Maternal and fetal predictors of therapy

Transcrição

Universitätsfrauenklinik Jena
Kompetenzzentrum für Diabetes und Schwangerschaft
Maternal and fetal predictors of therapymanagement in gestational diabetes
Dr. Tanja Groten
Kompetenzzentrum Diabetes und Schwangerschaft
Universitätsfrauenklinik Abteilung Geburtshilfe
Direktor: Univ. Prof. Dr. med. E. Schleußner
Klinik und Poliklinik für Innere Medizin III
Direktor: Univ. Prof. Dr. med. G. Wolf
Note: for non-commercial purposes only
Dr. Tanja Groten
Background
Cascade of pathophysiologic events in gestational diabetes
Glucose intolerance of the mother
Normoglycaemia
of the
mother
Hyperglycaemia
of the
mother
Hyperglycaemia of the fetus
Hyperinsulinaemia of the fetus
02.04.2014
Macrosomia
postnatal hypoglyceamia
Inhibition of surfactant production
postnatal respiratory distress
Hypoxia leading to polycythaemia
postnatal icterus
Fetal programming
elevated risk for diabetes and
obesity
2
Background
Treatment of GDM:

The preliminary goal of intervention in GDM is the
prevention of fetal hyperinsulinaemia by monitoring
and controlling maternal blood glucose levels.

The preliminary therapeutic strategies are medical
nutrition therapy (MNT) and physical activity.

Patients who fail to maintain glycaemic control
should receive additional pharmacological
treatment. In Germany this means: insulin.
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3
When to start insulin therapy – goals for glucose control
Previous German
guidelines
New German
guidelines
ADA
< 95 mg/dl
< 5.3 mmol/l
ACOG
fasting
< 95 mg/dl
< 5.3 mmol/l
(≤ 5.0 mmol/l)
< 95 mg/dl
< 5.3 mmol/l
< 95 mg/dl
< 5.3 mmol/l
1 h pp
< 140 mg/dl
< 7.8 mmol/l
< 140 mg/dl
< 7.8 mmol/l
2 h pp
< 120 mg/dl
< 6.7 mmol/l
< 120 mg/dl
< 6.7 mmol/l
< 120 mg/dl
< 6.7 mmol/l
Start insulin if more than
three elevated
measurements at two
different days within one
week
Start insulin if 50%
of the values in one
week are elevated
If euglycaemia isn`t achieved by
nutrition therapy and exercise
within 10 days,
insulin therapy is started
< 140 mg/dl
< 7.8 mmol/l
< 120 mg/dl
< 6.7 mmol/l
… or/and in the case of accelerating or macrosomic growth of the fetus
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4
German guidelines: … incorporating fetal growth
parameters
 Individual definition of blood sugar goals depending on fetal growth
(abdominal circumference, asymetric growth favouring the abdomen)
However, here therapeutic
intervention starts when fetal
hyperinsulinaemia already
caused growth acceleration in
the fetus… and prevention of
fetal hyperinsulinaemia failed?
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5
Study population – perinatal outcome
267 pregnant women presenting for 75 g oGTT
Exclusion:
5 x Twins. 7 x decline study participation
255 pregnant women to analyse
GDM was diagnosed in 135 women
Insulin therapy 60
75 medical nutrition
therapy (MNT)
120 healthy pregnant women
Lost of follow
up: 5
Analysis of 115
perinatal outcomes
Control group
1 case of IUFT
Analysis of 59 perinatal
outcomes
Insulin group
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Analysis of 75 perinatal
outcomes
MNT group
6
Perinatale Outcome
Healthy
controls
(n = 115)
GDM
(n=134)
GDM
MNT (n=75)
GDM
Insulin-therapy
(n=59)
74.1
11.2
14.7
64.9
20.9
14.2
67.5
20.8
11.7
61.4
21.1
17.5
3452 ± 485
[2260-4620]
3330 ± 701
[695-4680]
3242 ± 769
[695-4430]
3470 ± 571
[1380-4680]
Birth weight > 95 percentile (%)
11.3
10.4
7.7
14.3
SGA (%)
6.1
6.0
6.0
0
Neonatal hypoglycaemia (%)
3.5
14.9**
5.3
27.1**
Neonatal hyperbilirubinaemia (%)
21.9
26.3
23.4
30.4
Respiratory distress (%)
6.1
9.0
9.1
8.9
Mode of delivery (%):
Vaginal
planned caesarean
Secondary caesarean
Birth weight (g)
** p<0.01
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Further questioning

Why is the outcome of GDM patients receiving
insulin therapy less sufficient? Is therapy started to
late?
 In 14% (n=8) of the insulin cases insulin therapy was started due to
fetal growth parameters. In these cases treatment was started after
fetal hyperinsulinaemia occured and effected abnormal fetal growth.

How can we identify patients who need insulin
earlier? Are there parameters at the time of GDM
diagnosis predicting the necessity of insulin
therapy?
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8
Results: Maternal predictors of insulin therapy at the time of
diagnosis of GDM
MNT (n=79)
Insulin group
(n=60)
p
25.0 ± 5.2
41.0
16.7
29.0 ± 6.2
66.7
40.0
<0.001
<0.01
<0.01
5.1
22.8
<0.01
HbA1c at diagnosis (%)
5.2 ± 0.4
5.6 ± 0.6
<0.001
Maternal age (years)
30.8 ± 5.7
31.2 ± 6.7
n.s.
Wait gain during pregnancy (kg)
14.6 ± 6.6
15.3 ± 6.3
n.s.
BMI before pregnancy (kg/m²)
BMI before pregnancy ≥ 25 kg/m² (%)
BMI before pregnancy ≥ 30 kg/m² (%)
History of GDM (%)
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Results: Kaplan-Meier Analysis HbA1c at diagnosis
and BMI prior to pregnancy
Discriminated for
HbA1c > 5.2% at the time of diagnosis
Discriminated for BMI > 25 prior to
pregnancy
1,0
0,8
<= 5,2
> 5,2
0,6
<= 5,2-zensiert
> 5,2-zensiert
0,4
0,2
p<0,01
0,0
0
5
10
15
20
Diagnosestellung bis Beginn einer
TimeZeitraum
fromvon
diagnosis
of GDM
Insulintherapie (Wochen)
to start of insulin therapy (weeks)
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Anteil ohne Insulintherapie
HbA1c-Wert bei
Diagnosestellung (%)
Percetage of GDM patients
without insulin therapy
Anteil ohne Insulintherapie
Percetage of GDM patients
without insulin therapy
1,0
BMI vor der
Gravidität (kg/m²)
0,8
< 25
0,6
>= 25
< 25-zensiert
0,4
>= 25-zensiert
0,2
p<0,01
0,0
0
5
10
15
20
Zeitraum
von Diagnosestellung
Time from
diagnosis bis
of Beginn
GDMeiner
Insulintherapie
(Wochen)
to start of insulin therapy (weeks)
10
Results: Fetal predictors of insulin therapy at the time
of diagnosis of GDM
Estimated fetal weight
>75. percentile (%)
>90. percentile (%)
Abdominal circumference
>75. percentile (%)
>90. percentile (%)
Fetal fat layer (mm)
MNT (n=78)
Insulin therapy (n=57)
p
26.7
13.3
44.0
26.0
<0.05
n.s.
14.9
5.4
24.1
11.1
n.s.
n.s.
3.1 ± 0.6
3.5 ± 0.9
<0.05
Fetal fat layer =
63% variability of abdominal
circumference
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Results: Predictive value
Logistic regression analysis revealed the combination of
Maternal age >30 years
BMI > 25 prior to pregnancy
 History of GDM.
HbA1c > 5.2% at diagnosis
and
estimated fetal weight >75. percentile at diagnosis
as predictors for the need of insulin therapy.

The positive predictive value is 77.6%.
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Conclusion and Discussion

The presented data show, that maternal and
fetal parameters at the time of diagnosis
could predict the need of insulin therapy.

These predictors may help to identifying
women in whom therapy should be started
earlier.
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13
Discussion and open Questions
? Is it possible to completely prevent fetal alteration in
cases of impaired Glucose tolerance of the mother
by initiating insulin therapy earlier?
? Do we need to more extensively rule out the
possibilities of medical nutritional therapy (MNT) and
exercise or start insulin earlier? Do we need more
strict indications for insulin therapy?
? Will the general screening of all pregnant women
lead to prevention of delay in diagnosis and therapy
initiation?
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14
Thank you for your attention!
… and the team of the Kompetenzzentrum für Diabetes und
Schwangerschaft Jena for their contribution.
PD Dr. W. Battefel
Dr. F. Weschenfelder
C. Helbich (diabetes advisor)
B. Milke (diabetes advisor)
C. Spreda (midwife)
A. Fiedler-Pape (midwife)
S. Nestler (midwife)
C. Mantschew (diabetes advisor assistence)
02.04.2014
15

Maternal and fetal predictors of therapy

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