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Life style factors and Gastroschisis

Life style factors and Gastroschisis. Elizabeth S Draper 7 th October 2007 CARIS Meeting Cardiff. Gastroschisis 1. Paraumbilical (right) anterior abdominal wall defect Evisceration of fetal intestine through defect Stomach, bladder and gonads are also often extra-abdominal – not liver

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Life style factors and Gastroschisis

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  1. Life style factors and Gastroschisis Elizabeth S Draper 7th October 2007 CARIS Meeting Cardiff

  2. Gastroschisis 1 • Paraumbilical (right) anterior abdominal wall defect • Evisceration of fetal intestine through defect • Stomach, bladder and gonads are also often extra-abdominal – not liver • Intestines exposed to amniotic fluid as they are not enclosed in a sac. • Maternal serum AFP raised

  3. Baby in NICU with a gastroschisis. Note the position: right of the umbilicus

  4. Gastroschisis 2 • Increasing birth prevalence over last 10-15 years (0.5/10,000 to 3/10,000 births) – Rankin ‘99

  5. Gastroschisis 2 • Increasing birth prevalence over last 10-15 years (0.5/10,000 to 3/10,000 births) – Rankin ‘99 • 75+% mothers of infants with gastroschisis are <25 years – UK registers

  6. Proportions of gastroschisis cases and overall births by maternal age for areas covered by BINOCAR registers, 1994 to 2004.

  7. Gastroschisis 2 • Increasing birth prevalence over last 10-15 years (0.5/10,000 to 3/10,000 births) – Rankin ‘99 • 75+% mothers of infants with gastroschisis are <25 years – UK registers • Occurs between the fifth and eighth week after conception – Hoyme ‘83

  8. Gastroschisis 2 • Increasing birth prevalence over last 10-15 years (0.5/10,000 to 3/10,000 births) – Rankin ‘99 • 75+% mothers of infants with gastroschisis are <25 years – UK registers • Occurs between the fifth and eighth week after conception – Hoyme ‘83 • Results from a disruption or compromise of the right omphalomesenteric artery – Hoyme ‘83

  9. Gastroschisis 2 • Increasing birth prevalence over last 10-15 years (0.5/10,000 to 3/10,000 births) – Rankin ‘99 • 75+% mothers of infants with gastroschisis are <25 years – UK registers • Occurs between the fifth and eighth week after conception – Hoyme ‘83 • Results from a disruption or compromise of the right omphalomesenteric artery – Hoyme ‘83 • Few associated anomalies

  10. Gastroschisis 2 • Increasing birth prevalence over last 10-15 years (0.5/10,000 to 3/10,000 births) – Rankin ‘99 • 75+% mothers of infants with gastroschisis are <25 years – UK registers • Occurs between the fifth and eighth week after conception – Hoyme ‘83 • Results from a disruption or compromise of the right omphalomesenteric artery – Hoyme ‘83 • Few associated anomalies • Low recurrence risk

  11. Gastroschisis 2 • Increasing birth prevalence over last 10-15 years (0.5/10,000 to 3/10,000 births) – Rankin ‘99 • 75+% mothers of infants with gastroschisis are <25 years – UK registers • Occurs between the fifth and eighth week after conception – Hoyme ‘83 • Results from a disruption or compromise of the right omphalomesenteric artery – Hoyme ‘83 • Few associated anomalies • Low recurrence risk • More males than females

  12. Gastroschisis 2 • Increasing birth prevalence over last 10-15 years (0.5/10,000 to 3/10,000 births) – Rankin ‘99 • 75+% mothers of infants with gastroschisis are <25 years – UK registers • Occurs between the fifth and eighth week after conception – Hoyme ‘83 • Results from a disruption or compromise of the right omphalomesenteric artery – Hoyme ‘83 • Few associated anomalies • Low recurrence risk • More males than females • Associated with IUGR

  13. Gastroschisis 2 • Increasing birth prevalence over last 10-15 years (0.5/10,000 to 3/10,000 births) – Rankin ‘99 • 75+% mothers of infants with gastroschisis are <25 years – UK registers • Occurs between the fifth and eighth week after conception – Hoyme ‘83 • Results from a disruption or compromise of the right omphalomesenteric artery – Hoyme ‘83 • Few associated anomalies • Low recurrence risk • More males than females • Associated with IUGR • 90% cases detected by antenatal US

  14. Gastroschisis 2 • Increasing birth prevalence over last 10-15 years (0.5/10,000 to 3/10,000 births) – Rankin ‘99 • 75+% mothers of infants with gastroschisis are <25 years – UK registers • Occurs between the fifth and eighth week after conception – Hoyme ‘83 • Results from a disruption or compromise of the right omphalomesenteric artery – Hoyme ‘83 • Few associated anomalies • Low recurrence risk • More males than females • Associated with IUGR • 90% cases detected by antenatal US • Survival rate approx 90% all cases

  15. Suggested Risk Factors for Gastroschisis – 2 main case control studies • maternal age < 25 years • low social class • smoking • heavy alcohol consumption • recreational drug use – cocaine • vasoactive medications: salicylates (aspirin), pseudoephedrine, phenylpropanolamine • solvents • other factors including: poor diet, influenza, landfill sites, seasonality

  16. Trent Congenital Anomalies Register (CAR) Aims of the register: • record congenital anomalies in infants born to mothers resident in the Trent region • investigate putative aetiological factors using optimal social & biological methods • use the findings of the aetiological studies to influence public policy and thereby improve the public health

  17. Background to study • Recreational Drug Use • Perinatal methodology • Hair Analysis

  18. Recreational drug use • Significant increase in past decade • Cannabis most popular • Increase in dance or ‘rave’ drugs since late 1980’s especially ecstasy (MDMA). • General assumption that more men than women take drugs • No longer restricted to inner city or deprived areas

  19. Prevalence (%) of any illicit drug use in the last year and last month, adapted from British Crime Surveys 1994 – 2002/3.

  20. Prevalence (%) of any class A drug use in the last year/last month, adapted from the British Crime Survey 2000 – 2002/3.

  21. Recreational drug use during pregnancy • Prevalence uncertain • Up to 2.6% cannabis use (ALSPAC 1992 cohort) • Suggested increased morbidity / mortality • Increased prevalence of Gastroschisis, SIA –(Torfs et al, Werler et al)

  22. Methodological issues in perinatal epidemiology - collecting information about risk behaviours • Reliability using interviews questionable • Historical recall bias • Truthfulness • Validation method required – biological markers • Urinary analysis – detects short term drug use only

  23. Hair analysis • First mooted in 1979 by Baumgartner et al. • RIA and GC-MS, LC-MS techniques used • Used for range of drugs • Used in forensics, drug rehabilitation, screening etc. • Rate of hair growth: population rate 1 cm /month (Wilkinson ’82), pregnancy rate 0.9 cm / month (Pecoraro ’69) – allows for timed analysis

  24. detects long term drug use easy collection & storage difficult to adulterate sample recollection possible detects short term drug use collection guidelines & refrigeration required adulteration easy both biological & chemical recollection not possible Advantages of Hair vs Urine analysis

  25. Study hypothesis • the incidence of gastroschisis is positively associated with the use of recreational drugs in the weeks following conception Data collected at maternal interview concerning recreational drug use validated using maternal hair analysis

  26. Methods • Design: case-control study • Setting: Trent, West Midlands & Northern regions • Period: 01/01/2001 – 31/08/2003 • Subjects: all cases of gastroschisis plus matched controls • Data collection: regional congenital anomaly registers

  27. Controls • 3 matched controls – mothers of congenitally normal births matched by region of residence and age (to within one year) selected from the initial intended place of delivery of the case Any refusing control mother replaced until full complement of 3 controls per case achieved.

  28. Methods cont: • Case ascertainment and validation • Network of local contacts • Approach to mothers • Data collection

  29. Data Collection • Notes review • Previous history, maternal details, demographic, current pregnancy, labour, delivery, outcome, post mortem results • Maternal Interview • Socio-demographics, occupational exposures, drug history (prescribed, over the counter, recreational), other risk behaviours, hair treatments • Collection of hair sample • LMP, EDD, date of collection

  30. Results 1 • 164 mothers delivered 165 cases gastroschisis • Overall prevalence 4.22 / 10,000 total births+ia • Birth prevalence 4.01 / 10,000 total births Region Overall prev Birth prev Northern 4.21 4.21 West Midlands 3.94 3.76 Trent 4.59 4.18

  31. Results 2 • Response • Gastroschisis mothers 88% • Control mothers 77% • Hair samples collected for • 99% gastroschisis case mothers • 98% control mothers

  32. Characteristics of gastroschisis case mothers and infants • Median maternal age : 20.5 yrs (IQR 18.5 – 24.7) • Median gestational age : 36.0 wks (IQR 35.0 – 37.0)* • Singleton : 98% • Isolated anomaly : 93%* • Male : 53% • TOP : 6%* *significant difference between responders and non responders

  33. Recreational Drug Use – maternal interview

  34. Adjusted conditional regression model for any RDU

  35. Adjusted odds ratios for the use of recreational drugs in the first trimester in gastroschisis mothers OR adjusted for BMI, marital status, aspirin use, home owner, gynae disease & smoking

  36. Suitability of hair samples for analysis

  37. Hair analysis cont: • major problems • vaso-constrictive recreational drug use • limited number of hair samples: • 39.5% cases & 26.3% controls (targetted analysis) • identified: 3 (2.1%) gastroschisis case mothers & 6 (1.4%) control mothers

  38. Multiple Imputation of first trimester vaso-constrictive drug status for subjects without hair analysis • Estimated proportions of vaso-constrictive users: • Gastroschisis mothers: 14.8% (range 9.8% to 18.9%) • Control mothers: 8.1% (range 5.2% to 10.8%)

  39. Adjusted odds ratios for the use of vaso-constrictive recreational drugs in the first trimester for gastroschisis mothers OR adjusted for BMI, marital status, aspirin use, home owner, gynae disease & smoking

  40. Study Conclusions 1: • Statistically significant increased risk of gastroschisis with first trimester use of : • Any recreational drug • Vaso-constrictive recreational drugs

  41. Study Conclusions 2: • Hair analysis can be used to validate data collected at maternal interview - problems with adequate hair weight for 1st trimester analysis • An additional 2.1% case mothers and 1.4% control mothers were identified as users of vaso-constrictive recreational drugs from hair analysis. • Although adjusted ORs increased when results from hair analysis included within the conditional logistic regression model they were reduced following multiple imputation for missing hair analysis data • Mothers taking vaso-constrictive recreational drugs during early pregnancy are between two and three times more likely to have an infant with gastroschisis than those who don’t.

  42. Summary: • Birth prevalence of gastroschisis is still increasing • North South gradient with highest rates reported in the UK – esp. Wales • Risk factor profile for gastroschisis mothers Current Welsh study with BINOCAR registers: • Investigation of lifestyle, dietary & environmental exposures.

  43. Collaborators Judith Rankin NORCAS Ann Tonks & Mike Wyldes West Midlands CAR Jenny Kurinczuk Keith Abrams Paul Burton Webster Madira Interviewers:Caroline Lamming, Claire Shuter, Theresa Regis, Gill Thompson

  44. Thank you

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