Sex and fetal genome influence gene expression in pig endometrium at the end of gestation.

BACKGROUND: A fine balance of feto-maternal resource allocation is required to support pregnancy, which depends on interactions between maternal and fetal genetic potential, maternal nutrition and environment, endometrial and placental functions. In particular, some imprinted genes have a role in regulating maternal-fetal nutrient exchange, but few have been documented in the endometrium. The aim of this study is to describe the expression of 42 genes, with parental expression, in the endometrium comparing two extreme breeds: Large White (LW); Meishan (MS) with contrasting neonatal mortality and maturity at two days of gestation (D90-D110). We investigated their potential contribution to fetal maturation exploring genes-fetal phenotypes relationships. Last, we hypothesized that the fetal genome and sex influence their endometrial expression. For this purpose, pure and reciprocally crossbred fetuses were produced using LW and MS breeds. Thus, in the same uterus, endometrial samples were associated with its purebred or crossbred fetuses. RESULTS: Among the 22 differentially expressed genes (DEGs), 14 DEGs were differentially regulated between the two days of gestation. More gestational changes were described in LW (11 DEGs) than in MS (2 DEGs). Nine DEGs were differentially regulated between the two extreme breeds, highlighting differences in the regulation of endometrial angiogenesis, nutrient transport and energy metabolism. We identified DEGs that showed high correlations with indicators of fetal maturation, such as ponderal index at D90 and fetal blood fructose level and placental weight at D110. We pointed out for the first time the influence of fetal sex and genome on endometrial expression at D90, highlighting AMPD3, CITED1 and H19 genes. We demonstrated that fetal sex affects the expression of five imprinted genes in LW endometrium. Fetal genome influenced the expression of four genes in LW endometrium but not in MS endometrium. Interestingly, both fetal sex and fetal genome interact to influence endometrial gene expression. CONCLUSIONS: These data provide evidence for some sexual dimorphism in the pregnant endometrium and for the contribution of the fetal genome to feto-maternal interactions at the end of gestation. They suggest that the paternal genome may contribute significantly to piglet survival, especially in crossbreeding production systems.

Protective role of macrophages from maternal-fetal interface in unvaccinated coronavirus disease 2019 pregnant women.

Pregnant women represent a high-risk population for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. The presence of SARS-CoV-2 has been reported in placenta from infected pregnant women, but whether the virus influences placenta immune response remains unclear. We investigated the properties of maternal-fetal interface macrophages (MFMs) in a cohort of unvaccinated women who contracted coronavirus disease 2019 (COVID-19) during their pregnancy. We reported an infiltration of CD163+ macrophages in placenta from COVID-19 women 19 whereas lymphoid compartment was not affected. Isolated MFMs exhibited nonpolarized activated signature (NOS2, IDO1, IFNG, TNF, TGFB) mainly in women infected during the second trimester of pregnancy. COVID-19 during pregnancy primed MFM to produce type I and III interferon response to SARS-CoV-2 (Wuhan and δ strains), that were unable to elicit this in MFMs from healthy pregnant women. COVID-19 also primed SARS-CoV-2 internalization by MFM in an angiotensin-converting enzyme 2-dependent manner. Activation and recall responses of MFMs were influenced by fetal sex. Collectively, these findings support a role for MFMs in the local immune response to SARS-CoV-2 infection, provide a basis for protective placental immunity in COVID-19, and highlight the interest of vaccination in pregnant women.

Maternal APOE ε2 as a possible risk factor for elevated prenatal Pb levels.

Lead (Pb) is a global contaminant associated with multiple adverse health effects. Humans are especially vulnerable during critical developmental stages. During pregnancy, exposure to Pb can occur through diet and release from maternal bones. Apolipoprotein E gene (APOE) variants (ɛ2, ɛ3, ɛ4 alleles) may influence sex steroid hormones, bone metabolism, and Pb kinetics. We examined the interplay among maternal APOE (mAPOE) genotypes, fetal sex, parity, and Pb in maternal and cord blood (mB-Pb, CB-Pb) using linear regression models. Our study involved 817 pregnant women and 772 newborns with measured adequate levels of zinc and selenium. We compared carriers of the ε2 and ε4 alleles to those with the ε3/ε3 genotype. The geometric means (range) of mB-Pb and CB-Pb were 11.1 (3.58-87.6) and 9.31 (1.82-47.0) ng/g, respectively. In cases with female fetuses, the maternal mAPOE ε2 allele was associated with higher, while the mAPOE ε4 allele was associated with lower mB-Pb and CB-Pb levels. Nulliparity increased the strength of the observed associations. These findings highlight the significance of mAPOE genetics, fetal sex, and parity in prenatal Pb kinetics. Notably, the maternal ε2 allele may increase the risk of Pb exposure.

Induced abortion after advent of fetal sex detection technology and child sex at birth.

BACKGROUND: National level Sex Ratio at Birth (SRB) is normal in Bangladesh despite its patriarchal social structures, strong son preference, and low fertility level, widely recognized as preconditions for Gender-Biased Sex Selection (GBSS). To better understand this anomaly, we examine the trend in SRB in a sub-district in Bangladesh and assess the impact of the introduction of fetal sex-detection technology and the history of induced abortion on child sex using longitudinal data. METHODS: We have used secondary data collected routinely by icddr, b's Matlab Health and Demographic Surveillance System (HDSS) between 1982 and 2018. All births occurring during this period (N = 206,390) were included in the analyses. We calculated the SRB and used multivariate logistic regression analyses to assess the likelihood of birth of a male child before and after the introduction of ultrasonogram in Matlab. RESULTS: Overall, SRB was within the natural limit (106) during 1982-2018 in Matlab. SRB among women with a history of induced abortion was 109.3 before the introduction of ultrasonography in 2001 and 113.5 - after 2001. Women's history of induced abortion prior to introduction of ultrasonogram (1982-2000) increased the likelihood of birth of a male child 1.06 times (AOR 1.06; 95% CI- 1.01-1.11). In the period after, however, this likelihood was 1.08 (AOR 1.08; 95% CI- 1.02-1.15). CONCLUSIONS: In a context with normal SRB, it was found to be skewed among women who had induced abortion. SRB was relatively more skewed among such women after the advent of ultrasonogram compared to a period without ultrasonogram. Moreover, induced abortion after introduction of fetal sex determination technology increased the likelihood of birth of a male child. These findings suggest the plausibility of GBSS in a sub-group. Further research is needed, particularly in regions with skewed SRB to examine whether GBSS is indeed a threat to Bangladesh.

First trimester identification of fetal sex by ultrasound.

PURPOSE: The hypothesis was fetal sex determination by ultrasound at 11-14 weeks' gestation has sufficient accuracy to be clinically relevant. METHODS: Fetal sex assessment by transabdominal ultrasound was performed in 567 fetuses at 11-14 weeks' gestation (CRL: 45-84 mm). A mid-sagittal view of the genital region was obtained. The angle of the genital tubercle to a horizontal line through the lumbosacral skin surface was measured. The fetus was assigned male sex if the angle was > 30°, and female sex if the genital tubercle was parallel or convergent (< 10°). At an intermediate angle of 10-30°, the sex was not assigned. The results were divided into three categories based on gestational age: 11 + 2 to 12 + 1, 12 + 2 to 13 + 1, and 13 + 2 to 14 + 1 weeks' gestation. To establish its accuracy, the first trimester fetal sex determination was compared to fetal sex determined on a mid-second trimester ultrasound. RESULTS: Sex assignment was successful in 534/683 (78%) of the cases. The overall accuracy of fetal sex assignment across all gestational ages studied was 94.4%. It was 88.3%, 94.7%, and 98.6% at 11 + 2 to 12 + 1, 12 + 2 to 13 + 1, and 13 + 2 to 14 + 1 weeks' gestation, respectively. CONCLUSION: Prenatal sex assignment at the time of first trimester ultrasound screening has a high accuracy rate. The accuracy improved with increasing gestational age, which suggests that if clinically important decisions, such as chorionic villus sampling, are to be made based on fetal sex, they should be delayed until the latter part of the first trimester.

The impact of fetal sex on pregnancy and neonatal outcomes in twin gestation.

PURPOSE: Fetal sex is independently associated with pregnancy complications and impacts neonatal outcomes. Evidence suggests that females have an advantage over males, with a better outcome in the perinatal period. In addition, fetal outcome in twin gestations is also related to the intrauterine position of the fetus, such as the first, the presenting or second twin. It has been demonstrated that the neonatal outcome of the second fetus is worse than that of the first fetus. This study aimed to examine the influence of fetal sex on obstetric outcomes in twin pregnancies based on the location of the fetus in the uterus. METHODS: Retrospective study. Maternal and obstetric outcomes were compared among three groups: male‒male, female‒female, and male‒female groups. Comparisons of neonatal outcomes were performed among the four groups: male A-male B, male A-female B, female A-male B, and female A-female B. RESULTS: A total of 1073 twin gestations were included, comprising 288 male‒male, 288 female‒female, and 497 male‒female gestations. A greater percentage of neonates admitted to the NICU was observed for male fetuses than for female fetuses. Adverse composite neonatal outcome was more common in the male‒male group than in the female‒male group and in the female‒female group. CONCLUSION: Twin gestation with a first twin male tends to have worse neonatal outcomes than does twin gestation with a first twin female. The presence of a male co-twin increases the risk of adverse outcomes.

DNA concentrations in amniotic fluid according to gestational age and fetal sex: data from 2573 samples.

PURPOSE: In some cases of prenatal genetic testing, an ample amount of fetal DNA is needed, to allow for parallel testing (conducting several genetic tests simultaneously). This study investigated the association between amniotic fluid DNA concentration and various factors. We aimed to define the required amount of amniotic fluid to be extracted in amniocentesis, to allow parallel testing throughout gestational weeks. METHODS: DNA concentration was analyzed from amniocentesis samples taken during the years 2016-2022. Sex association was also analyzed in postnatal whole blood samples from a separate cohort. Theoretical minimum volume of amniotic fluid needed to ensure enough DNA for chromosomal microarray analysis and exome sequencing was calculated. RESULTS: We focused our analysis on 2573 samples, which were taken during weeks 17-23 and 30-35. DNA concentrations increased from weeks 17 to 21, with relatively stable concentrations thereafter. Significantly higher DNA concentrations were seen in pregnancies of female fetuses. DNA concentrations in postnatal whole blood samples did not show this association. Across most weeks, the volume needed to extract 2 µg of DNA from 95% of the samples was about 34 ml. CONCLUSION: DNA concentrations in amniotic fluid vary according to gestational age and are higher in pregnancies of female fetuses. This should be considered when determining the volume of fluid extracted and the timing of amniocentesis, with greater volumes needed in earlier stages of pregnancy.

Fetal gender prediction by monitoring circulating steroid hormones and some biochemical parameters in maternal dromedary camels.

To predict the sex of the foetus, healthy pregnant dromedary camels (n = 24) were included. Blood samples were collected for measurements of progesterone, estradiol, testosterone, and cortisol as well as total proteins, albumin, glucose, creatinine, blood urea nitrogen, phosphorus, calcium, creatine kinase, alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), calcium, phosphorus, and magnesium. Statistical analysis revealed differences between pregnant camels and pregnant camels in terms of female or male foetuses depending on the actual sex of the born calf. The results revealed that testosterone and ALP concentrations were significantly (P < 0.001) greater in camels given to males than in those given to calves. There were strong positive correlations between male calf birth and testosterone and ALP concentrations (r = 0.864; P < 0.0001 and r = 0.637; P < 0.001, respectively). On the other hand, the cortisol, glucose and creatinine concentrations were significantly lower (P lower in camel calved males than in females). There were significant negative correlations between male calf birth and the cortisol, glucose and creatinine concentrations (r =-0.401; P = 0.052; r =-0.445; P = 0.029 and r =-0.400; P = 0.053, respectively). The concentrations of calcium, phosphorus, calcium/phosphorus ratio, magnesium, and albumin and the albumin/globulin ratio were not significantly different (P > 0.05) between the two groups. In conclusion, testosterone could be used as a biomarker to determine the sex of foetuses in dromedary camels.

Myo-inositol alters the effects of glucose, leptin and insulin on placental palmitic acid and oleic acid metabolism.

Well-regulated placental palmitic acid (PA) and oleic acid (OA) metabolism is vital for optimal placental function and fetal development, but dysregulation occurs with gestational diabetes (GDM). We hypothesized that such dysregulation might arise from increased maternofetal glucose, leptin or insulin concentrations present in GDM, and that dysregulated PA and OA lipid metabolism could be moderated by myo-inositol, a natural polyol and potential GDM intervention. Placental explants from 21 women were incubated with stable isotope-labelled 13 C-PA or 13 C-OA for 48 h. Explants were treated with glucose (5, 10 mm) or leptin (13 nm) or insulin (150 nm) in combination with myo-inositol (0.3, 30, 60 µm). Forty-seven 13 C-PA lipids and 37 13 C-OA lipids were measured by liquid chromatography-mass spectrometry (LCMS). Compared with controls (5 mm glucose), glucose (10 mm) increased 19 13 C-OA lipids and nine 13 C-PA lipids, but decreased 13 C-OA phosphatidylethanolamine 38:5 and 13 C-PA phosphatidylethanolamine 36:4. The effects of leptin and insulin were less prominent than glucose, with leptin increasing 13 C-OA acylcarnitine 18:1, and insulin increasing four 13 C-PA triacylglycerides. Most glucose, leptin and insulin-induced alterations in lipids were attenuated by co-incubation with myo-inositol (30 or 60 µm), with attenuation also occurring in all subgroups stratified by GDM status and fetal sex. However, glucose-induced increases in acylcarnitine were not attenuated by myo-inositol and were even exaggerated in some instances. Myo-inositol therefore appears to generally act as a moderator, suppressing the perturbation of lipid metabolic processes by glucose, leptin and insulin in placenta in vitro. Whether myo-inositol protects the fetus and pregnancy from unfavourable outcomes requires further research. KEY POINTS: Incubation of placental explants with additional glucose, or to a lesser extent insulin or leptin, alters the placental production of 13 C-lipids from 13 C-palmitic acid (PA) and 13 C-oleic acid (OA) in vitro compared with untreated controls from the same placenta. Co-incubation with myo-inositol attenuated most alterations induced by glucose, insulin or leptin in 13 C-lipids, but did not affect alterations in 13 C-acylcarnitines. Alterations induced by glucose and leptin in 13 C-PA triacylglycerides and 13 C-PA phospholipids were influenced by fetal sex and gestational diabetes status, but were all still attenuated by myo-inositol co-incubation. Insulin differently affected 13 C-PA triacylglycerides and 13 C-PA phospholipids depending on fetal sex, with alterations also attenuated by myo-inositol co-incubation.

Performance of prenatal cfDNA screening for sex chromosomes.

PURPOSE: The aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation. METHODS: This was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies. RESULTS: A total of 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs, and fetal sex was determined in 17,297, 10,333, and 14,486 pregnancies, respectively. Sensitivity, specificity, and positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%. CONCLUSION: Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.

Cadmium reduces growth of male fetuses by impairing development of the placental vasculature and reducing expression of nutrient transporters.

In utero exposure to the toxic metal cadmium (Cd) alters fetoplacental growth in rodents and has been inversely associated with birth weight and infant size in some birth cohorts. Moreover, studies suggest that Cd may have differential effects on growth and development according to offspring sex. The purpose of the current study was to evaluate changes in male and female fetoplacental development following a single injection of saline (5 ml/kg ip) or cadmium chloride (CdCl2, 2.5, 5 mg/kg, ip) on gestational day (GD) 9. By GD18, no changes in fetal or placental weights were observed after treatment with 2.5 mg/kg CdCl2. By comparison, the weight and length of male fetuses and their placentas were reduced following treatment with 5 mg/kg CdCl2 whereas no change was observed in females. In addition, the area of maternal and fetal blood vessels as well as the expression of the glucose transporters, Glut1 and Glut3, and the endothelial marker, CD34, were reduced in the placentas of CdCl2-treated male offspring compared to females. Interestingly, the placentas of females accumulated 80% more Cd than males after CdCl2 (5 mg/kg) administration. Female placentas also had higher concentrations of zinc and the zinc transporter Znt1 compared to males which may explain the limited changes in fetal growth observed following CdCl2 treatment. Taken together, disruption of vasculature development and reduced expression of glucose transporters in the placenta provide potential mechanisms underlying reduced fetal growth in male offspring despite the greater accumulation of Cd in female placentas.

Sexual dimorphism in placental development and function: Comparative physiology with an emphasis on the pig.

Across mammalian species, it has been demonstrated that sex influences birth weight, with males being heavier than females; a characteristic that can be observed from early gestation. Male piglets are more likely to be stillborn and have greater preweaning mortality than their female littermates, despite the additional maternal investment into male fetal growth. Given the conserved nature of the genome between the sexes, it is hypothesized that these developmental differences between males and females are most likely orchestrated by differential placental adaptation. This review summarizes the current understanding of fetal sex-specific differences in placental and endometrial structure and function, with an emphasis on pathways found to be differentially regulated in the pig including angiogenesis, apoptosis, and proliferation. Given the importance of piglet sex in agricultural enterprises, and the potential for skewed litter sex ratios, it is imperative to improve understanding of the relationship between fetal sex and molecular signaling in both the placenta and endometria across gestation.

Maternal Iron Status Is Dynamic Throughout Pregnancy and Might Predict Birth Outcomes in a Sex Dependent Manner: Results from the Alberta Pregnancy Outcomes and Nutrition (APrON) Cohort Study.

BACKGROUND: Developmental responses to nutrient deprivation may differ by fetal sex. Despite this, relationships between maternal prenatal iron biomarkers and birth outcomes when stratifying by offspring sex are poorly described, especially in healthy cohorts. OBJECTIVES: This study aimed to determine associations between maternal iron biomarkers and birth weights (BWs) and birth head circumferences (BHCs) among female and male newborns to assess whether the potential predictive ability of iron biomarkers on birth outcomes differs by offspring sex. METHODS: The Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study recruited 2189 pregnant individuals from Calgary and Edmonton, Canada. Maternal blood was drawn at each trimester and 3 mo postpartum. Maternal serum ferritin (SF) concentrations were measured using chemiluminescent immunoassays and erythropoietin (EPO), hepcidin, and soluble transferrin receptor (sTfR) using enzyme-linked immunosorbent assays. Ratios of sTfR:SF and hepcidin:EPO were calculated and birth outcomes accessed through delivery records. Directed acyclic graphs informed multivariate regression models. RESULTS: The risk of maternal iron deficiency increased throughout pregnancy because ∼61% showed depleted iron stores (SF < 15 µg/L) by the third trimester. Maternal hepcidin, SF, sTfR, and sTfR:SF concentrations changed across time (P < 0.01), and participants carrying female fetuses consistently (across 6 biomarkers) showed a lower iron status during the third trimester compared with those with male fetuses (P < 0.05). Higher maternal SF and hepcidin:EPO during the third trimester was associated with lower BWs in males (P = 0.006 for SF; P = 0.03 for hepcidin:EPO) and females (P = 0.02 for SF; P = 0.02 for hepcidin:EPO). There were additional inverse associations between BWs and third trimester maternal hepcidin (P = 0.03) and hemoglobin (P = 0.004) and between BHCs and maternal SF (second trimester; P < 0.05) and Hb (third trimester P = 0.02) but only in males. CONCLUSIONS: Relationships between maternal iron biomarkers and BWs and BHCs may depend on the timing of pregnancy and offpsring sex. There was a high risk of third trimester iron storage depletion among generally healthy pregnant individuals.

A 10-Year Observational Study on Twin Pregnancy: Role of Fetal Sex Pairing on Obstetric Outcome.

Fetal sex contributes to the determination of obstetric outcome, as pregnancies carrying male babies seem to have an increased risk of maternal-fetal complications. Most studies have been conducted on singleton pregnancies, whereas less evidence is available for twins. A 10-year retrospective observational study was conducted on a cohort of 1180 women with twin pregnancy delivered at a single tertiary hospital. Clinical data on maternal characteristics, and obstetric and neonatal outcomes were collected, and the analysis was performed on monochorionic (MC) and dichorionic (DC) diamniotic twins separately. The group of DC twins included 837 cases, and those conceived by assisted reproductive technologies (ART) were more likely to have one or both female fetuses rather than males. The incidence of hypertensive disorders of pregnancy (HDP) was higher in same-sex pairs than in opposite-sex pairs. No differences were found regarding other obstetric and neonatal outcomes among the three sex-pairing groups. The MC twins group included 228 cases, and in female-carrying pregnancies a higher incidence of gestational diabetes (GDM) was observed compared to the male group. Furthermore, male pairs had significantly lower Apgar scores than females. Fetal sex seems to have a mild effect in twins compared to singleton pregnancies, suggesting a more complex set of factors contributing to pregnancy outcome in multiple pregnancies. However, we observed a higher incidence of HDP among same-sex DC pairs, a higher rate of GDM among MC female-female pairs, and a worse adaptation to extrauterine life among male-male pairs in MC twins.

Association between fetal sex and pregnancy outcomes among women with twin pregnancies: a multicenter cross-sectional study.

PURPOSE: To examine the frequency and to what extent fetal sex is associated with pregnancy outcomes among twin pregnancies, stratified by chorionicity. METHODS: This registry-based multicenter cross-sectional study was conducted using the Japan Society of Obstetrics and Gynecology perinatal database between 2007 and 2016. The sample population was restricted to women with twin pregnancies. The main pregnancy-related outcomes included preterm birth, very preterm birth, extremely preterm birth, preeclampsia, twin-to-twin transfusion syndrome (TTTS), and selective intrauterine growth restriction (s-IUGR). Birth weight, small for gestational age (SGA), and fetal death were also investigated. RESULTS: The primary analysis was performed based on 37,953 women, including 23,804 women with dichorionic diamniotic (DD) twins and 14,149 women with monochorionic diamniotic (MD) twins. Women with male/male DD twins had a significantly higher risk of preterm birth (adjusted risk ratio [aRR]: 1.07, 95% confidence interval [CI]: 1.03-1.10) and a lower risk of preeclampsia (aRR: 0.74, 95% CI: 0.62-0.88) than women with female/female DD twins. Women with male/male MD twins also had a significantly higher risk of preterm birth (aRR: 1.06, 95% CI: 1.04-1.09) than women with female/female MD twins. Risks of preeclampsia, TTTS, and s-IUGR did not differ by sex among MD pregnancies. Male SGA risk was significantly higher among male/male twins than among male/female DD twins. Among MD twins, risks of SGA and fetal death were significantly higher in male/male fetuses. CONCLUSIONS: This study demonstrated significant associations between fetal sex and several pregnancy outcomes in twin pregnancies, some of which differed by chorionicity.

Electrochemical impedance biosensor based on Y chromosome-specific sequences for fetal sex determination.

A new electrochemical biosensor based on the sequence of chromosome Y (SRY) has been introduced to determine the gender of the fetus. At first, the DNA probe was designed based on the SRY gene sequence on chromosome Y. Then, a suitable functional group was added to the DNA probe, and it has been immobilized on the surface of the electrode modified with a nanocomposite containing Cu(OH)2 @N-C n-boxes. This substrate causes more DNA probes to connect to the electrode surface by increasing the effective surface area. The presence of the SRY sequence in the DNA sample extracted from blood was detected by the electrochemical signal of the bio-sensor. After optimizing the parameters, the fabricated genosensor showed linear responses in the two concentration ranges containing 0.5 fM to 50 pM and 50 pM to 500 nM. The limit of detection (LOD) for the proposed method was 0.16 fM. The proposed genosensor has been successfully used to determine the gender of the fetus using cell-free fetal DNA (cffDNA) in the blood plasma of several pregnant mothers. This method has advantages such as being simple, portable, accurate, and non-invasive for early determination of the gender of the fetus and early diagnosis of X-linked genetic disorders.

Sonographic Assessment of Fetal Sex: More than External Genitalia.

Early identification of fetal sex is possible due to both improved ultrasound resolution and the incorporation of cell-free DNA testing into routine prenatal screening services. While ultrasound assessment of the external genitalia generally suffices, there are instances where identification of the internal genitalia becomes vital to allow accurate prenatal diagnosis and comprehensive counseling. This manuscript outlines the methodology and clinical utility of assessing fetal genitalia beyond conventional sonography from the second trimester onward and is the first to describe direct visualization of the fetal vagina.

Regulating non-invasive prenatal testing (NIPT) for fetal sex determination.

Non-invasive prenatal testing (NIPT) can be used to determine the chromosomal sex of the fetus at an early stage in a pregnancy. The use of NIPT for fetal sex determination raises concerns about potential selective termination of pregnancy by prospective parents who desire a child of a particular sex. Although sex selection for medical reasons is generally accepted, non-medical sex selection (NMSS) has been the subject of considerable controversy. In this article, we explore the current regulatory landscape around reproductive genetic testing techniques that may lead to NMSS, both internationally and within Australia. Specifically, we contrast the approach to regulating preimplantation genetic testing (PGT) with the minimal regulation of NIPT in Australia as a case study for reform. We examine ethical concerns raised in relation to NMSS, which form the basis of the current moratorium on the use of PGT for NMSS. We then highlight some key differences between using PGT for NMSS and NIPT for fetal sex determination to determine whether access to the latter should be regulated and, if so, how. We conclude that there is insufficient evidence to restrict access to NIPT for fetal sex determination and, based on our Australian case study, recommend a facilitative approach to regulating NIPT that would support individuals to make informed reproductive decisions.

Increased risk of preterm delivery with high cortisol during pregnancy is modified by fetal sex: a cohort study.

BACKGROUND: Previous studies show an association between maternal plasma and salivary cortisol and preterm birth but have been primarily conducted in high-income countries. It is unknown whether salivary cortisol is a risk factor for preterm birth in Ghana. Our objective was to determine whether maternal salivary cortisol during pregnancy was associated with pregnancy duration and preterm delivery in Ghana. METHODS: We conducted a cohort study of 783 pregnant women in Ghana. We measured salivary cortisol at baseline (mean 16 wk), 28 wk., and 36 wk. gestation. Pregnancy duration was determined primarily by ultrasound. We used adjusted linear regression models to examine the association between cortisol and pregnancy duration and Poisson regression models to determine the risk of preterm delivery among women with high cortisol at baseline or 28 wk. gestation. RESULTS: Mean pregnancy duration was 39.4 ± 1.8 wk. and 6.6% had a preterm delivery. Mean maternal cortisol increased throughout pregnancy, from 4.9 ± 2.7 nmol/L at baseline (16 wk) to 6.4 ± 3.2 nmol/L at 28 wk. and 7.9 ± 3.0 nmol/L at 36 wk. gestation. In adjusted analyses, higher cortisol concentrations at baseline (ß = - 0.39, p = .002) and 28 wk. (ß = - 0.49, p = .001), but not 36 wk. (ß = - 0.23, p = .084) were associated with a shorter pregnancy duration. Women with high cortisol at baseline (> 6.3 nmol/L) had an increased relative risk of preterm delivery (RR (95% CI): 1.96 (1.13, 3.40)), but the association between high cortisol at 28 wk. and preterm delivery was not significant. There was a significant interaction with fetal sex (p-for-interaction = 0.037): among women carrying male fetuses, high cortisol at baseline increased the risk of preterm delivery threefold (3.18 (1.51, 6.71)) while there was no association (1.17 (0.50, 2.74)) among women carrying female fetuses. CONCLUSION: Higher maternal cortisol is associated with a shorter pregnancy duration and an increased risk of preterm delivery. Subgroup analysis by fetal sex revealed that this association is evident primarily among women carrying male fetuses. Future studies of cortisol and preterm delivery should include consideration of fetal sex as a potential effect modifier.

Sex-dependent influence of maternal predictors on fetal anthropometry in pregnancies with gestational diabetes mellitus.

BACKGROUND: Third trimester fetal anthropometric parameters are known to predict neonatal complications. A better understanding of predictors of adverse fetal parameters might help to personalize the use and frequency of fetal ultrasound. The objectives of this study were: (a) to evaluate the utility of maternal sociodemographic, anthropometric and metabolic predictors to predict 3rd trimester fetal anthropometric parameters in women with gestational diabetes mellitus (GDM), (b) to assess whether the impact of these maternal predictors is fetal sex-dependent, and (c) to provide a risk stratification for markers of fetal overgrowth (fetal weight centile (FWC) and fetal abdominal circumference centile (FACC) depending on prepregnancy BMI and gestational weight gain (GWG) until the 1st GDM visit. METHODS: This prospective study included 189 women with GDM. Maternal predictors were age, ethnicity, prepregnancy BMI, GWG and excessive weight gain until the 1st GDM visit, fasting, 1-hour and 2-hour blood glucose oral glucose tolerance test values, HbA1c at the 1st visit and medical treatment requirement. Fetal outcomes included FWC, FWC >90% and <10%, FACC, FACC >90% and <10%, at 29 0/7 to 35 6/7 weeks of gestational age. We performed univariate and multivariate regression analyses and probability analyses. RESULTS: In multivariate analyses, prepregnancy BMI was associated with FWC, FWC > 90% and FACC. GWG until the 1st GDM visit was associated with FWC, FACC and FACC > 90% (all p ≤ 0.045). Other maternal parameters were not significantly associated with fetal anthropometry in multivariate analyses (all p ≥ 0.054). In female fetuses, only GWG was associated with FACC (p= 0.044). However, in male fetuses, prepregnancy BMI was associated with FWC, FWC > 90% and FACC and GWG with FWC in multivariate analyses (all p ≤ 0.030). In women with a prepregnancy BMI of ≥ 25 kg/m2 and a GWG until the 1st GDM visit ≥ 10.3 kg (mean GWG), the risk for FWC > 90% and FACC > 90% was 5.3 and 4 times higher than in their counterparts. CONCLUSIONS: A personalized fetal ultrasound surveillance guided by fetal sex, prepregnancy BMI and GWG may be beneficial in reducing adverse fetal and neonatal outcomes.