Prenatal exposure: The effects of prenatal cocaine and methamphetamine exposure on the developing child

Prenatal substance use remains a significant issue in the United States. Initial reports regarding prenatal cocaine and methamphetamine exposure suggested profound adverse effects on child development. However, subsequent prospective, longitudinal investigations have found more subtle effects. What follows is a brief review of the health, growth, behavioral, and intellectual outcomes for children exposed to prenatal cocaine and prenatal methamphetamine. Factors that may mitigate or intensify subtle adverse effects manifested in exposed children will also be discussed. Birth Defects Research (Part C) 108:142–146, 2016. © 2016 Wiley Periodicals, Inc.     

Relationship between DHA status at birth and child problem behaviour at 7 years of age

Animal studies have demonstrated behavioural effects of long-chain polyunsaturated fatty acid (LC-PUFA) deficiencies and in humans, several psychiatric disorders have been linked to abnormal essential fatty acid metabolism. The aim of this study was to examine the relationship between LC-PUFA status at birth and the later development of problem behaviour. In a sample of 393 children, higher levels of docosahexaenoic acid (DHA) at birth were associated with lower levels of internalising problem behaviour at age 7 years. The association was markedly present in the infants fed with artificial formula (n=215, Beta=-0.32, P=0.000), but absent in the infants fed with human milk (n=170, Beta=0.11, P=0.325). The associations between arachidonic acid and internalising or externalising behaviour were neither large nor significant. The results suggest that perinatal DHA status may have long-term behavioural consequences. Therefore, we suggest to include measures of problem behaviour in future trials of LC-PUFA supplementation of mothers and/or infants.     

Prenatal polymetallic exposure and small for gestational age: A case-control study in Taiyuan,China

BackgroundStudies focused on independent effects of metals on small for gestational age, failing to account for potential interdependence among metals.MethodsIn this case-control study, we selected 187 pregnant women and 187 matched controls from the First Hospital of Shanxi Medical University. Determination of 12 elements in the venous blood of pregnant women before delivery by ICP-MS. Logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to estimate the overall effect and identify important mixture components that drive the associations with SGA.ResultsAn increased risk of SGA was associated with As (OR= 1.06,95%CI: 1.01,1.12), Cd (OR= 1.24,95%CI: 1.04,1.47) and Pb (OR= 1.05,95%CI: 1.02,1.08), while Zn (OR= 0.58,95%CI: 0.45,0.76) and Mn (OR= 0.97,95%CI: 0.94,0.99) were protective factors for SGA. In the WQSR positive model, the mixture of heavy metals has a positive combined effect on SGA (OR= 1.74,95%CI: 1.15, 2.62), with Sb and Cd having the highest weights. The BKMR models confirmed that the metal mixture was associated with decreased risk of SGA when the concentration of 12 metals was between the 30th percentile and the 65th percentile, and Zn and Cd had the greatest independent effect. Zn and SGA may not be linearly correlated, higher Zn level may reduce the effect of Cd on the risk of SGA.ConclusionsOur study suggested that exposure to multiple metals was associated with risk of SGA, and the observed association with multiple metals was dominated by Zn, Cd. Sb exposure during pregnancy may also increase the risk of SGA.     

Prenatal stress and balance of the child's cardiac autonomic nervous system at age 5-6 years

Objective

Autonomic nervous system (ANS) misbalance is a potential causal factor in the development of cardiovascular disease. The ANS may be programmed during pregnancy due to various maternal factors. Our aim is to study maternal prenatal psychosocial stress as a potential disruptor of cardiac ANS balance in the child.

Methods

Mothers from a prospective birth cohort (ABCD study) filled out a questionnaire at gestational week 16 [IQR 12–20], that included validated instruments for state anxiety, depressive symptoms, pregnancy-related anxiety, parenting daily hassles and job strain. A cumulative stress score was also calculated (based on 80^th percentiles). Indicators of cardiac ANS in the offspring at age 5–6 years are: pre-ejection period (PEP), heart rate (HR), respiratory sinus arrhythmia (RSA) and cardiac autonomic balance (CAB), measured with electrocardiography and impedance cardiography in resting supine and sitting positions.

Results

2,624 mother-child pairs, only single births, were available for analysis. The stress scales were not significantly associated with HR, PEP, RSA and CAB (p≥0.17). Accumulation of maternal stress was also not associated with HR, PEP, RSA and CAB (p≥0.07).

Conclusion

Results did not support the hypothesis that prenatal maternal psychosocial stress deregulates cardiac ANS balance in the offspring, at least in rest, and at the age of five-six years.     

Aspirin exposure during the first 20 weeks of gestation and IQ at four years of age

The relationship between maternal aspirin use during the first 20 weeks of pregnancy and the child's IQ at 4 years of age was investigated in 19,226 pregnancies occurring from 1959 to 1966 in the Collaborative Perinatal Project. The mean IQ of children exposed to aspirin was 98.3, which was 2.1 points higher (95% confidence interval = 1.7, 2.6; P less than 0.0001) than that of unexposed children. Adjustment for multiple social, demographic, and other confounders reduced this difference to less than one point in favor of the aspirin exposed group, although statistical significance remained. Total days of exposure was used as an index of dose, and no dose-response relationship between aspirin use and IQ was found. The effect of prenatal aspirin exposure did not vary by infant sex. It is concluded that an adverse effect of aspirin exposure on IQ is unlikely.     

Prenatal diagnosis of trisomy 12 mosaicism: normal development of a 3 years old female child

Trisomy 12 mosaicism is a rare chromosomal mosaicism in prenatal diagnosis by amniocentesis. In the literature we found at least 27 cases. 13 Pregnancies were terminated, with multiple congenital anomalies (MCA) in 2 out of 13. Of the 12 liveborns with follow-up ranging from 0 to 5 years, 5 presented MCA and died within the first weeks. 2 Fetus died during pregnancy and further data are lacking. A normal outcome, with limited follow up however, was reported in 7/12 liveborns without congenital anomalies and is well demonstrated in the presently reported girl. We describe the 3-years follow up in a girl with trisomy 12 mosaicism, detected by amniocentesis for advanced maternal age. She is a healthy girl with normal physical and psychomotor development.     

Childhood asthma in adult life: a further study at 28 years of age.

A group of 323 subjects who had wheezed in childhood and 48 control subjects of the same age were studied prospectively from 7 to 28 years of age. A classification system based on wheezing frequency was found to correlate well with clinical and spirometric features of airway obstruction. The amount of wheezing in early adolescence seemed to be a guide for severity in later life with 73% of those with few symptoms at 14 continuing to have little or no asthma at 28 years. Similarly 68% of those with frequent wheezing at 14 still suffered from recurrent asthma at 28 years. Most subjects with frequent wheezing at 21 continued to have comparable asthma at 28 years. Of those with infrequent wheezing at 21, 44% had worsened at 28 years. Women fared better than men between 21 and 28 with 19% having worse symptoms compared with 28% of men. Treatment at all ages was generally inadequate. The number of smokers among those with asthma was of concern.     

The Le Fort III advancement osteotomy in the child under 7 years of age

This is a longitudinal study of 12 patients with craniofacial synostosis syndromes (Crouzon's, Apert's, Pfeiffer's) who underwent Le Fort III advancement under the age of 7 years (average age 5.1 years, range 4.0 to 6.7 years). The average follow-up was 5.0 years and included clinical, dental, and cephalometric examinations according to a prescribed protocol. The study demonstrated that the procedure could be safely performed in the younger child with an acceptable level of morbidity. There was a remarkable degree of postoperative stability of the maxillary segment. However, although vertical (inferior) growth or movement of the midfacial segment was demonstrated, there was minimal, if any, anterior or horizontal growth. Any occlusal disharmony developing during the period of follow-up could be attributed to anticipated mandibular development and could be corrected by orthognathic surgery. The roles of surgical overcorrection and anterior-pull headgear therapy after release of intermaxillary fixation are also discussed. The Le Fort III osteotomy is justifiably indicated during early childhood for psychological and physiologic reasons.     

The cognitive and identity development of twins at 16 years of age: a follow-up study of 32 twin pairs.

This is a follow up study of twins within the Stockholm area, including 32 families and their twins attending grade nine. The twins have been followed from birth to 16 years of age. The main purpose of this study from its inception was to assess mental and cognitive development at different ages. Another aim was to see how the twins who were born prematurely are developing during the school ages. A third aim has been to gain a deeper insight into the relationship between co-twins and the development of their identities, which is the focus of this paper. Several ability tests have been used, as well as questionnaires about interests, attitudes toward school, and leisure activities. At the 16-year follow-up, a psychological method, the Wartegg drawing test, designed to examine identity, ego strength, dependency, ambition, anxiety, willpower, creativity, empathy and coping strategies has been used. The results indicate that it is difficult for twins to develop independence and a positive identity, as they have to emancipate themselves both from their parents and from their co-twins. Some differences in identity, anxiety and ambition were observed between female and male twins, MZ and DZ twins, preterm and fullterm twins. Prematurity, sex and zygosity no longer had any relation to cognitive development at 16 years of age.     

Longitudinal association of maternal attempt to lose weight during the postpartum period and child obesity at age 3 years

The effect of maternal attempt to lose weight during the postpartum period on later child weight has not been explored. Among 1,044 mother-infant pairs in Project Viva, we estimated longitudinal associations of maternal attempt to lose weight during the postpartum period with child weight and adiposity at age 3 years and examined differences in associations by type of weight loss strategy used. Using covariate-adjusted linear and logistic regression models, we estimated associations before and after adjusting for maternal weight-related variables including prepregnancy BMI. At 6 months postpartum, 53% mothers were trying to lose weight. At age 3 years, mean (s.d.) child BMI z-score was 0.44 (1.01) and 8.9% of children were obese. Children whose mothers were trying to lose weight at 6 months postpartum had higher BMI z-scores (0.30 (95% confidence interval (CI) 0.18, 0.42)) and were more likely to be obese (3.0 (95% CI 1.6, 5.8)) at 3 years of age. Addition of maternal prepregnancy BMI to the models attenuated but did not eliminate the associations seen for BMI z-score (0.24 (95% CI 0.12, 0.36) and obesity (2.4 (95% CI 1.2, 4.7)). Attempting to lose weight by exercising alone was the only weight loss strategy that consistently predicted higher child BMI z-score (0.36 (95% CI 0.14, 0.58)) and odds of obesity (6.0 (95% CI 2.2, 16.5)) at age 3 years. In conclusion, we observed an association between maternal attempt to lose weight at 6 months postpartum, particularly through exercise alone, measured using a single item and child adiposity at age 3 years. This association should be thoroughly examined in future studies.     

Parents' age at birth of their offspring and child survival

This study presents some new results on parental age as a risk factor for child survival. The study is based on individual registration forms for live births and infant deaths collected in Hungary from 1984 to 1988. Logistic regression models have been fitted for early neonatal and neonatal mortality on the one hand, and post-neonatal mortality on the other hand. Children of older males and females have significantly higher early neonatal and neonatal mortality rates compared to those of younger males and females. The impact of age of both parents remains, however, slighter than that of other biological characteristics such as previous number of fetal deaths, induced abortions, or live births. The authors discuss possible biological explanations.     

抗生素暴露对早产儿肠道菌群及2岁时过敏性疾病的影响

目的 探讨抗生素暴露对早产儿肠道菌群及2岁时过敏性疾病的影响。 方法 回顾性分析2016年1月至2018年1月在杭州市余杭区妇幼保健院新生儿科出生的早产儿130例。其中经验性使用抗生素患儿88例为暴露组,未使用抗生素42例作为未暴露组。经验性使用抗生素早产儿中,根据早产儿抗生素使用时间分为短期暴露组(抗生素持续使用时间7 d)30例。收集未暴露组和长期暴露组共72例早产儿出生后(结果 出生后12 h内、3 d时未暴露组和长期暴露组早产儿Shannon指数、检测物种数指数比较差异无统计学意义;出生后5 d、7 d时,长期暴露组早产儿Shannon指数、检测物种数指数均显著低于未暴露组[5 d时Shannon指数为2.25±0.85 vs 1.81±0.90(t=2.113,P=0.038),检测物种数指数为10.00±0.43 vs 7.50±0.49(t=22.944,P2=12.953,P2=14.400,P2=4.640,P=0.031),特异性皮炎为10.34%(6/58)vs 30.00%(9/30)(χ2=5.402,P=0.020],且未暴露组低于短期暴露组[过敏性鼻炎为2.38%(1/42)vs 13.79%(8/58)(χ2=3.874,P=0.049),特异性皮炎为0.00%(0/42)vs 10.34%(6/58)(χ2=4.622,P=0.032)]。3组早产儿在智力发育等方面比较差异无统计学意义。 结论 抗生素暴露会降低早产儿肠道菌群数量,使肠道菌群多样性下降,可能与早产儿2岁时发生过敏性疾病相关。     

Lung cancer in French and Czech uranium miners: Radon-associated risk at low exposure rates and modifying effects of time since exposure and age at exposure

Radon is recognized as a public health concern for indoor exposure. Precise quantification derived from occupational exposure in miners is still needed for estimating the risk and the factors that modify the dependence on cumulated exposure. The present paper reports on relationship between radon exposure and lung cancer risk in French and Czech cohorts of uranium miners (n = 10,100). Miners from these two cohorts are characterized by low levels of exposure (average cumulated exposure of less than 60 WLM) protracted over a long period (mean duration of exposure of 10 years) and by a good quality of individual exposure estimates (95% of annual exposures based on radon measurements). The modifying effect of the quality of exposure on the risk is analyzed. A total of 574 lung cancer deaths were observed, which is 187% higher than expected from the national statistics. This significantly elevated risk is strongly associated with cumulated radon exposure. The estimated overall excess relative risk per WLM is 0.027 (95% CI: 0.017-0.043, related to measured exposures). For age at exposure of 30 and 20 years since exposure, the ERR/WLM is 0.042, and this value decreases by approximately 50% for each 10-year increase in age at exposure and time since exposure. The present study emphasizes that the quality of exposure estimates is an important factor that may substantially influence results. Time since exposure and simultaneously age at exposure were the most important effect modifiers. No inverse exposure-rate effect below 4 WL was observed. The results are consistent with estimates of the BEIR VI report using the concentration model at an exposure rate below 0.5 WL.     

Prenatal exposure to bereavement and type-2 diabetes: a danish longitudinal population based study

Background

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.

Methods

We utilized data from the Danish Civil Registration System to identify singleton births in Denmark born January 1^st 1979 through December 31^st 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.

Results

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).

Conclusions

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.