Prenatal Steroid Exposure Research Articles

Association between the digit ratio (2D:4D), handgrip strength, wrist ratio, and body fat distribution in women with different carpal tunnel syndrome severity

BackgroundTo evaluate the relationship of the second to fourth digit ratio (2D:4D), a biomarker of prenatal sex hormone exposure, with wrist ratio (WR), wrist-palm ratio (WPR), body mass index (BMI), waist-hip ratio (WHR), and handgrip strength (HGS) in different carpal tunnel syndrome (CTS) severity. MethodThis study involved 90 female participants (aged 18 to 83) with CTS. According to CTS severity, the participants were divided into four groups: normal, mild, moderate, and severe. All parameters of hand anthropometry and body fat distribution were measured, and the mean 2D:4D, WR, WPR, HGS, BMI, and WHR values were compared based on CTS severity. Data were collected with a visual analog scale (VAS) for pain and a Likert (LS) scale for numbness severity. ResultsThe mean age, 2D:4D, WD, WW, WR, WPR, BMI, and HGS values showed a significant differences between CTS severity groups. We found that lower 2D:4D and higher WPR and BMI were associated with increased risk of CTS (AUC = 0.728) after removing the effect of age. Bilateral hands were affected in 38.9 % (70/180) of participants. Regression analysis showed that lower HGS can be used as independent variable for predicting the females having bilateral affected hands. The LS score was considerably higher in the severe and moderate groups. Also, the VAS score was significantly higher in the severe group. ConclusionThe findings of the study demonstrated an association between 2D:4D, WPR, and BMI among women, emphasizing the effect of intrauterine sex hormone exposure on late life CTS severity.

Association of antenatal corticosteroids with mortality and morbidities in very preterm infants born to women with hypertensive disorders of pregnancy: a multicenter prospective cohort study

BackgroundHypertensive disorders of pregnancy (HDP) is the most common cause of indicated preterm delivery, but the impact of prenatal steroid exposure on the outcomes of preterm infants born to HDP mothers, who may be at risk for intrauterine hypoxia-ischemia, remains uncertain. The study objective is to evaluate the mortality and morbidities in HDP for very preterm infants (VPIs) exposed to different course of ANS.MethodsThis is a prospective cohort study comprising infants with < 32 weeks gestation born to women with HDP only from 1 Jan. 2019 to 31 Dec. 2021 within 40 participating neonatal intensive care units (NICUs) in Sino-northern network. ANS courses included completed, partial, repeated, and no ANS. Univariate and multivariable analyses were performed on administration of ANS and short-term outcomes before discharge.ResultsAmong 1917 VPIs born to women with HDP only, 987(51.4%) received a complete course of ANS within 48 h to 7 days before birth, 560(29.2%) received partial ANS within 24 h before delivery, 100(5.2%) received repeat ANS and 270 (14.1%) did not receive any ANS. Compared to infants who received complete ANS, infants unexposed to ANS was associated with higher odds of death (AOR 1.85; 95%CI 1.10, 3.14), Severe Neurological Injury (SNI) or death (AOR 1.68; 95%CI 1.29,3.80) and NEC or death (AOR 1.78; 95%CI 1.55, 2.89), the repeated ANS group exhibits a significant negative correlation with the duration of oxygen therapy days (correlation coefficient − 18.3; 95%CI-39.2, -2.1). However, there were no significant differences observed between the full course and partial course groups in terms of outcomes. We can draw similar conclusions in the non-SGA group, while the differences are not significant in the SGA group. From KM curve, it showed that the repeated group had the highest survival rate, but the statistical analysis did not indicate a significant difference.ConclusionsEven partial courses of ANS administered within 24 h before delivery proved to be protective against death and other morbidities. The differences mentioned above are more pronounced in the non-SGA group. Repeat courses demonstrate a trend toward protection, but this still needs to be confirmed by larger samples.

Patients with developmental dysplasia of the hip shows higher digit ratio (2D:4D)

BackgroundDevelopmental dysplasia of the hip (DDH) encompasses a range of hip disorders, from dysplasia to dislocation. One key factor is sex, with women being four to eight times more susceptible to DDH than men. However, there have been no studies investigating the second-to-fourth digit ratio (2D:4D), a biomarker of prenatal sex steroid exposure, in DDH patients. This study aimed to explore whether there is an association between the 2D:4D ratio and DDH. MethodsDigital calipers were used to measure the second and fourth finger lengths of 250 patients treated for DDH and 200 patients in the healthy control group between January 2020 and January 2023. The Mann-Whitney U test was used for non-normally distributed variables and two-way analysis of variance to assess differences in measurements between DDH patients based on sex, side, and the interaction of sex and side. The intraclass correlation coefficient (ICC) was used to assess measurement repeatability. ResultsThe median (min-max) age was 10.00 (6–16) years in the DDH group, 12.00 (6–16) years in the control group, and 10 (6–16) years for the whole cohort. There was no significant difference in terms of age between the patient and control groups (p = 0.083). When comparing the DDH group with controls the former showed higher right 2D:4D and Δ2D:4D and these differences were significant in both males and females. Among the patients, controlling for side of dysplasia did not affect right 2D:4D, left 2D:4D or Δ2D:4D. ConclusionThere was a significant association between higher 2D:4D ratios (both right and left hands) and DDH in both men and women. This indicates that the 2D:4D ratio, a marker of intrauterine estrogen/testosterone balance, is associated with DDH.

Digit Ratio (2D:4D) Is Not Associated with Alzheimer's Disease in the Elderly.

The development of Alzheimer's disease (AD) is influenced by sex hormones-estrogens and androgens in particular. However, the impact of prenatal sex hormone exposure is less clear; very few investigations have examined the relationship between the second-to-fourth digit length ratio (2D:4D), a putative proxy for the ratio of prenatal estrogens to androgens, and AD, with inconsistent results among the few that have. Therefore, we aimed to investigate this relationship using methodologically robust metrics. In a 2 (sex) × 4 (group) MANOVA incorporating 108 participants (30 AD patients, 19 patients with tauopathy but no amyloidopathy, 31 clinical and 28 healthy age- and education-matched controls), the effects of sex and group on the dependent variables right and left 2D:4D were examined. We also explored the association between 2D:4D and the severity of AD symptoms assessed via neuropsychological examination. We did not find any significant differences in the right- and left-hand 2D:4D between patients with AD and the other groups; no significant associations between 2D:4D and neuropsychological task performances were found in the dementia groups. The 2D:4D of healthy women was significantly lower than that of depressed women without AD, i.e., clinical controls, but not significantly different from depressed female patients with AD. This investigation does not support the role of 2D:4D in the development or severity of AD in general, but suggests a potential role of 2D:4D for depression in women. Future studies are warranted to clarify whether 2D:4D can distinguish between early- and late-onset depression in women.

Urinary Tract Infection Epidemiology in NICUs in the United States.

Our objective was to characterize the incidence, associated clinical factors, timing of infection, microbiology, and incidence of concordant blood culture of urinary tract infections (UTIs) in very low birth weight (VLBW <1,500g) infants. Multicenter observational cohort study of VLBW infants with gestational age (GA) ≤32 weeks, still hospitalized on postnatal day 7, and discharged 2010 to 2018 from Pediatrix Medical Group neonatal intensive care units. Demographic and clinical characteristics of infants with and without UTI were compared. Multivariable logistic regression evaluated adjusted odds of UTI diagnosis. Of 86,492 included infants, 5,988 (7%) had a UTI. The most common pathogen was Enterococcus spp. (20%), followed by Escherichia coli (19%) and Klebsiella spp. (18%). Candida spp. (6%) was the most common nonbacterial pathogen. Concordant-positive blood culture was present in 8% of infants with UTI diagnoses. UTI was associated with lower GA, male sex, vaginal delivery, prenatal steroid exposure, and longer duration of hospitalization. UTI is a common cause of infection in VLBW infants, especially among the smallest, most premature, male infants, and those with a longer duration of hospitalization. Neonatal clinicians should consider obtaining urine culture in the setting of late-onset sepsis evaluations in VLBW infants. · UTI is a common cause of LOS in VLBW infants.. · The most common pathogens are Enterococcus spp. and E. coli.. · UTI risk varies among different VLBW infant populations.. · Next steps should include evaluation of preventative measures..

The effect of patient volume on mortality and morbidity of extremely low birth weight infants in Taiwan

To assess whether the number of extremely low birth weight (ELBW) infants treated annually in neonatal intensive care units (NICUs) in Taiwan affects the mortality and morbidity of this patient population. This retrospective cohort study included preterm infants with ELBW (≤1000g). NICUs were divided into three subgroups according to the annual admissions of ELBW infants (low, ≤10; medium, 11-25; and high, >25). Perinatal characteristics, mortality, and short-term morbidities were compared between groups. A total of 1945 ELBW infants from 17 NICUs were analyzed (low-volume, n=263; medium-volume, n=420; and high-volume, n=1262). After risk adjustments, infants from NICUs with low patient volumes were at a higher risk of death. The risk-adjusted odds ratios (aOR) for mortality were 0.61 (95% CI, 0.43-0.86) in the high-volume NICUs and 0.65 (95% CI, 0.43-0.98) in medium-volume NICUs, compared with infants admitted to low-volume NICUs. Infants in medium-volume NICUs had the lowest incidence of prenatal steroid exposure (58.1%, P<0.001) and were associated with the highest risk of necrotizing enterocolitis (aOR, 2.35 [95% CI, 1.48-3.72]), severe intraventricular hemorrhage (aOR, 1.55 [95% CI, 1.01-2.28]), and bronchopulmonary dysplasia (aOR, 1.61 [95% CI, 1.10-2.35]). However, survival without major morbidity did not differ between the groups. The mortality risk was higher among ELBW infants admitted to NICUs with a low annual patient volume. This may emphasize the importance of systematically referring patients from these vulnerable populations to appropriate care settings.

Meta-analysis of the correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates

Objective: To systematically evaluate the correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates. Methods: Eight databases in either Chinese or English, including PubMed, the Cochrane Library, Embase, Medline, Scopus, CNKI, Wanfang and VIP, were searched to extract the studies on the correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates published from the establishment of each database to December 2022. The Meta-analysis was performed using Stata 14.0 statistical software. Results: A total of 9 studies were included in this Meta-analysis, including 6 retrospective cohort studies, 2 prospective cohort studies and 1 randomized controlled trial (RCT) study, involving 9 143 premature infants. The Meta-analysis showed that prenatal steroid exposure increased the risk of late preterm neonatal hypoglycemia (RR=1.55, 95%CI 1.25-1.91, P<0.001). The similar correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates was all found in the following subgroups: North America (RR=1.57, 95%CI 1.37-1.80, P<0.001), enrolling pregnant women with gestational diabetes (RR=1.62, 95%CI 1.26-2.08, P<0.001), A-grade literature quality (RR=1.43, 95%CI 1.14-1.79, P=0.002), criteria for hypoglycemia ≤40 mg/dl (1 mg/dl=0.056 mmol/L, RR=1.49, 95%CI 1.28-1.73, P<0.001), sample size of 501-1 500 (RR=1.69, 95%CI 1.19-2.40, P=0.003) and >1 500 (RR=1.65, 95%CI 1.48-1.83, P<0.001), steroid injection dosage and frequency of 12 mg 2 times (RR=1.66, 95%CI 1.50-1.84, P<0.001), the time interval from antenatal corticosteroid administration to delivery of 24-47 h (RR=1.98, 95%CI 1.26-3.10, P=0.003), unadjusted gestational age (RR=1.78, 95%CI 1.02-3.10,P=0.043) and unadjusted birth weight (RR=1.80, 95%CI 1.22-2.66, P=0.003). Meta-regression results showed that steroid injection frequency and dose were the main sources of high heterogeneity among studies (P=0.030). Conclusion: Prenatal steroid exposure may be a risk factor for hypoglycemia in late preterm neonates.

Developmental programming: Adipose depot-specific regulation of non-coding RNAs and their relation to coding RNA expression in prenatal testosterone and prenatal bisphenol-A -treated female sheep

Inappropriate developmental exposure to steroids is linked to metabolic disorders. Prenatal testosterone excess or bisphenol A (BPA, an environmental estrogen mimic) leads to insulin resistance and adipocyte disruptions in female lambs. Adipocytes are key regulators of insulin sensitivity. Metabolic tissue-specific differences in insulin sensitivity coupled with adipose depot-specific changes in key mRNAs, were previously observed with prenatal steroid exposure. We hypothesized that depot-specific changes in the non-coding RNA (ncRNA) - regulators of gene expression would account for the direction of changes seen in mRNAs. Non-coding RNA (lncRNA, miRNA, snoRNA, snRNA) from various adipose depots of prenatal testosterone and BPA-treated animals were sequenced. Adipose depot-specific changes in the ncRNA that are consistent with the depot-specific mRNA expression in terms of directionality of changes and functional implications in insulin resistance, adipocyte differentiation and cardiac hypertrophy were found. Importantly, the adipose depot-specific ncRNA changes were model-specific and mutually exclusive, suggestive of different regulatory entry points in this regulation.

Prenatal Sex Hormone Exposure Is Associated with the Development of Autism Spectrum Disorder.

Sexual differentiation is a major developmental process. Sex differences resulting from sexual differentiation have attracted the attention of researchers. Unraveling what contributes to and underlies sex differences will provide valuable insights into the development of neurodevelopmental disorders that exhibit sex biases. Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects an individual's social interaction and communication abilities, and its male preponderance has been consistently reported in clinical studies. The etiology of male preponderance remains unclear, but progress has been made in studying prenatal sex hormone exposure. The present review examined studies that focused on the association between prenatal testosterone exposure and ASD development, as well as sex-specific behaviors in individuals with ASD. This review also included studies on maternal immune activation-induced developmental abnormalities that also showed striking sex differences in offspring and discussed its possible interacting roles in ASD so as to present a potential approach for future studies on sex biases in ASD.

The 2D:4D index is associated with the development of excess body weight in adults, but not with the rate of weight loss following bariatric surgery

2D:4D finger length ratio is a proxy of prenatal sex hormone exposure. Prenatal testosterone decreases and prenatal estrogens increase this index. In the current study we investigated whether the 2D:4D index, as a marker of the prenatal hormonal environment, is associated with the development of overweight and obesity in adults, and whether is it correlated with the rate of weight loss in patients after bariatric surgery. We tested 125 adults with obesity (BMI ≥ 30.0 kg/m2), 125 adults with overweight (BMI 25.0–29.9 kg/m2) and 153 persons with normal body weight (BMI < 25 kg/m2) of both sexes. We have found that the development of excessive body weight in men and women, and fat accumulation in the upper arms, thighs and lower legs in women with obesity (but not men) are associated with increased prenatal estrogen exposure. This relationship indicates a new area of activity in the field of obesity prevention. Moreover, it seems that the 2D:4D index (especially of the right hand) may be a useful factor in early prediction of the risk of developing excessive body weight in humans. The rate of weight loss after bariatric surgery is independent of prenatal exposure to sex hormones.

Association of prenatal sex steroid exposure estimated by the digit ratio (2D:4D) with birth weight, BMI and muscle strength in 6- to 13-year-old Polish children.

ObjectivesThe aim of this paper was to provide evidence for the impact of prenatal sex steroid exposure on prenatal and postnatal body size parameters, and muscle strength in children.MethodsThe following anthropometric data were studied in a group of 1148 children (536 boys and 612 girls) aged 6–13 years: the 2D:4D digit ratio, birth weight and length, and birth head and chest circumference. Postnatal parameters (6–13 years) included body weight and height, BMI, waist and hip circumference, WHR, as well as grip strength in both hands. All parameters that required it were adjusted for sex and gestational or chronological age. A general linear model, Pearson’s correlation, t-statistics and Cohen’s Δ were used in statistical analysis.ResultsAmong birth size parameters, only birth weight was significantly negatively correlated with the 2D:4D digit ratio in children. Higher (feminized) digit ratios were significantly correlated with postnatal parameters such as body weight, BMI, and waist and hip circumference (positively), as well as hand grip strength–a proxy for muscular strength (negatively).ConclusionProblems with maintaining adequate body size parameters and muscle strength may be programmed in fetal life and predicted on the basis of the 2D:4D digit ratio. Body weight at birth and in early ontogenesis are additive correlates of the 2D:4D ratio. The present findings suggest that the 2D:4D digit ratio is related to postnatal phenotypes such as birth weight, overweight, and obesity as well as muscle strength in 6–13-year-old children of both sexes.

Prenatal exposure to bisphenol analogues and digit ratio in children at ages 4 and 6 years: A birth cohort study.

Bisphenol analogues (BPs), including bisphenol A (BPA), have been shown to exhibit similar endocrine disrupting activities. However, epidemiological evidence on the reproductive and developmental toxicities of BPs other than BPA is scarce. The second to fourth digit ratio (2D:4D), an endocrine-sensitive endpoint, has been suggested to be a biomarker of prenatal sex steroid exposure and associated with reproductive outcomes in later life. Using the data of 545 mother-child pairs from the Shanghai-Minhang Birth Cohort Study, we prospectively assessed the effects of prenatal exposure to BPs on 2D:4D in children at ages 4 and 6 years. Single-spot urine samples were collected in the third trimester and analyzed for BPs. Digit lengths were measured using a vernier caliper in children at ages 4 and 6 years, and the 2D:4D values for both hands were calculated. A multivariable linear regression model was applied to examine associations between prenatal BPs exposure and 2D:4D digit ratios at each age separately. The generalized estimating equation (GEE) model was used to deal with repeated 2D:4D measures obtained at ages 4 and 6 years. We found that prenatal exposure to BPA alternatives including BPF, BPS, and BPAF was associated with higher digit ratio in boys and/or girls (feminizing), while TCBPA, a halogenated bisphenol, was associated with lower 2D:4D in boys (masculinizing). These associations were more pronounced at 4 years of age, and tended to remain after further considering the potential confounding from prenatal co-exposure to other BPs and childhood BPs exposure. Our study provides epidemiological evidence that BPs exposure during pregnancy may alter the digit development in children, indicative of disrupted reproductive development in later life. Given these new findings, further studies are needed to corroborate our results.

Digit ratio (2D:4D) and amniotic testosterone and estradiol: an attempted replication of Lutchmaya etal. (2004).

The ratio of length between the second (index) and fourth (ring) fingers (digit ratio or 2D:4D) is frequently employed as a retrospective marker of prenatal sex hormone exposure. Lutchmaya etal. (2004) reported that the ratio of testosterone (T) to estradiol (E) present in second-trimester amniotic fluid was negatively correlated with digit ratios for the right hand (but not the left hand) in a sample of 29 children at 2-year follow-up. This observation is frequently cited as evidence for the measure's validity but has not been replicated. We therefore present the findings of another study of amniotic T and E that did not find evidence for these effects at 4½-year follow-up. The confidence intervals were large, the direction of correlations observed was generally erratic, and the overall findings question the premise that second-trimester sex hormones affect the development of digit length ratios in humans.

An examination of the influence of prenatal sex hormones on handedness: Literature review and amniotic fluid data

Competing theories have posited roles for foetal androgen exposure in the development of human handedness. However, due to practical and ethical considerations, few studies have used hormonal measures to examine this possibility. The current paper reviews this literature and reveals a generally inconsistent pattern of results. We also present data from a longitudinal study of prenatal sex hormone exposure and subsequent handedness. More specifically, we examine correlations between testosterone and estradiol measured from second trimester amniotic fluid and hand preference (Dutch language version of the Edinburgh Handedness Inventory) and hand skill asymmetry (pegboard task) measured at 15 years of age. Prenatal sex hormone exposure was not associated with the direction of hand preference in either males or females. However, in females, high levels of prenatal testosterone were associated with weaker lateralisation of hand skill, and high levels of prenatal estradiol were associated with weaker hand preference. In addition, high levels of prenatal testosterone were associated with increased task duration (i.e., slow hand speed) for the right and left hands of males. The pattern of results observed here is not entirely consistent with any of the main theories linking sex hormones with handedness, suggesting that an association between these variables may be more complex than initially thought.

Correlation between Second and Fourth Digit Length Ratio with Height, Body Mass Index and Axial Length of Eyeball in Adult Population of Burdwan, West Bengal, India

Introduction: Studies are being conducted to correlate second (2D) to fourth digit (4D) length ratio as an anthropometric marker of prenatal sex steroid exposure with human body. As 2nd digit: 4th digit(2D:4D)ratio is an anthropometric window into the interplay of sex hormones in-utero, this tool may be tested to note if there is any correlation between the sexual dimorphism of axial length and the Digit length ratio. Aim: To find a correlation between digit length ratio (2D:4D) with physical parameters like height, BMI and axial length of eyeball in the adult population of South Bengal presenting in a tertiary care hospital, in Burdwan, West Bengal, India. Materials and Methods: A cross-sectional study with simple random sampling was conducted on 500 patients (age ≥20 years) from March 2016 to February 2017 in the Departments of Anatomy and Ophthalmology Out Patients Department (OPD) of a tertiary care Hospital and Medical College in West Bengal, India. Height, weight, axial length of eyeball were measured and the BMI was computed for the study population. Statistical analysis was done with Statistical Package for Social Sciences(SPSS) version 16.0. Unpaired t-test was used for determining possible group differences in 2D:4D length ratios. Pearson’s correlation coefficients were used to find a correlation between second and fourth digit length ratio (2D:4D) with height, BMI and axial length of eyeball in the study population. The p-value &lt;0.05 was considered significant. Results: The study included 280 males and 220 females with a minimum age above 20 years and most of the patients belonged to the age group of 50-69 years. A 2D:4D length ratio was significantly lower in males compared to females (For Right hand t=34.91, p&lt;0.001, and for left hand t=14.30, p&lt;0.001). Correlation analysis of 2D:4D length ratio of right and left hands with height of males revealed significant negative correlation (Right hand: r=-0.679, p&lt;0.001; Left hand: r=-0.0463, p&lt;0.001). In females, the result was positively significant for both hands (Right hand: r=0.313, p&lt;0.05; left hand: r=0.21, p&lt;0.05). A 2D:4D length ratio and BMI of males showed significant positive correlation for both Right hand (r=0.18, p&lt;0.05) as well as for the left hand (r=0.137 p&lt;0.05). In case of females, however 2D:4D ratio and BMI showed weakly negative correlation for both hands but the values were not significant. Correlation of 2D:4D length ratio of right and left hands on axial length of eyeball in males revealed significant negative correlation (right hand: r=-0.706, p&lt;0.001; left hand: r=-0.25, p&lt;0.05) but in females, there was significant positive correlation for the right hand (r=0.145, p &lt;0.05*) and positive but non-significant correlation for the left hand at 95% CI (r=0.087, p&gt;0.05) Conclusion: In this study, we have tried to establish that 2D:4D ratio (which is significantly higher in females) can be used as a putative non-invasive anthropometric marker to differentiate between males and females, which presumably is prenatally determined by in-utero sex steroid hormone exposure. By correlation studies, we have also tried to prove that this parameter correlates well with other anthropometric measurements like height, BMI and ocular axial length which are already known to be significantly different in males and females

Effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on the second to fourth digit ratio in children aged 4 years.

The second to fourth digit ratio (2D:4D) is assumed to be a biomarker of prenatal sex steroid exposure, correlating negatively with prenatal testosterone and positively with prenatal estrogen. The ratio has been suggested to be influenced by endocrine disrupting chemicals (EDCs). However, evidence regarding effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on 2D:4D of children was sparse. We investigated the associations between prenatal exposure to PBDEs and 2D:4D of children aged 4 years. Participants were mother-child pairs from the Shanghai-Minhang Birth Cohort Study (S-MBCS) which enrolled pregnant women at 12-16 weeks of gestation from April to December 2012. Nine PBDE congeners in venous umbilical cord plasma of 340 children were measured. Digit lengths were measured using a vernier caliper in children aged 4 years and 2D:4D for left and right hands and average 2D:4D value of both hands were calculated. A total of 281 children (160 boys and 121 girls) who had data on both 2D:4D and PBDE concentrations were included in the final analysis. Associations between prenatal PBDE exposures and 2D:4D were investigated using multiple linear regression models. Among the nine congeners, BDE-47 had the highest detection rate of 86.12% with the highest median concentration of 0.20ng/ml lipid. Five PBDE congeners with detection rates greater than or close to 50% (BDE-28, -47, -99, -100 and -153) and Σ5PBDEs (the sum of them) were included in final analysis. For girls, a consistent pattern for the positive associations between prenatal PBDE exposures and 2D:4D of children was observed mainly for the left hand, where those in the highest exposure groups had higher 2D:4D compared to the lowest exposure groups (a feminizing effect), with statistically significant associations observed for BDE-47 (β=0.0247, 95% confidence interval (CI): 0.0017, 0.0477), -100 (β=0.0264, 95% CI: 0.0087, 0.0441) and Σ5PBDEs (β=0.0201, 95% CI: 0.0027, 0.0374). For boys, compared with the lowest exposure groups, statistically significantly higher (feminized) 2D:4D for both hands was observed in those with the highest exposure levels of BDE-100 (β=0.0147, 95% CI: 0.0005, 0.0289 for the left hand; β=0.0182, 95% CI: 0.0046, 0.0318 for the right hand) and those with the middle and the highest exposure levels of BDE-153 (middle vs. undetected, β=0.0215, 95% CI: 0.0072, 0.0358 for the left hand; β=0.0155, 95% CI: 0.0015, 0.0295 for the right hand; highest vs. undetected, β=0.0162, 95% CI: 0.0017, 0.0307 for the left hand; β=0.0152, 95% CI: 0.0011, 0.0294 for the right hand). Our study provides preliminary evidence that prenatal exposure to PBDEs might be associated with higher 2D:4D in boys and girls.

Depression, neuroticism and 2D:4D ratio: evidence from a large, representative sample

A body of literature reports higher rates of depression and neuroticism in female samples compared to male samples. Numerous studies have investigated the role of prenatal sex hormone exposure in this sex difference, using the ratio between the second and fourth digit of the hand (“2D:4D”) as a putative marker. However, the sample sizes of those studies were mostly small and results remained inconclusive. The aim of the present study is to test the suggested associations between depression, neuroticism and the 2D:4D ratio in a large, representative sample of over 3,000 German individuals. It was hypothesized that a higher 2D:4D (supposedly representing a more “feminine” prenatal hormone exposure) would positively predict (1) one’s history of depression as well as (2) neuroticism rates and (3) acute depressive symptom scores. Controlling for biological sex, we only found suggestive evidence for linear associations with neuroticism in the case of left hand 2D:4D ratios and the mean 2D:4D of both hands. However, additional analyses indicated that these results may have been spurious due to confounding. Our findings suggest that the 2D:4D ratio is not a relevant predictor of depression, while there was mixed evidence in the case of neuroticism.

Prenatal sex hormones and finger length: Digit ratio (2D:4D) as a biological marker of early developmental processes in patients with obsessive-compulsive disorder (OCD)

Sex differences (e.g., regarding age at onset and content of symptoms) suggest a potential role of sex hormones in the prenatal etiopathogenesis of obsessive-compulsive disorder (OCD). To investigate whether these hormones are associated with OCD, the study used the 2D:4D digit ratio as phenotypic marker of prenatal sex hormone exposure. The study included 43 patients with OCD, 35 patients with depression, and 36 nonclinical controls. Diagnostic groups did not differ with regard to 2D:4D. In men with OCD, analyses showed a negative association between 2D:4D and OC symptom severity after controlling for depression. Moreover, a positive relationship between 2D:4D and the symptom dimension “washing” and a negative with “checking” was found in men, a positive association with age at onset in women (nonsignificant after correction for multiple testing). Future research should further pursue the hypothesis of a disturbed balance of sex hormones as a factor in the etiopathogenesis of OCD.

Digit ratio (2D : 4D) and prosocial behaviour in economic games: no direct correlation with generosity, bargaining or trust-related behaviours.

Prenatal exposure to sex hormones exerts organizational effects on the brain which have observable behavioural correlates in adult life. There are reasons to expect that social behaviours-fundamental for the evolutionary success of humans-might be related to biological factors such as prenatal sex hormone exposure. Nevertheless, the existing literature is inconclusive as to whether and how prenatal exposure to testosterone and oestrogen, proxied by the second-to-fourth digit ratio (2D : 4D), may predict non-selfish behaviour. Here, we investigate this question using economic experiments with real monetary stakes and analyse five different dimensions of social behaviour in a comparatively large sample of Caucasian participants (n = 560). For both males and females, our results show no robust association between right- or left-hand 2D : 4D and generosity, bargaining or trust-related behaviours. Moreover, no differences in behaviour were found according to sex. We conclude that there is no direct correlation between 2D : 4D and these social behaviours.

Sexual Dimorphism in Titi Monkeys' Digit (2D:4D) Ratio is Associated with Maternal Urinary Sex Hormones During Pregnancy.

The second-to-fourth digit (2D:4D) ratio is a sexually-dimorphic biomarker for prenatal sex hormone exposure. We investigated whether titi monkeys (Plecturocebus cupreus) exhibit sexually-dimorphic 2D:4D ratio, and whether variation in 2D:4D ratio correlates with maternal testosterone and estrogen levels during early pregnancy. Subjects were 61 adult titi monkeys (32 males, 29 females). For 26 subjects, maternal urine samples were collected approximately 15-20weeks before birth and assayed for testosterone and estrone conjugate (E1 C). Titi monkeys exhibited a human-like pattern of sexual dimorphism in right-hand 2D:4D ratio, with females exhibiting higher 2D:4D ratio than males (β=-0.29, p=0.023). For left-hand 2D:4D ratio, high levels of maternal E1 C predicted low offspring 2D:4D ratio (β=-0.48, p=0.009). For right-hand 2D:4D ratio, high levels of testosterone (β=-0.53, p=0.005) and testosterone-to-E1 C ratio (β=-0.41, p=0.028) predicted low offspring 2D:4D ratio. For 2D:4D ratio asymmetry (right-hand - left-hand), high levels of testosterone (β=-0.43, p=0.03) and testosterone-to-E1 C ratio (β=-0.53, p=0.003) predicted low (right-biased) asymmetry. This is the first report of sexually-dimorphic 2D:4D ratio in New World monkeys, and the results support a growing literature suggesting prenatal sex hormones may modulate offspring 2D:4D ratio.