Spectrum Of Adverse Pregnancy Outcomes Research Articles

Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome.

Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these three chronic inflammatory placental syndromes.

Zika Virus and the Risk of Developing Microcephaly in Infants: A Systematic Review.

The global epidemic of Zika virus has been a major public health problem affecting pregnant women and their infants. Zika virus causes a viral disease transmitted to humans mainly by the infected Aedes mosquito bite. The infection is not severe in most cases; however, there is evidence that infection during pregnancy may be associated with fetal genetic abnormalities (including microcephaly). In addition to microcephaly and other malformations, some specific lesions in the central nervous system have been reported. The aim of this systematic review was to determine the risk of developing microcephaly in infants whose mothers were infected with Zika virus in pregnancy. Epidemiological studies and case reports were incorporated in our review, finally including 15 articles from an initial pool of 355 related papers. Most studies have linked maternal infection during pregnancy to the development of neonatal microcephaly. The period considered most dangerous is the first trimester and the beginning or the whole of the second trimester. In order to understand the relationship between Zika virus and microcephaly in infants, a cohort study will be able to estimate the time from the onset of Zika infection and the full spectrum of adverse pregnancy outcomes.

The Spectrum of Adverse Pregnancy Outcomes Based on Kidney Disease Diagnoses: A 20-Year Population Study

Background and Objectives: Kidney disorders in pregnancy may be under-recognized and have variable impact on outcomes depending on diagnosis. Population-level data are limited, particularly for Australia, and comparison of impact of different kidney disorders on pregnancy has rarely been assessed. This study examined the prevalence and outcomes of varied kidney disorders using population-level perinatal data from a large cohort. Methods: Women with singleton pregnancies > 20 weeks’ gestation from the South Australian Pregnancy Outcomes Unit (1990–2012). Women with a kidney disorders diagnostic code were grouped into categories (immunological, cystic/genetic, urological, vesicoureteral reflux (VUR), pyelonephritis and “other”). Key pregnancy outcomes were assessed, with adjustment for demographic variables. Results: Kidney disorders were reported in 1,392 (0.3%) of 407,580 births. These pregnancies had increased risk of pregnancy-induced hypertension (OR 2.16, 95% CI 1.82–2.56), induction of labor (RRR vs. spontaneous birth 2.10, 95% CI 1.87–2.36), all Caesarean section (OR 1.31, 95% CI 1.17–1.47) as well as Caesarean section without labor (RRR 1.82, 95% CI 1.57–2.10), preterm birth (< 37 weeks; 2.76, 95% CI 2.40–3.18), low birth weight (< 2,500 g) infants (OR 2.43, 95% CI 2.07–2.84), and neonatal intensive care admission (OR 2.64, 95% CI 2.12–3.29). Diagnostic subgroups demonstrated differing patterns of adverse outcomes, enabling the development of a matrix of risk. Women with immunological renal conditions and VUR had greatest risk overall, and only women with immunological diseases had increased risk of small-for-gestational age < 10th centile (OR 2.36, 95% CI 1.26–4.42). Women with nonchronic urological conditions and pyelonephritis had increased risk of preterm birth, but not other adverse events. VUR conferred particularly increased risk of Caesarean section and induced labor. Conclusions: In a cohort of > 1,300 women with varied kidney disorders, increased adverse obstetric and perinatal events were observed, and the nature and magnitude of risk differed according to diagnosis. In particular, vesicoureteric reflux is not a benign condition in pregnancy. Women with nonchronic conditions still had increased risk of preterm birth. We confirm that women with kidney disorders warrant vigilant and tailored prepregnancy care and clinical care in pregnancy.

Omega-3 fatty acids suppress Fusobacterium nucleatum-induced placental inflammation originating from maternal endothelial cells.

Fusobacterium nucleatum is an oral anaerobe prevalent in intrauterine infection associated with a wide spectrum of adverse pregnancy outcomes. We demonstrate here that F. nucleatum triggers placental inflammation through maternal, rather than paternal, TLR4-mediated signaling. Elimination of TLR4 from maternal endothelial cells alleviated placental inflammation and reduced fetal and neonatal death, while elimination of TLR4 in the hematopoietic cells had no effect. The placental inflammatory response followed a spatiotemporal pattern, with NF-κB activation observed first in the maternal endothelial cells and then in the decidual cells surrounding the endothelium, followed by induction of inflammatory cytokines and chemokines. Supplementation of pregnant mice with fish oil as a source of omega-3 fatty acids suppressed placental inflammation, reduced F. nucleatum proliferation in the placenta, and increased fetal and neonatal survival. In vitro analysis illustrates that omega-3 fatty acids inhibit bacterial-induced inflammatory responses from human umbilical cord endothelial cells. Our study therefore reveals a mechanism by which microbial infections affect pregnancy and identifies a prophylactic therapy to protect against intrauterine infections.

The chasm between public health and reproductive research: what history tells us about Zika virus.

Zika transmission from mother to fetus and its possible sexual transmission have become a media focus in the past months as a major public health concern. While mother-to-fetus transmission, fetal neurologic manifestations or sexual transmission have never been documented for this virus before, other viruses that belong to the same family are very well known to reproductive health workers, clinicians, and researchers. As a member of Flaviviridae family, including hepatitis C and bovine viral diarrhea virus (BVDV), Zika's pathogenesis may have some parallels with these infections which may pose future questions for public health and research. Vertical transmission of hepatitis C virus from mother to child is known to occur in up to 10% of pregnancies. BVDV, a member of Pestivirus genus of Flaviviridae family is not known to be transmitted to humans but is known for its vertical transmission in cattle. BVDV infection at different stages of gestation may lead to a spectrum of adverse pregnancy outcomes, including pregnancy loss and neurologic manifestations (including deformations such as hydrocephalus and microcephaly) in the offspring. Similar to hepatitis C, which is a virus of Hepacivirus genus, BVDV is capable of persistent infection, meaning that virus may stay in mother and future generations of calves may be infected as well, which may, in turn, result in persistence of infection in offspring. Would this be a case with Zika virus? Along with mother-to-fetus transmission, sexual transmission is a concerning implication for Zika virus. Would woman become a persistent career or male be able to persistently carry virus with its sperm is yet unknown; yet, there is a concern for the reservoir of infection. Animal models of the disease are urgently needed not only to demonstrate the mother-to-fetus transmission and confirm the fetal neurologic manifestations but also to address the effects of virus on life-long host's immunity and reproductive health. Along those lines, women desiring pregnancies who are identified to travel, have a partner traveling to, or living in the areas of Zika infections should be encouraged to have a preconception consultation with maternal-fetal medicine.

Effect of obesity on the length of the first and second stages of labor

Objective This study was designed to evaluate the length of the first and second stages of labor in nulliparous obese Egyptian women and compare them with those in women with normal BMI. Background Maternal obesity is now the most common risk factor for maternal mortality in developed countries and is also associated with a wide spectrum of adverse pregnancy outcomes. The duration of first stage of labor, the rate of cesarean delivery, and inadequate progress of cervical dilatation during labor were found to be higher in women with BMI more than 30 compared with women of average weight. Participants and methods Nulliparous women of more than 37 gestational weeks who were in labor were included in this study. First-visit BMI was used to categorize weight as normal (≤24) or obese (≥30). Over 12 months (study period), we observed 603 deliveries; 239 were nulliparous and 211 were term singleton. Eighty women met the inclusion criteria: 40 women with normal BMI constituting the control group and 40 obese women who constituted the study group. Results The duration of first stage of labor was significantly longer in obese women compared with normal weight women (19.76 ± 0.77 vs. 16.87 ± 0.66 h; P < 0.001), whereas the duration of the second stage of labor showed no significant difference between obese and normal weight women (61.0 ± 34.8 vs. 60.9 ± 34.3 min; P = 0.990). When adjusted for age, hypertension, and induction, the likelihood of completing stages I and II was significantly lower among obese nulliparous than among those with BMI 24 or less. Conclusion About half of nulliparous women in our population are obese and the duration of stage I is significantly longer among them, whereas the second stage of labor may be independent of maternal BMI. The second stage in the nulliparous parturient woman does not appear to be longer or more likely to end in cesarean delivery on the basis of prepregnancy BMI

The Shared Pathoetiological Effects of Particulate Air Pollution and the Social Environment on Fetal-Placental Development

Exposure to particulate air pollution and socioeconomic risk factors are shown to be independently associated with adverse pregnancy outcomes; however, their confounding relationship is an epidemiological challenge that requires understanding of their shared etiologic pathways affecting fetal-placental development. The purpose of this paper is to explore the etiological mechanisms associated with exposure to particulate air pollution in contributing to adverse pregnancy outcomes and how these mechanisms intersect with those related to socioeconomic status. Here we review the role of oxidative stress, inflammation and endocrine modification in the pathoetiology of deficient deep placentation and detail how the physical and social environments can act alone and collectively to mediate the established pathology linked to a spectrum of adverse pregnancy outcomes. We review the experimental and epidemiological literature showing that diet/nutrition, smoking, and psychosocial stress share similar pathways with that of particulate air pollution exposure to potentially exasperate the negative effects of either insult alone. Therefore, socially patterned risk factors often treated as nuisance parameters should be explored as potential effect modifiers that may operate at multiple levels of social geography. The degree to which deleterious exposures can be ameliorated or exacerbated via community-level social and environmental characteristics needs further exploration.

Maternal Birthweight Is Associated with Subsequent Risk of Vitamin D Deficiency in Early Pregnancy

Maternal low birthweight and vitamin D deficiency in pregnancy are associated with a similar spectrum of adverse pregnancy outcomes including pre-eclampsia and gestational diabetes. However, the relationship between maternal birthweight and subsequent vitamin D concentrations in early pregnancy is largely unknown. We assessed whether self-reported maternal birthweight was associated with risk of early pregnancy vitamin D deficiency (≤20 ng/mL) among a pregnancy cohort (n = 658). Serum 25-hydroxyvitamin D [25(OH)D] was measured using liquid chromatography-tandem mass spectroscopy. Adjusting for maternal characteristics and month of blood draw, a 100-g higher maternal birthweight was associated with a 5.7% decreased risk of early pregnancy 25(OH)D deficiency [odds ratio (OR) = 0.94; 95% confidence interval (CI) 0.90, 0.99]. Low-birthweight (<2500 g) women were 3.7 times as likely to have early pregnancy 25(OH)D deficiency compared with normal-birthweight women [OR = 3.69; 95% CI 1.63, 8.34]. These relationships were not modified by either pre-pregnancy overweight status [body mass index (BMI) ≥25 kg/m(2)] or adulthood weight trajectory (BMI change ≥2 kg/m(2) from age 18 to pre-pregnancy). Further research on shared developmental mechanisms that determine birthweight and vitamin D homeostasis may help identify targets and related preventative measures for adverse pregnancy and birth outcomes.

Obesity in pregnancy: outcomes and economics

Maternal obesity is an important aspect of reproductive care. It is the commonest risk factor for maternal mortality in developed countries and is also associated with a wide spectrum of adverse pregnancy outcomes. Maternal obesity may have longer-term implications for the health of the mother and infant, which in turn will have economic implications. Efforts to prevent, manage and treat obesity in pregnancy will be costly, but may pay dividends from reduced future economic costs, and subsequent improvements to maternal and infant health. Decision-makers working in this area of health services should understand whether the problem can be reduced, at what cost; and then, what cost savings and health benefits will accrue in the future from a reduction of the problem.

Maternal and perinatal outcome in obese pregnant patients

Introduction. Obesity represents a rapidly emerging epidemic amongst pregnant patients in South Australia, in particular in Adelaide's Northern suburbs, one of the poorest urban areas in Australia. The aim of the current study was to prepare a comprehensive overview of maternal and perinatal outcome in overweight, obese and morbidly obese pregnant patients.Material and methods. Retrospective review of women with singleton pregnancies delivering in the first 6 months of 2006; 100 with normal BMI (group I: BMI 19.1–25 kg/m2), 100 overweight (group II: BMI 25.1–30 kg/m2), 110 obese (group III: BMI 30.1–40 kg/m2) and 60 morbidly obese women (group IV: BMI >40 kg/m2) were identified with access to complete medical records. Outcome measures included booking demographics, booking blood pressures, glucose challenge and glucose tolerance results, hypertensive complications, pre-existing and gestational diabetes, instrumental deliveries, caesarean deliveries, blood loss, birth weights, Apgar scores, post-partum complications and psychological problems.Results. Women in group II, III and IV were characterised by higher systolic booking blood pressure (mean differences: 3.92, 9.94 and 9.84 respectively for group II, III and IV) and higher diastolic booking blood pressures (mean differences 3.02, 6.92 and 9.22 respectively). As a combined group II–IV, women were at increased risk for pre-existing morbidity (OR 2.33) and requiring medication (OR 2.13). Pregnancy hypertension occurred significantly more in group III and IV with OR 2.38 and 3.75. Women without pre-existing hypertension were also found to be at increased risk to develop gestational hypertension only if they belonged to group IV (OR 3.69). Women in group III and IV are at increased risk at gestational diabetes with OR 8.82 and 27.38. Women in group III and IV are less likely to have a spontaneous onset of labour with ORs of 2.18 and 3.51 for not having spontaneous onset of labour. Induction of labour occurred more often in group IV (OR 3.17). Requirement of instrumental deliveries or lower segment caesarean section occurred more often in group II, III and IV with OR 2.20, 3.28 and 5.47 respectively. Significant more blood loss was found in group III and IV with mean differences of 135.42 and 207.94 ml compared with group I. The birthweight in group III and IV are significantly higher with mean differences of 104.86 and 324.94 g. Macrosomia occurred more often in group IV (OR 4.04). Women in group III and IV had a longer overall hospital stay with mean differences of 0.58 and 1.09 days. Mental health issues were more common in group II, III and IV with OR 3.16, 3.53 and 4.17 respectively.Conclusion. These South Australian data from a socio-economically deprived area in Adelaide's Northern suburbs confirm that obesity during pregnancy represents a major risk for adverse outcome for patients with a whole spectrum of adverse pregnancy outcomes; obesity represents a major challenge for health care providers.

Review on genetic variants and maternal smoking in the etiology of oral clefts and other birth defects.

A spectrum of adverse pregnancy outcomes, including preterm birth, low birth weight, and birth defects has been linked with maternal smoking during pregnancy. This article includes a review of studies investigating interactions between genetic variants and maternal smoking in contributing to birth defects using oral clefting as a model birth defect. The primary gene-smoking studies for other major birth defects are also summarized. Gene-environment interaction studies for birth defects are still at an early stage with several mixed results, but evolving research findings have begun to document clinically and developmentally important interactions. As samples and data become increasingly available, more effort is needed in designing innovative analytical methods to study gene-environment interactions.

The Role of Macrophages in Utero-placental Interactions During Normal and Pathological Pregnancy

The intimate association between maternal and placental tissues elicits an interesting immunological paradox. Placental tissue contains paternal antigens, but under normal circumstances the semi-allogeneic fetus and placenta are not attacked by the maternal immune system. Interestingly, this tolerance to fetal antigens occurs in the presence of a large number of maternal leukocytes, almost all of which are members of the innate immune system. Macrophages are one of the most abundant leukocytes in the decidua and their numbers remain constant throughout gestation. They are recruited to the decidua by both stromal cells and trophoblast cells, where they adopt a specialized phenotype that may assist in various aspects of decidual homeostasis, placental development, and tolerance to the semi-allogeneic trophoblast. Aberrant behavior of these macrophages can affect trophoblast function and placental development, potentially leading to a spectrum of adverse pregnancy outcomes ranging from pre-eclampsia to fetal growth restriction or demise. This review will focus on the phenotype and putative functions of decidual macrophages in normal pregnancy, and how abnormal activation of these cells can affect various aspects of placental development.

Postmarketing surveillance for human teratogenicity: a model approach.

Most congenital defects associated with prenatal exposures are notable for a pattern of major and minor malformations, rather than for a single major malformation. Thus, traditional epidemiological methods are not universally effective in identifying new teratogens. The purpose of this report is to outline a complementary approach that can be used in addition to other more established methods to provide the most comprehensive evaluation of prenatal exposures with respect to teratogenicity. We describe a multicenter prospective cohort study design involving dysmorphological assessment of liveborn infants. This design uses the Organization of Teratology Information Services, a North American network of information providers who also collaborate for research purposes. Procedures for subject selection, methods for data collection, standard criteria for outcome classification, and the approach to analysis are detailed. The focused cohort study design allows for evaluation of a spectrum of adverse pregnancy outcomes ranging from spontaneous abortion to functional deficit. While sample sizes are typically inadequate to identify increased risks for single major malformations, the use of dysmorphological examinations to classify structural anomalies provides the unique advantage of screening for a pattern of malformation among exposed infants. As the known human teratogens are generally associated with patterns of structural defects, it is only when studies of this type are used in combination with more traditional methods that we can achieve an acceptable level of confidence regarding the risk or safety of specific exposures during pregnancy.