Well-being of children born after medically assisted reproduction

Background: The increasing number and proportion of children born after medically assisted reproduction (MAR) has raised concerns and motivated research about the impact of MAR on the well-being and development of children. // Objective: We summarize existing studies on the well-being and development of children conceived through MAR. // Materials and methods: Review of existing studies. // Results: Children conceived through MAR are at increased risk of adverse birth outcomes such as low birthweight and preterm delivery compared to naturally conceived children. The higher rates of multiple births amongst MAR-conceived children continue to represent an important driving factor behind these disparities. Reassuringly, elective single embryo transfer (eSET)—which is associated with more favourable pregnancy outcomes among MAR-conceived children—is becoming more common. Despite the early life health disadvantages, the evidence on later life outcomes such as physical, cognitive and psychosocial development is generally reassuring. On average, MAR-conceived children show similar or better outcomes than naturally conceived children. The selected and advantaged socioeconomic characteristics of parents who conceive through MAR are likely to play an important role in explaining why, on average, MAR-conceived children perform better than naturally conceived children—particularly in terms of cognitive outcomes. In contrast, there is some evidence pointing to potentially increased risks of mental health problems among MAR-conceived children. // Conclusion: There is need for continued monitoring and longer follow-up studies on the well-being of these children in order to better understand whether their outcomes are similar to or different from those of naturally conceived children, and, if so, why

Medically Assisted Reproduction Treatment Types and Birth Outcomes: A Between- and Within-Family Analysis

OBJECTIVE: To compare risks of adverse birth outcomes among pregnancies conceived with and without medically assisted reproduction treatments. METHODS: Birth certificates were used to study birth outcomes of all neonates born in Utah from 2009 through 2017. Of the 469,919 deliveries, 52.8% (N=248,013) were included in the sample, with 5.2% of the neonates conceived through medically assisted reproduction. The outcome measures included birth weight, gestational age, low birth weight (LBW, less than 2,500 g), preterm birth (less than 37 weeks of gestation), and small for gestational age (SGA, birth weight less than the 10th percentile). Linear models were estimated for the continuous outcomes (birth weight, gestational age), and linear probability models were used for the binary outcomes (LBW, preterm birth, SGA). First, we compared the birth outcomes of neonates born after medically assisted reproduction and natural conception in the overall sample (between-family analyses), before and after adjustment for parental background and neonatal characteristics. Second, we employed family fixed effect models to investigate whether the birth outcomes of neonates conceived through medically assisted reproduction differed from those of their naturally conceived siblings (within-family comparisons). RESULTS: Neonates conceived through medically assisted reproduction weighed less, were born earlier, and were more likely to be LBW, preterm, and SGA than neonates conceived naturally. More invasive treatments (assisted reproductive technology [ART] and artificial insemination [AI] or intrauterine insemination) were associated with worse birth outcomes; for example, the proportion of LBW and preterm birth was 6.1% and 7.9% among neonates conceived naturally and 25.5% and 29.8% among neonates conceived through ART, respectively. After adjustments for various neonatal and parental characteristics, the differences in birth outcomes between neonates conceived through medically assisted reproduction and naturally were attenuated yet remained statistically significant; for example, neonates conceived through ART were at 3.2 percentage points higher risk for LBW (95% CI 2.4–4.1) and 4.8 percentage points higher risk for preterm birth (95% CI 3.9–5.7). Among siblings, the differences in the frequency of adverse outcomes between neonates conceived through medically assisted reproduction and neonates conceived naturally were small and statistically insignificant for all types of treatments. CONCLUSION: Medically assisted reproduction treatments are associated with adverse birth outcomes; however, those risks are unlikely to be associated with the infertility treatments itself

A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia

Introduction Acute lung injury and acute respiratory distress syndrome are common complications in patients with coronavirus disease 2019 (COVID-19). Poor outcomes in patients with COVID-19 are associated with cytokine release syndrome. Binding of interleukin-8 (CXCL8/IL-8) to its chemokine receptors, CXCR1/2, may mediate this inflammatory process. The aim of this clinical trial was to determine if CXCR1/2 blockade with reparixin can improve clinical outcomes in hospitalized patients with severe COVID-19 pneumonia. The dose and safety of reparixin have been investigated in clinical trials of patients with metastatic breast cancer. Methods This was a phase 2, open-label, multicenter, randomized study in hospitalized adult patients with severe COVID-19 pneumonia from May 5, 2020 until November 27, 2020. Patients were randomized 2:1 to receive 1200 mg reparixin orally three times daily or standard of care (SOC) for up to 21 days. The primary endpoint was defined as a composite of clinical events: use of supplemental oxygen, need for mechanical ventilation, intensive care unit admission, and/or use of rescue medication. Results Fifty-five patients were enrolled between reparixin (n = 36) and SOC (n = 19). The rate of clinical events was statistically significantly lower in the reparixin group compared with the SOC group (16.7% [95% CI 6.4-32.8%] vs. 42.1% [95% CI 20.3-66.5%], P = 0.02). The sensitivity analysis based on the Cox regression model provided an adjusted hazard ratio of 0.33 with statistical significance lower than 0.05 (95% CI 0.11-0.99; P = 0.047). Reparixin treatment appeared to be well tolerated. Conclusion In patients with severe COVID-19, reparixin led to an improvement in clinical outcomes when compared with the SOC. A larger phase 3 clinical study is needed to confirm these results

Surgery versus Watchful Waiting in Patients with Craniofacial Fibrous Dysplasia – a Meta-Analysis

Fibrous dysplasia (FD) is a benign bone tumor which most commonly involves the craniofacial skeleton. The most devastating consequence of craniofacial FD (CFD) is loss of vision due to optic nerve compression (ONC). Radiological evidence of ONC is common, however the management of this condition is not well established. Our objective was to compare the long-term outcome of patients with optic nerve compression (ONC) due to craniofacial fibrous dysplasia (CFD) who either underwent surgery or were managed expectantly.We performed a meta-analysis of 27 studies along with analysis of the records of a cohort of patients enrolled in National Institutes of Health (NIH) protocol 98-D-0145, entitled Screening and Natural History of Fibrous Dysplasia, with a diagnosis of CFD. The study group consisted of 241 patients; 122 were enrolled in the NIH study and 119 were extracted from cases published in the literature. The median follow-up period was 54 months (range, 6-228 months). A total of 368 optic nerves were investigated. All clinically impaired optic nerves (n = 86, 23.3%) underwent therapeutic decompression. Of the 282 clinically intact nerves, 41 (15%) were surgically decompressed and 241 (85%) were followed expectantly. Improvement in visual function was reported in fifty-eight (67.4%) of the clinically impaired nerves after surgery. In the intact nerves group, long-term stable vision was achieved in 31/45 (75.6%) of the operated nerves, compared to 229/241 (95.1%) of the non-operated ones (p = 0.0003). Surgery in asymptomatic patients was associated with visual deterioration (RR 4.89; 95% CI 2.26-10.59).Most patients with CFD will remain asymptomatic during long-term follow-up. Expectant management is recommended in asymptomatic patients even in the presence of radiological evidence of ONC

Efficacy and safety of reparixin in patients with severe covid-19 Pneumonia. A phase 3, randomized, double-blind placebo-controlled study

Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia. Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge. The primary endpoint was the proportion of patients alive and free of respiratory failure at Day 28, with key secondary endpoints being the proportion of patients free of respiratory failure at Day 60, incidence of intensive care unit (ICU) admission by Day 28 and time to recovery by Day 28. Results: Of 279 patients randomized, 182 received at least one dose of reparixin and 88 received placebo. The proportion of patients alive and free of respiratory failure at Day 28 was similar in the two groups {83.5% versus 80.7%; odds ratio 1.63 [95% confidence interval (CI) 0.75, 3.51]; p = 0.216}. There were no statistically significant differences in the key secondary endpoints, but a numerically higher proportion of patients in the reparixin group were alive and free of respiratory failure at Day 60 (88.7% versus 84.6%; p = 0.195), fewer required ICU admissions by Day 28 (15.8% versus 21.7%; p = 0.168), and a higher proportion recovered by Day 28 compared with placebo (81.6% versus 74.9%; p = 0.167). Fewer patients experienced adverse events with reparixin than placebo (45.6% versus 54.5%), most mild or moderate intensity and not related to study treatment. Conclusions: This trial did not meet the primary efficacy endpoints, yet reparixin showed a trend toward limiting disease progression as an add-on therapy in COVID-19 severe pneumonia and was well tolerated. Trial registration: ClinicalTrials.gov: NCT04878055, EudraCT: 2020-005919-51

Childbearing postponement and child well-being: a complex and varied relationship?

Over the past several decades, U.S. fertility has followed a trend toward the postponement of motherhood. The socioeconomic causes and consequences of this trend have been the focus of attention in the demographic literature. Given the socioeconomic advantages of those who postpone having children, some authors have argued that the disadvantage experienced by certain groups would be reduced if they postponed their births. The weathering hypothesis literature, by integrating a biosocial perspective, complicates this argument and posits that the costs and benefits of postponement may vary systematically across population subgroups. In particular, the literature on the weathering hypothesis argues that as a consequence of their unique experiences of racism and disadvantage, African American women may experience a more rapid deterioration of their health, which could offset or eventually reverse any socioeconomic benefit of postponement. But because very few African American women postpone motherhood, efforts to find compelling evidence to support the arguments of this perspective rely on a strategy of comparison that is problematic because a potentially selected group of older black mothers are used to represent the costs of postponement. This might explain why the weathering hypothesis has played a rather limited role in the way demographers conceptualize postponement and its consequences for well-being. In order to explore the potential utility of this perspective, we turn our attention to the UK context. Because first-birth fertility schedules are similar for black and white women, we can observe (rather than assume) whether the meaning and consequences of postponement vary across these population subgroups. The results, obtained using linked UK census and birth record data, reveal evidence consistent with the weathering hypothesis in the United Kingdom and lend support to the arguments that the demographic literature would benefit from integrating insights from this biosocial perspective

Fertility History and Physical and Mental Health Changes in European Older Adults

Previous studies have shown that aspects of reproductive history, such as earlier parenthood and high parity, are associated with poorer health in mid and later life. However, it is unclear which dimensions of health are most affected by reproductive history, and whether the pattern of associations varies for measures of physical, psychological and cognitive health. Such variation might provide more insight into possible underlying mechanisms. We use longitudinal data for men and women aged 50–79 years in ten European countries from the Survey of Health, Ageing and Retirement in Europe to analyse associations between completed fertility history and self-reported and observed health indicators measured 2–3 years apart (functional limitations, chronic diseases, grip strength, depression and cognition), adjusting for socio-demographic, and health factors at baseline. Using multiple imputation and pattern mixture modelling, we tested the robustness of estimates to missing data mechanisms. The results are partly consistent with previous studies and show that women who became mothers before age 20 had worse functional health at baseline and were more likely to suffer functional health declines. Parents of 4 or more children had worse physical, psychological and cognitive health at baseline and were more likely to develop circulatory disease over the follow-up period. Men who delayed fatherhood until age 35 or later had better health at baseline but did not experience significantly different health declines. This study improves our understanding of linkages between fertility histories and later life health and possible implications of changes in fertility patterns for population health. However, research ideally using prospective life course data is needed to further elucidate possible mechanisms, considering interactions with partnership histories, health behaviour patterns and socio-economic trajectories

Association Between Advanced Maternal Age and Maternal and Neonatal Morbidity: A Cross-Sectional Study on a Spanish Population

Background and objective: Over recent decades, a progressive increase in the maternal age at childbirth has been observed in developed countries, posing a health risk for both women and infants. The aim of this study was to analyze the association between advanced maternal age (AMA) and maternal and neonatal morbidity. Material and methods: A cross-sectional study of 3,315 births was conducted in the north of Spain in 2014. We compared childbirth between women aged 35 years or older, with a reference group of women aged between 24 and 27 years. AMA was categorized based on ordinal ranking into 35-38 years, 39-42 years, and >42 years to estimate a dose-response pattern (the older the age, the greater the risk). As an association measure, crude and adjusted Odds Ratios (OR) were estimated by non-conditional logistic regression and 95% Confidence Intervals (95%CI) were calculated. Results: Repeated abortions were more common among women of AMA in comparison to pregnant women aged 24-27 years (reference group): adjusted OR = 2.68; 95%CI (1.52-4.73). A higher prevalence of gestational diabetes was also observed among women of AMA, reaching statistical significance when restricted to first time mothers: adjusted OR = 8.55; 95%CI (1.12-65.43). In addition, the possibility of an instrumental delivery was multiplied by 1.6 and the possibility of a cesarean by 1.5 among women of AMA, with these results reaching statistical significance, and observing a dose-response pattern. Lastly, there were associations between preeclampsia, preterm birth (<37 weeks) and low birthweight, however without reaching statistical significance. Conclusion: Our results support the association between AMA and suffering repeated abortions. Likewise, being of AMA was associated with a greater risk of suffering from gestational diabetes, especially among primiparous women, as well as being associated with both instrumental deliveries and cesareans among both primiparous and multiparous women