BACKGROUND: Choosing the optimal season for conception is a part of family planning since it can positively influence the pregnancy outcome. Changes in the monthly number of infants born with a birth defect can signal prenatal damage - death or malformation - related to a harmful seasonal factor. The aim of our paper was to search for possible seasonal differences in the numbers of new-borns with an orofacial cleft and thus for a period of conception that can increase the risk of orofacial cleft development. METHODS: Mean monthly numbers of live births in the Bohemia region of the Czech Republic during the years 1964-2000 were compared within a group of 5619 new-borns with various types of orofacial clefts and the control group derived from natality data on 3,080,891 new-borns. RESULTS: The control group exhibited regular seasonal variation in the monthly numbers of new-borns: significantly more babies born during March-May and fewer babies born during October-December. Similar natural seasonal variation was also found in the group of babies with an orofacial cleft. However, after subdividing the cleft group according to gender and cleft type, in comparison to controls, significant differences appeared in the number of new-born girls with cleft lip during January-March and in the number of boys born with cleft palate in April - May. CONCLUSIONS: We found significant differences from controls in the number of new-born girls with CL and boys with CP, whose dates of birth correspond to conception from April to August and to the estimated prenatal critical period for cleft formation from May to October. The latter period includes the warm season, when various injurious physical, chemical and biological factors may act on a pregnant woman. This finding should be considered in pregnancy planning. Future studies are necessary to investigate the putative injurious factors during the warm season that can influence pregnancy outcome.

Cleft Centre Plastic Surgery Clinic at Kralovske Vinohrady Hospital Prague Prague Czech Republic

Department of Teratology Institute of Experimental Medicine Czech Academy of Sciences Videnska 1083 142 20 Prague 4 Czech Republic

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Condon RG. Birth seasonality, photoperiod, and social change in the Central Canadian Arctic. Hum Ecol. 1991;19:287–321. doi: 10.1007/BF00888980. PubMed DOI

Bronson FH. Seasonal variation in human reproduction: environmental factors. Q Rev Biol. 1995;70:141–164. doi: 10.1086/418980. PubMed DOI

Lam DA, Miron JA. Global patterns of seasonal variation in human fertility. Ann N Y Acad Sci. 1994;709:9–28. doi: 10.1111/j.1749-6632.1994.tb30385.x. PubMed DOI

Cowgill UM. Recent variations in the season of birth in Puerto Rico. Proc N A S. 1964;52:1149–1151. doi: 10.1073/pnas.52.5.1149. PubMed DOI PMC

Bobak M, Gjonca A. The seasonality of live birth is strongly influenced by socio-demographic factors. Hum Reprod. 2001;16:1512–1517. doi: 10.1093/humrep/16.7.1512. PubMed DOI

Peterka M, Peterkova R, Likovsky Z. Chernobyl: relationship between number of missing newborn boys and the level of radiation in the Czech regions. Environ Health Perspect. 2007;115:1801–1806. doi: 10.1289/ehp.10779. PubMed DOI PMC

Castilla EE, Orioli IM, Lugarinho R, et al. Monthly and seasonal variations in the frequency of congenital anomalies. Int J Epidemiol. 1990;19:399–404. doi: 10.1093/ije/19.2.399. PubMed DOI

Caton AR. Exploring the seasonality of birth defects in the New York state congenital malformations registry. Birth Defects Res A Clin Mol Teratol. 2012;94:424–437. doi: 10.1002/bdra.23006. PubMed DOI

Slater BC, Watson GI, Mcdonald JC. Seasonal variation in congenital abnormalities. Preliminary report of a survey conducted by the research committee of council of the college of general practitioners. Br J Prev Soc Med. 1964;18:1–7. PubMed PMC

Edwards JH. Seasonal incidence of congenital disease in Birmingham. Ann Hum Genet. 1961;25:89–93. doi: 10.1111/j.1469-1809.1961.tb01502.x. PubMed DOI

Coupland MA, Coupland AI. Seasonality, incidence and sex distribution of cleft lip and palate births in Trent region, 1973-1982. Cleft Palate J. 1988;25:33–37. PubMed

Wehrung DA, Hay S. A study of seasonal incidence of congenital malformations in the United States. Brit J Prev Soc Med. 1970;24:24–32. PubMed PMC

Elliott RF, Jovic G, Beveridge M. Seasonal variation and regional distribution of cleft lip and palate in Zambia. Cleft Palate Craniofac J. 2008;45:533–538. doi: 10.1597/07-086.1. PubMed DOI

De la Vega A, Martinez E. Seasonal variation in the incidence of cleft lip and palate based on the age of conception. P R Health Sci J. 2006;25:343–346. PubMed

Rintala A, Pönkä A, Sarna S, et al. Cleft lip and palate in Finland in 1948-75: correlations to infections, seasonal and yearly variations. Scand J Plast Reconstr Surg. 1983;17:197–201. doi: 10.3109/02844318309013119. PubMed DOI

Yin J, Yin N, Liu L, et al. Seasonal variation in birth months of patients with oral-facial clefts. J Craniofac Surg. 2013;24:18–21. doi: 10.1097/SCS.0b013e3182670045. PubMed DOI

Siffel C, Alverson CJ, Correa A. Analysis of seasonal variation of birth defects in Atlanta. Birth Defects Res A Clin Mol Teratol. 2005;73:655–662. doi: 10.1002/bdra.20207. PubMed DOI

Amidei RL, Hamman RF, Kassebaum DK, et al. Birth prevalence of cleft lip and palate in Colorado by sex distribution, seasonality, race/ethnicity, and geographic variation. Spec Care Dentist. 1994;14:233–240. doi: 10.1111/j.1754-4505.1994.tb01072.x. PubMed DOI

Gregg TA, Leonard AG, Hayden C, et al. Birth prevalence of cleft lip and palate in Northern Ireland (1981 to 2000) Cleft Palate Craniofac J. 2008;45:141–147. doi: 10.1597/06-045.1. PubMed DOI

Krost B, Schubert J. Influence of season on prevalence of cleft lip and palate. Int J Oral Maxillofac Surg. 2006;35:215–218. doi: 10.1016/j.ijom.2005.08.007. PubMed DOI

Brender JD, Weyer PJ. Agricultural compounds in water and birth defects.Curr Environ Health Rep 2016;3(2):144–152. doi: 10.1007/s40572-016-0085-0. Review. PubMed

Sabbagh HJ, Alamoudi NM, Abdulhameed FD, Innes NP, Al-Aama JY, Hummaida T, Almalik M, El Derwi DA, Mossey PA. Environmental risk factors in the etiology of nonsyndromic orofacial clefts in the western region of Saudi Arabia. Cleft Palate Craniofac J. 2016;53:435–443. doi: 10.1597/14-136. PubMed DOI

Schutte BC, Murray JC. The many faces and factors of orofacial clefts. Hum Mol Genet. 1999;8:1853–1859. doi: 10.1093/hmg/8.10.1853. PubMed DOI

Chung MK, Lao TT, Ting YH, et al. Environmental factors in the first trimester and risk of oral-facial clefts in the offspring. Reprod Sci. 2013;20:797–803. doi: 10.1177/1933719112466311. PubMed DOI

Czeizel AE, Tóth M, Rockenbauer M. Population-based case control study of folic acid supplementation during pregnancy. Teratology. 1996;53:345–351. doi: 10.1002/(SICI)1096-9926(199606)53:6<345::AID-TERA5>3.0.CO;2-Z. PubMed DOI

Botto LD, Ericson JD, Mulinare J, et al. Maternal fever, multivitamin use, and selected birth defects: evidence of interaction? Epidemiology. 2002;13:485–488. doi: 10.1097/00001648-200207000-00019. PubMed DOI

Van Rooij IA, Ocké MC, Straatman H, et al. Periconceptional folate intake by supplement and food reduces the risk of nonsyndromic cleft lip with or without cleft palate. Prev Med. 2004;39:689–694. doi: 10.1016/j.ypmed.2004.02.036. PubMed DOI

Fogh-Andersen P. Inheritance of harelip and cleft lip. Nyt Nordisk Torlag: Copenhagen; 1942.

Peterka M, Peterkova R, Halaskova M, Tvrdek M, Fara M, Likovsky Z. Sex differences in the incidence of orofacial clefts and the question of primary prevention in families with genetic risk. Acta Chir Plast. 1996;38:57–60. PubMed

Czech Statistical Office. http://(www.czso.cz).

Dixon WJ, Massey FJ. Introduction to statistical analysis. 1969.

WinPepi Portal . Version 11.65. http://www.brixtonhealth.com/.

Social Science Statistics. http://www.socscistatistics.com/Default.aspx.

Peterka M, Peterková R, Likovsky Z. Chernobyl: prenatal loss of four hundred male fetuses in the Czech Republic. Reprod Toxicol. 2004;18:75–79. doi: 10.1016/j.reprotox.2003.10.010. PubMed DOI

Odegard O. Season of birth in the population of Norway, with particular reference to the September birth maximum. Br J Psychiatry. 1977;131:339–344. doi: 10.1192/bjp.131.4.339. PubMed DOI

Cesario SK. The “Christmas effect” and other biometeorologic influences on childbearing and the health of women. J Obstet Gynecol Neonatal Nurs. 2002;31:526–535. doi: 10.1111/j.1552-6909.2002.tb00077.x. PubMed DOI

Polasek O, Kolcić I, Vorko-Jović A, et al. Seasonality of births in Croatia. Coll Antropol. 2005;29:249–255. PubMed

Mastroiacovo P, Spagnolo A, Marni E, et al. Birth defects in the Seveso area after TCDD contamination. JAMA. 1988;259:1668–1672. doi: 10.1001/jama.1988.03720110030030. PubMed DOI

Peterka M, Havránek T, Jelínek R. Dose-response relationships in chick embryos exposed to embryotoxic agents. Folia Morphol (Warsz) 1986;34:69–77. PubMed

Peterka M, Peterkova R, Likovsky Z. Environmental risk and sex ratio in newborns. In: Nicolopoulou-Stamati P, Hens L, Howard CV, editors. Congenital Diseases and the Environment. Springer, 2007b; p.295–319.

Wilson JG, Fraser FC. General principles and etiology. New York: Plenum Press; 1977. Handbook of teratology. Vol. I.

Jarrell J. Rationale for the study of the human sex ratio in population studies of polluted environments. Cad Saude Publica. 2002;18:429–434. doi: 10.1590/S0102-311X2002000200007. PubMed DOI

Jongbloet PH, Roeleveld N, Groenewoud HM. Where the boys aren't: dioxin and the sex ratio. Environ Health Perspect. 2002;110:1–3. doi: 10.1289/ehp.021101. PubMed DOI PMC

Nicolich MJ, Huebner WW, Schnatter AR. Influence of parental and biological factors on the male birth fraction in the United States: an analysis of birth certificate data from 1964 through 1988. Fertil Steril. 2000;73:487–492. doi: 10.1016/S0015-0282(99)00576-2. PubMed DOI

Ryan JJ, Amirova Z, Carrier G. Sex ratios of children of Russian pesticide producers exposed to dioxin. Environ Health Perspect. 2002;110:A699–A701. doi: 10.1289/ehp.021100699. PubMed DOI PMC

Owens JR, Jones JW, Harris F. Epidemiology of facial clefting. Arch Dis Child. 1985;60:521–524. doi: 10.1136/adc.60.6.521. PubMed DOI PMC

Heikkinen T, Järvinen A. The common cold. Lancet. 2003;4(361):51–59. doi: 10.1016/S0140-6736(03)12162-9. PubMed DOI PMC

Wat D. The common cold: a review of the literature. Eur J Intern Med. 2004;15:79–88. doi: 10.1016/j.ejim.2004.01.006. PubMed DOI PMC

Molnarova A, Brozman M, Schwanzerova I, et al. Prenatal virus infections and orofacial clefts. Bratisl Lek Listy. 1992;93:469–476. PubMed

Peterka M, Tvrdek M, Likovsky Z, et al. Maternal hyperthermia and infection as one of possible causes of orofacial clefts. Acta Chir Plast. 1994;36:114–118. PubMed

Saxen I. Associations between oral clefts and drugs taken during pregnancy. Int J Epidemiol. 1975;4:37–44. doi: 10.1093/ije/4.1.37. PubMed DOI

Métneki J, Puhó E, Czeizel AE. Maternal diseases and isolated orofacial clefts in Hungary. Birth Defects Res A Clin Mol Teratol. 2005;73:617–623. doi: 10.1002/bdra.20177. PubMed DOI

Wang W, Guan P, Xu W, et al. Risk factors for oral clefts: a population-based case-control study in Shenyang, China. Paediatr Perinat Epidemiol. 2009;23:310–320. doi: 10.1111/j.1365-3016.2009.01025.x. PubMed DOI

Bernard SM, Samet JM, Grambsch A, et al. The potential impacts of climate variability and change on air pollution-related health effects in the United States. Environ Health Perspect. 2001;109(Suppl 2):199–209. doi: 10.2307/3435010. PubMed DOI PMC

Hwang BF, Jaakkola JJ. Ozone and other air pollutants and the risk of oral clefts. Environ Health Perspect. 2008;116:1411–1415. doi: 10.1289/ehp.11311. PubMed DOI PMC

Czech Hydrometeorological Institute. http://portal.chmi.cz/files/portal/docs/uoco/isko/grafroc/13groc/gr13e/IV4_O3_GB.html

Dubrovsky M, et al. Variability of daily and annual cycles of mean erythemal solar irradiance related to total ozone variability. In: Zerefos CS, et al., editors. Chemistry and Radiation Changes in the Ozone Layer. Printed in the Netherlands: Kluwer Academic Publishers; 2000. pp. 179–186.

Strestik J, Roznovsky J, Stepanek P, et al. In: Increase of annual and seasonal air temperatures in the Czech Republic during 1961-2010. Rožnovský J, Litschmann T, et al., editors. Brno: Mendel a bioklimatologie; 2014.

Braun T, Challis JR, Newnham JP, et al. Early-life glucocorticoid exposure: the hypothalamic-pituitary-adrenal Axis, placental function, and Longterm disease risk. Endocr Rev. 2013;34:885–916. doi: 10.1210/er.2013-1012. PubMed DOI

Baxter H, Fraser FC. The production of congenital defects in the offspring of female mice treated with cortisone. A preliminary report. McGill Med J. 1950;19:245–249. PubMed

Peterka M, Jelinek R. Origin of hydrocortisone induced orofacial clefts in the chick embryo. Cleft Palate J. 1983;20:35–46. PubMed

Sípek A, Gregor V, Horácek J. Birth defects in the Czech Republic in the period 1994–2005—perinatology data. Ceska Gynekol. 2007;72:103–109. PubMed

Peterka M, Hrudka J, Tvrdek M, et al. Extension of orofacial cleft size and gestational bleeding in early pregnancy. Acta Chir Plast. 2012;54:39–44. PubMed

Anti-asthma Drugs Formoterol and Budesonide (Symbicort) Induce Orofacial Clefts, Gastroschisis and Heart Septum Defects in an In Vivo Model