Original Research
Perinatal Outcomes in a Longitudinal Birth Cohort of First Nations Mothers With Pregestational Type 2 Diabetes and Their Offspring: The Next Generation Study

https://doi.org/10.1016/j.jcjd.2020.05.001Get rights and content

Abstract

Objectives

There is emerging evidence that First Nations women with diabetes in pregnancy and their offspring have poorer health outcomes than non-First Nations women. The aim of this study was to describe the perinatal outcomes of pregnancies complicated by type 2 diabetes.

Methods

The Next Generation longitudinal study is a First Nations birth cohort of children born to mothers diagnosed in childhood with type 2 diabetes. Pregnant women were prospectively enrolled in the birth cohort, and a review of medical records (including stored fetal ultrasound images) was performed to determine perinatal outcomes for 112 child-mother pairs between 2005 and 2015. Maternal demographics, antenatal variables, fetal ultrasound findings, obstetric and delivery information and neonatal birth outcomes were collected and analyzed.

Results

Mothers in our cohort were young and most were overweight at the start of pregnancy. Most had suboptimal glycemic control in the first trimester (median glycated hemoglobin, 9.3%). The cesarean section rate was high at 41%. Over one-half of newborns had macrosomia at birth, and almost 1 in 5 were born with a structural anomaly, mainly renal. Fetal ultrasound significantly underestimated the proportion of infants born with macrosomia (p<0.05) and missed 3 of 7 cardiac defects in this cohort.

Conclusions

High rates of anomalies, macrosomia and cesarean deliveries provide insight into pregnancy management and disease processes for First Nations women with pregestational type 2 diabetes and their offspring, and highlights opportunities for improvement in prenatal care of these women.

Résumé

Objectifs

De nouvelles données établissent que les femmes des Premières Nations qui sont atteintes du diabète durant la grossesse et leur enfant connaissent de plus mauvaises issues que les femmes qui ne sont pas des Premières Nations. L’objectif de la présente étude était de décrire les issues périnatales des grossesses des femmes atteintes de diabète de type 2.

Méthodes

L’étude longitudinale Next Generation porte sur une première cohorte de naissances d’enfants des Premières Nations nés de mères qui ont reçu un diagnostic de diabète de type 2 durant l’enfance. Nous avons inscrit de manière prospective les femmes enceintes à la cohorte de naissances, et avons passé en revue les dossiers médicaux (notamment les images des échographies fœtales conservées) pour déterminer les issues périnatales de 112 paires enfant-mère entre 2005 et 2015. Nous avons recueilli et analysé les données démographiques des mères, les variables anténatales, les résultats des échographies fœtales, les renseignements en obstétrique et des accouchements, et les issues néonatales.

Résultats

La cohorte regroupait des jeunes mères, dont la plupart étaient en surpoids au début de la grossesse. La plupart avaient une régulation glycémique sous-optimale au premier trimestre (hémoglobine glyquée médiane, 9,3 %). Le taux élevé de césariennes était de 41 %. Plus de la moitié des nouveau-nés avaient une macrosomie à la naissance, et presque 1 sur 5 était né avec une anomalie structurale, principalement rénale. Les échographies fœtales ont montré une sous-estimation significative de la proportion de bébés atteints de macrosomie (p < 0,05) à la naissance et raté 3 anomalies cardiaques sur 7 dans cette cohorte.

Conclusions

Les taux élevés d’anomalies, de macrosomie et d’accouchements par césarienne donnent une idée de la prise en charge de la grossesse et des processus de la maladie des femmes des Premières Nations atteintes du diabète prégestationnel de type 2 et de leur enfant, et met en évidence les possibilités d’amélioration des soins prénataux de ces femmes.

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

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