University of Glasgow, Department of Obstetrics and Gynaecology, The Queen Mother's Hospital, Yorkhill, Glasgow G3 8SH, UK
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Abstract |
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Key words: duration/human/pregnancy/proportional hazards models/survival analysis
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Introduction |
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Modern obstetric techniques can be used to provide an unbiased estimate of gestational age. However, modern obstetric practice also involves routine elective delivery post-term (Grant, 1994). When attempting to estimate the duration of pregnancy, the effect of routine elective delivery cannot be avoided using current methods. If these pregnancies are excluded, then there is a systematic exclusion of pregnancies which are prolonged. If they are included, then the average duration of pregnancy includes cases where the end was never fully established.
A range of statistical techniques has been developed to estimate the average time period to the onset of a non-recurrent event, typically death (Hosmer and Lemeshow, 1999). These methods (typically referred to as `time to event analysis' or `survival analysis') take into account censored observations, i.e. observation of an individual to a given point until they no longer became at risk of the event. In the present study, it was sought to determine the average duration of human pregnancy among a previously described cohort of normal women (Smith et al., 1998
) where gestational age had been confirmed by first trimester ultrasound and where the estimate was adjusted for the effect of elective delivery using time to event analysis. A preliminary account of some of this work has been presented in abstract form (Smith, 2000
).
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Materials and methods |
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Over the 10 year period, 31269 embryos or fetuses had at least one scan and a known date of delivery. Gestational age at delivery was recorded in 31259 and birth weight was recorded in 30789. Of the 480 infants for whom birth weight was missing, 460 were delivered at <24 weeks.
Any pregnancies with the following (number of cases) were excluded: history of rhesus iso-immunization (279), essential hypertension (324), cardiac disease (128), type 1 diabetes mellitus (115), other medical problems (992), non-viable embryo or fetus at first scan (115), amniocentesis (1259), chorionic villous sampling (929), multiple pregnancy (364), antenatal detection of fetal abnormality (515), therapeutic termination of pregnancy (224), post-natal detection of fetal abnormality (560), intra-uterine contraceptive device seen on ultrasound (42), and second sac seen on ultrasound (85). There were a total of 4568 exclusions (some cases had multiple exclusions).
The crownrump length was measured by the sonographer using electronic callipers on a frozen image on a monitor. The technique is described elsewhere (Evans et al., 1990). The crownrump length was recorded as the equivalent number of days gestational age on the basis of an equation [gestational age (weeks) = 8.052 ÷ crownrump length + 23.73] previously derived at The Queen Mother's Hospital (Robinson and Fleming, 1975
). The scans analysed in the present study were performed by real-time ultrasonography using several machines, the majority were trans-abdominal scans through a full bladder.
The inclusion criteria based on the ultrasonography record were a single viable embryo or fetus present at the first ultrasound scan and a crownrump length at the time of this scan less than the expected size after having amenorrhoea for 13 weeks. A total of 11314 of the 26701 non-excluded cases fulfilled these criteria.
The inclusion criteria from the menstrual history were: (i) there was a date recorded for the first day of the last menstrual period and that it was recorded as certain; (ii) there had been no oral contraceptive use in the preceding 3 months, and (iii) the menstrual cycle was 28 days and regular. Of the 11 314 cases with no exclusion criteria who had an early ultrasound scan, 4229 fulfilled the menstrual inclusion criteria and had a birth weight recorded. The study group consisted of 1514 cases where the discrepancy between the estimated gestational age by the menstrual history was within ±1 day of the ultrasound estimate.
Statistical analysis
Delivery by emergency Caesarean section or vaginal birth following non-induced labour were taken to be the event. Elective Caesarean section or any mode of delivery following an induced labour were taken as censoring. The cumulative probability of non-elective delivery at each day of gestation was estimated using the KaplanMeier product limit estimate. Univariate comparisons were made using the log rank test. Multivariate modelling was performed using Cox's proportional hazard's method. These techniques are described in detail elsewhere (Hosmer and Lemeshow, 1999). Statistical analysis was performed using Stata version 6.0 (Stata Corporation, College Station, TX, USA).
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Results |
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Discussion |
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Unlike previous studies (Bergsjo et al., 1990), there was no apparent difference in the duration of pregnancy comparing male and female fetuses (Tables II and III
). Previous findings of a difference in gestational duration according to fetal sex may reflect a relationship between the timing of fertilization relative to the LMP and fetal sex (James, 1994
). The duration of pregnancy was approximately two days longer in nulliparous women. This was not due to a confounding effect of associated variables (maternal age, previous abortions etc) since nulliparity was still associated with later delivery after adjusting for these variables (Table III
). The event used in the current analysis was birth, rather than the onset of labour. Labour in nulliparous women is, on average, three hours longer than in multiparous women (Nesheim, 1988
). This is clearly not sufficient to explain the observed 2 day difference in duration of pregnancy comparing nulliparous and multiparous women.
The physiological regulation of the onset of parturition in the human is still only partially understood. Current models postulate key roles for the fetal hypothalamopituitaryadrenal axis (Nathanielsz et al., 1998) and for the placenta (Majzoub and Karalis, 1999
). The observed effect of parity does not exclude a key role for the fetus and placenta since important fetal variables, such as weight, differ between nulliparous and multiparous women (Kramer, 1987
).
The clinical significance of this study is that it provides a basis for predicting the probability of labour at a given gestational age at term. This may be useful when planning trials of, for instance, routine induction of labour, or for the timing of procedures such as elective Caesarean section. The present data allow the probability that a woman might go into labour prior to a scheduled date for elective delivery to be estimated. Furthermore, the cumulative probability of delivery tended towards 1.0 at 300 days. However, the increased risk of stillbirth with very advanced gestational age (Yudkin et al., 1987) means that virtually no pregnancy would be allowed to continue into the 43rd week and very high rates of censoring undermine the estimates of the probability of delivery at these advanced gestational ages.
The observation that bleeding in the third trimester was associated with an earlier onset of spontaneous delivery is plausible. However, given the relatively small number of women affected by third trimester bleeding, there was virtually no effect on the median duration of pregnancy when these cases were excluded (Table II). It is likely that a proportion of these cases were due to abruption which can initiate uterine activity. It is likely that labour in these women was initiated before the physiologically determined onset by a pathological process. However, the `event' was non-elective delivery, i.e. including delivery by emergency Caesarean section. This was done since over 75% of emergency Caesarean sections are performed after the onset of labour (Macara and Murphy, 1994
). It might be argued that third trimester bleeding due both to abruption and placenta praevia could lead to emergency Caesarean section before the onset of labour and that the apparent association between third trimester bleeding and early onset of labour may simply reflect an association between bleeding and emergency Caesarean section. However, the hazard ratios associated with both third trimester bleeding and nulliparity were very similar when emergency Caesarean sections were excluded. Treating emergency Caesarean sections as spontaneous births might also be criticized since a small proportion of these will have been performed prior to the onset of labour. Furthermore, when Caesarean section is performed during labour, birth necessarily occurs earlier than if vaginal birth had been awaited. However, the influence of these factors would be expected to be relatively minor and, indeed, treating emergency Caesarean section as censoring had no significant effect on the estimated median duration of pregnancy (Table II
).
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Acknowledgements |
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Notes |
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References |
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Submitted on November 1, 2000; accepted on March 14, 2001.