Risk Of Major Labour-Related Complications For Pregnancies Progressing To 42 Weeks Or Beyond

RESEARCH ARTICLE Open Access

Risk of major labour-related complications for pregnancies progressing to 42 weeks or beyond Anthea C. Lindquist1,2* , Roxanne M. Hastie1,2, Richard J. Hiscock1,2, Natasha L. Pritchard1,2, Susan P. Walker1,2 and Stephen Tong1,2

Abstract

Background: Post-term gestation beyond 41+6 completed weeks of gestation is known to be associated with a sharp increase in the risk of stillbirth and perinatal mortality. However, the risk of common adverse outcomes related to labour, such as shoulder dystocia and post-partum haemorrhage for those delivering at this advanced gestation, remains poorly characterised. The objective of this study was to examine the risk of adverse, labour- related outcomes for women progressing to 42 weeks gestation or beyond, compared with those giving birth at 39 completed weeks.

Methods: We performed a state-wide cohort study using routinely collected perinatal data in Australia. Comparing the two gestation cohorts, we examined the adjusted relative risk of clinically significant labour-related adverse outcomes, including macrosomia (≥ 4500 at birth), post-partum haemorrhage (≥1000 ml), shoulder dystocia, 3rd or 4th degree perineal tear and unplanned caesarean section. Parity, maternal age and mode of birth were adjusted for using logistic regression.

Results: The study cohort included 91,314 women who birthed at 39 completed weeks and 4317 at ≥42 completed weeks. Compared to 39 weeks gestation, those giving birth ≥42 weeks gestation had an adjusted relative risk (aRR) of 1.85 (95% CI 1.55–2.20) for post-partum haemorrhage following vaginal birth, 2.29 (95% CI 1.89–2.78) following instrumental birth and 1.44 (95% CI 1.17–1.78) following emergency caesarean section; 1.43 (95% CI 1.16–1.77) for shoulder dystocia (for non- macrosomic babies); and 1.22 (95% CI 1.03–1.45) for 3rd or 4th degree perineal tear (all women). The adjusted relative risk of giving birth to a macrosomic baby was 10.19 (95% CI 8.26–12.57) among nulliparous women and 4.71 (95% CI 3.90–5.68) among multiparous women. The risk of unplanned caesarean section was 1.96 (95% CI 1.86–2.06) following any labour and 1.47 (95% CI 1.38–1.56) following induction of labour.

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* Correspondence: anthea.lindquist@unimelb.edu.au 1Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia 2Mercy Perinatal, Mercy Hospital for Women, 163 Studley Rd., Heidelberg, Victoria 3084, Australia

Lindquist et al. BMC Medicine (2021) 19:126 https://doi.org/10.1186/s12916-021-01988-5http://crossmark.crossref.org/dialog/?doi=10.1186/s12916-021-01988-5&domain=pdfhttp://orcid.org/0000-0002-8662-5188http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/publicdomain/zero/1.0/mailto:anthea.lindquist@unimelb.edu.au

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Conclusions: Giving birth at ≥42 weeks gestation may be an under-recognised risk factor for several important, labour- related adverse outcomes. Clinicians should be aware that labour at this advanced gestation incurs a higher risk of adverse outcomes. In addition to known perinatal risks, the risk of obstetric complications should be considered in the counselling of women labouring at post-term gestation.

Keywords: Obstetric, Relative risk, Perinatal, Labour, Macrosomia, Shoulder dystocia, Post-partum haemorrhage, Caesarean section

Background Post-term gestation is defined as a pregnancy advancing be- yond 41+6 completed weeks of gestation [1]. The sharp in- crease in the risk of stillbirth and perinatal mortality beyond this gestation is well-established [1, 2]. As a consequence, post-term induction of labour by 41+6 weeks is routinely rec- ommended in many Western jurisdictions. The NICE guide- lines in the UK state that induction of labour should be recommended to women with uncomplicated pregnancies between 41+0 and 42+0 weeks [3], the WHO recommends in- duction of labour for any women who have reached 41+0 weeks [4] and the Australian and New Zealand College of Obstetricians and Gynaecologists advises that women be counselled about induction of labour after 41 weeks [5], in line with both NICE [3] and the American College of Obste- tricians and Gynaecologists guidelines [6]. However, the risk of common adverse outcomes related to labour, such as macrosomia, shoulder dystocia and post-partum haemor- rhage for those delivering at this advanced gestation, remains poorly characterised. The US-based ARRIVE trial, published in 2018, rando-

mised 6000 low-risk nulliparous women to induction of labour or expectant management at 39 weeks gestation. This landmark trial demonstrated a reduced risk of caesarean sec- tion and severe perinatal complications following elective in- duction of labour in low-risk women at 39 weeks and thus provided reassurance to many women and clinicians about the safety of elective delivery at this gestation [7]. Many women still opt to await spontaneous labour beyond their expected date of birth. For women who continue their preg- nancy, approximately 7% will progress beyond 41+6 weeks of pregnancy without labouring [8]. Given the assurances of the ARRIVE trial, offering an induction of labour is a viable alter- native management pathway that is unlikely to increase the risk of complications. It may therefore be informative to both clinicians and patients to characterise the degree of risk for significant labour complications for those who opt to wait 2 weeks beyond their expected date of birth, in the hope of avoiding an induction and undergoing spontaneous labour. Our study compared labour-related outcomes among

women who gave birth at 42 completed weeks and beyond (42+0–43+6) with those who gave birth at 39 completed weeks (39+0–39+6). The aim of this study was to determine labour- related risks of progressing to 42 weeks of pregnancy or

beyond, compared with those giving birth at 39 completed weeks of pregnancy. Thirty-nine weeks completed gestation was chosen as a reference due to the evidence of favourable perinatal outcomes at this gestation and the findings of the ARRIVE trial which identified this as a viable birth choice that does not increase obstetric risk and avoids the risk of progres- sing to a significantly advanced gestation undelivered [7].

Methods We performed a retrospective cohort study of 95,631 women who gave birth in the Australian state of Victoria between 2009 and 2014. Validated data were obtained from the Consultative Council on Obstetric and Paediat- ric Mortality and Morbidity (CCOPMM) for all births in Victoria [9–11]. CCOPMM is the central agency that collects data on obstetric and perinatal outcomes within the state. These data are populated by state-wide hos- pital documentation of outcomes by the midwives caring for the patients. We examined singleton pregnancies that reached term

gestation (≥37+0 weeks) and delivered a liveborn neonate between 1st Jan 2009 and 31st Dec 2014. Both compari- son groups included parous and nulliparous women, spontaneous and induced labours, spontaneous and assisted vaginal birth and unplanned, emergency caesar- ean section (elective ceasarean sections were excluded). Given the structure of the dataset, it was not possible to identify maternal clusters (children born to the same mother). Cases were excluded if they had missing or in- complete gestational age data. Completed week of gesta- tional age was the primary exposure in this analysis with gestation in days calculated using the date of birth of the baby relative to the estimated due date. The outcomes we selected to investigate were major

adverse labour-related complications with clinical rele- vance. These were macrosomia ≥4500g at birth, post- partum haemorrhage (documented as ≥1000ml, typically a weighed estimate), shoulder dystocia (formally docu- mented following the birth) or obstetric anal sphincter injury (documented 3rd or 4th degree tear) following va- ginal birth. We also examined the risk of unplanned (emergency) caesarean section following any labour and following induction of labour.

Lindquist et al. BMC Medicine (2021) 19:126 Page 2 of 8

The distribution of covariates between exposures, ges- tational age at birth (39 vs ≥42 completed weeks), was examined using univariable logistic regression for cat- egorical data and non-parametric Wilcoxon rank-sum test for continuous data. Potential confounding variables were selected based on a priori evidence of likely con- founding between these variables and the outcomes examined, and the results of univariate analysis demon- strating significant variation between the gestation co- horts. Potential confounders included in the regression model to produce adjusted risk estimates for each out- come of interest were parity (defined as the number of previous births over 20 weeks gestation and modelled as binary (nulliparous/multiparous)), maternal age (re- corded to the nearest year at prenatal booking and centred at 30 years) and mode of birth (as a three-level nominal variable: normal vaginal birth, instrumental va- ginal birth and emergency caesarean section). Interactions were assessed between exposure (gesta-

tional age 39 vs 42 weeks) and all covariates included in the adjusted models. Where an interaction was identi- fied, stratified risk measures were determined and pre- sented accordingly. Unadjusted and adjusted relative risk (RR) and 95% confidence intervals (95% CI) were com- puted using predicted probabilities derived from logistic regression, with 95% CI calculated using natural loga- rithms and back transformed to the standard metric [12]. Adjusted risk difference (RD) and 95% CI were computed using ordinary least squares linear regression with robust standard errors [13]. Statistical analysis was performed using Stata v15 stat-

istical software. The two-sided significance level was set at 0.05 and not adjusted for multiple comparisons. An a priori decision was made not to impute missing outcome data unless outcome missingness was different across exposure status and to only perform multiple imputation of covariates used in adjusted analyses if missingness exceeded 1%. By design, missingness did not occur for the exposure, gestational age at birth (39 vs ≥42 com- pleted weeks). At a two-sided significance level of 0.05 and a referent

rate of 5%, this study has a power greater than 90% to detect a RD of 1% or a RR of 1.22 given a cohort size of 100,000 and 5000 in exposure arms and a RD of 1.75% or RR of 1.41 for outcomes with 20,000 and 1500 in comparison arms.

Results Following exclusions, the study cohort included 332,413 births during the period 2009–2014. This comprised 91, 314 births at 39 completed weeks and 4317 at ≥42 com- pleted weeks (Fig. 1). Figure 1 depicts the number of births excluded by each criterion.

Table 1 shows the clinical characteristics of the two ges- tation cohorts. Pairwise comparisons indicated that women giving birth at ≥42 weeks were more likely to be nulliparous (58.9 vs 45.5%, p