Guideline No. 393-Diabetes in Pregnancy

ObjectivesThis guideline reviews the evidence relating to the diagnosis and obstetrical management of diabetes in pregnancy.OutcomesThe outcomes evaluated were short and long-term maternal outcomes including pre-eclampsia, Caesarean section, future diabetes and other cardiovascular complications; and fetal outcomes including congenital anomalies, stillbirth, macrosomia, birth trauma, hypoglycemia and long-term effects.EvidencePublished literature was retrieved through searches of PubMed and The Cochrane Library using appropriate controlled vocabulary (MeSH terms “diabetes” and “pregnancy”). Where appropriate, results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date limits but results were limited to English or French language materials.ValuesThe quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care.Summary Statements

• 1The adverse outcomes associated with diabetes in pregnancy are substantially associated with hyperglycemia as well as the co-existing metabolic environment. Women with pre-existing diabetes should receive preconception care to optimize blood sugar control and other co-morbidities. Outcomes for the fetus/neonate and the mother in both pre-gestational diabetes mellitus and gestational diabetes mellitus pregnancies are improved by multidisciplinary management whose goal is achieving optimal blood sugar control and appropriate fetal surveillance (II-2).
• 2Retrospective studies indicate that women with pre-gestational diabetes mellitus have an increased risk of stillbirth before 40 weeks of gestation when compared with the general obstetrical population. Similarly, large recent cohort and simulation studies of women with gestational diabetes mellitus pregnancies also indicate a higher risk of stillbirth between 36-39 weeks gestation (II-2).
• 3Women with gestational diabetes mellitus have a higher risk of pre-eclampsia, shoulder dystocia, Caesarean section and large for gestational age infants (II-2).
• 4Treatment of women with gestational diabetes mellitus and optimization of glycemic control reduces the risk of pre-eclampsia, shoulder dystocia, and large for gestational age infants (I).
• 5The occurrence of gestational diabetes mellitus increases the risk of developing type 2 diabetes in the future for the mother (II-2).

Recommendations 

• 1The “preferred screening and diagnostic 2-step” approach for gestational diabetes mellitus from Diabetes Canada's 2018 guidelines is endorsed. All pregnant women should be offered screening between 24-28 weeks using a standardized non-fasting 50-g glucose challenge screening test (GCT) with plasma glucose (PG) measured 1 hour later (III-B).
  • 1.1If the value is <7.8 mmol/L, no further testing is required.
  • 1.2If the value of the GCT is 7.8–11.0, a 2-hour 75-g oral glucose tolerance test with fasting PG (FPG), 1-hour PG, 2-hour PG should be performed.Gestational diabetes mellitus is diagnosed if 1 value is met or exceeded:
    • iFPG ≥5.3 mmol/L
    • ii1-h PG ≥10.6 mmol/L
    • iii2-h PG ≥9.0 mmol/L
  • 1.3If the value of the GCT is ≥11.1 mmol/L, gestational diabetes mellitus is diagnosed
• 2The “alternative 1-step diagnostic” approach from Diabetes Canada's 2018 guidelines is acceptable. In this strategy pregnant women should be offered testing between 24-28 weeks using a standardized 2-hour 75-g oral glucose tolerance test with fasting plasma glucose (FPG), 1-hour plasma glucose (PG), 2-hour PG (III-B).Gestational diabetes mellitus is diagnosed if 1 value is met or exceeded:
  • iFPG ≥5.1 mmol/L
  • ii1-h PG ≥10.0 mmol/L
  • iii2-h PG ≥8.5 mmol/L
  It is recognized that the use of different diagnostic thresholds for the “preferred” and “alternate” strategies could cause confusion in certain settings. Despite this the committee has identified the importance of remaining aligned with the current Diabetes Canada guidelines as being a priority. It is thus recommended that each care centre strategically align with one of the two strategies and implement protocols to ensure consistent and uniform reporting of test results.
• 3If there is a high risk of gestational diabetes mellitus based on multiple risk factors, screening or testing should be offered during the first half of the pregnancy and repeated at 24-28 weeks gestation if initially normal. If for any reason it was missed or if there is a clinical suspicion of later onset gestational diabetes, a screening or diagnostic test should be performed (II-2B).
• 4Women with pre-existing or gestational diabetes mellitus should be provided with care by a multidisciplinary team aimed at attaining and then maintaining euglycemia (II-2B).
• 5For patients with pre-gestational diabetes mellitus or gestational diabetes mellitus, starting at 28 weeks as a baseline, with subsequent serial assessment of fetal growth every 3-4 weeks is suggested to assess the effect of maternal glycemic control on fetal growth rate and amniotic fluid volume (II-2B).
• 6Initiation of weekly assessment of fetal well-being at 36 weeks is recommended in pre-gestational diabetes mellitus and in gestational diabetes mellitus. It is also reasonable to consider weekly fetal assessment for women with diet controlled gestational diabetes mellitus beginning at 36 weeks. Acceptable methods of assessment of fetal well-being near term can include the non-stress test, non-stress test + amniotic fluid index, biophysical profile or a combination of the above (III-A).
• 7If co-morbid factors are present such as obesity, evidence of suboptimal glycemic control, large for gestational age (>90%), previous stillbirth, hypertension or small for gestational age (<10%) are present, earlier onset and/or more frequent fetal health surveillance is recommended. In specific cases where fetal growth restriction is suspected, the addition of umbilical artery and fetal middle cerebral artery Doppler assessment may be helpful (II-2A).
• 8Pregnant women with gestational diabetes mellitus or with pre-gestational diabetes mellitus should be offered induction between 38-40 weeks of gestation depending on their glycemic control and other co-morbidity factors (II2-B).
• 9Antenatal corticosteroid therapy should be administered to women with insulin-treated gestational diabetes mellitus and pregestational diabetic women at the same dosage, according to the same indications, and in the same gestational age range as that recommended for non-diabetic women (Skoll A, et al. No. 364-Antenatal Corticosteroid Therapy for Improving Neonatal Outcomes. J Obstet Gynaecol Can 2018;40:1219-39). When administered to women with preexisting or poorly controlled diabetes, close maternal glycemic surveillance is recommended (III-B). Following the first dose of betamethasone, the following insulin adjustments are recommended as per Diabetes Canada guidelines (Diabetes Canada Clinical Practice Guidelines Expert C, et al. Diabetes and Pregnancy. Can J Diabetes 2018;42 Suppl 1:S255-S82):
  • •Day 1: Increase the night insulin dose by 25%
  • •Days 2 and 3: Increase all insulin doses by 40%
  • •Day 4: Increase all insulin doses by 20%
  • •Day 5: Increase all insulin doses by 10% to 20%
  • •Days 6 and 7: Gradually taper insulin doses to pre-betamethasone doses
• 10If not previously done, in women with threatened preterm labour requiring betamethasone, a screening and diagnostic test for gestational diabetes mellitus should be performed either before or at least 7 days after the administration of betamethasone (III-B).
• 11Women with GDM should be offered testing with a 75-g oral glucose tolerance test between 6 weeks and 6 months postpartum to detect prediabetes and diabetes (Diabetes Canada Clinical Practice Guidelines Expert C, et al. Diabetes and Pregnancy. Can J Diabetes 2018;42 Suppl 1:S255-S82) (II-2A).
  • 11.1 Normal
    • iFasting plasma glucose (FPG) <6.1 mmol/L
    • ii2h <7.8 mmol/L
    • iiiHbA_1C <6.0%
  • 11.2 Pre-diabetic
    • iFPG 6.1-6.9 mmol/L or
    • ii2h plasma glucose (PG) 7.8-11.0 mmol/L or
    • iiiHbA_1C 6.0-6.4%
  • 11.3 Type 2 Diabetes mellitus
    • iFPG ≥ 7.0 mmol/L
    • iiRandom PG or 2h PG ≥11.1 mmol/L
    • iiiHbA_1C ≥6.5%
• 12Breastfeeding is strongly recommended after delivery for all women with pre-gestational diabetes mellitus or gestational diabetes mellitus (II-2A).

     

Hood versus mask nebulization in infants with evolving bronchopulmonary dysplasia in the neonatal intensive care unit.

OBJECTIVE: To compare infants' discomfort, nursing-time and caregiver preference, and assess the clinical efficiency (as a secondary outcome) of hood versus facemask nebulization in infants with evolving bronchopulmonary dysplasia (BPD) in the neonatal intensive care unit. STUDY DESIGN: A prospective, open, randomized, controlled crossover clinical trial. In total, 10 infants with BPD who were on inhaled beta-agonist bronchodilators and corticosteroids were randomly assigned to receive their nebulized treatments either by a facemask, or by a hood for 2-3 days, and then crossover to receive the same treatments with the other technique for another 2-3 days. Infants' discomfort, nursing-time, caregiver preference and clinical efficiency were compared. RESULTS: At baseline there was no significant clinical difference between the groups. Nurse-time required for administering the hood nebulization (mean+/-s.e.m.: 1.9+/-0.1 min) was significantly shorter than the time for mask nebulization (12.0+/-0.6 min, P<0.0001). Infants' discomfort score was significantly lower (0.1+/-0.04) for hood versus mask nebulization (2.5+/-0.2, P<0.0001). Nurses and parents unequivocally preferred the hood treatment. During both mask and hood nebulization therapies (2-3 days) clinical efficiency was comparable. While both methods caused an immediate (20 min post) clinical improvement, the immediate respiratory assessment change score was significantly greater for the hood versus the mask nebulization (0.62+/-0.27 versus 0.13+/-0.14, P<0.05). CONCLUSIONS: Nebulization of aerosolized medications in infants with evolving BPD by hood was less time-consuming for caregivers and was much better tolerated by the infants while being at least as effective as the conventional facemask nebulization.     

Gonadotropin-releasing hormone antagonists increase follicular fluid insulin-like growth factor-I and vascular endothelial growth factor during ovarian stimulation cycles.

The aim of the present study was to investigate the effect of gonadotropin-releasing hormone (GnRH) antagonists (GnRH-ant) on follicular fluid (FF) insulin-like growth factor-I (IGF-I) and FF vascular endothelial growth factor (VEGF) levels. Sixty women undergoing assisted reproduction were randomized and assigned to two different GnRH analog regimens: GnRH agonist (GnRH-a) and GnRH-ant. FF VEGF and FF IGF-I concentrations were significantly increased in the patients treated with GnRH-ant (p < 0.001). In the same patients we observed a statistically significant reduction in serum luteinizing hormone (LH) and estradiol (E2) levels (p < 0.001 and p < 0.05, respectively), FF E2 and FF androstenedione levels (p < 0.05 and p < 0.001, respectively), as well as a reduction in the number of pregnancies although this was not statistically significant. In the GnRH-ant group, FF VEGF levels were positively correlated with FF IGF-I levels, and both were negatively correlated with serum LH levels. The increase in FF IGF-I and FF VEGF levels in women treated with GnRH-ant could be explained by a deleterious follicular environment in response to profound suppression of LH and E2 levels.     

Effect of albumin on neonatal serum ionized magnesium in vitro.

BACKGROUND: Human serum albumin (HAS) is used to treat hypoproteinaemia in neonates and as a volume expander. The aim of this study was to quantify the decrease in serum concentration of ionized magnesium ([Mg2+]) when human serum albumin is added to neonatal serum in vitro. METHODS: Human serum albumin was added to 20 cord serum samples of term infants to reach incremental concentrations of 0 to 20.0 g/l and [Mg2+] were measured. RESULTS: Serum [Mg2+] decreased significantly with the addition of serum albumin. At incremental serum albumin concentration of 10 to 20 g/l, which is within the range of the desired aim in the treatment of hypoalbuminaemia, the magnitude of the decrease in serum [Mg2+] was approximately 0.041 to 0.052 mmol/l (10 to 13 per cent) from the average baseline value. CONCLUSION: The addition of albumin causes a decrease in [Mg2+]. From this in vitro study we speculate that fast infusion of albumin in human neonates may potentially cause a clinically significant decrease in serum [Mg2+].     

The effectiveness of intrauterine transfusions

The results of treatment with intrauterine transfusion are presented. The analysis comprised 48 successful transfusions into 29 foetuses. The reference group consisted of 11 transfusions which proved nonfeasible or ineffective and 54 untreated cases. Following blood treatment, the newborn mortality rate dropped more than threefold. Long-term follow-up of 21 children generally showed their good physical and mental development. We also present 4 cases of supsequent pregnancies after intrauterine blood treatment in a preceding pregnancy, showing that it is possible to save the next baby of the same mother.     

Lenticulostriate vasculopathy in twin-to-twin transfusion syndrome.

Intracranial pathology is a common and important complication in extremely low birth weight babies. Lenticulostriate vasculopathy (LSV) is an abnormal finding on cranial ultrasounds of sick babies and has been associated with congenital infection, chromosomal aberration and twin-to-twin transfusion. We describe a previously unreported situation of LSV being detected in both donor and recipient twin. This pair of monochorionic, diamniotic twins was admitted to the Neonatal Intensive Care Unit at 28 weeks of gestation. The mother underwent an emergency caesarean section because ultrasound and Doppler studies showed stage III twin-to-twin transfusion syndrome. The first twin weighed 998 g and second twin weighed 600 g. The first twin had an uneventful stay, whereas the second twin needed prolonged continuous positive airway pressure and indomethacin for patent ductus arteriosus. Both of them developed LSV. The clinical significance of this condition on the neuro-developmental outcome of a neonate has not yet been fully determined.     

Toll-like receptor signaling inhibits structural development of the distal fetal mouse lung.

We tested the hypothesis that innate immune signaling in utero could disrupt the structural development of the fetal lung, contributing to the pathogenesis of bronchopulmonary dysplasia. Injection of Escherichia coli lipopolysaccharide (LPS) into the amniotic fluid of E15 BALB/cJ mice increased the luminal volume density of fetal mouse lungs at embryonic day (E) 17 and E18. LPS also increased luminal volume and decreased distal lung branching in fetal mouse lung explants. This effect required NF-kappaB activation and functional Toll-Like Receptor 4. Airway branching may require fibronectin-dependent epithelial-mesenchymal interactions, representing a potential target for innate immune signaling. Anti-fibronectin antibodies and LPS both blocked distal lung branching. By immunofluorescence, fibronectin localized to the clefts between newly formed airways but was restricted to peripheral mesenchymal cells in LPS-exposed explants. These data suggest that LPS may alter the expression pattern of mesenchymal fibronectin, potentially disrupting epithelial-mesenchymal interactions and inhibiting distal airway branching and alveolarization. This mechanism may link innate immune signaling with defects in structural development of the fetal lung.