Response to Comment on: Chakera et al. Antenatal Diagnosis of Fetal Genotype Determines if Maternal Hyperglycemia due to a Glucokinase Mutation Requires Treatment. Diabetes Care 2012;35:1832–1834
0
Department of Diabetes and Endocrinology
1
Peninsula College of Medicine and Den- tistry, University of Exeter
,
Exeter
,
U.K.; the
-
W Tartaglia et al. (1) in response to
e appreciate the comments by
our study. We agree with Tartaglia
et al. that maternal glucose management
in glucokinase (GCK) pregnancy should
be guided by knowledge of whether the
fetus has inherited the mutation from the
mother. In our article (2), we propose that
fetal genetic testing should be performed
if chorionic villus sampling (CVS) or
amniocentesis is performed for another
reason. Amniocentesis/CVS cannot be
recommended as a routine procedure in the
management of pregnant women with
GCK mutations, as the 1% miscarriage
rate is unacceptably high and outweighs
the potential benefits of knowing fetal
GCK genotype.
At present, fetal growth on ultrasound
is used as a surrogate marker for fetal GCK
status with increasing growth seen when
the fetus has not inherited the mutation.
Tartaglia et al. raise a valid point that the
optimal cutoff is unclear, especially given
uncertainty in measurements. If the fetus
does not inherit the GCK mutation,
maternal hyperglycemia results in an
approximately sixfold increase in macrosomia,
with mean increase in corrected birth
weight of 700 g, ;1 SD difference (3).
Using data from Hindmarsh et al. (4), we
estimate that if the abdominal circumference
exceeds the 75th percentile, the odds ratio
that the child is unaffected is increased by
3.5-fold. If the abdominal circumference
exceeds the 90th percentile, this odds ratio
increases to sevenfold. The variability in
measurement will determine the
confidence limits around these estimates, but
this will be reduced if repeated measures
are used. For this reason we suggest having
two values over the 75th percentile in scans
separated by 2 weeks before starting
insulin. One advantage of this cutoff is that it
has an evidence base to support it
because Buchanan et al. (5) used this cutoff
in a randomized controlled trial.
Ultimately, noninvasive prenatal
diagnosis (6) will replace the need to
make an indirect assessment based on
ultrasound and result in individualized
care for pregnant women with GCK
mutations.
ALI J. CHAKERA, MBCHB1,2
VICTORIA L. CARLETON, MBBS3,4
BEVERLEY SHIELDS, PHD1
GLYNIS P. ROSS, MBBS3
ANDREW T. HATTERSLEY, DM1,2
c c c c c c c c c c c c c c c c c c c c c c c c
References
1. Tartaglia E, Iafusco D, Giuliano P, et al. Com
ment on: Chakera et al. Antenatal diagnosis
of fetal genotype determines if maternal
hyperglycemia due to a glucokinase mutation
requires treatment. Diabetes Care 2012;35:
18321834 (Letter). Diabetes Care 2013;36:
e14. DOI: 10.2337/dc12-1364
2. Chakera AJ, Carleton VL, Ellard S, et al.
Antenatal diagnosis of fetal genotype
determines if maternal hyperglycemia due
to a glucokinase mutation requires
treatment. Diabetes Care 2012;35:18321834
3. Spyer G, Macleod KM, Shepherd M, Ellard
S, Hattersley AT. Pregnancy outcome in
patients with raised blood glucose due to a
heterozygous glucokinase gene mutation.
Diabet Med 2009;26:1418
4. Hindmarsh PC, Geary MP, Rodeck CH,
Kingdom JC, Cole TJ. Intrauterine growth
and its relationship to size and shape at
birth. Pediatr Res 2002;52:263268
5. Buchanan TA, Kjos SL, Montoro MN, et al.
Use of fetal ultrasound to select metabolic
therapy for pregnancies complicated by
mild gestational diabetes. Diabetes Care
1994;17:275283
6. Lo YM. Fetal nucleic acids in maternal
blood: the promises. Clin Chem Lab Med
2011;50:995998
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