Recent Increase in Sex Ratio at Birth in Viet Nam

Introduction

Since the 1980s, sex ratio at birth (male births per 100 female births) has increased in many Asian countries as a result of selective abortions, but to date there has been no such evidence for Viet Nam. Our aim in this paper is to ascertain the situation with respect to sex ratio at birth in Viet Nam over the past five years.

Materials and Methods

Original data were obtained from sample population surveys in Viet Nam recording annual birth rates since 2000 of about 450,000 women, as well as from two successive birth surveys conducted for the first time in 2007 (1.1 million births). The annual population surveys include specific information on birth history and mothers'' characteristics to be used for the analysis of trends and differentials in sex ratio at birth.

Results and Discussion

Birth history statistics indicate that the SRB in Viet Nam has recorded a steady growth since 2001. Starting from a level probably close to the biological standard of 105, the SRB reached 108 in 2005 and 112 in 2006, a value significantly above the normal level. An independent confirmation of these results comes from the surveys of births in health facilities which yielded a SRB of 110 in 2006–07. High SRB is linked to various factors such as access to modern health care, number of prenatal visits, level of higher education and employment status, young age, province of residence and prenatal sex determination. These results suggest that prenatal sex determination followed by selective abortion has recently become more common in Viet Nam. This recent trend is a consequence of various factors such as preference for sons, declining fertility, easy access to abortion, economic development as well as the increased availability of ultrasonography facilities.     

Ownership of Dwelling Affects the Sex Ratio at Birth in Uganda

Background

Socio-economic conditions can affect the secondary sex ratio in humans. Mothers under good environmental conditions are predicted to increase the birth rates of sons according to the Trivers-Willard hypothesis (TWH). This study analyzed the effects of ownership and non-ownership of dwellings on the sex ratio at birth (SRB) on a Ugandan sample.

Methodology/Principal Findings

Our investigation included 438,640 mothers aged between 12 and 54 years. The overall average SRB was 0.5008. Mothers who live in owned dwellings gave increased births to sons (0.5019) compared to those who live in non-owned dwellings (0.458). Multivariate statistics revealed the strongest effects of dwelling ownership when controlling for demographic and social variables such as marital status, type of marriage, mothers’ age, mothers’ education, parity and others.

Conclusions/Significance

The results are discussed in the framework of recent plausible models dealing with the adjustment of the sex ratio. We conclude that the aspect of dwelling status could represent an important socio-economic parameter in relation to SRB variations in humans if further studies are able to analyze it between different countries in a comparative way.     

Thyroid-Stimulating Antibody/Thyroid-Stimulating Hormone Receptor Antibody Ratio as a Sensitive Screening Test for Active Graves’ Orbitopathy

ObjectiveGraves’ orbitopathy (GO), an extrathyroidal manifestation of Graves’ disease, can seriously threaten a patient's quality of life. Given that immunosuppressive treatment during the early active phase of GO has been found to reduce both disease activity and severity, sensitive screening tests are needed.MethodsThe present study included 86 patients with GO, in whom serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (T3), free thyroxine, thyroid-stimulating antibody, TSH receptor antibody, thyroid peroxidase antibody, thyroglobulin, and thyroglobulin antibody were measured within 2 months before magnetic resonance imaging (MRI) for orbit assessment.ResultsThe thyroid-stimulating antibody/TSH receptor antibody ratio was able to distinguish MRI results with a correct classification rate of 81%. When focusing on patients without T3 predominant Graves’ diseases, the ratio distinguished MRI results at a rate of 92%. Receiver operating characteristic curve analysis revealed a cutoff antibody ratio of 87, which yielded a sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 91%, 95%, 18.2, and 0.0957, respectively, for distinguished MRI results.ConclusionsThe thyroid-stimulating antibody/TSH receptor antibody ratio is a highly sensitive and specific indicator for active GO, especially in patients without T3 predominance, and serves as a good screening test for active GO in primary care settings.     

Lack of Sex-Biased Maternal Investment in spite of a Skewed Birth Sex Ratio in White-Headed Langurs (Trachypithecus leucocephalus)

Numerous hypotheses have been developed to explain sex allocation. In male-dispersing, female cooperatively breeding species, the local resource competition model predicts male-biased birth sex ratio, the local resource enhancement model predicts female-biased birth sex ratio, and the population adjustment model predicts that biased birth sex ratio should not be favored if the two sexes are equally costly to rear. The male quality model predicts that, in polygynous species, females in better physical condition will either produce more sons than daughters or invest more heavily in sons than in daughters. White-headed langurs are a female philopatry and female cooperatively breeding species. During a 11-yr study, a total of 133 births were recorded, among which birth sex ratio (M:F = 73:49) was significantly male-biased. This is consistent with the prediction of the local resource competition model. On the other hand, if mothers balanced their investment between the two sexes, according to Fisher's population adjustment model, males should be the less-costly-to-rear sex. However, we found no sex difference for infant mortality (12.3% in males and 12.2% in females), and sons induced slightly longer interbirth interval (son: 26.4 ± 1.1 mo, daughter: 24.1 ± 0.6 mo) and lactational period (son: 20.9 ± 1.0 mo, daughters: 19.6 ± 0.5 mo) for their mothers. Thus, the population adjustment model was not supported by this study. The local resource enhancement model was not supported because birth sex ratio did not bias to females who provided more reproductive assistance. On the individual level, probit regression showed no relation between birth sex ratio and group size. Because the group size was considered to be negatively related to female physical condition, our study did not support the male-quality model. We suggested several possibilities to explain these results.     

Winning the Genetic Lottery: Biasing Birth Sex Ratio Results in More Grandchildren

Population dynamics predicts that on average parents should invest equally in male and female offspring; similarly, the physiology of mammalian sex determination is supposedly stochastic, producing equal numbers of sons and daughters. However, a high quality parent can maximize fitness by biasing their birth sex ratio (SR) to the sex with the greatest potential to disproportionately outperform peers. All SR manipulation theories share a fundamental prediction: grandparents who bias birth SR should produce more grandoffspring via the favored sex. The celebrated examples of biased birth SRs in nature consistent with SR manipulation theories provide compelling circumstantial evidence. However, this prediction has never been directly tested in mammals, primarily because the complete three-generation pedigrees needed to test whether individual favored offspring produce more grandoffspring for the biasing grandparent are essentially impossible to obtain in nature. Three-generation pedigrees were constructed using 90 years of captive breeding records from 198 mammalian species. Male and female grandparents consistently biased their birth SR toward the sex that maximized second-generation success. The most strongly male-biased granddams and grandsires produced respectively 29% and 25% more grandoffspring than non-skewing conspecifics. The sons of the most male-biasing granddams were 2.7 times as fecund as those of granddams with a 50∶50 bias (similar results are seen in grandsires). Daughters of the strongest female-biasing granddams were 1.2 times as fecund as those of non-biasing females (this effect is not seen in grandsires). To our knowledge, these results are the first formal test of the hypothesis that birth SR manipulation is adaptive in mammals in terms of grandchildren produced, showing that SR manipulation can explain biased birth SR in general across mammalian species. These findings also have practical implications: parental control of birth SR has the potential to accelerate genetic loss and risk of extinction within captive populations of endangered species.     

Plurihormonal Pituitary Adenoma Immunoreactive for Thyroid-Stimulating Hormone,Growth Hormone,Follicle-Stimulating Hormone,and Prolactin

ObjectiveTo describe the case of a patient with an unusual plurihormonal pituitary adenoma with immunoreactivity for thyroid-stimulating hormone (TSH), growth hormone, follicle-stimulating hormone, prolactin, an α-subunit.MethodsWe report the clinical, laboratory, imaging, and pathology findings of a patient symptomatic from a plurihormonal pituitary adenoma and describe her outcome after surgical treatment.ResultsA 60-year-old woman presented to the emergency department with headaches, blurry vision, fatigue, palpitations, sweaty hands, and weight loss. Her medical history was notable for hyperthyroidism, treated intermit with methimazole. Magnetic resonance imaging disclosed a pituitary macroadenoma (2.3 by 2.2 by 2.0 cm), and preoperative blood studies revealed elevated levels of TSH at 6.11 mIU/L, free thyroxine at 3.6 ng/dL, and free triiodothyronine at 6.0 pg/mL. She underwent an uncomplicated transsphenoidal resection of the pituitary adenoma. Immunostaining of tumor tissue demonstrated positivity for not only TSH but also growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. The Ki-67 index of the tumor was estimated at 2% to 5%, and DNA repair enzyme O6-methylguanine-DNA methyltransferase immunostaining was mostly negative. Electron microscopy showed the ultrastructural phenotype of a glycoprotein-producing adenoma. Postoperatively, her symptoms and hyperthyroidism resolved.ConclusionThyrotropin-secreting pituitary adenomas are rare. Furthermore, recent reports suggest that 31% to 36% of adenomas may show evidence of secretion of multiple pituitary hormones. This case emphasizes the importance of considering pituitary causes of thyrotoxicosis and summarizes the clinical and pathology findings in a patient with a plurihormonal pituitary adenoma. (Endocr Pract. 2012;18:e121-e126)     

Pre-Ablation Thyroglobulin and Thyroglobulin to Thyroid-Stimulating Hormone Ratio may be Associated with Pulmonary Metastases in Children with Differentiated Thyroid Cancer

Objective: Pediatric differentiated thyroid cancer (DTC) frequently presents with extensive disease. We studied the value of pre-ablation thyroglobulin (Tg) and Tg normalized to thyroid-stimulating hormone (TSH) levels in predicting distant metastases in pediatric patients with DTC.Methods: This is a retrospective cohort study of patients <21 years old who underwent thyroidectomy followed by ¹³¹I ablation for DTC at 3 university hospitals over 20 years. Tg levels and the Tg/TSH ratio following surgery but prior to ¹³¹I ablation were assessed. The presence of distant metastatic disease was determined from the postablation whole-body scan.Results: We studied 44 patients with a mean age of 15.2 years (range 7 to 21 years) and mean tumor size of 2.8 cm. Eight patients had distant metastases and had a higher mean pre-ablation Tg value compared to patients without distant metastases (1,037 μg/L versus 93.5 μg/L, P<.01). The pre-ablation Tg/TSH ratio was also associated with the presence of distant metastases: 12.5 ± 18.8 μg/mU in patients with distant metastases versus 0.7 ± 1.8 μg/mU in patients without (P<.01). A nomogram to predict distant metastases yielded areas under the receiver operating characteristic curve of 0.85 for Tg and 0.83 for Tg/TSH ratio.Conclusion: After initial thyroidectomy, elevated preablation Tg and Tg/TSH ratio are associated with distant metastatic disease in pediatric DTC. This may inform the decision to ablate with ¹³¹I, as well as the dosage.Abbreviations:ATA = American Thyroid AssociationCI = confidence intervalDTC = differentiated thyroid cancerOR = odds ratioROC = receiver operating characteristicTg = thyroglobulin     

Evidence that Mammalian Sex Ratios at Birth are Partially Controlled by Parental Hormone Levels at The Time of Conception

Evidence is adduced for the hypothesis that mammalian (including human) sex ratios at birth are partially controlled by the hormone levels of both parents at the time of conception. Sex ratio variation is considered under three main headings viz that identified by Clutton-Brock & Iason (1986); that identified since that paper; and other variation mainly relating to human beings. Some of the evidence is strong.     

Level of Thyroid-Stimulating Hormone (TSH) in Patients with Acute Schizophrenia,Unipolar Depression or Bipolar Disorder

The aim of this study is to investigate differences in thyroid-stimulating hormone (TSH) level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania. Serum level of TSH was measured in 1,685 Caucasian patients (1,064 women, 63.1 %; mean age 46.4). Mean serum TSH concentration was: schizophrenia (n = 769) 1.71 μIU/mL, unipolar depression (n = 651) 1.63 μIU/mL, bipolar disorder (n = 264) 1.86 μIU/mL, bipolar depression (n = 203) 2.00 μIU/mL, bipolar mania (n = 61) 1.38 μIU/mL (H = 11.58, p = 0.009). Depending on the normal range used, the overall rate of being above or below the normal range was 7.9–22.3 % for schizophrenia, 13.9–26.0 % for unipolar depression, 10.8–27.6 % for bipolar disorder, 12.2–28.5 % for bipolar depression, and 11.4–24.5 % for bipolar mania. We have also found differences in TSH levels between the age groups (≤20, >20 years and ≤40, >40 years and ≤60 years and >60 years). TSH level was negatively correlated with age (r = ? 0.23, p < 0.001). Weak correlations with age have been found in the schizophrenia (r = ? 0.21, p < 0.001), unipolar depression (r = ? 0.23, p < 0.001), bipolar depression (r = ? 0.25, p = 0.002) and bipolar disorder (r = ? 0.21, p = 0.005) groups. Our results confirm that there may be a higher prevalence of thyroid dysfunctions in patients with mood disorders (both unipolar and bipolar) and that these two diagnostic groups differ in terms of direction and frequency of thyroid dysfunctions.     

Prevalence of Elevated Thyroid-Stimulating Hormone Levels in Obese Children and Adolescents

ObjectiveTo determine the prevalence of elevated thyroid-stimulating hormone (TSH) levels in obese children and adolescents referred to pediatric endocrinology clinics.MethodsWe undertook a retrospective review of medical records of 191 obese and 125 nonobese children (younger than 18 years old). Data about age, sex, body mass index, TSH, thyroid functions, thyroid antibodies, thyroid size, and medications were collected.ResultsSix obese patients had Hashimoto disease and TSH values from 0.73 to 12.73 mIU/L; they were excluded from the study analyses. Of the remaining 185 obese subjects, 20 (10.8%) had TSH levels > 4 mIU/L, but no control subject measurement exceeded this TSH value. The highest TSH concentration in an obese study subject was 7.51 mIU/L. When obese children with TSH levels > 4 mIU/L were classified in a third group, the mean TSH in the rest of the obese children was comparable with that in the control group (1.98 ± 0.84 [SD] and 1.95 ± 0.80 mIU/L, respectively; post hoc analysis of variance, P = .945). Obese subjects with increased TSH values had a mean body mass index similar to that for obese subjects with normal TSH levels (34.98 ± 6.12 [SD] and 34.29 ± 7.84 kg/m², respectively).ConclusionMild elevation of TSH values in the absence of autoimmune thyroid disease is not uncommon in some obese children and adolescents. This is the second study in the United States to report this observation. Our study did not identify any special characteristics of obese subjects with TSH elevation in comparison with obese children with normal TSH levels and the control group. Current medical knowledge does not support routine screening for thyroid dysfunction in obese children. (Endocr Pract. 2010;16:187-190)     

Effect of Proton Pump Inhibitors on Serum Thyroid-Stimulating Hormone Level in Euthyroid Patients Treated with Levothyroxine for Hypothyroidism

ObjectiveTo examine retrospectively the effect of proton pump inhibitors (PPIs) on thyrotropin (thyroid-stimulating hormone or TSH) values in patients with hypothyroidism and normal TSH levels receiving levothyroxine (LT₄) replacement therapy.MethodsThe data collection was done by retrospective review of electronic medical records from the period of December 2002 to August 2005 from patients with hypothyroidism who were receiving at least 25 μg of LT₄ replacement daily at Queens Hospital Center. The first 92 patients meeting all inclusion and exclusion criteria were included in the study. The study group (N = 37) patient data were collected by selecting euthyroid patients who had received stable LT₄ replacement for at least 6 months and in whom PPI therapy (lansoprazole) was later initiated. TSH levels were collected before and at least 2 months after the PPI treatment was started. The control group (N = 55) patient data were collected by reviewing TSH levels among euthyroid patients with a history of hypothyroidism receiving stable LT₄ therapy and not receiving a PPI during the period of data collection. The statistical analysis was done by comparing the mean change in TSH level in each group with use of the Student t test.ResultsIn the study group, the mean change in the TSH level from before to at least 2 months after initiation of PPI therapy, 0.69 ± 1.9 μIU/mL, was statistically significant (P = 0.035). In the control group, the mean change in the TSH level during the study period, 0.11 ± 1.06 μIU/mL, was not statistically significant (P = 0.45).ConclusionTo our best knowledge, this is the first study in humans with hypothyroidism demonstrating the effect of PPIs on serum TSH levels. PPIs should be added to the list of medications affecting the level of thyroid hormone in patients with hypothyroidism treated with LT₄ replacement. Patients with hypothyroidism and normal TSH values during LT₄ replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT₄ dose. (Endocr Pract. 2007;13:345-349)     

Maternal Natal Environment and Breeding Territory Predict the Condition and Sex Ratio of Offspring

Females in a variety of taxa adjust offspring sex ratios to prevailing ecological conditions. However, little is known about whether conditions experienced during a female’s early ontogeny influence the sex ratio of her offspring. We tested for past and present ecological predictors of offspring sex ratios among known-age females that were produced as offspring and bred as adults in a population of house wrens. The body condition of offspring that a female produced and the proportion of her offspring that were male were negatively correlated with the size of the brood in which she herself was reared. The proportion of sons within broods was negatively correlated with maternal hatching date, and varied positively with the quality of a female’s current breeding territory as predicted. However, females producing relatively more sons than daughters were less likely to return to breed in the population the following year. Although correlative, our results suggest that the rearing environment can have enduring effects on later maternal investment and sex allocation. Moreover, the overproduction of sons relative to daughters may increase costs to a female’s residual reproductive value, constraining the extent to which sons might be produced in high-quality breeding conditions. Sex allocation in birds remains a contentious subject, largely because effects on offspring sex ratios are small. Our results suggest that offspring sex ratios are shaped by various processes and trade-offs that act throughout the female life history and ultimately reduce the extent of sex-ratio adjustment relative to classic theoretical predictions.     

Non-Invasive Prenatal Testing of Trisomy 18 by an Epigenetic Marker in First Trimester Maternal Plasma

Background

Quantification of cell-free fetal DNA by methylation-based DNA discrimination has been used in non-invasive prenatal testing of fetal chromosomal aneuploidy. The maspin (Serpin peptidase inhibitor, clade B (ovalbumin), member 5; SERPINB5) gene, located on chromosome 18q21.33, is hypomethylated in the placenta and completely methylated in maternal blood cells. The objective of this study was to evaluate the accuracy of non-invasive detection of fetal trisomy 18 using the unmethylated-maspin (U-maspin) gene as a cell-free fetal DNA marker and the methylated-maspin (M-maspin) gene as a cell-free total DNA marker in the first trimester of pregnancy.

Methodology/Principal Findings

A nested case-control study was conducted using maternal plasma collected from 66 pregnant women, 11 carrying fetuses with trisomy 18 and 55 carrying normal fetuses. Median U-maspin concentrations were significantly elevated in women with trisomy 18 fetuses compared with controls (27.2 vs. 6.7 copies/mL; P<0.001). Median M-maspin concentrations were also significantly higher in women with trisomy 18 fetuses than in controls (96.9 vs. 19.5 copies/mL, P<0.001). The specificities of U-maspin and M-maspin concentrations for non-invasive fetal trisomy 18 detection were 96.4% and 74.5%, respectively, with a sensitivity of 90.9%.

Conclusions

Our results suggest that U-maspin and M-maspin concentrations may be useful as potential biomarkers for non-invasive detection of fetal trisomy 18 in the first trimester of pregnancy, irrespective of the sex and genetic variations of the fetus.     

Effects of Maternal Smoking on the Placental Expression of Genes Related to Angiogenesis and Apoptosis during the First Trimester

Objective

Maternal cigarette smoking is reportedly associated with miscarriage, fetal growth restriction and placental abruption, and is paradoxically associated with a decreased risk of developing preeclampsia. In the present study, we investigated the gene expression levels of villous tissues in early gestation. We compared the expression levels of the genes related to angiogenesis and apoptosis in the villous tissues obtained from smoking and non-smoking pregnant women.

Materials and Methods

We collected villous tissue samples from 57 women requesting surgical termination due to non-medical reasons at 6–8 weeks of gestation. The maternal cigarette smoking status was evaluated by the level of serum cotinine and patients were divided into active smokers and non-smokers by the serum cotinine level. The placental levels of VEGFA, PGF, FLT1, HIF1A, TP53, BAX and BCL2 mRNA were quantified by real time PCR.

Results

The gene expression level of PGF and HIF1A in the active smoker group was significantly higher than that in the non-smoker group. We did not observe any significant differences in the VEGFA or FLT1 expression between the groups. In active smoker group, the gene expression levels of TP53 and BAX were significantly higher than those in the non-smoker group. The ratio of BAX/BCL2 mRNA in the active smoker group was significantly higher than that in the non-smoker group.

Conclusions

Our findings revealed that smoking might affect the placenta during early pregnancy. Maternal cigarette smoking in early pregnancy may be associated with villus hypoxia, which may influence angiogenesis and apoptosis.     

A Bioplex Analysis of Cytokines and Chemokines in First Trimester Maternal Plasma to Screen for Predictors of Miscarriage

Background

We have previously shown in two independent cohorts that circulating first trimester Macrophage Inhibitory Cytokine-1 (MIC-1) levels are lower in women in early pregnancy who are destined to miscarriage. While promising, the diagnostic performance of measuring MIC-1 alone was not sufficient for it to be a useful predictive test for miscarriage. Besides MIC-1, there are other cytokines, as well as chemokines, involved in facilitating early pregnancy. We reasoned that screening these factors in maternal plasma could uncover other predictive markers of miscarriage.

Methods

This was a nested case control study, of 78 women from a prospective study of 462 attending the Early Pregnancy Assessment Unit in the first trimester (EPAU) with a threatened miscarriage; 34 of these subsequently miscarried (cases) and 44 went on to have a normal delivery (controls) Cytokines IL-1β, IL-6 and IL-10, and the chemokines, CXCL8, CCL2, CCL5, CCL7 and CX3CL1 were measured in plasma from our cohort.

Results

The cytokines IL-1β, IL-6, IL-10 and the chemokine CXCL8 were not detectable in first trimester plasma. The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in all samples but levels did not vary across 5–12 weeks of gestation among controls. Plasma levels of these chemokines were no different in the miscarriage cohort compared to controls.

Conclusion

The chemokines CCL2, CCL5, CCL7 and CX3CL1 were detectable in plasma during the first trimester while IL-1β, IL-6, IL-10 and CXCL8 were not. However, none of the cytokines and chemokines screened were different in maternal plasma in cases or controls. These therefore do not appear to have potential for application as predictive biomarkers of miscarriage.     

Dating of Pregnancy in First versus Second Trimester in Relation to Post-Term Birth Rate: A Cohort Study

Objectives

To evaluate in a national standardised setting whether the performance of ultrasound dating during the first rather than the second trimester of pregnancy had consequences regarding the definition of pre- and post-term birth rates.

Methods

A cohort study of 8,551 singleton pregnancies with spontaneous delivery was performed from 2006 to 2012 at Copenhagen University Hospital, Holbæk, Denmark. We determined the duration of pregnancy calculated by last menstrual period, crown rump length (CRL), biparietal diameter (1^st trimester), BPD (2^nd trimester), and head circumference and compared mean and median durations, the mean differences, the systematic discrepancies, and the percentages of pre-term and post-term pregnancies in relation to each method. The primary outcomes were post-term and pre-term birth rates defined by different dating methods.

Results

The change from use of second to first trimester measurements for dating was associated with a significant increase in the rate of post-term deliveries from 2.1–2.9% and a significant decrease in the rate of pre-term deliveries from 5.4–4.6% caused by systematic discrepancies. Thereby 25.1% would pass 41 weeks when GA is defined by CRL and 17.3% when BPD (2^nd trimester) is used. Calibration for these discrepancies resulted in a lower post-term birth rate, from 3.1–1.4%, when first compared to second trimester dating was used.

Conclusions

Systematic discrepancies were identified when biometric formulas were used to determine duration of pregnancy. This should be corrected in clinical practice to avoid an overestimation of post-term birth and unnecessary inductions when first trimester formulas are used.