Parent-Reports of Sex-Typed Play Preference in Preschool Children: Relationships to 2D:4D Digit Ratio and Older Siblings' Sex.

Sex-typed play behavior shows large sex differences and seems to be affected by prenatal sex hormones. For example, a smaller, more male-typical ratio between the second and fourth digit length (2D:4D), a proposed marker for prenatal testosterone exposure, has been shown to be related to sex-typed play preference in childhood. Nevertheless, it is still being debated whether 2D:4D displays a stable sex difference throughout childhood, as there are few longitudinal studies. In the present study, children's 2D:4D was measured on both hands on four occasions from early infancy to early childhood (T1: 5 months, T2: 9 months, T3: 20 months, and T4: 40 months) providing the rare possibility to test the temporal stability of the sex difference. Parents completed the Preschool Activities Inventory at T4 and reported on the number of older brothers and sisters as a measure for socialization influences. Parents described boys as playing more masculine and less feminine than girls. Boys had smaller 2D:4D than girls at all measurements (T1-T4) and on both hands (right/left). Nevertheless, 2D:4D increased significantly from T3 to T4 in both sexes. Girls, but not boys, who were described as playing more masculine and less feminine had more masculine 2D:4D ratios at T1-T4 on both hands (except for right 2D:4D at T2 and T3) and had more older brothers and fewer older sisters. These data underline the stability of the sex difference in 2D:4D and show the importance of both biological and social influences on sex-typed play behavior.

Mycophenolate mofetil following glucocorticoid treatment in Henoch-Schönlein purpura nephritis: the role of early initiation and therapeutic drug monitoring.

BACKGROUND: Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood and traditionally considered as a self-limiting disease. However, renal involvement can unfavorably determine long-term prognosis. The reported regimens to treat HSP nephritis (HSPN) are diverse, indicating that the most effective treatment remains controversial. METHODS: This retrospective, single-center study involved 18 patients presenting with HSPN and nephrotic-range proteinuria. We aimed to investigate the efficacy and safety of mycophenolate mofetil (MMF) and identify a cut-off level for estimated mycophenolic acid area under the curve (eMPA-AUC0-12h) values, which can predict complete remission with high sensitivity. RESULTS: Despite prior insufficient therapeutic response to corticosteroids, 89% of patients showed a significant decrease in proteinuria after 1 month of MMF treatment. None of them relapsed during treatment; however, two children relapsed after discontinuation. Based on results of a receiver operating characteristic (ROC) analysis, an eMPA-AUC0-12h >56.4 mg*h/l was a predictor for complete remission within 3 months (80% sensitivity, 83.3% specificity, p = 0.035). During MMF administration, we encountered no adverse event requiring discontinuation of treatment. CONCLUSION: Our study demonstrates that MMF is a safe and potentially effective secondary treatment option for children with HSPN to achieve and maintain long-term remission without serious side effects. To achieve complete remission within 3 months, resolve severe inflammatory glomerular lesions, and avoid progression to chronic kidney disease, we propose timely diagnosis and early initiation of MMF with an eMPA-AUC0-12h value of 56.4 mg*h/l.

The association between 2D:4D digit ratio and sex-typed play in children with and without siblings.

The 2D:4D digit ratio is commonly used as a surrogate possibly reflecting prenatal testosterone levels. Indirect evidence comes from studies investigating the association between 2D:4D and human characteristics that likely relate to prenatal testosterone. In children, sex-typed play reveals large sex differences early in development and an influence of prenatal testosterone is likely. Findings on the association between 2D:4D and children's sex-typed play are heterogeneous and other influences on the development of sex-typed play have been suggested, most of all social influences like siblings, their sex and birth order. The current study examined the association between right and left 2D:4D, a proposed surrogate for prenatal testosterone exposure, which was assessed in right and left hands of N = 505 6-month-old children, and sex-typed play behavior, which was evaluated 3.5 years later using the Pre-School Activities Inventory (PSAI), and the influence of siblings. To capture differential effects of siblings' sex and birth order, dummy-coded variables were used reflecting having no siblings as well as older or younger sisters or brothers. Multiple regression models were used to investigate the association between PSAI scores and sex, right and left 2D:4D, being a singleton as well as having an older or younger sister or brother. It was shown that sex and having an older brother were significant predictors for sex-typed play. Effects were further disentangled by conducting separate regression analyses in boys and girls. In boys, a significant association between PSAI scores and having an older brother was revealed, in girls, no significant associations were found. Results are discussed highlighting the non-significant association between 2D:4D and children's sex-typed play, which weakens the applicability of 2D:4D as a surrogate reflecting influences of prenatal T. Further, the importance of social factors like siblings on children's sex-typed play is discussed.

Transitional Neonatal Hypoglycemia and Adverse Neurodevelopment in Midchildhood.

Importance: The circumstances under which neonatal hypoglycemia leads to brain damage remain unclear due to a lack of long-term data on the neurodevelopment of affected children. As a result, diagnostic strategies and treatment recommendations are inconsistent. Objective: To evaluate whether the occurrence of severe transitional neonatal hypoglycemia (defined as having at least 1 blood glucose measurement of 30 mg/dL or below) is associated with adverse neurodevelopment in midchildhood. Design, Setting, and Participants: This cohort study using neurodevelopmental testing of a retrospectively recruited cohort was conducted at a single-center tertiary hospital in Germany between March 2022 and February 2023. Children with neonatal blood glucose screening data were randomly selected from all births between 2010 and 2015. Frequency matching for sex, birth weight, gestational age, socioeconomic status, and primary risk factors for neonatal hypoglycemia was performed. Children with persistent hypoglycemia diseases or any risk factor for adverse neurodevelopment except hypoglycemia were excluded. Data were analyzed between February 2023 and March 2023. Exposure: At least 1 neonatal hypoglycemia measurement with blood glucose measuring 30 mg/dL or below vs all measured blood glucose levels above 30 mg/dL during postnatal blood glucose screening starting on the first day of life. Main Outcomes and Measures: Cognitive function measured by full-scale IQ test. Secondary outcomes included standardized scales of motor, visual, and executive functions, and child behavior, each measured at ages 7 to 11 years. Results: A total of 140 children (mean [SD] age 9.1 [1.3] years; 77 male [55.0%]) participated in the study. Children with severe neonatal hypoglycemia had a 4.8 points lower mean full-scale IQ than controls (107.0 [95% CI, 104.0-109.9] vs 111.8 [95% CI, 108.8-114.8]). They showed a 4.9-fold (95% CI, 1.5-15.5) increased odds of abnormal fine motor function and a 5.3-fold (95% CI, 2.1-13.3) increased odds of abnormal visual-motor integration. Significantly higher T scores for attention problems (58.2 [95% CI, 56.1-60.2] vs 54.6 [95% CI, 52.6-56.6]) and attention-deficit/hyperactivity disorder symptoms (58.2 [95% CI, 56.2-60.2] vs 54.7 [95% CI, 52.8-56.7]) were reported by parents. Conclusions and Relevance: Neonatal hypoglycemia with blood glucose levels of 30 mg/dL or below was associated with an increased risk for suboptimal neurodevelopmental outcomes in midchildhood. These findings imply that treatment strategies should aim to prevent episodes of hypoglycemia at these severely low levels.

The association of prenatal amniotic sex hormones and digit ratio (2D:4D) in children aged 5 to 70 months: A longitudinal study.

The sex difference of the 2D:4D digit ratio (female > male)-a proposed marker for prenatal testosterone exposure-is well established. Studies suggest it already exists in utero and is of moderate effect size in adulthood. However, evidence for the claim that 2D:4D reflects prenatal androgen action is limited, and the sex difference may exhibit lability during childhood. In the present study, 244 mothers were recruited in the course of an amniocentesis examination (performed between gestational weeks 14 and 18). Prenatal testosterone (T) and estradiol (E) levels were determined from amniotic fluid for boys and girls. The majority (97.4%, n = 114) of available female T levels (n = 117) were found below the level of quantification. Therefore, only male amniotic fluid data (n = 117) could be included for the analysis of associations between amniotic sex hormones (T levels and T to E ratio (T/E)) and 2D:4D. The families were then invited to each of the five consecutive follow-ups (ages: 5, 9, 20, 40, and 70 months) where children's 2D:4D was measured for both hands. The alternative marker D[r-l] reflects the directional asymmetry of 2D:4D (right subtracted by left 2D:4D) and was subsequently calculated as an additional measure for prenatal T exposure. No significant correlations between amniotic T or the T/E ratio (measured between week 14 and 18 of gestation) with 2D:4D respectively D[r-l] were observed for any time point. There was a significant sex difference (females > males) and a significant age effect with moderate correlations of 2D:4D between time points. 2D:4D increased between 20 and 40 months and between 40 and 70 months of age. The findings raise questions regarding the applicability of 2D:4D as a marker for prenatal androgen action and are discussed in terms of the reliability of obtained digit ratio data as well as in terms of the developmental timing of amniocentesis.

Investigating the reliability and sex differences of digit lengths, ratios, and hand measures in infants.

Hands and digits tend to be sexually dimorphic and may reflect prenatal androgen exposure. In the past years, the literature introduced several hand and digit measures, but there is a lack of studies in prepubertal cohorts. The available literature reports more heterogeneous findings in prepubertal compared to postpubertal cohorts. The comparability of the available studies is further limited by the study design and different measurement techniques. The present study compared the reliability and sex differences of available hand and digit measures, namely digit lengths of 2D, 3D, 4D, 5D, digit ratios 2D:4D, 2D:5D, 3D:4D, 3D:5D, 4D:5D, relative digit lengths rel2, rel3, rel4, rel5, directional asymmetry of right and left 2D:4D (Dr-l), hand width, length, and index of 399 male and 364 female 6-month-old German infants within one study using only indirect and computer-assisted measurements. The inter-examiner reliability was excellent while the test-retest reliability of hand scans was only moderate to high. Boys exhibited longer digits as well as wider and longer hands than girls, but smaller digit ratios, with ratios comprising the fifth digit revealing the largest effect sizes. Other hand and digit ratios revealed sex differences to some extent. The findings promote the assumption of sexual dimorphic hand and digit measures. However, by comparing the results of the available literature, there remains an uncertainty regarding the underlying hypothesis. Specifically in prepubertal cohorts, i.e. before the influence of fluctuating hormones, significant effects should be expected. It seems like other factors than the influence of prenatal androgens contribute to the sexual dimorphism in hand and digit lengths.

Prenatal testosterone exposure is associated with delay of gratification and attention problems/overactive behavior in 3-year-old boys.

Sex differences in self-control become apparent during preschool years. Girls are better able to delay their gratification and show less attention problems and overactive behavior than boys. In this context, organizational effects of gonadal steroids affecting the neural circuitry underlying self-control could be responsible for these early sex differences. In the present study testosterone levels measured in amniotic fluid (via ultra performance liquid chromatography and tandem mass spectrometry) were used to examine the role of organizational sex hormones on self-control. One hundred and twenty-two 40-month-old children participated in a delay of gratification task (DoG task) and their parents reported on their attention problems and overactive behavior. Girls waited significantly longer for their preferred reward than boys, and significantly more girls than boys waited the maximum period of time, providing evidence for sex differences in delay of gratification. Boys that were rated as suffering from more attention problems and overactive behavior waited significantly shorter in the DoG task. Amniotic testosterone measures were reliable in boys only. Most importantly, boys who waited shorter in the DoG task and boys who were reported to suffer from more attention problems and overactive behavior had higher prenatal testosterone levels. These findings extend our knowledge concerning organizational effects of testosterone on the brain circuitry underlying self-control in boys, and are of relevance for understanding how sex differences in behavioral disorders are connected with a lack of self-control.