Journal Club Papers
- Meta-analysis of individual participant data (rather than aggregate data) to investigate perinatal outcomes following induction of labour (IOL) at 41weeks’ gestation vs expectant management until 42 weeks among low-risk singleton pregnancies.
- IPDs are considered a stronger design compared to usual meta-analyses’.
- 3 RCTs including a total of 5,163 women were included, with 2 studies providing individual participant data (IPD n=4,561)
- Of the 2 studies in the IPD meta-analysis, IOL reduced the risk of perinatal mortality and severe neonatal morbidity (composite primary outcome) by 57% (RR 0.43 [95% CI 0.21, 0.91]; 0.4% vs 1.0%; NNT 175).
- Perinatal mortality was significantly reduced in the IOL group (OR 0.21 [95% CI 0.06, 0.78] 0.04% vs 0.35%; NNT 326). 1/2281 perinatal deaths occurred in the IOL group (stillbirth after randomisation but before IOL) compared to 8/2280 in the expectant management group (6/8 unexplained).
- Among secondary outcomes, NICU admission and macrosomia (>4500g) were significantly reduced in the IOL group. IOL also reduced the risk hypertensive disorders of pregnancy (RR 0.39 [95% CI 0.25, 0.61] 1.1% vs 2.9%).
- No difference in caesarean or operative vaginal delivery was found between groups.
- Additional subgroup analyses were performed to investigate effect of parity:
- Among nulliparous women, IOL reduced the risk of perinatal mortality and severe neonatal morbidity by 80% (RR 0.20 [95% C I 0.07, 0.60] 0.3% vs 1.6%), rather than the 57% seen in the total population.
- For multiparous women, IOL did not alter the risk of perinatal mortality and severe neonatal morbidity (RR 1.93 [95% CI 0.48, 7.72] 0.6% vs 0.3%).
- Due to the low rate of perinatal mortality, analyses by parity were not performed. However, the incidence of perinatal mortality among nulliparous was 0% (0/1219) for IOL vs 0.9% (7/1264) for expectant management and for multiparous women; 0.1% (1/1062) for IOL vs 0.1% (1/1016) for expectant management.
- There was no difference in the effect of IOL on caesarean delivery or any other outcome by parity.
Overall, these findings confirm IOL at 41 weeks among low-risk women reduces the risk of severe adverse perinatal outcomes, including perinatal mortality, without increasing the risk of caesarean or operative vaginal delivery. Although this benefit was not seen for multiparous women this may be due to a lack of power to detect severe adverse outcome that have a low incidence among uncomplicated multiparous women.
Furthermore, these findings are in agreement with a meta-analysis of observational studies we presented as part of JCOTR last year (Grobman et al AMJOG 2019, see our Mercy Perinatal website for a summary).
- Population-based cohort study using record-linkage of birth and NHS hospital admission data in England
- The cohort included >1 million live singleton births between Jan 2005 – Dec 2006, followed up from birth through to March 2015
- The study examined the association between gestational age at birth and hospital admissions up to age 10, and changes in admission rates throughout childhood
- Primary outcome: any inpatient hospital admission from birth to age 10, or death; secondary outcome: medical cause of admission (ICD-10 code)
- Analyses were adjusted for maternal age at delivery, marital status, socioeconomic position, child’s ethnicity, mother’s country of birth, mode of birth, parity, month of birth, sex and small for gestational age
- More than 1.3 million hospital admissions occurred during the study period, with 52% of children admitted to hospital at least once during this time
- The study found that hospital admission rates were significantly associated with week of gestational age at birth
- Compared with children born at 40 weeks’ gestation, the adjusted admission rate ratio was 6.34 (95%CI 5.8-6.85) for children born earlier than 28 weeks (ie 6.3 times more likely be the admitted in hospital prior to age 10 compared to 40 weekers); and 4.92 (95%CI 4.58-5.30) for those born at 28 weeks.
- Importantly, there were even differences between 40 weeks and those born at 38 and 39 weeks: a rate ratio of 1.19 (95%CI 1.16-1.22) for those born at 38 weeks and 1.10 (95%CI 1.08-1.11) for those born at 39 weeks (rate ratio 1.19 = 19% higher rate of hospital admissions)
- The adjusted RR reduced but remained significantly higher for all groups even when high risk children (those with malignancy, cystic fibrosis, chronic kidney disease or a congenital anomaly for example) were excluded from the analysis
- Before the age of 3, being born at 41 or 42 weeks was associated with lower admission rates than for those born at 40 weeks (non-significant after age 3)
- The association between hospital admission and gestational age decreased with age (ie risk higher at younger age) but excess risk remained for all groups up to age 10, including those born at 38 and 39 weeks
- Infection was leading case of hospital admission, followed by respiratory and gastrointestinal conditions
- The findings from this study demonstrate that gestational age is a strong predictor of childhood morbidity and that the risk of hospital admission during childhood is increased, even for those born close to term
- These data are in line with observational data from Scotland published a decade ago that found those who birthed at more advanced gestations (including 40,41 and 42 weeks) have a decreased risk of requiring specialist education needs (MacKay et al PloS Medicine 2010).
In digesting both papers (as well as prior literature) it is becoming increasingly clear that timing of birth represents competing risks. The longer you wait for labour to happen, the greater the risk of obstetric and neonatal adverse outcomes. Including some really nasty ones.
But if birth is delayed until 40 weeks’ and the baby is birthed safely, there may be health gains compared to birth at earlier term gestations (such as induction at 38- or 39-weeks’ gestation).
Possibly, the best balance may be to try withholding induction of labour (unless there is a medical indication) until 40 weeks’ gestation, but to not venture much beyond 41(+0 days) weeks.