Short communication
DOI: 10.1111/j.1471-0528.2010.02526.x www.bjog.org
Diurnal variation is lost in preterm deliveries before 28 weeks of gestation M Vatish,a,b PJ Steer,c AM Blanks,a M Hon,a S Thorntona a
Warwick Medical School, Clinical Sciences Research Institute, Coventry, UK b Albert Einstein College of Medicine, New York, USA Academic Department of Obstetrics & Gynaecology, Chelsea & Westminster Hospital, London, UK Correspondence: Prof. S Thornton, Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK. Email
[email protected]
c
Accepted 20 January 2010. Published Online 12 March 2010.
Preterm delivery is the primary cause of neonatal mortality and morbidity worldwide. Labour at term occurs as a culmination of maturational events in both the fetus and maternal uterus. This process exhibits diurnal variation, with the onset of labour being more common at night. We have confirmed that this diurnal variation is present in gestations between 28 and 36 weeks, but is absent below 28 weeks. We hypothesise that this is because before
28 weeks of gestation, the onset of labour may result from a pathological rather than a physiological process. This may have important implications regarding any pharmacological approach to the prevention and/or treatment of very early preterm labour. Keywords Diurnal variation, first stage, preterm labour, spontane-
ous rupture of membranes, tocolysis.
Please cite this paper as: Vatish M, Steer P, Blanks A, Hon M, Thornton S. Diurnal variation is lost in preterm deliveries before 28 weeks of gestation. BJOG 2010;117:765–767.
Introduction Preterm labour occurs in about 10% of pregnancies. It is a major obstetric problem requiring a multidisciplinary approach. The causes of preterm labour are multifactorial.1 The majority of neonatal mortality and morbidity occurs below 28 weeks of gestation, when the aetiology may be different to that at later gestational ages.2 Labour normally occurs as a result of a culmination of maturational events in the fetus and maternal uterus.1 Although the physiological process has a diurnal variation, so that the onset of labour is more common at night, our hypothesis was that this variation may not occur in very preterm (before 28 weeks of gestation) labour, because the mechanism of onset is pathological. If correct, this may have important implications for tocolysis.
Methods St Mary’s maternity information system, covering 15 maternity units in the North-West Thames region, recorded data from all deliveries of spontaneous onset Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#Online Open_Terms
(n = 19 335) at 24–36 weeks of gestation during the period 1988–98. Data regarding the date and time of (a) spontaneous rupture of membranes (SROM), (b) the onset of the first stage (S1), (c) the onset of the second stage of labour (S2) and (d) the delivery were determined. The number of nocturnal (22.00–03.00 hours) compared with daytime (10.00–15.00 hours) deliveries were calculated. Data was entered by trained clerks or midwives, with online validation and prompting. Standard definitions were used for all clinical measurements. Chorioamnionitis was assumed if the maternal temperature exceeded 37.5C. Data entry has been validated previously, and was of high quality.3 Times were truncated to the nearest hour. Data analysis was performed using a Student’s t-test.
Results Data were incomplete for SROM and S2 (3.7% n = 715 and 12.8% n = 2474 cases missing, respectively), but were complete for S1 and delivery time. At gestational ages of 28–36 weeks, there was a marked diurnal variation in the time of SROM and S1 (Figure 1). This was maintained when women with chorioamnionitis were excluded (data not shown). There was no diurnal variation in the timing of SROM or S1 below 28 weeks of gestation, nor in S2 or delivery at any gestational age (data not shown), although
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Vatish et al.
A
B
C SROM (n)
S1 (n)
10–15.00
22–03.00
p
10–15.00
22–03.00
p
28–36
3886
5545
0.002
4220
5503
0.017
24–27+6
250
268
NS
302
292
NS
Time
Gestational age
Figure 1. Onset of the first stage (S1) and time of spontaneous rupture of membranes (SROM) expressed as a percentage of the total for each gestational age group at: (A) 24–27 + 6 weeks of gestation, and (B) 28–36 weeks of gestation. (C) The numbers at night (22.00–0300 hours) and during the day (10.00–15.00 hours) are shown for each group. The P value is given for a comparison of night and day by the Student’s t-test; NS, not significant.
data cannot be adjusted for tocolytic administration. The peak time of SROM was 03.00 hours at 28–36 weeks of gestation. The peak onset of S1 was 02.30 hours for 28–36 weeks of gestation. In contrast, there was no diurnal variation in SROM or S1 using the smaller data set of deliveries before 28 weeks of gestation.
Discussion Our data demonstrate that the marked diurnal variation in the time of SROM and S1 in preterm labour does not occur at gestational ages below 28 weeks. The diurnal variation between 28 and 36 weeks of gestation is consistent with previous publications,4 and suggests that a proportion of these labours are caused by early maturation of the term physiological process. Therapies that are based on the mechanism of term labour are therefore most likely to be effective at these gestations. It is interesting that the results were not influenced by the exclusion of women with chorioamnionitis, which may modify the diurnal variation.5,6 We have now demonstrated, in contrast to earlier results using a smaller data set,5 that there is no diurnal variation in very early preterm labour. This may be because of the immaturity of the fetal hypothalamopituitary axis, which normally
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mediates the diurnal variation in uterine contractility,7 but it is more likely that other pathological aetiologies bypass the physiological process. This is important clinically because the aetiology influences management. Tocolysis is contraindicated in preterm labour caused by events that could be detrimental to the fetus, such as infection or abruption. These causes are also likely to circumvent the physiological mechanism of labour responsible for diurnal variation, so identification of these may allow treatment to be restricted to those who will benefit most. Furthermore, tocolytics developed principally on the mechanism of term labour may be less effective at very early gestational ages. In conclusion, our data suggests that preterm labour invokes an early activation of the normal labour process after, but not before, 28 weeks of gestation. This has important implications for the management of early preterm labour.
Disclosure of interests ST performs commercial consultancy work.
Contribution to authorship All authors contributed to the design, analysis, interpretation of the results, or the writing of the manuscript. MV
ª 2010 The Authors Journal compilation ª RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology
Diurnal variation in preterm deliveries
and PJS contributed equally and should be considered joint first authors.
Details of ethics approval Not needed, as the study involved an anonymous retrospective data analysis.
Funding None.
Acknowledgements Our work is supported by MRC, Wellbeing of Women, Action Medical Research, the Fulbright Commission, and University Hospitals of Coventry and Warwickshire. j
2 Gomez R, Romero R, Edwin SS, David C. Pathogenesis of preterm labour and preterm premature rupture of membranes associated with intraamniotic infection. Infect Dis Clin North Am 1997;11: 135–76. 3 Cleary R, Beard RW, Coles J, Devlin HB, Hopkins A, Roberts S, et al. The quality of routinely collected maternity data. Br J Obstet Gynaecol 1994;101:1042–7. 4 Lindow SW, Jha RR, Thompson JW. 24 hour rhythm to the onset of preterm labour. BJOG 2000;107:1145–8. 5 Cooperstock M, England JE, Wolfe RA. Circadian incidence of premature rupture of the membranes in term and preterm births. Obstet Gynecol 1987;69:936. 6 Cooperstock M, England JE, Wolfe RA. Circadian incidence of labor onset hour in preterm birth and chorioamnionitis. Obstet Gynecol 1987;70:852. 7 Nathanielsz PW, Jenkins SL, Thane JD, Winter JA, Guller S, Giussani DA. Local paracrine effects of estradiol are central to parturition in the rhesus monkey. Nature Med 1998;4:456–9.
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