Is Maternal Menstrual Cycle Length Associated with Twinning? Author 1 Author 2 Background Menstrual Cycles & Twinning – Shorter cycles -- ↑ Twinning Time to Pregnancy (TTP) & Twinning – ↓ TTP -- ↑ Twinning Menstrual Cycles & Fertility – Regular menstrual cycles -- ↑ Fertility – Short & long cycles -- ↑ Spontaneous abortion Body Mass Index – ↑ BMI -- long, irregular cycles – ↑ BMI -- ↑ twinning Why this question? Goal to determine whether menstrual cycle characteristics can act as a surrogate for reproductive health “Natural” twinning trends may be used as an indicator of reproductive health Unique cohort to study twinning – 223 Twins – Before ART and OC use were common Menstrual cycle length was asked before birth outcome (less recall bias) Study Population In iti a l D a ta set N= 2 05 30 Mis s ing Men s tr u al C y cle L ength (N = 8847) M en str ua l Cycles N= 1 16 83 O r al con tra cep tion (N = 66 8 ) N o Or a l Co n tr a ce p tio n N= 1 10 15 M e d ica tions fo r th y ro id, fer ti li ty, o r any oth e r ho r mo n al m ed ic a tion (N=1 58 4) N o Ot h er H o rm ona l M ed ic a tion s Fi na l D a ta set N= 9 431 97 Twins Disc o rdan t S ex T w in s D a ta set N= 9 465 31 Twins Sa m e sex tw ins (N=66) Exposure & Outcome Menstrual Cycle Length: – Short (<25 days) – Average (25-35 days) – Long/Irregular (> 35 days) Twinning: – In CHDS: 223/20307 births (1.07%) – Final dataset - 97 twins – Discordant sex twin dataset - 31 twins Univariate Analyses Age* Race* Education* Pre-pregnancy BMI Current BMI Smoking status* Cigarettes/day* Alcohol use Coffee intake* Tea intake Age of menarche* Pregnancy outcome Parity Interval between pregnancies * Associated with menstrual cycle length Associated with twinning Chi Square Analyses Number and percents of singletons and twins for each category of menstrual cycle length, Child Health and Development Studies, Oakland, CA, 1959-1967. Menstrual Cycle Length Outcome Singletons Twins Short n=597 (6.3%) Average n=6639 (69.7%) Long/ Irregular n=777 (24.0%) 575 (98.1) 6492 (98.9) 2267 (99.4) 11 (1.9) 73 (1.1) 13 (0.6) Pvalue 9.3 0.01 Bivariate Analyses Proportion of Twinning (%) Characteristic All Short Cycle n=586 Average Cycle n=6565 StratumSpecific RR (95% CI) 1.9 1.1 NA Education <= High School 0.7 1.0 0.7 (0., .7) > High School 3.2 1.2 .6 (1.3, 5.3) Log likelihood test: Wald =3.88 p=0.14 MantelHaenszel RR (95% CI) BreslowDay Test for Homogeneity 1.7 (0.9, 3.2) NA NA 3.2 (0.1) Bivariate Analysis Proportion of Twinning (%) Characteristic All Long/ Irreg n=2280 Average Cycle n=6565 StratumSpecific RR (95% CI) 0.6 1.1 NA Age <20 0.8 0.0 NA 20-24 0.3 1.1 0.2 (0.1, 1.1) 25-29 0.4 1.2 0.3 (0.1, 1.1) 30-34 0.8 1.4 0.6 (0.1, 2.5) >34 0.8 1.4 0.6 (0.1, 2.5) Log likelihood test: Wald =12.0 p=0.21 MantelHaenszel RR (95% CI) BreslowDay Test for Homogeneity 0.5 (0.3, 0.9) NA NA 9.7 (0.1) Multivariable Analyses Crude Model Odds Ratio 95% CI Short 1.70 (0.90, 3.23) Long/ Irregular 0.51 (0.28, 0.92) Multivariable Analyses Crude Model Odds Ratio 95% CI Short 1.70 (0.90, 3.23) Long/ Irregular 0.51 (0.28, 0.92) Short 1.83 (0.96, 3.51) Long/ Irregular 0.53 (0.29, 0.98) Age 1.01 (0.98, 1.05) Pre-pregnancy BMI 1.10 (0.64, 1.90) Race 1.41 (0.92, 2.16) Parity 1.99 (1.09, 3.63) Smoke 1.52 (0.99, 2.33) Age of menarche 1.36 (0.83, 2.22) Adjusted Model Multivariable Analyses Crude Model Odds Ratio 95% CI Short 1.70 (0.90, 3.23) Long/ Irregular 0.51 (0.28, 0.92) Short 3.08 (1.24, 7.63) Long/ Irregular 0.39 (0.12, 1.31) Restricted to Different Sex Twins Conclusion Found association between menstrual cycle length and twinning Limitations include the large amount of missing data Potential confounders did not change the estimate of the effect Interaction was not significant Future Directions Restricted Data Set DZ ♀♂ Potential Exclusions DZ MZ MZ ♀♀ ♀♀ ♀♀ ♂♂ ♂♂ ♂♂