A randomized controlled trial using glycemic plus fetal ultrasound parameters versus glycemic parameters to determine insulin therapy in gestational diabetes with fasting hyperglycemia.

OBJECTIVE: To compare management based on maternal glycemic criteria with management based on relaxed glycemic criteria and fetal abdominal circumference (AC) measurements in order to select patients for insulin treatment of gestational diabetes mellitus (GDM) with fasting hyperglycemia. RESEARCH DESIGN AND METHODS: In a pilot study, 98 women with fasting plasma glucose (FPG) concentrations of 105-120 mg/dl were randomized. The standard group received insulin treatment. The experimental group received insulin if the AC, measured monthly, was > or =70th percentile and/or if any venous FPG measurement was >120 mg/dl. Power was projected to detect a 250-g difference in birth weights. RESULTS: Gestational ages, maternal glycemia, and AC percentiles were similar at randomization. After initiation of protocol, venous FPG (P = 0.003) and capillary blood glucose levels (P = 0.049) were significantly lower in the standard group. Birth weights (3,271 +/- 458 vs. 3,369 +/- 461 g), frequencies of birth weights >90th percentile (6.3 vs 8.3%), and neonatal morbidity (25 vs. 25%) did not differ significantly between the standard and experimental groups, respectively. The cesarean delivery rate was significantly lower (14.6 vs. 33.3%, P = 0.03) in the standard group; this difference was not explained by birth weights. In the experimental group, infants of women who did not receive insulin had lower birth weights than infants of mothers treated with insulin (3,180 +/- 425 vs. 3,482 +/- 451 g, P = 0.03). CONCLUSIONS: In women with GDM and fasting hyperglycemia, glucose plus fetal AC measurements identified pregnancies at low risk for macrosomia and resulted in the avoidance of insulin therapy in 38% of patients without increasing rates of neonatal morbidity.

Management of hypothyroidism during pregnancy.

Hypothyroidism during pregnancy occurs in 1/1600-2000 deliveries, according to the most recent publications. The most common causes are chronic autoimmune thyroid disease, radiodine-131 treatment, or surgical removal. The diagnosis is difficult to make on clinical grounds alone, even in advanced cases, and a high index of suspicion is needed. Some women are at high risk of developing hypothyroidism, and they should be screened. These women may have had previous treatment for hyperthyroidism; high-dose neck irradiation, evidence of thyroid autoimmunity, amiodarone therapy, suspected hypopituitarism, and type I diabetics. The best laboratory test is the serum TSH, followed, if elevated, by a free T4 index and a TPO-ab titer. Thyroid antibodies have been associated with an increased (double) risk of miscarriage and postpartum thyroiditis. Frequent (22-44%) pregnancy-induced hypertension leading to preterm delivery, and prematurity is the main complication observed in those still hypothyroid near term. Proper therapy eliminates or reduces the risk. No congenital anomalies have been reported in the most recent studies, and the data available shows that both physical and mental development have been normal until children are 10 years old. However, one study reported lower IQs in children of euthyroid women with positive TPO-ab than in children of TPO-ab negative mothers. Levothyroxine is the treatment of choice. Euthyroidism must be reached and maintained in a timely fashion. Many women need more thyroxine during pregnancy, and surveillance of thyroid function is needed throughout gestation to make dose adjustments when needed. During the postpartum periods the thyroxine requirements decrease to preconception levels.

Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism.

OBJECTIVE: To determine whether control of hyperthyroidism during pregnancy reduces the risk of low birth weight infants and severe preeclampsia. METHODS: Labor, delivery, and postpartum records of 181 hyperthyroid women were reviewed for maternal and fetal outcomes. Subjects were separated into three groups based on their thyroid status: controlled (n = 34), including women who were euthyroid at presentation and delivery; controlled during pregnancy (n = 90), including women who were hyperthyroid at presentation and euthyroid at delivery; and uncontrolled (n = 57), including women who were hyperthyroid at presentation and delivery. RESULTS: The risk of low birth weight infants was 0.74 (95% confidence interval [CI] 0.18-3.08) among controlled women, 2.36 (95% CI 1.36-4.12) among women who were controlled during pregnancy, and 9.24 (95% CI 5.47-15.6) among women who were uncontrolled during pregnancy compared to the incidence among nonhyperthyroid mothers. The risk of severe preeclampsia was significantly higher (odds ratio 4.74, 95% CI 1.14-19.7) among uncontrolled women compared with those who were controlled during their pregnancies. Elevated TSH-receptor antibody levels were not related to preeclampsia. Maternal thioamide therapy did not adversely affect neonatal outcomes. CONCLUSION: Lack of control of hyperthyroidism significantly increases the risk of low birth weight infants and severe preeclampsia.

Use of fetal ultrasound to select metabolic therapy for pregnancies complicated by mild gestational diabetes.

OBJECTIVE: To determine whether fetal ultrasound early in the third trimester can identify Latina with mild gestational diabetes mellitus (GDM) whose fetuses are at risk for macrosomia and, if so, whether maternal insulin therapy can reduce that risk. RESEARCH DESIGN AND METHODS: Study subjects included 303 consecutive women with GDM and a fasting serum glucose level < 5.8 mM on diet therapy who had a fetal ultrasound between 29 and 33 weeks gestation. Of the women, 98 (32%) had a fetal AC > or = 75th percentile for gestational age, and 59 women completed a randomized trial of diet therapy (n = 29) or diet plus twice daily insulin (n = 30). Maternal nutrient levels were assessed by meal tolerance testing (MTT) before and during therapy and by capillary glucose monitoring four to seven times a day. Birth weights corrected for gestational age and neonatal glycemia and skin folds were the primary outcome variables compared between treatment groups. RESULTS: Diet and diet-plus-insulin groups were well matched for maternal age, prepregnancy relative weight, weight gain during pregnancy, and glycemia at entry. Insulin therapy reduced maternal capillary (P < 0.005) and MTT (P < 0.001) glucose levels and prevented a diet-associated rise in MTT triglyceride levels (P < 0.002). Gestational age at delivery was similar in insulin- and diet-treated groups (39.6 +/- 0.2 vs. 39.5 +/- 0.2 weeks). Birth weights (3,647 +/- 67 vs. 3,878 +/- 84 g; P < 0.02), the prevalence of large-for-gestational age infants (13 vs. 45%, P < 0.02), and neonatal skin-fold measurements at three sites (P < 0.005) were reduced in the insulin-treated group. Rates of transient neonatal hypoglycemia were low in both treatment groups (14 and 18%, respectively) and did not differ significantly between groups. CONCLUSIONS: Fetal ultrasound early in the third trimester identified women with mild GDM whose infants were at high risk for fetal macrosomia in the absence of standard glycemic criteria for insulin therapy. Insulin treatment reduced the macrosomia, indicating that fetal ultrasound can be used to guide metabolic therapy in pregnancies complicated by mild GDM.

A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy.

OBJECTIVE: Our purpose was to demonstrate that propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism during pregnancy. STUDY DESIGN: Between 1974 and 1990 records were available on 185 pregnant patients with a history or diagnosis of hyperthyroidism. Ninety-nine patients were treated with propylthiouracil and 36 with methimazole. The response to therapy was compared with respect to the time to normalization of the free thyroxine index and the incidences of congenital anomalies and hypothyroidism. RESULTS: The time to normalization of the free thyroxine index was compared in the two groups by means of survival analysis. The median time to normalization of the free thyroxine index on propylthiouracil and methimazole was 7 and 8 weeks, respectively (p = 0.34, log-rank test). The incidence of major congenital malformations in mothers treated with propylthiouracil and methimazole was 3.0% and 2.7%, respectively. No neonatal scalp defects were seen. One infant was overtly hypothyroid at delivery. CONCLUSION: Propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism in pregnancy.

Outcome of pregnancy in diabetic ketoacidosis.

To evaluate the outcome of pregnancy in diabetic women who had an episode of ketoacidosis during gestation, 20 consecutive cases of ketoacidosis in type I diabetic pregnant women were studied. They were divided into two groups for comparison: Group 1, 13 patients (65%), had a live fetus and group 2, seven patients (35%), had a fetal death on admission. Both groups were similar in age, gravidity, parity, abortions, height, weight, serum sodium and potassium, arterial pH, carbon dioxide tension, bicarbonate, base excess, and anion gap. Significantly different between groups 1 and 2 were: gestational age (24 versus 31 weeks; p < 0.05), serum glucose (374 versus 830 mg/dl; p < 0.005), blood urea nitrogen (14 versus 23 mg/dl; p < 0.025), osmolality (295 versus 311 mmol/kg; p < 0.025), insulin requirements (127 versus 202 U; p < 0.05), and length of resolution (28 versus 38 hours; p < 0.05). Two patients had serum glucoses less than 200 mg/dl despite profound ketoacidosis. Precipitating factors included infections, poor compliance, and very importantly, unrecognized new onset of diabetes (6 patients). All stillborns were grossly normal and those autopsied had no discernible cause of death. There were no maternal deaths. A high fetal mortality (35%) was found but there were no fetal losses once therapy was initiated. The unrecognized new onset diabetics accounted for almost a third (30%) of the cases of ketoacidosis and for 57% of the fetal deaths. Attentiveness to the symptoms of uncontrolled diabetes and appropriate screening can be effective preventive measures.

Management of hyperparathyroidism in pregnancy with oral phosphate therapy.

Hyperparathyroidism during pregnancy is associated with greatly increased perinatal morbidity and mortality. Severe neonatal hypocalcemia and tetany is a particularly serious complication. Surgical removal of the abnormal parathyroid glands is currently recommended during pregnancy in view of the severity of the complications in the untreated patients and the favorable results in patients who have had surgery during pregnancy. Two patients are reported in whom surgery during pregnancy could not be performed. They were treated with oral phosphate, which successfully decreased serum calcium; their infants remained normocalcemic throughout the neonatal period. It is suggested that in selected cases medical treatment with oral phosphate can be an effective therapeutic alternative and surgery may be postponed until after delivery.