Real-world experience of metformin use in pregnancy: Observational data from the Northern Territory Diabetes in Pregnancy Clinical Register.

BACKGROUND: In Australia's Northern Territory, Indigenous mothers account for 33% of births and have high rates of hyperglycemia in pregnancy. The prevalence of type 2 diabetes (T2D) in pregnancy is up to 10-fold higher in Indigenous than non-Indigenous Australian mothers, and the use of metformin is common. We assessed birth outcomes in relation to metformin use during pregnancy from a clinical register. METHODS: The study included women with gestational diabetes (GDM), newly diagnosed diabetes in pregnancy (DIP), or pre-existing T2D from 2012 to 2016. Data were analyzed for metformin use in the third trimester. Regression models were adjusted for maternal age, body mass index, parity, and insulin use. RESULTS: Of 1649 pregnancies, 814 (49.4%) were to Indigenous women, of whom 234 (28.7%) had T2D (vs 4.6% non-Indigenous women; P < 0.001). Metformin use was high in Indigenous women (84%-90% T2D, 42%-48% GDM/DIP) and increased over time in non-Indigenous women (43%-100% T2D, 14%-35% GDM/DIP). Among Indigenous women with GDM/DIP, there were no significant differences between groups with and without metformin in cesarean section (51% vs 39%; adjusted odds ratio [aOR] 1.25, 95% confidence interval [CI] 0.87-1.81), large for gestational age (24% vs 13%; aOR 1.5, 95% CI 0.9-2.5), or serious neonatal adverse events (9.4% vs 5.9%; aOR 1.32, 95% CI 0.68-2.57). Metformin use was independently associated with earlier gestational age (37.7 vs 38.5 weeks), but the risk did not remain independently higher after exclusion of women managed with medical nutrition therapy alone, and the increase in births <37 weeks was not significant on multivariate analysis. CONCLUSIONS: We found no clear evidence of any adverse outcomes related to the use of metformin for the treatment of hyperglycemia in pregnancy.

Sexually transmitted infections and preterm birth among Indigenous women of the Northern Territory, Australia: A case-control study.

BACKGROUND: The incidence of both sexually transmitted infection (STI) and preterm birth is high among Indigenous women in the Northern Territory, Australia. It was hypothesised that these factors are linked. AIMS: To analyse whether antenatal STI is associated with preterm birth among Northern Territory Indigenous women. MATERIALS AND METHODS: A retrospective case-control study was conducted at a tertiary maternity hospital in the Northern Territory. Rates of STI among pregnant Indigenous women were compared between cases (singleton births at <37 weeks gestation) and controls (singleton births at 37 or greater weeks gestation). The association between the composite of any STI (chlamydia, gonorrhoea, trichomonas or syphilis) and preterm birth was evaluated by logistic regression analysis, adjusting for confounders. Secondary endpoints were the associations between each of these infections and preterm birth. RESULTS: There were 380 cases and 380 controls. Diagnosis of any sexually transmitted infection (composite) in pregnancy was not associated with preterm birth (adjusted odds ratio (aOR) 0.9, 95%CI 0.58-1.39). Women were at increased risk of preterm birth if they had gonorrhoea in pregnancy (aOR 2.92, 95%CI 1.07-7.97); there was no association with chlamydia (aOR 1.38, 95%CI 0.63-3.04) or trichomonas (aOR 0.66, 95%CI 0.39-1.12). There were three syphilis diagnoses among controls and none among cases. CONCLUSIONS: Sexually transmitted infection (considered overall) in pregnancy did not affect preterm birth risk among Northern Territory Indigenous women. An association with preterm birth was observed for gonorrhoea in pregnancy but not with chlamydia, trichomonas or syphilis.

Pregnancy And Neonatal Diabetes Outcomes in Remote Australia: the PANDORA study-an observational birth cohort.

BACKGROUND: In Australia's Northern Territory, 33% of babies are born to Indigenous mothers, who experience high rates of hyperglycemia in pregnancy. We aimed to determine the extent to which pregnancy outcomes for Indigenous Australian women are explained by relative frequencies of diabetes type [type 2 diabetes (T2DM) and gestational diabetes (GDM)]. METHODS: This prospective birth cohort study examined participants recruited from a hyperglycemia in pregnancy register. Baseline data collected were antenatal and perinatal clinical information, cord blood and neonatal anthropometry. Of 1135 women (48% Indigenous), 900 had diabetes: 175 T2DM, 86 newly diagnosed diabetes in pregnancy (DIP) and 639 had GDM. A group of 235 women without hyperglycemia in pregnancy was also recruited. RESULTS: Diabetes type differed for Indigenous and non-Indigenous women (T2DM, 36 vs 5%; DIP, 15 vs 7%; GDM, 49 vs 88%, p < 0.001). Within each diabetes type, Indigenous women were younger and had higher smoking rates. Among women with GDM/DIP, Indigenous women demonstrated poorer birth outcomes than non-Indigenous women: large for gestational age, 19 vs 11%, p = 0·002; neonatal fat 11.3 vs 10.2%, p < 0.001. In the full cohort, on multivariate regression, T2DM and DIP were independently associated (and Indigenous ethnicity was not) with pregnancy outcomes. CONCLUSIONS: Higher rates of T2DM among Indigenous women predominantly contribute to absolute poorer pregnancy outcomes among Indigenous women with hyperglycemia. As with Indigenous and minority populations globally, prevention or delay of type 2 diabetes in younger women is vital to improve pregnancy outcomes and possibly to improve the long-term health of their offspring.

Placental inflammation is associated with rural and remote residence in the Northern Territory, Australia: a cross-sectional study.

BACKGROUND: The Northern Territory has the highest rates of perinatal morbidity and mortality in Australia. Placental histopathology has not been studied in this high-risk group of women. METHODS: This is the first study to detail the placental pathology in Indigenous women and to compare the findings with non-Indigenous women in the Northern Territory. There were a total of 269 deliveries during a three-month period from the 27(th) of June to the 27(th) of August 2009. Seventy-one (71%) percent of all placentas were examined macroscopically, sectioned then reviewed by a Perinatal Pathologist, blinded to the maternal history and outcomes. RESULTS: Indigenous women were found to have higher rates of histologically confirmed chorioamnionitis and or a fetal inflammatory response compared with non-Indigenous women (46% versus 26%; OR 2.4, 95% CI 1.3-4.5). In contrast, non-Indigenous women were twice as likely to show vascular related pathology (31% versus 14%; OR 2.77, 95% CI 1.3-5.9). Indigenous women had significantly higher rates of potentially modifiable risk factors for placental inflammation including genitourinary infections, anaemia and smoking. After adjusting for confounders, histological chorioamnionitis and fetal inflammatory response was significantly associated with rural or remote residence (Adjusted OR 2.5, 95% CI 1.08 - 5.8). CONCLUSION: This study has revealed a complex aetiology underlying a high prevalence of placental inflammation in the Northern Territory. Placental inflammation is associated with rural and remote residence, which may represent greater impact of systemic disadvantage, particularly affecting Indigenous women in the Northern Territory.

Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study.

BACKGROUND: Diabetes in pregnancy carries an increased risk of adverse pregnancy outcomes for both the mother and foetus, but it also provides an excellent early opportunity for intervention in the life course for both mother and baby. In the context of the escalating epidemic of chronic diseases among Indigenous Australians, it is vital that this risk is reduced as early as possible in the life course of the individual. The aims of the PANDORA Study are to: (i) accurately assess rates of diabetes in pregnancy in the Northern Territory (NT) of Australia, where 38% of babies are born to Indigenous mothers; (ii) assess demographic, clinical, biochemical, anthropometric, socioeconomic and early life development factors that may contribute to key maternal and neonatal birth outcomes associated with diabetes in pregnancy; and (iii) monitor relevant post-partum clinical outcomes for both the mothers and their babies. METHODS/DESIGN: Eligible participants are all NT women with diabetes in pregnancy aged 16 years and over. Information collected includes: standard antenatal clinical information, diagnosis and management of diabetes in pregnancy, socio-economic status, standard clinical birth information (delivery, gestational age, birth weight, adverse antenatal and birth outcomes). Cord blood is collected at the time of delivery and detailed neonatal anthropometric measurements performed within 72 hours of birth. Information will also be collected regarding maternal post-partum glucose tolerance and cardio-metabolic risk factor status, breastfeeding and growth of the baby up to 2 years post-partum in the first instance. DISCUSSION: This study will accurately document rates and outcomes of diabetes in pregnancy in the NT of Australia, including the high-risk Indigenous Australian population. The results of this study should contribute to policy and clinical guidelines with the goal of reducing the future risk of obesity and diabetes in both mothers and their offspring.