Maternal type 1 and gestational diabetes: postnatal differences in insulin secretion in offspring at preschool age

Background: It is well known that children born to mothers with diabetes in pregnancy are more likely to develop metabolic abnormalities in later life. Most prior studies have not differentiated between offspring of mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) or lack a control group of non‐exposed offspring. Subjects: Offspring of T1DM (n = 16), GDM (n = 22) and mothers without diabetes (n = 25) born at Oulu University Hospital. Aim: To assess insulin secretion and insulin resistance in the offspring of T1DM and GDM at preschool age in comparison with offspring of non‐diabetic mothers. Methods: Anthropometric measurements and intravenous glucose tolerance testing were performed. First‐phase insulin response (FPIR) and homoeostasis model assessment (HOMA) values were calculated. Pregnancy and birth data were analysed in relation to later metabolic parameters in all three groups using one‐way analysis of variance (anova ) and analysis of covariance (ancova ). Results: At a mean age of 4.9 yr, offspring of T1DM had increased fasting serum insulin concentrations (p = 0.044), FPIR (p = 0.034) and HOMA‐B values (p = 0.008) compared with offspring of GDM or with offspring of healthy controls (statistically non‐significant). The GDM gained least weight during pregnancy, and when adjusted for maternal weight gain during pregnancy, there were no statistically significant differences between study groups. Conclusions: Prenatal exposures to maternal type 1 and gestational diabetes may have different effects on postnatal glucose metabolism in the offspring assessed at a mean age close to 5 yr. Maternal weight gain in pregnancy may affect the postnatal glucose metabolism in the offspring.     

Developmental outcome of offspring of pregestational diabetic mothers

The aim of this study was to investigate the one-year developmental outcome of offspring of mothers with pregestational diabetes mellitus (PGDM). We prospectively evaluated 31 women with PGDM (21 with type 1 DM and 10 with type 2 DM) and 41 nondiabetic controls during pregnancy and for one year follow-up. Data showed that offspring of mothers with PGDM scored lower than controls in all aspects of development--mental, psychomotor, and exploration/orientation. Despite the good metabolic control of the mothers with PGDM, their offpsring showed a less favorable developmental outcome at one year than infants of nondiabetic mothers. MDI score and PDI score were significantly lower in the diabetic group than in the controls (91.04 vs 98.15, p<0.05 and 85.15 vs 95.54, p<0.05, respectively). In addition, the orientation/engagement score was lower in the diabetic group as compared with the nondiabetic group (41.04 vs 45.50, p<0.05). Whereas no significant difference was found between the type 1 and type 2 groups with regard to the MDI score, type 2 infants scored lower on the PDI than infants in the type 1 group (78.1 vs 89.3) but higher on the motor quality score (34.0 vs 31.3). These preliminary findings support the need for ongoing large scale developmental follow-up studies of offspring born to diabetic mothers in order to elucidate whether they have cognitive impairment later in life.     

Intrauterine diabetic environment confers risks for type 2 diabetes mellitus and obesity in the offspring, in addition to genetic susceptibility

Numerous studies have reported that offspring whose mothers had type 2 diabetes mellitus (DM) are more likely to develop type 2 DM, impaired glucose tolerance, and obesity at an early age than offspring whose fathers had DM. Exposure to the diabetic intrauterine environment has been shown to be an important risk factor for all these conditions. To what extent transmission of type 2 DM from mother to offspring is the effect of genetic inheritance and to what extent it is the long-term consequence of exposure to maternal hyperglycemia is still uncertain. There are, of course, interactions between the diabetic intrauterine environment and genetics. Several data in experimental animals as well as in humans suggest, however, that exposure of the fetus to the mother's DM confers a risk for type 2 DM and obesity that is above any genetically transmitted susceptibility. In the Pima Indian population much of the increase in childhood type 2 DM can be attributed to the diabetic intrauterine environment. This suggests that intensive glucose control during pregnancy might have extended beneficial effects, contributing to a decrease in the prevalence of childhood type 2 DM.     

Impact of early growth delay on subsequent fetal growth and functional development: a study on diabetic pregnancy.

In the first trimester of type-1 diabetic pregnancy, the embryo and fetus are often smaller than normal (early growth delay). We examined the impact of early growth delay on subsequent growth (birth weight) and functional development near term (organizational level of fetal behavioral states) in 21 and 10 fetuses of diabetic women, respectively. There was no relationship between the degree of early growth delay and birth weight (centiles). Mean growth delay per fetus in early diabetic pregnancy was negatively correlated with the occurrence of no-coincidence between behavioral state parameters at 36 weeks (R = -0.59; P < 0.05). These results indicate that disorders occurring in early life may underlie abnormal functional development in later life, whereas (catch up) growth is mainly determined during the second half of pregnancy.     

大鼠不同时期高脂饮食对子代糖脂代谢的影响及机制研究

目的 探讨Sprague-Dawley母鼠不同时期高脂饮食对子代糖脂代谢的影响及相关机制。 方法 根据孕前及孕期哺乳期饮食的不同,将母鼠随机分为4组（n=9）：CC组（孕前、孕期哺乳期均正常饮食）、HC组（孕前高脂饮食、孕期哺乳期正常饮食）、CH组（孕前正常饮食、孕期哺乳期高脂饮食）、HH组（孕前、孕期哺乳期均高脂饮食）;子代生后3周断奶后,全部给予正常饮食。记录母鼠孕前、孕期体重及仔鼠体重。取各组幼年期（3周）、成年期（12周）雄性仔鼠,检测空腹血糖（glucose,GLU）、胰岛素（insulin,INS）及肝脏三酰甘油（triglyceride,TG）、总胆固醇（total cholesterol,TC）水平,计算胰岛素抵抗指数（homeostasis model assessment of insulin resistance,HOMA-IR）、糖耐量试验（glucose tolerance test,GTT）及胰岛素耐量试验（insulin tolerance test,ITT）的曲线下面积（area under the curve,AUC）;取肝脏组织行苏木精-伊红染色和油红O染色,观察肝脏脂质沉积;检测肝脏糖脂代谢关键基因IR、IRS、AKT和FASN、SREBP1c、PPARα的mRNA及其蛋白表达水平。 结果 孕前高脂饮食组（HC组、HH组）母鼠体重较正常饮食组（CC组、CH组）显著增加（P<0.001）;HC组、CH组、HH组母鼠孕期增重较CC组显著增加（P<0.001）。生后3周时,HC组、CH组、HH组的仔鼠体重、肝脏TG及TC含量,以及FASN、SREBP1c、PPARα的mRNA及其蛋白表达水平均较CC组显著增加（P<0.05）,肝脏脂质沉积增加,其中HH组增加最显著;HH组的空腹GLU及INS水平、HOMA-IR、GTT-AUC、ITT-AUC及肝脏p-IRS蛋白表达水平均较CC组显著增加,肝脏IR、IRS的mRNA及其蛋白表达水平均较CC组显著降低（P<0.05）。生后12周时,HC组、CH组、HH组的仔鼠体重、空腹GLU及INS水平、HOMA-IR、GTT-AUC、ITT-AUC、肝脏TG及TC含量、p-IRS蛋白表达水平,以及FASN、SREBP1c、PPARα的mRNA及其蛋白表达水平均较CC组显著增加（P<0.05）,肝脏脂质沉积增加,其中HH组增加最显著;HC组、CH组、HH组IR、IRS、AKT的mRNA水平均较CC组显著降低,IR、IRS、p-AKT蛋白表达水平均较CC组显著降低（P<0.05）。HC组与CH组在不同时期的糖脂代谢水平未见显著性差异（P>0.05）。 结论 大鼠怀孕前后不同时期的高脂饮食对子代的糖脂代谢具有不同的影响,孕前、孕期、哺乳期全程高脂饮食对子代糖脂代谢影响最大;大鼠高脂饮食对其子代糖脂代谢的影响考虑与糖脂代谢基因的表达改变有关。 引用格式:     

Congenital abnormalities in the offspring of pregnant women with type 1, type 2 and gestational diabetes mellitus: A population‐based case‐control study

To estimate the risk of structural birth defects (i.e. congenital abnormalities [CA]) in the offspring of pregnant women with type 1 (DM‐1), type 2 (DM‐2) and gestational diabetes mellitus (GDM) and to check the efficacy of recent specific care of diabetic pregnant women in the reduction of DM‐related CA. Comparison was made of the occurrence of medically recorded types of diabetes mellitus in pregnant women who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population‐based Hungarian Case‐Control Surveillance System of Congenital Abnormalities, 1980–1996. In the case group, which included 22 843 offspring, there were 79 (0.35%) pregnant women with DM‐1, 77 (0.34%) pregnant women with DM‐2 and 120 (0.53%) pregnant women with GDM. The control group comprised 38 151 newborns, and 88 (0.23%), 141 (0.37%) and 229 (0.60%) pregnant women with DM‐1, DM‐2 and GDM, respectively. The total rate of cases with CA was higher only in the DM‐1 group (adjusted OR with 95% CI: 1.5, 1.1–2.0) and within four specific types/groups: isolated renal a/dysgenesis, obstructive CA of the urinary tract, cardiovascular CA and multiple CA; namely, caudal dysplasia sequence. The risk of total CA was lower in the present study compared to the risk in previous studies and the DM‐1‐related spectrum of CA was also different. There was no higher risk of total CA in the offspring of pregnant women with DM‐2 and GDM. The certain part of maternal teratogenic effect of DM‐1 is preventable with appropriate periconceptional and prenatal care of diabetic women.     

Growth and motor development in fetuses of women with type-1 diabetes. II. Emergence of specific movement patterns.

In 20 women with type-1 diabetes, the emergence of fetal movement patterns was studied using real-time ultrasound. One-hour recordings were made once a week between the 7th and 17th week of gestation. Data were compared to those obtained in uncomplicated pregnancy. The diabetic women were being treated with continuous subcutaneous insulin infusion (CSII) therapy. Except for breathing movements, there was a 1-2 week delay in the first appearance of all movement patterns which normally emerge during the first 12 weeks of pregnancy. Breathing movements were observed for the first time at an earlier age than in the control fetuses (P less than 0.02). When the emergence of frequently occurring movement patterns was plotted against fetal crown-rump length, which is usually smaller in diabetic pregnancy, there was still a general delay in comparison with the control group. The delay in motor development therefore does not run completely parallel with the delay in growth. This indicates the possible existence of a specific diabetes-related influence on the functional development of the embryonic and fetal nervous system. Hyperglycaemia, for example, may be responsible, as the delay in the emergence of fetal general movements was most profound in the women whose periconceptional quality of glucose control was poor.     

Delayed developmental sequences in rodent diabetic embryopathy

Diabetes induced by alloxan at day 6 of gestation in Wistar rats produced decreased fetal growth, delayed skeletal ossification, decreased fetal kidney beta-glucuronidase, and an increased frequency of fetal birth defects which correlated with the degree of diabetic control. Offspring of severely diabetic mothers (mean blood glucose greater than 501 mg/dl) sacrificed at 20 days had a mean weight of 2.12 +/- 0.16 g, a mean of 1.8 +/- 0.46 caudal ossification centers, and a 28% incidence of birth defects as compared to 3.70 +/- 0.22 g, 5.9 +/- 0.42 caudal centers, and 1.1% defects for controls. Offspring of severely diabetic mothers sacrificed at 21 days had mean numbers of caudal and sternal ossification centers which did not significantly differ from controls, indicating that decreased ossification observed at 20 days of gestation is a delayed developmental sequence which is mostly corrected by 21 days. Offspring of moderately diabetic (mean blood glucose 300-500 mg/dl) and insulin-treated dams (mean blood glucose 152-168 mg/dl) had intermediate degrees of growth or ossification delay and birth defect frequency at both the 20- and 21-day sacrifices. Maternal diabetes also retards the developmental increase in fetal kidney beta-glucuronidase such than 20-day offspring of severely diabetic mothers had a mean specific activity of 1.1 nmol/min/mg compared to 3.0 nmol/min/mg for controls. The results support prior studies in rodents suggesting a progression of early growth delay, altered developmental sequences, and birth defects in diabetic pregnancy. This progression is suggested as a common teratogenic mechanism which has implications for evaluating analogous pregnancies in man.     

母亲糖尿病及UCP2基因多态性与子代先天性心脏病关联的病例对照研究

目的 探讨母亲糖尿病、解偶联蛋白2基因（UCP2）多态性及两者的交互作用与子代先天性心脏病（CHD）的关系。方法 采用以医院为基础的病例对照研究,选择2018年3月至2019年8月在湖南省儿童医院确诊的464例单纯CHD患儿的母亲为病例组,选择同期住院、无先天畸形的504例患儿的母亲为对照组。通过问卷调查,收集相关暴露信息,同时采集母亲静脉血5 mL,用于UCP2基因多态性检测。采用多因素logistic回归分析探讨母亲糖尿病、UCP2基因多态性及两者交互作用与子代CHD的关联性。结果 多因素logistic回归分析显示,在控制混杂因素后,患有妊娠期糖尿病（OR=2.96,95% CI：1.57~5.59）、有妊娠期糖尿病史（OR=3.16,95% CI：1.59~6.28）和妊娠前患有糖尿病（OR=4.52,95% CI：2.41~8.50）均显著增加子代CHD的风险（P < 0.05）。母亲UCP2基因两个位点rs659366（T/C vs C/C：OR=1.49,95% CI：1.02~2.16;T/T vs C/C：OR=2.77,95% CI：1.67~4.62）和rs660339（A/A vs G/G：OR=2.19,95% CI：1.34~3.58）的多态性与子代CHD的风险存在关联（P < 0.05）。交互作用分析显示,UCP2基因两个位点（rs659366和rs660339）的多态性与母亲糖尿病在子代CHD发生中存在交互作用（P < 0.05）。结论 母亲糖尿病、UCP2基因多态性及其交互作用与子代CHD发病相关。     

Preterm birth and maternal smoking in pregnancy are strong risk factors for aortic narrowing in adolescence

AIM: Preterm transition from foetal to neonatal circulation might permanently alter aortic growth and development. To test this hypothesis, we measured aortic dimensions in adolescents born very preterm. METHODS: Eighty-six healthy 15-year-old subjects were studied; 45 born very preterm at an average gestational age of 28 weeks (birth weight < 1500 g) and 41 controls born at term. Using a pulse-gated Fiesta sequence on a 1.5T MR-scanner, 25 images were collected within the heart cycle at several levels of the descending aorta. End-diastolic cross-sectional areas were semi-automatically calculated using an active contour model. RESULTS: Subjects born preterm had narrower aortic lumen. The difference was 16% in the thoracic and 19% in the abdominal aorta after adjustment for body surface area and gender (p < 0.001). Maternal smoking in pregnancy was also found to be an independent risk factor for aortic narrowing in the offspring (difference 10%-13% throughout the aorta vs. offspring to nonsmoking mothers). Adolescents born preterm had higher systolic and diastolic blood pressures; however, blood pressures did not correlate with aortic size or maternal smoking during pregnancy. CONCLUSION: Very preterm birth and exposure to maternal smoking in foetal life are independent and strong risk factors for general aortic narrowing 15 years after birth.     

Fetal growth retardation due to maternal tobacco smoke exposure in the rat

Smoking during pregnancy results in offspring with an average birth weight 200 g less than those of non-smoking mothers. The pathogenesis of this effect is still unknown and there is no general agreement about the causal relationship between maternal smoking and subsequent fetal growth retardation. In the present study, a model of maternal smoking during pregnancy in the rat was established using the P & I Walton Exposure Machine. The study consisted of three groups: control, pair-fed, and smoke-exposed. Smoke-exposed animals were exposed continuously to tobacco smoke for cycles of 7 min, 16 times a day from d 5 to d 20 of gestation. On d 21 of gestation, fetuses from all groups were removed by cesarean section, weighed, and dissected. The fetal brain, liver, and lungs as well as the placentas were weighed and analyzed for nucleic acid content. Fetal weight was found to be significantly reduced in both pair-fed and smoke-exposed groups compared with the control group. There was also a significant reduction in fetal body weight of the animals in the smoke-exposed group in comparison to those in the pair-fed group. Exposing the mother to smoke affected neither fetal brain weight nor nucleic acid content whereas fetal liver and lungs showed a significant decrease in both weight and nucleic acid content. These results indicate that the fetal growth retardation associated with maternal exposure to tobacco smoke in the rat corresponds to a disproportionate type.(ABSTRACT TRUNCATED AT 250 WORDS)     

Research priorities in diabetic pregnancy today: the role of animal models

Strict metabolic control has resulted in a striking fall in the rates for stillbirths, neonatal deaths and neonatal morbidity in diabetic pregnancy. However, clinical problems and challenges for research remain, particularly in relation to a high incidence of congenital malformation, low birth weight, and early growth delay; the detection and management of gestational diabetes; insulin delivery systems; the consequences of maternal hypoglycaemia on organogenesis and fetal well-being; the mechanisms underlying various categories of neonatal morbidity, and possible long-term morbidity in the children born to diabetic mothers. The nature of these problems determines that certain fundamental aspects of reproduction which are difficult to study in human pregnancy will have high priority for research. Progress in this field will be heavily dependent on animal models in the foreseeable future.     

Perinatal risk factors for early childhood onset type 1 diabetes in Austria – a population-based study (1989–2005)

Background:  To investigate the rapid increase in incidence of type 1 diabetes mellitus (T1DM) in children <5 yr in Austria.
Methods:  Data of children born between 1989 and 2005 (n = 444) from the T1DM children incidence registry were linked with birth certificates (n = 1 407 829).
Results:  Age of mother, level of education, birth weight, birth length, body mass index, and APGAR score at 10 min were not significant. Boys have about 25% higher risk than girls [hazard ratio = 0.75, 95% confidence interval (CI): 0.62–0.91]. The risk of developing diabetes increases over time significantly (1989–1991 vs. 2001–2005, hazard ratio = 2.86, 95% CI: 2.07–3.94). The linear effect of parity is borderline significant (p = 0.045), with lower risks for second and later born siblings. Marital status is significant [hazard ratio = 0.73, 95% CI: 0.57–0.90)]. Native-born children exhibit twice as high risk as non-native children (hazard ratio = 0.51, 95% CI: 0.37–0.71). Birth weight shows a positive but not significant effect on risk of T1DM.
Conclusions:  In this very young and rapidly increasing cohort of diabetic children <5 yr of age, no association with birth weight but with year of birth, gestational age, nationality and parity could be observed.     

Naturally occurring intrauterine growth retardation and adult blood pressure in rats

In humans, infants who are born small have been reported to have higher blood pressure in adulthood than do larger infants. This suggests that factors in the intrauterine environment that affect fetal growth can program the individual for hypertension later in life. The present study determined whether there is a similar, naturally occurring relationship between birth weight and adult blood pressure in rats. Female Sprague-Dawley rats bred in our colony were fed a normal diet during pregnancy. On the day of delivery, any pups that weighed <90% of the mean pup weight for the litter were identified as runts. For each runt, a sex-matched littermate of normal weight was also identified and assigned to this study. These pairs were chronically instrumented at approximately 20 wk of age. Mean arterial pressure was significantly higher in runt male and female offspring compared with their normal birth weight littermates (males: 149 +/- 7, runts versus 129 +/- 4 mmHg, controls; females: 128 +/- 1, runts versus 119 +/- 2 mmHg, controls). Although the runts had smaller body weights at study than did their littermate controls, the kidney-to-body weight ratio and renal function normalized to kidney or body weight were not different. These studies indicate that adult blood pressure is related to birth weight in rats, as it is in humans. The relative hypertension in runt animals is not due to gross differences in renal function but may be related to more subtle renal structural and/or functional differences.     

Outcome of very-low-birth-weight (< 1,500 grams) infants born to mothers with diabetes

Premature delivery is common in pregnancies complicated by maternal diabetes. However, the outcome of very-low-birth-weight infants (VLBWI) born to mothers with diabetes is not known. Employing a matched double-cohort design, we investigated the influence of maternal diabetes on the outcome of VLBWI born in Winnipeg from 1988 to 1994. We compared mortality rates and early and late morbidity rates in VLBWI born to mothers with diabetes mellitus (DM) (cases, n = 43, 23 with gestational DM and 20 with pregestational DM) and without DM (controls, n = 539). Controls were matched for gestational age (GA), sex, and the year of birth. All subjects were enrolled in the Newborn Follow-Up Program. Relative risks and 95% confidence limits were calculated for each variable and Chi 2 analysis, Student t-test, and Mann-Whitney test were used as appropriate for analysis. Diabetes mellitus control was assessed by conventional criteria. There were no differences between cases and controls in mode of delivery, birth weight (mean +/- SD, 1,160 +/- 25 g vs 1,110 +/- 26 g), GA (29 +/- 2.8 wk vs 29 +/- 2.4 wk), smallness for gestational age (35% vs 30%), head circumference (26.5 +/- 1.9 vs 26.2 +/- 2.2 cm), length (38.8 +/- 2.8 vs 37.5 +/- 3.7 cm), Apgar score < 4 at 1 min (42% vs 40%) and < 7 at 5 min (37% vs 42%). Incidence of hyaline membrane disease (60% vs 71%), bronchopulmonary dysplasia (33% vs 31%), patent ductus arteriosus (30% vs 43%), necrotizing enterocolitis (12% vs 12%), sepsis (23% vs 25%), acute renal failure (9% vs 10%), intraventricular hemorrhage--all grades (74% vs 64%), retinopathy of prematurity--all stages (30% vs 26%), median days on ventilator (4 vs 4 days), and median days on supplemental oxygen (46 vs 42 days) were similar in both groups (p = NS, 95% confidence limits included 1 for all of these variables). There was no significant difference in mortality (21% vs 15%) or the incidence of major congenital anomalies. Weight, head circumference, and length at 6, 12, and 18 months were similar in both groups. There were no group differences in developmental quotients, prevalence of neurodevelopmental impairments, respiratory morbidity, or number of hospitalizations up to the last follow-up (18 months). Our data suggest that with contemporary perinatal care there is no significant increase in mortality rates or early and late morbidity rates between VLBWI born to mothers with DM and VLBWI of nondiabetic mothers. It seems that with reasonable diabetic control, prematurity rather than the diabetic state determines the neonatal outcome, and this knowledge can be useful in parental counselling.     

Psychomotor and audiological assessment of infants born to mothers with subclinical thyroid dysfunction in early pregnancy

BACKGROUND: To investigate the frequency and the effects of various degrees of maternal thyroid dysfunction in the first trimester of pregnancy, before the onset of fetal thyroid function, on psychomotor and audiological outcome of the offspring. METHODS: In a cohort of 691 pregnant women, undergoing thyroid screening between the 8th and 10th gestational week, eight were found to have a subclinical form of hypothyroidism and one was frankly hypothyroid. Treatment with L-thyroxine was started soon after diagnosis was made. Their nine offspring had a psychomotor and audiological assessment at the age of nine months. Psychomotor development was evaluated with the Brunet-Lèzine test, while audiological function was assessed with auditory brainstem responses (ABR's). RESULTS: Psychomotor developmental quotients were not different in patients and controls (99 +/- 6 vs 101 +/- 4). Regarding ABR pattern, there were no significant differences between patients and controls. Moreover, no correlation was found between maternal fT4 and psychomotor as well as audiological outcome in the offspring. CONCLUSIONS: These findings are reassuring, since various degrees of maternal thyroid dysfunction in early pregnancy seem to have no adverse effects on the psychomotor and audiological outcome of the offspring up to nine months of age. A longer follow-up however is needed before definitive statements can be made.     

Seasonality of month of birth among African American children with diabetes mellitus in the city of Chicago

AIM: To study the seasonality of month of birth among African American children with insulin-treated diabetes mellitus (DM) in the city of Chicago, in order to determine whether perinatal exposures play a significant role in diabetes risk among children of non-European origin. METHOD: The Chicago Childhood Diabetes Registry ascertains new cases of insulin-treated DM among minority children < 18 years of age; these cases were compared with birth certificate data for the general African American population in Chicago. The chi2 test and Poisson regression were used to compare the pattern of month of birth of children with DM (n = 604) to that of the general population (n = 758,658) over the same period of years (1968-1995). RESULTS: In a month-by-month comparison, there were significantly fewer children who later developed DM born during October (chi2 = 6.74, df = 1). This seasonal pattern was stronger among males (n = 284) than females (n = 320), and among those who apparently developed type 2 DM (n = 155) compared to those who developed type 1 DM (n = 449). Children who were diagnosed between 15 and 17 years of age (n = 131) demonstrated significant seasonality (chi2 = 27.6, df = 11) compared to the general population. CONCLUSIONS: The apparent protective effect of October birth, and the significant overall seasonality among those diagnosed at ages 15-17 years, suggest the possibility that seasonal environmental factors at conception, during pregnancy or in the neonatal period may affect DM risk in adolescence. The greater impact of month of birth in adolescent type 2 DM patients is surprising and seems to indicate a role for mechanisms other than the immunological ones previously suggested.     

Congenital Malformations in Diabetic Pregnancies Clinical Viewpoints

ABSTRACT. A consecutive series of 2 587 newborn infants of diabetic mothers treated during pregnancy and delivery in the period 1926 to 1983 has been analysed. The malformation rate was 6.6%. The series has been divided into five consecutive periods each comprising around 500 infants. During the first four periods the frequency of congenital malformations (CM) was remarkably constant also when related to the severity of the maternal diabetes. During the latest period from 1979 to 1983 a significant decrease in the frequency and severity of CM in infants of diabetic mothers was seen, most marked in the group with more severe maternal diabetes (White's classes D + F). One hundred and thirty-five insulin-dependent diabetic women with regular menstrual histories were examined by ultrasonic scanning in the 7th to 14th week of pregnancy. As judged by the crown-rump length 53 fetuses were smaller than normal. The term early growth delay is used for this phenomenon. Nine of the 135 fetuses had major CM and seven of them were smaller than normal in early pregnancy. These observations show that fetuses that are significantly smaller than normal in early pregnancy carry a higher risk of being malformed and suggest a common mechanism behind early growth delay and induction of abnormal embryogenesis.     

Teratogenic potential of pholedrine: A sympathomimetic vasoconstrictive drug – A population‐based case‐control study

Pholedrine was a frequently used drug for the treatment of severe hypotension in some countries, including Hungary. The possible teratogenic effect of pholedrine was not checked; therefore; the birth outcomes, particularly congenital abnormalities (CAs), of infants born to women treated with pholedrine during pregnancy, and pregnancy complications were evaluated in the population‐based large dataset of the Hungarian Case‐Control Surveillance System of Congenital Abnormalities. Cases with CA and their matched controls without CA born to mothers with pholedrine use during pregnancy were compared. Of 22 843 cases and 38 151 controls, 768 (3.4%) and 1509 (4.0%) were born to mothers with pholedrine treatment, respectively (adjusted odds ratios [OR] with 95% CI: 0.9, 0.8–1.0). There was no higher risk for any CA group in the offspring of mothers who used pholedrine during the second and/or third month of pregnancy (i.e. the critical period of most major CA). The mean gestational week at delivery and birthweight was similar in newborns of women with or without pholedrine treatment during pregnancy. The pattern of pregnancy complications was characteristic (lower incidence of preeclampsia/eclampsia, while higher incidence of severe nausea/vomiting and anemia), explained mainly by the underlying maternal hypotension. In conclusion, pholedrine treatment in pregnant women was not associated with a higher risk for CA or other adverse birth outcomes, such as preterm birth or low birthweight. The knowledge of the teratogenic potential of pholedrine may contribute to the evaluation of other sympathomimetic drugs.     

Maternal phenylketonuria in Western Australia: pregnancy outcomes and developmental outcomes in offspring

OBJECTIVE: To examine the outcomes of phenylketonuric (PKU) pregnancies in Western Australia including birth characteristics and cognitive and behavioural outcomes in offspring. METHODS: A cross-sectional study of women and their offspring who were identified from the Western Australian Maternal PKU Program (WAMPKUP) from 1991 to 2000 was carried out. Cognitive assessments (K-BIT or Griffiths scales) were conducted on women and their children, and behavioural assessments (CBCL) were conducted on the children. RESULTS: Thirty pregnancies by nine women were registered on the WAMPKUP between 1991 and 2000. There were 16 live births, with one preterm delivery at 32 weeks. There were no congenital abnormalities. Five of the nine mothers and their nine children (aged 18 months-10 years) participated in developmental assessments. A linear relationship was shown between lower maternal IQ scores and later attainment of metabolic control in pregnancy (rs = -0.828; P = 0.01). There was significant correlation between lower offspring IQ scores and later attainment of metabolic control in pregnancy (rs = -0.734; P = 0.02). Correlation between maternal and offspring cognitive scores was not significant. Four of nine (44%) children rated in the clinical range for behavioural problems. Compared to children with no behavioural difficulties, these children had lower cognitive abilities (P = 0.05) and maternal metabolic control during pregnancy was poor (P = 0.05). CONCLUSIONS: Poor metabolic control in pregnancy is associated with poorer cognitive outcomes and increased behavioural difficulties in offspring of mothers with PKU. The results have implications for the implementation of appropriate dietary measures before conception in PKU pregnancies, and indicate a need for the establishment of multidisciplinary teams to follow up individuals with PKU to communicate the importance of pregnancy planning, to manage PKU pregnancies, and to follow up the offspring.