Non-diabetic Mothers Research Articles

Cord blood islet autoantibodies and seasonal association with the type 1 diabetes high-risk genotype

Human leukocyte antigen DQ (HLA-DQ) genetic factors and islet autoantibodies are strongly associated with type 1 diabetes (T1D) and are currently used to predict T1D. This study examined whether islet autoantibodies in the cord blood of newborns to nondiabetic mothers were associated with the (T1D) high-risk genotype HLA-DQ2/8, gestational infections or both. Cord blood samples were taken from 33 683 newborns and used for HLA typing and analyses of islet autoantibodies. Parents completed questionnaires when the child was 2 months of age. The prevalence of newborn islet autoantibodies consistently varied with season over 4 years (P<0.0001); lowest in first quarter (1.2%) and highest in third (2.4%). Cord blood islet autoantibodies were associated with HLA-DQ2/8 in the second (OR, 2.30; P=0.02), third (OR, 2.12; P=0.008) and fourth quarters (OR, 2.49; P=0.007), but not in the first (OR, 1.13). Reported gastroenteritis was additionally associated with islet autoantibodies in the third quarter (OR, 1.80, P=0.04). An association between HLA and islet autoimmunity may depend on environmental exposure during pregnancy. Follow-up of mothers and children will determine risk of T1D.

Number of islet autoantibodies present in newly diagnosed type 1 diabetes children born to non-diabetic mothers is affected by islet autoantibodies present at birth

Cord blood islet autoantibodies in children born to mothers with type 1 diabetes may be associated with a reduced risk of islet autoimmunity and diabetes. The aim of this study was to investigate in children with type 1 diabetes but born to non-diabetic mothers whether islet autoantibodies at birth affected their presence at diagnosis. Serum samples at birth and at diagnosis were available from 141 children who developed type 1 diabetes between 1 and 19 yr of age (median 9.0 yr; male/female ratio 83/58). The samples were tested for autoantibodies against glutamic acid decarboxylase, insulinoma-associated antigen 2, and insulin as well as for islet cell antibodies. The human leukocyte antigen genotype was also determined. The frequency of islet autoantibodies in the umbilical cord blood was 11% compared with 91% at diagnosis. Children with fewer islet autoantibodies at diagnosis were more likely to have had autoantibodies at birth (p = 0.02). Autoantibodies present in cord blood at birth were observed in 25% (3/12) of children with no islet autoantibodies at diagnosis, in 17% (7/42) of children with one or two antibodies at diagnosis, and in only 5% (4/86) of children with more than two antibodies, demonstrating an inverse relationship between autoantibodies at birth and at diagnosis (test for trend, p < 0.001). Our preliminary data suggest that exposure to cord blood islet autoantibodies may influence the presence of islet autoantibodies at the time of diagnosis of type 1 diabetes and explain why some type 1 diabetes children are islet autoantibody negative at clinical diagnosis.

Leptin, Insulin, and Glucose Serum Levels in Large-for-Gestational-Age Infants of Diabetic and Non-Diabetic Mothers

It has been suggested that hyperleptinemia could be caused by hyperinsulinemia in infants of diabetic mothers (IDMs). To compare leptin, insulin, and glucose levels in large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) infants. A cross-sectional study was conducted in IDMs, infants of non-diabetic mothers (INDM) and AGA infants. Seventy-seven newborns were studied (11 IDM, 16 INDM, and 50 AGA infants). Leptin levels were significantly higher in LGA infants than in the AGA group and a trend for higher levels in IDM than NIDM was observed. Insulin levels and insulin resistance were significantly higher in IDMs. Glucose levels were lower in both groups of LGA infants. We found insulin resistance, hyperinsulinism and hyperleptinemia in IDMs, and the trend of higher leptin levels in IDMs than INDMs shows that leptin could be related to insulin resistance in these infants.

Large cross‐sectional area of the umbilical cord as a predictor of fetal macrosomia

To determine whether a large cross-sectional area of the umbilical cord is a predictor of fetal macrosomia. Consecutive patients of > 34 weeks' gestation, who presented for sonographic examination and who delivered within 4 weeks of the examination, were included in the study. The sonographic cross-sectional areas of the umbilical cord, the umbilical vessels and the Wharton's jelly were measured in a free loop of the umbilical cord. Logistic regression analysis was used to determine significant predictors of macrosomia (actual birth weight > 4000 g and > 4500 g). Fetal biometric parameters (biparietal diameter, abdominal circumference and femur length), sonographic estimated fetal weight and umbilical cord area > 95(th) centile for gestational age were used as covariates. During the study period, 1026 patients were enrolled. Fifty-three (5.2%) newborns had a birth weight > 4000 g, and 22 (2.1%) weighed > 4500 g. The proportion of cases with a large umbilical cord was significantly higher in the group of macrosomic compared with non-macrosomic infants (54.7% vs. 8.7%, P < 0.0001). Multiple regression models demonstrated an independent contribution of the large cord in the prediction of birth weight > 4000 g and > 4500 g (odds ratio (95% CI), 20.6 (9.2-45.9) and 4.2 (1.2-17.7), respectively). The sensitivity, specificity and positive and negative predictive values of a sonographic large umbilical cord were 54.7%, 91.3%, 25.4%, and 97.4%, respectively. The combination of abdominal circumference > 95(th) centile and large cord predicted 100% of macrosomic infants. The proportion of umbilical cords with a Wharton's jelly area > 95(th) centile for gestation was significantly higher in macrosomic fetuses of diabetic compared with non-diabetic mothers. Sonographic assessment of umbilical cord area may improve the prediction of fetal macrosomia.

Cardiopulmonary adaptation in large for gestational age infants of diabetic and nondiabetic mothers

To compare cardiopulmonary adaptation in large for gestational age infants of diabetic and nondiabetic mothers. Color Doppler echocardiography was performed in 113 (22 large for gestational age infants of diabetic mothers, 21 of nondiabetic mothers and 70 adequate for gestational age newborns) full-term infants. Pulmonary arterial pressure was significantly higher in infants of diabetic mothers than in those of nondiabetic mothers and normal infants at 24 h (38.5 vs. 32.5, and 35.5 mmHg, respectively). However, slow fall in this parameter was shown in all large for gestational age infants. Open ductus arteriosus was frequent in all large for gestational age infants, but its closure was significantly delayed in infants of diabetic mothers. Septal hypertrophy was higher in infants of diabetic mothers than in large for gestational age infants of nondiabetic mothers. Large for gestational age infants born from nondiabetic mothers showed delayed fall in pulmonary arterial pressure similar to those born from diabetic mothers but showed lower proportion of septal hypertrophy. Patent ductus arteriosus persisted for longer period of time in all large for gestational age infants than in normal infants, but its closure was significantly delayed in infants of diabetic mothers.

APGAR scores are lower in offspring from mothers with type 1 diabetes – results from the BABY DIAB study

Infants born to women with type 1 diabetes (T1D) are at increased risk of neonatal morbidity. Intrapartum monitoring is therefore essential to minimize complications. We analyzed APGAR scores after 5 and 10min. in BABYDIAB offspring from mothers with T1D (n=1047) compared to offspring from non-diabetic mothers whose partners had T1D (n=592). Sectio rates in mothers with T1D were increased more than two-fold (48.1%) compared to mothers w/o T1D (21.4%, p<0.0001). 16 of 927 offspring (1.7%) suffered from initial asphyxia as defined by an APGAR (5') <7. Neonates from mothers with T1D had lower mean APGAR scores compared to offspring from non-diabetic mothers (p<0.0001). Translated into clinical practice, that was a lower rate of maximally good APGAR scoring of 10 (47%) in children from mothers with T1D compared with offspring from non-diabetic mothers (71.8%, p<0.0001) while rates of early asphyxia were not different (1.9% vs. 1.7%). Since mean APGAR scores were decreased in offspring delivered by sectio compared with neonates born spontaneously (p<0.0001), APGAR scores by maternal diabetes status were controlled for the mode of delivery. Again, rates of low APGAR 5' scores were higher and rates of maximally good scores lower both in offspring from diabetic mothers delivered by sectio and in children born spontaneously compared to offspring from non-diabetic mothers (p<0.034, p<0.0001). HbA1c levels at delivery were slightly higher in mothers who gave birth by sectio (5.86%) compared to mothers who delivered spontaneously (5.69%, p<0.035). Mean APGAR5'scores were also lower in offspring from mothers with elevated HbA1c levels when comparing HbA1c-subgroups defined by an HbA1c >8% vs. 7–8% vs. 6–7% vs. 5–6%, p<0.007, Kruskal-Wallis). In conclusion, offspring of mothers with well controlled T1D may not be at risk of severely compromised vitality at birth, however, they less often score maximum points on the APGAR scale compared to offspring from non-diabetic mothers.

Antioxidant status and circulating lipids are altered in human gestational diabetes and macrosomia

Fetuses from mothers with gestational diabetes are at increased risk of developing neonatal macrosomia and oxidative stress. We investigated the modulation of antioxidant status and circulating lipids in gestational diabetic mothers and their macrosomic babies and in healthy age-matched pregnant women and their newborns. The serum antioxidant status was assessed by employing anti-radical resistance kit (KRL; Kirial International SA, Couternon, France) and determining levels of vitamin A, C, and E and the activity of superoxide dismutase (SOD). Circulating serum lipids were quantified, and lipid peroxidation was measured as the concentrations of serum thiobarbituric acid-reactive substances (TBARS). As compared with non-diabetic mothers, gestational diabetic women exhibited decreased levels of vitamin E and enhanced concentrations of vitamin C without any changes in vitamin A. Vitamin A and C levels did not change in macrosomic babies except vitamin E whose levels were lower in these infants than in the newborns of non-diabetic mothers. Gestational diabetes mellitus (GDM) and macrosomia were also associated with impaired SOD activities and enhanced TBARS levels. Globally, total serum antioxidant defense status in diabetic mothers and their macrosomic babies was diminished as compared with control subjects. Triglyceride and cholesterol concentrations did not differ significantly between gestational diabetic and control mothers; however, macrosomia was associated with enhanced plasma cholesterol and triglyceride levels. These results suggest that human GDM and macrosomia are associated with downregulation of antioxidant status, and macrosomic infants also exhibit altered lipid metabolism.

Relationship between increased relative birthweight and infections during pregnancy in children with a high-risk diabetes HLA genotype

Children with high-risk type 1 diabetes HLA genotype have increased risk of high relative birthweight (HrBW), while cord blood islet autoantibodies decrease the risk. As gestational infections may affect offspring type 1 diabetes risk, the aims were to test whether: (1) children of mothers reporting gestational infections have increased HrBW; (2) gestational infections explain islet autoantibody reduction of HrBW; and (3) gestational infections affect the association between HLA and HrBW. HLA genotypes and autoantibodies to glutamic acid decarboxylase, insulinoma-associated protein 2 and insulin were determined in cord blood of children born to non-diabetic mothers in the Diabetes Prediction in Skåne (DiPiS) study. Mothers reported gestational infections when the child was 2 months old. Fever or gastroenteritis during pregnancy was reported by 2,848/19,756 mothers (14%); 339 in more than one trimester. Children whose mothers reported infections had increased risk of HrBW (p = 0.0003), particularly in the absence of cord blood islet autoantibodies (interaction between HrBW, islet autoantibodies and infections, p = 0.0005). The effect on HrBW by high-risk HLA-DQ2/8 was aggravated by infections in more than one trimester (odds ratio [OR] = 5.24; p = 0.003) (interaction; p = 0.022). When infections were reported, cord blood islet autoantibodies decreased HrBW (OR = 0.34; p = 0.0002). This study revealed that: (1) gestational fever, gastroenteritis, or both, increased the risk of HrBW; (2) cord blood islet autoantibodies decreased the risk of HrBW only in combination with infections; and (3) infections aggravated the association between HLA-DQ2/8 and HrBW. These data suggest an interaction between HLA, gestational infections, islet autoantibodies and fetal growth.

Breastfeeding habits in families with Type 1 diabetes

Breastfeeding is acknowledged to be beneficial for child development. Women with diabetes may be more likely not to breastfeed their children because of neonatal morbidity and instability in diabetes control. The aim of this study was to assess the effect of maternal Type 1 diabetes on breastfeeding habits. Full breastfeeding and any breastfeeding were reported in the first year of life in 1560 children born in Germany between 1989 and 2004. Of those, 997 children had a mother with Type 1 diabetes, and the remaining 563 children had a father or sibling with Type 1 diabetes. Fewer children of mothers with Type 1 diabetes were breastfed than children of non-diabetic mothers (77 vs. 86%; P < 0.0001) and, amongst breastfed children, there was a shorter duration of full breastfeeding (12 vs. 17 weeks; P < 0.0001) and any breastfeeding (20 vs. 26 weeks, P < 0.0001) in children of mothers with Type 1 diabetes compared with children of non-diabetic mothers. Other factors associated with reduced frequency and duration of breastfeeding were pre-term delivery (P < 0.0001), young maternal age (P < 0.0001), and firstborn children (P < 0.0001). After stratification for each of these factors, breastfeeding remained significantly less frequent and of less duration in children of mothers with Type 1 diabetes as compared with children of non-diabetic mothers. Mothers with Type 1 diabetes breastfeed their children less than international recommendations. Counselling to increase frequency and duration of breastfeeding may be warranted in this population.

Pre-pregnant body mass index, weight gain and the risk of delivering large babies among non-diabetic mothers

Objective Pre-pregnancy overweight and excess weight gain during pregnancy have each been associated with an increased risk of delivering large babies. However, previous studies have focused on the separate effects of these two indices of weight in diabetic women. Method This study analyzed both separate and combined effects of pre-pregnant body mass index and weight gain in relation to macrosomia (≥ 4000 g) in offspring among 815 non-diabetic women, using data collected from a retrospective study. Result Compared to mothers with normal pre-pregnancy BMI and pregnancy weight gain, risk of macrosomia in offspring was significantly elevated only in overweight women with excess weight gain (adjusted OR = 2.6, 95% CI [1.2,5.4]) but not among normal weight mothers with excess gain (adjusted OR = 1.1, 95% CI [0.5,2.4]) or overweight mothers with normal or low gain (adjusted OR = 1.1, 95% CI [0.4,3.1]). Conclusion Given the complications that are associated with delivering large babies, overweight women may benefit from not gaining excess weight in pregnancy.

Fetal growth is increased by maternal type 1 diabetes and HLA DR4-related gene interactions

Intrauterine growth in non-diabetic pregnancies is reported to be influenced by type 1 diabetes susceptibility genes. In particular, the high-risk HLA DR4_DQB1*0302 haplotype is associated with increased birthweight. The aim of this study was to determine whether HLA DR4 was associated with increased birthweight in a maternal diabetes environment and whether effects persisted during early childhood. Birthweight and gestational age were obtained in singleton births from mothers with type 1 diabetes (n = 1161) or whose fathers or siblings have type 1 diabetes (n = 872). Weight and height at ages 2 and 5 years were obtained from paediatric records. Data were adjusted for (gestational) age and sex and expressed as percentiles of German reference data. HLA DR typing was obtained for all children and 1090 children also had insulin gene (INS) variable number of tandem repeats (VNTR) typing. Maternal type 1 diabetes was associated with increased birthweight, gestational age and birthweight percentiles (all p < 0.0001). In children of mothers with type 1 diabetes, birthweight percentile was further related to maternal HbA(1c) during pregnancy (r = 0.26; p < 0.0001) and was independently increased if children had HLA DR4 alleles (76th vs 64th percentile; p < 0.0001). HLA DR4 was not associated with birthweight in children of non-diabetic mothers. Birthweight was not associated with INS VNTR genotypes. High birthweight, but not HLA DR4 was associated with increased weight and BMI at ages 2 and 5 years (p < 0.0001). Our findings are consistent with the hypothesis that a diabetic intrauterine environment interacts with gene(s) marked by the type 1 diabetes susceptibility HLA DR4 alleles to increase fetal growth.

Recurrence of fetal macrosomia in non-diabetic pregnancies

SummaryFetal macrosomia (birth weight ≥4,500 g) is known to increase a number of adverse maternal and perinatal outcomes. Although there is a clear association between maternal diabetes mellitus and fetal macrosomia, the majority of macrosomic infants are born to non-diabetic mothers. We wished to determine the recurrence rate of macrosomia in non-diabetic pregnancy and to see if a history of multiple prior macrosomic infants confers additional risk. A retrospective analysis of 14,461 term, singleton, infants born to non-diabetic mothers in 1997 and 1998 was performed, using a computerised hospital database. Among 14,461 term pregnancies, 529 infants (3.7%) were macrosomic, and the incidence was significantly higher in parous women (4.6%) compared with nulliparas (2.4%, p < 0.0001). Over the next 5 years, 164 of these women returned for another delivery. Women with a history of one macrosomic infant are at significantly increased risk of another macrosomic infant in a subsequent pregnancy (OR 15.8, 95% CI 11.45 – 21.91, p < 0.0001). For women with two or more macrosomic infants, the risk is even greater (OR 47.4, 95% CI 19.9 – 112.89, p < 0.0001). Macrosomia was associated with increased rates of instrumental delivery and anal sphincter injury regardless of parity, and additionally with increased rates of caesarean delivery and shoulder dystocia among nulliparas. Overall, 88% of women who laboured with a macrosomic infant achieved vaginal delivery.

Lipid Profile, Glucose Homeostasis, Blood Pressure, and Obesity-Anthropometric Markers in Macrosomic Offspring of Nondiabetic Mothers

Lipid Profile, Glucose Homeostasis, Blood Pressure, and Obesity-Anthropometric Markers in Macrosomic Offspring of Nondiabetic Mothers

Intrauteriner Tod des Feten bei präkonzeptionellem Diabetes, Gestationsdiabetes und Schwangerschaften ohne diabetische Stoffwechsellage. Ergebnisse der Perinatalstatistik Niedersachsen

The prevalence of intrauterine fetal death as well as the relevant risk factors in pregnancies of women with preconceptional and gestational diabetes mellitus and non-diabetic women were investigated. The data of the Perinatal Registry of Lower Saxony between 1987 and 1999 for pregnancies of women with preconceptional diabetes mellitus (PDM, n = 3351), gestational diabetes mellitus (GDM, n = 3954) and women without diabetes mellitus (non-diabetic pregnancies, NDM, n = 887,779) were retrospectively analysed. Intrauterine fetal death occurred in 46 women with PDM (1.35 %), 32 women with GDM (0.79 %) and 2756 non-diabetic women (0.31 %). The odds ratio (OR, 95 % CI) for PDM vs. NDM was 4.468 (3.332 - 5.992; p < 0.01) and for GDM vs. NDM it was 2.595 (1.829 - 3.682; p < 0.01). The percentage of death, which occurs before the 32nd week of gestation, was 13 % in pregnancies with PDM, 12.5 % in pregnancies with GDM and 27.7 % in non-diabetic pregnancies. 50 % of fetal deaths in the PDM group, 43.8 % of those in the GDM group and 39.3 % of those in the NDM group occurred after the 36th week of gestation. The percentages of dead fetuses who were under the 10th percentile of growth (small for gestational age, SGA), in pregnancies with PDM, GDM and NDM were 15.2 %, 6.3 %, and 28.7 %, respectively. The percentages of dead fetuses above the 90th percentile of growth (large for gestational age, LGA) were 41.3 % (PDM), 37.5 % (GDM), and 8.7 % (NDM), (p < 0.01 for PDM vs. NDM and for GDM vs. NDM). The risk of intrauterine fetal death in pregnancies of diabetic women is still increased. It seems that especially the LGA fetuses of diabetic mothers and SGA fetuses of non-diabetic mothers are at greater risk of intrauterine death.

Does anterior abdominal wall thickness reflect glycaemic control and can it predict birthweight?

AND CAN IT PREDICT BIRTHWEIGHT? NOIRIN RUSSELL, CECELIA MULCAHY, MICHAEL FOLEY, FIONNUALA MCAULIFFE, University College Dublin, Dublin, Ireland, National Maternity Hospital, Holles St., Dublin, Ireland, University College Dublin, Obstetrics and Gynaecology, Dublin, Ireland, University College Dublin, Obstetrics & Gynecology, Dublin, Ireland OBJECTIVE: Ultrasound prediction of birthweight is an inaccurate science especially at the extremes of growth. In utero measurements of fetal anthropometric measurements have been used in an attempt to increase accuracy. The aim of the study is to determine if there is an association between third trimester anterior abdominal wall thickness and birth weight and also whether booking HbA1C in type 1 diabetic pregnancy is associated with an increased fetal anterior abdominal wall thickness. STUDY DESIGN: This is a prospective study with institutional ethics approval and written maternal consent. A measurement of the fetal anterior abdominal wall (AAW) was taken at the traditional abdominal circumference view, 2-3 cm lateral to the cord insertion, and included fetal skin and subcutaneous tissue. Measurements were recorded at 33-37 week’s gestation in 167 patients. Birth weight and birth weight centile was recorded. RESULTS: Of 167 measurements taken, 90 were in fetuses of type 1 diabetic mothers, 54 in fetuses of gestational diabetic mothers, 15 in fetuses of nondiabetic mothers and 8 in fetuses of type 2 diabetic mothers. Booking HbA1c in the pregestational diabetic population correlated positively with third trimester AAW measurements (p!0.05). Third trimester anterior abdominal wall thickness correlated positively with birth weight (p!0.01) and with birth weight centile at delivery (p!0.001). Third trimester AAW measurements are significantly higher in babies with a birth weight O/=90th centile compared to those with a birth weight less than the 90th centile (5.4C/ 1.1mm vs. 4.9C/ 1.2 p!0.05). CONCLUSION: Poorer periconceptual glycaemic control results in thickened fetal anterior abdominal wall thickness in the third trimester in type 1 diabetes. An AAW measurement of greater than 5mm in the third trimester may help to identify fetuses at risk of macrosomia.

Dietary insulin as an immunogen and tolerogen

We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula induces an insulin-specific immune response in infants. Here we studied the role of human insulin (HI) in breast milk as a modulator of the immune response to insulin. In a group of 128 children participating in the TRIGR pilot study, maternal breast milk samples were collected 3-7 days and/or 3 months after delivery. After exclusive breast-feeding, the children received either CM formula or casein hydrolysate during the first 6-8 months of life. Insulin concentration in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were measured by EIA. The levels of insulin in breast milk samples were higher in mothers affected by type 1 diabetes than in non-diabetic mothers (p = 0.007 and p < 0.001). The concentration of insulin in breast milk correlated inversely with the plasma levels of IgG antibodies to BI at 6 months of age in children who received CM formula (r = -0.39, p = 0.013), and at 12 months of age in all children (r = -0.25, p = 0.029). The levels of breast milk insulin were higher in the mothers of nine children who developed beta-cell autoimmunity when compared with autoantibody-negative children (p = 0.030); this holds true also when only children of diabetic mothers were included (p = 0.045). BI in CM induces higher levels of IgG to insulin in infants than does HI in breast-fed children. Instead, HI in breast milk seems to be tolerogenic and may downregulate the IgG response to dietary BI. However, our results in infants who developed beta-cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance.

Cord Blood Islet Autoantibodies Are Related to Stress in the Mother during Pregnancy

A 2-month psychological questionnaire concerning pregnancy was answered by 20,920 nondiabetic mothers of singletons. Retrospective analysis showed increased levels of islet autoantibodies (IA) in 290 (1.4%) newborns. High IA levels in the child's cord blood correlated strongly with IA levels in the mother (GADA r = 0.91, P < 0.0001; IA-2A r = 0.75, P = 0.0001). High IA levels were found in newborns whose mothers during pregnancy had been more worried than usual (P = 0.04), had worried that the child would be sick (P = 0.01) or not survive (P = 0.002), or had experienced serious life events, like "serious accident in the family" (P < 0.0001) or "experienced violence" (P = 0.02). Associations with increased worries by the mother remained in newborns with high type 1 diabetes mellitus (T1DM)-human leukocyte antigen (HLA) risk, but not in non-HLA risk children. The prospective follow-up of these children will determine the importance of this early IA for postnatal islet autoimmunity, type 1 diabetes, or both.

Fetal and Neonatal Outcomes of Diabetic Pregnancies

To estimate whether the incidences of adverse fetal and neonatal outcomes in infants of mothers with preexisting types 1 and 2 diabetes 1) differ from infants of nondiabetic mothers in Nova Scotia (NS); and 2) have changed between 1988 and 2002. Population-based cohort study using the NS Atlee Perinatal Database, a well-validated source of standardized clinical information. A total of 516 infants of diabetic mothers and 150,589 infants of nondiabetic mothers from singleton pregnancies were studied. Infants of diabetic mothers had significantly higher rates of perinatal mortality (17.4/1,000 compared with 5.9/1,000, relative risk [RR] 3.01, 95% confidence interval [CI] 1.55-5.84), major congenital anomaly (9.1% compared with 3.1%, RR 2.97, 95% CI 2.25-3.90), and large for gestational age birth (LGA, more than 90th percentile weight for gestational age) (45.2% compared with 12.6%, RR 3.59, 95% CI 3.26-3.95) than infants of nondiabetic mothers. In infants of diabetic mothers, there was no improvement in perinatal mortality (23.4/1,000 in 1988-1995 compared with 11.5/1000 in 1996-2002, P = .340), incidence of LGA (48.0% in 1988-1995 compared with 42.3% in 1996-2002, P = .237), or rate of major congenital anomaly (8.2% in 1988-1995 compared with 10.0% in 1996-2002, P = .560). Diabetes remained an independent risk factor for LGA infants and major congenital anomaly after adjusting for possible confounders. Rates of adverse neonatal outcomes are 3-9 times greater in infants of diabetic mothers compared with those of nondiabetic mothers. There were no significant improvements in rates of perinatal mortality, congenital anomaly, or LGA birth in infants of diabetic mothers in 1996-2002 compared with 1988-95.

Lipid Profile, Glucose Homeostasis, Blood Pressure, and Obesity-Anthropometric Markers in Macrosomic Offspring of Nondiabetic Mothers

The study was to determine whether being the macrosomic offspring of a mother without detected glucose intolerance during pregnancy has an impact on lipid profile, glucose homeostasis, and blood pressure during childhood. Plasma total, HDL, and LDL cholesterol; triglycerides; apolipoprotein (Apo) A-1, -B, and -E; lipoprotein (a); fasting glucose and insulin; homeostasis model assessment of insulin resistance (HOMA-IR) index; blood pressure; BMI; and detailed anthropometry were evaluated in 85 children aged 3-10 years old, born appropriate for gestational age (AGA; n = 48) and large for gestational age (LGA; n = 37) of healthy mothers. At the time of the assessment, body weight, height, skinfold thickness, BMI, waist circumference, and blood pressure did not differ between the LGA and AGA groups with the exception of head circumference (P < 0.01). There were no significant differences in plasma total or LDL cholesterol; triglycerides; Apo A-1, -B, or -E; lipoprotein (a); Apo B-to-Apo A-1 ratio; or glucose levels between the groups. The LGA group had significantly higher HDL cholesterol levels (P < 0.01), fasting insulin levels (P < 0.01), and HOMA-IR index (P < 0.01) but lower values of the glucose-to-insulin ratio (P < 0.01) as compared with the AGA group. Children born LGA of mothers without confirmed impaired glucose tolerance during pregnancy show higher insulin concentrations than AGAs.

Fetal Growth Curves: Does Classification of Weight-for-Gestational Age Predict Risk of Hypoglycemia in the Term Newborn?

Our objective was to determine whether classification of birth weight as small, average, or large for gestational age using published fetal growth curves is predictive of a term infant's risk of hypoglycemia. This prospective, descriptive study measured and plotted birth weight measurements on six published fetal growth curves to classify infant birth weight as small, average, or large for gestational age. Glucose levels were measured 2 hours after birth to determine the prevalence of hypoglycemia. The sensitivity, specificity, and positive/negative predictive values were calculated for each fetal growth curve, and odds ratios were calculated. The patients were 157 clinically stable term Caucasian and African American infants of nondiabetic mothers from a community hospital in midwestern United States. Ten of the 20 (50%) infants with hypoglycemia were classified as average for gestational age on all six published fetal growth curves. Calculated odds ratios demonstrated that none of the six published fetal growth curves significantly predicted the risk of hypoglycemia based on classification of birth weight as small, average, or large for gestational age. The risk of hypoglycemia in term infants was not accurately predicted by classification of birth weight as small, average, or large for gestational age. Clinicians should use other methods to predict which term infants are at risk for hypoglycemia.