Objetivo: avaliar a associação dos níveis séricos de citocinas em gestantes assintomáticas no segundo trimestre e nascimentos pré-termo (NPT). Pacientes e métodos: Estudo caso-controle aninhado a uma coorte de conveniência prospectiva. Foram incluídas gestantes de feto único entre 20 e 25 semanas e 6 dias de idade gestacional de 2 cidades brasileiras, as quais foram submetidas a entrevista e coleta de amostras de sangue venoso e avaliadas por entrevista no momento do nascimento. Dos NPT, 197 foram consideradas como grupo de casos e o grupo controle foi selecionado por sorteio, totalizando 426 pacientes no grupo controle. Foram avaliadas 41 citocinas séricas e comparadas entre os grupos. Resultados: Na primeira análise, as citocinas GRO, PDGF-BB e sCD40L mostraram níveis séricos diminuídos no grupo dos partos pré-termo (PPT) (p<0,05). Analisando apenas os PPT espontâneos, as citocinas GRO, sCD40L e MCP-1 apresentaram níveis diminuídos no grupo de casos (p<0,05). As citocinas que apresentaram níveis séricos com valores discrepantes foram submetidas a uma transformação logarítmica para posterior comparação entre os grupos de casos e controles. No grupo de casos incluindo apenas PPT espontâneos, verificou-se níveis aumentados de IL-2 (p<0,05). Foi significativo entre os grupos caso e controle a incidência de tabagismo materno e histórico de parto pré-termo anterior, sendo então essas características consideradas como fatores de risco nas análises multivariadas das citocinas dosadas. Apenas GRO demonstrou diferença em suas concentrações séricas entre grupos caso e controle na análise multivariada. Conclusão: Níveis séricos menores de GRO no segundo trimestre estão associados a maior risco de prematuridade, podendo refletir uma deficiência na resposta inflamatória materna. / Objective: To evaluate the association between second trimester serum cytokine levels in asymptomatic pregnant women and preterm births (PTB). Patientes and methods: Cohort-nested case-control study including singleton pregnant women between 20 and 25 weeks and 6 days of gestation in two Brazilian cities. The patients were interviewed and collection of venous blood samples was performed. They were again interviewed at time of birth. Among PTB, 197 were considered as case group. The control group was selected among term births (426 patients). Fourty-one cytokines were compared between groups. Results: Cytokines GRO, PDGF-BB and sCD40L showed decreased serum levels in PTB group (p<0.05). When analyzing only spontaneous PTB, GRO, sCD40L and MCP-1 levels showed decreased levels in the case group (p <0.05). A logarithmic transformation was performed among cytokines with discrepant serum levels in an attempt of verifying the outliers influency, and it has shown increased levels of IL-2 in the group of spontaneous preterm delivery (p <0.05). In both analyzes, the incidence of maternal smoking and history of previous preterm delivery was significantly different between case and control groups. In multivariate analysis, only GRO demonstrated different serum levels between case and control groups. Conclusion: Lower second trimester serum levels of GRO in assymptomatic women are associated with increased number of preterm births. This finding may reflect a deficiency in maternal inflammatory response.

O parto pré-termo, definido como nascimento antes de 37 semanas de gestação, é causa importante de morbidade e mortalidade neonatais, além de possíveis sequelas a longo prazo. Este trabalho trata-se de uma coorte prospectiva cujo objetivo foi analisar quatro possíveis fatores etiológicos do parto pré-termo: estresse, depressão, violência e baixo suporte social, baseado nos dados do projeto temático original: \"Fatores etiológicos do nascimento pré-termo e consequências dos fatores perinatais na saúde da criança: coortes de nascimentos em duas cidades brasileiras\". Um total de 1400 gestantes da cidade de Ribeirão Preto foram entrevistadas durante o pré- natal e logo após o parto, obtendo-se informações sobre história obstétrica e sócioeconômica, grau de estresse, depressão, apoio social e violência doméstica; dados do parto e do recém nascido. Foram identificados 133 (9,7%) partos prematuros, dentre estes 95 (6,9%) partos prematuros espontâneos, excluindo-se partos induzidos e cesarianas eletivas. Foram realizadas análises simples entre os possíveis fatores e também análises ajustadas a diversos itens da história social e obstétrica de cada gestante. O estresse e a depressão foram os dois únicos itens que mostraram associação com o desfecho prematuridade. O estresse foi o único fator que manteve a associação nos modelos ajustados de análise. Verificou-se um risco relativo bruto de 1,82 (IC 1,2 - 2,7) e de 1,60 a 1,75, nos modelos ajustados. O apoio social e histórico de violência física, sexual ou psicológica não mostraram interferência estatisticamente significativa no desfecho. Os resultados são consistentes com dados da literatura atual e apontam a importância de se observar certos sinais e sintomas durante o pré-natal, assim como discutir novas estratégias de acolhimento e tratamento, consequentemente prevenindo o parto pré-termo. / Preterm birth, defined as birth before 37 weeks of gestation, is an important cause of neonatal morbidity and mortality, as well as possible long-term sequelae. This work is a prospective cohort whose objective was to analyze four possible etiological factors of preterm birth: stress, depression, violence and low social support, based on data from the original thematic project: \"Etiologic factors of preterm birth and consequences of perinatal factors on child health: birth cohorts in two Brazilian cities \". A total of 1400 pregnant women from the city of Ribeirão Preto were interviewed during prenatal care and after delivery, obtaining information on obstetric and social history, stress level, depression, social support, domestic violence, birth data and type of delivery. A total of 133 (9.7%) preterm births were identified, of which 95 (6.9%) were spontaneous preterm births, excluding induced births and elective cesareans. Straight analyzes were performed with the possible etiological factors and also adjusted analyzes with several items of the social and obstetric history of each woman. Stress and depression were the only two items that demonstrated association with prematurity. Stress was the only factor that maintained the association in the adjusted models of analysis. There was a crude relative risk of 1.82 (CI 1.2-2.7) and 1.60-1.75 in the fitted models. The social support and history of physical, sexual or psychological violence did not show statistically significant interference in the outcome.The results are consistent with data from the current literature and point out the importance of observing certain signs and symptoms during prenatal care, as well as discussing new strategies for the diagnosis and treatment, consequently preventing preterm delivery

Abstract Prematurity is the main cause of morbidity and mortality in infants. In 25–40% of the cases preterm birth is associated with intrauterine inflammation. Surfactant proteins (SPs) A, C, and D have roles in innate immunity. In the female reproductive tract and in amniotic fluid (AF), these proteins may modulate the inflammatory responses leading to preterm birth. The aim of the present study was to establish a mouse model of lipopolysaccharide (LPS)-induced preterm birth of live-born pups and to study the activation of the innate immune system. By using mice overexpressing either rat SP-A (rSP-A) or rSP-D the roles of SP-A and SP-D in inflammatory responses were investigated. In addition, the expression of SP-C in gestational tissues was analyzed. The association of SP-C single nucleotide polymorphism (Thr138Asn) with spontaneous preterm birth and preterm premature rupture of membranes (PPROM) was investigated in a homogenous northern Finnish population of mothers and infants. Wild-type (WT) mice were injected with a single dose of intraperitoneal LPS at 16 or 17 days of gestation (term 19–20 days) leading to preterm delivery of live-born fetuses. After LPS, cytokine levels increased rapidly in maternal serum and in the uterus. This maternal inflammatory response was followed by the modest inflammatory activation in fetal and feto-maternal compartments. In fetal lung the expression of SP-A and SP-D was downregulated. The overexpression of SP-A or SP-D was evident in gestational tissues of rSP-A or rSP-D mice, respectively. In addition, excess of these proteins was detected in AF. Overexpression of either rSP-A or rSP-D modulated the LPS-induced inflammatory response related to preterm birth. Most notably, the expression of IL-4 and IL-10 in uteri and IL-10 in fetal membranes was lower in overexpressing animals. SP-C was detected in mouse and human placentas, fetal membranes, and in uteri of pregnant mice. The fetal SP-C polymorphism strongly associated with the duration of PPROM. The present study provides new information about the molecular events in inflammation induced preterm birth, particularly about the roles of cytokines and SPs in this process. Understanding of the mechanisms involved in preterm parturition may provide means for prevention and management of preterm births in the future. / Tiivistelmä Ennenaikaisuus on suurin vastasyntyneiden terveyttä ja henkeä uhkaava vaara. Kohdunsisäiset tulehdusreaktiot ovat ennenaikaisten synnytysten yleisimpiä aiheuttajia. Surfaktanttiproteiinit (SP:t) A, C ja D osallistuvat synnynnäisen immuniteetin säätelyyn. Voidaan olettaa, että synnytyskanavassa ja lapsivedessä surfaktanttiproteiinit säätelevät ennenaikaiseen synnytykseen johtavia tulehdusreaktioita. Tutkimuksen tavoitteena oli luoda hiirimalli, jossa ennenaikainen synnytys saadaan aikaan lipopolysakkaridin (LPS:n) injektiolla vatsaonteloon. Hiirimallin avulla tutkittiin puolustusjärjestelmän aktivaatiota sekä äidin että sikiön kudoksissa. Rotan SP-A:ta (rSP-A:ta) tai rSP-D:tä yli-ilmentävien hiirten avulla selvitettiin, muuttavatko nämä proteiinit ennenaikaiseen syntymään johtavaa vastetta. Lisäksi määritettiin SP-C:n ilmentyminen hiiren ja ihmisen kohdussa, sikiökalvoilla ja istukassa. SP-C-geenin yhden emäksen polymorfian (Thr138Asn) liittymistä ennenaikaiseen synnytykseen tai sikiökalvojen puhkeamiseen tutkittiin homogeenisessä pohjoissuomalaisessa tutkimuspopulaatiossa. Villin tyypin hiirille raskauden 16. tai 17. päivänä annettu LPS-annos sai aikaan elävien poikasten ennenaikaisen syntymisen. Emon seerumissa havaittiin sytokiinipitoisuuksien nopea nousu LPS:n vaikutuksesta. Emon tulehdusvaste johti synnynnäisen immuniteetin aktivaatioon istukassa, sikiökalvoilla ja kohdussa, kun taas muutokset sikiön kudoksissa olivat pieniä. Sikiön keuhkoissa SP-A:n ja SP-D:n ilmentyminen väheni. SP-A:ta tai SP-D:tä yli-ilmentävillä hiirillä havaittiin lisääntynyt SP-A:n tai SP-D:n määrä kohdussa, sikiökalvoilla, istukassa ja lapsivedessä. SP-A:n tai SP-D:n yli-ilmentyminen muutti LPS:n aiheuttamaa tulehdusvastetta. Erityisesti IL-4:n ja IL-10:n ilmentyminen kohdussa ja IL-10:n ilmentyminen sikiökalvoilla vähenivät. SP-C:n ilmentyminen havaittiin hiiren ja ihmisen istukassa ja sikiökalvoilla sekä hiiren kohdussa raskauden aikana. Sikiön SP-C-geenin polymorfia liittyi sikiökalvojen ennenaikaisen puhkeamisen kestoon. Tutkimus antaa lisätietoa tulehduksen aiheuttaman ennenaikaisen synnytyksen mekanismista sekä sytokiinien ja SP-A:n SP-D:n osuudesta synnytystapahtumassa. Mekanismin ymmärtäminen on erittäin tärkeää, jotta ennenaikaiset synnytykset voitaisiin tulevaisuudessa ehkäistä tehokkaammin.

Preterm infants are exposed to high levels of modified early sensory experience in the Neonatal Intensive Care Unit (NICU). Reports that preterm infants show deficits in contingency detection and learning when compared to full-term infants (Gekoski, Fagen, & Pearlman, 1984; Haley, Weinberg, & Grunau, 2006) suggest that their exposure to atypical amounts or types of sensory stimulation might contribute to deficits in these critical skills. Experimental modifications of sensory experience are severely limited with human fetuses and preterm infants, and previous studies with precocial bird embryos that develop in ovo have proven useful to assess the effects of modified perinatal sensory experience on subsequent perceptual and cognitive development. In the current study, I assessed whether increasing amounts of prenatal auditory or visual stimulation can interfere with quail neonates’ contingency detection and contingency learning in the days following hatching. Results revealed that augmented prenatal visual stimulation prior to hatching does not disrupt the ability of bobwhite chicks to recognize and prefer information learned in a contingent fashion, whereas augmented prenatal auditory stimulation disrupted the ability of chicks to benefit from contingently presented information. These results suggest that specific types of augmented prenatal stimulation that embryos receive during late prenatal period can impair the ability to learn and remember contingently presented information. These results provide testable developmental hypotheses, with the goal of improving the developmental care and management of preterm neonates in the NICU setting.

L’objectif de cette thèse était d’étudier les associations potentielles entre les traitements antirétroviraux reçus par les femmes enceintes infectées par le VIH et les complications pouvant survenir au cours de la grossesse ou être diagnostiquées dans la période néonatale. Ce travail est issu en majeure partie des données de l’Enquête Périnatale Française (ANRS-EPF), cohorte nationale multicentrique ayant inclus plus de 20 000 couples mères-enfants depuis 1986. Actuellement, presque toutes les femmes sont traitées par combinaisons antirétrovirales puissantes (cART ; 98% en 2013) et le taux de transmission est inférieur à 1% : 0.6% (IC95% : 0.4%-0.8% pour la période 2005-2013). La première partie portait sur le risque d’accouchement prématuré dont le taux a augmenté significativement entre la période 1990-1993 et 2005-2009, passant de 9.2% à 14.3%. Le risque d’accouchement prématuré était significativement associé au traitement par cART, par rapport aux monothérapies et bithérapies d’INTI, et au traitement débuté avant la conception par rapport aux traitements débutés en cours de grossesse. La survenue d’une cytolyse hépatique était fréquente (17%), et était liée à la fois à la prématurité, et au type de traitement, plus fréquentes avec les IP qu’avec les inhibiteurs non nucléosidiques de la transcriptase inverse. La perturbation du bilan hépatique pourrait être un facteur intermédiaire dans la relation entre traitements et accouchement prématuré. La seconde partie portait sur les malformations congénitales. D’une part, elle a permis de mettre en évidence une association entre exposition à l’efavirenz au premier trimestre de grossesse et les malformations neurologiques, bien que concernant peu de cas (n=4) et n’atteignant la significativité que dans une analyse de sensibilité. Cette association incite à maintenir une vigilance chez les enfants exposés in utero à cette molécule classée tératogène par la FDA mais prescrite de plus en plus largement. D’autre part, l’exposition au premier trimestre à la zidovudine était associée à la survenue de malformations cardiaques. La troisième partie a complété cette étude par une analyse de la fonction cardiaque, des modifications infracliniques de la contractilité et de l’épaisseur des parois du ventricule gauche ont été mises en évidence chez les enfants exposés in utero à une combinaison de traitement contenant la zidovudine et la lamivudine. Ces résultats ne remettent pas en question l’efficacité majeure des traitements antirétroviraux pour la prévention de la transmission de la mère à l’enfant du VIH, mais incitent à la poursuite d’une surveillance épidémiologique des effets indésirables potentiels, de manière à optimiser les prescriptions pour un meilleur rapport bénéfice/risque. / Our objective was to study potential associations between antiretroviral treatment and obstetrical or neonatal complications in a population of HIV-positive pregnant women. Most of the analyses were conducted with data from the French Perinatal Cohort (ANRS-EPF), an ongoing multicenter national cohort with more than 20 000 mother-infant pairs included since 1986. In the recent years, most women receive combination antiretroviral therapies (cART ; 98% en 2013) and the trasnsmission rate is consistently under 1% : 0.6% (IC95% : 0.4%-0.8% for 2005-2013). Risk of preterm birth was significantly associated with cART, when compared to NRTI monotherapy or dual therapy, and with timing of treatment, higher for women treated at conception than for those initiating treatment during pregnancy. The occurrence of liver enzyme elevation was frequent (17%), and was associated both with preterm birth and with PI-based treatment, when compared to NNRTIs. LEE could be an intermediate factor between cART and preterm birth. The second part of this work was a study of congenital birth defect in the cohort, and showed an association between first trimester-exposure to efavirenz and neurological defects, but this concerned small numbers (n=4), and reached significance only in a sensitivity analysis. This association encourages us to maintain awareness concerning this molecule, considered teratogenic by the FDA but more and more largely prescribed. We also reported an association between first-trimester exposure to zidovudine and congenital heart defects. In a third part, we studied heart function, differences in contractility and septum thickness of the left ventricle was found, among girls exposed to a combination containing zidovudine and lamivudineThese results do not question the great progress of antiretroviral treatment in the prevention of mother-to-child transmission, but they encourage us to continue epidemiologic surveillance of potential side effects, in order to optimize prescriptions for an improved benefit/risk ratio.

Preterm birth affects 12% of infants in the United States annually and is the main contributor to infant deaths and long-term neurological disabilities in offspring. Obesity is a growing problem in the U.S., and is increasingly being considered a major risk factor for adverse health outcomes. Puerto Rican teenagers have disproportionately high rates of preterm birth and obesity when compared to non-Hispanic White teenagers. Studies evaluating risk factors for preterm birth among adolescents are sparse, have inconsistent findings, and were conducted among predominantly non-Hispanic populations. Therefore, we investigated the association between BMI and preterm birth among the 419 teenage (ages 16-19) participants in Proyecto Buena Salud, a prospective cohort study of predominantly Puerto Rican prenatal care patients in Massachusetts. Pre-pregnancy BMI was abstracted from medical records and defined using CDC adolescent BMI-for-age percentile categories. Preterm birth classifications were abstracted from the delivery record and confirmed by the study obstetrician. Seventy-six (18%) participants were overweight and 58 (14%) were obese. A total of 49 (11.7%) preterm births were observed, consisting of 36 (73%) spontaneous and 13 (27%) medically indicated. After adjusting for pregnancy complications, previous preterm birth, age, acculturation, and gestational weight gain, obese teens had a reduced odds of total preterm birth (OR: 0.12, 95% CI: 0.02, 0.61) and had a mean gestational age at delivery of 0.9 weeks higher (95% CI: 0.19, 1.56) as compared to normal weight teens. When evaluating preterm birth by subtype, overweight/obese teens had a reduced odds of spontaneous (OR: 0.36, 95% CI: 0.13, 1.02) and medically indicated (OR: 0.054, 95% CI: 0.004, 0.70) preterm birth compared to normal weight teens. This study adds to the body of literature on the impact of obesity on birth outcomes and extends this work to Hispanic teenagers.

Chronic inflammation is associated with the pathophysiology of obstetrical disorders (e.g. preterm birth [PTB]) and gynecological diseases (e.g. endometriosis); however, the exact mechanism(s) for these conditions are unknown. Numerous immunological conditions and disease states (e.g. inflammatory bowel disease, Crohn’s disease, systemic lupus erythematomus) also disrupt the microbiome homeostasis by inducing a number of changes in the microbial flora when compared to that of healthy individuals. Furthermore, the gastrointestinal (GI) microbiome is one of the principal regulators of circulating estrogens which are known to directly impact the female reproductive disorders endometriosis and PTB. Thus, an alteration of microbial species could indicate a shift in immune balance from homeostatic to pro-inflammatory, and an aberrant estrogen metabolism that precipitates the development of disease stages in endometriosis and/or PTB. The Braundmeier-Fleming lab has developed a systems biology model that investigates the interactions between the immune system, microbial dynamics (in the GI and reproductive system) and estrogen metabolism, in women, as a potential diagnostic tool for endometriosis and PTB. This dissertation, therefore, examined how inflammation triggered by female reproductive disorders (endometriosis or PTB) alter the systemic and localization immune responses, the microbial communities in the urogenital (UG), peritoneal and GI mucosal epithelium, as well as levels of excreted conjugated estrogen. The first specific hypothesis is that inflammation associated with endometriosis alters microbial dynamics and functions that are distinct from those of non-diseased patients. Preliminary data indicated that reproductive tract microbial communities from patients with endometriosis are unique when compared to non-disease patients. Therefore, the central aims of this study are to identify the immune and microbial profiles of patients diagnosed with endometriosis and determine if an alteration of these profiles impact estrogen signaling, thus driving disease pathogenesis. Additionally, I hypothesized that surgery or hormonal therapy will temporarily restore the microbiome and estrogen levels of patients with endometriosis. Differences in systemic (blood) regulatory T cell (Treg) and T-helper 17 (Th17) cell populations (tolerant and inflammatory, respectively) were measured by flow cytometry, and the immune mediators was measured by serum cytokine levels via 10-plex-ELISA kits. Immunohistochemistry was used to identify resident Th17/Treg immune cell distribution within the endometrium and ectopic endometriotic lesions, and RORγt+/FOXP3+ transcripts within these same tissues were analyzed by real-time-qPCR. We implemented high-throughput non genomic sequencing targeting bacterial-V4 16S rRNA and robust bioinformatics analyses to characterize microbial composition/diversity within the GI (fecal swab), vaginal (vaginal swab), and UG (urine) cavities. Alterations in estrogen metabolism, parent estrogens and metabolites, in urine were analyzed via LC-MS/MS. Patients with endometriosis exhibit 1) systemic and localized inflammation within ectopic and endometrial tissues, 2) altered GI/UG microbial dynamics, 3) aberrant levels of endogenous estrogen and estrogen metabolites, 4) dampened inflammation (caused by disease) due to hormonal therapy, 5) altered bacteria populations in the gut and vaginal canal of patients with endometriosis due to hormonal therapy treatment, and 6) increased post-surgical variability in microbial community dynamics. The second specific aims examined the hypothesis that induction of endometriosis in baboons (P. Anubis) results in chronic systemic and tissue specific inflammation through regulation of Th17 and Treg populations. Further, the induction of endometriosis altered GI/UG/peritoneal cavity microbial communities that are distinct from non-diseased animals. Utilizing a non-human primate animal model of induced endometriosis allowed us to characterize factors involved at the early onset of endometriosis and throughout the disease progression. We collected samples from 8 baboons at pre-inoculation (no evidence of disease) and at 3, 6, 9, and 15 months post-induction of the disease. We found that the induction of endometriosis decreased peripheral Tregs cells while Th17 cells increased at all post-induction collections with reduced ratio of total Tregs to Th17 cells indicating systemic inflammation. Microbial community diversities as well as abundances at each sample site (GI, UG [vagina, urine] tracts and peritoneal cavity) were also altered at post-induction. These results therefore suggest that induction of endometriosis in non-human primates caused an inflammatory shift. Disease induction also resulted in altered vaginal, urinary and fecal microbial profiles, which may drive inflammation through the production of inflammatory mediators. The last specific aims studied the hypothesis that patients who deliver preterm have a systemic and placental inflammatory phenotype and abnormal estrogen levels during pregnancy that are distinct from those of patients with term delivery. Biological samples were collected at 8-12 weeks, 20-24 weeks, 32-36 weeks, at delivery and 6 weeks postpartum. Subjects with PTB showed signs of systemic inflammation with an elevation in Th17:Treg ratio, greater Th17 and lower levels of natural Tregs during the 2nd trimester, and lower inducible Tregs during the 3rd trimester and at delivery. Placental tissues from subjects with PTB also had an inflammatory immune phenotype (higher Th17) within the decidua basalis and maternal-fetal interface. Immunological shifts from tolerant to inflammatory were observed in both patient groups, but these shifts occurred early in gestation for subjects with PTB and at a later gestational age for subjects delivering at term. Levels of conjugated parent estrogens and estrogen metabolites were reduced in subjects with PTB, indicative of an abnormal production of estrogen. These analyses gave us a better understanding of the inflammatory cascade with estrogen metabolism associated with pregnancy, and how these effects are correlated with premature labor. The data from this study suggest that the levels of endogenous estrogen and estrogen metabolites of estrogen metabolism were abnormal in PTB and endometriosis disease models of inflammation compared to their respective controls. In the human and non-human primate model of endometriosis studies, we observed that both patients and baboons with endometriosis had systemic and resident inflammatory phenotypes and an alteration in mucosal microbial community dynamics compared to their respective controls. All together, our long-term goal is to identify factors from the microbiome and/or the immune system that would allow us to have early non-invasive diagnostics for endometriosis or to predict which mothers are most at risk to encounter PTB. Furthermore, it would allow us to determine whether the mucosal microbiome may be a good indicator of immune stress, and if alternative therapies can alter microbial community dynamics—thereby eliminating immune stress associated with female reproductive diseases. These findings may have a substantial impact on the obstetrical care and management of patients with endometriosis and women at risk for PTB, as well as provide evidence to support the development of novel therapeutics to treat these diseases.

Since fetal alcohol syndrome was first reported, studies have demonstrated a range of perinatal/developmental abnormalities that fall under the umbrella term fetal alcohol spectrum disorders. Of these, low birth weight in exposed children is among the most commonly observed and widely accepted. However, in the past, assertion of an association between prenatal alcohol exposure and preterm birth was controversial. Methodological difficulties may have contributed to failure to consistently detect such a relationship. However, new evidence suggests that pregnancy drinking may be a major contributor to extreme, but not mild prematurity. Extreme prematurity is a major cause of severe perinatal morbidity and mortality. If recent findings are confirmed, it suggests that extreme prematurity might be reduced by eliminating prenatal alcohol exposure.

Infant mortality (IM) rates in the United States remains high. The higher rates of IM among specific groups in the United States is believed to be fueled by the high rates of adverse birth outcomes including low birthweight (LBW) and preterm births (PTB) among these groups. Adverse birth outcomes have also been linked to the presence of hypertensive disorders during pregnancy. The purpose of this cross-sectional study was to explore the association between hypertensive disorders during pregnancy and adverse birth outcomes and the impact of the residential neighborhood of expectant mothers on this association. The life course health development theory guided the framework for this study. Study data were obtained from the 2010 New York City birth records and the 2010 US Census. Descriptive statistics and logistic regression analysis were used to address the 3 research hypotheses of the study. The study found that prepregnancy hypertension (HTN) (AOR: 2.84 & 3.25), gestational HTN (AOR: 2.28 & 3.33) and eclampsia (AOR: 4.41 & 6.70) were significantly associated with PTB and LBW respectively. Neighborhood segregation was not significant for PTB (AOR: 1.01) or LBW (AOR: 1.03). Neighborhood poverty was significant for PTB (AOR: 0.86) but not for LBW (AOR: 1.05). Neighborhood segregation and poverty had significant moderating effects on the prepregnancy HTN (p = 0.00), gestational HTN (p = 0.00), eclampsia (p = 0.00) and PTB and LBW association. Results from this study can help to address disparities in birth outcomes among women of differing races and ethnicities and thereby contribute to positive social change.

Foreign-born Black women giving birth in the United States have superior preterm birth outcomes compared to their U.S-born Black peers. Many studies have focused on tobacco use and medical risk factors, but few have focused solely on preconception health. The purpose of this study was to examine preconception health and preterm birth differences among U.S.-born and foreign-born Black women. Three theoretical frameworks guided this study: the life course theory, healthy migrant theory/immigrant paradox, and weathering theory. Primary research questions assessed (a) if there were an association between chronic preconception risk factors, prepregnancy obesity, diabetes, and hypertension, in U.S.-born and foreign-born Black women, (b) if U.S.-born Black women had a higher risk of having a preterm infant compared to foreign-born Black women, and (c) if weathering existed in U.S.-born and foreign-born Black women. A quantitative design using the 2017 Natality Public Use File was employed that included non-Hispanic Black women ages 15 to 44 years. Chi-square test and binary logistic regression were used for the data analysis. Key findings revealed (a) a statistically significant association between preterm birth and chronic preconception health risk factors in both groups of women, (b) U.S.-born women were roughly 1.4 times more likely to have a preterm infant than foreign-born women, and (c) both groups experienced weathering. This study might positively impact social change by offering an alternative perspective to the reproductive health advantage of foreign-born Black women. This perspective can aid in advancing policy and systems change strategies to address the root causes of racial and ethnic disparities in birth outcomes, advance health equity, and improve maternal health.