Evaluation of the three-hour oral glucose tolerance test in detection of significant hyperglycemia and hypoglycemia in pregnancy.

Analysis of 2,000 consecutive patients who had a three-hour 50-gm. oral glucose tolerance test done in the third trimester of pregnancy has shown that the three-hour reading was not necessary for the diagnosis of gestational diabetes. It was found that hyperglycemia and hypoglycemia (95th and 5th percentiles, respectively, for plasma glucose levels) were significantly associated with an increased risk for perinatal mortality. Furthermore, hyperglycemia was associated with an increased incidence of large-for-dates placentas and hypoglycemia with small-for-dates infants and small-for-dates placentas. These associations with hypoglycemia were seen to be greatest when this occurred at the three-hour level, and it was concluded that the three-hour measurement should be retained until the clinical significance of hypoglycemia in pregnancy is fully determined.

Congenital malformations, abnormal glucose tolerance, and estriol excretion in pregnancy.

Study of 10,454 consecutive newborn infants showed that 4.1% had a major malformation and 6.5% had a minor malformation. The incidence of major fetal malformations was increased in stillborn infants (14.1%), neonatal deaths (36.7%), and dysmature infants (8.6%), and when there was maternal hypoglycemia (5.8%, hyperglycemia (5.8%), or subnormal urinary estriol excretion (9.8%). Minor malformations were associated with fetal dysmaturity (9.7%) and subnormal estriol excretion (8.8%). Abnormalities of maternal glucose tolerance and urinary estriol excretion were associated with specific types of major malformations. These data showed that hypoglycemia was as important as hyperglycemia in the etiology of fetal malformations.

Maternal glucose tolerance during pregnancy with excessive size infants.

A study of maternal glucose tolerance conducted during 137 pregnancies in which the infant weighed 4540 g or more at birth revealed an increased incidence of hyperglycemia (20.4% P less than 0.01). Only when a birth weight of more than the 99th percentile was considered was a significant association with maternal hyperglycemia evident. However, 105 of the 137 patients (77%) had normal glucose tolerance, which indicated that hyperglycemia is not necessarily the cause of fetal overgrowth. When a woman delivers an infant with a birth weight of 4540 g or more, it cannot be assumed that she was a gestational diabetic.

The significance of abnormal glucose tolerance (hyperglycaemia and hypoglycaemia) in pregnancy.

Maternal hypoglycaemia (plasma glucose below 5th centile) had a highly significant association with fetal growth retardation, and perinatal mortality was significantly increased in the presence of both hypoglycaemia and hyperglycaemia (plasma glucose above 95th centile) when pregnancy outcome was analyzed in 5000 consecutive patients who had a glucose tolerance test performed during the third trimester of pregnancy. This study confirms the significance of abnormal glucose tolerance as a causative factor of feto-placental dysfunction. The flat glucose tolerance test pattern had no significance beyond the presence of associated hypoglycaemia, but reactive hypoglycaemia, and persistent abnormalities of plasma glucose levels during the test, were associated with higher incidences of complicated outcome. Hypertonic dextrose therapy administered to the patient with persistently subnormal urinary oestriol excretion was less likely to cause a favourable response in oestriol excretion if glucose tolerance was abnormal, perhaps because the adverse influences of abnormal glucose tolerance were not reversible by the third trimester of pregnancy. Hypoglycaemia and hyperglycaemia, additional to diabetes mellitus, are significant factors in the aetiology and diagnosis of abnormal pregnancy, and point to the need to investigate therapeutic measures.

Are there recognizable symptoms of abnormal glucose tolerance (hypoglycaemia and hyperglycaemia) in pregnancy.

The symptoms noted by 1,291 consecutive patients undergoing a glucose tolerance test during the third trimester of pregnancy were studied to determine whether their presence was attributable to obstetrically important hypoglycaemia or hyperglycaemia. Relevant symptoms were common and, apart from the more frequent occurrence of palpitations in patients with hyperglycaemia, did not have a significant relationship to maternal glucose tolerance patterns. Patients with hypoglycaemia weighed less, but did not evidence a reduced dietary intake, whereas those with hyperglycaemia smoked less. Symptoms classically associated with biochemical hypoglycaemia and hyperglycaemia were not reliable indicators for selection of patients with obstetrically significant hypoglycaemia or hyperglycaemia.

The influence of abnormal glucose tolerance (hyperglycaemia and hypoglycaemia) on pregnancy outcome when oestriol excretion is subnormal.

Subnormal urinary oestriol excretion was present in 611 (13.9 per cent) of 4403 consecutive patients in whom a glucose tolerance test had been performed and urinary oestriol excretion measured during the third trimester of pregnancy. Hypoglycaemia (less than 5th centile) had a significant association with subnormal oestriol excretion. The perinatal mortality rate was significantly higher in the presence of abnormal glucose tolerance when oestriol excretion was low. Normoglycaemia was associated with a perinatal mortality rate of 1.7 per cent when oestriol excretion was persistently low, whereas in the presence of hyperglycaemia (greater than 95th centile) the perinatal mortality rate was 12.5 per cent (P less than 0.01) and when there was hypoglycaemia the rate was 14.8 per cent (P less than 0.001). Small-fordates babies occurred in 46.3 per cent of pregnancies complicated by hypoglycaemia and persistently subnormal urinary oestriol excretion. The advantage of routine urinary oestriol assay and glucose tolerance testing in pregnancy is emphasized.

Fetal growth and placental function assessed by urinary estriol excretion before the onset of pre-eclampsia.

In a series of 1,316 patients with pre-eclampsia 744 had urinary estriol excretion measured before and 366 after the onset of clinical signs of the disease. Low estriol excretion had a highly significant association with fetal growth retardation and perinatal death both before and after the onset of clinical signs (p less than 0.001). As assessed by the incidences of low estriol excretion, fetal growth retardation, and perinatal wastage, pre-eclampsia of early onset (before 37 weeks) was a malignant disease in comparison with pre-eclampsia of late onset (after 37 weeks). Patients destined to develop early-onset pre-eclampsia had a high incidence of subnormal estriol excretion (25.4%; p less than 0.001). Although further deterioration of placental function occurred after the onset of clinical signs (41.3%; p less than 0.01), fetal growth and prognosis were already determined.

Carcinoma of the cervix, endometrium, and ovary: an 11-year review.

Over an 11-year period, 164 patients with genital tract carcinoma were managed at the Austin Hospital, Melbourne. For patients receiving primary treatment at the hospital, the five-year survival rates of patients with carcinoma of the cervix, endometrium, and ovary were 47.8%, 41.6% and 4.3% respectively. Improved results rest upon earlier diagnosis and alternative therapeutic measures, especially for carcinoma of the endometrium and ovary. Routine surveillance after initial therapy may detect asymptomatic metastatic disease when curative treatment is still possible.

Parity and pre-eclampsia.

In a series of 26,209 patiens, the incidence of pre-eclampsia was 9.3%, being significantly higher in primiparae (14.1%) than multiparae (5.7%) (P less than 0.001). In patients with early-onset pre-eclampsia there were highly significant (P less than 0.001) increases in the incidences of proteinuria, severe hypertension, placental abruption, fetal growth retardation, neonatal asphyxia and perinatal mortality. There were no significant differences between the incidences of these complications in primiparae and multiparae. The incidence of subnormal oestriol excretion was increased before the emergence of early-onset pre-eclampsia with equal to significance (P less than 0.001) in primiparae and multiparae. Eclampsia was more common in patients with late-onset pre-eclampsia, but not significantly so.

Importance of abnormal glucose tolerance (hypoglycaemia and hyperglycaemia) in the aetiology of pre-eclampsia.

In a series of 794 patients who had glucose tolerance tests done before the onset of pre-eclampsia, both hypoglycaemia (less than 5th percentile) and hyperglycaemia (P less than 95th percentile) had a significant association with early-onset severe pre-eclampsia ( less than 0.05). In the total series of 794 patients, hypoglycaemia had a significant association with low oestriol excretion (p less than 0.01), fetal growth retardation (p less than 0-05), low Apgar score (p less than 0.05), and perinatal mortality (p less than 0.05). These data indicate that, in patients with pre-eclampsia, hypoglycaemia is directly related to the cause of perinatal death.

Incidence of anencephaly and other major malformations when oestriol excretion is very low.

A study of 533 women with very low urinary oestriol excretion during the third trimester of pregnancy showed an incidence of major fetal malformations among their infants of 7-1% and a perinatal mortality rate of 14-6%. Thirteen of the malformations were cases of anencephaly, and 26 of the 78 perinatal deaths were due to or associated with major fetal malformations. The incidence of these complications was higher when maternal oestriol excretion was lower. Routine screening by urinary oestriol assay, with fetal radiography when values below 20-8 mumol/24 hours (6 mg/24 h) are detected is the most reliable method of detecting anencephaly before birth.

Intrauterine growth retardation.

Fetal growth retardation ranks third after prematurity and malformations as a cause of perinatal deaths. Antenatal fetal monitoring (biochemical testing of fetoplacental function plus cardiotocography) has emerged as the most important means of reduction in the number of stillbirths and improvement in the quality of survival of infants who are born alive. Clinical acumen combined with biochemical and/or ultrasonographic testing will identify no more than 70% of growth retarded fetuses. However, not all small for dates fetuses are at risk, and many doomed to die in utero are not by definition, growth retarded. It should be the obstetrician's aim to identify the fetus at risk of death from hypoxia whether growth retarded or not. Biochemical and ultrasonographic methods of testing are not truly comparable, since some aim to identify the growth retarded fetus, irrespective of his state of health, whereas others aim to detect fetoplacental dysfunction, irrespective of whether or not the fetus is growth retarded. With present methods of antenatal diagnosis and treatment and timing of delivery determined by nonstressed cardiotocography, the physical and intellectual prognosis of growth retarded infants is most satisfactory; follow-up studies have shown that only about 2% of these infants are severely handicapped.

Mortality and morbidity of fetal growth retardation.

This study reports the fetal outcome in 500 pregnancies when the baby weighed less than the 10th centile for gestational age at birth, compared with that in a series of 500 pregnancies where there was a normal weight for gestation. Fetal growth retardation (0-9th centile) had a significant positive association with perinatal mortality (5.2% versus 1.2%, P greater than 0.001) and low oestriol excretion (42.4% versus 15%, P greater than 0.001), but not with major fetal malformations or fetal asphyxia. In the study group, 20 of the 26 perinatal deaths were associated with subnormal oestriol excretion. When severe fetal growth retardation was considered (less than the 5th centile), the associations with perinatal mortality (19%) and subnormal oestriol excretion (63%) were stronger and a significant correlation with major malformations emerged (17%, P greater than 0.001). Detection of subnormal oestriol excretion allows identification and appropriate treatment of severe fetal growth retardation which should improve survival and neurological development in these infants. This study confirms that birth-weight below the 10th centile is an appropriate definition of fetal growth retardation in terms of perinatal mortality and morbidity.

Antenatal pregnancy complications and fetal growth retardation.

This study reports the associations between antenatal complications, subnormal urinary oestriol excretion and perinatal death in 500 pregnancies when the baby weighed less than the 10th centile for gestational age at birth, compared with those in a series of 500 pregnancies when the baby was of a normal weight for gestation. The overall incidence of antenatal complications was not higher in those pregnancies in which the fetus was growth retarded, although early onset pre-eclampsia, threatened abortion, diabetes mellitus and accidental haemorrhage were commoner (P less than 0.05). The incidence of subnormal urinary oestriol excretion was significantly higher in pregnancies in which the fetus was growth retarded, both when other antenatal complications were present (54.7% in the study group, 18.4% in the control group P less than 0.001) and in uncomplicated pregnancies (37.7% and 13.3%, respectively, P less than 0.001). Subnormal oestriol excretion identified 20 of the 26 perinatal deaths in the growth retardation group and 4 of the 6 perinatal deaths in the control group. Perinatal mortality was 10 times higher in growth retarded infants than in infants of appropriate size for gestation when pregnancy was not complicated antenatally. This study confirms the need to identify the presence of fetal growth retardation antenatally to enable appropriate treatment and improvement in perinatal mortality. The presence of antenatal complications is not appropriate for identification, whilst subnormal urinary oestriol excretion was seen to have highly significant predictive value.

Fetal growth retardation and pre-eclampsia.

In a series of 2434 patients with pre-eclampsia, the prevalence of fetal growth retardation was 8.7 per cent compared with 8.6 per cent in the total hospital population. The prevalence was increased in early-onset pre-eclampsia (18.2 per cent) (P less than 0.001) and reduced in late-onset pre-eclampsia (5.6 per cent) (P less than 0.001). In patients who later developed early-onset pre-eclampsia with fetal growth retardation, the prevalence of subnormal oestriol excretion was significantly increased (79.5 per cent) (P less than 0.001) as was the prevalence of hypoglycaemia (33.3 per cent) (P less than 0.001) suggesting that fetal growth retardation in these pregnancies preceded the clinical signs of pre-eclampsia. The prevalence of placental abruption (8.3 per cent) and the prevalence of perinatal deaths (28.7 per cent) were both significantly higher in pregnancies with early-onset pre-eclampsia and fetal growth retardation (P less than 0.001).

The association between abnormal glucose tolerance (hyperglycemia and hypoglycemia) and estriol excretion in pregnancy.

In 2,000 consecutive patients having glucose tolerance tests in pregnancy hyperglycemia (greater than or equal to ninety-fifth percentile) was associated with increased placental weight (p less than 0.01) but not with increased fetal birth weight. Patients with hypoglycemia (less than or equal to fifth percentile) were more likely to have small-for-dates babies (p less than 0.01). Perinatal death was related to maternal glucose tolerance, being reduced from 1.3% in the total series to 0.6% when normoglycemia was present (p less than 0.05); it was significantly increased in the presence of maternal hyperglycemia (p less than 0.001) and hypoglycemia (p less than 0.01). A combination of abnormal glucose tolerance and subnormal estriol excretion detected pregnancies with significantly higher incidences of fetal and placental growth retardation, major fetal malformations, and perinatal deaths. Moreover, the combination of normoglycemia and normal estriol excretion (62.3% of patients) was associated with a very favorable pregnancy outcome (0.4% perinatal death rate). Hypoglycemia was at least as significant as hyperglycemia in terms of unfavorable pregnancy outcome, especially when associated with subnormal estriol excretion.