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

BACKGROUND: Paternal age at childbirth has been increasing worldwide, and we assessed whether this increase affects growth, body composition and metabolism in their children. METHODS: We studied 277 children (aged 3-12 years) born to fathers aged 19·8-51·8 years. Clinical assessments were height and weight adjusted for parental measurements, DEXA-derived body composition, fasting lipids, glucose homoeostasis and hormonal profiles. RESULTS: Children born to fathers aged 31-35 (P = 0·009) and >35 years (P = 0·021) were 2 cm taller than those of fathers aged ≤30 years. Children of fathers aged >35 years at childbirth had a lower body mass index (BMI) (-0·32 SDS) than offspring of fathers aged 31-35 (-0·01 SDS; P = 0·043) and ≤30 (0·22 SDS; P = 0·019). There were marked effects of paternal age at childbirth on childhood blood lipids. LDL-C concentrations in children born to fathers aged >35 years were 11% and 21% higher than in children of fathers aged 31-35 and ≤30 years, respectively (P < 0·01). Total cholesterol to HDL-C ratio was also higher among the children of fathers aged 31-35 (12%; P = 0·014) and >35 (16%; P = 0·004) years at childbirth compared with the ≤30 group. In addition, HOMA-IR in girls (but not boys) born of fathers aged 31-35 (0·99) and >35 years (1·11) indicated better insulin sensitivity compared with offspring in the ≤30 group (1·63; P < 0·05). CONCLUSIONS: Increasing paternal age at childbirth is associated with a more favourable phenotype in their children (taller and slimmer, with better insulin sensitivity in girls) but with a less favourable lipid profile.

Birth order progressively affects childhood height.

BACKGROUND: 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. METHODS: We studied 312 healthy prepubertal children: 157 first-borns and 155 later-borns. Children were aged 3-10 years, born 37-41 weeks gestation, and of birth weight appropriate-for-gestational-age. Clinical assessments included measurement of children's height, weight, fasting lipid and hormonal profiles and DEXA-derived body composition. RESULTS: First-borns were taller than later-borns (P < 0·0001), even when adjusted for parents' heights (0·31 vs 0·03 SDS; P = 0·001). There was an incremental height decrease with increasing birth order, so that first-borns were taller than second-borns (P < 0·001), who were in turn taller than third-borns (P = 0·007). Further, among sibling pairs both height SDS (P = 0·009) and adjusted height SDS (P < 0·0001) were lower in second- vs first-born children. Consistent with differences in stature, first- (P = 0·043) and second-borns (P = 0·003) had higher IGF-I concentrations than third-borns. Both first- (P < 0·001) and second-borns (P = 0·004) also had reduced abdominal adiposity (lower android fat to gynoid fat ratio) when compared with third-borns. Other parameters of adiposity and blood lipids were unaffected by birth order. CONCLUSIONS: First-borns were taller than later-born children, with an incremental height reduction from first to third birth order. These differences were present after correction for genetic height, and associated to some extent with alterations in plasma IGF-I. Our findings strengthen the evidence that birth order is associated with phenotypic changes in childhood.

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. Children's 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.

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.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) or familial Hibernian fever: presentation in a four-day-old infant.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is one of a number of well described hereditary periodic febrile syndromes. We report a case in an infant, with a strong family history of this disorder, who presented on day-of-life 4 with high fever, irritability, diarrhea, lethargy, and raised acute phase reactants. An extensive work-up, including a full sepsis evaluation, proved negative. Symptoms resolved spontaneously. Representation with similar symptoms at 7 months of age prompted successful diagnosis after full evaluation. Subsequent genetic mutation analysis has proven positive for the T50M mutation in exon 2 of the TNFRSF1A gene. To our knowledge, this is the youngest reported age of presentation of this rare autoinflammatory disorder which should be considered even at such a young age.

Modified N95 mask delivers high inspired oxygen concentrations while effectively filtering aerosolized microparticles.

STUDY OBJECTIVE: In a pandemic, hypoxic patients will require an effective oxygen (O2) delivery mask that protects them from inhaling aerosolized particles produced by others, as well as protecting the health care provider from exposure from the patient. We modified an existing N95 mask to optimize O2 supplementation while maintaining respiratory isolation. METHODS: An N95 mask was modified to deliver O2 by inserting a plastic manifold consisting of a 1-way inspiratory valve, an O2 inlet and a gas reservoir. In a prospective repeated-measures study, we studied 10 healthy volunteers in each of 3 phases, investigating (1) the fractional inspiratory concentrations of O2 (F(I)O2) delivered by the N95 O2 mask, the Hi-Ox80 O2 mask, and the nonrebreathing mask during resting ventilation and hyperventilation, each at 3 O2 flow rates; (2) the ability of the N95 mask, the N95 O2 mask, and the nonrebreathing mask to filter microparticles from ambient air; and (3) to contain microparticles generated inside the mask. RESULTS: The F(I)O2s (median [range]) delivered by the Hi-Ox80 O2 mask, the N95 O2 mask, and the nonrebreathing mask during resting ventilation, at 8 L/minute O2 flow, were 0.90 (0.79 to 0.96), 0.68 (0.60 to 0.85), and 0.59 (0.52 to 0.68), respectively. During hyperventilation, the FiO2s of all 3 masks were clinically equivalent. The N95 O2 mask, but not the nonrebreathing mask, provided the same efficiency of filtration of internal and external particles as the original N95, regardless of O2 flow into the mask. CONCLUSION: An N95 mask can be modified to administer a clinically equivalent FiO2 to a nonrebreathing mask while maintaining its filtration and isolation capabilities.

Anthropometry, glucose homeostasis, and lipid profile in prepubertal children born early, full, or late term.

To examine differences in growth and metabolism in prepubertal children born early term, full term, and late term. We retrospectively studied 294 prepubertal children aged 7.3 years (range 3.0-12.1 years). Children were separated into those born early term (37 0/7-38 6/7 weeks of gestation; n = 68), full term (39 0/7-40 6/7 weeks; n = 179), and late term (41 0/7-41 6/7 weeks; n = 47). Clinical assessments included anthropometry, DXA-derived body composition, fasting lipids, and glucose homeostasis. Statistical models accounted for important confounding factors, such as gender, age, birth weight SDS, birth order, and parental variables. When birth weight was adjusted for sex and gestational age (birth weight SDS), late terms were heavier than both early (p = 0.034) and full (p = 0.020) terms. Early term children were shorter than both full (p = 0.010) and late (p = 0.049) term children, but differences in height disappeared following correction for parents' heights. There were no differences in glucose homeostasis, BMI SDS, adiposity, or fat distribution between groups. Lipid profiles were also similar. When important confounding factors were accounted for, there were no meaningful differences in anthropometry, glucose homeostasis, and lipid profile among children born early term, full term, or late term.

First-born children have reduced insulin sensitivity and higher daytime blood pressure compared to later-born children.

BACKGROUND: Evidence suggests that first-born children and adults are phenotypically different to later-born children. Therefore, we aimed to assess whether birth order would be associated with changes in metabolism in childhood. METHODS: We studied 85 healthy prepubertal children aged 4 to 11 years, born 38 to 40 weeks' gestation, and birth weight appropriate for gestational age: 32 first-born and 53 later-born children. Clinical assessments included measurement of children's height, weight, fasting lipid and hormonal profiles, and dual-energy x-ray absorptiometry-derived body composition. Children also underwent 24-hour ambulatory blood pressure monitoring, and frequently sampled intravenous glucose tests with Bergman's minimal model. RESULTS: First-born children were approximately 3 cm taller (height SD scores 0.88 vs 0.39; P = .009) and were slimmer (body mass index SD scores -0.05 vs 0.39; P = .048) than later-born children. Consistent with their taller stature, first-born children also had a 27% increase in IGF-I concentrations (227 vs 173 ng/mL; P = .002). Insulin sensitivity was reduced by 21% among first-borns compared to later-borns (8.4 vs 10.6 × 10(-4)/min/[mU/L]; P = .019). Further, 24-hour ambulatory blood pressure monitoring showed that first-borns had higher daytime systolic (+5 mm Hg; P = .032) and diastolic (+4 mm Hg; P = .029) blood pressure. Blood lipids were unaffected by birth order. CONCLUSIONS: Although first-borns were taller and slimmer, these children had reduced insulin sensitivity and increased daytime blood pressure compared to later-borns. Thus, first-borns may be at a greater risk of metabolic and cardiovascular diseases in adult life. This finding may have important public health implications, in light of a worldwide trend toward smaller families.

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.