What are the most effective interventions during pregnancy for preventing stillbirth?

What is stillbirth?

A stillbirth is generally defined as the death of a baby before birth, at or after 22 weeks of development.

Why is this important?

Stillbirth can be very upsetting for families. It is most common in low- and middle-income countries but also affects people in high-income countries. Numbers of stillbirths have not fallen much in the last 20 years and, despite the high numbers, it is not widely recognised as a global health problem. It is important to raise awareness of effective methods of preventing stillbirths, particularly in low- and middle-income countries.

What did we do?

Cochrane systematic reviews of interventions aim to answer specific medical questions based on up-to-date research studies. We searched for all Cochrane systematic reviews that assessed ways of preventing stillbirth during pregnancy to produce an overview of Cochrane evidence on preventing stillbirth.

What evidence did we find?

We found 43 Cochrane reviews that assessed 61 different ways of preventing stillbirth during pregnancy, or infant deaths around the time of birth. However, few of these provided any clear evidence of an effect during pregnancy to reduce the risk of stillbirth or infant death.

We grouped them into four different areas: nutrition, preventing infection, managing mothers' other healthcare problems, and looking after the baby before it is born.

Nutrition

- Giving mothers balanced energy and protein supplements to increase the growth of the baby, particularly in undernourished pregnant women, probably reduces stillbirth by 40%.

- For Vitamin A alone versus placebo (sham) or no treatment, and multiple micronutrients with iron and folic acid compared with iron with or without folic acid, there was clear evidence of no effect.

Prevention and management of infections

- Insecticide-treated anti-malarial nets versus no nets may reduce loss of the baby in the womb (fetus) by 33%.

Prevention, detection and management of other healthcare problems

- Where midwives were the primary healthcare provider, particularly for low-risk pregnant women, loss of the fetus or infant deaths fell by 16%.

- Having a trained traditional birth attendant versus having an untrained traditional birth attendant probably reduces stillbirth in rural populations of low- and middle-income countries by 31% and infant death by 30%.

- A reduced number of antenatal care visits probably results in an increase in infant death around the time of birth.

- Community-based intervention packages (including community-support groups/women's groups, community mobilisation and home visits, or training traditional birth attendants who made home visits) may reduce stillbirth by 19%.

Checking the baby before birth

- Cardiotocography measures the baby's heart rate and contractions in the womb. It can be recorded automatically by computer or manually, with pen and paper. Computerised cardiotocography to monitor baby’s well-being in the womb, by measuring contractions, probably reduces the rate of infant deaths around the time of birth by 80% when compared with traditional cardiotocography.

We were uncertain about the effects of other methods.

What does this mean?

We found a large number of reviews but few produced clear evidence. The effectiveness of the methods used to prevent stillbirth varied depending on where they took place, highlighting that it is important to understand how they were tested. The findings cannot be applied to women in general and across all global settings.

Authors' conclusions: 

While most interventions were unable to demonstrate a clear effect in reducing stillbirth or perinatal death, several interventions suggested a clear benefit, such as balanced energy/protein supplements, midwife-led models of care, training versus not training traditional birth attendants, and antenatal cardiotocography. Possible benefits were also observed for insecticide-treated anti-malarial nets and community-based intervention packages, whereas a reduced number of antenatal care visits were shown to be harmful. However, there was variation in the effectiveness of interventions across different settings, indicating the need to carefully understand the context in which these interventions were tested.

Further high-quality RCTs are needed to evaluate the effects of antenatal preventive interventions and which approaches are most effective to reduce the risk of stillbirth. Stillbirth (or fetal death), perinatal and neonatal death need to be reported separately in future RCTs of antenatal interventions to allow assessment of different interventions on these rare but important outcomes and they need to clearly define the target populations of women where the intervention is most likely to be of benefit. As the high burden of stillbirths occurs in low- and middle-income countries, further high-quality trials need to be conducted in these settings as a priority.

Read the full abstract...
Background: 

Stillbirth is generally defined as a death prior to birth at or after 22 weeks' gestation. It remains a major public health concern globally. Antenatal interventions may reduce stillbirths and improve maternal and neonatal outcomes in settings with high rates of stillbirth. There are several key antenatal strategies that aim to prevent stillbirth including nutrition, and prevention and management of infections.

Objectives: 

To summarise the evidence from Cochrane systematic reviews on the effects of antenatal interventions for preventing stillbirth for low risk or unselected populations of women.

Methods: 

We collaborated with Cochrane Pregnancy and Childbirth's Information Specialist to identify all their published reviews that specified or reported stillbirth; and we searched the Cochrane Database of Systematic Reviews (search date: 29 Feburary 2020) to identify reviews published within other Cochrane groups. The primary outcome measure was stillbirth but in the absence of stillbirth data, we used perinatal mortality (both stillbirth and death in the first week of life), fetal loss or fetal death as outcomes. Two review authors independently evaluated reviews for inclusion, extracted data and assessed quality of evidence using AMSTAR (A Measurement Tool to Assess Reviews) and GRADE tools. We assigned interventions to categories with graphic icons to classify the effectiveness of interventions as: clear evidence of benefit or harm; clear evidence of no effect or equivalence; possible benefit or harm; or unknown benefit or harm or no effect or equivalence.

Main results: 

We identified 43 Cochrane Reviews that included interventions in pregnant women with the potential for preventing stillbirth; all of the included reviews reported our primary outcome 'stillbirth' or in the absence of stillbirth, 'perinatal death' or 'fetal loss/fetal death'. AMSTAR quality was high in 40 reviews with scores ranging from 8 to 11 and moderate in three reviews with a score of 7.

Nutrition interventions

Clear evidence of benefit: balanced energy/protein supplementation versus no supplementation suggests a probable reduction in stillbirth (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.39 to 0.94, 5 randomised controlled trials (RCTs), 3408 women; moderate-certainty evidence).

Clear evidence of no effect or equivalence for stillbirth or perinatal death: vitamin A alone versus placebo or no treatment; and multiple micronutrients with iron and folic acid versus iron with or without folic acid.

Unknown benefit or harm or no effect or equivalence: for all other nutrition interventions examined the effects were uncertain.

Prevention and management of infections

Possible benefit for fetal loss or death: insecticide-treated anti-malarial nets versus no nets (RR 0.67, 95% CI 0.47 to 0.97, 4 RCTs; low-certainty).

Unknown evidence of no effect or equivalence: drugs for preventing malaria (stillbirth RR 1.02, 95% CI 0.76 to 1.36, 5 RCTs, 7130 women, moderate certainty in women of all parity; perinatal death RR 1.24, 95% CI 0.94 to 1.63, 4 RCTs, 5216 women, moderate-certainty in women of all parity).

Prevention, detection and management of other morbidities

Clear evidence of benefit: the following interventions suggest a reduction: midwife-led models of care in settings where the midwife is the primary healthcare provider particularly for low-risk pregnant women (overall fetal loss/neonatal death reduction RR 0.84, 95% CI 0.71 to 0.99, 13 RCTs, 17,561 women; high-certainty), training versus not training traditional birth attendants in rural populations of low- and middle-income countries (stillbirth reduction odds ratio (OR) 0.69, 95% CI 0.57 to 0.83, 1 RCT, 18,699 women, moderate-certainty; perinatal death reduction OR 0.70, 95% CI 0.59 to 0.83, 1 RCT, 18,699 women, moderate-certainty).

Clear evidence of harm: a reduced number of antenatal care visits probably results in an increase in perinatal death (RR 1.14 95% CI 1.00 to 1.31, 5 RCTs, 56,431 women; moderate-certainty evidence).

Clear evidence of no effect or equivalence: there was evidence of no effect in the risk of stillbirth/fetal loss or perinatal death for the following interventions and comparisons: psychosocial interventions; and providing case notes to women.

Possible benefit: community-based intervention packages (including community support groups/women's groups, community mobilisation and home visitation, or training traditional birth attendants who made home visits) may result in a reduction of stillbirth (RR 0.81, 95% CI 0.73 to 0.91, 15 RCTs, 201,181 women; low-certainty) and perinatal death (RR 0.78, 95% CI 0.70 to 0.86, 17 RCTs, 282,327 women; low-certainty).

Unknown benefit or harm or no effect or equivalence: the effects were uncertain for other interventions examined.

Screening and management of fetal growth and well-being

Clear evidence of benefit: computerised antenatal cardiotocography for assessing infant's well-being in utero compared with traditional antenatal cardiotocography (perinatal mortality reduction RR 0.20, 95% CI 0.04 to 0.88, 2 RCTs, 469 women; moderate-certainty).

Unknown benefit or harm or no effect or equivalence: the effects were uncertain for other interventions examined.

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