Jennifer J. Kurinczuk

Birth defects in infants conceived by intracytoplasmic sperm injection: an alternative interpretation.

Abstract Objective: To test the hypothesis that liveborn infants conceived by intracytoplasmic sperm injection are at an increased risk of having a major birth defect. Design: Reclassification of the birth defects reported in infants born after intracytoplasmic sperm injection in Belgium and comparison with prevalence estimated in Western Australian population by means of same classification system. Setting and subjects: 420 liveborn infants who were conceived after intracytoplasmic sperm injection in Belgium and 100 454 liveborn infants in Western Australia delivered during the same period. Main outcome measures: Estimates of birth prevalence of birth defects and comparisons of odds ratios between cohort conceived after intracytoplasmic sperm injection and Western Australian infants. Results: Infants born after intracytoplasmic sperm injection were twice as likely as Western Australian infants to have a major birth defect (odds ratio 2.03 (95% confidence interval 1.40 to 2.93); P=0.0002) and nearly 50% more likely to have a minor defect (1.49 (0.48 to 4.66); P=0.49). Secondary data-led analyses, to be interpreted with caution, found an excess of major cardiovascular defects (odds ratio 3.99), genitourinary defects (1.33), and gastrointestinal defects (1.84), in particular cleft palate (5.11) and diaphragmatic hernia (7.73). Conclusions: These results do not confirm the apparently reassuring results published by the Belgian researchers of intracytoplasmic sperm injection. Further research is clearly required. Meanwhile, doctors practising intracytoplasmic sperm injection should bear this alternative interpretation in mind when they counsel couples and obtain informed consent for the procedure. Key messages Reports of data from Belgium concluded that there was no increase in the occurrence of major birth defects among infants conceived by intracytoplasmic sperm injection However, the Belgian researchers used a narrow definition of what constituted a major birth defect, and they might have underestimated the comparative prevalence of major defects We reclassified the birth defects in the infants born after intracytoplasmic sperm injection using a standard classification system and compared the results with data from Western Australia that were classified with the same system We found that the infants born after intracytoplasmic sperm injection were twice as likely to have a major birth defect and nearly 50% more likely to have a minor defect Further research is required to elucidate these results, but, meanwhile, they should be born in mind when counselling infertile couples about intracytoplasmic sperm injection

Assessment of separate contributions to perinatal mortality of infertility history and treatment: a case-control analysis

BACKGROUND Few studies have described the perinatal risks associated with infertility, other than for infertility treated by in-vitro fertilisation or gamete intrafallopian transfer. The aim of this analysis was to estimate the risks of perinatal death associated with treated and untreated infertility. METHODS A population-based case-control study of perinatal deaths was carried out in Leicestershire Health District over the period 1990-94, during which 60,922 babies were delivered. Of these, 567 perinatal deaths were associated with 542 women. 972 mothers were randomly selected as controls. Medical, obstetric, and social data were collected for cases and controls from the medical notes and interviews with the women. The relative risks of perinatal death associated with treated and untreated infertility before the index pregnancy were estimated as odds ratios by means of unconditional logistic regression analysis. FINDINGS 65 (10%) of cases and 34 (3.5%) of the controls had infertility before the index pregnancy. History of infertility in the index pregnancy, irrespective of treatment, increased the risk of perinatal death (odds ratio 2.9 [95% CI 1.8-4.5]). The population attributable risk fraction for perinatal death related to infertility was 6.2% (3.4-9.0). 45 (54%) of the deaths, even in the untreated group, were associated with immaturity. Compared with women without infertility, women with untreated infertility were at increased risk of perinatal death (3.3 [1.6-6.8]). The risk of perinatal death associated with multiple births did not explain this finding. Similarly, treated infertility also increased the risk of perinatal death (2.7 [1.5-4.7]); the risks associated with multiple births explained some, but not all, of this excess. In Leicestershire, the overall underlying risk of a mother experiencing at least one perinatal death over the study was 9.0 per 1000 women. For women who experience infertility, this risk increases by about 18 per 1000 (6-30). INTERPRETATION Counselling for women before any form of infertility treatment should include discussion of the risks of perinatal death. Our results would benefit from confirmation. However, we advocate that at antenatal booking a history of infertility, irrespective of treatment, should be sought, because these women have a significantly increased risk of perinatal death, particularly associated with prematurity.

Fetal growth and subsequent mental health problems in children aged 4 to 13 years.

To test the hypothesis that children with suboptimal fetal growth have significantly poorer mental health outcomes than those with optimal growth, a population random sample survey of children aged 4 to 16 years in Western Australia in 1993 was conducted. The Child Behavior Checklist (Achenbach 1991a) and the Teacher Report Form (Achenbach 1991b) were used to define mental health morbidity. Survey data for 1775 children aged 4 to 13 years were available for linkage with original birth information. The percentage of expected birth weight (PEBW) was used as the measure of fetal growth. Children below the 2nd centile of PEBW who had achieved only 57% to 72% of their expected birthweight given their gestation at delivery were at significant risk of a mental health morbidity (OR 2.9, 95% CI 1.18, 7.12). In addition, they were more likely to be rated as academically impaired (OR 6.0, 95% CI 2.25, 16.06) and to have poor general health (OR 5.1, 95% CI 1.69, 15.52).

Birth defects in children with newborn encephalopathy.

This study was designed to investigate birth defects found in association with newborn encephalopathy. All possible birth defects were ascertained in a population-based study of 276 term infants with moderate or severe encephalopathy and 564 unmatched term control infants. A strong association between birth defects and newborn encephalopathy was found with defects affecting 27.5% of children with encephalopathy and 4.3% of control children (odds ratio 8.55; 95% confidence interval 5.25 to 13.91;p<0.001). In 11.8% of infants with a birth defect the defect was not diagnosed until after the newborn period, illustrating one of the difficulties in attempting to exclude infants with birth defects from studies of newborn encephalopathy. The majority of defects (89%) were not specific anomalies of the CNS. In 36.8% of children with encephalopthy who had a birth defect, the defect was considered to be the probable cause of the encephalopathy. Infants with birth defects who had encephalopathy had a poorer prognosis than those without: they were twice as likely to die by the age of 2 years and three times more likely to have cerebral palsy. This study catalogues the spectrum of birth defects associated with newborn encephalopathy and illustrates the importance of their inclusion when investigating both the aetiology and outcome of this condition.

Why is the placenta being ignored

The relationship between the frequency of published recommended indications for placental pathological examination and the frequency of requests for such examination in a population‐based study of term newborn encephalopathy was examined. Only 11.2% of placentas among 276 case infants and 0.7% of placentas among 564 term control infants were examined. Using the criteria set out in a consensus statement by the American College of Pathologists, all 276 cases fulfilled multiple maternal, fetal and placental indications for placental examination. Furthermore 43.3% of control infants fulfilled at least one criterion. Of the 25 case placentas that underwent pathological review, 16 were reported as having no diagnostic abnormality. Six cases (24%) showed clinically important findings: four had evidence of infection, one had multiple chorangiomata and one had thrombosis and rupture of the umbilical vein. Of the three remaining placentas, one showed funisitis, one showed minor lymphohistiocytic villitis and one was from monochorionic twins. To our knowledge there are no agreed Australian guidelines for when a placenta should be submitted for pathological examination. We suggest that until guidelines based on properly designed studies are developed it may be appropriate to store all placentas for at least 72 hours. If the infant develops neurological symptoms or requires unexpected admission to a neonatal intensive care unit then placental examination may reveal important aetiological diagnostic and prognostic information.

Listeria awareness among new mothers in Western Australia

Objective: To assess awareness, knowledge and behaviour relating to Listeria among recent mothers (12 weeks post‐partum) in Western Australia and determine the usefulness of a Listeria information pamphlet.

Newborn encephalopathy in term infants: Three approaches to population-based investigation

Epidemiological studies of abnormal neonatal neurology—newborn encephalopathy—are of value not only because of their intrinsic interest, but also because newborn encephalopathy as a potential indicator of the quality of intrapartum care needs to be evaluated. As newborn encephalopathy has a closer temporal relationship to the exposures of interest than does cerebral palsy, it would have a significant advantage over cerebral palsy as an index of intrapartum care. However, the proportion of newborn encephalopathy cases which arise in labour needs to be determined accurately before we can contemplate using the occurrence of newborn encephalopathy as such an indicator. Few good epidemiological studies of newborn encephalopathy have been carried out and there are many challenges in elucidating its antecedents. This paper reviews these challenges and briefly describes and contrasts three ongoing studies.

Trends in the frequency and predictive value of reporting high grade abnormalities in cervical smears.

The “organized approach” to cervical screening in Australia includes standardized quality assurance measures for laboratories. This study examines changes in the frequency and the positive predictive value of reporting severe abnormalities in cervical smears over a 3‐year period as a guide to the effects of implementing these measures.

Barriers to immunisation in general practice

Objective: To identify barriers to immunisation in general practice.

Maternal thyroid disease: a risk factor for newborn encephalopathy in term infants

Two previously published studies of term newborn encephalopathy showed that maternal thyroid disease to be a risk factor. From these studies we identified 13 case and three control mothers with thyroid disease and investigated them further. The majority of affected case mothers had idiopathic or autoimmune hypothyroidism. Compared with control mothers, case mothers had fewer thyroid function tests in pregnancy, were more likely to remain on the same dose of medication throughout pregnancy and to have experienced other pregnancy complications. The association between maternal thyroid disease and encephalopathy may be the result of a series of different causal pathways, some of which are suggested by our data.