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Objective:
Gender plays a role in the development of a number of cardiovascular and metabolic diseases and it has been suggested that females may be more insulin resistant in utero. We sought to assess the relationship between infant gender and insulin resistance in a large pregnancy cohort.
Study design:
This is a secondary analysis of a cohort...
Similar publications
The purpose of the present study was monitoring of the first trimester of pregnancy in local goats through ultrasound visualisation and measurements of some biometric parameters. Eighteen local Bulgarian goats, 2 to 4 years of age, weighing 48–56 kg, reared in the Biobase of the Faculty of Veterinary Medicine – Stara Zagora were included in the exp...
Citations
... This probably also accounts for the lower HOMA-IR in our study compared with others. 30,35,41) 6. Reference HOMA-IR of healthy Nigerian newborn infants ...
Purpose: We prospectively evaluated the association of the insulin resistance of third-trimester Nigerian pregnant women with their newborn infants' insulin resistance and birth size. Pregnancy-associated insulin resistance (IR), often assessed with homeostatic model assessment of IR (HOMA-IR), is associated, especially among women with gestational diabetes (GDM), with abnormal neonatal birth size and body composition, predisposing the baby to metabolic disorders like diabetes and obesity. The associations of maternal IR with neonatal IR, birth size and body composition are less studied in nondiabetic pregnant women, especially in sub-Saharan settings like Nigeria.Methods: We originally recruited 401 third trimester, nondiabetic pregnant women to a prospective cohort study, followed up until birth. Blood samples of mothers and babies were obtained, respectively, at recruitment and within 24 hours postbirth for fasting serum glucose (FSG) and insulin (FSI) assays, and HOMA-IR was calculated as [(FSI × FSG)/22.5)].Results: Complete data for 150 mother-baby dyads was analysed: the mothers, with a mean (standard deviation [SD]) age of 31.6 (4.5) years, had live births at a mean (SD) gestational age of 39.2 weeks. The proportions of infants with wasting, stunting, impaired fetal growth (either wasting or stunted), small-for-gestation-age, large-for-gestational-age, low birthweight, and macrosomia were 4.2% (95% confidence interval, 1.1–10.3), 19.7% (12.9–28.0), 23.1% (15.8–31.8), 10.1% (5.3–17.0), 12.6% (7.2–19.9), 0.8% (0.02–4.5), and 5.0% (1.8–10.5), respectively. Maternal HOMA-IR was not associated with neonatal HOMA-IR ( p =0.837), birth weight ( p =0.416) or body composition measured with weight-length ratio ( p =0.524), but birth weight was independently predicted by maternal weight ( p =0.006), body mass index ( p =0.001), and parity ( p =0.012).Conclusion: In this nondiabetic/non-GDM cohort, maternal HOMA-IR was not associated with neonatal IR, body size or body composition. Larger studies are required to confirm these findings, with addi-tional inclusion of mothers with hyperglycaemia for comparison.
... Probably in femalefemale pairs, which are known to be more frequent following ART as mode of conception (Scott Sills et al., 2000), the high incidence of dysmetabolic pathologies and insulin resistance, a contributing factor for infertility, may have played a relevant role. Also, a female fetus is thought to be associated with greater maternal insulin resistance during pregnancy (Xiao et al., 2014), and higher leptin and C-peptide concentrations were observed in female neonates cord blood (Walsh et al., 2015). In terms of perinatal outcome, our results show that male pairs from MC twin pregnancies were more likely to report an Apgar score <7 at 5 minutes, confirming previous evidence, where male neonates have a higher rate of respiratory and neurologic morbidity compared to females (Melamed et al., 2009). ...
Fetal sex contributes to the determination of obstetric outcome, as pregnancies carrying male babies seem to have an increased risk of maternal-fetal complications. Most studies have been conducted on singleton pregnancies, whereas less evidence is available for twins. A 10-year retrospective observational study was conducted on a cohort of 1180 women with twin pregnancy delivered at a single tertiary hospital. Clinical data on maternal characteristics, and obstetric and neonatal outcomes were collected, and the analysis was performed on monochorionic (MC) and dichorionic (DC) diamniotic twins separately. The group of DC twins included 837 cases, and those conceived by assisted reproductive technologies (ART) were more likely to have one or both female fetuses rather than males. The incidence of hypertensive disorders of pregnancy (HDP) was higher in same-sex pairs than in opposite-sex pairs. No differences were found regarding other obstetric and neonatal outcomes among the three sex-pairing groups. The MC twins group included 228 cases, and in female-carrying pregnancies a higher incidence of gestational diabetes (GDM) was observed compared to the male group. Furthermore, male pairs had significantly lower Apgar scores than females. Fetal sex seems to have a mild effect in twins compared to singleton pregnancies, suggesting a more complex set of factors contributing to pregnancy outcome in multiple pregnancies. However, we observed a higher incidence of HDP among same-sex DC pairs, a higher rate of GDM among MC female-female pairs, and a worse adaptation to extrauterine life among male-male pairs in MC twins.
... It is established that the main function of the placenta is to transport nutrients and oxygen from the mother to the fetus and to conduct the waste products from the fetus. However, it has been observed that several endocrine, biochemical and immunological factors are synthesized in the placenta and they may influence the physiology of the maternal-fetal unit [6][7][8]. Previously, the placenta was considered an asexual organ regardless of the sex of the embryo [9]. Recently, it has been shown that the difference in growth as well as survival of the fetus itself are mediated via the sex-specific function of its placenta [9,10]. ...
... In a recent meta-analysis of 23 studies, Carpenter et al. noted that female offspring who were exposed to stressors had a significantly increased hypothalamic-pituitary-adrenal axis than males [31]. Several mediators, such as leptin, insulin-like growth factor, soluble endoglin acid labile, and C-peptide, have also been reported to have sex-specific characteristics [7,8]. Other factors, such as cAMP, can play an essential role as innate immune regulators, and Olmos-Ortiz recently reported that placentas from pregnancies complicated by UTI and placentas associated with female fetuses had higher cAMP content and anti-inflammatory cytokine expression; it is possible that this phenomenon could also occur with malaria [32]. ...
Introduction:
There are few published data on the influence of the sex of the fetus or the newborn on the rate of malaria infection. Moreover, the results of these studies are not conclusive. This study was conducted to investigate the association between sex of the newborn and placental malaria infection.
Methods:
A case-control study was conducted at Al Jabalian maternity hospital in central Sudan during the rainy and post rainy seasons from May to December 2020. The cases were women who had placental malaria, while the controls were subsequent women who had no placental malaria. A questionnaire was filled out by each woman in the case and control groups in order to gather demographic data as well as medical and obstetric history. Malaria was diagnosed using blood films. Logistic regression analyses were performed.
Results:
There were 678 women in each arm of the study. Compared with the women without placental malaria (controls), women with placental malaria had a significantly lower age and parity. A significantly higher number of the cases had delivered female newborns, 453 (66.8%) vs. 208 (30.7%), P < 0.001. In logistic regression, women with placental malaria: lived in rural areas, had low antenatal attendance, did not use bed nets, and had more female newborns (adjusted odds ratio, AOR = 2.90, 95% CI = 2.08-4.04).
Discussion:
Women who delivered female were more likely to have placental malaria. Further research into the immunologic and biochemical parameters is warranted.
... An earlier study failed to find a fetal sex effect on maternal insulin sensitivity [16], instead finding mothers carrying male fetuses having higher circulating glucose concentrations but lower pancreatic β-cell function. Another study found that mothers carrying male fetuses were actually more insulin resistant than those carrying females, when tested early in pregnancy [17]. A recent review of how placental endocrine function varies according to fetal sex called for more studies of fetal sex-mediated differences in the regulation of glucose metabolism in pregnancy in relatively homogeneous populations to try and clarify discrepancies in the literature in this area [18]. ...
... In this study we have found pregnant women carrying male fetuses had lower fasting circulating glucose and insulin concentrations than those carrying females at around week 28 of pregnancy. Surrogate indices also suggest that those carrying male fetuses were more insulin sensitive, which is consistent with some [15,25] but not all [16,17] published studies. We also found that women Fig. 1 Fasting a glucose and b carrying male fetuses had higher insulin disposition indices, suggesting higher insulin secretion for their degree of insulin sensitivity. ...
... Males had higher birth weights, lengths and head circumferences. Females had regions of greater adiposity, as suggested by increased skinfold thicknesses in the flank, quadriceps and subscapular regions, as observed previously [17,40]. This decreased adiposity in males was regionalised as it was not observed with the triceps region. ...
Background
It has been suggested that fetal sex may be able to modify maternal metabolism and physiology during pregnancy. Recently pregnant women carrying a male fetus were reported to be more insulin sensitive than those carrying females, although related evidence is inconsistent.
Methods
In this study we administered a 75 g oral glucose tolerance test at around week 28 of pregnancy in 813 pregnant women from a contemporary birth cohort (the Cambridge Baby Growth Study), derived surrogate indices of insulin secretion and sensitivity, and related them to the fetal sex.
Results
Carrying a male fetus was associated with lower fasting glucose (difference in mean concentrations ≈ 0.1 mmol/L; β ′ = 0.063; p = 0.02) and insulin (≈ 1.1 pmol/L; β ′ = 0.075; p = 0.01) concentrations but not with post-load glucose or insulin concentrations. Male fetal sex was also associated with lower HOMA IR (≈ 1.08 units; β ′ = 0.071; p = 0.02) and higher QUICKI (≈ 1.06 units; β ′ = 0.080; p = 0.007) values suggesting increased basal insulin sensitivity. There were no differences in indices of insulin secretion, except for the insulin disposition index which was higher in women carrying a male fetus (≈ 1.15 units; β ′ = 0.090; p = 0.007). Birth weights were higher in male offspring.
Conclusions
Women carrying a male fetus were relatively more insulin sensitive in the fasting state and secreted more insulin relative to this degree of insulin sensitivity. These results are consistent with the idea that the fetal sex may be able to modify the maternal glucose-insulin axis.
... In the present study, UC C-peptide concentration was not affected by infant sex. One study on 582 Irish women and their children reported higher concentrations of C-peptide and Leptin in the UC blood of the female infants and lower insulin resistance in their mothers [47]. The authors hypothesized that due to their smaller placental mass, female fetuses might possess lower concentrations of placental hormones associated with increased insulin resistance, such as placental lactogen [48]. ...
Abstract Background C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration. Methods For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration. Results In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 − 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 − 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 − 0.42, p
... However, since differences in fetal insulin levels between pregnancies in people with T1DM and pregnancies in people without T1DM are higher early than late in the third trimester 78 , the above effects may operate before term of pregnancy and not be detectable at term. This circumstance might also explain why insulin is capable of inducing manifold responses despite systemic fetal insulin resistance found at term [79][80][81][82][83] . ...
... Some sex-dependent responses are induced by fetal insulin. Indirect evidence suggests that female fetuses are less insulin-sensitive at delivery [79][80][81] . It is unclear whether any of the insulin-induced responses to low oxygen vary with fetal sex. ...
Despite improvements in clinical management, pregnancies complicated by pre-existing diabetes mellitus, gestational diabetes mellitus or obesity carry substantial risks for parent and offspring. Some of the endocrine and metabolic changes in parent and fetus in diabetes mellitus and obesity lead to fetal oxygen deficit, mostly due to insulin-induced accelerated fetal metabolism. The human fetus deals with reduced oxygenation through a wide range of adaptive responses that act at various levels in the placenta as well as the fetus. These responses ensure adequate oxygen delivery to the fetus, increase the oxygen transport capacity of fetal blood and redistribute oxygen-rich blood to vital organs such as the brain and heart. The liver has a central role in adapting to reduced oxygenation by increasing its oxygen extraction and stimulating erythropoietin synthesis to increase haematocrit. The type of adaptive response depends on the onset and duration of hypoxia and the severity of the metabolic disturbance. In pregnancies characterized by diabetes mellitus or obesity, these adaptive systems come under additional strain owing to the increased maternal supply of glucose and resultant fetal hyperinsulinaemia, both of which stimulate oxidative metabolism. In the rare situation that the adaptive responses are overwhelmed, stillbirth can ensue.
... However, results show different specific effects of sex on the modulation of glucose metabolism in different cohorts. Analyzing a cohort of 582 primarily overweight women, Walsh et al. [30] observed higher insulin resistance (HOMA-IR) in pregnancies with boys at the end of the first trimester. In a cohort of 877 women, Geng et al. [31] found higher fasting blood glucose and lower HOMA-β, a measure for β-cell function, in the second trimester of pregnancies with male fetuses. ...
... Whether a sex dependent difference exists in maternal leptin levels seems controversial: A small study analyzing maternal plasma throughout pregnancy in 37 pregnant women revealed higher leptin levels in all trimesters when women were pregnant with girls [101]. However, investigating leptin in first and second trimester blood samples of 582 pregnant women did not identify any sex dependent difference [30]. Angiopoietin levels seem not different between women carrying a boy vs. women carrying a girl [102]. ...
The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with glucose. Therefore, during pregnancy, maternal insulin resistance arises, which elevates maternal blood glucose levels, and consequently ensures an adequate glucose supply for the developing fetus. At the same time, maternal β-cell mass and function increase to compensate for the higher insulin demand. These adaptations are also regulated by the endocrine function of the placenta. Excessive insulin resistance or the inability to increase insulin production accordingly disrupts physiological modulation of pregnancy mediated glucose metabolism and may cause maternal gestational diabetes (GDM). A growing body of evidence suggests that this adaptation of maternal glucose metabolism differs between pregnancies carrying a girl vs. pregnancies carrying a boy. Moreover, the risk of developing GDM differs depending on the sex of the fetus. Sex differences in placenta derived hormones and bioactive proteins, which adapt and modulate maternal glucose metabolism, are likely to contribute to this sexual dimorphism. This review provides an overview on the adaptation and maladaptation of maternal glucose metabolism by placenta-derived factors, and highlights sex differences in this regulatory network.
... With regards to the low insulin sensitivity observed among our females, emerging evidence from type 2 diabetes studies in young populations i.e. childhood [47,48] and adolescence [49] have demonstrated that females are more insulin resistant compared to males [50]. Studies show that the sex difference may be due to genetic differences and/or in utero programming [50,51]. A higher cord blood insulin levels has been reported in neonate females compared to males, though females weigh less at birth, indicative of intrinsic insulin resistance in females [50] which suggest this may be under genetic control [50,51] and thus sex-associated genes may be responsible for the intrinsic sex disparity [47]. ...
... Studies show that the sex difference may be due to genetic differences and/or in utero programming [50,51]. A higher cord blood insulin levels has been reported in neonate females compared to males, though females weigh less at birth, indicative of intrinsic insulin resistance in females [50] which suggest this may be under genetic control [50,51] and thus sex-associated genes may be responsible for the intrinsic sex disparity [47]. At the onset of conception, both maternal and neonatal metabolic milieu, as well as hormones, are involved in sex specific development of the placenta. ...
... The placenta further modulates the sex-specific variations in non-communicable diseases through epigenetic processes which are further influenced by hormonal activities [52]. Taken together differences in placental hormones or genetic susceptibility in some females may be related to vulnerability to insulin resistance [51] yet, the sex difference in insulin resistance could also be due to differences in adiposity [53]. ...
Background and Aims
Early life exposures could be pertinent risk factors of cardiometabolic diseases in adulthood. We assessed the prospective associations of early life factors with markers of cardiometabolic risk among healthy German adults.
Methods and results
We examined 348 term-born DONALD Study participants with measurement of fasting blood at the age of 18-24 years to assess metabolic indices: fatty liver index (FLI), hepatic steatosis index (HSI), pro-inflammatory score and insulin sensitivity (HOMA2-%S).
Early life factors (maternal weight in early pregnancy, maternal early pregnancy BMI, gestational weight gain (GWG), maternal age, birth weight and full breastfeeding (>17 weeks)) were assessed at enrolment of the offspring into the study. Multivariable linear regression models were used to analyze associations between early life factors and markers of cardiometabolic risk in early adulthood with adjustment for potential confounders.
A higher early pregnancy BMI was related to notably higher levels of offspring FLI, HSI, pro-inflammatory score and a lower HOMA2-%S (all p<0.0001). Similarly, a higher gestational weight gain was associated with a higher FLI (p=0.044), HSI (p=0.016), pro-inflammatory score (p=0.032) and a lower HOMA2-%S among females (p=0.034). Full breastfeeding was associated with a lower adult FLI (p=0.037). A casual mediation analysis showed that these associations were mediated by offspring adult waist circumference (WC).
Conclusion
This study suggests that early pregnancy BMI, gestational weight gain, and full breastfeeding are relevant for offspring markers of cardiometabolic risk which seems to be mediated by body composition in young adulthood.
... Fetal responses also differ by sex. Female neonates born to GDM pregnancies are less insulin-sensitive than males (45). Since insulin is a key determinant of fetal phenotype in maternal overnutrition, this may represent a protective mechanism that is especially pronounced in females. ...
Excess nutritional supply to the growing fetus, resulting from maternal diabetes and obesity, is associated with increased risks of fetal maldevelopment and adverse metabolic conditions in postnatal life. The placenta, interposed between mother and fetus, serves as the gateway between the two circulations and is usually considered to mediate maternal exposures to the fetus through a direct supply line. In this Perspective, however, we argue that the placenta is not an innocent bystander and mounts responses to fetal "signals of distress" to sustain its own adequate function and protect the fetus. We describe several types of protection that the placenta can offer the fetus against maternal metabolic perturbations and offer a theoretical model of how the placenta responds to the intrauterine environment in maternal diabetes and obesity to stabilize the fetal environment. Our approach supports growing calls for early screening and control of pregnancy metabolism to minimize harmful fetal outcomes.
... Male sex has been associated with higher incidence of preterm labor, higher cesarean rate, increased risk of cord problems, and increased risk of gestational diabetes mellitus [13][14][15] . Meanwhile, female sex has been reported to increase the risk of hypertensive diseases of pregnancy and type 2 diabetes mellitus after pregnancy compared with male sex 16,17 . These observed sex differences may be affected by differences in genes and hormones, as well as differences in responses to and interactions with environmental factors 18 . ...
Since fetal programming is sex-specific, there may also be sex-specific in parental influences on newborn birth weight. We aimed to investigate the influence of parental factors on small-for-gestational-age (SGA) infants of different sexes. Based on a pre-pregnancy cohort, multivariate logistic regression was used. 2275 couples were included for analysis. Significant associations were observed among paternal height, pre-pregnancy body mass index (BMI), and SGA in male infants; among maternal height, pre-pregnancy BMI, and SGA in female infants, and among other maternal factors and SGA in both male and female infants. Such sex specificity may be related to genetic, epigenetic, or hormonal influences between parents and infants. In conclusion, there is a sex specificity in the effect of parental height and pre-pregnancy BMI on SGA. The data suggest that future studies on infants should consider the sex-specific differences between the effects of genetic or environmental factors and infants.
