Fetal size at birth in relation to quality of blood glucose control in pregnancies complicated by pregestational diabetes mellitus

Abstract

Objective To determine the relation between maternal levels of blood glucose and glycated haemoglobin (HbAlc) and infant size at birth in pregestational diabetes. Design Longitudinal study from 6 to 14 weeks gestation. Women were treated intensively with insulin, aiming at normoglycaemia but avoiding hypoglycaemia. Blood glucose was determined six times daily, HbAlc every four weeks. Individual mean fasting and postprandial glucose levels were calculated for three‐week periods of gestation. Birthweight > 2 SD or within ±2 SD for gestational age and gender was classified as large (LGA) or appropriate (AGA), respectively. Birthweight ratio was calculated as the ratio of birthweight to normal mean birthweight after correction for gestational age and gender. Participants One hundred and thirteen consecutive pregnant women with pregestational diabetes and their newborn infants. Results Perinatal mortality was nil, the rates of spontaneous preterm delivery (8.9 %) and severe maternal hypoglycaemia (4.4 %) were low. Mothers with LGA infants (26 %) had a significantly higher fasting glucose between weeks 27 and 32 than mothers of AGA infants (P < 0.01). Relative birthweight was significantly and independently associated with pre‐pregnancy bodyweight (r = 0.24, P 005) and fasting glucose at weeks 27 to 29 (r = 0.27, P 0.01) but together could only explain 12.3 % of the variation in birthweight (mult. r = 0.35, P 0.01). HbAlc correlated with glucose levels but was unrelated to birthweight ratio. The fasting glucose level between weeks 30 and 32 was significantly interrelated with the fasting glucose level from each of the six preceding three‐week periods. Conclusion Near normoglycaemia cannot be obtained in all patients, presumably due to intrinsic differences in glucoregulatory ability between individuals. The incidence of LGA infants was unexpectedly high. The modest abnormality in glycaemic control in mothers with LGA infants could only partly explain fetal oversize, suggesting that other factors must be implicated to explain fetal growth acceleration.

Effects of gestational diabetes on human placental glucose uptake, transfer, and utilisation

“…Fetal hyperinsulinaemia has been documented in diabetic pregnancy by a number of analytical techniques, including measurement of insulin and C-peptide in umbilical plasma and amniotic fluid and by cordocentesis [30±32]. Fetal hyperinsulinaemia has also been associated with neonatal macrosomia in both diabetic and non-diabetic pregnancy [32,33], while maternal glucose concentrations have been shown to be poorly correlated with fetal hyperinsulinaemia and the development of macrosomia [7,8,34]. All of the GDM patients in this study were diet-treated, thereby removing exogenous maternal insulin as a possible factor in the observed difference between GDM and control placentae.…”

“…For macrosomic neonates, birth weight has not been consistently shown to positively correlate with the degree of control of maternal blood glucose [7,8], suggesting that factors other than or in addition to maternal blood glucose are associated with adverse clinical outcomes during diabetes in pregnancy.Offspring from pregnant women with diabetes are more likely to develop diabetes mellitus and obesity later in life. This observation and evidence that development of diabetes is more closely related to maternal than paternal health, suggests that the intrauterine environment is possibly of importance [9, 10].…”

“…For macrosomic neonates, birth weight has not been consistently shown to positively correlate with the degree of control of maternal blood glucose [7,8], suggesting that factors other than or in addition to maternal blood glucose are associated with adverse clinical outcomes during diabetes in pregnancy.…”

Sibling birthweight as a predictor of macrosomia in women with type 1 diabetes

“…However, even in patients with near-normal HbA 1 c levels, macrosomia rates remain high [2,4,5]. Several studies on the relationship between HbA 1 c levels and birthweight have been published [15][16][17][18][19]. It has proved difficult to establish a clear relationship between HbA 1 c levels and infant birthweight.…”

What degree of maternal metabolic control in women with type 1 diabetes is associated with normal body size and proportions in full-term infants?

“…Nonetheless, the results of what, up until now, has been considered a tight glycemic control (average daily glucose levels ranging from 115 to 104 mg/dl [5][6][7][8]) remain unacceptable with respect to the levels of large-forgestational-age (LGA) infants, which range from 20 to 30% (6)(7)(8)(9). Indeed, the level of hyperglycemia that contributes to the development of fetal macrosomia seems to be much lower than that for complications such as fetal malformation and/or sudden intrauterine death in late pregnancy (5,10); therefore, it would seem that these goals for metabolic control are not strict enough to normalize intrauterine growth.…”