(January 2009) Each year, an estimated 9 million infants are born with a serious birth defect that may kill them or result in a lifelong disability. Such birth defects have an especially severe effect on children in developing countries. What are the causes of birth defects? Which defects can be treated or prevented? How can we fight the common misconceptions about them?
During a PRB Discuss Online, Arnold Christianson, director of the Division of Human Genetics at the University of the Witwatersrand, Johannesburg, South Africa, answered participants’ questions about birth defects in developing countries.
Jan. 22, 2009 1 PM EST
Transcript of Questions and Answers
Donna Villareal: Can birth defects such as spina bifida be diagnosed and cured in utero? If so, what risks are incurred by the mother and/or child?
Arnold Christianson: Let me start by defining birth defects. A birth defect is a structural or function abnormality that is present from birth. The causes of birth defects are divided into;
i. Genetic or preconception causes- chromosome abnormalities (numerical or structural), single gene defects and multifactorial congenital malformations.
ii. Fetal environmental or post conception causes. These include teratogens and constraint)
iii. Presently unknown causes
Some birth defects are diagnosable at birth or shortly thereafter, e.g. spina bifida, Down syndrome and cyanotic congenital heart defects. Other birth defects present later in life. Examples include cystic fibrosis, haemophilia, Huntingdon disease, and some congenital heart defects. With prenatal screening & diagnosis, which should be undertaken after appropriate counselling, certain birth defects are diagnosable in utero. Common examples include major structural abnormalities, Down syndrome and neural tube defects (spina bifida, anencephaly and encephalocoeles). There are many others. The risks to the fetus of the prenatal diagnostic proceedures (amniocentesis, cordocentesis and chorionic villus biopsy) are operator dependent but usually small. If a birth defect is diagnosed in utero there are very limited examples of fetal treatment and cure. In specialised units some fetal surgery has been successful for congenital malformations like diaphragmatic hernia. In the case of a mother diagnosed syphilis positive in pregnancy she can be treated with penicillin and this will cross the placenta and also treat the fetus if it is infected. Fetal blood transfusions have been successful in treating anaemia in fetuses affected by blood, particularily rhesus, incompatibility.However, for most birth defects diagnosed in utero the parents should be offered genetic counselling to fully inform them what the problem is, its cause if known, and what therapeutic options are available to them. These are most often limited to continuing the pregnacy or the offer of selective termination of pregnancy, if warranted and legally available in the country. Counselling should also inform the parents of the risk of recurrence of the problem and how this can be reduced or avoided in future pregnancies.
Sherry Meyer: What are the teratogenic impacts of Paternal and/or Maternal alcohol use? How do we best inform potential parents about these effects?
Arnold Christianson: The maternal effects of alcohol abuse are well described. Fetal alcohol Spectrum Disorder (FASD). The worst component of this spectrum is fetal alcohol syndrome (FAS). Affected individuals have growth retardation, including microcephaly, intellectual disability usually in the mild mental retardation range, behaviour problems which can be severe, and a recognisable pattern of dysmorphic, particularly facial, features. Todate no physical affects of paternal alcohol abuse have been described, but this is asubject of research. However, maternal alcohol abuse is associated with paternal alcohol abuse. How best to inform ‘potential’ parents of these effects. Firstly, the ideal is to inform ‘potential’ parents in an effort to ensure the parents stop drinking before conception, thus ensuring the problem does not occur. How to do this? Much work is ongoing in this field and the approach needed is probably country, regionally, culturally and individually specific. Certainly a broad based approach starting with community education from school age and through is needed, combined with an individual approach with counselling during opportunities such as family planning/pregnancy prevention and periconception care consultations.
jayashri desai: why [are] cases of autism on the rise in a developing country like India? What is their exact percentage? is it a lifestyle disease?
Arnold Christianson: I am not an expert on autism or autism spectrum disorder (ASD). My understanding of the aetiology is that most cases have a strong genetic basis and are considered as a complex multifactial disorder. However, X-linked forms of the disorder are described (OMIM). Autism has also rarely been described in some children affected by teratogens (e.g. in Fetal valproate syndrome) An increasing prevalence of autism over time has been described in industrialised countries as well. A recent review noted that the prevalence of ASD in the 1950s was 4/10 000 and this has risen to 40-60/10 000 now. No absolute reason for this has been given but consideration is given to the probability that increase public and professional awareness and better diagnostic capability has played a significant role in this increase. I must presume similar factors are at work in India.
Irene Nabusoba: What should a mother look out for in her child immediately after childbirth? Many just ask for sex, weight and who the baby resembles only to be discharged and discover that a baby has a defect.besides, what are the common defects, causes, any preventive measures?what should nationasl health systems do to address this issue?
Arnold Christianson: You raise an interesting issue. In my country, South Africa, as I suspect is the case throughout much of the developing world, most newborns are dischared from hospital or clinic within 24 hours of birth, because of pressure on maternity beds. And they are not assessed before discharge by a trained competent professional (primary care doctor or nursing sister/midwife). That is why only 16% of infants with Down syndrome are diagnosed during their newborn hospital or clinic stay in South Africa. So infants with potentially diagnosable birth defects are sent home only to become ill or have the problem recognised by the mother. Some of these will be fortunate and get back to a clinic or hospital for care. But in the often impoverished and difficult circumstances present in developing nations one can only wonder how many die before this is possible. I believe that every newborn born in a clinic or hospital, or brought to one after birth, is entitled to an assessment (basic history and examination) by a trained professional (primary care doctor or nursing sister/midwife) before discharge. This should be an intrinsic part of newborn care. Because many birth defects have externally obvious signs (dysmorphic features) it is possible to train nursing sisters/midwifes to examine newborns externally. Doctors should obtain this expertise in their medical training, but can be trained after graduation with their nursing colleagues as we are doing in SA. What should mothers look for. Once mothers have recovered from their delivery they begin their own thorough examination of their infants. If they express an concern, this should be taken seriously by medical staff. Unfortunately in the pressurised work environment of these professionals, this is not always the case. The matter of what national health systems need to do to address these issues requires a book to answer. May I refer you to the March of Dimes Birth Defects Report which you can obtain from www.marchofdimes.com/globalprograms. This covers all your other queries in a simple, easily readable manner.
Dr Maulik Baxi: Dear Dr Christianson, What would be the approximate burden of congenital heart diseases in developing countries? How many of these cases do get the surgery/intervention they require? Has there been any effort on part of any major international organization or donor agency to investigate and mitigate this? Thank you very much.
Arnold Christianson: Congenital heart defects (CHD) are numerically the commonest birth defect globally. There are just over a million children born annually with a CHD. Approximately 960 000 of these children are born in middle- and low-income countries. If you wish to see the numerical estimates by country please access the Modell Birth Defects Database in the March of Dimes Global Birth Defects Report
(www.marchofdimes.com/globalprograms) In middle- and low-income nations I would suspect that the majority of these children do not get the medical care they need, especially the specialised surgical interventions. The WHO’s Global Burden of Disease Programme 2005 is currently investigating the epidemiology of CHD including outcomes. Hopefully recommendations will derive from this.
A Thompson: I recently heard a news story of a 76-year old woman giving birth to a healthy first child. Due to the increasing avialability of new technology and much improved nutrition information, does the age of the mother at first pregnancy still determine the risks for birth defects? Or is this no longer relevant? Thanks.
Arnold Christianson: I am not aware of the case of this 76 year old woman. The age of the mother in any pregnancy is an issue. The risk of conceiving a fetus with a chromosomal trisomy, particularily Down syndrome (DS), increases with maternal age. There are many tables available that give the risk for a child with DS and all chromosome risk at specific ages. The one immediately available to me gives the following Lowest risks
Age 20- DS 1:1734 All chromosomal risk 1:526 Highest risks: Age 49 DS 1:11 All chromosomal risk 1:8 So maternal age remains relevant
Dr FN Chukwuneke: Please I would like to know the effect of exposure to noise polution and the risk of developing birth defect especially oro-facial cleft.
Arnold Christianson: I am aware of no connection between noise pollution and the development of birth defects.
J Kishore: Till now focus is on communicable diseases and recently non-communicable diseases are picked up in developing countries. However, majority of deaths are in [the] first week of life which are mainly genetic in origin. Another issue is repeated abortions which are again neglected. Quality of health can not improve if we do not give comprehensive health to the individual and community where conception and birth are equaly important. Myths are present not only in general public but also in health professionals that birth defects are non-preventable. They need to be removed through proper training and awareness programs.
Arnold Christianson: The process of the elimination of communicable disorders and the rise in public health significance of non-communicable disorders is known as epidemiological or health transition. It occured in industrialised countries in the first 60 years of the 20th century. It is currently happening in middle-and low-income nations, obviously at rates that vary according to the rate of improvement of their socioecoomic, educational and healthcare development. In those countries with wars, civil strife and poor governance there is negative health transition. (see March of Dimes Global Birth Defect Report at www.marchofdimes.com/global programs )The WHO estimates about 34% of under 5 deaths in children occur in the neonatal period. What the WHO labels congenital anomalies (this does not include all birth defects) is the fourth highest cause of neonatal death (8%) after preterm delivery, asphyxia and sepsis or pneumonia. I agree with you that health cannot improve if we do not give a comprehensive service that includes services for the care and prevention of birth defects. This includes preconception care to try and ensure the conception of a normal embryo and is ongoing health during the early embryonic period (1st eight weeks) until antenatal care takes over for the rest of pregnancy. Post delivery neonatal and childhood care is required. And it is still true that the public, health care professionals and policy developers still hang on to the myths that birth defects are rare, costly to care for and prevent. There is now ample documentation to refute these myths and how care and prevention for birth defects can be offered in middle- and low-income nations (WHO Human genetic Programme literature, the March of Dimes Global Birth Defects Report and the Disease Control Priorities in Developing Countries chapter that stimulated this online discussion.
Solomon Van Kanei: Which cost effective mechanisms can be put in place in recourse poor countries to identify such problems and how can programmes be designed to prevent them?
Arnold Christianson: This would take a long and involved discussion. May I refer you to the WHO’s Human Genetic Programmes literature on the topic (www.who.int), the Disease Controll Priorities article on the topic (www.dcp2.org/file/230/dcpp-twpcongenitaldefects_web.pdf) and the March of Dimes Global Birth Defects Report (www.marchofdimes.com/globalprograms). Should you wish to discuss any issues with me after that I can be contacted at firstname.lastname@example.org
Amy Rogers: Do genetic factors play a role in causing birth defects or is it mainly due to things such as poor nutrition or bad choices on the mother’s part?
Arnold Christianson: Birth defects have the following causes:
1. Genetic or preconception
a. Abnormalities of structure of numer of chromosomes
b. Mutations in a single gene- single gene defects
c. Multifactorial disorders. These are due to the interaction of genes and fetal environmental factors. They are called congenital malformations
2. Fetal environmental or post conception factors factors.
In these the genes and chromosomes are normal.
a. Teratogens. Pysical or chemical agents that go through the mother and damage the embryo or fetus.
Include i) Maternal infections like rubella (german measles) and syphilis)
ii) Altered maternal metabolic states or illness (maternal iodine deficiency, maternal insulin dependent diabetes mellitus)
iii) High doses of radiation
iv) Environmental toxins (toluene, methyl mercury)
v) Drugs (therapeutic drugs like warfarin, tetracycline, retinoic acid, valproic acid, phenytoin misoprostil and many more. Also recreational drugs, especially alcohol.
Florence Mutesi: Are some of the causes of birth defects in undeveloped countries uncontrolable, for example those caused by civil wars like: lack medical check up, lack of nutritious food? Which birth effects are as a result of family planning methods?Who are the key players in ensuring the decline in birth defect? What are the main causes of birth defects originating from mothers?
Arnold Christianson: Please look at the answer to Amy Rogers question for the causes of birth defects. Programs for the control of birth defects are well documented in thw WHO’s Human Genetic Programme literature (www.who.int), the March of Dimes Global Report on Birth Defects (www.marchofdimes.com/globalprograms) and in the book chapter that stimilated this discussion in Disease Control Priorities in Developing Countries (www.dcp2.org) Control of birth defects is a programme combining best possible care and prevention by means of community education, preconception care, genetic counselling, medical genetic screening, prenatal diagnosis and associated services (i.e. selective termination of pregnancy)if available and legal in a country. All children with a birth defect are entitled to the best possible care (diagnosis, treatment and genetic counselling) available in the prevailing circumstances. Early death is a reality for many of these infants in developing nations, so treatment may only comprise palliative care. But they are entitled to that. Prevention programmes are an issue for each country to assess their needs and resources and then put in the programme(s) they choose. With time more programmes can be added as necessary. I am not aware of a birth defect caused by family planning (contraception) methods. However, when misoprostil is used as an abortificant (often illegally) this can cause birth defects. The key players in the care and prevention of birth defects and their roles are discussed in the literature I gave above.
Adeline Azrack: As with the November discussion about stillbirths, the issue of birth defects should draw our attention back the nutrition status of mothers, particularly young mothers. I would appreciate your comments on this subject, particularly practical examples of how to integrate maternal nutrition interventions into antenatal care in developing countries.
Arnold Christianson: Maternal nutrition interventions into antenatal care are TOO late to prevent most birth defects. The majority of serious birth defects are already present by 36 days post conception- before the mother even knows she is pregnant. Nutritional intervention needs to be preconception- that is part of preconcetion care which should be undertaken under the auspices of Women’s Health. All women should obviously eat a healthy diet (macro and miro nutrients) if possible. Note that obesity has been associated with some birth defects.
Specific nutrition interventions should include: 1. Folic acid. Fortification of staple foods in developing countries, including my own S Africa, has resulted in a significant reduction in the birth prevalence of neural tube defects. Folic acid, 400mcg daily, can also be supplemented as part of a peri-conception (for at least 1 month before conception and 3 months after) vitamin regime. There is no harm in supplementing folic acid at this dose if food is also fortified in the country. Salt fortification with iodine has made a huge impact on the birth prevalence of iodine deficiency disorder in infants over the last 18 years. This has been a very successful UNICEF programme, but there are still countries and regions that need to come on board. Good nutrition also involves removing harmful substances from the diet. The most important substance is ALCOHOL. Having done this to ensure preconception and immediate post conception nutrition, the continuation of a good diet and appropriate nutritional supplementation into antenatal care is obviously important.
Rahat Bari Tooheen: Birth defects have hidden costs which do not express themselves immediately. How should developing countries, which already face severe resource constraints, face this situation?
Arnold Christianson: Let me start this discussion with my belief that ‘care is an absolute and prevention the ideal’. Undoubtedly the care (diagnosis, treatment and counselling) of children with birth defects can be expensive and therefore where possible prevention is very important to reduce that cost. Preconception (primary) prevention is best as it is often the least expensive and has the least social/legal/ethical consequences. However, secondary prevention also has a role to play. Having said that, in all situations a child born with a birth defect is entitled to the best possible care in the prevailing circumstances. The issue of how developing countries can approach the matter of developing and integrating medical genetic services into their health care is well covered in the WHO’s Human Genetic Programme literature (www.who.int), the March of Dimes Global Report on Birth Defects (www.marchofdimes.com/globalprograms) and in the book chapter that stimilated this discussion in Disease Control Priorities in Developing Countries (www.dcp2.org) The initiation and development of medical genetic servics in resource limited countries is not an all or nothing issue. Each country must assess the problems it has and the resources available to manage these. Some countries start with just 1 disorder- the most significant- develop a care and prevention program and then use the experience gained in developing further programmes. Iran is currently developing an excellent medical genetic service on this basis. Others like my own, South Africa, are initiation a more generalised service and trying to build it up. Low resource countries need to take a different approach to that in industrialised nations. They need to have their services strongly based and integrated into primary health care. Thes in turn then need to be linked to secondary and tertiary care.
Pushpanjali Swain: Birth defect of a child which leads to disability is a lifelong tension of the parents. Birth defect can be mild also. Can severe birth defects prevented in womb? Is the prevalence of birth defect higher in developing country? Does Malnutrition of mother have any contribution to birth defect of child?
Arnold Christianson: The birth prevalence of birth defects in middle- and low-income countries is on average 20% higher than in industrialised nations. Maternal malnutrition is certainly one reason for this, particularly maternal iodine deficiency. Maternal folic acid deficiency may also be a factor. Malnutrition also includes eating or drinking harmful substances. Fetal alcohol syndrome is a significant birth defect in developing countries where alcohol is available and used/abused by women. South Africa is one such country, but there are many more in which the problem has not been recognised. Severe birth defects cannot be prevented in the womb. They can be diagnosed during pregnancy.
Agatha Onovo: What about the impact of this on women. I know the whole family is affected but the mothers are the most affected. While discusing causes, prevention and management of birth defects, it is important to draw the worlds attention to the impact of defects on the mothers of the affected children. Apart from the shame, stigma, psychological, physical and financial impact, these women are treated like social outcasts. In most traditional African societ[ies]; if the child is the woman’s first child, the mother is termed evil and most often will be abandoned with the burden of caring for the child alone. If the child is not her first, she is acussed of infidelity and it is believed she is being punished by the Gods. I am of the opinion that though birth defects may be of genetic and other origin, sociologigical approach could be part of the solution to the problem.
Arnold Christianson: The 2 people most affected by the birth of a child with a birth defect are the affected child, obviously, and the mother. The mother bears a heavy burden for several reasons. Firstly she experiences the grief of giving birth to her child with the birth defect and thus the loss of her expectation of a normal child. She then has the major role in the care of the child. Then, in most societies, especially traditional societies in developing countries, she is frequently stigmatised and blamed for causing the problem. The solution. Knowledge- both community and individual- about the causes and available care and methods of prevention of birth defects. That takes time,effort and commitment from the medical profession, health and educational authorities, media etc
Evelyn Lirri: 1-What are the comon birth defects? 2-What is required to prevent them? 3-How can parents/health workers identify these defects? 4-How Big is the problem in a developing country like Uganda?
Arnold Christianson: 1.It is estimated that some 9 million children (~7%) are born annually with a serious birth defect. About 7.9 million of these have a genetic cause and the rest are due to fetal environmental problems, mainly teratogens. Please remember not all people with a birth defcts are diagnosed at birth. Most (~75%) present later in life. Globally the 5 commonest genetic birth defects born annually are congenital heart disease (~1040000), neural tube defects (~324000) the haemoglobin disorders sickle cell disorder and thalassaemia (~3080000), Down syndrome (~217000) & G6PD deficiency (~177000). They comprise about 25% of the annual number of infants born with a serious genetic birth defect.
Common teratogenic birth defects, for which accurate global information is not available are congenital syphilis, congenital rubella (~100000/year), iodine deficiency disorder and fetal alcohol spectrum disorder. 2&3. Medical genetic services that encompass both care & prevention. Please refer to the following literature: the WHO’s Human Genetic Programmes literature on the topic (www.who.int), the Disease Control Priorities in Developing Countries’ chapter on Controlling Birth Defects(www.dcp2.org/file/230/dcpp-twpcongenitaldefects_web.pdf) and the March of Dimes Global Birth Defects Report (www.marchofdimes.com/globalprograms) . 4. The birth prevalence of serious genetic birth defects in Uganda is estimated to be ~61/1000 live births. This will be about 85-90% 0f all the birth defects. Common individual genetic birth defects include congenital heart defects, sickle cell disorder, Down syndrome and neural tube defects.
James Scott: Are there any published or current studies showing correlation between the presence of specific toxins and pollutants and the occurrence of specific birth defects? Also, have scholars isolated which birth defects are naturally occurring in non-mutated human DNA?
Arnold Christianson: Please go to the answers to the questions posed by Amy Rogers and Donna Villareal for the causes of birth defects. Toxins that cause birth defects are teratogens:
1. Drugs- Therapeutic
i. Anti-acne. Retinoic acid
ii. Anti- ulcer (gastric. Misoprostil
iii. Antibiotics. Tetracyclines, Streptomycin,Thalidomide
iv. Anticoagulants. Warfarin
v. Anti cancer. All of them
vi. Antidepressants. Lithium
vii. Anti-epileptic. Phenytoin, Sodium valproate
viii.Antihypertensive. ACE inhibitors
2. Drugs- Recreational
3 Environmental toxins
There is a lot of published work on this. The birth defects in ‘non-mutated’individuals are all those caused by conditions other than single gene defects
Chinyere Fred-Adegbulugbe: What can mothers do to protect their unborn children from most or even all birth defects? And what [kind] of support system is available for a mother/parents who gave birth to such a child?
Arnold Christianson: Mothers first need to consider protecting their unconceived child. They must do all they can to ensure they conceive a normal child.Steps to follow: Plan the pregnancy. Before conception ensure they and their spouse are both physically and emotionall prepared for the pregnancy. To do this they should receive preconception care during which a family history will be taken to assess their risk for having a child with a birth defect from a genetic cause.If present they will be offered advice on how to reduce this risk. E.g. carrier screening for sickle cell anaemia or cystic fibrosis. Women over 35 years old should be counselled about their increased risk for a child with Down syndrome. The woman’s syphilis, HIV and rubella status can be checked. Syphilis can be treated. If sero-negative the woman can receive rubella immunisation. If HIV positive she can be counselled on the consequences of this for a future pregnancy and receive RX if necessary. Should she have an illness (e.g diabetes, epilepsy) she can have her medication checked and if necessary adjusted to ensure she has the optimal and least teratogenic therapeutic options. She can be counselled on optimal diet including not to use recreational drugs like alcohol and smoking throughout pregnancy. Peri-conception folic acid supplementation should be offered. Once the babe is conceived she should continue to have a good diet, including Fe and vitamin supplements and regularily attend antenatal care. The support systems available for children with a birth defect vary widely from country to country and even with a country. No matter what all children with a birth defect are entitled to the best possible available care. Care for children with birth defects is discussed in the MOD Global Birth Defects Report (www.marchofdimes.com/globalprograms)