Preterm Females Research Articles

Visual pathways functioning in healthy pre-term adolescents: Sex but not gestational age effect.

Visuo-spatial and visuo-perceptual functioning is widely studied in preterm child and is strongly sex-specific. However, little to no data is available regarding male-female differences in preterm children and adolescents and about the interaction effect between sex and preterm birth. We studied 30 adolescents born preterm with normal cognitive and clinical neurological outcomes and 34 age-matched controls to investigate the interaction between levels of prematurity and sex in predicting the outcome of visual pathways functioning and to explore the relation between psychophysiological perceptive processing and neuropsychological performance. In the presence of prematurity, a greater female vulnerability in central visuo-cognitive processing (Form Coherence Task), but not in neuropsychological accuracy (Street Completion Test and Visual Object and Space Perception battery), seems to be more evident. Moreover, the psychophysical threshold is correlated to neuropsychological accuracy only in preterm females and not in males. These results support the idea that the male vulnerability in cognitive functioning described in prematurity-related developmental conditions is negligible during school age in children-adolescents with normal cognitive and clinical neurological outcomes. Visuo-perceptual functioning is widely studied in prematurity. However, few data are available about the interaction effect between sex and preterm birth in predicting visuo-perceptual functioning. We evidenced that in females born preterm with preserved cognitive abilities, the efficiency of the psychophysical visuo-perceptual threshold is reduced, but not related to the neuropsychological performance. Females may implement compensation strategies to achieve good performance regardless of the perceptual threshold. The present study addresses an important gap in literature, suggesting possible sex-specific outcomes in visuo-perceptual ability among preterm children and adolescents with normal intelligence and neurological outcomes.

C.6 Sex differences in neurodevelopmental outcomes and brain development from early-life to 8-years in preterm males and females

Background: Sex is associated with differences in early outcomes with preterm males at greater risk for mortality and morbidity. The objective of this study was to examine preterm sex differences in neurodevelopmental outcomes and brain development from early-life to 8-years. Methods: A prospective cohort of preterm infants born 24-32 weeks gestation were followed to 8-years with standardized measures. MRI scans were performed after birth, term-equivalent age and 8-years. Associations between sex, risk factors, brain volumes, white matter fractional anisotropy (FA) and outcomes were assessed using generalized estimating equations. Results: Preterm males (N=83) and females (N=72) had similar risk factors, brain injury and pain exposure. Sex was a predictor of cognitive scores (P=0.02) and motor impairment (P=0.03), with males having lower cognitive scores and higher motor impairment over time. There was a sex effect for FA (P=0.04), with males having lower FA over time. There were significant sex-brain injury and sex-pain interactions for cognitive and motor outcomes. Conclusions: In this longitudinal study, preterm males had lower cognitive scores and greater motor impairment, which may relate to differences in white matter maturation. Effects of brain injury and pain on outcomes is moderated by sex, indicating a differential response to early-life adversity in preterm males and females.

Gender and sex hormone effects on neonatal innate immune function

Objectives Scientific evidence provides a widened view of differences in immune response between male and female neonates. The X-chromosome codes for several genes important in the innate immune response and neonatal innate immune cells express receptors for, and are inhibited by, maternal sex hormones. We hypothesized that sex differences in innate immune responses may be present in the neonatal population which may contribute to the increased susceptibility of premature males to sepsis. We aimed to examine the in vitro effect of pro-inflammatory stimuli and hormones in neutrophils and monocytes of male and female neonates, to examine the expression of X-linked genes involved in innate immunity and the miRNA profiles in these populations. Methods Preterm infants (n = 21) and term control (n = 19) infants were recruited from the Coombe Women and Infants University Hospital Dublin with ethical approval and explicit consent. The preterm neonates (eight female, 13 male) were recruited with a mean gestation at birth (mean ± SD) of 28 ± 2 weeks and corrected gestation at the time of sampling was 30 + 2.6 weeks. The mean birth weight of preterm neonates was 1084 ± 246 g. Peripheral blood samples were used to analyze immune cell phenotypes, miRNA human panel, and RNA profiles for inflammasome and inflammatory genes. Results Dividing neutrophil results by sex showed no differences in baseline CD11b between sexes among either term or preterm neonates. Examining monocyte CD11b by sex shows, that at baseline, total and classical monocytes have higher CD11b in preterm females than preterm males. Neutrophil TLR2 did not differ between sexes at baseline or following lipopolysaccharide (LPS) exposure. CD11b expression was higher in preterm male non-classical monocytes following Pam3CSK treatment when compared to females, a finding which is unique to our study. Preterm neonates had higher TLR2 expression at baseline in total monocytes, classical monocytes and non-classical monocytes than term. A sex difference was evident between preterm females and term females in TLR2 expression only. Hormone treatment showed no sex differences and there was no detectable difference between males and females in X-linked gene expression. Two miRNAs, miR-212-3p and miR-218-2-3p had significantly higher expression in preterm female than preterm male neonates. Conclusions This study examined immune cell phenotypes and x-linked gene expression in preterm neonates and stratified according to gender. Our findings suggest that the responses of females mature with advancing gestation, whereas male term and preterm neonates have very similar responses. Female preterm neonates have improved monocyte activation than males, which likely reflects improved innate immune function as reflected clinically by their lower risk of sepsis. Dividing results by sex showed changes in preterm and term infants at baseline and following LPS stimulation, a difference which is reflected clinically by infection susceptibility. The sex difference noted is novel and may be limited to the preterm or early neonatal population as TLR2 expression on monocytes of older children does not differ between males and females. The differences shown in female and male innate immune cells likely reflect a superior innate immune defense system in females with sex differences in immune cell maturation. Existing human studies on sex differences in miRNA expression do not include preterm patients, and most frequently use either adult blood or cord blood. Our findings suggest that miRNA profiles are similar in neonates of opposite sexes at term but require further investigation in the preterm population. Our findings, while novel, provide only very limited insights into sex differences in infection susceptibility in the preterm population leaving many areas that require further study. These represent important areas for ongoing clinical and laboratory study and our findings represent an important contribution to exiting literature.

Sex-specific gut microbiome profiles among preterm infants during the neonatal intensive care hospitalization.

The gut microbiota among preterm infants is shaped by sex and feeding types. However, sex-specific weekly patterns of gut microbiome profiles among preterm infants during their neonatal intensive care unit (NICU) hospitalization remain unclear. This study aimed to investigate the effect of sex on the weekly development of preterm neonatal gut microbiota in the first 4 weeks of NICU hospitalization. This secondary data analysis included 28 preterm neonates with 261 stool samples collected from January 2014 to February 2015 in the Northeastern United States. The 16S rRNA V4 gene regions of the stool samples were sequenced and aligned against the SILVA 132 database by using Mothur 1.42.3. The sex-specific weekly diversity indexes and relative abundance of bacterial taxonomic composition were generated by Mothur and analyzed by R packages. Sex-specific weekly compositional patterns of the gut microbiome and predicted metabolic functions of gut microbiome profiles were compared, respectively. In each week of the NICU hospitalization, preterm females and males had significantly distinguished β-diversity indices and compositions of gut microbiota. Both females and males had significantly enriched Bifidobacterium, a protection feature, in stool samples collected in the third week compared with those in the second week. The predicted metabolic pathways were significantly different between females and males in the second, third, and fourth week of the NICU hospitalization. Both females and males had significantly abundant pathways. Males consistently had more abundance of "lipopolysaccharide biosynthesis" than females in the second, third, and fourth week. Males also had a significant abundance of "membrane and intracellular structural molecules" and "glycan biosynthesis and metabolism" in the second and third week. Sex shaped the weekly patterns of preterm neonatal gut microbiome profiles during the first 4 weeks of the NICU hospitalization. Further clinical interventions should consider the distinct gut microbiota compositions and predicted functional profiles between female and male preterm neonates.

Sex differences in preterm nutrition and growth: the evidence from human milk associated studies

Sexual dimorphism of the fetus manifests itself even during pregnancy. Preterm births are more common in pregnancies with male fetuses. Intrauterine and postnatal growth nomograms are sex-specific. The human milk composition in term infants appears to be sex-specific. Early nutrition has sex-specific effects and neurodevelopmental outcomes. A large same-sex twin study suggests that a mother's own milk (MOM) provides sex-specific growth advantages probably related to the calibration of a mother's milk based on her newborn's sex. Formula composition does not vary with infant sex, which may be one reason why body composition data favors the use of MOM over formula. However, given the lack of data on this subject, we need more detailed information on how the sex-specific micronutrients in MOM influence infant well-being. We also need more information to ascertain the sex differences in infants' macronutrient requirements, such as whether preterm females have higher fat requirements and preterm males have higher protein requirements for optimal growth and neurodevelopmental outcomes. This information may also influence milk banking and the use of donor human milk (DBM). Further research may help us determine if we should provide sex-specific DBM to those preterm infants who cannot get their MOM.

Minipuberty in born small for gestational age infants: A case control prospective pilot study.

To evaluate minipuberty (MP) in small for gestational age (SGA) infants, both preterm and full-term, during the first year of life. 33 SGA healthy newborns (group A), 21 of which full-term (subgroup A1) and 12 preterm (A2) were enrolled. Control group (B) consisted of 27 AGA, 17 full-term (subgroup B1) and 10 preterm (B2) infants. Growth parameters, FSH, LH, and Estradiol (E2) or Testosterone (T) serum levels were monitored at 3, 6, and 12 months. The gonadotropin surge reached greater increase of LH in males at 3 months and FSH in females at 3, 6 and 12 months (p < 0.001). In male infants: T at 3 months was higher in subgroup A2 vs A1(p = 0.001), and correlated negatively with gestational age (GA, p < 0.005), length and weight at birth (p < 0.05); LH was higher in subgroup B2 vs B1 at 6 months (p = 0.003), and in group A vs B at 12 months (p = 0.03). Females displayed higher E2 at 6 months in B2 vs B1 (p < 0.05), negatively correlated with GA and weight gain (p < 0.05); LH at 6 months was increased in A2 vs A1 (p = 0.03). Overall, preterm males displayed higher T at 3 months (p = 0.001), LH at 3, 6 and 12 months (p < 0.05), and LH/FSH ratio at 6 months (p = 0.001). Preterm females exhibited increased LH/FSH ratio at 3 and 6 months (p < 0.05). Irrespectively of GA, MP occurred with a typical sexual dimorphism and exhibited sex-specific correlations between hormones and perinatal parameters. SGA condition and prematurity seemed to enhance and protract MP over time in both sexes.

Effect of gender on growth-restricted fetuses born preterm.

Objective To assess the effect of fetal gender in small-for-gestational age (SGA) neonates with birth weight less than the fifth percentile by gestational age. Methods We compared male and female SGA neonates for maternal and neonatal outcomes in the following gestational age subgroups: at <32 + 6, 33 + 0-36 + 6 and at ≥37 + 0 weeks of gestation. Results We examined 159, 154 and 2363 SGA neonates born at <32 + 6, 33 + 0 to 36 + 6 and ≥37 weeks of pregnancy, respectively, whose birth weight was below the fifth percentile for gestational age and who met our inclusion criteria. Overall, there were no significant differences between the mothers of males and females, except that there were more males at term and the incidence of nulliparas was greater among the mothers of males. In terms of outcomes, males had a similar incidence of respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) and admissions to intensive care. Interestingly, low Apgar scores were more common in preterm females born at 33-37 weeks and vice versa in births over 37 weeks. Conclusion Our data do not support an advantage of either gender in preterm birth of infants who are most likely growth restricted.

Visual function is reduced in young adults formerly born prematurely: a population-based study

AimsTo assess visual function in young adults born preterm and compare with full-term individuals of the same age.MethodsYoung adults, born preterm (birth weight ≤1500 g) in 1988–1990, previously included in...

Conditioned pain modulation identifies altered sensitivity in extremely preterm young adult males and females

BackgroundConditioned pain modulation is a potential biomarker for risk of persistent pain. As early-life experience can alter subsequent somatosensory processing and pain response, we evaluated conditioned pain modulation after extremely preterm birth. MethodsThis observational study recruited extremely preterm (<26 weeks gestation; n=98) and term-born control (n=48) young adults (19–20 yr) from the longitudinal EPICure cohort. Pressure pain threshold (PPT; variable test stimulus lower leg) was measured before, during, and after a conditioning stimulus (contralateral hand immersion; 5°C water; 30 s). Questionnaires assessed current pain, medication use, anxiety, and pain catastrophising. ResultsFor participants tolerating conditioning, there were significant main effects of extremely preterm status, sex, and time on PPT during and after hand immersion. Inhibitory modulation was evoked in 64/98 extremely preterm (3, no change) and 38/48 term-born control (3, facilitation) subjects. The conditioned pain modulation effect (percentage change in PPT) did not differ between the extremely preterm and term-born control groups {53% [95% confidence interval (CI): 41–65] vs 57% [95% CI: 42–71]}. Reduced cold tolerance (<20 s) hampered conditioned pain modulation quantification in a higher proportion of extremely preterm participants [extremely preterm vs term-born control: 31/98 (32%) vs 7/48 (15%); P=0.03]. One-third of extremely preterm females withdrew the hand before parallel PPT (<15 s), and had lower baseline PPT than term-born control females [4.9 (95% CI: 4.8–5.1) vs 5.3 (95% CI: 5.1–5.5) ln kPa; P=0.02]. Higher anxiety, pain catastrophising, and medication use correlated with pain intensity, but not conditioned pain modulation effect. ConclusionsCold conditioning evoked inhibitory modulation in the majority of young adults and identified a subgroup of extremely preterm females with increased baseline sensitivity. Early-life experience and sex/gender should be considered when evaluating persistent pain risk with conditioned pain modulation.

Beckwith Wiedemann syndrome: A population-based study on prevalence, prenatal diagnosis, associated anomalies and survival in Europe

Beckwith Wiedemann syndrome is a complex developmental disorder characterized by somatic overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. We present epidemiological and clinical aspects of patients with Beckwith Wiedemann syndrome diagnosed prenatally or in the early years of life, using data from EUROCAT (European Surveillance of Congenital Anomalies) registries. The study population consisted of 371 cases identified between January 1990 and December 2015 in 34 registries from 16 European countries. There were 15 (4.0%) terminations of pregnancy after prenatal detection of severe anomaly/anomalies, 10 fetal deaths (2.7%), and 346 (93.3%) live-births. Twelve (3.6%) of the 330 live-births with available information on survival died in the first week of life, of those eleven (91.6%) were preterm. First-year survival rate was 90.9%. Prematurity was present in 40.6% of males and 33.9% of females. Macrosomia was found in 49.2% and 43.3% of preterm males and females, respectively. Of term newborns, 41.1% of males and 24% of females were macrosomic. Out of 353 cases with known time of diagnosis, 39.9% were suspected prenatally, 36.3% at birth, 7.6% were diagnosed in the first week of life, and 16.2% in the first year of life. The mean gestational age at prenatal diagnosis by obstetric ultrasound was 19.8 ± 6.2 (11–39) gestational weeks. The mean prenatal diagnosis of cases where parents opted for termination of pregnancy was 15.3 ± 2.4 (11–22) gestational weeks, and the mean gestational age at termination was 19.3 ± 4.1 (13–26) gestational weeks. The prenatal detection rate was 64.1% (141/220) with no significant change over time. There were 12.7% of familial cases. The study confirmed the association of assisted reproductive technologies with Beckwith Wiedemann syndrome, as 7.2% (13/181) of patients were conceived by one of the methods of assisted reproductive technologies, which was three times higher compared to the general population of the countries included in the study. Twin pregnancies of undetermined zygosity were recorded in 5.7% (21/365) cases, and were on average three to four times more common than in European countries that participated in the study. The estimated mean prevalence of classical Beckwith Wiedemann syndrome in Europe was 3.8 per 100,000 births or 1:26,000 births.

Procedural pain and oral glucose in preterm neonates: brain development and sex-specific effects.

Our objectives were to determine whether procedural pain and glucose exposure are associated with altered structural and functional brain development differently in preterm males and females, and neurodevelopment at 18-month corrected age. Fifty-one very preterm neonates (22 males; median [interquartile range] gestational age 27.6 [2.0] weeks) underwent 3 serial scans including T1-weighted and resting-state functional magnetic resonance imaging (MRI) at median postmenstrual weeks: 29.4, 31.9, and 41.1. Thalamus, basal ganglia, and total brain volumes were segmented. Functional resting-state MRI data were extracted from the independent-components maps. Pain was operationalized as the total number of neonatal intensive care unit-administered invasive procedures. Neurodevelopmental outcomes at 18-month corrected age were assessed with the Bayley Scales of Infant Development, second edition. Generalized estimating equations assessed the association of pain and glucose exposure with brain structural and functional development. More invasive procedures were independently associated with slower growth of thalamic (P < 0.001), basal ganglia (P = 0.028), and total brain volumes (P = 0.001), particularly in females. Similar relationships were observed between glucose exposure and brain volumes. Functional connectivity between thalamus and sensorimotor cortices was negatively associated with number of invasive procedures. Greater procedural pain and higher glucose exposure were related to poorer neurodevelopmental outcomes. These findings suggest that structural and functional brain development is vulnerable to procedural pain. Glucose used for analgesia does not appear to mitigate the adverse impact of pain on brain development. The vulnerability of brain development in females towards early pain is distinct from other neonatal morbidities. The link between pain and glucose with neurodevelopment suggests that these factors have long-lasting impact.

Disruptions to the cerebellar GABAergic system in juvenile guinea pigs following preterm birth

BackgroundChildren that are born preterm are at an increased risk of developing cognitive problems and behavioural disorders, such as attention deficit hyperactivity disorder (ADHD). There is increasing interest in the role of the cerebellum in these processes and the potential involvement of GABAergic pathways in neurodevelopmental disorders. We propose that preterm birth, and the associated loss of the trophic intrauterine environment, alters the development of the cerebellum, contributing to ongoing neurobehavioral disorders. MethodsGuinea pigs were delivered preterm (GA62) or spontaneously at term (GA69), and tissues collected at corrected postnatal day (PND) 28. Neurodevelopmental and GABAergic markers myelin basic protein (MBP), neuronal nuclei (NeuN), calbindin (Purkinje cells), and GAD67 (GABA synthesis enzyme) were analysed in cerebellar lobules IX and X by immunohistochemistry. Protein expression of GAD67 and GAT1 (GABA transporter enzyme) were quantified by western blot, whilst neurosteroid-sensitive GABAA receptor subunits were measured by RT-PCR. ResultsMBP immunostaining was increased in lobule IX of preterm males, and reduced in lobule X of preterm females when compared to their term counterparts. GAD67 staining was decreased in lobule IX and X of the preterm males, but only in lobule X of the preterm females compared to term cohorts for each sex. Internal granule cell layer width of lobule X was decreased in preterm cohorts of both sexes compared to terms. There were no differences between gestational age groups for NeuN staining, GAD67 and GAT1 protein expression as measured by western blotting, or GABAA receptor subunits as measured by RT-PCR between preterm and term for either sex. ConclusionsThe present findings suggest that components of the cerebellar GABAergic system of the ex-preterm cerebellum are disrupted. The higher expression of myelin in the preterm males may be due to a deficit in axonal pruning, whereas females have a deficit in myelination at 28 corrected days of age. Together these ongoing alterations may contribute to the neurodevelopmental and behavioural disorders observed in those born preterm.

Experimentally Induced Preterm Birth in Sheep Following a Clinical Course of Antenatal Betamethasone: Effects on Growth and Long-Term Survival.

Preterm births account for approximately 10% of births worldwide, with the majority (∼80%) being moderate preterm. Our aim was to determine the effects of moderate preterm birth on survival and long-term growth of male and female offspring using an ovine model of preterm birth that was preceded by a clinically relevant dose of corticosteroids. Ewes were induced to deliver preterm or at term; those assigned to deliver preterm were administered antenatal betamethasone (11.4 mg, 2 doses, 24 hours apart). The growth (body weight and body dimensions) of offspring was monitored to adulthood (62 weeks) when the animals were humanely killed for organ collection. Survival in the immediate period following preterm birth was high (75% for both sexes). However, there were unexpected deaths between 5 and 12 weeks of age, as a result of vitamin E/selenium deficiency; this only occurred in preterm offspring. From birth until adolescence, preterm lambs were lighter than term lambs (controls). After this time, there was gradual catch-up in body weight in preterm females, whereas in preterm males, body weight remained lower than in controls. Preterm sheep were smaller in stature than controls throughout life. This clinically relevant model of preterm birth leads to equally high survival rates in both sexes and is an excellent animal model in which to examine the effects of moderate preterm birth on growth and development of organ systems into adulthood.

High-risk and low-risk human papilloma virus in association to spontaneous preterm labor: a case-control study in a tertiary center, Egypt

Introduction: This study aimed to detect the correlation between human papillomavirus (HPV) and spontaneous preterm labor in Egyptian women and its association to the human papilloma viral load and MPP2 gene expression.Material and methods: We performed an observational comparative case-control study in Department of Obstetric and Gynecology, Mansoura University Hospitals over women presented with spontaneous preterm labor, besides females admitted for giving birth at full term to detect conserved sequence in HPV-L1 gene (GP5/GP6) followed by genotype detection of high- and low-risk HPVs with quantification of the viral load and the MMP2 gene expression using real-time polymerase chain reaction (PCR).Results: The prevalence of HPV was 18.1% in preterm females, but only 4% in full-term women (p value = 0.019*). Twenty percent were PCR positive for HPV 16 and 40% for HPV 18 whereas none of the control was positive for any of the studied high-risk genotypes. Thirty percent were PCR positive for HPV 6 and 10% were positive for HPV 11. MMP2 gene expression was significantly higher in preterm than full term. Human papilloma viral load was found to be positively correlated to the rate of MMP2 expression and the gestational age was significantly related to the viral load and the rate of expression of MMP2 gene.Conclusion: Human pabilloma virus especially high-risk genotypes was correlated to spontaneous preterm labor in Egyptian females through increasing early expression of MMP2 gene. The time of occurrence of preterm labor was affected by the viral load and so the rate of expression of MMP2 gene.

Betamethasone-exposed preterm birth does not impair insulin action in adult sheep.

Preterm birth is associated with increased risk of type 2 diabetes (T2D) in adulthood; however, the underlying mechanisms are poorly understood. We therefore investigated the effect of preterm birth at ~0.9 of term after antenatal maternal betamethasone on insulin sensitivity, secretion and key determinants in adulthood, in a clinically relevant animal model. Glucose tolerance and insulin secretion (intravenous glucose tolerance test) and whole-body insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were measured and tissue collected in young adult sheep (14 months old) after epostane-induced preterm (9M, 7F) or term delivery (11M, 6F). Glucose tolerance and disposition, insulin secretion, β-cell mass and insulin sensitivity did not differ between term and preterm sheep. Hepatic PRKAG2 expression was greater in preterm than in term males (P = 0.028), but did not differ between preterm and term females. In skeletal muscle, SLC2A4 (P = 0.019), PRKAA2 (P = 0.021) and PRKAG2 (P = 0.049) expression was greater in preterm than in term overall and in males, while INSR (P = 0.047) and AKT2 (P = 0.043) expression was greater in preterm than in term males only. Hepatic PRKAG2 expression correlated positively with whole-body insulin sensitivity in males only. Thus, preterm birth at 0.9 of term after betamethasone does not impair insulin sensitivity or secretion in adult sheep, and has sex-specific effects on gene expression of the insulin signalling pathway. Hence, the increased risk of T2D in preterm humans may be due to factors that initiate preterm delivery or in early neonatal exposures, rather than preterm birth per se.

Identification of Eight Different Isoforms of the Glucocorticoid Receptor in Guinea Pig Placenta: Relationship to Preterm Delivery, Sex and Betamethasone Exposure.

The placental glucocorticoid receptor (GR) is central to glucocorticoid signalling and for mediating steroid effects on pathways associated with fetal growth and lung maturation but the GR has not been examined in the guinea pig placenta even though this animal is regularly used as a model of preterm birth and excess glucocorticoid exposure. Guinea pig dams received subcutaneous injections of either vehicle or betamethasone at 24 and 12 hours prior to preterm or term caesarean-section delivery. At delivery pup and organ weights were recorded. Placentae were dissected, weighed and analysed using Western blot to examine GR isoform expression in nuclear and cytoplasmic extracts. A comparative examination of the guinea pig GR gene identified it is capable of producing seven of the eight translational GR isoforms which include GRα-A, C1, C2, C3, D1, D2, and D3. GRα-B is not produced in the Guinea Pig. Total GR antibody identified 10 specific bands from term (n = 29) and preterm pregnancies (n = 27). Known isoforms included GRγ, GRα A, GRβ, GRP, GRA and GRα D1-3. There were sex and gestational age differences in placental GR isoform expression. Placental GRα A was detected in the cytoplasm of all groups but was significantly increased in the cytoplasm and nucleus of preterm males and females exposed to betamethasone and untreated term males (KW-ANOVA, P = 0.0001, P = 0.001). Cytoplasmic expression of GRβ was increased in female preterm placentae and preterm and term male placentae exposed to betamethasone (P = 0.01). Nuclear expression of GRβ was increased in all placentae exposed to betamethasone (P = 0.0001). GRα D2 and GRα D3 were increased in male preterm placentae when exposed to betamethasone (P = 0.01, P = 0.02). The current data suggests the sex-specific placental response to maternal betamethasone may be dependent on the expression of a combination of GR isoforms.

Preterm at birth is not associated with greater cardiovascular risk in adolescence

Objective: To determine the effects of preterm birth and gender on subsequent cardiovascular risk factors among urban adolescents in a capital in the Brazilian northeast and to compare them with a group of adolescents term at birth.Methods: In a retrospective double cohort, data of birth weight were extracted from hospital registers of children born in a same day of birth, between 1992 and 2002. We classified the preterm as a unique group born before 37 weeks of gestation. A total of 134 adolescents, aged 10–20 years were found and investigated. We measured anthropometric and clinical data, blood lipid profile and glucose after overnight fasting.Results: Preterm subjects had less years of scholar education, especially between females (p = 0.01). Preterm females also had lower height (p = 0.00) and waist-hip circumference ratio (p = 0.01). Preterm males had lower cesarean delivery (p = 0.05) and greater family history of cardiovascular disease (p = 0.05). Although the differences on clinical or laboratorial measurements were small and non-significant for cardiovascular risk factors, systolic blood pressure (SBP) and diastolic blood pressure (DBP) tended to be higher in preterm groups, especially for females (SBP = 4.1 mmHg and DBP = 1.6 mmHg, p = 0.12 and p = 0.38, respectively).Conclusion: Premature did not increase cardiovascular risk adolescents in this sample. The lower association between premature and poor health outcomes among adolescents in a low average socioeconomic status population from a capital in the Brazilian northeast corroborates previous findings in other countries.

The Effects of Preterm Birth on Cerebral Pressure‐Flow Dynamics

Altered cortical and neurodevelopmental outcomes have been described following very preterm birth and imparied blood pressure (BP) and cerebral blood flow regulation have been implicated as possible mechanisms. However, whether haemodynamic impairment persists into early childhood following preterm birth remains unclear. To test the hypothesis that cerebrovascular dysfunction persists in early childood (age 6.6 yrs ±0.8) following preterm brith, we recorded BP and middle cerebral blood velocity (MCAv) in 10 preterm children (5 males, mean gestastion age at birth =32.2 weeks ±2.7) and 10 children born at term (5 males, mean gestation age at birth =39.7 weeks ±1.0) under spontaneous baseline conditions. Cerebral BP-MCAv dynamics were assessed using linear transfer function analysis. Additionally, we applied Granger's causlity test to determine the direction and strength of BP-MCAv interactions using Vector Autoregressive Moving Average Models. Results showed that compared to term children, BP-MCAv coherence was higher in preterm females (0.35±0.079 vs. 0.58±0.086, p=0.08) but similar in males (0.41±0.072 vs. 0.049±0.10, p=0.53). The average directionality index was similar between term and preterm children but the standard deviation was greater in preterm children (-7.2±13.33 vs -7.8±32.25). Further, the directionality index was positively correlated to the transfer function coherence (r=48, p<0.05). These results indicate that preterm females may have impaired cerebrovacular regulation and that, as a group, preterm children are more likley to exhibit pressure-flow dynamics that are dominated by either BP or cerebral blood flow.

Gestational Deficits have Selectively Negative Long‐Term Effects on Cognitive Control among Female Preadolescents

Long‐term cognitive impairments following extreme preterm delivery are well recognized, however, it was unknown whether these effects are present among infants born closer to term or vary based on sex. Herein, cognitive control was assessed among 8‐9‐year‐olds (preterm/&lt;37 wk [n=60] or term/蠅37 wk [n=60]). Children were matched for age, pubertal stage, sex (28 females/group), SES, IQ, BMI, and VO2max. Cognitive control was assessed using a flanker task and groups were compared on measures of accuracy, reaction time, and interference control. While no effects were observed for accuracy, an effect of birth status on overall (d=0.65, P=0.02) and incongruent trial reaction time (d=0.75, P&lt;0.01) was observed among females. Further, preterm females exhibited over two‐fold greater reaction time interference (incongruent ‐ congruent) compared to preterm males, and term females and males (all P&lt;0.01), reflecting compromised ability to up‐regulate cognitive control when faced with higher task demands. This work shows that even relatively small gestational deficits have a lasting influence on cognitive health. Specifically, preterm birth status was selectively and negatively related to cognitive control among female preadolescents. Future studies should elucidate the effects of early life factors on a wider range of cognitive tasks and determine the source of these sex differences. Funding sources: NIH HD055352 and HD069381.

Fetal gender and pregnancy outcomes in Libya: a retrospective study

Objective: The relationship between pregnancy outcomes and fetal gender is well reported from different areas in the world, but not from Africa. In this study, we try to understand whether the recorded phenomenon of association of adverse pregnancy outcomes with a male fetus applies to our population.Materials and methods: A total of 29,140 patient records from 2009 and 2010 were retrieved from Aljalaa Maternity Hospital, Tripoli, Libya. Analysis was carried out to find the correlation between fetal gender and different pregnancy outcomes.Results: A male fetus was associated with an increased incidence of gestational diabetes mellitus (odds risk 1.4), preterm delivery (6.7% for males, 5.5% for females, odds risk 1.24), cesarean section (23.9% for males, 20% for females, odds risk 1.25), and instrumental vaginal delivery (4.4% for males, 3.1% for females, odds risk 1.48), p<0.005. Preeclampsia was more frequent among preterm females and postterm males, p<0.005. It was also more frequent in male-bearing primigravids, p<0.01.Conclusion: We confirm the existence of an adverse effect of a male fetus on pregnancy and labor in our population. We recommend further research to understand the mechanisms and clinical implications of this phenomenon.