Post on 01-Oct-2021
Exploring the Seasonality of Birth Defects in theNew York State Congenital Malformations Registry
Alissa R. Caton*
University at Albany, Department of Epidemiology and Biostatistics, Rensselaer, New York
Received 19 December 2011; Revised 8 February 2012; Accepted 10 February 2012
BACKGROUND: Examining seasonal patterns of birth defects may help to identify environmental risk fac-tors. Because the teratogenic window for most birth defects is during gestational weeks 3 to 8, investigatingexposures closer to the timing of conception is important. However, studies are usually based on month ofbirth, which is not the biologically relevant exposure period and does not account for differences in gesta-tional length. We aimed to determine whether the occurrence of birth defects varied by month of conceptionusing the population-based New York State Congenital Malformations Registry (CMR). METHODS: Wemerged live birth certificates (n 5 2,044,091) with CMR records for mothers residing in New York State,excluding New York City, for the years 1992 through 2006. We categorized birth defects according to theNational Birth Defects Prevention Network guidelines and performed Cochran-Armitage trend, Hewitt-Rog-erson, and Walter-Elwood tests on month of conception and chi-square tests on season of conception. Wegraphed seasonal distributions and seasonality test results. We performed stratified analyses by maternaland infant characteristics. RESULTS: Of 42 groups examined in the 15-year period, 24 (57%) had at least onestatistically significant test result, suggesting a trend or seasonal variation: Cochran-Armitage (18), Hewitt-Rogerson (17), Walter-Elwood (4), and chi-square (5). Ventricular septal defect showed the most consistentresults: Cochran-Armitage (p 5 0.0006), Hewitt-Rogerson (December to May; p 5 0.0130), Walter-Elwood(March 14; p 5 0.0027), and chi-square (winter; p 5 0.0046). Congenital cataract, pulmonary valve atresia/stenosis, coarctation of aorta, biliary atresia, and renal agenesis or hypoplasia had at least three significanttests. DISCUSSION: These results may help to generate hypotheses about environmental factors that vary byseason for further studies. Birth Defects Research (Part A) 00:000–000, 2012. � 2012 Wiley Periodicals, Inc.
Key words: birth defects; epidemiology; registry; seasonality; surveillance
INTRODUCTION
Although major birth defects occur in approximately3% of births (Centers for Disease Control and Prevention,2008), the causes of most birth defects are unknown(Nelson and Holmes, 1989). Examining seasonal patternsusing routinely collected birth defects surveillance datamay help us generate hypothesis about environmentalrisk factors that can be tested in analytic studies. Resultsof seasonality studies in the literature have been inconsis-tent by geography and time period and are often basedon month of birth, which is not the biologically relevantexposure period and does not account for differences inlength of gestation (Bound et al., 1989; Castilla et al.,1990; Siffel et al., 2005). For most birth defects, the criticalperiod of exposure is in the 3rd to 8th weeks after con-ception during organogenesis (Sadler, 2004); therefore, itis important to examine environmental factors closer tothe timing of conception and early pregnancy. Our objec-
tive was to determine whether the occurrence of birthdefects in upstate New York varied by month of concep-tion by using the population-based New York State Con-genital Malformations Registry (CMR).
MATERIALS AND METHODS
Appropriate institutional review board approvals weregranted to access New York State birth certificate datafrom vital records and birth defects data from the CMR.We linked live birth certificates (n 5 2,044,091) withCMR records for mothers residing in upstate New York(New York State, excluding New York City) at birth for
*Correspondence to: Alissa R. Caton, Department of Epidemiology and Bio-statistics, University at Albany, School of Public Health, One University Place,Room 131, Rensselaer, NY 12144-3456. E-mail: arc05@health.state.ny.usPublished online in Wiley Online Library (wileyonlinelibrary. com).DOI: 10.1002/bdra.23006
Birth Defects Research (Part A): Clinical and Molecular Teratology 00:000�000 (2012)
� 2012 Wiley Periodicals, Inc. Birth Defects Research (Part A) 00:000�000 (2012)
the years 1992 to 2006 to construct a 15-year live birthcohort. The CMR is a population-based registry thatreceives mandated reports on children who were born inNew York State and were diagnosed with birth defects,metabolic defects, or chromosomal anomalies up until 2years of age from hospitals and physicians. Hospitalaudits are conducted to capture the unreported cases.On-site hospital medical record audits documented thatthe CMR reports were greater than 90% correct (Wanget al., 2010), which is comparable to that of the Metro-politan Atlanta Congenital Defects Program, an activesurveillance system that is regarded as the gold standard(Honein and Paulozzi, 1999). The birth certificate containsdata on maternal and infant characteristics, such asmaternal age, race or ethnicity, education level, date oflast menses, infant date of birth, sex, birth weight, andgestational age. Roohan et al. (2003) assessed the accu-racy of the date of last menses recorded on the NewYork State birth certificate by checking medical records;they found the date to be correct 87% of the time and93% accurate within 1 week of the actual date.
Using the International Classification of Disease ClinicalModification, Ninth Revision, diagnosis codes from theCMR records, we grouped birth defects into 45 categoriesas defined in the guidelines of the National Birth DefectsPrevention Network (NBDPN; National Birth DefectsPrevention Network, 2010). We excluded three casegroups with fewer than 50 cases from our analyses: aniri-dia (n 5 9), common truncus (n 5 44), and bladderexstrophy (n 5 23). The remaining 42 case groupsselected for analyses are listed in Table 1.
We estimated date of conception by adding 14 days tothe maternal date of last menses. Based on this referencepoint, we categorized each birth into 12 months and fourseasons of conception: winter (December–February),spring (March–May), summer (June–August), and fall(September–November). Because there is a seasonal vari-ation in live births, it is important to account for that var-iation in analyses of the distribution of adverse birth out-comes (Darrow et al., 2009). To visualize the distributionsacross seasons, we plotted birth defects prevalence ratesper 10,000 live births (No. of birth defects 3 10,000 7No. of live births) by month and season of conception.We performed four statistical tests to examine trend andseasonal variation of the birth defects groups based ontiming of conception. According to the statistical methodsrecommended for analyzing the seasonal variation ofbirth defects proposed and described in detail by Siffelet al. (2005), we conducted the Cochran-Armitage trendtest, the Hewitt-Rogerson test, and the Walter-Elwoodtest using month of conception. Each test accounts forthe seasonal variation of live births. The Cochran-Armit-age test is used to detect an underlying trend in datawith binomial proportions (Cochran, 1954; Armitage,1955). The Hewitt-Rogerson test is a nonparametric testfor seasonality that ranks monthly prevalence rates fromlowest to highest, sums all possible sequences of six con-secutive months, and identifies the 6-month period withthe maximum rank sum (i.e., the Hewitt Score; Hewittet al., 1971; Rogerson, 1996). The test requires at least 6months with nonzero frequencies. The Walter-Elwoodtest is a parametric test for seasonality that uses a simpleharmonic curve and allows for a variable population atrisk (Walter and Elwood, 1975). The test estimates theamplitude of the seasonal variation, the date at which the
maximum occurs, and the goodness of fit. The testrequires at least 50 cases. Because New York has fourdistinct seasons, we also performed a chi-square testusing season of conception. The chi-square test is used totest for the relationship between two discrete variablesby comparing observed versus expected values (Cochran,1954). It is recommended that no more than one fifth ofcells have expected values less than 5. To perform theHewitt-Rogerson and Walter-Elwood tests, we used theStatistical Analysis Battery for Epidemiologic Research(SABER) version 1.96, developed by LM James anddownloaded from the Centers for Disease Control andPrevention (Atlanta, GA; http://www.cdc.gov/ncbddd/birthdefects/research-tools.html). Other analyses wereperformed in SAS version 9.1 (SAS Institute, Cary, NC).Because seasonal patterns of births varied by maternal
sociodemographics in a study in metropolitan Atlanta(Darrow et al., 2009), and because some studies havereported sex differences in seasonality of birth defects(Heikkila, 1984; Puri and Singh, 1995; Fraser and Gwyn,1998; Krost and Schubert, 2006; Liu et al., 2011), we alsoexamined seasonality within strata of maternal age (<20,20–34, �35 years), race or ethnicity (non-Hispanic white,non-Hispanic black, Hispanic), education level (<12, 12–15, �16 years), and infant sex (male, female). The Walter-Elwood test was limited to case groups with at least 50subjects, and the Hewitt-Rogerson and chi-square testswere limited to case groups with at least 20 subjects.
RESULTS
Of the 2,044,091 live births within the 1992 to 2006study period, 1,967,654 (96.3%) infants with dates of lastmenstrual period were included in the analyses. Livebirth prevalence rates per 10,000 live births and results ofthe four statistical tests for the selected birth defectsgroups are displayed in Table 1. Twenty-four (57%) ofthe 42 groups examined had at least one statistically sig-nificant test result, suggesting a trend or seasonal varia-tion. The Cochran-Armitage trend test was significantand suggested heterogeneity of monthly distributions fornine groups of congenital heart defects (i.e., tetralogy ofFallot, ventricular septal defect, atrial septal defect, endo-cardial cushion defect, pulmonary valve atresia or steno-sis, Ebstein anomaly, aortic valve stenosis, patent ductusarteriosus, and coarctation of the aorta) and nine otherbirth defects groups: hydrocephalus without spina bifida,anophthalmia or microphthalmia, congenital cataract, bil-iary atresia, renal agenesis/hypoplasia, lower limb reduc-tion, Down syndrome, trisomy 18, and fetal alcohol syn-drome. The Hewitt-Rogerson test was significant for cer-tain 6-month intervals in 17 birth defect groups:pulmonary valve atresia or stenosis, coarctation of theaorta, and amniotic bands (January–June); biliary atresia,lower limb reduction, and trisomy 18 (March–August);congenital megacolon (April–September); congenital cata-ract and renal agenesis or hypoplasia (June–November);endocardial cushion defect (July–December); hydrocepha-lus without spina bifida and transposition of the greatarteries (August–January); upper limb reduction (Septem-ber–February); anotia or microtia (October–March); andencephalocele, ventricular septal defect, and fetal alcoholsyndrome (December–May). The Walter-Elwood test wassignificant for ventricular septal defect (peak, March 14),pulmonary valve atresia/stenosis (peak, October 14),
2 CATON
Birth Defects Research (Part A) 00:000�000 (2012)
Tab
le1
SummaryofTrendan
dSeasonalityTests
forSelectedBirth
Defects
inUpstateNew
York,1992–2006
Group
Live
births
Rate
per
10,000
livebirths
Coch
rane-Arm
itag
eHew
itt-Rogerson
Walter-Elw
ood
Chi-square
pvalue,
2-sided
Hew
itt
score
Peak6-month
period
pvalue
Peak
pvalue,
centerofgravity
pvalue,
goodness
offit
Peak
season
pvalue
LiveBirths
1,967,65
4CentralNervousSystem
Anen
cephalus
920.47
0.12
948
Oct–M
ar0.09
0Feb
10.571
0.80
9W
inter
0.834
Spinabifidawithoutan
encephalus
359
1.82
0.43
844
Mar–A
ug
0.24
2Mar
20.976
0.46
1Spring
0.968
Hydrocephaluswithoutsp
inabifida
989
5.03
0.048a
51Aug–Jan
0.033a
Nov3
0.651
0.87
2W
inter
0.812
Encephalocele
970.49
0.06
851
Dec–M
ay0.033a
Feb
190.427
0.56
1W
inter
0.270
Microcephalus
634
3.22
0.15
448
Nov–A
pr
0.09
0Dec
190.773
0.93
8Fall
0.799
Eye
Anophthalmia,microphthalmia
990.50
0.013a
48Dec–M
ay0.09
0Mar
60.308
0.35
8Spring
0.101
Congen
ital
cataract
236
1.20
0.007a
53Jun–N
ov
0.013a
Mar
200.231
0.01
2Summer
0.027a
Ear
Anotia,
microtia
105
0.53
0.13
652
Oct–M
ar0.021a
Dec
100.668
0.67
8Fall
0.927
Cardiovascular
Transp
ositionofgreat
arteries
234
1.19
0.15
252
Aug–Jan
0.021a
Nov7
0.199
0.98
6Fall
0.645
TetralogyofFallot
386
1.96
0.020a
46Jul–Dec
0.15
5Nov1
0.681
0.16
6Fall
0.055
Ven
tricularseptaldefect
4923
25.02
0.001a
53Dec–M
ay0.013a
Mar
140.003a
0.16
8W
inter
0.005a
Atrialseptaldefect
2645
13.44
0.027a
48Jan–Jun
0.09
0Mar
270.196
0.04
4Spring
0.090
Endocard
ialcu
shiondefect
156
0.79
0.013a
56Jul–Dec
0.002a
Mar
280.060
0.00
1Fall
0.327
Pulm
onaryvalveatresiaorsten
osis
1408
7.16
0.010a
53Jan–Jun
0.013a
Oct
140.018a
0.00
3Spring
0.034a
Tricu
spid
atresiaorsten
osis
140
0.71
0.11
748
Sep
–Feb
0.09
0Jan7
0.741
0.34
6W
inter
0.413
Ebsteinan
omaly
960.49
0.049a
46Oct–M
ar0.15
5Nov24
0.179
0.33
7Fall
0.772
Aortic
valvesten
osis
269
1.37
0.042a
47Jan–Jun
0.12
0Oct
260.503
0.04
9W
inter
0.307
Hypoplastic
leftheart
syndrome
284
1.44
0.18
448
May
–Oct
0.09
0Feb
50.614
0.35
3Fall
0.620
Paten
tductusarteriosu
s(�
2500
gm)
1789
9.09
0.024a
49Feb
–Jul
0.06
6Nov23
0.125
0.05
9Summer
0.564
Coarctationofao
rta
706
3.59
0.008a
56Jan–Jun
0.002a
Oct
60.044a
0.00
5W
inter
0.048a
Orofacial
Cleftpalatewithoutcleftlip
1087
5.52
0.07
547
Nov–A
pr
0.12
0Feb
20.490
0.42
3W
inter
0.781
Cleftlipwithan
dwithoutcleftpalate
1509
7.67
0.13
946
Mar–A
ug
0.15
5Dec
170.780
0.07
4Summer
0.614
Choan
alatresia
312
1.59
0.08
548
Mar–A
ug
0.09
0Dec
180.777
0.16
2Summer
0.450
Gastrointestinal
Esophag
ealatresia,
tracheo
esophag
ealfistula
363
1.84
0.13
047
May
–Oct
0.12
0Dec
10.788
0.58
0W
inter
0.726
Rectalan
dlargeintestinal
atresiaorsten
osis
555
2.82
0.11
244
May
–Oct
0.24
2Feb
40.641
0.22
6Summer
0.763
Pyloricsten
osis
4026
10.46
0.10
545
Jun–N
ov
0.19
7NC
Summer
0.226
Hirschsp
rungdisease
(congen
ital
meg
acolon)
394
2.00
0.14
750
Apr–Sep
0.047a
Jan2
0.411
0.47
5Summer
0.711
Biliary
atresia
152
0.77
0.014a
56Mar–A
ug
0.002a
Dec
60.027a
0.00
1Summer
0.056
Genitourinary
Ren
alag
enesis
orhypoplasia
567
2.88
0.001a
51Jun–N
ov
0.033a
Mar
160.142
<0.00
1Summer
0.010a
Obstructivegen
itourinarydefect
5091
25.87
0.20
347
Jun–N
ov
0.12
0Mar
180.926
0.15
6Fall
0.610
Hyposp
adias,
epispad
ias
7623
75.68
0.27
342
Jan–Jun
0.35
0NC
Summer
0.561
Musculosk
eletal
Upper
limbreductiondeform
ity
381
1.94
0.05
750
Sep
–Feb
0.047a
Jan3
0.124
0.86
6W
inter
0.124
Lower
limbreductiondeform
ity
243
1.23
0.029a
51Mar–A
ug
0.033a
Nov11
0.246
0.10
5Spring
0.114
Gastroschisis
344
1.75
0.10
244
Mar–A
ug
0.24
3Feb
90.925
0.51
8Summer
0.908
Omphalocele
246
1.25
0.32
745
Nov–A
pr
0.19
7Nov22
0.861
0.70
9Fall
0.875
Congen
ital
hip
dislocation
2467
12.54
0.10
149
Mar–A
ug
0.06
6Dec
190.305
0.31
7Spring
0.191
3SEASONALITY OF BIRTH DEFECTS
Birth Defects Research (Part A) 00:000�000 (2012)
coarctation of the aorta (peak, October 6), and biliaryatresia (peak, December 6); however, only the peak forventricular septal defect fell within the time periods indi-cated by the Hewitt-Rogerson and chi-square tests. Thechi-square test for season of conception was significantfor congenital cataract (summer peak), ventricular septaldefect (winter peak), pulmonary valve atresia/stenosis(spring peak), coarctation of the aorta (winter peak), andrenal agenesis/hypoplasia (summer peak).Figure 1 displays the results of the four statistical tests
graphically for the 17 birth defect groups with at leastone statistically significant seasonality test during 1992 to2006. Each panel in the figure provides a visual summaryof the results for one birth defect group. The bars repre-sent the rates by season of conception, with darker grayshading indicating a statistically significant chi-squaretest. The line shows the rates by month of conception,with solid black indicating statistical significance of theCochran-Armitage test for trend. The boxes on the x-axismark the peak 6-month period of conception with thesolid black indicating a statistically significant Hewitt-Rogerson test. Finally, the triangle near the top of theplot marks the peak month of conception with the solidblack indicating statistical significance of the Walter-Elwood test.In stratified analyses of maternal characteristics and
infant sex, each of the 25 birth defect groups that did notexhibit a seasonal pattern in the total live birth cohortdisplayed a positive seasonality test within at least onestratum. Among infants of mothers younger than 20years (7.5% of live births), seasonal patterns weredetected for tetralogy of Fallot, omphalocele, congenitalhip dislocation, diaphragmatic hernia, and Down syn-drome (Table 2). Infants of mothers 20 to 34 years old(75.2% of live births) displayed seasonal patterns formicrocephalus, atrial septal defect, Ebstein anomaly, andpatent ductus arteriosus. Seasonal variation in infants ofmothers 35 years and older (17.3% of live births) wasapparent for spina bifida, hypoplastic left heartsyndrome, esophageal atresia–tracheoesophageal fistula,pyloric stenosis, obstructive genitourinary defect, hypo-spadias or epispadias, congenital hip dislocation, andfetal alcohol syndrome.Infants of non-Hispanic white mothers (76.4% of live
births) demonstrated seasonality for microcephalus, atrialseptal defect, hypoplastic left heart syndrome, patentductus arteriosus, rectal and large intestinal atresia or ste-nosis, biliary atresia, renal agenesis or hypoplasia,omphalocele, and congenital hip dislocation (Table 3).Infants of non-Hispanic black mothers (10.4% of livebirths) displayed seasonality for omphalocele, congenitalhip dislocation, and diaphragmatic hernia. Infants of His-panic mothers (9.7% of live births) showed seasonal pat-terns for microcephalus, atrial septal defect, aortic valvestenosis, cleft palate, choanal atresia, rectal and large in-testinal atresia/stenosis, pyloric stenosis, and hypospa-dias or epispadias.Infants of those with less than a high school education
(14.2% of live births) displayed seasonality for tetralogyof Fallot, esophageal atresia–tracheoesophageal fistula,rectal and large intestinal atresia or stenosis, pyloric ste-nosis, biliary atresia, congenital hip dislocation, andDown syndrome (Table 4). Tetralogy of Fallot, patentductus arteriosus, gastroschisis, omphalocele, trisomy 13,and Down syndrome exhibited seasonal patterns in
Tab
le1
SummaryofTrendan
dSeasonalityTests
forSelectedBirth
Defects
inUpstateNew
York,1992–2006(C
ontinued
)
Group
Live
births
Rate
per
10,000
livebirths
Coch
rane-Arm
itag
eHew
itt-Rogerson
Walter-Elw
ood
Chi-square
pvalue,
2-sided
Hew
itt
score
Peak6-month
period
pvalue
Peak
pvalue,
centerofgravity
pvalue,
goodness
offit
Peak
season
pvalue
Diaphragmatic
hernia
346
1.76
0.173
45Jun–N
ov
0.19
7Feb
160.888
0.690
Summer
0.462
Chromosomal
Trisomy13
136
0.69
0.191
48Feb
–Jul
0.09
0Nov19
0.880
0.892
Winter
0.854
Downsyndrome(trisomy21
)22
5411
.46
0.04
6a45
Dec–M
ay0.19
5Mar
190.401
0.243
Winter
0.114
Trisomy18
202
1.03
0.00
9a51
Mar–A
ug
0.033a
Nov16
0.361
0.080
Summer
0.108
Other
Fetal
alcoholsyndrome
231
1.17
0.02
9a50
Dec–M
ay0.047a
Feb
140.071
0.202
Winter
0.089
Amnioticban
ds
790.40
0.115
50Jan–Jun
0.047a
Feb
70.562
0.809
Winter
0.709
aStatistically
significanttren
dorseasonalitytest
(p�
0.05).
NC,notcomputed.
4 CATON
Birth Defects Research (Part A) 00:000�000 (2012)
infants of mothers with high school or some collegeeducation (55.3% of live births). Infants of women with acollege degree (30.5% of live births) demonstrated sea-
sonality for microcephalus, anophthalmia or microphthal-mia, tetralogy of Fallot, atrial septal defect, tricuspid atre-sia or stenosis, Ebstein anomaly, hypoplastic left heart
Figure 1. Graphical summaries of trend and seasonality tests for birth defects groups with at least one statistically significant seasonalitytest. The line shows the live birth prevalence rates by month of conception, with solid black indicating statistical significance (p � 0.05)of the Cochrane-Armitage test for trend. The boxes on the x-axis mark the peak 6-month period of conception, with solid black indicatinga statistically significant (p � 0.05) Hewitt-Rogerson test. The triangle near the top of the plot marks the peak month of conception, withsolid black indicating statistical significance (p � 0.05) of the Walter-Elwood test. The bars represent the rates by season of conceptionwith darker gray shading indicating a statistically significant (p � 0.05) chi-square test.
5SEASONALITY OF BIRTH DEFECTS
Birth Defects Research (Part A) 00:000�000 (2012)
Tab
le2
SummaryofSeasonalityTests
byMaternal
AgeforSelectedBirth
Defects
inUpstateNew
York,1992–2006
<20
years
20–34years
�35years
Group
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
Births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
LiveBirths
147,91
41,479,28
433
9,80
5CentralNervousSystem
Anen
cephalus
10NC
NC
NC
65Jan–Jun
Jan10
Winter
17NC
NC
NC
Spinabifidawithoutan
encephalus
31Jun1–
Dec
1NC
Fall
269
Mar–A
ug
Dec
28Summer
59Sep
–Feb
aDec
18a
Wintera
Hydrocephaluswithoutsp
inabifida
108
Oct–M
arNov21
Winter
728
Aug–Jan
aOct
16W
inter
152
Dec–M
ayApr1
Spring
Encephalocele
8NC
NC
NC
71Dec–M
ayFeb
6W
inter
18NC
NC
NC
Microcephalus
61Nov–A
pr
Jan27
Spring
466
Sep
–Feb
aDec
30Fall
107
Jul–Dec
Feb
26Summer
Eye
Anophthalmia,microphthalmia
5NC
NC
NC
75Dec–M
ayFeb
21Spring
19NC
NC
NC
Congen
ital
cataract
21Nov1–
May
1NC
Summer
178
Jun–N
ova
Mar
10Summer
a37
Aug–Jan
NC
Winter
Ear
Anotia,
microtia
10NC
NC
NC
73May
–Oct
aJan14
Spring
22Nov–A
pra
NC
Winter
Cardiovascular
Transp
ositionofgreat
arteries
20Jul–Dec
aNC
Fall
169
Oct–M
arJan2
Fall
45Aug–Jan
aNC
Winter
TetralogyofFallot
29Jun15
–Dec
16NC
Falla
288
Dec–M
ayDec
1Spring
69Feb
–Jul
Mar
23Fall
Ven
tricularseptaldefect
347
Dec–M
aya
Mar
14W
inter
3629
Jan–Jun
Mar
14a
Wintera
946
Feb
–Jul
Oct
19Spring
Atrialseptaldefect
212
Aug–Jan
Jan4
Spring
1920
Jan–Juna
Mar
11Spring
511
Mar–A
ug
Spring
Endocard
ialcu
shiondefect
7NC
NC
NC
122
Aug–Jan
aOct
12Fall
27May
–Oct
NC
Fall
Pulm
onaryvalveatresiaorsten
osis
130
May
–Oct
aFeb
6Summer
1019
Jan–Juna
Oct
17a
Springa
258
Dec–M
ayFeb
24Spring
Tricu
spid
atresiaorsten
osis
13NC
NC
NC
102
Sep
–Feb
Mar
16W
inter
25Nov–A
pr
NC
Winter
Ebsteinan
omaly
6NC
NC
NC
76Dec–M
aya
Dec
11W
inter
14NC
NC
NC
Aortic
valvesten
osis
15NC
NC
NC
210
Jan–Jun
Oct
15W
inter
44Feb
–Jul
NC
Summer
Hypoplastic
leftheart
syndrome
18NC
NC
NC
230
Sep
–Feb
Feb
10Fall
36Apr–Sep
aNC
Spring
Paten
tductusarteriosu
s(�
2500
gm)
123
May
–Oct
Jan26
Fall
1313
Feb
–Jula
Nov16
Summer
353
Nov–A
pr
Oct
8Spring
Coarctationofao
rta
47Jan–Juna
NC
Winter
524
Dec–M
ayOct
7W
intera
134
Jan–Jun
Nov23
Summer
Orofacial
Cleftpalatewithoutcleftlip
83May
–Oct
Dec
10W
inter
800
Jun–N
ov
Jan14
Winter
203
Sep
–Feb
Mar
8Fall
Cleftlipwithan
dwithoutcleftpalate
143
Jun–N
ov
Oct
17Fall
1134
Mar–A
ug
Nov26
Spring
231
Jun–N
ov
NC
Fall
Choan
alatresia
19NC
NC
NC
214
Aug–Jan
Mar
25Spring
79Mar–A
ug
Nov1
Spring
Gastrointestinal
Esophag
ealatresia,
tracheo
esophag
ealfistula
24Jul–Dec
NC
Winter
256
Dec–M
ayMar
1W
inter
83May
–Oct
aJan7
Summer
Rectalan
dlargeintestinal
atresiaorsten
osis
46Aug–Jan
NC
Spring
408
Jul–Dec
Feb
17Summer
101
May
–Oct
Jan10
Spring
Pyloricsten
osis
399
Nov–A
pr
Feb
17Spring
3052
Jun–N
ov
NC
Winter
573
Jun–N
ova
Mar
14Summer
Hirschsp
rungdisease
(congen
ital
meg
acolon)
39Nov–A
pr
NC
Spring
289
Apr–Sep
aJan6a
Summer
66Nov–A
pr
Dec
8W
inter
Biliary
atresia
22Feb
1–Aug1
NC
Spring
108
Mar–A
uga
Dec
11a
Summer
a22
Jan–Jun
NC
Winter
Genitourinary
Ren
alag
enesis
orhypoplasia
53Jul–Dec
aMar
17Summer
424
Jun–N
ov
Mar
26Summer
90Jun–N
ova
Mar
10Fall
Obstructivegen
itourinarydefect
341
Sep
–Feb
Mar
29Fall
3721
Apr–Sep
NC
Summer
1029
Sep
–Feb
aOct
24Fall
Hyposp
adias,
epispad
ias
555
Jan–Jun
Nov1
Summer
5720
Oct–M
arJan12
Summer
1352
Apr–Sep
aJan6
Summer
Musculosk
eletal
Upper
limbreductiondeform
ity
31Jan1–
Jul1
NC
Wintera
292
Oct–M
arJan7
Winter
58Aug–Jan
Oct
6Fall
Lower
limbreductiondeform
ity
20Mar
1–Sep
1aNC
Spring
193
Mar–A
uga
Nov16
Spring
30May
–Oct
NC
Spring
Gastroschisis
116
Mar–A
ug
Nov7
Summer
222
Jun–N
ov
Dec
1Fall
5NC
NC
NC
6 CATON
Birth Defects Research (Part A) 00:000�000 (2012)
syndrome, patent ductus arteriosus, hypospadias or epis-padias, and omphalocele.Male infants (51.2% of live births) displayed seasonal
patterns for anencephalus, anophthalmia or microphthal-mia, Ebstein anomaly, hypoplastic left heart syndrome,cleft lip with and without cleft palate, omphalocele, con-genital hip dislocation, diaphragmatic hernia, trisomy 13,and Down syndrome (Table 5). Female infants (48.8% oflive births) demonstrated seasonality for spina bifida,patent ductus arteriosus, cleft lip with and without cleftpalate, pyloric stenosis, and trisomy 13.
DISCUSSION
To generate hypotheses about environmental causes ofbirth defects, we used a large, population-based birthdefects registry to examine the seasonality of specificbirth defects in geographically diverse upstate New York.A trend or seasonal pattern was detected in 24 (57%) ofthe 42 NBDPN surveillance birth defect groups examinedin the 15-year birth cohort. Eighteen birth defects groupshad a statistically significant Cochran-Armitage test fortrend, 17 groups had a significant Hewitt-Rogerson test,four groups had a significant Walter-Elwood test, andfive groups had a significant chi-square test. Ventricularseptal defect showed the most consistent results withfour statistically significant tests: Cochran-Armitage (p 50.0006), Hewitt-Rogerson (December–May; p 5 0.0130),Walter-Elwood (March 14; p 5 0.0027), and chi-square(winter; p 5 0.0046). Pulmonary valve atresia or stenosisand coarctation of the aorta tested positive in all fourtests; however, the peaks in the Walter-Elwood tests (Oc-tober 14 and October 6, respectively) fell outside the peri-ods identified by the Hewitt-Rogerson (January–Junepeaks for both) and chi-square tests (spring and winter,respectively). Both congenital cataract and renal agenesisor hypoplasia showed a 6-month peak in June to Novem-ber conceptions with the Hewitt-Rogerson test and asummer peak with the chi-square test. Biliary atresia hada significant Hewitt-Rogerson test (March–August peak)but a conflicting December 6 peak in the Walter-Elwoodtest.In the total live birth cohort for the study period, we
detected some evidence of seasonality in upstate NewYork for 17 groups of birth defects. These findings areconsistent with other seasonality analyses of ventricularseptal defect, endocardial cushion defect, and renal defect(Bound et al., 1989). There have been mixed results ofseasonality reported in the literature for encephalocele(Castilla et al., 1990; Roux et al., 2009), anotia and micro-tia (Castilla et al., 1990; Liu et al., 2011), pulmonary valveatresia or stenosis (Bound et al., 1989; Bosshardt et al.,2005; Siffel et al., 2005), biliary atresia (Caton et al., 2004;The et al., 2004; Wada et al., 2007; Yoon et al., 1997; Live-sey et al., 2009), and trisomy 18 (Gadow et al., 2006;Tonelli et al., 2006). In contrast, there have been only neg-ative reports of hydrocephalus (Sandahl, 1977b; Castillaet al., 1990), congenital cataract (Haargaard et al., 2005),transposition of the great arteries (Bound et al., 1989), co-arctation of the aorta (Bound et al., 1989; Tikkanen andHeinonen, 1993), and limb reduction (Bound et al., 1989).No literature on the seasonality of congenital megacolon,fetal alcohol syndrome, and amnionic bands was identi-fied.
Tab
le2
SummaryofSeasonalityTests
byMaternal
AgeforSelectedBirth
Defects
inUpstateNew
York,1992–2006(C
ontinued
)
<20
years
20–3
4years
�35years
Group
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
Births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Omphalocele
26Nov–A
pra
NC
Spring
173
Sep
–Feb
Mar
15Summer
47Mar–A
ug
NC
Summer
Congen
ital
hip
dislocation
155
Feb
–Jula
Dec
1Summer
1899
Jun–N
ov
Feb
7Fall
413
Jan–Juna
Oct
15Spring
Diaphragmatic
hernia
24Nov1–
May
1aNC
Summer
264
Aug–Jan
NC
Summer
58Mar–O
ctJan17
Summer
Chromosomal
Trisomy13
9NC
NC
NC
89Feb
–Jul
Oct
23W
inter
38Jul–Dec
NC
Summer
Downsyndrome(trisomy21
)10
5Sep
–Feb
aJan9
Winter
1148
Nov–A
pr
Mar
5W
inter
1001
Apr–Sep
NC
Winter
Trisomy18
9NC
NC
NC
110
Sep
–Feb
Jan20
Summer
83Mar–A
ug
Jan9
Summer
Other
Fetal
alcoholsyndrome
13NC
NC
NC
163
Sep
–Feb
Jan20
Winter
54Dec–M
aya
Feb
23a
Springa
Amnioticban
ds
8NC
NC
NC
61Jan–Jun
Feb
13W
inter
10NC
NC
NC
aStatistically
significanttren
dorseasonalitytest
(p�
0.05).
NC,notcomputed.
7SEASONALITY OF BIRTH DEFECTS
Birth Defects Research (Part A) 00:000�000 (2012)
Tab
le3
SummaryofSeasonalityTests
byMaternal
Race/
EthnicityforSelectedBirth
Defects
inUpstateNew
York,1992–2006
Non-H
ispan
icW
hite
Non-H
ispan
icBlack
Hispan
ic
Group
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
LiveBirths
1,498,49
820
3,08
118
9,51
2CentralNervousSystem
Anen
cephalus
69Dec–M
ayFeb
18W
inter
8NC
NC
NC
12NC
NC
NC
Spinabifidawithoutan
encephalus
275
May
–Oct
Feb
21Spring
30May
–Oct
NC
Winter
41Feb
–Jul
NC
Spring
Hydrocephaluswithoutsp
inabifida
671
Jun–N
ova
Mar
15Summer
163
Nov–A
pra
Feb
25Spring
129
Sep
–Feb
Dec
8W
inter
Encephalocele
70Dec–M
ayMar
6W
inter
14NC
NC
NC
12NC
NC
NC
Microcephalus
411
Nov–A
pra
Jan27
Winter
143
Sep
–Feb
Dec
14W
inter
70Jun–N
ova
Feb
8aSummer
a
Eye
Anophthalmia,microphthalmia
74Feb
–Jul
Oct
22Spring
10NC
NC
NC
10NC
NC
NC
Congen
ital
cataract
181
Jun–N
ov
Oct
7Summer
a32
Jun–N
ov
NC
Falla
15NC
NC
NC
Ear
Anotia,
microtia
68Oct–M
arOct
1W
inter
4NC
NC
NC
26Oct–M
arNC
Fall
Cardiovascular
Transp
ositionofgreat
arteries
188
Oct–M
ara
Dec
1W
inter
20Jul1–
–Jan
1NC
Winter
19NC
NC
NC
TetralogyofFallot
286
Jul–Dec
Dec
20Spring
46Apr–Sep
NC
Fall
36Oct–M
arNC
Spring
Ven
tricularseptaldefect
3763
Dec–M
aya
Mar
21a
Wintera
506
Feb
–Jul
Mar
13Spring
480
Jun–N
ov
NC
Fall
Atrialseptaldefect
1891
Jan–Juna
Mar
15Spring
370
Nov–A
pr
Dec
27Summer
281
Apr–Sep
aDec
29Spring
Endocard
ialcu
shiondefect
118
Jul–Dec
aMar
3Summer
17NC
NC
NC
16NC
NC
NC
Pulm
onaryvalveatresiaorsten
osis
967
Mar–A
uga
Oct
29a
Springa
260
Jan–Jun
Mar
13W
inter
130
Jan–Jun
Jan30
Winter
Tricu
spid
atresiaorsten
osis
98Sep
–Feb
Dec
11W
inter
20Jan1–
Jul1
NC
Winter
19NC
NC
NC
Ebsteinan
omaly
70Oct–M
arNov17
Fall
5NC
NC
NC
15NC
NC
NC
Aortic
valvesten
osis
227
Feb
–Jul
Nov16
Winter
13NC
NC
NC
20Jan–Juna
NC
Winter
Hypoplastic
leftheart
syndrome
210
Apr–Sep
aJan18
Fall
38Aug–Jan
NC
Winter
29Jan–Jun
NC
Fall
Paten
tductusarteriosu
s(�
2500
gm)
1172
Jan–Juna
Nov2
Summer
332
Jun–N
ova
Feb
9Falla
186
Mar–A
ug
Dec
6Summer
Coarctationofao
rta
572
Jan–Juna
Oct
4aW
inter
61Aug–Jan
Oct
29W
inter
52Mar–A
uga
Nov5
Spring
Orofacial
Cleftpalatewithoutcleftlip
883
Nov–A
pr
Feb
8Fall
61Jan–Jun
Feb
9W
inter
95Feb
–Jula
Feb
20Summer
Cleftlipwithan
dwithoutcleftpalate
1220
Mar–A
ug
Jan3
Spring
105
Sep
–Feb
Nov17
Fall
131
Mar–A
ug
Dec
9Summer
Choan
alatresia
256
Mar–A
ug
Nov14
Summer
23Apr–Sep
NC
Spring
26Apr–Sep
aNC
Summer
Gastrointestinal
Esophag
ealatresia,
tracheo
esophag
ealfistula
303
May
–Oct
Dec
2W
inter
26May
–Oct
NC
Fall
26Mar–A
ug
NC
Summer
Rectalan
dlargeintestinal
atresiaorsten
osis
427
Jul–Dec
aFeb
20Fall
49May
–Oct
Oct
11Fall
51Jan–Juna
Mar
29a
Spring
Pyloricsten
osis
3364
Apr–Sep
Jan26
Summer
220
Jun–N
ov
Oct
24Summer
371
Oct–M
ara
Jan20
Winter
Hirschsp
rungdisease
(congen
ital
meg
acolon)
286
Apr–Sep
aJan19
Summer
62Oct–M
ara
Jan24
Winter
29Mar–A
uga
NC
Spring
Biliary
atresia
101
Mar–A
uga
Dec
1Summer
29Feb
–Jul
NC
Spring
14NC
NC
NC
Genitourinary
Ren
alag
enesis
orhypoplasia
433
Jun–N
ov
Apr1
Summer
a70
Jun–N
ova
Feb
11Summer
44Jun–N
ov
NC
Fall
Obstructivegen
itourinarydefect
3904
Feb
–Jul
NC
Fall
440
Aug–Jan
Mar
28Fall
552
Sep
–Feb
Oct
20W
inter
Hyposp
adias,
epispad
ias
6256
Jun–N
ov
Jan25
Summer
714
Feb
–Jul
Dec
18Fall
455
Jan–Juna
Nov3a
Summer
Musculosk
eletal
Upper
limbreductiondeform
ity
306
Aug–Jan
Dec
15W
inter
34Dec
1–Jun1a
NC
Wintera
28Sep
1–Mar
1NC
Winter
Lower
limbreductiondeform
ity
187
Mar–A
uga
Dec
1Spring
23Jan31
–Jul31
NC
Spring
23Feb
–Jul
NC
Fall
Gastroschisis
272
Mar–A
ug
Feb
11Summer
31Jun–N
ov
NC
Fall
34Apr–Sep
NC
Summer
Omphalocele
186
Nov–A
pra
Feb
15W
inter
38Jun–N
ova
NC
Fall
16NC
NC
NC
8 CATON
Birth Defects Research (Part A) 00:000�000 (2012)
We found no evidence of seasonality for the othertwenty-five NBDPN birth defects groups in the entirelive birth cohort. These findings are in agreement withother negative seasonality findings for esophageal atresia(Kyyronene et al., 1988; Bound et al., 1989; Castilla et al.,1990), rectal atresia or stenosis (Kyyronene and Hem-minki, 1988; Bound et al., 1989; Castilla et al., 1990), ob-structive genitourinary defects (Bound et al., 1989), hypo-spadias (Castilla et al., 1990; Skriver et al., 2004), ompha-locele (Bound et al., 1989), and diaphragmatic hernia(Bound et al., 1989; Castilla et al., 1990; Torfs et al., 1992).Mixed results have been published for anencephaly (San-dahl, 1977a; Jorde et al., 1984; Fraser et al., 1986; Boundet al., 1989; Castilla et al., 1990; Siffel et al., 2005), spinabifida (Sandahl, 1977a; Jorde et al., 1984; Fraser et al.,1986; Bound et al., 1989; Castilla et al., 1990; Siffel et al.,2005; Beyer et al., 2011), aortic valve stenosis (Boundet al., 1989; Bosshardt et al., 2005; Siffel et al., 2005),hypoplastic left heart syndrome (Tikkanen and Heinonen,1994; Siffel et al., 2005; Eghtesady et al., 2011), oral clefts(Sandahl, 1977b; Coupland and Coupland, 1988; Boundet al., 1989; Castilla et al., 1990; Amidei et al., 1994; Fraserand Gwyn, 1998; Cooper et al., 2000; Siffel et al., 2005;Krost and Schubert, 2006; Elliott et al., 2008; Gregg et al.,2008; de la Vega and Lopez-Cepero, 2009; Chung et al.,2011), esophageal atresia (Kyyronene et al., 1988; Boundet al., 1989; Castilla et al., 1990), rectal atresia or stenosis(Kyyronene and Hemminki, 1988; Bound et al., 1989; Cas-tilla et al., 1990), obstructive genitourinary defects (Boundet al., 1989), hypospadias (Castilla et al., 1990; Skriveret al., 2004), gastroschisis (de la Vega and Lopez-Cepero,2009; Waller et al., 2010), omphalocele (Bound et al.,1989), congenital hip dislocation (Chen et al., 1970; Heik-kila, 1984; Bound et al., 1989; Siffel et al., 2005; Anandet al., 1992), diaphragmatic hernia (Bound et al., 1989;Castilla et al., 1990; Torfs et al., 1992), trisomy 13 (Gadowet al., 2006; Tonelli et al., 2006), and Down syndrome(Videbech and Nielsen, 1984; Bound et al., 1989; Castillaet al., 1990; Puri and Singh, 1995; Stolwijk et al., 1997;Morris et al., 1998; Gadow et al., 2006; Tonelli et al.,2006). Our findings differ from other reports of positiveseasonality tests for atrial septal defect (Bound et al.,1989), tricuspid atresia and stenosis (Bosshardt et al.,2005), and patent ductus arteriosus (Bound et al., 1989).No seasonality studies of microcephalus, anophthalmia,microphthalmia, tetralogy of Fallot, Ebstein anomaly,choanal atresia, and pyloric stenosis were detected.Because some studies have reported sex differences in
seasonality of birth defects, we performed stratified anal-yses by infant sex. Our findings of sex differences in sea-sonal patterns agree with earlier findings in cleft lip andpalate (Fraser and Gwyn, 1998; Krost and Schubert, 2006)and microtia (Liu et al., 2011). Whereas births in femaleswith congenital hip dislocation (Heikkila, 1984) andDown syndrome (Puri and Singh, 1995) displayed sea-sonal variation in prior studies, we found positiveHewitt-Rogerson tests in males for both groups. BecauseDarrow et al. (2009) showed that seasonal patterns ofbirths in metropolitan Atlanta varied by maternal socio-demographics, we also performed stratified analyses bymaternal age, race/ or ethnicity, and education level. Ourstratified analyses revealed additional seasonal patternsamong strata for the 25 birth defects groups that did notdemonstrate seasonality in the total live birth cohort.These findings suggest that inconsistencies in seasonality
Tab
le3
SummaryofSeasonalityTests
byMaternal
Race/
EthnicityforSelectedBirth
Defects
inUpstateNew
York,1992–2006(C
ontinued
)
Non-H
ispan
icW
hite
Non-H
ispan
icBlack
Hispan
ic
Group
Live
births
Hew
itt-
Rogerson
(peak6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peakseason)
Congen
ital
hip
dislocation
2058
Mar–A
uga
Dec
17Spring
101
Oct–M
ara
Dec
25W
inter
219
May
–Oct
Dec
25Summer
Diaphragmatic
hernia
259
Jun–N
ov
Apr1
Summer
38Apr–Sep
aNC
Summer
30Nov1–
May
1NC
Fall
Chromosomal
Trisomy13
94May
–Oct
Dec
8W
inter
19NC
NC
NC
16NC
NC
NC
Downsyndrome(trisomy21
)17
58Dec–M
ayMar
21W
inter
198
Jan–Jun
Mar
27W
inter
227
Apr–Sep
Jan23
Summer
Trisomy18
145
Apr–Sep
Dec
19Summer
32Nov–A
pra
NC
Winter
22Jan14
–Jul14
aNC
Spring
Other
Fetal
alcoholsyndrome
78Oct–M
ara
Jan8
Winter
138
Dec–M
ayFeb
23W
inter
9NC
NC
NC
Amnioticban
ds
59Jan–Jun
Jan23
Summer
15NC
NC
NC
3NC
NC
NC
aStatistically
significanttren
dorseasonalitytest
(p�
0.05).
NC,notcomputed.
9SEASONALITY OF BIRTH DEFECTS
Birth Defects Research (Part A) 00:000�000 (2012)
Tab
le4
SummaryofSeasonalityTests
byMaternal
EducationforSelectedBirth
Defects
inUpstateNew
York,1992–2006
Lessthan
highschool(<
12years)
Highschoolorsomecolleg
e(12–
15years)
Colleg
edeg
ree(�
16years)
Group
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak6-
month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
LiveBirths
274,47
91,069,926
589,11
1CentralNervousSystem
Anen
cephalus
23Feb
–Jul
NC
Spring
40Nov–A
pr
NC
Winter
22Aug1–
Feb
1NC
Fall
Spinabifidawithoutan
encephalus
50Mar–A
ug
Nov1
Summer
217
Oct–M
arDec
21W
inter
84Oct–M
arMar
18Spring
Hydrocephaluswithoutsp
inabifida
211
May
–Oct
Feb
17Summer
545
Aug–Jan
aOct
14Fall
208
Nov–A
pr
Feb
23Spring
Encephalocele
20Dec
1–Jun1a
NC
Winter
58Jan–Jun
Mar
12W
inter
17NC
NC
NC
Microcephalus
145
Dec–M
ayMar
11Spring
367
Nov–A
pr
Jan15
Winter
108
Jun–N
ova
Mar
21Fall
Eye
Anophthalmia,microphthalmia
12NC
NC
NC
48May
–Oct
NC
Fall
35Dec–M
aya
NC
Springa
Congen
ital
cataract
36Jun–N
ova
NC
Summer
122
Sep
–Feb
Dec
30W
inter
66Jun–N
ova
Mar
7Summer
Ear
Anotia,
microtia
31Jul–Dec
aNC
Fall
46Mar–A
ug
NC
Summer
27Jan–Juna
NC
Winter
Cardiovascular
Transp
ositionofgreat
arteries
38Jan–Jun
NC
Spring
133
Aug–Jan
aOct
10Summer
58Aug–Jan
aNov26
Fall
TetralogyofFallot
65Jul–Dec
Nov25
Falla
204
Jul–Dec
aOct
16Fall
110
Mar–A
ug
Oct
26Springa
Ven
tricularseptaldefect
680
Dec–M
ayJan26
Winter
2,673
Jan–Juna
Oct
8Spring
1484
Dec–M
aya
Mar
3W
intera
Atrialseptaldefect
401
Apr–Sep
Dec
19Spring
1454
Jan–Jun
Oct
13Spring
735
Dec–M
aya
Feb
23W
inter
Endocard
ialcu
shiondefect
32Jun–N
ova
NC
Falla
79Jul–Dec
Nov9
Fall
37Apr–Sep
NC
Summer
Pulm
onaryvalveatresiaorsten
osis
242
Apr–Sep
Dec
3Summer
799
Jan–Juna
Oct
11W
inter
337
Mar–A
uga
Oct
3Springa
Tricu
spid
atresiaorsten
osis
17NC
NC
NC
84May
–Oct
Dec
10Fall
35Nov–A
pra
NC
Winter
Ebsteinan
omaly
16NC
NC
NC
47Mar–A
ug
NC
Spring
29Aug1–
Feb
1aNC
Fall
Aortic
valvesten
osis
29Jan1–
Jul1
NC
Winter
153
Jan–Jun
Oct
20W
inter
80May
–Oct
Jan9
Summer
Hypoplastic
leftheart
syndrome
39May
–Oct
NC
Fall
163
May
–Oct
Feb
15Summer
66Jan–Juna
Mar
10Spring
Paten
tductusarteriosu
s(�
2500
gm)
276
Apr–Sep
Oct
19W
inter
927
Apr–Sep
aJan3
Summer
555
Feb
–Jula
Oct
17Spring
Coarctationofao
rta
93Oct–M
arJan3
Fall
412
Jan–Juna
Oct
25a
Wintera
189
Nov–A
pra
Mar
3Spring
Orofacial
Cleftpalatewithoutcleftlip
149
Jan–Jun
Feb
3W
inter
619
Nov–A
pr
Mar
13Fall
296
Dec–M
ayJan22
Winter
Cleftlipwithan
dwithoutcleftpalate
250
Dec–M
ayMar
13Spring
861
Mar–A
ug
Dec
29Summer
353
Jul–Dec
Nov8
Fall
Choan
alatresia
34Feb
–Jul
NC
Spring
168
Apr–Sep
Dec
26Summer
102
Mar–A
ug
Oct
10Spring
Gastrointestinal
Esophag
ealatresia,
tracheo
esophag
ealfistula
42Aug–Jan
aNC
Fall
196
May
–Oct
Dec
5Spring
122
Mar–A
ug
Oct
16W
inter
Rectalan
dlargeintestinal
atresiaorsten
osis
84Aug–Jan
aOct
5Fall
307
Jun–N
ov
Feb
9Summer
153
Feb
–Jul
Oct
23Spring
Pyloricsten
osis
679
Aug–Jan
aDec
17W
inter
2387
Feb
–Jul
NC
Summer
909
Jun–N
ov
Mar
19Summer
Hirschsp
rungdisease
(congen
ital
meg
acolon)
66Apr–Sep
Mar
28Spring
217
May
–Oct
aJan17
Summer
107
Nov–A
pr
NC
Summer
Biliary
atresia
35Feb
–Jula
NC
Spring
84Mar–A
uga
Dec
2a
Summer
28Sep
–Feb
NC
Winter
Genitourinary
Ren
alag
enesis,hypoplasia
94Jul–Dec
Mar
1Summer
303
Jun–N
ova
Mar
5Summer
a14
3Aug–Jan
Jan18
Winter
Obstructivegen
itourinarydefect
668
Sep
–Feb
Dec
4Fall
2610
Jun–N
ov
Feb
4Fall
1722
Apr–Sep
Jan19
Fall
Hyposp
adias,
epispad
ias
951
Mar–A
ug
Mar
19Summer
4148
Oct–M
arNC
Winter
2423
Mar–A
uga
Dec
18Spring
Musculosk
eletal
Upper
limbreductiondeform
ity
60Oct–M
arJan19
aW
intera
224
Sep
–Feb
aDec
9Fall
91Apr–Sep
Oct
23Summer
Lower
limbreductiondeform
ity
53Feb
–Jula
Oct
21a
Springa
124
Mar–A
ug
Oct
30Spring
58May
–Oct
Feb
3Fall
10 CATON
Birth Defects Research (Part A) 00:000�000 (2012)
across studies can be partly attributed to sociodemo-graphic differences in the live birth populations.There are a number of strengths and limitations to this
type of analysis. The strengths are that we used a large,population-based birth defects registry with NBDPNbirth defects surveillance definitions and examined sea-sonality based on timing of conception. Using NBDPNdefinitions permits the analysis of birth defects groupsthat are more etiologically homogeneous than body sys-tem classifications and allows other birth defects surveil-lance systems to perform comparable analyses. Analyzingseasonal variation of month of conception controls fordifferences in length of gestation and is closer to the rele-vant biologic period of exposure for most birth defectsthan month of birth. Nevertheless, it is important to notethat the biologically relevant exposure period for somebirth defects can occur before conception (e.g., chromo-somal anomalies) or after the first trimester (e.g., amni-otic bands, fetal alcohol syndrome). The limitations arethat we examined seasonality among live births only, weestimated the date of conception using the last menstrualperiod as recorded on the birth certificate, seasonal pat-terns may vary by the selected time-frame, and chancefindings could result from multiple testing. Because ouranalyses were limited to live births, we were unable todetect patterns among birth defects that could result ininduced termination, miscarriage, or stillbirth. Strandet al. (2011) reviewed four studies of stillbirths anddescribed geographic variations in seasonal peaks. Ourpragmatic use of last menstrual period plus 14 days toestimate the date of conception may be inaccuratebecause of recording errors or poor recall of the date oflast menses and the assumption of a 28-day menstrualcycle with ovulation on day 14 (Lynch and Zhang, 2007).In our birth certificate data, 3.7% of live births and 4.8%of birth defects cases with missing dates for last men-strual period were identified. However, we expect boththe misclassification and missing data to be nondifferen-tially distributed across seasons. In an analysis of datafrom the Metropolitan Atlanta Congenital Defects Pro-gram (Siffel et al., 2005) and in Flyde of Lancashire(Bound et al., 1989), variations in the seasonality findingsacross selected time frames were noted.In this exploratory analysis without prior assumptions
of underlying seasonal patterns, we performed multiplestatistical tests on 42 groups of birth defects; some statis-tically significant findings may be the result of chance.We summarized the results of the four statistical testsgraphically for each birth defect to allow the reader tovisualize the consistency of the results. Siffel et al. (2005)describe the strengths and limitations of the Cochran-Armitage trend, the Hewitt-Rogerson test, and Walter-Elwood tests. The Hewitt-Rogerson test assumes nounderlying model for the seasonal pattern and is sensi-tive, specific, and robust in its detection of a 6-monthpeak period, whereas the Walter-Elwood test assumes asinusoidal pattern (i.e., a cyclic variation with one peakin the 12-month period) and measures the goodness-of-fitto that curve. The chi-square test of the four distinctiveseasons was a simple test of observed versus expectedvalues in a two-by-four contingency table.These seasonality tests and graphical summaries can
be incorporated into our ongoing birth defects surveil-lance activities in New York State. Based on our findings,the next steps are to generate hypotheses about potential
Tab
le4
SummaryofSeasonalityTests
byMaternal
EducationforSelectedBirth
Defects
inUpstateNew
York,1992–2006(C
ontinued
)
Lessthan
highschool(<
12years)
Highschoolorsomecolleg
e(12–
15years)
Colleg
edeg
ree(�
16years)
Group
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak6-
month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Gastroschisis
106
Jun–N
ov
Feb
17Summer
202
Nov–A
pra
Feb
16Spring
29May
–Oct
NC
Summer
Omphalocele
36Jul1–
Jan1
NC
Summer
145
Jun–N
ova
Oct
12Fall
55Jan–Juna
Oct
27a
Springa
Congen
ital
hip
dislocation
274
Mar–A
uga
Nov28
Spring
1300
Feb
–Jul
Dec
4Spring
846
Jun–N
ov
Jan27
Fall
Diaphragmatic
hernia
60Nov–A
pr
Nov26
Winter
203
Jun–N
ov
Jan20
Summer
74Apr–Sep
Mar
12W
inter
Chromosomal
Trisomy13
20Feb
15–A
ug17
NC
Summer
69Mar–A
uga
Nov12
Summer
39Sep
–Feb
NC
Winter
Downsyndrome(trisomy21
)27
5Dec–M
ayFeb
25W
intera
1195
Jan–Juna
Oct
10W
inter
725
Nov–A
pr
Dec
24W
inter
Trisomy18
26Dec–M
ayNC
Spring
118
Mar–A
uga
Nov13
Summer
50Jun–N
ova
Mar
24Summer
a
Other
Fetal
alcoholsyndrome
91Sep
–Feb
Dec
28Fall
115
Dec–M
aya
Mar
8a
Winter
7NC
NC
NC
Amnioticban
ds
8NC
NC
NC
47Jun–N
ov
NC
Summer
21Nov1–
May
1aNC
Winter
aStatistically
significantseasonalitytest
(p�
0.05).
NC,notcomputed.
11SEASONALITY OF BIRTH DEFECTS
Birth Defects Research (Part A) 00:000�000 (2012)
Tab
le5
SummaryofSeasonalityTests
byInfantSex
forSelectedBirth
Defects
inUpstateNew
York,1992–2006
Male
Fem
ale
Group
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
Square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
LiveBirths
1,007,241
960,37
4CentralNervousSystem
Anen
cephalus
37Nov–A
pra
NC
Winter
55Dec–M
ayMar
8Spring
Spinabifidawithoutan
encephalus
164
Dec–M
ayFeb
20Spring
195
May
–Oct
aFeb
23Summer
Hydrocephaluswithoutsp
inabifida
562
Nov–A
pra
Jan27
Winter
427
Aug–Jan
aMar
18Fall
Encephalocele
49Dec–M
ayNC
Winter
48Dec–M
ayNC
Winter
Microcephalus
247
Jun–N
ov
NC
Fall
387
Nov–A
pr
Jan8
Winter
Eye
Anophthalmia,microphthalmia
55Dec–M
aya
Feb
22Spring
a44
Jan–Jun
NC
Spring
Congen
ital
cataract
120
Jun–N
ova
Apr2a
Falla
116
Feb
–Jul
Dec
9Summer
a
Ear
Anotia,
microtia
65Oct–M
ara
Dec
12a
Winter
40Feb
–Jula
NC
Summer
Cardiovascular
Transp
ositionofgreat
arteries
152
Aug–Jan
aNov13
Winter
82Oct–M
arOct
27Summer
TetralogyofFallot
231
Dec–M
ayDec
29Spring
155
Jul–Dec
Mar
30Fall
Ven
tricularseptaldefect
2316
Dec–M
ayMar
9W
inter
2607
Dec–M
aya
Mar
18a
Wintera
Atrialseptaldefect
1317
Jan–Jun
Mar
16Spring
1328
Jan–Jun
Oct
12Spring
Endocard
ialcu
shiondefect
77Aug–Jan
aOct
21Fall
79Jul–Dec
aMar
10Fall
Pulm
onaryvalveatresiaorsten
osis
669
Dec–M
aya
Apr1
Springa
739
Jan–Juna
Nov3
Summer
Tricu
spid
atresiaorsten
osis
72Jan–Jun
Jan9
Winter
68May
–Oct
Jan7
Winter
Ebsteinan
omaly
54Oct–M
ara
Dec
17Spring
42Jul–Dec
NC
Fall
Aortic
valvesten
osis
179
Feb
–Jul
Nov8
Summer
90Dec–M
ayJan20
Winter
Hypoplastic
leftheart
syndrome
175
May
–Oct
aFeb
3Fall
109
Nov–A
pr
Feb
7W
inter
Paten
tductusarteriosu
s(�
2500
gm)
880
Nov–A
pr
Feb
9Fall
909
Mar–A
uga
Dec
8aSummer
a
Coarctationofao
rta
406
Jan–Juna
Oct
16Spring
300
Jan–Jun
Mar
22W
inter
Orofacial
Cleftpalatewithoutcleftlip
469
Oct–M
arJan12
Winter
618
Jan–Jun
Feb
12W
inter
Cleftlipwithan
dwithoutcleftpalate
972
Jul–Dec
aOct
23Fall
537
Feb
–Jula
Nov9a
Springa
Choan
alatresia
152
Jul–Dec
Feb
23Summer
160
Mar–A
ug
Nov8
Spring
Gastrointestinal
Esophag
ealatresia,
tracheo
esophag
ealfistula
196
Apr–Sep
Dec
24Summer
167
Jan–Jun
Feb
6Spring
Rectalan
dlargeintestinal
atresiaorsten
osis
281
Apr–Sep
Jan29
Summer
274
Oct–M
arNC
Spring
Pyloricsten
osis
3286
Mar–A
ug
Mar
20Summer
740
Sep
–Feb
aOct
16Fall
Hirschsp
rungdisease
(congen
ital
meg
acolon)
273
Apr–Sep
aJan6
Spring
121
Feb
–Jul
Oct
1Summer
Biliary
atresia
73Mar–A
ug
Jan6
Summer
79Feb
–Jula
Nov22
aSpring
Genitourinary
Ren
alag
enesis
orhypoplasia
346
Jun–N
ova
Mar
21Summer
221
Jun–N
ova
Mar
11Summer
a
Obstructivegen
itourinarydefect
3589
Apr–Sep
Jan9
Fall
1502
Jun–N
ov
NC
Fall
Hyposp
adias,
epispad
ias
7623
Jan–Jun
NC
Summer
Musculosk
eletal
Upper
limbreductiondeform
ity
212
Oct–M
ara
Dec
28W
inter
169
Sep
–Feb
Jan4
Winter
Lower
limbreductiondeform
ity
145
Nov–A
pr
Mar
14Spring
96Mar–A
uga
Dec
9aSpringa
Gastroschisis
177
Mar–A
ug
Dec
19Summer
167
Sep
–Feb
Dec
25Fall
Omphalocele
118
Oct–M
ara
Dec
14W
inter
128
Apr–Sep
Dec
20Summer
12 CATON
Birth Defects Research (Part A) 00:000�000 (2012)
etiologic factors that vary by season in New York, suchas meteorological factors, environmental chemicals, andmaternal infections. For example, influenza displays aseasonal and regional variation in New York (New YorkState Department of Health, 2011), and maternal feverhas been associated certain birth defects in animals andhumans (Edwards, 2006). A time series analysis could beperformed to assess the correlation between the seasonalpattern of influenza and the occurrence of birth defectsin infants. Alternatively, a case-control study could beperformed to examine birth defects in infants of motherswhose first trimesters occurred during influenza season.
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Tab
le5
SummaryofSeasonalityTests
byInfantSex
forSelectedBirth
Defects
inUpstateNew
York,1992–2006(C
ontinued
)
Male
Fem
ale
Group
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
Square
(peak
season)
Live
births
Hew
itt-
Rogerson
(peak
6-month
period)
Walter-
Elw
ood
(peak)
Chi-
square
(peak
season)
Congen
ital
hip
dislocation
611
Jun–N
ova
Feb
13Summer
1856
Mar–A
ug
Nov25
Spring
Diaphragmatic
hernia
203
Jul–Dec
aNov9
Winter
141
Mar–A
ug
Dec
9Summer
Chromosomal
Trisomy13
73Apr–Sep
aDec
28Summer
63Dec–M
aya
Jan30
Winter
Downsyndrome(trisomy21
)11
87Nov–A
pra
Mar
4W
inter
1067
Apr–Sep
NC
Winter
Trisomy18
73Mar–A
uga
Oct
6Summer
129
Apr–Sep
Dec
22Summer
Other
Fetal
alcoholsyndrome
127
Dec–M
aya
Feb
16a
Springa
104
Feb
–Jul
Jan25
Fall
Amnioticban
ds
31Jan–Juna
NC
Winter
48Jun–N
ov
NC
Summer
aStatistically
significantseasonalitytest
(p�
0.05).
NC,notcomputed.
13SEASONALITY OF BIRTH DEFECTS
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