The Impact of Cardiac Diseases during Pregnancy on Severe Maternal Morbidity and Mortality in Brazil

Background

To evaluate maternal heart disease as a cause or complicating factor for severe morbidity in the setting of the Brazilian Network for Surveillance of Severe Maternal Morbidity.

Methods and Findings

Secondary data analysis of this multicenter cross-sectional study was implemented in 27 referral obstetric units in Brazil. From July 2009 to June 2010, a prospective surveillance was conducted among all delivery hospitalizations to identify cases of severe maternal morbidity (SMM), including Potentially Life-Threatening Conditions (PLTC) and Maternal Near Miss (MNM), using the new criteria established by the WHO. The variables studied included: sociodemographic characteristics, clinical and obstetric history of the women; perinatal outcome and the occurrence of maternal outcomes (PLTC, MNM, MD) between groups of cardiac and non-cardiac patients. Only heart conditions with hemodynamic impact characterizing severity of maternal morbidity were considered. 9555 women were included in the Network with severe pregnancy-related complications: 770 maternal near miss cases and 140 maternal death cases. A total of 293 (3.6%) cases were related to heart disease and the condition was known before pregnancy in 82.6% of cases. Maternal near miss occurred in 15% of cardiac disease patients (most due to clinical-surgical causes, p<0.001) and 7.7% of non-cardiac patients (hemorrhagic and hypertensive causes, p<0.001). Maternal death occurred in 4.8% of cardiac patients and in 1.2% of non-cardiac patients, respectively.

Conclusions

In this study, heart disease was significantly associated with a higher occurrence of severe maternal outcomes, including maternal death and maternal near miss, among women presenting with any severe maternal morbidity.     

不同类型妊娠高血压疾病对产妇妊娠结局的影响

目的:探讨不同类型妊娠高血压疾病(PIH)对产妇妊娠结局的影响。方法:选取2011年1月~2013年12月我妇产科院收治的妊娠期出现高血压症状的产妇106例为观察组,并选取同期正常孕产妇100例为对照组,根据诊断标准将观察组患者再分为PIH组(75例)、子痫前期组(21例)以及子痫组(10例),对比4组产妇的胎儿窘迫、胎盘早剥、早产、剖宫产、产后出血以及新生儿窒息的发生率。结果:观察组产妇的胎儿窘迫、胎盘早剥、早产、剖宫产、产后出血以及新生儿窒息的发生率明显高于对照组,差异有统计学意义(P0.05);妊娠期高血压组、子痫前期组、子痫组的胎儿窘迫、胎盘早剥、早产、剖宫产、产后出血以及新生儿窒息的发生率,依次升高,差别有统计学意义(P0.05)。结论:应正确认识到不同类型PIH对妊娠结局的影响以及其并发症的规律,做好预防措施,以减少不良妊娠结局的发生。     

Developmental Trajectories of Body Mass Index Among Japanese Children and Impact of Maternal Factors during Pregnancy

Background

The aims of this study were to 1) determine the distinct patterns of body mass index (BMI) trajectories in Japanese children, and 2) elucidate the maternal factors during pregnancy, which contribute to the determination of those patterns.

Methodology/Principal Findings

All of the children (1,644 individuals) born in Koshu City, Japan, between 1991 and 1998 were followed in a longitudinal study exploring the subjects’ BMI. The BMI was calculated 11 times for each child between birth and 12 years of age. Exploratory latent class growth analyses were conducted to identify trajectory patterns of the BMI z-scores. The distribution of BMI trajectories were best characterized by a five-group model for boys and a six-group model for girls. The groups were named “stable thin,” “stable average,” “stable high average,” “progressive overweight,” and “progressive obesity” in both sexes; girls were allocated to an additional group called “progressive average.” Multinomial logistic regression found that maternal weight, smoking, and skipping breakfast during pregnancy were associated with children included in the progressive obesity pattern rather than the stable average pattern. These associations were stronger for boys than for girls.

Conclusions/Significance

Multiple developmental patterns in Japanese boys and girls were identified, some of which have not been identified in Western countries. Maternal BMI and some unfavorable behaviors during early pregnancy may impact a child’s pattern of body mass development. Further studies to explain the gender and regional differences that were identified are warranted, as these may be important for early life prevention of weight-associated health problems.     

Potential of the Newborn Rabbit for Circadian Rhythms Research

Developmental studies of circadian function in mammals are generally difficult because of the close interaction between mother and young. The European rabbit presents an exception, providing developmental chronobiologists with an unusual opportunity to study the early development of circadian function. Doe rabbits only visit their newborn young once a day to nurse for a few minutes, and pups anticipate this regular event with heightened arousal and by uncovering of the nest. Both the mother's nursing visit and pups' anticipatory arousal represent well synchronized circadian rhythms. They also represent discrete, quantifiable events that can be readily manipulated by controlling does' access to the pups, by cross-fostering or by eliminating a nursing either before, during or after the development of visual function. The doe's long absence makes it possible to carry out surgical or other interventions without disrupting the normal pattern of maternal care, and the correspondence between pups' anticipatory arousal and the expression of c-Fos in hypothalamic nuclei demonstrates the suitability of this model for investigating the neural basis of early circadian function.     

Potential of the Newborn Rabbit for Circadian Rhythms Research

Developmental studies of circadian function in mammals are generally difficult because of the close interaction between mother and young. The European rabbit presents an exception, providing developmental chronobiologists with an unusual opportunity to study the early development of circadian function. Doe rabbits only visit their newborn young once a day to nurse for a few minutes, and pups anticipate this regular event with heightened arousal and by uncovering of the nest. Both the mother's nursing visit and pups' anticipatory arousal represent well synchronized circadian rhythms. They also represent discrete, quantifiable events that can be readily manipulated by controlling does' access to the pups, by cross-fostering or by eliminating a nursing either before, during or after the development of visual function. The doe's long absence makes it possible to carry out surgical or other interventions without disrupting the normal pattern of maternal care, and the correspondence between pups' anticipatory arousal and the expression of c-Fos in hypothalamic nuclei demonstrates the suitability of this model for investigating the neural basis of early circadian function.     

重度妊娠期肝内胆汁淤积症对母婴结局影响的临床分析

目的：分析重度妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy,ICP）对母婴结局的影响,以提高对ICP的认识与治疗水平。方法：选择ICP产妇58例,根据ICP分度标准分为轻度组（n=26例）和重度组（n=32例）,比较两组产妇的母婴结局。结果：与轻度组相比,重度组产妇剖宫产率、产后出血与平均产后出血量显著升高或增加,阴道分娩率显著降低,组间比较差异均具有统计学意义（P〈0.05）;重度组新生儿早产、胎儿窘迫、羊水污染和新生儿窒息的发生率均显著上升,新生儿平均出生体重显著降低,组间比较差异均具有统计学意义（P〈0.05）。结论：ICP对产妇及新生儿均有不良影响,对ICP严重程度进行划分,有利于临床处理。对于重度ICP产妇,应尽早采取剖宫产分娩的方式终止妊娠。     

Association between Maternal Smoking during Pregnancy and Low Birthweight: Effects by Maternal Age

Background

Maternal smoking during pregnancy has been consistently related to low birthweight. However, older mothers, who are already at risk of giving birth to low birthweight infants, might be even more susceptible to the effects of maternal smoking. Therefore, this study aimed to examine the modified association between maternal smoking and low birthweight by maternal age.

Methods

Data were obtained from a questionnaire survey of all mothers of children born between 2004 and 2010 in Okinawa, Japan who underwent medical check-ups at age 3 months. Variables assessed were maternal smoking during pregnancy, maternal age, gestational age, parity, birth year, and complications during pregnancy. Stratified analyses were performed using a logistic regression model.

Results

In total, 92641 participants provided complete information on all variables. Over the 7 years studied, the proportion of mothers smoking during pregnancy decreased from 10.6% to 5.0%, while the prevalence of low birthweight did not change remarkably (around 10%). Maternal smoking was significantly associated with low birthweight in all age groups. The strength of the association increased with maternal age, both in crude and adjusted models.

Conclusions

Consistent with previous studies conducted in Western countries, this study demonstrates that maternal age has a modifying effect on the association between maternal smoking and birthweight. This finding suggests that specific education and health care programs for older smoking mothers are important to improve their foetal growth.     

Epigenetic Maternal Effects on Endogenous Rhythms in Precocial Birds

Development involves interactions between genetic and environmental influences. Vertebrate mothers are generally the first individuals to encounter and interact with young animals. Thus, their role is primordial during ontogeny. The present study evaluated non‐genomic effects of mothers on the development of rhythms of precocial Japanese quail (Coturnix c. japonica). First, we investigated the influence of mothering on the ontogeny of endogenous rhythms of young. We compared circadian and ultradian rhythms of feeding activity of quail reared with or without adoptive mothers. More brooded than non‐brooded quail presented a circadian and/or an ultradian rhythm. Thus, the presence of the mother during the normal brooding period favors, in the long term, expression of rhythms in the young. Second, we investigated the influence of rhythmic phenotype of the mother on the development of endogenous rhythms of young by comparing quail brooded by circadian‐rhythmic adoptive mothers (R) to quail brooded by circadian‐arrhythmic adoptive mothers (A). More R‐brooded than A‐brooded quail expressed circadian rhythmicity, and circadian rhythm clarities were greater in R‐brooded than A‐brooded quail. Ultradian rhythmicity did not differ between R‐ and A‐brooded quail, nor between R and A adoptive mothers. Thus, the rhythmic phenotypes of quail mothers influence the rhythmic phenotypes of their young. Our results demonstrate that mothers of precocial birds influence epigenetically the ontogeny of endogenous rhythms of the young they raise.     

Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy

Metabolic profiles of amniotic fluid and maternal blood are sources of valuable information about fetus development and can be potentially useful in diagnosis of pregnancy disorders. In this study, we applied ¹H NMR-based metabolic profiling to track metabolic changes occurring in amniotic fluid (AF) and plasma (PL) of healthy mothers over the course of pregnancy. AF and PL samples were collected in the 2^nd (T2) and 3^rd (T3) trimester, prolonged pregnancy (PP) until time of delivery (TD). A multivariate data analysis of both biofluids reviled a metabolic switch-like transition between 2^nd and 3^rd trimester, which was followed by metabolic stabilization throughout the rest of pregnancy probably reflecting the stabilization of fetal maturation and development. The differences were further tested using univariate statistics at α = 0.001. In plasma the progression from T2 to T3 was related to increasing levels of glycerol, choline and ketone bodies (3-hydroxybutyrate and acetoacetate) while pyruvate concentration was significantly decreased. In amniotic fluid, T2 to T3 transition was associated with decreasing levels of glucose, carnitine, amino acids (valine, leucine, isoleucine, alanine, methionine, tyrosine, and phenylalanine) and increasing levels of creatinine, succinate, pyruvate, choline, N,N-dimethylglycine and urocanate. Lactate to pyruvate ratio was decreased in AF and conversely increased in PL. The results of our study, show that metabolomics profiling can be used to better understand physiological changes of the complex interdependencies of the mother, the placenta and the fetus during pregnancy. In the future, these results might be a useful reference point for analysis of complicated pregnancies.     

Effects of Pregnancy and Parturition on Free-Running Circadian Activity Rhythms in the Rat

Alterations in circadian rhythms have previously been associated with estrous and seasonal changes in reproductive state. In the present study we explored the effects of the reproductive events of pregnancy and parturition on free-running circadian activity rhythms in the rat. Free-running rhythms were monitored before mating, during pregnancy, and following parturition and removal of pups. Systematic and long-lasting alterations of the period of the free-running activity rhythm were seen following parturition. The effects of estrous, seasonal, and gestational reproductive states on circadian rhythms may be mediated by the endocrine events which accompany these states.     

Effects of Pregnancy and Parturition on Free-Running Circadian Activity Rhythms in the Rat

Alterations in circadian rhythms have previously been associated with estrous and seasonal changes in reproductive state. In the present study we explored the effects of the reproductive events of pregnancy and parturition on free-running circadian activity rhythms in the rat. Free-running rhythms were monitored before mating, during pregnancy, and following parturition and removal of pups. Systematic and long-lasting alterations of the period of the free-running activity rhythm were seen following parturition. The effects of estrous, seasonal, and gestational reproductive states on circadian rhythms may be mediated by the endocrine events which accompany these states.     

Maternal Responsiveness Increases during Pregnancy and after Estrogen Treatment in Macaques

Maternal responsiveness in primates has long been considered emancipated from endocrine factors and entirely dependent on experience and cognition. Here we report that group-living pigtail macaque females increased their rate of interaction with infants in the last weeks of pregnancy in correspondence with an increase in plasma levels of estradiol and progesterone. Estrogen treatment increased the rate at which ovariectomized rhesus females interacted with infants. This is the first evidence that steroid hormones influence maternal responsiveness in anthropoid primates. All untreated ovariectomized females and nonpregnant females interacted with infants, indicating that although estrogen can enhance responsiveness to infants, ovarian or pregnancy hormones are not necessary for the expression of infant-directed behavior in female macaques. The findings of this study suggest fundamental similarities, rather than differences, in the endocrine modulation of maternal responsiveness in primates and other mammals.     

Light Pollution Modifies the Expression of Daily Rhythms and Behavior Patterns in a Nocturnal Primate

Among anthropogenic pressures, light pollution altering light/dark cycles and changing the nocturnal component of the environment constitutes a threat for biodiversity. Light pollution is widely spread across the world and continuously growing. However, despite the efforts realized to describe and understand the effects of artificial lighting on fauna, few studies have documented its consequences on biological rhythms, behavioral and physiological functions in nocturnal mammals. To determine the impacts of light pollution on nocturnal mammals an experimental study was conducted on a nocturnal primate, the grey mouse lemur Microcebus murinus. Male mouse lemurs (N = 8) were exposed 14 nights to moonlight treatment and then exposed 14 nights to light pollution treatment. For both treatments, chronobiological parameters related to locomotor activity and core temperature were recorded using telemetric transmitters. In addition, at the end of each treatment, the 14^th night, nocturnal and feeding behaviors were explored using an infrared camera. Finally, throughout the study, body mass and daily caloric food intake were recorded. For the first time in a nocturnal primate, light pollution was demonstrated to modify daily rhythms of locomotor activity and core temperature especially through phase delays and increases in core temperature. Moreover, nocturnal activity and feeding behaviors patterns were modified negatively. This study suggests that light pollution induces daily desynchronization of biological rhythms and could lead to seasonal desynchronization with potential deleterious consequences for animals in terms of adaptation and anticipation of environmental changes.     

Effects of Maternal LPS Exposure during Pregnancy on Metabolic Phenotypes in Female Offspring

It is increasingly recognized that intra-uterine growth restriction (IUGR) is associated with an increased risk of metabolic disorders in late life. Previous studies showed that mice exposed to LPS in late gestation induced fetal IUGR. The present study investigated the effects of maternal LPS exposure during pregnancy on metabolic phenotypes in female adult offspring. Pregnant mice were intraperitoneally injected with LPS (50 µg/kg) daily from gestational day (GD)15 to GD17. After lactation, female pups were fed with standard-chow diets (SD) or high-fat diets (HFD). Glucose tolerance test (GTT) and insulin tolerance test (ITT) were assessed 8 and 12 weeks after diet intervention. Hepatic triglyceride content was examined 12 weeks after diet intervention. As expected, maternal LPS exposure during pregnancy resulted in fetal IUGR. Although there was an increasing trend on fat mass in female offspring whose dams were exposed to LPS during pregnancy, maternal LPS exposure during pregnancy did not elevate the levels of fasting blood glucose and serum insulin and hepatic triglyceride content in female adult offspring. Moreover, maternal LPS exposure during pregnancy did not alter insulin sensitivity in adipose tissue and liver in female adult offspring. Further analysis showed that maternal LPS exposure during pregnancy did not exacerbate HFD-induced glucose tolerance and insulin resistance in female adult offspring. In addition, maternal LPS exposure during pregnancy did not aggravate HFD-induced elevation of hepatic triglyceride content in female adult offspring. In conclusion, LPS-induced IUGR does not alter metabolic phenotypes in adulthood.     

逆转座子对灵长目动物基因组结构的影响

逆转座子(retroposon)是动物基因组中一类可移动的元件,它们首先通过转录产生一个RNA拷贝,然后利用逆转录酶将该RNA拷贝逆转录为c DNA后,再插入到基因组的新位点上。逆转座子在动物基因组中含量极为丰富,种类也很繁多,并随着动物进化在基因组中不断扩增。它们可通过形成插入突变、侧翼序列转导、基因逆转座、DNA断裂与修复、异常重组等机制对动物基因组结构的稳定性产生重要影响,并成为推动基因组进化的重要动力。本文综述了灵长目动物主要的逆转座子类型及其对基因组结构的影响方式,从而为深入理解逆转座子在灵长目动物基因组中的功能及灵长目动物的进化提供参考。     

Trans-Generational Effect of Maternal Lactation during Pregnancy: A Holstein Cow Model

Epigenetic regulation in mammals begins in the first stages of embryogenesis. This prenatal programming determines, in part, phenotype expression in adult life. Some species, particularly dairy cattle, are conceived during the maternal lactation, which is a period of large energy and nutrient needs. Under these circumstances, embryo and fetal development compete for nutrients with the mammary gland, which may affect prenatal programming and predetermine phenotype at adulthood. Data from a specialized dairy breed were used to determine the transgenerational effect when embryo development coincides with maternal lactation. Longitudinal phenotypic data for milk yield (kg), ratio of fat-protein content in milk during first lactation, and lifespan (d) from 40,065 cows were adjusted for environmental and genetic effects using a Bayesian framework. Then, the effect of different maternal circumstances was determined on the residuals. The maternal-related circumstances were 1) presence of lactation, 2) maternal milk yield level, and 3) occurrence of mastitis during embryogenesis. Females born to mothers that were lactating while pregnant produced 52 kg (MonteCarlo standard error; MCs.e. = 0.009) less milk, lived 16 d (MCs.e. = 0.002) shorter and were metabolically less efficient (+0.42% milk fat/protein ratio; MCs.e.<0.001) than females whose fetal life developed in the absence of maternal lactation. The greater the maternal milk yield during embryogenesis, the larger the negative effects of prenatal programming, precluding the offspring born to the most productive cows to fully express their potential additive genetic merit during their adult life. Our data provide substantial evidence of transgenerational effect when pregnancy and lactation coincide. Although this effect is relatively low, it should not be ignored when formulating rations for lactating and pregnant cows. Furthermore, breeding, replacement, and management strategies should also take into account whether the individuals were conceived during maternal lactation because, otherwise, their performance may deviate from what it could be expected.     

妊娠期糖代谢异常对新生儿出生结局的影响

目的:探讨妊娠期不同程度的糖代谢异常对胎儿发育及结局的影响。方法:前瞻性收集我院2009年1月至2010年1月分娩的糖代谢异常的331例单胎妊娠孕妇,分为糖筛查异常组69例、糖耐量异常组126例、妊娠期糖尿病(Gestaional DiabetesMellitus,GDM)组136例,并选择同期糖代谢正常的751例单胎孕妇为对照组,比较四组新生儿出生的最终结局。结果:糖筛查异常组与对照组新生儿结局差异无显著性意义(P>0.05);糖耐量异常组中巨大儿及新生儿窒息、早产儿的发生率与对照组差异有显著性意义(P<0.05);GDM组与对照组差异有显著性意义(P<0.05)。结论:母亲妊娠期不同程度的糖代谢异常对新生儿影响不同。口服葡萄糖耐量试验(Oral Glucose Tolerance Test,OGTT)异常与GDM一样对新生儿发育及结局均有影响,可使巨大儿、新生儿窒息、早产儿的发生率增高。     

温度对红尾沙蜥代谢昼夜节律的影响

爬行动物很多生理、生化和行为指标都表现出昼夜节律。代谢昼夜节律不仅涉及内在因子的固有控制,而且受到多种外部因素的影响。为了探究温度对代谢昼夜节律的影响,在恒定的温度下(18℃和28℃)测定了红尾沙蜥Phrynocephalus erythrurus体温、心率、标准代谢率(SMR)和血糖浓度的昼夜变化。结果表明:(1)在2个温度下红尾沙蜥体温没有明显的昼夜变化;(2)昼间SMR明显高于夜间,18℃下SMR水平以及SMR昼夜变化的范围都低于28℃下的结果;(3)心率的变化也与代谢率的变化一致,但最低点提前了2 h;(4)28℃下的血糖浓度整体水平显著高于18℃下的,而波动规律却不同:28℃条件下白天平均值高于晚上,血糖浓度在16∶00显著高于20∶00、00∶00和12∶00;18℃条件下,血糖浓度在20∶00和08∶00明显低于00∶00和12∶00(P0.05),而在04∶00和16∶00处于中间水平。该研究证实了红尾沙蜥SMR、心率和血糖浓度等生理生化指标也存在明显的昼夜节律,虽然这种现象受环境温度的影响,但主要还是由内在因子决定,这可能与某些激素的分泌活动有关。     

妊娠期糖代谢异常对新生儿出生结局的影响

目的：探讨妊娠期不同程度的糖代谢异常对胎儿发育及结局的影响。方法：前瞻性收集我院2009年1月至2010年1月分娩的糖代谢异常的331例单胎妊娠孕妇,分为糖筛查异常组69例、糖耐量异常组126例、妊娠期糖尿病（Gestaional DiabetesMellitus,GDM）组136例,并选择同期糖代谢正常的751例单胎孕妇为对照组,比较四组新生儿出生的最终结局。结果：糖筛查异常组与对照组新生儿结局差异无显著性意义（P〉0.05）;糖耐量异常组中巨大儿及新生儿窒息、早产儿的发生率与对照组差异有显著性意义（P〈0.05）;GDM组与对照组差异有显著性意义（P〈0.05）。结论：母亲妊娠期不同程度的糖代谢异常对新生儿影响不同。口服葡萄糖耐量试验（Oral Glucose Tolerance Test,OGTT）异常与GDM一样对新生儿发育及结局均有影响,可使巨大儿、新生儿窒息、早产儿的发生率增高。