Lack of association between antiphospholipid antibodies and first-trimester spontaneous abortion: prospective study of pregnancies detected within 21 days of conception.

OBJECTIVE: To determine the role of antiphospholipid antibodies and anticardiolipin antibodies in first-trimester losses, addressing experimental pitfalls that preclude excluding the possibility that these antibodies reflect merely the selection bias of studying couples only after they have already experienced losses. DESIGN: Given that retrospective studies cannot exclude the possibility that such antibodies arise as a result of the fetal death, blood samples were obtained either before pregnancy or very early in pregnancy. Sera were obtained within 21 days of conception. SETTING: Multicenter university-based hospitals (National Institute of Child Health and Human Development collaborative study). PATIENT(S): Subjects for the current study were 93 women who later experienced pregnancy loss (48 diabetic; 45 nondiabetic), matched 2:1 with 190 controls (93 diabetic and 97 nondiabetic) who subsequently had normal live-born offspring. INTERVENTION(S): Sera from these 283 women were analyzed for antiphospholipid antibodies by enzyme immunoassay. In 260 of the 283 women (87 with pregnancy losses; 173 with live-born infants), sera were also available to perform assays for anticardiolipin antibodies by enzyme immunoassay. MAIN OUTCOME MEASURE(S): Pregnancy losses. RESULT(S): No association was observed between pregnancy loss and the presence of antiphospholipid antibodies or anticardiolipin antibodies. Levels of antiphospholipid antibodies were 6-19 PL/mL in 62.4% of the pregnancies that ended in losses and > or = 20 PL/mL in 5.4%; among pregnancies resulting in live-born infants, the percentages were 56.8% and 6.8%, respectively. Of the pregnancies that ended in a loss, 5.7% had anticardiolipin antibodies > or = 16 GPL/mL, compared with 5.2% of those ending in a live birth. CONCLUSION(S): This prospective study suggests that anticardiolipin antibodies and antiphospholipid antibodies are not associated with an increased risk for first-trimester pregnancy loss.

The Rubenesque pregnancy: a progression towards higher blood pressure correlates with a measure of endogenous and exogenous insulin levels.

Women with gestational diabetes tend to progress to noninsulin-dependent diabetes (NIDDM) with a high cumulative incidence relative to the general population. These women have also been shown to be insulin resistant and may represent a variant of the insulin resistance syndrome or Syndrome X. Our previous studies indicated that administered insulin was associated with an increase in blood pressure in women with gestational diabetes, raising the question that insulin levels per se contribute to blood pressure in these women. We developed a means by which the insulin levels of a given pregnant individual might be estimated called the Fraction of Circulating Insulin Level Relative to Normal (FOCILRN = C-PEPTIDE/2.0 + TOTAL DAILY INSULIN DOSE/CALCULATED DAILY INSULIN REQUIREMENT BASED ON WEIGHT AND GESTATIONAL WEEK). The formula was applied to 15 nonhypertensive pregnant women of comparable obese phenotype (Rubenesque) with varying degrees of glucose tolerance (4 normal, 5 gestational diabetes treated with diet alone, 4 gestational diabetes treated with insulin, and 2 noninsulin-dependent diabetes). Blood pressure was quantified at the beginning of the study (gestational weeks 24-34) and again 4-8 weeks later using a 24-hr monitor. Correlation analysis was used to test for a relationship between the FOCILRN and blood pressure. The increase in mean arterial pressure was found to be continuous and linear with increasing insulin exposure as quantified by FOCILRN. The correlation was significant for all subjects (r = 0.961, p < 0.001) and remained significant even with removal of patients with NIDDM (r = 0.857, p < 0.001). The nighttime heart rate, systolic and diastolic blood pressures were found to be significantly correlated with FOCILRN (r = 0.651, p < 0.01, r = 0.724, p < 0.001, and r = 0.831, p < 0.001, respectively). The difference between the maximum and minimum diastolic blood pressure values between 12:00 AM and 6:00 AM between sessions 1 and 2 significantly differed among the groups with women on insulin having the highest FOCILRN having the least variation in blood pressure. In nonhypertensive women of obese phenotype (Rubenesque), increasing insulin exposure is associated with increasing mean arterial blood pressure and less variability of nocturnal blood pressure. These data provide support for the hypothesis that insulin may mediate blood pressure response in genetically vulnerable individuals. The identification of the Rubenesque phenotype during gestation may be a clinically useful marker for individuals at risk for Syndrome X.

The Santa Barbara County Health Care Services program: birth weight change concomitant with screening for and treatment of glucose-intolerance of pregnancy: a potential cost-effective intervention?

Macrosomic infants still suffer birth trauma in excess of the general population; thus, while debated, the medical and legal sequelae of macrosomia appear to be costly. The clinical role of maternal hyperglycemia below the threshold for the diagnosis of gestational diabetes (GDM) in the etiology of macrosomia remains an area of controversy. Based on the hypothesis that increasing glucose levels result in an increasing prevalence of macrosomia, we designed a study to observe the impact on birth weight and on cost of a treatment program for glucose-intolerant pregnant women in The Santa Barbara County Health Care Services (SBCHCS). In 1985, 18% of 4364 births (85% Mexican-American in origin) in the SBCHCS were > 90th percentile birth weight. In 1986, we began a program to treat all glucose-intolerant pregnant women who had a positive glucose challenge test (GCT > 140 mg/dL after a 50-g oral glucose load), even if they had a negative glucose tolerance test. All glucose-tolerant pregnant women were placed on a 40% carbohydrate, 1800 kcal diet and taught to monitor their blood glucose. Insulin was begun if the fasting blood glucose was > 90 mg/dL and/or the 1-hour post meal was > 120 mg/dL. After introduction of the screening/ treatment program, the prevalence of macrosomia in 1992 was 7% and the cesarean section rate had dropped from 30 to 20%. The cost to SBCHC to educate and treat the additional glucose-intolerant women was $233,650. Assuming that there would have been an additional 398 macrosomic infants with some requiring cesarean delivery and intensive care, total potential savings could be estimated at $833,870 per year. Thus, treatment of glucose-intolerant pregnant women was associated with a decrease in macrosomia and may be cost-effective.

Prospective study showing that antisperm antibodies are not associated with pregnancy losses.

OBJECTIVE: To obtain prospective data on the relationship between presence of antisperm antibodies in maternal sera and first trimester pregnancy losses. DESIGN: First trimester sera obtained from diabetic and nondiabetic women recruited within 21 days of conception were analyzed using the indirect immunobead test for immunoglobulin (Ig)G, IgA, and IgM antisperm antibodies. Regional binding also was considered: sperm head, midpiece, and sperm tail. Results were correlated with pregnancy outcome. SETTING: Five university centers. PATIENTS: One hundred eleven women who experienced pregnancy loss (55 diabetic; 56 nondiabetic) were matched 2:1 with 104 diabetic and 116 nondiabetic women (controls) who subsequently had a normal liveborn infant. INTERVENTION: None. MAIN OUTCOME MEASURE: Pregnancy outcome (spontaneous abortion, liveborn) correlated with presence or absence of antisperm antibodies. RESULTS: Analyzing samples without knowledge of clinical status, no differences were observed with respect to IgG, IgA, and IgM binding when a positive test was defined as 50% of sperm showing antibody binding. Likewise, no association was found for IgG and IgM antisperm antibodies at 20% binding. The only positive finding was observed for IgA antisperm antibodies at 20% binding (Fisher's Exact test). This one positive finding merely could reflect multiple comparisons. No significant differences between groups were observed when analysis was stratified according to location of antibody binding (head, midpiece, tail tip, entire sperm). When the sample was stratified into those having and not having a prior loss, a relationship between antisperm antibodies and pregnancy loss still was not evident. CONCLUSION: Further work is necessary to determine whether IgA antisperm antibodies truly are associated with pregnancy loss or whether antisperm antibodies play any role in repetitive aborters. Findings in this study suggest that antisperm antibodies do not play a major role in pregnancy loss.

Lessons learned from the non-obese diabetic mouse II: Amelioration of pancreatic autoimmune isograft rejection during pregnancy.

To determine whether pregnancy provides an improved milieu for fetal/neonatal pancreas/islet transplantation, we studied neonatal pancreatic implants into non-obese diabetic (NOD) female mice during early gestation. We monitored maternal glycemic status, birthweight of the offspring, and graft histology to assess the efficacy of transplantation. One hundred and thirteen twelve-week-old NOD female mice were randomized into four groups as follows: (1) non-pregnant NOD mice received a sham operation; (2) non-pregnant NOD mice received neonatal pancreatic transplants; (3) pregnant NOD mice received a sham operation; and (4) pregnant NOD mice received neonatal pancreatic transplants. Pancreas segments from 3 neonatal NOD mice were placed via an incision 1 to 2 mm distal to the ear-skull junction of each of the recipients. Maternal blood glucose and glycated hemoglobin were determined between days 18 and 20 after the surgery. Pups were weighed within 5 to 6 hours after delivery. Pregnant NOD that received transplants (n = 29) had lower glucose and glycated hemoglobin (GHb) than sham operated pregnant controls (n = 26) (4.9 +/- 0.05 versus 9.0 +/- 5.0 mmol/L, p < 0.001 for glucose and 2.0 > or = 0.2 versus 3.0 > or = 1.2%, p < 0.008 for GHb) at 18 to 20 days of gestation. Controlling for litter size showed a decrease in birthweight for offspring of transplant recipients versus offspring of pregnant controls (1.59 +/- 0.08 versus 1.65 +/- 0.08 g, p < 0.002). Histological scoring of transplanted tissue at day 21 indicated that the lymphocytic infiltration in the pregnant group was significantly less than the control group (2.9 +/- 1.2 versus 4.9 +/- 0.2, p < 0.0001). We conclude that the pregnant NOD mouse provides a useful transplant model, that pregnancy provides an opportunity to increase beta-cell mass with transplanted tissue, and that pancreatic transplantation decrease birthweight and macrosomia in the offspring of NOD mice.

Rationale for prevention and treatment of glucose-mediated macrosomia: a protocol for gestational diabetes.

OBJECTIVE: To formulate a rationale for preventing and treating hyperglycemia during pregnancy and the concomitant risk of macrosomia. METHODS: We reviewed pertinent studies in the literature and personal experience with patients who had gestational diabetes. In addition, dietary and exercise interventions in the management of such patients were assessed. RESULTS: During pregnancy, sequential hormonal increases occur to provide glucose substrate to the fetus. When a pregnant woman has a limited insulin secretory capacity and cannot produce enough insulin to compensate for the effect of diabetogenic hormones, gestational diabetes occurs (usually during the second trimester). Maternal hyperglycemia reportedly increases fetal secretion of insulin, and fetal hyperinsulinemia may predispose the fetus to macrosomia. Thus, metabolic abnormalities associated with diabetes during pregnancy result in long-term effects on the offspring, including insulin resistance, obesity, and diabetes, which in turn may contribute to transmission of risk for development of the same problems in subsequent generations. Insulin therapy, dietary measures, and exercise have helped to achieve euglycemia in patients with gestational diabetes. CONCLUSION: Universal screening for gestational diabetes is optimally performed at 26 weeks of gestation. Treatment of diagnosed cases, by insulin, diet, and exercise regimens, will decrease the occurrence of glucose-related macrosomia, improve the outcome of the pregnancy, and reduce the risks for obesity, hypertension, and diabetes in future progeny.

The art and science of maintenance of normoglycemia in pregnancies complicated by insulin-dependent diabetes mellitus.

OBJECTIVE: To provide a "how-to" manual for achieving and maintaining normoglycemia in pregnant women with insulin-dependent diabetes. METHODS: We describe a detailed program that has successfully maintained normoglycemia before, during, and after diabetes-complicated pregnancies. Insulin and glucose requirements throughout pregnancy, during labor, and in the postpartum period are outlined. RESULTS: With preconception planning and careful dietary and blood glucose management during pregnancy, complications can be minimized and an optimal outcome of pregnancy can be achieved in women with diabetes. CONCLUSION: Women with type I, insulin-dependent diabetes can now have the same chances as women without diabetes to have a healthy infant. The reduction of risks associated with pregnancies complicated by diabetes can be ensured if normoglycemia is achieved before and during the pregnancy.

Infectious processes: an infrequent cause of first trimester spontaneous abortions.

A systematic assessment of infections beginning early in pregnancy is necessary to determine the true role of infections in pregnancy loss, given that infections could readily arise only after fetal demise. To this end, we have prospectively determined the frequency of infections in pregnant women who were subjects in a multi-centre US study. Insulin-dependent diabetic subjects and controlled subjects were recruited either before conception (86%) or at the latest within 21 days of conception (14%). We collected data prospectively on all important risk factors and potential confounding variables, seeing 386 diabetic subjects weekly and 432 control subjects every other week during the first trimester. At each visit we inquired about untoward events and explicitly about fever or infections. We found no clinical evidence that infection occurred more often in the 116 subjects experiencing pregnancy loss as compared to the 702 having successful pregnancies. This held both for the 2 week interval in which a given loss was recognized clinically as well as in the prior 2 week interval. Similar findings were not only observed for both the control as well as diabetic subjects but also when data were stratified by genital infection only or by systemic infection only. Our prospective data suggest that the attributable risk of infection in first trimester spontaneous abortion is small.

Exercise and the nutritional management of diabetes during pregnancy.

Although exercise is widely accepted as an important component in programs of maintaining a healthy lifestyle, the question of safety and utility of an exercise program for pregnant diabetic women is still controversial. Pregnant women who have diabetes want some direction as to what their possibilities are regarding exercise programs, as there is accumulating evidence that exercise during pregnancy has some advantages for them. In addition, there is now a consensus of thought that the ideal nutritional therapy for the gestational diabetic woman is a diet that facilitates normoglycemia. This article outlines a program that not only improves metabolic control through dietary principles and exercise prescriptions to achieve and maintain normoglycemia, but also will be safe for the mother and her baby, is enjoyable, and also has physical benefits for the mother.

Vitamin and mineral deficiencies which may predispose to glucose intolerance of pregnancy.

There is an increased requirement for nutrients in normal pregnancy, not only due to increased demand, but also increased loss. There is also an increased insulin-resistant state during pregnancy mediated by the placental anti-insulin hormones estrogen, progesterone, human somatomammotropin; the pituitary hormone prolactin; and the adrenal hormone, cortisol. If the maternal pancreas cannot increase production of insulin of sustain normoglycemia despite these anti-insulin hormones, gestational diabetes occurs. Gestational diabetes is associated with excessive nutrient losses due to glycosuria. Specific nutrient deficiencies of chromium, magnesium, potassium and pyridoxine may potentiate the tendency towards hyperglycemia in gestational diabetic women because each of these four deficiencies causes impairment of pancreatic insulin production. This review describes the pathophysiology of the hyperglycemia and the nutrient loss in gestational diabetes and further postulates the mechanism whereby vitamin/mineral supplementation may be useful to prevent or ameliorate pregnancy-related glucose intolerance.

Randomized crossover study of 40% vs. 55% carbohydrate weight loss strategies in women with previous gestational diabetes mellitus and non-diabetic women of 130-200% ideal body weight.

OBJECTIVE: The optimum diet composition for weight loss in obese women with or without previous gestational diabetes mellitus remains to be determined. Weight loss may be especially important for the latter group in terms of preventing future gestational as well as non-insulin dependent diabetes mellitus. We studied 40% vs. 55% carbohydrate calorically restricted diets to compare weight loss and metabolic response. METHODS: We performed a prospective, 12-week, blinded, randomized crossover study of 25 obese women; 13 of whom had previous gestational diabetes. Each woman was allocated to a treatment regimen for 6 weeks and then "crossed over" to the alternative regimen for an additional 6 weeks. Calories were provided in the form of nutritional supplement bars except for the evening meal that comprised 1/3 of the caloric needs. All subjects were seen and weighed weekly. Metabolic variables including glucose tolerance, glycated proteins, lipids, and percent body fat were measured at the beginning, crossover, and end of the study. RESULTS: Women with previous gestational diabetes mellitus were comparable to obese women without a history of previous gestational diabetes except that the former had higher maximum levels of glucose on a glucose tolerance test and higher fasting insulin levels consistent with greater insulin resistance. Weight loss was comparable for all groups during the first 6 weeks but attenuated in all groups during the second 6 weeks of the trial regardless of diabetes history or treatment group allocation. Women with or without a previous history of gestational diabetes had higher triglycerides while on a 55% carbohydrate diet than while on a 40% carbohydrate diet. CONCLUSIONS: A weight loss regimen consisting of 40% carbohydrate results in lower triglyceride levels than those achieved with a 55% carbohydrate content diet in obese women. Thus, the hypocaloric diet with the higher fat content produced the more favorable lipid profile in all obese women.

Fasting plasma glucose and glycosylated plasma protein at 24 to 28 weeks of gestation predict macrosomia in the general obstetric population.

The purpose of this study was to modify the traditional gestational diabetes screening process in order to provide a test that might more reliably detect those women at risk of delivering a macrosomic infant despite a negative test for gestational diabetes mellitus (GDM). Pregnant women (n = 160) were screened for GDM at 24 to 28 weeks' gestation using the traditional 50 g glucose challenge test (GCT). In addition, glycosylated hemoglobin, glycosylated serum protein, and glycosylated plasma protein (GPP) were analyzed from blood drawn at this same time. If the patient's challenge test was positive (140 mg/dL or higher), a 100 g oral glucose tolerance test (OGTT) was performed. Twenty-three women had a positive GCT (14.4%) and five (3.13%) were excluded from further study because they received treatment for gestational diabetes based on a positive OGTT. None of the GCT-negative or the GCT-positive-OGTT-negative patients received treatment. Gestational age at delivery, infant gender, and birthweight were retrieved from birth records. Although several correlations with infant birthweight were found, the fasting plasma glucose (FPG) and GPPs proved most significant. The FPG on the OGTT significantly correlated with infant birthweight (p < 0.001; r = 0.94). A value greater than 90 mg/dL proved to be 100% sensitive and 64% specific for infant birthweight more than 4000 g. The relationship of the GPP and subsequent infant birthweight was also significant (p < 0.001; r = 0.81). A GPP greater than 23% proved to be 100% sensitive in predicting birthweight above 4000 g (11 of 11 infants); however, the test had a 52% specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic control and progression of retinopathy. The Diabetes in Early Pregnancy Study. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.

OBJECTIVE: To evaluate the role of metabolic control in the progression of diabetic retinopathy during pregnancy. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study of 155 diabetic women in the Diabetes in Early Pregnancy Study followed from the periconceptional period to 1 month postpartum. Fundus photographs were obtained shortly after conception (95% within 5 weeks of conception) and within 1 month postpartum. Glycosylated hemoglobin was measured weekly during the 1st trimester and monthly thereafter. RESULTS: In the 140 patients who did not have proliferative retinopathy at baseline, progression of retinopathy was seen in 10.3, 21.1, 18.8, and 54.8% of patients with no retinopathy, microaneurysms only, mild nonproliferative retinopathy, and moderate-to-severe nonproliferative retinopathy at baseline, respectively. Proliferative retinopathy developed in 6.3% with mild and 29% with moderate-to-severe baseline retinopathy. Elevated glycosylated hemoglobin at baseline and the magnitude of improvement of glucose control through week 14 were associated with a higher risk of progression of retinopathy (adjusted odds ratio for progression in those with glycohemoglobin > or = 6 SD above the control mean versus those within 2 SD was 2.7; 95% confidence interval was 1.1-7.2; P = 0.039). CONCLUSIONS: The risk for progression of diabetic retinopathy was increased by initial glycosylated hemoglobin elevations as low as 6 SD above the control mean. This increased risk may be due to suboptimal control itself or to the rapid improvement in metabolic control that occurred in early pregnancy. Excellent metabolic control before conception may be required to avoid this increase in risk. Those with moderate-to-severe retinopathy at conception need more careful ophthalmic monitoring, particularly if their diabetes was suboptimally controlled at conception.

Pancreatic disorders of pregnancy. Diagnosis, management, and outcome of gestational diabetes.

Gestational diabetes is one of the more common medical problems of pregnancy. This article reviews the literature regarding the diagnosis and treatment and the controversy that surrounds gestational diabetes. The need for stricter guidelines for diagnosis and treatment and the evidence supporting this need are presented. Long-term follow-up evaluation for women with gestational diabetes and for their children is discussed.

Pancreatic disorders of pregnancy. Pregestational diabetes.

The outcome of pregnancies complicated by pregestational diabetes, both insulin-dependent and non-insulin-dependent, has changed dramatically since the discovery of insulin in the early 1920s. Now, patients with pregestational diabetes can safely undergo a pregnancy and be assured that the infant will be healthy. Unfortunately, a finite risk of problems still may occur, including congenital malformations, spontaneous abortions, and diabetic fetopathy classically manifest as a macrosomic infant. Treatment strategies, although tedious and sometimes onerous, do minimize these risks.

Blood pressure predicts insulin requirement and exogenous insulin is associated with increased blood pressure in women with gestational diabetes mellitus.

Fifty gestational diabetic women were studied to determine the interaction of blood pressure, insulin resistance, and the effect of exogenous insulin on blood pressure response. Gestational diabetes was diagnosed according to the criteria affirmed by the Third International Workshop-Conference on Gestational Diabetes at 20 to 32 weeks' gestation. At diagnosis, all women were placed on a standard diet and performed glucose monitoring on rising and 1 hour after meals. The criteria for initiation of insulin included fasting whole blood finger stick glucose more than 90 mg/dL, ketonuria that could only be cleared by increasing carbohydrate to a level causing postprandial hyperglycemia, or postprandial glucose levels at 1 hour above 140 mg/dL. Of the initial cohort, 28 required insulin to maintain target glycemia. Within this group, there was a significant positive correlation between mean arterial pressures at initiation of therapy for gestational diabetes mellitus and insulin requirement quantified by the amount of insulin required to maintain euglycemia at term (r2 = 0.259; P = 0.006). The initiation of insulin was associated with a significant blood pressure increase in this group when compared with values prior to insulin administration or to values in the group treated with diet alone. These observations are consistent with an interaction of blood pressure and insulin resistance as reflected by insulin requirement in women with gestational diabetes mellitus.

The Santa Barbara County diabetic retinopathy screening feasibility study: significance of diabetes duration and systolic blood pressure.

The objective of this study was to examine the feasibility and utility of screening for eye disease and hypertension in a group of diabetic patients. A sample of 338 outpatients in Santa Barbara County were included and had non-mydriatic retinal photography and measurement of blood pressure and visual acuity. Each patient completed a questionnaire including age, type of diabetes (type I or type II), duration of diabetes, and smoking history. Photographs were read by an internist and ophthalmologist, and grouped into one of five categories: (1) normal, (2) background retinopathy, (3) preproliferative retinopathy, (4) proliferative retinopathy, and (5) other abnormality. Patients with abnormalities were referred for treatment. Thirty-two percent of the population had retinopathy, and 16% had disease requiring urgent referral for treatment. Mean systolic blood pressure (MSBP) was found to be higher in patients with all types of retinopathy (132 mm Hg versus 124 mm Hg, p < 0.001). The relationship remained significant when smokers and nonsmokers were considered separately. No significant difference was found in MSBP between patients with severe retinopathy (preproliferative or proliferative) and those with background changes (133 mm Hg versus 131 mm Hg, respectively, p > 0.5). The other factor found to be related to retinopathy was the duration of diabetes. Type I patients with retinopathy had diabetes for 19 years versus 12 for those without (p < 0.01). Type II patients with retinopathy had diabetes for 10 years versus 6 for those without retinopathy (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal hyperglycemia is not the only cause of macrosomia: lessons learned from the nonobese diabetic mouse.

Maternal hyperglycemia has been implicated as the major cause of neonatal macrosomia, yet clinicians frequently report the birth of large-for-gestational-age infants in normoglycemic pregnancies. We examined the relationship between birthweight, maternal blood glucose (BG), glycosylated hemoglobin (GHb) levels, litter size, maternal age, gestational duration, and parity using the non-obese diabetic (NOD) mouse model. We observed 133 litters and analyzed the birthweight in relation to BG, GHb, litter size, maternal age, gestational duration, and parity. We found that mean litter birthweight was significantly negatively correlated with the total number of pups in each litter (r = -0.39; P < 0.01) and significantly positively correlated with parity (r = 0.19; P < 0.05) and maternal age (r = 0.22; P < 0.05). The total number of pups was significantly negatively correlated with parity (r = -0.33; P < 0.01) and with parent age (r = -0.21; P < 0.05). The relationship between birthweight and GHb was bimodal. No relationship was found with a GHb less than 2.5%, a significant positive correlation was found for GHb between 2.6% and 4.0% (r = 0.67; P < 0.01), and a negative relationship was found when GHb was above 4.0%. Thus, increased parity, maternal age and glucose are associated with increased birthweight. Mild hyperglycemia plays the major role when age, maternal size, gestational duration, and parity are controlled.