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Objectives Early onset severe pre-eclampsia is ideally managed in a tertiary setting. We investigated the possibility of safe management at secondary level, in close co-operation with the tertiary centre.
Design Prospective case series over 39 months.
Setting Secondary referral centre.
Population All women (n= 131) between 24 and 34 weeks of gestation with severe pre-eclampsia, where both mother and fetus were otherwise stable.
Methods After admission, frequent intensive but non-invasive monitoring of mother and fetus was performed. Women were delivered on achieving 34 weeks, or if fetal distress or major maternal complications developed. Transfer to the tertiary centre was individualised.
Main outcome measures Prolongation of gestation, maternal complications, perinatal outcome and number of tertiary referrals.
Results Most women [n= 116 (88.5%)] were managed entirely at the secondary hospital. Major maternal complications occurred in 44 (33.6%) cases with placental abruption (22.9%) the most common. One maternal death occurred and two women required intensive care admission. A mean of 11.6 days was gained before delivery with the mean delivery gestation being 31.8 weeks. The most frequent reason for delivery was fetal distress (55.2%). There were four intrauterine deaths. The perinatal mortality rate (≥1000 g) was 44.4/1000, and the early neonatal mortality rate (≥500 g) was 30.5/1000.
Conclusions The maternal and perinatal outcomes are comparable to those achieved by other tertiary units. This model of expectant management of early onset, severe pre-eclampsia is encouraging but requires close co-operation between secondary and tertiary institutions. Referrals to the tertiary centre were optimised, reducing their workload and costs, and patients were managed closer to their communities.
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Severe pre-eclampsia is one of the more serious problems facing obstetricians in the course of their practice, with a substantially raised associated mortality and morbidity, both of mother and baby.1,2 In general, there is agreement that women presenting with this condition after 34 weeks of gestation should be delivered, as the risks to mother and fetus outweigh any benefit to be gained by delaying delivery. On the other hand, there is much controversy around the management of patients with pregnancies between 24 and 34 weeks of gestational age, who present with severe pre-eclampsia. In first-world situations, many obstetricians take the line of immediate delivery, and rely on neonatologists with sophisticated facilities to deal with any of the problems with the child that may arise. Others have taken a more conservative approach, recognising that prematurity is a major risk factor in neonatal outcome.2,3 Much can be gained for the child by winning time and by giving steroids to accelerate lung maturity. The increased risks of such an approach can be minimised by adequate monitoring of the mother and the fetus.4,5 This has been the case at Tygerberg Hospital, Cape Town, South Africa, where perinatal mortality in this group of high risk cases has been brought to around 25/1000, a figure not markedly different from that of the population at large in Cape Town.6 Uniformly, where this expectant approach has been advocated, there has been agreement that these cases are most appropriately managed in tertiary/academic hospitals, where skills and resources are sufficiently concentrated to allow for the safe care of these women and their infants.1,5–9
Tertiary/academic hospitals in South Africa have been hampered by a reduction in funding, without a concomitant reduction in the referral workload. Recent provincial initiatives have resulted in an expansion of capacity in staffing and funding at regional hospital level. It was with this in mind that we developed a model of expectant management of early onset, severe pre-eclampsia at regional hospital level, with a much more restricted referral policy to the tertiary centre. The results of this change in policy are presented in this paper.
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The regional hospital is a 230-bed government institution. It serves a population of around 160,000 people and functions as a referral centre for the region's eight district hospitals. It has one full time specialist obstetrician, a registrar seconded from the tertiary institution, two medical officers and an intern that rotate through the department. After-hours cover is shared between the full time specialist and four private specialist obstetricians. Around 3000 deliveries per year are performed. The hospital has no formal adult or neonatal intensive care unit (ICU), although there are facilities for ventilating patients prior to transfer. It is situated about 100 km by tarred road from the referral academic hospital, and has a functioning ambulance service.
The study was performed over a period of 39 months, from October 1998 to December 2001. All women presenting between 24 and 34 weeks of gestation, with early onset, severe pre-eclampsia, who were stable and had no evidence of fetal distress, were admitted to the antenatal ward for conservative management. The group included both singleton and multiple pregnancies. Patients falling outside the gestational age category, or with major maternal complications of pre-eclampsia (mentioned below) or fetal distress, were excluded from the study. All recruited patients were included for analysis.
The diagnosis of severe pre-eclampsia was made when a diastolic blood pressure was measured ≥110 mmHg on two or more occasions, or ≥120 mmHg on one or more occasions, in the context of significant proteinuria (≥300 mg/24 hours, or persistent ≥1+ on dipstick).
Gestational assessment was based on the best available evidence, using ultrasound, the first symphysis–fundal height measurement and the menstrual history. Most patients in this study did not have an ultrasound assessment before 24 weeks of gestation. Symphysis–fundal measurements were documented using the locally appropriate chart of Theron and Thompson.10
On admission, patients were monitored as follows:
Six-hourly cardiotocograph (CTG) recording of fetuses ≥28 weeks of gestation. Fetal distress was defined as baseline variability less than 5 over 60 minutes, repeated late decelerations or both. The CTG tracings were assessed by trained nursing staff, and shown to the doctor on call if the pattern was not reassuring.
Six-hourly blood pressure measurement. This frequency increased to half-hourly if a diastolic blood pressure of ≥110 mmHg was recorded, until control of the blood pressure had been achieved.
Daily urine dipstix. When urine dipstick testing was inconclusive, a 24-hour collection of urine was done.
Twice weekly blood tests, viz. potassium, urea, creatinine, LDH, AST, ALT, haemoglobin and platelets. In cases of HELLP syndrome, a bilirubin and clotting profile were done as well.
A baseline ultrasound was performed, to assess fetal weight and amniotic fluid volume, and to exclude the presence of fetal abnormalities or maternal ascites. Umbilical artery Doppler was added if IUGR was suspected, although it was not routinely available for the entire study period. The ultrasound was repeated every second week, to assess growth. Reversed end-diastolic flow was an indication for delivery.
Patients were reviewed twice daily by the medical staff to detect potential complications at an early stage.
The following management was instituted:
Blood pressure control: Methyldopa 500 mg 6-hourly was used initially. Good control was regarded as not more than one diastolic blood pressure of ≥110 mmHg per 24 hours. If this was not achieved on methyldopa alone, prazosin was added, increasing from 1 mg 8-hourly stepwise to a maximum of 7 mg 8-hourly. If this too was inadequate, nifedipine 10 mg 8-hourly was added. All the agents were administered orally. From the start, nifedipine 10 mg as a stat oral dose was used for acute control of diastolic pressure peaks (≥110 mmHg), and repeated half-hourly until the diastolic blood pressure was <110 mmHg.
Prevention of fits: Magnesium sulphate was used if there was a clinical picture of imminent eclampsia (viz. blurred vision, increased reflexes, severe headache and epigastric pain), or if eclampsia developed. It was continued with monitoring of respiratory rate, pulse rate, urine output and reflexes for at least 24 hours after delivery.
Prenatal steroids: Betamethasone 12 mg was given intramuscularly on admission to those women at ≥27 weeks of gestation, repeated 24 hours later, and thereafter weekly until delivery or 33 weeks of gestation.
The patients were delivered electively after reaching 34 weeks of gestation. Indications for earlier delivery included: uncontrolled blood pressure despite the use of three drugs, non-reassuring fetal heart rate pattern, Doppler studies showing reversed end-diastolic flow in the umbilical arteries, intrauterine death or if the mother developed major complications. These were ascites, HELLP syndrome, pulmonary oedema, severe renal impairment (serum urea >10 mmol/L), eclampsia or placental abruption.
The route of delivery was that deemed appropriate by the attending consultant. Induction of labour with intracervical dinoprostone was used when there was no urgency, otherwise caesarean section was done. Cases were referred by the local specialist to the tertiary centre on an individualised basis, and in consultation with the specialist obstetricians who run the high care unit there. Referrals generally were of women with a major maternal complication or with a very small baby.
The mothers were kept in hospital after delivery until stable, and then discharged on treatment. It is the policy of the hospital to discharge those who have had uncomplicated caesarean sections after three to four days.
Well neonates weighing 1800 g or more were kept with their mothers in the ward. Sick neonates, and those weighing less than 1800 g, were admitted to the high care neonatal unit until they had stabilised and gained weight. Kangaroo Mother Care was used where possible.11 Babies were transferred to the tertiary hospital on the opinion of the attending paediatrician, in consultation with the neonatal ICU staff there. For the purposes of this study, admission to the ICU in the tertiary institution was used as a marker for neonatal morbidity.
The data collected were coded, tabulated and entered into a computer. Statistical analysis was performed by a biostatistician attached to the referral hospital. The number and percentage of qualitative variables, and the mean and standard deviation (SD) of quantitative data were calculated. The main outcome measures were: prolongation of gestation, maternal complications, perinatal outcome and number of cases needing referral to the tertiary institution.
The local ethics committee approved the study protocol.
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A total of 131 women were included in the study, of whom 116 (88.5%) were managed entirely at the secondary hospital. Eighty-eight (67.2%) of the women were multigravidas, and there were four twin pregnancies. The median age was 26 years (range 15–41). The mean gestation on admission was 29.9 weeks (SD 2.4).
One hundred and sixteen (88.5%) of the women were admitted with a diastolic blood pressure of ≥110 mmHg; the remaining 11.5% arrived at the hospital with their blood pressure already controlled with anti-hypertensive agents. The mean blood pressure on admission was 173/115 mmHg [SD 20/8].
A mean of 11.6 (SD 12.5) and median of eight days (range 1–89) were gained by expectant management. Ninety-two percent of the women gained 48 hours or more, allowing adequate time for the steroids given to work. The mean gestation at delivery was 31.8 weeks (SD 2.2). The indications for delivery are given in Table 1. Twenty-nine women (22.1%) reached 34 weeks of gestation without complications. Of these, 17 had labour induced electively, of which 12 (70.6%) delivered normally. Overall, 101 women (77.1%) required caesarean section. Major maternal complications occurred in 44 patients (33.6%) and are shown in Table 2.
Table 1. Indications for delivery.
|Fetal distress||71 (54.2)|
|Elective delivery at 34 weeks||29 (22.1)|
|Spontaneous labour||12 (9.2)|
|Maternal reasons||10 (7.6)|
|Intrauterine death||4 (3.1)|
|Fetal reasons other than distress||3 (2.3)|
|Maternal/fetal reasons||2 (1.5)|
Table 2. Maternal complications. Patients may have more than one complication.
|Placental abruption||30 (22.9)|
|HELLP syndrome||6 (4.6)|
|Loss of BP control||4 (3.1)|
|Severe renal impairment||3 (2.3)|
|Admission to ICU||2 (1.5)|
|Pulmonary oedema||1 (0.76)|
|Cerebrovascular accident||1 (0.76)|
|Maternal death||1 (0.76)|
The maternal death was a 23 year old P2G3 who presented at 29 weeks of gestation. Biochemistry showed raised ALT, AST and LDH values, but the platelet count was above 100 × 109/L. Thirty-six hours after admission, the CTG showed signs of fetal distress. At caesarean section a live infant was delivered, and ascites and a 15% abruption were noted. Her oxygen saturation dropped shortly after extubation, and aspiration was suspected. She was reintubated, ventilated and transferred to the ICU, where a HELLP syndrome and disseminated intravascular coagulation (DIC) were confirmed. Her haemoglobin continued to fall, and her abdomen became progressively distended. No significant bleeding was found at re-laparotomy 4 hours after the first surgery. She was then transferred to the tertiary ICU, where she developed sepsis and acute renal failure, from which she died two days after her initial surgery. One case included in the study was not managed according to our protocol. She was a massively obese woman (136 kg) admitted at 26 weeks of gestation with a blood pressure of 220/130 mmHg, and 302 mg of protein in a 24-hour urine sample. Her blood pressure responded to therapy and she was discharged for high risk outpatient follow up. Her subsequent diastolic blood pressure ranged between 75 and 100 mmHg, and her urine never had more than a trace of protein on dipstick. She presented in labour at 39 weeks and delivered a 3800 g live baby. Review of hospital records showed hypertension outside of pregnancy. She was probably chronically hypertensive with mild renal dysfunction, and not a pre-eclamptic patient.
Women stayed in hospital for a median of four days (1–13) after delivery.
There were 15 transfers to the referral hospital, of which 13 took place in the antenatal period. Five women were referred for purely maternal reasons that included HELLP syndrome, pulmonary oedema, renal failure and morbid obesity. Four cases were referred where an extremely low birthweight was anticipated in the face of imminent delivery; while in three cases there were combined reasons (ascites, HELLP, renal failure in the setting of very low estimated fetal weight). A single case was kept inadvertently by the referring hospital after being referred for a Doppler investigation. During the postpartum period, one woman was referred for HELLP, ascites and a DIC, while another accompanied her infant, which needed ventilation.
A total of 135 babies were delivered, of which four (3.1%) were intrauterine deaths. The mean birthweight was 1624 g (SD 486) and 20 (15.3%) had 5-minute Apgar scores of 6 or less. The mean birthweight of the 15 transfers to TBH was 1272 g (SD 498). The male/female ratio was 44:56. Of the 117 live born babies delivered at the secondary hospital, 73 (62.4%) required admission to the neonatal high care unit, where the median stay was 18 days (1–72). Overall, 15 (11.5%) of the 131 live born babies needed ventilation.
The perinatal mortality rate was 44.4/1000 (for all babies ≥1000 g) and 59.2/1000 for babies ≥500 g. A total of 14 (10.7%) live born babies died; four died within the first week, another six died in the next three weeks and a further four died before discharge. This represents an early neonatal mortality rate of 30.5/1000 for babies ≥500 g. Three of the four stillbirths occurred as a result of placental abruption. The remaining death was as a result of severe placental insufficiency with intrauterine growth restriction.
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Expectant management of early onset, severe pre-eclampsia has been shown to be worthwhile in a tertiary setting.4–6,8 However, the decision to manage these very high risk pregnancies expectantly at a regional hospital is controversial, and was taken with a number of factors in mind. The obstetrician at the regional hospital trained in the tertiary hospital, and was familiar with their protocols of management, all of which (with the initial exception of umbilical artery doppler studies) were possible at a regional level. There was close association with the academic unit. The distance between the units was relatively small (100 km), on good roads, with access to a functioning ambulance service. Other factors considered were the budgetary constraints of the tertiary hospital and the benefit gained from keeping patients closer to their homes.
The results are for the most part therefore representing this combined model of management (i.e. they pool data from the secondary hospital and the referred cases).
The perinatal mortality rate for all deliveries at the regional hospital during the study period was 23/1000 for babies ≥1000 g and 37/1000 for those ≥500 g. Although the perinatal mortality rate (44/1000 for babies ≥1000 g and 59/1000 for those ≥500 g) achieved for these high risk pregnancies was not as good as that reported by Hall et al.,6 who achieved a rate of 24/1000 for babies ≥1000 g, it nonetheless compares favourably with that of other studies from tertiary institutions, which have ranged from 70 to 380/1000.1–3,7,12–15
It is of special note that close to 90% of these women could be managed at the secondary level. Although 33.6% of the women developed major complications, the overall impact was relatively low. Close monitoring allowed one to detect their development early, and to expedite delivery. Notably, placental abruption, by far the most common major complication, could often be picked up by changes in the CTG. The maternal death is a reminder of the fact that the disease is one of high risk. In South Africa, hypertension in pregnancy is the leading direct primary obstetric cause of maternal death. It accounted in 1998 for 36.6% and in 1999 for 32.2% of these deaths.16
In our study, multigravidas outnumbered primigravidas with the disease by more than two to one. This is against received wisdom, but has been borne out by other South African studies.2,7,8,17
The rates of major maternal complications in this study are comparable with those from studies on a similar population in the referral hospital.6,8 Similarly, the rates of fetal distress, caesarean section and induction of labour were comparable with those reported by Hall et al. This is probably a reflection of the similarity of populations studied, and of an agreement on diagnosis and endpoints between the two centres. A skewed sex ratio with a preponderance of female babies was also noted by Hall et al.6 Its significance is uncertain. The abruption rate in this Western Cape, South African population is very much higher than that reported in studies elsewhere, where it has ranged between 4.2% and 8.5%.1,5,7,14,18 The population studied has high rates of smoking, as well as alcohol use, and these may play a causative role.
Despite the maternal morbidity, and the fact that 77% of the women needed caesarean section, it is noteworthy that the median length of hospital stay (four days) was very similar to that which one would expect from uncomplicated caesarean sections, as per hospital policy. This is in keeping with a fairly rapid return to normality after delivery.
Antenatal steroids have been shown to improve fetal outcome by reducing the incidence of hyaline membrane disease. Ninety-two percent of the women managed expectantly gained at least 48 hours (i.e. enough time for the steroids to work). The proportion of babies requiring ventilation (11.5%) was much lower than in other studies. Hall et al.6 reported 34.1% that needed ventilation. The policy of weekly administration of steroids has since been revised in keeping with the current evidence.
Under the prevailing circumstances, we feel that this model of close association between secondary and tertiary centres offers practical advantages. If all cases had been directly referred to the tertiary institution, it would have resulted in a 53% increase in admissions to the high care unit there. It does not require complex equipment or a NICU at the regional level. It does however require competent and motivated staff, both on the antenatal and the neonatal sides who can give adequate care to the mothers and their babies, and who have the insight to know when to consult. Similarly, the continued support of the tertiary unit staff is essential, both in giving advice and in being prepared to accept transfers. These are exceptionally high risk cases, and there is no room for complacency in their management.