ResearchPad - pregnancy-complications https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Temperature and preeclampsia: Epidemiological evidence that perturbation in maternal heat homeostasis affects pregnancy outcome]]> https://www.researchpad.co/article/elastic_article_15767 This study aims to determine the association between temperature and preeclampsia and whether it is affected by seasonality and rural/urban lifestyle.MethodsThis cohort study included women who delivered at our medical center from 2004 to 2013 (31,101 women, 64,566 deliveries). Temperature values were obtained from a spatiotemporally resolved estimation model performing predictions at a 1×1km spatial resolution. In “Warm” pregnancies >50% of gestation occurred during the spring-summer period. In cold pregnancies >50% of gestation occurred during the fall and winter. Generalized estimating equation multivariable models were used to estimate the association between temperature and incidence of preeclampsia.Results1) The incidence of preeclampsia in at least one pregnancy was 7% (2173/64,566); 2) during “warm” pregnancies, an elevation of one IQR of the average temperature in the 1st or the 3rd trimesters was associated with an increased risk to develop preeclampsia [patients with Jewish ethnicity: 1st trimester: relative risk (RR) of 2.38(95%CI 1.50; 3.80), 3rd trimester 1.94(95%CI 1.34;2.81); Bedouins: 1st trimester: RR = 2.91(95%CI 1.98;4.28), 3rd trimester: RR = 2.37(95%CI 1.75;3.20)]; 3) In “cold” pregnancies, an elevation of one IQR of average temperature was associated with a lower risk to develop preeclampsia among patients with Bedouin-Arab ethnicity RR = 0.68 (95% CI 0.49–0.94) for 1st trimester and RR = 0.62 (95% CI 0.44–0.87) for 3rd trimester.Conclusions1) Elevated averaged temperature during the 1st or 3rd trimesters in “warm” pregnancies confer an increased risk for the development of preeclampsia, especially in nomadic patients; 2) Of interest, during cold pregnancies, elevated averaged temperature was associated with a lower risk to develop preeclampsia for nomadic patients. 3) These findings suggest temperature might be associated with perturbations in maternal heat homeostasis resulting in reallocation of energy resources and their availability to the fetus that may increase the risk for preeclampsia. This observation is especially relevant in the context of global warming and its effects on maternal/fetal reproductive health. ]]> <![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[Variation in plasma 25-hydroxyvitamin D2 and D3 in normal pregnancy with gestational age, sampling season, and complications: A longitudinal cohort study]]> https://www.researchpad.co/article/Ndf1a2733-e0b1-4fc7-90ad-b2bfa4368f5f

Introduction

Low levels of vitamin D in pregnancy have been associated with the risk of a variety of pregnancy outcomes. Few studies have investigated vitamin D concentrations throughout pregnancy in healthy women, and most guidelines recommend high vitamin D levels. In the present study, we investigated 25-hydroxyvitamin D concentrations in healthy Caucasian Danish women in relation to season, gestational age and possible vitamin D-linked complications.

Materials and methods

Eight hundred and one healthy Caucasian Danish women with an expected normal pregnancy were recruited among 2147 women attending first trimester screening. Seven blood samplings were planned throughout the pregnancy and delivery period. The 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3) concentrations were measured by LC-MS/MS and total 25-hydroxyvitamin D (25(OH)D) were calculated.

Results

A total of 3304 samples from 694 women were available for 25(OH)D measurements. The mean (25th-75th percentiles) concentrations of 25(OH)D, 25(OH)D3, and 25(OH)D2 were 54.6 (38.8–68.6) nmol/L, 52.2 (36.4–66.4) nmol/L, and 2.4 (2.2–2.2) nmol/L, respectively. Season was the strongest predictor of 25(OH)D concentration, with the lowest values observed in winter and spring, where only 42% and 41% of samples, respectively, were above 50 nmol/L. Nearly all women had values below the suggested optimal level of 75 nmol/L, independent of season. 25(OH)D peaked at gestational weeks 21–34. Plasma 25(OH)D2 levels were low in all seasons. Women with complications during pregnancy had higher 25(OH)D (estimated difference 9.8 nmol/L, standard error 2.7, p<0.001) than did women without complications, and women giving birth vaginally had lower 25(OH)D than did those delivering via elective (10.0 nmol/L, standard error 2.1, p<0.001) or emergency cesarean section (6.8 nmol/L, standard error 2.2, p<0.001).

Conclusion

The 25(OH)D concentrations vary with both season and gestational age. Healthy women had lower 25(OH)D concentrations than recommended, without an association with an increased risk of pregnancy complications. Guidelines for vitamin D in pregnancy may require revision.

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<![CDATA[The role of the erythrocyte in the outcome of pregnancy with preeclampsia]]> https://www.researchpad.co/article/5c897713d5eed0c4847d23cc

The objective of this study was to analyze the relationships of osmotic and mechanical stability of erythrocytes with anthropometric, biochemical, hematologic and hemodynamic variables in pregnant women with preeclampsia (PE). The studied population consisted of 20 normotensive patients and 16 patients with PE. Patients with PE presented worse gestational outcome, greater hematologic impairment, erythrocytes osmotically more stable in vitro, but in conditions of isotonicity with the in vivo medium, in addition to hyperflow in orbital territory, when compared to normotensive patients. The correlation analysis between anthropometric, hematologic and hemodynamic variables in patients with PE indicated that erythrocytes with lower volumes and lower levels of hemoglobin favor the occurrence of a better gestational outcome, because they are more stable and because they are associated with a decrease in the hemodynamic changes present in the disease. This should mean that the tendency to microcytosis, probably due to a mechanism of compensatory mechanical selection, is a desirable characteristic in the disease.

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<![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.

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<![CDATA[Prescription medication use during pregnancies that resulted in births and abortions (2001-2013): A retrospective population-based study in a Canadian population]]> https://www.researchpad.co/article/5c897711d5eed0c4847d23a9

We aimed to describe medication use in pregnancies that resulted in births and abortions, as well as use after a pregnancy-related visit to characterize the receipt of medication after knowledge of pregnancy. Abortions included both spontaneous and induced abortions. Rates of medication use among women with a pregnancy outcome (2001–2013) were described using the Manitoba Population Research Data Repository at the Manitoba Centre for Health Policy. Use was determined as ≥ 1 prescription filled during pregnancies that resulted in births (livebirth/stillbirth) and abortions. Rates were calculated at any time during pregnancy and after a pregnancy-related visit. Rates were additionally characterized by risk in pregnancy using Briggs classification (2017). Of 174,848 birth pregnancies, overall 64.9% filled ≥ 1 prescription during pregnancy (a significant increase from 62.3% to 68.8% from 2001–2013, p<0.0001); 55.4% filled ≥ 1 prescription after a pregnancy-related visit. Of 71,967 abortions, 44.7% filled ≥ 1 prescription (a significant increase from 42.6% to 46.8% from 2001–2013, p<0.0001). Only 3.7% of birth pregnancies had at least one prescription for a contraindicated medication (according to Briggs classification), whereas 10.8% of abortions filled a prescription for a contraindicated medication. The most common drugs used in pregnancy were amoxicillin, doxylamine, codeine combinations, nitrofurantoin, cephalexin, salbutamol and ranitidine. Fewer women filled prescriptions for undesirable medications according to Briggs classification during pregnancy after a pregnancy-related visit.

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<![CDATA["Not taken seriously"—A qualitative interview study of postpartum Rwandan women who have experienced pregnancy-related complications]]> https://www.researchpad.co/article/5c6dc9bdd5eed0c48452a10e

Background

There is limited knowledge on the women’s experiences of pregnancy-related complications in Rwanda. This study aimed to investigate women’s experiences and perceptions of specific complications during pregnancy and delivery and the consequences of these complications on postpartum health and family situation.

Methods

Data were collected through individual in-depth interviews (N = 15). Participants who experienced complications such as postpartum haemorrhage, caesarean section due to prolonged labour/dystocia, pre-eclampsia, or fistula and who were 13–24 months postpartum were invited to participate in the study in July 2015. Interviews were held in Kinyarwanda, digitally recorded, transcribed verbatim, translated into English, and analysed using qualitative content analysis.

Results

Most participants reported that they were previously unaware of the complications they had developed, and they claimed that at discharge they should have been better informed about the potential consequences of these complications. Most participants blamed the health care system as the cause of their problems due to the provision of inadequate care. Participants elaborated different strategies for coping with persistent health problems. Pregnancy-related complications negatively affected participants’ economic situation due to increased health care expenses and lowered income because of impaired working capacity, and participants expressed fear of encountering the same pregnancy-related health problems during future pregnancies.

Conclusions

The findings of this study demonstrate how participants felt that inadequate health care provision during pregnancy, delivery, and the postpartum period was the source of their problems. Participants reported different coping strategies to improve their respective life situation despite persistent health problems. Women’s individual postpartum experiences need to be considered and actions taken at the policy level and also by the local community, in terms of the quality of antenatal and postpartum care services, and in sensitizing the local community about the existence of these complications and preparing the community to support the affected women.

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<![CDATA[Associations between use of macrolide antibiotics during pregnancy and adverse child outcomes: A systematic review and meta-analysis]]> https://www.researchpad.co/article/5c75abfad5eed0c484d07f62

Background

Evidence on adverse effects of maternal macrolide use during pregnancy is inconsistent. We conducted a systematic review and meta-analysis to investigate the association between macrolide use during pregnancy and adverse fetal and child outcomes.

Methods and findings

We included observational studies and randomised controlled trials (RCTs) that recorded macrolide use during pregnancy and child outcomes. We prioritized comparisons of macrolides with alternative antibiotics (mainly penicillins or cephalosporins) for comparability of indication and effect. Random effects meta-analysis was used to derive pooled odds ratios (OR) for each outcome. Subgroup analyses were performed according to specific types (generic forms) of macrolide.

Of 11,186 citations identified, 19 (10 observational, 9 RCTs) studies were included (21 articles including 228,556 participants). Macrolide prescribing during pregnancy was associated with an increased risk of miscarriage (pooled ORobs 1·82, 95% CI 1·57–2·11, three studies, I2 = 0%), cerebral palsy and/or epilepsy (ORobs 1·78, 1·18–2·69; one study), epilepsy alone (ORobs 2·02, 1·30–3·14, one study; ORRCT 1.03, 0.79–1.35, two studies), and gastrointestinal malformations (ORobs 1·56, 1·05–2·32, two studies) compared with alternative antibiotics. We found no evidence of an adverse effect on 12 other malformations, stillbirth, or neonatal death. Results were robust to excluding studies with high risk of bias.

Conclusions

Consistent evidence of an increased risk of miscarriage in observational studies and uncertain risks of cerebral palsy and epilepsy warrant cautious use of macrolide in pregnancy with warnings in drug safety leaflets and use of alternative antibiotics where appropriate. As macrolides are the third most commonly used class of antibiotics, it is important to confirm these results with high quality studies.

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<![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.

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<![CDATA[‘We are always desperate and will try anything to conceive’: The convoluted and dynamic process of health seeking among women with infertility in the West Coast Region of The Gambia]]> https://www.researchpad.co/article/5c5ca29dd5eed0c48441e77a

Introduction

In many Sub-Saharan African countries, women with infertility search relentlessly for treatment. Guided by the Partners for Applied Social Sciences model for health seeking behaviour and access to care research, this study aims to understand the health seeking behaviour of women with infertility in the West Coast region of The Gambia and the influence of aetiological beliefs on health seeking paths.

Methodology

A qualitative approach was used to generate both primary and secondary data for thematic analysis. The data collection methods included in-depth interviews (36), observations (18), informal conversations (42), group discussion (7) and made use of pile-sorting exercises. Sources of secondary data included government and non-governmental reports and media outputs.

Results

The health seeking approaches of women living in both rural and urban areas were extremely complex and dynamic, with women reporting that they looked for biomedical treatment as well as seeking indigenous treatment provided by local healers, sacred places and kanyaleng groups. While treatment choice was related to the perceived aetiology of infertility, it was also strongly influenced by the perceived effectiveness of the treatment available and the duration of the fertility problems. Other relevant factors were the affordability, accessibility and availability of treatment and respondents’ family and social networks, whereby access to the biomedical health sector was strongly influenced by people’s socio-economic background.

Conclusion

On the basis of this analysis and our wider research in the area, we see a need for health authorities to further invest in providing information and counselling on issues related to infertility prevention and treatment. The availability of locally applicable guidelines for the management of infertility for both men and women at all levels of the health system would facilitate such work. In addition, the public sphere should provide more space for alternative forms of social identity for both men and women.

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<![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.

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<![CDATA[Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon]]> https://www.researchpad.co/article/5c4b7f5dd5eed0c4848412b9

Zika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to as Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and non-human primates (NHPs). In macaques, fetal CZS outcomes from maternal ZIKV infection range from none to significant. In the present study we develop the olive baboon (Papio anubis), as a model for vertical transfer of ZIKV during pregnancy. Four mid-gestation, timed-pregnant baboons were inoculated with the French Polynesian ZIKV isolate (104 ffu). This study specifically focused on the acute phase of vertical transfer. Dams were terminated at 7 days post infection (dpi; n = 1), 14 dpi (n = 2) and 21 dpi (n = 1). All dams exhibited mild to moderate rash and conjunctivitis. Viremia peaked at 5–7 dpi with only one of three dams remaining mildly viremic at 14 dpi. An anti-ZIKV IgM response was observed by 14 dpi in all three dams studied to this stage, and two dams developed a neutralizing IgG response by either 14 dpi or 21 dpi, the latter included transfer of the IgG to the fetus (cord blood). A systemic inflammatory response (increased IL2, IL6, IL7, IL15, IL16) was observed in three of four dams. Vertical transfer of ZIKV to the placenta was observed in three pregnancies (n = 2 at 14 dpi and n = 1 at 21 dpi) and ZIKV was detected in fetal tissues in two pregnancies: one associated with fetal death at ~14 dpi, and the other in a viable fetus at 21 dpi. ZIKV RNA was detected in the fetal cerebral cortex and other tissues of both of these fetuses. In the fetus studied at 21 dpi with vertical transfer of virus to the CNS, the frontal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, disorganized migration of immature neurons to the cortical layers, and signs of pathology in immature oligodendrocytes. In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL6 expression. Of interest, in one fetus examined at 14 dpi without detection of ZIKV RNA in brain and other fetal tissues, increased neuroinflammation (IL6 and microglia) was observed in the cortex. Although the placenta of the 14 dpi dam with fetal death showed considerable pathology, only minor pathology was noted in the other three placentas. ZIKV was detected immunohistochemically in two placentas (14 dpi) and one placenta at 21 dpi but not at 7 dpi. This is the first study to examine the early events of vertical transfer of ZIKV in a NHP infected at mid-gestation. The baboon thus represents an additional NHP as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs.

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<![CDATA[Usefulness of uterine artery Doppler velocimetry as a predictor for hypertensive disorders in pregnancy in women with prehypertension before 20 weeks gestation]]> https://www.researchpad.co/article/5c5b52d4d5eed0c4842bd0ce

Hypertensive disorders of pregnancy (HDP) is major complication of maternal-fetal outcomes in obstetric field. Although HDP is mainly defined by high blood pressure, the information about the relationship between prehypertension (preHTN, 120-139mmHg and 80-89mmHg) and HDP development is limited. The objective of this study is to determine the usefulness of preHTN before 20 weeks gestation and uterine artery (UtA) Doppler velocimetry as a predictor of HDP. A total of 2039 singleton pregnant women who had received continuous prenatal care were included in this study. The participants were classified into 2 groups based on the highest blood pressure (BP) under 20 gestational weeks as defined by the Joint National Committee 7: Normotensive (n = 1816) and preHTN pregnant women (n = 223). All preHTN pregnant women were assessed using UtA Doppler velocimetry, and the numbers of preHTN assessments were recorded. The risk of HDP was assessed in the PreHTN groups through patient history and Doppler velocimetry. Compared to normotensive patients, a total of 223 preHTN patients had a higher risk of preeclampsia (OR: 2.3; CI: 1.2–4.3), gestational hypertension (OR: 3.3; CI: 2.0–5.4) and any HDP (OR: 3.0; CI: 2.0–4.5). In the preHTN group, 134 (60.1%) patients had preHTN measured at least twice and 89 (39.9%) patients had preHTN. The results showed that two or more preHTN measurements have high sensitivity for predicting HDP (OR: 1.9; CI: 1.0–3.1; sensitivity: 83.8%; specificity: 47.2%). Additionally, the combination of abnormal UtA Doppler velocimetry results and at least two preHTN measurements showed a high accuracy in predicting HDP (OR: 2.9; CI: 1.1–4.1; sensitivity: 67.6%; specificity: 98.4%). In conclusion, close BP monitoring and recording of every preHTN event are important for pregnant women with preHTN history, and UtA Doppler examination in those women during the 2nd trimester can be a further aid in determining the risk of HDP.

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<![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.

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<![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.

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<![CDATA[Fetal and infant mortality of congenital syphilis reported to the Health Information System]]> https://www.researchpad.co/article/5c390b99d5eed0c48491d6f8

Background

Congenital syphilis (CS) is a major cause of mortality in several countries, especially in Latin America and the Caribbean. This study aimed to analyze fetal and infant mortality of CS reported to the Health Information System in a State in Northeastern Brazil.

Methods and results

This was a cross-sectional study that analyzed the deaths of CS from 2010 to 2014 through the linkage of the Mortality Information System (SIM) and the Notifiable Diseases Information System (Sinan). The Statistical Package for the Social Sciences (SPSS) version 23.0 was used to calculate the rates of Fetal, Perinatal, Neonatal (early and late), and Postneonatal Mortality. Simple linear regression was performed. Fisher's exact test or Pearson's chi-square test were used for comparison of proportions and Student's t-test was used for comparison of means.

Of the 414 cases reported to the SIM as deaths possibly caused by CS, 44 (10.6%) presented CS as the underlying cause. From 2010 to 2014 the Infant Mortality Rate of CS was 16.3 per 100,000 live births (y = 0.65x + 14.33, R2 = 0.2338, p = 0.003). There was an 89.4% underreporting of deaths. Perinatal deaths and fetal deaths of CS accounted for 87.7% and 73.9% of total deaths, respectively.

Conclusions

The results of the study revealed a significant Fetal and Infant Mortality rate of CS and demonstrated the importance of using the linkage method in studies that involve the analysis of secondary data obtained from mortality and disease reporting systems. The underreporting of CS as a cause of fetal and infant mortality leads to unawareness of the reality of deaths from this disease, hindering the development of public policies aimed at its prevention.

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<![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.

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<![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.

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<![CDATA[RNA-sequencing analysis of umbilical cord plasma microRNAs from healthy newborns]]> https://www.researchpad.co/article/5c0ed761d5eed0c484f14028

MicroRNAs are a class of small non-coding RNA that regulate gene expression at a post-transcriptional level. MicroRNAs have been identified in various body fluids under normal conditions and their stability as well as their dysregulation in disease has led to ongoing interest in their diagnostic and prognostic potential. Circulating microRNAs may be valuable predictors of early-life complications such as birth asphyxia or neonatal seizures but there are relatively few data on microRNA content in plasma from healthy babies. Here we performed small RNA-sequencing analysis of plasma processed from umbilical cord blood in a set of healthy newborns. MicroRNA levels in umbilical cord plasma of four male and four female healthy babies, from two different centres were profiled. A total of 1,004 individual microRNAs were identified, which ranged from 426 to 659 per sample, of which 269 microRNAs were common to all eight samples. Many of these microRNAs are highly expressed and consistent with previous studies using other high throughput platforms. While overall microRNA expression did not differ between male and female cord blood plasma, we did detect differentially edited microRNAs in female plasma compared to male. Of note, and consistent with other studies of this type, adenylation and uridylation were the two most prominent forms of editing. Six microRNAs, miR-128-3p, miR-29a-3p, miR-9-5p, miR-218-5p, 204-5p and miR-132-3p were consistently both uridylated and adenylated in female cord blood plasma. These results provide a benchmark for microRNA profiling and biomarker discovery using umbilical cord plasma and can be used as comparative data for future biomarker profiles from complicated births or those with early-life developmental disorders.

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<![CDATA[Metabolic syndrome in pregnancy and risk for adverse pregnancy outcomes: A prospective cohort of nulliparous women]]> https://www.researchpad.co/article/5c1028f6d5eed0c484248a19

Background

Obesity increases the risk for developing gestational diabetes mellitus (GDM) and preeclampsia (PE), which both associate with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in women in later life. In the general population, metabolic syndrome (MetS) associates with T2DM and CVD. The impact of maternal MetS on pregnancy outcomes, in nulliparous pregnant women, has not been investigated.

Methods and findings

Low-risk, nulliparous women were recruited to the multi-centre, international prospective Screening for Pregnancy Endpoints (SCOPE) cohort between 11 November 2004 and 28 February 2011. Women were assessed for a range of demographic, lifestyle, and metabolic health variables at 15 ± 1 weeks’ gestation. MetS was defined according to International Diabetes Federation (IDF) criteria for adults: waist circumference ≥80 cm, along with any 2 of the following: raised trigycerides (≥1.70 mmol/l [≥150 mg/dl]), reduced high-density lipoprotein cholesterol (<1.29 mmol/l [<50 mg/dl]), raised blood pressure (BP) (i.e., systolic BP ≥130 mm Hg or diastolic BP ≥85 mm Hg), or raised plasma glucose (≥5.6 mmol/l). Log-binomial regression analyses were used to examine the risk for each pregnancy outcome (GDM, PE, large for gestational age [LGA], small for gestational age [SGA], and spontaneous preterm birth [sPTB]) with each of the 5 individual components for MetS and as a composite measure (i.e., MetS, as defined by the IDF). The relative risks, adjusted for maternal BMI, age, study centre, ethnicity, socioeconomic index, physical activity, smoking status, depression status, and fetal sex, are reported. A total of 5,530 women were included, and 12.3% (n = 684) had MetS. Women with MetS were at an increased risk for PE by a factor of 1.63 (95% CI 1.23 to 2.15) and for GDM by 3.71 (95% CI 2.42 to 5.67). In absolute terms, for PE, women with MetS had an adjusted excess risk of 2.52% (95% CI 1.51% to 4.11%) and, for GDM, had an adjusted excess risk of 8.66% (95% CI 5.38% to 13.94%). Diagnosis of MetS was not associated with increased risk for LGA, SGA, or sPTB. Increasing BMI in combination with MetS increased the estimated probability for GDM and decreased the probability of an uncomplicated pregnancy. Limitations of this study are that there are several different definitions for MetS in the adult population, and as there are none for pregnancy, we cannot be sure that the IDF criteria are the most appropriate definition for pregnancy. Furthermore, MetS was assessed in the first trimester and may not reflect pre-pregnancy metabolic health status.

Conclusions

We did not compare the impact of individual metabolic components with that of MetS as a composite, and therefore cannot conclude that MetS is better at identifying women at risk. However, more than half of the women who had MetS in early pregnancy developed a pregnancy complication compared with just over a third of women who did not have MetS. Furthermore, while increasing BMI increases the probability of GDM, the addition of MetS exacerbates this probability. Further studies are required to determine if individual MetS components act synergistically or independently.

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