First-trimester biochemical markers of aneuploidy and the prediction of small-for-gestational age fetuses. 2008

K Spencer, and N J Cowans, and K Avgidou, and F Molina, and K H Nicolaides
Prenatal Screening Unit, Clinical Biochemistry Department, Harold Wood Hospital, Romford, Essex, UK. KevinSpencer1@aol.com

OBJECTIVE 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. METHODS 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. RESULTS 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%. CONCLUSIONS 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.

UI MeSH Term Description Entries
D007231 Infant, Newborn An infant during the first 28 days after birth. Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D007236 Infant, Small for Gestational Age An infant having a birth weight lower than expected for its gestational age.
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011256 Pregnancy Outcome Results of conception and ensuing pregnancy, including LIVE BIRTH; STILLBIRTH; or SPONTANEOUS ABORTION. The outcome may follow natural or artificial insemination or any of the various ASSISTED REPRODUCTIVE TECHNIQUES, such as EMBRYO TRANSFER or FERTILIZATION IN VITRO. Outcome, Pregnancy,Outcomes, Pregnancy,Pregnancy Outcomes
D011261 Pregnancy Trimester, First The beginning third of a human PREGNANCY, from the first day of the last normal menstrual period (MENSTRUATION) through the completion of 14 weeks (98 days) of gestation. Early Placental Phase,Pregnancy, First Trimester,Trimester, First,Early Placental Phases,First Pregnancy Trimester,First Pregnancy Trimesters,First Trimester,First Trimester Pregnancies,First Trimester Pregnancy,First Trimesters,Phase, Early Placental,Phases, Early Placental,Placental Phase, Early,Placental Phases, Early,Pregnancies, First Trimester,Pregnancy Trimesters, First,Trimesters, First
D011266 Pregnancy-Associated Plasma Protein-A A product of the PLACENTA, and DECIDUA, secreted into the maternal circulation during PREGNANCY. It has been identified as an IGF binding protein (IGFBP)-4 protease that proteolyzes IGFBP-4 and thus increases IGF bioavailability. It is found also in human FIBROBLASTS, ovarian FOLLICULAR FLUID, and GRANULOSA CELLS. The enzyme is a heterotetramer of about 500-kDa. PAPP-A,IGFBP-4 Metalloproteinase,IGFBP-4 Protease,IGFBP-4-Specific Proteinase,Insulin-Like Growth Factor-Dependent IGF Binding Protein-4 Protease,Insulin-Like-Growth Factor Binding Protein-4 Protease,PAPP-alpha,Pregnancy Associated alpha Plasma Protein,Pregnancy-Associated alpha-Plasma Protein,IGFBP 4 Metalloproteinase,IGFBP 4 Protease,Insulin Like Growth Factor Binding Protein 4 Protease,Insulin Like Growth Factor Dependent IGF Binding Protein 4 Protease,Metalloproteinase, IGFBP-4,PAPP alpha,Pregnancy Associated Plasma Protein A,Protease, IGFBP-4
D011296 Prenatal Diagnosis Determination of the nature of a pathological condition or disease in the postimplantation EMBRYO; FETUS; or pregnant female before birth. Diagnosis, Prenatal,Fetal Diagnosis,Fetal Imaging,Fetal Screening,Intrauterine Diagnosis,Antenatal Diagnosis,Antenatal Screening,Diagnosis, Antenatal,Diagnosis, Intrauterine,Prenatal Screening,Antenatal Diagnoses,Antenatal Screenings,Diagnosis, Fetal,Fetal Diagnoses,Fetal Imagings,Fetal Screenings,Imaging, Fetal,Intrauterine Diagnoses,Prenatal Diagnoses,Prenatal Screenings,Screening, Antenatal,Screening, Fetal,Screening, Prenatal
D005260 Female Females
D005317 Fetal Growth Retardation Failure of a FETUS to attain expected GROWTH. Growth Retardation, Intrauterine,Intrauterine Growth Retardation,Fetal Growth Restriction,Intrauterine Growth Restriction
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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