Long-term Offspring Outcomes Research Articles

Research Hotspots on Systemic Lupus Erythematosus in Pregnancy Based on Bibliometrics

Objective To explore the research hotspots on systemic lupus erythematosus (SLE) in pregnancy based on the bibliometric analysis of the related articles published from 2018 to 2023 and provide directions for the future research in this field. Methods PubMed,Web of Science,and Embase were searched for the articles on SLE in pregnancy that were published from January 1,2018 to December 31,2023.VOSviewer was used to visualize the high-frequency keywords in the selected articles. Results A total of 266 articles were selected,from which 25 high-frequency keywords were extracted.The bibliometric analysis showed that the available studies about SLE in pregnancy mainly focused on maternal complications,maternal and fetal outcomes,and medications.The studies were limited regarding the predictors,autoimmunity,immunotherapy,and long-term outcomes of offspring. Conclusion Maternal complications,maternal and fetal outcomes,and medications are currently hotspots in the research on SLE in pregnancy,while predictors,autoimmunity,immunotherapy,and long-term outcomes of offspring may become future research directions.

Vitamin K Antagonists for Pregnant Women With Antiphospholipid Antibodies: A Scoping Review.

To describe characteristics of published research on the safety and efficacy of vitamin K antagonists (VKA) for pregnant patients with antiphospholipid antibodies (aPL), including their methodological characteristics and knowledge gaps. This study followed the Joanna Briggs Institute methodology for scoping reviews and used the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews protocol system. Studies were primarily identified through searching electronic databases including MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. Study characteristics and outcomes were reported and described using customized charting tables. Of 1528 publications, 17 remained in the final analysis. These reported up to 190 VKA-treated aPL-positive pregnancies diagnosed as antiphospholipid syndrome (APS); pregnancy cases were likely overlapping in some publications. In the 17 reports, there were 723 individuals in comparison groups, including healthy pretreatment pregnancies and women with APS treated with standard therapies without VKA. However, only 4 (23.5%) of the 17 publications stated a study objective focusing on VKA use, of which only one was a full-length article. In addition, information on VKA doses, disease diagnostic criteria, and the long-term outcomes of offspring were largely absent. The current evidence is insufficient to assess VKA efficacy and safety profiles in aPL-positive pregnant patients. Studies with a defined focus on VKA use in this population are lacking, and reporting of key information is not consistent. The relative lack of knowledge of VKA use in pregnant women with APS is concerning, and efficacy and safety questions remain.

Long-term Neurobehavioral and Metabolic Outcomes in Offspring of Mothers With Diabetes During Pregnancy: A Large, Population-Based Cohort Study in Ontario, Canada.

Offspring of women with diabetes are at increased risk of developing neurobehavioral and cardiometabolic disorders, but there is scant evidence regarding the association between glycemic level during pregnancy and these long-term offspring outcomes. We conducted a population-based, cohort study of deliveries in Ontario between April 1991 and March 2018. Women had preexisting diabetes, gestational diabetes, or no diabetes. We applied a Cox proportional hazard model to examine the risk of developing attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and cardiometabolic outcomes in offspring and assessed the association between pregnancy HbA1c levels and risk of outcomes, adjusting for confounders. A total of 3,407,961 mother/infant pairs were followed up to 29 years. Using a Cox proportional hazard model, offspring of women with type 1 diabetes had the highest risk of ADHD (adjusted hazard ratio [aHR] 1.43 [95% CI 1.36-1.49]), ASD (aHR 1.94 [1.80-2.09]), diabetes (aHR 4.73 [4.34-5.16]), hypertension (aHR 2.32 [2.07-2.61]), and cardiovascular disease (CVD) (aHR 1.72 [1.56-1.90]), followed by offspring of women with type 2 diabetes and gestational diabetes compared with those unexposed. Among women with preexisting diabetes, there was an association between level of pregnancy HbA1c and offspring diabetes (aHR 1.22 [95% CI 1.12-1.32]), hypertension (aHR 1.42 [1.29-1.57]), and CVD (aHR 1.20 [1.11-1.29]) but no statistically significant association with neurobehavioral outcomes. In utero exposure to maternal diabetes was associated with an increase in ADHD, ASD, and cardiometabolic outcomes in offspring, with differences seen across diabetes subtypes. Pregnancy glycemia was associated with cardiometabolic outcomes, but not neurobehavioral outcomes, and provides a potentially modifiable risk factor to decrease cardiometabolic outcomes in offspring.

The influence of advanced maternal age on congenital malformations, short- and long-term outcomes in offspring of nulligravida: a Korean National Cohort Study over 15 years.

To assess the influence of advanced maternal age on congenital malformations, short- and long-term outcomes in offspring of nulligravida. A retrospective study was conducted using the Korean National Health Insurance Service database spanning from January 2005 to December 2019. All live-born offspring of nulligravida (n=3,685,817) were included. The maternal age was subdivided into the following subgroups: <25 years (n=153,818), 25-29 years (n=845,355), 30-34 years (n=1,738,299), 35-39 years (n=787,530), 40-44 years (n=151,519), and >44 years (n=9,296). Outcomes were assessed based on International Classification of Diseases-10 codes. Adjusted odds ratios (aOR) were calculated with the group of 25-29 years as a reference. Most congenital malformations showed an age dependent increase, but cleft lip and abdominal wall defect exhibited a U-shape curve, indicating an increase even in those <25 years old. Similarly, various disorders included in the neonatal composite outcomes from short-term outcomes showed aged dependent escalation. However, the preterm birth from the short-term outcome and most of the long-term developmental outcomes, except for motor developmental delay and Tics, showed a U-shaped pattern. The aOR of autism and cerebral palsy, showing the most obvious U-shaped curved in the long-term outcomes, was 1.50 (95% confidence interval [CI], 1.24-1.82) and 1.54 (95% CI, 1.17-2.03), respectively in the group >44 years old and 1.18 (95% CI, 1.11-1.25) and 1.19 (95% CI, 1.09-1.30) in <25 years old group. Overall, an advanced maternal age has an age-dependent correlation with most congenital malformations and shortand long-term outcomes of neonates.

Maternal and long-term offspring outcomes of obesity during pregnancy.

Obesity`s prevalence is rising in women of reproductive age worldwide and has become the most common medical condition at this age group. Besides, its occurrence is also rising during pregnancy. This condition not only increases the risk of noncommunicable diseases on the mother, such as cardiovascular disease and diabetes, but also transfers this risk to the offspring. This is a narrative review based on scientific and review articles on the matter. Obesity is associated with an increased risk of gestational diabetes mellitus, gestational hypertension and preeclampsia, venous thromboembolism, infection, and mental health problems. Furthermore, it has an impact on the progress of labor and induction matters. Regarding offspring outcomes, it is related to higher incidence of congenital anomalies, perinatal mortality, and the occurrence of large for gestational age newborns. Still, it has implications on cardiometabolic risk and neurodevelopment in offspring. It is, therefore, imperative to encourage the adoption of healthy lifestyles, especially in the peri-conception and interpregnancy periods. Likewise, there must be support in the multidisciplinary monitoring of these pregnant women to minimize associated complication rates.

Glucocorticoid use and varying doses on the long-term outcomes of offspring born to patients with systemic lupus erythematosus.

This study aims to assess the impact of non-fluorinated glucocorticoid use and varying doses on the long-term physical, neurological, and social-emotional development outcomes of offspring born to patients with systemic lupus erythematosus (SLE). The goal is to provide guidance on the appropriate dosage of glucocorticoids during pregnancy in SLE patients. We conducted a follow-up study on the offspring of SLE patients who had pregnancies and were admitted to our obstetrics department between January 1, 2016, and September 30, 2021. Patients who received immunosuppressants and dexamethasone were excluded from the study. The SLE patients were categorized into three groups based on their glucocorticoid use during pregnancy: hormone-free group, ≤ 10mg/day group, and > 10mg/day group (equivalent to prednisone). Most patients in the three groups were used hydroxychloroquine during pregnancy. We assessed the physical development status, including weight, height (length), and other relevant factors in three groups. Additionally, we utilized the Age and Stages Questionnaires, Third Edition (ASQ-3) to evaluate the development of communication, gross motor, fine motor, problem-solving, and personal-social. The social-emotional development status was assessed using the Age and Stages Questionnaires: Social-Emotional (ASQ: SE). We standardized the weight, height (length), body mass index, and ASQ-3 domain scores of children of different ages and genders into Z-scores for comparison. The results of this study demonstrated no statistically significant differences in the long-term physical development, neurological development, and social-emotional development outcomes of the offspring of SLE patients in three groups. However, while not reaching statistical significance, it was found that the offspring of the > 10mg/day group had lower height (length) Z-scores and communication Z-scores compared to the other groups. Conclusion: The use of non-fluorinated glucocorticoids during pregnancy and varying doses did not have a significant impact on the long-term physical, neurological, and social-emotional development outcomes of offspring born to SLE patients. However, the offspring of SLE patients treated with glucocorticoids > 10mg/day during pregnancy may be necessary to strengthen the monitoring of height (length) and communication skills in the long term. What is Known: • Fetal exposure to glucocorticoids can have implications for the development of multiple systems and may persist after birth, potentially increasing the risk of neurological abnormalities and other diseases. • There is limited research on the long-term development of offspring born to SLE patients, especially the patients treated with glucocorticoids. What is New: • The use of non-fluorinated glucocorticoids during pregnancy and varying doses did not have a significant impact on the long-term outcomes of offspring born to SLE patients. • The offspring of SLE patients treated with glucocorticoids >10 mg/day during pregnancy may be necessary to strengthen the monitoring of height (length) and communication skills in the long term.

Perinatal and childhood outcomes of children born to female cancer survivors in South Korea

Despite the increasing number of female cancer survivors, uncertainty remains regarding potential adverse health outcomes for their offspring. Comprehensive population-based studies would be invaluable for female cancer survivors in making decisions about their future. This study uses the National Health Information Database to investigate perinatal and long-term outcomes of offspring born to mothers with a history of cancer. In a South Korean cohort of 95,264 women aged 15–40 diagnosed with cancer between 2007 and 2010, we evaluated the outcomes of 15,221 children born to 11,092, cancer survivors. We selected 147,727 women without a history of cancer and 201,444 children as a control group. Our study found that children of female cancer survivors have a significantly higher odds ratio of primary outcomes including preterm birth, low birth weight, neonatal intensive care unit admission, and death. While there was no difference in the rate of death within 1 year of birth between the two groups, the total death rate during the follow-up period was significantly higher in children born to mothers with cancer. After adjusting for gestational age and birth weight, there was no statistically significant increased hazard ratio of secondary outcomes including cancer, chromosomal abnormalities, cerebral palsy, delayed development, epilepsy, language disorder, or hearing impairment.

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

BackgroundSerotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects. We investigated associations between maternal metabolic parameters—pre-pregnancy body mass index (pBMI), gestational weight gain (GWG), and glucose tolerance status (GTS), i.e., gestational diabetes mellitus (GDM) versus normal glucose tolerance (NGT)—and cord blood methylation of SLC6A4, MAOA, and HTR2A in participants from our PlaNS birth cohort. CpG sites (15, 9, and 2 in each gene, respectively) were selected based on literature and in silico data. Methylation levels were quantified by bisulfite pyrosequencing. We also examined the stability of methylation patterns in these genes in circulating blood cells from birth to adolescence using longitudinal DNA methylation data from the ARIES database.ResultsNone of the 203 PlaNS mothers included in this study had preexisting diabetes, 99 were diagnosed with GDM, and 104 had NGT; all neonates were born at full term by planned Cesarean section. Methylation at most CpG sites differed between male and female newborns. SLC6A4 methylation correlated inversely with maternal pBMI and GWG, while methylation at HTR2A site -1665 correlated positively with GWG. None of the maternal metabolic parameters statistically associated with MAOA methylation. DNA methylation data in cord blood and peripheral blood at ages 7 and 15 years were available for 808 participants from the ARIES database; 4 CpG sites (2 in SLC6A4 and 2 in HTR2A) overlapped between the PlaNS and ARIES cohorts. A positive correlation between methylation levels in cord blood and peripheral blood at 7 and 15 years of age was observed for both SLC6A4 and HTR2A CpG sites.ConclusionsMethylation of 5-HT regulating genes in cord blood cells is influenced by neonatal sex, with maternal metabolism playing an additional role. Inter-individual variations present in circulating blood cells at birth are still pronounced in childhood and adolescence.

Long-term outcomes of offspring from multiple gestations: a two-sample Mendelian randomization study on multi-system diseases using UK Biobank and FinnGen databases

BackgroundAssisted reproductive technologies (ART) have increased the incidence of multiple births, which can have a negative impact on maternal and offspring health. The study aimed to investigate the association between genetically predicted multiple birth and the risk of 42 common diseases of the nervous, psychiatric, cardiovascular, respiratory, digestive, and endocrine systems.MethodsThe study utilized two-sample Mendelian randomization (MR) analysis to explore the potential causal relationship between genetically predicted multiple birth and the genetically predicted risk of diseases. The study used the FinnGen and UK Biobank datasets for analysis.ResultsThe study found no significant causal relationship between multiple birth and psychiatric disorders. However, the lower limits of the 95% confidence intervals for bipolar affective disorder and anxiety disorders were not robust, indicating a need for further investigation. The study found that multiple birth may be a strong risk factor for infantile cerebral palsy, and caution is necessary in both natural and ART multiple births. The study revealed a potential causal relationship between multiple birth and coronary heart disease, ischemic heart disease, and deep vein thrombosis, which may be related to abnormal intrauterine environments in multiple pregnancies. Surprisingly, multiple birth appears to have a protective effect against some respiratory diseases, such as chronic obstructive pulmonary disease and asthma.ConclusionsThe study highlights the need for caution regarding the risk of infantile cerebral palsy, cardiovascular diseases, and psychiatric disorders in multiple birth. Our study can lead to the development of preventive strategies and improved clinical management for affected infants.

MP01-06 DELTA-9-TETRAHYDROCANNABINOL USE ALTERS SPERM DNA METHYLATION IN RHESUS MACAQUES

You have accessJournal of UrologyCME1 Apr 2023MP01-06 DELTA-9-TETRAHYDROCANNABINOL USE ALTERS SPERM DNA METHYLATION IN RHESUS MACAQUES Jason Hedges, Lyndsey Shorey-Kendrick, Carol Hanna, Jasper Bash, Eliot Spindel, Charles Easley, Susan Murphy, and Jamie Lo Jason HedgesJason Hedges More articles by this author , Lyndsey Shorey-KendrickLyndsey Shorey-Kendrick More articles by this author , Carol HannaCarol Hanna More articles by this author , Jasper BashJasper Bash More articles by this author , Eliot SpindelEliot Spindel More articles by this author , Charles EasleyCharles Easley More articles by this author , Susan MurphySusan Murphy More articles by this author , and Jamie LoJamie Lo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003212.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cannabis is the most commonly used drug by reproductive age males. Our objective was to determine the effect of chronic delta-9-tetrahydrocannabinol (THC) use on the sperm epigenome and whether these changes are permanent or temporary with discontinuation of THC in a rhesus macaque (RM) model. METHODS: We performed whole genome bisulfite sequencing (WGBS) of DNA extracted from sperm collected from 6 adult RM at baseline (pre-THC), at a high-THC dose (2.5 mg/7kg/day), and post-THC discontinuation for 140 days (∼2 spermatogenesis cycles). Bioinformatic analysis included QA/QC assessments, alignment to the rhesus reference genome, and identification of differentially methylated regions (DMRs). RESULTS: Overlap of genes annotated to DMRs in our RM following THC with published gene lists of human cannabis users and non-users was more than expected by chance (p=2.00e-82; Figure 1A). Pre-THC vs post-THC DMRs were similarly enriched for genes annotated to methylation differences between pre-cannabis exposure vs. post-cannabis discontinuation in humans (Figure 1B). Pre-THC vs high-THC DMRs annotated to 3,902 unique genes annotated and were significantly enriched for genes previously associated with autism spectrum disorder (ASD) (Figure 1C). We identified 2,759 DMRs between pre-THC and high-THC that intersected DMRs in high-THC vs post-THC sperm samples and demonstrated a reversal in methylation post-THC toward the level of methylation pre-THC (Figure 1D). A smaller number of DMRs between pre-THC and high-THC (n=1,898) did not return to baseline levels after THC abstinence (Figure 1E). Using Ingenuity Pathway Analysis, the top canonical pathway associated with THC and restored to baseline levels was the “synaptogenesis signaling pathway” and top biofunctions included “nervous system development and function” and “tissue development”. Similarly, the 1,898 non-restored DMRs were also enriched for genes in the “synaptogenesis signaling pathway” and “nervous system development and function”, as well as for genes in the “sperm motility” canonical pathway. CONCLUSIONS: Chronic THC use in RM alters genes related to nervous system development and function, and autism spectrum disorder that may impact longterm offspring outcomes. Discontinuation of THC resulted in restored methylation in only a subset of DMRs. Source of Funding: NICHD, NIDA, Silver Family © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e3 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jason Hedges More articles by this author Lyndsey Shorey-Kendrick More articles by this author Carol Hanna More articles by this author Jasper Bash More articles by this author Eliot Spindel More articles by this author Charles Easley More articles by this author Susan Murphy More articles by this author Jamie Lo More articles by this author Expand All Advertisement PDF downloadLoading ...

In utero exposure to ADHD medication and long-term offspring outcomes.

Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has long-term adverse effects on the offspring. The authors investigated whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The population-based cohort study in the Danish national registers included 1,068,073 liveborn singletons from 1998 to 2015 followed until any developmental diagnosis, death, emigration, or December 31, 2018. Children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy and children of mothers who discontinued ADHD medication before pregnancy were compared using Cox regression. Main outcomes were neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment during childhood or adolescence. In total, 898 children were exposed to ADHD medication during pregnancy compared to 1270 children whose mothers discontinued ADHD medication before pregnancy. After adjustment for demographic and psychiatric characteristics of the mother, no increased risk of any offspring developmental disorders was found combined (aHR 0.97, 95% CI 0.81 to 1.17) or for separate subcategories. Similarly, no increased risk was found for any sub-categories of outcomes in the negative control or sibling controlled analyses. Neurodevelopment and growth in offspring do not differ based on antenatal exposure to ADHD medication. These findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy.

A nutritional supplement containing zinc during preconception and pregnancy increases human milk zinc concentrations.

During pregnancy and lactation minerals such as zinc are required to support maternal and infant health. Zinc is involved in various cellular processes, with requirements increasing in pregnancy and lactation. In the setting of a randomized trial, we investigated the effects on human milk (HM) zinc concentrations of a micronutrient-containing supplement including zinc in the intervention (but not control) group, started preconception and taken throughout pregnancy until birth. Additionally, we characterized longitudinal changes in HM concentrations of zinc and other minerals (calcium, copper, iodine, iron, magnesium, manganese, phosphorus, potassium, selenium, and sodium). HM samples were collected across 7 time points from 1 week to 12 months from lactating mothers from Singapore (n = 158) and New Zealand (n = 180). HM minerals were quantified using sector field inductively coupled plasma mass spectrometry. Potential intervention effects on HM mineral concentrations were assessed using linear mixed models with a repeated measures design and time-weighted area-under-the-curve analyses. Over the first 3 months of lactation, HM zinc concentrations were 11% higher in the intervention group compared to the control group (p = 0.021). Higher HM zinc concentrations were most evident at 6 weeks of lactation. The intervention had no effect on HM concentrations of other minerals, which were not differently supplemented to the control and intervention groups. Temporal changes in HM minerals over 12 months of lactation were studied in the New Zealand mothers; HM zinc and copper concentrations progressively decreased throughout 12 months, while iron, potassium, sodium, and phosphorus decreased until 6 months then plateaued. HM calcium and magnesium initially increased in early lactation and iodine remained relatively constant throughout 12 months. HM manganese and selenium fell over the initial months of lactation, with a nadir at 6 months, and increased thereafter. The contrasting patterns of changes in HM mineral concentrations during lactation may reflect different absorption needs and roles at different stages of infancy. Overall, this study indicates that HM zinc concentrations are influenced by maternal supplementation during preconception and pregnancy. Further studies are required to understand the associations between HM zinc and other minerals and both short- and long-term offspring outcomes. ClinicalTrials.gov, identifier: NCT02509988, Universal Trial Number U1111-1171-8056. Registered on 16 July 2015. This is an academic-led study by the EpiGen Global Research Consortium.

The Global Pregnancy Collaboration (CoLab) symposium on short- and long-term outcomes in offspring whose mothers had preeclampsia: A scoping review of clinical evidence.

Preeclampsia is a maternal syndrome characterized by the new onset of hypertension after 20 weeks of gestation associated with multisystemic complications leading to high maternal and fetal/neonatal morbidity and mortality. However, sequelae of preeclampsia may extend years after pregnancy in both mothers and their children. In addition to the long-term adverse cardiovascular effects of preeclampsia in the mother, observational studies have reported elevated risk of cardiovascular, metabolic, cerebral and cognitive complications in children born from women with preeclampsia. Less clear is whether the association between maternal preeclampsia and offspring sequelae are causal, or to what degree the associations might be driven by fetal factors including impaired growth and the health of its placenta. Our discussion of these complexities in the 2018 Global Pregnancy Collaboration annual meeting prompted us to write this review. We aimed to summarize the evidence of an association between maternal preeclampsia and neurobehavioral developmental disorders in offspring in hopes of generating greater research interest in this important topic.

Under and overtreatment with thyroid hormone replacement during pregnancy.

Among pregnant women on thyroid hormone replacement therapy undertreatment is common, while overtreatment is rare. Both deficient and excessive maternal thyroid hormone have been related to adverse maternofetal and long-term offspring outcomes, although studies' results are inconsistent. This review aims to discuss recent evidence regarding the effects of under- and overtreatment with thyroid hormone replacement during pregnancy and how current practices could be improved. Whether or not thyroid hormone therapy needs to be initiated for maternal subclinical hypothyroidism remains unclear, but recent meta-analyses have confirmed associations between adverse maternal, neonatal, and offspring outcomes in both overt and subclinical hypothyroidism. Subclinical hyperthyroidism in pregnancy is related to fewer adverse outcomes. Current adherence to levothyroxine during pregnancy and medication counseling by healthcare providers are suboptimal. Undertreatment of maternal hypothyroidism may increase risks for adverse maternofetal and offspring effects more than overtreatment does. If thyroid hormone replacement therapy is indicated and initiated in pregnancy, frequent thyroid function monitoring is required to avoid under- or overtreatment. Effective communication between clinicians and patients is imperative to increase medication adherence.

Strategies for Prevention or Treatment of Tobacco and Cannabis Use Disorder.

Tobacco and cannabis use in pregnancy are associated with increased adverse perinatal and long-term offspring outcomes. Products for both have evolved with various forms available on the market, challenging accurate counseling of risks and quantification of tobacco and cannabis usage during the perinatal period. Health care providers are recommended to screen for any type of use, provide consistent messaging of harms of tobacco and cannabis use in pregnancy, and offer individualized interventions. The journey to cessation can be complicated by barriers and triggers, lack of social supports, and mental health challenges that should be addressed to prevent relapse and withdrawals.

Perinatal outcomes of singletons born after blastocyst or cleavage-stage embryo transfer in FET cycles

PurposeTo compare perinatal outcomes of singletons after blastocyst versus cleavage-stage embryo transfer in frozen-thawed embryo transfer (FET) cycles. MethodsThis was a retrospective cohort study of 4835 women who conceived after frozen-thawed embryo transfer and delivered a singleton baby from January 2015 to March 2020. The perinatal outcomes of the singletons born after blastocyst transfer (N = 3364) were compared to the singletons born after cleavage-stage transfer (N = 1471), including gestational week, birth weight, newborn gender and Apgar score. ResultsUnivariate and multivariate analysis found that infants born after blastocyst transfer had a higher risk of preterm birth (PTB) [adjusted odds ratio (aOR) 1.480; 95% confidence interval (CI) 1.213–1.807], large for gestational age (LGA) (aOR 1.329, 95%CI 1.149–1.536) and very large for gestational age (VLGA) (aOR 1.317, 95%CI 1.092–1.590) compared to infants born after cleavage-stage embryo transfer. When categorized by gestational weeks, the proportion of LGA was significantly higher for boys born after BT between GW 37 to 41 (aOR 1.301, 95%CI 1.051–1.609) and for girls born after BT between GW 32 to 41 (aOR 2.690, 95%CI 1.154–6.271, aOR 1.377, 95%CI 1.094–1.733), compared to boys and girls born after CT. ConclusionOur data suggested that the risk of PTB and LGA increased after blastocyst transfer versus cleavage-stage embryo transfer in FET cycles, and the risk of LGA is more apparent in the last trimester of pregnancy. Further studies are needed to confirm our findings and explored the association between the extended embryo culture and long-term outcomes of offspring.

Maternal Dietary Quality and Dietary Inflammation Associations with Offspring Growth, Placental Development, and DNA Methylation

The ‘Developmental Origins of Health and Diseases’ hypothesis posits that prenatal maternal diet influences offspring growth and later life health outcomes. Dietary assessment has focused on selected nutrients. However, this approach does not consider the complex interactions between foods and nutrients. To provide a more comprehensive approach to public health, dietary indices have been developed to assess dietary quality, dietary inflammation and risk factors for non-communicable diseases. Thus far, their use in the context of placental development is limited and associations with offspring outcomes have been inconsistent. Although epidemiological studies have focused on the role of maternal diet on foetal programming, the underlying mechanisms are still poorly understood. Some evidence suggests these associations may be driven by placental and epigenetic changes. In this narrative review, we examine the current literature regarding relationships between key validated diet quality scores (Dietary Inflammatory Index [DII], Mediterranean diet [MD], Healthy Eating Index [HEI], Alternative Healthy Eating Index [AHEI], Dietary Approaches to Stop Hypertension [DASH], Glycaemic Index [GI] and Glycaemic Load [GL]) in pregnancy and birth and long-term offspring outcomes. We summarise findings, discuss potential underlying placental and epigenetic mechanisms, in particular DNA methylation, and highlight the need for further research and public health strategies that incorporate diet quality and epigenetics.

Prenatal infection and schizophrenia: A decade of further progress

Epidemiologic studies have provided evidence that prenatal exposure to maternal infection is associated with an increased risk of developing schizophrenia in the offspring. Research over the past decade has added further to our understanding of the role of prenatal infection in schizophrenia risk. These investigations include several well-powered designs, and like some earlier studies, measured maternal antibodies to specific infectious agents in stored serum samples and large registers to identify clinically diagnosed infections during pregnancy. Convergent findings from antibody studies suggest that prenatal maternal infection with Toxoplasma gondii is associated with increased schizophrenia risk in the offspring, while associations with HSV-2 infection are likely attributable to confounding. Maternal influenza infection remains a viable candidate for schizophrenia, based on an early serological study, though there has been only one attempt to replicate this finding, with a differing methodology. A prior association between maternal serologically confirmed cytomegalovirus infections require further study. Clinically diagnosed maternal infection, particularly bacterial infection, also appears to be associated with increased risk of offspring schizophrenia, and heterogeneity in these findings is likely due to methodological differences between studies. Further clarification may be provided by future studies that address the timing, type, and clinical features of infections. Important insight may be gained by examining the long-term offspring outcomes in emerging epidemics such as Zika virus and COVID-19, and by investigating the interaction between exposure to prenatal infection and other risk or protective factors.

Antenatal corticosteroids and preterm offspring outcomes in hypertensive disorders of pregnancy: A Japanese cohort study

To estimate whether antenatal corticosteroids (ACS) improve short- and long-term preterm offspring outcomes in singleton pregnancies complicated by hypertensive disorders of pregnancy (HDP) similar to pregnancies without HDP. This population-based retrospective study was conducted based on an analysis of data collected by the Neonatal Research Network of Japan on 21,014 singleton neonates weighing ≤1,500 g between 24 and 31 weeks’ gestation during 2003–2016. Logistic regression analyses were performed to compare short- and long-term offspring outcomes between mothers receiving ACS treatment and those who did not among pregnancies with HDP and without HDP. Of 21,014 neonates, 4,806 (22.9%) were born to mothers with HDP. ACS treatment was associated with significant decreases in short-term adverse outcomes in the both HDP and non-HDP groups, with similar reduced odds of neonatal death, respiratory distress syndrome, and intraventricular haemorrhage (IVH). However, ACS treatment did not significantly decrease severe IVH (aOR 0.76; 95% CI 0.51–1.13) and periventricular leukomalacia (1.14; 0.78–1.66) in the HDP group. In addition, ACS treatment in mothers without HDP significantly decreased cerebral palsy (aOR 0.70; 95% CI 0.58–084), developmental quotient scores <85 (0.79; 0.69–0.90), and composite adverse outcomes (0.85; 0.75–0.96) at 3 years of age, whereas ACS treatment in mothers with HDP did not significantly improve these outcomes (1.04; 0.69–1.57, 1.11; 0.88–1.39, 0.96; 0.75–1.22, respectively). ACS treatment was associated with significantly decreased major short-term morbidities and mortality among extremely and very preterm neonates of mothers with HDP, with ACS treatment having a decreased effect compared to that observed in neonates of mothers without HDP. Although ACS treatment has no additional effects on offspring outcomes at 3 years of age, our results did not suggest that ACS treatment should be withheld from mothers with HDP.

Variations in long-term outcome reporting among offspring followed up after lifestyle interventions in pregnancy: a systematic review.

Background Mothers and their offspring may benefit from lifestyle interventions during pregnancy. We systematically reviewed the literature to map and evaluate the quality of long-term offspring outcomes in follow-up cohorts of randomised controlled trials (RCTs). Methods We searched MEDLINE, EMBASE, CINAHL, Database of Abstracts of Reviews of Effects and Cochrane Central (until March 2019) for all RCTs evaluating any lifestyle (diet or exercise) intervention during pregnancy and their follow-up cohorts. Two reviews evaluated the extracted outcomes using two standardised assessment tools, one for quality of reporting (score range 0-6) and another for the variation in outcome selection. We extracted data in duplicate and reported using natural frequencies, medians, ranges, means and standard deviation (SD). Results We captured 30 long-term offspring outcomes reported in six articles (four studies). Offspring anthropometric measurements were the most commonly reported outcomes. There was a large variation in the measurement tools used. The mean overall quality score for outcome reporting was 3.33 (SD 1.24), with poor reporting of secondary outcomes and limited justification for the choice of the reported outcomes. Most studies showed selective reporting for both their primary and secondary outcomes. Conclusion The quality of reporting for long-term offspring outcomes following lifestyle interventions in pregnancy is varied with evidence of selective outcome reporting. Developing a core outcome set will help to reduce the variations in outcome reporting to optimise future research.