Development of inherent safety and health index for formulated product design

The numerous formulated products which are introduced to the market consist of chemical ingredients that may cause various safety and health hazards to the consumers. Therefore, it is extremely important to practice a systematic methodology to formulate products with acceptable safety and health performances. This work presents an index-based methodology to assess the safety and health hazards of the ingredients during the early formulation stage of product design. Hence, new inherent safety and health sub-indexes are introduced to improve the current safety and health hazards that are needed in formulated product design. The inherent safety and health sub-indexes are assigned with scores based on the degree of potential hazards. A higher score indicates a higher safety risk or severe health effect, and vice versa. The proposed methodology will greatly assist the users to identify the adverse safety and health effects caused by the ingredients. Hence, it is pivotal to eliminate or reduce the safety and health impacts from product usage. A case study on common ingredients used in the formulation of paint is presented on this study to describe the proposed method.     

Successful outcome of pregnancy after treatment of maternal anti-ro (SSA) antibodies with immunosuppressive therapy and plasmapheresis

In this short communication we describe a patient with anti-SSA and anti-SSB antibodies whose first child died of congenital complete heart block (CCHB). During her second pregnancy she was treated with prednisolone, azathioprine, and plasmapheresis, and levels of anti-SSA and anti-SSB antibodies fell significantly. The pregnancy evolved uneventfully and resulted in the birth of an unaffected male infant. This is the fourth reported case of a successful outcome of pregnancy after treatment with immunosuppressive drugs in a woman with a significant risk of recurrence of CCHB.     

An evaluation of a shared experience group for women and their support persons following prenatal diagnosis and termination for a fetal abnormality

Objectives Support after fetal diagnosis of abnormality (SAFDA), is a facilitated shared experience group for women and their partners or support person, in Victoria, Australia, who have had a pregnancy termination for a fetal abnormality. The objective of this study was to evaluate the SAFDA-facilitated group. Methods A questionnaire-based study was undertaken between 2001 and 2005 to evaluate SAFDA. A deidentified self-completed questionnaire was given to participants at the end of each group and included questions relating to the referring professional, participants' prior expectations of the group, helpfulness of participation, preferred group format, length, and venue. In addition, there was also opportunity for participants to make general comments on their experiences of participating in SAFDA. Results A total of 85 participants (100% response) completed the questionnaire. Seventy-one participants (84%) considered it ‘very helpful’ to participate in the group. Seventy-eight participants (92%) considered that a shared-experience group was the most beneficial format. Comments written by participants affirmed that the present format of SAFDA was a highly valued opportunity to listen to and share experiences in a confidential small group. Conclusion SAFDA is a beneficial forum for women and their partners or support person to share their experiences after having had a pregnancy termination for a fetal abnormality. Further, SAFDA provides information and insights for health professionals who are considering how best to support women. Copyright © 2007 John Wiley & Sons, Ltd.     

The prognostic factors in the prenatal diagnosis of the echogenic fetal lung

The prenatal diagnosis of an echogenic fetal lung (EFL) is now often made in the early second trimester using high-resolution ultrasound. This ultrasound appearance is usually caused by a congenital cystic adenomatoid lung malformation (CCAM), an intrapulmonary lung sequestration or obstruction of a major airway. In order to provide prognostic guidelines to parents who may be considering termination of a fetus with these findings, we have analysed a series of 11 cases diagnosed in our centre over the past 2 years in conjunction with 60 cases from major published series. The data suggest that in the absence of non-immune hydrops fetalis (NIHF) or other anomalies, the outcome for the fetuses is excellent, with over 90 per cent survival. Neither early diagnosis (24 weeks) nor the presence of mediastinal shift is a poor prognostic indicator. In addition, it appears that if NIHF is absent at diagnosis, the chance that it will develop as the pregnancy continues is small (6 per cent). Furthermore, there is a significant (up to 30 per cent) chance that this ultrasound finding will resolve in utero. The development of in utero fetal surgical techniques may be the only hope for those hydropic fetuses who appear to have a dismal prognosis.     

Fetal diagnosis of toxoplasmosis in 190 women infected during pregnancy

One hundred and ninety women who contracted toxoplasmosis after the seventh week of pregnancy underwent antenatal diagnosis, including ultrasound examination and biological tests. Tests included Toxoplasma isolation in fetal blood and amniotic fluid by mouse inoculation, specific IgM and IgA in fetal blood, and non-specific tests. Twenty fetuses had positive specific as well as non-specific tests for Toxoplasma infection. At birth, four of these presented with clinical congenital toxoplasmosis and 12 with subclinical forms. Antenatal diagnosis enabled the detection of 83 per cent of the infected fetuses. Under specific conditions, cordocentesis permits early diagnosis and considerably reduces the number of terminations of pregnancy.     

Repeat maternal serum testing in multiple marker down's syndrome screening programmes

The effect of repeat testing in maternal serum multiple marker screening for Down's syndrome was estimated using samples stored in an antenatal serum bank. Human chorionic gonadotropin (hCG) and unconjugated oestriol (uE₃) levels were determined in 142 pairs of routinely collected samples which had already been tested for alpha-fetoprotein (AFP). For each marker, about two-thirds of the pairs of values were within 20 per cent of each other and most were within 40 per cent. A multivariate Gaussian model was used to estimate the detection and false-positive rates for different repeat testing policies. A policy of repeat testing those with a high risk of a Down's syndrome term pregnancy given age and marker levels would reduce the false-positive rate but there would also be a reduction in the detection rate. For example, using all three markers and a 1 in 250 cut-off risk, the estimated false-positive rate would fall from 5·3 to 3·8 per cent but the detection rate would decrease from 58 to 55 per cent. A policy of repeating those with either high or borderline risks would produce a modest improvement in screening efficiency. Repeating the 11 per cent with a risk exceeding 1 in 500 yields an estimated false-positive rate of 5·0 per cent and a detection rate of 60 per cent. A policy of selective repeat testing is not recommended as it would not substantially improve screening efficiency. Nonetheless, if a repeat test has been performed, the parameters given in this paper will enable an unbiased estimate of the Down's syndrome risk to be calculated for individual women.     

Prenatal exclusion of X-linked hydrocephalus-stenosis of the aqueduct of sylvius sequence using closely linked DNA markers

X-linked hydrocephalus-stenosis of the aqueduct of Sylvius sequence (H-SAS, MIM number 307 000) is a rare genetic disorder characterized by hydrocephalus, macrocephaly, adducted thumbs, spasticity, mental retardation, and cerebral malformations. This regularly lethal condition is usually diagnosed at birth or prenatally by ultrasound, but hydrocephalus may be moderate or even undetectable on fetal ultrasound examination. Moreover, since heterozygous women are asymptomatic, carrier detection is at present impossible before the birth of an affected son. Therefore, mapping the H-SAS locus to distal Xq (Xq28) was of primary importance for genetic counselling and prenatal diagnosis. Here, we report prenatal exclusion of H-SAS with a probability of 97.6 per cent in two male fetuses with a 50 per cent a priori risk of being affected using closely linked Xq28 DNA markers.     

The time of appearance and disappearance of fetal DNA from the maternal circulation

A single copy Y-chromosome DNA sequence was amplified using the polymerase chain reaction (PCR) from the peripheral blood of 30 women who had achieved a pregnancy through an in vitro fertilization (IVF) programme. The time of conception was known precisely and was confirmed by serial ultrasound scans. Conceptions were dated as the number of weeks after fertilization plus 2, to give a time equivalent to the obstetric menstrual dating of the pregnancy (LMP). Y-chromosome-specific DNA was detected in all pregnancies with a male fetus (18/30). The earliest detection was at 4 weeks and 5 days, and the latest at 7 weeks and 1 day. Y-chromosome-specific sequences were no longer detected in any of the male pregnancies 8 weeks after delivery. No Y-chromosome sequences were detected in any of the pregnancies where only female babies were delivered. This demonstrates that fetal DNA appears in the maternal circulation early in the first trimester, that it can be identified in all pregnancies tested by 7 weeks, that it continues to be present throughout pregnancy, and that it has been cleared from the maternal circulation 2 months after parturition. Early non-invasive prenatal diagnosis for aneuploidies and inherited disorders will be possible in all pregnancies if fetal cells can be isolated free from maternal contamination (or identified accurately in the presence of maternal cells) without problems of contamination from previous pregnancies.     

Prenatal diagnosis of a left ventricular aneurysm

In a fetus with ventricular extrasystoles a congenital aneurysm of the left ventricle was diagnosed prenatally. At 32 weeks of gestation, echocardiography showed a large apical left ventricular aneurysm with a thin, hypokinetic wall. Congestive heart failure did not occur. Prenatal and postnatal examinations did not detect the aetiology of the aneurysm, but excluded the majority of possible causes. The 2-year-old child is now asymptomatic and normally developed. Neither medication nor surgical treatment have been necessary, except for antithrombotic prophylaxis with low-dose aspirin.