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.     

Gestational diabetes and offspring body disproportion

Aim:  It has been demonstrated that females born large for gestational age (LGA) in weight but not length are at increased risk of being obese at childbearing age. We addressed the question whether women with gestational diabetes mellitus (GDM) are at increased risk of giving birth to such infants.
Methods:  Birth characteristics of 884 267 infants of non-diabetic mothers and 7817 of mothers with GDM were analysed. LGA was defined as birth weight or birth length >2 standard deviation scores for gestational age. Multiple logistic regression analysis was performed.
Results:  The odds ratio (OR) for a woman with GDM to give birth to an LGA infant that was heavy alone was four times increased (OR: 3.71, 95% CI: 3.41–4.04). Furthermore, in the population of mothers giving birth to LGA infants, the proportion heavy alone was 68% in the group of women with GDM compared with 64.4% in the group of non-diabetic women. The risks were independent of gender of the foetus.
Conclusion:  Women with GDM have an almost four times higher risk of delivering an LGA infant that is heavy alone. The noted disproportion between weight and length in infants of such mothers may have an impact on the risk of later obesity.     

Ponderal index of large-for-gestational age infants: comparison between infants of diabetic and non-diabetic mothers

Ponderal index (PI) is a weight-height related parameter that is mainly used to assess the pattern of fetal growth in small-for-gestational age infants. We aimed to use PI for large-for-gestational age (LGA) infants who were born to diabetic or non-diabetic mothers, in order to predict the fetal growth pattern. One hundred sixty-six LGA infants born at the Department of Obstetrics, Hacettepe University Hospital, Ankara, Turkey were included in the study. The PI was calculated by using the following formula: PI = weight (g) x 100/(height, cm)3. Sixty-seven (40%) of these infants were born to diabetic mothers. Maternal age, maternal weight and maternal weight gain during pregnancy were similar in the diabetic and non-diabetic groups. Mean birthweight, height and head circumference were similar in both groups, but median PI of infants of diabetic mothers was significantly higher than of infants of non-diabetic mothers (3.02 and 2.89, respectively, p < 0.05). Fetal growth was different between LGA infants of diabetic and non-diabetic mothers, and PI provided useful information on the proportionality of fetal growth in LGA infants.     

Differential leukocyte count in infants of diabetic mothers. Increased band count associated with macrosomia

The differential leukocyte count was studied within the first 24 hours of life in 115 infants of diabetic mothers (IDMs) appropriate for gestational age (AGA), 16 IDMs large for gestational age (LGA), 104 infants of non-diabetic mothers (INM's) AGA, and 22 INMs-LGA. A significant "shift to the left" was found in IDM's-LGA only. The usual cause of "shift to the left" such as maternal hypertension or fever, respiratory distress syndrome, meconium aspiration, neonatal asphyxia, sepsis, convulsions, or hypoglycemia could not explain this finding. It is hypothesized that increased glucocorticoid secretion may possibly play a role.     

Females born large for gestational age have a doubled risk of giving birth to large for gestational age infants

AIM: To analyse if females born large for gestational age (LGA) have an increased risk to give birth to LGA infants and to study anthropometric characteristics in macrosomic infants of females born LGA. METHODS: The investigation was performed as an intergenerational retrospective study of women born between 1973 and 1983, who delivered their first infant between 1989 and 1999. Birth characteristics of 47,783 females, included in the Swedish Birth Register both as newborns and mothers were analysed. LGA was defined as >2 SD in either birth weight or length for gestational age. The infants were divided into three subgroups: born tall only, born heavy only and born both tall and heavy for gestational age. Multiple logistic and linear regression analyses were performed. RESULTS: Females, born LGA with regard to length or weight, had a two-fold (adjusted OR 1.96, 95% Cl 1.54-2.48) increased risk to give birth to an LGA infant. Females, born LGA concerning weight only, had a 2.6 (adjusted OR 2.63, 95%, 1.85-3.75) fold increased risk of having an LGA offspring heavy only and no elevated risk of giving birth to an offspring that was tall only, compared to females born not LGA. In addition, maternal obesity was associated with a 2.5 (adjusted OR 2.56, 95%, 2.20-2.98) fold increased risk of having an LGA newborn, compared to mothers with normal weight. CONCLUSION: Females, born LGA, have an increased risk to give birth to LGA infants, compared to mothers born not LGA. Maternal overweight increases this risk even further.     

Mid-arm circumference/head circumference ratios for identification of symptomatic LGA, AGA, and SGA newborn infants

Mid-arm circumference/head circumference ratios (MAC/HC) and birth weights obtained in 73 neonates were studied to compare which of these growth measurements could more accurately predict risk of metabolic complications resulting from either acceleration or retardation of fetal growth. The MAC/HC ratio was more sensitive than birth weight in distinguishing symptomatic large for gestational age (LGA) infants who were born to diabetic mothers from other LGA infants who were asymptomatic, and symptomatic from asymptomatic small for gestational age infants. In addition, the MAC/HC ratio identified symptomatic appropriate for gestational age (AGA) infants born to diabetic mothers and AGA infants with signs and symptoms of growth retardation. The MAC/HC is more useful than birth weight in assessing newborn infants at risk for the metabolic complications associated with fetal growth disorders.     

Disproportionate alterations in body composition of large for gestational age neonates

OBJECTIVE: The objective was to compare dual-energy x-ray absorptiometry-measured body composition between large (LGA) and appropriate (AGA) birth weight for gestational age neonates.Study design: LGA term infants (n = 47) with birth weights > or =4000 g were compared with 47 gestational age-matched AGA infants; 11 LGA infants were born to mothers with gestational (9) or pregestational diabetes (2). Dual-energy x-ray absorptiometry scans were performed at 1.8 +/- 1.0 days after birth. RESULTS: Body weight and length were the dominant predictors of body composition in LGA and AGA neonates. However, LGA neonates had significantly (P <.001, all comparisons) higher absolute amounts of total body fat, lean body mass, and bone mineral content and had significantly (P <.001, all comparisons) higher proportions of total body fat and bone mineral content but lower lean body mass as a percent of body weight. The changes for total body fat and lean body mass as a percent of body weight were greatest (P <.001) in LGA infants whose mothers had impaired glucose tolerance. CONCLUSION: LGA neonates have higher body fat and lower lean body mass than AGA infants. Impaired maternal glucose tolerance exaggerated these body composition changes.     

Vascular retinal abnormalities in neonates of mothers who smoked during pregnancy

OBJECTIVE: To investigate whether maternal smoking during pregnancy causes retinal abnormalities in the newborn. STUDY DESIGN: One hundred sixty-two neonates of smoking mothers and 162 matched neonates of nonsmoking mothers (112 appropriate for gestational age [AGA], 30 small for gestational age [SGA], 20 large for gestational age [LGA] in each group) were studied. RESULTS: Retinal arterial narrowing and straightening (RANS) was observed in 52 and 10 eyes of the newborns of smoking and nonsmoking mothers, respectively (P <. 000001) in association with elevated blood pressure in the neonates. The frequency of RANS was more than 3-fold greater in the SGA neonates than in the AGA and LGA neonates of the smoking mothers. Retinal venous dilatation and tortuosity (RVDT) was found in 100 and 36 eyes of neonates of smoking and nonsmoking mothers, respectively (P <.000001). The frequency of RVDT in the SGA neonates of the smoking mothers was 2.5-fold and 4.2-fold greater than in the AGA infants and the LGA infants, respectively. Also, intraretinal hemorrhages were found in 61 and 31 eyes of neonates of smoking and nonsmoking mothers, respectively (P =.0007) in association with elevated hematocrit and RVDT, whereas no intraretinal hemorrhages were found when RANS was present. All retinal abnormalities resolved by 6 months in infants of smoking mothers and by 2 months in infants of nonsmoking mothers. CONCLUSIONS: Maternal smoking during pregnancy causes increased frequency of RANS, RVDT, and intraretinal hemorrhages; but these retinal abnormalities resolve by 6 months of age.     

Evidence for the possible relationship of neonatal skinfold thickness to maternal glucose metabolism during the third trimester

Forty-eight infants, including 14 premature infants who were appropriate size for gestational age (AGA), 10 full-term AGA infants, 18 full-term infants who were large for gestational age (LGA), and six premature LGA infants of diabetic mothers (IDMs), had measurements of skinfold thickness (SFT) in the first 72 h of life. For the 24 LGA infants, there was a significant positive correlation between maternal glycohemoglobin (Hb AIc) in the post-partum period and SFT (r = 0.42, p less than 0.05). Our observations in this study support those of others, demonstrating that SFT increases with increasing gestational age. In addition, they support the hypothesis that, in diabetic pregnancies, or pregnancies associated with an elevated Hb AIc, a reflection of the time-integrated blood glucose level over the weeks preceding parturition, fetal hyperglycemia and hyperinsulinemia stimulate increased triglyceride synthesis in adipose cells and lead to an increase in fetal subcutaneous fat.     

Risks of congenital anomalies in large for gestational age infants

OBJECTIVES: To evaluate the association between large for gestational age (LGA) and demographic and medical risk factors as well as specific types of congenital anomalies. STUDY DESIGN: A retrospective, case-control study on 2,149,617 consecutive births was conducted. LGA was defined as 1.64 SD above the mean weight for gestational age, adjusted by sex and altitude. Risk factor frequency distributions were compared between LGA and normal birth weight neonates. Associations between LGA and 41 infants with isolated congenital anomalies were evaluated. RESULTS: Of 31,897 neonates with congenital anomalies, 1800 were LGA. Five anomalies were associated with LGA: talipes calcaneovalgus, hydrocephaly, combined angiomatoses, hip subluxation, and non-brown-pigmented nevi. Multiparity, vaginal bleeding, diabetes, and delivery by cesarean section were more frequent in LGA than in appropriate for gestational age infants' mothers. Several maternal but no paternal factors were statistically associated with an increased risk for LGA infants. CONCLUSIONS: The clinical observation that nevi are more commonly observed in LGA patients was supported. The higher frequencies of hip subluxation and talipes calcaneovalgus among LGA neonates reinforces their pathogenesis as deformations, whereas those of combined angiomatoses and hydrocephaly could reflect increased fluid or body mass.     

Visual evoked potentials in term light-for-gestational-age infants and infants of diabetic mothers

The latency and amplitude of the first negative peak of visual evoked potentials (VEP) were evaluated in 52 term infants, investigated within 48 h after birth. Sixteen were light-for-gestational-age (LGA), 16 were appropriate-for-gestational-age (AGA) and 20 were infants of diabetic mothers (IDM). The VEP latency was shorter in LGA infants compared to AGA infants, and it was closely related to the birth weight deviation. The VEP latency was inversely related to gestational age and positively related to head circumference. When corrected for gestational age and head circumference, the VEP latency was not significantly different between the subgroups, nor related to the birth weight deviation, ponderal index or skinfold thickness. Thus, it could be argued that the high conduction velocity in LGA infants is due to stress maturation or alternatively due to the smaller head circumference. The VEP amplitude was higher in LGA infants when compared with AGA infants, and inversely related to the birth weight deviation. No differences were found in VEP latency or VEP amplitude between IDM and AGA infants.     

IMMUNOELECTROPHORETIC DETERMINATION OF SERUM GLOBULINS 1N NEWBORN INFANTS OF DIABETIC MOTHERS

ABSTRACT. Davidsen, Otto (Diabetes Centre, Royal Maternity Department B, Rigshospitalet and Department of Clinical Chemistry, Sundby Hospital, Copenhagen, Denmark) Immunoelectrophoretic Determination of Serum Globulins in Newborn Infants of Diabetic Mothers. Acta Paediatr Scand, 63: 833, 1974.—Serum globulins were investigated by means of crossed immunoelectrophoresis in the cord blood from 40 infants of diabetic mothers and 92 infants with non-diabetic mothers. In infants of non-diabetic mothers the concentration of most globulins was lower than in adults and positively correlated to the gestational age of the infant. For α₂-HS-glycoprotein and an unidentified α₂-glob-uEn, however, a negative correlation to the gestational age was observed. Infants of diabetic mothers had a higher Concentration of transferrin and lower concentrations of α₂-macroglohulin and α₁-lipoprotein as compared with infants of the reference group. In the diabetes group the globulin concentrations were correlated neither to the gestational age nor to their increased birth weight, but the ratio α₂,-macroglobulin/α₂-HS-glycoprotein, which was expected to be independent of variations in the degree of hydremia of the infants, was significantly correlated to the gestational age. As judged from this parameter, infants of diabetic mothers are comparable to infants of non-diabetic mothers of about 4 weeks lower gestational age.     

Father's weight could contribute to large babies in overweight and obese mothers with and without gestational diabetes

We evaluated whether there was an association between fathers’ nutritional status and children's birth weight (BW) considering weight-matched mothers with and without gestational diabetes mellitus (GDM). In total, 86 trios of women, infants, and fathers were evaluated. BW was not different between the groups of obese and non-obese parents, frequency of maternal obesity, or GDM. The percentage of infants who were large for gestational age (LGA) was 25% in the obese group and 14% in the non-obese group (p = 0.44). There was a borderline significance for higher body mass index (p = 0.09) of the father in the LGA group compared with the adequate for gestational age group. These results corroborate the hypothesis that the father's weight can also be relevant for the occurrence of LGA.     

Insulin and Leptin Levels in Appropriate-for-Gestational-Age Infants of Diabetic Mother

Objective

Intensified management of gestational diabetes mellitus can normalize birth weight. However, it is still unknown whether intrauterine exposure to maternal diabetes is a risk factor for changing hormone levels involved in the development of insulin resistance in these infants. We compared insulin and leptin levels in appropriate for gestational age (AGA) infants of diabetic and non diabetic mothers.

Methods

We performed a cross-sectional study in the department of Neonatology of the Hospital of Gynecology-Pediatrics, in Leon, Mexico. We evaluated 182 full term AGA newborns (86 infants of diabetic and 96 of non-diabetic mothers). A venous blood sample was taken from cord blood immediately after the separation of the placenta and glucose, insulin and leptin levels were measured. In all diabetic mothers HbA1c was also evaluated immediately post-partum.

Findings

Leptin, insulin and insulin resistance index were significantly higher in infants of diabetic mothers. Leptin levels were positive correlated with insulin, parents‘ body mass index and age in the entire group. In infants of diabetic mothers only insulin levels showed a significantly correlation, whereas in those of non-diabetic mothers only mothers‘ age was significantly correlated with leptin levels.

Conclusion

AGA infants of diabetic mothers showed higher leptin, insulin levels and insulin resistance index than those of non-diabetic mothers.     

Leptin, insulin, and glucose serum levels in large-for-gestational-age infants of diabetic and non-diabetic mothers

BACKGROUND: It has been suggested that hyperleptinemia could be caused by hyperinsulinemia in infants of diabetic mothers (IDMs). AIM: To compare leptin, insulin, and glucose levels in large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) infants. Methods: A cross-sectional study was conducted in IDMs, infants of non-diabetic mothers (INDM) and AGA infants. RESULTS: 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. CONCLUSIONS: 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.     

Altered diastolic function in infants of mothers with gestational diabetes: No relation to macrosomia

In a previous study, asymptomatic infants of mothers with gestational diabetes (IGDMs) were observed to have altered left ventricular (LV) filling. In the present study, we reanalyzed the data to examine whether the observed abnormalities were related to maternal diabetes or due to the greater preponderance of macrosomic infants (32%) in the gestational diabetes group. No echocardiographic (systolic or diastolic) differences were observed when the data were compared in 16 large-for-gestational-age (LGA) and 24 appropriate-for-gestational-age (AGA) infants among IGDM. Comparison of 16 LGA IGDM and 17 LGA infants of control mothers revealed lower LV size during diastole and systole in the IGDM. The present analysis suggests that the cardiac alterations in the IGDMs are not due to the preponderance of macrosomia but, rather, the consequence of altered in utero metabolic environment.     

Longitudinal investigation of the relationship between breast milk leptin levels and growth in breast-fed infants

BACKGROUND: It has been shown that leptin is present in breast milk and human mammary epithelial cells are able to synthesize leptin. It has been suggested that leptin in human milk might be involved in the regulation of postnatal nutrition and growth. AIMS: To investigate whether there is a relationship between leptin levels in human milk and weight gain in the postnatal period and to compare variations of milk-borne maternal leptin concentrations for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) infants. INFANTS AND METHODS: Forty-seven healthy lactating women aged from 17-38 years and their infants were included in the study. The infants were separated into three groups according to birth weight as SGA (n = 11), LGA (n = 14) and AGA (n = 22). All infants were fed with breast milk during the study period. Anthropometric measurements were performed on the 15th day of life and at 1, 2, and 3 months of age, and the body mass index (BMI) of the infants' mothers was calculated. Breast milk leptin levels were analyzed by radioimmunoassay. RESULTS: Breast milk leptin levels were found reduced in the SGA group and increased in the LGA group compared to the AGA group at 15 days of life (13.4 +/- 2.2, 28.5 +/- 4.4 and 18.4 +/- 2 ng/ml, respectively; p <0.05). At 1 month of age, leptin levels in breast milk were significantly lower in the LGA group than in the AGA group (15.5 +/- 4.9, 19.4 +/- 1.7 ng/ml, respectively; p<0.05). There was no difference among the three groups at 2 and 3 months of age (p>0.05). There was a positive correlation between birth Weight and breast milk leptin levels on the 15th day (r = 0.47, p = 0.001). A negative correlation was found between weight gain during the first 15 days and 1 month of life and breast milk leptin levels on the 15th day (r = -0.44, p = 0.002; r = -0.40, p = 0.005, respectively). No relationship could be determined between breast milk leptin levels and BMI of the mothers. CONCLUSION: Maternal milk of SGA, LGA and AGA infants had different leptin levels, especially during the first month of life. More rapid growth was shown in the SGA infants during the first postnatal 15 days compared to AGA and LGA infants, and human milk leptin levels were significantly reduced in the SGA group. However, LGA infants gained more weight during the second 15 days of life and breast milk leptin levels were dramatically decreased in LGA and increased in SGA infants at the end of first month of life. These findings suggest that the presence of leptin in breast milk might have a significant role in growth, appetite and regulation of nutrition in infancy, especially during the early lactation period, and the production of leptin in breast tissue by human mammary epithelial cells might be regulated physiologically according to necessity and state of the infant.     

The influence of gestational age, size for dates, and prenatal steroids on cord transferrin levels in newborn infants

Serum transferrin levels assess protein status in older children and adults. To generate standards for its use in newborn infants, we measured umbilical cord serum transferrin levels in 161 appropriate (AGA), 25 large (LGA) and 16 small (SGA) for gestational age infants between 25 and 43 weeks' gestation. We also assessed the effects of intrauterine growth, exposure to prenatal steroids, and presence of pulmonary maturity on neonatal transferrin levels. Cord transferrin levels in AGA infants were significantly correlated with increasing gestational age (r = 0.60; p less than 0.001). Infants born before 37 weeks' gestation had significantly lower transferrin levels, when compared with those born at term (p less than 0.001). LGA infants had significantly higher levels than age-matched AGA infants (253 +/- 75 vs. 214 +/- 53 mg/dl; p less than 0.025). Despite significantly lower mean birth weights (p less than 0.001), SGA infants also had significantly higher levels than gestational age-matched AGA controls (227 +/- 63 vs. 167 +/- 40 mg/dl; p less than 0.005). For infants less than 35 weeks' gestation, neither the 20 preterm infants with exposure to prenatal steroids (maternal betamethasone), nor the 26 infants with pulmonary maturity had significantly elevated transferrin levels, when compared with gestational age-matched control infants. Newborn transferrin levels correlate well with gestational age and are significantly affected by size for dates, but not by a brief course of prenatal steroids or by pulmonary maturity.     

High incidence of Down's syndrome in infants of diabetic mothers

The incidence of Down''s syndrome was studied in 1870 infants of diabetic mothers out of 22 300 neonates born between January 1987 and April 1994 in our institution. All pregnancies were screened for diabetes and all cases of Down''s syndrome were confirmed by chromosome analysis.
Down''s syndrome (all trisomy 21) was diagnosed in 35 infants: seven were born to mothers with gestational diabetes and 28to non-diabetic mothers. The incidence of Down''s syndrome was higher in infants of diabetic mothers (3.75 per 1000 v 1.36 per 1000) (p= 0.02) with a relative risk of 2.75. No significant difference was found in maternal age between both groups (p= 0.67) and the rate of Down''s syndrome was higher in infants of diabetic mothers when compared with infants of non-diabetic mothers of similar age.
Down''s syndrome should be added to the congenital malformations already known to occur more frequently in infants of diabetic mothers.

     

Cord prealbumin values in newborn infants: effect of prenatal steroids, pulmonary maturity, and size for dates

We assessed cord prealbumin concentrations in 214 appropriate for gestational age newborn infants, 21 small for gestational age infants, and 27 large for gestational age infants to establish normal values and to assess the effect of intrauterine growth, prenatal steroids, and pulmonary maturity on prealbumin levels. Cord prealbumin values were significantly correlated with increasing gestational age (r = 0.33; P less than 0.001) and birth weight (r = 0.40, P less than 0.001) in the AGA neonates. Neonates born before 37 weeks gestation had significantly lower prealbumin levels than those born at term (P less than 0.001). The SGA infants had significantly lower levels than age-matched AGA controls (P less than 0.01), and LGA infants had significantly higher levels than age-matched AGA controls (P less than 0.001). In preterm infants, those with exposure to prenatal steroids (betamethasone or premature rupture of membranes) had significantly higher prealbumin values than control infants of comparable age and weight (P less than 0.001). Infants without respiratory distress syndrome had higher levels than those of comparable age and weight with hyaline membrane disease (P less than 0.05). This study demonstrates that a correlation of gestational age and birth weight exists with cord prealbumin levels, and that the large variability at each gestational age may be accounted for in part by appropriateness of size for dates, prenatal steroid exposure, and pulmonary maturity.