The etiology of type-2 diabetes is only partly known, and a possible role of prenatal stress in programming offspring for insulin resistance has been suggested by animal models. Previously, we found an association between prenatal stress and type-1 diabetes. Here we examine the association between prenatal exposure to maternal bereavement during preconception and pregnancy and development of type-2 diabetes in the off-spring.
We utilized data from the Danish Civil Registration System to identify singleton births in Denmark born January 1st 1979 through December 31st 2008 (N = 1,878,246), and linked them to their parents, grandparents, and siblings. We categorized children as exposed to bereavement during prenatal life if their mothers lost an elder child, husband or parent during the period from one year before conception to the child’s birth. We identified 45,302 children exposed to maternal bereavement; the remaining children were included in the unexposed cohort. The outcome of interest was diagnosis of type-2 diabetes. We estimated incidence rate ratios (IRRs) from birth using log-linear poisson regression models and used person-years as the offset variable. All models were adjusted for maternal residence, income, education, marital status, sibling order, calendar year, sex, and parents’ history of diabetes at the time of pregnancy.
We found children exposed to bereavement during their prenatal life were more likely to have a type-2 diabetes diagnosis later in life (aIRR: 1.31, 1.01–1.69). These findings were most pronounced when bereavement was caused by death of an elder child (aIRR: 1.51, 0.94–2.44). Results also indicated the second trimester of pregnancy to be the most sensitive period of bereavement exposure (aIRR:2.08, 1.15–3.76).
Our data suggests that fetal exposure to maternal bereavement during preconception and the prenatal period may increase the risk for developing type-2 diabetes in childhood and young adulthood.
It has been suggested that prenatal stress contributes to the risk of obesity later in life. In a population–based cohort study, we examined whether prenatal stress related to maternal bereavement during pregnancy was associated with the risk of overweight in offspring during school age.
We followed 65,212 children born in Denmark from 1970–1989 who underwent health examinations from 7 to 13 years of age in public or private schools in Copenhagen. We identified 459 children as exposed to prenatal stress, defined by being born to mothers who were bereaved by death of a close family member from one year before pregnancy until birth of the child. We compared the prevalence of overweight between the exposed and the unexposed. Body mass index (BMI) values and prevalence of overweight were higher in the exposed children, but not significantly so until from 10 years of age and onwards, as compared with the unexposed children. For example, the adjusted odds ratio (OR) for overweight was 1.68 (95% confidence interval [CI] 1.08–2.61) at 12 years of age and 1.63 (95% CI 1.00–2.61) at 13 years of age. The highest ORs were observed when the death occurred in the period from 6 to 0 month before pregnancy (OR 3.31, 95% CI 1.71–6.42 at age 12, and OR 2.31, 95% CI 1.08–4.97 at age 13).
Our results suggest that severe pre-pregnancy stress is associated with an increased risk of overweight in the offspring in later childhood.
We aimed to examine whether exposure to prenatal stress following maternal bereavement is associated with an increased risk of febrile seizures. In a longitudinal population-based cohort study, we followed 1,431,175 children born in Denmark. A total of 34,777 children were born to women who lost a close relative during pregnancy or within 1 year before the pregnancy and they were included in the exposed group. The exposed children had a risk of febrile seizures similar to that of the unexposed children (hazard ratio (HR) 1.00, 95% CI 0.94–1.06). The HRs did not differ according to the nature or timing of bereavement. Our data do not suggest any causal link between exposure to prenatal stress and febrile seizures in childhood.
Prenatal stress; Bereavement; Febrile seizures; Fetal programming; Longitudinal study
Exposures to psychological stress in early life may contribute to the development or exacerbation of asthma. We undertook a cohort study based on data from several population-based registers in Denmark and Sweden to examine whether bereavement in childhood led to increased asthma hospitalization.
All singleton children born in Denmark during 1977-2008 and in Sweden during 1973-2006 were included in the study (N=5,202,576). The children were followed from birth to the date of first asthma hospitalization, emigration, death, their 18th birthday, or the end of study (31 December 2007 in Sweden and 31 December 2008 in Denmark), whichever came first. All the children were assigned to the non-bereaved group until they lost a close relative (mother, father or a sibling), from when they were included in the bereaved group. We evaluated the hazard ratio (HR) of first hospitalization for asthma in bereaved children using Cox proportional hazards regression models, compared to those who were in the non-bereaved group. We also did a sub-analysis on the association between bereavement and first asthma medication.
A total of 147,829 children were hospitalized for asthma. The overall adjusted HR of asthma hospitalization in bereaved children was 1.10 (95% confidence interval (CI): 1.04-1.16), compared to non-bereaved children. The risk of asthma hospitalization was increased in those who lost a close relative at age of 14-17 years (HR=1.54, 95% CI: 1.23-1.92), but not in younger age groups. The association between bereavement and asthma hospitalization did not change over time since bereavement. In the sub-analysis in singleton live births during 1996-2008 recorded in the DMBR, bereavement was associated with a lower use of asthma medication (HR=0.87, 95% CI: 0.80-0.95).
Our data suggests that psychological stress following bereavement in late adolescence is associated with an increased risk of asthma hospitalization or lowers the threshold for asthma hospitalization.
To examine whether prenatal exposure to parental type 1 diabetes, type 2 diabetes, or gestational diabetes is associated with an increased risk of malignant neoplasm or diseases of the circulatory system in the offspring.
We conducted a population-based cohort study of 1,781,576 singletons born in Denmark from 1977 to 2008. Children were followed for up to 30 years from the day of birth until the onset of the outcomes under study, death, emigration, or December 31, 2009, whichever came first. We used Cox proportional hazards model to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for the outcomes under study while adjusting for potential confounders. An increased risk of malignant neoplasm was found in children prenatally exposed to maternal type 2 diabetes (HR = 2.2, 95%CI: 1.5–3.2). An increased risk of diseases of the circulatory system was found in children exposed to maternal type 1 diabetes (HR = 2.2, 95%CI: 1.6–3.0), type 2 diabetes (HR = 1.4, 95%CI: 1.1–1.7), and gestational diabetes (HR = 1.3, 95%CI: 1.1–1.6), but results were attenuated after excluding children with congenital malformations. An increased risk of diseases of the circulatory system was also found in children exposed to paternal type 2 diabetes (HR = 1.5, 95%CI: 1.1–2.2) and the elevated risk remained after excluding children with congenital malformations.
This study suggests that susceptibility to malignant neoplasm is modified partly by fetal programming. Diseases of the circulatory system may be modified by genetic factors, other time-stable family factors, or fetal programming.
To examine maternal pre-pregnancy (preconception) predictors of birthweight and fetal growth for singleton live births occurring over a 2-year period in a prospective study.
Data are from a population-based cohort study of 1,420 women who were interviewed at baseline and 2-years later; self-report data and birth records were obtained for incident live births during the followup period. The analytic sample includes 116 singleton births. Baseline preconception maternal health status and health-related behaviors were examined as predictors of birthweight and fetal growth, controlling for prenatal and sociodemographic variables, using multiple regression analysis.
Preconception BMI (overweight or obese) and vegetable consumption (at least one serving per day) had statistically significant independent and positive effects on birthweight and fetal growth. Maternal weight gain during pregnancy, a prenatal variable, was an additional independent predictor of birthweight and fetal growth. Sociodemographic variables were not significant predictors after controlling for preconception and prenatal maternal characteristics.
Findings confirm that preconception maternal health status and health-related behaviors can affect birthweight and fetal growth independent of prenatal and socioeconomic variables. Implications for preconception care are discussed.
Preconception health; Birthweight; Body mass index; Nutrition; Cohort study
OBJECTIVE: To emphasize preconception care of women with type 1 diabetes and the role of primary care physicians in evaluating and counseling them. QUALITY OF EVIDENCE: Substantial level II evidence indicates that tight glycemic control before conception and early in pregnancy reduces the rate of congenital malformations. Most evidence concerning maternal and fetal risks during pregnancy in patients with type 1 diabetes is level III or IV. Little is published on the role of family physicians in providing preconception counseling or care. MAIN MESSAGE: Preconception care is effective in improving glycemic control early in pregnancy and in reducing the rate of congenital malformations. Preconception evaluation of type 1 diabetic patients involves assessment of prepregnancy glycemic control and diabetic complications. Preconception counseling includes discussing the rate of transmission of diabetes, the effects of pregnancy on maternal and fetal complications, and the use of contraception until optimal glycemic control can be attained. CONCLUSION: Primary care physicians often have frequent and early contact with women of reproductive age; they are ideal candidates for providing type 1 diabetic women with preconception evaluation and counseling.
Prenatal stress may increase the susceptibility to childhood cancer by affecting immune responses and hormonal balance. We examined whether antenatal stress following maternal bereavement increased the risk of childhood cancer.
All children born in Denmark from 1968 to 2007 (N=2 743 560) and in Sweden from 1973 to 2006 (N=3 400 212) were included in this study. We compared cancer risks in children born to women who lost a first-degree relative (a child, spouse, a parent, or a sibling) the year before pregnancy or during pregnancy with cancer risks in children of women who did not experience such bereavement.
A total of 9795 childhood cancer cases were observed during follow-up of 68 360 707 person years. Children born to women who lost a child or a spouse, but not those who lost other relatives, had an average 30% increased risk of any cancer (hazard ratio (HR) 1.30, 95% confidence interval (CI) 0.96–1.77). The HRs were the highest for non-Hodgkin disease (512 cases in total, HR 3.40, 95% CI 1.51–7.65), hepatic cancer (125 cases in total, HR 5.51, 95% CI 1.34–22.64), and testicular cancer (86 cases in total, HR 8.52, 95% CI 2.03–37.73).
Our data suggest that severe antenatal stress following maternal bereavement, especially due to loss of a child or a spouse, is associated with an increased risk of certain childhood cancers in the offspring, such as hepatic cancer and non-Hodgkin disease, but not with childhood cancer in general.
childhood cancer; bereavement; prenatal stress; mother; association
In a population-based case-control study of 642 childhood cancer cases and the same number of matched controls in Shanghai, China, we evaluated the relationship between diagnostic X-ray (preconception, pre- and post-natal) and antenatal ultrasound exposure and the subsequent risk of developing three major types of childhood cancer (acute leukaemia, lymphoma and brain tumours) and all childhood neoplasms combined. Consistent with previous studies, prenatal X-ray exposure was found to be associated with an 80% increased risk of childhood cancers, although the estimation was based on 4% and 2% exposed cases and controls and was only marginally statistically significant (P = 0.08). Post-natal X-ray exposure was also linked with a small elevation in the risk of all cancers and the major categories of malignancies in children. Little evidence, however, was found to relate parental preconception X-ray exposure with the subsequent cancer risk in offspring, regardless of the exposure window and the anatomical site of X-ray exposures. This study adds further to the growing literature indicating that antenatal ultrasound exposure is probably not associated with an increased risk of childhood cancer.
Common genetic and environmental risk factors may explain the concurrent increase in the incidence of both inflammatory bowel disease (IBD) and asthma. We examined whether IBD in a parent is associated with an increased asthma risk in offspring.
This was a registry-based cohort study of all children born alive in Denmark in 1979–2009, followed through 2010. IBD and asthma were identified using hospital diagnoses; antiasthma medication was also used to identify asthma. We computed risk of asthma and estimated adjusted incidence rate ratios (aIRRs) with 95% confidence intervals (CIs) using Cox proportional-hazards regression. We evaluated asthma risk according to maternal and paternal IBD, Crohn's disease (CD), and ulcerative colitis (UC). Children without parental IBD were the comparison cohort for all comparisons.
We identified 1,845,281 children, of whom 14,952 (0.8%) had a parent with IBD. The 10-year risk of asthma was 6.9% among offspring of parents with CD, 5.6% among offspring of parents with UC, and 5.0% among offspring of parents without IBD. The aIRR for asthma associated with parental IBD was 0.98 (95% CI: 0.91–1.04). The aIRR was 1.09 (95% CI: 0.98–1.22) for parental CD and 0.92 (95% CI: 0.84–1.00) for parental UC. Results were similar regardless of parent of origin or inclusion of antiasthma medication to define asthma.
Our data do not provide evidence for an increased risk of asthma in offspring with a parental history of IBD.
Women with type 2 diabetes were less likely to have diabetes related complications than women with type 1. Women with type 1 diabetes had a high prepregnancy care and showed a worse glycemic control than women with type 2 both in the preconception period and during pregnancy. Obstetrical outcomes showed that preeclampsia and stillbirth rate is almost doubled in type 1 patients while perinatal deaths and SGA importantly increased in type 2 diabetes. In modern obstetrical care it is mandatory to maintain glucose levels as close to normal as possible particularly in diabetic population. HbA1C no higher than 6% before pregnancy and during the first trimester seems to decrease the risk of adverse obstetrical outcomes. Both the preconceptional counseling and glycemic profile optimization represent a fundamental step to improve pregnancy outcomes in women with preexisting diabetes. A systematic approach to family planning and the availability of preconception care for all diabetic women who desire pregnancy could be an essential step for diabetic management program.
Vitamin D deficiency is common among otherwise healthy pregnant women and may have consequences for them as well as the early development and long-term health of their children. However, the importance of maternal vitamin D status on offspring health later in life has not been widely studied. The present study includes an in-depth examination of the influence of exposure to vitamin D early in life for development of fractures of the wrist, arm and clavicle; obesity, and type 1 diabetes (T1D) during child- and adulthood.
The study is based on the fact that in 1961 fortifying margarine with vitamin D became mandatory in Denmark and in 1972 low fat milk fortification was allowed. Apart from determining the influences of exposure prior to conception and during prenatal life, we will examine the importance of vitamin D exposure during specific seasons and trimesters, by comparing disease incidence among individuals born before and after fortification. The Danish National databases assure that there are a sufficient number of individuals to verify any vitamin D effects during different gestation phases. Additionally, a validated method will be used to determine neonatal vitamin D status using stored dried blood spots (DBS) from individuals who developed the aforementioned disease entities as adults and their time and gender-matched controls.
The results of the study will contribute to our current understanding of the significance of supplementation with vitamin D. More specifically, they will enable new research in related fields, including interventional research designed to assess supplementation needs for different subgroups of pregnant women. Also, other health outcomes can subsequently be studied to generate multiple health research opportunities involving vitamin D. Finally, the results of the study will justify the debate of Danish health authorities whether to resume vitamin D supplementation policies.
Vitamin D; Food fortification; Prenatal exposure; Prevention; Type 1 diabetes; Obesity; Fractures
The family physician may conduct preventive screening of children yet unborn, beginning with assessing the rubella-immunity status of 12-year-old females and continuing through the preconception period, the prenatal period, and the process of birth. Knowledge of both parents and their family history allows family physicians to deal effectively with the very sensitive issues of risks of congenital disorders and the effects of teratogenic drugs during pregnancy. Prenatal monitoring for various disorders and risks and assessing the growth curve of pregnancy will help to improve fetal outcomes. Proper use of suctioning, oxygen, and application of the Apgar score to monitor and detect evidence of asphyxia at birth can result in healthier babies.
preventive health examinations; prenatal management
To evaluate the reliability and validity of the Bereaved Parent Needs Assessment, a new instrument to measure parents' needs and need fulfillment around the time of their child's death in the pediatric intensive care unit. We hypothesized that need fulfillment would be negatively related to complicated grief and positively related to quality of life during bereavement.
Five U.S. children's hospital pediatric intensive care units.
Parents (n = 121) bereaved in a pediatric intensive care unit 6 months earlier.
Surveys included the 68-item Bereaved Parent Needs Assessment, the Inventory of Complicated Grief, and the abbreviated version of the World Health Organization Quality of Life questionnaire. each Bereaved Parent Needs Assessment item described a potential need and was rated on two scales: 1) a 5-point rating of importance (1 = not at all important, 5 = very important) and 2) a 5-point rating of fulfillment (1 = not at all met, 5 = completely met). Three composite scales were computed: 1) total importance (percentage of all needs rated ≥4 for importance), 2) total fulfillment (percentage of all needs rated ≥4 for fulfillment), and 3) percent fulfillment (percentage of important needs that were fulfilled). Internal consistency reliability was assessed by Cronbach's α and Spearman-Brown–corrected split-half reliability. Generalized estimating equations were used to test predictions between composite scales and the Inventory of Complicated Grief and World Health Organization Quality of Life questionnaire.
Measurements and Main Results
Two items had mean importance ratings <3, and 55 had mean ratings >4. reliability of composite scores ranged from 0.92 to 0.94. Total fulfillment was negatively correlated with Inventory of Complicated Grief (r = −.29; p < .01) and positively correlated with World Health Organization Quality of Life questionnaire (r = .21; p < .05). Percent fulfillment was also significantly correlated with both outcomes. Adjusting for parent's age, education, and loss of an only child, percent fulfillment remained significantly correlated with Inventory of Complicated Grief but not with World Health Organization Quality of Life questionnaire.
The Bereaved Parent Needs Assessment demonstrated reliability and validity to assess the needs of parents bereaved in the pediatric intensive care unit. Meeting parents' needs around the time of their child's death may promote adjustment to loss. (Crit Care Med 2012; 40:3050–3057)
bereavement; death; grief; intensive care; parents; pediatrics; quality of life
Background: The results of previous studies suggest that prenatal exposure to bis[p-chlorophenyl]-1,1,1-trichloroethane (DDT) and to its main metabolite, 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), impairs psychomotor development during the first year of life. However, information about the persistence of this association at later ages is limited.
Objectives: We assessed the association of prenatal DDE exposure with child neurodevelopment at 42–60 months of age.
Methods: Since 2001 we have been monitoring the neurodevelopment in children who were recruited at birth into a perinatal cohort exposed to DDT, in the state of Morelos, Mexico. We report McCarthy Scales of Children’s Abilities for 203 children at 42, 48, 54, and 60 months of age. Maternal DDE serum levels were available for at least one trimester of pregnancy. The Home Observation for Measurement of the Environment scale and other covariables of interest were also available.
Results: After adjustment, a doubling of DDE during the third trimester of pregnancy was associated with statistically significant reductions of –1.37, –0.88, –0.84, and –0.80 points in the general cognitive index, quantitative, verbal, and memory components respectively. The association between prenatal DDE and the quantitative component was weaker at 42 months than at older ages. No significant statistical interactions with sex or breastfeeding were observed.
Conclusions: These findings support the hypothesis that prenatal DDE impairs early child neurodevelopment; the potential for adverse effects on development should be considered when using DDT for malaria control.
McCarthy scale; Mexico; neurodevelopment; organochlorines compounds; prenatal exposure; prospective cohort
The authors evaluated the association between gestational age, birth weight, intrauterine growth and epilepsy in a population-based cohort of 1.4 million singletons born in Denmark (1979-2002). A total of 14,334 individuals were registered with epilepsy in the Danish National Hospital Register as inpatients (1979-2002) and outpatients (1995-2002). Information on gestational age and birth weight was obtained from Danish Medical Birth Registry. Children small at birth were identified through two methods: 1) sex-, birth order-, and gestational-age-specific z-score, and 2) deviation from the expected birth weight estimated based on the birth weight of an older sibling. The incidence rates of epilepsy increased consistently with decreasing gestational age and birth weight. The incidence rate ratios (IRR) for epilepsy in the first year of life were more than five-fold in children born at 22-32 weeks compared with children born at 39-41 weeks, and in children with a birth weight <2,000 grams compared with children of 3,000-3,999 grams. The IRRs decreased with age, but remained elevated into early adulthood. Children identified as growth-restricted according to either of the two methods had increased IRRs for epilepsy, even among children with a ‘normal’ birth weight of 3,500-3,999 grams. Low gestational age at birth and low birth weight are associated with an increased risk of epilepsy throughout childhood and persisting into puberty. Intrauterine growth restriction is associated with an increased risk of epilepsy, even among children with a birth weight in a normal range.
The National Children's Study is a national household probability sample designed to identify 100,000 children at birth and follow the sampled children for 21 years. Data from the study will support examining numerous hypotheses concerning genetic and environmental effects on the health and development of children. The goals of the study present substantial challenges. For example, the need for preconception, prenatal, and postnatal data require identifying women in the early stages of pregnancy, the collection of many types of data, and the retention of the children over time. In this paper, we give an overview of the sample design used in a pilot study called the Vanguard Study, and highlight the approaches used to address these challenges. We will also describe the rationale for the sampling choices made at each stage, the unique organizational structure of the NCS and issues we expect to face during implementation.
Multistage sample; area probability sample; primary sampling unit; segment; listing
Children exposed prenatally to cocaine show deficits in emotion regulation and inhibitory control. While controlling for the measures of medical complication in the perinatal period, environmental risk, and prenatal polydrug exposure (alcohol, tobacco, and marijuana), we examined the effects of prenatal cocaine exposure and gender on attention and inhibitory control in 203 children at ages 6, 9, and 11. Cocaine exposure affected the performance of males, but not females. Heavily exposed males showed deficits in the attention and the inhibition tasks. In addition, a significantly greater proportion of heavily exposed males (21%) than unexposed males (7%) or heavily exposed females (7%) failed to complete the task (p < .01). Even without those poorest performing subjects, the overall accuracy for heavily exposed males (81%) was significantly reduced (p < .05) compared to lightly exposed males (87%) and unexposed males (89%). The findings highlight the importance of considering gender specificity in cocaine exposure effects. Processes by which cocaine effects may be specific to males are discussed.
attention; inhibitory control; prenatal cocaine exposure
While the etiology of most childhood cancers is largely unknown, epidemiologic studies have consistently found an association between exposure to medical radiation during pregnancy and risk of childhood cancer in offspring. The relation between early life diagnostic radiation exposure and occurrence of pediatric cancer risks is less clear. This review summarizes current and historical estimated doses for common diagnostic radiologic procedures as well as the epidemiologic literature on the role of maternal prenatal, children’s postnatal and parental preconception diagnostic radiologic procedures on subsequent risk of childhood malignancies Risk estimates are presented according to factors such as the year of birth of the child, trimester and medical indication for the procedure, and the number of films taken. The paper also discusses limitations of the methods employed in epidemiologic studies to assess pediatric cancer risks, the effects on clinical practice of the results reported from the epidemiologic studies, and clinical and public health policy implications of the findings. Gaps in understanding and additional research needs are identified. Important research priorities include nationwide surveys to estimate fetal and childhood radiation doses from common diagnostic procedures, and epidemiologic studies to quantify pediatric and lifetime cancer risks from prenatal and early childhood exposures to diagnostic radiography, computed tomography, and fluoroscopically-guided procedures.
ionizing radiation; pediatric neoplasms; cancer risks; diagnostic radiography; CT
Prenatal factors such as prenatal psychological stress might influence the development of childhood asthma.
Methodology and Principal Findings
We assessed the association between maternal bereavement shortly before and during pregnancy, as a proxy for prenatal stress, and the risk of childhood asthma in the offspring, based on two samples of children 1–4 (n = 426 334) and 7–12 (n = 493 813) years assembled from the Swedish Medical Birth Register. Exposure was maternal bereavement of a close relative from one year before pregnancy to child birth. Asthma event was defined by a hospital contact for asthma or at least two dispenses of inhaled corticosteroids or montelukast. In the younger sample we calculated hazards ratios (HRs) of a first-ever asthma event using Cox models and in the older sample odds ratio (ORs) of an asthma attack during 12 months using logistic regression. Compared to unexposed boys, exposed boys seemed to have a weakly higher risk of first-ever asthma event at 1–4 years (HR: 1.09; 95% confidence interval [CI]: 0.98, 1.22) as well as an asthma attack during 12 months at 7–12 years (OR: 1.10; 95% CI: 0.96, 1.24). No association was suggested for girls. Boys exposed during the second trimester had a significantly higher risk of asthma event at 1–4 years (HR: 1.55; 95% CI: 1.19, 2.02) and asthma attack at 7–12 years if the bereavement was an older child (OR: 1.58; 95% CI: 1.11, 2.25). The associations tended to be stronger if the bereavement was due to a traumatic death compared to natural death, but the difference was not statistically significant.
Our results showed some evidence for a positive association between prenatal stress and childhood asthma among boys but not girls.
In humans, cancer may be caused by genetics and environmental exposures; however, in the majority of instances the identification of the critical time window of exposure is problematic. The evidence for exposures occurring during the preconceptional period that have an association with childhood or adulthood cancers is equivocal. Agents definitely related to cancer in children, and adulthood if exposure occurs in utero, include: maternal exposure to ionizing radiation during pregnancy and childhood leukemia and certain other cancers, and maternal use of diethylstilbestrol during pregnancy and clear-cell adenocarcinoma of the vagina of their daughters. The list of environmental exposures that occur during the perinatal/postnatal period with potential to increase the risk of cancer is lengthening, but evidence available to date is inconsistent and inconclusive. In animal models, preconceptional carcinogenesis has been demonstrated for a variety of types of radiation and chemicals, with demonstrated sensitivity for all stages from fetal gonocytes to postmeiotic germ cells. Transplacental and neonatal carcinogenesis show marked ontogenetic stage specificity in some cases. Mechanistic factors include the number of cells at risk, the rate of cell division, the development of differentiated characteristics including the ability to activate and detoxify carcinogens, the presence of stem cells, and possibly others. Usefulness for human risk estimation would be strengthened by the study of these factors in more than one species, and by a focus on specific human risk issues.
A recent randomized trial compared prandial insulin aspart (IAsp) with human insulin in type 1 diabetic pregnancy. The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled during early pregnancy.
RESEARCH DESIGN AND METHODS
IAsp administered immediately before each meal was compared with human insulin administered 30 min before each meal in 99 subjects (44 to IAsp and 55 to human insulin) randomly assigned preconception and in 223 subjects (113 for IAsp and 110 for human insulin) randomly assigned in early pregnancy (<10 weeks). NPH insulin was the basal insulin. Severe hypoglycemia (requiring third-party assistance) was recorded prospectively preconception (where possible), during pregnancy, and postpartum. Relative risk (RR) of severe hypoglycemia was evaluated with a gamma frailty model.
Of the patients, 23% experienced severe hypoglycemia during pregnancy with the peak incidence in early pregnancy. In the first half of pregnancy, the RR of severe hypoglycemia in women randomly assigned in early pregnancy/preconception was 1.70 (95% CI 0.91–3.18, P = 0.097); the RR in the second half of pregnancy was 1.35 (0.38–4.77, P = 0.640). In women randomly assigned preconception, severe hypoglycemia rates occurring before and during the first and second halves of pregnancy and postpartum for IAsp versus human insulin were 0.9 versus 2.4, 0.9 versus 2.4, 0.3 versus 1.2, and 0.2 versus 2.2 episodes per patient per year, respectively (NS).
These data suggest that initiation of insulin analog treatment preconception rather than during early pregnancy may result in a lower risk of severe hypoglycemia in women with type 1 diabetes.
To investigate whether SIRT1, a nutrient-sensing histone deacetylase, influences fetal programming during malnutrition.
RESEARCH DESIGN AND METHODS
In 793 individuals of the Dutch Famine Birth Cohort, we analyzed the interaction between three SIRT1 single nucleotide polymorphisms (SNPs) and prenatal exposure to famine on type 2 diabetes risk.
In the total population (exposed and unexposed), SIRT1 variants were not associated with type 2 diabetes. A significant interaction was found between two SIRT1 SNPs and exposure to famine in utero on type 2 diabetes risk (P = 0.03 for rs7895833; P = 0.01 for rs1467568). Minor alleles of these SNPs were associated with a lower prevalence of type 2 diabetes only in individuals who had been exposed to famine prenatally (odds ratio for rs7895833 0.50 [95% CI 0.24–1.03], P = 0.06; for rs1467568 0.48 [0.25–0.91], P = 0.02).
SIRT1 may be an important genetic factor involved in fetal programming during malnutrition, influencing type 2 diabetes risk later in life.
To evaluate the impact of a preconception counseling program tailored for teens with type 1 diabetes on cognitive, psychosocial, and behavioral outcomes and to assess its cost-effectiveness.
RESEARCH DESIGN AND METHODS
A total of 88 teens with type 1 diabetes from two sites were randomized into the READY-Girls (Reproductive-health Education and Awareness of Diabetes in Youth for Girls) intervention (IG) (n = 43) or standard care (SC) (n = 45) groups. During three diabetes clinic visits, IG subjects viewed a two-part CD-ROM, read a book, and met with a nurse. Program effectiveness was measured by knowledge, attitudes, intentions, and behaviors regarding diabetes, pregnancy, sexuality, and preconception counseling. Assessments occurred at baseline, before and after viewing program materials, and at 9 months. Economic analyses included an assessment of resource utilization, direct medical costs, and a break-even cost analysis.
Age range was 13.2–19.7 years (mean ± SD 16.7 ± 1.7 years); 6% (n = 5) were African American, and 24% (n = 21) were sexually active. Compared with baseline and SC subjects, IG subjects demonstrated a significant group-by-time interaction for benefit and knowledge of preconception counseling and reproductive health: increasing immediately after the first visit (P < 0.001) and being sustained for 9 months (P < 0.05 benefits; P < 0.001 knowledge). For IG subjects, preconception counseling barriers decreased over time (P < 0.001), and intention and initiation of preconception counseling and reproductive health discussions increased (P < 0.001). Costs of adverse reproductive outcomes are high. Direct medical costs of READY-Girls were low.
READY-Girls was beneficial and effects were sustained for at least 9 months. This low-cost self-instructional program can potentially empower young women with type 1 diabetes to make well-informed reproductive health choices, adding little time burden or cost to their diabetes management.
Understanding associated risk for obesity is a prerequisite to develop early life interventions to arrest the increasing epidemic of metabolic syndrome and obesity among preterm born children and adolescents.
A retrospective review of 160 charts was conducted to determine the associated risk of being obese during childhood and adolescent period in preterm children. Birth weight, gestational age, weight gain, demographics, maternal health, socioeconomics, and clinical factors during early neonatal life were evaluated. The number of obese children increased with age and was observed more in the adolescent population. Obese children were significantly heavier at age 24 months old compared to their peers (p = 0.001). Analysis of associated risk for maternal demographics, maternal age, maternal marital status or race, prenatal factors, maternal substance abuse or diabetes, neonatal factors, weight for gestational age or birth weight did not show any statistically significant risk for future obesity. Duration of gestational age (OR 1.6; p = 0.017) and heavier birth weight (OR 3.2; p = 0.001) were associated with risk of obesity.
Among preterm born babies in the study, the highest risk of developing excessive weight during childhood and adolescent periods are babies born at more advanced gestational age. Strong positive association was found between birth weight and body weight in childhood. By 24 months old, there was a distinguished group of toddlers, who were heavier than their peers and remained with excessive weight as they got older. Primary care pediatricians should draw attention to premature babies, overweight infants and toddlers.
Obesity; Prematurity; Low birth weight; Large for gestational age; Postnatal care