Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies

OBJECTIVE - The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders.
RESEARCH DESIGN AND METHODS - Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies.
RESULTS - Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2-9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I 2 = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates. CONCLUSIONS - There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.

Bariatric surgery in women of child-bearing age, timing between an operation and birth, and associated perinatal complications

Thesis (Master's)--University of Washington, 2016-06

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64–0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother–offspring (r=0.42; P-value=3.60 × 10−61) than father–offspring correlation (r=0.33; P-value=7.01 × 10−5), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10−5). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10−30) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10−23) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10−10). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.

Birth order and childhood type 1 diabetes risk: A pooled analysis of 31 observational studies

Background: The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies. Methods: Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity. Results: Data were available for 6 cohort and 25 case-control studies, including 11 955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second-or later born children became apparent [fully adjusted OR=0.90 95% confidence interval (CI) 0.83-0.98; P=0.02] but this association varied markedly between studies (I 2=67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children <5years of age (n=25 studies, maternal age adjusted OR=0.84 95% CI 0.75, 0.93; I 2=23%). Conclusion: Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged <5 years. This finding could reflect increased exposure to infections in early life in later born children. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2010; all rights reserved.

Do perinatal and early life exposures influence the risk of malignant melanoma?:A Northern Ireland birth cohort analysis

Aim: Intrauterine, early life and maternal exposures may have important consequences for cancer development in later life. The aim of this study was to examine perinatal and birth characteristics with respect to Cutaneous malignant melanoma (CMM) risk. Methods: The Northern Ireland Child Health System database was used to examine gestational age adjusted birth weight, infant feeding practices, parental age and socioeconomic factors at birth in relation to CMM risk amongst 447,663 infants delivered between January 1971 and December 1986. Follow-up of histologically verified CMM cases was undertaken from the beginning of 1993 to 31st December 2007. Multivariable adjusted unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) of CMM risk. Results: A total of 276 CMM cases and 440,336 controls contributed to the final analysis. In reference to normal (gestational age-adjusted) weight babies, those heaviest at birth were twice as likely to develop CMM OR 2.4 (95% CI 1.1-5.1). Inverse associations with CMM risk were observed with younger (

Preterm birth, infant weight gain, and childhood asthma risk: A meta-analysis of 147,000 European children

BACKGROUND Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. OBJECTIVES We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). METHODS First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes. RESULTS Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). CONCLUSION Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.

Content of prenatal care and spontaneous preterm birth: Findings from the 1988 National Maternal and Infant Health Survey

The purposes of this study were to examine (1) the relationship between selected components of the content of prenatal care and spontaneous preterm birth; and (2) the degree of comparability between maternal and caregivers' responses regarding the number of prenatal care visits, selected components of the content of prenatal care, and gestational age, based on analyses of the 1988 National Maternal and Infant Health Survey conducted by the National Centers for Health Statistics. Spontaneous preterm birth was subcategorized into very preterm and moderately preterm births, with term birth as the controls. The study population was limited to non-Hispanic Anglo- and African-American mothers. The racial differences in terms of birth outcomes were also compared.^ This study concluded that: (1) there was not a high degree of comparability (less than 80%) between maternal and prenatal care provider's responses regarding the number of prenatal care visits and the content of prenatal care; (2) there was a low degree of comparability (less than 50%) between maternal and infant's hospital of delivery responses regarding gestational age at birth; (3) there were differences in selected components of the content of prenatal care between the cases and controls, overall and stratified by ethnicity (i.e., hemoglobin/hematocrit test, weight measurement, and breast-feeding counseling), but they were confounded with missing values and associated preterm delivery bias; (4) there were differences in selected components of the content of prenatal care between Anglo- and African-American cases (i.e., vitamin/mineral supplement advice, weight measurement, smoking cessation and drug abuse counseling), but they, too, were difficult to interpret definitively due to item nonresponse and preterm delivery biases; (5) no significant predictive association between selected components of the content of prenatal care and spontaneous preterm birth was found; and (6) inadequate/intermediate prenatal care and birth out of wedlock were found to be associated with moderately preterm birth.^ Future research is needed to examine the validity of maternal and prenatal care providers' responses and identify the sources of disagreement between their responses. In addition, further studies are needed to examine the relationship between the quality of prenatal care and preterm birth. Finally, the completeness and quality of patient and provider data on the utilization and content of prenatal care needs to be strengthened in subsequent studies. ^

Comparisons of Mortality and Pre-discharge Respiratory Outcomes in Small-for-gestational-age and Appropriate-for-gestational-age Premature Infants.

BACKGROUND: There are differences in the literature regarding outcomes of premature small-for-gestational-age (SGA) and appropriate-for gestational-age (AGA) infants, possibly due to failure to take into account gestational age at birth. OBJECTIVE: To compare mortality and respiratory morbidity of SGA and AGA premature newborn infants. DESIGN/METHODS: A retrospective study was done of the 2,487 infants born without congenital anomalies at RESULTS: Controlling for GA, premature SGA infants were at a higher risk for mortality (Odds ratio 3.1, P = 0.001) and at lower risk of respiratory distress syndrome (OR = 0.71, p = 0.02) than AGA infants. However multivariate logistic regression modeling found that the odds of having respiratory distress syndrome (RDS) varied between SGA and AGA infants by GA. There was no change in RDS risk in SGA infants at GA 32 wk (OR = 0.41, 95% CI 0.27 - 0.63; p < 0.01). After controlling for GA, SGA infants were observed to be at a significantly higher risk for developing chronic lung disease as compared to AGA infants (OR = 2.2, 95% CI = 1.2 - 3.9, P = 0.01). There was no significant difference between SGA and AGA infants in total days on ventilator. Among infants who survived, mean length of hospital stay was significantly higher in SGA infants born between 26-36 wks GA than AGA infants. CONCLUSIONS: Premature SGA infants have significantly higher mortality, significantly higher risk of developing chronic lung disease and longer hospital stay as compared to premature AGA infants. Even the reduced risk of RDS in infants born at >/=32 wk GA, (conferred possibly by intra-uterine stress leading to accelerated lung maturation) appears to be of transient effect and is counterbalanced by adverse effects of poor intrauterine growth on long term pulmonary outcomes such as chronic lung disease.

A sex difference in seasonal timing of birth in a livebearing fish

Sex differences in seasonal timing include differences in hatch- or birth-date distribution and differences in the timing of migration or maturation such as protandrous arrival timing (PAT), which is early male arrival at breeding sites. I describe a novel form of protandrous arrival timing, as a sex difference in birth-date distribution in a live-bearing fish (Dwarf Perch, Micrometrus minimus). In this species, birth coincides with arrival at breeding sites because newborn males are sexually active. A series of samples of pregnant females and young of year was collected in Tomales Bay, CA. I analyzed the daily age record in otoliths to estimate the conception date of broods and the age that young-of-year individuals were born. Males were born at a younger age than females, as indicated by the daily age record and also by the predominance of females in broods from which some young had already been born, which was a common occurrence in pregnant females with older embryos. Sex ratio of broods varied with conception date such that early-season broods were predominantly male, possibly as a result of temperature-dependent sex determination. The combined effects of the sex difference in age at birth and seasonal shift in sex ratio were to shift the mean birth date of males relative to females by five days. The most likely ultimate explanation for PAT in the Dwarf Perch is that it arises from exploitation (scramble) competition for mating opportunities among recently-born young-of-year males.

Psychoeducational outcome at school age of preterm infants with bronchopulmonary dysplasia

Objective: To investigate the cognitive performance and educational attainment at school-age of children with bronchopulmonary dysplasia (BPD), compared with a preterm control group of children. Methods: Seventy preterm infants with BPD and 61 birth weight matched controls were prospectively followed-up to school-age. The Weschler Intelligence Scale for Children - III (WISC), the Wide Range Achievement Test (WRAT) and the Developmental Test of Visual Motor Integration (VMI) were administered. The results were compared between the two groups and multiple regression analyses were performed to determine the effect of confounding variables. Results: The children in the BPD group performed less well on the Full Scale IQ (mean 86.7 vs 93.5; 95% CI, 1.9-11.7), Verbal IQ (mean 87.1 vs 94.1; 95% CI, 2.0-12.0) and the Performance IQ (mean 88.6 vs 95.2; 95% CI, 2.0-11.2) of the WISC, the reading component of the WRAT (mean 93.8 vs 98.9; 95% CI, 0.3-9.8) and the VMI (mean 88.9 vs 93.3; 95%, CI 1.1-7.8). Despite controlling for social and biological variables, statistical differences persisted for Full Scale and Verbal IQ and reading. A Verbal IQ >1 SD below the mean was found in 41% of BPD children compared to 21% of controls, while on the reading component of the WRAT a greater proportion of BPD children also had scores>1 SD below the mean. Conclusion: Impaired psychoeducational performance was found in preterm children with BPD compared to controls, especially in the areas of language abilities and reading skills. This supports a greater need for special educational services and counseling for parents for these children.

Assessment of preterm infants' readiness to commence breastfeeding

Preterm infants commence breastfeeding when health-care professionals deem them to be ready. However, the optimal timing for commencement of breastfeeding is unclear. Currently, there is little guidance for neonatal care providers to decide when to initiate breastfeeding among preterm infants. A mixed-methods study was conducted to develop and test the Preterm Sucking Readiness (PTSR) scale in four phases. The first phase involved a chart audit to explore the use of age as a criterion by investigating when preterm infants meet feeding milestones as well as other factors that may affect an infant’s readiness to engage in nutritive sucking behaviour. The second phase utilised focus groups to explore and define how neonatal care providers decide when to commence breastfeeding. To gain consensus on the criteria mentioned by the focus groups, a Delphi survey was conducted in phase 3, involving neonatal providers across Australia and New Zealand. Phase 4 of the study involved an observational study that was used to test the six-item PTSR. The age at which specific feeding milestones were reached was consistent with what has been previously described in the literature. The chart audit showed that the time taken to the first feeding attempt in the preterm infant population was affected by gestational age at birth, birth weight, and specific interventions. Staff also considered age along with other criteria when deciding when to initiate feeding. Consensus on nine criteria for inclusion into the six-item PTSR was achieved using the Delphi technique. Three items of PTSR showed significant differences between the preterm and fullterm infant groups. Only two items, feeding-readiness behaviour and low pulse oximetry during handling, explained the variance in breastfeeding behaviour. The inter-rater variability ranged between moderate and very good for the PTSR items. The results of this study indicate the importance of assessing behavioural cues as an indication of breastfeeding readiness in the preterm infant population, once an infant is deemed physiologically stable. Age continues to be a factor in some clinicians' decisions to commence breastfeeding. However, age alone cannot be used to decide if an infant is ready to engage in breastfeeding. Further research is needed to confirm these findings.

The association between maternal infant feeding practices and child weight at 11-17 months in first-time Australian mothers

Introduction: Emerging evidence reveals that early feeding practices are associated with child food intake, eating behaviour and weight status. This cross-sectional analysis examined the association between maternal infant feeding practices/beliefs and child weight in Australian infants aged 11-17 months. Methods: Participants were 293 first-time mothers of healthy term infants (144 boys, mean age 14±1 months) enrolled in the NOURISH RCT. Mothers self-reported infant feeding practices and beliefs using the Infant Feeding Questionnaire (Baughcum, 2001). Anthropometric data were also measured at baseline (infants aged 4 months). Multiple regression analysis was used, adjusting for infant age, gender, birth weight, infant feeding mode (breast vs. formula), maternal perceptions of infant weight status, pre-pregnancy weight, weight concern, age and education. Results: The average child weight-for-age z-score (WAZ) was 0.62±0.83 (range:-1.56 to 2.94) and the mean change in WAZ (WAZ change) from 4 to 14 months was 0.62±0.69 (range:-1.50 to 2.76). Feeding practices/beliefs partly explained child WAZ (R2=0.28) and WAZ change (R2=0.13) in the adjusted models. While child weight status at 14 months was inversely associated with responsive feeding (e.g. baby feeds whenever she wants, feeding to stop baby being unsettled) (β=-0.104, p=0.06) and maternal concern about the child becoming underweight (β=-0.224, p<0.001), it was positively associated with mother’s concern about child overweight (β=0.197, p<0.05). Birth weight, infant’s age, maternal weight concern and perceiving her child as overweight were significant covariates. WAZ change was only significantly associated with responsive feeding (β=-0.147, p<0.05). Conclusion: Responsive feeding may be an important strategy to promote healthy child weight.

Expression Profiles of Mitochondrial Genes in the Frontal Cortex and the Caudate Nucleus of Developing Humans and Mice Selectively Bred for High and Low Fear

A growing body of evidence suggests that mitochondrial function may be important in brain development and psychiatric disorders. However, detailed expression profiles of those genes in human brain development and fear-related behavior remain unclear. Using microarray data available from the public domain and the Gene Ontology analysis, we identified the genes and the functional categories associated with chronological age in the prefrontal cortex (PFC) and the caudate nucleus (CN) of psychiatrically normal humans ranging in age from birth to 50 years. Among those, we found that a substantial number of genes in the PFC (115) and the CN (117) are associated with the GO term: mitochondrion (FDR qv <0.05). A greater number of the genes in the PFC (91%) than the genes in the CN (62%) showed a linear increase in expression during postnatal development. Using quantitative PCR, we validated the developmental expression pattern of four genes including monoamine oxidase B (MAOB), NADH dehydrogenase flavoprotein (NDUFV1), mitochondrial uncoupling protein 5 (SLC25A14) and tubulin beta-3 chain (TUBB3). In mice, overall developmental expression pattern of MAOB, SLC25A14 and TUBB3 in the PFC were comparable to the pattern observed in humans (p<0.05). However, mice selectively bred for high fear did not exhibit normal developmental changes of MAOB and TUBB3. These findings suggest that the genes associated with mitochondrial function in the PFC play a significant role in brain development and fear-related behavior.

Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear

Although the endocannabinoid system (ECS) has been implicated in brain development and various psychiatric disorders, precise mechanisms of the ECS on mood and anxiety disorders remain unclear. Here, we have investigated developmental and disease-related expression pattern of the cannabinoid receptor 1 (CB1) and the cannabinoid receptor 2 (CB2) genes in the dorsolateral prefrontal cortex (PFC) of humans. Using mice selectively bred for high and low fear, we further investigated potential association between fear memory and the cannabinoid receptor expression in the brain. The CB1, not the CB2, mRNA levels in the PFC gradually decrease during postnatal development ranging in age from birth to 50 years (r 2 > 0.6 & adj. p < 0.05). The CB1 levels in the PFC of major depression patients were higher when compared to the age-matched controls (adj. p < 0.05). In mice, the CB1, not the CB2, levels in the PFC were positively correlated with freezing behavior in classical fear conditioning (p < 0.05). These results suggest that the CB1 in the PFC may play a significant role in regulating mood and anxiety symptoms. Our study demonstrates the advantage of utilizing data from postmortem brain tissue and a mouse model of fear to enhance our understanding of the role of the cannabinoid receptors in mood and anxiety disorders