Incidence and timing of pregnancy losses: Relevance to evaluating safety of early prenatal diagnosis

Abstract

Knowing the frequency and timing of pregnancy loss during normal gestation is integral to evaluating the safety of prenatal diagnostic techniques. That preclinical loss rates are high in humans has long been suspected, but in the past decade new data concerning these losses have become available. Cohort studies indicate that many women who show positive beta-HCG assays never show clinical evidence of pregnancy. Cytogenetic abnormalities have also recently been documented in 20% of ostensibly normal in vitro fertilization embryos. All the above are consistent with the sentinel studies of Hertig and Rock, who showed high frequencies of morphological abnormalities in preimplantation embryos. The frequency of fetal losses after clinical recognition of pregnancy is 12-15%; however, more sensitive (ultrasonographic) methods of detecting fetal demise now indicate that most clinically recognized pregnancies occur prior to 8-9 weeks, being retained in utero 2-3 weeks prior to expulsion. Loss rates are influenced by maternal age, smoking, alcohol, and other confounding variables that if not taken into account could yield spurious results concerning safety of prenatal diagnostic techniques. After 8 weeks gestation the likelihood of losing a viable pregnancy is only 3% and after 16 weeks only 1%.

The lack of routine surveillance of Parvovirus B19 infection in pregnancy prevents an accurate understanding of this regular cause of fetal loss and the risks posed by occupational exposure

“…In the UK in 2007, infection was recorded as a cause of stillbirth in 3.5 % of cases, with the majority, up to 72 %, remaining unexplained, and less than half having a standard or coroner's post-mortem (CEMACH, 2007). In obstetric practice up to 12-15 % of clinically recognized pregnancies miscarry, with the likelihood of losing a viable pregnancy falling to 3 % after 8 weeks gestation and to 1 % after 16 weeks gestation (Simpson, 1990). Recurrent miscarriage is the spontaneous loss of three or more consecutive pregnancies with the same biological father and affects 1-2 % of couples (Duckitt & Qureshi, 2011), with 25-50 % of women experiencing one or more sporadic miscarriages.…”

Risk of abnormal pregnancy outcome in carriers of balanced reciprocal translocations involving the Miller-Dieker syndrome (MDS) critical region in chromosome 17p13.3

“…The rate of pregnancy loss was 28/127, or 22.4 ± 3.7%, including a miscarriage rate of 26/127, or 20.5 ± 3.6%, which is not significantly elevated over the general population rate of 10-20% [Gardner and Sutherland, 1996;Simpson, 1990;Laferia, 1986], and a stillbirth rate of 2/127, or 1.6 ± 1.1%, which is also similar to the population frequency of 1% [Curry, 1992].…”

Detection of confined placental mosaicism in trisomy 18 conceptions using interphase cytogenetic analysis

“…The vast majority of trisomy 18 conceptions are spontaneously aborted in the first or second trimester (Jacobs and Hassold 1987;Simpson 1990). Approximately 5% progress to the third trimester and are delivered as stillborn or liveborn infants.…”