.M.D., Dublin, August 1988 and a letter on the same cases has been printed in Giorn. Neuropsich. Età Evol. 1988, 8: 256-257. |
Reprinted with the permission of Renato Cocchi Via A. Rabbeno, 3 42100 Reggio Emilia, Italy +39 0522 320 716 Mobile +39 348 5145 520 URL: http://www.stress-cocchi.net |
An epidemiological investigation on the possible influence of seasonal factors on conceptions of Trisomy 21 subjects was carried out, as the following of a previous paper (Cocchi R., Occhialini O.: It. J. Intellect. Impair. 1989, 2 1-7) The monthly conception's periods of a representative sample of 487 Italian Down Ss born between 1973 and 1992 were compared with the same monthly periods of all Italian live-born babies of the same years, minus 1/700 as the rate of Down births.
The seasonal distribution of conceptions of Down Ss has been found significantly different (.018), having increased rates particularly in spring and in first and second month of autumn and decreased in 3rd autumn and 2nd winter month. Cutting off the sample according to mother's age on giving birth, the conceptions of Down Ss born from less than 36 year old mothers present the same seasonal distribution (.0009), while in more than 35 year old mothers' sons a seasonal influence seems masked by the well-known maternal age effect.
Strong significant correlation exists between the monthly distribution of the whole sample conceptions and the distribution of the children born from less than 36 years mothers, while this does not occurs for children of mothers with 36 or more years at delivery. Key words: Down syndrome; epidemiology; conception; seasonal influence, stress.
In a first research [3] we found a higher prevalence of Down's syndrome births in the months of July and November, while there was a reduction in September. Also with regards probable months of conception, a higher number of conceptions were found in the months of August and October, while deficit was evident in the months of July, November and December.
Although having focused attention to this discordance, the subject was merely touched upon rather than attempting a deeper analysis, also because of our awareness that the methods with which we had investigated the problem were too simplistic. We returned to the subject in a following investigation with more rigorous criteria and a larger sample [2]. Now I come back to it with an increased sample and 20 years' period of survey.
The Ss were then subdivided according to the month in which they were born.
With the help of an obstetrician's rule, starting from the day of birth and adding or subtracting any weeks of prematurity or postmaturity, I identified the presumable day of conception.
Using the available ISTAT yearbooks [6], I found the total number of living births in Italy, month by month, between 1973 and 1992 inclusive. From each of these monthly totals, 1/700 was subtracted which represents the total number of Down's syndrome births for that same period. It is known that approximately one new-born child in 700 suffers from Down's syndrome. It was assumed that prematurity and postmaturity in non-Down babies are both distributed equally, each one in itself throughout the entire population.
Given that a birth is always preceded by a conception (though the opposite is not sometimes true) and calculating that this conception took place 280 days earlier, from the monthly totals of such new-borns I was able to arrive at the number of respective conceptions.
The monthly conception period was considered to be between the 8th day of a month and the 7th day of the next one; (e.g.: Punctual births or those which, if not premature or postmature, should have happened in the month of January, had their conceptions between 8th of April and 7th of May in the preceding year).
I therefore reconstructed the monthly total of conceptions of non-Down living births using 20-23 parts (= days) of the total number of births in a specified month ( according to its total days number) and 7 parts (= days) of the total number of births in the following month, moving the period back 280 days.
For example: Of those born in the January period, about 3/4th were conceived in last 22 days of the previous April period, while about 1/4th were conceived in first 7 days of the previous May. So, remembering that conception usually takes place 9 months and 10 days previously, the total number of conceptions in the September 8-October 7 period, through these calculations, constitutes about 3/4th of all the living births in the month of December between 1973 and 1992, plus 1/4th of all the living births in the month of January between 1973 and 1992.
The conceptions dates of all the Down subjects which make up our sample were subdivided according to the same monthly time periods (e.g.: April 8 - May 7).
We then further subdivided the Down subject conceptions on the basis of the mother's age when the child was born. In order to do this we chose the age of 36 as a limit, which corresponds approximately with a conception when the mother was 35 year old.
This age is considered by obstetricians to be the starting point of increased risk and therefore a prenatal diagnosis is advised. To evaluate the significance of the various factors we used Chi Square test and "r" coefficient of correlation.
Year | no. of Ss |
% | Year | No. of Ss |
% |
---|---|---|---|---|---|
1973 | 23 | 4.72 | 1983 | 35 | 7.19 |
1974 | 21 | 4.31 | 1984 | 41 | 8.42 |
1975 | 21 | 4.31 | 1985 | 29 | 5.95 |
1976 | 26 | 5.34 | 1986 | 22 | 4.52 |
1977 | 23 | 4.72 | 1987 | 19 | 3.90 |
1978 | 26 | 5.34 | 1988 | 17 | 3.49 |
1979 | 25 | 5.13 | 1989 | 18 | 3.70 |
1980 | 26 | 5.34 | 1990 | 15 | 3.08 |
1981 | 37 | 7.80 | 1991 | 10 | 2.05 |
1982 | 40 | 8.21 | 1992 | 13 | 2.67 |
Month | Live births (tot) | Tot. -1/700th | % | Sample births | % |
---|---|---|---|---|---|
January | 1087867 | 1086312 | 8.27 | 42 | 8.62 |
February | 986228 | 984819 | 7.50 | 39 | 8.01 |
March | 1097166 | 1095599 | 8.35 | 40 | 8.21 |
April | 1051147 | 1049645 | 8.00 | 44 | 9.03 |
May | 1166822 | 1165155 | 8.88 | 40 | 8.21 |
June | 1118938 | 1117340 | 8.51 | 39 | 8.01 |
July | 1179041 | 1177357 | 8.97 | 50 | 10.26 |
August | 1126481 | 1124872 | 8.57 | 37 | 7.60 |
Septem. | 1115636 | 1114042 | 8.49 | 32 | 6.57 |
October | 1187283 | 1185587 | 9.02 | 37 | 7.60 |
Novemb. | 1009827 | 1008384 | 7.68 | 49 | 10.06 |
Decemb. | 1020145 | 1018688 | 7.76 | 38 | 7.80 |
Totals | 13127800 | 100.00 | 487 | 100.00 |
Monthly period | No. of nonDown conceptions |
% | No. of sample conceptions |
% |
---|---|---|---|---|
8 Apr. - 7 May | 1045179 | 7.96 | 47 | 9.65 |
8 May - 7 June | 1081647 | 8.24 | 57 | 11.70 |
8.June - 7 July | 1055074 | 8.04 | 29 | 5.95 |
8 July - 7 Aug. | 1109608 | 8.45 | 42 | 8.62 |
8 Aug. - 7 Sept. | 1158445 | 8.82 | 47 | 9.65 |
8 Sept.- 7 Oct. | 1112958 | 8.48 | 50 | 10.27 |
8 Oct. - 7 Nov. | 1158967 | 8.83 | 44 | 9.03 |
8 Nov. - 7 Dec. | 1091323 | 8.31 | 25 | 5.13 |
8 Dec. - 7 Jan. | 1162007 | 8.85 | 32 | 6.57 |
8 Jan. - 7 Feb. | 1138245 | 8.67 | 43 | 8.83 |
8 Feb. - 7 Mar. | 960913 | 7.32 | 36 | 7.39 |
8 Mar. - 7 Apr. | 1053434 | 8.02 | 35 | 7.19 |
Totals | 13127800 | 100.00 | 487 | 100.00 |
Monthly period | a | b | c | d |
---|---|---|---|---|
No. of non | No. of sample | Sample Ss: maternal age | ||
Down Ss | Ss | < 36 years | ≥ 36 years | |
8 Apr. - 7 May | 1045179 | 47 | 34 | 13 |
8 May - 7 June | 1081647 | 55 | 35 | 20 |
8 June - 7 July | 1055074 | 28 | 12 | 16 |
8 July - 7 Aug. | 1109608 | 40 | 30 | 10 |
8 Aug. - 7 Sep. | 1158445 | 46 | 22 | 24 |
8 Sep. - 7 Oct. | 1112958 | 50 | 32 | 18 |
8 Oct. - 7 Nov. | 1158967 | 41 | 23 | 18 |
8 Nov. - 7 Dec. | 1091323 | 23 | 9 | 14 |
8 Dec. - 7 Jan. | 1162007 | 31 | 17 | 14 |
8 Jan. - 7 Feb. | 1138245 | 41 | 26 | 15 |
8 Feb. - 7 Mar. | 960913 | 35 | 12 | 23 |
8 Mar. - 7 Apr. | 1053434 | 35 | 24 | 11 |
Totals | 13127800 | 472 | 276 | 196 |
The M/F ratio, which slightly exceed the Italian trends at birth [1]; the distribution of chromosomal diagnoses which is well within both Italian and International averages [1;5;9-10], the nationwide provenance indicate that these 487 cases can be considered a representative sample of Italian Down subjects.
The results punctually confirm the previous research [3]. A seasonal influence on a biological process such as the one leading to chromosomal non disjunction during the gamete formation phase (meiotic phase) and during the first mitotic divisions (for mosaic forms), should not seem either impossible or extraordinary.
If we look at schizophrenia, it has been reported since more than 20 years that there exists a significant but unexplainable excess of cases born in the winter months.
This is a definite fact, confirmed and reconfirmed by a whole series of researchers [8], and which is difficult to reconcile with a purely psychological etiology.
On the other hand, being the chromosomal anomaly in Down Ss a process that has its developing point in the conception, although the anomaly in itself nearly always has a gamete origin, it seems possible to approximate the problem only by taking into consideration the conception's periods. Some investigations based on birth's periods conducted to debatable results [7;11-13], in my opinion, due to the excess presence of prematurity among deliveries of Down Ss as well as to the additional or prevalent effect of the maternal age. As far as this survey is concerned, I found an excess of trisomy 21 conceptions in spring months and in the first two autumn months.
Together with this we found two other peaks six months nearly apart from each other, namely August-September, and January-February.
The seasonal trend for Down subjects born to mothers under 36 years old is almost super impossible to conceptions' distribution of the whole sample and significantly different from the distribution of non Downs' conceptions. Regarding the subjects born to mothers of 36 years or older, no significant Chi Square figure and coefficient of correlation have been found in comparison with the seasonal trend for the population as a whole. This leads to infer that in this subgroups the seasonal influence on conceptions, if any, is completely masked by the well known maternal age effect.
The causes of incomplete chromosomal disjunctions, in Down subjects too, are still elusive [4], but if a seasonal influence should be finally confirmed, the field of stress reactions, mainly the parasympathetic ones, seems to me the next step to be investigated, even in 36 years and older mothers.
This investigation into the influence on the conception of Down subjects, as far as our 487 Italian individuals born in 1973-1992 are concerned, leads to confirm a different seasonal distribution in conceptions of 21 trisomics as compared to the seasonal distribution of all non-Down living births in Italy in the same time-period. This divergence was seen significant both for the whole sample and the sub-group of subjects born to mothers of less than 36 years old, but not for subjects born from mothers of 36 years and older. These results suggest that there exists a complex influence which we still are unable to well understand in its various aspects.
[1] Camera G., Mastroiacovo P.: Epidemiologia della Sindrome di Down. In:Ce.Pi.M.: Aspetti epidemiologici, genetici, clinici, riabilitativi e sociali della Sindrome di Down. Ce.Pi.M., Genova 1984: 225-230.
[2] Cocchi R., Occhialini O.: Is there any seasonal influence in the conceptions of Down's syndrome subjects? It. J. Intellect. Impair. 1989, 2: 1-7.
[3] Cocchi R., Occhialini O., Cocchi Cercolani P.: Alcuni dati epidemiologici su una serie consecutiva, non selezionata, di 241 soggetti Down. Rass. Studi Psichiat. 1985, 74: 785-790.
[4] Editor's writing: The elusive cause of Down's Syndrome. Lancet 1983, May 21: 1143-1144.
[5] Hook E.B.: Down Syndrome: Frequency in human population and factors pertinent to variation in rates. In: De La Cruz F.F., Gerald P.S. (eds): Trisomy 21 (Down Syndrome) research perspectives. University Park Press. Baltimore 1981.
[6] ISTAT: Annuari di Statistiche Demografiche 1973-1992. ISTAT, Roma 1974-1993.
[7] Iselius L., Lindsten J.: Changes in the incidence of Down syndrome in Sweden during 1968-1982. Hum. Genet. 1986, 72: 133-139.
[8] Kendall R.E., Kemp I.W.: Winter-born v summer-born schizophrenics. Br. J.Psychiat. 1987, 151: 499-505.
[9] Lambert J.L., Rondal J.A.: Le mongolisme. Mardaga, Bruxelles 1979.
[10] Lindsten G., Marsk L., Berklund K., Iselius L., Ryman N., Anneren G., Kjessler B., Mitelman F., Walstroem J., Vejlens L.: Incidence of Down's Syndrome in Sweden during the years 1968-1977. In: Burgio G.R., Fraccaro M., Tiepolo L., Wolf U. (eds): Trisomy 21. Human Genet. 1981 (suppl. 2): 195-210.
[11] Rothman K.J., Fabia J.J.: Place and time aspects of the occurence of Down's syndrome. Am. J. Epidem. 1976, 103: 560-564.
[12] Seifert C., Sommer A.: A summertime peak of Down's syndrome in Franklin County, Ohio. Am. J. Dis. Child. 1986, 140: 822-824.
[13] Videbech P., Neilsen J.: Chromosomal anomalies and season of birth. Human Gen. 1984, 65: 221-231.