EVIDENCE-BASED ANSWER
In pregnant women with preexisting type 1 diabetes mellitus, maintaining near-normal blood glucose levels decreases the rate of major congenital anomalies (defined as those causing death or a serious handicap necessitating surgical correction or medical treatment). Prolonged preconception control of blood sugar to near normal levels reduces the rate of major congenital anomalies close to those seen in women without diabetes (strength of recommendation [SOR]: A, based on prospective cohort studies and randomized controlled trial [RCT]).
Intensive management reduces the risk of congenital anomalies more than conventional therapy, and lowers the risk of neonatal hypoglycemia (SOR: B, based on RCT). Very tight control does not reduce clinically significant neonatal morbidity but does increase the risk of maternal hypoglycemia (SOR: B, based on a systematic review). Evidence is insufficient about whether or not these statements hold true for women with type 2 diabetes.
In women with impaired glucose tolerance, dietary control reduces neonatal hypoglycemia. To date, studies have not found statistically significant reductions in admission rates to the special care nursery or birth weights above the 90th percentile (SOR: B, systematic review). Evidence is insufficient to suggest improved outcomes with therapy in women with gestational diabetes. Standard recommendations typically recommend tight control in this population as well.
Evidence summary
Two studies show that in type 1 diabetes mellitus, elevated blood glucose levels in early pregnancy (HbA1c=6%–8%) are associated with a threefold increase in fetal malformations.1,2 Maintaining preconception and early pregnancy blood glucose levels in the normal range can reduce this risk. A meta-analysis comparing 16 studies of women with pregestational diabetes—13 of which included only women with type 1 diabetes—found that women receiving preconception care had lower early first trimester HbA1c levels than those who did not (7.9% vs 9.6%) and delivered fewer infants with major congenital anomalies (relative risk [RR]=0.36; 95% confidence interval [CI], 0.22–0.59).2 One limitation of this study was that preconception care was not consistently defined among the included studies.
A 10-year RCT evaluated the outcomes of 270 pregnancies in women who had received either intensive (SQ infusion or multiple daily injections) or conventional insulin regimens prior to pregnancy. Women were advised to use intensive therapy when they were trying to conceive, and all were changed to intensive therapy if pregnancy was confirmed. Women in the intensive therapy group had normal HbA1c levels for an average of 40 months before conception. Women receiving intensive therapy had lower mean HbA1c levels at conception (7.4 ± 1.3 SD vs 8.1 ± 1.7 SD) and fewer major congenital anomalies (0.7% vs 5.9%; number needed to treat=19) than did women in the conventional group. When infants with genetic malformations were excluded from the analysis, rates of congenital malformations were similar in women switched to intensive therapy either before or after conception (3.8% vs 3.6%). No differences were seen between neonatal mortality, spontaneous abortion rates, birth weights, Apgar scores, and hypocalcemia or hypoglycemia rates.3
When tight and very tight control of glucose in pregnant women with pregestational diabetes were compared in a Cochrane systematic review, rates of maternal hypoglycemia in the very tightly controlled group were higher (odds ratio [OR]=25.96; 95% CI, 4.91–137.26).5 An RCT of 118 women with pregestational diabetes compared 4-times-daily vs twice-daily doses of insulin. Infants born to women receiving 4-times-daily insulin had significantly lower rates of neonatal hypoglycemia (RR=0.17; 95% CI, 0.04–0.74). While the trend was toward improved neonatal metabolic effects in the trials, the clinical significance of these findings is not clear.
Whether or not treatment of gestational diabetes improves outcomes is uncertain. A Cochrane systematic review evaluating a small number of trials, with variable quality and inconsistent outcome measures, compared dietary management to routine care in gestational diabetics. While fewer infants with birth weights >4000 g were delivered in the diet therapy group (OR=0.78; 95% CI, 0.45–1.35), the results were not statistically significant. No other important clinical differences were found.6
Another Cochrane systematic review evaluated the effects of dietary treatment of women with impaired glucose tolerance and gestational diabetes. Three trials with a total of 223 women with impaired glucose tolerance found a significant reduction in the rate of neonatal hypoglycemia (RR=0.25; 95% CI, 0.07–0.86). There was no significant change in the rates of cesarean section (RR=0.86; 95% CI, 0.51–1.45), admission to the special care nursery (RR=0.49; 95% CI, 0.19–1.24), or birth weights greater than the 90th percentile (RR=0.55; 95% CI, 0.19–1.61). Inadequate power may well account for the failure to reach significance in these outcomes.7