Prediction of birth weight by fetal crown-rump length and maternal serum levels of pregnancy-associated plasma protein-A in the first trimester.

To determine whether the first trimester crown-rump length (CRL), maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotropin (fbeta-hCG) are independent predictors of birth weight. This was an observational study over 1.5 years in Chinese patients who underwent first-trimester combined screening for Down syndrome in a University fetal medicine unit. After excluding cases with multiple pregnancies, congenital malformations and in-utero deaths, the relationship between fetal CRL (expressed as standardized Z-score (Z-CRL)), maternal PAPP-A and fbeta-hCG levels (expressed as log(10) of multiples of the median) and birth weight (Z-BW) were analyzed by Pearson's correlation test followed by multiple regression to check for their independency. The predictive power of the independent predictors for small-for-gestational age (SGA, defined as birth weight < 10(th) centile) was then assessed using receiver-operating characteristics (ROC) curves, and the likelihood ratios were derived. A total of 2760 cases were included. Z-CRL, log(10) PAPP-A(MoM), and log(10) fbeta-hCG were positively correlated with Z-BW (P < 0.0001), but only Z-CRL and log(10) PAPP-A(MoM) were independent predictors (P < 0.0001). The areas under the ROC curves of PAPP-A(MoM) and Z-CRL were 0.608 and 0.593, respectively (P < 0.0001). Likelihood ratios increased with decreasing PAPP-A(MoM) and Z-CRL, but were around 1 when the markers were at or above the mean. First-trimester CRL and PAPP-A are independent factors that influence final birth weight. The lower the PAPP-A and the smaller the CRL, the higher the risk of a fetus becoming SGA. However, their predictive powers are not sufficiently good for them to be used alone for SGA screening.

Leung TY ，Sahota DS ，Chan LW ，Law LW ，Fung TY ，Leung TN ，Lau TK ... -  《ULTRASOUND IN OBSTETRICS & GYNECOLOGY》

First-trimester maternal serum levels of placental hormones are independent predictors of second-trimester fetal growth parameters.

To determine whether first-trimester maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (fbeta-hCG) are independent predictors of second-trimester fetal growth parameters. This was a cohort study over a 1-year period involving 594 Chinese women who underwent both first-trimester combined screening for Down syndrome and a routine second-trimester ultrasound examination. Maternal PAPP-A and fbeta-hCG levels (expressed in log(10) of multiples of median (MoM)), crown-rump length (CRL) (expressed in standardized Z-score (Z-CRL)), and maternal height and weight, were correlated with the Z-score of biparietal diameter (Z-BPD), femur length (Z-FL) and abdominal circumference (Z-AC) measured in the second trimester, using the Pearson test, followed by multiple regression analysis. Z-BPD, Z-FL and Z-AC were positively correlated with log(10) PAPP-A MoM, CRL and maternal height (all P < 0.05), while log(10) fbeta-hCG MoM was negatively correlated with Z-AC (P < 0.05). After controlling for the effects of CRL, maternal height and weight, log(10) PAPP-A MoM was found to be an independent positive predictor of Z-FL (r = 0.797, P < 0.001) and Z-AC (r = 0.305, P = 0.049), and log(10) fbeta-hCG MoM was an independent negative predictor of Z-FL (r = -0.381, P = 0.023) and Z-AC (r = -0.418, P = 0.002). Neither hormonal level was related to Z-BPD. First-trimester PAPP-A and fbeta-hCG are independent factors that influence subsequent fetal growth. PAPP-A level is positively correlated with FL and AC in the second trimester, while fbeta-hCG level is negatively correlated with them. However, BPD is not affected by either of the hormones.

Leung TY ，Chan LW ，Leung TN ，Fung TY ，Sahota DS ，Lau TK ... -  《ULTRASOUND IN OBSTETRICS & GYNECOLOGY》

First-trimester biochemical markers of aneuploidy and the prediction of small-for-gestational age fetuses.

To examine the clinical utility of the first-trimester biochemical markers of aneuploidy in their ability to predict subsequent delivery of a small-for-gestational age (SGA) infant. We examined singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the expected normal median (MoM) for a pregnancy of the same gestation. The association between free beta-hCG and PAPP-A and the incidence of SGA were assessed by comparing the relative incidence at MoM cut-offs and birth-weight centile cut-offs. At various marker levels the likelihood ratios (LR) for SGA were also calculated after excluding other adverse pregnancy complications. There were 46,262 pregnancies resulting in live births with birth weight at or above the 10(th) centile, and 3,539 below the 10(th) centile for gestation (SGA). There was a significant inverse association between the risk for SGA and maternal serum PAPP-A MoM but not free beta-hCG MoM. At the 5(th) centile of the normal outcome group for PAPP-A (0.415 MoM) the odds ratios for SGA below the 10(th), 5(th) and 3(rd) centiles of normal were 2.70, 3.21 and 3.66 and the respective detection rates for SGA were 12.0%, 14.0% and 16.0%. Low levels of maternal serum PAPP-A are associated, in the absence of an abnormal karyotype, with an increased risk for subsequent delivery of an SGA infant.

Spencer K ，Cowans NJ ，Avgidou K ，Molina F ，Nicolaides KH ... -  《ULTRASOUND IN OBSTETRICS & GYNECOLOGY》

Which ultrasound or biochemical markers are independent predictors of small-for-gestational age?

Law LW ，Leung TY ，Sahota DS ，Chan LW ，Fung TY ，Lau TK ... -  《-》

First-trimester ultrasound and biochemical markers of aneuploidy and the prediction of preterm or early preterm delivery.

To examine the clinical utility of the first-trimester markers of aneuploidy in their ability to predict preterm delivery. We examined 54 722 singleton pregnancies with no chromosomal abnormality and with complete outcome data that had undergone screening for trisomy 21 by a combination of fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 and 13 + 6 weeks' gestation. The biochemical markers were converted to multiples of the median (MoM) of the expected normal median for a pregnancy of the same gestation and the measurements of fetal NT were expressed as the difference (delta) from the normal median NT for crown-rump length. The association between free beta-hCG, PAPP-A and delta NT and the incidence of preterm delivery before 37 weeks or early preterm delivery before 34 weeks was assessed by comparing the relative incidence at a number of MoM or delta NT cut-offs and at various centile cut-offs. At various marker levels the likelihood ratios (LR) for preterm delivery and early preterm delivery were also calculated after excluding other adverse pregnancy complications. The risk of preterm delivery increased with decreasing maternal serum PAPP-A. In the 3132 cases delivering before 37 weeks the PAPP-A MoM was 0.91 and in the 1060 cases delivering before 34 weeks the PAPP-A MoM was 0.90. At the 5th centile of the normal outcome group for PAPP-A (0.415 MoM) the odds ratios for delivery before 37 weeks and before 34 weeks were 1.92 and 2.35, respectively. The respective values for the 5th centile of free beta-hCG (0.41 MoM) were 1.18 and 1.08 and for the 95th centile of delta NT they were 0.91 and 0.77, respectively. Low levels of maternal serum PAPP-A are associated, in the absence of an abnormal karyotype, with an increased risk of preterm or early preterm delivery. The LR profiles provided at various levels of PAPP-A may be of some help in counseling women with such results and may raise awareness among healthcare professionals for increased surveillance in such cases.

Spencer K ，Cowans NJ ，Molina F ，Kagan KO ，Nicolaides KH ... -  《ULTRASOUND IN OBSTETRICS & GYNECOLOGY》