Inverse changes in fetal insulin-like growth factor (IGF)-1 and IGF binding protein-1 in association with higher birth weight in maternal diabetes.

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.

Maternal nutritional risk factors for small for gestational age babies in a developed country: a case-control study.

AIMS: To assess the effect of maternal diet during pregnancy on the risk of delivering a baby who is small for gestational age (SGA). METHODS: Case-control study of 844 cases (SGA) and 870 controls (appropriate size for gestational age (AGA)). Only term (37+ completed weeks of gestation) infants were included. Retrospective food frequency questionnaires were completed at birth on the diet at the time of conception and in the last month of pregnancy. RESULTS: At the time of conception, mothers of AGA infants ate significantly more servings of carbohydrate rich food and fruit, and were more likely to have taken folate and vitamin supplements than mothers of SGA infants. There was some evidence that mothers of AGA infants also ate more servings of dairy products, meat, and fish (0.05 < p < 0.1). However, after adjustment for maternal ethnicity, smoking, height, weight, hypertension, and occupation, fish intake (p = 0.04), carbohydrate-rich foods (p = 0.04), and folate supplementation (p = 0.02) were associated with a reduced risk of SGA. In the last month of pregnancy, only iron supplementation was associated with a reduced risk of SGA (p = 0.05) after adjustment for potential confounders. CONCLUSIONS: This study suggests that small variations in maternal diets within the normal range during pregnancy in developed countries are associated with differences in birth weight.

An online tool for investigating clinical decision making.

BACKGROUND: Induction of labour is a common clinical intervention. There has been a recent rise in rates of induction of labour and wide variation between published hospital rates without obvious explanation. Clinician variation has been suggested as a reason. OBJECTIVE: The study described aimed to examine clinical decision making, whilst removing individual patient bias. To achieve this clinical behaviour was studied by the use of imaginary clinical scenarios presented to clinicians by computer. Unlike retrospective audit, the rates thus generated are unaffected by differences in casemix, pressure of time, work or other factors and allow direct comparison between clinicians and comparison with clinical guidelines. METHODS: Data about 15 imaginary pregnant women are presented to the clinician, each may have symptoms or signs of hypertensive disorders, intrauterine growth restriction (IUGR) and/or postdates. From the decision made in each scenario, and the information revealed about each scenario, a set of 'decision rules' is created for each clinician, describing in what circumstances they would induce labour. Data from the National Women's Hospital (Auckland, New Zealand) is then examined using these rules and the induction of labour rate thus generated presented to the clinician. RESULTS: Sixteen clinicians were interviewed. Their induction of labour rate ranged from 10-31%. CONCLUSIONS: Clinician variation in decision making is evident about the intervention when to induce labour. The system is available on the WWW at http://csrs2.aut.ac.nz/scenario

Stress and lack of social support as risk factors for small-for-gestational-age birth.

AIM: To determine the contributions of social support and perceived stress to the risk of small-for-gestational-age birth. METHODS: The investigation was a case-control study of mothers of infants born at 37 or more completed weeks of gestation. Cases weighed less than the sex-specific 10th percentile for gestational age at birth (small for gestational age (SGA), n = 836), and controls (appropriate for gestational age (AGA), n = 870) comprised a random selection of heavier babies. RESULTS: In univariate analyses measures of informal social support, but not perceived stress or formal social support, were associated with SGA birth. It was found that Asian mothers are less likely to receive support from families and friends. After adjustment for ethnicity, informal social support was not associated with SGA. CONCLUSIONS: Support appears to reduce the risk of SGA births, but after adjustment for ethnicity this is no longer the case. Stress during pregnancy was not associated with SGA birth.

Smoking, nicotine and tar and risk of small for gestational age babies.

AIMS: To assess the effect of maternal smoking and environmental tobacco smoke (ETS) on risk of small for gestational age infants (SGA). METHODS: Case-control study of 844 cases and 870 controls. RESULTS: Maternal smoking in pregnancy was associated with an increased risk of SGA (adjusted odds ratio (OR)= 2.41; 95% confidence interval (CI) = 1.78, 3.28). We could not detect an increased risk of SGA with paternal smoking, or with other household smokers when the mother was a non-smoker, but did find an increased risk with exposure to ETS in the workplace or while socializing. Infants of mothers who ceased smoking during pregnancy were not at increased risk of SGA, but those who decreased but did not stop remained at risk of SGA. There was no evidence that the concentration of nicotine and tar in the cigarettes influenced the risk of SGA. CONCLUSIONS: Maternal smoking in pregnancy is a major risk factor for SGA. This study suggests that mothers should be advised to cease smoking completely during pregnancy, and that a reduction in the number of cigarettes smoked or smoking low tar or nicotine concentration cigarettes does not reduce the risk of SGA.

Risk factors for small-for-gestational-age babies: The Auckland Birthweight Collaborative Study.

OBJECTIVE: This case-control study determined whether internationally recognized risk factors for small-for-gestational-age (SGA) term babies were applicable in New Zealand. METHODOLOGY: All babies were born at 37 or more completed weeks of gestation in one of three hospitals in Auckland. Cases weighed less than the sex specific 10th percentile for gestational age at birth, and controls (appropriate-for-gestational-age (AGA)) were a random selection of heavier babies. Information was collected by maternal interview and from obstetric databases. RESULTS: Information from 1714 completed interviews (844 SGA and 870 AGA) was available for analysis. Computerized obstetric records were available for 1691 of the 1701 women who consented to such access. In a multivariate analysis allowing for sex, gestational age at birth, social class and other potential confounders, mothers who smoked had a significantly increased risk of an SGA baby (adjusted OR 2.41; 95% CI 1.78-3.28), as did primiparous mothers (adjusted OR 1.34; 95% CI 1.03-1.73), mothers of Indian ethnicity (adjusted OR 3.22; 95% CI 1.95-5.30), women with pre-eclamptic toxaemia (adjusted OR 2.42; 95% CI 1.08-5.40) and those with pre-existing hypertension toxaemia (adjusted OR 5.49; 95% CI 1.81-16.71). Mothers of SGA infants were shorter (P < 0.001) and reported lower prepregnancy body weights (P < 0.001) than mothers of AGA infants. The population attributable fraction for smoking suggests that up to 18% of SGA infants born in the ABC Study could be related to maternal smoking. CONCLUSIONS: Risk factors associated with SGA births in other countries are also important in New Zealand. Smoking in pregnancy is an important and potentially modifiable behaviour, and efforts to decrease the number of women who smoke during pregnancy should be encouraged.

Ultrasonographic surveillance in red blood cell alloimmunization.

OBJECTIVE: This study was undertaken to audit ultrasonographic measurements of fetal liver length and middle cerebral artery peak velocity in cases of red blood cell alloimmunization between 1986 and 1999. STUDY DESIGN: A total of 200 fetuses at risk for anemia because of red blood cell alloimmunization underwent ultrasonographic measurement of the length of the right lobe of the liver, 45 underwent Doppler recording of middle cerebral artery peak velocity, and 119 underwent fetal blood sampling. RESULTS: The overall survival was 188 of 200 (94%). Among 69 fetuses found to have anemia, liver length values in 64 (93%) were at the 95th percentile or greater, and the other 5 were in the upper part of the normal range. The middle cerebral artery peak velocity was > or =95th percentile in 15 of the 19 cases of anemia in which this value was measured (79%). Among those measured within 1 week of birth, all liver lengths were at least in the upper part of the normal range, with most >95th percentile, including 1 case with a cord blood hemoglobin concentration <90 g/L. CONCLUSIONS: All fetuses with anemia identified at fetal blood sampling had enlarged livers with 93% at > or =95th percentile. The peak velocity in the middle cerebral artery was abnormal in most fetuses with anemia.

Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome? A randomized controlled trial.

OBJECTIVE: This pilot investigation was undertaken to assess the efficacy of low-dose aspirin therapy for the treatment of women with antiphospholipid antibodies when recurrent miscarriage is the only sequela. STUDY DESIGN: A double-blind, randomized, placebo-controlled trial was conducted in the setting of the recurrent miscarriage clinic of a tertiary referral obstetric hospital. The participants were 50 women with a history of recurrent miscarriages (>/=3) and antiphospholipid antibodies. Women with systemic lupus erythematosus or a history of thrombosis were excluded. Women were recruited after full investigative screening at the recurrent miscarriage clinic. Women with >/=3 fetal losses and persistently positive results for antiphospholipid antibodies were randomly allocated to receive either aspirin (75 mg daily) or placebo. Investigators, clinicians, and patients were blinded to the treatment. Rates of live births, antenatal complications, and delivery and neonatal outcomes were recorded prospectively. Data were compared by chi(2) analysis with Yates' correction, the Fisher exact test, or the Student t test as appropriate. RESULTS: There were 10 exclusions after random assignment because of inappropriate inclusion. Eighty-five percent of the placebo (17/20) group and 80% of the aspirin-treated group (16/20) were delivered of live infants. This difference was not significant. There were no significant differences in antenatal complications or neonatal morbidity between the groups. CONCLUSIONS: This preliminary study suggests that low-dose aspirin has no additional benefit when added to supportive care for women for whom recurrent early fetal loss is the only sequela of the antiphospholipid syndrome. This live birth rate with supportive care alone exceeds the published live birth rates for women with antiphospholipid antibody-mediated recurrent fetal loss who were treated with heparin or corticosteroids. This trial, like all other trials in this field, is small, but its results bring into question the need for pharmacologic intervention for women with antiphospholipid syndrome for whom recurrent fetal loss is the only sequela. Our results highlight the need for a large randomized controlled trial to identify the optimal treatment for this group of women and justify the inclusion of a placebo arm in any such trial.

Fetal fibronectin detection in preterm labor: evaluation of a prototype bedside dipstick technique and cervical assessment.

OBJECTIVE: The aims of this study were to evaluate a prototype bedside test for fetal fibronectin detection in women with symptoms of preterm labor, to compare the efficacy of obtaining fetal fibronectin swabs with and without a speculum, and to assess the value of combining the fetal fibronectin test with cervical dilatation for predicting delivery within 10 days. STUDY DESIGN: This investigation prospectively studied a cohort of women with symptoms of preterm labor (n = 121), gestational age between 24 and 33 6/7 weeks, and cervical dilatation /=1 cm predicted delivery within 10 days with sensitivity, specificity, and positive and negative predictive values of 71%, 87%, 46%, and 95%, respectively, with positive and negative likelihood ratios of 5.5 and 0.33, respectively. Combination of fetal fibronectin testing with cervical dilatation >/=1 cm did not significantly improve the fetal fibronectin test characteristics. After exclusion of women with slight vaginal bleeding, cervical dilatation >/=1 cm and fetal fibronectin status remained the only independent variables associated with delivery within 10 days. CONCLUSION: Fetal fibronectin testing according to this prototype may have a limited role in clinical decision analysis. In this study a cervical dilatation >/=1 cm had predictive values equivalent to those of the fetal fibronectin test, and it should be evaluated further in a clinical setting.

Female sterilisation: National Women's Hospital 1988-9.

AIM: To determine the failure rate of all female sterilisation procedures performed at National Women's Hospital in order to identify ways of improving the service. METHODS: A review was made of all sterilisation procedures performed at National Women's Hospital in 1988 and 1989. All patient notes and theatre records were examined. A consumer questionnaire was mailed to all patients monthly for 3 months. If there was no response efforts were made to contact these women via their last known general practitioner. Epsom Day Hospital where 95% of all terminations of pregnancy in Auckland are performed also examined their records. RESULTS: 1094 procedures were performed at National Women's Hospital in Auckland during 1988 and 1989. Failures were classified into two groups: those pregnant at the time of surgical procedure (administrative failures) and those pregnant after the procedure (surgical failure). There were 15 surgical failures (1.4%). Laparoscopy using Filshie clips was the most common method used and had a 1.2% surgical failure rate. Registrars had a 1.3% failure rate, consultants 1.9% and when both a consultant and registrar performed the procedure a failure rate of 0.7% was recorded. Eighty-six percent (6/7) of women who had a subsequent laparotomy after a failed sterilisation were found to have surgical misapplication of the occlusive device. There were 7 (0.6%) women who were pregnant at the time of the procedure. There were no patient or procedure-related factors which were associated with failures. CONCLUSION: Sterilisation is associated with a significant failure rate. Contraception counselling at the time of booking for the procedure needs to be improved. Preoperative pregnancy testing should be introduced to avoid sterilisation procedures in early pregnancy. Surgical misapplication of devices was a common cause of failure, not recanalisation as found elsewhere. From this review it would appear that the involvement of two surgeons lowers the failure rate.

The effect of human anticardiolipin antibodies on murine pregnancy.

Anticardiolipin antibodies (aCL) were affinity purified or isolated in the IgG fraction of serum from 6 patients with antiphospholipid antibody syndrome. Anticardiolipin antibodies from one patient consistently compromised murine pregnancy. However in 92% (45 of 49) of cases injection of human anticardiolipin antibodies had no adverse effect on murine pregnancy, regardless of whether affinity purified aCL or IgG fractions were used. It is concluded that in most cases human anticardiolipin antibodies alone do not induce murine fetal loss.

Comparison of tests for the lupus anticoagulant and antiphospholipid antibodies in systemic lupus erythematosus.

A variety of laboratory assays are used to screen for the presence of the lupus anticoagulant. Six commonly used coagulation tests, and the ELISA assay for antiphospholipid antibody using three different substrate phospholipids, have been evaluated in 110 patients with systemic lupus erythematosus or lupus-like disease. One or more coagulation assays was abnormal in 41% (45/110) of the patients. No individual test detected more than 78% of these abnormalities, indicating that a single phospholipid based coagulation test cannot be used to screen for a possible lupus anticoagulant. A combination of Actin FSL, DTTA and DRVVT detected all the abnormalities. The most sensitive two-test combination was Actin FSL and DRVVT. Approximately half (56%) of the patients with a positive clotting test had an abnormal antiphospholipid antibody assay. A similar proportion (58%) of the aPL positive patients had a prolonged coagulation test. The marked discordance between the coagulation assays and a positive antiphospholipid antibody test further complicates the laboratory definition of this abnormality, at least in patients with systemic lupus erythematosus.

Elution of anticardiolipin antibodies and their cofactor beta 2-glycoprotein 1 from the placentae of patients with a poor obstetric history.

Anticardiolipin antibodies (aCL) were eluted from the placentae of four women with elevated serum levels of aCL, demonstrating that these antibodies are bound to affected placentae. Anticardiolipin antibodies bound to affected placentae were only of the IgG isotype and the level of aCL in placental eluates did not reflect serum levels. Anticardiolipin antibodies were not isolated from placental eluates of control normal pregnancies. beta 2-Glycoprotein 1, the anticardiolipin antibody cofactor, was present in the placental eluates from both control and antiphospholipid antibody (aPL) affected pregnancies and was localised in the syncytiotrophoblast by immunohistochemical analysis. Antinuclear antibodies were present in the placental eluates of 3 of the 4 patients with antiphospholipid antibody syndrome and were absent from the placental eluates of control pregnancies. The authors propose that anticardiolipin antibody binds directly to placental tissue, disrupting uteroplacental blood flow and/or transport through the villi.

Antiphospholipid antibodies in pregnancy: prevalence and clinical associations.

OBJECTIVE: To determine prevalence, clinical association and predictive power of antiphospholipid antibodies in pregnancy. DESIGN: To test for the presence of anticardiolipin antibodies and lupus anticoagulant in order to confirm prevalence data which imply that each antibody has the same clinical significance. A detailed obstetric history and the outcome measures were obtained from each patient in the study. SETTING: National Women's Hospital, Auckland, New Zealand. SUBJECTS: Nine hundred and thirty-three consecutively booked pregnant women. MAIN OUTCOME MEASURES: Prevalence of auto-antibodies; perinatal morbidity and mortality; incidence of pre-eclampsia, growth retardation and fetal distress. RESULTS: Nine women (1.0%) had anticardiolipin antibodies, 11 (1.2%) had lupus anticoagulant and two had both antibodies. The fetal mortality rate for women with antibodies was 167/1000. Pre-eclampsia occurred significantly more often in women with auto-antibodies. CONCLUSION: The presence of antiphospholipid antibodies is frequently associated with adverse pregnancy outcome (9/18 pregnancies). High titre anticardiolipin antibodies carry a poor prognosis.

Antiphospholipid antibodies in pregnancy: clinical associations.

Antiphospholipid antibodies are a group of pathogenic antibodies associated with adverse pregnancy outcome. Pregnancies complicated by the presence of antibodies require careful surveillance and in specific situations therapy with low-dose aspirin, corticosteroids and/or heparin.

Inhibition of heparin/antithrombin III cofactor activity by anticardiolipin antibodies: a mechanism for thrombosis.

Anticardiolipin antibodies (aCL) are autoantibodies which react with negatively charged phospholipids and are associated with thrombotic disease and recurrent fetal loss. We have found that 11% of aCL are cross-reactive with the glycosaminoglycans heparin and heparan sulphate. One of these antibodies was studied in detail and was found to inhibit the heparin dependent activation of antithrombin III by up to 80%. The inhibition of heparin dependent antithrombin III activation represents a new mechanism by which anticardiolipin antibodies may induce thrombosis or fetal loss in some patients with these antibodies.

An obstetric scoring system: its development and application in obstetric management.

OBJECTIVE: To develop a statistically derived but clinically usable antenatal risk scoring system. METHODS: Data from 20,985 pregnancies were statistically analyzed to identify significant risk factors. Logistic regression analysis was then used to produce a final scoring system, which was subsequently tested for validity on a separate population of 3120 pregnancies. RESULTS: Twenty-seven significant antenatal variables were included in the final scoring system. Application of the system in early pregnancy resulted in a predictive accuracy of 0.73; at the onset of labor, predictive accuracy was 0.91. At the time of labor, 87% of poor outcomes were accurately identified by allocation of only 16% of the women to the high-risk group. CONCLUSIONS: It was possible to develop a risk scoring system with a predictive accuracy higher than any previously reported statistically derived score. Summation of the logistic coefficients provides a score that by comparison with a chosen threshold identifies a high-risk pregnancy. In this way, despite the complexity of statistical analysis, all clinicians can quickly apply this scoring system.

Intrauterine fetal transfusion, 1963-90.

The first fetal transfusion was performed at the National Women's Hospital in Auckland in 1963. From that time until the end of 1990, a total of 1041 transfusions have been completed on 459 fetuses. The survival rate for affected pregnancies rose significantly from 39% in 1963-65 to 90% in 1986-90. The initial 409 patients had fetal transfusions performed via the intraperitoneal cavity with X-ray guidance. Since 1986, 50 pregnancies have been treated with intravascular transfusions under ultrasound guidance and 45 fetuses survived.