Maternal Preconception Research Articles

Early Life Energy Balance: The Development of Infant Energy Expenditure and Intake in the Context of Obesity.

This review aims to provide a summary of the current knowledge on measurement tools and most recent evidence for prenatal and postnatal modulators of energy balance in young infants. The prevention of pediatric obesity depends upon curating the perfect imbalance of energy intake to energy expenditure, taking into consideration the energy needs for healthy growth. We summarize the recent evidence for the programming of fetal and infant metabolism influenced by maternal preconception health, prenatal metabolic milieu, and physical activity behaviors. In the early postnatal environment, caregiver feeding behaviors shape the extent of energy imbalance through dictating quantity and modality of infant energy intake. There are biological and behavioral contributors to improper infant energy imbalance. Furthermore, caregiver and clinician education on overfeeding and clinical tools to prescribe and monitor infant overgrowth are absent. Ultimately, the lack of high-quality and modern research of infant energy expenditure underpins the lack of advancement in clinical guidelines and the needed prevention of pediatric obesity.

Maternal weight status at conception predicts offspring body fat at age 11 years: population data from the Japan Kids Body Composition Study using dual-energy X-ray absorptiometry

BackgroundMaternal preconception overweight status has been reported to be associated with an increased risk of overweight offspring. However, there are no published population-based studies on the association between maternal preconception weight and offspring body fat measured by dual-energy X-ray absorptiometry (DXA). The present population-based retrospective cohort study aimed to examine the association between maternal weight at conception and offspring body fat measured by DXA.MethodsThe source population consisted of 5th-grade students (1244 students aged 11 years) registered at 8 municipal elementary schools in Kitakata, Fukuroi, Hamamatsu, and Himeji in Japan. The present analyses included 964 participants who provided complete information. Maternal body mass index (BMI) at conception was calculated using records in the Mother and Child Health Handbook (MCHH). Offspring body fat at age 11 years was measured with the same QDR-4500A DXA instrument in a mobile test room that was brought to each school. With regard to the prediction of excess fat in offspring, the area under the curve (AUC) calculated with receiver operating characteristic curve analysis was used to quantify the diagnostic accuracy of maternal BMI at conception.ResultsAdjusted odds ratios for excess body fat in offspring of the overweight mother group (odds ratios, 4.93 to 15.32) were significantly higher than those in the non-overweight mother group. For the prediction of excess offspring fat, AUCs and 95% confidence intervals for maternal BMI at conception were greater than 0.5.ConclusionMaternal overweight status at conception might be a risk factor for excess body fat in offspring. Maternal BMI values calculated using MCHH data have the potential to distinguish between the presence and absence of excess fat in the next generation.

Maternal periconception hyperglycemia, preconception diabetes, and risk of major congenital malformations in offspring.

What are the roles of maternal preconception diabetes and related periconceptional hyperglycemia on the risk of major congenital malformations (MCMs) in offspring? Maternal periconceptional glycated hemoglobin (HbA1c) levels over 5.6% were associated with an increased risk of congenital heart defects (CHD) in the offspring, and maternal preconception diabetes was associated with an increased risk of CHD, including when HbA1c levels were within euglycemic ranges. Maternal preconception diabetes has been linked with MCMs in the offspring. However, evidence concerning associations with specific periconception serum measures of hyperglycemia, and susceptibility of different organ systems, is inconsistent. Moreover, limited evidence exists concerning the effectiveness of antidiabetic medications in mitigating diabetes-related teratogenic risks. A large Israeli birth cohort of 46534 children born in 2001-2020. Maternal HbA1c test results were obtained from 90 days before conception to mid-pregnancy. Maternal diabetes, other cardiometabolic conditions, and MCMs in newborns were ascertained based on clinical diagnoses, medication dispensing records, and laboratory test results using previously validated algorithms. Associations were modeled using generalized additive logistic regression models with thin plate penalized splines. Maternal periconceptional HbA1c value was associated with CHD in newborns, with the risk starting to increase at HbA1c values exceeding 5.6%. The association between HbA1c and CHD was stronger among mothers with type 2 diabetes mellitus (T2DM) compared to the other diabetes groups. Maternal pre-existing T2DM was associated with CHD even after accounting for HbA1C levels and other cardiometabolic comorbidities (odds ratio (OR)=1.89, 95% CI 1.18, 3.03); and the OR was materially unchanged when only mothers with pre-existing T2DM who had high adherence to antidiabetic medications and normal HbA1c levels were considered. The rarity of some specific malformation groups limited the ability to conduct more granular analyses. The use of HbA1c as a time-aggregated measure of glycemic control may miss transient glycemic dysregulation that could be clinically meaningful for teratogenic risks. The observed association between pre-existing diabetes and the risk of malformations within HbA1c levels suggests underlying causal pathways that are partly independent of maternal glucose control. Therefore, treatments for hyperglycemia might not completely mitigate the teratogenic risk associated with maternal preconception diabetes. The work was supported by NIH grants K99ES035433, R01HD097778, and P30ES000002. None of the authors reports competing interests. N/A.

Quantifying the effect of interpregnancy maternal weight and smoking status changes on childhood overweight and obesity in a UK population-based cohort.

Maternal preconception and pregnancy exposures have been linked to offspring adiposity. We aimed to quantify the effect of changes in maternal weight and smoking status between pregnancies on childhood overweight/obesity (≥ 85th centile) and obesity (≥ 95th centile) rates in second children. Records for 5612 women were drawn from a population-based cohort of routinely collected antenatal healthcare records (2003-2014) linked to measured child body mass index (BMI) age 4-5 years. We applied the parametric G-formula to estimate the effect of hypothetical changes between pregnancy-1 and pregnancy-2 compared to the natural course scenario (without change) on child-2 BMI. Observed overweight/obesity and obesity in child-2 at age 4-5 years were 22.2% and 8·5%, respectively. We estimated that if all mothers started pregnancy-2 with BMI 18·5-24·9 kg/m² and all smokers stopped smoking, then child-2 overweight/obesity and obesity natural course estimates of 22.3% (95% CI 21.2-23.5) and 8·3% (7·6-9·1), would be reduced to 18.5% (17.4-19.9) and 6.2% (5.5-7.0), respectively. For mothers who started pregnancy-1 with BMI 18·5-24·9 kg/m², if all smokers stopped smoking, child-2 overweight/obesity and obesity natural course estimates of 17.3% (16.0-18.6) and 5·9% (5·0-6·7) would be reduced to 16.0% (14.6-17.3) and 4·9% (4·1-5·7), respectively. For mothers who started pregnancy-1 with BMI ≥30 kg/m², if BMI was 18·5-24·9 kg/m² prior to pregnancy-2, child-2 overweight/obesity and obesity natural course estimates of 38.6% (34.7-42.3) and 17·7% (15·1-20·9) would be reduced to 31.3% (23.8-40.0) and 12.5 (8.3-17.4), respectively. If BMI was 25.0-29.9 kg/m² prior to pregnancy-2, these estimates would be 34.5% (29.4-40.4) and 14.6% (11.2-17.8), respectively. Interventions supporting women to lose/maintain weight and quit smoking between pregnancies could help reduce rates of overweight/obesity and obesity in second children. The most effective interventions may vary by maternal BMI prior to the first pregnancy.

Maternal Preconception COVID-19 Vaccination and Its Protective Effect on Infants after a Breakthrough Infection during Pregnancy.

The transplacental vertical transfer of maternal antibodies was determined to be a crucial factor in conferring protective immunity to infants following delivery, and this study aimed to evaluate the protective effect of maternal preconception COVID-19 vaccination on infants. A prospective cohort study was conducted at the National Clinical Medical Research Center for Child Health and Diseases in Chongqing, China, spanning from July 2022 to April 2023. The study included infants from mothers with a preconception COVID-19 vaccination and (or) a SARS-CoV-2 infection during pregnancy. Titers of SARS-CoV-2 immunoglobulin G (IgG) and cross-neutralizing activity against SARS-CoV-2 variants were detected. In this cohort study comprising 158 infants, it was observed that infants born to mothers who experienced a pregnancy-related breakthrough infection following a preconception vaccination had the highest titers of SARS-CoV-2 IgG and cross-neutralizing antibody activity against different variants compared to those with either of these factors alone. The transplacental vertical transmission of anti-SARS-CoV-2 antibodies decreased significantly with increasing age, from 3.16 ODs at birth to 2.29 ODs at two months, and persisted for approximately four months after birth. The predominant subclass of passively transmitted antibodies via the placenta was found to be IgG1, and a positive correlation was observed between the titers of SARS-CoV-2 IgG and IgG1 (R = 0.59, p < 0.001; Slope: 0.49 ± 0.070, p < 0.001). Maternal preconception COVID-19 vaccination represents a promising immunological strategy for conferring postnatal protection to infants, especially during the period of heightened risk of exposure to SARS-CoV-2 infection. It is imperative to underscore the significance of vaccination for women who are preparing to become pregnant or are pregnant, and concerted efforts must be made to promote vaccination among eligible women.

Maternal Hypertension and Fecundability: A Population-Based Cohort Study.

The association of hypertension and blood pressure control with fecundability among women is not yet elucidated. The purpose of this study was to evaluate the hypothesis that maternal preconception hypertension would be associated with reduced fecundability and that blood pressure control could reduce excess risk. Using the National Free Preconception Checkup Projects in Guangdong Province, China, 1422 couples whose female partners had been diagnosed with hypertension and 997 703 reference couples whose female partners were without hypertension were included in this prospective cohort study. Fecundability was measured by time to pregnancy (TTP) and infertility (TTP >12 months). Compared with women without hypertension, those with controlled hypertension (time ratio, 1.47 [95% CI, 1.24-1.73]) or uncontrolled hypertension (time ratio, 1.59 [95% CI, 1.34-1.90]) were associated with prolonged TTP and increased risk of infertility (relative risk, 1.19 [95% CI, 1.09-1.31]; relative risk, 1.24 [95% CI, 1.14-1.34]). However, using instrumental variable analyses, there was no significant association between blood pressure control and TTP (time ratio, 0.68 [95% CI, 0.34-1.36]; P=0.270) or infertility (relative risk, 0.97 [95% CI, 0.70-1.34]; P=0.849) among women with hypertension. These results were consistent in the propensity score matching and inverse probability of treatment weighting analyses. Maternal hypertension, with or without controlled blood pressure, was independently associated with prolonged TTP and an increased risk of infertility. These findings may provide insights for the implementation of preconception hypertension screening and the design of future trials.

Преконцептивное облучение матерей: Риск фетоинфантильных потерь

Safety of female personnel exposed to occupational radiation is still a topical issue of radiation epidemiology. Mayak Production Association is the first Russian atomic enterprise and women made a quarter of its personnel. Fetal and infant losses (FILs) that include stillbirths and infant mortality could be used as an important criterion for assessing the effects of maternal preconception (prior to conception) exposure. The aim of this study was to assess FILs risk among the offspring of female Mayak PA workers exposed to occupational preconception external gamma-radiation. A retrospective analysis was performed among 15307 children born in 1949–1973; mothers of 4880 of them were Mayak PA workers. FILs were analyzed taking into account sex of the offspring, period of their birth, nosologies, parental age, and dose categories of preconception exposure. Methods of non-parametrical statistics were used and calculation of relative risk was performed with 95 % confidence interval. In general, fetal and infant losses demonstrated no statistical differences, 44.5 for 103 in the main group, 38.7 for 103 in the reference group, χ2 =2.79, p = 0.95. A statistically significant increase of FILs, stillbirths and infantile mortality was detected among the offspring with only their mothers working at Mayak PA. Dynamics analysis established the period from 1949 to 1953, in which FILs, stillbirths and infantile mortality were higher among the offspring of exposed mothers. Statistically significant differences in the FILs structure were obtained for fetal death that was more often registered in the main group, 3.48 vs 1.34 for 103, χ2 = 7.54, p = 0.006. FILs risk among mothers working at Mayak PA aged under 20 was statistically significantly higher for girls, 2.42 (1.25–4.67), and for both sexes, 2.16 (1.37–3.4). FILs were associated with the dose range of preconception external gamma-radiation of mothers from 0.16 mGy to 3006 mGy. The study also established certain categories of preconception exposure of the ovaries with significantly higher stillbirth risk in the main group as opposed to the reference one.

Preconception maternal exposure: Risk of fetal and infant losses

Safety of female personnel exposed to occupational radiation is still a topical issue of radiation epidemiology. Mayak Production Association is the first Russian atomic enterprise and women made a quarter of its personnel. Fetal and infant losses (FILs) that include stillbirths and infant mortality could be used as an important criterion for assessing the effects of maternal preconception (prior to conception) exposure. The aim of this study was to assess FILs risk among the offspring of female Mayak PA workers exposed to occupational preconception external gamma-radiation. A retrospective analysis was performed among 15307 children born in 1949–1973; mothers of 4880 of them were Mayak PA workers. FILs were analyzed taking into account sex of the offspring, period of their birth, nosologies, parental age, and dose categories of preconception exposure. Methods of non-parametrical statistics were used and calculation of relative risk was performed with 95 % confidence interval. In general, fetal and infant losses demonstrated no statistical differences, 44.5 for 103 in the main group, 38.7 for 103 in the reference group, χ2 =2.79, p = 0.95. A statistically significant increase of FILs, stillbirths and infantile mortality was detected among the offspring with only their mothers working at Mayak PA. Dynamics analysis established the period from 1949 to 1953, in which FILs, stillbirths and infantile mortality were higher among the offspring of exposed mothers. Statistically significant differences in the FILs structure were obtained for fetal death that was more often registered in the main group, 3.48 vs 1.34 for 103, χ2 = 7.54, p = 0.006. FILs risk among mothers working at Mayak PA aged under 20 was statistically significantly higher for girls, 2.42 (1.25–4.67), and for both sexes, 2.16 (1.37–3.4). FILs were associated with the dose range of preconception external gamma-radiation of mothers from 0.16 mGy to 3006 mGy. The study also established certain categories of preconception exposure of the ovaries with significantly higher stillbirth risk in the main group as opposed to the reference one.

Pre-delivery BMI and the Accuracy of Fetal Weight Estimation in Very Preterm Infants

ObjectivesTo examine the relation between maternal pre-delivery BMI and the accuracy of sonographic estimated fetal weight (EFW) in very preterm infants (<32 weeks gestation). MethodsThis retrospective study included singleton infants born between January 2010 and March 2023, at gestational ages 230 to 316 weeks, at a tertiary university-affiliated hospital. Absolute weight, percentage error, absolute percentage error, and overestimation and underestimation of EFW were compared between women with pre-delivery normal weight (BMI 18.5–24.99 kg/m2), overweight (BMI 25.0–29.99 kg/m2), and obesity (BMI >35.0 kg/m2). Multivariate linear regression analyses adjusted for potential confounders were performed to assess relations of maternal pre-conception and of pre-delivery BMI, with EFW accuracy. ResultsIncluded were 286 pregnancies. The absolute difference, percentage error, absolute percentage error, error within the 10% range, and underestimation or overestimation of EFW were similar between the groups. The multivariate linear regression analyses did not show significant associations of pre-conceptional BMI or of pre-delivery BMI with the percentage error. However, for small for gestational age compared to appropriate for gestational age fetuses, the percentage error was greater (8.9% vs. –0.6%, β = 0.35, P < 0.001) and the absolute percentage error was greater (11.0% vs. 6.7%, P < 0.001). Small for gestational age fetuses were at risk of fetal weight overestimation (percentage error exceeding 15%); OR 7.20 (95% CI 2.91–17.80). ConclusionsMaternal pre-delivery BMI was not found to be related to EFW accuracy in very preterm infants. Nevertheless, EFW should be interpreted carefully, as it may underdiagnose poor fetal growth in this population.

Influence of gestational window on offspring vascular health in rodents with in utero exposure to electronic cigarettes.

Studies have shown cerebrovascular dysfunction in offspring with full-gestational electronic cigarette (Ecig) exposure, but little is known about how individual trimester exposure impacts offspring health. This study aimed to determine if there is a critical window during gestation that contributes to vascular and anxiety-like behavioural changes seen with full-term exposure. To test this, rats were time-mated, and the pregnant dams were randomly assigned to Ecig exposure during first trimester (gestational day, GD2-7), second trimester (GD8-14), third trimester (GD15-21) or full-term gestation (GD2-21). We also assessed the effect of maternal preconception exposure. Both male and female offspring from all maternal exposure conditions were compared to offspring from dams under ambient air (control) conditions. Ecig exposure consisted of 60-puffs/day (5days/week) using either 5 or 30watts for each respective exposure group. We found that maternal exposure to Ecig in the second and third trimesters resulted in a decrease (23-38%) in vascular reactivity of the middle cerebral artery (MCA) reactivity in 3- and 6-month-old offspring compared to Air offspring. Further, the severity of impairment was comparable to the full-term exposure (31-46%). Offspring also displayed changes in body composition, body mass, anxiety-like behaviour and locomotor activity, indicating that Ecigs influence neurodevelopment and metabolism. Maternal preconception exposure showed no impact on offspring body mass, anxiety-like behaviour, or vascular function. Thus, the critical exposure window where Ecig affects vascular development in offspring occurs during mid- to late-gestation in pregnancy, and both 5W and 30W exposure produce significant vascular dysfunction compared to Air. KEY POINTS: Exposure to electronic cigarettes (Ecigs) is known to increase risk factors for cardiovascular disease in both animals and humans. Maternal Ecig use during pregnancy in rodents is found to impair the vascular health of adolescent and adult offspring, but the critical gestation window for Ecig-induced vascular impairment is not known. This study demonstrates Ecig exposure during mid- and late-gestation (i.e. second or third trimester) results in impaired endothelial cell-mediated dilatation (i.e. middle cerebral artery reactivity) and alters anxiety-like behaviour in offspring. Maternal exposure prior to conception did not impact offspring's vascular or anxiety-like behavioural outcomes. Rodent models have been a reliable and useful predictor of inhalation-induced harm to humans. These data indicate maternal use of Ecigs during pregnancy should not be considered safe, and begin to inform clinicians and women about potential long-term harm to their offspring.

The efficacy of evening primrose seed oil supplements on ART outcomes: A triple-blinded randomized placebo-controlled clinical trial

BackgroundEvening primrose oil (EPO) has been extensively documented for its potential benefits in various medical conditions, including gestational diabetes, inflammatory diseases, cyclic breast pain, cancer, premenstrual syndrome, menopausal syndrome, and female reproductive disorders. ObjectivesThe aim of this study was to investigate the impact of evening primrose oil (EPO) supplementation on the outcomes of assisted reproductive technology (ART). MethodsA randomized, triple-blinded, placebo-controlled clinical trial was conducted. A total of 84 infertile women who were candidates for intracytoplasmic sperm injection (ICSI) were randomly assigned to either the EPO supplementation group or the placebo (p) group with a 1:1 ratio. The EPO capsule was given from day 1–2 of the ART cycle at a dosage of 1000 mg every eight hours for two weeks. Finally, the ART outcomes parameters as well as the treatment side effects were evaluated. ResultsThe results illustrated no statistically significant disparities between the groups in terms of the number of oocytes retrieved, ovarian sensitivity index (OSI), rate of fertilization, and number and quality of embryos (p>0.05). However, a notably enhanced incidence of pregnancy and implantation rates in the EPO group was observed when compared to the P group (42.9 % vs. 17.4 % and 23±30.5 % vs. 10.87±26 %, respectively). Moreover, none of the patients experienced side effects from the intervention. ConclusionsEPO consumption for two weeks could improve ART outcomes by increasing implantation and pregnancy rates without significantly affecting the number of mature oocytes, rate of fertilization, and the quantity and quality of embryos. These findings highlight the significance of a maternal preconception diet.

Maternal Preconception Omega-6, Omega-3, and Omega-6:Omega-3 Intake and Uterine Artery Indices in Mid-Gestation.

Maternal preconception diet influences pregnancy health and fetal outcomes. We examined the relationship between preconception fatty acid (FA) intake and uterine artery indices in mid-gestation in a large, heterogeneous cohort of nulliparous individuals. This is a secondary analysis of the nuMom2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be) study. Dietary ω-6 and ω-3 FA intake was assessed with food frequency questionnaires and uterine artery indices were obtained via Doppler studies in the second trimester. For our primary outcome of pulsatility index (PI) > 1.6, we compared proportions by each dichotomous FA exposure and tested differences with chi-square test. For PI > 1.6, odds ratio for the unfavorable FA quartile compared with remaining quartiles for the exposures were 0.96 to 1.25, p = 0.157 (ω-6 FA); 0.97 to 1.26, p = 0.124 (ω-3 FA); 0.87 to 1.14, p = 1.00 (ω-6:ω-3 FA ratio). No significant associations between self-reported maternal preconception ω-6 and ω-3 FA intake and uterine artery Doppler indices measured during the second trimester were observed. · Maternal diet impacts pregnancy health/fetal outcomes.. · ω-3 and ω-6 FA intake influences cardiovascular health.. · FA intake may affect blood flow to fetoplacental unit.. · Results are limited by inadequate adherence to dietary recommendations..

Association of ambient PM2.5 and its components with in vitro fertilization outcomes: The modifying role of maternal dietary patterns

Despite the associations of dietary patterns and air pollution with human reproductive health have been demonstrated, the interaction of maternal preconception diet and PM2.5 and its components exposure on in vitro fertilization (IVF) treatment outcomes has not been investigated. A total of 2688 couples from an ongoing prospective cohort were included. Principle component analysis with varimax rotation was performed to determine dietary patterns. One-year and 85-day average PM2.5 and its components exposure levels before oocyte retrieval were estimated. Generalized linear regression models were conducted to assess the association of dietary patterns and PM2.5 and its components exposure with IVF outcomes. Interactive effects of dietary patterns on the association between PM2.5 and its components and IVF outcomes were evaluated by stratified analyses based on different dietary patterns. A positive association between the “Fruits-Vegetables-Dairy” pattern and normal fertilization (p-trend = 0.009), Day 3 available embryos (p-trend = 0.048), and top-quality embryos (p-trend = 0.041) was detected. Conversely, women with higher adherence to the “Puffed food-Bakery-Candy” pattern were less likely to achieve Day 3 available embryos (p-trend = 0.042) and top-quality embryos (p-trend = 0.030), clinical pregnancy (p-trend = 0.049), and live birth (p-trend = 0.020). Additionally, increased intake of animal organs and seafood improved the odds of live birth (p-trend = 0.048). Exposure to PM2.5, SO42-, organic matter (OM), and black carbon (BC) had adverse effects on embryo development and pregnancy outcomes. Furthermore, our findings indicated that the effects of PM2.5 components exposure on normal fertilization and embryo quality were modified by the “Grains-Tubers-Legumes”. Moreover, moderate intake of animal organs and seafood appeared to attenuate the effect of NO3- and NH4+ on the risk of early abortion. Our findings provide human evidence of the interaction between dietary patterns and PM2.5 exposure on IVF outcomes during preconception, implicating the potential for dietary interventions in infertile women to improve reproductive outcomes under conditions of unavoidable ambient air-pollutant exposure.

The associations between pre-conception urinary phthalate concentrations, the serum metabolome, and live birth among women undergoing assisted reproduction

BackgroundPhthalates are ubiquitous endocrine disruptors. Past studies have shown an association between higher preconception urinary concentrations of phthalate metabolites and lower fertility in women; however, the biological mechanisms remain unclear. Our exploratory study aimed to understand the metabolites and pathways associated with maternal preconception phthalate exposure and examine if any may underline the association between phthalate exposure and live birth using untargeted metabolomics. MethodsParticipants (n = 183) were part of the Environment and Reproductive Health (EARTH) study, a prospective cohort that followed women undergoing in vitro fertilization (IVF) at the Massachusetts General Hospital Fertility Center (2005–2016). On the same day, women provided a serum sample during controlled ovarian stimulation, which was analyzed for metabolomics using liquid chromatography coupled with high-resolution mass spectrometry and two chromatography columns, and a urine sample, which was analyzed for 11 phthalate metabolites using targeted approaches. We used multivariable generalized linear models to identified metabolic features associated with urinary phthalate metabolite concentrations and live birth, followed by enriched pathway analysis. We then used a meet-in-the-middle approach to identify overlapping pathways and features. ResultsMetabolic pathway enrichment analysis revealed 43 pathways in the C18 negative and 32 pathways in the HILIC positive columns that were significantly associated (p < 0.05) with at least one of the 11 urinary phthalate metabolites or molar sum of di-2-ethylhexyl phthalate metabolites. Lipid, amino acid, and carbohydrate metabolism were the most common pathways associated with phthalate exposure. Five pathways, tryptophan metabolism, tyrosine metabolism, biopterin metabolism, carnitine shuttle, and vitamin B6 metabolism, were also identified as being associated with at least one phthalate metabolite and live birth following IVF. ConclusionOur study provides further insight into the metabolites and metabolomics pathways, including amino acid, lipid, and vitamin metabolism that may underlie the observed associations between phthalate exposures and lower fertility in women.

Educational Opportunities and Benefits of a Maternal Fetal Medicine-Based Preconception Clinic

Educational Opportunities and Benefits of a Maternal Fetal Medicine-Based Preconception Clinic

Maternal preconception and prenatal stressful life events in association with child neurodevelopmental outcome in MARBLES: A high familial likelihood cohort

BackgroundPrenatal stressful life events (SLEs) have been inconsistently associated with autism spectrum disorder (ASD). Mothers who are already raising a child with ASD could experience compounding effects of prenatal SLEs. This study prospectively examined prenatal SLEs in association with child neurodevelopmental outcomes in a high familial likelihood cohort. MethodsParticipants were 317 mother-child pairs from the Markers of Autism Risk in Babies: Learning Early Signs (MARBLES) Study, where pregnant women have previously had at least one other child with ASD. Mothers were interviewed during and at the end of pregnancy about whether they had experienced any of 7 SLE categories relating to finance, marriage, death, and more.Child neurodevelopment at three years old was classified as typically developing (TD), Non-TD, or ASD using an algorithm applied to Autism Diagnostic Observation Schedule (ADOS) and the Mullen Scales of Early Learning (MSEL) scores. Relative risk ratios (RRR) with TD as the reference outcome were estimated using multinomial logistic regression. ResultsExperiencing legal problems was significantly associated with an increased relative risk of child Non-TD (RRR 3.75; 95% CI: 1.15, 12.22). However, this finding was based on a small sample size (n = 6) and should be interpreted with caution. All other associations with Non-TD and ASD were non-significant. ConclusionsFindings agree with previous literature suggesting prenatal SLEs might not increase likelihood for ASD and most were not associated with Non-TD. Future studies measuring perceived stress or stress biomarkers are warranted to further understand the true association of prenatal stress and likelihood of ASD.

The mediation effect of breastfeeding duration on the relationship between maternal preconception BMI and childhood nutritional risk.

Higher maternal preconception body mass index (BMI) is associated with lower breastfeeding duration, which may contribute to the development of poor child eating behaviours and dietary intake patterns (components of nutritional risk). A higher maternal preconception BMI has been found to be associated with higher child nutritional risk. This study aimed to determine whether breastfeeding duration mediated the association between maternal preconception BMI and child nutritional risk. In this longitudinal cohort study, children ages 18 months to 5 years were recruited from The Applied Research Group for Kids (TARGet Kids!) in Canada. The primary outcome was child nutritional risk, using The NutriSTEP®, a validated, parent-reported questionnaire. Statistical mediation analysis was performed to assess whether total duration of any breastfeeding mediated the association between maternal preconception BMI and child nutritional risk. This study included 4733 children with 8611 NutriSTEP® observations. The mean (SD) maternal preconception BMI was 23.6 (4.4) and the mean (SD) breastfeeding duration was 12.4 (8.0) months. Each 1-unit higher maternal preconception BMI was associated with a 0.081 unit higher nutritional risk (95% CI (0.051, 0.112); p < 0.001) (total effect), where 0.011(95% CI (0.006, 0.016); p < 0.001) of that total effect or 13.18% (95% CI: 7.13, 21.25) was mediated through breastfeeding duration. Total breastfeeding duration showed to mediate part of the association between maternal preconception BMI and child nutritional risk. Interventions to support breastfeeding in those with higher maternal preconception BMI should be evaluated for their potential effect in reducing nutritional risk in young children.

Maternal and Paternal Preconception Serum Concentrations of Per and Polyfluoroalkyl Substances in Relation to Birth Outcomes.

Prenatal per and polyfluoroalkyl substances (PFAS) exposure is associated with adverse birth outcomes. There is an absence of evidence on the relationship between maternal and paternal preconception PFAS exposure and birth outcomes. This study included 312 mothers and 145 fathers with a singleton live birth from a preconception cohort of subfertile couples seeking fertility treatment at a U.S. clinic. PFAS were quantified in serum samples collected before conception. Gestational age (GA) and birthweight (BW) were abstracted from delivery records. We also assessed low birthweight (BW < 2500 g) and preterm birth (GA < 37 completed weeks). We utilized multivariable linear regression, logistic regression, and quantile-based g computation to examine maternal or paternal serum concentrations of individual PFAS and mixture with birth outcomes. Maternal serum concentrations of perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS), and the total PFAS mixture were inversely associated with birthweight. Maternal PFOS concentration was associated with a higher risk of low birthweight. Conversely, paternal PFOS and PFHxS concentrations were imprecisely associated with higher birthweight. No associations were found for gestational age or preterm birth. The findings have important implications for preconception care. Future research with larger sample sizes would assist in validating these findings.

Parental preconception stress in zebrafish induces long-lasting anxiety in offspring

The growth and function of the vertebrate brain are impacted by environmental stimuli and early life stress. Adults who experience chronic stress during early life are more likely to suffer various neurodevelopmental and health issues. However, our understanding of how these specific environmental signals at different developmental stages affect brain development is poorly understood. In this study, we investigated if stress in parents prior to conception modulates neurodevelopment in offspring. We used a chronic unpredictable stress model adapted to zebrafish, which is an increasingly popular vertebrate model in neuroscience research to investigate the effects of both maternal and paternal preconception stress on offspring behavior. We evaluated the responsiveness of three anxiety-related behavioral paradigms in zebrafish: the novel tank test, thigmotaxis, and shoaling behavior. We found larvae from stressed females exhibited anxiety-like behavior in a thigmotaxis assay. As these larvae matured into adults, they continued to exhibit anxiety-like behavior in a novel tank and shoaling behavioral assay. These studies indicate preconception stress exposure in parents can induce life-long alterations in offspring neurodevelopment. Further, these results expand the hypothesis that chronically elevated glucocorticoid signaling not only in stressed mothers, but also stressed dads can affect neurodevelopment in offspring. We propose that zebrafish may be a useful model to study the transgenerational effects of chronic stress mediated via the maternal and paternal line.

Preconception Blood Pressure and Adverse Pregnancy Outcomes: A Population-Based Cohort Study.

Adverse pregnancy outcomes (APOs) share clinical features and risk factors with cardiovascular disease and there is an increasing prevalence of hypertension among reproductive women. However, the associations between maternal preconception blood pressure (BP) and APOs remain controversial and inconclusive. This population-based cohort study used data of 567 127 mother-neonate-father triads from the National Free Preconception Checkup Project in Guangdong Province, China. Maternal BP levels within 1 year before pregnancy were classified using the American College of Obstetricians and Gynecologists definition of hypertension. The primary outcome was a composite of APOs, including preterm birth, small for gestational age, and perinatal infant death. Log-binomial and marginal structural binomial regressions were employed to estimate adjusted risk ratios and absolute risk differences, respectively. Compared with women with normal BP, women with elevated BP (adjusted risk ratio, 1.07 [95% CI, 1.05-1.09]; absolute risk difference, 1.03% [95% CI, 0.72%-1.29%]), hypertension (adjusted risk ratio, 1.25 [95% CI, 1.18-1.32]; and absolute risk difference, 3.42% [95% CI, 1.97%-5.42%]) had a higher risk of a composite of APOs. Compared with women with normal BP, women with elevated BP and hypertension had higher risks of multiple APOs, preterm birth, small for gestational age, and perinatal infant death. However, these associations attenuated with increasing duration of pregnancy preparation and were not statistically significant beyond 90 days of pregnancy preparation. Women with elevated BP or hypertension before pregnancy were associated with an increased risk of APOs. Preconception hypertension screening and control among women should not be ignored by policymakers, clinicians, and the general population.