SEASONAL INFLUENCE IN THE CONCEPTIONS
OF DOWN PERSONS IN ITALY:
A 20 YEARS SURVEY
Renato COCCHI
MD, neurologist and medical psychologist
Summary
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
*Down's
syndrome
*Mental
retardation
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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.
Materials and methods
The
medical records of 535 Ss affected by Down's syndrome were reexamined. These
constitute a consecutive non-selected series of 21 trisomic Ss, coming from all
parts of Italy and which I visited personally, between January 1979 and April
1997 inclusive. I estracted the records of those individuals born between 1973
and 1992 and the following information was collected:
sex; date
of birth; chromosomal diagnosis; period, expressed in weeks, of any
non-pathological or pathological prematurity or postmaturity (reference: 40
weeks); maternal age on
giving birth
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 indentified 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.
Results
The
results of this research are as follows:
Suitable
Ss for the investigation: 487 out of 535 = (91.03 %)
This is
due to the fact that 40 Ss were born between 1944 and 1972 and 8 Ss after 1992,
therefore all they do not fall within the period in question.
Gender
distribution: M: 284 Ss = 57.29 %
F: 203 Ss
= 42.71 %
sex ratio
M/F: 137.44
Distribution
of the chromosomal anomalies:
standard
trisomy 21: 446 Ss = 91.59 %
mosaicisms:
16 Ss = 3.28 %
translocations:
16 Ss = 3.28 %
unknown:
9 Ss = 1.85 %
Table
1 shows the stratification of the sample as regards the year of birth.
Table
1:
stratification and rates of the sample subjects according to the year of birth
|
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 |
The total
number of births per months, whether Down subjects considered in this sample or
non Down, is presented in Table 2.
Table
2:
Monthly distribution and rates of the whole population of Italian
livebirths
in 1973-1992; the same minus 1/700th, as the rate of Down births;
monthly
distribution and rates of births of sample subjects, all born in the same time
period.
|
|
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 |
Chi
Square = 9.615 with 11 df and p = .572
The
minimax difference in monthly percentages is 1.52 in the whole population vs
3.69 in sample subjects. There is not any significant difference between
monthly distributions of the births.
Table 3
lists the total number of monthly conceptions of live births between 8th April
1972 and 7th April 1992 minus 1/700th, together with the total monthly
conceptions of our 487 Down subjects, in same periods.
Table
3:
Monthly distribution of conceptions of live births non-Down subjects
and
conceptions of 487 sample subjects from 8 April 1972 to 7 April 1992
|
Monthly period |
No. of
nonDown concepttions |
% |
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 |
Chi Square = 22.952; df = 11; p < 0.018
The
distribution of the conceptions significantly differs. The minimax difference
in monthly percentages is 1.53 in the whole population vs 6.57 in sample
subjects.
Table 4
shows data referring to the conceptions of 472 of our 487 Down subjects,
grouped as far as the mother's age on giving birth is concerned, having placed
the cut-off at 36 years of age.
Table 4: Monthly distribution of conceptions of live births non-Down Ss and
conceptions of 472 (*) sample Ss according to mother's age at delivery
|
|
a |
b |
c |
d |
|
Monthly period |
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 |
(*) maternal age at delivery was lacking in the records of 15 Ss.
Chi
Square: a vs b = 22.081; df = 11 and p = .011
a
vs c = 37.636; df = 11; p < 0.0009
vs
d = 14.545; df=11; p = .205 N.S.a
"r"
coefficient of correlation:
[b
vs c: r = .885; t = 6.013; df = 10; p < .0009]*
[b
vs d: r = . 333; t = 1.122; df = 10; p = .288]*
c
vs d: r = - 0.143; t = - .456; df 10; p = .658
*being c and d subsamples of b, tests are debatable
Down
individuals born to mothers of less than 36 years old parallels the same
seasonal trend with regards conceptions and this distribution leads to a highly
significant Chi Square figure. The same cannot be said of Down subjects born to
mothers of 36 years or older. A non significant correlation was also found
between the monthly conception distribution of all 487 Down subjects in this
sample and the monthly distribution of those born to mothers with 36 years and
more, although the latter is a subsample of the former. There is non
significant correlation between the distributions of the two subsamples.
Discussion
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 subiects.
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 psychologcal 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
superimposable to conceptions’ distribution of the whole sample and signicantly
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.
Conclusion
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.
References
[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.
Paper presented durig
the 6th World Down Sindrome 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. Eta` Evol. 1988, 8: 256-257.
Printed on It. J. Intellect. Impair. 1997, 10: 115-120
Author's address: Renato COCCHI MD, via Rabbeno, 3
42100
Reggio Emilia (Italy)
renatococchi@libero.it
*Down's syndrome
*Mental retardation
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