Systematic review of exposure to albendazole or mebendazole during pregnancy and effects on maternal and child outcomes,with particular reference to exposure in the first trimester

Soil-transmitted helminth infections cause an important burden of morbidity worldwide, primarily from blood loss and malabsorption of nutrients. Where STH endemicity ≥20%, the World Health Organization (WHO) recommends preventive chemotherapy with single dose anthelminthic drugs: albendazole or mebendazole. Although WHO recommends that women of reproductive age, including pregnant women after the first trimester, be included in large-scale deworming programs, there are concerns related to the use of anthelminthic drugs during pregnancy, especially inadvertent use in the first few weeks when the pregnancy may not yet be confirmed. We therefore conducted a systematic review using the MEDLINE database with the aim of appraising all peer-reviewed evidence, published up to July 1, 2018, on the association between exposure to albendazole or mebendazole and outcomes in pregnant women, including those in the first trimester of pregnancy, and their children. From a yield of 205 papers based on titles alone, 58 papers, reporting results from 46 originator studies conducted in pregnant populations, constituted the initial evidence base. Among the nine originator observational studies which had included women in the first trimester of pregnancy within their study population, five compared birth outcomes between women exposed in the first trimester with women who were not exposed, and none reported higher rates of adverse birth outcomes in the exposed group. Due to heterogeneity in terms of study design, sample size, deworming drug, dosage and outcomes measured, data from these studies could not be pooled. Based on this cumulative evidence, it is unlikely that inadvertent exposure to albendazole or mebendazole in the first trimester carries an additional risk of adverse birth outcomes. To optimize relevance for policy making, future research in pregnant populations should aim to provide data disaggregated by trimester and to report on maternal and child adverse events, whenever possible.     

阴道微生物与多囊卵巢综合征相关性的研究进展

多囊卵巢综合征（PCOS）是育龄期女性最常见的内分泌失调性疾病,具有高度的异质性和复杂性,是女性不孕的常见因素之一,且PCOS会显著增加2型糖尿病、肥胖、心血管疾病、高血压和心理疾病的风险,严重危害患者健康。阴道微生物群是每个女性特有的,正常的阴道微生物群在维持女性生殖健康方面起着至关重要的作用,而异常的阴道微生物定植与不良生殖结局密切相关。结合PCOS患者不孕症、高流产率、高早产率和胚胎停育等不良妊娠事件的发生,阴道乃至整个生殖道的不良微生物群可能通过免疫和炎症反应等途径影响着PCOS的发生发展,但其机制仍不清楚。因此,本文综述了阴道微生物群和PCOS患者相关性的研究概况,包括PCOS患者阴道微生物群的组成、阴道微生物群与PCOS的发生机制以及PCOS患者阴道微生物对生殖结局的影响,以期为PCOS的诊疗提供新思路。

     

Peripheral Dendritic Cells and CD4+CD25+Foxp3+ Regulatory T Cells in the First Trimester of Normal Pregnancy and in Women with Recurrent Miscarriage

The development of pregnancy is possible due to initiation of immune response in the body of the mother resulting in immune tolerance. Miscarriage may be caused by the impaired maternal immune response to paternal alloantigens located on the surface of trophoblast and fetal cells. The aim of the study was to compare the population of circulating dendritic cells (DCs) and CD4+CD25+Foxp3+ regulatory T cells (TREGs) in the first trimester of a normal pregnancy and in women with recurrent miscarriage and an attempt to determine the relationship between these cells and the role they may play in human reproductive failures. The study was conducted in a group of 33 first trimester pregnant women with recurrent miscarriage and in a group of 20 healthy pregnant women in the first trimester of normal pregnancy. Among mononuclear cells isolated from peripheral blood, the populations of DCs and TREGs were assessed by flow cytometry. The percentage of myeloid DCs and lymphoid DCs showed no significant difference between study and control group. Older maternal age and obesity significantly reduced the pool of circulating myeloid and lymphoid DCs (R=-0.39, p=0.02). In miscarriages the percentage of circulating TREGs was significantly lower compared to normal pregnancies (p=0.003). Among the analysed factors the percentage of TREGs was the most sensitive and the most specific parameter which correlated with the pregnancy loss. The reduction in the population of circulating TREGs suggests immunoregulatory mechanisms disorder in a pregnancy complicated by miscarriage.     

Effects on pregnancy outcome of changing partner between first two births: prospective population study

Objective To compare the effects on pregnancy outcomes of changing partner between the first two births with having the same partner for both births.Design Prospective population study.Setting Norway.Participants 31 683 women who changed partner between their first two births and 456 458 women with the same partner for both births.Results After adjustment for maternal age and education, interval between births, and decade of birth, the risk of adverse pregnancy outcomes for the second birth was higher for women who changed partner between the first two births compared with those who had the same partner for both births: preterm birth (< 37 weeks; relative risk 2.0, 95% confidence interval 1.9 to 2.1), low birth weight (< 2500 g; 2.5, 2.3 to 2.6), and infant mortality (1.8, 1.6 to 2.1). For the first birth, the risk of these adverse pregnancy outcomes was only slightly higher for mothers who subsequently had a second birth with another partner.Conclusion Women who change partner between their first two births are at an increased risk of delivering a preterm, low birthweight baby with an increased risk of infant mortality compared with women who have the same partner for both births.     

Maternal Vaccination to Prevent Adverse Pregnancy Outcomes: An Underutilized Molecular Immunological Intervention?

Adverse pregnancy outcomes including maternal mortality, stillbirth, preterm birth, intrauterine growth restriction cause millions of deaths each year. More effective interventions are urgently needed. Maternal immunization could be one such intervention protecting the mother and newborn from infection through its pathogen-specific effects. However, many adverse pregnancy outcomes are not directly linked to the infectious pathogens targeted by existing maternal vaccines but rather are linked to pathological inflammation unfolding during pregnancy. The underlying pathogenesis driving such unfavourable outcomes have only partially been elucidated but appear to relate to altered immune regulation by innate as well as adaptive immune responses, ultimately leading to aberrant maternal immune activation. Maternal immunization, like all immunization, impacts the immune system beyond pathogen-specific immunity. This raises the possibility that maternal vaccination could potentially be utilised as a pathogen-agnostic immune modulatory intervention to redirect abnormal immune trajectories towards a more favourable phenotype providing pregnancy protection. In this review we describe the epidemiological evidence surrounding this hypothesis, along with the mechanistic plausibility and present a possible path forward to accelerate addressing the urgent need of adverse pregnancy outcomes.     

Locus-specific DNA methylation in the placenta is associated with levels of pro-inflammatory proteins in cord blood and they are both independently affected by maternal smoking during pregnancy

We investigated the impact of maternal smoking during pregnancy on placental DNA methylation and how this may mediate the association between maternal smoking and pro-inflammatory proteins in cord blood. The study population consisted of 27 individuals exposed to maternal smoking throughout pregnancy, 32 individuals exposed during a proportion of the pregnancy, and 61 unexposed individuals. Methylation of 11 regions within 6 genes in placenta tissue was assessed by pyrosequencing. Levels of 7 pro-inflammatory proteins in cord blood were assessed by electrochemiluminescence. Differential methylation was observed in the CYP1A1 promoter and AHRR gene body regions between women who smoked throughout pregnancy and non-smokers on the fetal-side of the placenta and in the GFI1 promoter between women who quit smoking while pregnant and non-smokers on the maternal-side of the placenta. Maternal smoking resulted in elevated levels of IL-8 protein in cord blood, which was not mediated by DNA methylation of our candidate regions at either the maternal or the fetal side of the placenta. Placental DNA methylation was associated with levels of inflammatory proteins in cord blood. Our observations suggest that maternal smoking during pregnancy affects both placental DNA methylation and the neonate's immune response.     

Coerced first sexual intercourse and selected reproductive health outcomes among young women in KwaZulu-Natal, South Africa

Coercion may play an important role in compelling young women to engage in sexual intercourse at an early age. With a decline in age at first intercourse and increased reporting of coercive first sex, concerns of adverse reproductive health outcomes such as unintended pregnancy and sexually transmitted infections (STIs), including HIV, have become important issues, particularly in the context of a high HIV prevalence. This paper uses data collected in 2001 from the second round of a longitudinal study of 1130 sexually experienced young women in KwaZulu-Natal to investigate the relationship between coerced first intercourse and selected reproductive health outcomes and behaviours. Nearly 46% of all sexually experienced young women had reported that their first sexual encounter had been coerced. Young women who reported being coerced at first sex were significantly more likely to be Black and living in an urban area. Those who had been coerced at first sex were also more likely to report having had an STI and having experienced unintended pregnancy, than those who had not been coerced at first sex. Coercion at first sex is an important social and public health problem that has a serious impact on the reproductive health and behaviours of young women. Interventions should directly address the issue of sexual coercion by ensuring young women are aware of their reproductive rights.     

Maternal inflammatory diet and adverse pregnancy outcomes: Circulating cytokines and genomic imprinting as potential regulators?

Excessive inflammation during pregnancy alters homeostatic mechanisms of the developing fetus and has been linked to adverse pregnancy outcomes. An anti-inflammatory diet could be a promising avenue to combat the pro-inflammatory state of pregnancy, particularly in obese women, but we lack mechanistic data linking this dietary pattern during pregnancy to inflammation and birth outcomes. In an ethnically diverse cohort of 1057 mother-child pairs, we estimated the relationships between dietary inflammatory potential [measured via the energy-adjusted dietary inflammatory index (E-DII?)] and birth outcomes overall, as well as by offspring sex and maternal pre-pregnancy body mass index (BMI). In a subset of women, we also explored associations between E-DII, circulating cytokines (n = 105), and offspring methylation (n = 338) as potential modulators of these relationships using linear regression. Adjusted regression models revealed that women with pro-inflammatory diets had elevated rates of preterm birth among female offspring [β = ?0.22, standard error (SE) = 0.07, P<0.01], but not male offspring (β=0.09, SE = 0.06, P<0.12) (P_interaction = 0.003). Similarly, we observed pro-inflammatory diets were associated with higher rates of caesarean delivery among obese women (β = 0.17, SE = 0.08, P = 0.03), but not among women with BMI <25 kg/m² (P_interaction = 0.02). We observed consistent inverse associations between maternal inflammatory cytokine concentrations (IL-12, IL-17, IL-4, IL-6, and TNFα) and lower methylation at the MEG3 regulatory sequence (P<0.05); however, results did not support the link between maternal E-DII and circulating cytokines. We replicate work by others on the association between maternal inflammatory diet and adverse pregnancy outcomes and provide the first empirical evidence supporting the inverse association between circulating cytokine concentrations and offspring methylation.     

妊娠妇女阴道微生态和B族链球菌与胎膜早破及母婴结局的相关性

探讨妊娠妇女阴道微生态状况和B族链球菌（GBS）感染与妊娠晚期胎膜早破及母婴结局的相关性。

回顾性收集2021年1月至2022年12月我院114例临床确诊足月胎膜早破妊娠妇女为研究对象（胎膜早破组）,随机选取同期分娩的129例健康妊娠妇女为对照组。收集两组对象临床资料,比较两组对象阴道微生态变化、GBS感染及不良母婴结局发生情况。

两组妊娠妇女阴道假丝酵母菌菌体及孢子检出情况比较差异均无统计学意义（均P＞0.05）。胎膜早破组患者阴道pH≥4.5、细菌性阴道病、需氧菌性阴道炎的发生率及微生态失衡率高于对照组（均P＜0.05）。胎膜早破组妊娠妇女绒毛膜羊膜炎、产褥感染、胎儿窘迫及新生儿肺炎等不良母婴结局发生率高于对照组（均P＜0.05）。单因素分析结果显示,阴道pH≥4.5、有GBS感染、阴道微生态失调与不良母婴结局有关（均P＜0.05）。

妊娠晚期阴道微生态失衡、GBS感染与妊娠晚期胎膜早破的发生相关,同时会增加不良母婴结局的发生率。加强相关危险因素的干预可降低妊娠晚期女性胎膜早破发生率,改善不良母婴结局。

     

阴道微生态与围产期不良结局的研究进展

阴道微生态对围产期结局的影响已成为近期医学研究的焦点。阴道内定植有多种微生物,其中优势菌为乳杆菌,维持着阴道内正常pH。当机体免疫防御能力降低或者内分泌系统紊乱时,机会致病菌占据优势,极易诱发阴道炎性病变,严重影响妊娠期女性正常生活,并且对胎儿的发育及健康成长造成威胁,导致早产和胎膜早破等不良妊娠结局的发生。由于阴道菌群毒力强弱具有差异性,感染所致的阴道炎性疾病容易复发且不易根除,因此在治疗方面,临床医师需要根据个体化原则指导用药。本文对近年来阴道微生态与妊娠不良结局的相关性研究进行简要综述。     

Risk of Cerebral Palsy and Childhood Epilepsy Related to Infections before or during Pregnancy

Background and Aim

Maternal infections during pregnancy have been associated with several neurological disorders in the offspring. However, given the lack of specificity for both the exposures and the outcomes, other factors related to infection such as impaired maternal immune function may be involved in the causal pathway. If impaired maternal immune function plays a role, we would expect infection before pregnancy to be associated with these neurological outcomes.

Methods/Principal Findings

The study population included all first-born singletons in Denmark between January 1 1982 and December 31 2004. We identified women who had hospital-recorded infections within the 5 year period before pregnancy, and women who had hospital-recorded infections during pregnancy. We grouped infections into either infections of the genitourinary system, or any other infections. Cox models were used to estimate adjusted hazard ratios (aHRs) with 95% confidence interval (CI). Maternal infection of the genitourinary system during pregnancy was associated with an increased risk of cerebral palsy (aHR = 1.63, 95% CI: 1.34–1.98) and epilepsy (aHR = 1.27, 95% CI: 1.13–1.42) in the children, compared to children of women without infections during pregnancy. Among women without hospital-recorded infections during pregnancy, maternal infection before pregnancy was associated with an increased risk of epilepsy (aHR = 1.35, 95% CI: 1.21–1.50 for infections of the genitourinary system, and HR = 1.12, 95% CI: 1.03–1.22 for any other infections) and a slightly higher risk of cerebral palsy (aHR = 1.20, 95% CI: 0.96–1.49 for infections of the genitourinary system, and HR = 1.23, 95% CI: 1.06–1.43 for any other infections) in the children, compared to children of women without infections before (and during) pregnancy.

Conclusions

These findings indicate that the maternal immune system, maternal infections, or factors related to maternal immune function play a role in the observed associations between maternal infections before pregnancy and cerebral diseases in the offspring.     

Aberrant 5’-CpG Methylation of Cord Blood TNFα Associated with Maternal Exposure to Polybrominated Diphenyl Ethers

Growing evidence suggests that maternal exposures to endocrine disrupting chemicals during pregnancy may lead to poor pregnancy outcomes and increased fetal susceptibility to adult diseases. Polybrominated diphenyl ethers (PBDEs), which are ubiquitously used flame-retardants, could leach into the environment; and become persistent organic pollutants via bioaccumulation. In the United States, blood PBDE levels in adults range from 30–100 ng/g- lipid but the alarming health concern revolves around children who have reported blood PBDE levels 3 to 9-fold higher than adults. PBDEs disrupt endocrine, immune, reproductive and nervous systems. However, the mechanism underlying its adverse health effect is not fully understood. Epigenetics is a possible biological mechanism underlying maternal exposure-child health outcomes by regulating gene expression without changes in the DNA sequence. We sought to examine the relationship between maternal exposure to environmental PBDEs and promoter methylation of a proinflammatory gene, tumor necrosis factor alpha (TNFα). We measured the maternal blood PBDE levels and cord blood TNFα promoter methylation levels on 46 paired samples of maternal and cord blood from the Boston Birth Cohort (BBC). We showed that decreased cord blood TNFα methylation associated with high maternal PBDE47 exposure. CpG site-specific methylation showed significantly hypomethylation in the girl whose mother has a high blood PBDE47 level. Consistently, decreased TNFα methylation associated with an increase in TNFα protein level in cord blood. In conclusion, our finding provided evidence that in utero exposure to PBDEs may epigenetically reprogram the offspring’s immunological response through promoter methylation of a proinflammatory gene.     

Chikotsa--secrets, silence, and hiding: social risk and reproductive vulnerability in central Mozambique

In this article, I examine pregnancy narratives and patterns of reproductive health seeking among women of fertile age in central Mozambique. I map the interplay between gendered economic marginalization, maternal risk perceptions, and pregnancy management strategies. By interpreting my data in light of Shona illness theories, I illuminate the ways that embodied experiences of reproductive vulnerability, risk perceptions, and social inequalities are linked: women attribute the most serious maternal complications to human- or spirit-induced reproductive threats of witchcraft and sorcery. This construction of reproductive vulnerability as social threats related to material and social competition significantly influences prenatal health seeking. Data reveal the structural and cognitive gap between biomedical constructions of risk and lay social threat perceptions. Plural health care systems are strategically utilized by women seeking to minimize both social and biological harm. On-the-ground ethnography shows that maternal health initiatives must take this plurality into full and accommodative account to achieve viable improvements in reproductive care and outcomes.     

Transgenerational effects of maternal diet on metabolic and reproductive ageing

The early-life environment, in particular maternal diet during pregnancy, influences a wide range of organs and systems in adult offspring. Mounting evidence suggests that developmental programming can also influence health and disease in grand-offspring. Transgenerational effects can be defined as those persisting into an F2 generation, where the F0 mother experiences suboptimal diet during her pregnancy. In this review, we critically examine evidence for transgenerational developmental programming effects in human populations, focusing on metabolic and reproductive outcomes. We discuss evidence from historical cohorts suggesting that grandchildren of women exposed to famine and other dietary alterations during pregnancy may experience increased rates of later health complications than their control counterparts. The methodological difficulties with transgenerational studies in human cohorts are explored. In particular, the problems with assessing reproductive outcomes in human populations are discussed. In light of the relative paucity of evidence available from human cohorts, we consider key insights from transgenerational experimental animal models of developmental programming by maternal diet; data are drawn from a range of rodent models, as well as the guinea-pig and the sheep. The evidence for different potential mechanisms of transgenerational inheritance or re-propagation of developmental programming effects is evaluated. Transgenerational effects could be transmitted through methylation of the gametes via the paternal and maternal lineage, as well as other possible mechanisms via the maternal lineage. Finally, future directions for exploring these underlying mechanisms further are proposed, including utilizing large, well-characterized, prospective pregnancy cohorts that include biobanks, which have been established in various populations during the last few decades.     

Reproductive and developmental toxicity of formaldehyde: a systematic review

Formaldehyde, the recently classified carcinogen and ubiquitous environmental contaminant, has long been suspected of causing adverse reproductive and developmental effects, but previous reviews were inconclusive, due in part, to limitations in the design of many of the human population studies. In the current review, we systematically evaluated evidence of an association between formaldehyde exposure and adverse reproductive and developmental effects, in human populations and in vivo animal studies, in the peer-reviewed literature. The mostly retrospective human studies provided evidence of an association of maternal exposure with adverse reproductive and developmental effects. Further assessment of this association by meta-analysis revealed an increased risk of spontaneous abortion (1.76, 95% CI 1.20-2.59, p=0.002) and of all adverse pregnancy outcomes combined (1.54, 95% CI 1.27-1.88, p<0.001), in formaldehyde-exposed women, although differential recall, selection bias, or confounding cannot be ruled out. Evaluation of the animal studies including all routes of exposure, doses and dosing regimens studied, suggested positive associations between formaldehyde exposure and reproductive toxicity, mostly in males. Potential mechanisms underlying formaldehyde-induced reproductive and developmental toxicities, including chromosome and DNA damage (genotoxicity), oxidative stress, altered level and/or function of enzymes, hormones and proteins, apoptosis, toxicogenomic and epigenomic effects (such as DNA methylation), were identified. To clarify these associations, well-designed molecular epidemiologic studies, that include quantitative exposure assessment and diminish confounding factors, should examine both reproductive and developmental outcomes associated with exposure in males and females. Together with mechanistic and animal studies, this will allow us to better understand the systemic effect of formaldehyde exposure.     

急诊危重孕产妇5分钟紧急剖宫产的临床效果及新生儿不良结局的危险因素分析

摘要 目的：探讨急诊危重孕产妇5分钟紧急剖宫产的临床效果,并分析新生儿不良结局的危险因素。方法：回顾性分析2018年1月~2022年6月在河北省儿童医院妇产科收治的急诊危重孕产妇139例的临床资料。根据急诊剖宫产流程分为对照组（n=68,常规紧急剖宫产流程下进行手术）及观察组（n=71,5分钟紧急剖宫产）。观察两组孕产妇的手术情况、手术反应时间、孕产妇并发症、新生儿不良结局发生率。采用多因素Logistic回归模型分析新生儿不良结局的危险因素。结果：两组住院时间、术中出血量、术中输血情况组间对比,未见统计学差异（P>0.05）。与对照组相比,观察组进手术室至手术开始时间、决定手术至胎儿娩出的时间间隔（DDI）、决定手术至进手术室时间、手术开始至胎儿娩出时间均更短,新生儿不良结局发生率、并发症发生率更低（P<0.05）。根据新生儿不良结局将孕产妇分为不良组（n=38）、良好组（n=101）。单因素分析结果显示：新生儿不良结局与受教育程度、新生儿体重、孕周、剖宫产类型、DDI、妊娠合并症、采用辅助生殖技术有关（P<0.05）。多因素Logistic回归分析结果显示,受教育程度为小学及其以下、新生儿体重偏低、剖宫产类型为I类剖宫产、孕周偏短、DDI偏长均是新生儿不良结局的危险因素（P<0.05）。结论：急诊危重孕产妇5分钟紧急剖宫产可缩短各项手术反应时间,降低孕产妇并发症和新生儿不良结局发生率。此外,新生儿不良结局的发生与受教育程度、新生儿体重、剖宫产类型、孕周、DDI等因素有关。     

High risk maternal factors related to fetal wastage in rural Bangladesh

An analysis of the relationship between fetal mortality (early fetal death and stillbirth), pregnancy order, maternal age, and previous fetal deaths in a rural Bangladesh population characterized by high fertility and mortality and the virtual absence of obstetric and other medical care indicates that early fetal wastage and stillbirth are higher among pregnancy orders 1 and 6, or higher than among orders 2 and 3, with the increased risk particularly apparent among those pregnancies following 2 or more previous fetal deaths. The data consist of the 21,144 pregnancies that occurred to the women in Matlab, Bangladesh, 1966-1969. By a multiple regression technique allowing for pregnancy order and previous fetal deaths, adjustments were made for age of the mother, and after allowances were made for previous fetal deaths, adjustments were made for pregnancy order. Results show the fewest fetal deaths in 2nd and 3rd pregnancies, and most at the highest parities. 10% of all pregnancy terminations 1966-1969 were registered as fetal deaths. Women in the higher pregnancy orders who have not experienced previous fetal deaths or only 1 fetal death have only a slight increase in the risk of fetal death compared to women in pregnancy orders 2 and 3. It is concluded that the virtual absence of medical care facilities is responsible for the large numbers of fetal deaths due to complications of gestation, delivery, and environmental influences. It also results in a higher maternal mortality of women with pregnancy complications related to fetal deaths. This absence of obstetric care and the high maternal mortality in this population may allow only women without reproductive impairments to reach the higher pregnancy orders.     

下生殖道病原微生物感染对孕妇妊娠结局的影响

目的了解本地区孕妇孕中期下生殖道病原微生物感染与不良妊娠结局的关系。方法真菌、滴虫、各种细菌、厌氧菌、支原体采用体外培养和生化反应的方法进行培养和鉴定,加德纳菌采用化学反应的方法检测唾液酸酶,沙眼衣原体采用金标法检测其抗原。结果有病原微生物感染所造成的不良妊娠结局明显高于无感染者（P〈0．01、P〈0．05）,其中多种病原微生物感染所造成的危害大于单一病原微生物感染。结论孕妇孕中期病原微生物感染会增加不良妊娠结局的发生率。     

肠道菌群与妊娠期甲状腺疾病患者的常见不良妊娠结局

目前, 肠道菌群被认为是影响机体内环境的潜在因素, 一旦失调, 可能导致多系统的疾病。妊娠期妇女由于机体代谢及免疫状态的变化, 是罹患妊娠期甲状腺疾病的高危人群。而妊娠期甲状腺疾病可导致流产、早产和出生体质量过低等常见不良妊娠结局, 对产妇、新生儿及其家庭造成十分恶劣的影响。妊娠期妇女作为特殊群体, 其肠道菌群的研究备受关注, 但目前关于妊娠期甲状腺疾病的肠道菌群研究仍较少。为更好地指导临床以及寻求改善妊娠期甲状腺疾病患者常见不良妊娠结局, 本文对肠道菌群与妊娠期甲状腺疾病患者的常见不良妊娠结局的相关研究进行综述。

     

Behavioral perinatology: biobehavioral processes in human fetal development

Behavioral perinatology is as an interdisciplinary area of research that involves conceptualization of theoretical models and conduct of empirical studies of the dynamic time-, place-, and context-dependent interplay between biological and behavioral processes in fetal, neonatal, and infant life using an epigenetic framework of development. The biobehavioral processes of particular interest to our research group relate to the effects of maternal pre- and perinatal stress and maternal-placental-fetal stress physiology. We propose that behavioral perinatology research may have important implications for a better understanding of the processes that underlie or contribute to the risk of three sets of outcomes: prematurity, adverse neurodevelopment, and chronic degenerative diseases in adulthood. Based on our understanding of the ontogeny of human fetal development and the physiology of pregnancy and fetal development, we have articulated a neurobiological model of pre- and perinatal stress. Our model proposes that chronic maternal stress may exert a significant influence on fetal developmental outcomes. Maternal stress may act via one or more of three major physiological pathways: neuroendocrine, immune/inflammatory, and vascular. We further suggest that placental corticotropin-releasing hormone (CRH) may play a central role in coordinating the effects of endocrine, immune/inflammatory, and vascular processes on fetal developmental outcomes. Finally, we hypothesize that the effects of maternal stress are modulated by the nature, duration, and timing of occurrence of stress during gestation. In this paper, we elaborate on the conceptual and empirical basis for this model, highlight some relevant issues and questions, and make recommendations for future research in this area.