Tim Savage

Childhood outcomes of assisted reproductive technology

There is a large population of children conceived via assisted reproductive technology (ART), which continues to increase worldwide, without a clear understanding of associated long-term outcomes. ART children are more likely to be the result of multiple pregnancies, and thus to be born prematurely or low birthweight. There is growing evidence that ART children are phenotypically and biochemically different from naturally conceived children, but the mechanism(s) leading to these changes have not been elucidated. There is a possible increased risk of rare imprinted gene disorders in these children. However, it remains unclear whether more subtle changes in DNA methylation occur commonly, leading to differences in gene expression and phenotype in ART children. Although an increased risk of cancer among ART children has been reported, the role of ART in the development of cancer has not been demonstrated. Further research and ongoing surveillance of ART children is essential to better understand the possible effects of ART on the long-term health of this population.

Increasing Maternal Age Is Associated with Taller Stature and Reduced Abdominal Fat in Their Children

Background Maternal age at childbirth continues to increase worldwide. We aimed to assess whether increasing maternal age is associated with changes in childhood height, body composition, and metabolism. Methods 277 healthy pre-pubertal children, born 37–41 weeks gestation were studied. Assessments included: height and weight corrected for parental measurements, DEXA-derived body composition, fasting lipids, glucose, insulin, and hormonal profiles. Subjects were separated according to maternal age at childbirth: <30, 30–35, and >35 years. Results Our cohort consisted of 126 girls and 151 boys, aged 7.4±2.2 years (range 3–10); maternal age at childbirth was 33.3±4.7 years (range 19–44). Children of mothers aged >35 and 30–35 years at childbirth were taller than children of mothers aged <30 years by 0.26 (p = 0.002) and 0.23 (p = 0.042) SDS, respectively. There was a reduction in childhood BMISDS with increasing maternal age at childbirth, and children of mothers aged >35 years at childbirth were 0.61 SDS slimmer than those of mothers <30 years (p = 0.049). Children of mothers aged 30–35 (p = 0.022) and >35 (p = 0.036) years at childbirth had abdominal adiposity reduced by 10% and 13%, respectively, compared to those in the <30 group. Children of mothers aged 30–35 years at childbirth displayed a 19% increase in IGF-I concentrations compared to offspring in <30 group (p = 0.042). Conversely, IGF-II concentrations were lower among the children born to mothers aged 30–35 (6.5%; p = 0.004) and >35 (8.1%; p = 0.005) compared to those of mothers aged <30 years. Girls of mothers aged 30–35 years at childbirth also displayed improved HOMA-IR insulin sensitivity (p = 0.010) compared to girls born to mothers aged <30 years. Conclusions Increasing maternal age at childbirth is associated with a more favourable phenotype (taller stature and reduced abdominal fat) in their children, as well as improved insulin sensitivity in girls.

Ovarian stimulation leads to shorter stature in childhood

BACKGROUND We aimed to determine whether children conceived with ovarian stimulation alone (OS(A)) would differ phenotypically and biochemically from naturally conceived children of fertile and subfertile parents. METHODS Healthy pre-pubertal children aged 3-10 years, born at term, after singleton pregnancies were recruited in Auckland (New Zealand) and were allocated into three groups: (i) children conceived following OS(A) and naturally conceived children of (ii) subfertile and (iii) fertile parents. Anthropometric, endocrine and metabolic parameters were recorded. Childrens heights and body mass index (BMI) were expressed as standard deviation scores (SDS) and corrected for genetic potential (i.e. parental height or BMI). RESULTS Three hundred fifty-two children were studied: 84 OS(A) subjects and 268 naturally conceived controls consisting of 54 children of subfertile parents and 214 children of fertile parents. Children of subfertile and fertile parents did not differ in measured outcomes. Overall, OS(A) children were shorter than children of both subfertile (SDS: -0.08 ± 0.09 versus 0.32 ± 0.07; P= 0.001) and fertile (SDS: -0.08 ± 0.09 versus 0.45 ± 0.10; P= 0.004) parents when corrected for genetic height potential. OS(A) boys were shorter than boys of subfertile (SDS:-0.18 ± 0.14 versus 0.42 ± 0.16; P= 0.03) and fertile (SDS: -0.18 ± 0.14 versus 0.35 ± 0.08; P= 0.01) parents. There was also a trend towards OS(A) girls being shorter than girls of subfertile parents (P= 0.06), but not significantly shorter than those of fertile parents (P= 0.17). OS(A) children also had a lower corrected BMISDS than children of subfertile (SDS-0.90 ± 0.15 versus -0.37 ± 0.17; P= 0.06) and fertile (-0.90 ± 0.15 versus -0.34 ± 0.10; P= 0.008) parents. Among metabolic parameters, fasting glucose was lower in OS(A) children than that in children of fertile parents (4.62 ± 0.07 versus 4.81 ± 0.04; P= 0.006). CONCLUSIONS Conception after OS(A) was associated with shorter stature, particularly in boys, compared with naturally conceived children of fertile and subfertile parents.

Birth order progressively affects childhood height

There is evidence suggesting that first‐born children and adults are anthropometrically different to later‐borns. Thus, we aimed to assess whether birth order was associated with changes in growth and metabolism in childhood.

Increasing paternal age at childbirth is associated with taller stature and less favourable lipid profiles in their children

Paternal age at childbirth has been increasing worldwide, and we assessed whether this increase affects growth, body composition and metabolism in their children.

Shorter mothers have shorter pregnancies

We assessed whether maternal height was associated with gestational age in a cohort of 294 children born at term. Increasing maternal height was associated with longer pregnancy duration (p = 0.002). Stratified analyses showed that the main effect on pregnancy length appears to occur among shorter mothers (<165 cm tall), whose pregnancies were ∼0.6 and ∼0.7 weeks shorter than pregnancies of mothers 165–170 cm (p = 0.0009) and >170 cm (p = 0.0002) tall, respectively. Further, children of shorter mothers were more likely to be born early term than those of average height (p = 0.021) and taller (p = 0.0003) mothers. Maternal stature is likely to be a contributing factor influencing long-term outcomes in the offspring via its effect on pregnancy length.

The addition of FSH to clomiphene citrate for ovarian stimulation does not affect offspring stature but may alter body composition in childhood

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First born children are taller, insulin resistant and have higher blood pressure.

Background There is a strong trend towards couples having fewer children, leading to a marked increase in the population of first born compared to later born children. Aims and hypotheses We aimed to determine if birth order influences childhood physical or metabolic parameters. We hypothesised that first born children would have a different auxological and metabolic profile to later born children. Methods Prepubertal children aged 3–10 years, (born at full term and not SGA) were recruited and grouped by birth order. All children had height, weight, body composition by DEXA scan and fasting serum IGF-1, IGF-2, IGFBP3, lipids, leptin, adiponectin, glucose and insulin levels recorded. Children’s heights and BMI were expressed as an SDS, and corrected for mean parental height and BMI SDS. A subgroup of children underwent 24 hr ambulatory BP monitoring and a frequently sampled IVGTT to determine insulin sensitivity with the minimal model. Results are expressed as mean ±SEM. Results