Stillbirth epidemiology, diabetes, and other risk factors among all

pregnancies in Alberta from 2000 to 2009 Richard T. Oster and Ellen L. Toth Department of Medicine, University of Alberta

INTRODUCTION

Despite the first comprehensive set of worldwide estimates suggesting

that 2.6 million stillbirths occurred in 2009 (1), previously stillbirths have

been given little recognition compared to other pregnancy complications

or causes of maternal and neonatal deaths. The tragedy and impact of

stillbirth is however receiving new warranted attention clinically and

academically, as highlighted in a recent special series of the Lancet (2).

In Canada, women of First Nations descent have been shown to be at an

elevated risk of numerous adverse pregnancy outcomes, including

stillbirths which are 68% more likely among pregnant First Nations

women according to a systematic review and meta-analysis (3). This has

sparked new research into stillbirth rates and risk factors among First

Nations women, with Auger et al (4) pointing toward diabetes (driven by

obesity) as a major cause. However, the epidemiology of First Nations

stillbirths is still poorly understood as stillbirth type (antepartum or

intrapartum) has not been considered, longitudinal changes have not

been rigorously explored, and data on risk factors (including diabetes in

pregnancy type) is limited.

The purpose of this study was to gain a better understanding of extent of

the problem of stillbirths and the relationship between stillbirth and other

potential pregnancy-related factors may yield knowledge to better inform

intervention type and timing, with the goal of lowering risk of stillbirth in

First Nations pregnancies. We used provincial administrative data to: 1)

determine and compare the age-adjusted annual prevalence rates of

stillbirth longitudinally by First Nations and non-First Nations ethnicity;

and 2) examine the relationship between pre-existing diabetes and

gestational diabetes mellitus (GDM), stillbirths, and other possible

underlying factors amongst First Nations and non-First Nations

pregnancies.

METHODS

Ethical approval was obtained from the Human Research Ethics Board of

the University of Alberta. We conducted a secondary analysis of data

previously obtained (5). Briefly, anonymized data from all provincial

delivery records for the years 2000-2009 was requested from the Alberta

Perinatal Health Program, which compiles perinatal data from hospital

births and registered midwife attended home births. Specifics on how the

APHP collects and characterizes data can be found elsewhere (5).

Importantly, prior to our acquisition, the data was sent to Alberta Health

for First Nations ethnicity ascertainment. Three unique and distinct

populations of Canadian Aboriginal people are recognized by the federal

government: First Nations, Métis (mixed blood) and Inuit. De-identified

complete data was returned by AHW in STATA format. The data were

matched using the Personal Health Number and First Nations individuals

were classified as any Alberta resident registered under the Indian Act of

Canada and entitled to Treaty status with the federal Government.

Women delivering in Alberta with a First Nations identifier (First Nations

or Inuit) were considered “First Nations” whereas all other women

(including First Nations individuals without Treaty status and Métis

individuals) were considered “non-First Nations”.

All analyses were conducted using STATA statistical software (version 11)

and Joinpoint (version 3.5.1). Annual age-adjusted rates of stillbirth

(antepartum and intrapartum) for the entire province by ethnicity were

calculated and compared. Rates were age-standardized to the maternal age

distribution of the total number of pregnancies in 2005 from the Canadian Vital

Statistics by the direct method. Crude prevalence rates were also calculated to

make comparisons with previous studies. For longitudinal analyses, the

Average Annual Percent Change (AAPC) in stillbirth prevalence over time was

computed and compared between ethnicities. Tests of parallelism were

performed to determine if trends over time differed by ethnicity. Statistical

modeling (purposeful) using logistic regression was used to evaluate the

relationships between stillbirth (antepartum and intrapartum), diabetes in

pregnancy, and other potential explanatory variables.

RESULTS

Between 2000-2009 there were 433,445 pregnancies in Alberta. Only records

with gestational age ≥ 20 weeks were included in the analysis. Records with

missing stillbirth data were not included. A total 426,945 pregnancy records

were explored, of which 28,296 (6.63%) were First Nations women.

The overall age-adjusted rates of antepartum and intrapartum stillbirth were

significantly (p < 0.05) higher in the First Nations group (1.30% and 0.39%

respectively) compared to non-First Nations (0.46% and 0.22% respectively).

The rate ratios (First Nations to non-First Nations) for age-adjusted antepartum

and intrapartum stillbirth prevalence were and 2.86 and 1.80 respectively.

Between 2000 and 2009, age-adjusted prevalence rates of both antepartum

and intrapartum stillbirth remained stable in both groups (Figure 1, Figure 2,

Table 1). No longitudinal between group differences (parallelism) were noted.

In multivariate analysis, First Nations ethnicity was an independent predictor of

antepartum stillbirth (OR 1.70, 95% CI 1.47-1.97) and intrapartum stillbirth (OR

1.62, 95% CI 1.29-2.03) (Table 2). Age ≥ 35, history of abortion, history of

stillbirth, and pregestational diabetes were significant risk factors for both

antepartum and intrapartum stillbirth regardless of ethnicity. Gestational

diabetes was not a risk factor for stillbirths.

IMPLICATIONS

Stillbirth rates have remained stable in Alberta over 10 years, but are higher in

First Nations pregnancies compared to non-First Nations. This may be at least

in-part due to the higher incidence and prevalence of type 2 diabetes amongst

young First Nations women. Increased awareness of pregestational diabetes

could lead to better recognition and management and decreased numbers of

stillbirths.

REFERENCES 1. Cousens S et al. The Lancet. 2011;377(9774):1319-30.

2. The Lancet. 2011;377 (9774).

3. Shah PS et al. Women’s Health Issues. 2011;21(1):28-39.

4. Auger N et al. Canadian Medical Association Journal. 2013. Epub.

5. Oster RT. Dissertation. University of Alberta. 2013

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Year

Pre

vale

nce x

First Nations Non-First Nations

0

0.1

0.2

0.3

0.4

0.5

0.6

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Year

Pre

vale

nce x

First Nations Non-First Nations

First Nations Non-First Nations P-value for Comparison

Antepartum Stillbirths 1.63 (-6.79-10.81) 0.47 (-1.11-2.07) 0.475

Intrapartum Stillbirths 0.37 (-8.33-9.90) -1.13 (-5.15-3.05) 0.649

All women

(n = 426 945)

First Nations women

(n = 28 296)

OR for antepartum

stillbirth

OR for intrapartum

stillbirth

OR for antepartum

stillbirth

OR for intrapartum

stillbirth

Age ≥ 35 1.58 (1.42-1.76) 1.37 (1.16-1.63) 1.67 (1.15-2.42) 1.78 (1.03-3.24)

Parity (0)† 1.37 (1.24-1.51) 1.27 (1.10-1.46) 1.47 (1.07-2.04) -

Parity (≤ 3)† 1.40 (1.22-1.62) 0.65 (0.50-0.86) 1.50 (1.10-2.04) -

Multiple gestation 2.84 (2.44-3.31) 1.80 (1.37-2.35) - -

Ethnicity 1.70 (1.47-1.97) 1.62 (1.29-2.03) NA NA

Pregestational

hypertension

2.46 (1.83-3.29) 1.95 (1.16-3.27) - -

Gestational diabetes - 0.32 (0.18-0.57) - -

Pregestational diabetes 2.11 (1.48-3.00) 2.38 (1.42-3.99) 2.13 (1.07-4.63) 3.20 (1.14-8.97)

Pregestational weight ≥

91kg

- 0.62 (0.47-0.82) - -

Anemia 1.84 (1.29-2.64) 2.26 (1.35-3.78) - -

Drug dependant 2.04 (1.59-2.62) - 2.12 (1.463.07) -

Smoker 1.29 (1.16-1.44) - - -

History of abortion 1.52(1.30-1.78) 2.35 (1.92-2.88) 1.71 (1.19-2.46) 2.90 (1.73-4.87)

History of neonatal death 1.74 (1.20-2.52) - 2.84 (1.47-5.53) -

History of stillbirth 3.85 (3.10-4.78) 3.83 (2.68-5.46) 3.06 (1.88-4.98) 2.89 (1.30-6.41)

History of C-section - 0.62 (0.48-0.80) - -

History of fetal anomaly 1.80 (1.27-2.54) 2.84 (1.82-4.44) - -

History of LGA 0.58 (0.34-0.98) - - -

x

Figure 1. Age-adjusted prevalence of stillbirth over time in Alberta by ethnicity. A = antepartum stillbirth ; B =

intrapartum stillbirth.

x

Table 1. Ethnicity comparisons of antepartum and intrapartume stillbirth prevalence over time in Alberta,

2000-2009. Values are AAPC (95% CI) in age-adjusted rates.

x

Table 2. Multivariate predictors of antepartum and intrapartum stillbirth among Albertan women by ethnicity.

Values are ORs (95% CI).

A

B