Reducing stillbirths: prevention and management of medical disorders and infections during pregnancy.
BACKGROUND
An 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.


METHODS
We 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.


RESULTS
Few 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.


CONCLUSIONS
Evidence 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.
Menezes
Esme V
EV
Division of Maternal and Child Health, The Aga Khan University, Karachi-74800, Pakistan. doc_menezes@yahoo.com
Yakoob
Mohammad Yawar
MY
Soomro
Tanya
T
Haws
Rachel A
RA
Darmstadt
Gary L
GL
Bhutta
Zulfiqar A
ZA
D000871:Anthelmintics / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D015984:Causality; D002780:Cholestasis, Intrahepatic / Q000453:epidemiology / Q000517:prevention & control; D015897:Comorbidity; D003729:Dental Care / Q000379:methods; D019587:Dietary Supplements; D019317:Evidence-Based Medicine; D005260:Female; D005313:Fetal Death / Q000453:epidemiology / Q000517:prevention & control*; D005322:Premature Rupture of Fetal Membranes / Q000453:epidemiology / Q000517:prevention & control; D014943:Global Health; D015658:HIV Infections / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000517:prevention & control; D046110:Hypertension, Pregnancy-Induced / Q000453:epidemiology / Q000517:prevention & control*; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000453:epidemiology / Q000517:prevention & control*; D011251:Pregnancy Complications, Infectious / Q000453:epidemiology / Q000517:prevention & control* / Q000628:therapy*; D011295:Prenatal Care / Q000379:methods; D012307:Risk Factors; D050497:Stillbirth / Q000453:epidemiology*; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000517:prevention & control
D000871:Anthelmintics; D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D000959:Antihypertensive Agents; D000975:Antioxidants; D000998:Antiviral Agents; D010975:Platelet Aggregation Inhibitors