Abstract
BackgroundAn estimated two-thirds of the world's 3.2 million stillbirths occur antenatally, prior to labour, and are often overlooked in policy and programs. Poorly recognised, untreated or inadequately treated maternal infections such as syphilis and malaria, and maternal conditions including hypertensive disorders, are known risk factors for stillbirth.MethodsWe undertook a systematic review of the evidence for 16 antenatal interventions with the potential to prevent stillbirths. We searched a range of sources including PubMed and the Cochrane Library. For interventions with prior Cochrane reviews, we conducted additional meta-analyses including eligible newer randomised controlled trials following the Cochrane protocol. We focused on interventions deliverable at the community level in low-/middle-income countries, where the burden of stillbirths is greatest.ResultsFew of the studies we included reported stillbirth as an outcome; most that did were underpowered to assess this outcome. While Cochrane reviews or meta-analyses were available for many interventions, few focused on stillbirth or perinatal mortality as outcomes, and evidence was frequently conflicting. Several interventions showed clear evidence of impact on stillbirths, including heparin therapy for certain maternal indications; syphilis screening and treatment; and insecticide-treated bed nets for prevention of malaria. Other interventions, such as management of obstetric intrahepatic cholestasis, maternal anti-helminthic treatment, and intermittent preventive treatment of malaria, showed promising impact on stillbirth rates but require confirmatory studies. Several interventions reduced known risk factors for stillbirth (e.g., anti-hypertensive drugs for chronic hypertension), yet failed to show statistically significant impact on stillbirth or perinatal mortality rates. Periodontal disease emerged as a clear risk factor for stillbirth but no interventions have reduced stillbirth rates.ConclusionEvidence for some newly recognised risk factors for stillbirth, including periodontal disease, suggests the need for large, appropriately designed randomised trials to test whether intervention can minimise these risks and prevent stillbirths. Existing evidence strongly supports infection control measures, including syphilis screening and treatment and malaria prophylaxis in endemic areas, for preventing antepartum stillbirths. These interventions should be incorporated into antenatal care programs based on attributable risks and burden of disease.
Highlights
Of the world's 3.2 million annual stillbirths, at least 98% occur in low-/middle-income countries, and on average, as many as two-thirds of these stillbirths are thought to occur antenatally, prior to labour [1,2]
Inverse relationships between calcium intake and hypertensive disorders of pregnancy were observed among the Mayan Indians in Guatemala [11], whose diet includes corn soaked in lime, and in Ethiopia, where dietary intake of calcium is high [12]; both populations have low incidence of preeclampsia and eclampsia
There was no significant effect of calcium supplementation in pregnant women on the risk of stillbirth or the baby dying before discharge from hospital, regardless of the mother's risk of hypertensive disorders of pregnancy
Summary
Of the world's 3.2 million annual stillbirths, at least 98% occur in low-/middle-income countries, and on average, as many as two-thirds of these stillbirths are thought to occur antenatally, prior to labour [1,2]. Antenatal stillbirths typically show signs of maceration, and result from an insult occurring in utero [3]. Interventions targeting this period can play a major part in reducing the burden of stillbirths. Many known causes of antenatal stillbirths, including infections and maternal conditions including gestational diabetes and hypertension, are potentially preventable or treatable; relatively simple interventions may reduce their incidence. Recognised, untreated or inadequately treated maternal infections such as syphilis and malaria, and maternal conditions including hypertensive disorders, are known risk factors for stillbirth
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