British Journal of Obstetrics and Gynaecology October 1986, VoI. 93, pp. 1088-1090

Ketoacidosis in pregnancy: an unusual presentation of diabetes mellitus. Case reports

GREG ROBERTSON, TREVOR WHEATLEY, RALPH E. ROBINSON

Case reports Patient 1

A previously fit 29-year-old white European gravida 2, para 0, presented at 29 weeks gesta- tion with a 3-day history of nausea, vomiting, polyuria and polydipsia. Since she had had a 16-week incomplete abortion 44 weeks before booking followed by secondary amenorrhoea, the expected date of delivery of her current preg- nancy was uncertain. On booking examination there were no abnormal findings and in particu- lar she was normotensive and at her ideal body weight. Ultrasound scan showed a normal fetus whose biparietal diameter and abdominal girth measurements were consistent with 25.5 weeks gestation. Although initial urinalysis with Ames multistix had shown 0.25% glycosuria, sub- sequent testing by her general practitioner and in the antenatal clinic was negative. There was neither a past nor family history of insulin- dependent diabetes or risk factors for develop- ing gestational diabetes.

On admission she was orientated, apyrexial but dehydrated and ketotic with Kussmaul res- piration. Her pulse was 100 beats/min and her supine blood pressure 120/80 mmHg. There were no signs of diabetic retinopathy or neu- ropathy. Doppler ultrasound confirmed the presence of a fetal heart. The results of bio- chemical investigations are shown in Table 1.

Rosie Maternity Hospital, Robinson Way, Cambridge CB2 2SW GREG ROBERTSON Registrar in Obstetrics and Gynaecology RALPH E. ROBINSON Consultant Obstetrician and Gynaecologist

Department of Diabetes and Endocrinology, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QQ TREVOR WHEATLEY Senior Registrar in Medicine

Correspondence: G. Robertson

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Routine therapy for diabetic ketoacidosis was commenced using intravenous normal saline, potassium supplements and insulin administered through a continuous infusion pump. Sub- sequently she was treated with Actrapid insulin thrice daily with Monotard insulin at night and her daily insulin requirement of 52 i.u. rose to 75 i.u. as the pregnancy proceeded. Further serial fetal ultrasound scans showed growth on the 50th centile and regular cardiotocographs were normal. Labour was induced at 38 weeks and as the cervix was unfavourable induction was facili- tated by two vaginal prostaglandin tablets 3 mg (Upjohn, UK). The ensuing labour, which was continuously monitored, proceeded rapidly and 6 h later she gave birth to a healthy female infant of 3.45 kg. There was no problem with neonatal hypoglycaemia or other complications referra- ble to maternal diabetes mellitus. No insulin was required in the puerperium but subsequent blood glucose levels confirmed persisting diabetes mellitus which, at 3 months, required treatment with insulin at a daily dose of 30 i.u.

Patient 2

A 31-year-old white European woman, gravida 4, para 1, was admitted at 29 weeks gestation with diabetic ketoacidosis. Eight years pre- viously a right tuba1 pregnancy had resulted in a salpingectomy and 6 years later following an intervening incomplete abortion, she was delivered of a 2-8 kg male infant at 38 weeks gestation. In the current pregnancy, booking examination at 13 weeks was normal and showed her to be normotensive and at her ideal body weight. There was no past nor family history of insulin-dependent diabetes or risk factors for developing gestational diabetes. Subsequent routine urinalysis at antenatal checks had not revealed glycosuria. On admission she was hyperventilating and ketotic but not dehy- drated, with a pulse of 70 beatshin and a supine brachial blood pressure of 105/60 mmHg. Physi-

Ketoacidosis in pregnancy 1089

Table 1. Biochemical findings in two patients on admission

Normal range Patient 1 Patient 2 for pregnancy

~ ~

Plasma glucose (mmoM) 19.5 29.5 <6 Plasma Na+ (mmol/l) 125.0 129.0 13C-142 Plasma K+ (mmol/l) 4.6 3.9 3.154.65 Plasma HC03 (mmoV1) 6-0 11.1 23.2-24.6 Plasma urea (rnmolll) 6.2 4.5 3.3 mmol/l Blood H+ (mmol/l) 71.0 50.0 3 w 4

Pa co2 (kPA) 1.5 2.93 4 G 5 . 3 Base excess -23.0 - 12.4 -2.2--4’6

Pa o2 (kPA) 16.9 15.1 9.3-12 Urine ketones +++ +++ Negative Plasma ketones +++ +++ Negative

Islet cell antibodies Not done Positive Negative Hb Al. (% total Hb) 8.0 8.0 5.5-8.5

cal examination was otherwise normal and the fetal heart sounds were present. The results of biochemical investigations on admission are shown in Table 1. Routine treatment with intra- venous normal saline, potassium and insulin cor- rected the metabolic abnormalities and satisfactory diabetic control was rapidly estab- lished with an appropriate diet and daily sub- cutaneous insulin dose of 103units which subsequently fell to 60 units. Ultrasound scan showed a normal fetus with abdominal girth well above the 90th centile and biparietal diameter just below the 50th centile. The abdominal girth returned to the 50th centile as the pregnancy progressed. At 37 weeks, because of falling material weight and decreased fetal movements, labour was induced with prostaglandin E2 tablets (Upjohn, UK) and accelerated by artificial rup- ture of membranes and oxytocin infusion. After 3 h of labour she was delivered of a 3.19 kg male. At birth the infant was noted to be dusky and examination revealed a cardiac defect, later diagnosed as transposition of the great vessels and treated by septostomy. There were no neo- natal complications attributable to maternal diabetes mellitus.

In the puerperium, maternal blood glucose concentrations were all 6mmol/l and a 75 g glucose tolerance test at 6 weeks postpartum showed a fasting blood sugar of 4-8 mmolll and a 2-h value of 6.9 mmol/l. However, the value at 30min was elevated at 11.2 mmolil. The patient’s serum was positive for complement fix- ing islet cell antibodies. Discussion When diabetes mellitus is first seen during pregnancy the diagnosis is usually either pre-

viously undiagnosed non-insulin-dependent (Type 2) diabetes mellitus, or gestational diabetes in which the glucose tolerance test returns to normal after delivery. In these condi- tions although insulin secretion is inadequate to maintain euglycaemia it is usually sufficient to prevent ketoacidosis (Hollingsworth 1984).

As the more severe beta cell deficiency of insulin-dependent (Type 1) diabetes mellitus develops over several months or even longer (Srikantha etaf. 1983; Gorsuchetaf. 1981), occa- sionally such patients might be expected to pres- ent with diabetic ketoacidosis, particularly during the third trimester of pregnancy when developing insulin deficiency would be com- pounded by the insulin resistance of late preg- nancy (Kuhl et af. 1985). Although ketoacidosis in the known insulin-dependent patient is well recognized, the only previously reported case arising de novo during pregnancy was a 32-year- old multiparous Jamaican who presented at 21 weeks gestation with hyperglycaemia and keto- acidosis following 2 weeks of vomiting (Livesley & Neary 1968). In this case, although the blood glucose values were only reported 1 month post- partum, there was no suggestion of subsequent insulin dependence. Also, she had previously given birth to a baby weighing 5 kg and it seems likely that prolonged vomiting in a patient with a non-insulin dependent diabetes mellitus resulted in hyperglycaemia and severe starva- tion ketosis, a condition to which the pregnant woman is particularly prone (Metzgar et af. 1982). The contention by Livesley & Neary (1968) that the primary diagnosis was lactic acid- osis seems unlikely in the clinical setting and was

1090 G. Robertson et al.

not supported by the plasma lactate concentrations.

In contrast, our first patient required insulin therapy within 3 months of delivery and is clearly insulin-dependent. While the type of diabetes remains to be established in our second patient, hyperglycaemia following a glucose load and positive complement fixing islet cell antibodies are, in context, suggestive of developing insulin- dependent diabetes mellitus (Irvine et af. 1980).

In view of the high perinatal mortality of up to 90% reported in diabetic ketoacidosis of preg- nancy (Kitzmiller 1982; Brumfield & Hud- dleston 1984), the successful delivery of live infants without complications attributable to maternal diabetes in our two patients is notewor- thy. The extent to which ketoacids per se are toxic to the fetus is controversial but the findings in our patients and in the one described by Live- sley & Neary (1968) suggest that the fetus, which is able to utilize ketone bodies (Robinson & Williamson 1980), may not be adversely affected by a single episode of ketoacidosis. Thus, fetal morbidity and mortality in diabetic ketoacidosis may be more influenced by previously poor dia- betic control (Karlsson & Kjeller 1972) and the reduction in feto-placental blood flow caused by maternal hypovolaemia (Arias 1975). This is consistent with the findings in our patients in whom the haemoglobin A1 was normal and marked intravascular hypovolaemia, as esti- mated from the plasma urea concentration, was not present.

As diabetic ketoacidosis could result in fetal and maternal mortality, earlier diagnosis of hyperglycaemia would clearly be valuable. The advantages of routine screening at 28-32 weeks are proven for detecting gestational diabetes (Lind & Anderson 1984) and it is of interest that our patients and the one reported by Livesley & Neary (1968) would have been diagnosed and episodes of ketoacidosis prevented by 28-week screening.

Finally, as it is probable that patients with sufficient insulin deficiency to develop diabetic ketoacidosis during pregnancy will subsequently develop insulin-dependent diabetes mellitus and as other autoimmune diseases are known to deteriorate in the postpartum period (Walfish & Chan 1985) such patients should be followed-up even though their routine postpartum glucose tolerance testing may be normal. Intermittent testing for glycosuria and estimation of

haemoglobin A1 will facilitate the early detec- tion of deteriorating glucose tolerance and avoid a prolonged period of potentially harmful asymptomatic hyperglycaemia.

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Hollingsworth, D. R. (1984) Metabolic changes in normal and diabetic pregnancy. In Pregnancy Diabetes and Birth. Williams & Wilkins, Baltimore/ London, pp. 21-38.

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Received I 1 December 1985 Accepted 24 February 1986