Original ResearchPerinatal Outcomes in a Longitudinal Birth Cohort of First Nations Mothers With Pregestational Type 2 Diabetes and Their Offspring: The Next Generation Study
Introduction
In Canada, pregestational type 2 diabetes affects approximately 7.5 per 1,000 live births and is increasing steadily (1). Pregestational type 2 diabetes increases the risk of miscarriage, stillbirth and fetal anomalies (2,3). In addition, macrosomia increases the risk of operative delivery, shoulder dystocia and related neonatal injury (fractures, nerve palsies and ischemic brain injuries), maternal trauma and obstetric hemorrhage (4,5). The immediate postnatal complications for neonates born to mothers with diabetes include hypoglycemia, hyperbilirubinemia and associated jaundice and other metabolic concerns (5,6). However, the long-term risks of intrauterine exposure to hyperglycemia, including the risk of developing type 2 diabetes and other cardiovascular sequelae, are still being elucidated. One of the main challenges of studying the impact of maternal diabetes on perinatal outcomes relates to the difficulty in confidently differentiating women with gestational diabetes from those with undiagnosed, pregestational type 2 diabetes. Furthermore, there can be issues related to the long duration and loss to follow up, which often plague studies about perinatal exposures and long-term outcomes in offspring.
Evidence exists demonstrating an impact of in utero exposure to maternal diabetes on the health of the offspring (7,8). The 2 cohorts commonly cited in the literature, which have attempted to assess the generational impact of pregestational diabetes on pregnancy and fetal/neonatal outcomes, are the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) and Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) studies (9,10). The TODAY study has examined the outcomes of teen pregnancies complicated by type 2 diabetes (9). In that small cohort of 39 live births, maternal management was closely monitored and preconceptional glycemic control was good (glycated hemoglobin [A1C], 7%). The rate of anomalies was 20.5% (4 cases of cardiac anomalies and 1 case each of polycystic kidney disease, microcephaly, cleft palate and jejunal atresia) (9). Unfortunately, there were no details provided about obstetric complications nor postnatal outcomes. The PANDORA study was established in 2011 and examines pregnancy outcomes in the setting of both gestational diabetes and pregestational type 2 diabetes in northern Australia (10). The PANDORA cohort exists in a region where approximately one-third of babies are born to women of Indigenous ancestry (10). Given the relatively recent establishment of the PANDORA cohort, less is known about the long-term outcomes of these offspring.
The Next Generation (NextGen) longitudinal study is a birth cohort of children born to mothers of First Nations heritage with pregestational type 2 diabetes from Manitoba, Canada (11). To our knowledge, this is the largest longitudinal study of northern First Nations women with type 2 diabetes and their offspring in the country. The province of Manitoba has the highest rate of youth-onset diabetes in Canada, with an incidence of 26 per 100,000 children per year (12). The overall prevalence of type 2 diabetes in offspring of the NextGen cohort is 25%, and there is evidence of increasing diabetes risk with each successive generation (11, 12, 13). Most of these offspring (71%) are also obese (11, 12, 13). The Oji-Cree population from which a proportion of the NextGen cohort is sampled represents a group with significant heterogeneity of diabetes phenotypes and disease outcomes (11, 12, 13, 14, 15, 16). Presently, approximately 64% of our cohort is Oji-Cree. This was also one of the earliest populations described with youth-onset type 2 diabetes in the world (11, 12, 13, 14, 15, 16). The Oji-Cree have a variant of the HNF1α gene that increases the risk for the development of type 2 diabetes and predisposes to early onset disease (14, 15, 16). Unlike the teen mothers from the TODAY study who were found to have incidental pregnancies during the course of a randomized controlled trial about management of type 2 diabetes in youth, mothers of the NextGen cohort were purposefully recruited prospectively and reside in remote, northern locations with limited access to preconception and early pregnancy medical care (9,11). The NextGen mothers are also distinctive from the PANDORA cohort given that all are of First Nations heritage and all have type 2 diabetes preceding pregnancy (10,11).
This paper reports on the pregnancy outcomes of a cohort of First Nations women diagnosed in childhood with type 2 diabetes. Maternal, fetal and neonatal data from the NextGen cohort were used to describe the characteristics of this unique prenatal population and summarize their perinatal outcomes. Future goals of the NextGen study include longitudinal follow up of offspring into adolescence to determine the longer-term impacts of pregnancy exposures including pregestational diabetes on longer-term cardiometabolic outcomes.
Section snippets
Methods
This study involved abstraction of data from a research database and hospital records for child-mother pairs prospectively enrolled in the NextGen birth cohort study in Winnipeg, Canada, between 2005 and 2015. The NextGen cohort, established in 2003, consists of First Nations mothers with pregestational type 2 diabetes diagnosed before 18 years of age and their offspring. The diagnosis of type 2 diabetes in the mothers had been determined by the clinical diabetes team using the Diabetes Canada
Results
Over the 10-year study period, 178 pregnant First Nations women were approached to participate and 149 (82%) were enrolled in the NextGen cohort study. Overall, we retained 98% of the women and infants through pregnancy and childbirth. We think these women are representative of the population because they are all First Nations women and most reside on remote Frist Nations reserve lands where type 2 diabetes in childhood is the most prevalent. After excluding cases of multiples (n=4), missing
Discussion
This cohort is the first and largest of its kind to examine the impact of pregestational type 2 diabetes on pregnancy outcomes in First Nations women in Canada. Data from the NextGen cohort demonstrates the need for preconceptional optimization of maternal health given the high rates of smoking, obesity and suboptimal glycemic control.
Conclusions
The NextGen cohort provides valuable insight into the potential effects of pregestational type 2 diabetes on the health of First Nations mothers and their offspring. By assessing prepregnancy maternal factors, we have identified opportunities for improving perinatal outcomes by targeting optimization of preconceptional glycemic control, smoking cessation and weight loss, plus breastfeeding supports postpartum. These findings will lay the foundation for future work correlating prenatal findings
Acknowledgments
This cohort study has been supported by grants from the Lawson Foundation and the Children's Hospital Research Institute of Manitoba.
This project would not have been possible without the support and commitment of the families who participated in the study and the long-term commitment from staff at the nursing stations and health centres of the participating First Nations communities. We are also thankful for the foresight of Dr Heather Dean, who initiated the Next Generation birth cohort and
References (48)
- et al.
Clinical and demographic characteristics of type 2 diabetes in youth at diagnosis in Manitoba and northwestern Ontario (2006-2011)
Can J Diabetes
(2012) - et al.
Obesity in pregnancy
J Obstet Gynaecol Can
(2010) - et al.
The prevalence of CKD in rural Canadian Indigenous peoples: Results from the First Nations community based screening to improve kidney health and prevent dialysis (FINISHED) screen, triage, and treat program
Am J Kidney Dis
(2016) - et al.
Should an early anatomy ultrasound scan be offered routinely to obese pregnant women?
J Obstet Gynaecol Can
(2018) - et al.
Shoulder dystocia: Definitions and incidence
Semin Perinatol
(2014) - et al.
Impact of pre-pregnancy diabetes mellitus on congenital anomalies, Canada, 2002-2012
Health Promot Chronic Dis Prev Can
(2015) - et al.
Teratogenicity associated with pre-existing and gestational diabetes
J Obstet Gynaecol Can
(2007) - et al.
Congenital malformations among infants whose mothers had gestational diabetes or pre-existing diabetes
Early Human Develop
(2001) - et al.
Hyperglycemia and adverse pregnancy outcomes
N Eng J Med
(2008) - et al.
Impact of type 2 diabetes, obesity and glycaemic control on pregnancy outcomes
Aust N Z J Obstet Gynaecol
(2017)
Hyperglycemia and risk of adverse perinatal outcomes: Systematic review and meta-analysis
BMJ
Type 2 diabetes mellitus in children: Prenatal and early infancy risk factors among native Canadians
Arch Pediatr Adolesc Med
Association of intrauterine exposure to maternal diabetes and obesity with type 2 diabetes in youth: The SEARCH case-control study
Diabetes Care
Pregnancy outcomes in youth with type 2 diabetes: The TODAY Study experience
Diabetes Care
Pregnancy and Neonatal Outcomes in Remote Australia (PANDORA) study
BMC Pregnancy Childbirth
Obesity and type 2 diabetes mellitus in a birth cohort of First Nation children born to mothers with pediatric-onset type 2 diabetes
Pediatric Diabetes
Non-insulin dependent diabetes mellitus in Indian children in Manitoba
Can Med Assoc J
The prevalence of the HNF-1alpha G319S mutation in Canadian aboriginal youth with type 2 diabetes
Diabetes Care
Diabetes susceptibility in the Canadian Oji-Cree population is moderated by abnormal mRNA processing of HNFαG319S transcripts
Diabetes
Youth-onset type 2 diabetes (Y2DM) associated with HFN1A S319 in aboriginal Canadians
Diabetes Care
The Next Generation cohort: A description of a cohort at high risk for childhood onset type 2 diabetes
J Dev Orig Health Dis
Charts of fetal size: 3. Abdominal measurements
Br J Obstet Gynaecol
Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant
BMC Pediatr
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