Abstract
Objective
To estimate the incidence and predictors of severe obstetric morbidity.
Design
Development of definitions of severe obstetric morbidity by literature review. Case-control study from a defined delivery population with four randomly selected pregnant women as controls for every case.
Setting
All 19 maternity units within the South East Thames region and six neighbouring hospitals caring for pregnant women from the region between 1 March 1997 and 28 February 1998.
Participants
48 865 women who delivered during the time frame.
Results
There were 588 cases of severe obstetric morbidity giving an incidence of 12.0/1000 deliveries (95% confidence interval 11.2 to 13.2). During the study there were five maternal deaths attributed to conditions studied. Disease specific morbidities per 1000 deliveries were 6.7 (6.0 to 7.5) for severe haemorrhage, 3.9 (3.3 to 4.5) for severe pre-eclampsia, 0.2 (0.1 to 0.4) for eclampsia, 0.5 (0.3 to 0.8) for HELLP (Haemolysis, Elevated Liver enzymes, and Low Platelets) syndrome, 0.4 (0.2 to 0.6) for severe sepsis, and 0.2 (0.1 to 0.4) for uterine rupture. Age over 34 years, non-white ethnic group, past or current hypertension, previous postpartum haemorrhage, delivery by emergency caesarean section, antenatal admission to hospital, multiple pregnancy, social exclusion, and taking iron or anti-depressants at antenatal booking were all independently associated with morbidity after adjustment.
Conclusion
Severe obstetric morbidity and its relation to mortality may be more sensitive measures of pregnancy outcome than mortality alone. Most events are related to obstetric haemorrhage and severe pre-eclampsia. Caesarean section quadruples the risk of morbidity. Development and evaluation of ways of predicting and reducing risk are required with particular emphasis paid on the management of haemorrhage and pre-eclampsia.
What is already known on this topic
Maternal mortality is used internationally as a measure of the quality of obstetric intervention, although it is now rare in the developed world
Hospital based series estimating the incidence of severe obstetric morbidity have used different definitions
Estimated incidence of severe obstetric morbidity ranges from 0.05 to 1.09
What this study adds
With clear definitions and population based estimates of some severe obstetric morbidities this study estimated the overall incidence of severe obstetric morbidity as 1.2 % of deliveries
Two thirds of the cases are related to severe haemorrhage, one third to hypertensive disorders
Risk factors for severe maternal morbidity include maternal age >34, social exclusion, non-white, hypertension, previous postpartum haemorrhage, induction of labour, and caesarean section
Introduction
Maternal mortality has been used as a measure of the success of obstetric intervention but is now too rare for use in local practice in the developed world.1 Severe maternal morbidity has been suggested as an alternative measure.2,3 Most previous studies of severe maternal morbidity have been small (ranging from 21802 to 13 429 deliveries4) and undertaken in a maximum of two units,4 though one study examined intensive care admissions of obstetric patients in two regions of France.5 Most have been retrospective studies,2,3,6 with only one prospective study,3 and all were hospital based. They have used clinical definitions,2,4 counted admissions to intensive care,3,6 or investigated only the characteristics of women receiving obstetric intensive care.3,5–15 Definitions have differed and have included management decisions that are open to bias, depending on the facilities available and local customs. Consequently, the reported incidence of severe maternal morbidity varies from 0.05 %3 to 1.09 %.4 There are no data on the predictors of severe maternal morbidity.
We report on a multicentre population based study using reproducible clinical definitions. We estimated the incidence of severe obstetric morbidity and, by the use of a control population, investigated its predictors.
Methods
Developing definitions
We searched Medline using key words (severe maternal morbidity, obstetric intensive care, obstetric haemorrhage, uterine rupture, obstetric sepsis, HELLP (Haemolysis, Elevated Liver enzymes, and Low Platelets) syndrome, eclampsia, maternal mortality). We selected definitions that were clinically based and routinely measurable and that did not include management processes. When no definition relevant to the specific condition was available (for example, sepsis) we modified the standard definition to take into account the physiological changes in pregnancy. We focused on morbidity associated specifically with pregnancy and for which the management usually involves maternity care professionals. We excluded those conditions that are difficult to diagnose accurately or ascertain completely, the most important examples being pulmonary and amniotic fluid emboli. The box details the conditions investigated and their definitions in this study.
Definition of severe obstetric morbidity
Severe pre-eclampsia
Blood pressure 170/110 mm Hg on two occasions 4 hours apart or >170/110 mm Hg once plus ⩾0.3 g in 24 hours proteinuria or ⩾++ on dipstick
OR
Diastolic blood pressure >90 mm Hg plus proteinuria (as above) on one occasion plus one of the following signs/symptoms:
Oliguria (<30 ml/h for 2 hours)
Visual disturbances (flashing lights or blurred vision)
Epigastric/right upper quadrant pain or tenderness
Thrombocytopenia (<100x109/l)
Pulmonary oedema
Eclampsia16
Convulsions during pregnancy or in the first 10 days postpartum together with at least two of the following features within 24 hours after the convulsions:
Hypertension (⩾170/110 mm Hg)
Proteinuria (⩾+ on random dipstick analysis or ⩾0.3 g in 24 hours)
Thrombocytopenia (<100x109/l)
Increased aspartate aminotransferase (⩾42 U/l)
HELLP syndrome17
Haemolysis (abnormal peripheral smear or raised total bilirubin concentration (⩾20.5 μmol/l)), raised liver enzyme activity (raised aspartate aminotransferase (⩾70 U/l)) or raised γ-glutamyltransferase (⩾70 U/l), and low platelets (<100x109/l))
Severe haemorrhage18
Estimated blood loss >1500 ml, peripartum fall in haemoglobin concentration ⩾40 g/l or acute transfusion of 4 or more units of blood
Sepsis is systemic response to infection manifested by two or more of:
Temperature >38°C or <36°C (unless after prolonged caesarean)
Heart rate >100 beats/minute
Respiratory rate >20/min or PaCO2 <32 mm Hg
White cell count >17x109/l or <4x109/l or >10% immature forms
Plus bacteraemia (that is, positive blood cultures) or positive swab culture
Severe sepsis is sepsis associated with one of:
Organ dysfunction—for example, acute renal failure
Hypoperfusion—for example, lactic acidosis, oliguria, or acute alteration in mental state
Hypotension—that is, systolic blood pressure <90 mm Hg or drop of ⩾40 mm Hg in the absence of other causes of hypotension
Uterine rupture
Acute dehiscence of the uterus leading to the emergency delivery of the infant
Sampling frame for cases and controls
Cases included women from the South East Thames region who delivered after 24 weeks' gestation between 1 March 1997 and 28 February 1998 and met the definition criteria for severe morbidity. Controls were women from the same region who delivered without severe morbidity. Cases were identified from all 19 maternity units within the region and from six neighbouring hospitals to ascertain residents who delivered out of region. Cases were identified from multiple sources (maternity computer databases, labour ward and postnatal ward diaries, staff reporting, and medical records). A single investigator (MW) visited the hospitals every two to four weeks and reviewed all the medical records.
Social categories were grouped with the UK registrar general's categories: I and IIa (non-manual) and IIb, III, IV, and V (manual).21 Ethnic origin was grouped into white, black (black African and Caribbean), and other (all other ethnic groups). As measures of socioeconomic status (for example, marital status, male partner's employment) alone are inadequate for pregnant women, data were collected on indicators of social exclusion. This concept is currently in use by the UK government.22 We considered social exclusion to be present when any of the following were identified in the notes: concealed pregnancy, age <16 years, poor housing, low income (“on income support” written in notes), previous minor/child in local authority or state care (either currently or in past), in trouble with the law (currently or previously), living alone (partner abroad or “unsupported” written in notes), unbooked, unwanted pregnancy, currently or previously in foster care, care order being considered on potential child, social worker involved, and drug or alcohol dependency. Table 1 summarises the demographic data for all the women.
Table 1.
Demographic data for cases and controls. Figures are numbers (percentage) of women
| Cases (n=588) | Controls (n=2350) | |
|---|---|---|
| Ethnic group (%): | ||
| White | 448 (76.2) | 1986 (84.5) |
| Black | 98 (16.6) | 263 (11.2) |
| Other | 42 (7.2) | 101 (4.3) |
| Mean (SD) age (years) | 29.6 (5.8) | 28.7 (5.6) |
| Class (%): | ||
| Non-manual | 342 (58.2) | 1347 (57.3) |
| Manual | 111 (18.8) | 524 (22.3) |
| Unemployed | 85 (14.5) | 268 (11.4) |
| Unknown | 50 (8.5) | 209 (8.9) |
| Marital status (%): | ||
| Married | 349 (59.3) | 1398 (59.5) |
| Single supported | 199 (33.8.0) | 801 (34.1) |
| Single unsupported | 32 (5.5) | 108 (4.6) |
| Divorced | 8 (1.4) | 35 (1.5) |
| Unknown | 0 | 9 (0.4) |
| Parity (%): | ||
| 0 | 247 (42.0) | 752 (32.0) |
| 1 | 153 (26.0) | 705 (30.0) |
| 2 | 82 (14.0) | 423 (18.0) |
| ⩾3 | 106 (18.0) | 470 (20.0) |
We used power calculations to estimate the total number of women required. If we used a rise from 5% to 20% in incidence of postpartum hypertension23 we would require only 180 women in total (cases and controls) for a power of 90% at the 5% level. The estimated number of deliveries in the study region was 50 000, which, using the previous estimates of incidence of severe obstetric morbidity, would have given us between 25 and 545 cases. We collected data over one year to avoid seasonal variations in the calculation of incidence.
We selected four controls per case to increase the power to detect any differences in predictive factors between cases and controls. We generated a random list of all the unit numbers (1-19) with each unit's chance of being selected weighted to take into account the number of deliveries per year to remove selection bias towards the smaller units. The unit numbers were grouped consecutively into four for each case. In each unit, a further two digit random number was generated to select the woman to act as a control. This number matched the delivery number, with 1 being the first woman to deliver that week. A “week” ran from 0000 hours on Saturday and finished at 2359 on Friday.
Statistical analysis
We considered four forms of severe maternal morbidity: severe haemorrhage, severe pre-eclampsia (including HELLP syndrome and eclampsia), severe sepsis, and uterine rupture. For each of these the incidence of severe maternal morbidity was calculated with 95% confidence intervals. Unconditional logistic regression models were constructed with Stata (StataCorp, College Station, Texas, release 5, 1997) with severe maternal morbidity as the dependent variable. In the analysis of individual conditions we used all the controls. Unadjusted odds ratios were estimated with logistic regression for each of the data variables collected. Those variables with a significance level of P<0.05 were then included in a multivariate analysis. We also included variables that were thought to be clinically important but, because of factors such as small numbers, were not significant in the univariate analysis.
Age was grouped into 5 year bands. In univariate analysis the only significant age band was 35 years and over, and this was therefore used in the multivariate analysis. Women who had more than one condition (for example, both severe pre-eclampsia and severe haemorrhage) were considered only once in the incidence figures, and the most severe morbidity was counted. These cases were, however, used in the univariate and multivariate analyses for each condition involved. We adjusted odds ratios for severe maternal morbidity for all of the variables shown in table 3. A detailed list of the factors used for multivariate analysis is available from the authors.
Table 3.
Adjusted odds ratios for all cases and for each specific condition. Figures are odds ratios (95% confidence interval)
| Risk factors | All cases | Severe PET | Severe haemorrhage | Severe sepsis | Uterine rupture |
|---|---|---|---|---|---|
| Age ⩾35 years | 1.46 (1.11 to 1.92) | 1.83 (1.24 to 2.70) | 1.41 (1.03 to 1.95) | NA | NA |
| Blood pressure at booking | 1.23 (1.12 to 1.34) | 1.36 (1.21 to 1.52) | 1.18 (1.06 to 1.31) | NA | NA |
| Black | 1.16 (0.85 to 1.58) | 1.83 (1.22 to 2.74) | 0.97 (0.66 to 1.42) | 0.33 (0.03 to 3.38) | NA |
| Other race | 1.93 (1.24 to 2.99) | 2.43 (1.36 to 4.34) | 1.82 (1.09 to 3.03) | 7.02 (1.49 to 33.15) | NA |
| Social exclusion | 2.64 (1.69 to 4.11) | 1.99 (1.07 to 3.72) | 2.91 (1.76 to 4.82) | 2.96 (0.53 to 16.58) | 2.89 (0.22 to 37.71) |
| Smoker | 0.68 (0.49 to 0.93) | 0.47 (0.26 to 0.84) | 0.65 (0.44 to 0.96) | 3.56 (1.16 to 10.87) | NA |
| Previous PET | 1.52 (1.02 to 2.27) | 3.79 (2.13 to 6.74) | NA | 6.61 (1.81 to 24.18) | 1.30 (0.28 to 6.10) |
| Previous PPH | 2.41 (1.53 to 3.77) | NA | 2.74 (1.69 to 4.44) | NA | NA |
| Hypertension | 1.10 (0.63 to 1.95) | 1.92 (1.04 to 3.56) | 0.82 (0.37 to 1.80) | NA | NA |
| Diabetes | 1.76 (0.43 to 7.20) | 6.10 (1.13 to 32.75) | 1.85 (0.38 to 9.14) | NA | NA |
| Multiple pregnancy | 2.21 (1.24 to 3.96) | 3.27 (1.61 to 6.63) | 2.29 (1.20 to 4.37) | 3.05 (0.34 to 27.52) | NA |
| Antenatal admission | 1.75 (1.37 to 2.23) | 1.82 (1.30 to 2.54) | 1.85 (1.39 to 2.47) | NA | NA |
| Taking iron at booking | 5.53 (2.28 to 13.41) | 2.53 (0.67 to 9.59) | 5.98 (2.28 to 15.65) | 29.48 (2.50 to 347.83) | NA |
| Taking antiepileptics at booking | 5.31 (1.40 to 20.13) | 4.99 (0.85 to 29.15) | 5.75 (1.28 to 25.72) | 16.17 (0.40 to 661.17) | 35.50 (0.12 to 10472) |
| Taking antidepressants at booking | 4.30 (0.91 to 1.88) | NA | 10.55 (2.19 to 50.71) | NA | NA |
| IOL because overdue | 1.36 (0.99 to 1.88) | NA | 1.38 (0.95 to 1.99) | NA | 4.84 (1.11 to 21.22) |
| IOL on medical grounds | 2.45 (1.68 to 3.57) | NA | 1.33 (0.87 to 1.07) | NA | 8.61 (1.47 to 50.33) |
| Oxytocin augmentation | 0.99 (0.76 to 1.28) | NA | 1.61 (1.20 to 2.15) | NA | NA |
| Manual removal of placenta | 9.60 (5.67 to 16.28) | NA | 13.12 (7.72 to 22.30) | NA | 14.62 (1.35 to 158.80) |
| Emergency caesarean | 4.31 (3.39 to 5.49) | NA | 3.09 (2.29 to 4.17) | 11.85 (4.42 to 31.73) | NA |
PET=pre-eclamptic conditions including HELLP syndrome and eclampsia, PPH=postpartum haemorrhage, IOL=induction of labour, NA=not applicable as condition not included in multivariate analysis because not significant in univariate analysis.
Results
There were 48 865 deliveries and 588 cases identified, giving an incidence of severe obstetric morbidity of 12.0 per 1000 deliveries (95% confidence interval 11.2 to 13.2). During the same time period there were five maternal deaths directly attributable to the study conditions (three from sepsis, one from haemorrhage, one from HELLP), giving a severe morbidity to mortality ratio of 118:1 (97 to 140)
Table 2 shows the incidence of severe morbidity by condition. Although the population of south east England is not the same as throughout the United Kingdom, we could extrapolate these incidence figures to the whole of the United Kingdom. With 2 197 640 deliveries over three years in the United Kingdom,1 there would have been 14 724 cases of severe haemorrhage, 10 109 of the combined hypertensive conditions, 879 of severe sepsis, and 659 of uterine rupture.
Table 2.
Severe obstetric morbidity
| Category of morbidity | No of women | Percentage of deliveries |
|---|---|---|
| All cases | 588 | 1.20 |
| Pre-eclampsia: | ||
| Severe pre-eclampsia | 187 | |
| Eclampsia | 12 | |
| HELLP syndrome | 25 | |
| All | 224 | 0.46 |
| Haemorrhage: | ||
| Estimated blood loss >1500 ml | 180 | |
| Haemoglobin drop ⩾40 g/l | 96 | |
| Transfused ⩾4 units blood | 51 | |
| All | 327 | 0.67 |
| Severe sepsis | 17 | 0.04 |
| Uterine rupture | 12 | 0.03 |
| Others* | 8 | |
Acute fatty liver of pregnancy (n=3), anaphylaxis, severe hypertension, isolated pulmonary oedema, complications related to anaesthetic (cardiac arrest, total spinal block).
Risk factors associated with the individual conditions studied are shown in table 3. Few factors were independently significantly associated with the development of severe sepsis or uterine rupture. When we excluded data from the women with more than one condition the results were no different.
Discussion
In this large multicentre study that used standardised definitions the incidence of severe obstetric morbidity was 12 per 1000 deliveries, with a severe morbidity:mortality ratio of 118:1. This incidence is higher than previously estimated, although the conditions studied do vary between studies.2,3,6 The incidence of eclampsia was similar to that reported for the whole of the United Kingdom by the BEST survey.23
Case definition
We deliberately excluded thromboembolic disease, which is recognised as the leading cause of maternal mortality in the United Kingdom1 but is difficult to diagnose accurately when it is not fatal. The method of diagnosis differs from unit to unit, and some units in our region may rely entirely on clinical suspicion. Furthermore, as most cases occur in the postnatal period many women present to physicians and may never see an obstetrician. In view of these factors it would be impossible to ascertain if cases gathered represented an accurate reflection of the incidence. We did develop definitions in this study for severe thromboembolism but no cases were identified.
There is debate surrounding what constitutes the optimum definition of severe obstetric morbidity. The definitions that we developed and used represent a spectrum of severity of the morbidity under study and are open to modification. An example of this is severe haemorrhage. The definition has components that cover measurable blood loss, fall in haemoglobin concentration, and transfusion. Further work will be able to identify those elements of the definition that are associated with poorer outcomes.
Incidence
The estimates of incidence probably underestimate the true incidence as case ascertainment is unlikely to be complete, especially if events occur outside the delivery suite and are not recognised; this may be particularly true of less serious cases. However, we used several measures to minimise this loss of ascertainment. Data were collected contemporaneously, reducing the number of cases lost because of an inability to find notes or information. There were several site visits at frequent intervals to collect data, and information about cases was obtained from several sources.
Predictors
The main predictors of severe maternal morbidity were demographic (age over 34 years, non-white, and social exclusion), general medical (diabetes, hypertension), and obstetric factors (previous postpartum haemorrhage, multiple pregnancy, antenatal admission, emergency caesarean section). Anaemia may be a predictor as taking iron supplements at booking increased the risk of severe morbidity fivefold overall.
One could argue that very few of these predictors are amenable to change, but they may be useful in the identification of women who require extra vigilance. Previous studies have observed an increased risk of morbidity in women aged 35 years and over when they delivered their first child.24–30 The trend to defer childbearing in the developed world may lead to increasing maternal morbidity, and women should be advised that deferring childbearing has maternal as well as fetal risks. Social exclusion is a major public health issue that applies worldwide. This is another study highlighting the fact that those least advantaged are most likely to suffer harm.27,31 Smoking has a protective effect on severe morbidity in general and haemorrhage and pre-eclampsia in particular but is a predictor for severe sepsis. The protection against pre-eclampsia has been noted previously,32,33but the deleterious effects of smoking on the fetus are well documented.32 The five and tenfold risk of severe haemorrhage with antiepileptic and antidepressant drugs, respectively, is unexplained.
The predictors most amenable to change are those linked to obstetric interventions, specifically the risk from induction of labour (odds ratio 2.35) and emergency caesarean section (4.31). The adjusted odds ratio of developing severe sepsis after an emergency caesarean section was 11.85. Efforts to reduce the rapidly rising rate of caesarean section would be justified by the consequent reduction of severe maternal morbidity.
The only significant predictors of uterine rupture were induction of labour and manual removal of the placenta. This may, however, be a function of the small numbers of cases observed. Though a previous caesarean section was a significant predictor on univariate analysis this association was no longer significant after we adjusted for other risk factors.
The severe maternal morbidity:mortality ratio is a possible new indicator of maternal care and could be used to compare improvements in treatments more accurately than mortality data alone. Over 1 in 100 pregnant women suffer a life threatening event, and there are 118 events for each direct maternal death, most of which are related to obstetric haemorrhage and pre-eclampsia. This major health risk to childbearing women has been relatively underinvestigated. Severe obstetric morbidity is measurable and may be a more meaningful way to measure improvements in health care.
Acknowledgments
We thank all the clinicians and women who participated in this study for their time and Paul Seed and Richard Hooper, who provided statistical advice.
Footnotes
Funding: MW was funded by a research fellowship from the Research and Development Department of the South Thames NHS Executive.
Competing interests: None declared.
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