Absence of nasal bone by first trimester ultrasound was significantly associated with Down syndrome. When a proper view of the fetal face was obtained, the nasal bone was visible in more than 99% of karyotypically normal fetuses.

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BackgroundPreterm birth (PTB) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. This study was designed to identify genetic variation associated with PTB in oxytocin pathway genes whose role in parturition is well known.MethodsTo identify common genetic variants predisposing to PTB, we genotyped 16 single nucleotide polymorphisms (SNPs) in the oxytocin (OXT), oxytocin receptor (OXTR), and leucyl/cystinyl aminopeptidase (LNPEP) genes in 651 case infants from the U.S. and one or both of their parents. In addition, we examined the role of rare genetic variation in susceptibility to PTB by conducting direct sequence analysis of OXTR in 1394 cases and 1112 controls from the U.S., Argentina, Denmark, and Finland. This study was further extended to maternal triads (maternal grandparents-mother of a case infant, N=309). We also performed in vitro analysis of selected rare OXTR missense variants to evaluate their functional importance.ResultsMaternal genetic effect analysis of the SNP genotype data revealed four SNPs in LNPEP that show significant association with prematurity. In our case–control sequence analysis, we detected fourteen coding variants in exon 3 of OXTR, all but four of which were found in cases only. Of the fourteen variants, three were previously unreported novel rare variants. When the sequence data from the maternal triads were analyzed using the transmission disequilibrium test, two common missense SNPs (rs4686302 and rs237902) in OXTR showed suggestive association for three gestational age subgroups. In vitro functional assays showed a significant difference in ligand binding between wild-type and two mutant receptors.ConclusionsOur study suggests an association between maternal common polymorphisms in LNPEP and susceptibility to PTB. Maternal OXTR missense SNPs rs4686302 and rs237902 may have gestational age-dependent effects on prematurity. Most of the OXTR rare variants identified do not appear to significantly contribute to the risk of PTB, but those shown to affect receptor function in our in vitro study warrant further investigation. Future studies with larger sample sizes are needed to confirm the findings of this study.

Objective Limb reduction defects were considered as possible indicators of environmental teratogenesis; it was suggested that also invasive prenatal procedures could increase the risk for limb reduction defects. The purpose of this work is to give a baseline frequency for limb reduction defects, using data from a population not exposed to prenatal diagnosis procedures.Design Using data collected in the period 1967 to 1992 within the frame of the Latin American Collaborative Study of Congenital Malformations which clinically examined 2,917,074 newborn infants, a total of 1715 with limb reduction defects were found. All cases were classified and analysed in 25 categories. Geographic differences in recorded rates were tested by χ2 for homogeneity. Secular trends were analysed using χ2 test for linear trends.Results The overall birth prevalence rate of limb reduction defects among liveborn infants was 4.91 (per 10,000 births) (3.05 for isolated and 1.85 for associated cases). For stillbirths, the total prevalence was 2673/10,000 (553 for isolated and 21.20 for associated cases). The inclusion of the brachydactylies increased those figures to 5.55110,000 (3.39 for isolated and 2.16 for associated cases), and 27.42, respectively, (5.53 for isolated and 21.89 for associated cases). When isolated and associated cases were considered together, a geographic heterogeneity was found in pre‐axial limb reduction defects; there was also some heterogeneity for amputations. A maternal age effect was found for the isolated hypoplasias. Standardising by maternal age, the overall prevalence of limb reduction in liveborn infants was 5.66 per 10,000 (95% CI = 5.38–5.93). An increasing trend was suggested by the isolated form of distal amputations which involved hands, feet, or digits.Conclusions Our data suggest that clustering limb reduction defects in wide groups as transverse and longitudinal may lead to heterogeneous entities. When a possible association is suspected, it would be preferable to present and analyse data in the most discriminant form available. Due to the maternal age effect, it would be advisable to standardise the rates of transversal limb reduction defects by this variable.