Encouraging Results from a CDC-Massachusetts Department of Public Health Collaborative Project

1. Linking Data from a Population-Based Assisted Reproductive Technology Registry to Vital Statistics Data: Encouraging Results from a CDC-Massachusetts Department of Public Health Collaborative Project NAPHSIS/NCHS Joint Meeting Bruce Cohen, PhD June 2007

2. Background Evaluation of ART reporting on the birth certificate Characteristics of mothers using ART Associations between ART and maternal and perinatal outcomes Future direction for linkage of fertility clinic data and birth certificates Presentation Outline

3. Background • Use of ART has steadily increased over the past decade, and accounts for 1% of all live-born children in the USA • Safety concerns demand large-scale studies of adverse outcomes of ART • Whereas the ART registry maintained by CDC can be used to address certain outcomes (e.g., multiple gestation, pre-term delivery), its scope is limited (e.g., poor data on birth defects, no data on infant mortality) • Massachusetts state law mandates health insurance coverage of ART, and fertility assistance now accounts for about 3% of all live-born children in that state (based on birth certificate data) • Massachusetts has considerable experience with research based on record linkage

4. Objectives of the Linkage Project • To link information from CDC’s assisted reproductive technology (ART) surveillance data files with Massachusetts state birth records • To create a population-based dataset of ART mother-infant pairs including data on circumstances surrounding conception and delivery and data on maternal and infant outcomes • To compare infants conceived using ART and their mothers with other Massachusetts infants and their mothers

5. Study Population The study population was drawn from MA birth certificate data base: • infants born in 1997-2000 • maternal residency listed as MA. • birth occurred in MA, RI, CT, NH N=158,229 deliveries and 161,539 total infants in 1997-1998 N=158,771 deliveries and 162,260 total infants in 1999-2000 Information abstracted: demographic characteristics, prenatal care use, maternal history, pregnancy complications, delivery outcomes and complications

6. Study Population Data from live births reported to ART Registry were linked to the study population if: • ART treatment was in a MA or RI clinic (11 clinics total) • Infant(s) born in 1997-1998, 1999-2000 • Maternal residency at time of ART listed as MA or unknown. N=2703 deliveries and 3704 total infants in 1997-1998; N=3330 deliveries and 4494 total infants in 1999-2000; Information abstracted: patient history, ART treatment information, ART outcome information

7. Data Linkage Strategy STAGE 1: • link ART record to birth record using mother’s date of birth and infant’s date of birth • further evaluate potential matches using ancillary variables -- plurality, parity and birth weight STAGE 2: • further linkage by maternal name for a portion of records -- ART record names obtained through follow-up with ART clinics

8. Stage 1 Linkage Results

9. Final Linkage Results

10. For additional details on linkage methods and 1997-1998 results: Sunderam S, Schieve LA, Cohen B, et al.: Linking Birth and Infant Death Records With Assisted Reproductive Technology Data: Massachusetts, 1997–1998.Maternal and Child Health Journal, 2005: 9, 1 – 11

11. Evaluation of ART Reporting on the MA Birth Certificates: Background • Massachusetts is one of the first states that collect information on assisted reproductive technology (ART) and fertility during use via the birth certificate, started in 1996 • ART information was extracted by hospital staff from medical records, recorded on the birth certificates, then sent to the state Registry of Vital Records as part of the routine data transmission. • The completeness and quality of reporting has not been systematically evaluated, thus limiting the potential of use in our surveillance and research work related to the assisted reproductive technology.

12. Massachusetts Birth Certificate Medical Worksheet Questions

13. Research Questions • How consistent is the ART information reported on the Massachusetts birth certificate with ART reported in ART Registry? • What are the predictors of checking off the ART variable on the Massachusetts birth certificate ?

14. Methods • Data sources: live-birth deliveries to MA resident mothers occurring in 1997-2000 in MA, NH, RI, and CT • Unit of analysis: live-birth deliveries • Use linked SART-BC records as “gold standard” for “true” ART births • Validity measures : sensitivity and specificity

15. Results – Overall Sensitivity and Specificity

16. Concordance of ART Information between the Massachusetts Birth Certificate and the SART Database, 1997-2000

17. Sensitivity of Reporting ART on Birth Certificate by Plurality

18. Sensitivity of Reporting ART on Birth Certificate by Kotelchuck Index

19. Variation in Sensitivity by Hospital Characteristics • Range of sensitivity by facility : 0-60+ % • Teaching hospitals: sensitivity > 60% in 3 out of 7 • Non-teaching hospitals: sensitivity > 60% in 2 out of 49 • Variation also observed by number of ART deliveries/year and hospital level

20. Summary/Comments • While specificity of reporting ART on the birth certificates is high, the sensitivity is low • Results probably reflect experience of early stage of collecting ART information on the birth certificate in Massachusetts • Definitional differences could affect linkage rates: birth certificate response category includes non-invasive procedures--artificial insemination (AI) or intrauterine insemination (IUI) whereas CDC ART definition is “all treatments or procedures that include the handling of human oocytes and sperm for the purpose of establishing a pregnancy.  This includes, but is not limited to in vitro fertilization and transcervical embryo transfer, gamete intrafallopian transfer, zygote intrafallopian transfer, tubal embryo transfer, embryo cryopreservation, oocyte or embryo donation, and gestational surrogacy.  ART does not include assisted insemination using sperm from either a woman's partner or sperm donor.

21. Summary/Comments • Consider alternative reporting methods for ART on the birth certificate (PRAMS pilot testing indicated much higher response from MA mothers than recorded on birth certificate) • What are the implications of these results for the new revised certificate items? For research using these items?

22. Characteristics of Mothers using ART or Fertility Assistance in Massachusetts

23. Comparison Groups The following slides use three comparison groups: • ART Births/Deliveries: Massachusetts births/deliveries linked to the CDC ART Registry (1.7%) • FA on BC: Evidence of fertility assistance on the birth certificate but not linked to the CDC ART registry (0.6%) • NO FA on BC: All other births or deliveries (97.8%)

24. Percentage of Deliveries, Age ≥35, Massachusetts 1997-2000

25. Percentage of Deliveries that are Multiple Births, Massachusetts 1997-2000

26. Percentage of Deliveries that are first Deliveries, Massachusetts 1997-2000

27. Percentage of Non-Hispanic White Mothers, Massachusetts 1997-2000

28. Percentage of Mothers with College Education, Massachusetts 1997-2000

29. Percentage of Mothers Privately Insured, Massachusetts 1997-2000

30. Percentage of Deliveries in Boston Hospitals, Massachusetts 1997-2000

31. Percentage of Deliveries with Kotelchuck Index = Adequate +, Massachusetts 1997-2000

32. Percentage of C-Section Deliveries, Massachusetts 1997-2000

33. Percentage of Low Birthweight Infants, Massachusetts 1997-2000

34. Percentage of Multiple Deliveries where Plurality = 3+, Massachusetts 1997-2000 ?

35. Summary • These linked data provide the first population-based assessment of the prevalence and characteristics of ART mothers in the US • Women who use other methods of fertility assistance are more similar to those who use ART than the general population, with some notable differences • These unadjusted data provide a preliminary, baseline snapshot and need to be examined more closely to fully understand the implications for public health practice

36. Associations Between Assisted Reproductive Technology and Maternal and Perinatal Outcomes Schieve LA, Cohen BB, Naninni A, Ferre C, Reynolds, MA, Zhang Z, Macaluso, M, and Wright V. “A Population-Based Study of Maternal and Perinatal Outcomes Associated with Assisted Reproductive Technology in Massachusetts.” Maternal Child Health J. March 8, 2007.

37. Summary • After considering numerous potential confounding factors through sample restriction and matching, ART was associated with: • Pre-existing diabetes • Incompetent cervix • Pregnancy induced hypertension • Uterine bleeding • Placental abruption • Placenta previa • Preterm delivery • Very preterm delivery • Low birth weight • Infant not discharged home • Although confidence intervals overlapped 1.0, there was also a suggestion of increased risk among ART births for: • Gestational diabetes • Very low birth weight

38. Summary • Findings of associations with pre-existing diabetes and incompetent cervix are supported by the literature. Both are conditions associated with infertility disorders treated with ART. • Findings of associations with pregnancy-induced hypertension, uterine bleeding placenta abruption, placenta previa (and marginal association with gestational diabetes) confirm and expand on previous studies by more fully considering potential confounders. • Negative finding for cesarean section contradicts several previous studies reporting association. • While C-section rates were high in women who conceived via ART in comparison to the general population of births in MA, ART does not appear to be the reason. • C-section rates for ART births were comparable to those observed in women who did not conceive with ART after matching on birth place and time, age, parity, and race/ethnicity. • Findings of associations with preterm and low birth weight also support previous studies. • Supplemental analysis in a subgroup without maternal health or labor and delivery complications suggests the increase in perinatal risk among ART births is not solely explained by maternal health factors.

39. Future Directions • Update linkages for currently available data • Continue research using these data: extend etiologic and descriptive analyses • Explore linkages with other data sources such as hospital discharge data bases, birth defects registries…perhaps through PELL

41. Future Directions • Investigate limitations of linkage-based analyses (sensitivity analyses, potential for information/detection bias) • Explore the feasibility of augmented studies (nested follow-up, case-control studies) • Explore application of the linkage methods to other states with high ART prevalence