Pregnancy associated plasma protein A: An indicator of adverse obstetric outcomes in a South India population.

OBJECTIVE: First trimester aneuploidy screening (FTAS) has become an integral part of antenatal care in most of centers in India. The serum markers used for FTAS are pregnancy-associated plasma protein A (PAPP-A) and beta human chorionic gonadotropin. In the present study, we aimed to assess the role of PAPP-A in specific adverse fetal maternal events. To analyze pregnancy outcomes with low maternal PAPP-A (≤5th percentile) at the FTAS screening test in southern India, and them compared with a control group of >5th percentile value. MATERIALS AND METHODS: A total of 1800 consecutive pregnancies in the first trimester were followed up with PAPP-A levels. The study group consisted 108 subjects, which was compared with a matched control group of 288 subjects. The outcomes considered were spontaneous abortions, fetal anomalies, preterm delivery (PTD), hypertension in pregnancy, intrauterine growth restriction, gestational diabetes, mode of delivery, and birthweight. RESULTS: For our grouped data, the 5th percentile value for PAPP-A was 0.49 multiple of medians, (incidence-6%). The incidence of fetal major anomalies was higher in the study group [odds ratio (OR): 1.87]. The incidence of minor anomalies, gestational diabetes, and hypertensive disorders was higher in the study group but not statistically significant. The total rate of PTDs (OR:2.1), small-for-gestation-age fetuses (OR:2.3), and low birthweight babies (OR- 2.12) was significantly higher in the study group. We found positive likelihood ratio of 1.4 for PTD, 2 for <5th percentile birthweight, and 1.7 for <10th centile birthweight. CONCLUSION: Low PAPP-A pregnancies are at risk of various obstetric complications. Hence, such a pregnancy should have closer surveillance. Further research work on intervention strategy is needed.

A novel mutation (g.106737G>T) in zone of polarizing activity regulatory sequence (ZRS) causes variable limb phenotypes in Werner mesomelia.

Werner mesomelia is characterized by a sequence variation in the specific region (position 404) of the enhancer ZRS of SHH. The phenotype comprises variable mesomelia, abnormalities of the thumb and great toe and supernumerary digits. We describe extensive variation in limb phenotype in a large family and report on a novel sequence variation NG_009240.1: g.106737G>T (traditional nomenclature: ZRS404G>T) in the ZRS within the LMBR1 gene. The newly recognized clinical features in this family include small thenar eminence, sandal gap, broad first metatarsals, mesoaxial polydactyly, and postaxial polydactyly. We provide information on 12 affected family members. We review the literature on how a sequence variation in ZRS may cause such diverse phenotypes.