Association between hyperglycaemia in pregnancy and growth of offspring in early childhood: The PANDORA study

First published: 29 May 2022Background: Few studies have assessed whether children exposed to in utero hyperglycaemia experience different growth trajectories compared to unexposed children.Objectives:To assess association of type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) with early childhood weight, length/height and body mass index(BMI) trajectories, and with timing and magnitude of peak BMI in infancy.Methods:PANDORA is a birth cohort recruited from an Australian hyperglycaemia in pregnancy register, and women with normoglycaemia recruited from the community.Offspring growth measures were obtained from health records over a median follow-up of 3.0 years (interquartile range 1.9–4.0). This analysis included children born to Aboriginal mothers with in utero normoglycaemia (n=95), GDM (n=228) or T2D(n=131). Growth trajectories (weight, length/height and BMI) were estimated usinglinear mixed models with cubic spline functions of child age. Results:After adjustment for maternal factors (age, BMI, parity, smoking, and socio-economic measures) and child factors (age, gestational age at birth, and sex), children born to mothers with T2D or GDM had lower weight, length/height and BMI trajectories in infancy than children born to mothers with normoglycaemia, but similar weight and BMI by completion of follow-up. Children exposed to T2D had lower mean peak BMI 17.6 kg/m2(95% confidence interval [CI] 17.3–18.0) than childrenexposed to normoglycaemia (18.6 kg/m2[18.1–18.9]) (p=0.001). Conclusions: Maternal hyperglycaemia was associated with differences in early child-hood growth trajectories after adjustment for maternal BMI. Exploration of associations between in utero hyperglycaemia exposure and growth trajectories into later childhood is required.Angela Titmuss, Danielle K. Longmore, Federica Barzi, Elizabeth L. M. Barr, Vanya Webster, Anna Wood, Alison Simmonds, Alex D. H. Brown, Christine Connors, Jacqueline A. Boyle, Jeremy Oats, H. David McIntyre, Jonathan E. Shaw, Maria E. Craig, Louise J. Maple-Brown, the PANDORA Study Research Tea

Breastfeeding and infant growth in offspring of mothers with hyperglycaemia in pregnancy: The pregnancy and neonatal diabetes outcomes in remote Australia study

Background: Benefits of breastfeeding on infant growth in children born to mothers with gestational diabetes mellitus (GDM) are uncertain. Objectives: To describe growth trajectories between birth and 14 months according to breastfeeding and maternal hyperglycaemia in pregnancy, and assess associations between breastfeeding and 14 month growth outcomes among children born to mothers with GDM. Subjects/methods: Data on 258 Aboriginal and Torres Strait Islander infants from the PANDORA study born to mothers with normoglycaemia (n = 73), GDM (n = 122), or with pre-existing type 2 diabetes (n = 63) in pregnancy were assessed. Infant weight and BMI growth trajectories according to predominant breastfeeding at 6 months and hyperglycaemia in pregnancy were developed using mixed-effect models and cubic splines. Associations between breastfeeding and 14-month growth outcomes (z-scores: weight-for-age, weight-for-length and BMI) were evaluated using linear regression in a subgroup of infants born to mothers with GDM. Results: Predominantly breastfed infants had lower BMI trajectories compared to those not predominantly breastfed, irrespective of maternal hyperglycaemia in pregnancy status (p < 0.01 for all groups), and lower weight trajectories among those born to mothers with GDM (p = 0.006). Among offspring of women with GDM, predominant breastfeeding was only associated with lower weight-for-age at 14 months, however adjusting for maternal obesity, smoking, and parity attenuated observed associations. Maternal obesity remained significantly associated with greater infant growth. Conclusions: Predominant breastfeeding was associated with reduced growth among children born to women with and without hyperglycaemia in pregnancy. However, among children exposed to GDM in utero, maternal obesity largely explained this association.Danielle K. Longmore, Angela Titmuss, Elizabeth Barr, Federica Barzi, Alison Simmonds, I-Lynn Lee, Eyvette Hawthorne, Ruth Derkenne, Christine Connors, Jacqueline Boyle, Paul Zimmet, Kerin O'Dea, Jeremy Oats, Harold D. McIntyre, Alex Brown, Jonathan Shaw, Louise J. Maple-Brow

Gestational diabetes is associated with postpartum hemorrhage in Indigenous Australian women in the PANDORA study: a prospective cohort.

Objective To assess associations of hyperglycemia in pregnancy with the risk of postpartum hemorrhage (PPH) in a prospective cohort of Indigenous and non-Indigenous women, compared to normoglycemia.MethodsData were from 1,102 (48% Indigenous) women of the Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study. Age-adjusted associations of gestational diabetes mellitus (GDM) or pre-existing type 2 diabetes mellitus (T2DM), obstetric and demographic covariables with PPH (blood loss ≥500ml) were assessed using logistic regression. Multivariable-adjusted models included Indigenous ethnicity, diabetes type and their interaction.ResultsA higher proportion of Indigenous women developed PPH than non-Indigenous women (32% vs. 22%; p<0.001). Compared to non-Indigenous women with normoglycemia, risks of PPH for Indigenous women with GDM or T2DM were (OR=1.83 [95%CI: 1.11-3.02] and 1.72 [0.99-3.00] after age adjustment, 1.84 [1.06-3.19] and 1.33 [0.70-2.54] after adjustment for school education and delivery mode, and 1.62 [0.95-2.77] and 0.99 [0.53-1.86] after adjustment for birth weight). Importantly, Indigenous women without hyperglycemia in pregnancy were not at increased risk of PPH. Conclusion The significantly higher rates of PPH experienced by Indigenous compared to non-Indigenous women may be explained by a greater effect of GDM among Indigenous women that was only partly accounted for by birth weight.Isabelle M. Lucas, Elizabeth L. M. Barr, Federica Barzi, Danielle K. Longmore, I-Lynn Lee, Marie Kirkwood ... et al

Maternal body mass index, excess gestational weight gain, and diabetes are positively associated with neonatal adiposity in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study

Background: In‐utero exposures likely influence the onset and severity of obesity in youth. With increasing rates of type 2 diabetes mellitus (T2DM) and maternal adiposity in pregnancy globally, it is important to assess the impact of these factors on neonatal adipose measures. Objectives: To evaluate the contribution of maternal ethnicity, body mass index (BMI), gestational weight gain, and hyperglycaemia to neonatal adiposity. Methods: Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) is a longitudinal cohort study of Australian mother and neonate pairs. In this analysis, Indigenous (n = 519) and Europid (n = 358) women were included, of whom 644 had hyperglycaemia (type 2 diabetes [T2DM], diabetes in pregnancy [DIP], or gestational diabetes [GDM]). Associations between maternal ethnicity, hyperglycaemia, BMI and gestational weight gain, and the neonatal outcomes of length, head circumference, sum of skinfolds, total body fat, and percentage body fat were examined. Models were adjusted for maternal age, smoking status, parity, education, neonatal gender, and gestational age. Results: Among those with hyperglycaemia in pregnancy, Indigenous women had a higher proportion of T2DM and DIP (36%, 13%) compared with Europid women (4%, 3%). In multivariate analysis, maternal T2DM (compared with no hyperglycaemia), BMI during pregnancy, and excess compared with appropriate gestational weight gain, were significantly associated with greater neonatal measures. DIP was associated with greater sum of skinfolds, total body fat, and percentage body fat. Indigenous ethnicity was associated with greater sum of skinfolds. Conclusions: Maternal BMI, excess gestational weight gain, and hyperglycaemia operated as independent factors influencing neonatal adiposity. Interventions addressing these factors are needed to reduce neonatal adiposity.Danielle K. Longmore, Elizabeth L.M. Barr, I‐Lynn Lee, Federica Barzi, Marie Kirkwood... Alex D.H. Brown ... et al. (on behalf of the PANDORA study research team

Social and economic factors, maternal behaviours in pregnancy and neonatal adiposity in the PANDORA cohort

Background: Australian Indigenous women experience high rates of social disadvantage and type 2 diabetes (T2D) in pregnancy, but it is not known how social factors and maternal behaviours impact neonatal adiposity in offspring of women with hyperglycaemia in pregnancy. Methods: Participants were Indigenous (n=404) and Europid (n=240) women with gestational diabetes mellitus (GDM) or T2D in pregnancy and their offspring in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study. Social, economic factors, and maternal behaviours were measured in pregnancy and six neonatal anthropometric outcomes were examined after birth. Results: On univariate analysis, maternal education 2 times/week (p=0.002) were associated with increased sum of skinfolds (SSF) in offspring. Smoking was significantly associated with a reduction in anthropometric measures, except SSF. In multivariable models adjusted for ethnicity, BMI and hyperglycaemia, social and economic factors were no longer significant predictors of neonatal outcomes. Smoking was independently associated with a reduction in length, head circumference and fat free mass. Frequent fast food intake remained independently associated with SSF (β-coefficient 1.08mm, p=0.02). Conclusion: In women with hyperglycaemia in pregnancy, social factors were associated with neonatal adiposity, particularly skinfold measures. Promoting smoking cessation and limited intake of energy-dense, nutrient-poor foods in pregnancy are important to improve neonatal adiposity and lean mass outcomes. Addressing inequities in social and economic factors are likely to be important, particularly for Indigenous women or women experiencing social disadvantage.Danielle K. Longmore, Elizabeth L.M. Barr, Federica Barzi, I-Lynn Lee, Marie Kirkwood, Christine Connors, Jacqueline Boyle, Kerin O’Dea, Paul Zimmet, Jeremy Oats, Patrick Catalano, H. David McIntyre, Alex D.H. Brown, Jonathan E. Shaw, Louise J. Maple-Brown, on behalf of the PANDORA study research tea

Associations of gestational diabetes and type 2 diabetes during pregnancy with breastfeeding at hospital discharge and up to 6 months: the PANDORA study

Published online: 10 September 2020AIMS/HYPOTHESIS:Women with gestational diabetes mellitus (GDM) and obesity experience lower rates of breastfeeding. Little is known about breastfeeding among mothers with type 2 diabetes. Australian Indigenous women have a high prevalence of type 2 diabetes in pregnancy. We aimed to evaluate the association of hyperglycaemia, including type 2 diabetes, with breastfeeding outcomes. METHODS:Indigenous (n = 495) and non-Indigenous (n = 555) participants of the Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) cohort included women without hyperglycaemia in pregnancy (n = 222), with GDM (n = 684) and with type 2 diabetes (n = 144). The associations of hyperglycaemia in pregnancy and breastfeeding at hospital discharge, 6 weeks and 6 months post-partum were evaluated with logistic regression, after adjustment for maternal obesity, ethnicity, maternal and neonatal characteristics. RESULTS:Indigenous women were more likely to predominantly breastfeed at 6 weeks across all levels of hyperglycaemia. Compared with women with no hyperglycaemia in pregnancy, women with type 2 diabetes had lower odds for exclusive breastfeeding at discharge (adjusted OR for exclusive breastfeeding 0.4 [95% CI 0.2, 0.8] p = 0.006). At 6 weeks and 6 months, the relationship between type 2 diabetes and predominant breastfeeding was not statistically significant (6 weeks 0.7 [0.3, 1.6] p = 0.40, 6 months 0.8 [0.4, 1.6] p = 0.60). Women with gestational diabetes were as likely to achieve predominant breastfeeding at 6 weeks and 6 months as women without hyperglycaemia in pregnancy. CONCLUSIONS/INTERPRETATION:Indigenous women had high rates of breastfeeding. Women with type 2 diabetes had difficulty establishing exclusive breastfeeding at hospital discharge. Further research is needed to assess the impact on long-term breastfeeding outcomes. Graphical abstract.Danielle K. Longmore, Elizabeth L. M. Barr, Alyce N. Wilson, Federica Barzi, Marie Kirkwood, Alison Simmonds ... et al

Type 2 diabetes after a pregnancy with gestational diabetes among First Nations women in Australia: the PANDORA study.

Aims: To determine among First Nations and Europid pregnant women the cumulative incidence and predictors of postpartum type 2 diabetes and prediabetes and describe post-partum cardiovascular disease (CVD) risk profiles. Methods: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy.Ethnic-specific rates of postpartum type 2 diabetes and prediabetes were reported for women with diabetes in pregnancy (DIP), gestational diabetes (GDM) or normoglycaemia in pregnancy over a short follow-up of 2.5 years (n = 325). Pregnancy characteristics and CVD risk profiles according to glycaemic status, and factors associated with postpartum diabetes/prediabetes were examined in First Nations women. Results: The cumulative incidence of postpartum type 2 diabetes among women with DI Por GDM were higher for First Nations women (48%, 13/27, women with DIP, 13%, 11/82, GDM), compared to Europid women (nil DIP or GDM p < 0.001). Characteristics associated with type 2 diabetes/prediabetes among First Nations women with GDM/DIP included, older age, multiparity, family history of diabetes, higher glucose values, insulin use and body mass index (BMI). Conclusions: First Nations women experience a high incidence of postpartum type 2 diabetes after GDM/DIP, highlighting the need for culturally responsive policies at an individual and systems level, to prevent diabetes and its complications.Anna J. Wood, Jacqueline A. Boyle, Elizabeth L.M. Barr, Federica Barzi, Matthew J.L. Hare, Angela Titmuss, Danielle K. Longmore, Elizabeth Death, Joanna Kelaart, Marie Kirkwood, Sian Graham, Christine Connors, Elizabeth Moore, Kerin O, Dea, Jeremy J.N. Oats, Harold D. McIntyre, Paul Z. Zimmet, Zhong X. Lu, Alex Brown, Jonathan E. Shaw, Louise J. Maple-Brow