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Biomedical subjects

P A Lancaster

Publications and source records attributed to P A Lancaster.

At least 19 recordsLinked to original sources

Teratogenic effects of antiepileptic drugs: use of an International Database on Malformations and Drug Exposure (MADRE).

PURPOSE: The study goal was to assess teratogenic effects of antiepileptic drugs (AEDs) through the use of a surveillance system (MADRE) of infants with malformations. METHODS: Information on all malformed infants (1990-1996) with maternal first-trimester drug exposure was collected by the International Clearinghouse for Birth Defects and Monitoring Systems (ICBDMS). Cases were defined as infants presenting with a specific malformation, and controls were defined as infants presenting with any other birth defect. Exposure was defined by the use of AEDs during the first trimester of pregnancy. The association of AEDs with malformations was then estimated by calculating the odds ratios with 95% confidence intervals and testing their homogeneity among registries. RESULTS: Among 8005 cases of malformations, 299 infants were exposed in utero to AEDs. Of those exposed to monotherapy, 65 were exposed to phenobarbital, 10 to methylphenobarbital, 80 to valproic acid, 46 to carbamazepine, 24 to phenytoin, and 16 to other AEDs. Associations were found for spina bifida with valproic acid. Infants exposed to phenobarbital and to methylphenobarbital showed an increased risk of oral clefts. Cardiac malformations were found to be associated with phenobarbital, methylphenobarbital, valproic acid, and carbamazepine. Hypospadias was associated with valproic acid. Porencephaly and other specified anomalies of brain, anomalies of face, coarctation of aorta, and limb reduction defects were found to be associated with valproic acid. CONCLUSIONS: Using the MADRE system, we confirmed known teratogenic effects of AEDs. We also found increased risks for malformations that had never been reported associated with AEDs or for which the association was suggested by case reports.

Abnormalities, Drug-Induced↗

Australian national birthweight percentiles by gestational age.

OBJECTIVE: To develop national birthweight percentiles by gestational age for male and female singleton infants born in Australia, and to compare the birthweight percentiles of Indigenous and non-Indigenous infants. DESIGN AND SETTING: Cross-sectional study of singleton live births to Australian-born mothers from 1991 to 1994. MAIN OUTCOME MEASURES: Birthweight percentiles by gestational age. RESULTS: During 1991-1994 Australian-born women gave birth to 769,077 live singleton infants. Of these, 28,230 (3.7%) were reported as births to Aboriginal or Torres Strait Islander women. Birthweight was missing for 581 (0.1%) births and gestational age was missing for 3014 (0.4%). An additional 3283 (0.4%) births were excluded because the recorded birthweights were extreme outliers for their recorded gestational ages. Indigenous women were more likely to be recorded as giving birth preterm (< 37 weeks' gestation) than non-Indigenous women (11.6% v. 5.4%) and were more likely to give birth to small-for-gestational-age infants at term. After 34 weeks' gestation, the median birthweights of Indigenous infants were consistently lower than those of non-Indigenous infants. At 40 weeks' gestation the difference in the median birthweights between these two groups was 160 g for males and 130 g for females. CONCLUSIONS: We present recent birthweight percentiles by gestational age based on national data in Australia. These percentiles provide current Australian norms for clinicians and researchers, and can provide a baseline for monitoring Indigenous perinatal outcomes.

Australia↗

National birthweight percentiles by gestational age for twins born in Australia.

OBJECTIVE: To develop national charts of birthweight percentiles by gestational age and infant sex for liveborn twins born in Australia. METHODOLOGY: National data on live twin births to non-Indigenous Australian-born mothers during 1991-94 were derived from perinatal data collected by midwives in each State and Territory. RESULTS: During 1991-4 there were 20,075 liveborn twin infants. Of these births, missing data included: birthweight 36 (0.2%) births, gestational age 95 (0.5%) births, and sex (missing or indeterminate) 13 (0.06%) births. These births were excluded from the study. An additional 0.6% births were excluded because the recorded birthweights were extreme outliers for the recorded gestational ages. Forty-seven per cent of live twin births were preterm (< 37 weeks). At all gestational ages, the median birthweight of male twins was higher than that of female twins. At model gestational age of 38 weeks, the difference in the median birthweight was 130 g. CONCLUSIONS: The charts produced as a result of the study provide birthweight percentiles by gestational age for twins based on national data in Australia. They provide current population norms for the use of Australian clinicians and researchers.

Adult↗

Perinatal death associated with planned home birth in Australia: population based study.

OBJECTIVE: To assess the risk of perinatal death in planned home births in Australia. DESIGN: Comparison of data on planned home births during 1985-90, notified to Homebirth Australia, with national data on perinatal deaths and outcomes of home births internationally. RESULTS: 50 perinatal deaths occurred in 7002 planned home births in Australia during 1985-90: 7.1 per 1000 (95% confidence interval 5.2 to 9.1) according to Australian definitions and 6.4 per 1000 (4.6 to 8.3) according to World Health Organisation definitions. The perinatal death rate in infants weighing more than 2500 g was higher than the national average (5.7 versus 3.6 per 1000: relative risk 1.6; 1.1 to 2.4) as were intrapartum deaths not due to malformations or immaturity (2.7 versus 0.9 per 1000: 3.0; 1. 9 to 4.8). More than half (52%) of the deaths were associated with intrapartum asphyxia. CONCLUSIONS: Australian home births carried a high death rate compared with both all Australian births and home births elsewhere. The two largest contributors to the excess mortality were underestimation of the risks associated with post-term birth, twin pregnancy and breech presentation, and a lack of response to fetal distress.

Asphyxia Neonatorum↗

Is the male involved in the aetiology of ectopic pregnancy?

We have previously observed a low incidence of ectopic pregnancies in couples having gamete intra-Fallopian transfer (GIFT) with donated spermatozoa. Based on findings in both animal and human models, we proposed the hypothesis that sperm defects may be associated with the expression of paternal genes which cause abnormal early embryo development and predispose the embryos to interact inappropriately with the genital tract epithelium, and so increase the risk of an ectopic implantation. To both confirm and extend the initial observation, GIFT and in-vitro fertilization (IVF) pregnancies entered on the Australian and New Zealand national database between 1979 and 1993 were analysed with regard to the incidence of ectopic pregnancy. There was an increased risk of ectopic pregnancy for IVF relative to GIFT and when spermatozoa from the male partner were used rather than donor spermatozoa. However, when couples were categorized with respect to the aetiology of their infertility, we were unable to show a significant association between ectopic pregnancy and whether spermatozoa from the male partner or a donor were used. We have therefore been unable to confirm a direct association between the source of spermatozoa and ectopic pregnancy.

Female↗

The spectrum of congenital anomalies of the VATER association: an international study.

The spectrum of the VATER association has been debated ever since its description more than two decades ago. To assess the spectrum of congenital anomalies associated with VATER while minimizing the distortions due to small samples and referral patterns typical of clinical series, we studied infants with VATER association reported to the combined registry of infants with multiple congenital anomalies from 17 birth defects registries worldwide that are part of the International Clearinghouse for Birth Defects Monitoring Systems (ICB-DMS). Among approximately 10 million infants born from 1983 through 1991, the ICB-DMS registered 2,295 infants with 3 or more of 25 unrelated major congenital anomalies of unknown cause. Of these infants, 286 had the VATER association, defined as at least three of the five VATER anomalies (vertebral defects, anal atresia, esophageal atresia, renal defects, and radial-ray limb deficiency), when we expected 219 (P<0.001). Of these 286 infants, 51 had at least four VATER anomalies, and 8 had all five anomalies. We found that preaxial but not other limb anomalies were significantly associated with any combination of the four nonlimb VATER anomalies (P<0.001). Of the 286 infants with VATER association, 214 (74.8%) had additional defects. Genital defects, cardiovascular anomalies, and small intestinal atresias were positively associated with VATER association (P<0.001). Infants with VATER association that included both renal anomalies and anorectal atresia were significantly more likely to have genital defects. Finally, a subset of infants with VATER association also had defects described in other associations, including diaphragmatic defects, oral clefts, bladder exstrophy, omphalocele, and neural tube defects. These results offer evidence for the specificity of the VATER association, suggest the existence of distinct subsets within the association, and raise the question of a common pathway for patterns of VATER and other types of defects in at least a subset of infants with multiple congenital anomalies.

Abnormalities, Multiple↗

A cohort study of pregnancy outcome after amniocentesis in twin pregnancy.

We conducted a retrospective cohort study to assess the risk of amniocentesis in twin pregnancy for adverse outcomes. The study base consisted of women who had an amniocentesis performed during twin pregnancy and a comparison representative sample of women who carried a twin pregnancy, but did not have invasive prenatal diagnosis. The 227 women in each of the exposed and non-exposed groups were residents of the state of New South Wales, Australia, over the period 1980-92, and were matched on maternal age and period of the infant's birth. Nearly 10% of twin pregnancies among the women having an amniocentesis were affected by a stillbirth, and the stillbirth rate among exposed fetuses (5.3%) was nearly twice as high as among non-exposed fetuses (3.1%). After adjustment for confounding and excluding abnormalities, there was a non-significant elevated relative risk of stillbirth after exposure to amniocentesis. The analysis by type of amniocentesis (with and without methylene blue dye) was limited by small numbers, but the burden of risk was primarily among women who had dye exposure during amniocentesis (relative risk = 3.64, 95% confidence interval = 1.15, 11.48). This increase remained after adjusting for confounding, although the confidence interval was wide. In conclusion, we were unable to establish with certainty whether an increased risk of stillbirth could be ruled out among women who had any type of amniocentesis in twin pregnancy.

Adult↗

Fetal death after exposure to methylene blue dye during mid-trimester amniocentesis in twin pregnancy.

Methylene blue dye use during mid-trimester amniocentesis in twin pregnancy is associated with a high risk of small intestinal atresia. It is plausible that the effects of methylene blue as a fetotoxic agent may also lead to fetal death. We conducted a retrospective cohort study of all women who had an amniocentesis during twin pregnancy from 1980 through 1991 in New South Wales, Australia. Women who were exposed to methylene blue dye during the procedure were compared with women who had amniocentesis without dye exposure. Fetal death occurred in 31.8 per cent of pregnancies that had exposure to a high concentration of methylene blue, compared with 14.5 per cent of pregnancies exposed to a low concentration and 4.3 per cent of pregnancies with no exposure to dye. The unadjusted and adjusted risks and 95 per cent confidence intervals (CIs) for fetal death after any exposure to dye were 5.03 (2.12-11.91) and 8.52 (2.28-31.80), respectively. The adjusted odds ratio and 95 per cent CIs for the low and high concentration dye solutions were 4.63 (0.93-23.13) and 14.98 (3.40-66.08), respectively (chi-squared test for trend P < 0.001). Fetus papyraceous was significantly more likely among pregnancies exposed to a high concentration of methylene blue (P < 0.001) than among unexposed pregnancies. These results support the hypothesis that methylene blue dye use during mid-trimester amniocentesis in twin pregnancy increases the risk of fetal death.

Amniocentesis↗

Registers of in-vitro fertilization and assisted conception.

Many countries now have registers of assisted conception that were initially set up to evaluate the effectiveness of treatment, to monitor pregnancy outcomes and the health of treated women, and to assess any immediate risks for the women and their children. World reports, based on information from national registers, have enabled international comparisons of the extent to which the various techniques of assisted conception are used to treat infertile couples, as well as comparisons of pregnancy outcome. The reports also provide comparative data on pregnancy rates in populations rather than in single in-vitro fertilization (IVF) centres. To determine whether newly introduced techniques such as intracytoplasmic sperm injection are associated with any increased risks of birth defects or other adverse outcomes, information notified to registers will often need to be supplemented by clinical reports or by linkage of data in IVF registers and other health data systems. Further efforts to improve the quality of information on assisted conception within each country and internationally need to be well supported so that the effectiveness of treatment and the outcomes of treated couples and their children can be evaluated properly.

Abortion, Spontaneous↗

Limb deficiencies, chorion villus sampling, and advanced maternal age.

Record linkage between a prenatal diagnosis register and a congenital malformation register in the state of Victoria, Australia, has enabled further evaluation of the suggested association between limb deficiencies and early chorion villus sampling (CVS). We found 3 anomalies in this category after later CVS (i.e., 9 weeks and beyond), but our data suggest that advanced maternal age may be a risk factor for both terminal and all limb deficiencies. The data from Victoria are tabulated with data obtained from other registers. Different birth prevalence figures are obtained by different registers, therefore limiting comparisons between registers.

Adult↗

The epidemiology of three serious cardiac defects. A joint study between five centres.

The paper reports a joint study made by five member programs of the International Clearinghouse for Birth Defects Monitoring Systems. Three specific heart malformations were studied, hypoplastic left heart syndrome (HLHS), transposition of the great vessels (TGV), tetralogy of Fallot, and some epidemiological characteristics were analyzed. The prevalence at birth was estimated to be 2.0, 2.9, and 2.2 per 10,000 births, respectively. No time trend in the prevalence at birth was observed for any one of the three malformations in the total study population. When only isolated defects were considered (infants without major non-cardiac malformations), all three cardiac anomalies showed an increased rate in infants with low birth weight, short gestational duration and probably twinning. A preponderance for males was observed for each defect but was strongest among infants with tetralogy of Fallot (sex ratio 2.5 for Fallot, 1.4 to 1.5 for the other conditions). There were also differences between the three cardiac defects with respect to percentage of low birth weight, preterm births, and rate and type of associated extracardiac malformations. This paper stresses the advantage of pooling data from different registries in studies of uncommon specific malformations and infrequent characteristics.

Adult↗

The incidence of congenital heart defects in the first year of life.

Data on the incidence of congenital heart defects (CHD) in the first year of life were collected on a cohort of infants born between 1981 and 1984 in New South Wales and the Australian Capital Territory. There was a total of 1479 cases among 343,521 births, an incidence of 4.3 per 1000 livebirths. The following results were obtained after restricting the analysis to cases diagnosed definitively by echocardiography, cardiac catheterization, operation or autopsy. A significant association was found between older maternal age and having an infant with CHD, both before (RR = 1.27, CI = 1.13, 1.44) and after (RR = 1.17, CI = 1.02, 1.33) excluding chromosomally related cases. Significant associations were found between having an infant with ventricular septal defect and Italian parentage (RR = 2.50, CI = 1.11, 5.65), and for having an infant with coarctation of the aorta and Lebanese parentage (RR = 3.82, CI = 1.71, 8.52). The incidence of CHD in this Australian population is similar to overseas studies that used comparable diagnostic criteria and ascertainment. An active surveillance system for CHD is recommended as is further investigation of the factors associated with having an infant with CHD.

Heart Defects, Congenital↗

Absence of limbs and gross body wall defects: an epidemiological study of related rare malformation conditions.

The study is based on almost 10 million births and reports on 215 infants with two unusual malformations: amelia and gross body wall defect. Amelia without body wall defect was present in 116 cases, 67 had body wall defects without amelia, and 32 had both. The total rate was 2.2 per 100,000 births. The infants were divided into five mutually exclusive groups. There were 40 infants (0.4 per 100,000) with agenesis of the body stalk, 18 with amelia and other types of gross body wall defects (0.2 per 100,000), 56 with amelia and malformations other than gross body wall defects (0.6 per 100,000), 41 with amelia (with or without other limb reduction defects) but no nonlimb malformations (0.4 per 100,000), and 60 infants with gross body wall defects of a type other than agenesis of body stalk and without amelia (0.6 per 100,000). A weak trend of decreasing prevalence of these malformations was found during the observation period. Infants with agenesis of the body stalk and infants with amelia combined with other types of gross body wall defects occurred at an increased rate in infants of young women. This maternal age effect is also found with gastroschisis, but not with omphalocele, and may indicate etiological or pathogenetic similarities between gastroschisis and the two former groups of defect. In infants with amelia, additional limb reduction defects could be of any type: transverse, longitudinal, or intercalary. Therefore, amelia may be the end result of different types of disturbances of limb morphogenesis. There was an increased rate of twinning. The relationship with amniotic band syndrome is discussed.

Abdominal Muscles↗

An international case-control study on hypospadias. The problem with variability and the beauty of diversity.

The paper describes problems and advantages in an international cooperative study of a case-control design, aimed at investigating the possible association between exogenous hormones and hypospadias. The varying degrees of the ascertainment of specific exposures and risk factors, in spite of the use of a standardized questionnaire is illustrated. Definite support for the existence of recall or interviewer bias is presented. On the other hand, the multipopulation design offers possibilities to make use of the diversity of the populations: differences in reproductive patterns and in specific exposures such as drug use, smoking and maternal occupation.

Bias↗

Increased pregnancy failure rates after clomiphene following assisted reproductive technology.

The obstetric outcome of 1941 in-vitro fertilization (IVF) and 1436 gamete intra-Fallopian transfer (GIFT) pregnancies reported from 25 units in Australia and New Zealand have been reviewed. Recently, gonadotrophin-releasing hormone analogues (GnRHa) have replaced clomiphene as part of many ovarian stimulation protocols. Clinical abortion rates after clomiphene (24.4% for IVF; 23.0% for GIFT) were not significantly higher than after GnRHa (20.7% for IVF; 17.9% for GIFT) when IVF and GIFT data were considered separately. However, the abortion rate for combined IVF and GIFT was significantly higher after clomiphene than after GnRHa. This pattern was found for most maternal age groups and causes of infertility although differences were not significant in all categories. The combined IVF and GIFT ectopic pregnancy rate of 6.7% for clomiphene was significantly higher than 4.1% for GnRHa. Because the mechanism of action of clomiphene for oocyte recruitment during folliculogenesis means that GnRHa cannot be used with clomiphene, luteinizing hormone (LH) levels are higher in clomiphene cycles than in GnRHa cycles. Clomiphene itself could cause the increase in pregnancy wastage or increased levels of LH during follicule genesis associated with the use of clomiphene may cause the observed pregnancy failures.

Abortion, Spontaneous↗