UMBILICAL BLOOD FLOW INDICES IN PREGNANCIES COMPLICATED BY TYPE 1 DIABETES MELLITUS Finn Lauszus, Hanne Søndergaard, Carsten Byrialsen, Ervin Kallfa Obstetrical Dept., Herning Hospital, Denmark

What do we do with umbilical indices? Estimate symptoms of distress in umbilical arteries, i.e. clinical anticipated risk correspondind to physiological signal of distress Types of measurements: ratios between peak systolic velocity (A), end-diastolic peak velocity (B) and mean velocity (mean). Most common in clinical practice are pulsatility index (PI = (A - B)/mean), resistant index (RI = (A - B)/A), and S/D ratio (A/B).

What do we know for sure about umbilical indices What do we know for sure about umbilical indices ? (Evidence group 1, Cochrane Coll.) We do umbilical blood flow as an indicator for fetal distress and serial measurements are an established tool used for timing of delivery of fetuses with intrauterine growth retardation (IUGR). However, the latest review is from 1996, stating: ”The use of Doppler ultrasound in high risk pregnancies appears to improve a number of obstetric care outcomes and appears promising in helping to reducing perinatal deaths.”

What did they find? Doppler ultrasound for fetal assessment in high risk pregnancies by Neilson JP, Alfirevic Z. Cochrane Database of Systematic Reviews 1996, Issue 4. 11 eligable studies Less inductions (OR=0.85, p<0.006) Less perinatal deaths (mainly neonatal) (OR=0.71, p<0.06) Less hospital admissions (OR=0.61, p<0.0001) Less cesareans for fetal distress (OR=0.36, p<0.0016) A new review is under way……

High risk pregnancies… For most researchers, ‘high risk’ will include maternal diseases like DM, hypertensive disorders, cardiac, renal and autoimmune disorders. All of these conditions are associated with increased perinatal mortality and morbidity One shortcoming in fetal conditions of high risk is our inability to discern between IUGR, SGA, and fetuses that are constitutionally small with no increased perinatal mortality and mortality

Studies - on T1DM pregnancies Bracero L 1986 (n=43) Maternal hyperglycemia correlate with S/D ratios Salvesen DR 1992 (n=14 with nephropathy) Fetuses acidemic and hypoxemic (by amniocenthesis) despite normal umbilical flow values 24 hours before delivery Zimmermann 1992 (n=53) Vascular resistance declined during the course of pregnancy (measured 3 times range 1-7), no correlation with glycemia Johnstone FD 1992 (n=128) Abnormal RI is a significant predictor of fetal compromise

T1DM-studies cont’d Yoon BH 1993 (n=24) A strong relationship between the degree of fetal acidemia and hypercarbia (by cordocentesis) and Doppler velocimetry Grunewald C 1996 (n=24) Decline in pulsatility indices was absent and not influenced by glycemia (measured two times with one month’s interval) Wong SF 2003 (n=104) Umbilical artery Doppler velocimetry is not a good predictor of adverse perinatal outcomes in diabetic pregnancies (only 54 had scans within one week of delivery, 4 scans from week 28-38).

Our study Consecutive, n=129 Weekly measurement, gestational week 31-36 (total 450), median 4, mean 3.5, range 2-6 Calculations performed on complete data Umbilical pH measured in 101 at birth 77 delivered before week 37 and 8 before week 34, 42 in week 36

Clinical data (1) 107 16 6 129 29 ±5 28 30 ±4 0.50 9±7 14±7 21±5** Albuminuria Normo Micro Macro All ANOVA No 107 16 6 129 Age (yrs) 29 ±5 28 30 ±4 0.50 Duration (yrs) 9±7 14±7 21±5** 10±8 0.0001 Simple/ Proliferative 37/3 9/3 6/0 52/6 § HbA1c (%) in 1st tr. 7.2 ±1.1 7.9 ±1.2 7.3 ±1.1 0.045

Clinical data (2) 70±6# 75±4 80±5 71±6 0.0001 117 ±8 123 ±5 131 ±9** Albuminuria Normo Micro Macro All Anova DiaBT in 1st tr.(mmHg) 70±6# 75±4 80±5 71±6 0.0001 SysBT in 1st tr.(mmHg) 117 ±8 123 ±5 131 ±9** 118 ±9 Clearance in 1st tr.(ml/min) ±28 127 ±27 108 ±24 129 0.20 Birthweight (g) 3820 ± 696# 3144 ± 698 3271 ± 572 3711 ±728 0.001 BWTratio 1.37 ±0.26 1.14 ± 0.21 1.18 ±0 .15 1.33 ± 0.26 0.002 Umb-pH 7.26 ± 0.09 7.25 7.32 ± 0.5 ± 0.9 0.31

Albumin excretion rate Normo- Micro- Macro- All (95% CI) No. 31 1.10 1.32 1.45 1.15 (0.68,1.72) 87 32 1.13 1.18 1.13(0.70,1,63 101 33 1.05 1.34 1.25 1.09 (0.7,1.6) 93 34 1.09 1.41 1.19 1.14 (0.74,1.68) 85 35 1.03 1.06 (0.71,1.48) 81 36 1.11 1.26 1.04 1.11 (0.53,1.79) 50 107 16 6 129

pH and the last PI (within 2 days prior to delivery)

pH at birth and PI in week 36 no deliberate coincidence?

The best fitting model According to SPSS

Model summary and parameter estimates R square F df1 df2 Sig Constant b1 Linear .075 7.984 1 99 .003 7.339 -.07 Quadratic .131 7.389 2 98 .001 7.457 .267 .072

Conclusions No decrease in umbilical arterial flow indices is seen with progressing gestational age from week 32. We confirm that newborn of diabetic mothers are more likely to have acidemia and that it is associated with umbilical arterial flow indices.

Strength and weakness Numbers and consecutive design Non-randomization, non-blinding Bias by other (maternal )factors (known or unknown) Predictive value compared to other variables If this is standard care what is standard values to aim at? What are we looking at? Prematurity?