Maternal and Fetal Complications in Diabetes Pregnancy Helen R Murphy Professor of Medicine (Diabetes & Antenatal Care), UEA Professor of Women s Health, Kings College London hm386@medschl.cam.ac.uk 1
2018 ATDC Conference: Conflict of Interest I have the following Conflicts of Interest to report: Stock Shareholder None Speakers Bureau NovoNordisk, Eli Lilly, Sanofi, Abbott, Medtronic Grants/Research Johnson & Johnson, Medtronic, Abbott Diabetes Care Consultant Medtronic Employee None No Other I will not be speaking on off-label topics.
Fetal development at 5 weeks 5 week human fetus
Early Cardiac Development Srivastava D, Nature 2000
Early neural tube development
Pre-pregnancy care Diabetes and Pregnancy Project
400,00 singleton pregnancies, 1677 diabetes 9,488 1 malformation, 129 diabetes HbA1c % (mmol/mol) 1000 Pregnancy 6.5 (48) 30.3 1 in 33 7.0 (53) 38.4 1 in 26 7.5 (58) 50.6 1 in 20 8.0 (64) 60.1 1 in 17 9.5 (80) 95.3 1 in 10 71.6/1,000 pregnancies, RR 3.8 OR 1.3 per 1% HbA1c >6.3% (11>45mmol/mol) Bell R Diabetologia 2012
Glycaemic control in T1D (NPID 2016) 240 (<15%) T1D mothers achieved target HbA1c There has been no improvement in antenatal glucose control in T1D since 2002-03 NPID 2016 First trimester HbA 1c vs CEMACH 2002-03 Type 1 diabetes Type 2 diabetes HbA 1c <48 mmol/mol 15% 38% HbA 1c >=86 mmol/mol 12% 7% NPID HbA 1c median (10-90 th centile) 61 (45-89) 51 (39 to 81) 2002-03 HbA1c median (IQR) 58 (48 69) 8
Preterm births (NPID 2016) 43% T1D and 21% T2D preterm < 37 +0 weeks Reduction in T1D births > 38 weeks since 2002-03 Gestation at delivery for singleton live births, 2016 percentage of pregnancies 40 Type 1 Type 2 30 20 10 0 24 to 27 28 to 30 31 to 32 33 to 34 35 to 36 37 38 39 40 and over gestation (weeks)
Birthweight centiles (NPID 2016) LGA 47% in T1D, 23% in T2D offspring Unchanged in T1D since 2002-03 60 50 47.62 40 30 20 10 22.92 5.57 13.31 Expected level 0 Birthweight >=90th centile Type 1 diabetes Type 2 diabetes Birthweight <10th centile a GROW centiles adjust birthweight for maternal ethnicity, height, weight and gestational age at delivery.
NICU admissions (NPID 2016) 40% T1D went to NICU 60% T1D preterm <37 weeks, ~ 90% <34 weeks Percentage of babies admitted to a neonatal unit a, 2016 Percentage of Type 1 diabetes Type 2 diabetes babies 100 80 60 40 20 0 148 77 309 136 190 187 Born at <34 weeks Born at 34 to 36 weeks Born at 37 weeks and over a Neonatal unit includes special care and intensive care
What contributes to neonatal complications?
T1D Pregnancy summary Pre-pregnancy care associated with reduced rates of congenital anomaly, SB and NND Women T1D spend 10-12 hrs/day with glucose levels outside the target range (3.5-7.8mmol/l) One in two babies of T1D mothers have complications associated with maternal hyperglycaemia in second and third trimester New technologies needed for consistent glucose control T1D?
Continuous Glucose Monitor (CGM)
Primary Outcome: Change in HbA1c from randomisation to 34 weeks gestation CGM Control mean difference -0.2% 95% CI -0.34, -0.03; p = 0.0207
% Time in target range 63-140mg/dl Pregnant Baseline Week 34 CGM N=107 Control N=107 CGM N=77 Control N=77 P-value % CGM 3.5-7.8 mmol/l 52% ± 13% 12.5hrs/day 52% ± 14% 12.5hrs/day 68% ± 13% 16.3hrs/day 61% ± 15% 14.6hrs/day 0.0034 Pregnancy Trial Yamamoto J CDR 2018
Newborn health outcomes LGA: 53% CGM vs 69% control OR 0.51; 95% CI 0.28-0.90 p=0.0210 NNT 6 Hypoglycaemia requiring dextrose infusion 15% CGM vs 28% control OR 0.45; 95%CI 0.22-0.89 p=0.0250 NNT 8 NICU admission >24h: 27% CGM vs 43% control OR 0.48; 95% CI 0.26-0.86; p=0.0157 NNT 6 Feig DS Lancet 2017
Infant length of hospital stay CGM Control P-value N=100 N=100 Total number of hospital admission days 455 697 Median (IQR) infant hospital stay 3.1 (2.1-5.7) 4.0 (2.4-7.0) 0.0157
Food diaries Dietplan 6.0
Increased energy from protein & fat, less from carbs Energy or macronutrient Mean (95% CI) Mean as % total energy UK average for women 19-64y UK Dietary Recommended Values Total energy (kcal) 1630 (1535-1726) 1613 (derived from food diaries) 2175 (derived from doubly labelled water) Protein 65 g (61-68) 16 % 65 g (17 %) 45 g Carbohydrate 184 g (171-198) 42 % 197 g (48 %) 47 % of total energy Fat 69 g (64-75) 38 % 60 g (34.5 %) 33 % of total energy
Carbohydrate sources at main meals Cereal 32 % Bread 27.5 % Pastries, cakes 8 % Beverages 6 % Fruit 5.5 % Potatoes 19 % Vegetables 11 % Bread 10 % Pasta 10 % Rice 10 % Bread 30 % Pastry and Cake 10 % Crisps 8.5 % Vegetables 7.5 % Fruit 6 % Breakfast Lunch Dinner Vegetables includes beans, lentils, peas, salad, vegetable dishes but not potato (potato does not include crisps)
Carbohydrate sources at snack times Confectionery 32% Fruit 20% Biscuits 17% Beverages 12% Crisps 7% Confectionery 20 % Biscuits 15 % Pastry and cake 14 % Fruit 13 % Bread 9.5 % Confectionery 24 % Beverages 14.5 % Pastry and cake 14 % Biscuits 9 % Fruit 7 % Morning Tea Afternoon Tea Supper
Overall non-recommended sources contribute 50 % of average daily carb intake (92 g) ADA Dietary Guidelines: Recommended = vegetables (not potato), whole grains (incl bread), fruit, legumes, dairy Non-recommended = everything else
CLIP_04 Study devices
CLIP_04 Baseline maternal characteristics CLIP_04 N = 16 Age years; mean (SD) 32.8 (5.0) BMI kg/m 2 ; mean (SD) 26.6 (4.4) *HbA1c mmol/mol, %; mean (SD) 63.7 (12.1) 8.0 (1.1) Duration of diabetes years (SD) 19.4 (10.2) Pump (n) 8 (50%) TDD units; mean (SD) 0.51 (0.09) Gestation randomisation week; mean (SD) 16.4 (4.9) Primiparous (n) 6 (38%) * 9 women had booking HbA1c 58mmol/mol (7.5%) 6 women with previous pregnancy losses (6 miscarriages and 1 stillbirth), 2 had TOP for congenital anomaly.
CLIP_04 Overnight results (23-07.00hr) SAP therapy Closedloop Effect size (CI 95% ) P value Time in target 60.6 67.7-7.2 (-0.8 to 15.2) 0.058 (%; 3.5-7.8 mmol/l) Time >7.8 mmol/l 36.7 31.1-5.5 (-14.0 to 2.9) 0.18 Time > 10 mmol/l 14.1 11.7-2.4 (-7.0 to 2.3) 0.29 Time <3.5 mmol/l 2.7 1.1-1.6 (-2.8 to -0.4) 0.0008 Time < 2.8 mmol/l 0.5 0.2-0.3 (-0.6 to 0.0) 0.058 Mean glucose (mmol/l) 7.2 7.2-0.04 (-0.5 to 0.4) 0.83
CLIP_04 results Day and night SAP therapy CLIP Effect (CI 95% ) P value Time in target (3.5-7.8 mmol/l) 60.1 62.3 2.1 (-4.1 to 8.3) 0.47 Time >7.8 mmol/l 36.6 36.1-0.6 (-7.4 to 6.3) 0.86 Time <3.5 mmol/l 2.7 1.6-1.1 (-0.2 to -2.1) 0.02 Time <2.8mmol/L 0.5 0.2-0.2 (-0.0 to -0.5) 0.03 Number of hypo events (range) 12.5 (1-53) 8 (1-17) 0.04 Mean glucose 7.3 7.3 0 (-0.3 to 0.4) 0.85
CLIP_04 antenatal feasibility 28-32 weeks gestation (n = 8) 32-36 weeks gestation (n = 16) 36+ weeks gestation (n = 9) 0-6 weeks postnatal (n = 12) % time in target (3.5-7.8 mmol/l) 70.6 (64.2, 75.4) 71.5 (68.9,75.9) 72.3 (67.3, 80.3) 77.1 (75.1, 90.4) % time above target (>7.8 and >10 mmol/l) % time below target (<3.5 and 3.9mmol/L) 28.0 (23.0, 34.0) 24.4 (22.8, 29.3) 23.7 (17.7, 31.5) 22.1 (9.5, 24.4) 1.9 (1.7, 2.3) 2.0 (1.1, 3.9) 2.3 (1.0, 3.0) 2.4 (0.8, 3.7) Mean glucose (mmol/l) 6.9 (6.6, 7.2) 6.7 (6.4, 6.9) 6.6 (6.4, 6.9) 7.7 (7.1, 8.2) Women maintained >70% time in target throughout pregnancy Diab care 2018
Practical take-home Pearls Safe effective contraception/pre-pregnancy care is most important intervention in T1D pregnancy Use of CGM is associated with improved neonatal outcomes, attributed to reduced fetal exposure to maternal hyperglycemia More attention to maternal dietary intake is needed Preliminary data suggest that closed-loop may be beneficial, but larger trials needed
Pre-pregnancy care
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