Search Results (168)

Objective: Shoulder dystocia (ShD) is a rare but serious obstetric emergency associated with significant neonatal morbidity. This study aimed to evaluate the predictive performance of machine learning (ML) models based on fetal biometric ratios and clinical characteristics for the identification of ShD in pregnancies without clinical suspicion of macrosomia. Methods: We conducted a retrospective case-control study including 284 women (84 ShD cases and 200 controls) who underwent spontaneous vaginal delivery between 37 and 42 weeks of gestation. All participants had an estimated fetal weight (EFW) below the 90th percentile according to Hadlock reference curves. Univariate and multivariate logistic regression analyses were performed on maternal and neonatal parameters, and statistically significant variables (p < 0.05) were used to construct adjusted odds ratio (aOR) models. Supervised ML models—Logistic Regression (LR), Random Forest (RF), and Extreme Gradient Boosting (XGB)—were trained and tested to assess predictive accuracy. Performance metrics included AUC-ROC, sensitivity, specificity, accuracy, and F1-score. Results: The BPD/AC ratio and AC/FL ratio markedly enhanced the prediction of ShD. When added to other features in RF models, the BPD/AC ratio got an AUC of 0.884 (95% CI: 0.802–0.957), a sensitivity of 68%, and a specificity of 83%. On the other hand, the AC/FL ratio, along with other factors, led to an AUC of 0.896 (95% CI: 0.805–0.972), 68% sensitivity, and 90% specificity. Conclusions: In pregnancies without clinical suspicion of macrosomia, ML models integrating fetal biometric ratios with maternal and labor-related factors significantly improved the prediction of ShD. These models may support clinical decision-making in low-risk deliveries where ShD is often unexpected. Full article

Introduction: Systemic lupus erythematosus (SLE) is associated with infection-related morbidity. The risk of adverse outcomes secondary to infections was exacerbated during the recent COVID-19 pandemic, prompting mass vaccination with the novel mRNA-based and viral-vectored vaccines. Limited data exist on the long-term impact of vaccination in patients with SLE. Methods: A post-vaccine group (PVG, n = 284) from a multicentric cohort of vaccinated patients with SLE from six tertiary referral centres in Northen Italy was compared with a control group (CG, n = 223) of similar demographics observed in the 2015–2019 period to investigate survival, hospitalisation, pregnancy, disease flare, disease progression, infection, and chronic complication accrual rates. Results: We did not observe excess SLE flares, SLE progression, hospitalisation, or pregnancy complications in the PVG. Cardiovascular complications due to comorbidities or to SLE were lower in the PVG than in the CG. Infections were more frequent in the PVG, related to COVID-19 in half of the cases, and were associated with SLE flares. Conclusions: Taken together, these data indicate that anti-COVID-19 vaccines are safe in the long-term when administered to patients with SLE. Stable, non-null rates of chronic comorbidity accrual and hospitalisation point out the existence of persistently unmet needs in patients with SLE. Full article

Background: Vitamin D is increasingly recognized not only for its role in skeletal development but also for its immunomodulatory and gastrointestinal effects. Maternal and neonatal vitamin D deficiency (VDD) has been associated with alterations in gut microbiota, impaired intestinal barrier integrity, and increased susceptibility to inflammatory conditions in neonates. However, the exact mechanisms linking perinatal vitamin D status to neonatal gastrointestinal morbidity remain incompletely understood. Methods: This review synthesizes current evidence (2015–2024) from clinical studies, animal models, and mechanistic research on the impact of VDD during pregnancy and the neonatal period on gastrointestinal health. Databases such as PubMed, Scopus, and Web of Science were systematically searched using keywords, including “vitamin D”, “neonate”, “gut microbiome”, “intestinal barrier”, and “necrotizing enterocolitis”. Results: Emerging data suggest that VDD in utero and postnatally correlates with dysbiosis, increased intestinal permeability, and elevated inflammatory responses in neonates. Notably, low 25(OH)D levels in mothers and newborns have been linked with a higher incidence of necrotizing enterocolitis (NEC), delayed gut maturation, and altered mucosal immunity. Vitamin D appears to modulate the expression of tight junction proteins, regulate antimicrobial peptides, and maintain microbial diversity through the vitamin D receptor (VDR). Conclusions: Understanding the gastrointestinal implications of early-life VDD opens a potential window for preventive strategies in neonatal care. Timely maternal supplementation and targeted neonatal interventions may mitigate gut-related morbidities and improve early-life health outcomes. Further longitudinal and interventional studies are warranted to clarify causality and optimal intervention timing. Full article

Background: Hypertensive disorders of pregnancy (HDPs) are a major cause of maternal morbidity and mortality worldwide. Very little progress has been made in reducing HDP-related maternal deaths in low- and middle-income countries (LMICs), including South Africa, over the past decade. Aim: The aim of this study was to describe maternal deaths arising from HDPs at tertiary/quaternary hospital in Johannesburg, South Africa, with specific focus on maternal characteristics, management, timing of death, causes, and avoidable factors and to use the information to inform clinical practice. Methods: We conducted a retrospective review of patient clinical records covering the period 1 January 2015 to 31 December 2018. Data on maternal demographic and pregnancy characteristics, management, causes, and timing of death were extracted from the clinical records and transferred into a Microsoft Excel^® Spreadsheet and analysed using descriptive statistics. Results: During the study period, 70 maternal deaths were recorded, of which 23 (32.8%) were due to HDP-related complications. The majority of the maternal deaths, 20 (86.9%), occurred during the postpartum period, predominantly affecting Black African women, 23 (100%), with a median age of 27 years. Notably, 18 (78.2%) of the deceased had booked early and attended antenatal care (ANC). Eclampsia emerged as the most common final cause of death. Key avoidable factors included non-adherence to established protocols, particularly failure to initiate aspirin prophylaxis in at-risk women, as well as incorrect or inadequate administration of antihypertensive therapy and magnesium sulphate (MgSO₄) prophylaxis. Conclusions: HDP-related maternal deaths are largely preventable. They primarily result from poor quality of care due to a lack of adherence to evidence-based protocol. Full article

Background: Maternal vaccination is a critical primary preventive approach and an integral part of life-course immunization strategy, influencing the infection-associated morbidity and mortality in pregnant women, foetuses, and young infants. Despite clear guidelines for the administration of vaccines against tetanus, diphtheria, pertussis (Tdap), influenza, and COVID-19 during pregnancy, maternal vaccination rates remain suboptimal in Ireland as per the National Immunisation Office of the Health Service Executive (HSE). Aim: This review explores the prevailing status, uptake factors, and maternal immunization-specific vaccine hesitancy in Ireland. Method: A scoping review was conducted, searching nine electronic databases, including the Irish health research repository Lenus. The search strategy utilised a Population–Concept–Context framework (pregnant women—vaccine uptake/hesitancy—Ireland). Key factors identified and categorised according to the 5A framework: access, affordability, awareness, acceptance, and activation. Results: Searches yielded 2457 articles, and 12 eligible studies were included for review. Influencing factors were identified in each of the 5A dimensions, with the majority relating to acceptance and awareness. Positively associated factors included healthcare provider (HCP) recommendation and knowledge of vaccine safety. Potential antenatal barriers were maternal lack of knowledge of vaccine-preventable illness severity, infection risks, and vaccine safety concerns. A pregnant woman’s primary motivation for antenatal immunization was protection of her infant; however, the reluctance of HCPs to prescribe all recommended antenatal vaccines, inadequate immunization-specific discussion during antenatal consultations, and suboptimal knowledge of pregnancy-specific vaccine safety hampered potential positive influences. The Irish national immunization policy was a facilitator of affordability. Activation can be achieved through public health awareness campaigns and interdisciplinary promotion of maternal vaccination uptake. Conclusions: Maternal vaccination uptake in Ireland remains suboptimal, and a coordinated, targeted approach updating HCP recommendations, enhancing maternal awareness, and highlighting vaccine safety in pregnancy would be required to meet the life-course immunization goals recommended by WHO. By adopting a life-course immunization approach for healthy living, with maternal vaccination as the pivotal central point, vaccination programmes could close immunity gaps at various life stages. Full article

Background: Preeclampsia (PE) is a pregnancy-specific disorder and a leading cause of maternal and fetal morbidity and mortality. Impaired trophoblast invasion is a hallmark of PE, and alternative splicing (AS) is crucial for trophoblast differentiation and placental development. However, the exact mechanisms of AS in PE remain poorly understood. Methods: To elucidate AS-mediated regulatory pathways in PE, a total of 38 fresh-frozen placental samples, including 13 pre-eclampsia samples and 25 normal control samples, were collected from Renmin Hospital of Wuhan University between 1 February and 30 July 2022. We performed transcriptome sequencing of seven PE and seven normal placentas to identify differentially spliced events. After quality control and adapter trimming, raw sequencing reads were aligned to the human reference genome using STAR. Differential exon usage was analyzed using DEXSeq (version 1.36.0), and exons with an adjusted p-value < 0.05 and a fold change greater than 2 or less than 0.5 were considered significantly differentially spliced. Functional assays, including CCK8, colony formation, and cell cycle analyses, were conducted to assess trophoblast proliferation, whereas wound healing and Transwell assays were used to evaluate trophoblast migration and invasion using the HTR-8/SVneo cell line. RNA immunoprecipitation sequencing (RIP-seq) and RNA stability assays were employed to investigate mRNA interactions and stability. Results: Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) emerged as a key RNA-binding protein associated with alternative splicing regulation, intersecting both AS-related candidate genes and known splicing factors, although it is not a classical splicing factor itself. IGF2BP3 overexpression markedly enhanced HTR-8/SVneo trophoblast proliferation, migration, and invasion while suppressing ROS activation. RNA-seq, RIP-seq, and RNA stability assays revealed that IGF2BP3 directly interacts with and enhances the stability of PDE3A mRNA. Functional rescue experiments confirmed that PDE3A knockdown partially abrogated IGF2BP3-mediated trophoblast progression. Furthermore, miR-196a-5p was identified as a negative regulator of IGF2BP3 via miRNA inhibitor/mimic transfection, qRT-PCR, and functional assays, confirming that miR-196a-5p overexpression downregulates IGF2BP3, thereby impairing trophoblast migration and proliferation. Notably, restoring IGF2BP3 expression reversed these inhibitory effects. Conclusions: Our findings reveal a previously unrecognized regulatory axis in PE in which miR-196a-5p suppresses IGF2BP3 expression, leading to PDE3A mRNA destabilization and impaired trophoblast function. This study offers mechanistic insights into PE pathogenesis and identifies IGF2BP3 as a potential therapeutic target. Full article

Pre-eclampsia is a severe pregnancy complication affecting 5–8% of pregnancies worldwide, marked by high blood pressure and organ damage typically occurring after 20 weeks of gestation. It is a leading cause of maternal and fetal morbidity and mortality. Though its exact cause is unknown, it involves placental abnormalities and improper blood vessel development. Risk factors include a history of pre-eclampsia, chronic hypertension, diabetes, obesity, and autoimmune disorders. Symptoms include high blood pressure, proteinuria, headaches, vision changes, and abdominal pain. Untreated, it can lead to seizures, stroke, preterm birth, or death. Delivery is the definitive treatment, with management strategies such as monitoring and blood pressure control. Pre-eclampsia significantly increases long-term cardiovascular disease (CVD) risks, including hypertension, ischemic heart disease, and stroke, linked to shared mechanisms like endothelial dysfunction and inflammation. Women with severe or recurrent pre-eclampsia have heightened risks, often developing chronic hypertension within a decade postpartum. It also impacts offspring, with daughters at elevated risk for pre-eclampsia and CVD. Hypertensive disorders of pregnancy, including pre-eclampsia, induce changes like left ventricular hypertrophy and diastolic dysfunction, raising risks for heart failure with preserved ejection fraction and coronary atherosclerosis. Overlapping with peripartum cardiomyopathy, pre-eclampsia underscores a spectrum of pregnancy-related cardiovascular disorders. Long-term monitoring and lifestyle interventions are crucial for managing risks, with research into genetic and biological mechanisms offering the potential for targeted prevention. Full article

Background/Objectives: In the United States, maternal morbidity is 2–3 times higher than in other high-income nations and continues to rise among non-White women. One potential driving factor is whether labor and childbirth pain are assessed and addressed in a timely and effective manner. Pain during labor and childbirth can be symptomatic of maternal morbidity (e.g., pelvic pain, bleeding, high blood pressure, cardiovascular issues) and/or an independent predictor of adverse postpartum outcomes (e.g., chronic postpartum pain, postpartum depression). Methods: Since racial and ethnic disparities in pain reporting and treatment are well documented in other settings—such as chronic pain conditions, pregnancy-related pain, and postpartum care—we hypothesize that similar disparities persist during labor and delivery. In this manuscript, we evaluate differences in pain reporting and provider treatment response (or lack thereof) based on self-reported race and ethnicity during childbirth admission. Results: In a large, representative sample of women giving birth at a large hospital system (N = 46,671), we assessed race- and ethnicity-related disparities in pain reporting, evaluation, and treatment. There are racial disparities in the frequency of pain assessments, values of pain ratings, and delivery of pharmacological vs. non-pharmacological treatment. Conclusions: A large-scale investigation into racial and ethnic differences in pain assessment, reporting, and treatment during childbirth may help identify mechanisms that mitigate disparities in maternal morbidity and mortality. Full article

Fetal growth restriction (FGR) is an obstetric condition most frequently caused by placental dysfunction. It is a major cause of perinatal morbidity with limited treatment options, so identifying the underpinning mechanisms is important. Peptidylarginine deiminases (PADs) are calcium-activated enzymes that mediate post-translational citrullination (deimination) of proteins, through conversion of arginine to citrulline. Protein citrullination leads to irreversible changes in protein structure and function and is implicated in many pathobiological processes. Whether placental protein citrullination occurs in FGR is poorly understood. We assessed protein citrullination and PAD isozyme abundance (PAD1, 2, 3, 4 and 6) in human placental samples from pregnancies complicated by early- and late-onset FGR, compared to appropriate-for-gestational-age (AGA) controls. Proteomic mass spectrometry demonstrated that the placental citrullinome profile changed in both early- and late-onset FGR, with 112 and 345 uniquely citrullinated proteins identified in early- and late-onset samples, respectively. Forty-four proteins were citrullinated only in control AGA placentas. The proteins that were uniquely citrullinated in FGR placentas were enriched for gene ontology (GO) terms related to neurological, developmental, immune and metabolic pathways. A greater number of GO and human phenotype pathways were functionally enriched for citrullinated proteins in late- compared with early-onset FGR. Correspondingly, late-onset but not early-onset FGR was associated with significantly increased placental abundance of PAD2 and citrullinated histone H3, determined by Western blotting. PAD3 was downregulated in early-onset FGR while abundance of PAD 1, 4 and 6 was less altered in FGR. Our findings show that placental protein citrullination is altered in FGR placentas, potentially contributing to the pathobiology of placental dysfunction. Full article

Background: Pregnancy induces hormonal, immunologic, and vascular changes that profoundly affect dermatologic health. This systematic review aimed to assess the impact of pregnancy on dermatological disorders in terms of disease incidence, severity, maternal-fetal outcomes, and optimal management strategies. Methods: A systematic search was performed in PubMed, MEDLINE, and Web of Science databases, following PRISMA guidelines. Studies evaluating pregnant women with dermatological disorders, pregnancy-related dermatoses, and pre-existing morbidities, were included. The collaboratively extracted data included patient demographics, disease severity, treatment approaches, and pregnancy outcomes. Results: A total of 8490 pregnant cases with dermatologic changes and conditions caused by pregnancy were studied. The dermatological conditions were divided into physiological changes, pregnancy-related exacerbation of pre-existing skin conditions, and pregnancy-specific dermatoses. Intrahepatic cholestasis of pregnancy and pemphigoid gestationis were associated with increased rates of adverse fetal outcomes in patients with specific dermatoses, including increased preterm birth and fetal distress rates. The atopic eruption of pregnancy and polymorphic eruption of pregnancy were highly relevant, but their effect on fetal health was minimal. The efficacy and safety of treatment modalities, including corticosteroids, antihistamines, and ursodeoxycholic acid, were variable. Conclusions: Pregnancy drastically affects dermatological health, but the nature of the impact depends on the condition. Optimal maternal and fetal outcomes rely on early diagnosis and individualized management strategies. More randomized controlled trials are required to develop standardized diagnostic and treatment guidelines to enhance the quality of dermatologic care during pregnancy. Full article

Background/Objectives: We examined the association between bean consumption and the risk of gestational diabetes mellitus (GDM). Methods: We analyzed data from 1397 U.S. pregnant women from Infant Feeding Practices Study II. By using a Diet History Questionnaire, pregnant women were asked about the frequency of consumption and portion size of dried beans, chili, and bean soup over the previous month. They also reported the status of GDM. We used multivariable logistic regression models to examine associations between maternal bean consumption and the risk of GDM, adjusting for socio-demographic and pregnancy-related confounders. Results: Mean bean consumption was low among pregnant women: 0.31 cups/week of dried beans, 0.16 cups/week of chili, and 0.10 cups/week of bean soup. Dried bean consumption was relatively high in Hispanic mothers (mean, 0.65 cups/week) and mothers from the East South Central region (0.44). Chili consumption was relatively high in mothers who were Black (0.33), who did not attend college (0.18), who had a household size of 4+ (0.19), whose household income was <USD 25,000/year (0.20), who were WIC recipients (0.18), or who lived in the East South Central region (0.26). Pregnant women who consumed chili one time per month had a lower risk of GDM, compared with never consumers (3.5% vs. 7.4%; confounder-adjusted odds ratio or OR, 0.37 [95% confidence interval or CI, 0.17–0.79]; p = 0.011). However, there was no significant association between dried bean (6.6% for one time per week or more vs. 7.0% for never; confounder-adjusted OR, 0.82 [95% CI, 0.41–1.62]; p-value = 0.569) or bean soup (4.9% for two–three times per month or more vs. 6.6% for never; confounder-adjusted OR, 0.40 [95% CI, 0.05–3.08]; p-value = 0.382) consumption and GDM. Conclusions: Bean consumption during pregnancy is low and varies by socio-demographics in the U.S. A moderate frequency of chili consumption may offer some protection against GDM. Replication is needed in larger cohorts with more diverse populations, detailed measures of bean consumption, gold standards of GDM diagnosis, and experimental design. Research in this field can potentially inform dietary approaches to addressing GDM and related morbidities. Full article

Pregnancy involves extracellular vesicles (EVs) through mechanisms that are poorly understood to date. Furthermore, it is not surprising that EVs may also be involved in the pathophysiology of pre-eclampsia (PE) and gestational hypertension, two clinical conditions with high morbidity and mortality, given their capacity to mediate intracellular communications and regulate inflammation and angiogenesis. We searched major online scientific search engines (PubMed, Google Scholar, Scopus, WES, Embase, etc.) using the terms “Preeclampsia”, “Pregnancy”, “Hypertension”, “Pregnancy-related hypertension”, “Extracellular vesicles”, “Biomarkers”, “Gestation” AND “Obstetrics”. Finding potential early biomarkers of risk or illness progression would be essential for the optimum care of expectant mothers with the aforementioned conditions. Nevertheless, none of the various screening assays that have been discovered recently have shown high predictive values. The analysis of EVs in the peripheral blood starting from the first trimester of pregnancy may hold great promise for the possible correlation with gestational hypertension problems and represent a marker of the early stages of the disease. EVs use may be a novel therapeutic approach for the management of various illnesses, as well. In order to define EVs’ function in the physiopathology of pregnancy-associated hypertension and PE, as well as their potential as early biomarkers and therapeutic tools, we have compiled the most recent data in this review. Full article

Congenital diaphragmatic hernia (CDH) is a relatively rare and severe developmental disease. Even with the most recent multidisciplinary therapies, the risk for neonatal mortality and morbidity remains high. Recent advancements in prenatal treatments, alongside experimental and clinical data, suggest that fetoscopic endoluminal tracheal occlusion (FETO) promotes lung development and offers a promising strategy against lung hypoplasia and pulmonary hypertension. It is the only existing direct mechanical therapy that intervenes in the regulation of pulmonary pressure. Its influence on lung development also interferes with tissue homeostasis and cell differentiation; it also enhances inflammation and apoptosis. Its physiopathology on cellular and molecular levels is still poorly understood. Unfortunately, the procedure also carries significant pregnancy-, maternal-, and fetus-related risks. Assessing a multifaceted intervention requires a collective view of all aspects. This scoping review uncovers potential materno-fetal procedure-related risks and highlights innovative solutions. Future research on lung development therapies in CDH may focus on the “dual hit” mechanism, combining molecular-targeting drugs and regenerative medicine with the mechanical nature of FETO for synergistic effects. Full article

Pregnancy induces significant hemodynamic changes, and cardiovascular diseases (CVDs) are one of the leading causes of non-obstetric maternal morbidity and mortality during pregnancy or the postpartum period in developed countries. The effective diagnosis and management of CVDs in pregnant women require a thorough evaluation that considers the health of both the mother and the fetus. Imaging plays a pivotal role in this evaluation, offering essential insights into the most significant pregnancy-related CVDs. However, due to concerns about fetal exposure, the use of contrast agents and radiation exposure must be carefully managed. Following to the principle of “As Low As Reasonably Achievable” (ALARA), strategies to minimize these risks are crucial for ensuring patient safety while maintaining diagnostic accuracy. This review highlights the contribution of cardiovascular imaging techniques, particularly computed tomography (CT) and magnetic resonance imaging (MRI), in the assessment of common pregnancy-related CVDs, and outlines strategies to reduce radiation exposure and limit contrast agent use when feasible, aiming to increase radiologists’ awareness of this crucial topic. Full article

The data about pregnancy while having a low ejection fraction are scarce, since pregnancy is not recommended for women with an ejection fraction of less than 30%. There is an increased risk of obstetrical complications and adverse maternal-fetal outcomes. Pregnancy is a rough journey for this group of patients. However, a successful pregnancy can be achieved when cardiac complications are managed during pregnancy. The early recognition of women at risk of cardiovascular events and early referral can optimize the maternal and neonatal outcomes with close collaboration between the maternal-fetal medicine specialist and the cardiologist. The study’s aim was to assess the experience of our tertiary center with regard to the adverse maternal outcome for women with an ejection fraction ≤ 30% compared to those with an EF > 30% in our tertiary center. The fetal and obstetric outcome for pregnancies with an EF ≤ 30% was compared to that for pregnancies with an EF > 30%. Methodology: After receiving the approval of the local Ethical Board Review, a retrospective study was conducted at King Faisal Specialist Hospital and Research Center (KFSHRC) in the city of Riyadh, Kingdom of Saudi Arabia. Our study population included women with cardiomyopathy (acquired or congenital) who were followed up or delivered in KFSHRC from the period of January 2004 till March 2020. Cases were identified by reviewing the database from the Cardiac Center Echocardiograph and maternal fetal medicine unit. The data on the maternal and fetal outcome were gathered from the hospital medical records. An adverse maternal outcome included: death, hospitalization due to decompensated heart failure, and worsening cardiovascular status during pregnancy. Adverse fetal outcomes included: miscarriages, termination of pregnancy, FGR, and placental insufficiency. Obstetrics complications included: complications related to the mode of delivery, antepartum hemorrhage, postpartum hemorrhage, or preeclampsia. Results: Our study included 44 subjects, examining the differences between those with an ejection fraction greater than 30 (n = 21 subjects) and those with an ejection fraction less than or equal to 30 (n = 23) with respect to demographics, co-morbidities, and outcomes (maternal, pregnancy, fetal, ultrasound, and baby). There was no evidence of any differences in the demographics. From among the co-morbidities, there was a statistically higher rate of dilated cardiomyopathy and lower rate of rheumatic heart disease in those with a lower ejection fraction. Also, women with a lower ejection fraction tended to deliver through a means other than simple vaginal delivery. There was a significant association (p = 0.0296) indicating that individuals with a lower ejection fraction tended to have a lower gestational age at delivery. The information on whether the pregnancy resulted in a live birth was available for all but one of the mothers. Across all the mothers, 32 (74%) resulted in a live birth and 11 did not. The percentage of pregnancies resulting in a live birth in the group for which the ejection fraction was greater than 30 was 90% and that in the group for which the ejection fraction was less than or equal to 30 was 59% (p = 0.0339). From among the ultrasound and baby outcomes, only the rate of the babies being discharged alive differed statistically between the two ejection fraction groups, with those mothers having a lower ejection fraction experiencing fewer babies being discharged alive (p = 0.0310). Conclusions: In conclusion, women with a low ejection fraction are at an increased risk of maternal-fetal complications. In our study, the lower the EF (≤30) the worse were the fetal and neonatal outcomes; however, in terms of the maternal outcomes, it was the same whether the EF was low or ultra-low. Yet, these groups of patients need to be counseled about the facts of poor obstetrical outcomes with an emphasis on preconceptual counseling. Full article