Hindawi Publishing Corporation
Journal of Environmental and Public Health
Volume 2012, Article ID 635097, 6 pages
History of Cesarean SectionAssociated withChildhoodOnsetof
T1DM inNewfoundlandandLabrador, Canada
J. Phillips,1N. Gill,1K. Sikdar,1S.Penney,2andL.A.Newhook2,3
1Newfoundland and Labrador Centre for Health Information, St. John’s, NL, Canada A1B 2C7
2Janeway Pediatric Research Unit, 4th Floor Janeway Hostel, Memorial University of Newfoundland, 300 Prince Philip Drive,
St. John’s, NL, Canada A1B 3V6
3Janeway Children’s Health and Rehabilitation Centre, 300 Prince Philip Drive, St. John’s, NL, Canada A1B 3V6
Correspondence should be addressed to L. A. Newhook, firstname.lastname@example.org
Received 27 February 2012; Accepted 20 April 2012
Academic Editor: V. Mohan
Copyright © 2012 J. Phillips et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objectives. Newfoundland and Labrador (NL) has one of the highest incidences of Type 1 diabetes mellitus (T1DM) worldwide.
Rates of T1DM are increasing and the search for environmental factors that may be contributing to this increase is continuing.
Methods. This was a population-based case control design involving the linkage of data from a diabetes database with live birth
registration data. 266 children aged 0–15 years with T1DM were compared to age- and gender-matched controls. Chi-square
analysis and multivariate conditional logistic regression were carried out to assess maternal and infant factors (including maternal
age, marital status, education, T1DM, hypertension, birth order, delivery method, gestational age, size-for-gestational-age, and
birth weight). Results. Cases of T1DM were more likely to be large-for-gestational-age (P = 0.024) and delivered by C-section
(P = 0.009) as compared to controls. C-section delivery was associated with increased risk of T1DM (HR 1.41, P = 0.015)
when birth weight and gestational age were included in the model, but not when size-for-gestational-age was included (HR 1.3,
P = 0.076). Conclusions. Birth by C-section was found to be a risk factor for the development of T1DM in a region with high rates
of T1DM and birth by C-section. These findings may have an impact on health practice, health care planning, and future research.
chronic diseases in childhood and results from autoimmune
destruction of pancreatic β-cells, leading to insulin defi-
ciency. T1DM is thought to originate through a combination
of genetic and unknown environmental factors, of which
environmental factors remain poorly defined. Newfound-
land and Labrador (NL), Canada, is recognized as having
one of the highest rates of T1DM worldwide . A study
on hospitalizations of children in NL reported an increase in
diabetes-related hospitalizations among children aged 0–19
years . T1DM is a significant disease in NL with its
associated acute and chronic complications as well as the
economic costs to both families and the health care system.
Identification of potential perinatal environmental risk fac-
tors is examined in this study to try and elucidate potential
reasons of why the disease is so common in this region of
This study was a case control design involving the linkage of
data extracted from the Newfoundland and Labrador Dia-
betes Database (NLDD) with the Live Birth System (LBS).
The NLDD is maintained by the Janeway Pediatric Research
Unit at the Janeway Child Health Care Centre (JCHCC) in
St. John’s, NL. The JCHCC is the only tertiary care pediatric
hospital in the province. The NLDD includes data for the
majority of cases of T1DM diagnosed in NL from 1987 to
present. Children are included in the database as part of a
prospective provincial study on the epidemiology of T1DM
in NL. They have a confirmed diagnosis of T1DM accord-
ing to Canadian Diabetes Association (CDA) criteria .
The LBS is maintained by the Newfoundland and Labrador
Centre for Health Information (NLCHI). Data for this
system are acquired from Live Birth Notification forms that
are completed in all provincial health care facilities. The
forms are provided to NLCHI by the Vital Statistics Division,
2 Journal of Environmental and Public Health
currently contains data on all births from 1992 to 2011.
Patient records were individually linked across datasets.
Cases included children born in NL from 1992 onwards
which have been diagnosed with T1DM before 15 years of
age. Children with type 2 diabetes, maturity-onset diabetes
of youth, transient hyperglycemia, and diabetes caused by
chemotherapy or cystic fibrosis are excluded from the NLDD
and thus were not included in the study. Children born
prior to 1992 were not included in the study because there
are no electronic birth notification data available before this
A unique identifier, such as the provincial health insur-
ance plan number, was not available for all children in the
NLDD. As a result case subjects were linked to the LBS
available, child’s name was used to verify the linkage. Of
the 301 cases in the NLDD, 23 were excluded because they
were born out of province. Of the remaining 278, 6 were
excluded as duplicate records. Linkage was possible for all
but six children resulting in a total of 266 cases included in
the study. Three control subjects (N = 798) were selected for
each case matched on year of birth, sex, and health authority
of mother’s residence at time of delivery. Power analysis was
performed to determine whether this sample size would be
sufficient to detect statistical significant associations between
T1DM and the risk factors of interest. The power analysis
was conducted considering an overall rate of birth by C-
section in NL as 30.9% , in order to achieve a power
of 80% with a desired odds ratio of 1.5. Using the method
described by Kelsey et al.  the power analysis confirmed
that a sample size of 266 cases and 798 controls is sufficient
and delivery by C-section.
Cases and controls were grouped into two gestational
age categories: preterm and term/postterm. Birth weight
in grams was used to classify cases and controls as high
birth weight (>4,000 grams) or not (≤4,000 grams). Cases
and controls were also classified as small/appropriate-for-
described by Kramer et al. . Method of delivery was
categorized as vaginal or C-section. Cases and controls were
years. Mothers were also classified by their T1DM status and
hypertension status. Mother’s marital status was categorized
education level was classified into three categories: not
beyond high school.
Descriptive statistics were generated to describe the
distribution of cases and controls. Demographic and clinical
factors of mothers, including age, marital status, education,
place of residence, parity (number of live born children
delivered), and complications of pregnancy, were included.
Cases and controls were analyzed by sex, place of residence,
age of onset, length of gestation, type of delivery, birth
weight, size for gestational age, and birth order.
Chi-square tests were used to predict diabetes status on
the basis of the independent variables. Conditional multiple
T1DM risk and the variables of interest. Two conditional
logistic regression models were employed. The first model
contained birth weight, gestational age, parity, delivery
method, mother’s marital status, mother’s education level,
mother’s age, maternal hypertension, and mother’s T1DM
status. The second model incorporated all variables in the
age which were replaced with size-for-gestational-age. Birth
weight and gestational age were not included in the same
model as size-for-gestational-age as they are components of
was used to generate descriptive statistics and chi-squares.
SAS 9.2 was used to conduct the conditional multivariate
This study received approvals from the Human Investi-
gation Committee of Memorial University, from each of the
hospital boards and the Secondary Uses Committee of the
Newfoundland and Labrador Centre for Health Information
(NLCHI) prior to commencement.
Table 1 presents the descriptive characteristics of the cases
of T1DM. The percentages of male and female cases were
similar (50.8 and 49.2, resp.). Table 1 also demonstrates the
age distribution of cases as well as their age of diagnosis.
group; however, this finding was not statistically significant.
Table 2 presents maternal and perinatal characteristics
of the study population. A higher percentage of cases than
there was no significant difference observed between birth
weight of the cases and controls, there was a significant
difference observed for size-for-gestational-age with a higher
percentage of cases than controls born large-for-gestational-
age (18.2% versus 12.8%, resp., P = 0.024). It was more
common for cases to be delivered by C-section than controls
(30.8% versus 22.1%, P = 0.009). T1DM was more common
among first or second born cases compared to those born
third or higher (P = 0.022).
Table 3 presents the results of the conditional logistic
regression models. In the model which included birth weight
and gestational age, delivery by C-section was associated
with increased risk of T1DM. Children delivered by C-
section were 1.41 times as likely to develop T1DM (Hazard
ratio (HR) 1.41, P = 0.015). In the second model, which
included size-for-gestational-age, C-section delivery was not
associated with increased risk of T1DM (HR 1.3, P = 0.076).
Both parity and size-for-gestational-age were found to be
significant risk factors for T1DM from chi-square analysis
(Table 2); these factors did not remain statistically significant
in the conditional logistic regression models.
Journal of Environmental and Public Health3
Table 1: Characteristics of children diagnosed with T1DM in Newfoundland and Labrador, by sex, 1992–2010.
Males Females Total
Year of birth
Year of diagnosis
Age at diagnosis
Findings of this study indicate that C-section delivery was
a significant risk factor for T1DM in children aged 0–15
years. This finding is in line with a recent meta-analysis
of 20 studies which found that the combined effect of C-
section delivery was 1.23 (95% CI 1.15–1.32) . Theories
of why this may be associated with the development of
T1DM in offspring includes the involvement of the role of
gut bacteria in the development of the immune system .
Studies have shown a difference between the compositions
of gut microbiota in vaginally delivered children and those
delivered by C-section. Children delivered by C-section may
be primarily exposed to bacteria in the hospital and not
maternal bacteria, hence the increased risk of T1DM may be
linked to a different composition of gut flora . Another
possible explanation is related to the hygiene hypothesis
which proposes that the risk of diabetes may be increased
when children are not exposed to infections in early life .
Children delivered by C-section have decreased exposures to
infections compared to children born vaginally and, in turn,
have increased risk for diabetes . Another theory suggests
that the observed increased risk of diabetes after C-section
may be related to perinatal stress . NL has a high rate of
birth by C-section as compared to other regions in Canada.
2006 versus the Canadian rate of 26.3% . The rates of C-
section have increased in NL to 33% in 2010 .
In the present study, maternal age at time of birth was
not found to be significantly associated with risk of T1DM in
offspring; other studies have found significant relationships
of 37 studies found that the odds of T1DM increased by
10% for children whose mothers were over 35 years of age at
time of birth (OR = 1.10 95% CI 1.01, 1.20; P = 0.03) .
Conversely, a matched case-control study of 196 cases in the
were older than mothers of cases (OR = 0.900 95% CI 0.854,
0.948; P < 0.001). For other maternal factors, such as edu-
cation level and marital status, there were no associations
found which is consistent with other similar studies [14, 15].
The present study also did not find any associations between
maternal hypertension and risk of T1DM in offspring. Other
studies have found an increased risk of T1DM in offspring
with maternal history of T1DM [13, 16, 17]; however, these
studies also included information on paternal history of
T1DM. A 2009 study by Algert and colleagues  did not
find an association between maternal T1DM and risk of
T1DM in children. Similar to the present study, the study by
Algert et al. did not contain information on paternal T1DM.
There was no significant relationship between parity and
of T1DM diagnosed by the age of 15 that found a significant
decrease in T1DM with increasing birth order .
Birth weight and gestational age were not found to be
associated with risk of T1DM in the present study; however,
chi-squaredanalysisrevealed asignificant differencebetween
T1DM and size-for-gestational-age with a higher percentage
of cases than controls born large-for-gestational-age, but
this was no longer significant in the conditional logistic
regression models. Our findings do not support the findings
of a meta-analysis of 11 studies examining birth weight
which found that a birth weight greater than 4,000 grams
was associated with an increased odds of T1DM (OR = 1.17
95% CI 1.09, 1.26; P < 0.05) . Findings related to the
association between gestational age and T1DM appear to be
mixed. A case-control study conducted in Austria found that
babies born at 34–39 weeks had a significantly higher risk for
T1DM compared to those born before 33 or after 40 weeks
dren born after 40 weeks gestation had a significantly lower
risk of T1DM than children born prior to 40 weeks. While
size-for-gestational-age has not been extensively studied,
4 Journal of Environmental and Public Health
Table 2: Maternal and perinatal characteristics of the study population.
No. of cases (N = 266)
No. of controls (N = 798)
Gestational age (completed weeks)
Birth weight (grams)
Method of delivery
Mother’s age (years)
Mother has T1DM
Mother has hypertension
Mother’s marital status
Single, separated, widowed, divorced
Birth order (including current live birth)
Not graduated high school
Graduated high school
Education beyond high school
∗P value of less than 0.05 was considered significant.
some studies have found significant associations. A cohort
study of 272 children in New South Wales, Australia, with
T1DM found that children who were small-for-gestational-
age had a significantly decreased risk of T1DM compared to
children born appropriate-for-gestational age .
The findings of this study should be considered in
the context of its strengths and weaknesses. An important
strength is that the use of a record linkage case-control
study design eliminates recall bias that is apparent in cross-
sectional study designs. Secondly, data contained in the LBS
were collected at time of birth by healthcare professionals,
and the NLDD data were collected from physician charts at
time of T1DM diagnosis which contributes to the reliability
of the data. A limitation of this study is that there was
very little information available pertaining to fathers as the
majority of the information collected at the time of birth
for the LBS is related to the mother and child. Thus, paternal
factors and family history could not be considered for
This study identified C-section as a significant risk factor
for the development of T1DM among children aged 0–15
years in NL, a region with very high rates of T1DM. Findings
may have an impact on health practice, health care planning
and future research related to T1DM among children.
Further research should be undertaken to understand the
nature of this association.
L. A. Newhook is the senior investigator and was responsible
for the intellectual conception and design of the study, fund-
ing application, paper preparation and is the guarantor of
Journal of Environmental and Public Health5
Table 3: Risk of T1DM associated with specified maternal and perinatal factors.
Birth weight/gestational age model
HRP valueP value
Mother’s age (years)
Mother has T1DM
Mother has hypertension
Mother’s marital status
Single, separated, widowed, divorced
Has not graduated high school
Graduated high school
Education beyond high school
1.304 0.015 0.076
T1DM: type 1 diabetes mellitus.
the research. J. Phillips was responsible for overall coordina-
tion of the study and contributed intellectually to the meth-
ods, literature review, database development, analysis, logis-
tics, paper preparation, and approvals. N. Gill contributed
intellectually to the methods, database development, anal-
ysis, logistics, and approvals. S. Penney was the research
nurse who was responsible for study approvals, as well as
gathering, confirming, and entering of data and maintaining
the NLDD. K. Sikdar was responsible for overseeing the
statistical analysis. All authors contributed to and approved
the final paper submission.
This study was funded by the AR Cox Research Award,
Memorial University. Thanks are due to the diabetes nurses
across the province of NL for their efforts and support of
diabetes research. Authors wish to acknowledge the efforts
of Tracy Parsons who performed the data linkage for this
project. There are no conflict of interests to disclose.
 L. A. Newhook, M. Grant, A. Sloka et al., “Very high and
increasing incidence of type 1 diabetes mellitus in Newfound-
land and Labrador, Canada,” Pediatric Diabetes, vol. 9, part 2,
no. 3, pp. 62–68, 2008.
 R. Alaghehbandan, K. D. Collins, L. A. Newhook, and D.
MacDonald, “Childhood type 1 diabetes mellitus in New-
foundland and Labrador, Canada,” Diabetes Research and
Clinical Practice, vol. 74, no. 1, pp. 82–89, 2006.
2008 Clinical Practice Guidelines, Canadian Diabetes Associa-
 Canadian Institute for Health Information, Giving Birth in
Canada: Regional Trends from 2001-2002 to 2005-2006, Cana-
dian Institute for Health Information, 2007.
6 Journal of Environmental and Public Health
Methods in Observational Epidemiology, Oxford University
Press, Oxford, UK, 2nd edition, 1996.
 M. S. Kramer, R. W. Platt, S. W. Wen et al., “A new and
improved population-based Canadian reference for birth
weight for gestational age,” Pediatrics, vol. 108, no. 2, article
 C. R. Cardwell, L. C. Stene, G. Joner et al., “Caesarean section
is associated with an increased risk of childhood-onset type
1 diabetes mellitus: a meta-analysis of observational studies,”
Diabetologia, vol. 51, no. 5, pp. 726–735, 2008.
 J. Penders, C. Thijs, C. Vink et al., “Factors influencing the
composition of the intestinal microbiota in early infancy,”
Pediatrics, vol. 118, no. 2, pp. 511–521, 2006.
 E. A. Gale, “A missing link in the hygiene hypothesis?” Diabe-
tologia, vol. 45, no. 4, pp. 588–594, 2002.
 G. Dahlquist and B. Kallen, “Maternal-child blood group
incompatibility and other perinatal events increase the risk
for early-onset type 1 (insulin-dependent) diabetes mellitus,”
Diabetologia, vol. 35, no. 7, pp. 671–675, 1992.
 Research and Evaluation Department: Newfoundland Centre
for Health Information, “Live Birth Trends 2006–2010,” 2011.
 C. R. Cardwell, L. C. Stene, G. Joner et al., “Maternal age at
birth and childhood type 1 diabetes: a pooled analysis of 30
observational studies,” Diabetes, vol. 59, no. 2, pp. 486–494,
 A. L. Marshall, A. Chetwynd, J. A. Morris et al., “Type 1
Lancashire and Cumbria, UK,” Diabetic Medicine, vol. 21, no.
9, pp. 1035–1040, 2004.
 S. Sipetic, H. Vlajinac, N. Kocev, and S. Saji, “The Belgrade
childhood diabetes study: prenatal and social associations for
no. 1, pp. 33–39, 2004.
 S. B. Sipetic, H. D. Vlajinac, N. I. Kocev, J. M. Marinkovic, S.
Z. Radmanovic, and M. D. Bjekic, “The Belgrade childhood
diabetes study: a multivariate analysis of risk determinants for
diabetes,” European Journal of Public Health, vol. 15, no. 2, pp.
 J. Svensson, B. Carstensen, H. B. Mortensen, and K. Borch-
Johnsen, “Early childhood risk factors associated with type 1
diabetes—is gender important?” European Journal of Epidemi-
ology, vol. 20, no. 5, pp. 429–434, 2005.
 A. Haynes, C. Bower, M. K. Bulsara, J. Finn, T. W. Jones,
and E. A. Davis, “Perinatal risk factors for childhood type
1 diabetes in Western Australia—a population-based study
(1980–2002),” Diabetic Medicine, vol. 24, no. 5, pp. 564–570,
 C. S. Algert, A. McElduff, J. M. Morris, and C. L. Roberts,
“Perinatal risk factors for early onset of type 1 diabetes in a
2000–2005 birth cohort,” Diabetic Medicine, vol. 26, no. 12,
pp. 1193–1197, 2009.
 T. Harder, K. Roepke, N. Diller, Y. Stechling, J. W. Duden-
hausen, and A. Plagemann, “Birth weight, early weight gain,
and subsequent risk of type 1 diabetes: systematic review and
12, pp. 1428–1436, 2009.
 T. Waldhoer, B. Rami, E. Schober et al., “Perinatal risk factors
for early childhood onset type 1 diabetes in Austria—a popu-
lation-based study (1989–2005),” Pediatric Diabetes, vol. 9,
part 1, no. 3, pp. 178–181, 2008.
 C. R. Cardwell, D. J. Carson, and C. C. Patterson, “Parental
age at delivery, birth order, birth weight and gestational age
are associated with the risk of childhood type 1 diabetes: a UK
regional retrospective cohort study,” Diabetic Medicine, vol.
22, no. 2, pp. 200–206, 2005.