Dataset Information

Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study.

ABSTRACT: We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestational age (GA). Viable non-malformed singleton pregnancies were selected for cerebellar measurements; transcerebellar diameter, (TCD), left and right cerebellar diameters (LCD, RCD). Linear mixed models were performed to estimate associations between questionnaire data on the timing of maternal folic acid supplement initiation and longitudinal cerebellar measurements as a function of crown-rump length (CRL) and GA. Maternal red blood cell folate concentrations were analysed before 8 weeks GA to validate the associations. A total of 263 serial high quality three-dimensional ultrasound scans of 135 pregnancies were studied. Preconceptional compared to postconceptional initiation of folic acid use was associated with slightly larger cerebellar diameters per millimetre increase of CRL (TCD: ? = 0.260mm, 95%CI = 0.023-0.491, p<0.05; LCD: ? = 0.171mm, 95%CI = 0.038-0.305, p<0.05; RCD: ? = 0.156mm, 95%CI = 0.032-0.280, p<0.05) and with proportional cerebellar growth (TCD/CRL:? = 0.015mm/mm, 95%CI = 0.005-0.024, p<0.01; LCD/CRL:? = 0.012mm/mm, 95%CI = 0.005-0.018, p<0.01; RCD/CRL:? = 0.011mm/mm, 95%CI = 0.005-0.017, p<0.01). Cerebellar growth was significantly highest in the third quartile of maternal red blood cell folate levels (1538-1813 nmol/L). These first findings show that periconceptional maternal folate status is associated with human embryonic cerebellar development. Implications of these small but significant variations for fetal cerebellar growth trajectories and the child's neurodevelopmental outcome are yet unknown and warrant further investigation.

SUBMITTER: Koning IV

PROVIDER: S-EPMC4619586 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study.

Koning Irene V IV Groenenberg Irene A L IA Gotink Anniek W AW Willemsen Sten P SP Gijtenbeek Manon M Dudink Jeroen J Go Attie T J I AT Reiss Irwin K M IK Steegers Eric A P EA Steegers-Theunissen Régine P M RP

PloS one 20151022 10

We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestational age (GA). Viable non-malformed singleton pregnancies were selected for cerebellar measurements; transcerebellar diameter, (TCD), left and right cerebellar diameters (LCD, RCD). Linear mixed models ...[more]

PMID: 26491876

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Project description:Study questionIs periconceptional multiple-micronutrient supplement (MMS) use including folic acid (FA) compared to FA use only associated with increased embryonic growth, development, and birth weight in a high-risk population?Summary answerWomen with MMS intake show no significant differences in first-trimester morphological embryo development, but increased first-trimester embryonic growth trajectories and fewer neonates born small for gestational age (SGA), less than the 3rd percentile (<p3), compared to women using only FA.What is known alreadyPericonceptional maternal FA intake in the general population is associated with increased embryonic and fetal growth, and reduced risks of neural tube defects, other congenital malformations, low birth weight, and neonates born SGA.Study design, size, durationA prospective tertiary hospital-based cohort study (the Rotterdam Periconceptional Cohort) was conducted from January 2010 to December 2020.Participants/materials, setting, methodsWe included 1076 women from the Rotterdam Periconceptional Cohort, before 10 weeks of pregnancy with follow-up until delivery. Embryonic growth was assessed by measurement of crown-rump length (CRL) and embryonic volume (EV), and embryonic morphology was described by Carnegie stages using longitudinal three-dimensional ultrasound scans and virtual reality techniques. Birth outcomes were extracted from medical records. General characteristics and supplement use were extracted from research questionnaires.Main results and the role of chanceThis study showed increased embryonic growth trajectories (adjusted models, CRL: β = 0.052, 95% CI 0.012-0.090, EV: β = 0.022, 95% CI 0.002-0.042) in women using MMS compared to those using only FA. Moreover, a 45% reduced risk of a neonate-born SGA (<p3) was shown in women using MMS compared to FA users (adjusted OR = 0.546, 95% CI 0.308, 0.969). Embryonic morphological development (Carnegie stages) and the occurrence of miscarriages did not differ between women using MMS or solely FA.Limitations, reasons for cautionFollowing the heterogeneity of the composition and dose of MMS preparations, it is unclear which specific micronutrient, combination, or dose explains the increased embryonic growth trajectory and reduction in risk for SGA. This also hampers the possibility of differentiating between the effects of FA alone or as a component of MMS.Wider implications of the findingsOur findings emphasize the importance of periconceptional maternal MMS use as a potential preventative intervention against reduced embryonic growth and neonates born SGA. Therefore, we recommend the periconceptional use of MMS in women at risk of inadequate micronutrient intake. However, awareness of potentially harmful side effects of high doses and combinations of micronutrients is essential, therefore the optimal composition and dose need to be investigated, and careful surveillance is recommended.Study funding/competing interest(s)This research was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, and the ZonMw grant Open Competition 2018 (09120011910046). The authors declare that they have no conflict of interest.Trial registration numberNTR4356.

Project description:BackgroundOverweight and obesity affect millions of people globally, which has also serious implications for reproduction. For example, treatment outcomes after in vitro fertilisation (IVF) are worse in women with a high body mass index (BMI). However, the impact of maternal BMI on embryo quality is inconclusive. Our main aim is to study associations between preconceptional maternal BMI and morphokinetic parameters of preimplantation embryos and predicted implantation potential. In addition, associations with clinical IVF outcomes are investigated.MethodsFrom a tertiary hospital, 268 women undergoing IVF or IVF with intracytoplasmic sperm injection (ICSI) were included; 143 normal weight, 79 overweight and 46 obese women. The embryos of these women were cultured in the EmbryoScope, a time-lapse incubator. The morphokinetic parameters of preimplantation embryos and predicted implantation potential, assessed by the KIDScore algorithm were longitudinally evaluated as primary and secondary outcomes, respectively. The tertiary outcomes included clinical outcomes, i.e., fertilization, implantation and live birth rate.ResultsAfter adjustment for patient- and treatment-related factors, we demonstrated in 938 embryos that maternal BMI is negatively associated with the moment of pronuclear appearance (βtPNa -0.070 h (95%CI -0.139, -0.001), p = 0.048), pronuclear fading (βtPNf -0.091 h (95%CI -0.180, -0.003), p = 0.043 and the first cell cleavage (βt2 -0.111 h (95%CI -0.205, -0.016), p = 0.022). Maternal BMI was not significantly associated with the KIDScore and tertiary clinical treatment outcomes. In embryos from couples with female or combined factor subfertility, the impact of maternal BMI was even larger (βtPNf -0.170 h (95%CI -0.293, -0.047), p = 0.007; βt2 -0.199 h (95%CI -0.330, -0.067), p = 0.003). Additionally, a detrimental impact of BMI per point increase was observed on the KIDScore (β -0.073 (se 0.028), p = 0.010).ConclusionsHigher maternal BMI is associated with faster early preimplantation development. In couples with female or combined factor subfertility, a higher BMI is associated with a lower implantation potential as predicted by the KIDScore. Likely due to power issues, we did not observe an impact on clinical treatment outcomes. However, an effect of faster preimplantation development on post-implantation development is conceivable, especially since the impact of maternal BMI on pregnancy outcomes has been widely demonstrated.

Project description:ObjectiveTo investigate whether first-trimester maternal haemodynamic adaptation impacts placental, embryonic and fetal development as well as birth outcomes in pregnancies with and without placenta-related complications.DesignProspective observational cohort.SettingA Dutch tertiary hospital.PopulationTwo hundred and fourteen ongoing pregnancies.MethodsAt 7, 9 and 11 weeks of gestation, we assessed maternal haemodynamic adaptation (mean arterial blood pressure [MAP], uterine artery [UtA] blood flow) and placental development (placental volume [PV], uteroplacental vascular volume [uPVV]) using three-dimensional power Doppler ultrasound volumes, and embryonic development (crown-rump length, embryonic volume). At 22 and 32 weeks of gestation, fetal development was assessed by estimated fetal weight. Birth outcomes (birthweight, placental weight) were extracted from medical records. Linear mixed modelling and linear regression analyses were applied.Main outcome measuresBirthweight centile and placental weight.ResultsIn placenta-related complications (n= 55, 25.7%), reduced haemodynamic adaptation, i.e. higher UtA pulsatility index (PI) and resistance index (RI) trajectories, was associated with smaller increase in PV (β = -0.559, 95% CI -0.841 to -0.278, P< 0.001; β = -0.579, 95% CI -0.878 to -0.280, P< 0.001) and uPVV trajectories (UtA PI: β = -0.301, 95% CI -0.578 to -0.023, P= 0.034). At birth, reduced haemodynamic adaptation was associated with lower placental weight (UtA PI: β = -0.502, 95% CI -0.922 to -0.082, P= 0.022; UtA RI: β = -0.435, 95% CI -0.839 to -0.032, P= 0.036). In pregnancies without placenta-related complications, higher MAP trajectories were positively associated with birthweight centile (β = 0.398, 95% CI 0.049-0.748, P= 0.025).ConclusionsReduced first-trimester maternal haemodynamic adaptation impacts both placental size and vascularisation and birthweight centile, in particular in pregnancies with placenta-related complications.Tweetable abstractReduced first-trimester maternal haemodynamic adaptation to pregnancy impairs early placental development.

Project description:BackgroundIn patients with azoospermia, pregnancy can be achieved after surgical techniques using sperm retrieved from the testis or epididymis, which can impact on DNA integrity and epigenetics. DNA of the fetus and placenta is equally derived from both parents; however, genes important for placental development are expressed from the paternal alleles. Therefore, the origin of sperm may affect fetal and placental development.ObjectivesTo investigate whether first-trimester trajectories of embryonic and placental development of pregnancies conceived after intracytoplasmic sperm injection (ICSI) with testicular sperm extraction (TESE) or microsurgical epididymal sperm aspiration (MESA), are different from pregnancies after ICSI with ejaculated sperm or natural conceptions.Materials and methodsA total of 147 singleton ICSI pregnancies, including pregnancies conceived after TESE (n = 23), MESA (n = 25) and ejaculated sperm (n = 99), and 380 naturally conceived and 140 after IVF treatment without ICSI were selected from the prospective Rotterdam periconception cohort. Crown-rump length (CRL), embryonic volume (EV), Carnegie stages, and placental volume (PV) at 7, 9, and 11 weeks of gestation were measured using 3D ultrasound and virtual reality technology.ResultsLinear mixed model analysis showed no differences in trajectories of CRL, EV, and Carnegie stages between pregnancies conceived after ICSI with testicular, epididymal, and ejaculated sperm. A significantly positive association was demonstrated for PV between pregnancies conceived after TESE-ICSI (adjusted beta: 0.28(95%CI: 0.05-0.50)) versus ICSI with ejaculated sperm. Retransformation to original values showed that the PV of pregnancies after TESE-ICSI is 14.6% (95%CI: 1.4%-25.5%) larger at 11 weeks of gestation compared to ICSI pregnancies conceived with ejaculated sperm.Discussion and conclusionHere we demonstrate that the first-trimester growth trajectory of the placenta is increased in pregnancies conceived after TESE-ICSI compared to those conceived after ICSI with ejaculated sperm. Findings are discussed in the light of known differences in sperm DNA integrity, epigenetics, and placental gene expression.

Project description:PurposeTo investigate the association between oocyte area and fertilization rate, embryo usage, and preimplantation embryo development in order to establish if oocyte area can be a marker for optimal early embryo development.MethodsFrom 2017 to 2020, 378 couples with an indication for IVF (n = 124) or ICSI (n = 254) were included preconceptionally in the Rotterdam Periconception Cohort. Resulting oocytes (n = 2810) were fertilized and submitted to time-lapse embryo culture. Oocyte area was measured at the moment of fertilization (t0), pronuclear appearance (tPNa), and fading (tPNf). Fertilization rate, embryo usage and quality, and embryo morphokinetics from 2-cell stage to expanded blastocyst stage (t2-tEB) were used as outcome measures in association with oocyte area. Oocytes were termed "used" if they were fertilized and embryo development resulted in transfer or cryopreservation, and otherwise termed "discarded". Analyses were adjusted for relevant confounders.ResultsOocyte area decreased from t0 to tPNf after IVF and ICSI, and oocytes with larger area shrank faster (β - 12.6 µm2/h, 95%CI - 14.6; - 10.5, p < 0.001). Oocytes that resulted in a used embryo were larger at all time-points and reached tPNf faster than oocytes that fertilized but were discarded (oocyte area at tPNf in used 9864 ± 595 µm2 versus discarded 9679 ± 673 µm2, p < 0.001, tPNf in used 23.6 ± 3.2 h versus discarded 25.6 ± 5.9 h, p < 0.001). Larger oocytes had higher odds of being used (oocyte area at tPNf ORused 1.669, 95%CI 1.336; 2.085, p < 0.001), were associated with faster embryo development up to the morula stage (e.g., t9 β - 0.131 min, 95%CI - 0.237; - 0.025, p = 0.016) and higher ICM quality.ConclusionOocyte area is an informative marker for the preimplantation development of the embryo, as a larger oocyte area is associated with higher quality, faster developing embryos, and higher chance of being used. Identifying determinants associated with oocyte and embryo viability and quality could contribute to improved preconception care and subsequently healthy pregnancies.

Project description:ImportanceThe first pediatric lead screening typically occurs at 1-year well-child care visits. However, data on the extent of maternal lead exposure and its long-term consequences for child health are lacking.ObjectiveTo investigate the associations between maternal red blood cell (RBC) lead levels and intergenerational risk of overweight or obesity (OWO) and whether adequate maternal folate status is associated with a reduction in OWO risk.Design, setting, and participantsProspective birth cohort study. The analysis was conducted from July 14, 2018, to August 2, 2019, at Johns Hopkins Bloomberg School of Public Health. This study included 1442 mother-child pairs recruited at birth from October 27, 2002, to October 10, 2013, and followed up prospectively at Boston Medical Center.Main outcomes and measuresChild body mass index (BMI) z score, calculated according to US national reference data, and OWO, defined as BMI at or exceeding the 85th percentile for age and sex. Maternal RBC lead levels and plasma folate levels were measured in samples obtained 24 to 72 hours after delivery; child whole-blood lead level was obtained from the first pediatric lead screening.ResultsThe mean (SD) age of mothers and children was 28.6 (6.5) years and 8.1 (3.1) years, respectively; 50.1% of children were boys. The median maternal RBC lead level and plasma folate level were 2.5 (interquartile range [IQR], 1.7-3.8) μg/dL and 32.2 (IQR, 22.1-44.4) nmol/L, respectively. The median child whole-blood lead level and child BMI z score were 1.4 (IQR, 1.4-2.0) μg/dL and 0.78 (IQR, -0.08 to 1.71), respectively. Maternal RBC lead level was associated with child OWO risk in a dose-response fashion, with an odds ratio (OR) of 1.65 (95% CI, 1.18-2.32) for high maternal RBC lead level (≥5.0 μg/dL) compared with low maternal RBC lead level (<2.0 μg/dL). Child OWO was highest among children of OWO mothers with high RBC lead levels (adjusted OR, 4.24; 95% CI, 2.64-6.82) compared with children of non-OWO mothers with low RBC lead levels. Children of OWO mothers with high RBC lead levels had 41% lower OWO risk (OR, 0.59; 95% CI, 0.36-0.95; P = .03) if their mothers had adequate plasma folate levels (≥20.4 nmol/L) compared with their counterparts.Conclusions and relevanceIn this sample of a US urban population, findings suggest that maternal elevated lead exposure was associated with increased risk of intergenerational OWO independent of postnatal blood lead levels. Adequate maternal folate status appeared to be associated with lower OWO risk. If confirmed by additional studies, these findings have implications for prenatal lead screening and management to minimize adverse health consequences on children.

Dataset Information

Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study.

Publications

Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study.

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