International Stillbirth Research Alert


Issue 1, January 2008
 

Introduction

This Stillbirth Research Alert is a collaborative activity of the International Stillbirth Alliance and the Australian and New Zealand Stillbirth Alliance –ANZSA*.
The aim of this alert is to provide plain language summaries of recent key papers on stillbirth. For further details about the Alert, ISA and ANZSA,
please go to the ISA website : http://www.stillbirthalliance.org

(*ANZSA is the ANZ regional office of ISA)
 

Research Alert Index  ( Search period: October – December 2007 )

1. Conference proceedings
2. Overviews/Guidelines
3. Risk factors/Causes
4. Investigation/audit/classification
5. Bereavement
6. Intervention/Prevention
 


1. Conference proceedings

The 2007 ISA Conference in Birmingham in November was a great success.
Visit the ISA website ( www.stillbirthalliance.org ) and follow the link on the first page to access the Conference Proceedings, General Assembly minutes and summaries of the scientific meetings. These include a workshop on the definition of stillbirth, protocols and investigations and classification systems.

2. Overviews/Guidelines

Stillbirth. Gordon, C. Smith, S. Fretts, R. (2007). The Lancet 370(9600): 1715-25
 
Stillbirths account for 60% of all deaths during the period roughly defined as starting 20 to 28 weeks prior to birth and 7 to 28 days after birth and 75% of all are potentially preventable losses. The rates of stillbirth have slightly increased recently in England and Wales and the causes are unknown.

This article aims to provide an overview of the causes of stillbirth and to summarize present practice and future strategies to reduce the number of stillbirths. The authors found that a systematic approach to classification of stillbirths is a crucial step in design of prevention strategies. A definitive classification system will continue to be difficult until the unexplained causes for stillbirth can be identified and risk factors can be isolated from actual causes.  Future work on population-based screening for stillbirth should be preceded by high-quality, non-interventional prospective new methods of risk assessment in an unselected population.

Pregnancy Loss and the Death of a Baby: Guidelines for Professionals. SANDS UK.
 
The Sands Guidelines are an essential benchmark for good practice when caring for parents who have a childbearing loss at any stage during pregnancy, at birth or shortly afterwards. This new edition of the Guidelines is comprehensive and is rooted in principles of informed choice and of parent-centred, individual care. It is based on research, on discussions with many different health professionals and on parents’ perspectives.

To obtain a copy, visit
www.fundraisingforsands.org  where copies for U.K. addresses can be purchased (£16.99) or email fundraising@uk-sands.org  to find out postage rates for your country.
 
 
Understanding the Basics of Stillbirth. An ISA wikipedia article.

The ISA Parent Advisory Committee collaborated to write a short article about stillbirth for Wikipedia and for the ISA website. These parent leaders from New Zealand, Australia, Norway, England, and the US were led by Vicki Culling, Sands NZ and Ros Richardson, SIDS and Kids Australia.

This article gives a layman's overview of stillbirth (a medical portion will be added soon) which addresses some of the key choices parents should have when their baby dies. From creating memories to autopsy and funeral, the importance of saying hello before saying goodbye is emphasized. Involvement of all family members is encouraged and a discussion of the natural grief response is also included. To read the entire article visit  : www.stillbirthalliance.org and follow the link on the first page.

3. Risk factors/Causes

Reddy, U. (2007). “Prediction and Prevention of Recurrent Stillbirth”. Obstetrics and Gynecology. 110 (5): 1151-1164

Stillbirth is one of the most common poor pregnancy outcomes in the United States. This study looked at whether it is more likely to occur in future pregnancies in women who have had one previously. According to this study, a woman who has had a stillbirth is 2 – 10 times more likely to have another stillbirth if they have another pregnancy. It concludes that growth restricted infants, maternal race, and previous preterm and small for gestational age births are risk factors for future stillbirths and pregnancy complications.
 
 
Redecha, P., R. Tilley, et al. (2007). "Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody induced fetal injury." Blood Rev 110(7): 2423-31.
 
It is believed that antiphospholipid antibodies (aPL) could lead to fetal loss due to clotting of placental vessels. In a study using a mouse model of aPL antibody-induced pregnancy loss, Redecha and others found that inflammation can affect the development of the fetus. The authors found that either blocking or genetically reducing tissue factor (TF), an inflammation producing factor, prevented inflammation caused by aPL and pregnancy loss in mice. This may assist in developing a new therapy to prevent pregnancy loss in antiphospholipid syndrome.


Cundy, T., G. Gamble, et al. (2007). "Differing causes of pregnancy loss in type 1 and type 2 diabetes." Diabetes Care 30(10): 2603-7.
 
Cundy and others carried out a study to compare the differences in causes of pregnancy loss in women with type 1 and 2 diabetes. The information was collected over a 20-year-period from 1986 – 2005 from a single center with a high rate of type 2 diabetes. The study found that while the rates of pregnancy loss were similar, the causes of losses differed with losses from Type 1 diabetes mostly due to congenital abnormalities and prematurity, while for type 2 diabetes was more frequently associated with stillbirth and chorioamnionitis. The authors suggest that other conditions present in diabetes type 2 such as obesity, add to the risk of stillbirth.
 
Bagga, R., N. Aggarwal, et al. (2007). "Pregnancy complicated by severe chronic hypertension: a 10- year analysis from a developing country." Hypertension in pregnancy 26(2): 139-49.
 
The objective of this study by Bagga et al was to assess pregnancy outcome in patients with severe high blood pressure (severe chronic hypertension). They looked at data from a north Indian hospital from 1995-2004 and compared those findings with women who presented with mild chronic hypertension to the pregnancy clinic. The results suggest that preeclampsia (a condition in pregnancy where the patient has high blood pressure and fluid retention), premature delivery and death of the baby around the time of birth, was increased in patients with long term hypertension when compared with those with mild hypertension. Overall, women generally came to the clinic in their third trimester of pregnancy, which made it difficult to see whether they had high blood pressure before the pregnancy. Poor outcomes and problems were more likely to occur in patients with severe chronic hypertension rather than those with mild hypertension.
 
Silverman, J. G., J. Gupta, et al. (2007). "Intimate partner violence and unwanted pregnancy, miscarriage, induced abortion, and stillbirth among a national sample of Bangladeshi women." Bjog 114(10): 1246-52.

This study, using the 2004 MEASURE Bangladesh Demographic Health Survey, presented results suggesting that violence within couples is extremely common in Bangladesh. It links this violence to unwanted pregnancy and higher rates of pregnancy loss such as miscarriage, induced abortion and stillbirth. The study recommends investigating causes for these links to improve health for mothers and their babies.
 
Kwak-Kim, J., S. K. Lee, et al. (2007). "Elevated Th1/Th2 cell ratios in a pregnant woman with a history of RSA, secondary Sjogren's syndrome and rheumatoid arthritis complicated with one fetal demise of twin pregnancy." American journal of Reproductive Immunology 58(4): 325-9.

Women with a history of miscarriage and repeated failure of artificial insemination have been found to have high levels of Th1/Th2 cytokine producing CD3(+) and CD4(+) cell ratios (immune cells). In this case report, levels of these cells were found to be increased 3 weeks before the loss of a twin during pregnancy, and continued to get worse after. Due to this it is believed that the placenta is not a factor in the Th1/Th2 immune response.
 
Pusl, T. and U. Beuers (2007). "Intrahepatic cholestasis of pregnancy." Orphanet J Rare Dis 2: 26.

Intrahepatic cholestasis of pregnancy (ICP) is a disorder characterised by itching starting in second or third trimester, increased levels of liver enzymes and bile acid levels, and relief of signs and symptoms (without assistance) within 2 – 3 weeks after delivery. ICP increases the risk of premature delivery, slowing of fetal heartbeat, fetal distress and stillbirth. Genetic, hormonal and environmental factors are thought to contribute to ICP. The bile acid ursodeoxycholic acid (10-20 mg/kg/d) is today regarded as the first treatment for ICP. Delivery of the baby has been recommended in the 38th week of pregnancy when lung maturity has been established.

Chigbu, C. O. and G. C. Iloabachie (2007). "The burden of caesarean section refusal in a developing country setting." Bjog 114(10): 1261-5.

A study in 2 Nigerian hospitals including 62 women who declined caesarean sections was undertaken to investigate the frequency, causes and outcomes of choosing not to have a caesarean section. Information was gained via questionnaire and delivery outcomes were compared with woman who accepted caesarean section. Results show that there is a high level of caesarean section refusal in south-eastern Nigeria relating to fear of death, economic reasons, desire to experience vaginal delivery and inadequate counselling. The risk of poor outcomes, including mortality for mothers and babies are higher for women who decline caesarean sections in south-eastern Nigeria.

Lansky, S., S. V. Subramanian, et al. (2007). "Higher perinatal mortality in National Public Health System hospitals in Belo Horizonte, Brazil, 1999: a compositional or contextual effect?" Bjog 114(10): 1240-5.
 
Brazillian authors Lansky and others (2007) found that hospitals contracted to the National Public Health System in Brazil are more likely to influence the risk of death of babies around the time of birth. As most babies in Brazil are born in public hospitals this is considered an urgent priority to assist in reducing the rate of newborn and infant mortality.

Sibley, L. M., T. A. Sipe, et al. (2007). "Traditional birth attendant training for improving health behaviours and pregnancy outcomes." Cochrane Database Syst Rev(3): CD005460.

Plain language summary extracted from the Cochrane Library:
“Traditional birth attendant training for improving health behaviours and pregnancy outcomes

In the developing world, many women give birth at home assisted by family members or traditional birth attendants (TBAs). TBAs lack formal training and governments and other organizations have conducted training programs to improve their skills. There is disagreement that these training programs are effective. This review included four studies and examined the effect of TBA training on TBA behaviour and on pregnancy outcomes. We conclude that the potential of TBA training to decrease newborn death is promising, when combined with improved health services. The number of studies, however, is insufficient to provide the necessary evidence for TBA training effectiveness”.

4. Investigation/audit/classification

Please refer to:

Item 1. Conference proceedings for abstracts and meeting summaries from the International Stillbirtth Alliance 2008 Conference.

Item 2. Overviews/ Guidelines

5. Bereavement

Please refer to:

Item 1. Conference proceedings for abstracts and meeting summaries from the International Stillbirtth Alliance 2008 Conference; and

Item 2. Overviews/ Guidelines

6. Intervention/Prevention

Crombleholme, T. M., D. Shera, et al. (2007). "A prospective, randomized, multicenter trial of amnioreduction vs selective fetoscopic laser photocoagulation for the treatment of severe twin-twin transfusion syndrome." Am J Obstet Gynecol 197(4): 396 e1-9.

This article compares the use of fetal laser therapy known as selective fetoscopic laser photocoagulation (SFLP) (a procedure which seals the blood vessels that connect the babies in the womb) and AR (serial amnioreduction) (repeated removal of amniotic fluid) in pregnancies complicated with severe twin-twin transfusion syndrome (TTTS). TTTS is a life threatening problem of placental blood circulation which can occur in identical twins. While there was no conclusion as to which therapy works better, the study found that cardiomyopathy (a disease affecting the heart muscle) seems to be important in the survival of twins with TTTS. 

Zhang, X., R. Platt, et al. (2007). “The use of customised versus population-based birthweight standards in predicting perinatal mortality.” BJOG 114(4): 474-7.

In a correspondence to the authors of the article “The use of customised versus population-based birthweight standards in predicting perinatal mortality” by Zhang et al, McCowan et al suggested that the paper in question contained misleading information for clinicians. Both McCowan et al and Gardosi et al question the conclusion by Zhang stating that ‘the large increase in perinatal mortality risk among infants classified as SGA based on customised standards is largely an artefact due to inclusion of more preterm births’.  The consensus of both letters is that customised centiles identify an increased proportion of preterm babies as SGA as they are at increased risk of perinatal mortality, and this is an important advantage of customised over population centiles.  In addition, both letters question the correctness of adjusting for gestational age when calculating the adjusted odds of stillbirth, due to the fact that gestational age is not a cause of stillbirth.

References:
Gardosi, J., Clausson, B., Francis, A. (2007). “The use of customised versus population-based birthweight standards in predicting perinatal mortality.” BJOG 114 (10): 1301-2.
McCowan, L., Groom, K., Stewart, A. (2007). “The use of customised versus population-based birthweight standards in predicting perinatal mortality.” BJOG 114(10): 1302-3. 

 
Mahomed, K., Bhutta Z, Middleton P. (2007). "Zinc supplementation for improving pregnancy and infant outcome." Cochrane Database Syst Rev(2): CD000230.

Plain language summary extracted form the Cochrane Library:
“Taking zinc during pregnancy helps to slightly reduce preterm births, but does not help prevent other problems such as low birthweight babies

Many women of childbearing age may have mild to moderate zinc deficiency. Low zinc levels may cause preterm birth or they may prolong labour. It is also possible that zinc deficiency may affect infant growth as well. The review of 17 trials, involving over 9000 women and their babies, found that although zinc supplementation has a small effect on reducing preterm births, it does not help to prevent low birthweight babies. Finding ways to improve women's overall nutritional status, particularly in low-income areas, will do more to improve the health of mothers and babies than supplementing pregnant women with zinc”.  

Fauveau, V. (2007). "New indicator of quality of emergency obstetric and newborn care." Lancet 370(9595): 1310.
 
The Lancet, Volume 370, issue 9595 October 2007 includes a published letter by Vincent Fauveau of the United Nations describing a new system of care for women and babies during pregnancy. A new indicator – ‘the intrapartum case fatality rate’ will be included in the new WHO guidelines on monitoring the availability and use of obstetric services. Its aim is to address the quality of care of the unborn or newborn baby, instead of just the mother in emergency obstetric care The intrapartum case fatality rate is the number of deliveries that result in stillbirth and deaths of newborns which occur during the first 24 hours after birth). The author outlines 3 main difficulties in collecting the information:

  • identification, reporting and recording of very early neonatal deaths, as some woman only stay in the facility for 6 or 12 hours after the delivery. He suggests perhaps making the definition of early neonatal deaths to those which happen within the first 6 – 12 hours after birth.
  • to make sure it is the quality of obstetric care given and not risks due to the babies small size, he proposes that data should only be used on babies weighing 2500g or more (or 2000g where babies are all small).
  • instead of identifying stillbirths by presence of heart beats able to be heard at the beginning of labour, he suggests examination of the fetus for freshness and absence of signs of deterioration.

It is hoped people interested in this topic will act as a team with each other and exchange information.

Duke, C. W., C. J. Alverson, et al. (2007). "Fetal death certificates as a source of surveillance data for stillbirths with birth defects." Public Health Rep 122(5): 664-9.

The quality of data sources is important so that up to date and correct information is available. This is demonstrated in the article by Duke and others (2007) which examines whether fetal death certificates (FDC) and information on the Metropolitan Atlanta Congenital Defects Program (MACDP) have the same information. It was found that the majority of FDC’s were identified within the MACDP’s and that stillbirth, birth defects and autopsies were more likely to be issued an FDC.


Acknowledgment

We would like to acknowledge the volunteers and staff who gave generously of their time in compiling this Alert: Belinda Perkins, Sharon Egan, Dawn McNeil, Kristen Gilshenan, and ISA secretariat Anais Gschwind and Yanlin Liu. 
 

International Stillbirth Alliance (c) 2008 www.stillbirthalliance.org