Charles H. Rodeck

First and Second Trimester Antenatal Screening for Down's Syndrome: The Results of the Serum, Urine and Ultrasound Screening Study (SURUSS):

Objectives To identify the most effective, safe and cost-effective method of antenatal screening for Downs syndrome using nuchal translucency (NT), maternal serum and urine markers in the first and second trimesters of pregnancy, and maternal age in various combinations.Design A prospective study of women who booked for their antenatal care at about 8-14 weeks of gestation, with follow-up to identify pregnancies with Downs syndrome ascertained through second trimester screening or at birth.Setting Twenty-five maternity units (24 in the UK and one in Austria) offering second trimester Downs syndrome serum screening that agreed to collect observational data in the first trimester.Participants The results were based on 47,053 singleton pregnancies, including 101 pregnancies with Downs syndrome.Measurements and tests NT measurements were included if obtained between 9 and 13 weeks of pregnancy; serum and urine samples were also taken and stored. Another pair of serum and urine samples was collected in the second trimester and included if obtained between 14 and 20 weeks. Urine and serum samples from each affected pregnancy and five matched controls were tested for:Serum:alphafetoprotein (AFP)total human chorionic gonadotrophin (hCG)unconjugated oestriol (uE(3))pregnancy associated plasma protein A (PAPP-A)free beta-hCG.dimeric inhibin-A.Urine:invasive trophoblast antigen (ITA)beta-core fragmenttotal hCGfree beta-hCG.The matching criteria were gestation (using an ultrasound crown-rump length or biparietal diameter measurement), duration of storage, and centre. Screening performance of the individual markers and combinations of markers together with maternal age was assessed using standard methods. In addition pairs of first and second trimester serum samples from 600 controls were tested to secure a larger set in which screening performance could be determined using distribution parameters based on dates (time since first day of the last menstrual period).Main outcome measures The following were determined for different combinations of markers:efficacy (by assessing screening performance, focusing on the false-positive rate (FPR) for an 85% detection rate (DR))safety (focusing on the number of fetal losses due to amniocentesis (or chorionic villus sampling) in 100,000 women screened)cost-effectiveness (focusing on the cost of screening 100,000 women and the cost per Downs syndrome pregnancy diagnosed).Results Efficacy (screening performance) The false-positive rates for an 85% detection rate for the main screening tests are shown in the above table, in decreasing order of screening performance:With the serum integrated test, 10 weeks is the preferred time in pregnancy for the PAPP-A measurement. For the integrated test and the combined test, the timing of the measurement of the first trimester markers is less critical.Safety The lower false-positive rate with the integrated test compared with other tests means that at an 85% detection rate there would be nine diagnostic procedure-related unaffected fetal losses per 100,000 women screened compared with 44 using the combined test or 45 with the quadruple test.Cost-effectiveness Screening using the integrated test is less costly than might be expected because the extra screening costs tend to be offset by savings in the cost of diagnosis arising from the low false-positive rate. It was estimated that to achieve an 85% detection rate the cost to the UK NHS would be pound15,300 per Downs syndrome pregnancy detected. The corresponding cost using the second trimester quadruple test would be pound16,800 and using the first trimester combined test it would be pound19,000.Conclusions Implications for healthcare The results showed that screening performance in the first trimester of pregnancy was virtually the same as that in the second trimester, and in either it was much less effective than integrating screening measurements from both trimesters into a single test. In applying these results to screening practice several conclusions can be drawn. The following tests offer the most effective and safe method of screening:overall: the integrated testif an NT measurement is not available: the serum integrated testfor women who do not attend for antenatal care until the second trimester of pregnancy: the quadruple testfor women who choose to have a screening test in the first trimester: the combined test.At a constant detection rate, the cost-effectiveness of these four tests is broadly similar, any extra screening costs tending to be offset by fewer diagnostic costs. The evidence presented in this report does not support retaining the double test, the triple test, or NT measurements on their own (with or without maternal age) because each would lead to many more women having invasive diagnostic tests, without increasing the proportion of Downs syndrome pregnancies detected.

Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls

BACKGROUND There is uncertainty over whether maternal smoking is associated with birth defects. We conducted the first ever comprehensive systematic review to establish which specific malformations are associated with smoking. METHODS Observational studies published 1959–2010 were identified (Medline), and included if they reported the odds ratio (OR) for having a non-chromosomal birth defect among women who smoked during pregnancy compared with non-smokers. ORs adjusted for potential confounders were extracted (e.g. maternal age and alcohol), otherwise unadjusted estimates were used. One hundred and seventy-two articles were used in the meta-analyses: a total of 173 687 malformed cases and 11 674 332 unaffected controls. RESULTS Significant positive associations with maternal smoking were found for: cardiovascular/heart defects [OR 1.09, 95% confidence interval (CI) 1.02–1.17]; musculoskeletal defects (OR 1.16, 95% CI 1.05–1.27); limb reduction defects (OR 1.26, 95% CI 1.15–1.39); missing/extra digits (OR 1.18, 95% CI 0.99–1.41); clubfoot (OR 1.28, 95% CI 1.10–1.47); craniosynostosis (OR 1.33, 95% CI 1.03–1.73); facial defects (OR 1.19, 95% CI 1.06–1.35); eye defects (OR 1.25, 95% CI 1.11–1.40); orofacial clefts (OR 1.28, 95% CI 1.20–1.36); gastrointestinal defects (OR 1.27, 95% CI 1.18–1.36); gastroschisis (OR 1.50, 95% CI 1.28–1.76); anal atresia (OR 1.20, 95% CI 1.06–1.36); hernia (OR 1.40, 95% CI 1.23–1.59); and undescended testes (OR 1.13, 95% CI 1.02–1.25). There was a reduced risk for hypospadias (OR 0.90, 95% CI 0.85–0.95) and skin defects (OR 0.82, 0.75–0.89). For all defects combined the OR was 1.01 (0.96–1.07), due to including defects with a reduced risk and those with no association (including chromosomal defects). CONCLUSIONS Birth defects that are positively associated with maternal smoking should now be included in public health educational materials to encourage more women to quit before or during pregnancy.

Catheter Shunts for Fetal Hydronephrosis and Hydrocephalus

Abstract In the period 1982 to 1985, 73 placements of catheter shunts for fetal obstructive uropathy and 44 drainage procedures for obstructive hydrocephalus were reported to a voluntary international registry. The attempts to decompress the obstructed fetal urinary tracts resulted in the survival of 30 fetuses (41 percent), with a procedure-related death rate of 4.6 percent. Pulmonary hypoplasia was the major cause of death in both untreated and treated fetuses. Although the natural history of fetal obstructive uropathy has not been well studied, the outcome of intervention for selected fetuses with posterior urethral valve syndrome was encouraging. The results of shunt procedures for obstructive hydrocephalus were less encouraging. Although 34 of 44 fetuses (83 percent) survived, the procedure-related death rate was 10.25 percent, 18 of the 34 survivors (52.9 percent) have serious neurologic handicaps, 4 (11.8 percent) have less severe handicaps, and only 12 (35.3 percent) are developing normally. Analy...

Fetal cerebral blood flow redistribution in late gestation: identification of compromise in small fetuses with normal umbilical artery Doppler

Objective To evaluate the role of middle cerebral artery Doppler in small fetuses during the late third trimester.

First trimester fetal nuchal translucency: Problems with screening the general population 1.

Objective To evaluate the feasibility of measuring first trimester nuchal translucency in an unselected population, to assess the relationship with gestation and maternal age and to measure reproducibility.

Efficacy of second-trimester selective termination for fetal abnormalities: International collaborative experience among the world's largest centers

OBJECTIVE Our goal was to develop the most comprehensive database possible to counsel patients about selective termination for fetal abnormalities, because no one center has sufficient data to assess much more than crude loss rates. STUDY DESIGN A total of 183 completed cases of selective termination from 9 centers in 4 countries were combined (169 twins, 11 triplets, 3 quadruplets). Variables included indications, methods, (potassium chloride, exsanguination, air embolus), gestational age at procedure, pregnancies lost (< or = 24 weeks), gestational age at delivery, and neonatal outcome. RESULTS Indications for selective termination were 96 chromosomal, 76 structural, and 11 mendelian. Selective termination was technically successful in 100% of cases. In 23 of 183 (12.6%) miscarriage occurred before 24 weeks; 2 of 37 (5.4%) occurred when the procedure done at < or = 16 weeks and 21 of 146 (14.4%) when it was done thereafter. Air embolization had a higher loss rate: 10 of 24 (41.7%) compared with 13 of 156 (8.3%) by potassium chloride (chi 2 = 117, p < 0.0001). Three cases of selective termination performed in monochorionic pregnancies all resulted in pregnancy loss. Among 183 potentially viable deliveries, 7 occurred before 28 weeks, 19 at 29 to 32 weeks, 41 at 33 to 36 weeks, and 93 at > or = 37 weeks. Gestational age at delivery was not influenced by the technique used or the indication but was negatively correlated with gestational age at the time of selective termination. No coagulopathy or ischemic damage was observed in survivors. There was no maternal morbidity. CONCLUSIONS (1) Selective termination in experienced hands for a dizygotic abnormal twin is safe and effective when done with potassium chloride. A total of 83.8% of viable deliveries occurred after 33 weeks and only 4.3% at 25 to 28 weeks. (2) Gestational age at the procedure correlated positively with loss rate and inversely with gestational age at delivery; this emphasizes the need for early diagnosis in multifetal pregnancies. (3) Coagulopathy tests are probably unnecessary.

Erythropoietic suppression in fetal anemia because of Kell alloimmunization.

OBJECTIVE Our purpose was to test the hypothesis that maternal anti-Kell alloimmunization produces fetal anemia by erythroid suppression. STUDY DESIGN Erythropoiesis in 11 anemic fetuses from maternal anti-Kell alloimmunization was compared with that in 11 fetuses where the mother was alloimmunized to RhD; each was matched for hematocrit, gestational age, hydrops, and perinatal outcome. Comparisons of the difference were performed by either paired t or Wilcoxon tests. RESULTS The anti-Kell group had reduced reticulocytosis (p = 0.007) and erythroblastosis (p = 0.045) and lower amniotic fluid bilirubin concentrations (p = 0.02) in comparison with the anti-D group. No correlation was found between hematocrit and reticulocytosis in the anti-Kell group, whereas the anti-D group had a significant linear relationship (r = 0.63, p < 0.05), indicating a progressive reticulocytosis in response to the degree of anemia. CONCLUSION These findings suggest that erythroid suppression, rather than hemolysis, is the predominant mechanism in producing fetal anemia related to maternal Kell alloimmunization. Fetal blood sampling is the investigation of choice in the evaluation of anemia related to maternal Kell alloimmunization, because reduced hemolysis means amniotic fluid bilirubin concentrations correlate poorly with anemia.

Intrauterine growth and its relationship to size and shape at birth

Birth size and shape are commonly used as indicators of fetal growth. Epidemiologic studies have suggested a relationship between birth size and the risk of developing cardiovascular disease in later life. Certain “growth phenotypes” have been linked to the development of certain components of cardiovascular disease, particularly babies who display disproportional growth in utero. These observations are based on retrospective analysis of historical data sets. If the “Fetal Origins of Adult Disease” hypothesis is to be generalisable to the present day, then it is essential to establish whether these “growth phenotypes” exist within the normal distribution of birth size. The UCL Fetal Growth Study is a prospective study of antenatal fetal growth assessed by ultrasound at 20 and 30 wk gestation in 1650 low risk, singleton, white pregnancies. Measures of birth size were obtained and analyzed by principal components to explain shape at birth. Birth measures were also related to antenatal growth measurements to determine the strength of ultrasound evaluation in determining subsequent growth.There was significant sexual dimorphism in all measures at birth, with males heavier, longer, and leaner than females. From 20 wk of gestation onwards, males had a significantly larger head size than females. Parity, maternal height, and body mass index were important determinants of birth weight (p < 0.001). Cigarette smoking influenced birth weight, length, and head circumference (p < 0.001) but had no effect on placental size. Principal component analysis revealed that proportionality was the predominant size/shape at birth (55% of variance explained). A further 18% of variance was explained by a contrast between weight, head circumference, and length versus three skinfolds. Anthropometric measures as assessed by ultrasound at 20 and 30 wk gestation were poor predictors of birth length, weight, and head circumference (adjusted R2 18, 40, and 28% at 30 wk gestation scan, respectively). These predictions were not improved by including growth patterns between 20 and 30 wk. There is sexual dimorphism in a number of anthropometric measures at birth and in utero. These sex differences are important determinants of body size and shape. In a low risk population delivering at term, body shape was largely determined by proportionality between anthropometric measures. The low correlations between antenatal measures and birth size suggest that it is unwise to ascribe birth shape phenotypes to adverse events at any particular stage of gestation. The weak relationship also suggests that routine antenatal scans around 30 wk of gestation to predict growth problems are unlikely to be of benefit in the majority of cases.

Fetal treatment 1982.

Perinatal obstetricians, surgeons, ultrasonographers, pediatricians, bioethicists, and physiologists from centers active in fetal treatment (13 centers in 5 countries) gathered at Santa Ynez Valley...

Fetal urine biochemistry: an index of renal maturation and dysfunction

Objective To construct a reference range for fetal urinary sodium, potassium, urea, creatinine, calcium and phosphate with gestation and to assess to what extent these biochemical indices are modified in fetuses with lower urinary tract obstruction.