Placental transfer of IgG antibodies specific to Klebsiella and Pseudomonas LPS and to group B Streptococcus in twin pregnancies.

Group B Streptococcus (GBS), Klebsiella spp. and Pseudomonas spp. are important aetiological agents of neonatal infections in Brazil. There is a lack of data in the literature regarding the specific transport of immunoglobulin G (IgG) against these pathogens in multiple pregnancies. Maternal (n = 55) and umbilical cord (n = 110) blood samples were prospectively collected at birth from 55 twin pregnancies. The factors associated with cord levels and transfer ratios of IgG against GBS, Klebsiella and Pseudomonas were examined. The IgG umbilical cord serum levels specific to GBS, Klebsiella LPS and Pseudomonas LPS were significantly associated with maternal-specific IgG concentrations and the presence of diabetes. The anti-Klebsiella IgG cord serum concentrations were also related to birthweight and the presence of hypertension. The transfer ratios against GBS and Pseudomonas LPS were associated with maternal-specific IgG concentrations. The transfer ratios for GBS and Pseudomonas LPS were associated with gestational age at delivery and the presence of diabetes, respectively. None of the examined parameters were related to Klebsiella LPS transfer ratios. We conclude that in twin pregnancies, specific maternal IgG serum concentrations and diabetes were the parameters associated with umbilical cord serum IgG concentrations reactive with the three pathogens investigated. All the other parameters investigated showed different associations with neonatal-specific IgG levels according to the antigen studied. There was no uniformity of the investigated parameters regarding association with placental IgG transfer ratios against the GBS, Pseudomonas LPS and Klebsiella LPS.

Longitudinal reference range for umbilical cord cross-sectional area in twin pregnancies at 18-32 weeks of gestation.

OBJECTIVES: The objectives of this study were to establish gestational age-specific reference ranges for cross-sectional area of the umbilical cord, and its components, in twin pregnancies and to compare them with previously reported singleton reference ranges. METHODS: This was a prospective longitudinal study involving uncomplicated dichorionic twin pregnancies. Sonographic measurements of the cross-sectional area of the umbilical cord, umbilical vein and arteries and Wharton's jelly were obtained in a plane adjacent to the fetal abdomen, every 3 weeks, between 18 and 32 weeks of gestations. Multilevel regression analysis was used to determine gestational age-specific reference ranges for each parameter, and these were plotted against singleton pregnancy references. RESULTS: Three hundred and thirty four ultrasound scans were performed in 44 twin pregnancies, between 18 and 32.9 weeks (mean: 3.8 ± 0.7 scans/pregnancy and mean interval between scans: 3.3 ± 0.9 weeks). All umbilical cord cross-sectional areas (total, vein, artery and Wharton's jelly) showed a significant increase with gestational age. Compared with singleton pregnancy ranges, mean values were considerably lower in twin pregnancies and resemble the lower limits observed in singletons. CONCLUSION: In twin pregnancies, cross-sectional area of the umbilical cord, and its components, increases between 18 and 32 weeks, and mean values are substantially lower compared with singleton pregnancies.

Fetal venous circulation in monochorionic twin pregnancies with placental insufficiency: prediction of acidemia at birth or intrauterine fetal death.

OBJECTIVES: To investigate fetal venous Doppler measurements in monochorionic twin pregnancies complicated by placental insufficiency and the relationship between fetal venous flow and acidemia at birth or intrauterine fetal death. METHODS: This was a prospective study of 18 monochorionic twin pregnancies with placental insufficiency. Inclusion criteria were monochorionic-diamniotic twin pregnancy, abnormal umbilical artery (UA) Doppler indices, intact membranes and absence of fetal congenital abnormalities. Cases of twin-to-twin transfusion syndrome were excluded. The following Doppler measurements were studied: UA pulsatility index (PI), ductus venosus PI, middle cerebral artery PI and peak systolic velocity, intra-abdominal umbilical vein (UV) time-averaged maximum velocity (TAMXV) and left portal vein (LPV) TAMXV. Doppler parameters were transformed into Z-scores (SD values from the mean) or multiples of the median according to normative references. RESULTS: UA pH < 7.20 occurred in nine (25.0%) neonates, pH < 7.15 in four (11.1%) and intrauterine death in four (11.1%) fetuses. The UV-TAMXV and LPV-TAMXV Z-scores were significantly lower in the group with pH < 7.20 or intrauterine fetal death (-1.79 vs -1.22, P = 0.006 and -2.26 vs -1.13, P = 0.04, respectively). In cases with pH < 7.15 or intrauterine fetal death, UV pulsations were more frequent (50.0% vs 10.7%, P = 0.03) and UV-TAMXV Z-score was significantly lower (-1.89 vs -1.26, P = 0.003). Mixed effects logistic regression analysis, accounting for the paired nature of the outcomes for the two twins in each pregnancy, demonstrated that the UV-TAMXV Z-score significantly predicted UA pH at birth < 7.20 or intrauterine fetal death. The Doppler parameter that independently predicted pH < 7.15 or intrauterine fetal death was presence of pulsation in the UV. CONCLUSION: UV Doppler parameters may predict acidemia at birth or intrauterine fetal death in monochorionic twins complicated by placental insufficiency.

Second-trimester soft markers: relation to first-trimester nuchal translucency in unaffected pregnancies.

OBJECTIVE: Genetic sonography following first-trimester combined screening appears to increase substantially detection rates for Down syndrome but it relies on the unproved assumption of independence between these tests. In this study we aimed to investigate the relationship between first-trimester nuchal translucency (NT) and a series of second-trimester soft markers and structural defects in unaffected pregnancies. METHODS: NT measurement in the first trimester was followed by second-trimester scan (18 to 23 + 6 weeks) including examination for three categorical markers (intracardiac echogenic foci, hyperechogenic bowel and structural defects) and measurement of nasal bone length, nuchal-fold thickness, femur length, humerus length, renal pelvis diameter and prenasal thickness. All continuous variables were expressed in multiples of the median (MoM) for gestation and correlation coefficients between log-transformed NT and second-trimester variables were calculated. In addition, frequencies of soft markers and structural defects in cases with increased NT were compared to those with normal NT, using MoM cut-offs. RESULTS: In a dataset of 1970 cases, NT was significantly correlated (P < 0.05) with all second-trimester continuous variables, the correlation being strongest for nuchal-fold thickness (r = 0.10). There was a higher frequency of cases with second-trimester nuchal-fold thickness above the 97.5(th) centile (10.7 vs. 2.2%) and hyperechogenic bowel (2.4 vs. 0.1%) in cases with increased NT. CONCLUSIONS: Straightforward reassessment of risk using likelihood ratios derived from the second-trimester genetic sonogram might lead to inaccurate estimates. Multivariate models using continuous second-trimester variables might be preferable in sequential screening strategies.

Conjoined twins pregnancies: experience with 36 cases from a single center.

OBJECTIVE: To review a single center's experience in the management of twin pregnancies with conjoined fetuses. METHODS: Retrospective study describing prenatal findings, delivery details, surgical treatment and perinatal outcome. RESULTS: The study included 36 twin pregnancies with conjoined twins seen over a period of 12 years in a single tertiary hospital: 69.4% were thoracopagus, 13.9% parapagus, 8.3% omphaloischiopagus 5.6% omphalopagus and 2.8% cephalopagus. Cardiac defects were present in 91.6% of twin pairs and associated malformations were present in 61.8% of the cases: limb abnormalities in 36.1%, abdominal wall defects in 25.0%, cleft lip and/or palate in 13.9% and congenital diaphragmatic hernia in 5.5%. Surgical separation was considered not feasible and prognosis lethal in 30 (83.3%) cases. Termination of pregnancy was performed in 12 pregnancies of poor prognosis. Cesarean section was performed in all remaining cases. Five sets of twins underwent surgical separation and six children survived. Overall survival in our series was 8.3% and, among the livebirths, 13.6%. CONCLUSION: Conjoined twin pregnancies should be referred to tertiary centers for detailed fetal anomaly and echocardiographic assessment to evaluate prognosis and determine the possibility of postnatal surgical separation.

First-trimester maternal serum levels of placenta growth factor as predictor of preeclampsia and fetal growth restriction.

OBJECTIVE: To determine whether the reported decrease in maternal serum placenta growth factor concentration in preeclampsia is evident from the first trimester and before clinical onset of the disease. We also examined levels in pregnancies that subsequently resulted in fetal growth restriction (FGR). METHODS: Placenta growth factor concentration was measured in stored maternal serum samples obtained at 11-14 weeks of gestation from 131 women who subsequently developed preeclampsia, 137 women who subsequently developed FGR, and 400 randomly selected controls who did not develop preeclampsia or FGR. Preeclampsia was defined as diastolic blood pressure of 90 mmHg or more on two occasions 4 hours apart, accompanied by proteinuria (more than 300 mg of total protein in a 24-hour urine collection or a positive test for albumin on reagent strip) in women with no pre-existing hypertensive or renal disease. Fetal growth restriction was considered present if a woman subsequently delivered a live infant with a birth weight below the fifth centile for gestation. RESULTS: In the control group, maternal serum placenta growth factor concentration increased with gestation. Compared with the controls (median multiple of the median 0.98, standard deviation [SD] 0.51), levels in the preeclampsia group (median multiple of the median 1.09, SD 0.52) were not significantly different (t = 1.83, P = .07), but in the FGR group (median multiple of the median 1.57, SD 0.74), levels were significantly increased (t = 10.85, P < .001). CONCLUSION: The previously reported decrease in serum placenta growth factor levels in women with preeclampsia might not precede clinical onset of the disease and is not apparent in the first trimester of pregnancy. Levels are significantly increased in pregnancies resulting in FGR.

First-trimester maternal serum activin A in pre-eclampsia and fetal growth restriction.

OBJECTIVE: To investigate whether the reported increase in maternal serum activin A concentration in pre-eclampsia is evident from the first trimester. DESIGN: This was a case-control study carried out in antenatal clinics among singleton pregnancies at 10-14 weeks of gestation. METHODS: Activin A concentration was measured in stored maternal serum samples obtained at 11-14 weeks of gestation from 131 women who subsequently developed pre-eclampsia, 77 who developed non-proteinuric pregnancy-induced hypertension, 141 with fetal growth restriction in the absence of hypertensive complications and from 494 normotensive controls. RESULTS: Compared to the median activin A level in the control group (1.00 MoM), the median MoM in the patients who subsequently developed pre-eclampsia and pregnancy-induced hypertension (1.49 MoM and 1.32 MoM, respectively) was significantly increased (p < 0.001), and in patients with fetal growth restriction (1.02 MoM) it was not significantly different (p = 0.57). In the pre-eclampsia group (n = 131) the disease was considered to be sufficiently severe to necessitate iatrogenic delivery before 35 weeks in 25 patients, and in this group the median MoM was 1.92. CONCLUSION: Maternal serum activin A concentration at 12 weeks of gestation in pregnancies which subsequently develop hypertensive disease is increased, whereas in those complicated by fetal growth restriction it is normal.

Trichorionic triplet pregnancies at 10-14 weeks: outcome after embryo reduction compared to expectant management.

OBJECTIVE: To compare the outcome of trichorionic triplet pregnancies managed expectantly with those reduced to twins or singletons. METHODS: This was a retrospective study of trichorionic triplet pregnancies with three live fetuses at 10-14 (median 12) weeks' gestation referred to our unit for consideration of embryo reduction. Women were counselled as to the available options of either expectant management or embryo reduction. In those choosing reduction, a needle was inserted into the uterus transabdominally and potassium chloride was injected into the fetal heart. Using data derived from this study and from a review of studies reporting on survival and handicap by gestational age in singletons, the effects of embryo reduction on survival and handicap rates were estimated. Main outcome measures were miscarriage before 24 weeks of gestation, preterm delivery before 32 weeks, perinatal death and handicap rates. RESULTS: In total, there were 280 trichorionic triplet pregnancies and 125 of these were managed expectantly, 133 were reduced to two fetuses and 22 were reduced to one fetus. The rates of miscarriage were 3.2% for those managed expectantly, 8.3% for those reduced to twins and 13.6% for those reduced to singletons. The rates of early preterm delivery in those pregnancies that did not miscarry were 23.1%, 9.8% and 5.3%, respectively. The percentages for pregnancies with at least one survivor were 95.2%, 91.0% and 81.8%, respectively, and the median gestation at delivery was 34 weeks for the non-reduced, 36 weeks for those reduced to twins and 38 weeks for those reduced to singletons. From the published series on early preterm delivery, it was estimated that survival increases from about 27% at 24 weeks to about 98% at 32 weeks, and handicap decreases from 28% at 24 weeks to less than 5% at 32 weeks. From these estimates and the data on triplet pregnancies, it was calculated that, in triplets reduced to twins, compared to those managed expectantly, the chance of survival is similar (90.3% compared to 93.3%), but the risk of handicap may be lower (0.6% compared to 1.5% per fetus). CONCLUSIONS: In trichorionic triplet pregnancies, embryo reduction to twins does not improve the chance of survival but may reduce the rate of handicap. Reduction from triplets to singletons may reduce both the survival rate and the handicap rate among survivors.

The 11-14 week scan.

Fetal nuchal translucency thickness (NT) at the 11-14 week scan has been combined with maternal age to provide an effective method of screening for trisomy 21; for an invasive testing rate of 5%, about 75% of trisomic pregnancies can be identified. When maternal serum free-beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A at 11-14 weeks are also taken into account, the detection rate of chromosomal defects is about 90%. Increased NT can also identify a high proportion of other chromosomal abnormalities and is associated with major defects of the heart and great arteries, and a wide range of skeletal dysplasias and genetic syndromes. Other benefits of the 11-14 week scan include early diagnosis of major fetal defects and the detection of multiple pregnancies, as well as reliable identification of chorionicity. As with the introduction of any new technology into routine clinical practice, it is essential that those undertaking the 11-14 week scan are adequately trained and that their results are subjected to rigorous audit.

Tandem separation schemes for preparative high-performance liquid chromatography of proteins.

Preparative chromatography of protein mixtures was carried out by tandem separation schemes involving frontal chromatography followed by stepwise desorption or displacement. In this way, with columns and instruments generally employed in analytical high-performance liquid chromatography, proteins could be purified in quantities similar to those typically separated by a preparative-scale system. A mixture of beta-lactoglobulin A and B was loaded onto an anion-exchange column, and, in the process, a large fraction of the less-retained beta-lactoglobulin B was recovered in pure form. The column was then flushed with the carrier, and subsequent desorption of the substances bound on the stationary phase was carried out by single-step desorption, two-step desorption, or displacement. With this mixture, the last two methods yielded approximately the same results in terms of the amount of product obtained per unit column volume. Whereas stepwise desorption is a simpler technique than displacement, the latter is required for the separation of components having similar adsorption behavior. In another set of experiments, a protein mixture obtained by heat treatment of human growth hormone was fractionated on a reversed-phase column. After loading the column by frontal chromatography, which separated a large fraction of the main product from the other components retained by the column, four desorption steps were applied to recover the individual components. These separation schemes offer an approach to preparative chromatography of proteins that is superior to conventional linear elution in terms of column load capacity, low mobile phase consumption, simultaneous separation and concentration, as well as enrichment of trace components.

The influence of fetal sex in screening for trisomy 21 by fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation.

In a study of 2923 normal pregnancies and 203 pregnancies affected by trisomy 21 we have shown a significant difference in the median MoM of the markers: fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A in the presence of a female fetus compared with a male fetus. For maternal serum free beta-hCG levels are higher by 15% if the fetus is chromosomally normal and by 11% if the fetus has trisomy 21. For maternal serum PAPP-A the levels in chromosomally normal fetuses are 10% higher in the presence of a female fetus and 13% higher if the fetus has trisomy 21. In contrast, fetal nuchal translucency is 3-4% lower in both chromosomally normal and trisomy 21 female fetuses. The consequence of such changes when screening for trisomy 21 will be a reduction in the detection rate in female fetuses by a factor of 1-2%. Correction of risk algorithms for fetal sex, however, is probably not feasible, since ultrasound detection of fetal sex is only 70-90% accurate in the 10-14 week period.

Cervical length at 23 weeks in triplets: prediction of spontaneous preterm delivery.

OBJECTIVES: To establish the distribution of cervical length at 23 weeks of gestation in triplet pregnancies and to examine the relation to preterm delivery before 33 weeks. METHODS: Cervical length was measured by transvaginal sonography at 23 (range 22-24) weeks of gestation in 43 triplet pregnancies. The distribution of cervical length was determined and the relationship between cervical length and the rate of spontaneous preterm delivery before 33 weeks was calculated. RESULTS: The cervical length distribution was skewed to the left with a median of 34 mm. The rate of spontaneous labor and delivery before 33 weeks increased exponentially with decreasing cervical length at 23 weeks from 8% at 36-48 mm, to 11% at 26-35 mm, 33% at 16-25 mm and 67% at 15 mm or less. Cervical length was < or = 30 mm, < or = 25 mm and < or = 15 mm in 37%, 16% and 8% of cases, respectively, and the corresponding sensitivities in the prediction of spontaneous delivery before 33 weeks were 67%, 50% and 33%. CONCLUSIONS: In triplet pregnancies, measurement of cervical length provides a useful prediction of risk for spontaneous early preterm delivery.

Fetal heart rate in chromosomally abnormal fetuses.

OBJECTIVES: To determine the effects of chromosomal defects on fetal heart rate at 10-14 weeks of gestation. METHODS: Fetal heart rate at 10-14 weeks of gestation in 1061 chromosomally abnormal fetuses was compared to that from 25,000 normal pregnancies. The chromosomally abnormal group included 554 cases of trisomy 21, 219 cases of trisomy 18, 95 of trisomy 13, 50 of triploidy, 115 of Turner syndrome and 28 of sex chromosome abnormalities other than Turner syndrome. RESULTS: In the normal group, fetal heart rate decreased from a mean value of 170 beats per minute (bpm) at 35 mm of crown-rump length to 155 bpm at 84 mm crown-rump length. In trisomy 21, trisomy 13 and Turner syndrome fetal heart rate was significantly higher, in trisomy 18 and triploidy the heart rate was lower and in other sex chromosome defects it was not significantly different from normal. Fetal heart rate was above the 95th centile of the normal range in 10%, 67% and 52% of fetuses with trisomy 21, trisomy 13 and Turner syndrome, respectively. The fetal heart rate was below the 5th centile in 30% of fetuses with triploidy and 19% of those with trisomy 18. CONCLUSIONS: Trisomy 21, trisomy 13 and Turner syndrome are associated with fetal tachycardia, whereas in trisomy 18 and triploidy there is fetal bradycardia. Inclusion of fetal heart rate in a first-trimester screening program for trisomy 21 by a combination of maternal age and fetal nuchal translucency thickness is unlikely to provide useful improvement in sensitivity.

Megacystis at 10-14 weeks of gestation: chromosomal defects and outcome according to bladder length.

AIMS: To examine the prevalence of chromosomal defects and outcome of fetuses with megacystis at 10-14 weeks of gestation. METHODS: At the 10-14-week scan fetal megacystis was defined by a longitudinal bladder diameter of 7 mm or more. In 145 such fetuses the fetal karyotype and pregnancy outcome were examined in relation to the longitudinal diameter of the fetal bladder. RESULTS: Chromosomal defects, mainly trisomies 13 and 18, were present in 30 cases. In the group with longitudinal bladder diameter of 7-15 mm the incidence of chromosomal defects was 23.6% (26/110), whereas in those with bladder diameter > 15 mm the incidence was 11.4% (4/35). The fetal nuchal translucency (NT) was above the 95th centile of the normal range for crown-rump length in a higher proportion of cases with abnormal rather than normal karyotype (76.7% compared to 31.3%; Chi-square P < 0.0001). The expected number of cases of trisomy 21, estimated on the basis of maternal age, gestational age and fetal NT, was 6.2 rather than the observed 2 and the corresponding numbers for trisomies 13 or 18 were 4.2 for expected and 24 for observed. In the chromosomally normal group with longitudinal bladder diameter of 7-15 mm follow-up scans demonstrated spontaneous resolution of the megacystis in 90% of the cases and enlargement of the megacystis and/or the development of echogenic kidneys in 10%. In contrast, none of the cases with bladder diameter > 15 mm demonstrated spontaneous resolution of the megacystis. CONCLUSIONS: In fetal megacystis with longitudinal bladder diameter of 7-15 mm there is a risk of about 25% that the fetus will have a chromosomal defect but in the chromosomally normal group there is spontaneous resolution of the megacystis in about 90% of cases. If the bladder diameter is > 15 mm the risk of chromosomal defects is about 10% and in the chromosomally normal group the condition is invariably associated with progressive obstructive uropathy.

Screening for trisomy 13 by fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation.

In 42 cases of trisomy 13 at 10-14 weeks of gestation, compared with 947 controls, the median multiple of the median (MoM) of maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy associated plasma protein A (PAPP-A) was significantly decreased (0.506 MoM and 0.248 MoM respectively), whilst fetal nuchal translucency was increased (2.872 MoM). In 38% and 71% of cases of trisomy 13 maternal serum free beta-hCG and PAPP-A was below the 5th centile of the appropriate normal range for gestation and in 62% of cases the nuchal translucency was above the 95th centile. When combined together in a multivariate algorithm with maternal age, 90% of cases of trisomy 13 could be detected at a 0.5% false positive rate or 84% at a 0.1% false positive rate. We conclude that specific trisomy 13 risks should be part of developing risk algorithms combining maternal serum biochemistry and nuchal translucency for use in first trimester screening alongside those for trisomy 21 and trisomy 18.

The influence of ethnic origin on first trimester biochemical markers of chromosomal abnormalities.

In a first trimester study of 5422 Caucasian women, 752 Afro-Caribbean women and 170 Asian women we have shown that the median maternal serum marker MoMs for free beta-hCG and PAPP-A were 19% and 48% higher in Afro-Caribbean women and 19% higher and 35% higher in Asian women, compared to Caucasian women. Correcting for maternal weight made very little difference to the effect in Afro-Caribbeans (21% and 57% higher after weight correction) but reduced the effect in Asians (4% and 17% higher after weight correction ). It is estimated that correcting for maternal weight and ethnicity overall would increase the detection rate by a modest 1.4%. However, the effect on an individual's risk could result in as much as a two-fold increase in the patient specific risk for trisomy 21. The impact of ethnic origin seems to be greater than that observed with second trimester biochemical markers and larger studies are required in order to develop robust algorithms for correcting for ethnic origin in the first trimester.

Screening for triploidy by fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation.

In 25 cases of triploidy at 10-14 weeks of gestation, compared with 947 controls, the median multiple of the median (MoM) fetal nuchal translucency (NT) thickness was significantly increased (1.89 MoM), and maternal serum total and free beta-human chorionic gonadotrophin (hCG) were increased (3.13 MoM and 4.59 MoM respectively), alpha fetoprotein (AFP) was increased (2.14 MoM), and pregnancy associated plasma protein A (PAPP-A) was decreased (0.12 MoM). There are two types of triploidy. In type I, where the additional chromosome set is of paternal origin, the placenta is partially molar and the fetus is relatively well-grown. Type II, where the extra chromosome set is of maternal origin, is characterized by a small normal looking placenta and severe asymmetrical fetal growth restriction. In type I triploidy there was increased fetal NT (2.76 MoM), maternal serum total hCG (4.91 MoM), free beta-hCG (8.04 MoM), and AFP (3.22 MoM), and mildly decreased PAPP-A (0.75 MoM). In type II triploidy fetal NT was not increased (0.88 MoM), and there was a decrease in maternal serum total hCG (0.16 MoM), free beta-hCG (0.18 MoM), PAPP-A (0.06 MoM) and AFP (0.77 MoM). We conclude that a large proportion of triploidy cases of both phenotypes could be identified in the first trimester using NT, maternal serum free beta-hCG and PAPP-A with a combination of trisomy 21 risk and an atypicality approach.

The influence of parity and gravidity on first trimester markers of chromosomal abnormality.

We have studied changes in first trimester fetal nuchal translucency (NT) and maternal serum free beta-hCG and PAPP-A with gravidity and parity in 3252 singleton pregnancies unaffected by chromosomal abnormality or major pregnancy complications. We have shown that gravidity and parity is associated with a small but progressive decrease in fetal NT and a small but progressive increase in free beta-hCG and PAPP-A. None of these small changes with increasing gravidity or parity are statistically significant and hence correction for these variables is not necessary when considering first trimester screening for chromosomal abnormalities.

First trimester maternal serum free beta human chorionic gonadotrophin and pregnancy associated plasma protein A as predictors of pregnancy complications.

OBJECTIVE: To examine the value of first trimester maternal serum free beta human chorionic gonadotrophin (beta hCG) and pregnancy associated plasma protein A (PAPP-A) as predictors of pregnancy complications. DESIGN: Screening study. SETTING: Antenatal clinics. POPULATION: Singleton pregnancies at 10-14 weeks of gestation. METHODS: Maternal serum free beta hCG and PAPP-A were measured at 10-14 weeks of gestation in 5,584 singleton pregnancies. In the 5,297 (94.9%) pregnancies with complete follow up free beta hCG and PAPP-A were compared between those with normal outcome and those resulting in miscarriage, spontaneous preterm delivery, pregnancy induced hypertension or fetal growth restriction and in those with pre-existing or gestational diabetes. RESULTS: Maternal serum PAPP-A increased and beta hCG decreased with gestation. The multiple of median maternal serum PAPP-A was significantly lower in those pregnancies resulting in miscarriage, pregnancy induced hypertension, growth restriction and in those with pre-existing or gestational diabetes mellitus, but not in those complicated by spontaneous preterm delivery. The level was < 10th centile of the reference range in about 20% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 27% of those that developed gestational diabetes. Maternal serum free beta hCG was < 10th centile of the reference range in about 15% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 20% of those that developed gestational diabetes. CONCLUSION: Low maternal serum PAPP-A or beta hCG at 10-14 weeks of gestation are associated with subsequent development of pregnancy complications.

Maternal serum activin A and inhibin A in trisomy 18 pregnancies at 10-14 weeks.

In 45 cases of trisomy 18 and 493 control pregnancies at 10-14 weeks of gestation, maternal serum inhibin A, total activin A, free beta-hCG and PAPP-A were measured. In the trisomy 18 pregnancies the median values were 0.74 MoM for inhibin A, 1.23 MoM for activin A, 0.38 MoM for free beta-hCG and 0.16 MoM for PAPP-A. The degree of deviation from normal in the levels of inhibin and activin is small in comparison with free beta-hCG and PAPP-A and they are therefore unlikely to be of value in improving the sensitivity of 90% for a 1% false-positive rate achieved by screening with fetal nuchal translucency and maternal serum free beta-hCG and PAPP-A.