sabdr annual report 2003 - women's and children's hospital€¦ · annual prenatal...

2003

Annual Report

of

The South Australian

Birth Defects Register

Children born from 1986 to 2003 with birth defects

notified to the Register by 31st March 2004

and incorporating the Annual Report of Prenatal Diagnosis

in South Australia, 2003

i

The South Australian Birth Defects Register

Location South Australian Clinical Genetics Service Women's and Children's Hospital Campus Children, Youth and Women’s Health Service 8th Floor, Clarence Rieger Building 72 King William Road North Adelaide, South Australia 5006 Telephone: (08) 8161 7368 Fax: (08) 8161 6088 Email: [email protected]

Specialist Advisers to the Register A/Prof Andrew Ford Paediatric Surgery A/Prof Bruce Foster Orthopaedic Surgery Mr Peter Cundy Orthopaedic Surgery Prof David David Craniofacial Surgery Dr Malcolm Richardson Cardiology Dr Ben Saxon Oncology/Haematology Dr Hilary Boucaut Urology Dr Steve Santoreneos Neurosurgery

Staff Professor Eric Haan Clinical Geneticist, Director Dr Annabelle Chan Public Health Physician Ms Heather Scott Project Officer Ms Phillipa van Essen Senior Project Officer

Advisory Committee Dr Judy Jaensch Paediatrician Dr Geoffrey Martin General practitioner Mrs Barbara Walrut Consumer & legal practitioner Dr Karen Shand Obstetrician Dr Brian Peat Obstetrician Dr Annabelle Chan Representing SA Department of Health, Epidemiology Branch Professor Eric Haan Representing the SA Birth Defects Register Printing Rainbow Press PO Box 2221 Regency Park SA 5942 Email: [email protected]

ISSN 1033-6907

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Contents

Annual Report of the South Australian Birth Defects Register

Highlights 2003 vi

Introduction vii

Register Activities 2004 / 2005 viii

Prevalence of Birth Defects 1

Demographic Information 2

Types of Birth Defects Notified 6

Trends in Selected Birth Defects 9

Sentinel Defects 11

Deaths Associated with Birth Defects 13

Sources of Notification 15

Birth Defects Detected/Notified after Discharge from the Birth Hospital 15

Publications and Presentations 27

Annual Report of Prenatal Diagnosis

Introduction to Prenatal Diagnosis Report 17

Amniocentesis and Chorionic Villus Sampling 18

Fetal Blood Sampling 20

Maternal Serum Screening for Neural Tube Defects in the Second Trimester 21

Screening for Down Syndrome 22

Trends in Utilisation of Amniocentesis and CVS 24

ii

Tables

Table 1 Birth defects in children born in South Australia, 1986-2003 1

Table 2 Cases with birth defects by residence of mother at time of birth, SA 1986-2003 2

Table 3 Cases with birth defects by sex of child, SA 1986-2003 4

Table 4 Cases with birth defects by mother’s race, SA 1986-2003 5

Table 5 Cases with birth defects by plurality, SA 1986-2003 5

Table 6 Cases with specified birth defects by diagnostic category, SA 1986-2003 7

Table 7 Cases of sentinel defects by CURB region, SA 1986-2003 11

Table 8 Deaths associated with birth defects, SA 1986-2003 14

Table 9 Cases with birth defects notified after discharge from the birth hospital by major diagnostic category, SA 1986-2003

16

Table 10 Amniocentesis and chorionic villus sampling, SA 2003: Indications 18

Table 11 Amniocentesis and chorionic villus sampling, SA 2003: Utilisation rate by maternal age

19

Table 12 Disorders diagnosed by molecular or biochemical techniques, SA 2003 20

Table 13 Fetal blood sampling, SA 2003: Indications 20

Table 14.1 Maternal serum screening for neural tube defects, SA 2003: Women’s and Children’s Hospital and Gribbles Pathology

21

Table 14.2 Detection of neural tube defects by screening, SA 2003 21

Table 14.3 Outcome of neural tube defect pregnancies, SA 2003 21

Table 15.1 Screening for Down syndrome, SA 2003: All testing laboratories 22

Table 15.2 Down syndrome cases, SA 2003: Detected / Not detected 22

Table 15.3 Down syndrome cases, SA 2003: Pregnancy outcome 22

Table 15.4 First trimester combined biochemical and nuchal translucency screening Women’s and Children’s Hospital Laboratory only, SA 2003

23

Table 15.5 First trimester combined biochemical and nuchal translucency screening FMF software generated risks, SA 2003

23

Table 15.6 Second trimester maternal serum screening by maternal age: Women’s and Children’s Hospital Laboratory only, SA 2003

24

Table 16 Prenatal diagnosis - By technique, SA 2003 24

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Figures and Appendices

Figure 1 South Australian CURB (Committee on Uniform Regional Boundaries) regions 3

Figure 2 Cases with birth defects by major diagnostic grouping, SA 1986-2003 (prevalence rates per 1000 births)

6

Figure 3 Trends in selected birth defects, SA 1986-2003 9

Figure 4 Deaths associated with birth defects by death category, SA 1986-2003 13

Figure 5 Sources of notification, SA 1986-2003: Total notifications received 15

Figure 6 Percentage of cases with birth defects notified after discharge from the birth hospital by diagnostic category, SA 1986-2003

16

Figure 7 Amniocentesis and chorionic villus sampling, SA 2003: Utilisation rate by maternal age

19

Figure 8 Percentage of amniocentesis and CVS by year for all women, SA 1986-2003: all indications

25

Figure 9 Percentage of amniocentesis and CVS by year for maternal age � 35 yrs, SA 1986-2003: all indications

25

Figure 10 Indications for amniocentesis by year, SA 1991-2003: Percentage of confinements 26

Figure 11 Indications for CVS by year, SA 1991-2003: Percentage of all confinements 26

Appendix 1 Background information on SABDR 29

Appendix 2 Confidentiality guidelines 30

Appendix 3 Birth defect inclusions and exclusions 33

Appendix 4 Notification form 35

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South Australian Birth Defects Register Staff

Left to right

Ms Phillipa van Essen Senior Project Officer

Dr Annabelle Chan Public Health Physician

Professor Eric Haan Clinical Geneticist, Director

Ms Heather Scott Project Officer

v

Thanks to Notifiers Acknowledgments

We wish to thank all the notifiers who supplied the information on which this report is based. We greatly appreciate their support and advice, the time and effort they spend on completing the forms and their cooperation in supplying extra information when requested. In particular, we would like to express our thanks to the staff of the particular departments of the Children, Youth and Women’s Health Service which have data collections or registers with which the Birth Defects Register interfaces: Children, Youth and Women’s Health Service: • The Department of Cardiology for data on

congenital heart defects. • The Department of Genetic Medicine for

cytogenetics reports, Down syndrome data, information on maternal serum screening, inborn errors of metabolism, abnormal neonatal screening results and data on prenatal diagnostic tests such as amniocentesis and chorionic villus sampling.

• The Division of Medical Imaging for

radiology and ultrasound requests.

• The Departments of Physiotherapy and Orthotics for data on musculoskeletal defects.

• The Department of Histopathology for

autopsy reports. • The Medical Records Department. Other notifiers: • The Medical Records Departments of South

Australian metropolitan and regional hospitals, in particular Flinders Medical Centre, Modbury Hospital, Lyell McEwin Health Service and The Queen Elizabeth Hospital.

We would like to thank all those people who have contributed to the South Australian Birth Defects Register since its inception. Their ongoing support and practical contribution is much appreciated. Special thanks are due to Joan Scott and the staff of the Pregnancy Outcome Statistics Unit for providing the important perinatal data and to Kevin Priest and Anh-Minh Nguyen, the staff of the Health Statistics Unit of the Epidemiology Branch, Department of Health for assistance with data linkage and statistical support. The Birth Defects Register Advisory Committee was established in June 1989 to advise the Register on issues of confidentiality and to review the activities of the Register. We thank its members for their time, expertise and valuable advice. Dr Judy Jaensch, paediatrician Dr Geoffrey Martin, general practitioner Mrs Barbara Walrut, consumer and legal practitioner Dr Annabelle Chan, representing the Department of Health, Epidemiology Branch Professor Eric Haan, representing the Birth Defects Register Dr Karen Shand, Obstetrician Dr Brian Peat, Obstetrician The advice of many clinicians has been sought on the classification and coding of defects in specialised areas, eg. orthopaedics, craniofacial malformations, urology, neurosurgery and cardiology. We would like to express our gratitude to these consultants for their guidance. Thank you to Dr Bill Carey of Softcare Software for the creation and continued support of our computing software. Thanks to the Birth Defects Registry of Western Australia, the Congenital Malformations Registry of Victoria and the National Perinatal Statistics Unit for their ongoing support.

vi

Highlights 2003

Annual Birth Defects Report

• The Register received 798 notifications of children with one or more birth defects. This represents 4.5% of the total births in that year. The proportion of total births with birth defects for the period 1986 – 2003 was 5.7%. The difference represents the additional notifications received over the Register’s 5 year ascertainment period.

• There were 21 neural tube defects notified in 2003. A significant decreasing trend in the prevalence of neural tube defects between 1986 and 2003 can be seen.

• 42 Down syndrome cases were notified in 2003. There was an increasing trend in the total prevalence of Down syndrome between 1986 and 2003 due to increasing maternal age. The percentage of live born cases of Down syndrome in 2003 was 24%.

• The Eyre CURB region recorded the highest proportion of birth defects with 5.3% of total births, compared to the lowest proportion of 3.0% seen in the Murraylands CURB region.

• As seen in previous years, male sex and multiple births were associated with an increased risk of birth defects.

• Births to Caucasian mothers had the highest proportion of birth defects (4.6%) compared to births to Aboriginal and Asian mothers (4.0% and 2.2% respectively).

• The most commonly reported birth defects were: Musculoskeletal abnormalities (eg. developmental dysplasia of the hip) and Urogenital abnormalities (eg. vesico-ureteric reflux), with 15.0 and 9.9 cases per 1,000 births respectively. In comparison, Chromosomal abnormalities (eg. Down syndrome) had a prevalence of 4.5 per 1,000 births.

• 3.0% of spontaneous stillbirths and 24% of neonatal deaths had birth defects.

• 50% of haematological and immune system and 42% of cardiovascular birth defects were identified after discharge from the birth hospital.

Annual Prenatal Diagnosis Report

• There were 1338 amniocenteses and 173 chorionic villus samplings performed on South Australian women, representing 7.6% and 1.0% of all pregnancies respectively.

• Maternal age was a factor in 57% (764) of amniocenteses and 63% (109) of chorionic villus samplings.

• 17 fetal blood samplings in 8 fetuses were performed, all were undertaken for Rh or other isoimmunization. There were 9 fetal transfusions (4 fetuses).

• The Women’s and Children’s Hospital or Gribbles Pathology screened 7,324 pregnancies (42% of all pregnancies) at 15-20 weeks gestation for a fetal neural tube defect by estimation of maternal serum alpha-fetoprotein.

• All 21 cases of neural tube defect were detected prenatally by either maternal serum screening or ultrasound screening or both.

• The Women’s and Children’s Hospital and Gribbles Pathology screened 12,603 pregnancies (72% of all pregnancies) for Down syndrome. 32 out of 34 cases (94%) for which a screening or diagnostic test was performed prenatally were detected. Two cases were missed by screening. The screening or testing methods used were first trimester combined screen (nuchal translucency and maternal serum screen), second trimester maternal serum screen, chorionic villus sampling, amniocentesis or ultrasound alone as the first indication of Down syndrome.

• There have been significant changes over time in the proportion of pregnancies in which prenatal diagnosis by amniocentesis or chorionic villus sampling is performed; from 5% in 1986 to a peak of 12% in 1996, followed by a gradual fall to 9% in 2003. A contributing factor to the fall in recent years has been a small decrease in the proportion of women 35 years and older using amniocentesis and chorionic villus sampling, following the introduction of first trimester screening.

vii

Introduction

The South Australian Birth Defects Register is a population-based collection of information on birth defects from a population with an average of 17937 births per year, over the past five years. The Register collects information on all children born in South Australia on or after 1st January l986 who have a significant birth defect detected in the first five years of life. It thus complements and extends the collection of congenital abnormalities detected in the perinatal period and notified by doctors to the Pregnancy Outcome Statistics Unit of the Department of Health.

A birth defect is defined as any abnormality, structural or functional, identified up to five years of age, provided that the condition had its origin before birth.

The Register includes terminations of pregnancy at any gestation because of diagnosis of a birth defect, stillbirths and newborn babies with birth defects and children diagnosed with a birth defect after the neonatal period and prior to their fifth birthday.

The Register is located in the Women's and Children's Hospital in the South Australian Clinical Genetics Service. This is an ideal location for the following reasons:

• The majority of children with birth defects requiring medical or surgical care are referred to the Women’s and Children's Hospital for assessment or further management at some stage.

• The major paediatric diagnostic services and perinatal / paediatric pathology services are located at the Women’s and Children’s Hospital.

• The existence of the Register within the South Australian Clinical Genetics Service improves classification and coding of birth defects.

Notifications are received from a wide range of health professionals who care for children with birth defects. The Register receives notifications from the wards and other relevant departments within the Women’s and Children's Hospital. It also receives notifications from other South Australian hospitals, paediatricians, and other specialists (eg. cardiologists, physiotherapists), child treatment centres, other metropolitan and country hospitals and general practitioners.

This annual report presents information for the years 1986-2003, including birth defects notified up to March 2004 for children born in 2003. It also updates numbers and rates for the years 1998 to 2002. Notifications for the cohorts of children born between 1986 and 1998 are now complete. All children in the 1998 cohort reached their fifth birthday by the end of 2003 and notifications of defects received by the 31st March 2004 have been accepted for inclusion. After this date the 1998 cohort is considered complete and no further notifications are included. Similarly, the 2004 report will record complete numbers for the 1999 birth cohort.

This report also describes prenatal diagnosis in South Australia for the year 2003, combining information from the Children, Youth and Women’s Health Service, Department of Genetic Medicine, the Institute of Medical and Veterinary Science and Gribbles Pathology.

viii

Register Activities 2004 / 2005

Diabetes and birth defects. Mothers with pre-existing diabetes are known to have an increased risk of having a child with a birth defect. In 2002 the Register undertook a study to determine the prevalence of birth defects associated with maternal pre-existing and gestational diabetes in the South Australian population between 1986 and 2000. The results of this study showed that both maternal pre-existing and gestational diabetes were significantly associated with an increase in birth defects (OR=2.01 and OR=1.19 respectively). The types of defects involved were nervous system, cardiovascular system and urogenital defects. The findings from this study were presented at the Australian Birth Defects Society meeting in Melbourne, May 2005 and were published in Birth Defects Research in 2005. Cerebral Palsy Register The Register published its 2004 Annual Report in August 2005. The report includes children born between 1993 –1999 diagnosed with cerebral palsy. There were 285 children notified to the Register with cerebral palsy over this period. Experience has shown that some of the ascertained cases will not have cerebral palsy when assessed at five years of age. For this reason minimum and maximum prevalences are calculated for each year from 1993 to 1999. The minimum represents the confirmed cases and the maximum represents the total notified cases. The minimum and maximum prevalences of cerebral palsy for the period 1993-1999 were 1.46 and 2.13 per 1,000 live births respectively. Requests for Information The Register answers many requests for information from government departments, health professionals in the community, other birth defect registers and students who require statistics on the prevalence of birth defects occurring in South Australia. In 2005, one example has been the provision of data to the ongoing South Australian Burden of Disease Study, undertaken by the Department of Health.

Audit of pregnancy outcome following use of assisted reproductive technology Assisted reproductive technology (ART) provides infertile couples with an option for having children, and the technology has been available in South Australia for over 20 years. The technology has changed during this time, and examples of approaches used at different times are in vitro fertilisation (IVF), gamete intra-fallopian transfer (GIFT) and intracytoplasmic sperm injection (ICSI). The Birth Defects Register and the Cerebral Palsy Register are participating in a collaborative study with the Reproductive Medicine Unit at The Queen Elizabeth Hospital, the Reproductive Medicine Unit at Flinders Medical Centre, and the Pregnancy Outcome Statistics Unit of the Department of Health. The aim is to audit the outcome of ART in terms of pregnancy outcome, birth defects and cerebral palsy. The question of safety has not yet been adequately addressed and South Australia is in an excellent position to carry out an audit because of its capacity to link relevant databases. In 2004, this project was awarded an NHMRC grant and the Register’s involvement is ongoing. Diaphragmatic hernia A study on the clinical characteristics and outcomes of cases of diaphragmatic hernia for the period 1986 – 2001 has commenced. A literature review has been completed and cases retrieved from the SA Birth Defects Register. The study will examine both live births and deaths associated with diaphragmatic hernia in terms of treatment and survival for live births, prenatal diagnosis and causes of death. A questionnaire has been designed for the data collection from patient case notes. Patient case notes have been reviewed and data recorded in an Access database. During 2005, Register staff have been following up missing data and have begun to prepare a paper for publication.

ix

Register Activities 2004 / 2005 (continued)

Different epidemiology of late diagnosed developmental dysplasia of the hip (DDH). This study was undertaken with the Department of Orthopaedic Surgery at the Women’s and Children’s Hospital. Cases of DDH born between 1988 and 1996 were ascertained from the SA Birth Defects Register and case notes were reviewed to establish whether or not they were late diagnosed. The aim was to evaluate the epidemiological differences between early and late diagnosed DDH. Late diagnosis was defined as at or after three months of age. Twenty-seven cases of late diagnosed DDH were identified. Twenty-two of these had previously been identified in a study of DDH cases born between 1988 and 1993 (Chan A et al, 1999). Five additional cases born in 1994-1996 were identified. A case-control study was undertaken to identify risk factors for late diagnosis using the late diagnosed children as cases and the other children with DDH as controls. The results from this study showed births in rural settings, female gender, vertex presentation and discharge from the birth hospital at less than four days of age, significantly increased the risk of late diagnosis of DDH. The results of this study will be published in Archives of Disease in Childhood in late 2005.

Thrombophilia and cerebral palsy

Over the past few years, the Register has participated in a study to determine whether cerebral palsy is associated with variations in genes involved in susceptibility to thrombosis. The genetic variations being studied are in factor V, prothrombin and MTHFR. The project is a collaborative effort between members of the South Australian Cerebral Palsy Research Group from the Women’s and Children’s Hospital, the University of Adelaide, and the Institute for Medical and Veterinary Science. This research group has produced a number of publications from this work (see References section). The group is continuing to collaborate on a number of other studies using data from the SA Cerebral Palsy Register and the Pregnancy Outcome Unit of the Department of Health.

Promotion of periconceptional folic acid Promotion of the need to increase periconceptional intake of folic acid for the prevention of neural tube defects was undertaken in October 1994 - August 1995 during the ‘Folate before pregnancy’ project. This has been continued by the Women’s and Children’s Hospital through the use of a telephone message, leaflets, messages in the Messenger newspapers and an occasional television announcement. There has been a significant downward trend in the prevalence of neural tube defects in recent years. Prevalence in the years 1998-2003 was 1.41 per 1,000 births compared with 1.92 per 1,000 births in 1986-1994. The folic acid message needs to be reinforced periodically, and promotion of periconceptional folic acid is now part of the “Healthy Pregnancy” project coordinated by the Centre for Health Promotion at the Women’s and Children’s Hospital and Health Promotion SA, Department of Health. This will also focus on advising women about the adverse effects of smoking and alcohol during pregnancy. �

Antenatal risk factors for congenital talipes equinovarus

Congenital talipes equinovarus is a significant birth defect with a prevalence of 2.1/1000 births. It is usually obvious at birth and can be treated with surgery or splinting. Talipes equinovarus is most often isolated but can be associated with conditions such as spina bifida and cerebral palsy. Little has been published on the antenatal risk factors for talipes. This study was completed in 2002. It was found that four factors were significantly associated with an increased risk of congenital talipes equinovarus. These were maternal Aboriginal race, maternal anaemia, maternal hyperemesis and male gender. A paper describing the research was published in Paediatric and Perinatal Epidemiology in early 2005.

1

Prevalence of Birth Defects

This report includes all notifications of birth defects for births (and terminations of pregnancy) occurring in South Australia in the years 1986 – 2003 received by 31st March, 2004. The percentages of births with birth defects for the years 1986 – 2003 are provided in Table 1. It is interesting to note that the percentage of total births with birth defects has not changed significantly since the Register began to collect data in 1986.

Table 1 Birth defects in children born in South Australia, 1986-2003 Year of Total Cases of Percentage of Births Birth Births Birth Defects with Birth Defects 1986-98 254346 14784 5.8% 1999 18519 1109 6.0% 2000 17871 997 5.6% 2001 17704 998 5.6% 2002 17745 891 5.0% 2003 17844 798 4.5% Total 344029 19577 5.7%

The numerator used in calculating the percentage is all South Australian births and terminations with birth defects. These consist of livebirths and stillbirths of at least 400g birthweight or 20 weeks gestation, and terminations of pregnancies of fetuses with birth defects. The denominator used is the total number of livebirths and stillbirths only, and excludes terminations of pregnancy before 20 weeks gestation. This makes our statistics comparable with those of other registers, but slightly overestimates the percentage of births with defects. This denominator has been selected also because accurate statistics on terminations may not be available elsewhere (as they are in South Australia), and fetuses from terminations in early pregnancy may not be examined for birth defects. Spontaneous fetal deaths, where weight is less than 400g or gestation is less than 20 weeks, are not

included among the Register cases as accurate statistics on them are also not available. Notifications of children with birth defects who were born outside South Australia in the years 1986 – 2003 but who are currently resident in South Australia are not included in the statistics. As birth defects continue to be diagnosed and notified to the Register in children up to the age of 5 years, the percentage of births with birth defects is higher in the cohorts with 5 completed years of ascertainment than in more recent cohorts. This is particularly true for defects such as congenital heart disease and urogenital malformations, which often are not diagnosed at birth.

2

Demographic Information

Residence of mother Table 2 shows the distribution of cases by residence of mother at time of birth (see Figure 1). Births to mothers resident interstate had the highest prevalence of birth defects due to the referral of high risk pregnancies from interstate to Adelaide tertiary hospitals. Among South Australian CURB (Committee on Uniform Regional Boundaries) regions the Central Northern region had the highest overall percentage of birth defects with 6.2%; the lowest percentage of 4.6% of birth defects was seen in the South East region for the period 1986 – 2003. Over this period there was significant (χ2= 162.82, p<0.0001) variation in the prevalence of birth defects between CURB regions. However, this difference was not significant (χ2= 2.28, p=0.13) for the more readily identifiable sentinel defects (Table 7) and suggests that the variation seen is due to differences in ascertainment between CURB regions.

Table 2 Cases of birth defects by residence of mother at time of birth, SA 1986-2003 Year of Birth Total 1986-98 1999 2000 2001 2002 2003 1986-2003 CURB No. No. No. No. No. No. No. Region (%*) (%*) (%*) (%*) (%*) (%*) (%*)

Central Northern 4615 339 301 281 255 234 6025 (6.5) (6.5) (5.8) (5.5) (5.1) (4.5) (6.2) Central Western 2043 130 128 139 136 101 2677 (6.1) (5.3) (5.6) (6.1) (6.0) (4.4) (6.0) Central Eastern 2264 197 160 152 150 125 3048 (6.2) (7.2) (5.8) (5.4) (5.4) (4.4) (6.1) Central Southern 2825 237 209 223 197 199 3890 (5.1) (5.9) (5.4) (5.9) (5.0) (5.0) (5.2) Yorke & Lower Nth 410 24 27 32 17 18 528 (5.5) (5.1) (6.1) (7.1) (3.6) (4.3) (5.5) Murraylands 658 51 48 49 35 24 865 (5.2) (5.7) (5.6) (5.8) (4.3) (3.0) (5.1) South East 579 35 42 36 35 27 754 (4.8) (3.9) (5.3) (4.4) (4.1) (3.3) (4.6) Northern 862 61 60 47 39 36 1105 (4.8) (5.3) (5.6) (4.6) (4.0) (3.7) (4.8) Eyre 357 21 14 27 13 22 454 (5.2) (4.4) (3.0) (5.5) (2.7) (5.3) (4.9) Residence - Interstate** 171 14 8 12 14 12 231 or Unknown (9.0) (12.0) (8.2) (10.4) (9.5) (9.8) (9.2) Total 14784 1109 997 998 891 798 19577 (5.8) (6.0) (5.6) (5.6) (5.0) (4.5) (5.7) * Number of children with birth defects in the region divided by the total number of births in the region x 100 ** Usual residence interstate but born in South Australia

3


Figure 1 South Australian CURB Regions

4


Sex of child The sex distribution of children born between 1986 and 2003 in South Australia with notified birth defects is shown in Table 3. For 1986 – 2003 the ratio of males to females for births with birth defects was 1.36:1, with 36% more male births being notified with a birth defect. This contrasts with a male to female ratio of 1.06:1 for all births. The percentage of male births with notified defects for the period 1986 – 2003 was 6.3%; this was significantly higher, relative risk (RR) = 1.29 (95% CI 1.25, 1.32) p<0.0001, than for female births (4.9%). There are a number of birth defects that are specific to each sex (eg, undescended testis). Taking into account these gender specific defects, there is still a greater prevalence of certain defects in males for example, pyloric stenosis, short segment Hirschsprung’s disease and congenital talipes equinovarus.

Table 3 Cases with birth defects by sex of child, SA 1986-2003 Year of Birth Total 1986-98 1999 2000 2001 2002 2003 1986-2003 Sex No. No. No. No. No. No. No. (%*) (%*) (%*) (%*) (%*) (%*) (%*)

Male 8400 641 581 551 502 428 11103 (6.4) (6.8) (6.3) (6.2) (5.5) (4.7) (6.3) Female 6182 450 393 426 348 338 8137 (5.0) (5.0) (4.5) (4.9) (4.0) (3.9) (4.9) Indeterminate 12 0 0 1 1 2 16 - - - - - - - Not Specified# 190 18 23 20 40 30 321 - - - - - - - Total 14784 1109 997 998 891 798 19577 (5.8) (6.0) (5.6) (5.6) (5.0) (4.5) (5.7) # These were all terminations of pregnancy * Percentage of births of that category in that year

5


Race The percentage of births with birth defects by mother's race is shown in Table 4. There were significant differences between the prevalences of birth defects according to mother’s race for 2003 (χ2= 13.02, p=0.0003) as well as over the period 1986-2003 (χ2= 39.94, p<0.0001). For 1986-2003, there was a significantly higher prevalence of birth defects among Caucasian mothers compared with Asians (RR = 1.24 (95% CI 1.15, 1.35) and Other races (RR = 1.31 (95% CI 1.11, 1.53).

Table 4 Cases with birth defects by mother's race, SA 1986-2003 Year of Birth Total 1986-98 1999 2000 2001 2002 2003 1986-2003 Mother's Race No. No. No. No. No. No. No. (%*) (%*) (%*) (%*) (%*) (%*) (%*)

Caucasian 13872 1046 959 926 852 751 18406 (5.8) (6.1) (5.9) (5.7) (5.3) (4.6) (5.7)

Aboriginal 290 30 9 27 15 19 390 (5.6) (6.7) (2.0) (6.7) (3.3) (4.0) (5.3)

Asian 456 27 21 38 17 18 577 (5.4) (3.5) (2.6) (4.9) (2.0) (2.2) (4.6)

Other 110 6 8 6 7 9 146 (5.7) (2.4) (3.4) (2.4) (2.2) (2.6) (4.4)

Unspecified 56 0 0 1 0 1 58 - - - - - - -

Total 14784 1109 997 998 891 798 19577 (5.8) (6.0) (5.6) (5.6) (5.0) (4.5) (5.7) * Percentage of births of that category in that year

Plurality The distribution of cases of birth defects by plurality is shown in Table 5. The percentage of cases among multiple births was 7.0%; this was significantly higher, RR =1.24 (95% CI 1.15, 1.33), p<0.0001, than among singleton births, with 5.6% for the 18 year period 1986 – 2003. Certain birth defects are associated with twin pregnancies, in particular monozygotic twins. Examples of defects that occur more often in monozygotic twins are sirenomelia, VATER association, holoprosencephaly and anencephaly.

Table 5 Cases with birth defects by plurality, SA 1986-2003 Year of Birth Total 1986-98 1999 2000 2001 2002 2003 1986-2003 Plurality No. No. No. No. No. No. No. (%*) (%*) (%*) (%*) (%*) (%*) (%*)

Single 14258 1081 958 952 838 767 18854 (5.8) (6.0) (5.5) (5.6) (4.9) (4.5) (5.6)

Multiple 526 28 39 46 53 31 723 (7.2) (4.9) (6.7) (8.3) (8.2) (4.8) (7.0)

Total 14784 1109 997 998 891 798 19577 (5.8) (6.0) (5.6) (5.6) (5.0) (4.5) (5.7) * Percentage of births of that category in that year

6

Types of Birth Defects Notified

The rates of birth defects per 1,000 total births for major diagnostic groupings (ie. not all birth defects) are provided in Figure 2. The most commonly reported birth defects between 1986 and 2003 were: Urogenital abnormalities (eg. vesico-ureteric reflux) with 16.4 per 1000 births, and Musculoskeletal abnormalities (eg. development dysplasia of the hip), with 16.3 per 1,000 births. The diagnostic categories used by the Register for coding are those of the British Paediatric Association (BPA) Classification of Diseases, 1979, a 5-digit system compatible at the 4-digit level with the ninth revision of the International Classification of Diseases (ICD9). Its Congenital Anomaly codes are those in the range 74000 – 75999. The BPA also provides codes outside this range for some disorders which are included in the Register's collection. For disorders without a BPA code the Register uses the ICD9 classification.

We anticipate a change in coding to the tenth revision of the International Classification of Diseases. In Table 6 we present the number of cases with specified birth defects by diagnostic category. Children with multiple defects will appear in more than one category. For example, a child with trisomy 18 who has spina bifida will appear in Chromosome defects and also under Nervous system defects. It should be noted that the number of cases in each body system total does not necessarily equal the sum of the individual defects listed under it. For example with Nervous system defects the total is smaller than the number obtained by adding together cases with anencephaly, spina bifida and encephalocele. This is because some cases of neural tube defects have more than one lesion, for example the combination of spina bifida and anencephaly.

Figure 2 Cases with birth defects by major diagnostic grouping 1986-2003 (prevalence rates per 1,000 births)

16.4

16.3

12

6.4

3.8

3.7

1.6

1.3

0.9

0 2 4 6 8 10 12 14 16 18

Cases per 1000 births

Urogenital Musculoskeletal Cardiovascular

Gastrointestinal Nervous system

Chromosomal Respiratory

Metabolic

Haem/Immune

7


Table 6 Cases with specified birth defects by diagnostic category, SA 1986-2003

Year of Birth Total 1986-98 1999 2000 2001 2002 2003 1986-2003 Diagnostic Category No. No. No. No. No. No. (BPA Code) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) No. Rate* Nervous System 990 75 75 69 58 50 1317 3.8 (74000-74299) (3.9) (4.0) (4.2) (3.9) (3.3) (2.8) Neural Tube Defects 467 21 32 27 23 21 591 1.7 Anencephaly 191 7 11 11 12 7 239 0.7 Spina Bifida 242 10 17 14 11 12 306 0.9 Encephalocele 42 4 4 2 1 2 55 0.2 Microcephaly 126 9 6 12 10 6 169 0.5 Congenital Hydrocephalus 211 23 11 14 10 11 280 0.8 Cardiovascular 3133 238 208 201 169 164 4113 12.0 (74500-74799) (12.3) (12.9) (11.6) (11.4) (9.5) (9.2) Transposition of Great Vessels 169 13 9 13 11 9 224 0.7 Tetralogy of Fallot 87 4 8 5 7 5 116 0.3 Ventricular Septal Defect 1614 116 113 96 77 87 2103 6.1 Atrial Septal Defect 781 35 41 56 41 24 978 2.8 Hypoplastic Left Heart Syndrome 68 6 10 4 11 1 100 0.3 Patent Ductus Arteriosus 453 37 31 36 38 25 620 1.8 Coarctation of Aorta 160 12 12 8 7 12 211 0.6 Respiratory 378 44 31 34 36 38 561 1.6 (74800-74899) (1.5) (2.4) (1.7) (1.9) (2.0) (2.1) Pulmonary Hypoplasia/Dysplasia 195 28 22 20 19 22 306 0.9 Gastrointestinal 1651 130 96 131 102 102 2212 6.4 (74900-75199) (6.5) (7.0) (5.4) (7.4) (5.7) (5.7) Cleft Palate 253 14 15 19 20 15 336 1.0 Cleft Lip 110 8 10 5 3 5 141 0.4 Cleft Lip with Cleft Palate 188 15 11 12 14 11 251 0.7 Tracheo-Oesophageal Fistula, Oesophageal Atresia & Stenosis 115 8 2 11 3 3 142 0.4 Pyloric Stenosis 500 38 24 37 21 24 644 1.9 Rectal/Anal Atresia & Stenosis 135 6 10 8 12 7 178 0.5 Hirschsprung Disease 48 1 2 7 2 3 63 0.2 Urogenital 4372 294 255 281 266 177 5645 16.4 (75200-75399) (17.2) (15.9) (14.3) (15.9) (15.0) (9.9) Undescended Testicle 1292 73 62 57 70 27 1581 4.6 Hypospadias 919 85 73 69 75 55 1276 3.7 Renal Agenesis & Dysgenesis 153 5 7 11 9 13 198 0.6 Vesico-ureteric Reflux 940 25 19 27 30 17 1058 3.1 *Rate per 1,000 total births

8


Table 6 (Continued) Cases with specified birth defects by diagnostic category, SA 1986-2003 Year of Birth Total 1986-98 1999 2000 2001 2002 2003 1986-2003 Diagnostic Category No. No. No. No. No. No. (BPA Code) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) No. Rate* Musculoskeletal 4196 316 305 279 255 267 5618 16.3 (75400-75699) (16.5) (17.1) (17.1) (15.8) (14.4) (15.0) Developmental Dysplasia of Hip 1804 125 118 111 102 108 2368 6.9 Talipes Equinovarus 548 39 55 23 40 45 750 2.2 Polydactyly 259 17 30 20 21 14 361 1.0 Syndactyly 205 18 11 10 7 9 260 0.8 Reduction Deformity of Limbs 209 11 16 11 11 9 267 0.8 Diaphragmatic Hernia 94 8 10 6 8 4 130 0.4 Exomphalos 101 4 8 9 13 8 143 0.4 Gastroschisis 51 5 4 6 4 7 77 0.2 Achondroplasia 16 1 0 0 0 0 17 0.0 Osteogenesis Imperfecta 27 5 1 5 3 1 42 0.1 Chromosome 855 90 75 79 82 81 1262 3.7 (75800-75899) (3.4) (4.9) (4.2) (4.5) (4.6) (4.5) Down Syndrome 404 42 37 36 44 42 605 1.8 Trisomy 13 40 2 5 3 3 2 55 0.2 Trisomy 18 92 13 11 12 6 9 143 0.4 Turner Syndrome 60 9 5 7 9 3 93 0.3 Metabolic 326 24 22 22 15 26 435 1.3 (24390-27790) (1.3) (1.3) (1.2) (1.2) (0.8) (1.5) Congenital Hypothyroidism 88 8 5 6 6 6 119 0.3 Phenylketonuria 17 2 2 1 0 0 22 0.1 Galactosaemia 7 3 1 1 0 0 12 0.0 Albinism 17 0 0 0 0 1 18 0.1 Cystic Fibrosis 103 5 9 7 3 8 135 0.4 Other Metabolic 93 6 5 7 6 10 127 0.4 Haematological 279 3 12 12 4 4 314 0.9 (28200-28699) (1.1) (0.2) (0.7) (0.7) (0.2) (0.2) Haemolytic Anaemias 155 0 4 2 1 1 163 0.5 Thalassaemias 30 0 1 2 1 1 35 0.1 Coagulation Defects 47 0 3 4 0 0 54 0.2 Other Selected Congenital Syphilis Syndrome 6 1 0 0 0 0 7 0.0 Congenital Rubella Syndrome 2 0 0 0 0 0 2 0.0 Fetal Alcohol Syndrome 9 0 0 0 0 1 10 0.0 Non-immune Fetal Hydrops 97 18 10 7 13 8 153 0.4 Haemangioma 146 16 10 12 7 12 203 0.6 Lymphangioma 91 14 13 8 12 8 146 0.4 Congenital Neoplasms of Brain 16 0 0 0 1 0 17 0.0 Anotia / Microtia 36 2 5 3 4 3 53 0.2 *Rate per 1,000 total births

9

Trends in Selected Birth Defects, SA 1986-2003

Figure 3.1 Prevalence of Neural Tube Defects 1986 - 2003

0

0.5

1

1.5

2

2.5

1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Year

Rate per 1000 Total Births

Neural TubeDefects

Spina Bif ida

Anencephaly

Figure 3.2 Prevalence of Total Cleft Lip* 1986 - 2003

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

1986 1988 1990 1992 1994 1996 1998 2000 2002

Year

Rate per1000TotalBirths

Total CleftLip

There was a significant downward trend in the prevalence of all Neural Tube Defects for the period 1986 – 2003 (poisson regression, p<0.0001) and also for Anencephaly and Spina Bifida (poisson regression, p=0.0046 and p<0.0001 respectively). A paper describing the impact of the ‘folate before pregnancy’ campaign on women and health professionals in South Australia was published in the Medical Journal of Australia in 2001 (see References section).

There was no overall increasing or decreasing trend in the rate of Total Cleft Lip for the years 1986-2003 (poisson regression, p=0.79) however, there was a significant decreasing trend from 1995 onwards, p= 0.02. There has been some suggestion that periconceptional folic acid supplementation may reduce the prevalence of cleft lip with or without cleft palate (IA van Rooij et al. Prev Med. 2004 Oct;39(4):689-94). A campaign to promote folic acid in the prevention of neural tube defects occurred in South Australia between 1994 and 1995.

*Total Cleft Lip = Cleft Lip plus Cleft Lip with Cleft Palate

10

Trends in Selected Birth Defects, SA 1986-2003

Figure 3.3 Prevalence of Transposition of Great Vessels 1986 - 2003

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.80.9

1

1986 1988 1990 1992 1994 1996 1998 2000 2002

Year


Transpositionof GreatVessels

Figure 3.4 Prevalence of Down Syndrome 1986 - 2003

0

0.5

1

1.5

2

2.5

3

1986 1988 1990 1992 1994 1996 1998 2000 2002

Year


Total Dow nSyndrome

There was a significant decreasing trend in the prevalence of Transposition of Great Vessels over the period 1986 to 2003 (poisson regression, p=0.01).

Over the period 1986-2003, there was a significant increasing trend in the prevalence of total Down syndrome (poisson regression, p<0.0001). This increase is attributed to increasing maternal age over the 18 year period. The trend ceases to be significant after adjustment for maternal age (poisson regression p=0.10).

11

Sentinel Defects

A number of readily identifiable defects have been chosen as 'sentinel' defects for monitoring purposes by the International Clearinghouse for Birth Defects Monitoring Systems. Table 7 presents sentinel defects by CURB region for the period 1986-2003. The totals for individual defects may be less than those shown in Table 6 as births to women who are interstate residents have been excluded from this table. This tabulation is an important tool for detecting regional and temporal clusters of birth defects. The SABDR monitors the occurrence of defects over time and by geographical area in this way. The Register assesses the significance of variations in prevalence rates by comparing the

observed and expected numbers for each region using the poisson distribution. The rate of Down syndrome in the Central Eastern Region between 1986 and 2003 was again significantly greater than the rest of South Australia RR=1.49 (95%CI 1.22, 1.82) p<0.01. This was shown to be related to the older age of mothers in that region. After adjustment for maternal age, no significant trend was seen, Mantel-Haenszel RR=1.07 (95%CI 0.88, 1.31) p=0.52. There were no other significant regional increases in prevalence (p<0.01) between 1986 and 2003.

Table 7 Cases of sentinel defects by CURB region, SA 1986 - 2003

CURB Region Central Central Central Central Yorke & Murray South Northern Eyre Total Northern Western Eastern Southern Low Nth Lands East Total Births 96816 44815 50213 74519 9681 16847 16373 23034 9232 344029 % State Births 28% 13% 15% 22% 3% 5% 5% 7% 3% 100% No. No. No. No. No. No. No. No. No. No (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*)

Anencephaly 59 30 36 54 7 12 6 18 6 228 (0.61) (0.67) (0.72) (0.72) (0.72) (0.71) (0.37) (0.78) (0.65) (0.66)

Spina Bifida 80 54 37 57 8 18 13 22 7 296 (0.83) (1.20) (0.74) (0.76) (0.83) (1.07) (0.79) (0.96) (0.76) (0.86)

Encephalocele 19 7 6 9 3 1 3 4 1 53 (0.20) (0.16) (0.12) (0.12) (0.31) (0.06) (0.18) (0.17) (0.11) (0.15)

Hydrocephalus 76 37 40 69 6 9 12 18 5 272 (0.78) (0.83) (0.80) (0.93) (0.62) (0.53) (0.73) (0.78) (0.54) (0.79)

Cleft Palate 112 46 40 66 6 16 16 18 13 333 (1.16) (1.03) (0.80) (0.89) (0.62) (0.95) (0.98) (0.78) (1.41) (0.97)

Total Cleft Lip# 121 38 51 81 14 19 17 28 14 383 (1.25) (0.85) (1.02) (1.09) (1.45) (1.13) (1.04) (1.22) (1.52) (1.11)

Tracheo- Oesophageal 41 14 27 28 5 8 4 11 4 142 Fistula, Atresia (0.42) (0.31) (0.54) (0.38) (0.52) (0.47) (0.24) (0.48) (0.43) (0.41) & Stenosis

Ano-Rectal 50 23 25 37 4 9 7 13 4 172 Atresia & (0.52) (0.51) (0.50) (0.50) (0.41) (0.53) (0.43) (0.56) (0.43) (0.50) Stenosis # cleft lip with or without cleft palate * Rate per 1000 total births in region

12

Sentinel Defects

Table 7 (Continued) Cases of sentinel defects by CURB region, SA 1986 - 2003 CURB Region Total Central Central Central Central Yorke & Murray South Northern Eyre Northern Western Eastern Southern Low Nth Lands East Total Births 96816 44815 50213 74519 9681 16847 16373 23034 9232 344029 % State Births 28% 13% 15% 22% 3% 5% 5% 7% 3% 100% No No No No No No No No No No (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*) (Rate*)

Hypospadias 393 162 166 258 38 74 50 85 42 1268 (4.06) (3.61) (3.31) (3.46) (3.93) (4.39) (3.05) (3.69) (4.55) (3.69)

Renal Agenesis 51 29 32 38 8 9 6 20 2 195 & Dysgenesis (0.53) (0.65) (0.64) (0.51) (0.83) (0.53) (0.37) (0.87) (0.22) (0.57)

Limb Reduction 67 36 39 50 11 18 13 22 7 263 Defects (0.69) (0.80) (0.78) (0.67) (1.14) (1.07) (0.79) (0.96) (0.76) (0.76)

Diaphragmatic 32 17 17 21 6 7 9 12 5 126 Hernia (0.33) (0.38) (0.34) (0.28) (0.62) (0.42) (0.55) (0.52) (0.54) (0.37)

Exomphalos 32 18 27 29 6 5 4 14 3 138 (0.33) (0.40) (0.54) (0.39) (0.62) (0.30) (0.24) (0.61) (0.32) (0.40)

Gastroschisis 26 13 5 6 1 5 5 9 1 71 (0.27) (0.29) (0.10) (0.08) (0.10) (0.30) (0.31) (0.39) (0.11) (0.21)

Transposition 59 37 30 57 6 10 8 9 4 220 of Great Vessels (0.61) (0.83) (0.6) (0.76) (0.62) (0.59) (0.49) (0.39) (0.43) (0.64)

Hypoplastic 23 17 15 24 2 2 6 5 2 96 Left Heart (0.24) (0.38) (0.30) (0.32) (0.21) (0.12) (0.37) (0.22) (0.22) (0.28)

Down Syndrome 160 80 122 139 21 25 21 19 10 597 (1.65) (1.79) (2.43) (1.87) (2.17) (1.48) (1.28) (0.82) (1.08) (1.74)

Anotia 11 12 7 13 1 0 3 2 2 51 & Microtia (0.11) (0.27) (0.14) (0.17) (0.10) (0) (0.18) (0.09) (0.22) (0.15)

Total 1310 621 663 953 133 227 190 298 123 4518 (13.5) (13.9) (13.2) (12.8) (13.7) (13.5) (11.6) (12.9) (13.3) (13.1)

* rate per 1000 total births in region

13

Deaths Associated with Birth Defects

In Table 8, the number of deaths which are associated with birth defects is listed by death category. Note that the birth defect is not necessarily the cause of death. Spontaneous stillbirths with birth defects represented 11.1% of all spontaneous stillbirths in South Australia in 1986-2003; neonatal deaths with birth defects represented 31.6% of all neonatal deaths in the same period. Figure 4 shows deaths associated with birth defects for the years 1986-2003 by category of death. The different death categories are mutually exclusive. For example, the stillbirth category does not include terminations of pregnancy > 20 weeks.

In the category "Termination of Pregnancy (< 20 weeks)", the Register distinguishes between first and second trimester diagnoses. Some notifications specify whether testing has been by chorionic villus sampling or amniocentesis. Otherwise, classification into these two groups is based on gestation. At a gestation of < 14 weeks, diagnosis is assumed to be via chorionic villus sampling or ultrasound. At a gestation of >14 weeks, diagnosis is assumed to be via amniocentesis or ultrasound.

Figure 4 Deaths associated with birth defects by death category, SA 1986 – 2003

Stillbirths >20 w eeks 252 (10%)

Neonatal Deaths 386 (15%)

Post Neonatal Deaths 182 (7%)

TOP <20 w eeks 1223 (48%)

TOP >20 w eeks 490 (19%)

14

Deaths Associated with Birth Defects

Table 8 Deaths associated with birth defects, SA 1986-2003 Year of Birth Total 1986-98 1999 2000 2001 2002 2003 1986-2003 Death No No No No No No No Category (%*) (%*) (%*) (%*) (%*) (%*) (%*) Post Neonatal Death 142 9 3 7 9 12 182 (death of a liveborn infant (7.9) (6.3) (2.1) (4.8) (5.6) (7.0) (7.2) between 28 days of age and the first birthday)

Neonatal Death 316 13 18 16 13 10 386 (death of a liveborn infant (17.6) (9.2) (12.4) (11.0) (8.1) (5.8) (15.2) before 28 days of age) Stillbirth 176 12 12 19 29 4 252 (spontaneous fetal death (9.8) (8.5) (8.3) (13.1) (18.1) (2.3) (9.9) > 20 weeks)

Termination of 323 42 26 39 22 38 490 Pregnancy (18.0) (29.6) (17.9) (26.9) (13.8) (22.2) (19.3) (> 20 weeks)

Termination of Pregnancy (< 20 weeks) • diagnosis by chorionic villus sampling and/or 134 7 10 12 12 15 190 ultrasound in first trimester (7.5) (4.9) (6.9) (8.3) (7.5) (8.8) (7.5) • diagnosis by amniocentesis, cordocentesis and/or 705 59 76 52 75 66 1033 ultrasound after first (39.3) (41.5) (52.4) (35.9) (46.9) (38.6) (40.8) trimester

Total Termination of Pregnancy (at all gestations) 1162 108 112 103 109 119 1713 (64.7) (76.1) (77.2) (71.0) (68.1) (69.6) (67.6)

Total 1796 142 145 145 160 171 2533 * (%) of total deaths associated with birth defects in that year

15

Sources of Notification

The sources of notification for cases born in 1986 – 2003 are provided in Figure 5. As outlined earlier, each case may be notified by more than one source.

Notifications from the Pregnancy Outcome Statistics Unit are obtained from all obstetric units as well as homebirth midwives in South Australia.

Figure 5 Sources of notification, SA 1986 –2003: Total notifications received*

Perinatal Autopsies 1277 (4%)

Pregnancy Outcome Unit 9804 (29%)

Other Sources 3098 (9%)

Women's and Children's Hospital 19675 (58%)

Birth Defects Detected/Notified after Discharge from the Birth Hospital

Table 9 and Figure 6 use diagnostic category to show the number and proportion of cases of birth defects in 1986 – 2003 which were detected and notified after discharge from the birth hospital, and included in the Register's data. A higher proportion of cases of chromosomal, respiratory, nervous and musculoskeletal system defects were notified by the birth hospital than for the categories of urogenital, cardiovascular and gastrointestinal systems, and metabolic and haematological/immune defects.

The value of the Register in collecting later diagnosed defects is clearly illustrated by the proportions of cases in these latter categories, especially for earlier birth cohorts where collection has been of longer duration. Examples of birth defects that are commonly notified after discharge from the birth hospital are ventricular septal defects, vesico-ureteric reflux and pyloric stenosis.

* Each case may have multiple notifications

16

Birth Defects Detected/Notified after Discharge from the Birth Hospital

Table 9 Cases with birth defects notified after discharge from the birth hospital by major diagnostic category, SA 1986-2003

Year of Birth Total 1986-98 1999 2000 2001 2002 2003 1986-2003 Diagnostic No No No No No No No Category (%*) (%*) (%*) (%*) (%*) (%*) (%*)

Nervous System 269 22 19 27 17 9 363 (27.2) (29.3) (25.3) (39.1) (29.3) (18.0) (27.6)

Cardiovascular 1772 131 103 105 81 68 2260 (56.6) (55.0) (49.5) (52.2) (47.9) (41.5) (54.9)

Respiratory 57 10 4 8 4 9 92 (15.1) (22.7) (12.9) (23.5) (11.1) (23.7) (16.4)

Gastrointestinal 673 61 39 61 35 34 903 (40.8) (46.9) (40.6) (46.6) (34.3) (33.3) (40.8)

Urogenital 2667 173 136 148 135 69 3328 (61.0) (58.8) (53.3) (52.7) (50.8) (39.0) (59.0)

Musculoskeletal 1234 113 115 106 84 83 1735 (29.4) (35.8) (37.7) (38.0) (32.9) (31.1) (30.9)

Chromosome 132 8 7 5 2 2 156 (15.4) (8.9) (9.3) (6.3) (2.4) (2.5) (12.4)

Metabolic 224 15 11 16 10 6 282 (68.7) (62.5) (50.0) (72.7) (66.7) (23.1) (64.8)

Haematological/ 211 0 7 5 0 2 225 Immune Disorders (75.6) (0.0) (58.3) (41.7) (0.0) (50.0) (71.7) * Percentage of total cases per category, per year

Figure 6 Percentage of cases with birth defects notified after discharge from the birth hospital by diagnostic category, SA 1986-2003

71.7

64.8

59.0

54.9

40.8

30.9

27.6

16.4

12.4

0 10 20 30 40 50 60 70 80 90 100

Percentage

Haem/Immune

Metabolic

Urogenital

Cardiovascular

Gastrointestinal

Musculoskeletal

Nervous System

Respiratory

Chromosomal

17

Prenatal Diagnosis in South Australia, 2003 Introduction

The Annual Report of Prenatal Diagnosis in South Australia records the 2003 experience based on the techniques of amniocentesis, chorionic villus sampling (CVS), fetal blood sampling and screening for neural tube defects and Down syndrome. No attempt has been made to compile information on pregnancies where ultrasound was the sole diagnostic technique used to detect birth defects. Its role in the detection of neural tube defects is recorded in the review of the maternal serum alpha-fetoprotein screening program. It should be noted that this report includes cases screened in each calendar year. This contrasts with the SA Birth Defects Register report which includes cases born or terminated in each calendar year.

We are grateful to the following groups for providing data for this report: • Department of Genetic Medicine, Women’s and Children’s Hospital. • Division of Molecular Pathology, Institute of Medical and Veterinary Science. • Department of Haematology and Genetic Pathology, Flinders Medical Centre. • Gribbles Pathology. • Pregnancy Outcome Statistics Unit, Department of Health. • Clinical Information Services, Women’s and Babies Division, Women’s and Children’s Hospital.

18

Amniocentesis and Chorionic Villus Sampling

The number of amniocenteses performed in 2003 on South Australian women was 1338, a 17% decrease from 2002. The number of chorionic villus samplings performed in 2003 was 173, a 7% increase compared to 2002.

Maternal age was a factor in 764 women having amniocentesis (57% of all amniocenteses) and 109 women having chorionic villus sampling (63% of all CVS).

Table 10 Amniocentesis and chorionic villus sampling, SA 2003: Indications Indication Amniocentesis CVS Total

< 35 > 35 Unk < 35 > 35 Unk years years years years

Maternal age > 35 years 0 465 0 0 72 0 537 Maternal anxiety/maternal age < 35 years 68 0 0 1 0 0 69 Following abnormal CVS result 0 2 0 N/A� N/A� N/A� 2 Previous child with 1. Down syndrome 0 3 0 0 1 0 4 2. Other chromosomal abnormality (not Down) 5 8 0 3 8 0 24 3. Neural tube defect 0 0 0 0 0 0 0 Family history of 1. Down syndrome 1 1 0 2 1 0 5 2. Other chromosomal abnormality including translocation carrier parent 3 1 0 5 1 0 10 3. Neural tube defect 0 0 0 N/A� N/A� N/A� 0 At increased risk of chromosomal abnormality following screening by MSS*or NT#

1. 1st trimester combined screen 114 96 0 18 12 0 240 2. 1st trimester NT alone 0 2 0 2 3 0 7 3. 1st trimester MSS alone 1 1 0 0 1 0 3 4. 2nd trimester MSS alone 233 117 0 0 0 0 350 At increased risk of NTD^ following MSS* 8 2 0 N/A� N/A� N/A� 10

Abnormality found on ultrasound 108 50 1 5 3 0 167

At increased risk of a disorder diagnosed by molecular or biochemical techniques 4 1 0 20 6 0 31

Other (including Rh, failed cordocentesis) 19 11 0 6 1 0 37

Multiple reasons 7 4 0 0 0 0 11

Unknown indication 2 0 0 2 0 0 4

Total 573 764 1 64 109 0 1511 *MSS = Maternal Serum Screening # NT = Nuchal Translucency ^ Neural tube defect ‡ N/A = Not applicable

19


Table 11 Amniocentesis and chorionic villus sampling, SA 2003: Utilisation rate by maternal age Age* Amniocentesis CVS Total Rate^

< 20 9 4 13 13.9 20 – 24 70 15 85 31.9 25 – 29 177 22 199 39.8 30 – 34 317 23 340 58.5 35 – 39 545 71 616 238.4 40 – 44 212 37 249 498.0 45+ 7 1 8 381.0 Unknown 1 0 1 - Total 1338 173 1511 86.3 * Age in years at expected delivery date ^ Rate per 1000 confinements in that age range

Figure 7 Amniocentesis and chorionic villus sampling, SA 2003: Utilisation rate by maternal age

0.0

50.0

100.0

150.0

200.0

250.0

300.0

350.0

400.0

450.0

500.0

< 20 20 – 24 25 – 29 30 – 34 35 – 39 40 – 44 45+

Age at delivery (in years)

Rat

e pe

r 1,

000

conf

inem

ents

Amniocentesis

CVS

* Rate per 1,000 confinements in that age range

20


Table 12 Disorders diagnosed by molecular or biochemical techniques, SA 2003

Amniocentesis CVS+

Indication Tested Affected TOP* Tested Affected TOP*

Dept. Genetic Medicine, WCH^ Autosomal recessive polycystic kidney disease (ARPKD) 0 0 0 1 0 0 Cystic fibrosis 1 1 1 2 0 0 D2-Hydroxyglutaric aciduria 1 0 0 0 0 0 Duchene muscular dystrophy 0 0 0 2 0 0 Fragile X syndrome 0 0 0 1 0 0 Incontinentia pigmenti 0 0 0 1 0 0 IPEX^^ syndrome 1 0 0 0 0 0 Mucopolysaccharidosis-IIA 1 0 0 0 0 0 Myotubular myopathy 0 0 0 1 0 0 Myotonic dystrophy 0 0 0 1 0 0 Spinal muscular atrophy 0 0 0 1 1 1 Tay-Sachs disease 0 0 0 3 0 0 Tuberous sclerosis 0 0 0 1 0 0 Uniparental disomy 3 0 0 1 0 0

Division of Molecular Pathology, IMVS# Alpha-thalassaemia 0 0 0 1 0 0 Beta-thalassaemia 0 0 0 4 0 0 Beta-thalassaemia / HbE 1 1**

0 0 0 0

HbE 1 0 0 0 0 0 Blood group testing (including Rhesus) 12 - N/A++ 0 - N/A++

Dept. Haematology and Genetic Pathology, FMC##

Huntington disease 3 1 1 0 0 0 + CVS – Chorionic villus sampling, * TOP – Termination of pregnancy, ^ WCH – Women’s and Children’s Hospital, ^^IPEX – Immunodysregulation, polyendocrinopathy, and enteropathy, X-Linked, # IMVS – Institute of Medical and Veterinary Science, ** Possible mild transfusion-dependent anaemia, ++ N/A – Not applicable, ## FMC – Flinders Medical Centre

Fetal Blood Sampling

Fetal blood is obtained from the umbilical cord or a blood vessel in the fetal liver by an ultrasound guided needle technique. In 2003, 17 fetal blood samplings were performed; a 31% increase compared with 2002. As in 2002, all of the fetal blood samplings were performed because of Rh or other isoimmunization. Fetal transfusions were performed in 50% of fetuses sampled.

Table 13 Fetal blood sampling, SA 2003: Indications Indication No. Procedures No. Fetuses Outcome

Rhesus or other isoimmunization 17 8 9 Fetal transfusions (4 fetuses) Total 17 8

21

Maternal Serum Screening for Neural Tube Defects in the Second Trimester

In 2003, 7,324 pregnancies were screened by estimation of maternal serum alpha-fetoprotein by the Women’s and Children’s Hospital or Gribbles Pathology at 15-20 weeks gestation for a fetal neural tube defect. This represents 41.8% of all pregnancies.

There were 20 cases of neural tube defect in SA births whose mothers reached 15 weeks of pregnancy between 1.1.03 and 31.12.03 and hence would have been eligible for maternal serum

alpha-fetoprotein screening during the 2003 screening year. This figure includes all neural tube defects confirmed in terminations of pregnancy or in births (� 400g or � 20 weeks gestation).

100% of the fetuses with a neural tube defect that had screening by either maternal serum alpha-fetoprotein screening or ultrasound screening or both were detected prenatally.

Table 14.1 Maternal serum screening for neural tube defects, SA 2003: Women’s and Children’s Hospital and Gribbles Pathology

Number of pregnancies screened in 2003 7,324

Total confinements in SA in 2003 17,517

Percentage of pregnancies screened 41.8%

Table 14.2 Detection of neural tube defects by screening, SA 2003

Method of detection Spina bifida Anencephaly Encephalocele Total 1. AFP screen abnormal, 1 1 0 2 as first indication of NTD#

2. Ultrasound abnormal as first indication of NTD# (a) No serum AFP 9 2 0 11 (b) Serum AFP normal 3 0 0 3 (c) Too early for AFP 0 4 0 4 (c) Serum (or amniotic fluid) 0 0 0 0 AFP abnormal 3. Screened by AFP &/or Ultrasound 0 0 0 0 Not detected

Total # 13 7 0 20

Table 14.3 Outcome of neural tube defect pregnancies, SA 2003 Outcome Spina bifida Anencephaly Encephalocele Total Livebirth 2 0 0 2 Termination of pregnancy 11 7 0 18 Total # 13 7 0 20 # Neural tube defects detected as a result of serum AFP and/or ultrasound screening or elective testing because of previous affected child, or from examination of child at delivery

# NTD = Neural tube defect + NND = Neonatal death

22

Screening for Down Syndrome There are both screening tests and diagnostic tests for Down syndrome during pregnancy. The screening and diagnostic testing methods used are chorionic villus sampling performed after 1st trimester screening (nuchal translucency (NT) plus maternal serum screening (MSS)), amniocentesis performed after 1st trimester screening (NT + MSS) or 2nd trimester MSS, chorionic villus sampling or amniocentesis performed independently of a screening test, or ultrasound screening. Pregnancies are screened in the first trimester by the combination of nuchal translucency screening (NT) and maternal serum screening (free �HCG and PAPP-A). Software developed by the Women’s and Children’s Hospital or the Fetal Medicine Foundation (FMF) is used to produce an odds risk for each pregnancy, based on blood analyte and nuchal translucency results and maternal age-related risk. Pregnancies are screened in the second trimester by maternal serum screening. For both screening methods, a risk of 1 in 300 or greater is used as the cut-off point for recommending consideration of chorionic villus sampling or amniocentesis for karyotyping.

NT thickness for each fetus in multiple pregnancies parallels that of singleton pregnancies. A Down syndrome risk for each fetus is issued using the combination of NT thickness and maternal age related risk. Monochorionic twins have an identical maternal age related Down syndrome risk but may show different NT thickness, the greater risk is recommended for counselling. 75% detection of affected multiple pregnancies is achievable according to published data using 1:300 as the cut off. The use of serum markers for multiple pregnancies is currently not offered in SA but marker levels are measured for future studies to assess their possible utility. There were 41 cases of Down syndrome that reached a gestation appropriate for screening between 1.1.03 and 31.12.03. This figure includes all Down syndrome cases confirmed in terminations of pregnancy or in births (� 400g or � 20 weeks gestation) in South Australia. Of the 34 Down syndrome cases prenatally screened or tested by one or more screening or testing method, 32 (94%) were detected.

Table 15.1 Screening for Down syndrome, SA 2003: All testing laboratories First trimester screening - number of pregnancies screened 5,564

Second trimester screening - number of pregnancies screened 7,039

Total number of pregnancies screened 12,603

Total confinements in SA 17,517

Percentage of pregnancies screened 71.9%

* A further 3.5% of confinements (615 cases) were investigated for Down syndrome (maternal age indication, maternal anxiety, previous child with or family history of Down syndrome) using amniocentesis and CVS, resulting in a total of 75.5% of pregnancies being investigated for Down syndrome.

Table 15.2 Down syndrome cases, SA 2003: Detected / Not detected

1. Detected: Pregnancies screened (by screening method) First trimester screening (Nuchal translucency plus MSS+) 10

Second trimester screening (MSS+) 10* Amniocentesis (without prior screening) 9 Ultrasound 3

2. Not detected First trimester screening (Nuchal translucency plus MSS+) 1 Second trimester screening (MSS+) 1 Not screened 7

Total 41 + MSS = Maternal Serum Screening * Includes 1 ‘increased risk’ pregnancy which proceeded to CVS at 14 weeks

Table 15.3 Down syndrome cases, SA 2003: Pregnancy outcome Termination of pregnancy 31 Livebirth 10 Total 41

23

Screening for Down Syndrome

Table 15.4 First trimester combined biochemical and nuchal translucency screening Women’s and Children’s Hospital Laboratory only, SA 2003

Maternal Age < 35 years > 35 years Total

Number of pregnancies screened with valid risks reported* 3390 857 4247

Initially identified as “increased risk” 151 106 257 (% of pregnancies screened) (4.5%) (12.4%) (6.1%)

Identified as “increased risk” after correction of gestational age 147 108 255 (% of pregnancies screened) (4.3%) (12.6%) (6.0%)

CVS performed on pregnancies 15 13 28 identified as “increased risk” (%) (10.2%) (12.0%) (11.0%)

Amniocentesis performed on pregnancies 104 70 174 identified as “increased risk” (%) (70.7%) (64.8%) (68.2%) Total CVS/Amniocentesis performed on pregnancies 119 83 202 identified as “increased risk” (%) (81.0%) (76.9%) (79.2%)

Affected pregnancies in screened population 2 4 6**

Affected pregnancies among those screened as “increased risk” 2 4 6

Affected pregnancies among those who proceeded to CVS or amniocentesis 2 4 6

Sensitivity 100% 100% 100%

Risk of an affected pregnancy in those at “increased risk” (risk �1:300) on screening (positive predictive value or PPV) 1 in 74 1 in 27 1 in 43 * “Pregnancies screened with valid risks reported” exclude pregnancies which are <10weeks and >14weeks gestation, duplicate samples and those which had Down syndrome risk calculated from FMF software. ** The number of pregnancies is less than expected. In 4247 pregnancies we would expect to see between 12 and 15 cases with Down syndrome. There is a significant lack of Down syndrome cases in the group <35years.

Table 15.5 First trimester combined biochemical and nuchal translucency screening

FMF# software generated risks, SA 2003

Maternal Age < 35 years > 35 years Total

Number of pregnancies submitted for biochemistry 949 422 1371


Risk �1:300 22 44 66 (% of pregnancies screened) (2.4%) (10.9%) (5.0%)

CVS performed on pregnancies with risk �1:300 4 2 6 (%) (18.2%) (4.5%) (9.1%)

Amniocentesis performed on pregnancies with risk �1:300 12 33 45 (%) (54.5%) (75.0%) (68.2%) Total CVS/Amniocentesis performed on pregnancies with risk �1:300 16 35 51 (%) (72.7%) (79.5%) (77.3%) Affected pregnancies in screened population 2 3 5 Affected pregnancies among those with risk �1:300 2 3 5 Affected pregnancies among those with risk �1:300 2 3 5 and proceeded to CVS or amniocentesis

Sensitivity 100% 100% 100%

Risk of an affected pregnancy in those with risk �1:300 on screening (positive predictive value or PPV) 1 in 11 1 in 15 1 in 13 *“Pregnancies screened with valid risks reported” are singleton pregnancies for which SAMSAS received a copy of FMF risk report. There were 54 for which SAMSAS did not receive an FMF report. These were a combination of fetal deaths, twin pregnancies, “too early” bloods and patients that did not present for a scan or were too advanced for a Nuchal Translucency scan. # Fetal Medicine Foundation

24

Screening for Down Syndrome

Table 15.6 Second trimester maternal serum screening by maternal age:

Women’s and Children’s Hospital Laboratory only, SA 2003 Maternal Age < 35 years > 35 years Total


Initially identified as “increased risk” 372 157 529 (% of pregnancies screened) (7.0%) (20.6%) (8.7%)

Identified as “increased risk” after correction of gestational age 248 144 392 (% of pregnancies screened) (4.7%) (18.9%) (6.5%)

Amniocentesis performed on pregnancies 190 103 293 identified as “increased risk” (%) (76.6%) (71.5%) (74.7%)

Affected pregnancies in screened population 4 5 9

Affected pregnancies among those screened as “increased risk” 4 3 7

Affected pregnancies among those who proceeded to amniocentesis 3** 3** 6**

Sensitivity 100% 60% 77.8%

Risk of an affected pregnancy in those at “increased risk” (risk �1:300) on maternal serum screening (positive predictive value or PPV) 1 in 62 1 in 48 1 in 56 * “Pregnancies screened with valid risks reported” exclude pregnancies which are multiple, <14wks and >20wks gestation and duplicate samples and those requested for NTD risk only. ** This figure includes 1 “increased risk” pregnancy which proceeded to CVS at 14 weeks.

Trends in Utilisation of Amniocentesis and CVS

Table 16 Prenatal diagnosis - By technique , SA 2003

Year Amniocentesis CVS Total Percentage of confinements 1986 897 80 977 5% 1987 883 110 993 5% 1988 1005 134 1139 6% 1989 1005 188 1193 6% 1990 1020 235 1255 6% 1991 1102 279 1381 7% 1992 1267 299 1566 8% 1993 1508 304 1812 9% 1994 1570 292 1862 10% 1995 1565 238 1803 9% 1996 1926 242 2168 12% 1997 1719 195 1914 10% 1998 1798 206 2004 11% 1999 1848 153 2001 11% 2000 1617 199 1816 10% 2001 1490 138 1628 9% 2002 1608 161 1769 10% 2003 1338 173 1511 9%

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Since 1986 there has been an overall increase in the percentage of all women undertaking prenatal diagnostic amniocentesis and CVS (Fig. 8). In 2003, the proportion was slightly less than for 2002, 9% compared to 10% of all confinements. However, this is still almost double the percentage undertaken in 1986. In comparison, Figure 9 shows the proportion of amniocentesis or CVS undertaken by women �35yrs of age which has decreased between 1986 and 2003.

Although the number of confinements in women 35 years and over has risen from 1285 in 1986 to 3105 in 2003, the proportion of women in this age group having a test has decreased over time (Fig. 9). This is most evident from 1996 onwards. In the last few years, this decrease could be due to an increasing proportion of women having First Trimester Combined Screening and therefore, less women going directly to amniocentesis or CVS. (See Figures 10 and 11)

Figure 8 Percentage of Amniocentesis and CVS by year for all women, SA 1986-2003: all indications

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Year

% o

f all

conf

inem

ents

Total*

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Figure 9 Percentage of Amniocentesis and CVS by year for maternal age �35yrs, SA 1986-2003: all

indications

0.0

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20.0

30.0

40.0

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1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

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26


Figure 10 Indications for Amniocentesis by year, SA 1991* – 2003 Percentage of all confinements

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

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1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

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ents

Maternal age >= 35 years

2nd tri MSS alone - all ages

Abnormality found onultrasound - all ages

Maternal anxiety, < 35 years

1st Trimesterscreening

Figure 11 Indications for Chorionic Villus Sampling by year, SA 1991* – 2003 Percentage of all confinements

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Year

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ents

M aternal age, >=35 years

M aternal anxiety,<35yr

1st Trimester screening

* No routine screening prior to 1991

* No routine screening prior to 1991

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Publications and Presentations

Publications Sharpe PB, Mulpuri K, Chan A, Cundy P. Differences in risk factors between early and late diagnosed DDH. Archives of Disease in Childhood. 2005 (in press). Sharpe PB, Chan A, Haan EA, Hiller JE. Maternal diabetes and congenital anomalies in South Australia 1986-2000: A population based cohort study. Birth Defects Res A Clin Mol Teratol. 2005: 73:605-611 Gibson CS, MacLennan AH, Hague WM, Haan EA, Priest K, Chan A, Dekker GA; South Australian Cerebral Palsy Research Group. Associations between inherited thrombophilias, gestational age, and cerebral palsy. Am J Obstet Gynecol. 2005;193(4):1437 Byron-Scott R, Sharpe P, Hasler C, Cundy P, Hirte C, Chan A, Scott H, Baghurst P, Haan E. A South Australian population-based study of congenital talipes equinovarus. Paediatr Perinat Epidemiol. 2005;19(3):227-37 Gibson CS, MacLennon AH, Rudski Z, Hague WH, Haan EA, Sharpe P, Priest K, Chan A, Dekker GA. Writing for the South Australian Cerebral Palsy Research Group. The prevalence of inherited thrombophilias in a Caucasian Australian population. Pathology. 2005; 37(2):160-3 Metz MP, Ranieri E, Gerace RL, Priest KR, Luke CG, Chan A. Newborn screening in South Australia: is it universal? MJA 2003;179:412-415. Chan A. Invited commentary: Parity and the risk of Down syndrome – caution in interpretation. Am J Epidemiol 2003;158:509-511.6. Chan A, Pickering J, Haan EA, Netting M, Burford A, Johnson A, Keane RJ. ‘Folate before pregnancy’: the impact on women and health professionals of a population-based health promotion campaign in South Australia. MJA 2001;174:631-636. Chan A, Foster BK, Cundy PJ. Invited commentary. Problems in the diagnosis of neonatal hip instability. Acta Paediatr 2001;90:837-9. Cheffins T, Chan A, Haan EA, Ranieri E, Ryall RG, Keane RJ, Byron-Scott R, Scott H, Gjerde EM, Nguyen A-M, Ford JH, Sykes S. The impact of maternal serum screening on the birth prevalence of Down syndrome and the use of amniocentesis and chorionic villus sampling in South Australia. Br J Obstet Gynaecol 2000;107:1453-9. Chan A, Haan EA. Universal periconceptional folate supplementation: chasing a dream? (letter) Med J Aust 2000; 173:223. Chan A, Cundy PJ, Foster BK, Keane RJ, Byron-Scott R. Screening for developmental dysplasia of the hip (letter). Lancet 2000; 355:232-33. Chan A, Cundy PJ, Foster BK, Keane RJ, Byron-Scott R. Late diagnosis of developmental dysplasia of the hip and presence of a screening programme. South Australian population-based study. Lancet 1999;354:1514-17. Chan A, McCaul K, Keane RJ, Haan EA. Effect of parity, gravidity, previous miscarriage, and age on the risk Down syndrome: population-based study. BMJ 1998;317:923-4. Cheffins T, Chan A, Keane RJ, Haan EA, Hall R. The impact of rubella immunisation on the incidence of rubella, congenital rubella syndrome and rubella-related terminations of pregnancy in South Australia. Br J Obstet Gynaecol 1998;105:998-1004. Byron-Scott R, Haan E, Chan A, Bower C, Scott H, Clark K. A population-based study of abdominal wall defects in South Australia and Western Australia. Paediatr Perinatal Epidemiol 1998;12:136-151. Chan A, McCaul KA, Cundy PJ, Haan EA, Byron-Scott R. Perinatal risk factors for developmental dysplasia of the hip. Arch Dis Child 1997;76:F94-F100. Yiv BC, Saidin R, Cundy PJ, Tgetgel JD, Aguilar J, McCaul KA, Keane RJ, Chan A, Scott H. Developmental dysplasia of the hip in South Australia in 1991: Prevalence and risk factors. J Paediatr Child Health 1997;33:151-6. Chan A, Hanna M, Abbott M, Keane RJ. Oral retinoids and pregnancy. Med J Aust 1996;165:164-7. Chan A, Robertson EF, Haan EA, Ranieri E, Keane RJ. The sensitivity of ultrasound and serum alpha-fetoprotein in population based antenatal screening for neural tube defects in South Australia 1986-1991. Br J Obstet Gynaecol 1995;102:370-376. Bower C, Norwood F, Knowles S, Chambers H, Haan E, Chan A. Amniotic band syndrome: a population-based study in two Australian states. Paediatr Perinatal Epidemiol 1993;7:395-403. Chan A, Robertson EF, Haan EA, Keane RJ, Ranieri E, Carney A. Prevalence of neural tube defects in South Australia, 1966-91: effectiveness and impact of prenatal diagnosis. BMJ 1993;307:703-706.

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Presentations

“Folate awareness in South Australian: Results from the South Australian Computer Assisted Telephone Interview surveys 1994 – 2004”. South Australian Department of Health. Australian Birth Defects Society Annual meeting, May 2005, Melbourne. (P Sharpe) “Maternal diabetes and congenital anomalies in South Australia 1986 – 2000: A population based cohort study”. P Sharpe, A Chan, EA Haan, JE Hiller. Australian Birth Defects Society Annual meeting, May 2005, Melbourne. (P Sharpe) “Termination of pregnancy for birth defects and its role in congenital malformations and birth defects monitoring”. Congenital Malformations and Birth Defects National Data Collection Review Committee meeting, 12th May 2003, Sydney. (A Chan) “Fetal thrombophilic polymorphisms are not a risk factor for cerebral palsy”. Authors: CS Gibson, AH MacLennan, WM Hague, Z Rudzki, P Sharpe, A Chan, GA Dekker. Podium presentation at the Medicine and Pregnancy Conference 2003, Fremantle, Western Australia, October 21-25, 2003. (CS Gibson) “Late diagnosis of developmental dysplasia of the hip: risk factors and outcomes in South Australia”. Poster presentation. Australian Birth Defects Society Inc. Annual Scientific Meeting, Royal Hospital for Women, February 22, 2002. Randwick New South Wales. (P Sharpe) “Folate before pregnancy: impact of a South Australian health promotion campaign on women and health professionals.” Abstract Booklet. The Royal Australasian College of Physicians Annual Scientific Meeting, Adelaide Convention Centre, May 2-5, 2000. (A Chan) “Prevalence and prenatal diagnosis of neural tube defects.” National meeting of Perinatal Statistics Units, Sydney, Nov 1998. (R Keane) “A comparison of selected birth defects in Aboriginal and non-Aboriginal births in South Australia.” Poster presentation, Australian Birth Defects Society, Annual Scientific Meeting, Sydney, Nov 1998. (R Byron-Scott) “A validation study of congenital heart defects in South Australia.” Australian Birth Defects Society, Annual Scientific Meeting, Sydney, Nov 1998. (R Byron-Scott) “Down syndrome screening in South Australia.” Australasian Faculty of Public Health Medicine, South Australian Branch general meeting, Adelaide, Sep 1998 (T Cheffins, A Chan) “A validation study of congenital heart defects in South Australia.” The Australian Society for Medical Research, South Australian Division, Medical Research Week Annual Scientific Meeting, May 1998. (R Byron-Scott) “Effect of rubella immunisation in South Australia”. Rights to Health. Public Health Association of SA Inc. 29th Annual Conference, Melbourne, October 1997. (T. Cheffins) “Prevalence of Down syndrome in South Australia: effectiveness and impact of prenatal diagnosis”. Seminar, Department of Chemical Pathology, Women’s and Children’s Hospital, August 1997. (T. Cheffins, A Chan) “Gastroschisis and Exomphalos.” Poster presentation, Annual Conference, Human Genetics Society of Australasia, July 1997. (D Baulderstone, R Byron-Scott, E Haan, G Suthers) “Update on folate.” Grand Round, Women’s and Children’s Hospital, February 1997. (A Chan) “A population-based study of abdominal wall defects in South Australia and Western Australia, 1980-1990.” Poster presentation, Annual Conference, The Perinatal Society of Australia and New Zealand, March 1996. (R Byron-Scott) Approximately 24 presentations on the prevention of neural tube defects, as part of the ‘Folate before Pregnancy health prevention program’, were made by Jane Dounton in 1994 and 1995 to hospital staff (in particular midwives and paediatric nurses), women’s health professionals, midwifery students, childbirth educators and community groups. These included the Health Development Foundation, the Family Planning Association, the Pharmaceutical Society, the Child, Adolescent and Family Health Service and the South Australian Health Commission Public and Environmental Health Service. “A population-based study of abdominal wall defects in South Australia and Western Australia, 1980-1990.” Poster presentation, Annual Conference, Human Genetics Society of Australasia, September 1996. (R Byron-Scott) "Folate before Pregnancy Project". Health Promotion Grand Round, Women's and Children's Hospital. November 1994 (E Haan, M Netting, J Dounton) "Folate before Pregnancy Program." Australia's Role in Public Health in Asia and the Pacific Region. Building Partnerships. Public Health Association of Australia 26th Annual Conference, Adelaide, September 1994. (J Dounton, A Chan, M Netting) "How effective is prenatal screening for neural tube defects in South Australia?" Seminars in Genetics, Women's and Children's Hospital, May 1994 (A Chan) "Can ultrasound replace serum alpha fetoprotein in population based antenatal screening for neural tube defects?" First International Congress on Teratology in China, Chengdu, P.R. China, May 1994 (A. Chan)

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Appendix 1

Background Information on the S.A. Birth Defects Register

1. Aims

The Birth Defects Register aims to provide complete, accurate and up-to-date information for the following purposes:

• Establishing local prevalence rates for birth defects

• Monitoring the occurrence of defects over time and by geographical area to allow investigation of suspected teratogens

• To facilitate access to genetic counselling services

• Increasing community knowledge about birth defects through education and by acting as a source of information

• Utilisation of local prevalence rates to plan health care facilities

• Epidemiological studies on the causation of birth defects

• As an accurate diagnostic index for clinical research. 2. Sources of Notification

Cases notified to the Register include those with birth defects detected in a variety of circumstances:

• Pregnancies terminated because of diagnosis of a birth defect in the fetus;

• Late fetal deaths (stillbirths);

• newborn babies;

• Children diagnosed after the neonatal period and prior to their fifth birthday.

The sources of notification include:

• Doctors and other health professionals involved with the care of children with birth defects in hospitals, special paediatric assessment, treatment and rehabilitation centres and private practices.

• The Pregnancy Outcome Statistics Unit of the S.A. Department of Health.

• The State Perinatal Autopsy Service and other pathology services.

• Diagnostic services including laboratories diagnosing cytogenetic or biochemical abnormalities, and organ imaging departments.

While notifications of defects detected perinatally are made by doctors to the Pregnancy Outcome Statistics Unit, it is recognised that many defects, for example, some

congenital heart defects or malformations of the urinary tract, may not be detected at the time of birth. Moreover, diagnoses made in the neonatal period may change with time. The Register, by extending the period of time for receiving notifications, and receiving them from multiple sources, achieves more complete ascertainment of birth defects in South Australian children. (The notification form is included in Appendix 1). 3. Definition of a Birth Defect A birth defect is defined within the Register as any abnormality, structural or functional, identified up to five years of age, provided that the condition had its origin before birth. Thus structural (eg. spina bifida), chromosomal (eg. Down syndrome) and biochemical (eg. phenylketonuria) defects are included. For Register purposes, single gene defects eg. neurofibromatosis, cystic fibrosis and muscular dystrophy, are also considered to be birth defects, although clinical manifestations may not appear until well after birth, and some may not cause malformations. Most minor malformations are excluded unless they are disfiguring, require treatment or accompany another defect. (A list of inclusions and exclusions is provided in Appendix 2). 4. Ascertainment and Accuracy of Diagnoses Ascertainment of birth defects will be incomplete in the first few years of life of each birth cohort. Data collection to five years of age, the use of multiple notification sources, and confirmation of diagnoses by clinicians and pathologists increases the accuracy of final diagnoses, and with it the value of the Register. 5. Confidentiality of Data The Register has detailed and comprehensive confidentiality guidelines. (Appendix 3) The guidelines ensure the confidentiality of the Register's data, while allowing research to be carried out in accordance with the National Health & Medical Research Council Guidelines for Epidemiological Research. Confidentiality of Register data is overseen by the Birth Defects Register Advisory Committee. This Committee reviews the operation of the Register and comments on research proposals involving Register data.

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Appendix 2

Confidentiality Guidelines

The South Australian Birth Defects Register has been receiving notifications of children with birth defects under the provisions of Section 64d of the South Australian Health Commission Act, 1976, Amendment Act, 1987 (see Appendix). Notification has been voluntary. Although notification does not require parental consent, provisions are made to inform the public and parents about the Register. Section 64d requires the Register to maintain the confidentiality of notified information, while allowing release of data to certain persons for specified purposes. The Register has developed guidelines to enable the confidential management of personal information in accordance with the provisions of Section 64d. Since September 1999, notification of children with birth defects identified later, ie after discharge from the hospital of birth but before the child’s fifth birthday, has been required under legislation (South Australian Health Commission (Pregnancy Outcome Statistics) Regulations 1999). This notification is required to be made to the Pregnancy Outcome Statistics Unit of the Department of Health, which also receives notifications of birth defects detected at birth under the same legislation. The Pregnancy Outcome Statistics Unit has asked the SA Birth Defects Register to assist it in the collection of late notifications of children with birth defects. This legislation does not alter the confidentiality guidelines under which the Register functions. Purpose of Confidentiality Guidelines The purpose of confidentiality guidelines is: • to protect the privacy of children and women notified to the Register and the confidentiality of the information received;

• to ensure confidentiality by documenting procedures for managing personal information in a confidential manner;

• to ensure a balance between individual privacy and the confidentiality of information held by the Register, and the public benefit arising from knowledge of the frequency, cause, prevention and treatment of birth defects through the use of the Register;

• to ensure that the Register data are of the best quality possible. Data quality is dependent on the use of identified personal information in a confidential manner in accordance with these guidelines;

• to ensure that the Register retains the support of notifying health professionals by managing the information they notify in a confidential manner ;

• to facilitate the best possible use of Register data for the benefit of the community and promotion of best practice medicine.

Responsibility for Confidentiality Responsibility for the confidentiality of the Birth Defects Register’s data lies with the Head, SA Clinical Genetics. Service and ultimately with the Board of Management of the Women’s and Children’s Hospital through the hospital’s line management structure. The SA Birth Defects Advisory Committee advises the Register on the preservation of confidentiality of data collected by the Register. Membership of the Advisory Committee is: Professor Eric Haan, Clinical Geneticist, Director Dr Annabelle Chan, Public Health Physician Dr Judy Jaensch, Paediatrician Dr Geoff Martin, General Practitioner Mrs Barbara Walrut, Consumer/Lawyer Dr Karen Shand, Obstetrician Dr Brian Peat, Obstetrician

Ethical Principles Governing Research Conducted by the Register The Register uses the National Health and Medical Research Council’s National Statement on Ethical Conduct in Research Involving Humans (1999) when considering research proposals. Section 14, “Epidemiological Research” describes the conditions under which research can be undertaken. Principles and Procedures for Ensuring Confidentiality While Managing Personal Information 1. Release of Information 1.1 Routine Reports All routine reports from the Register, such as the Annual Report, are in statistical form without the identification of individual patients, doctors or hospitals. Unnamed statistical information that may be identifiable to particular recipients is not released. 1.2 Non-routine Statistical Reports Ad hoc requests for grouped statistical information on birth defects will, in general, be provided freely. Information which may be of concern to the public will be released at the discretion of the SA Birth Defects Register Advisory Committee. Unnamed statistical information that may be identifiable to particular recipients is not released to the person or agency making the request.

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Appendix 2 (continued)


1.3 Release of Identifying Data No information about identified individuals is provided to non-Register staff unless that person was the original notifier or that person is assisting the Register in its work. 1.3.1 Release of identifying data for purposes other than research The Register does not provide personal information for individual patient management, insurance, sick fund, child disability allowance or other administrative purposes. Section 64d of the South Australian Health Commission Act, 1976, Amendment Act, 1987, protects staff from any legal obligation to divulge information. The Register does not provide any information directly to parents or children about notified birth defects. The parent or child is referred to their doctor as information provided by their doctor is more clinically relevant, up to date, clinically accurate and accompanied by appropriate counselling. Because the information collected by the Register was not given by the family in the first instance, the Register would risk harm to the doctor-patient relationship by divulging information gained from medical notes without consultation with that doctor. In some circumstances, notified information may be provided to the doctor for release to parents and children as part of the broader information available to the doctor, and with relevant counselling. Identifying data will not be released for clinical audit or another clinical purpose unless the clinician or agency requiring the information was the original source of all cases required for that purpose. 1.3.2 Release of identifying information for research projects No information about identified individuals is provided to people for research projects unless that person was the original notifier or that person is assisting the Register in its work. The following section provides guidelines for facilitating research with Register data while maintaining the Register’s ethical and legal obligations for confidentiality.

2. Research Projects The Register encourages and facilitates research, using personal information where necessary, and in accordance with these guidelines. In particular, access to personal information is provided for research projects that promote the understanding, prevention or alleviation of health problems associated with pregnancy, delivery, infancy and birth defects and result in no harm to notified individuals in any way.

2.1 Research conducted by Register staff

Research projects performed by Register staff or other people/agencies authorised under Section 64d of the South Australian Health Commission Act, 1976, Amendment Act, 1987 are considered internal research projects. The Register defines “research” as a project designed to generate new knowledge, with the aim of publishing the results in a peer reviewed journal. Approval from the Women’s and Children’s Hospital Research Ethics Committee is required for internal research projects, in compliance with the NHMRC Statement on the Ethical Conduct in Research involving Humans (1999).

The Register conducts internal research projects in accordance with the section 2.4, “Procedures for ensuring confidentiality while conducting research projects”.

2.2 Co-opted researchers

From time to time the Register co-opts researchers to perform a research project in collaboration with its staff. The Register retains control over the conduct of the research and the output from the research group.

Access to personal information on the Register is granted to co-opted outside people/agencies for epidemiological or other research purposes only if:

• it is considered that the proposed use of the data would promote the understanding, prevention or alleviation of health problems associated with pregnancy, delivery, infancy and birth defects;

• it is considered unlikely to harm notified individuals in any way;

• any costs incurred for the research are borne by the relevant body;

• a copy of final reports or papers for publication is provided, prior to publication, to the Register.

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The minimum data set needed for the research project is provided to the co-opted researcher. This data set may include identifying information.

The co-opted researcher must undertake to comply with the confidentiality procedures of the Register, in particular section 2.4, “Procedures for ensuring confidentiality while conducting research projects” and to return the data set to the Register after completion of the project.

Approval from the Women’s and Children’s Hospital Research Ethics Committee must be sought before identified data can be released.

2.3 Other researchers

Identified information will not be provided to researchers from outside the Register who are not co-opted by the Register. However, unidentified information on individuals may be sufficient to achieve the aims of the research. The Register makes every effort to encourage and facilitate research and will try to provide information for research projects within the constraints of these confidentiality guidelines.

2.4 Procedures for ensuring confidentiality while conducting research projects

The need for confidentiality must be balanced with the benefits of research and the need to facilitate participation of notifiers in research projects. The following procedures are considered within the interpretation of “not divulging confidential information”.

2.4.1 When additional clinical information is required for a research project but no contact with patients is needed.

• The Register will review the medical records which it is authorised to access.

• If further information is required, the original notifier will be approached first.

• If the original notifier does not have the required information, permission will be sought from him/her to contact the appropriate health professional. It may also be necessary to identify the patient’s most appropriate health professional from the original notifier.

• The appropriate health professional can then be approached for their assistance with the research project.

• If the Pregnancy Outcome Statistics Unit (POSU) of the South Australian Health Commission is the only notifier, it will approach its original notifier to obtain the information. 2.4.2 When contact with patients is required for the research project.

• Permission in writing will be sought from the original notifier to contact a family for the purposes of gathering data for a research study.

• If the original notifier does not consider himself/herself to be the child’s managing clinician then permission will be sought from the managing clinician.

• The family will be contacted through the managing clinician.

• Subsequently, the procedures for obtaining consent from families to enter their child into a research study will be followed. 3. Other Specific Aspects of Confidentiality 3.1 Staff aspects All Register staff are instructed regarding the need for and maintenance of confidentiality. On appointment to the Register, staff are required to sign a declaration, as part of their contract of service, that no information on data in the Register will be disclosed except under the conditions stated in the above section “Release of Information”. This also applies to any other information of a confidential nature they might hear or see in respect to subjects notified or their families, and apply even after employment ceases. The terms of employment make it clear that a deliberate breach of confidentiality may lead to severe disciplinary action. 2.2 Storage of Data Keys giving access to files are held by members of the Register staff only. Files are locked when not in use or when the rooms are unattended. Data are kept on a stand alone computing system within the Register and are not accessible from outside the Register.

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Appendix 3

Birth Defect Inclusions and Exclusions

Diagnostic Information A birth defect is defined by the Register as any abnormality of prenatal origin. Thus, structural (eg spina bifida), genetic and chromosomal (eg Down Syndrome) and biochemical (eg phenylketonuria) defects are included. Excluded are most minor malformations unless they are disfiguring or require treatment.

THE FOLLOWING LIST OF BIRTH DEFECTS IS NOT COMPLETE, BUT MANY OF THE

COMMON DEFECTS INCLUDED IN THE REGISTER ARE MENTIONED. THIS LIST CONTAINS

EXAMPLES ONLY. IF A BIRTH DEFECT IS NOT LISTED HERE OR IF IN DOUBT, PLEASE

NOTIFY THE DEFECT, UNLESS IT IS ON THE EXCLUSION LIST

INCLUSIONS (examples only) Nervous System Anencephaly Spina bifida Encephalocoele Congenital hydrocephalus Microcephaly Dandy Walker syndrome Craniosynostosis Cerebral palsy

Gastro-Intestinal System Cleft lip, palate Tracheo-oesophageal fistula Pyloric stenosis Intestinal atresia Hirschsprung disease Ectopic anus Imperforate anus Exomphalos

Genital System Undescended testis (requiring treatment) Hypospadias Indeterminate sex

Musculo-Skeletal System Developmental dysplasia of hip Congenital talipes equinovarus Polydactyly Syndactyly Absence (complete or partial) of limbs Osteogenesis imperfecta Congenital spinal anomalies Congenital torticollis Congenital scoliosis Bone dysplasias Muscular dystrophy

Eye Microphthalmia/Anophthalmia Congenital glaucoma Congenital cataract Coloboma

Urinary System Cystic kidney Absent kidney Ectopic kidney Double ureter Ectopic ureter + ureterocoele Vesico-ureteric reflux

Chromosomal Anomalies Down Syndrome Trisomy 13 Trisomy 18 Turner syndrome Cri-du-chat syndrome Fragile X

Skin Cystic hygroma Birthmarks ) if > 4cm2 Haemangiomas ) multiple or Naevi ) requiring surgery Ichthyosis congenita Epidermolysis bullosa

Cardiovascular System Congenital heart defects Coarctation of the aorta Patent ductus arteriosus* Dextrocardia

Respiratory System Pulmonary hypoplasia Diaphragmatic hernia Choanal atresia Congenital lung cyst

Blood Thalassaemia major Sickle cell anaemia Haemophilia G6PD deficiency

(continued over)

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Birth Defect Inclusions and Exclusions

Metabolic Disorders - Inborn Errors of Metabolism Phenylketonuria Cystic fibrosis Congenital hypothyroidism Adreno-genital syndrome Glycogen storage disorders Lipid storage disorders Mucopolysaccharidoses Albinism

Teratogens Fetal alcohol syndrome Fetal hydantoin syndrome

Congenital Infection Toxoplasmosis Rubella Cytomegalovirus Herpes simplex Syphilis

* CRITERIA FOR INCLUSION OF PATENT DUCTUS ARTERIOSUS (P.D.A.) 1 All term babies (37 weeks and beyond) where the duct remains open after 72 hours 2 All preterm babies where the duct remains open past the expected date of delivery NB If P.D.A. exists in the presence of other congenital heart disease it is always notified CRITERIA FOR INCLUSION OF PATENT FORAMEN OVALE (P.F.O.) Patent Foramen Ovale is only included if there is another intra-cardiac defect present EXCLUSION LIST Excluded from the Register are the following, when occurring in isolation:

THIS IS NOT A COMPLETE LIST OF EXCLUSIONS. IF IN DOUBT, PLEASE NOTIFY

Balanced translocation in normal individual Blocked tear duct Broncho-pulmonary dysplasia Calcaneovalgus deformity Clicky hips Congenital pneumonia Delayed milestones Deviated nasal septum Ear anomalies - minor Epigastric hernia Epilepsy Failure to thrive Foot deformities - minor positional not requiring treatment Gastro-oesophageal reflux Hydrocoele testis Hydrops - immune. Include non-immune hydrops Hypoglycaemia Imperforate hymen Infection in utero if no associated birth defect

Inguinal hernia Intrauterine growth retardation Intussusception Labial adhesion or fusion Large fontanelles Laryngeal stridor unless treated Laryngomalacia Low birth weight Lymphangioma, haemangioma, naevus or other birthmark under 4cm2 Include if > 4cm2 or multiple Meconium ileus (unless the result of cystic fibrosis) Mental retardation in isolation Metatarsus adductus even if treated Mongolian blue spot Persistent fetal circulation Pilonidal sinus Sacral dimple Sacral sinus unrelated to occult spinal dysraphism Single palmar crease

Skin tag Single umbilical artery Strabismus Submucous retention cyst Supraventricular tachycardia Thalassaemia minor Toe anomalies - minor Tongue tie, even if surgery Trigger finger/thumb Umbilical hernia Undescended testis (unless treated) Wide suture lines Webbing of 2nd and 3rd toes (minor degrees)

Revised December 1990

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Appendix 4

Notification Form

sabdr annual report 2003 - women's and children's hospital€¦ · annual prenatal...

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