Infant Mortality, Birth Defects and other birth outcomes in Nunavut: The challenge of translating data collection into improved health

1
Infant Mortality, Birth Defects and other birth
outcomes in Nunavut The challenge of translating
data collection into improved health

• Laura Arbour
• UBC Department of Medical Genetics
• Uvic Division of Medical Sciences

2
Understanding adverse birth outcomes in Nunavut

• Understanding the causes of birth defects/heart
  defects in Nunavut
• Understanding whether there is sufficient folic
  acid fortification in the North to prevent birth
  defects (and other adverse birth outcomes)-Kait
  Duncan
• Birth outcomes and smoking in Nunavut- Kate
  Maheffey
• Understanding Infant mortality
• Review of causes in infant mortality in
  Nunavut-Sorcha Collins
• CPT1 P479L What is the prevalence and does it
  confer risk for infant mortality? Sorcha Collins
• Safe Sleep position and breast feeding practices
  in all Inuit regions (ACS) Sirisha Asuri

-Qiturngatta our children,
Sam Lauson
3

• Most children in Nunavut are born healthy!
• But when compared by jurisdiction Nunavut has the
  highest rates of infant mortality, prematurity,
  low birth weight, birth defects in the country.
• Why is that??

4
Nunavut facts (2006 census)

• Became a territory April 1, 1999
• Population 29,474 (Inuit 85)
• Land mass 2 mil sq km (1/5 Canadas land mass)
• Birth rate 29/1,000 (twice national average)
• population under 25 60
• About 1/3 of Inuit currently finish high school
• Average household income 31,470 (compared to
  45,250)
• Cost of living 1.6-3x that of southern Canada
• Nearly 30 of income for food (compared to 10
  for the rest of Canada)

5
Nunavut

• Primary and tertiary health care delivered
  through support of three different regional
  centres (Ottawa, Winnipeg , and
  Yellowknife/Edmonton)
• Public Health mandate is Nunavut alone

6
Estimated RR for Congenital Anomalies in Inuit
infants (to one year) from Baffin Island and
Arctic Quebec the baseline
Arbour, Gilpin et al, 2004 IJCH 63(3) 251-265
Based on chart review of 2567 live births
1989-1994
7
Folic acid and congenital anomalies

• Evidence that 50-75 of spina bifida, can be
  prevented with supplemental vitamins containing
  folic acid. (Wald, 1991/ Czeizal,1992, )
• Estimated that 20 of all birth defects, in
  addition to SB, could also be prevented with the
  use of vitamin supplements (Botto et al AJMG,
  2004)
• Evidence that Folic acid supplementation
  specifically reduces heart defects-(Czeizel 1998,
  2004 Shaw et al 1995, Botto et al 2000, Godwin
  et al 2008)
• Public health efforts to encourage all women of
  childbearing years to take a multivite containing
  400µg of folic acid
• But variable willingness to adopt the daily use,
  aboriginal populations often more hesitant to
  adopt use
• Mandatory fortification of flour commenced in
  Canada, US in 1998 equivalent amounts projected
  to increase daily intake by 100µg

8
Folate is considered a nutrient of concernin
the Canadian North

• Pre fortification 219 Cree women in the James
  Bay region, the average intake of folate was less
  than 98-128 µg/day. Arbour, Delormier T, IJCH
  2002 61341-351
• Post-fortification Dietary Folate/Folic acid
  (DFE) intake after fortification of women of CB
  years on Baffin
• 2 seasons 24 hour recalls,
• FFQ, and 7 day food record 15-18 years 209
  µg/day
• 20-40, with 263 µg/day

Folate is obtained largely with fortified foods
Kuhnlein HV Egeland G J. Nutrition
20041341447-1453
9
Then and Now Has folic acid fortification
reduced the rate of congenital anomalies in
Nunavut (2000-2006)?

• Identical to the first review of 1989-1994
• 2018 perinatal and pediatric charts of children
  residing on Baffin Island 2000-2006 were reviewed
• As per international standards, congenital
  anomalies collected until 1 year, exclusions for
  specific birth defects associated with
  prematurity
• Only confirmed CA recorded (echocardiogram
  confirmed)
• Compared to previous review and ACASS and OR with
  95 CI

10
Demographics and risk factors n2018

• 25 of births to mothers under 20 years.
• Preterm births 12, Vs 8 nationally

• Alcohol use 13
• Any substance (alcohol, marijuana, cocaine) 16
• gt80 were smoking at first prenatal appointment
  Vs 12 nationally
• 20 were smoking gt10 cigarettes/day

11
Post-fortification Post-fortification Pre-fortification Pre-fortification Odds ratio/
of BD rate/1000 of BD rate/1000 Confidence
ICD-9 code n 2019   n 2567   Interval
740-741 ntd 0 0.00 2 0.78 0.25 (0.01-5.30)
742 other cns 14 6.93 18 7.01 0.85 (0.41-1.76)
743 Eye 2 0.99 2 0.78 1.27 (0.18-9.04)
744 Ear/face/trunk 2 0.99 5 1.95 0.51 (0.09-.2.6)
745 Bulbus cordis 37 18.33 59 22.98 0.79 (0.5-1.2)
cardiac septal VSD 23 11.39 36 14.02 0.81 (0.48-1.40)
ASD 14 6.93 19 7.40 0.94 (0.47-1.88)
Other 0 0.00 4 1.56  
746 Valvular and other heart 7 3.47 9 3.51 0.99 ( 0.37 to 2.6)
747 Other cir (PDA) 8 3.96 14 5.45 0.73 ( 0.30 to 1.7)
748 Resp 2 0.99 4 1.56 0.64 (0.12-3.47)
749 CL/P 5 2.48 8 3.12 0.79 (0.26-2.34)
750 Upper GI 9 4.46 13 5.06 .88 (0.37to 2.10)
7505 pyloric stenosis 9 4.46 12 4.67 0.95 (0.40-2.27)
751 Lower GI 3 1.49 12 4.67 0.42 (0.14-1.31)
752 Genital 17 8.42 23 8.96 0.94 (0.50- 1.76)
753 Upper GU 10 4.95 9 3.51 1.41 (0.57-3.49)
754/755/756 MSK 21 10.40 40 15.58 0.66 (0.39 to 1.13)
757 skin 2 0.99 0 0.00 6.3 (0.311 to 132.71
758 chromosome 3 1.49 3 1.17 1.27 (0.26-6.3)
           
Totals 142 70.33 221 86.09 0.80 (0.64-1.0)
12
Compared to the ACASS
ICD code Baffin (n2019) ACASS (n235381) OR (95 CI)
Total 745 37 /18.3 per 1000 1451/6.2 per 1000 3.0 (2.2-4.2)
13
2000-2006 Chart review-all BD (excluding
chromosome abnormalities, genetic syndromes and
birth defects associated with prematurity)
Candace Sy MD UBC
14
2000-2006 chart review -cardiac defects
(excluding chromosome abnormalities, genetic
syndromes and birth defects associated with
prematurity)
Candace Sy MD UBC
15
Are there genetic, nutrient, other factors
influencing the rate of heart defects?
16
Genetic/Nutrient determinants of heart defects
Methods

• Inuit children with heart defects confirmed with
  echocardiography (85 VSD/ASD) and their mothers
  were invited to participate in a case-control
  study (recruited through cardiology clinic and
  home communities)
• Nutrient intake, pregnancy exposures, RBC folate,
  serum cobalamin, homocysteine, and six functional
  polymorphisms for genes important in folate
  metabolism and uptake (MTHFR A222V, E429A, MTRR
  I22M, RFC-1 H27R, BHMT R239Q, MTHFD1 R653Q).
• Controls were mothers (ages 18-45) of Inuit
  children without heart defects, invited from the
  same community, reducing the risk of population
  stratification.
• HWE was evaluated for each polymorphism in the
  controls, and odds ratios with confidence
  intervals were calculated for both cases and
  their mothers using the controls as referent.

17
Participants

• 8 Communities
• Cases61
• Mothers of cases60
• Mothers of controls58

18
Results

• No mothers of cases or controls were taking
  vitamins peri-conceptionally
• No mothers of cases or controls were taking
  vitamins at the time of the study
• Most took some vitamins during pregnancy
• There was no difference in pregnancies exposed to
  alcohol (25) in cases or controls
• There was no difference in pregnancies exposed to
  cigarette smoking during pregnancy (80)

19
Results
p0.96
P0.36
p0.94
953 Vs 957 nmol/L p.94
20
RFC-1 H27R (80A?G) MTHFR A222V (677C?T) MTHFD1 R653Q (1958G?A)
Cases N50 HH-15 HR-21 RR-14 OR 3.2 (1.1-9.2) P.03 AA-36 AV-10 VV-4 OR 10.0 (.6-200) p.04 RR-15 RQ-20 QQ-14 OR. 72 (.31-1.4) p.53
Mothers of cases N57 HH-19 HR-19 RR-18 OR 3.9 (1.43-10.9) P.01 AA-45 AV-10 VV-1 OR 6 (CI .3-133) p.2 RR-12 RQ-26 QQ-17 OR .8 (.36-1.7) P.68
Mothers of controls n58 HH-20 HR-30 RR-6 AA-41 AV-15 VV-0 RR-14 RQ-21 QQ-20
Rima Rozen McGill
21
In summary

• The causes of heart defects and other birth
  defects in Nunavut are likely multifactorial
  including genetic predisposition, maternal
  exposures, diet and other complex factors that
  also predispose to prematurity.
• Folate fortification alone is not likely to be a
  panacea. But is the amount of fortification
  sufficient for this Northern population?

22
3rd International Polar Year Inuit Health Survey
(2007-2008)
Dr. Grace Egeland
Steering Committees From the Inuvialuit
Settlement Region, Nunatsiavut Region, and
Nunavut guided the research
Funded by Canadian Federal Program for IPY,
ArcticNet, Indian and Northern Affairs Canada and
Health Canada
23
The Inuit Health SurveyFolate levels in women of
childbearing years

• RBC folate measured in women of childbearing
  years (18-40)
• Survey
• 24 hour dietary recall
• Education, level of food security (food insecure,
  moderate insecurity, secure), number of
  cigarettes smoked, number of years smoking

• Total participants 249 (77 were from Nunavut)
• Average age 29. 1 ( 6) years
• 83.2 current smokers
• 6 taking vitamins
• Kait Duncan

24
Results

• Average RBC folate (without vitamin users)
  922.9nmol/L
• Total population935.7 nmol/L
• All regions lower than Canadian average -1,279.0
  ? 50.9 nmol/L (Canadian Health Measures Survey
  2007-2009)
• But still reach target RBC of about 900 nmol/L to
  prevent birth defects

25
Red cell folate from Inuit women of childbearing
age
Average 935.7 ?192.0 nmol/L
Kait Duncan UBC
26
Can we identify those who might benefit from
supplements?
Kait Duncan UBC
27
(No Transcript)
28
(No Transcript)
29
Can we recognize who would benefit from
supplements?
  Quartile 1 Lowest (303-806 nmol/L) Quartile 4 highest (1054-1441 nmol/L) Overall Significance level (p values)

Food insecure 69.0 61.1 65.4 0.484
Completed secondary school 34.9 38.5 36.5 0.702
Mean age 30.16 29.83 30.01 0.748
Mean cigarettes per day 10.54 8.24 9.58 0.057
Mean yrs smoking 16.04 13.52 14.88 0.067
Mean age started smoking 13.56 14.35 13.92 0.231
30

• Some women may benefit by the use of
  multivitamins pre-conceptionally and throughout
  pregnancy
• To identify those women for targeted
  interventional prevention programs will be a
  challenge

31
What about other birth outcomes?

• A chart review of those born between January 1st
  2003 and January 1st 2006 were utilized (1022
  births) since smoking status was recorded at the
  first prenatal visit on 90 (N918) of prenatal
  charts, and of those smoking, 80 of charts also
  included number of cigarettes smoked per day.
• Birth weight at term, prematurity, low birth
  weight, SGA, and substance use was assessed by
  category for those not smoking (n175) as
  recorded on first prenatal visit, smoking 1-4 (n
  215) 5-9 (n196), gt10 (n181), and smoking but
  no quantity recorded (n151). Total smokers n743
  (81).

Mehaffey et al Rural and Remote Health 10 1484.
2010 http//www.rrh.org.au
32
Birth weight of term infants according to smoking
categories
one way ANOVA, plt0.05
33
Preterm birth according to smoking status
34
Small for gestational age according to quantity
of smoking
35
Low birth weight according to smoking categories
36
Is there an association with drug other substance
use and smoking gt 10 cigarettes per day
37
Percent income for food
38
In summary

• For Inuit women smoking less than 5 cigarettes
  per day pregnancy outcomes were consistently
  better than average outcomes in the rest of
  Canada!
• Smoking gt 10 cigarettes per day at first
  pregnancy visit is associated with a
  significantly increased risk for preterm birth,
  sGA, and low birth weight
• The reasons for the increased risk in this group
  are likely multifactorial, and not due to smoking
  alone, more information is needed to understand
  the complex interactions
• Recognizing and supporting those women who
  report smoking greater than 10 cigarettes per day
  at first prenatal visit might improve outcomes

39
Infant mortality

• "The infant mortality ratethe rate at which
  babies of less than one year of age diereflects
  economic and social conditions for the health of
  mothers and newborns, as well as the
  effectiveness of health systems," states the OECD
  Factbook 2010

40
Infant Mortality in Inuit Inhabited Areas of
Canada (1990-2000)

• Compared to the rest of Canada, Inuit inhabited
  areas had higher rates of
• Prematurity ( RR 1.45)
• Infant mortality (comparable to 1970s)
• Post-neonatal infant mortality (RR 6.21)
• SIDS (RR 7.15)
• Infant deaths due to infections (RR 8.3)
• Rates still higher when Inuit inhabited areas
  were compared to rural and Northern Canada

Infant mortality rates in Inuit inhabited areas
and the rest of Canada (1990-2000) per 1,000 live
births Data and graph courtesy of Sacha Senécal,
Indian and Northern Affairs Canada and the
University of Western Ontario
Luo et al CMAJ 182 (3) 235-242
41
Methods

• Data collected when available
• Age at death
• Cause of Death
• Sex
• Gestational Age (wks)
• Place of Residence
• Sleep Position - found
• Sleep Position - placed
• Bed-sharing
• Smoking present in environment
• Alcohol present in environment
• Breast feeding 
• CPT-1 P479L results

• Research Partner Nunavut Tunngavik Inc
• As part of a study exploring a metabolic cause of
  infant mortality (CPT1A P479L) all causes of
  infant mortality cases available were reviewed
  for the years 1999-2008
• Ethics review UBC and NRI
• Data Sources-CMOH office, coroners office
  (Iqaluit) and vital statistics (Rankin Inlet)

S. Collins. MSc Candidate UBC
42
SIDS and SUD in Nunavut2000-2008

• SIDS and SUDI deaths as a proportion of all
  deaths under 1 year of age in Nunavut (2000-2008
  Nunavut Coroners Office) and Canada (2000-2005
  Statistics Canada)

S. Collins MSc candidate
43
SIDS - causes

• When an infant suddenly dies in his/her sleep
  with no apparent illness or physical harm, it is
  termed as SIDS
• Genetic variants can predispose infants to SIDS
  (eg. Genetic causes of cardiac arrhythmia, fatty
  acid abnormalities)
• Physiological factors such as anemia, respiratory
  infection, neuronal (brain cell) immaturity can
  all be involved
• Smoking prenatally increases the risk for SIDS
  (by altering the brainstem, arousal from sleep,
  blood vessels of the infants).
• The other significant component involved is the
  physical environment soft mattress, hyperthermia
• Physiological factors (eg. neuronal immaturity)
  vulnerable environment (eg. prone sleeping) may
  be fatal

S. Asuri
44
Sleep Position

• Sleeping on the back is the safest sleep position
  for infants
• SIDS worldwide was decreased by 50-90 by laying
  infants to sleep on their backs
• Sleeping prone can physically block infants
  airways, alter the arousal responses of infants
  in response to respiratory stress (sleep deeper)

• Not on my tum mum
• Look up to our ancestors
• Back to Sleep

www.nichd.nih.gov/sids/
S. Asuri
45
But Mothers in Nunavut less likely to adopt
supine position (lt50)

• 2006 Maternity Experiences Survey
• 2006 Aboriginal Childrens Survey

46
A tri-territorial case cohort study to determine
prevalence of the CPT1A variant and whether there
is an increased risk for infant mortality-S.
Collins

• Genotyping prevalence study of all those born in
  2006 in Nunavut, NWT and Yukon (Collins et al
  2010 Molecular Genetics and Metabolism)
• Genotype all unexpected infant deaths from
  1999-2008 present Odds Ratio for Nunavut 3.86
  (95 CI 1.185-22.3841)

Research team L. Arbour (S. Collins), H.
Vallance, C. Greenberg, G. Sinclair
47
Understanding and preventing infant mortality in
Nunavut

• Collaborative effort with NTI, Health and Social
  Services and Arctic Health Research network

-Focus groups -Health promotion according to
focus group response -Qiturngattaour children
48

• The QSS surveillance system has now been
  initiated from 16 weeks gestation to 5 years of
  age.
• Food security, blood glucose in pregnancy,
  paternal and maternal occupations, exposures,
  birth outcomes, newborn screening results, safe
  sleep practices, well child visits, developmental
  assessments will be part of a public health
  maternal child health surveillance system which
  builds and expands from regional models of
  perinatal and birth defect surveillance.

Samantha Lauson (QSS coordinator, Uvic)
49
Summary

• Most women in Nunavut have positive birth
  outcomes
• But food insecurity, sub-optimal folate levels,
  high smoking rates, lack of adoption of supine
  sleep position and genetic factors .all likely
  influence birth outcomes.
• Priority efforts to further understand and reduce
  infant mortality are under way.
• More information is needed to understand the
  complex interactions involved in smoking
  practices that seem to influence rates of
  prematurity, low birth weight, and possibly birth
  defects.

50

• This information is just the tip of the
  iceberg..More is needed to act effectivelybut
  translating the data collection into health
  improvement will remain the greatest challenge.

51
Contributors and funders

• Department of Health and Social Services of
  Nunavut
• Dr. Geraldine Osborne, Isaac Sobol
• Amy Caughey
• Dr. S MacDonald
• Hamlet support/Nursing Stations
• Mehrun Forth, Martha Nowdluk
• Rosemarie Rupps
• Dr. Cindy Orlaw
• Jason Cowan
• Kait Duncan, Dr. Kate Mehaffey
• Dr. Candace Sy
• Dr. Sirisha Asuri
• Dr. Rima Rozen
• Dr. Grace Egeland

• Sharon Edmunds-Potvin
• Gwen Healey, Terry Creigh, (many others)
• Samantha Lauson
• Sarah McInstosh

52
Thank-you!
53
Infant Mortality rate and SIDS in infants born
prematurely and at term in Nunavut 2000-2007 (N
and Rate / 1,000 births)

Premature Term
Births (2000-2007) 703 5195
Mortality rate 24.5(15) 5.4(28)
Cause of death
SIDS 12.8(9) 2.9(15)



54
Do these heart defects make a difference?

• Chart review all infants born 2000 2004 (1688
  infants) Baffin (Qikiqtaaluk) region.
• Admissions for LRTI and the presence of a heart
  defect until age 1.
• Annualized incidence (AI) rates/1000 and odds
  ratios (OR) with 95 confidence intervals (CI)
  were calculated and compared

55
Hospital admissions for lung infection with and
without heart defects

• 408 infants admitted for LRTI, with a total of
  597 admissions (354/1000 AI rate)
• But for those with heart defects (n59) the AI
  was 826/1000 with an OR 2.36 95 CI 1.44-3.86
  for at least one admission and they were also
  more likely to have repeat admissions (OR 2.6
  95 CI 1.23-5.63)

Peters et al. IJCH (70), 2010