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Sixty babies, delivered over a six and a half year period, who had absent end diastolic frequency (AEDF) in the umbilical artery, were studied. Individually matched control pregnancies for gestational age, birth-weight, maternal clinical condition and date of delivery, in whom umbilical artery recordings showed end diastolic frequency, were also studied. Matching was achieved in 36 cases. Neonates from case pregnancies showed no increase in necrotising enterocolitis, intraventricular haemorrhage, pneumothorax, neonatal death or bronchopulmonary dysplasia. However, they were significantly less likely to require ventilation for respiratory distress syndrome (P = 0.02). Although AEDF indicates a fetus under vascular stress, this finding alone will include a spectrum of response in the baby, from the well compensated to the irreversibly damaged. Delivery at different points in the deteriorating fetal environment may explain discrepant study results. This intrauterine stress, by increasing fetal corticosteroid and thyroid hormones, may account for enhanced lung maturity. Predictions of neonatal course need to be based on more comprehensive awareness of fetal status. [ABSTRACT FROM AUTHOR]

Objective: Offspring of mothers with type 1 diabetes (OT1DM) demonstrate increased fat deposition, hyperinsulinemia, and hyperleptinemia in utero. We examined the influence of maternal diabetes on cord lipids at birth and relationship to body composition, cord insulin, leptin, and other hormonal measures., Research Design and Methods: We performed an observational study measuring fetal, HDL, and LDL cholesterol; triglycerides; and nonesterified fatty acids (NEFAs) in a total of 139 OT1DM and 48 control subjects at birth and assessed cross-sectional relationships with birth weight, fetal insulin, leptin, adiponectin, and IGF-1., Results: Concentrations of total cholesterol (male OT1DM [mean +/- SD] 1.49 +/- 0.45 mmol/l and male control subjects 1.74 +/- 0.33 mmol/l; P < 0.001), HDL cholesterol (0.53 +/- 0.21 and 0.74 +/- 0.19 mmol/l, respectively; P < 0.001), and NEFA (median 0.17 [interquartile range 2.30-2.95] and 0.21 [0.18-0.36], respectively; P < 0.001) were significantly lower in male OT1DM, with no significant differences in female subjects. Differences in male subjects were independent of mode of delivery. Cord lipids were unrelated to birth weight in OT1DM and did not show consistent relationships with fetal insulin. Unexpectedly, IGF-1 was a strong correlate of HDL cholesterol in control subjects (r = 0.40, P = 0.002) and OT1DM (r = 0.32, P < 0.001) but a negative correlate of triglycerides in control subjects (r = -0.48, P < 0.001) and OT1DM (r = -0.21, P = 0.004), with these relationships present in both sexes. In OT1DM, leptin was also independently correlated (negatively, P < 0.001) with HDL cholesterol in male and female subjects., Conclusions: Maternal diabetes is associated with significant alterations in lipid levels in male fetuses. IGF-1, leptin, and male sex rather than insulin may be the major determinants of HDL cholesterol and triglycerides in utero.

Objective: The insulin like growth factor (IGF) system plays a key role in regulating fetal growth, is metabolically regulated, and may influence development of increased birth weight in offspring of mothers with diabetes. We examined IGF-1 and IGF binding protein-1 (IGFBP-1) concentrations in cord blood samples from offspring of mothers with gestational and type 2 diabetes., Design and Patients: Case-control study of Maori and Pacific Island mothers recruited prospectively at Middlemore Hospital, South Auckland, New Zealand., Measurements: Cord blood (for insulin, IGF-1 and IGFBP-1) was taken from umbilical vein at birth from singleton babies born after 32 weeks of gestation from138 mothers with gestational diabetes (GDM), 39 mothers with type 2 diabetes (T2DM) and 95 control mothers., Results: Babies born to mothers with both GDM and T2DM had significantly increased birth weight (Z-score birth weight mean +/- SD: GDM 0.94 +/- 1.31, T2DM 0.53 +/- 1.1) compared to controls (Z-score birth weight -0.08 +/- 1.10). IGFBP-1 was significantly reduced in both diabetic groups (median interquartile range: GDM 67(31-137) ng/ml, T2DM 59(29-105) ng/ml, control 114(56-249) ng/ml). Cord IGF-1 was significantly increased in cord blood of infants of mothers with GDM (42.2 +/- 16.3 ng/ml vs. control 34.7 +/- 18.5 ng/ml) but not T2DM (38.7 +/- 17.4 ng/ml). In all offspring, IGF-1 and IGFBP-1 were positively and negatively correlated with birth weight, respectively., Conclusions: Maternal diabetes results in inverse changes of circulating fetal IGF-1 and IGFBP-1 at birth. A decrease in circulating IGFBP-1 and to a lesser extent an increase in circulating IGF-1 may present an important mechanism that contributes to increased birth weight in diabetic pregnancies.

Objective: In genetically diabetes-prone populations, maternal diabetes during pregnancy increases the risk of their children developing diabetes and obesity (the vicious cycle of type 2 diabetes). Fetal hyperinsulinemia at birth acts as a marker of this risk. We therefore examined whether cord insulin and leptin concentrations are increased in offspring of Maori and Pacific Island mothers with type 2 and gestational diabetes mellitus (GDM) and varying degrees of glycemic control (HbA(1c))., Research Designs and Methods: Maori and Pacific Island mothers were prospectively recruited at Middlemore Hospital, South Auckland. Cord blood was taken from umbilical vein at birth from singleton babies born after 32 weeks of gestation to 138 mothers with GDM, 39 mothers with type 2 diabetes, and 95 control mothers., Results: Babies born to mothers with both type 2 diabetes and GDM had higher birth weight and skinfold thickness and markedly higher concentrations of insulin (median [interquartile range] type 2 diabetes 77 pmol/l [42-143], GDM 67 pmol/l [42-235], and control subjects 33 pmol/l [18-62]; P < 0.001) and leptin (type 2 diabetes 39 ng/ml [18-75], GDM 31 ng/ml [17-58], and control subjects 13 ng/ml [8-22]; P < 0.001) in cord blood. Cord insulin concentrations >120 pmol/l were found in 29% of offspring of mothers with GDM and 31% of mothers with type 2 diabetes. Many mothers with GDM had abnormalities of glucose tolerance postpartum (20% type 2 diabetes, 34% impaired glucose tolerance or impaired fasting glucose). Higher cord insulin (57 pmol/l [40-94]) and leptin (26 ng/ml [17-39]) concentrations were found even in offspring of GDM mothers with normal glucose tolerance postpartum., Conclusions: Raised cord insulin and leptin concentrations are a common finding in offspring of mothers with type 2 diabetes and GDM in this population.

Objective: Maternal diabetes is associated with excess foetal growth. We have assessed the influence of maternal diabetes on hormones associated with foetal growth and the relationship of these hormones to birthweight., Design: Case-control study., Patients: Singleton offspring of mothers with type 1 diabetes (ODM, n = 140) and control mothers (Control, n = 49)., Measurements: Birthweight, cord blood insulin, proinsulin, 32-33 split proinsulin, leptin, IGF-1, IGFBP-3, cortisol., Results: Maternal diabetes was associated with higher birthweight (ODM 3.80 +/- 0.69 kg; Control; 3.56 +/- 0.52 kg, P = 0.02) and marked increases in insulin (median [interquartile range]: ODM 110 [60-217] pmol/l; Control 22 [15-37] pmol/l; P < 0.0001) and leptin (ODM 32 [15-60] ng/ml; Control 9 [4-17] ng/ml; P < 0.0001) but no absolute difference in IGF-1 (ODM 7.9 [6.2-9.8] nmol/l, Control 7.5 [6.2-9.8] nmol/l, P = 0.24) or its principle binding protein IGFBP-3 (ODM 1.63 +/- 0.38 micro g/ml, Control 1.63 +/- 0.28 micro g/ml; P = 0.12). Individually, insulin, insulin propeptides, leptin, IGF-1 and IGFBP-3 were significantly (P < 0.05) correlated with birthweight (in ODM and Control). IGF-1 and leptin were positively related to birthweight independently of each other and insulin in both ODM and Control. By contrast, insulin showed independent relationships to birthweight in ODM (P < 0.0001) but not in Control (P = 0.4)., Conclusions: Maternal diabetes is associated with marked elevation of insulin and leptin in cord blood of their offspring. Hormonal correlates of birthweight differ between ODM and Control with an independent relationship of insulin to birthweight observed only in ODM.

During pregnancy, maternal type 1 diabetes-associated autoantibodies may cross the placenta. It is proposed that insulin antibodies (IA) allow transfer of insulin across the placenta, contributing to fetal hyperinsulinemia and macrosomia. We assessed the prevalence of IA, the tyrosine phosphatase IA-2, and glutamic acid decarboxylase (GADA) in cord blood from offspring of mothers with type 1 diabetes (ODM, n = 138) and control mothers (control, n = 47) and further assessed cross-sectional relationships of antibody titers to birth weight and fetal insulin. In ODM, antibodies were frequently present in cord blood; 124 ODM (95%) were positive for IA, 82 (59%) were positive for GADA antibodies, and 61 (44%) were positive for IA-2 antibodies. In controls, GADA and IA-2 antibodies were absent, whereas seven controls (15%) were positive for IA at low titers (P < 0.0001 ODM vs. controls for all).ODM with IA (IA positive) or without IA (IA negative) had similar birth weights (mean +/- sd: IA positive, 3.8 +/- 0.7 kg; IA negative, 4.0 +/- 0.6 kg; P = 0.31) and cord insulin concentrations (IA positive: median, 112 pmol/liter; interquartile range, 62-219 pmol/liter; IA negative: median, 114 pmol/liter; interquartile range, 59-194 pmol/liter; P = 0.96). Similarly, the presence of GADA and/or IA-2 autoantibodies (n = 103) was not associated with differences in birth weight or insulin concentrations. Antibody titers were not associated with birth weight or insulin as continuous variables in either controls or ODM. Islet autoantibodies and IA are a common finding in cord blood of ODM, but we found no evidence that they influence offspring insulin concentrations or weight at birth.

Objective: In adults, adiponectin is reduced in association with excess adiposity, type 2 diabetes, and hyperinsulinemia. We assessed whether adiponectin was 1) present in the fetal circulation, 2) altered in the fetal circulation in the presence of maternal diabetes, and 3) had relations to fetal cord blood insulin or adiposity., Research Design and Methods: We assessed adiponectin in cord blood in a large cohort of singleton offspring of diabetic mothers (ODM; n = 134) and control mothers (n = 45)., Results: Adiponectin was present in cord blood and, in ODM, was higher in those delivered at later gestational ages (Spearman r = 0.18, P = 0.03). Adiponectin was slightly lower in ODM than control subjects (ODM 19.7 +/- 6.1 vs. control 21.8 +/- 5.3 micro g/ml; P = 0.04), although this difference could potentially reflect different gestational ages in the two groups (ODM 37.6 +/- 1.5 and control 40.1 +/- 1.1 weeks). In contrast to adults, adiponectin levels in the fetus were unrelated to the degree of adiposity, blood insulin, or leptin in either control subjects or ODM., Conclusions: Adiponectin is present in cord blood but does not show expected physiological relations with adiposity as observed in adults.

Maternal diabetes during pregnancy is associated with excess fetal growth and increased fetal insulin production. We hypothesized that insulin propeptides (proinsulin and 32-33 split proinsulin) might be more robust indicators of chronic fetal overproduction of insulin. We examined insulin-like molecules in cord blood (ILM) (insulin, proinsulin, and 32-33 split proinsulin) in relation to birth weight, maternal glycemia, and cord glucose in 140 offspring of mothers with type 1 diabetes (ODM) and 49 offspring of mothers who did not have diabetes (CONTROL) as well as degradation of ILM in response to sampling conditions at birth. Insulin propeptides were abundant in cord blood, comprising 50% of ILM in CONTROL and 36% in ODM (P < 0.0001) and more resistant to degradation than insulin (P < 0.05). Concentrations of all three ILM were highly intercorrelated with median values 2- to 5-fold higher in ODM than CONTROL [e.g. median (range): insulin ODM 110 (60-217) pmol/liter; CONTROL 22 (15-37) pmol/liter; P < 0.0001]. In ODM, 32-33 split proinsulin and proinsulin were more closely related to birth weight (Spearman r for ILM: r(32-33 split)= 0.54; r(PROINSULIN): r = 0.54; r(INSULIN) = 0.40: r(32-33 split) and r(PROINSULIN) > r(INSULIN)P < 0.05) and fetal leptin (r(32-33 split)= 0.55; r(PROINSULIN); r = 0.54; r(INSULIN) = 0.22: r(32-33 split) and r(PROINSULIN) > r(INSULIN)P < 0.05) than insulin). By contrast, insulin was more closely related to cord glucose (r(32-33 split) = 0.15; r(PROINSULIN): r = 0.10; r(INSULIN) = 0.42: r(INSULIN) > r(32-33 split) and r(PROINSULIN)P < 0.05). In CONTROL, 32-33 split proinsulin was also more closely related to fetal leptin r(32-33 split)= 0.61; r(PROINSULIN): r = 0.29; r(INSULIN) = 0.33: r(32-33 split) > r(INSULIN)P < 0.05). In ODM, 32-33 split proinsulin and proinsulin have closer relationships to fetal growth and leptin concentrations at birth than insulin. Measurement of insulin propeptides may be advantageous in assessment of the influence of maternal hyperglycemia on the newborn.

Objective: To identify factors independently affecting fetal weight in women with type I diabetes., Design: Prospectively recorded data in consecutive women with type I diabetes, between 1975-1992., Setting: Simpson Memorial Maternity Hospital, Edinburgh. Population Three hundred and two pregnancies with type I diabetes identified before pregnancy, with antenatal care and delivery in the Simpson Memorial Maternity Hospital, a singleton pregnancy, and the same diabetic physician., Methods: Normal ranges for birthweight were established for the total hospital population. All cases and the total population had pregnancy dating by ultrasound. The relation between standardised birthweight and explanatory variables was investigated using correlation analysis, t tests and chi2 tests as appropriate, and subsequently using multiple linear regression., Results: Standardised birthweight in cases, compared with the reference population, showed a unimodal, approximately normal distribution, markedly shifted to the right (mean + 1.26 SD). The most predictive variable was glycated haemoglobin concentration at 27-33 weeks, which explained 6.3% of the birthweight variance, while smoking explained 2.7% and maternal weight 2.0%. There was a trend towards a negative relationship with glycated haemoglobin concentration at 6-12 weeks. Smoking and glycated haemoglobin concentration were strongly intercorrelated., Conclusions: Most of the variance in standardised birthweight remains unexplained, but glycated haemoglobin concentration at 27-33 weeks is the most powerful explanatory variable. Possible reasons why there is not a stronger relationship between markers of maternal glycaemia and birthweight are discussed.

Before any new antenatal screening test is introduced, the opinions of pregnant women should be considered. This is particularly relevant with HIV testing. This qualitative study reports the views of 29 women attending an antenatal clinic in a large maternity hospital in Scotland where a trial of different ways of offering HIV testing on a universal, voluntary basis occurred. Women were in favour of a test offer, although they did not necessarily wish to accept testing for themselves. Generally they were more worried about having an unhealthy baby. There was a commonly held view that routine testing would cause less anxiety because it would eliminate the stigma of saying yes to testing. A move towards the HIV test being recommended to pregnant women as opposed to merely offered is likely to be acceptable, would probably increase uptake rates and should therefore be assessed.

Objective: To determine the uptake and acceptability of different methods of a universal offer of voluntary HIV testing to pregnant women., Design: Randomised controlled trial involving four combinations of written and verbal communication, followed by the direct offer of a test. The control group received no information and no direct offer of a test, although testing was available on request., Setting: Hospital antenatal clinic covering most of the population of the city of Edinburgh., Subjects: 3024 pregnant women booking at the clinic over a 10 month period., Main Outcome Measures: Uptake of HIV testing and women's knowledge, satisfaction, and anxiety., Results: Uptake rates were 6% for those in the control group and 35% for those directly offered the test. Neither the style of leaflet nor the length of discussion had an effect on uptake. Significant independent predictors of uptake were a direct test offer; the midwife seen; and being unmarried, previously tested, and younger age. Knowledge of the specific benefits of testing increased with the amount of information given, but neither satisfaction nor anxiety was affected by the type of offer., Conclusions: The universal offer of HIV testing is not intrusive and is acceptable to pregnant women. A policy of offering the HIV test to all women resulted in higher uptake and did not increase anxiety or dissatisfaction. Uptake depends more on the midwife than the method of offering the test. Low uptake rates and inadequate detection of HIV infection point to the need to assess a more routine approach to testing.

Objective: To explore the effect of human immunodeficiency virus (HIV) infection and drug use on birth weight, length, and gestational duration at delivery., Methods: Subjects had a history of injection drug use or a sexual partner who was an injection drug user, were Scottish, and their HIV serostatus during pregnancy was known. Control pregnancies were matched for age, parity, ethnic group, year of delivery, and postal code sector of home address. In addition, some were matched for smoking and housing deprivation score. Birth weights were standardized for gestational age by expressing them as z scores with a mean of zero and a standard deviation of unity. Statistical analysis was by univariate and multiple regression with multilevel modeling., Results: Regression analysis for birth weight, gestational age, and gestation-adjusted birth weights (z score) included 789 pregnancies in 693 women. Human immunodeficiency virus seropositivity was associated with a z score that was 0.27 lower (P = .03), but there was no significant difference in gestational duration at delivery. Current oral or injection drug use were associated with a reduction in standardized birth weight (z score -0.27, P = .06, and z score -0.28, P = .04, respectively), and injection drug use with a reduction in occipitofrontal circumference only (1.8 cm reduction, P = .05). Injection drug use, but not the other factors, had an effect on gestational age at delivery (1.54 weeks earlier, P < .001)., Conclusion: Although HIV seropositivity is associated with a small reduction in standardized birth weight, this effect is less than that attributable to smoking and may not be of clinical significance. The effect seems to be associated with placental size. Opiate use, regardless of route, had a small association with reduced birth weight, suggesting a specific drug effect. However, only injection drug use had a strong association with early delivery, and this effect was likely to be clinically significant at the population level.

Objective: To study prospectively the prediction power, at different gestations, of clinical and ultrasound measurements for fetal size in diabetic pregnancy., Setting: A large combined obstetric diabetic clinic in a teaching hospital., Participants: One hundred and eighty-one pregnancies in which women had scans at least two of three specific time points and who were delivered of singletons after 34 weeks: 73% were pre-gestational insulin-dependent diabetics, the others were pre-gestational White class A or gestational diabetics., Interventions: Clinical estimates of fundal height and fetal size and ultrasound estimates of abdominal circumference and head circumference were routinely carried out at gestational ages of 28, 34 and 38 weeks or before delivery., Main Outcome Measures: Standardised birthweight, corrected for gestation and parity. The relation with clinical and ultrasound measurements was investigated using multiple linear regression and the capability of the measurements to predict macrosomic births (> 95th centile of normals) using receiver-operator characteristic curves., Results: All measurements are poor predictors of eventual standardised birthweight. Prediction improves with closeness to delivery. Prediction is significantly improved by adding ultrasound to clinical information, but at 34 weeks or later this only contributes 8% of the variance. There is no difference in the prediction power for macrosomia between clinical and ultrasound measurements., Conclusions: Even regular serial scanning and clinical examination will not always diagnose the macrosomic fetus in diabetic pregnancy. In our hands, clinical examination is as predictive as ultrasound measurements. Ultrasound does add to clinical prediction power but only to a small extent. Ultrasound should be used in a selected way, as defined by clinical findings, and with recognition and understanding of the errors and biases involved.

Objective: To assess whether a simple urine based estimate of relative daily nicotine intake could predict smoking related birthweight deficits more accurately than self-reported cigarette consumption., Design: Active smokers were identified by a simple qualitative colorimetric urine test procedure and their relative nicotine intakes assessed by determining the ratios of the urinary concentrations of nicotine plus its metabolites to creatinine using automated colorimetric methods., Setting: A large teaching hospital., Participants: Three thousand and thirty-eight mothers from whom smoking histories had been elicited and who gave birth to live singleton babies after 28 weeks of gestation., Main Outcome Measures: Birthweights (adjusted for maternal weight, maternal age, baby's sex, parity and length of gestation), maternal weight gains during pregnancy and placental weights., Results: The adjusted birthweight deficits of babies born to proven active smokers averaged 226 g (95% confidence interval 194 g to 258 g), but dose dependent effects were only apparent when nicotine intake was based on urinary nicotine metabolites/creatinine ratios. Among the smokers, adjusted birthweights fell linearly with increasing nicotine intakes but gave a predicted mean birthweight for nonsmokers that was 102 g (95% CI 50 g to 154 g) lighter than that actually found (P < 0.0001). Maternal weight gains during pregnancy were substantially reduced in smokers and correlated more closely with urinary nicotine metabolite excretions than with reported daily cigarette consumptions. Placental weights were unaffected by smoking., Conclusion: There was a closer dose-effect relationship between birthweight deficits and urinary nicotine metabolites/creatinine ratios than with self-reported daily cigarette consumptions. The influence of nicotine exposure on birthweight appears to be biphasic, with one mechanism operating at very low levels of tobacco smoke intake and the other causing seemingly linearly related effects over the whole range of nicotine intakes of active smokers. These findings support recent evidence that passive smoking can cause substantial birthweight deficits.

The infant of an insulin-dependent diabetic mother is at increased risk of perinatal death, neonatal problems and major congenital malformations: Many of these problems are preventable. All young women with diabetes should receive contraceptive advice and information about pregnancy. The objects of pre-pregnancy care are to assess suit-ability for pregnancy, to optimise control in early pregnancy and to improve pregnancy outcome through the provision of individualised education and information. Pre-pregnancy care can reduce the congenital malformation rate to approximately that of the nondiabetic. In each area there should be one designated diabetologist and one designated obstetrician who, together with their team, should see all pregnant women in a combined clinic in a hospital with an intensive care baby unit. All pregnant women with diabetes should have 24-hour access to the specialist team. Tight glycaemic control during pregnancy can reduce complications of pregnancy greatly, improving infant mortality and morbidity. Insulin requirements usually change during pregnancy. Education about hypoglycaemia and avoidance of ketoacidosis is essential. Women should have regular examination of the fundi and renal function. They should have ultrasound scanning to assess gestation, to look for abnormalities and to assess fetal growth. Fetal monitoring should be used, particularly for those at high risk. Women with good diabetic control and no complications of diabetes or pregnancy may be delivered at 39 to 40 weeks but those at high risk earlier. During labour or caesarean section blood glucose should be normalised using intravenous glucose and insulin supervised by a specialist team. An experienced paediatrician should be available. Breast feeding should be encouraged.

A retrospective analysis of routine child health surveillance information was performed on health visitor records of 459 children, to examine the independent effects of maternal HIV infection and drug use during pregnancy on morbidity in the first 3 years of life. No significant differences were observed in the developmental progress of children born to HIV infected or drug using women when compared to community controls. The pattern of medical consultations in the first 18 months of life was significantly different, maternal drug use exerting a negative influence on outpatient visits (odds ratio 0.6, 95% confidence interval 0.4 to 1.0). At 6 weeks, the majority of children lived with their birth parent(s), and no differences were observed between the groups. By 10 months of age, only 81% of children born to HIV infected drug using women lived with their parent(s). While maternal drug use and HIV did not have adverse effects on child health and development, these findings highlight the social implications for children affected by the heterosexual spread of HIV.

Objective: To determine the separate effects of maternal HIV infection and drug use during pregnancy on growth of uninfected children in their first 3 years., Design: Retrospective analysis of measurements from health visitor records made during routine child health surveillance at 6 weeks, 10 months, and 3 years of age. Multilevel analysis allowed for between-infant variation in fitted growth lines, and adjustment for other factors. Growth was described in terms of an intercept (z score at term) and growth slopes (change in z score per year) up to, and from, 4 months., Subjects: 290 case babies delivered in Edinburgh hospitals to women who reported injection drug use by either themselves or their HIV infected partner, and 186 community controls. A total of 131 (45%) of the case babies were born to women who used drugs, predominantly opiates, during pregnancy and 93 (32%) to HIV infected women. The eight infected children were excluded from analysis., Main Outcome Measures: Age and sex standardised z scores for height, weight, and body mass index., Results: 459 (96%) of the 476 records for cases and controls were traced, yielding 1432 weight and 939 height measurements. Maternal HIV infection was not found to affect growth; at 3 years the estimated effect on weight z score was 0.16 with 95% confidence interval (-0.25 to 0.57) and for height 0.18 (-0.19 to 0.55). Drug use during pregnancy was associated with lighter babies at 40 weeks followed by depressed growth in the first four months, these infants remaining just slightly smaller at 3 years with an estimated effect on z scores of -0.5 for weight with 95% confidence interval (-0.89 to -0.11) and -0.37 (-0.72 to -0.02) for height., Conclusions: Maternal HIV infection does not adversely affect growth in uninfected infants, and the effect of drug use during pregnancy is limited to small decrease in size at 3 years.

Objective: To identify the date of ovulation in pregnant women with Type 1 diabetes in order to assess the validity of the concept of early growth delay., Design: Identification of ovulation by measurement of urinary luteinising hormone and assessment of fetal growth using ultrasound scan., Setting: Diabetic pre-pregnancy and antenatal clinic in a teaching hospital., Subjects: Twenty women with Type 1 diabetes who had attended a pre-pregnancy clinic., Measures: Urinary LH, by laboratory and kit methods, during conception cycles. Human chorionic gonadotrophin measured in early pregnancy. Early ultrasound scans by a single observer blind to menstrual and ovulation dates., Outcome: Gestation calculated from ovulation date and gestation estimated from menstrual dates, compared with gestation at age indicated by early ultrasound scan., Results: When the date of ovulation was identified in 20 women with Type 1 diabetes there was no evidence of growth delay in any pregnancy. When gestation was estimated from menstrual dates there was apparent early growth delay in six pregnancies., Conclusion: This study, together with others discussed, indicates that early growth delay is probably an artefact of incorrectly estimated ovulation date.

In Scotland since January 1990, unlinked anonymous testing of Guthrie cards has documented maternal HIV-1 antibody in neonatal blood. District postcode and quarter year of birth determined prevalence and spread of infection. The Fujirebio particle agglutination assay screened for HIV-1 antibody, with confirmation by ELISA and full western blotting. Births to known HIV infected women were reported to the Royal College of Obstetricians and Gynaecologists. 0.3/1000 childbearing women were infected with HIV-1 with no significant increase from 1990 to 1992. Spread of infection from 11 to 26 districts has occurred. In 1990, 74%(14/19) of HIV positive deliveries were known to obstetricians falling to 33%(7/21) in 1992. Spread of HIV-1 infection has occurred to mothers who live outside closely defined areas and who do not belong to recognised high risk groups. In Scotland, two thirds of mothers and their infants will not receive early prophylactic care for their HIV disease.

Objective: To study a geographically defined population of women exposed to a drug-related risk for human immunodeficiency virus (HIV), together with carefully matched neighbourhood controls, in order to examine (1) the proportion of different groups having cervical cytopathology screening; (2) the association between HIV infection and cervical intraepithelial neoplasia; (3) the independent effect of CD4+ lymphocyte count and duration of HIV infection; and (4) the correspondence between cervical cytopathology and colposcopically directed biopsy., Design: A population-based study., Subjects: All women domiciled in Lothians with the following characteristics: between 1983 and 1987 they had a history of injection drug use or a seropositive partner with a history of injection drug use; they had a pregnancy after that exposure where their serostatus was known. In addition, neighbourhood controls were identified by computer matching for the following criteria--post-code sector, housing deprivation score, age, parity, pregnancy outcome, ethnic group, year of pregnancy, smoking., Main Outcome Measures: Search was carried out for the cervical smear nearest in time to the index pregnancy end date, providing serostatus was known at that time. All identified smears were assessed by a cytopathologist without knowledge of clinical information, study group or serostatus., Results: Of 376 women, appropriate cervical smears were identified for 336. The proportions screened in the different groups were similar. There were more abnormal smears in the seropositive group than in the drug-related seronegative (P < 0.01) or the neighbourhood control groups (P < 0.001). HIV-infected women with abnormal smears had lower CD4+ lymphocyte counts (P < 0.0005). There was a reasonable correspondence between cytopathological classification and histological grading, and this was of similar strength in cases and controls (weighted kappa 0.72, 0.74)., Conclusions: There is a definite relation between HIV infection and cervical intraepithelial neoplasia. This is related to immune depletion but whether this is the sole mechanism for the association is unclear.

Objective: To determine whether lymphocytic infiltration of the endometrium accompanies human immunodeficiency virus (HIV) infection., Methods: Endometrial samples from 12 HIV-infected women and from rigorously matched controls were examined. The following markers were used: common leukocyte antigen (CD45), T lymphocytes (CD3), monocytes-macrophages (CD68), and CD4 and CD8 lymphocytes. Cell counts were performed without knowledge of HIV status. Factors considered in relation to these markers were menstrual symptoms, pelvic pain, peripheral blood CD4+ count, and time since seroconversion., Results: Histology showed conventional features of chronic endometritis in only one case. In the remainder, the endometrium of HIV-infected women, compared with controls, showed an increase in CD45 cells (P < .02) and an increase in CD3 staining cells (P < .05). This appeared to be restricted to those with menstrual symptoms, and this group also had lower peripheral blood CD4 counts. There was no difference in cells of the monocyte-macrophage series (CD68). In contrast to control samples, CD4 lymphocytes were infrequent or absent in the endometrium of HIV-infected women, regardless of peripheral blood CD4 count or presence of menstrual symptoms; however, this was not universal, as one sample showed an area of dense CD4 cell infiltration. The ratio of CD4 to CD8 was reduced in HIV-seropositive samples compared with controls (P < .02)., Conclusion: We hypothesize that chronic endometritis of a nonclassical form may be common in advancing HIV disease, possibly directed against HIV-infected cells or self-determined antigens. This could be associated with morbidity and may represent a reservoir of infection. Endometrial depletion of CD4 cells is a common, but not universal, feature and may be independent of immune compromise.

The objective was to study the changes in pregnancy HIV prevalence with time. Data were collected from multiple sources to provide a comprehensive record of all HIV seropositive pregnant women identified in the Edinburgh area (Scotland) until December 1992. There were 177 pregnancies in 108 HIV seropositive identified women. Risk factors were injection drug use (79% of pregnancies) and a known HIV seropositive injection drug-using partner (16%). Prevalence has decreased for Edinburgh City women from 0.5% of all pregnancies in 1986 to 0.1% in 1992; It was higher for induced abortion (0.6%) than for delivery (0.2%). HIV testing in pregnancy has declined. Comparison with unlinked anonymized testing showed that in 1990-1991, 20/22 seropositive women were known. In 1992, only 3 of 10 seropositive pregnancies were identified. The cohort initially infected by exposure to a 'drug related' risk factor between 1983 and 1985 may have increasingly finished childbearing, deliberately decided against pregnancy because of HIV status, and declined because of death, illness and emigration from the area, There may not have been major early tertiary heterosexual spread; however, data from 1992 suggest that this could now be impacting on pregnancy prevalence. Local testing policies have not adapted to this possible change.

Objective: To assess the reports that maternal phosphoglucomutase-1 (PGM1) phenotype is highly related to macrosomia in diabetic pregnancy. This could be either a direct metabolic phenomenon, or the PGM1 locus could be a marker for a tightly linked gene involved in the maternal control of fetal growth., Design: A comparative biochemical genetic study., Setting: A large diabetic pregnancy clinic., Subjects: One hundred and fifty-two women who had diabetes during pregnancy, 136 being insulin dependent before pregnancy. Two hundred and thirty-six women without pre-existing medical or pregnancy complications who functioned as a control group., Measures: PGM1 phenotype was assessed by conventional electrophoresis and subgroups were examined using iso-electric focusing., Outcome: Standardised birthweight was corrected for sex, maternal parity and gestation confirmed in every case by early pregnancy ultrasound. Maternal diabetes control was assessed by glycosylated haemoglobin., Results: No differences were found in the observed phenotype frequencies for diabetics and control pregnant women. No association between PGM1 phenotype and macrosomia in diabetic pregnancy was found. PGM1 did not make a significant contribution to birthweight, standardised birthweight, length or ponderal index of the baby as assessed by multiple regression., Conclusions: Our study of a larger number of insulin dependent diabetics in Scotland makes the claim that macrosomia in diabetic pregnancy is associated with PGM1 phenotype unlikely to be of general significance.

Objectives: To document individual variations in the rise in insulin requirements during type I diabetic pregnancies, to relate the degree of increase to maternal characteristics and fetal outcome, and to examine these factors in a subgroup of patients experiencing a large fall in insulin requirement in the third trimester., Methods: Insulin dose was documented in 237 pregnancies in women with type I diabetes. Multiple regression analysis was performed to identify significant associations with maternal and fetal characteristics. Eighteen pregnancies with a fall in insulin requirement of 30% or more in the third trimester were considered in detail., Results: The mean absolute increase in insulin requirement was 52 units. The degree of rise was significantly related to maternal weight gain between 20-29 weeks and maternal weight at booking, and was inversely related to duration of diabetes. It was not related to the degree of diabetes control, complications of pregnancy, White class, or outcome of pregnancy. In the 18 women experiencing a large fall in insulin requirement, there was no relation with maternal characteristics or fetal outcome., Conclusion: There is a wide individual variation in the change in insulin requirements in type I diabetic pregnancy. The degree of increase is related only to maternal weight gain during weeks 20-29 and maternal weight at booking, and is inversely related to duration of diabetes. Large falls in insulin requirement remain unexplained and may not be associated with placental failure.

This study investigates reports that phosphoglucomutase-1 (PGM1) phenotype is associated with fetal growth and gestation length. A total of 350 women were studied, 234 having uncomplicated pregnancies and 114 with a baby weighing greater than 90th centile, corrected for parity, gestation and fetal sex. All women had gestation confirmed by early ultrasound. Conventional cellulose acetate electrophoresis was used to distinguish the three common PGM1 phenotypes and polyacrylamide gel isoelectric focusing to distinguish the ten PGM1 subtypes. Neither PGM1 phenotype nor subtype were found to be associated with gestation length or standardised birth weight. Logistic regression, where maternal age, parity, fetal sex, maternal weight, gestation and smoking were introduced as explanatory variables in addition to PGM1 phenotype testing against the dependent variables birth weight, standardised birth weight and gestation length, did not show differences related to PGM1 phenotype. Two possible reasons for the discrepancy with previously published data are discussed. We conclude that the study provides no support for the belief that PGM1 phenotype is related to fetal growth or gestation length and that the original observations could have arisen as a result of statistical artefact due to multiple testing.

Objective: To assess the effect on obstetric practice of clinician access to umbilical artery Doppler ultrasound results., Design: Randomised controlled trial., Setting: A large teaching hospital., Subjects: Two thousand two hundred and eighty-nine pregnancies defined as being at risk by referral for Doppler or fetal monitoring., Interventions: Continuous wave Doppler studies of umbilical artery. Results immediately available to clinicians., Main Outcome Measures: Fetal outcome: perinatal mortality, Apgar score and admission to the neonatal unit. Obstetric intervention: admission to hospital, induction of labour and caesarean section. Use of of fetal well being: cardiotocography, biophysical profile and ultrasound biometry., Results: The treatment and control groups were comparable in age, parity, gestation at point of entry and risk features. There were no overall differences in perinatal outcome, obstetric intervention or use of fetal monitoring. Examination of a subset recruited only because of hypertension or suspected intrauterine growth retardation (n = 754) similarly showed no difference attributable to group randomisation. Comparison of only those pregnancies retrospectively defined as low risk and high risk showed more use of cardiotocography in the high risk group with access to Doppler (P = 0.007) but no difference in the low risk group., Conclusion: Doppler umbilical artery recording has been shown to perform well in prediction power of antenatal fetal compromise. What has been examined in this study is the response of clinicians to the test. The results suggest that obstetricians do not use the test to modify their risk assessment, and, therefore, the need for fetal monitoring in particular pregnancies. There is a real need for accumulation of information from very large data sets, particularly in the prediction power of Doppler for antenatal fetal compromise from apparently chronic utero-placental cause to guide use of monitoring resources. If simply added to existing fetal monitoring techniques in a hospital where these are widely used, then umbilical artery Doppler recordings may at present simply involve extra resources of staff and expenses, without benefit.

In order to identify features associated with an increased risk of transmission of HIV from seropositive women to their offspring, 70 children of 58 HIV seropositive mothers were studied. Fifty-six children were followed prospectively from pregnancy; in 14 identified after the puerperium, obstetric notes were reviewed and stored serum was tested. Twelve infants of 10 mothers were HIV infected. Risk of transmission was increased in the first year after seroconversion; 5/9 infants born at this time were infected compared with 7/61 born subsequently (P < 0.001). Progression to stage IV in transmitters was more likely, occurring in the mothers of 9 infected children at a median of 3 years (range 0.5-6.5) and in mothers of 19 non-infected children at a median of 5 years (range 1-7) (P = 0.032). Maternal CD4+ counts < 400 x 10(6)/l were found in 7/12 transmitting and 7/49 non-transmitting pregnancies (P < 0.01). Differences in HIV antigenaemia did not reach significance. These factors may influence the counselling of mothers regarding their child's and their own prognosis.

HIV infection is a common medical problem in pregnancy in many parts of the world. Management involves supportive multiagency care, easy and effective communication, an awareness and understanding of other issues (which may be more important to the mother than her HIV infection), and specialists with both experience and an up-do-date knowledge base.

Objective: To examine the suggestion, based on theoretical considerations and case reports, that pregnancy decreases survival time after AIDS (acquired immunodeficiency syndrome)., Design: A total population study in Edinburgh., Setting: A city with a moderately high prevalence of human immunodeficiency virus (HIV) infection in women., Subjects: AIDS has been diagnosed in 22 women, five of whom had a pregnancy., Main Outcome Measures: Clinical characteristics, disease presentation, lymphocyte markers, pregnancy outcome, subsequent progress and survival time., Results: Pregnancy was not obviously associated with a difference in clinical findings. The mean survival time for the three women with a pregnancy who died was 24 months and for the 11 women without a pregnancy it was 15 months. (P = 0.63 log rank test)., Conclusions: The clinical presentation, severity of the illness and laboratory findings were not obviously different in pregnancy. All three women who had Pneumocystis carinii pneumonia for the first time in pregnancy survived this initial episode. Survival time was not obviously reduced by the conjunction of pregnancy with AIDS.

Abnormal anticardiolipin antibodies are associated with adverse pregnancy outcome in the general obstetric population. We studied 55 pregnancies in women infected with human immunodeficiency virus type 1 (HIV-1) to examine two hypotheses: that a substantial proportion of these women would have raised anticardiolipin antibodies, and that the affected pregnancies would be more likely to be complicated by preterm delivery and intrauterine growth retardation. Blood was taken at the initial antenatal visit, and was also taken from 15 HIV-seronegative intravenous (IV) drug users and 20 controls with no drug history. The reference for immunoglobulin G class antibodies to cardiolipin was calculated from 50 healthy young adults, and the upper limit of normal was defined as 4 standard deviations above the mean for this reference series. Twenty-four percent of the infected women, but none of the HIV-seronegative IV drug users and none of the control group, had raised anticardiolipin antibodies. There was no statistically significant relationship with birth weight, standardized birth weight, length, gestation, occipitofrontal circumference, or adverse pregnancy outcome. No women gave a history of thromboembolism or recurrent abortion, and in no pregnancy was there clinically apparent thromboembolism. We conclude that abnormal anticardiolipin antibodies provoked by HIV infection are common, but probably have a narrow specificity for cardiolipin, are unrelated to phospholipid antibody syndrome, and cannot explain adverse pregnancy outcome in HIV-infected women.