Dataset Information

Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes: the Rotterdam Periconception Cohort.

ABSTRACT:

Study question

Is 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 answer

Women 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 (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, duration

A prospective tertiary hospital-based cohort study (the Rotterdam Periconceptional Cohort) was conducted from January 2010 to December 2020.

Participants/materials, setting, methods

We 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 chance

This 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 (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 findings

Our 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 number

NTR4356.

SUBMITTER: Schenkelaars N

PROVIDER: S-EPMC11373404 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Publications

Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes: the Rotterdam Periconception Cohort.

Schenkelaars N N Schoenmakers S S Rousian M M Willemsen S P SP Faas M M MM Steegers-Theunissen R P M RPM

Human reproduction (Oxford, England) 20240901 9

<h4>Study question</h4>Is 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?<h4>Summary answer</h4>Women 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 3r ...[more]

PMID: 39025484

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Project description:Study questionIs early embryonic size and growth in the first trimester of pregnancy associated with adverse birth outcomes?Summary answerLarger embryonic crown-rump length (CRL) and embryonic volume (EV) are associated with lower odds of adverse birth outcomes, especially small for gestational age (SGA).What is already knownPreterm birth, SGA, and congenital anomalies are the most prevalent adverse birth outcomes with lifelong health consequences as well as high medical and societal costs. In the late first and second trimesters of pregnancy, fetuses at risk for adverse birth outcomes can be identified using 2-dimensional ultrasonography (US).Study design, size, durationBetween 2009 and 2018, singleton pregnancies were enrolled in this ongoing prospective Rotterdam Periconception Cohort.Participants/materials, setting, methodsThis study included 918 pregnant women from a tertiary hospital in the Netherlands. Pregnancy dating was based on either a regular menstrual cycle (for natural pregnancies) or a conception date (for ART pregnancies). CRL and EV were measured using Virtual Reality software on 3-dimensional (3D) ultrasound scans, repeatedly performed around 7, 9, and 11 weeks of gestation. The main outcome measure was adverse birth outcome, defined as the composite of SGA (birth weight <10th percentile), preterm birth (<37th week of gestation), congenital anomalies (Eurocat criteria), stillbirth (>16th week of pregnancy), or early neonatal mortality (≤7 days of life). Reference curves for CRL and EV were constructed. Cross-sectional (CRL/EV <20th percentile at 7, 9, and 11 weeks of gestation) and longitudinal (CRL/EV growth trajectories between 6th and 13th weeks) regression analyses were performed, with adjustments for the participants' educational level, smoking, parity, age, BMI, geographical background, mode of conception, and fetal sex.Main results and the role of chanceOf the 918 pregnant women included, the median age was 32.3 years, and 404 (44%) pregnancies had been conceived via ART. In 199 (22%) pregnancies, there was an adverse birth outcome. Regression analyses showed that at 7 weeks of gestation onwards, embryos with a CRL <20th percentile had an ∼2-fold increased odds of adverse birth outcome (adjusted odds ratio (aOR) 2.03, 95% CI 1.21-3.39, P = 0.007). Similar associations were found for EV <20th percentile but were not statistically significant. These findings were mainly driven by the strong association between embryonic size and SGA (e.g. 7-week CRL: aOR 2.18 (1.16-4.09), P = 0.02; 9-week EV: aOR 2.09 (1.10-3.97, P = 0.02). Longitudinal growth trajectories of CRL, but not of EV, were associated with adverse birth outcomes. Both CRL and EV growth trajectories were associated with SGA.Limitations, reasons for cautionThe tertiary hospital population and the availability of sophisticated 3D-ultrasound techniques limit the generalizability of this study to general populations and settings.Wider implications of the findingsAlready very early in the first trimester of pregnancy, embryos with increased risks of an adverse birth outcome can be identified by using 3D-US and Virtual Reality. This expands the window of opportunity to enable the development of future interventions to potentially improve pregnancy outcomes and offspring health during their life-course.Study funding/competing interest(s)This work was funded by the Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. The authors declare no conflicts of interest.Trial registration numberNL4115.

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.

Dataset Information

Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes: the Rotterdam Periconception Cohort.

Study question

Summary answer

Study design, size, duration

Participants/materials, setting, methods

Main results and the role of chance

Wider implications of the findings

Study funding/competing interest(s)

Trial registration number

Publications

Periconceptional maternal supplement intake and human embryonic growth, development, and birth outcomes: the Rotterdam Periconception Cohort.

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