EPI 824 Reproductive Epidemiology Fall 2002

1. EPI 824 Reproductive Epidemiology Fall 2002 Sex Ratio

2. Sex ratio in different developmental stages • Primary sex ratio of sperm • Primary sex ratio of fertilized eggs (zygotic SR) • Post-implantation SR • Secondary sex ratio in miscarriages and induced abortions • Secondary sex ratio at birth • Secondary sex in specific diseases (multiple sclerosis, malformations), other groups

3. Definition (1) The Sex-Ratio (SR) is defined as the number of males/number of females: SR = m/f. The numerator of the Sex-Ratio (males) is not part of the denominator (females), thus the SR is not a proportion, which would be Pmales = m/(m+f). • Problem: Modelling with logistic regression: Being a male is not a ‘rare disease’, thus the Odds-Ratio would be misleading.

4. Definition (2) • However, some authors define the sex-ratio as a proportion, but then use odds-ratios as point estimators. • Which distribution? • Poisson: Does the probability pmale remains constant throughout a woman’s childbearing years? Or does it vary unrelated to the sexes of the previous pregnancies? • Lexis: Does the probability pmale vary from one couple to another while remaining constant within a given couple? • Markov: Does the sex of one or more previous pregnancies affect the sex of the current one?

5. Data on sex ratio and data quality • The gender of child is easily and mostly accurate determined.E.g. repeated interviews to assess reliability indicates a kappa  1.Also: comparisons of interview data and birth registries. • Large data sets can be used to determine changes and trends (e.g. national data before and after wartime) • What about New York city a year after 9/11/01?

6. Change of sex ratio: Sperm to conception • Sex-ratio in sperm: 1:1 • Preferential binding of Y-bearing sperm to the oocyte? • It is assumed that approximately 40% of all conceptions survive (30-50%).If mortality during the intrauterine period differs: • for the two sexes • for children with and without malformation then secondary SR >< primary SR

7. Change of sex ratio during gestation • Sex ratio in chromosomal normal spontaneous abortions: • Equal distribution? • Sex ratio in chromosomal abnormal spontaneous abortions: • Abortion rate higher for boys

8. Change of sex ratio during gestation ? (Kukharenko 1973, Broer et al.) Sex-ratio: m/f

9. Secondary sex ratio at birth (1) • Worldwide, the secondary sex ratio at birth in human beings is fairly constant: • 106 men for every 100 women • Male proportion of total births (106 male births divided by 206 total births) is 0.514 (51.4%). • Trend to decreased proportion of male births in the general population in Denmark, Netherlands, USA, and Canada.

10. Secondary sex ratio at birth (2) • Several specific investigations: alterations in the sex ratio • industrial accident • occupational exposure, • exposure to air pollution from incinerators • lower sex ratio: Italian metropolitan areas compared with the rest of the country

11. Paternal effect? • The possible origin (paternal, maternal, or both) of the slight increase in female births is not clear. • Regarding environmental exposures, it is suggested that parental hormone concentrations at the time of conception are a main risk factor for lower sex ratio at birth.

12. Dioxin and PCB • Seveso: Lower sex ratio among the offspring of men who were exposed to dioxin during adulthood or before and during puberty • Comparable to potential effects of contaminants onalligators • Michigan fisheater (PCB, DDE), Veterans exposed to Agent Orange (dioxin), exposure to PCB and polychlorinated dibenzofurans (PCDF) from cooking oil (Yushoi, Japan):Higher sex ratio: more boys • Agreement: paternal role > maternal role

13. Birth Order 1980 1982 1984 1986 1988 1990 1992 1994 All births 103.9 106.8 108.3 111.8 113.4 116.8 114.0 115.4 First 106.1 105.4 106.1 107.3 107.4 108.7 106.4 106.1 Second 106.5 106.0 107.2 111.3 113.3 117.2 112.8 114.3 Third 106.3 109.2 116.9 138.7 166.3 191.9 195.6 205.6 Fourth and over 110.2 113.7 128.1 150.6 185.7 218.9 229.0 237.7 Trends in Male Sex (%) in South Korea Frequent sex selective abortions result in distortions of the natural sex ratio at birth. The male birth ratio increased between 1980 and 1994.

14. Factors that influence the secondary sex ratio (2) • Race: African American: lower sex ratio (less males) • Season: ? • Timing of fertilization: U-shaped distribution around cycle day of natural insemination (e.g. early  boys) • Parental selection of child’s gender • Social and psychological factors: • upper class: higher sex ratio • Legitimate: higher sex ratio

15. Factors that influence the secondary sex ratio (2) • Twins and sibs of twins: • Twins: lower sex ratio • Sibs of twins: higher sex ratio • Birth following artificial insemination: • -form relationship on cycle day of AI? • Wartime: • During or just after war: higher sex ratio • Decline in sex-ratio after the Kobe earthquake. • Patients with Non-Hodgkin’s Lymphoma: • Low sex ratio (of both sex with the disease) U

16. Factors that influence the secondary sex ratio (3) • Preeclampsia during pregnancy: higher sex ratio • 7 out 100 pregnant women: high blood pressure • Multiple sclerosis: higher sex ratio (male excess) • Nutrition and diet: ? • Placenta previa: higher sex ratio • Ectopic pregnancies: lower sex ratio (excess of girls) • Oral contraceptive failure: higher sex ratios (??) • Higher age of parents: lower sex ratio • Pollution: lower sex ratio (?)

17. Wrap-up • Why are epidemiologists interested in sex ratio? • Being a boy is not a disease. • Sex ratio my be a marker for other risk factors that cannot be established a easily. • Large data set provide information on the gender of offspring. • There is little dispute about the gender of the child.