804 Endocrine Care
Authors
A. B. König, S. Junginger, J. Reusch, F. Louwen, K. Badenhoop
Affiliation
Division Endocrinology & Diabetology, Department of Internal Medicine 1 and Department of Obstetrics of the University Hospital, Goethe-University, Frankfurt am Main, Germany
Key words ▶ body mass index ● ▶ metabolic syndrome in ● childhood ▶ insulin in pregnancy ●
Abstract
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The aim of the study was to examine obstetric outcomes and metabolic disorders in patients with gestational diabetes mellitus (GDM) and their offspring compared to mothers without GDM and their offspring. We performed a retrospective single center cohort study of mothers with GDM using a questionnaire with items concerning the maternal medical history, neonatal complications, and child development. Mothers with gestational diabetes (GDM; n = 130) and those with normal glucose tolerance (NGT; n = 77) were recruited. GDM mothers were older (37.58 years vs. 34.32 years, p < 0.0001) and had a greater body mass index (25.18 kg/m² vs. 23.37 kg/m², p < 0.01). There were no significant differences regarding the mean birth weight, the frequency of Cesarean sections, and the preva-
Introduction
▼ received 07.02.2014 accepted 23.04.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1375652 Published online: May 27, 2014 Horm Metab Res 2014; 46: 804–809 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0018-5043 Correspondence Dr. A. B. König Europa-Allee 57 60327 Frankfurt Germany Tel.: + 49/69/17526 727 Fax: + 49/69/15631 319 [email protected]
It is widely known that GDM is associated with an increased risk for the development of type 2 diabetes [1, 2] in mothers in later life as well as with obstetric and neonatal complications such as preterm delivery [3], miscarriages [4], macrosomia [5, 6], birth trauma [7], and neonatal respiratory distress [8]. Besides these effects, there is growing evidence for an impairment of somatometric development of children exposed to maternal hyperglycemia during pregnancy, especially concerning overweight and metabolic syndrome in childhood and adolescence [9]. The analysis of somatometric data of German children between 1998 and 2004 showed a continuously rising BMI at any age [10]. Maternal hyperglycemia during pregnancy may lead to metabolic alterations in the offspring such as obesity, insulin resistance, and higher blood pressure in comparison to children whose mothers were not affected by GDM [11–13]. The
König AB et al. Gestational Diabetes Outcome in … Horm Metab Res 2014; 46: 804–809
lence of macrosomia (> 4 000 g). At follow-up (pediatric U5 screening visit after 6 months of birth) children of mothers with GDM had significantly higher BMI than the children of the NGT group (17.07 kg/m² vs. 16.59 kg/m², p = 0.042). GDM women in need of insulin therapy during pregnancy had higher BMI than dieting GDM mothers and experienced more frequently an operative vaginal delivery (17.95 % vs. 6.17 %, OR 3.23, p = 0.04). We found less significant differences between GDM mothers with treatment of impaired glucose tolerance and NGT mothers concerning the neonatal outcome than expected. Despite higher BMI of the GDM group’s offspring at follow-up U5 visit, the children did not show any other development disorder. In conclusion treatment of GDM could minimize the frequency of obstetric and neonatal complications in this risk group.
present study’s aim was a follow-up evaluation of mothers and their children exposed to an impaired glucose homeostasis during pregnancy. The health situation of women who suffered from GDM and were treated in the University Hospital of Frankfurt am Main between 2002 and 2007 as well as the development of their children were studied in detail and compared to the health status of mothers with normal glucose homeostasis and their children.
Subjects and Methods
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Study design We performed a retrospective case control-study at the University Hospital of Frankfurt am Main after approval of the local ethics committee. The health status of women with GDM during pregnancy was assessed using a questionnaire developed specifically for this study at the University Hospital of Frankfurt. Furthermore, data from
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Gestational Diabetes Outcome in a Single Center Study: Higher BMI in Children After Six Months
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Study subjects The women who participated in the study were divided into 2 groups: Women were eligible for inclusion into the GDM group if they were diagnosed with GDM in pregnancy between July 2002 and December 2007 by using a 75 g oGTT and whose blood sugar adjustment was performed at the University Hospital of Frankfurt am Main. The exclusion criterion was a prepregnancy diagnosis of diabetes. Women with normal glucose tolerance in each preceding pregnancy could be included into the NGT group. All patients gave written informed consent.
lems with conception or necessity for assisted reproduction techniques. Eventually we focused on the course of pregnancy as well as the delivery. This included the maternal body weight, the duration of pregnancy, the mode of delivery and the somatometric data of the newborn as well as possible complications. GDM mothers were asked whether they were treated by diet alone or if they required insulin therapy. The children’s somatometric development when exposed to maternal GDM was analyzed based on the recordings in the children’s medical check-up booklet and their medical history was inquired for the same internal diseases the mothers were asked for.
Data analysis The data analyses were performed with the statistical program BiAS, version 9.08 for Windows. The data were summarized as means and standard deviation or medians and interquartile ranges for continuous variables and as frequencies and percentages for categorical variables. The statistical comparison between the patient-collective and the corresponding control group was made with the 2-sample t-test based on the calculated mean values and standard deviations in case of parametric data. The results of nonparametric data were tested on the basis of median, maximum and minimum using the Wilcoxon–Mann– Whitney test or the median test. Odds ratios were used to compare the GDM and NGT group concerning the frequency of maternal internal disorders as well as adverse obstetrical and neonatal outcomes. In addition to comparisons between the GDM and NGT groups, data from women in the GDM group who were treated by diet alone and those who had insulin treatment were analyzed separately. A p-value of < 0.05 was regarded as statistically significant.
Results
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Study subjects In total, 207 women living in and around Frankfurt am Main were enrolled in the study. Of these 130 were affected by GDM defined by OGT in at least one pregnancy. The NGT group constituted the remaining 77 mothers with constantly glucose tolerance in each pregnancy. Enrolment of GDM patients for the study occurred between May 2009 and April 2010. The enrolment of the 77 healthy mothers without a history of GDM was completed between March 2010 and August 2010. The majority (89.61 %) of these were recruited in the maternity wards of the University Hospital of Frankfurt and the hospital of Frankfurt-Höchst. The remaining 10.39 % of the NGT group could be contacted with the help of child care facilities in Frankfurt.
Maternal outcomes and clinical characteristics Data collection The multisided questionnaire developed in the University Hospital contained questions concerning maternal somatometric data like body weight, height, and the resultant body mass index at the present time as well as before conception. Furthermore the mothers were asked about maternal diabetes mellitus, dyslipidemia, hypertension, and thyroid diseases in their own as well as in first degree relative’s medical history. Moreover the patients were asked about their gynecological and obstetric history, for previous miscarriages, irregular menstruations, prob-
The special population pattern of Frankfurt needs to be considered when interpreting the maternal characteristics. In 2009, the city counted 678 353 inhabitants, about 24.3 % of them had a migratory background. It is well known that the incidence of GDM – similar to type 2 diabetes – varies according to race, origin, and place of residence [19]. However, since the study participants were not asked for their ethnicity or migration, we can only speculate that up to a quarter of our patients may have had such a background.
König AB et al. Gestational Diabetes Outcome in … Horm Metab Res 2014; 46: 804–809
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mothers affected by GDM and their children were compared with those of mother-child pairs not affected by maternal hyperglycemia. During the course of the study there were still international and regional differences regarding the cutoffs in an oGTT with 75 g glucose for the diagnosis of GDM. The German Diabetes Association (DDG) as well as the American Diabetes Association (ADA) recommended the threshold values according to Carpenter and Coustan [14], whereas the Land Hesse – and thus in Frankfurt – the stricter limits were applied that had been recommended by the Hesse Diabetes Society [15]: Fasting: ≥ 90 mg/dl, 1 h postprandial: ≥ 160 mg/dl, 2 h postprandial ≥ 140 mg/dl in venous plasma. However, only 3 of the women in our study underwent the 75 g OGTT at the University hospital, the others were diagnosed out of hospital and presented to our department afterwards. We also enrolled women, who exceeded only one of these 3 threshold values in a venous blood specimen. According to the DDG and the ADA, GDM was diagnosed if at least 2 measured values exceeded the limits of Carpenter and Coustan after ingestion of 75 g glucose, only one exceeded value was declared as impaired glucose tolerance. In accordance with the new Guidelines of the German Diabetes Association, GDM can also be diagnosed if only one of the predetermined cutoffs is exceeded, whereas these values – based on the results of the HAPO-Study [16] – differ slightly from the former criteria: Fasting: ≥ 92 mg/dl, 1 h postprandial: ≥ 180 mg/ dl, 2 h postprandial ≥ 153 mg/dl. Thus the more strict criteria of the Hesse GDM definition include slightly more women. In Frankfurt, treatment of GDM targeted blood sugar adjustment in accordance with the recommendations in the AWMF-Guideline of 2001 (fasting blood sugar 60–90 mg/dl, 1 h postprandial ≤ 140 mg/dl, 2 h postprandial ≤ 120 mg/dl) [17], which has now been replaced by the new guidelines of the German Diabetes Association (DDG) and the German Society of Gynecologists and Obstetricians published in August 2011 [18]. All women diagnosed with GDM were educated in glucose self-monitoring and change of lifestyle based on individual dietary and exercise regimens. The women were closely monitored, so that an insulin therapy was started if the blood glucose targets were exceeded.
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GDM mothers were older and had a greater body mass index at the time of assessment (37.58 years and 25.18 kg/m² vs. 34.32 years; p < 0.0001 and 23.37 kg/m; p < 0.01) There were no significant differences concerning the prevalence of the selected internal disorders between the 2 groups. The proportion of smokers among the women in the GDM was higher than that in the NGT group, which is a clinically meaningful difference (17.7 % vs. 7.89 %; OR 2.51, p = 0.051). Mothers with GDM were more likely to have a family history of gestational diabetes (19.23 % vs. 5.26 %; OR 4.29, p = 0.01). No significant differences ▶ Table 1 proexisted for the frequency of thyroid disorders. ● vides an overview of these characteristics.
There were no significant differences concerning the frequency of preeclampsia, Cesarean section (36.0 and 28.57 % in the GDM and NGT group, OR 1.41; p = 0.28) and the necessity for operative vaginal delivery (as compared with spontaneous delivery). We observed no significant differences between the groups regarding the mean birth weight (3406.62 g vs. 3456.09 g; p = 0.5) and no difference in the prevalence of macrosomia (6.19 % in the GDM and 9.68 % in the NGT group; p = 0.57). Furthermore, there were no differences concerning neonatal complications such as jaundice, respiratory distress, neonatal ▶ Table 2). infections or hypoglycemia (●
Irregular menstruations and problems with conception were not significantly more common in the GDM or the NGT group, whereas GDM was associated with a significantly higher rate of miscarriages in the women’s reproductive history (30.77 % vs. 9.09 %; OR 4.44, p < 0.001). Whereas the obstetric outcome data of the NGT group relate to the women’s first pregnancy, this was not the case in the GDM group, because not every patient developed GDM during her first pregnancy. At the time of the analyzed pregnancy GDM mothers were significantly older than those of the NGT group (32.59 years vs. 29.41 years; p < 0.0001) and showed a significantly higher prepregnant BMI (24.44 kg/m² vs. 22.38 kg/m²; p < 0.01). By contrast, the maternal weight gain during pregnancy was significantly higher in the NGT group (12.23 ± 5.73 vs. 14.17 ± 5.51; p = 0.04) regarding the pregnancies finished by term (38–41th week of pregnancy). The percentage of women in the GDM group who reached the recommendations for weight gain during pregnancy of the Institute of Medicine [20] was 35.05 % vs. 27.78 % in the NGT group. Thirty-three percent of women with GDM (vs. 40.74 % of NGT women) gained more and 31.96 % (vs. 12.96 %) gained less weight than recommended. GDM mothers who required an insulin therapy during pregnancy amounted to 32.5 %. These women showed a significantly higher BMI both at the time of assessment and before the analyzed pregnancy (27.04 ± 7.22 vs. 23.13 ± 3.64; p = 0.003 and 27.71 ± 6.77 vs. 23.75 ± 3.84; p = 0.002).
GDM mothers who required insulin therapy during pregnancy amounted to 32.5 %. Insulin therapy was started if glucose concentrations were repeatedly high (fasting, 1- and/or 2-h postprandial readings) and obstetrical characteristics like fetal biometrics suggested beneficial insulin effects. Insulin treatment was started in an interdisciplinary consultation with the gynecologists. For the purpose of this study the participant’s individual glucose readings and insulin requirements were not quantitated. Besides a significantly higher body mass index, women in need of insulin therapy experienced more frequently an instrumental vaginal mode of delivery (17.95 % vs. 6.17 %, OR 3.23; p = 0.04) and the rate of the diagnosis of type 1 diabetes diagnosed after the pregnancy was significantly higher. Thereby, all GDM mothers diagnosed with type 1 diabetes after delivery required insulin during pregnancy, but none of them was diagnosed with type ▶ Table 3). 1diabetes during pregnancy (●
Child development At the time of the U5 check-up (5th follow-up pediatric assessment in the 6th to 7th month of life) the children of mothers with GDM had a significantly higher BMI than the children of the NGT ▶ Fig. 1). A simigroup (17.07 kg/m² vs. 16.59 kg/m²; p = 0.042) (● lar trend is seen at check-up U6 (17.06 ± 1.57 vs. 16.63 ± 1.19, p = 0.051) (data not shown).
Table 1 Maternal biometric and clinical data.
Age (years) BMI (kg/m²)
GDM (n = 130)
NGT (n = 77)
95 % CI
37.58 ± 5.07 25.18 ± 5.49
34.32 ± 4.69 23.37 ± 3.88
1.83–4.69 0.32–3.29
53/123 (43.09) 9 (6.92) 10 (7.69) 5 (3.85) 3 (2.31) 25 (19.23) 35 (26.92) 24/35 (68.57) 3/35 (8.57) 8/35 (22.86) 23 (17.7 %)
18/68 (26.47) 7 (9.21) 2 (2.63) 0 (0) 1 (1.32) 4 (5.26) 14 (18.42) 10/14 (71.43) 2/14 (14.29) 2/14 (14.29) 6 (7.89 %)
2.1 (1.11–4.0) 0.73 (0.26–2.05) 3.08 (0.7–13.52) 6.71 (0.77–58.14) 1.77 (0.19–16.93) 4.29 (1.53–11.98) 1.63 (0.81–3.27) 0.87 (0.22–3.45) 0.56 (0.83–3.79) 1.78 (0.33–9.67) 2.51 (0.99–6.33)
p-Value < 0.0001 < 0.01
Internal disorders Odds Ratio (95 % CI) BMI > 25 kg/m² ( %) Dyslipidemia ( %) Hypertension ( %) Type 1 diabetes diagnosed after the analyzed pregnancy ( %) † Type 2 diabetes diagnosed after the analyzed pregnancy ( %) † First-degree relatives with a history of GDM ( %) Thyroid disease ( %) Total Hypothyroidism Hyperthyroidism Others Smoking
p-Value 0.02 0.55 0.14 0.08 0.62 0.01 0.17 0.85 0.55 0.51 0.051
Values are means ± SD †
A type 1 diabetes mellitus at the time of pregnancy was, such as a preexisting type 2 diabetes, an exclusion criterion. Thus, the reported frequency of type 1 and type 2
diabetes refers to cases diagnosed after pregnancy
König AB et al. Gestational Diabetes Outcome in … Horm Metab Res 2014; 46: 804–809
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Insulin therapy Obstetric characteristics
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Table 2 Maternal characteristics in the course of the pregnancy and the neonatal biometric data.
Age at analyzed pregnancy (years) Prepregnant BMI (kg/m²) Weight gain during pregnancy up to the 38th to 41st week (kg) Male/Female Newborns Birth weight (mean ± SD) Total Male Female
GDM (n = 130)
NGT (n = 77 )
95 % CI
32.59 ± 4.65 24.44 ± 5.49 12.23 ± 5.73 73/44 3 406.62 ± 463.69 3 498.2 ± 443.39 3 264.58 ± 483.5
29.41 ± 5.26 22.38 ± 3.13 14.17 ± 5.51 42/33 3 456.09 ± 463.25 3 545.74 ± 457.5 3 355.54 ± 464.97
1.74–4.61 0.61–3.50 − 3.84 to –0.04
p-Value < 0.0001 < 0.01 0.04
− 195.43–96.47 − 238.13–143.05 − 330.47–148.56
0.5 0.62 0.45
41/120 (34.17) 17/128 (14.17) 40 (30.77) 5/127 (3.94) 45/125 (36) 12/125 (9.6) 10/114 (8.77) 6/97 (6.19) 6/61 (9.84) 0/36 (0) 3/129 (2.33) 7/129 (5.43) 25/129(19.38) 4/129 (3.1) 3/129 (2.33)
13/66 (19.7) 14/76 (18.42) 7 (9.09) 4/76 (5.26) 22/77 (28.57) 9/77 (11.69) 10/76 (13.16) 6/62 (9.68) 4/34 (11.76) 2/28 (7.14) 4/75 (5.33) 1/75 (1.33) 17/75 (22.67) 1/75 (1.33) 4/75 (5.33)
2.12 (1.04–4.3) 0.68 (0.31–1.47) 4.44 (1.97–10.04) 0.74 (0.19–2.83) 1.41 (0.76–2.6) 0.8 (0.32–2.01) 0.63 (0.25–1.6) 0.62 (0.19–1.99) 0.82 (0.21–3.15) 0.15 (0.01–1.51) 0.42 (0.1–1.87) 4.25 (0.6–30.03) 0.82 (0.41–1.64) 2.37 (0.28–20.36) 0.42 (0.1–1.87)
Obstetric and neonatal outcome and complications
Total Male Female
Malformation ( %) Postpartal hypoglycemia ( %) Jaundice ( %) Respiratory distress ( %) Infection of the newborn ( %)
p-Value 0.04 0.32 < 0.001 0.66 0.28 0.64 0.34 0.42 0.77 0.11 0.26 0.15 0.58 0.43 0.26
Values are means ± SD
Table 3 Maternal biometric characteristics and clinical data in GDM mothers with and without insulin therapy during pregnancy.a Insulin therapy
Yes (n = 40)
No (n = 83)
95 % CI
p-Value
Age at analyzed pregnancy (years) Pregravid BMI (kg/m²) BMI at assessment (kg/m²) Internal disorders
32.26 ± 4.37 27.04 ± 7.22 27.71 ± 6.77
32.69 ± 4.9 23.13 ± 3.64 23.75 ± 3.84
− 2.27–1.42 1.91–5.91 2.01–5.92
0.65 0.003 0.002
Odds Ratio (95 % CI)
p-Value
Dyslipidemia ( %) Hypertension ( %) Operative vaginal delivery ( %) Cesarean delivery ( %) Type 1 diabetes diagnosed after the analyzed pregnancy ( %) Type 2 diabetes diagnosed after the analyzed pregnancy ( %) a
5/37 (13.51) 4/39 (10.26) 7/39 (17.95) 18/39 (46.15) 5/35 (14.29) 2/36 (5.56)
3/83 (3.61) 4/81 (4.94) 5/81 (6.17) 26/81 (32.1) 0/83 (0) 1/83 (1.2)
4.17 (1.03–16.88) 2.2 (0.53–9.09) 3.23 (1.03–10.76) 1.81 (0.83–3.97) 30.11 (4.48–202.29) 4.82 (0.52–44.72)
0.05 0.28 0.04 0.14 < 0.001 0.17
Seven GDM patients did not answer the questions concerning the conducted therapy
Discussion
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The main significant findings in GDM mothers are a higher body mass index, a higher age at pregnancy, and a positive family history for GDM. The higher BMI was also associated with a greater risk for the need of insulin treatment. There were nonsignificant differences in thyroid disorders that need to be further studied in larger data sets. Hereby it is possible that amongst these women later manifesting permanent hyperglycemia, a latent autoimmune diabetes in adults (LADA) may be hidden. Our findings are based on a retrospective evaluation of questionnaire data without immediate metabolic testing in the postpartal phase, which is a limitation of the study. However such data have proven useful in the assessment of postpartal medical issues when young mothers prefer to report in questionnaires rather than to an out-patient department [21].
While a higher prevalence of type 2 diabetes in the time course after a diabetic pregnancy has been reported [1, 2], we only find slightly more mothers in the GDM than in the NGT group with newly diagnosed type 2 diabetes postpartum. Five patients in the GDM group (3.85 %) were diagnosed with type 1 diabetes in the years following their diabetic pregnancy but none of the mothers in the NGT group. This observation is in contrast to previous studies [22, 23]. However, other address the increased risk of type 1 diabetes after GDM [24, 25], particularly in the case of insulin-controlled GDM [26]. Unfortunately, we had no information about islet antibodies, but 3 of the mothers with type 1 diabetes also suffer from hypothyreoidism. Among these, at least 2 were diagnosed with Hashimoto’s thyreoiditis, which can be seen as a combination of an autoimmune polyglandular syndrome.
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Odds Ratio (95 % CI) Prepregnant BMI ≥ 25 kg/m² ( %) Irregular menstruations ( %) History of abortion ( %) Pre-eclampsia ( %) Cesarean delivery ( %) Operative vaginal delivery ( %) Premature delivery < 37 + 0 SSW ( %) Macrosomia 4 000 g ( %)
Fig. 1 Relative distribution of the children’s body mass index according to the age and gender specific standards at the time of the U5 children’s examination. The table above the figure shows the rate of children falling above the 50th percentile.
The worldwide increase in childhood and adolescent obesity as well as type 2 diabetes [43, 44] underlines the significance of an effective prevention including maternal hyperglycemia in pregnancy [45]. It remains unclear whether a maternal GDM alone or its combination with maternal overweight and fetal macrosomia increases the risk of obesity and metabolic disorders in their offspring as early as in childhood or adolescence [11, 46]. Future studies should address somatometric and metabolic child development up to adolescence and adulthood in relation to maternal GDM treatment control. Such clinical studies are important since GDM may have long-lasting epigenetic effects by imprinting developmental genes [47] such as malprogramming of a paternally expressed mouse homolog of the mesoderm-specific transcript (MEST) gene, a finding that can also be made in adult obesity [48]. In conclusion, the treatment of GDM can limit obstetric and neonatal complications of GDM. Larger cohorts are needed to elucidate how treatment of GDM can improve the offspring’s metabolism also in adolescence and adulthood.
Acknowledgement
▼ The low prevalence of type 2 diabetes may be due to the limited time interval of 2–8 years observation after delivery and diabetes may manifest later. Recent studies on the development of type 2 diabetes after a pregnancy complicated by GDM showed rates between 5 and 30 %, depending upon the applied diagnostic criteria and the time of screening whereas the rate of prediabetic metabolic conditions was correspondingly higher [27, 28]. A better prediction of later diabetes may be achieved by measuring the HbA1c level during pregnancy [29]. There were less differences between the mothers in the GDM and the NGT group for their gynecologic and obstetric history than described previously [30, 31]. The reported rates of miscarriages in patients with GDM or preexisting diabetes vary. A trial carried out on 489 pregnant women in the early 80’s showed 12.5 % miscarriages in women with GDM, which was not significantly higher than in mothers with normal glucose tolerance [32]. In concordance with other trials [33, 34], we found a significantly higher rate of preceding miscarriages among the women in the GDM group. The frequency of pre-eclampsia and Cesarean section did not differ significantly between the groups, but assisted vaginal delivery was more frequent in the insulin treated GDM patients. A higher risk for operative deliveries has repeatedly been described in mothers with GDM [35–38]. Interestingly the risk appears to persist despite adequate therapy [39]. On the background of a high rate of Cesarian sections in Germany – 31.9 % in 2010 [40] – we found a trend to more frequent Cesarean sections in the GDM group. Nevertheless, early diagnosis and adequate therapy can reduce the frequency of Cesarean sections in GDM [41]. On the assumption that our patients complied with their treatment, we assume that this explains the small difference in the frequency of Cesarean sections to NGT mothers. Furthermore, we observed no differences in the frequency of neonatal complications such as preterm delivery, neonatal hypoglycemia, jaundice, or respiratory distress. This is in contrast to results from the Swedish Birth Registry, where the composite neonatal morbidity was enhanced in GDM [42]. That we detect fewer differences may be due to the inclusion of mild GDM forms and the limited size of our cohorts.
We thank Professor V. Möbus for helping us recruiting patients in Frankfurt-Höchst.
Conflict of Interest
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The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
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808 Endocrine Care
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31 Saydah SH, Chandra A, Eberhardt MS. Pregnancy experience among women with and without gestational diabetes in the US 1995 National Survey of Family Growth. 32 Crane JP, Wahl N. The role of maternal diabetes in repetitive spontaneous abortion. Fertil Steril 1981; 36: 477–479 33 Yang H, Wei Y, Gao X, Xu X, Fan L, He J, Hu Y, Liu X, Chen X, Yang Z, Zhang C.China National GDM Survey Working Group. Risk factors for gestational diabetes mellitus in Chinese women: a prospective study of 16286 pregnant women in China. Diabet Med 2009; 26: 1099–1104 34 Salzberger M, Liban E. Diabetes and antenatal fetal death. Isr J Med Sci 1975; 11: 623–628 35 Patel RR, Peters TJ. Prenatal risk factors for Cesarean section. Analyses of the ALSPAC cohort of 12944 women in England. Int J Epidemio 2005; 34: 353–367 36 Naylor CD, Sermer M, Chen E, Sykora K. Cesarean delivery in relation to birth weight and gestational glucose tolerance: pathophysiology or practice style? Toronto Trihospital Gestational Diabetes Investigators. JAMA 1996; 275: 1165–1170 37 Bhat M, Ramesha KM, Sarma Sankara P, Menon S, Ganesh KS. Outcome of Gestational Diabetes Mellitus from a Tertiary Referral Center in South India: A Case-Control Study. J Obst Gynecol India 2012; 62: 644–649 38 Remsberg KE, McKeown RE, McFarland KF, Irwin LS. Diabetes in pregnancy and cesarean delivery. Diabetes Care 1999; 22: 1561–1567 39 Jensen DM, Sorensen B. Maternal and perinatal outcomes in 143 Danish women with gestational diabetes mellitus and 143 controls with a similar risk. Diabet Med 2000; 17: 281–286 40 Faktencheck Gesundheit Kaiserschnitt-Bertelsmann-Stiftung. Caesarean sections in Germany: Marked increase and wide regional variations. Nearly one in three children are born by caesarean section. (Online, reported on 28 Jan 2014) https://faktencheck-gesundheit.de/filead min/daten_fcg/Dokumente/130828_Themenblatt_ENGLISCH_Kaiser schnitt.pdf 41 Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, Wapner RJ, Varner MW, Rouse DJ, Thorp JM Jr, Sciscione A, Catalano P, Harper M, Saade G, Lain KY, Sorokin Y, Peaceman AM, Tolosa JE, Anderson GB.Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A Multicenter, Randomized Trial of Treatment for Mild Gestational Diabetes. N Engl J Med 2009; 361: 1339–1348 42 Persson M, Fadl H, Hanson U, Pasupathy D. Disproportionate body composition and neonatal outcome in offspring of mothers with and without gestational diabetes mellitus. Diabetes Care 2013; 36: 3543–3548 43 Duncan GE, Li SM, Zhou XH. Prevalence and trends of a metabolic syndrome phenotype among US Adolescents, 1999–2000. Diabetes Care 2004; 27: 2438–2443 44 Kaufman FR. Type 2 diabetes in children and youth. Endocrinol Metab Clin North Am 2005; 34: 659–676 ix–x 45 Hillier TA, Pedula KL, Schmidt MM, Mullen JA, Charles MA, Pettitt DJ. Childhood obesity and metabolic imprinting: the ongoing effects of maternal hyperglycemia. Diabetes Care 2007; 30: 2287–2292 46 Catalano PM, Farrell K, Thomas A, Huston-Presley L, Mencin P, de Mouzon SH, Amini SB. Perinatal risk factors for childhood obesity and metabolic dysregulation. Am J Clin Nutr 2009; 90: 1303–1313 47 Bouchard L. Epigenetics and fetal metabolic programming: a call for integrated research on larger cohorts. Diabetes 2013; 62: 1026–1028 48 El Hajj N, Pliushch G, Schneider E, Dittrich M, Müller T, Korenkov M, Aretz M, Zechner U, Lehnen H, Haaf T. Metabolic programming of MEST DNA methylation by intrauterine exposure to gestational diabetes mellitus. Diabetes 2013; 62: 1320–1328
König AB et al. Gestational Diabetes Outcome in … Horm Metab Res 2014; 46: 804–809
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Endocrine Care 809
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Authors
A. B. König, S. Junginger, J. Reusch, F. Louwen, K. Badenhoop
Affiliation
Division Endocrinology & Diabetology, Department of Internal Medicine 1 and Department of Obstetrics of the University Hospital, Goethe-University, Frankfurt am Main, Germany
Key words ▶ body mass index ● ▶ metabolic syndrome in ● childhood ▶ insulin in pregnancy ●
Abstract
▼
The aim of the study was to examine obstetric outcomes and metabolic disorders in patients with gestational diabetes mellitus (GDM) and their offspring compared to mothers without GDM and their offspring. We performed a retrospective single center cohort study of mothers with GDM using a questionnaire with items concerning the maternal medical history, neonatal complications, and child development. Mothers with gestational diabetes (GDM; n = 130) and those with normal glucose tolerance (NGT; n = 77) were recruited. GDM mothers were older (37.58 years vs. 34.32 years, p < 0.0001) and had a greater body mass index (25.18 kg/m² vs. 23.37 kg/m², p < 0.01). There were no significant differences regarding the mean birth weight, the frequency of Cesarean sections, and the preva-
Introduction
▼ received 07.02.2014 accepted 23.04.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1375652 Published online: May 27, 2014 Horm Metab Res 2014; 46: 804–809 © Georg Thieme Verlag KG Stuttgart · New York ISSN 0018-5043 Correspondence Dr. A. B. König Europa-Allee 57 60327 Frankfurt Germany Tel.: + 49/69/17526 727 Fax: + 49/69/15631 319 [email protected]
It is widely known that GDM is associated with an increased risk for the development of type 2 diabetes [1, 2] in mothers in later life as well as with obstetric and neonatal complications such as preterm delivery [3], miscarriages [4], macrosomia [5, 6], birth trauma [7], and neonatal respiratory distress [8]. Besides these effects, there is growing evidence for an impairment of somatometric development of children exposed to maternal hyperglycemia during pregnancy, especially concerning overweight and metabolic syndrome in childhood and adolescence [9]. The analysis of somatometric data of German children between 1998 and 2004 showed a continuously rising BMI at any age [10]. Maternal hyperglycemia during pregnancy may lead to metabolic alterations in the offspring such as obesity, insulin resistance, and higher blood pressure in comparison to children whose mothers were not affected by GDM [11–13]. The
König AB et al. Gestational Diabetes Outcome in … Horm Metab Res 2014; 46: 804–809
lence of macrosomia (> 4 000 g). At follow-up (pediatric U5 screening visit after 6 months of birth) children of mothers with GDM had significantly higher BMI than the children of the NGT group (17.07 kg/m² vs. 16.59 kg/m², p = 0.042). GDM women in need of insulin therapy during pregnancy had higher BMI than dieting GDM mothers and experienced more frequently an operative vaginal delivery (17.95 % vs. 6.17 %, OR 3.23, p = 0.04). We found less significant differences between GDM mothers with treatment of impaired glucose tolerance and NGT mothers concerning the neonatal outcome than expected. Despite higher BMI of the GDM group’s offspring at follow-up U5 visit, the children did not show any other development disorder. In conclusion treatment of GDM could minimize the frequency of obstetric and neonatal complications in this risk group.
present study’s aim was a follow-up evaluation of mothers and their children exposed to an impaired glucose homeostasis during pregnancy. The health situation of women who suffered from GDM and were treated in the University Hospital of Frankfurt am Main between 2002 and 2007 as well as the development of their children were studied in detail and compared to the health status of mothers with normal glucose homeostasis and their children.
Subjects and Methods
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Study design We performed a retrospective case control-study at the University Hospital of Frankfurt am Main after approval of the local ethics committee. The health status of women with GDM during pregnancy was assessed using a questionnaire developed specifically for this study at the University Hospital of Frankfurt. Furthermore, data from
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Gestational Diabetes Outcome in a Single Center Study: Higher BMI in Children After Six Months
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Study subjects The women who participated in the study were divided into 2 groups: Women were eligible for inclusion into the GDM group if they were diagnosed with GDM in pregnancy between July 2002 and December 2007 by using a 75 g oGTT and whose blood sugar adjustment was performed at the University Hospital of Frankfurt am Main. The exclusion criterion was a prepregnancy diagnosis of diabetes. Women with normal glucose tolerance in each preceding pregnancy could be included into the NGT group. All patients gave written informed consent.
lems with conception or necessity for assisted reproduction techniques. Eventually we focused on the course of pregnancy as well as the delivery. This included the maternal body weight, the duration of pregnancy, the mode of delivery and the somatometric data of the newborn as well as possible complications. GDM mothers were asked whether they were treated by diet alone or if they required insulin therapy. The children’s somatometric development when exposed to maternal GDM was analyzed based on the recordings in the children’s medical check-up booklet and their medical history was inquired for the same internal diseases the mothers were asked for.
Data analysis The data analyses were performed with the statistical program BiAS, version 9.08 for Windows. The data were summarized as means and standard deviation or medians and interquartile ranges for continuous variables and as frequencies and percentages for categorical variables. The statistical comparison between the patient-collective and the corresponding control group was made with the 2-sample t-test based on the calculated mean values and standard deviations in case of parametric data. The results of nonparametric data were tested on the basis of median, maximum and minimum using the Wilcoxon–Mann– Whitney test or the median test. Odds ratios were used to compare the GDM and NGT group concerning the frequency of maternal internal disorders as well as adverse obstetrical and neonatal outcomes. In addition to comparisons between the GDM and NGT groups, data from women in the GDM group who were treated by diet alone and those who had insulin treatment were analyzed separately. A p-value of < 0.05 was regarded as statistically significant.
Results
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Study subjects In total, 207 women living in and around Frankfurt am Main were enrolled in the study. Of these 130 were affected by GDM defined by OGT in at least one pregnancy. The NGT group constituted the remaining 77 mothers with constantly glucose tolerance in each pregnancy. Enrolment of GDM patients for the study occurred between May 2009 and April 2010. The enrolment of the 77 healthy mothers without a history of GDM was completed between March 2010 and August 2010. The majority (89.61 %) of these were recruited in the maternity wards of the University Hospital of Frankfurt and the hospital of Frankfurt-Höchst. The remaining 10.39 % of the NGT group could be contacted with the help of child care facilities in Frankfurt.
Maternal outcomes and clinical characteristics Data collection The multisided questionnaire developed in the University Hospital contained questions concerning maternal somatometric data like body weight, height, and the resultant body mass index at the present time as well as before conception. Furthermore the mothers were asked about maternal diabetes mellitus, dyslipidemia, hypertension, and thyroid diseases in their own as well as in first degree relative’s medical history. Moreover the patients were asked about their gynecological and obstetric history, for previous miscarriages, irregular menstruations, prob-
The special population pattern of Frankfurt needs to be considered when interpreting the maternal characteristics. In 2009, the city counted 678 353 inhabitants, about 24.3 % of them had a migratory background. It is well known that the incidence of GDM – similar to type 2 diabetes – varies according to race, origin, and place of residence [19]. However, since the study participants were not asked for their ethnicity or migration, we can only speculate that up to a quarter of our patients may have had such a background.
König AB et al. Gestational Diabetes Outcome in … Horm Metab Res 2014; 46: 804–809
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mothers affected by GDM and their children were compared with those of mother-child pairs not affected by maternal hyperglycemia. During the course of the study there were still international and regional differences regarding the cutoffs in an oGTT with 75 g glucose for the diagnosis of GDM. The German Diabetes Association (DDG) as well as the American Diabetes Association (ADA) recommended the threshold values according to Carpenter and Coustan [14], whereas the Land Hesse – and thus in Frankfurt – the stricter limits were applied that had been recommended by the Hesse Diabetes Society [15]: Fasting: ≥ 90 mg/dl, 1 h postprandial: ≥ 160 mg/dl, 2 h postprandial ≥ 140 mg/dl in venous plasma. However, only 3 of the women in our study underwent the 75 g OGTT at the University hospital, the others were diagnosed out of hospital and presented to our department afterwards. We also enrolled women, who exceeded only one of these 3 threshold values in a venous blood specimen. According to the DDG and the ADA, GDM was diagnosed if at least 2 measured values exceeded the limits of Carpenter and Coustan after ingestion of 75 g glucose, only one exceeded value was declared as impaired glucose tolerance. In accordance with the new Guidelines of the German Diabetes Association, GDM can also be diagnosed if only one of the predetermined cutoffs is exceeded, whereas these values – based on the results of the HAPO-Study [16] – differ slightly from the former criteria: Fasting: ≥ 92 mg/dl, 1 h postprandial: ≥ 180 mg/ dl, 2 h postprandial ≥ 153 mg/dl. Thus the more strict criteria of the Hesse GDM definition include slightly more women. In Frankfurt, treatment of GDM targeted blood sugar adjustment in accordance with the recommendations in the AWMF-Guideline of 2001 (fasting blood sugar 60–90 mg/dl, 1 h postprandial ≤ 140 mg/dl, 2 h postprandial ≤ 120 mg/dl) [17], which has now been replaced by the new guidelines of the German Diabetes Association (DDG) and the German Society of Gynecologists and Obstetricians published in August 2011 [18]. All women diagnosed with GDM were educated in glucose self-monitoring and change of lifestyle based on individual dietary and exercise regimens. The women were closely monitored, so that an insulin therapy was started if the blood glucose targets were exceeded.
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GDM mothers were older and had a greater body mass index at the time of assessment (37.58 years and 25.18 kg/m² vs. 34.32 years; p < 0.0001 and 23.37 kg/m; p < 0.01) There were no significant differences concerning the prevalence of the selected internal disorders between the 2 groups. The proportion of smokers among the women in the GDM was higher than that in the NGT group, which is a clinically meaningful difference (17.7 % vs. 7.89 %; OR 2.51, p = 0.051). Mothers with GDM were more likely to have a family history of gestational diabetes (19.23 % vs. 5.26 %; OR 4.29, p = 0.01). No significant differences ▶ Table 1 proexisted for the frequency of thyroid disorders. ● vides an overview of these characteristics.
There were no significant differences concerning the frequency of preeclampsia, Cesarean section (36.0 and 28.57 % in the GDM and NGT group, OR 1.41; p = 0.28) and the necessity for operative vaginal delivery (as compared with spontaneous delivery). We observed no significant differences between the groups regarding the mean birth weight (3406.62 g vs. 3456.09 g; p = 0.5) and no difference in the prevalence of macrosomia (6.19 % in the GDM and 9.68 % in the NGT group; p = 0.57). Furthermore, there were no differences concerning neonatal complications such as jaundice, respiratory distress, neonatal ▶ Table 2). infections or hypoglycemia (●
Irregular menstruations and problems with conception were not significantly more common in the GDM or the NGT group, whereas GDM was associated with a significantly higher rate of miscarriages in the women’s reproductive history (30.77 % vs. 9.09 %; OR 4.44, p < 0.001). Whereas the obstetric outcome data of the NGT group relate to the women’s first pregnancy, this was not the case in the GDM group, because not every patient developed GDM during her first pregnancy. At the time of the analyzed pregnancy GDM mothers were significantly older than those of the NGT group (32.59 years vs. 29.41 years; p < 0.0001) and showed a significantly higher prepregnant BMI (24.44 kg/m² vs. 22.38 kg/m²; p < 0.01). By contrast, the maternal weight gain during pregnancy was significantly higher in the NGT group (12.23 ± 5.73 vs. 14.17 ± 5.51; p = 0.04) regarding the pregnancies finished by term (38–41th week of pregnancy). The percentage of women in the GDM group who reached the recommendations for weight gain during pregnancy of the Institute of Medicine [20] was 35.05 % vs. 27.78 % in the NGT group. Thirty-three percent of women with GDM (vs. 40.74 % of NGT women) gained more and 31.96 % (vs. 12.96 %) gained less weight than recommended. GDM mothers who required an insulin therapy during pregnancy amounted to 32.5 %. These women showed a significantly higher BMI both at the time of assessment and before the analyzed pregnancy (27.04 ± 7.22 vs. 23.13 ± 3.64; p = 0.003 and 27.71 ± 6.77 vs. 23.75 ± 3.84; p = 0.002).
GDM mothers who required insulin therapy during pregnancy amounted to 32.5 %. Insulin therapy was started if glucose concentrations were repeatedly high (fasting, 1- and/or 2-h postprandial readings) and obstetrical characteristics like fetal biometrics suggested beneficial insulin effects. Insulin treatment was started in an interdisciplinary consultation with the gynecologists. For the purpose of this study the participant’s individual glucose readings and insulin requirements were not quantitated. Besides a significantly higher body mass index, women in need of insulin therapy experienced more frequently an instrumental vaginal mode of delivery (17.95 % vs. 6.17 %, OR 3.23; p = 0.04) and the rate of the diagnosis of type 1 diabetes diagnosed after the pregnancy was significantly higher. Thereby, all GDM mothers diagnosed with type 1 diabetes after delivery required insulin during pregnancy, but none of them was diagnosed with type ▶ Table 3). 1diabetes during pregnancy (●
Child development At the time of the U5 check-up (5th follow-up pediatric assessment in the 6th to 7th month of life) the children of mothers with GDM had a significantly higher BMI than the children of the NGT ▶ Fig. 1). A simigroup (17.07 kg/m² vs. 16.59 kg/m²; p = 0.042) (● lar trend is seen at check-up U6 (17.06 ± 1.57 vs. 16.63 ± 1.19, p = 0.051) (data not shown).
Table 1 Maternal biometric and clinical data.
Age (years) BMI (kg/m²)
GDM (n = 130)
NGT (n = 77)
95 % CI
37.58 ± 5.07 25.18 ± 5.49
34.32 ± 4.69 23.37 ± 3.88
1.83–4.69 0.32–3.29
53/123 (43.09) 9 (6.92) 10 (7.69) 5 (3.85) 3 (2.31) 25 (19.23) 35 (26.92) 24/35 (68.57) 3/35 (8.57) 8/35 (22.86) 23 (17.7 %)
18/68 (26.47) 7 (9.21) 2 (2.63) 0 (0) 1 (1.32) 4 (5.26) 14 (18.42) 10/14 (71.43) 2/14 (14.29) 2/14 (14.29) 6 (7.89 %)
2.1 (1.11–4.0) 0.73 (0.26–2.05) 3.08 (0.7–13.52) 6.71 (0.77–58.14) 1.77 (0.19–16.93) 4.29 (1.53–11.98) 1.63 (0.81–3.27) 0.87 (0.22–3.45) 0.56 (0.83–3.79) 1.78 (0.33–9.67) 2.51 (0.99–6.33)
p-Value < 0.0001 < 0.01
Internal disorders Odds Ratio (95 % CI) BMI > 25 kg/m² ( %) Dyslipidemia ( %) Hypertension ( %) Type 1 diabetes diagnosed after the analyzed pregnancy ( %) † Type 2 diabetes diagnosed after the analyzed pregnancy ( %) † First-degree relatives with a history of GDM ( %) Thyroid disease ( %) Total Hypothyroidism Hyperthyroidism Others Smoking
p-Value 0.02 0.55 0.14 0.08 0.62 0.01 0.17 0.85 0.55 0.51 0.051
Values are means ± SD †
A type 1 diabetes mellitus at the time of pregnancy was, such as a preexisting type 2 diabetes, an exclusion criterion. Thus, the reported frequency of type 1 and type 2
diabetes refers to cases diagnosed after pregnancy
König AB et al. Gestational Diabetes Outcome in … Horm Metab Res 2014; 46: 804–809
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Insulin therapy Obstetric characteristics
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Table 2 Maternal characteristics in the course of the pregnancy and the neonatal biometric data.
Age at analyzed pregnancy (years) Prepregnant BMI (kg/m²) Weight gain during pregnancy up to the 38th to 41st week (kg) Male/Female Newborns Birth weight (mean ± SD) Total Male Female
GDM (n = 130)
NGT (n = 77 )
95 % CI
32.59 ± 4.65 24.44 ± 5.49 12.23 ± 5.73 73/44 3 406.62 ± 463.69 3 498.2 ± 443.39 3 264.58 ± 483.5
29.41 ± 5.26 22.38 ± 3.13 14.17 ± 5.51 42/33 3 456.09 ± 463.25 3 545.74 ± 457.5 3 355.54 ± 464.97
1.74–4.61 0.61–3.50 − 3.84 to –0.04
p-Value < 0.0001 < 0.01 0.04
− 195.43–96.47 − 238.13–143.05 − 330.47–148.56
0.5 0.62 0.45
41/120 (34.17) 17/128 (14.17) 40 (30.77) 5/127 (3.94) 45/125 (36) 12/125 (9.6) 10/114 (8.77) 6/97 (6.19) 6/61 (9.84) 0/36 (0) 3/129 (2.33) 7/129 (5.43) 25/129(19.38) 4/129 (3.1) 3/129 (2.33)
13/66 (19.7) 14/76 (18.42) 7 (9.09) 4/76 (5.26) 22/77 (28.57) 9/77 (11.69) 10/76 (13.16) 6/62 (9.68) 4/34 (11.76) 2/28 (7.14) 4/75 (5.33) 1/75 (1.33) 17/75 (22.67) 1/75 (1.33) 4/75 (5.33)
2.12 (1.04–4.3) 0.68 (0.31–1.47) 4.44 (1.97–10.04) 0.74 (0.19–2.83) 1.41 (0.76–2.6) 0.8 (0.32–2.01) 0.63 (0.25–1.6) 0.62 (0.19–1.99) 0.82 (0.21–3.15) 0.15 (0.01–1.51) 0.42 (0.1–1.87) 4.25 (0.6–30.03) 0.82 (0.41–1.64) 2.37 (0.28–20.36) 0.42 (0.1–1.87)
Obstetric and neonatal outcome and complications
Total Male Female
Malformation ( %) Postpartal hypoglycemia ( %) Jaundice ( %) Respiratory distress ( %) Infection of the newborn ( %)
p-Value 0.04 0.32 < 0.001 0.66 0.28 0.64 0.34 0.42 0.77 0.11 0.26 0.15 0.58 0.43 0.26
Values are means ± SD
Table 3 Maternal biometric characteristics and clinical data in GDM mothers with and without insulin therapy during pregnancy.a Insulin therapy
Yes (n = 40)
No (n = 83)
95 % CI
p-Value
Age at analyzed pregnancy (years) Pregravid BMI (kg/m²) BMI at assessment (kg/m²) Internal disorders
32.26 ± 4.37 27.04 ± 7.22 27.71 ± 6.77
32.69 ± 4.9 23.13 ± 3.64 23.75 ± 3.84
− 2.27–1.42 1.91–5.91 2.01–5.92
0.65 0.003 0.002
Odds Ratio (95 % CI)
p-Value
Dyslipidemia ( %) Hypertension ( %) Operative vaginal delivery ( %) Cesarean delivery ( %) Type 1 diabetes diagnosed after the analyzed pregnancy ( %) Type 2 diabetes diagnosed after the analyzed pregnancy ( %) a
5/37 (13.51) 4/39 (10.26) 7/39 (17.95) 18/39 (46.15) 5/35 (14.29) 2/36 (5.56)
3/83 (3.61) 4/81 (4.94) 5/81 (6.17) 26/81 (32.1) 0/83 (0) 1/83 (1.2)
4.17 (1.03–16.88) 2.2 (0.53–9.09) 3.23 (1.03–10.76) 1.81 (0.83–3.97) 30.11 (4.48–202.29) 4.82 (0.52–44.72)
0.05 0.28 0.04 0.14 < 0.001 0.17
Seven GDM patients did not answer the questions concerning the conducted therapy
Discussion
▼
The main significant findings in GDM mothers are a higher body mass index, a higher age at pregnancy, and a positive family history for GDM. The higher BMI was also associated with a greater risk for the need of insulin treatment. There were nonsignificant differences in thyroid disorders that need to be further studied in larger data sets. Hereby it is possible that amongst these women later manifesting permanent hyperglycemia, a latent autoimmune diabetes in adults (LADA) may be hidden. Our findings are based on a retrospective evaluation of questionnaire data without immediate metabolic testing in the postpartal phase, which is a limitation of the study. However such data have proven useful in the assessment of postpartal medical issues when young mothers prefer to report in questionnaires rather than to an out-patient department [21].
While a higher prevalence of type 2 diabetes in the time course after a diabetic pregnancy has been reported [1, 2], we only find slightly more mothers in the GDM than in the NGT group with newly diagnosed type 2 diabetes postpartum. Five patients in the GDM group (3.85 %) were diagnosed with type 1 diabetes in the years following their diabetic pregnancy but none of the mothers in the NGT group. This observation is in contrast to previous studies [22, 23]. However, other address the increased risk of type 1 diabetes after GDM [24, 25], particularly in the case of insulin-controlled GDM [26]. Unfortunately, we had no information about islet antibodies, but 3 of the mothers with type 1 diabetes also suffer from hypothyreoidism. Among these, at least 2 were diagnosed with Hashimoto’s thyreoiditis, which can be seen as a combination of an autoimmune polyglandular syndrome.
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Odds Ratio (95 % CI) Prepregnant BMI ≥ 25 kg/m² ( %) Irregular menstruations ( %) History of abortion ( %) Pre-eclampsia ( %) Cesarean delivery ( %) Operative vaginal delivery ( %) Premature delivery < 37 + 0 SSW ( %) Macrosomia 4 000 g ( %)
Fig. 1 Relative distribution of the children’s body mass index according to the age and gender specific standards at the time of the U5 children’s examination. The table above the figure shows the rate of children falling above the 50th percentile.
The worldwide increase in childhood and adolescent obesity as well as type 2 diabetes [43, 44] underlines the significance of an effective prevention including maternal hyperglycemia in pregnancy [45]. It remains unclear whether a maternal GDM alone or its combination with maternal overweight and fetal macrosomia increases the risk of obesity and metabolic disorders in their offspring as early as in childhood or adolescence [11, 46]. Future studies should address somatometric and metabolic child development up to adolescence and adulthood in relation to maternal GDM treatment control. Such clinical studies are important since GDM may have long-lasting epigenetic effects by imprinting developmental genes [47] such as malprogramming of a paternally expressed mouse homolog of the mesoderm-specific transcript (MEST) gene, a finding that can also be made in adult obesity [48]. In conclusion, the treatment of GDM can limit obstetric and neonatal complications of GDM. Larger cohorts are needed to elucidate how treatment of GDM can improve the offspring’s metabolism also in adolescence and adulthood.
Acknowledgement
▼ The low prevalence of type 2 diabetes may be due to the limited time interval of 2–8 years observation after delivery and diabetes may manifest later. Recent studies on the development of type 2 diabetes after a pregnancy complicated by GDM showed rates between 5 and 30 %, depending upon the applied diagnostic criteria and the time of screening whereas the rate of prediabetic metabolic conditions was correspondingly higher [27, 28]. A better prediction of later diabetes may be achieved by measuring the HbA1c level during pregnancy [29]. There were less differences between the mothers in the GDM and the NGT group for their gynecologic and obstetric history than described previously [30, 31]. The reported rates of miscarriages in patients with GDM or preexisting diabetes vary. A trial carried out on 489 pregnant women in the early 80’s showed 12.5 % miscarriages in women with GDM, which was not significantly higher than in mothers with normal glucose tolerance [32]. In concordance with other trials [33, 34], we found a significantly higher rate of preceding miscarriages among the women in the GDM group. The frequency of pre-eclampsia and Cesarean section did not differ significantly between the groups, but assisted vaginal delivery was more frequent in the insulin treated GDM patients. A higher risk for operative deliveries has repeatedly been described in mothers with GDM [35–38]. Interestingly the risk appears to persist despite adequate therapy [39]. On the background of a high rate of Cesarian sections in Germany – 31.9 % in 2010 [40] – we found a trend to more frequent Cesarean sections in the GDM group. Nevertheless, early diagnosis and adequate therapy can reduce the frequency of Cesarean sections in GDM [41]. On the assumption that our patients complied with their treatment, we assume that this explains the small difference in the frequency of Cesarean sections to NGT mothers. Furthermore, we observed no differences in the frequency of neonatal complications such as preterm delivery, neonatal hypoglycemia, jaundice, or respiratory distress. This is in contrast to results from the Swedish Birth Registry, where the composite neonatal morbidity was enhanced in GDM [42]. That we detect fewer differences may be due to the inclusion of mild GDM forms and the limited size of our cohorts.
We thank Professor V. Möbus for helping us recruiting patients in Frankfurt-Höchst.
Conflict of Interest
▼
The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.
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