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Hyperfertility: the Paradox of Plenty

Hyperfertility: the Paradox of Plenty. Louis Keith, MD, PhD Professor Emeritus, Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL Adjunct Professor, Department of Maternal and Child Health, School of Public Health, University of Alabama at Birmingham. Basic Premise.

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Hyperfertility: the Paradox of Plenty

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  1. Hyperfertility: the Paradox of Plenty Louis Keith, MD, PhD Professor Emeritus, Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL Adjunct Professor, Department of Maternal and Child Health, School of Public Health, University of Alabama at Birmingham

  2. Basic Premise • The effects of hyperfertility on mothers are well known: witness Shah Jehan’s wife • The effects of hyperfertility on fetal outcomes are not well known or studied

  3. Agreed Definitions of Parity • Nullipara-gravidas with no prior pregnancy > 20 weeks gestation • Primapara-gravidas with 1 prior pregnancy > 20 weeks gestation

  4. Variable Definitions of Parity (With no risk threshold for outcomes) • Multipara • Grand Multipara* • Great Grand Multipara** • Grand Grand Multipara** • Extreme Grand Multipara** * Generally at least 8 prior deliveries ** Variably used for greater than 10 prior deliveries

  5. Reclassification of Parity:the UAB Model

  6. Value of UAB Parity Classification • Permits comparisons across discrete clinically relevant groups for assessment of maternal and fetal outcome parameters

  7. Literature Prior to the UAB Hyperfertility Studies

  8. Frequency of “High” (>5) Parity(10 studies, 9 nations, 1954-2001)

  9. Uterine rupture Chronic renal disease Hypertensive disease Placenta previa Preeclampsia Uterine inertia Anemia PPH Abrubtio Diabetes Adverse Maternal Outcomes with Multiparity(37 studies, 17 nations, 1865-2004) Variously mentioned conditions

  10. Factors Confounding Relations Between High Parity and Adverse Maternal Outcomes • Selection bias, i.e., low SES • Maternal age • Disease accumulation with age

  11. Fetal Outcomes and Multiparity(38 studies, 13 nations, 1940-2004) • Stillbirths • Perinatal Mortality • Low Birthweight • Prematurity

  12. The Great Grand Multipara (>10 prior live births)(only 11 studies, 6 nations, 1992-2002) • 7 of these from Middle East • Definitions vary • Variable study sizes (139-2709) (ascertainment bias) • Non-adjustment for confounders (methodological bias)

  13. The UAB Hyperfertility Studies Thanks to Muktar Aliyu,DPh, University of Alabama at Birmingham

  14. Basic Hypotheses on Hyperfertility #1: Babies born to mothers with parity  15 are more likely to have adverse fetal outcomes compared to women of lower parity #2: Stillbirth rates are greater among mothers with parity  15 compared to mothers who are moderately fertile (parity 2-4)

  15. The Database • Combined natality data files and “fetal death files” from NCHS, 1989-2000 • Singleton live births and fetal deaths  20 weeks • Gestational age from LMP & DOB • Stillbirth (SB) / IUFD at  20 weeks • Term SB =  37 completed gest. wks. • Preterm SB = < 37 completed gest. wks. • SGA stillbirth = < 10th %tile of birthweight for gest. Age • Preterm SGA stillbirth

  16. Methodology • Exclude multiples • Race/ethnicity: non-Hispanic blacks, non-Hispanic whites, and Hispanics • Maternal age adjusted by direct method of standardization • Test of hypothesis two-tailed; type I error at 5% • Logistic regression used where needed

  17. The Evidence • Hyperfertility and Maternal Outcomes • Hyperfertility and Fetal Outcomes • Hyperfertility and Stillbirths

  18. The Sample

  19. Sociodemographic characteristics of US Mothers by Fertility Status, 1989-2000

  20. Temporal Trends in Rates of Birth by Fertility Status, USA 1989-2000

  21. Maternal Complications by Fertility Status, 1989-2000 A significant p value means that at least two of the tested groups are different

  22. Interim Conclusions(all data not previously shown) • Birthrates have declined over the study period among blacks as well as whites (by 10% and 9%, respectively) • Birthrates among Hispanics increased by 25% • About 75% of Hispanic births occur among immigrants • Racial/ethnic difference in fertility moderate for moderate level of fertility, and greatest for very high fertility status

  23. The Evidence • Hyperfertility and Maternal Outcomes • Hyperfertility and Fetal Outcomes • Hyperfertility and Stillbirths

  24. Crude Rates for Fetal Outcomes by Fertility Status, 1989-2000

  25. AORs for Growth Indices by Maternal Fertility Status, 1989-2000 * p for trend <0.001. Adjustment for maternal complications was performed using the confounding effects of maternal education, maternal age, maternal race, year of birth, marital status, adequacy of prenatal care, and maternal smoking during pregnancy.

  26. Interim Conclusions • Increasing fertility is a risk factor for LBW, VLBW, preterm and very preterm delivery in a dose-dependant fashion after 5 deliveries • Macrosomic babies occur in greater than expected incidence among women with greater than 5 births • Shortened gestation rather than size restriction (SGA) is affected by hyperfertility

  27. The Evidence • Hyperfertility and Maternal Outcomes • Hyperfertility and Fetal Outcomes • Hyperfertility and Stillbirths

  28. Crude Stillbirth Rates by Fertility Status, 1989-2000

  29. AORs for Stillbirth by Fertility Status, 1989-2000 Adjusted estimates were generated by taking into account the confounding effects of maternal education, maternal age, maternal race, year of birth, marital status, adequacy of prenatal care, maternal smoking during pregnancy and selected maternal complications (p for trend < 0.001).

  30. Type-specific stillbirth rates by fertility status, 1989-2000

  31. Type-specific stillbirth rates by fertility status, 1989-2000

  32. Stillbirth Rates in Type IV with Dose Effect, p for trend < 0.001

  33. Interim Conclusions • The risk of stillbirth increases incrementally with ascending fertility in hyperfertile women, implying a dose effect relationship • Women who are moderately fertile (2-4) have lowest risk and women who are hyperfertile ( 15) have highest risk

  34. Explanation for UAB findings • Micronutrient depletion has never been studied and could apply in US • “Maternal Depletion Syndrome” used in countries where under-nutrition is common — may not apply in US • Uterine overexhaustion may lead to fetal under-nutrition via scar tissue at prior placental sites • Maternal age and disease state may affect fetal outcomes but not studied in hyperfertile women

  35. Limitations • No access to autopsy data or cause of death • No data regarding birth spacing • No data regarding domestic activities which may relate to preterm labor • No data on negative health behaviors or psychosocial stressors • No data on religious influences on fertility

  36. Advantages • Population-based data minimizes bias due to selection • Sample size sufficient to provide acceptable level of precision in estimates • This data improves understanding of the link between extreme fertility and the risk of fetal demise

  37. Applications of UAB Hyperfertility Studies • Findings apply to counseling for women with increasing parity • Prenatal care less adequate with increasing fertility • Very preterm delivery increases in a dose-dependant fashion (after 5 deliveries) • Macrosomic babies increase among women with greater than 5 births • Stillbirths increase in a dose dependent fashion among hyperfertile women

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