ResearchPad - preterm-birth https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Associations of dog and cat ownership with wheezing and asthma in children: Pilot study of the Japan Environment and children's study]]> https://www.researchpad.co/article/elastic_article_14570 No previous study has used repeated measures data to examine the associations of dog/cat ownership with wheezing and asthma prevalence among children. This prospective study used repeated measurers analysis to determine whether dog/cat ownership in childhood is an independent risk factor for wheezing and asthma, after adjustment for gestational, socio-economical, and demographical confounders confounders, in Japan.MethodsWe conducted a multicenter pilot study of the Japan Environment and Children's Study (JECS) during 2009–2010. Among 440 newborn infants enrolled, 410 (52.8% males) were evaluated for dog/cat ownership in the home and history of wheezing and asthma in five follow-up questionnaire surveys (until age 6 years). Dog/cat ownership during follow-up period was categorized into four groups: 7.6% were long-term dog/cat owners, 5.9% were toddler-age owners, 5.9% were preschool-age owners, and 80.7% were never owners.ResultsThe prevalence of wheezing during follow-up period increased from 20.8% to 35.4% and the prevalence of asthma increased from 1.3% to 16.3%. A fitted logistic generalized estimating equation models including important confounders showed no significant associations of the interaction between dog and/or cat ownership and follow-up time with the risks of wheezing and asthma. However, the risks of wheezing and asthma were slightly lower for long-term and toddler-age dog/cat owners than for preschool-age and never owners.ConclusionsThe present findings suggest that dog and cat ownership from toddler-age does not increase the risks of wheezing and asthma compared with never owners among Japanese children. ]]> <![CDATA[Dynamics of leukocyte telomere length in pregnant women living with HIV, and HIV-negative pregnant women: A longitudinal observational study]]> https://www.researchpad.co/article/5c897779d5eed0c4847d2db4

Background

HIV-mediated inflammation and immune activation can accelerate telomere attrition. In addition, antiretrovirals can inhibit telomerase, possibly shortening telomeres. We examined the longitudinal dynamics of leukocyte telomere length (LTL) during pregnancy in a unique cohort of women living with HIV (WLWH) treated with combination antiretroviral therapy (cART), and HIV-negative control women.

Methods

Blood was collected at three visits during pregnancy, at 13–23, >23–30, and >30–40 weeks of gestation, and for WLWH only, at 6 weeks post-partum. LTL was measured by qPCR and both cross-sectional and longitudinal (MANOVA) models were used to examine possible predictors of LTL among participants who attended all three visits during pregnancy.

Results

Among WLWH (n = 64) and HIV-negative women (n = 41), within participant LTL were correlated throughout pregnancy (p<0.001). LTL was shorter among WLWH at first visit, but this difference waned by the second visit. WLWH who discontinued cART post-partum experienced a decrease in LTL. Longitudinally, LTL was similar in both groups and increased as gestation progressed, a change that was more pronounced among women under 35 years. Among WLWH, both smoking throughout pregnancy (p = 0.04) and receiving a ritonavir-boosted protease inhibitor-based regimen (p = 0.03) were independently associated with shorter LTL.

Conclusions

LTL increases as pregnancy progresses; the reasons for this are unknown but may relate to changes in blood volume, hormones, and/or cell subset distribution. While our observations need confirmation in an independent cohort, our data suggest that although some cART regimens may influence LTL, being on cART appears overall protective and that stopping cART post-partum may negatively impact LTL. The effect of smoking on LTL is clearly negative, stressing the importance of smoking cessation.

]]>
<![CDATA[Impact of different stages of intrauterine inflammation on outcome of preterm neonates: Gestational age-dependent and -independent effect]]> https://www.researchpad.co/article/5c6730e6d5eed0c484f382c7

Objective

To investigate the impact of different stages of intrauterine inflammation (IUI) on neonatal outcomes, before and after adjusting for gestational age (GA) and other perinatal confounders.

Methods

This was an observational, prospective, single-center cohort study including all eligible neonates with GA < 35 weeks and/or birth weight ≤ 1500 g born at a 3rd level Neonatal Intensive Care Unit between 2011 and 2014. Pathological patterns of placenta, membranes and cord were classified according to Redline’s criteria. Multivariable linear and logistic regression models were applied, either including or not GA among the covariates.

Results

Of the 807 enrolled neonates, 134 (16.6%) had signs of IUI: among these, 54.5% showed just histological chorioamnionitis (HCA), 25.4% had HCA + funisitis (FUN) stage 1, and 20.1% had HCA + FUN stage 2–3. At univariate analysis, HCA increased the risk for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia, while FUN (any stage) had a deleterious impact on all outcomes investigated. After adjustment for covariates not including GA, HCA was a risk factor only for ROP (OR = 2.8, CI: 1–7.8), while FUN (any stage) was still associated with increased ORs for all outcomes (p <0.01). Upon inclusion of GA in the regression model, the results differed remarkably. HCA was associated with lower risk for mechanical ventilation (OR = 0.3, CI: 0.1–0.7) and need for surfactant (OR = 0.5, CI: 0.2–0.9), while FUN (any stage) worsened clinical conditions at birth (p <0.05), increased the risk for early-onset sepsis (p <0.01), and increased the length of mechanical ventilation (FUN stage 2–3 only, RC = 6.5 days, CI: 2–11). No other outcome was affected.

Conclusions

IUI, especially FUN, negatively impact most neonatal morbidities, but its effect is partially reverted adjusting for GA. Considered that GA is an intermediate variable interposed between prenatal causes of prematurity and outcomes, the appropriateness of adjusting for GA may be questionable.

]]>
<![CDATA[Longitudinal growth and emotional and behavioral problems at age 7 in moderate and late preterms]]> https://www.researchpad.co/article/5c5ca2cad5eed0c48441eb0c

Objectives

Moderately and late preterm children (MLPs, 32.0–36.9 weeks gestational age) have a greater risk of poorer growth. This seems to be associated with poorer neuropsychological functioning. Evidence is limited on whether this also holds for emotional and behavioral (EB) problems. Therefore, we assessed whether longitudinal growth from birth until age 7 was associated with EB problems at age 7 in MLPs.

Study design

This study was part of the Longitudinal Preterm Outcome Project, a prospective cohort study. Data on growth (height, weight, head circumference, and extent of catch-up growth) were obtained from assessments from birth until age 7. EB problems were assessed at age 7 with the Child Behavior Checklist. We assessed whether growth and EB problems were associated using logistic regression analyses, adjusting for multiple birth, parity, and socioeconomic status.

Results

We included 248 MLPs. Median gestational age was 34 weeks (interquartile range: 33–35 weeks). Mean birth weight was 2.2 kg (standard deviation: 0.5 kg). Postnatal growth measures were below the Dutch reference norm. EB problems were more prevalent in MLPs than in the general Dutch population. Generally, we found no associations between growth and EB problems; odds ratios ranged from 0.20 to 2.72.

Conclusions

In MLPs, postnatal growth from birth until age 7 was not associated with EB problems at age 7. Poorer growth thus seems to relate to neuropsychological problems, but not to EB problems. This suggests that the etiologies of these problems differ at least partially.

]]>
<![CDATA[Genome-wide maps of distal gene regulatory enhancers active in the human placenta]]> https://www.researchpad.co/article/5c2e7fefd5eed0c48451c4e4

Placental dysfunction is implicated in many pregnancy complications, including preeclampsia and preterm birth (PTB). While both these syndromes are influenced by environmental risk factors, they also have a substantial genetic component that is not well understood. Precisely controlled gene expression during development is crucial to proper placental function and often mediated through gene regulatory enhancers. However, we lack accurate maps of placental enhancer activity due to the challenges of assaying the placenta and the difficulty of comprehensively identifying enhancers. To address the gap in our knowledge of gene regulatory elements in the placenta, we used a two-step machine learning pipeline to synthesize existing functional genomics studies, transcription factor (TF) binding patterns, and evolutionary information to predict placental enhancers. The trained classifiers accurately distinguish enhancers from the genomic background and placental enhancers from enhancers active in other tissues. Genomic features collected from tissues and cell lines involved in pregnancy are the most predictive of placental regulatory activity. Applying the classifiers genome-wide enabled us to create a map of 33,010 predicted placental enhancers, including 4,562 high-confidence enhancer predictions. The genome-wide placental enhancers are significantly enriched nearby genes associated with placental development and birth disorders and for SNPs associated with gestational age. These genome-wide predicted placental enhancers provide candidate regions for further testing in vitro, will assist in guiding future studies of genetic associations with pregnancy phenotypes, and aid interpretation of potential mechanisms of action for variants found through genetic studies.

]]>
<![CDATA[Cancer risk in children and young adults born preterm: A systematic review and meta-analysis]]> https://www.researchpad.co/article/5c390bcdd5eed0c48491e6b3

Introduction

Risk of developing a malignancy when born premature is unknown. We hypothesised that risk of certain cancers might be increased in youth born preterm versus term. We therefore performed a systematic review and meta-analysis to evaluate the incidence of malignancy in the context of preterm birth, according to various cancer types.

Methods

The study was designed per MOOSE and PRISMA guidelines. Articles were identified through November 2015. Observational studies exploring the association between childhood malignancy and birth characteristics were included. Of the 1658 records identified, 109 full text articles were evaluated for eligibility. Random effects meta-analyses were conducted on 10/26 studies retained; 95% confidence intervals were computed and adjusted following sensitivity analysis. Publication bias was evaluated using funnel plots, Begg’s and Egger’s tests.

Results

No differences in risk of primary central nervous system tumor [OR 1.05; 95% CI 0.93–1.17, 5 studies, 580 cases] and neuroblastoma [OR 1.09; 95% CI 0.90–1.32, 5 studies, 211 cases] were observed in individuals born <37 versus ≥37 weeks’ gestation. Preterm birth was consistently associated with hepatoblastoma [ORs 3.12 (95% CI 2.32–4.20), 1.52 (95% CI 1.1–2.1), 1.82 (95% CI 1.01–3.26), and 2.65 (95% CI 1.98–3.55)], but not leukemia, astrocytoma, ependymoma, medulloblastoma, lymphoma, nephroblastoma, rhabdomyosarcoma, retinoblastoma or thyroid cancer.

Conclusions

Children born premature may be at increased risk for hepatoblastoma but there is no strong evidence of an increased risk of primary central nervous system tumours or neuroblastoma. There is insufficient evidence to conclude whether prematurity modulates the risk of other childhood cancers.

]]>
<![CDATA[Poverty and a child’s height development during early childhood: A double disadvantage? A study of the 2006–2009 birth cohorts in Flanders]]> https://www.researchpad.co/article/5c3667e1d5eed0c4841a679d

Introduction

Poverty is a well-known risk factor for a child’s health and development. This paper aimed to establish whether poverty negatively affected both intra-uterine growth and early childhood growth, i.e., whether children facing poverty were at a double disadvantage.

Methods

For this study, we made use of routinely collected data on child development throughout early childhood from the 2006–2009 birth cohorts in Kind & Gezin’s Ikaros database collected during 2,605,975 consultations with 273,935 children from birth to 730 days old. Indicators for child development at birth were gestational age and height-at-birth. A standardized height-for-age indicator captured height development throughout early childhood. A multidimensional indicator measured the risk of poverty. For the analysis of development at birth, we used linear and logistic regression; for the analysis of height development during early childhood, we estimated linear and logistic growth curve models.

Results

The risk of poverty negatively affected both gestational age and height-at-birth. Throughout early childhood, we observed a negative relation between the risk of poverty and height-for-age indicators. However, the effect varied throughout childhood. Children at risk of poverty (over)compensated for their smaller stature at birth, and between ages 6 and 18 months, approximately, the negative effects of risk of poverty decreased substantially or disappeared. However, towards the end of the period studied, children born in households at risk of poverty started to lag again in height development.

Conclusion

This study found that the risk of poverty indeed negatively affected a child’s growth, both in utero and in early childhood. However, the results suggest that developmental lags later in childhood were not merely an extension of such lags at birth.

]]>
<![CDATA[Maternal dyslipidemia and risk for preterm birth]]> https://www.researchpad.co/article/5c269774d5eed0c48470f93b

Maternal lipid profiles during pregnancy are associated with risk for preterm birth. This study investigates the association between maternal dyslipidemia and subsequent preterm birth among pregnant women in the state of California. Births were identified from California birth certificate and hospital discharge records from 2007–2012 (N = 2,865,987). Preterm birth was defined as <37 weeks completed gestation and dyslipidemia was defined by diagnostic codes. Subtypes of preterm birth were classified as preterm premature rupture of membranes (PPROM), spontaneous labor, and medically indicated, according to birth certificate data and diagnostic codes. The association between dyslipidemia and preterm birth was tested with logistic regression. Models were adjusted for maternal age at delivery, race/ethnicity, hypertension, pre-pregnancy body mass index, insurance type, and education. Maternal dyslipidemia was significantly associated with increased odds of preterm birth (adjusted OR: 1.49, 95%CI: 1.39, 1.59). This finding was consistent across all subtypes of preterm birth, including PPROM (adjusted OR: 1.54, 95%CI: 1.34, 1.76), spontaneous (adjusted OR: 1.51, 95%CI: 1.39, 1.65), and medically indicated (adjusted OR: 1.454, 95%CI: 1.282, 1.649). This study suggests that maternal dyslipidemia is associated with increased risk for all types of preterm birth.

]]>
<![CDATA[Is the risk of low birth weight or preterm labor greater when maternal stress is experienced during pregnancy? A systematic review and meta-analysis of cohort studies]]> https://www.researchpad.co/article/5b6945c4463d7e3867f4acaa

Antenatal stress is linked to fetal risks that increase the chances of neonatal complications and reduction of child cognitive ability. Therefore, we aimed to evaluate if maternal stress affects fetal, neonatal or child development. The following databases were searched: MEDLINE (1966 to May 2016), Embase (1980 to May 2016), LILACS (1982 to May 2016) and CENTRAL (1972 to May 2016). Observational studies published in English and Portuguese were included whether there was any relationship between fetal and neonatal outcome, such as birth weight, preterm labor, child development with pregnant women that were subjected to any stress type during at least one month of follow-up. Two independent reviewers screened eligible articles, extracted data and assessed the risk of bias. Thus, 8 cohort studies with about 8,271 pregnant women and 1,081,151 children proved eligible. Results suggested a significant association between antenatal stress exposure and increasing rates of low birth weight (Odds ratio (OR) 1.68 [95% Confidential Interval (CI) 1.19, 2.38]). However, there was no statistically significance difference between non-exposed and exposed groups related to preterm labor (OR 1.98 [95% CI 0.91 to 4.31]; I2 = 68%, p = 0.04). Although, results were inconsistent with primary analysis suggesting a significant association between antenatal stress exposure and the occurrence of higher rates of preterm birth (OR 1.42 [95% CI 1.05 to 1.91]; I2 = 68%, p = 0.04) in the sensitivity analysis. Furthermore, the current review has suggested that stress perceived during antenatal negatively influences fetal life and child development. Yet, further studies are necessary with adequate sample size and longer follow-up time to confirm our findings.

]]>
<![CDATA[Estradiol alters the immune-responsiveness of cervical epithelial cells stimulated with ligands of Toll-like receptors 2 and 4]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc741

The mucosa of the female reproductive tract plays a pivotal role in host defence. Pregnancy must alter immunological mechanisms at this interface to protect the conceptus. We sought to determine how estradiol (E2) alters the immune-responsiveness of cervical epithelial cells to ligand stimulation of Toll-like receptor (TLR)-2 and -4. Human ectocervical epithelial cells (HECECs) were cultured and co-incubated with two concentrations of E2 and peptidoglycan (PGN) or lipopolysaccharide (LPS) over durations that ranged between 10 minutes and 18 hours. Cytometric Bead Array was performed to quantify eight cytokines in the supernatant fluid. In response to PGN, HECECs co-incubated with E2 released lesser quantities of IL-1ß and IFNγ, higher levels of RANTES, and variable levels of IL-6 and IL-8 than those not exposed to E2. In contrast, HECECs co-incubated with LPS and E2 secreted increased levels of IL-1ß, IL-6, IL-8, and IFNγ at 2 and 18 hours than HECECs not exposed to E2, and reduced levels of RANTES at same study time-points. Estradiol alters the immune-responsiveness of cultured HECECs to TLR2 and TLR4 ligands in a complex fashion that appears to vary with bacterial ligand, TLR subtype, and duration of exposure. Our observations are consistent with the functional complexity that this mucosal interface requires for its immunological roles.

]]>
<![CDATA[Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells – Liquid biopsies for monitoring complications of pregnancy]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc1b9

Our understanding of how cells communicate has undergone a paradigm shift since the recent recognition of the role of exosomes in intercellular signaling. In this study, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT) cells, modifying their bioactivity on endothelial cells (EC). Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE) and spontaneous preterm birth (SPTB). HTR-8/SVneo cells were used as an EVT model. The effect of oxygen tension (i.e. 8% and 1% oxygen) on exosome release was quantified using nanocrystals (Qdot®) coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte) was used to establish the effect of exosomes on EC. Plasma samples were obtained at early gestation (<18 weeks) and classified according to pregnancy outcomes. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from exosomal RNA obtained from EVT and plasma samples. The number of exosomes was significantly higher in EVT cultured under 1% compared to 8% oxygen. In total, 741 miRNA were identified in exosomes from EVT. Bioinformatic analysis revealed that these miRNA were associated with cell migration and cytokine production. Interestingly, exosomes isolated from EVT cultured at 8% oxygen increased EC migration, whilst exosomes cultured at 1% oxygen decreased EC migration. These changes were inversely proportional to TNF-α released from EC. Finally, we have identified a set of unique miRNAs in exosomes from EVT cultured at 1% oxygen and exosomes isolated from the circulation of mothers at early gestation, who later developed PE and SPTB. We suggest that aberrant exosomal signalling by placental cells is a common aetiological factor in pregnancy complications characterised by incomplete SpA remodeling and is therefore a clinically relevant biomarker of pregnancy complications.

]]>
<![CDATA[Urinary Microbiota Associated with Preterm Birth: Results from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study]]> https://www.researchpad.co/article/5989da22ab0ee8fa60b7f7c6

Preterm birth (PTB) is the leading cause of infant morbidity and mortality. Genitourinary infection is implicated in the initiation of spontaneous PTB; however, examination of the urinary microbiota in relation to preterm delivery using next-generation sequencing technologies is lacking. In a case-control study nested within the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study, we examined associations between the urinary microbiota and PTB. A total of 49 cases (delivery < 37 weeks gestation) and 48 controls (delivery ≥ 37 weeks gestation) balanced on health insurance type were included in the present analysis. Illumina sequencing of the 16S rRNA gene V4 region was performed on urine samples collected during the second trimester. We observed no difference in taxa richness, evenness, or community composition between cases and controls or for gestational age modeled as a continuous variable. Operational taxonomic units (OTUs) classified to Prevotella, Sutterella, L. iners, Blautia, Kocuria, Lachnospiraceae, and S.marcescens were enriched among cases (FDR corrected p≤ 0.05). A urinary microbiota clustering partition dominated by S. marcescens was also associated with PTB (OR = 3.97, 95% CI: 1.19–13.24). These data suggest a limited role for the urinary microbiota in PTB when measured during the second trimester by 16S rRNA gene sequencing. The enrichment among cases in several organisms previously reported to be associated with genitourinary pathology requires confirmation in future studies to rule out the potential for false positive findings.

]]>
<![CDATA[Pregnancy and Delivery in Patients with Mastocytosis Treated at the Polish Center of the European Competence Network on Mastocytosis (ECNM)]]> https://www.researchpad.co/article/5989db26ab0ee8fa60bd04cb

Objective

To present current guidelines regarding treatment of mastocytosis in pregnancy on the example of observed patients.

Design

Case control national study.

Setting

Polish Center of the European Competence Network on Mastocytosis (ECNM).

Population or Sample

23 singleton spontaneous pregnancies in 17 women diagnosed with mastocytosis in years 1999–2014, before becoming pregnant.

Methods

Prospective analysis outcomes of pregnancies and deliveries.

Main Outcome Measures

Survey developed in cooperation with the Spanish Instituto de Estudios de Mastocitosis de Castilla-La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Red Espańola de Mastocitosis (REMA), Spain.

Results

All 23 pregnancies resulted from natural conception. Obstetrical complications recorded in the first trimester included spontaneous miscarriage (5 pregnancies). Four patients delivered preterm, including one delivery due to preeclampsia at 26 weeks which resulted with neonate death due to extreme prematurity. Five women delivered via cesarean: four due to obstetrical indications and one due to mastocytosis, during which no anesthesia related complications were recorded. Of patients delivering vaginally, two received extradural anesthesia, three required oxytocin infusion due to uterine hypotonia. No labor complications were recorded. In one woman with pregnancy-induced hypertension, early puerperium was complicated by the presence of persistent arterial hypertension. One neonate was born with the signs of cutaneous mastocytosis. Another neonate was diagnosed with Patau syndrome. Four women were treated for mastocytosis prior to conception and continued therapy after becoming pregnant. One patient was put on medications in the first trimester due to worsening of her symptoms. Pregnancy exerted only a slight effect on the intensity and frequency of mastocytosis-related symptoms observed. Worsening of the disease-related symptoms was documented in only four patients (23%). None of the patients showed the signs of anaphylaxis, either before becoming pregnant, or during pregnancy and puerperium.

Conclusions

There is no contraindication to pregnancy when mastocystosis-related pathologies are under appropriate medical control.

]]>
<![CDATA[Maternal Prenatal Positive Affect, Depressive and Anxiety Symptoms and Birth Outcomes: The PREDO Study]]> https://www.researchpad.co/article/5989d9e1ab0ee8fa60b699fb

Background

We investigated whether maternal prenatal emotions are associated with gestational length and birth weight in the large PREDO Study with multiple measurement points of emotions during gestation.

Methods

Altogether 3376 pregnant women self-assessed their positive affect (PA, Positive and Negative Affect Schedule) and depressive (Center for Epidemiologic Studies Depression Scale, CES-D) and anxiety (Spielberger State Anxiety Scale, STAI) symptoms up to 14 times during gestation. Birth characteristics were derived from the National Birth Register and from medical records.

Results

One standard deviation (SD) unit higher PA during the third pregnancy trimester was associated with a 0.05 SD unit longer gestational length, whereas one SD unit higher CES-D and STAI scores during the third trimester were associated with 0.04–0.05 SD unit shorter gestational lengths (P-values ≤ 0.02), corresponding to only 0.1–0.2% of the variation in gestational length. Higher PA during the third trimester was associated with a significantly decreased risk for preterm (< 37 weeks) delivery (for each SD unit higher positive affect, odds ratio was 0.8-fold (P = 0.02). Mothers with preterm delivery showed a decline in PA and an increase in CES-D and STAI during eight weeks prior to delivery. Post-term birth (≥ 42 weeks), birth weight and fetal growth were not associated with maternal prenatal emotions.

Conclusions

This study with 14 measurements of maternal emotions during pregnancy show modest effects of prenatal emotions during the third pregnancy trimester, particularly in the weeks close to delivery, on gestational length. From the clinical perspective, the effects were negligible. No associations were detected between prenatal emotions and birth weight.

]]>
<![CDATA[Identification of Eight Different Isoforms of the Glucocorticoid Receptor in Guinea Pig Placenta: Relationship to Preterm Delivery, Sex and Betamethasone Exposure]]> https://www.researchpad.co/article/5989db42ab0ee8fa60bd71ec

The placental glucocorticoid receptor (GR) is central to glucocorticoid signalling and for mediating steroid effects on pathways associated with fetal growth and lung maturation but the GR has not been examined in the guinea pig placenta even though this animal is regularly used as a model of preterm birth and excess glucocorticoid exposure. Guinea pig dams received subcutaneous injections of either vehicle or betamethasone at 24 and 12 hours prior to preterm or term caesarean-section delivery. At delivery pup and organ weights were recorded. Placentae were dissected, weighed and analysed using Western blot to examine GR isoform expression in nuclear and cytoplasmic extracts. A comparative examination of the guinea pig GR gene identified it is capable of producing seven of the eight translational GR isoforms which include GRα-A, C1, C2, C3, D1, D2, and D3. GRα-B is not produced in the Guinea Pig. Total GR antibody identified 10 specific bands from term (n = 29) and preterm pregnancies (n = 27). Known isoforms included GRγ, GRα A, GRβ, GRP, GRA and GRα D1-3. There were sex and gestational age differences in placental GR isoform expression. Placental GRα A was detected in the cytoplasm of all groups but was significantly increased in the cytoplasm and nucleus of preterm males and females exposed to betamethasone and untreated term males (KW-ANOVA, P = 0.0001, P = 0.001). Cytoplasmic expression of GRβ was increased in female preterm placentae and preterm and term male placentae exposed to betamethasone (P = 0.01). Nuclear expression of GRβ was increased in all placentae exposed to betamethasone (P = 0.0001). GRα D2 and GRα D3 were increased in male preterm placentae when exposed to betamethasone (P = 0.01, P = 0.02). The current data suggests the sex-specific placental response to maternal betamethasone may be dependent on the expression of a combination of GR isoforms.

]]>
<![CDATA[Is the Risk of Preterm Birth and Low Birth Weight Affected by the Use of Antidepressant Agents during Pregnancy? A Population-Based Investigation]]> https://www.researchpad.co/article/5989dae2ab0ee8fa60bbc3ea

Background

Untreated depression during pregnancy increases the risk of morbidity and mortality in the mother and child. Therefore, specific treatments are required for this population.

Objective

The study aimed to investigating the effect of antidepressant medication used during pregnancy with reference to the risk of preterm birth (PTB) and low birth weight (LBW).

Methods

A population-based study was carried out with data provided by the healthcare utilization database of Lombardy, an Italian region with about ten million inhabitants. The study included 384,673 births from 2005 to 2010. Maternal use of antidepressants before and during pregnancy was investigated. Log-binomial regression was used to estimate the association between the use of antidepressants during pregnancy, compared to the non-use or use just before pregnancy, and the prevalence ratio of PTB and LBW.

Results

Women who used antidepressants during pregnancy had a 20% (95% CI: 10–40%) increased prevalence of both PTB and LBW compared to those who never used antidepressants. There was no evidence that women who used antidepressants during pregnancy had a higher prevalence of the considered outcomes compared to women who used antidepressants before pregnancy, but stopped during pregnancy. Such findings were confirmed by considering separately the effects of SSRIs and other antidepressants together.

Conclusions

Our findings suggest that depression in itself, rather than antidepressant medication, might be implicated in the causal pathway of PTB and LBW.

]]>
<![CDATA[Fetal outcomes and associated factors of adverse outcomes of pregnancy in southern Chinese women with systemic lupus erythematosus]]> https://www.researchpad.co/article/5989db59ab0ee8fa60bdf0b1

This study aims to investigate the fetal outcomes and associated factors of adverse pregnancy outcomes (APOs) in pregnant women with systemic lupus erythematosus (SLE). Clinical data from 251 SLE patients with 263 pregnancies from 2001 to 2015 were analyzed retrospectively. APOs occurred in 70.0% of pregnancies, in which pregnancy loss occurred in 28.5%; preterm delivery occurred in 21.3%; intrauterine growth retardation occurred in 12.2%; and fetal distress occurred in 8.0%. Over time, the rate of APOs decreased from 82.8% during 2001~2005 to 59.6% during 2011~2015. In multivariate analysis, predictors of APOs included positive antiphospholipid antibodies (OR 8.4, 95% CI 1.7~40.8, P = 0.008), lower complement (OR 3.6, 95% CI 1.3~9.9, P = 0.01), hypoalbuminemia (OR 3.2, 95% CI 1.2~8.3, P = 0.02), and hypertension (OR 14.6, 95% CI 1.5~141.6, P = 0.02). The use of antimalarial medications was associated with lower risk for APOs (OR 0.3, 95% CI 0.1~0.7, P = 0.01). In total, 109 patients underwent fetal umbilical artery Doppler in the third trimester. The The adjusted systole/diastole (S/D) ratio, pulsatility index (PI) and resistance index (RI) of SLE patients with APOs were higher than that of patients without APOs (2.9±0.9 vs. 2.4±0.5, P = 0.001). Lupus pregnancy was still at high risk of APOs in terms of pregnancy loss and preterm delivery. Umbilical artery Doppler was a good monitor method for APOs in the third trimester.

]]>
<![CDATA[Adverse Perinatal Outcome in Subsequent Pregnancy after Stillbirth by Placental Vascular Disorders]]> https://www.researchpad.co/article/5989da85ab0ee8fa60b9c12a

Objective

To evaluate outcome in the pregnancy following a stillbirth (SB) by a placental vascular disorders.

Study Design

A prospective, observational, multicenter study was conducted in woman with a history of stillbirth (> 22 weeks) between 2005 and June 2013, in 3 Italian University Hospitals. Causes of SB were previously identified after extensive investigations. Pregnant women were enrolled within the first trimester. The main outcome was “adverse neonatal outcome”, including perinatal death, fetal growth restriction, early preterm birth <33+6 weeks, hypoxic-ischemic encephalopathy, intracranial hemorrhage or respiratory distress.

Results

Out of 364 index pregnancies, 320 women (87.9%) had a subsequent pregnancy during the study period. Forty-seven had an early pregnancy loss. Out of 273 babies, 67 (24.5%) had an adverse perinatal outcome, including 1 SB and 1 early neonatal death (3.7/1000).

Women who had a SB related to placental vascular disorders (39.6%), were at higher risk of an adverse neonatal outcome compared with women whose SB was unexplained or resulted from other causes (Adj. OR = 2.1, 95%CI: 1.2–3.8). Moreover, also obesity independently predicts an adverse perinatal outcome (Adj OR = 2.1, 95%CI: 1.1–4.3).

Conclusion

When previous SB is related to placental vascular disorders there is a high risk for adverse neonatal outcomes in the subsequent pregnancy. Maternal obesity is an additional risk factor.

]]>
<![CDATA[Identifying Maternal Constraints on Fetal Growth and Subsequent Perinatal Outcomes Using a Multiple Embryo Implantation Model]]> https://www.researchpad.co/article/5989d9d9ab0ee8fa60b66f95

Introduction

Although the majority of singleton births after in vitro fertilization (IVF) are uncomplicated, studies have suggested that IVF pregnancies may be independently associated with low birth weight (LBW), preterm birth (PTB), and perinatal mortality. These outcomes complicate multiple gestations as expected, but have also been reported in singletons. A multiple embryo implantation model allows for assessment of the early in utero environment, and therefore, assessment of any maternal constraints on developing fetuses. We question whether adverse perinatal outcomes associated with assisted reproductive techniques (ART) occur as a result of maternal physiologic adaptations.

Patients and Methods

This is a retrospective, single center study of ART cycles, specifically intracytoplasmic sperm injection (ICSI) cycles during a 16-year period. For each positive pregnancy test 9–11 days after embryo transfer, an ultrasonogram was performed at 7 weeks of gestation to record the number of implanted fetal poles with cardiac activity. Controlled ovarian stimulation (COS), hCG trigger, oocyte retrieval and sperm injection were performed as per our standard protocols. First trimester implantation sites that resulted in live births were defined as “true” to distinguish them from those that spontaneously reduced called “virtual.” Birth outcomes analyzed included birth weight and gestational age at delivery.

Results

A total of 17,415 cycles were analyzed. The average maternal age was 36.9 (±5.0) years. An overall fertilization rate of 73.4% generated approximately 48,708 good quality cleavage-stage embryos. In most patients (92.8%), an average of 3 embryos were transferred. The clinical pregnancy rate was 39.2% (n = 6,281). The overall occurrence of multiple gestations was 38.2% (n = 2,608) consisting of 2,038 twin, 511 triplet, and 59 quadruplet pregnancies. Of these multiple gestations, 18.6% of twin, 54.2% of triplet and 76.3% of quadruplet gestations spontaneously reduced. Failure of the implanted embryo to progress was not related to maternal age. Singleton newborns resulting from multiple implantation sites had lower birth weights (P<0.01) and shorter gestational ages (P<0.01) than those from a single implanted embryo. The number of embryos transferred did not affect the gestational length of singleton newborns. Although the birth weights of singletons from multiple implantation sites (virtual singletons) were lower than true singletons, the birth weight of virtual singletons were comparable to the birth weights of true twin, triplet, and quadruplet live births. Multiple logistic regression revealed that virtual singletons were an independent risk factor for PTB (odds ratio: 4.55, 95% CI 2.23–9.29) and LBW (odds ratio: 3.61, 95% CI 1.78–7.32), even after controlling for the number of oocytes, stimulation protocol type, sperm source, total gonadotropins administered, age, embryo quality, and day of embryo transfer.

Conclusions

Our study highlights that embryonic implantation sites during early gestation set the growth profile of each embryo, dictating later growth patterns. Specifically, spontaneous reduction of an embryo after multiple embryo implantations can confer greater perinatal risk in the form of LBW and PTB to the surviving fetus. Our findings suggest that maternal constraints or physiologic adaptations maybe one of the mechanisms mediating adverse perinatal outcomes when multiple embryo implantation occurs.

]]>
<![CDATA[Weight change across the start of three consecutive pregnancies and the risk of maternal morbidity and SGA birth at the second and third pregnancy]]> https://www.researchpad.co/article/5989db5fab0ee8fa60be114f

Background

Weight-change across parities and/or current BMI may influence maternal and fetal morbidity and requires to be differentiated to better inform weight-management guidance.

Methods

Direction, pattern and magnitude of weight-change across three consecutive parities and thereby two inter-pregnancy periods was described in 5079 women. The association between inter-pregnancy weight-change versus current BMI and adverse maternal events, SGA-birth and preterm delivery at second and third pregnancy were investigated by logistic regression.

Results

More women gained weight across the defined childbearing period than lost it, with ~35% of normal and overweight women gaining sufficient weight to move up a BMI-category. Nine patterns of weight-change were defined across two inter-pregnancy periods and 50% of women remained weight-stable throughout (within 2BMI units/period). Women who were overweight/obese at first pregnancy had higher risk of substantial weight-gain and loss (>10kg) during each of two inter-pregnancy periods. Inter-pregnancy weight-gain (> 2BMI units) between first and second pregnancy increased the risk of maternal morbidity (1or more event of hypertensive disease, caesarean-section, thromboembolism) at second pregnancy, while weight-loss (>2BMI units) increased the risk of SGA-birth. Similarly, increased risk of maternal morbidity at the third pregnancy was influenced by weight-gain during both inter-pregnancy periods but not by current BMI-category. Both weight-gain between first and second pregnancy, and being overweight/obese by third pregnancy protected the fetus against SGA-birth whereas weight-loss between second and third pregnancy doubled the SGA risk.

Conclusion

Half the women studied exhibited significant weight-fluctuations. This influenced their risk of maternal morbidity and SGA-birth at second and third pregnancy.

]]>