Diabetic patient and reproduction

Current views and opinions on pregnancy in diabetic mothers are presented. Special attention is paid to carbohydrate metabolism, pregestational diabetes mellitus (PGDM), gestational diabetes mellitus (GDM) and unclear heterogenous etiology of gestational diabetes mellitus (GDM). Suggestions for identification, diagnosis and treatment of GDM with an emphasis on early screening strategy are given. Obstetrical management and possible perinatal complications are discussed.     

Diabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control study

Although the excess risk for birth defects among children of mothers with diabetes mellitus is well documented, there are few data concerning the risk for specific malformations. In the Atlanta Birth Defects Case-Control Study, those risks for malformations were evaluated. The population-based study included 4929 live and stillborn babies with major malformations ascertained by the Metropolitan Atlanta Congenital Defects Program in the first year of life born to residents of Metropolitan Atlanta between 1968 and 1980. The study also included 3029 nonmalformed live babies who were frequency-matched to case babies by race, period of birth, and hospital of birth. The relative risk for major malformations among infants of mothers with insulin-dependent diabetes mellitus (n = 28) was 7.9 (95% confidence interval [CI]1.9, 33.5) compared with infants of nondiabetic mothers. The relative risks for major central nervous system and cardiovascular system defects were 15.5 (95% CI = 3.3, 73.8) and 18.0 (95% CI = 3.9, 82.5), respectively. The absolute risks for major, central nervous system, and cardiovascular system malformations among infants of diabetic mothers were 18.4, 5.3, and 8.5 per 100 live births, respectively. Infants of mothers with gestational diabetes mellitus who required insulin during the third trimester of pregnancy were 20.6 (95% CI = 2.5, 168.5) times more likely to have major cardiovascular system defects than infants of nondiabetic mothers. The absolute risk for infants of this group of diabetic mothers was 9.7%. No statistically significant differences were found among infants of mothers with gestational diabetes mellitus who did not require insulin during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Are the neonatal outcomes similar in large-for-gestational age infants delivered by women with or without gestational diabetes mellitus?

Background

Infants are considered large for gestational age (LGA) if their birth weight is greater than the 90th percentile for gestational age and they have an increased risk for adverse perinatal outcomes. Maternal diabetes is one of the factors affecting birthweight. However there are limited data on the perinatal outcomes of infants of gestational diabetic mothers. The aim of the present study was to compare the neonatal outcomes of LGA infants delivered by women with and without gestational diabetes mellitus.

Methods

This was a retrospective study of LGA infants of ??36 weeks of gestation born at the Gazi University Medical School Hospital during the period of 2006?C2009. Neonatal outcomes included hypoglycemia and polycythemia in the early neonatal period and hospital admissions. The Chi-square and Student??s t test were used for comparing variables.

Results

Seven hundred eligible infant-mother pairs were enrolled in the study. Eighty-seven of them (12.4%) were infants of gestational diabetic mothers and 613 (87.6%) were infants of non-diabetic mothers. The incidence of hypoglycemia at the first hour was higher in infants of diabetic mothers (12.8%) than in infants of non-diabetic mothers (5.3%) (P=0.014). Polycythemia was also more frequently observed in infants of the gestational diabetic mothers (9.3%) than in infants of the non-diabetic mothers (3.0%) (P=0.010). Although overall hospital admission rates were not different between the two groups, infants of diabetic mothers were more likely to be admitted because of resistant hypoglycemia (P=0.045).

Conclusions

The results of this study suggested that LGA infants of mothers with gestational diabetes mellitus were at a greater risk for hypoglycemia and polycythemia in the early neonatal period than LGA infants of nondiabetic mothers.     

Long-term developmental follow-up of infants of diabetic mothers

The neurodevelopmental consequences of maternal insulin-dependent diabetes were studied in 109 infants of diabetic mothers and 90 control infants. The infants born to diabetic mothers included 70 "early entry" subjects and 39 "late entry" subjects. Maternal diabetes control during pregnancy was significantly better in "early entry" mothers than in late-entry mothers, as determined by glycosylated hemoglobin levels. Infants were examined by a psychologist and a developmental pediatrician unaware of group status at 6, 12, 24, and 36 months of age; 71% of the subjects completed the 3-year study. Neurodevelopment of early-entry subjects was similar to that of control subjects, whereas late-entry subjects scored less well on language measures. Mean head size in late-entry subjects was significantly less (p = 0.03) than in either control subjects or early-entry subjects at age 3 years, and correlated negatively with glycosylated hemoglobin levels during all three trimesters. Less optimal intellectual development was associated with reduced head circumference. In addition, the presence of major congenital malformations was associated with reduced developmental performance through age 2 years. Our results indicate that mothers with insulin-dependent diabetes who maintain good control during pregnancy can expect to have infants who are neurodevelopmentally normal; mothers whose diabetes is less well controlled may have infants with less optimal neurodevelopment. (J PEDIATR 1994;125:S9-17)     

Neonatal Hypoglycaemia in Infants of Diabetic Mothers given Sulphonylurea Drugs in Pregnancy

Three infants whose diabetic mothers were given chlorpropamide and one infant whose diabetic mother was given acetohexamide up to the time of delivery were studied in the neonatal period because each became severely hypoglycaemic. The sulphonylurea drugs given to the mother crossed the placenta, and fetal plasma concentrations were in the therapeutic range for adults with diabetes mellitus. Each baby had severe hyperinsulinaemia resulting in profound hypoglycaemia. These acutely ill infants needed vigorous and prolonged treatment to correct the hypoglycaemia. In two infants exchange transfusion was performed to remove the drug. These sulphonylurea drugs should not be used to control diabetes mellitus in pregnancy.     

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.     

Clinical-epidemiologic assessment of pattern of birth defects associated with human teratogens: application to diabetic embryopathy

The concepts of sensitivity, specificity, and predictive value can be used to assess patterns of birth defects associated with human teratogens. Although sensitivity of any single defect is generally low for many known teratogens, the presence of specific defect combinations is usually predictive of the teratogen. To evaluate the patterns of birth defects associated with diabetic embryopathy, a sensitivity-specificity analysis was performed on 4929 infants with major defects ascertained by the population-based Metropolitan Atlanta Congenital Defects Program between 1968 and 1980. By reviewing hospital records, maternal insulin-dependent diabetes mellitus was confirmed in 26 infants. Patterns of defects were evaluated among infants born to mothers with insulin-dependent diabetes mellitus and compared with the rest of the Metropolitan Atlanta Congenital Defects Program case population. Multiple logistic regression analysis was used to assess defect combinations that predict for insulin-dependent diabetes mellitus. Of 26 infants, 8 had multiple defects. However, most defects and their combinations were poorly sensitive and predictive for insulin-dependent diabetes mellitus. The predictive value for insulin-dependent diabetes mellitus was greatest for the combination of vertebral and cardiovascular anomalies (6.5%). Also, several pathogenetic mechanisms were noted among patients with insulin-dependent diabetes mellitus, such as cell migration defects, cell death events, deformations, and cardiac flow lesions. The inability to find a clear-cut phenotype for diabetic embryopathy may be due to several etiologic factors and mechanisms associated with diabetic embryopathy.     

Emergence of behavioural states in fetuses of type-1-diabetic women

The aim of this study was to investigate the effects of tightly controlled maternal (type-1-)diabetes mellitus on the development of fetal behavioural states. Seventeen diabetic women, who required insulin (White's class C predominantly) and were treated with continuous subcutaneous insulin infusion (CSII) therapy, participated in the study. Adjustment to an insulin-pump occurred before conception or during early pregnancy. In all diabetic women (near-)normoglycemia was achieved during pregnancy, with glycosylated hemoglobin-values within the normal range (6-8.5%). Fifty-three 2-h recordings of fetal heart rate, uterine contractions and of real-time ultrasound scanning for fetal body movements, breathing and eye movements were obtained from the 17 fetuses. The fetuses were longitudinally studied between 32 and 40 weeks post menstrual age, at intervals of 2 weeks. The 3 state variables, fetal heart rate, body movements and eye movements, were analyzed for the presence of combinations meeting the definitions of the four fetal behavioural states. Findings in the fetuses of diabetic women were compared with those obtained from 28 low risk fetuses. The criteria of states were met in only 3 of 8 fetuses studied at 38 weeks and in one of two studied at 40 weeks. For comparison: in low risk fetuses studied at 38 and 40 weeks, states were present in 70% and 90% of the cases, respectively. This poorly developed state organization exhibited by the near term fetuses of the diabetic group, was related to maternal parity, but not to pre- or postconceptional onset of CSII-treatment. Fetuses of nulliparous diabetic women showed more often asynchrony of transitions (greater than 3 min) and interruption of periods of concordant association. This resulted in significantly higher percentages of 'no-coincidence' and in low incidence of behavioural states as compared with control fetuses of nulliparous women. In the few multiparous diabetic cases studied near term the development of fetal behavioural states was normal. We conclude therefore that, despite tight control of maternal diabetes, the development of behavioural states is disturbed in fetuses of nulliparous diabetic women.     

Relationship of prospective diabetes control in pregnancy to neonatal cardiorespiratory function

We evaluated two groups of diabetic women in pregnancy who differed primarily in the time of initiation of careful diabetes management. Group A (early) were entered in the first trimester (n = 35); group B (late) were entered in the late second or early third trimester (n = 28). Normal women delivering at the same period were used as controls (n = 23). All infants were evaluated by a thorough clinical and echocardiographic examination between 24 and 72 hours of life. Both groups of infants of diabetic mothers had mild increase in mean thickness of ventricular and septal walls compared with those of normal newborn infants, and both had a significant percentage with septal hypertrophy (43% vs 39%). None of the infants in the early group had respiratory symptoms requiring oxygen therapy, compared with 19% in the late group. The early group had significantly fewer infants with elevated right ventricular systolic time interval ratios than did the late group (20% vs 50%); none of the normal infants had elevated ratios. We conclude that careful management of diabetes in pregnancy reduces the severity of hypertrophic cardiomyopathy, although no advantage of early vs late management was obvious. Early management does significantly reduce the number of infants of diabetic mothers who develop respiratory symptoms requiring oxygen therapy.     

Glucose disappearance in infants of diabetic mothers I. Relationship to maternal glucose tolerance and insulin production

Glucose disappearance and insulin response were determined in mother--infant pairs of normal, gestational diabetic and diabetic pregnancies following an intravenous glucose load. Mothers were studied in the third trimester of pregnancy and at least 6 wk postpartum. Significant differences were present in glucose disappearance and insulin response in both gestational diabetic and diabetic mothers during pregnancy compared with the control group. Infants were studied within 4 h of birth while fasting, and glucose and insulin levels followed through the first 3 days of life. Neonatal hypoglycemia did not occur and glucose disappearance (KT) was not different among the three groups. There was no correlation between maternal glucose tolerance or insulin production and that of their infants. The only distinguishing factor among the infants was higher insulin production in infants of diabetic mothers during the 60-min intravenous glucose tolerance test which persisted up to 4 h following the infusion. It is concluded that factors other than the degree of maternal glucose tolerance are responsible for the development of neonatal hypoglycemia in infants of diabetic mothers, most notably control of maternal diabetes, the amount of glucose infused immediately before delivery and neonatal glucose production.     

Psychomotor development in the children of mothers with type 1 diabetes mellitus or gestational diabetes mellitus

The purpose of this study was to examine psychomotor development in children born to mothers with type 1 diabetes mellitus (DM1) or gestational diabetes mellitus (GDM). The influence of metabolic control in pregnant diabetic mothers and complications during labor on their children's psychological and physical development was evaluated. The analysis included 59 children, 20 of mothers with GDM, 19 of mothers with DM1, and 20 children of healthy mothers. Clinical observations and medical history were recorded and children were assessed using the Brunet-Lezine Psychomotor Development Scale. Abnormalities were found more often in the children of mothers with DM1 whose illness was insufficiently controlled during pregnancy and of mothers with serious hypoglycemia while pregnant. Speech, eye-movement coordination and social aspects were affected.     

Follow-up of Children of Insulin Dependent (Type I) and Gestational Diabetic Mothers

ABSTRACT. Fifty-three children of insulin dependent (IDM) and 20 children of gestational diabetic mothers (IGDM) representing 80 and 91 %, respectively, of all surviving infants of diabetic mothers born between 1969 and 1972 at Sabbatsberg's hospital, Stockholm, participated in the follow-up study. The first follow-up examination was performed when the children had reached approximately 5 years of age and included measurement of height and weight, insulin response to intravenous glucose, and HLA typing. When the children were approximately 11 years old, a search was performed in the national register for type I diabetes in children in order to ascertain the frequency of type I diabetes mellitus in the total series ( n =88). The majority of children had a normal height for age and desirable weight for height. At the first follow-up all children had normal glucose disappearance rates ( k _t) and the insulin response including the early insulin response to glucose were not different between IDM and IGDM groups. The frequency distribution of HLA antigens (A, B, C) was not different from normal and there was no association between HLA B 8 and/or B 15 and early insulin respone or k _t values. At the second follow-up, two children of type I diabetic mothers had acquired type I diabetes, both were HLA B 15 positive, had normal k _t values at the first follow-up, one with low, one with a high early insulin response. The frequency of type I diabetes in offspring of insulin dependent diabetic mothers was 3%.     

Follow-up of children of insulin dependent (type I) and gestational diabetic mothers. Growth pattern, glucose tolerance, insulin response, and HLA types

Fifty-three children of insulin dependent (IDM) and 20 children of gestational diabetic mothers (IGDM) representing 80 and 91%, respectively, of all surviving infants of diabetic mothers born between 1969 and 1972 at Sabbatsberg's hospital, Stockholm, participated in the follow-up study. The first follow-up examination was performed when the children had reached approximately 5 years of age and included measurement of height and weight, insulin response to intravenous glucose, and HLA typing. When the children were approximately 11 years old, a search was performed in the national register for type I diabetes in children in order to ascertain the frequency of type I diabetes mellitus in the total series (n = 88). The majority of children had a normal height for age and desirable weight for height. At the first follow-up all children had normal glucose disappearance rates (kt) and the insulin response including the early insulin response to glucose were not different between IDM and IGDM groups. The frequency distribution of HLA antigens (A, B, C) was not different from normal and there was no association between HLA B 8 and/or B 15 and early insulin response or kt values. At the second follow-up, two children of type I diabetic mothers had acquired type I diabetes, both were HLA B 15 positive, had normal kt values at the first follow-up, one with low, one with a high early insulin response. The frequency of type I diabetes in offspring of insulin dependent diabetic mothers was 3%.     

Cardiomyopathy and cardiomegaly in stillborn infants of diabetic mothers.

To report the incidence of cardiomegaly in stillborn normally formed infants of mothers with diabetes mellitus. This is a retrospective study with institutional ethics approval. The presence of cardiomegaly was recorded in stillborn infants of diabetic mothers (N = 27) and compared with that recorded in stillborn large-for-gestational age (LGA > 90th percentile, n = 18) and stillborn appropriately grown (10th to 90th percentiles, n = 107) nondiabetic infants. Blinded to the clinical details, the histology slides were reviewed to measure cardiac wall thickness and to record the presence or absence of myocardial fiber disarray. Stillborn infants of mothers with diabetes mellitus, when compared with appropriately grown stillborn nondiabetic infants and when adjusted for birth weight, had heavier hearts, thicker ventricular free wall measurements, and lighter brains. While cardiomegaly was reported in 22% of stillborn LGA infants, comparison with stillborn appropriately grown infants revealed no difference in heart weights corrected for birth weight. Comparison of LGA nondiabetic infants with stillborn diabetes mellitus infants revealed greater actual heart weight/expected for birth weight (P < 0.05) and lighter brains (actual brain weight/expected for birth weight, P < 0.05) in the diabetes mellitus group. Cardiomegaly is a common finding in stillborn infants of mothers with diabetes mellitus and may contribute to the risk of fetal death in these pregnancies.     

Hypertrophic cardiomyopathy and transposition of great arteries associated with maternal diabetes and presumed gestational diabetes

Maternal diabetes mellitus affects the foetal heart both structurally and functionally. In early gestation, it has a teratogenic effect causing defects of primary cardiogenesis. In late gestation, it causes a unique form of hypertrophic cardiomyopathy. We report an infant of a diabetic mother and an infant where there was presumed gestational diabetes during the pregnancy who presented with combined severe hypertrophic cardiomyopathy and complex transposition of the great arteries. This rare combination of structural and functional cardiac abnormalities reflects the different mechanisms and timings of injury that may occur to the foetal heart in association with maternal diabetes and has not been previously reported. The combination has significant implications regarding medical and surgical management, and necessitates prolonged supportive therapy whilst awaiting regression of the hypertrophic cardiomyopathy followed by delayed arterial switch operation. CONCLUSION: We describe two infants with the unusual combination of both hypertrophic cardiomyopathy and transposition of the great arteries. One was an infant of a diabetic mother, and the second was associated with presumed gestational diabetes.     

Maternal and infant use of erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic pyloric stenosis

OBJECTIVES: To evaluate the risk for infantile hypertrophic pyloric stenosis (IHPS) among infants prescribed systemic erythromycin, infants prescribed a course of erythromycin ophthalmic ointment, and infants whose mothers were prescribed a macrolide antibiotic during pregnancy. STUDY DESIGN: Retrospective cohort study of infants born at an urban hospital from June 1993 through December 1999. RESULTS: Of 14,876 eligible infants, 43 (0.29%) developed IHPS. Infants prescribed systemic erythromycin had increased risk of IHPS, with the highest risk in the first 2 weeks of age (relative risk = 10.51 for erythromycin in first 2 weeks, 95% CI 4.48, 24.66). Erythromycin ophthalmic ointment for conjunctivitis was not associated with increased risk of IHPS. Maternal macrolide antibiotics within 10 weeks of delivery may have been associated with higher risk of IHPS but the data were not conclusive. CONCLUSIONS: This study confirms an association between systemic erythromycin in infants and subsequent IHPS, with the highest risk in the first 2 weeks of age. No association was found with erythromycin ophthalmic ointment. A possible association with maternal macrolide therapy in late pregnancy requires further study. Systemic erythromycin should be used with prudence in early infancy.     

Neonatal hypoglycaemia in infants of diabetic mothers

OBJECTIVE: To determine whether umbilical cord blood glucose correlates with subsequent hypoglycaemia after birth in infants of well-controlled diabetic mothers. METHODOLOGY: Thirty-eight term infants of well-controlled diabetic mothers were enrolled. Five mothers had pre-existing diabetes. Of the 33 gestational diabetic mothers, 16 were managed on insulin and 17 on diet. Maternal blood glucose was maintained between 4 and 8 mmol/L during labour and delivery. Infants' plasma glucose levels were measured from venous cord blood and serially, at less than 30 min, 1 h and 2 h of life by glucose hexokinase method. Blood glucose levels were further monitored by bedside Dextrostix for 24 h. RESULTS: Eighteen (47%) infants developed hypoglycaemia (blood glucose level less than 2 mmol/L) during the first 2 h of life. There was no difference in the cord blood glucose levels between infants with or without hypoglycaemia (3.7 +/- 1.1 vs 4.5 +/- 1.1 mmol/L, respectively). Infants of mothers with diabetes diagnosed prior to 28 weeks gestation were at a higher risk of developing hypoglycaemia (8 of 10 vs 10 of 28, OR 7.2, 95%CI 1.3-40.7). Hypoglycaemic infants were of significantly higher birthweight, and were more likely to be born to Caucasian mothers and by Caesarean section. Raised maternal fructosamine blood level, the need for insulin treatment or the infant's haematocrit were not different between infants with or without hypoglycaemia. CONCLUSIONS: In well-controlled diabetic mothers, the incidence of early hypoglycaemia in infants is still high, particularly in those mothers who had a longer duration of diabetes. Cord blood glucose level did not identify the infants with hypoglycaemia.     

Neonatal diabetes mellitus: patient report and review of the literature

A female infant born at 33 weeks gestation to a gestationally diabetic mother developed apnea and respiratory distress at 6 hours of age. Laboratory investigation demonstrated persistent hyperglycemia, and the patient was treated with continuous intravenous and subsequent subcutaneous insulin therapy. Detailed laboratory investigation to reveal the etiology of hyperglycemia and further endocrine evaluation were not significant. The baby's insulin requirement has continued thereafter, and she is being followed up in an outpatient clinic still under insulin therapy at 18 months of age. Neonatal diabetes mellitus should be considered in the differential diagnosis of neonatal hyperglycemia, and it may develop in newborns born to diabetic mothers, as well as neonatal hypoglycemia. Insulin treatment with close blood glucose monitoring is essential as long as hyperglycemia persists since neonatal diabetes mellitus may be either transient or permanent and it is not possible to differentiate these two outcomes before 18 months of age.     

Morbidity and mortality among a cohort of human immunodeficiency virus type 1-infected and uninfected pregnant women and their infants from Malawi, Zambia, and Tanzania

BACKGROUND: Morbidity and mortality patterns among pregnant women and their infants (before antiretroviral therapy was widely available) determines HIV-1 diagnostic, monitoring, and care interventions. METHODS: Data from mothers and their infants enrolled in a trial of antibiotics to reduce mother-to-child-transmission of HIV-1 at 4 sub-Saharan African sites were analyzed. Women were enrolled during pregnancy and follow-up continued until the infants reached 12 months of age. We describe maternal and infant morbidity and mortality in a cohort of HIV-1-infected and HIV-1-uninfected mothers. Maternal and infant factors associated with mortality risk in the infants were assessed using Cox proportional hazard modeling. RESULTS: Among 2292 HIV-1-infected mothers, 166 (7.2%) had a serious adverse event (SAE) and 42 (1.8%) died, whereas no deaths occurred among the 331 HIV-1 uninfected mothers. Four hundred twenty-four (17.8%) of 2383 infants had an SAE and 349 (16.4%) died before the end of follow-up. Infants with early HIV-1 infection (birth to 4-6 weeks) had the highest mortality. Among infants born to HIV-1-infected women, maternal morbidity and mortality (P = 0.0001), baseline CD4 count (P = 0.0002), and baseline plasma HIV-1 RNA concentration (P < 0.0001) were significant predictors of infant mortality in multivariate analyses. CONCLUSIONS: The high mortality among infants with early HIV-1 infection supports access to HIV-1 diagnostics and appropriate early treatment for all infants of HIV-1-infected mothers. The significant association between stage of maternal HIV-1 infection and infant mortality supports routine CD4 counts at the time of prenatal HIV-1 testing.     

Insulin oedema in a child with newly diagnosed diabetes mellitus

Insulin oedema is a rare complication of insulin therapy for diabetes mellitus. It has been reported in type 1 diabetes mellitus, in poorly controlled type 2 diabetes mellitus following either the initiation or intensification of insulin therapy and in underweight patients on large doses of insulin. There are only a few case reports since it was first described in 1928, showing that it is an uncommon and probably an under-reported complication. The majority of those reports have been in the adult population. The generalised oedema tends to develop shortly after initiation or intensification of insulin therapy and resolves spontaneously within few weeks. We present one of the youngest patients reported in the literature, a 9-year-old boy who developed insulin oedema within few days of presenting with diabetic ketoacidosis. The case highlights the importance of recognising this generally transient and self-resolving complication and differentiating it from other serious causes of oedema.