Higher risk of stillbirth in longer pregnancies — analysis of 15m women

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PregnantWith every week that a pregnancy continues past term (37 weeks), the risk of stillbirth increases, according to an analysis of more than 15m pregnancies led by Queen Mary University of London. The results also included a small but significantly increased risk of stillbirth in mothers who continued their pregnancy to 41 weeks’ gestation (when women are routinely offered induction of labour), compared to those who delivered at 40 weeks.

The researchers say that women who are 41 weeks pregnant should not be alarmed, as the risk is low – equivalent to one additional stillbirth for every 1,449 pregnancies, compared to delivering at 40 weeks. Compared to White women, Black women at term were also found to be 1.5 to 2 times more likely to suffer stillbirth at all gestational ages.

Lead researcher Professor Shakila Thangaratinam from Queen Mary University of London said: “While there is an additional risk of stillbirth at 41 weeks, compared to 40 weeks, it is small. Women who prefer not to have medical interventions such as induction of labour may therefore acknowledge this small additional risk, and choose to wait until 41 weeks so that they have more time to go into labour naturally. Meanwhile, other women may prefer to have discussions with their healthcare providers on induction after 40 weeks. So this is all about helping women make informed decisions on timing of delivery.”

More than 3,000 babies are stillborn every year in the UK – a third of these are term babies (37 weeks or beyond) who were considered to be ‘healthy’ prior to their death. Prolonged pregnancy is a known risk factor for stillbirth and women are routinely offered induction of labour after 41 weeks’ gestation. This recommendation is based on evidence of increased stillbirth risk beyond 41 weeks. However, one in three women with a stillbirth at term loses her baby before this period. The magnitude of this risk is not routinely communicated due to a previous lack of robust evidence.

The researchers have now analysed data from 13 separate studies in the UK, US, Denmark and Norway, which included 15,124,027 pregnancies, 17,830 stillbirths and 2,348 new-born deaths.

Despite the stillbirth risk figures, delivery before 41 weeks did not increase the risk of new-born death (defined as a death during the first 28 days of life) – the risk was unchanged for births between 38 and 41 weeks of gestation. The risk increased by 87% for deliveries at 42 weeks’ gestation compared to 41 weeks.

Thangaratinam added: “This is the largest study of its kind, and finally provides precise estimates of potential risks of stillbirth. Now that we understand the extent to which stillbirth risks increase with each week of pregnancy, we should be incorporating this information in all discussions around delivery plans in pregnant women at term.

“We were surprised to see how much poorer pregnancy outcomes were for Black women – they were up to twice more likely to experience stillbirth than White women. Healthcare professionals need to take these added risks into account when developing care plans for these women.”

Limitations of the study include variations in the definitions of low risk pregnancy, the wide time-span of the studies, loss of data due to exclusion of studies that did not provide stillbirth estimates in weekly intervals, and potential confounders affecting the outcome.

Abstract
Background: Despite advances in healthcare, stillbirth rates remain relatively unchanged. We conducted a systematic review to quantify the risks of stillbirth and neonatal death at term (from 37 weeks gestation) according to gestational age.
Methods and findings: We searched the major electronic databases Medline, Embase, and Google Scholar (January 1990–October 2018) without language restrictions. We included cohort studies on term pregnancies that provided estimates of stillbirths or neonatal deaths by gestation week. We estimated the additional weekly risk of stillbirth in term pregnancies that continued versus delivered at various gestational ages. We compared week-specific neonatal mortality rates by gestational age at delivery. We used mixed-effects logistic regression models with random intercepts, and computed risk ratios (RRs), odds ratios (ORs), and 95% confidence intervals (CIs). Thirteen studies (15 million pregnancies, 17,830 stillbirths) were included. All studies were from high-income countries. Four studies provided the risks of stillbirth in mothers of White and Black race, 2 in mothers of White and Asian race, 5 in mothers of White race only, and 2 in mothers of Black race only. The prospective risk of stillbirth increased with gestational age from 0.11 per 1,000 pregnancies at 37 weeks (95% CI 0.07 to 0.15) to 3.18 per 1,000 at 42 weeks (95% CI 1.84 to 4.35). Neonatal mortality increased when pregnancies continued beyond 41 weeks; the risk increased significantly for deliveries at 42 versus 41 weeks gestation (RR 1.87, 95% CI 1.07 to 2.86, p = 0.012). One additional stillbirth occurred for every 1,449 (95% CI 1,237 to 1,747) pregnancies that advanced from 40 to 41 weeks. Limitations include variations in the definition of low-risk pregnancy, the wide time span of the studies, the use of registry-based data, and potential confounders affecting the outcome.
Conclusions: Our findings suggest there is a significant additional risk of stillbirth, with no corresponding reduction in neonatal mortality, when term pregnancies continue to 41 weeks compared to delivery at 40 weeks.

Authors
Javaid Muglu, Henna Rather, David Arroyo-Manzano, Sohinee Bhattacharya, Imelda Balchin, Asma Khalil, Basky Thilaganathan, Khalid S Khan, Javier Zamora, Shakila Thangaratinam

Queen Mary University of London material
PLOS Medicine abstract


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