Maternal genetic disorders and fetal development

With improvements in early diagnosis and management of genetic diseases, more women with genetic disorders are reaching reproductive age and becoming pregnant. While pregnancy can have a significant impact on a woman's health when there is an underlying genetic disorder, there can also be fetal effects, including embryopathy, fetal growth restriction, and brain injury. Some maternal genetic disorders are associated with adverse perinatal outcomes, including a high risk of perinatal loss and preterm birth. In this article, we review several maternal genetic disorders associated with fetal risk that are important for clinicians and patients to understand and manage appropriately. These include phenylalanine hydroxylase (PAH) deficiency and other inborn errors of metabolism, tuberous sclerosis complex, myotonic dystrophy, cystic fibrosis, Turner syndrome, sickle cell disease, and connective tissue disorders.     

Etiology and management of early pregnancy renal anhydramnios: Is there a place for serial amnioinfusions?

Early pregnancy renal anhydramios (EPRA) comprises congenital renal disease that results in fetal anhydramnios by 22 weeks of gestation. It occurs in over 1 in 2000 pregnancies and affects 1500 families in the US annually. EPRA was historically considered universally fatal due to associated pulmonary hypoplasia and neonatal respiratory failure. There are several etiologies of fetal renal failure that result in EPRA including bilateral renal agenesis, cystic kidney disease, and lower urinary tract obstruction. Appropriate sonographic evaluation is required to arrive at the appropriate urogenital diagnosis and to identify additional anomalies that allude to a specific genetic diagnosis. Genetic evaluation variably includes karyotype, microarray, targeted gene testing, panels, or whole exome sequencing depending on presentation. Patients receiving a fetal diagnosis of EPRA should be offered management options of pregnancy termination or perinatal palliative care, with the option of serial amnioinfusion therapy offered on a research basis. Preliminary data from case reports demonstrate an association between serial amnioinfusion therapy and short-term postnatal survival of EPRA, with excellent respiratory function in the neonatal period. A multicenter trial, the renal anhydramnios fetal therapy (RAFT) trial, is underway. We sought to review the initial diagnosis ultrasound findings, genetic etiologies, and current management options for EPRA.     

A system-based approach to the genetic etiologies of non-immune hydrops fetalis

A wide spectrum of genetic causes may lead to nonimmune hydrops fetalis (NIHF), and a thorough phenotypic and genetic evaluation are essential to determine the underlying etiology, optimally manage these pregnancies, and inform discussions about anticipated prognosis. In this review, we outline the known genetic etiologies of NIHF by fetal organ system affected, and provide a systematic approach to the evaluation of NIHF. Some of the underlying genetic disorders are associated with characteristic phenotypic features that may be seen on prenatal ultrasound, such as hepatomegaly with lysosomal storage disorders, hyperechoic kidneys with congenital nephrosis, or pulmonary valve stenosis with RASopathies. However, this is not always the case, and the approach to evaluation must include prenatal ultrasound findings as well as genetic testing and many other factors. Genetic testing that has been utilized for NIHF ranges from standard chromosomal microarray or karyotype to gene panels and broad approaches such as whole exome sequencing. Family and obstetric history, as well as pathology examination, can yield additional clues that are helpful in establishing a diagnosis. A systematic approach to evaluation can guide a more targeted approach to genetic evaluation, diagnosis, and management of NIHF.     

Fallow deer polyandry is related to fertilization insurance

Polyandry is widespread, but its adaptive significance is not fully understood. The hypotheses used to explain its persistence have rarely been tested in the wild and particularly for large, long-lived mammals. We investigated polyandry in fallow deer, using female mating and reproduction data gathered over 10 years. Females of this species produce a single offspring (monotocous) and can live to 23 years old. Overall, polyandry was evident in 12 % of females and the long-term, consistent proportion of polyandrous females observed, suggests that monandry and polyandry represent alternative mating strategies. Females were more likely to be polyandrous when their first mate had previously achieved high numbers of matings during the rut or was relatively old. However, polyandry was not related to the following factors: female age, the stage of the rut, the dominance ranks of mates, or the number of daily matings achieved by males. Polyandrous and monandrous multiple-mating females were not more likely than single-mating females to be observed with an offspring during the following year, and there were no significant differences in offspring size between these females. These results provide support for a fertility insurance hypothesis, with females remating if fertilization from the first mating was uncertain due to possible sperm depletion. The potential for different female mating strategies among large, polygynous mammals has generally been overlooked. Our findings highlight the complexity of female reproductive strategies and the possible trade-offs between fertilization success, preferences for high-quality males, and potential costs of polyandry, particularly for monotocous species.     

Lipid and protein utilisation during early development of yellowtail kingfish (<Emphasis Type="Italic">Seriola lalandi</Emphasis>)

The pelagic yellowtail kingfish Seriola lalandi has become a target species for aquaculture in Asia and Australasia. Australasian production is reliant on larviculture from eggs of captive brood stock; however, knowledge regarding the nutritional requirements of larvae of this species is still scarce, particularly in relation to lipids. As a first step in establishing these requirements, eggs and larvae from captive S. lalandi brood stock were examined for differences in total protein, total lipid and lipid classes between individual spawning events, over the spawning season, and during larval development from fertilisation to 15 days post hatch. Results indicate that total protein egg⁻¹ varied significantly between individual spawning events within a season, but neither total lipid nor total protein egg⁻¹ varied significantly across the spawning season. Brood stock egg lipids were made up of approximately 60% phospholipid, 25% wax and/or sterol esters (WE), 15% triacylglycerol (TAG), and small amounts of sterols and free fatty acids. During the early larval period, both WE and TAG were utilised concurrently for energy. The larvae experienced very high mortality around 5–7 days post hatch, which coincided with very low levels of all neutral lipid classes. Although many other factors may also influence larval mortality, these results indicate that lipid provisioning may be an important factor in larval survival during the critical period around first-feeding in this species. Examination of ratios of TAG:ST, often used as a condition index in fish larvae, suggested that some of the larvae were suffering from starvation. However, as egg-derived WE appears to provide a significant source of energy during the early larval period in S. lalandi, it is suggested that WE should be included in any index of larval nutritional state.     

Estimating species occurrence, abundance, and detection probability using zero-inflated distributions

Researchers have developed methods to account for imperfect detection of species with either occupancy (presence absence) or count data using replicated sampling. We show how these approaches can be combined to simultaneously estimate occurrence, abundance, and detection probability by specifying a zero-inflated distribution for abundance. This approach may be particularly appropriate when patterns of occurrence and abundance arise from distinct processes operating at differing spatial or temporal scales. We apply the model to two data sets: (1) previously published data for a species of duck, Anas platyrhynchos, and (2) data for a stream fish species, Etheostoma scotti. We show that in these cases, an incomplete-detection zero-inflated modeling approach yields a superior fit to the data than other models. We propose that zero-inflated abundance models accounting for incomplete detection be considered when replicate count data are available.     

Efficacy of stable isotope ratios in assigning endangered migrants to breeding and wintering sites.

A primary constraint on effective conservation of migratory animals is our inability to track individuals through their annual cycle. One such animal is the endangered southwestern subspecies of the Willow Flycatcher, which is difficult to distinguish from conspecifics. Identifying wintering regions used by the endangered subspecies would be an important step in formulating an effective conservation strategy. Our objective was to use stable isotope ratios as a means of identifying wintering sites of Southwestern Willow Flycatchers. We analyzed stable isotope ratios of carbon, nitrogen, and hydrogen from feathers of breeding and wintering Willow Flycatchers. Based on winter samples, we document a positive trend in hydrogen isotope ratios across latitude. We also found that Willow Flycatchers use C4 food webs south of 8 degrees N latitude, but we found no evidence of use of C4 food webs farther north. Nitrogen stable isotope ratios of feathers showed no discernable geographic variation. Discriminant function analyses, based on stable isotope ratios of wintering Willow Flycatchers, were only useful (>50% accurate) for assigning individuals to winter regions if the regions were large and the threshold probability for assignment was relatively high. When using these discriminant functions, most breeding samples of Southwestern Willow Flycatchers were assigned to two wintering regions: central Mexico and Ecuador. We think that assignment of Southwestern Willow Flycatchers to Ecuador is unrealistic. Given the large percentages of samples that could not be classified with certainty, we are not confident that these two regions are truly more likely to harbor wintering Southwestern Willow Flycatchers than other winter regions. We think our inconclusive results are due primarily to weak and nonlinear gradients in isotope ratios across the winter range of Willow Flycatchers.