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 years (0.5/10,000 to 3/10,000 births) – Rankin ‘99

5. Gastroschisis 2
Increasing birth prevalence over last 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 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 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 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 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 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 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 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 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. Advantages of Hair vs Urine analysis
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

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 Maternal Interview
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 / 10,000 total births
Region Overall prev Birth prev
Northern
West Midlands
Trent

31. Results 2 Response Hair samples collected for
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 : yrs (IQR 18.5 – 24.7)
Median gestational age : wks (IQR 35.0 – 37.0)*
Singleton : %
Isolated anomaly : %*
Male : %
TOP : %*
*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