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European Heart Journal Advance Access originally published online on December 11, 2006
European Heart Journal 2007 28(11):1319-1325; doi:10.1093/eurheartj/ehl416
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Pathologic ventricular hypertrophy in the offspring of diabetic mothers: a retrospective study

Sandra Ullmo1, Yvan Vial2, Stefano Di Bernardo1, Matthias Roth-Kleiner3, Yvan Mivelaz1, Nicole Sekarski1, Juan Ruiz4 and Erik J Meijboom1,*

1 Department of Paediatric Cardiology, Centre Hospitalier Universitaire Vaudois, BH 11–626, Rue du Bugnon 46, 1011 Lausanne, Switzerland
2 Department of Gynaecology and Obstetrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
3 Department of Neonatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
4 Department of Endocrinology, Diabetology, and Metabolism, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

Received 3 August 2006; revised 11 August 2006; accepted 16 November 2006; online publish-ahead-of-print 11 December 2006.

* Corresponding author. Tel: +41 21 314 3553; fax: +41 21 314 3665. E-mail address: Erik.Meijboom{at}chuv.ch


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Aims Diabetes in pregnant women is increasing and with that the complications in their offspring. We studied our population of diabetic mothers (2003–2005) for pathologic ventricular hypertrophy (PVH).

Methods and results In our retrospective study of all 87 diabetic pregnancies (92 neonates), 16 were type 1, 17 were type 2, and 54 were gestational diabetes (GD). Haemoglobin glycated (HbA1c) median was 5.8% (5.3–6.5): 17 with HbA1c above normal 2 with congenital heart disease (CHD) and six with PVH. A total of 75 neonates were normal, five had CHD, and 12 had PVH (1/12 died post-natally, 1/12 stillborn, 2/12 required premature delivery, 8/12 normal). The 16 type 1 pregnancies resulted in three neonates with CHD and in 50% PVH, including one death, one premature Cesarean section because of PVH. The 17 neonates of type 2 pregnancies showed in one CHD and in 25% PVH. Of the 54 GD pregnancies, one had CHD and one had PVH.

Conclusion Pregnancies of both type 1 and 2 diabetes carry an increased risk for foetal development of PVH compared with those with GD. The insufficient effect of preventive glycaemia controls leads to conclude that although no definite predictive parameters for malignant outcome can be presented, close monitoring of these pregnancies may prevent perinatal catastrophes.

Key Words: Maternal diabetes • Fetal cardiopathy • Pathologic ventricular hypertrophy • Hypertrophic cardiomyopathy • Echocardiography


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Diabetes mellitus constitutes a significant risk for the foetus if present in pregnant women. Reports so far have focused predominantly on the population of mothers wioth type 1 diabetes.1–9 There is increasing evidence that foetuses of mothers with type 2 diabetes may be prone to a similar pathology inducing complications on a multitude of organ systems of the foetus and the placenta.10–19 If proven true, this would constitute an important problem and might change the current prenatal diagnostic approach. Our study will focus on the consequences of all types of maternal diabetes on the foetal cardiac development.

The foetal heart is threatened in a double fashion. First, at the beginning of gestation, the disease has a teratogenic effect, cardiogenesis is impaired in the correct expression of genes coding for the cardiac development.20,21 Early prenatal cardiac screening between 12 and 16 weeks gestation is generally advised to detect these pathologies. The incidence of cardiac malformations is 3–6% of the offspring,22 five times higher than in normal pregnancies and frequently includes complex lesions.1,4–5 Second, starting at the end of the second or beginning of the third trimester, the foetus may be affected by pathologic ventricular hypertrophy (PVH), commonly referred as hypertrophy cardiomyopathy.3,4 Additional echographic investigation is required at the third trimester of gestation. PVH is characterized by an enlargement of heart; more precisely, a disproportionate hypertrophy of septum and/or ventricular free walls. Microscopic examination shows hypertrophic fibres and areas of cellular disarray. The aetiology of this cardiac anomaly is not really clear, but it is suggested that foetal hyperinsulinism may trigger hyperplasia and hypertrophy of myocardial cells by increasing fat and protein synthesis.23,24 This condition may or may not be symptomatic. Most of cases of hypertrophic hearts return gradually to a normal size in the first months after birth. However, some patients develop severe perinatal cardiac dysfunction and may go on to die.25–27

Several studies presumed diminishing the incidence of complications by a stringent control of glycaemia of future mothers. This resulted in better glycaemic values and a positive effect on the incidence of congenital cardiac malformations,28,29 but not necessary on the late development of hypertrophic cardiomyopathy. This leads us to hypothesize that, although no definite predictive parameters25–27,30–37 for foetal demise or malignant outcome can be presented, close cardiac foetal monitoring in these pregnancies may be helpful to prevent perinatal catastrophes. In order to assess the risk of the foetus for congenital heart disease (CHD) and/or PVH, we studied a population of mothers with all types of diabetes, well controlled regarding their glycaemia passing through our perinatal unit between 2003 and 2005.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Subjects and protocol
This retrospective study includes all offspring of diabetic mothers passing through our perinatal unit of the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland. Criterion for inclusion was known diagnosis of maternal type 1 or type 2 diabetes or gestational diabetes (GD), treated with diet alone or associated with transient insulin therapy. All infants of mothers with those criteria admitted to our neonatal unit between 1 January 2003 and 31 December 2005 were also included.

The population consisted of 87 pregnancies, with twins in five pregnancies. The data included in the study consisted of prenatal echocardiographies, types of insulin therapy, glycaemia controls [haemoglobin glycated (HbA1c)], delivery details, postnatal conditions, and sequential echocardiographic follow-up until discharge. Criteria for the echographic diagnosis of a PVH are based to the wall thickness normalized to the body size.

Statistical analysis
Descriptive statistics were performed using the computer program StatView 5.0.1 (SAS Institute, USA). Continous variables were expressed in medians and interquartile ranges and were compared using the unpair comparison t-test (for normally distributed variables), Mann–Whitney U test (for non-normally distributed variables), and Fisher's exact test (for categorical values). Categorical variables were expressed in percentages. A P-value <0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Baseline data of all pregnancies included in the study are shown in Table 1. Of the 87 pregnancies, median age was 34 years old,29–38 median body mass index (BMI) 28 kg/m2,23–34 62 (71%) mothers were Caucasians, 10 (11%) Africans, six (7%) Asians, six (7%) Hispanics, 37 (43%) were nullipara, 19 (22%) primipara, and 26 (30%) multipara. Type 1 diabetes was the diagnosis in 16, type 2 diabetes in 17, and GD in 54 future mothers, of which 38 were treated by insulin. Insulin treatment was performed in 11 women by an insulin pump and in 60 by insulin subcutaneous injection. In 16 cases, treatment consisted on dietary measures only. Median HbA1c was 5.8% (5.3–6.5). Of the 17 patients with HbA1c above normal (range 6.5–10.5%), two had CHD: one Atrial Septal Defect II (ASD II) and one Hypoplasic Left Heart Syndrome (HLHS), and six PVH.


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  		Table 1 Baseline data for diabetic mothers and perinatal outcome

 
Premature delivery occurred in 34 of 87 pregnancies, of whom two because of severe PVH. Cesarean section (C-section) was performed in 53 (61%) cases, nine (10%) because of diabetic complications (suspicion of macrosomia, diabetic decompensation, and premature labour), and five (6%) because of pre-eclampsia. One pregnancy was terminated because of cardiac and renal malformations (HLHS and renal dysplasia) and one macrosomic stillborn with a cardiac hypertrophy diagnosed at autopsy. Macrosomia, defined as birth weight above percentile 90, occurred in 24 neonates. Treatment for hypoglycaemia was required in 48 neonates and 36 patients manifested respiratory distress. Postnatal echocardiography was normal in 75 (82%) neonates. Five (5%) neonates had CHD, one had Double Outlet Right Ventricle (DORV), one Ventricular Septal Defect (VSD), one Tetralogy of Fallot (TOF), one HLHS, all four diagnosed prenatally, and one ASD of the secundum type (ASD II). The TOF died shortly after birth, because of severe prematurity in association with the cardiac malformation. One termination was performed because of the antenatal diagnosis of a combination of HLHS and a renal dysplasia.

Outcome of the 12 neonates (13%) born with a PVH is given in Table 2.


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  		Table 2 Outcome of the 12 neonates born with a PVH

 
Two showed a catastrophic evolution following a severe PVH:
  1. One type 1 diabetic patient under subcutaneous insulin pump had a diabetic decompensation at 35 weeks [hydramnios (amniotic fluid index 25), pathologic cardiotocogram (CTG) (hyporeactivity), and high glucose level (8.52–10 mmol/L)]. The mother developed oedema and gained weight at 36 weeks. Repeated CTG worsened (micro-oscillations) and hydramnios aggravated (AFI 30–32). After C-section at 37 weeks, the neonate was hypotonic, areactive, and cyanotic (Apgar 0/0/1, 4.68 kg >95th percentile), requiring a resuscitation and a transfer to the neonatal unit. An echocardiography revealed a PVH with a severe hypertrophic interventricular septum and left ventricular posterior wall (IVS: 11.9, LVPW: 12.1), tricuspid insufficiency revealing supra-systemic pulmonary hypertension with right-to-left shunting through a Patent Ductus Arteriosus (PDA). Cardiac failure leads to neonatal demise a few hours after arrival. Post-mortem findings include cardiomegaly (64.2 g, normal: 23 ± 8 g), biventricular hypertrophy, right atrial dilatation, and fibroelastosis.
  2. One patient with a BMI at 30 kg/m2, referred for a gestational pruritus, was diagnosed during the hospitalization for a GD (HbA1c mean: 4,9%), which proved later to be a type 2 diabetes and a suspicion of a macrosomic foetus. Insulin therapy was proposed but cancelled owing to premature membrane rupture and the foetal death at 35th week of gestation. Autopsy revealed a macrosomic stillborn with an enlarged heart (31.7 g, normal: 13.4 ± 3.9 g) including a dilated left ventricle with fibroelastosis and a biventricular hypertrophy.

The three following patients showed a favourable development, but required close monitoring:

  1. One type 1 diabetic patient (BMI at 25 kg/m2) under insulin pump (HbA1c mean: 6.9%) showed echographically a macrosomic foetus, a mild hydramnios (AFI 24), a constrictive septal hypertrophy of 8 mm, and a small pericardial effusion at the 36th week (Figure 1). Therefore, a vaginal delivery was induced prematurely. The newborn showed a good adaptation (Apgar 7/9/10, 3.2 kg = 90th percentile), but was transferred to the intensive care unit because of PVH. The first ultrasound confirmed a right ventricular and septal moderate hypertrophy (4.6 and 5 mm, respectively) and a PDA. Cardiac function improved in 2 days. Echocardiographic follow-up showed the normalization of the IVS size (5 mm, still marginally elevated) and the decrease of the LVPW diameter (3.3 mm) a month later, which allowed the discharge from further cardiac follow-up.
  2. One obese type 2 diabetic patient (BMI: 49 kg/m2), treated by insulin (HbA1c mean: 7.8%), had ultrasound controls that showed a macrosomic foetus with a progressive severe septal cardiac hypertrophy at 36th week, necessitating a premature induced delivery. At birth, the newborn was hyporeactive, but improved on oxygen (Apgar 7/8/9, 3.4 kg >90th percentile). A non-obstructive septal hypertrophy of 11 mm was confirmed by ultrasound. The newborn remained in a stable circulatory condition and follow-up controls showed a slow reduction of the septal diameter at 4 (8.6 mm) and 15 months (6.7 mm).
  3. One woman, suffering of a type 2 diabetes since 3 years, showed good glycaemic controls (HbA1c mean: 6) before requiring subcutaneous insulin therapy from the 31st week. Echocardiographic control detected a macrosomic foetus with a septal hypertrophy of 5 mm at 34 weeks. A C-section was performed at 39 weeks. The neonate (Apgar 9/9/9, 4.4 kg >90th percentile) presented a respiratory distress syndrome and a 2/6 cardiac murmur. A moderate LV hypertrophy without sub-aortic obstruction was noted echocardiographically and normalized at 3 months (4.2 mm).


Figure 1
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  		Figure 1 (A) Prenatal bidimensional echocardiographic image showing the thickening of the cardiac septum (8 mm) and a small pericardial effusion; (B) Postnatal bidimensional echocardiographic image of a severe interventricular hypertrophy (RVAW, right ventricular anterior wall).

 
Seven neonates with PVH followed a relative unremarkable course:
  1. The mother with a HELLP syndrome at 34 weeks had premature, macrosomic, plethoric, and erythrodermic neonate (Apgar 5/8/9, 3.25 kg >90th percentile) and suffered of hypoglycaemias before being stabilized. The echocardiographic diagnosis showed septal hypertrophic cardiomyopathy (4.4 mm).
  2. Two patients had diabetic decompensation [HbA1c mean: 9.5% (first), 7% (second)] and threatening premature delivery. One was delivered at 32 weeks (Apgar 5/9/10, 2.5 kg >90th percentile) and the other at 31 weeks (Apgar 2/7/8, 1.99 kg 50–90th percentile). Both developed wet lung syndrome and hypoglycaemia and showed echocardiographically cardiac septal hypertrophy (4.2 and 2.3 mm, respectively).
  3. Four neonates showed only mild cardiomyopathic features:
    • One presented at birth an Apgar of 7/9/9, with a weight of 2.53 kg (<10 percentile). However, saturations remained below 75%. A cardiomegaly was noted on the chest X-ray, septal cardiac hypertrophy was confirmed using echocardiography.
    • The second had a bad neonatal adaptation with a respiratory distress syndrome (Apgar 5/7/8, 3.48 kg 50–90th percentile). Echocardiography showed a non-obstructive biventricular hypertrophy (IVS: 7.5 mm, LVPW: 3.9 mm) with mitral- (2/4), aortic- (1/4), and tricuspid-insufficiency (2/4). Ascites and a pleural effusion were present. After the institution of NO therapy, a favourable evolution occurred in 4 days.
    • The third had asphyxia accompanied by a central cyanosis (Apgar 4/5/8, 3.7 kg >90th percentile). Echocardiography showed an important unobstructive biventricular hypertrophy predominant at the interventricular septum (IVS: 6.6 mm, LVPW: 3.9 mm) with cardiac hyperkinesias.
    • A last patient presented good condition at birth (Apgar 9/10/10, 4.75 kg >90th percentile), but with a cardiac murmur. Echocardiography confirmed septal hypertrophy (10 mm).

All of them showed a slow regression of the myocardial hypertrophy during follow-up.

Distribution of all patients following the type of maternal diabetes
Baseline data for diabetic mothers and perinatal outcome are given in Table 1. Mean HbA1c in each group of mothers with different types of diabetes are shown in Figure 2.


Figure 2
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  		Figure 2 Mean HbA1c in each group of mothers with different types of diabetes represented with medians and interquartile range. Cross-hatched, patient without PVH. Grey, patient with PVH.

 
Type 1 Diabetic pregnancies
Sixteen pregnancies resulted in three neonates with CHD (HLHS, VSD, and TOF), one PVH mortality, one PVH delivered prematurely, and six PVH with spontaneous regression. The remaining six patients were normal.

Type 2 Diabetic pregnancies
Seventeen pregnancies resulted in one neonate with CHD (ASD II), four with PVH, of whom one delivered prematurely, one was stillborn, and 12 were normal.

GD pregnancies
Fifty-four GD pregnancies resulted in one CHD (DORV) and one with PVH and spontaneous postnatal regression. The patient with DORV and hypoplastic arch had a planned delivery, was started on prostaglandin, and subsequently underwent successful surgical correction.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Insulin-treated or type 1 diabetes was generally thought to be prevalent in 0.5% of pregnancies,38 but recent publications indicate that this percentage is increasing during the last two decades, mainly because of an expanding number of young patients developing a type 2 diabetes.12,39–42 This increase might even prove to be more pronounced when one considers that there is possibly a grey area of patients diagnosed with GD, who in fact might have previously not noted type 2 diabetes.14,43,44 Cardiac complications consisting of an increased risk of neonatal CHD and PVH is a major cause of diabetes-induced morbidity and mortality of foetus and newborn.4–5,10,45

PVH can be seen in hypertrophy cardiomyopathy (HCM), an autosomal dominant genetic heart disease that probably is the most frequently occuring cardiomyopathy. However, none of the diabetic mothers studied had HCM or a family history of this disease. A genetic cause for the ventricular hypertrophy in our foetal patients seems even more unlikely in view of regression of this pathology during follow-up. Therefore, we have not used the terminology HCM of the foetus of a diabetic mother, but rather used the term PVH, to prevent a misleading use and underscoring the difference from classical HCM.

Our retrospective study shows an important number of cases of cardiomyopathies, 5% neonates developed CHD and 13% had PVH. The number of patients with CHD coincides with previously published studies concerning the potential teratogenic effect of diabetes20,21 and the increased incidence of CHD22 among the offspring of diabetic mothers. Less detailed information exists on the incidence of PVH. Pildes46 gives a percentage of 30% of HCM in offspring of type 1 diabetic mothers, but prevalence in type 2 and GD pregnancies is much less known. Our study differs and we found relatively high number of cases with PVH: in type 1 diabetes mothers almost half of the newborns suffered from PVH and a quarter of pregnancies with a type 2 diabetes. In total, we found that the percentage of neonates suffering of PVH upon the pregnancies of women with the type 1 and 2 diabetes amounts to 33%, which is much higher than the rate of CHD among the same group of diabetic women (12%). Moreover, the mortality due to PVH in the population studied is relatively high (1/6 patients with PHV). The lowest risk for PVH was present for newborns of mothers with GD, this shows that the offspring of mothers with a type 1 and 2 diabetes are at a significantly increased risk to develop PVH, although we realize that we have not been able to compare this to the normal population.

In our study, the group of mothers with a GD showed not only to have the lowest percentage of neonates with PVH, but also to have significantly lower values of HbA1c than the one with a pre-existing diabetes. The emphasis in the literature on the tight control of glucose levels is generally accepted.28 In analysing the group of patients with and without PVH, we mark that the first group has a significant higher HbA1c median [6.9% (interquartile range: 5.9–8.0)] than the second one [5.7% (interquartile range: 5.2–6.3)]. Despite a serious effort in a well organized and readily available healthcare system, 21% of our patients had an HbA1c above the normal limit (>6.4%), which emphasizes the difficulty of realizing good glycaemic control—a fact that may be explained by technical difficulties to control diabetes, bad attendance in the follow-up during pregnancy, late discovery of GD, non-compliance with diet and insulin treatment, and the late referral by gynaecologist or endocrinologist for a specific high-risk multidisciplinary consultation, but also the different social-economical status and ethnicity may play a role. A disturbing factor is, however, that if we look at the 12 patients with PVH, half of them had an HbA1c below and the other half above 7%, implying that PVH can develop in well and less good controlled patients. We must be so aware that the rigorous glycaemic control of those pregnancies is not sufficient to prevent the occurrence of PVH.

Another problem concerns the cardiac implications of the GD diagnosis for the foetus or neonate. Even though we found only one patient in the offspring of mothers with a GD who presented a PVH and that this one does not represent any significance, we can ask ourself whether these women had really GD or was it not yet diagnosed type 2 diabetes, as retrospectively observed in some of our cases. The question whether GD may trigger cardiac complications, however, is nowadays not resolved and further screening of GDM may help solve this question.14

A serious point, however, becomes the fact that if PVH develops just as well in the offspring of type 2 diabetic women, the currently observed increase of this disease may cause an increased amount of foetuses in danger of developing PVH. Moreover, our study includes an important number of women, with a BMI well above the normal (44%). This phenomenon reflects the worldwide problem of the obesity, also present in our country, and underlines the problem of the increasing incidence of new women diagnosed with type 2 diabetes. This worry is underscored by the embryologic research in diabetic rats that shows a similar outcome in their foetuses.20,21

The occurrence of neonatal PVH complications has been described in several case reports,25–27 but there is little information in the literature on series. In comparing the first five case reports described earlier, the combination at the end of gestation of hydramnios, severe ventricular hypertrophy, and pericardial effusion, proved to be an ominous sign. According to our data, we think that these signs are indications for either close observation by more frequent echographic controls or immediate intervention (induction or C-section), suggesting that a timely diagnosis is very important to avoid complications and allows the escape of a premature delivery.

The inherent limitations of this study include its retrospective aspect and the limited number of pregnancies included. Especially, the numbers and outcome of mothers with GD are too small to draw conclusions. This study suggests the need of a prospective study on these high-risk women and their offspring.

To conclude, the presence of an important number of cases of PVH in the offspring of mothers with type 1 and 2 diabetes, despite an effort to achieve good glycaemic controls, suggest that PVH remains an unpreventable complication in these patients. This supports Hawthornes18 statement that ‘Diabetic pregnancy remains a high risk state with perinatal mortality and foetal malformations rates much higher than the back population’ and that the goal of the St. Vincent declaration47 of 1989, saying that the outcome of pregnancies, complicated by a diabetes should be the same of a non-diabetic pregnancy in 5 years, is not reached yet. We admit that we cannot provide definitive predictive parameters for foetal demise or malignant outcome but conclude that, according to the results of our study, close monitoring of these pregnancies may prevent perinatal catastrophes.

Conflict of interest: none declared.


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Schwartz R, Teramo KA. Effects of diabetic pregnancy on the fetus and newborn. Semin Perinatol (2000) 24:120–135.[CrossRef][Web of Science][Medline]
  2. Hohlfeld P, Marty F, De Grandi P, Tissot J-D, Bossart H. Le livre de l'interne obstétrique (1998) 2nd ed. Flammarion: Médecine–Sciences. 157–170.
  3. Long WA. Fetal and Neonatal Cardiology (1990) Ed.W.B. Saunders Company. 137–138, 502–503.
  4. Allan L, Hornberger L, Sharland G. Textbook of Fetal Cardiology (2000) Greenwich Medical Media. 49–462, 147.
  5. Elkayam U, Gleicher N. Cardiac problems in Pregnancy, Diagnosis and Management of Maternal and Fetal Heart Disease (1998) 3rd ed. New York: Wiley-Liss. 543–545, 713–716.
  6. Suhonen L, Hiilesmaa V, Teramo K. Glycaemic control during early pregnancy and fetal malformations in women with type I diabetes mellitus. Diabetologia (2000) 43:79–82.[CrossRef][Web of Science][Medline]
  7. Rennie JM, Roberton NRC. Textbook of Neonatology (2005) 4th ed. Edinburgh: Churchill Livingstone.
  8. Penney GC, Mair G, Pearson DW. Scottish diabetes in pregnancy group. outcomes of pregnancy in women with type 1 diabetes in Scotland: a national population-based study. BJOG (2003) 110:315–318.[Web of Science][Medline]
  9. Evers IM, de Valk HW, Visser GHA. Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands. BMJ (2004) 328:915–918.[Abstract/Free Full Text]
  10. Acolet D, Fleming K, Bailey J, Golightly S, Macintosh M. Perinatal outcome and standards of neonatal care of pregnancies in women with type 1 and 2 diabetes in England, Wales and Northern Ireland 2002/2003. Confidential Enquiry into Maternal and Child Health (CEMACH) Central Office.
  11. Pontiroli AE. Type 2 diabetes mellitus is becoming the most common type of diabetes in school children. Acta Diabetol (2004) 41:85–90.[CrossRef][Web of Science][Medline]
  12. Rosenbloom A, Joe J, Young R, Winter W. Emerging epidemic of type 2 diabetes in youth. Diabetes Care (1999) 22:345–534.[Abstract/Free Full Text]
  13. Ostlund I, Hanson U, Bjorklund A, Hjertberg R, Eva N, Nordlander E, Swahn ML, Wager J. Maternal and fetal outcomes if gestational impaired glucose is not treated. Diabetes Care (2003) 7:2107–2111.
  14. Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care (2002) 10:1862–1868.
  15. Decorari AK, Saxena A, Singh M, Shrivastava S. Echocardiographic assessment of infants born to diabetic mothers. Arch Dis Child (1989) 5:721–724.
  16. Kitzmiller J, Buchanan T, Kjos S, Combs C, Ratner R. Pre-conception care of diabetes, congenital malformations, and spontaneous abortions. Diabetes Care (1996) 19:514–541.[Web of Science][Medline]
  17. Casson IF, Clarke CA, Howard CV, McKendrick O, Pennycook S, Pharoah PO, Platt MJ, Stanisstreet M, van Velszen D, Waltinshaw S. Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study. BMJ (1997) 315:275–278.[Abstract/Free Full Text]
  18. Hawthorne G, Robson S, Ryall EA, Sen D, Roberts SH, Ward Platt MP. Prospective population based survey of outcome of pregnancy in diabetic women: results of the Northern Diabetic Pregnancy Audit, 1994. BMJ (1997) 315:279–281.[Abstract/Free Full Text]
  19. Clausen TD, Mathiesen E, Ekbom P, Hellmuth E, Mandrup-Poulsen T, Damm P. Poor pregnancy outcome in women with type 2 diabetes. Diabetes Care (2005) 28:323–328.[Abstract/Free Full Text]
  20. Molin DG, Roest PA, Nordstrand H, Wisse LJ, Poelmann RE, Eriksson UJ. Gittenberger-De Groot AC. Distrubed morphogenesis of cardiac outflow tract and increased rate of aortic arch anomalies in the offspring of diabetic rats. Birth Defects Res Part A Clin Mol Teratol (2004) Dec;70:927–938.[CrossRef][Web of Science][Medline]
  21. Siman CM, Gittenberger-De Groot AC, Wisse B, Eriksson UJ. Malformations in offsprings of diabetic rats: morphometric analysis of neural crest-derived organs and effects of maternal vitamin E treatment. Teratology (2000) 61:355–367.[CrossRef][Web of Science][Medline]
  22. Weatherall DJ, Ledingham JGG, Warrell DA. Oxford Textbook of Medicine (1987) 1, 2nd ed. Oxford: Oxford University Press.
  23. Mehta A, Hussain K. Transient hyperinsulinism associated with macrosomia, hypertrophic obstructive cardiomyopathy, hepatomegaly and nephromegaly. Arch Dis Child (2003) 88:822–824.[Free Full Text]
  24. Veille JC, Hanson R, Sivakoff M, Hoen H, Ben-Ami M. Fetal cardiac size in normal, intrauterine growth retarded, and diabetic pregnancies. Am J Perinatol (1993) 10:275–279.[Web of Science][Medline]
  25. Sardesai MG, Gray AA, McGrath MMJ, Ford SE. Fatal hypertrophic cardiomyopathy in the fetus of a woman with diabetes. Obstet Gynecol (2001) 98:925–927.[CrossRef][Web of Science][Medline]
  26. Franzese A, Valerio G, Cicarelli NP, De Filippo G, Iannucci MP, AlfonsiL, Buono P, Farina V. Severe hypertrophic cardiomyopathy in an infant of a diabetic mother. Diabetes Care (1997) 20:676–677.[Web of Science][Medline]
  27. Leipold H, Worda C, Schwindt J, Kautzky-Willer A, Bancher-Todesca D, Husslein PW. Severe diabetic fetopathy despite strict metabolic control. Wien Klin Wochenschr (2005) 117:561–564.[CrossRef][Web of Science][Medline]
  28. Nelson RL. Diabetes and pregnancy: control can make a difference. Mayo Clin Proc (1986) 61:825–829.[Web of Science][Medline]
  29. Jensen DM, Damm P, Moelsted-Pedersen L, Ovesen P, Westergaard JG, Moeller M, Beck-Nielsen H. Outcomes in type 1 diabetic pregnancies. Diabetes Care (2004) 27:2819–2823.[Abstract/Free Full Text]
  30. Gutgesell HP, Speer ME, Rosenberg HS. Characterization of the cardiomyopathy in infants of diabetic mothers. Circulation (1980) 61:441–450.[Abstract/Free Full Text]
  31. Prefumo F, Celentano C, Presti F, De Biasio P, Venturini PL. Acute presentation of fetal hypertrophic cardiomyopathy in a type 1 diabetic pregancy. Diabetes Care (2005) 28:2084.[Free Full Text]
  32. McMahon JN, Berry PJ, Joffe HS. Fatal hypertrophic cardiomyopathy in an infant of a diabetic mother. Pediatr Cardiol (1990) 11:211–212.[CrossRef][Web of Science][Medline]
  33. Leslie J, Shen SC, Strauss L. Hypertrophic cardiomyopathy in a midtrimester fetus born to a diabetic mother. J pediatr (1982) 100:631–632.[CrossRef][Web of Science][Medline]
  34. Weber HS, Botti JJ, Baylen BG. Sequential longitudinal evaluation of cardiac growth and ventricular diastolic filling in fetuses of well controlled diabetic mothers. Pediatr Cardiol (1994) 15:184–189.[CrossRef][Web of Science][Medline]
  35. Koza'k-Ba'ra'ny A, Jokinen E, Kero P, Tuominen J, Rönnemaa T, Välimäki I. Impaired left ventricular diastolic function in newborn infants of mothers with pregestational or gestational diabetes with good glycemic control. Early Hum Dev (2004) 77:13–22.[CrossRef][Web of Science][Medline]
  36. Jaeggi ET, Fouron J-C, Proulx F. Fetal cardiac performance in uncomplicated and well-controlled maternal type I diabetes. Ultrasound Obstet Gynecol (2001) 17:311–315.[CrossRef][Web of Science][Medline]
  37. Tan AE, Norizah WM, Rahman HA, Aziz BA, Cheah FC. Umbilical artery resistance index in diabetic pregnancies: the associations with fetal outcome and neonatal septal hypertrophic cardiomyopathy. J Obstet Gynaecol Res (2005) 31:296–301.[CrossRef][Web of Science][Medline]
  38. Centres for Disease Control. Perinatal mortality and congenital malformations in infants born to women with insulin dependent diabetes: US Canada Europe 1940–1988. JAMA (1990) 264:437–440.[Free Full Text]
  39. Feig DS, Palda VA. Type 2 diabetes in pregnancy: a growing concern. Lancet (2002) 359:1690–1692.[CrossRef][Web of Science][Medline]
  40. Omori Y, Minei S, Testuo T, Nemoto K, Shimizu M, Sanaka M. Current status of pregnancy in diabetic women: a comparison of pregnancy in IDDM and NIDDM mothers. Diabetes Res Clin Pract (1994) 24(Suppl.):S273–S278.[CrossRef][Web of Science][Medline]
  41. Dean H. NIDDM-Y in first nation children in Canada. Clin Pediatr (1998) 39:89–96.
  42. Kitagawa T, Owada M, Urakami T, Yamauchi K. Increased incidence of non-insulin dependent diabetes mellitus among Japanese school children correlates with an increased intake of animal protein and fat. Clin Pediatr (1998) 37:111–115.[Abstract/Free Full Text]
  43. Noussitou P, Monbaron D, Vial Y, Ruiz J. Gestational diabetes and the risk of metabolic syndrome: a population-based study in Lausanne, Switzerland. Diabetes Metab (2005) 31:361–369.[Web of Science][Medline]
  44. Kieffer E. Obesity and gestational diabetes among African-American women and Latinas in Detroit: implications for disparities in women's health. J Am Med Womens Assoc (2001) 56:181–187.[Medline]
  45. Demirorem K, Cam L, Oran B, Koç H, Baspinar O, Baysal T. Echocardiographic measurements in infants of diabetic mothers and macrosomic infants of non diabetic mothers. J Perinat Med (2005) 33:232–235.[CrossRef][Web of Science][Medline]
  46. Pildes RS. Infants of diabetic mothers. N Engl J Med (1973) 289:902–904.[Web of Science][Medline]
  47. . Diabetes care:research in Europe: the Saint Vincent declaration. Diabet Med (1990) 7:360.[Web of Science][Medline]

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