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Zer, Shiran, Tamar Wainstock, Eyal Sheiner, Shayna Miodownik, and Gali Pariente. "Identifying the Critical Threshold for Long-Term Pediatric Neurological Hospitalizations of the Offspring in Preterm Delivery." Journal of Clinical Medicine 10, no. 13 (June 29, 2021): 2919. http://dx.doi.org/10.3390/jcm10132919.
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We opted to investigate whether a critical threshold exists for long-term pediatric neurological morbidity, and cerebral palsy (CP), in preterm delivery, via a population-based cohort analysis. Four study groups were classified according to their gestational age at birth: 24–27.6, 28–31.6, 32–36.6 weeks and term deliveries, evaluating the incidence of long-term hospitalizations of the offspring due to neurological morbidity. Cox proportional hazard models were performed to control for confounders. A Kaplan–Meier survival curve was used to compare the cumulative neurological morbidity incidence for each group. A total of 220,563 deliveries were included: 0.1% (118) occurred at 24–27.6 weeks of gestation, 0.4% (776) occurred at 28–31.6 weeks of gestation, 6% (13,308) occurred at 32–36.6 weeks of gestation and 93% (206,361) at term. In a Cox model, while adjusting for confounders, delivery before 25 weeks had a 3.9-fold risk for long-term neurological morbidity (adjusted HR (hazard ratio) = 3.9, 95% CI (confidence interval) 2.3–6.6; p < 0.001). The Kaplan–Meier survival curve demonstrated a linear association between long-term neurological morbidity and decreasing gestational age. In a second Cox model, adjusted for confounders, infants born before 25 weeks of gestation had increased rates of CP (adjusted HR = 62.495% CI 25.6–152.4; p < 0.001). In our population, the critical cut-off for long-term neurological complications is delivery before 25 weeks gestation.
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Christopoulos, Panagiotis, Anna Eleftheriades, George Paltoglou, Eleni Paschalidou, Emmanouil Kalampokas, Lina Florentin, Chrysanthi Billi, and Makarios Eleftheriades. "Familial Aggregation of a Novel Missense Variant of COL2A1 Gene Associated with Short Extremities: Case Report and Review of the Literature." Children 9, no. 8 (August 14, 2022): 1229. http://dx.doi.org/10.3390/children9081229.
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We present two cases of family members (first cousins) with short extremities caused by a novel variant of COL2A1 gene (NM_001844.5). Case 1 description: A 29-year-old woman presented in her first pregnancy for a second trimester anomaly scan at 23 weeks of gestation. Fetal long bones were measured below the third centile for gestational age. Follow-up scans revealed fetal long bone growth deceleration. Initial genetic work-up was negative and the rest of the maternal follow-up was unremarkable. A male baby weighing 3180 g was delivered at 39 weeks and 4 days of gestation. Case 2 description: A 33-year-old pregnant woman presented for a routine second trimester anomaly scan at 20 weeks and 4 days of gestation. All fetal measurements were appropriate for the gestational age. The routine growth scan performed at 32 weeks showed fetal long bone measurements below the third centile for gestational age, while the follow-up growth scan at 36 weeks and 4 days of gestation revealed consistent, below the third centile, fetal long bone growth. Given that the fetuses of these two cases were related (first cousins), whole exome sequencing (WES) was performed on Case 2. WES revealed a novel heterozygous missense variant c.1132G>A (p. Gly378Ser) of COL2A1 gene (NM_001844.5). Subsequently, targeted genetic sequencing for the variant was performed on Case 1 and the same novel variant was found. Targeted sequencing revealed the same variant in the mother of Case 1 and the father of Case 2 (siblings). A female baby weighing 3200 g was delivered at 40 weeks and 4 days of gestation.
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Prahlada, Prahlada. "Knowledge management in long gestation projects." International Journal of Information Technology and Management 2, no. 3 (2003): 237. http://dx.doi.org/10.1504/ijitm.2003.003477.
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Yudin, Mark H., Elizabeth V. Asztalos, Ann Jefferies, and Jon F. R. Barrett. "The Management and Outcome of Higher Order Multifetal Pregnancies: Obstetric, Neonatal and Follow-up Data." Twin Research 4, no. 1 (February 1, 2001): 4–11. http://dx.doi.org/10.1375/twin.4.1.4.
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AbstractThe objective of this study was to describe current obstetric, neonatal, and long-term neurodevelopmental outcomes of higher order multifetal gestations (≥ 3 fetuses) in the 1990s. We also intended to identify a target gestational age at which neonatal and neurodevelopmental morbidities are low. Records from all multifetal pregnancies (≥ 3 viable fetuses ≥ 20 weeks gestation) delivered at the two perinatal centers in Toronto, Ontario, Canada during the study period (January 1, 1990–December 31, 1996) were reviewed. Data were collected on obstetric, neonatal, and long-term neurodevelopmental outcomes. Follow up data were gathered regarding the presence of a severe deficit in four categories (vision, hearing, cognition, and motor skills). Statistical analysis was performed to determine a gestational age at which a significant decrease in deficit occurred. During the study period 165 multifetal pregnancies were delivered. This resulted in 511 fetuses, of which 496 were live births. Of these 496 infants, 453 survived to discharge. Follow up data were obtained on 332 (73.3 per cent) infants. Infant survival increased with gestational age, and was approximately 90 per cent or greater at 26 weeks or more. Of all infants followed, the proportion of those without deficit increased with increasing gestational age, such that the per cent without deficit was 96.9 at 31 weeks or greater. Of all infants followed, 301 (90.7 per cent) had no deficit. Statistical analysis revealed a significant difference in long-term neurodevelopmental outcome between infants born before and after 28 weeks gestation. The incidence of a major deficit was 44.1 per cent for those born earlier than and 5.4 per cent for those born later than this gestational age (p = 0.001). In our cohort, survival figures were high. Even in lower gestational groupings, survival was high, but not without serious concerns about severe morbidity. This information is useful when counseling parents of higher order multifetal pregnancies.
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Furse, Samuel, Sara L. White, Claire L. Meek, Benjamin Jenkins, Clive J. Petry, Matias C. Vieira, Susan E. Ozanne, David B. Dunger, Lucilla Poston, and Albert Koulman. "Altered triglyceride and phospholipid metabolism predates the diagnosis of gestational diabetes in obese pregnancy." Molecular Omics 15, no. 6 (2019): 420–30. http://dx.doi.org/10.1039/c9mo00117d.
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Imterat, Majdi, Tamar Wainstock, Jacob Moran-Gilad, Eyal Sheiner, and Asnat Walfisch. "The association between gestational age and otitis media during childhood: a population-based cohort analysis." Journal of Developmental Origins of Health and Disease 10, no. 02 (September 18, 2018): 214–20. http://dx.doi.org/10.1017/s2040174418000685.
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AbstractOtitis media (OM) carries a tremendous global health burden and potentially severe long-term consequences. The objective of this study was to determine the impact of birth at different gestational ages on the incidence of childhood OM.A population-based cohort analysis was conducted. All singleton deliveries occurring between 1991 and 2014 at a regional tertiary medical center were included. Gestational age on delivery was divided into six subgroups: early (<34 weeks gestation; 0 out of 7) and late (34 weeks gestation; 0 out of 7 to 36 weeks gestation; 6 out of 7) preterm, and early (37 weeks gestation; 0 out of 7 to 38 weeks gestation; 6 out of 7), full (39 weeks gestation; 0 out of 7 to 40 weeks gestation; 6 out of 7), late (41 weeks gestation; 0 out of 7 to 41 weeks gestation; 6 out of 7) and post (⩾42 weeks 0 out of 7) term deliveries. Rates of OM-related hospitalizations up to 18 years of age were assessed. Weibull parametric hazards model was used to study the association between gestational age at birth and the risk for OM-related hospitalizations while controlling for potential confounders.During the study period, 238,622 deliveries met the inclusion criteria. OM-related hospitalizations of the offspring (n=4724) were significantly more common in the preterm (early 3.6%, late 2.4%) and early-term born children (2.2%) and decreased gradually across the full (1.9%), late (1.7%) and post (1.6%) term groups (χ2-test for trends P<0.001). In the Weibull regression model, early preterm, as well as early-term deliveries exhibited an independent association with pediatric OM (adjusted hazard ratios: 1.67 and 1.09, respectively, P<0.02).Deliveries occurring at preterm and early term are associated with higher rates of pediatric OM-related hospitalizations, which decrease gradually as gestational age advances.
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Simons, Noor E., Emilie V. J. van Limburg Stirum, Aleid G. van Wassenaer-Leemhuis, Martijn J. J. Finken, Cornelieke S. H. Aarnoudse-Moens, Jaap Oosterlaan, Anneloes van Baar, et al. "Long-term follow-up of children exposed in-utero to progesterone treatment for prevention of preterm birth: study protocol of the AMPHIA follow-up." BMJ Open 11, no. 9 (September 2021): e053066. http://dx.doi.org/10.1136/bmjopen-2021-053066.
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IntroductionPreterm birth is one of the main problems in obstetrics, and the most important cause of neonatal mortality, morbidity and neurodevelopmental impairment. Multiple gestation is an important risk factor for preterm birth, with up to 50% delivering before 37 weeks. Progesterone has a role in maintaining pregnancy and is frequently prescribed to prevent (recurrent) preterm birth and improve pregnancy outcomes in high-risk patients. However, little is known about its long-term effects in multiple gestations. The objective of this follow-up study is to assess long-term benefits and harms of prenatal exposure to progesterone treatment in multiple gestations on child development.Methods and analysisThis is a follow-up study of a multicentre, double-blind, placebo-controlled randomised trial (AMPHIA trial, ISRCTN40512715). Between 2006 and 2009 women with a multiple gestation were randomised at 16–20 weeks of gestation to weekly injections 250 mg 17α-hydroxyprogesterone caproate or placebo, until 36 weeks of gestation or delivery. The current long-term follow-up will assess all children (n=1355) born to mothers who participated in the AMPHIA trial, at 11–14 years of age, with internationally validated questionnaires, completed by themselves, their parents and their teachers.Main outcomes are child cognition and behaviourAdditional outcomes are death (perinatal and up to age 14), gender identity, educational performance and health-related problems. We will use intention-to-treat analyses comparing experimental and placebo group. To adjust for the correlation between twins, general linear mixed-effects models will be used.Ethics and disseminationAmsterdam UMC MEC provided a waiver for the Medical Research Involving Human Subjects Act (W20_234#20.268). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders, patients and participants. This protocol is published before analysis of the results.Trial registration numberNL8933.
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Wilson, E. Nicole, Steve Mabry, Nataliya Rybalchenko, Rachel Engelland, Oluwadarasimi Fadeyibi, Oluwatobiloba Osikoya, Spencer Cushen, Styliani Goulopoulou, and Rebecca Lynn Cunningham. "Long-Term Effects of Late Gestation in Utero Hypoxic Stress on Neurodegeneration: Sex and Age Differences." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A751—A752. http://dx.doi.org/10.1210/jendso/bvab048.1528.
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Abstract Introduction: In utero insults have been proposed to lead to the onset of neurodegenerative diseases later in life, such as Parkinson’s disease (PD). In utero hypoxia is associated with a multitude of conditions, such as maternal sleep apnea, preeclampsia, gestational diabetes, and maternal hypertension. Exposure to in utero hypoxia may impact male progeny more than female progeny, which may underlie the male biased sex differences in PD. It is currently unknown whether late gestational hypoxic stress has a long-term effect on brain regions associated with PD, such as the nigrostriatal pathway. We hypothesized that exposure to late gestational hypoxia will result in nigrostriatal impairment in adult male progeny compared to adult female progeny. Methods: Timed pregnant female Long-Evans rats were exposed to five days (gestational days: 15-20) of chronic intermittent hypoxia (CIH) or room air (normoxia - 21% O2) for 8 hours during their sleep phase. Each CIH cycle was 6 min of 3 min hypoxia (10% O2) and 3 min normoxia (21% O2) for a total of 10 CIH cycles/hour. Gestational age at delivery was recorded and neonate’s body weights were measured within 12-16 hours from birth. At weaning (postnatal day, PND 28), progeny was pair-housed with a conspecific of the same sex and similar weight. To examine PD, we focused on PD associated characteristics of oxidative stress in the nigrostriatal pathway and behavioral impairments of motor (open field activity and ultrasonic vocalizations) and cognitive (spatial memory) function during puberty (PND 40-45) and young adulthood (PND 60-65). Results: Gestational CIH had no effect on the duration of gestation, litter size, and neonatal weight at birth. Gestational CIH did not impact circulating oxidative stress, regardless of sex or age of progeny. Offspring gross motor function (open field activity) and cognitive (Morris Water maze) function were unaffected by gestational CIH. In contrast, gestational CIH impaired ultrasonic vocalizations in adult male progeny. Gestational CIH increased the latency to vocalize and decreased the loudness of the vocalizations in adult male progeny. Conclusion: Exposure to CIH during gestation resulted in nigrostriatal impairment in adult male progeny, as evidenced by impaired ultrasonic vocalizations that require a functional nigrostriatal pathway. In utero hypoxia during late gestation may increase the risk for PD in males.
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Pixley, John S., Jessica L. Skopal-Chase, Alireza Torabi, Mihai C. Cenariu, Anupama Bhat, David S. Thain, Nicole M. Frederick, Daria M. Groza, and Esmail D. Zanjani. "Immune Ontogeny and Engraftment Receptivity in the Sheep Fetus." Blood 112, no. 11 (November 16, 2008): 3493. http://dx.doi.org/10.1182/blood.v112.11.3493.3493.
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Abstract The therapeutic application of in utero hematopoietic stem cell (HSC) transplantation (IUHSCT) is theoretically attractive for definitive treatment of congenital disease states. Investigating this technique in sheep, we have previously shown long-term engraftment and expression of both allogeneic and xenogeneic donor cells without cytoablation and, under appropriate conditions, without GVHD. The theoretical basis for IUHSCT is the well-recognized immune receptivity of the fetus to engraftment of donor cells. Engraftment and long-term expression of donor human and allogeneic sheep HSC reliably occur in the fetal sheep model if the IUHSCT is performed prior to day 71 of gestation (term: 145 days), during the period of presumed immuno-naïveté. Investigations using alternate animals have also noted that gestational age at transplantation is critical to achieving long-term engraftment, presumably as a result of inducing durable immune tolerance to the donor. Despite this presumption, however, the biologic explanation for fetal receptivity to donor engraftment and subsequent long-term tolerance following transplantation early in gestation is not known. In the present studies, we investigated the role fetal immune ontogeny plays in the induction of tolerance following IUHSCT in sheep. To this end, we performed parallel experiments examining engraftment receptivity of fetal sheep to allogeneic and xenogeneic HSC and the appearance of immune phenotypes in fetal sheep lymphoid organs at varying gestational ages (days 39 to birth), attempting to draw correlations between the appearance/absence of specific immune cells and the ability to achieve durable engraftment and immune tolerance. Engraftment receptivity was determined 60 days post-transplantation at different time points in sheep fetal gestation, while immune phenotypes were determined by flow cytometry using commercially available antibodies to immune cell surface markers. Our results indicate that the fetus is largely non-receptive to engraftment of both allogeneic and xenogeneic donor HSC prior to day 52 gestation and possesses a peak in engraftment receptivity between days 64–71 of gestation, which rapidly declines thereafter. With respect to the developing fetal immune system, the period of peak engraftment receptivity was associated with the expression of CD45 on all cells in the thymus. Double-positive and single-positive CD4 and CD8 cells began appearing in the thymus just prior (day 45 of gestation) to the beginning of the engraftment window, while single-positive CD4 or CD8 cells did not begin appearing in peripheral organs until late in the engraftment period, suggesting deletional mechanisms predominate during this time. In a similar fashion, surface IgM (sIgM)+ cells in the thymus were the first to express CD45, commencing expression around day 45 of gestation, with a comparable delay in the appearance of IgM+/CD45+ cells in the peripheral blood and spleen until late in the engraftment window. These findings support a central role for the thymus in multilineage immune cell maturation during the period of fetal transplantation receptivity. Further, they suggest that fetal engraftment receptivity/long-term engraftment and expression following IUHSCT is due to gestational age-dependent deletional tolerance. Further, our findings suggest that IUHSCT in humans may be more successful if performed during the comparable period in human gestation.
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Schierding, William, Jisha Antony, Ville Karhunen, Marja Vääräsmäki, Steve Franks, Paul Elliott, Eero Kajantie, et al. "GWAS on prolonged gestation (post-term birth): analysis of successive Finnish birth cohorts." Journal of Medical Genetics 55, no. 1 (October 10, 2017): 55–63. http://dx.doi.org/10.1136/jmedgenet-2017-104880.
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BackgroundGestation is a crucial timepoint in human development. Deviation from a term gestational age correlates with both acute and long-term adverse health effects for the child. Both being born preterm and post-term, that is, having short and long gestational ages, are heritable and influenced by the prenatal and perinatal environment. Despite the obvious heritable component, specific genetic influences underlying differences in gestational age are poorly understood.MethodsWe investigated the genetic architecture of gestational age in 9141 individuals, including 1167 born post-term, across two Northern Finland cohorts born in 1966 or 1986.ResultsHere we identify one globally significant intronic genetic variant within the ADAMTS13 gene that is associated with prolonged gestation (p=4.85×10−8). Additional variants that reached suggestive levels of significance were identified within introns at the ARGHAP42 and TKT genes, and in the upstream (5’) intergenic regions of the B3GALT5 and SSBP2 genes. The variants near the ADAMTS13, B3GALT5, SSBP2 and TKT loci are linked to alterations in gene expression levels (cis-eQTLs). Luciferase assays confirmed the allele specific enhancer activity for the BGALT5 and TKT loci.ConclusionsOur findings provide the first evidence of a specific genetic influence associated with prolonged gestation. This study forms a foundation for a better understanding of the genetic and long-term health risks faced by induced and post-term individuals. The long-term risks for induced individuals who have a previously overlooked post-term potential may be a major issue for current health providers.
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Hart, Peter, and Patrick Maume. "The Long Gestation: Irish Nationalist Life 1891-1918." American Historical Review 105, no. 5 (December 2000): 1809. http://dx.doi.org/10.2307/2652169.
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Mostyn, A., S. Pearce, H. Budge, M. Elmes, AJ Forhead, AL Fowden, T. Stephenson, and ME Symonds. "Influence of cortisol on adipose tissue development in the fetal sheep during late gestation." Journal of Endocrinology 176, no. 1 (January 1, 2003): 23–30. http://dx.doi.org/10.1677/joe.0.1760023.
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The present study examined the extent to which the late gestation rise in fetal plasma cortisol influenced adipose tIssue development in the fetus. The effect of cortisol on the abundance of adipose tIssue mitochondrial proteins on both the inner (i.e. uncoupling protein (UCP)1) and outer (i.e. voltage-dependent anion channel (VDAC)) mitochondrial membrane, together with the long and short forms of the prolactin receptor (PRLR) protein and leptin mRNA was determined. Perirenal adipose tIssue was sampled from ovine fetuses to which (i) cortisol (2-3 mg/day for 5 days) or saline was infused up to 127-130 days of gestation, and (ii) adrenalectomised and intact controls at between 142 and 145 days of gestation (term=148 days). UCP1 protein abundance was significantly lower in adrenalectomised fetuses compared with age-matched controls, and UCP1 was increased by cortisol infusion and with gestational age. Adrenalectomy reduced the concentration of the long form of PRLR, although this effect was only significant for the highest molecular weight isoform. In contrast, neither the short form of PRLR, VDAC protein abundance or leptin mRNA expression was significantly affected by gestational age or cortisol status. Fetal plasma triiodothyronine concentrations were increased by cortisol and with gestational age, an affect abolished by adrenalectomy. When all treatment groups were combined, both plasma cortisol and triiodothyronine concentrations were positively correlated with UCP1 protein abundance. In conclusion, an intact adrenal is necessary for the late gestation rise in UCP1 protein abundance but cortisol does not appear to have a major stimulatory role in promoting leptin expression in fetal adipose tIssue. It remains to be established whether effects on UCP1 protein are directly regulated by cortisol alone or mediated by other anabolic fetal hormones such as triiodothyronine.
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Mabry, Steve, E. Nicole Wilson, Nataliya Rybalchenko, Rachel Engelland, Oluwadarasimi Fadeyibi, Oluwatobiloba Osikoya, Spencer Cushen, Styliani Goulopoulou, and Rebecca Lynn Cunningham. "Long-Term Effects of Late Gestation in Utero Hypoxic Stress on Mood Disorders: Sex and Age Differences." Journal of the Endocrine Society 5, Supplement_1 (May 1, 2021): A751. http://dx.doi.org/10.1210/jendso/bvab048.1527.
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Abstract Introduction: In utero insults have been linked with increased fear and anxiety in progeny. In utero hypoxic stress is associated with a multitude of gestational complications such as pregnancy-associated hypertensive disorders and intrauterine growth restriction. Maternal hypertension during pregnancy is also associated with increased mood and anxiety disorders in progeny. However, it is unknown if these associations are due to in utero hypoxic stress. We hypothesized that exposure to late gestational hypoxia will have a long-term impact on anxiety in progeny. Methods: Timed pregnant female Long-Evans rats were exposed to five days (gestational days: 15-20) of chronic intermittent hypoxia (CIH) or room air (normoxia - 21% O2) for 8 hours during their sleep phase. Each CIH cycle was 6 min of 3 min hypoxia (10% O2) and 3 min normoxia (21% O2) for a total of 10 CIH cycles/hour. At weaning (PND 28), progeny was pair-housed with a conspecific of same sex and similar weight. To examine mood and anxiety disorders, we quantified anxiety-related behaviors (time spent in the center of open field arena, marble burying test, social and anti-social behaviors with conspecifics) along with quantifying food intake and circulating sex hormone levels during puberty (postnatal day, PND 40-45) and young adulthood (PND 60-65) in male and female progeny. Results: Gestational CIH did not impact circulating sex hormones or food intake, regardless of sex or age of progeny. However, gestational CIH increased anxiety related behaviors in pubertal females. These effects of gestational CIH on anxiety in pubertal females were not maintained, as these behaviors resolved in young adulthood. Gestational CIH did not impact male progeny, regardless of age. Conclusion: Exposure to CIH during gestation resulted in increased anxiety related behaviors in pubertal female progeny. In utero hypoxia during late gestation may temporarily increase the risk for mood and anxiety disorders in pubertal females.
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Gutvirtz, Gil, Tamar Wainstock, Eyal Sheiner, and Gali Pariente. "Prematurity and Long-Term Respiratory Morbidity—What Is the Critical Gestational Age Threshold?" Journal of Clinical Medicine 11, no. 3 (January 30, 2022): 751. http://dx.doi.org/10.3390/jcm11030751.
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Respiratory morbidity is a hallmark complication of prematurity. Children born preterm are exposed to both short- and long-term respiratory morbidity. This study aimed to investigate whether a critical gestational age threshold exists for significant long-term respiratory morbidity. A 23-year, population-based cohort analysis was performed comparing singleton deliveries at a single tertiary medical center. A comparison of four gestational age groups was performed according to the WHO classification: term (≥37.0 weeks, reference group), moderate to late preterm (32.0–36.6 weeks), very preterm (28.0–31.6 weeks) and extremely preterm (24.0–27.6 weeks). Hospitalizations of the offspring up to the age of 18 years involving respiratory morbidities were evaluated. A Kaplan–Meier survival curve was used to compare cumulative hospitalization incidence between the groups. A Cox proportional hazards model was used to control for confounders and time to event. Overall, 220,563 singleton deliveries were included: 93.6% term deliveries, 6% moderate to late preterm, 0.4% very preterm and 0.1% extremely preterm. Hospitalizations involving respiratory morbidity were significantly higher in children born preterm (12.7% in extremely preterm children, 11.7% in very preterm, 7.0% in late preterm vs. 4.7% in term, p < 0.001). The Kaplan–Meier survival curve demonstrated a significantly higher cumulative incidence of respiratory-related hospitalizations in the preterm groups (log-rank, p < 0.001). In the Cox regression model, delivery before 32 weeks had twice the risk of long-term respiratory morbidity. Searching for a specific gestational age threshold, the slope for hospitalization rate was attenuated beyond 30 weeks’ gestation. In our population, it seems that 30 weeks’ gestation may be the critical threshold for long-term respiratory morbidity of the offspring, as the risk for long-term respiratory-related hospitalization seems to be attenuated beyond this point until term.
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Johnson, Samantha, and Neil Marlow. "Early and long-term outcome of infants born extremely preterm." Archives of Disease in Childhood 102, no. 1 (August 10, 2016): 97–102. http://dx.doi.org/10.1136/archdischild-2015-309581.
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There is no question that birth at extremely low gestational ages presents a significant threat to an infant's survival, health and development. Growing evidence suggests that gestational age may be conceptualised as a continuum in which births before 28 weeks of gestation (extremely preterm: EP) represent the severe end of a spectrum of health and developmental adversity. Although comprising just 1%–2% of all births, EP deliveries pose the greatest challenge to neonatal medicine and to health, education and social services for the provision of ongoing support for survivors with additional needs. Studying the outcomes of these infants remains critical for evaluating and enhancing clinical care, planning long-term support and for advancing our understanding of the life-course consequences of immaturity at birth. Here we review literature relating to early and long-term neurodevelopmental, cognitive, behavioural and educational outcomes following EP birth focusing on key themes and considering implications for intervention.
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Braunstein, Glenn D. "The Long Gestation of the Modern Home Pregnancy Test." Clinical Chemistry 60, no. 1 (January 1, 2014): 18–21. http://dx.doi.org/10.1373/clinchem.2013.202655.
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Poon, Woei Bing, Selina KY Ho, and Cheo Lian Yeo. "Short- and Long-Term Outcomes at 2, 5 and 8 Years Old for Neonates at Borderline Viability—An 11-Year Experience." Annals of the Academy of Medicine, Singapore 42, no. 1 (January 15, 2013): 7–17. http://dx.doi.org/10.47102/annals-acadmedsg.v42n1p7.
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Introduction: Neurodevelopmental outcome of borderline viability neonates have lagged behind improvement in survival figures. Accurate figures based on local outcome allow us to better counsel parents and to prognosticate with greater accuracy on both short- and long-term outcomes. Materials and Methods: A retrospective cohort study of 101 consecutively born neonates, born from 21 to 26 weeks gestation over an 11-year period from 1 January 1994 to 31 December 2005 was conducted. Long-term outcomes were assessed at 2, 5 and 8 years of age in terms of mental developmental index (MDI) or intelligence quotient (IQ) scores, hearing and visual impairments, handicaps and impairments, school placement and interventions required. Results: Survival rates were 20.0%, 60.9%, 70.4% and 73.2% for neonates born at 21 to 23, 24, 25 and 26 weeks gestation respectively. Factors that predicted increased mortality included higher alveolar-arterial oxygen difference (AaDO2) with odds ratio (OR) 1.005 and lower birth weight OR 0.993. Rates of severe retinopathy of prematurity (ROP) (stage 3 or worse) were 100%, 57.1%, 42.1% and 26.7% for 21 to 23, 24, 25 and 26 weeks gestation respectively. Rates of bronchopulmonary dysplasia (BPD) were 100.0%, 57.1%, 63.2% and 60.0% respectively. Rates of severe intraventricular haemorrhage (IVH) were 0%, 7.1%, 5.3% and 10.0% respectively. Moderate to severe disability rates at 2 years old were 100%, 44.4%, 33.3% and 30.4% respectively. At 5 years old, moderate to severe disability rates were 16.7%, 22.2% and 14.3% respectively for those born at 24, 25 and 26 weeks gestation. Interpretation at 8 years was limited by small numbers. Conclusion: Our results indicated that local figures for mortality and morbidity remained high at the limits of viability, although they were comparable to outcomes for large scale studies in advanced countries. Key words: Borderline viability, Extremely low birth weight (ELBW), Extremely low gestational age, Neurodevelopmental outcomes, Very low birth weight (VLBW)
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Jin, Ju Hyun, Shin Won Yoon, Jungeun Song, Seong Woo Kim, and Hee Jung Chung. "Long-term cognitive, executive, and behavioral outcomes of moderate and late preterm at school age." Clinical and Experimental Pediatrics 63, no. 6 (June 15, 2020): 219–25. http://dx.doi.org/10.3345/kjp.2019.00647.
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Background: There is increasing concern that moderate preterm (32–33 weeks’ gestation) and late preterm (34–36 weeks’ gestation) birth may be associated with minor neurodevelopmental problems affecting poor school performance.Purpose: We explored the cognitive function, cognitive visual function, executive function, and behavioral problems at schoolage in moderate to late preterm infants.Methods: Children aged 7–10 years who were born at 32+0 to 36+6 weeks of gestation and admitted to the neonatal intensive care unit from August 2006 to July 2011 at the National Health Insurance Service Ilsan Hospital were included. We excluded children with severe neurologic impairments, congenital malformations, or chromosomal abnormalities. Neuropsychological assessments consisted of 5 neuropsychological tests and 3 questionnaires.Results: A total of 37 children (mean age, 9.1±1.2 years) participated. The mean gestational age at birth was 34.6±7.5 weeks, while the mean birth weight was 2,229.2±472.8 g. The mean full-scale intelligence quotient was 92.89±11.90; 24.3% scored between 70 and 85 (borderline intelligence functioning). An abnormal score was noted for at least one of the variables on the attention deficit hyperactivity disorder diagnostic system for 65% of the children. Scores below borderline function for executive quotient and memory quotient were 32.4% and 24.3%, respectively. Borderline or clinically relevant internalizing problems were noted in 13.5% on the Child Behavior Check List. There were no significant associations between perinatal factors or socioeconomic status and cognitive, visual perception, executive function, or behavior outcomes.Conclusion: Moderate to late preterm infants are at risk of developing borderline intelligence functioning and attention problems at early school age. Cognitive and executive functions that are important for academic performance must be carefully monitored and continuously followed up in moderate to late preterm infants.
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Kousta, Eleni, Adamantia Kontogeorgi, Stephen Robinson, and Desmond G. Johnston. "Long-Term Metabolic Consequences in Patients with a History of Gestational Diabetes." Current Pharmaceutical Design 26, no. 43 (December 22, 2020): 5564–72. http://dx.doi.org/10.2174/1381612826666201106092423.
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Gestational diabetes mellitus is a common metabolic complication of pregnancy. Universal guidelines on gestational diabetes have been impeded by the long-term controversies on its definition and screening strategies. The prevalence of gestational diabetes is rising all over the world, is significantly influenced by ethnicity and its rise is mainly attributed to increasing maternal obesity and age. Gestational diabetes mellitus has important long-term implications, including gestational diabetes recurrence, increased risk for developing type 2 diabetes, metabolic syndrome and cardiovascular disease for the mother. Gestational diabetes mellitus may be viewed as a chronic metabolic disorder that is identified in women during gestation and may provide a unique opportunity for the early identification and primary prevention of type 2 diabetes mellitus and cardiovascular disease in these women. In this mini-review, the evolution of screening tests for gestational diabetes and guidelines are briefly described and metabolic and cardiovascular long-term consequences of women with a history of gestational diabetes are summarized. A summary of our own St. Mary’s Hospital-UK Research series on long-term metabolic consequences of 368 women with a history of gestational diabetes of 3 different ethnic groups and 482 control women is also included. We found that approximately 2 years following delivery, 37% of women with a history of gestational diabetes had abnormal glucose concentrations, but, most importantly, even those who were normoglycaemic, postpartum displayed metabolic abnormalities on detailed testing. Future research needs to focus on the prevention of gestational diabetes long-term complications, but also in identification of pre-pregnancy predictors and risk reduction before conception.
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Brasil, Flavia Bittencourt, Luiz Henrique Amarante, and Marcos Roberto de Oliveira. "Maternal folic acid consumption during gestation and its long-term effects on offspring's liver: a systematic review." Revista Brasileira de Saúde Materno Infantil 17, no. 1 (March 2017): 7–15. http://dx.doi.org/10.1590/1806-93042017000100002.
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Abstract Objectives: describing the effects of maternal supplementation with folic acid (FA) exclusively during gestation on offspring's liver at later stages in life. Supplementation with FA during gestation has been recommended by the medical society worldwide. The liver has a central role on the substances of metabolism and homeostasis and some studies have shown that a high intake of FA at other periods in life may cause hepatic damage. Methods: a systematic review through which the following databases were consulted: Medline, through platforms of Pubmed, Lilacs and Scielo. The research was performed by keywords such as: "Folic acid", "Gestation", "Rat", "Offspring" and "Liver". Articles which evaluate the effect of FA consumption during both gestation and lactation were excluded. Results: FA consumption avoids disorders on expression of peroxisome proliferator-activated receptor alpha (PPARα) and glucocorticoid receptor (GccR), its lack did not change enzyme activity of the male offspring's liver in adulthood. Supplementation with FA during gestation did not change iron hepatic levels or lipid composition, but had an antioxidant effect on it. Conclusions: supplementation with FA at recommended doses did not cause toxic effects and is very likely to avoid deleterious effects in the liver of the offspring regarding the epigenetic level.
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Mendez, Natalia, Diego Halabi, Carlos Spichiger, Esteban R. Salazar, Karina Vergara, Pamela Alonso-Vasquez, Pamela Carmona, et al. "Gestational Chronodisruption Impairs Circadian Physiology in Rat Male Offspring, Increasing the Risk of Chronic Disease." Endocrinology 157, no. 12 (November 1, 2016): 4654–68. http://dx.doi.org/10.1210/en.2016-1282.
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Chronic exposure to light at night, as in shift work, alters biological clocks (chronodisruption), negatively impacting pregnancy outcome in humans. Actually the interaction of maternal and fetal circadian systems could be a key factor determining a fitting health in adults. We propose that chronic photoperiod shift (CPS) during pregnancy alter maternal circadian rhythms and impair circadian physiology in the adult offspring, increasing health risks. Pregnant rats were exposed to normal photoperiod (12 h light, 12 h dark) or to CPS until 85% of gestation. The effects of gestational CPS were evaluated on the mother and adult offspring. In the mother we measured rhythms of heart rate, body temperature, and activity through gestation and daily rhythms of plasma variables (melatonin, corticosterone, aldosterone, and markers of renal function) at 18 days of gestation. In adult offspring, we measured rhythms of the clock gene expression in the suprachiasmatic nucleus (SCN), locomotor activity, body temperature, heart rate, blood pressure, plasma variables, glucose tolerance, and corticosterone response to ACTH. CPS altered all maternal circadian rhythms, lengthened gestation, and increased newborn weight. The adult CPS offspring presented normal rhythms of clock gene expression in the SCN, locomotor activity, and body temperature. However, the daily rhythm of plasma melatonin was absent, and corticosterone, aldosterone, renal markers, blood pressure, and heart rate rhythms were altered. Moreover, CPS offspring presented decreased glucose tolerance and an abnormal corticosterone response to ACTH. Altogether these data show that gestational CPS induced long-term effects on the offspring circadian system, wherein a normal SCN coexists with altered endocrine, cardiovascular, and metabolic function.
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Bernard, Jonathan Y., Hong Pan, Izzuddin M. Aris, Margarita Moreno-Betancur, Shu-E. Soh, Fabian Yap, Kok Hian Tan, et al. "Long-chain polyunsaturated fatty acids, gestation duration, and birth size: a Mendelian randomization study using fatty acid desaturase variants." American Journal of Clinical Nutrition 108, no. 1 (June 6, 2018): 92–100. http://dx.doi.org/10.1093/ajcn/nqy079.
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ABSTRACT Background In randomized trials, supplementation of n–3 (ω-3) long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy has resulted in increased size at birth, which is attributable to longer gestation. Objective We examined this finding by using a Mendelian randomization approach utilizing fatty acid desaturase (FADS) gene variants affecting LC-PUFA metabolism. Design As part of a tri-ethnic mother-offspring cohort in Singapore, 35 genetic variants in FADS1, FADS2, and FADS3 were genotyped in 898 mothers and 1103 offspring. Maternal plasma n–3 and n–6 PUFA concentrations at 26–28 wk of gestation were measured. Gestation duration was derived from an ultrasound dating scan in early pregnancy and from birth date. Birth length and weight were measured. Eight FADS variants were selected through a tagging-SNP approach and examined in association with PUFA concentrations, gestation duration among spontaneous labors, and birth size with the use of ethnicity-adjusted linear regressions and survival models that accounted for the competing risks of induced labor and prelabor cesarean delivery. Results Maternal FADS1 variant rs174546, tagging for 8 other variants located on FADS1 and FADS2, was strongly related to plasma n–6 but not n–3 LC-PUFA concentrations. Offspring and maternal FADS3 variants were associated with gestation duration among women who had spontaneous labor: each copy of rs174450 minor allele C was associated with a shorter gestation by 2.2 d (95% CI: 0.9, 3.4 d) and 1.9 d (0.7, 3.0 d) for maternal and offspring variants, respectively. In survival models, rs174450 minor allele homozygotes had reduced time to delivery after spontaneous labor compared with major allele homozygotes [HR (95% CI): 1.51 (1.18, 1.95) and 1.51 (1.20, 1.89) for mothers and offspring, respectively]. Conclusions With the use of a Mendelian randomization approach, we observed associations between FADS variants and gestation duration. This suggests a potential role of LC-PUFAs in gestation duration. This trial was registered at http://www.clinicaltrials.gov as NCT01174875.
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Ghnenis, Adel, Vasantha Padmanabhan, and Arpita Vyas. "Sexual dimorphism in testosterone programming of cardiomyocyte development in sheep." American Journal of Physiology-Heart and Circulatory Physiology 322, no. 4 (April 1, 2022): H607—H621. http://dx.doi.org/10.1152/ajpheart.00691.2021.
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The present study demonstrates sex-specific effects of gestational T excess between days 30 and 90 of gestation on the cardiac phenotype. Furthermore, the sex-specific programming is likely secondary to perturbation in both estrogen and insulin signaling pathways collectively. These findings are supportive of the role of androgen excess to serve as early biomarkers of CVD and could be critical in identifying therapeutic targets for LV hypertrophy and predict long-term CVD.
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Ibarra, Adriana, Begoña Vega-Guedes, Yeray Brito-Casillas, and Ana Wägner. "Diabetes in Pregnancy and MicroRNAs: Promises and Limitations in Their Clinical Application." Non-Coding RNA 4, no. 4 (November 12, 2018): 32. http://dx.doi.org/10.3390/ncrna4040032.
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Maternal diabetes is associated with an increased risk of complications for the mother and her offspring. The latter have an increased risk of foetal macrosomia, hypoglycaemia, respiratory distress syndrome, preterm delivery, malformations and mortality but also of life-long development of obesity and diabetes. Epigenetics have been proposed as an explanation for this long-term risk, and microRNAs (miRNAs) may play a role, both in short- and long-term outcomes. Gestation is associated with increasing maternal insulin resistance, as well as β-cell expansion, to account for the increased insulin needs and studies performed in pregnant rats support a role of miRNAs in this expansion. Furthermore, several miRNAs are involved in pancreatic embryonic development. On the other hand, maternal diabetes is associated with changes in miRNA both in maternal and in foetal tissues. This review aims to summarise the existing knowledge on miRNAs in gestational and pre-gestational diabetes, both as diagnostic biomarkers and as mechanistic players, in the development of gestational diabetes itself and also of short- and long-term complications for the mother and her offspring.
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Waterbury, John. "The Long Gestation and Brief Triumph of Import-Substituting Industrialization." World Development 27, no. 2 (February 1999): 323–41. http://dx.doi.org/10.1016/s0305-750x(98)00135-1.
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Gemmill, Alan W. "The long gestation of screening programmes for perinatal depressive disorders." Journal of Psychosomatic Research 77, no. 3 (September 2014): 242–43. http://dx.doi.org/10.1016/j.jpsychores.2014.06.017.
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Ben-Shlomo, Izhar, Moshe Ben ami, and Johnny S. Younis. "Does twin gestation really have long-term maternal cardiac sequelae?" American Journal of Obstetrics and Gynecology 214, no. 3 (March 2016): 414. http://dx.doi.org/10.1016/j.ajog.2015.11.011.
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Davidesko, Sharon, Tamar Wainstock, Eyal Sheiner, and Gali Pariente. "Long-Term Infectious Morbidity of Premature Infants: Is There a Critical Threshold?" Journal of Clinical Medicine 9, no. 9 (September 18, 2020): 3008. http://dx.doi.org/10.3390/jcm9093008.
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In this study, we sought to ascertain a relationship between gestational age at birth and infectious morbidity of the offspring via population-based cohort analysis comparing the long-term incidence of infectious morbidity in infants born preterm and stratified by extremity of prematurity (extreme preterm birth: 24 + 0–27 + 6, very preterm birth: 28 + 0–31 + 6, moderate to late preterm birth: 32 + 0−36 + 6 weeks of gestation, and term deliveries). Infectious morbidity included hospitalizations involving a predefined set of International Classification of Diseases 9 (ICD9) codes, as recorded in hospital records. A Kaplan–Meier survival curve compared cumulative incidence of infectious-related morbidity. A Cox proportional hazards model controlled for confounders and time to event. The study included 220,594 patients: 125 (0.1%) extreme preterm births, 784 (0.4%) very preterm births, 13,323 (6.0%) moderate to late preterm births, and 206,362 term deliveries. Offspring born preterm had significantly more infection-related hospitalizations (18.4%, 19.8%, 14.9%, and 11.0% for the aforementioned stratification, respectively, p < 0.001). Multivariate analysis found being born very or late to moderate preterm was independently associated with long-term infectious morbidity (adjusted hazard ratio (aHR) 1.5, 95% confidence interval (CI) 1.27–1.77 and aHR 1.23, 95% CI 1.17–1.3, respectively, p < 0.001). A comparable risk of long-term infectious morbidity was found in the two groups of premature births prior to 32 weeks gestation. In our population, a cutoff from 32 weeks and below demarks a significant increase in the risk of long-term infectious morbidity of the offspring.
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Bakketeig, Leiv S., and Per Magnus. "Small-for-Gestational-Age (SGA) Definitions and Associated Risks." International Journal of Technology Assessment in Health Care 8, S1 (January 1992): 139–46. http://dx.doi.org/10.1017/s0266462300013039.
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AbstractSamples and methods vary in constructing birthweight charts. Introduction of ultrasound dating affects the distribution of gestation, increases the proportion of preterm births, and reduces postterm and small-for-gestational-age (SGA) births. The need for standardized charts is emphasized. Preferably such charts ought to be sex- and parity-specific, also taking into account the mother's previous pregnancy outcome in terms of birthweight. The risks associated with being bom SGA involve various morbidity as well as short- and long-term survival.
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Roque-Jiménez, José Alejandro, Milca Rosa-Velázquez, Juan Manuel Pinos-Rodríguez, Jorge Genaro Vicente-Martínez, Guillermo Mendoza-Cervantes, Argel Flores-Primo, Héctor Aarón Lee-Rangel, and Alejandro E. Relling. "Role of Long Chain Fatty Acids in Developmental Programming in Ruminants." Animals 11, no. 3 (March 10, 2021): 762. http://dx.doi.org/10.3390/ani11030762.
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Nutrition plays a critical role in developmental programs. These effects can be during gametogenesis, gestation, or early life. Omega-3 polyunsaturated fatty acids (PUFA) are essential for normal physiological functioning and for the health of humans and all domestic species. Recent studies have demonstrated the importance of n-3 PUFA in ruminant diets during gestation and its effects on pre-and postnatal offspring growth and health indices. In addition, different types of fatty acids have different metabolic functions, which affects the developmental program differently depending on when they are supplemented. This review provides a broad perspective of the effect of fatty acid supplementation on the developmental program in ruminants, highlighting the areas of a developmental program that are better known and the areas that more research may be needed.
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Nikolayenkov, Igor P., Tatyana U. Kuzminykh, Marina A. Tarasova, and Darya S. Seryogina. "Features of the course of pregnancy in women with polycystic ovary syndrome." Journal of obstetrics and women's diseases 69, no. 5 (December 23, 2020): 105–12. http://dx.doi.org/10.17816/jowd695105-112.
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Polycystic ovary syndrome is one of the most common pathologies in the practice of an obstetrician-gynecologist. Overcoming infertility characteristic of this syndrome is an important problem of endocrinology, gynecology, and reproductive medicine. Innovative therapeutic and surgical methods of treatment can correct hormonal and metabolic disorders, induce ovulation and achieve a long-awaited pregnancy. Early gestation periods in patients with polycystic ovary syndrome often occur with miscarriage, and the risks of developing gestational diabetes mellitus, cervical insufficiency, gestational arterial hypertension, preeclampsia, and placental insufficiency increase. We have analyzed modern ideas about the effect of various pathogenetic links of polycystic ovary syndrome on the course of pregnancy.
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Thomas, Sumesh, and Elizabeth Asztalos. "Gestation-Based Viability–Difficult Decisions with Far-Reaching Consequences." Children 8, no. 7 (July 13, 2021): 593. http://dx.doi.org/10.3390/children8070593.
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Most clinicians rely on outcome data based on completed weeks of gestational of fetal maturity for antenatal and postnatal counseling, especially for preterm infants born at the margins of viability. Contemporary estimation of gestational maturity, based on ultrasounds, relies on the use of first-trimester scans, which offer an accuracy of ±3–7 days, and depend on the timing of the scans and the measurements used in the calculations. Most published literature on the outcomes of babies born prematurely have reported on short- and long-term outcomes based on completed gestational weeks of fetal maturity at birth. These outcome data change significantly from one week to the next, especially around the margin of gestational viability. With a change in approach solely from decisions based on survival, to disability-free survival and long-term functional outcomes, the complexity of the parental and care provider’s decision-making in the perinatal and postnatal period for babies born at less than 25 weeks gestation remains challenging. While sustaining life following birth at the margins of viability remains our priority—identifying and mitigating risks associated with extremely preterm birth begins in the perinatal period. The challenge of supporting the normal maturation of these babies postnatally has far-reaching consequences and depends on our ability to sustain life while optimizing growth, nutrition, and the repair of organs compromised by the consequences of preterm birth. This article aims to explore the ethical and medical complexities of contemporary decision-making in the perinatal and postnatal periods. We identify gaps in our current knowledge of this topic and suggest areas for future research, while offering a perspective for future collaborative decision-making and care for babies born at the margins of viability.
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Carmody, J. B., and J. R. Charlton. "Short-Term Gestation, Long-Term Risk: Prematurity and Chronic Kidney Disease." PEDIATRICS 131, no. 6 (May 13, 2013): 1168–79. http://dx.doi.org/10.1542/peds.2013-0009.
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Whitfield, Lisa. "The early gestation period and long returns to oestrus in cattle." Livestock 24, no. 3 (May 2, 2019): 118–21. http://dx.doi.org/10.12968/live.2019.24.3.118.
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The fertility of dairy cattle has declined over the last 30 years. As a push for higher milk production has taken place, consideration of the negative impact on fertility has not been sufficiently addressed. As a result, it has become even more important for veterinarians to have a good understanding of normal reproduction processes in cattle, so that every cow has the best opportunity to reproduce successfully. This article aims to explore the early gestation period in dairy cattle, and some of the mechanisms of prolonged returns to oestrus when pregnancy is not established.
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Song, Lin, Jianqun Yan, Nan Wang, Xiaojing Wei, Xiao Luo, Kai Meng, and Bo Sun. "Prenatal exercise reverses high-fat-diet-induced placental alterations and alters male fetal hypothalamus during late gestation in rats†." Biology of Reproduction 102, no. 3 (November 19, 2019): 705–16. http://dx.doi.org/10.1093/biolre/ioz213.
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Abstract Maternal high-fat (HF) diet negatively affects maternal metabolism and placental function. This study aimed to determine whether gestational exercise prevents the effect of HF diet on placental amino acid transporter expression and nutrient-sensing signaling and the fetal response. Pregnant Sprague-Dawley rats were either fed with a CHOW (13.5% fat) or HF (60% fat) diet during gestation and further divided into two subgroups: voluntary exercised and sedentary. Placentae were collected on gestational day (GD) 14 and GD20, and male placentae were used in this study. We found that gestational exercise ameliorated the detrimental effects of HF diet on dams’ adiposity, plasma leptin, and insulin concentrations. Maternal exercise did not influence fetoplacental growth but affected male fetal hypothalamic Leprb, Stat3, Insr, Agrp, and Pomc expressions on GD20. Maternal HF diet decreased placental labyrinth thickness and increased system A amino acid transporter SNAT2 expression, while these changes were normalized by exercise. The activation of placental mechanistic target of rapamycin complex 1/4E-BP1 and LepRb/STAT3 signaling might contribute to the increased placental SNAT2 expression in HF-fed dams, which were reversed by exercise on GD20. These data highlight that gestational exercise reverses HF-diet-induced placental alterations during late gestation without influencing fetal growth. However, maternal exercise altered fetal hypothalamic gene expression, which may affect long-term offspring health.
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Panaitescu, Anca Maria, Mihaela Roxana Popescu, Anca Marina Ciobanu, Nicolae Gica, and Brindusa Ana Cimpoca-Raptis. "Pregnancy Complications Can Foreshadow Future Disease—Long-Term Outcomes of a Complicated Pregnancy." Medicina 57, no. 12 (December 1, 2021): 1320. http://dx.doi.org/10.3390/medicina57121320.
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During gestation, the maternal body should increase its activity to fulfil the demands of the developing fetus as pregnancy progresses. Each maternal organ adapts in a unique manner and at a different time during pregnancy. In an organ or system that was already vulnerable before pregnancy, the burden of pregnancy can trigger overt clinical manifestations. After delivery, symptoms usually reside; however, in time, because of the age-related metabolic and pro-atherogenic changes, they reappear. Therefore, it is believed that pregnancy acts as a medical stress test for mothers. Pregnancy complications such as gestational hypertension, preeclampsia and gestational diabetes mellitus foreshadow cardiovascular disease and/or diabetes later in life. Affected women are encouraged to modify their lifestyle after birth by adjusting their diet and exercise habits. Blood pressure and plasmatic glucose level checking are recommended so that early therapeutic intervention can reduce long-term morbidity. Currently, the knowledge of the long-term consequences in women who have had pregnancy-related syndromes is still incomplete. A past obstetric history may, however, be useful in determining the risk of diseases later in life and allow timely intervention.
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Quiclet, Charline, Farida Siti, Hervé Dubouchaud, Guillaume Vial, Phanélie Berthon, Eric Fontaine, Cécile Batandier, and Karine Couturier. "Short-term and long-term effects of submaximal maternal exercise on offspring glucose homeostasis and pancreatic function." American Journal of Physiology-Endocrinology and Metabolism 311, no. 2 (August 1, 2016): E508—E518. http://dx.doi.org/10.1152/ajpendo.00126.2016.
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Only a few studies have explored the effects of maternal exercise during gestation on adult offspring metabolism. We set out to test whether maternal controlled submaximal exercise maintained troughout all gestational periods induces persistant metabolic changes in the offspring. We used a model of 15-wk-old nulliparous female Wistar rats that exercised (trained group) before and during gestation at a submaximal intensity or remained sedentary (control group). At weaning, male offspring from trained dams showed reduced basal glycemia (119.7 ± 2.4 vs. 130.5 ± 4.1 mg/dl, P < 0.05), pancreas relative weight (3.96 ± 0.18 vs. 4.54 ± 0.14 g/kg body wt, P < 0.05), and islet mean area (22,822 ± 4,036 vs. 44,669 ± 6,761 μm2, P < 0.05) compared with pups from control dams. Additionally, they had better insulin secretory capacity when stimulated by 2.8 mM glucose + 20 mM arginine compared with offspring from control dams (+96%, P < 0.05). At 7 mo of age, offspring from trained mothers displayed altered glucose tolerance (AUC = 15,285 ± 527 vs. 11,898 ± 988 mg·dl−1·120 min, P < 0.05) and decreased muscle insulin sensitivity estimated by the phosphorylated PKB/total PKB ratio (−32%, P < 0.05) and tended to have a reduced islet insulin secretory capacity compared with rats from control dams. These results suggest that submaximal maternal exercise modifies short-term male offspring pancreatic function and appears to have rather negative long-term consequences on sedentary adult offspring glucose handling.
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Thomas, G. B., and A. N. Brooks. "Pituitary and gonadal responses to the long-term pulsatile administration of gonadotrophin-releasing hormone in fetal fetal sheep." Journal of Endocrinology 153, no. 3 (June 1997): 385–91. http://dx.doi.org/10.1677/joe.0.1530385.
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Abstract The fetal hypothalamo–pituitary–gonadal axis reaches a peak in activity at mid-gestation and this is followed by a period of suppression which persists until the onset of puberty. The decline in gonadotrophic activity during late gestation is thought to reflect the maturation of central and peripheral feedback signals. In order to establish if sustained pituitary responsiveness is rate limiting to the reinstatement of reproductive function, we have examined the endocrine consequences of repeated pulsatile GnRH administration to male and fetal sheep during late gestation. Beginning on day 121 of gestation (term=145 days) chronically catheterized fetal sheep were given i.v. pulses of either 500 ng GnRH or saline every 2 h for 14 days. Pituitary and gonadal responses were assessed by measuring changes in plasma concentrations of LH, FSH, inhibin and testosterone (in male fetuses) in response to the first pulse of GnRH on day 1 and to the corresponding pulse on days 4, 7, 10 and 14. In response to the first pulse of GnRH there was an immediate release of LH, with the peak response being significantly (P<0·01) greater than on subsequent days. In male fetuses each pulse of LH was followed by a rise in plasma testosterone concentrations within 40–60 min. The amplitude of these testosterone responses increased significantly (P<0·01) after 9 days of treatment despite a decline in the plasma LH response. Basal FSH concentrations increased progressively (P<0·05) during pituitary stimulation with GnRH in both male and female fetuses. Immunoreactive inhibin concentrations were significantly (P<0·05) higher in males than in females, and there was a gradual increase throughout the experimental period irrespective of treatment. We observed no inverse correlation between inhibin and FSH concentrations. These data show that pulsatile administration of GnRH to fetal sheep during late gestation results in sustained re-activation of pituitary–gonadal function. The decline in fetal gonadotrophins, which is a characteristic feature of late gestation, is therefore likely to result from inadequate GnRH secretion from the fetal hypothalamus rather than an inhibition of pituitary function by peripheral feedback signals. Journal of Endocrinology (1997) 153, 385–391
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Barclay, Kathryn, Kanyada Koysombat, Radhika Padmagirison, and Felicity Kaplan. "Hypertriglyceridaemia in pregnancy: an unexpected diagnosis and its management." BMJ Case Reports 15, no. 8 (August 2022): e249000. http://dx.doi.org/10.1136/bcr-2022-249000.
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A woman in her 30s with gestational diabetes presented at 36 weeks’ gestation with reduced fetal movements and diminishing insulin requirements. In view of her gestation, she was induced and incidentally found to have profound hyponatraemia. Further biochemical investigations confirmed severe hypertriglyceridaemia and hypercholesterolaemia. This raises the possibility of secondary causes such as familial dysbetalipoproteinemia and polygenetic hypertriglyceridaemia. She was successfully managed by aggressive dietary modification. This involved a supervised fast followed by a fat-free diet. A fenofibrate was proposed but declined due to our patient’s wish to breastfeed. Management required considerable input from the multidisciplinary team. Treatment options to consider are aggressive dietary restriction of fat or the addition of a cholesterol-lowering medication, such as a fibrate. In refractory cases, a supervised fast may be required or, in cases where complications have arisen, apheresis. The patient and her baby made a good recovery with no long-lasting health implications.
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Fahey, A. J., J. M. Brameld, T. Parr, and P. J. Buttery. "The effect of maternal undernutrition on muscle fibre type in the newborn lamb." Proceedings of the British Society of Animal Science 2003 (2003): 60. http://dx.doi.org/10.1017/s1752756200012199.
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Muscle fibre type can influence meat quality (Maltinet al1997). Muscle fibre formation occurs during gestation and in the sheep the total number of fibres in a muscle is essentially fixed at birth. (Ashmereet al1972). Postnatal growth of muscle is entirely due to elongation and widening of the existing muscle fibres. Therefore the gestational period is important in the long-term growth potential of the animal. By investigating changes in muscle fibre type, the aim of this study was to test the general hypothesis that the poor carcass quality sometimes seen in ruminant animals may be due to poor nutrition at strategic time points during the animal’s development. As agricultural practices continue to become more extensive, variation in the nutrient supply to the animal is becoming more common. Therefore it is important to understand the effect of any changes in nutrient supply to the mother, during gestation on the subsequent muscle development of the fetus and ultimately the effects on meat quality.
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Schwaberger, Bernhard, Berndt Urlesberger, and Georg M. Schmölzer. "Delivery Room Care for Premature Infants Born after Less than 25 Weeks’ Gestation—A Narrative Review." Children 8, no. 10 (October 2, 2021): 882. http://dx.doi.org/10.3390/children8100882.
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Premature infants born after less than 25 weeks’ gestation are particularly vulnerable at birth and stabilization in the delivery room (DR) is challenging. After birth, infants born after <25 weeks’ gestation develop respiratory and hemodynamic instability due to their immature physiology and anatomy. Successful stabilization at birth has the potential to reduce morbidities and mortalities, while suboptimal DR care could increase long-term sequelae. This article reviews current neonatal resuscitation guidelines and addresses challenges during DR stabilization in extremely premature infants born after <25 weeks’ gestation at the threshold of viability.
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Mukhia, Rajeev, and Bhawani Prasad Powar. "The relationship between the thyroid gland and body at different gestational age of developing human foetuses." Asian Journal of Medical Sciences 9, no. 6 (October 29, 2018): 40–44. http://dx.doi.org/10.3126/ajms.v9i6.20868.
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Background: Thyroid gland is one of the organs of interest for researchers since a long time. Though, detailed study about adult thyroid gland is there in the literature but thyroid gland at different stages in the foetal period is far less available.Aims and Objective: To find out the morphological and morphometric features on the development of foetal thyroid gland in relation with different gestational weeks.Materials and Methods: The study was carried in the Department of Anatomy, Manipal College of Medical Sciences, Pokhara, Nepal, on 40 human foetuses of known gestational age. The midline dissection of the neck was done to expose the thyroid gland. The shape and measurements like length, breadth and thickness of both lobe of the gland were noted.Results: The mean values of all parameters by gestational age were calculated. In the present study, the weight of foetuses showed gradual increase from 10th week to 38th weeks of gestation. In the normally developing foetuses the thyroid gland dimension and its weight also increases with increase gestational age.Conclusion: There was no more difference between the dimension of right and left lobe of thyroid gland. The study provides morphological and morphometric knowledge on the development of foetal thyroid gland from 10th week to 38th weeks of gestation. The knowledge of thyroid gland weight and dimension and body weight in relation to the gestational age might be helpful to judge the thyroid structure in preterm babies.Asian Journal of Medical Sciences Vol.9(6) 2018 40-44
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Edwards, J. F., A. L. Lassala, and T. E. Spencer. "Staphylococcus-associated Abortions in Ewes with Long-term Central Venous Catheterization." Veterinary Pathology 45, no. 6 (November 2008): 881–88. http://dx.doi.org/10.1354/vp.45-6-881.
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Forty-two ewes had an intravenous catheter sewn in place in a prepared area over the jugular vein and beginning at 60 days of gestation received an infusion 3 times daily. The infusion consisted of sterile saline or sterile saline containing arginine. Twenty-six ewes in both control and treatment groups aborted between 81 days of gestation and term. Fetuses from 16 ewes that aborted were examined. Most were autolyzed or had early mummification. Macroscopic placentitis and noncollapsing lungs were noted. Large numbers of coagulase-positive Staphylococcus were isolated from fetal abomasal content, lungs, brains, or placentas. Histologically, suppurative placentitis with necrosis and pulmonary aspiration of meconium and amniotic debris often with suppurative bronchopneumonia were observed in abortuses. Four ewes euthanized and examined after abortion had suppurative endometritis. Three ewes had severe, chronic, jugular thrombophlebitis from which coagulase-positive Staphylococcus was isolated. The fourth ewe had mild phlebitis, and Staphylococcus aureus was isolated from both the catheter and the blood. Catheter-associated staphylococcal abortion was diagnosed.
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Monthé-Drèze, Carmen, Sarbattama Sen, Sylvie Hauguel-de Mouzon, and Patrick M. Catalano. "Effect of Omega-3 Supplementation in Pregnant Women with Obesity on Newborn Body Composition, Growth and Length of Gestation: A Randomized Controlled Pilot Study." Nutrients 13, no. 2 (February 9, 2021): 578. http://dx.doi.org/10.3390/nu13020578.
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Maternal obesity, a state of chronic low-grade metabolic inflammation, is a growing health burden associated with offspring adiposity, abnormal fetal growth and prematurity, which are all linked to adverse offspring cardiometabolic health. Higher intake of anti-inflammatory omega-3 (n-3) polyunsaturated fatty acids (PUFA) in pregnancy has been associated with lower adiposity, higher birthweight and longer gestation. However, the effects of n-3 supplementation specifically in pregnant women with overweight and obesity (OWOB) have not been explored. We conducted a pilot double-blind randomized controlled trial of 72 pregnant women with first trimester body mass index (BMI) ≥ 25 kg/m2 to explore preliminary efficacy of n-3 supplementation. Participants were randomized to daily DHA plus EPA (2 g/d) or placebo (wheat germ oil) from 10–16 weeks gestation to delivery. Neonatal body composition, fetal growth and length of gestation were assessed. For the 48 dyads with outcome data, median (IQR) maternal BMI was 30.2 (28.2, 35.4) kg/m2. In sex-adjusted analyses, n-3 supplementation was associated with higher neonatal fat-free mass (β: 218 g; 95% CI 49, 387) but not with % body fat or fat mass. Birthweight for gestational age z-score (−0.17 ± 0.67 vs. −0.61 ± 0.61 SD unit, p = 0.02) was higher, and gestation longer (40 (38.5, 40.1) vs. 39 (38, 39.4) weeks, p = 0.02), in the treatment vs. placebo group. Supplementation with n-3 PUFA in women with OWOB led to higher lean mass accrual at birth as well as improved fetal growth and longer gestation. Larger well-powered trials of n-3 PUFA supplementation specifically in pregnant women with OWOB should be conducted to confirm these findings and explore the long-term impact on offspring obesity and cardiometabolic health.
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Carvalho, Elisa B., Letícia P. Sanglard, Karolina B. Nascimento, Javier M. Meneses, Daniel R. Casagrande, Marcio Duarte, Mateus P. Gionbelli, and Nick Serão. "PSVII-2 Differentially expressed genes and their biological function in skeletal muscle of calves born from cows with or without protein supplementation during mid-gestation." Journal of Animal Science 98, Supplement_3 (November 2, 2020): 165–66. http://dx.doi.org/10.1093/jas/skaa054.293.
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Abstract Gestating cows have an increased nutrient demand to meet the needs of developing the fetus and the mid-gestation is a critical period for the fetal skeletal muscle development. The aim of this study was to evaluate the skeletal muscle transcriptome in the progeny as a function of the maternal protein nutrition during mid-gestation. Eleven Tabapuã cows and their male calves were used in this study. In the first third of gestation (0 to 100 days of gestation; dg), all cows were kept on pasture. From 100 to 200 dg, the control group (CTRL; 7 animals) received a basal diet achieving 5.5% crude protein (CP), whereas the supplemented group (SUPPL; 4 animals) received a basal diet plus protein supplementation (40% CP). After 200 dg, all animals received the same diet. Weaning was performed at 205 ± 7.5 days of age and animals were kept on pasture until reaching 240 days of age, when they were transferred to a feedlot. Muscle samples were collected at 260 days of age and RNA was extracted for RNA-seq analysis. Gene expression data was analyzed with a negative binomial model to identify (q-value ≤ 0.05) differentially expressed genes (DEG) between treatments. A total of 716 DEG were identified (289 DEG up-regulated and 427 down-regulated in SUPPL group; q-value ≤ 0.05). From the 10 most significant down-regulated DEG in the SUPPL group, two genes associated with apoptotic process were identified: MAPK8IP1 and GRINA, with log2 Fold-Changes (log2FC) of 1.04 and 0.49, respectively. From the 10 most significant up-regulated DEG in the SUPPL group, mTOR was identified, with log2FC=0.31. This is a well-known gene involved in muscle protein synthesis. In conclusion, maternal protein supplementation during mid-gestation affects the expression of genes related to energy metabolism and muscle development, which can lead to long-term impacts on production efficiency.
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Stubert, Johannes, Kathleen Gründler, Bernd Gerber, Dagmar-Ulrike Richter, and Max Dieterich. "Prediction of Spontaneous Preterm Birth in At-risk Women Using Thrombospondin 1 from Cervicovaginal Fluid: A Prospective Observational Study." Geburtshilfe und Frauenheilkunde 81, no. 09 (September 2021): 1055–64. http://dx.doi.org/10.1055/a-1486-7148.
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Abstract Introduction Thrombospondin 1, desmoplakin and stratifin are putative biomarkers for the prediction of preterm birth. This study aimed to validate the predictive capability of these biomarkers in patients at risk of preterm birth. Materials and Methods We included 109 women with symptoms of threatened spontaneous preterm birth between weeks 20 0/7 and 31 6/7 of gestation. Inclusion criteria were uterine contractions, cervical length of less than 25 mm, or a personal history of spontaneous preterm birth. Multiple gestations were also included. Samples of cervicovaginal fluid were taken before performing a digital examination and transvaginal ultrasound. Levels of cervicovaginal thrombospondin 1, desmoplakin and stratifin were quantified by enzyme-linked immunosorbent assays. The primary endpoint was spontaneous preterm birth before 34 + 0 weeks of gestation. Results Sixteen women (14.7%) delivered before 34 + 0 weeks. Median levels of thrombospondin 1 were higher in samples where birth occurred before 34 weeks vs. ≥ 34 weeks of gestation (4904 vs. 469 pg/mL, p < 0.001). Receiver operator characteristics analysis resulted in an area under the curve of 0.86 (p < 0.0001). At an optimal cut-off value of 2163 pg/mL, sensitivity, specificity, positive predictive value and negative predictive value were 0.94, 0.77, 0.42 and 0.99, respectively, with an adjusted odds ratio of 32.9 (95% CI: 3.1 – 345, p = 0.004). Multiple gestation, cervical length, and preterm labor had no impact on the results. Survival analysis revealed a predictive period of more than eight weeks. Levels of desmoplakin and stratifin did not differ between groups. Conclusion Thrombospondin 1 allowed long-term risk estimation of spontaneous preterm birth.
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Koletzko, Berthold, Elvira Larqué, and Hans Demmelmair. "Placental transfer of long-chain polyunsaturated fatty acids (LC-PUFA)." Journal of Perinatal Medicine 35, s1 (February 1, 2007): S5—S11. http://dx.doi.org/10.1515/jpm.2007.030.
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AbstractConsiderable evidence exists for marked beneficial effects of omega-3 long-chain polyunsaturated fatty acids (LC-PUFA) during pregnancy. The omega-3 LC-PUFA docosahexaenoic acid (DHA) is incorporated in large amounts in fetal brain and other tissues during the second half of pregnancy, and several studies have provided evidence for a link between early DHA status of the mother and visual and cognitive development of her child after birth. Moreover, the supplementation of omega-3 LC-PUFA during pregnancy increases slightly infant size at birth, and significantly reduces early preterm birth before 34 weeks of gestation by 31%. In our studies using stable isotope methodology in vivo, we demonstrated active and preferential materno-fetal transfer of DHA across the human placenta and found the expression of human placental fatty acid binding and transport proteins. From the correlation of DHA values with placental fatty acid transport protein 4 (FATP 4), we conclude that this protein is of key importance in mediating DHA transport across the human placenta. Given the great importance of placental DHA transport for infant outcome, further studies are needed to fully appreciate the effects and optimal strategies of omega-3 fatty acid interventions in pregnancy, dose response relationships, and the potential differences between subgroups of subjects such as women with gestational diabetes or other gestational pathology. Such studies should contribute to optimize substrate intake during pregnancy and lactation that may improve pregnancy outcome as well as fetal growth and development.
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Adachi, Keiichi, Hikaru Umezaki, Kanchan M. Kaushal, and Charles A. Ducsay. "Long-term hypoxia alters ovine fetal endocrine and physiological responses to hypotension." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 287, no. 1 (July 2004): R209—R217. http://dx.doi.org/10.1152/ajpregu.00701.2003.
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Exposure to long-term hypoxia (LTH) results in altered cortisol responses in the ovine fetus. The present study was designed to test the hypothesis that LTH alters adrenal responsiveness to fetal hypotension. Pregnant ewes were maintained at high altitude (3,820 meters) from day 30 of gestation. Normoxic control and LTH fetuses were catheterized on day 132 of gestation. In the LTH group, maternal Po2 was maintained comparable to that observed at altitude (∼60 mmHg) by nitrogen infusion through a tracheal catheter. On day 137, fetuses received a 5-h saline infusion followed by infusion of sodium nitroprusside to reduce fetal arterial pressure by 30–35% for 10 min. The study was repeated on day 139 of gestation with a continuous cortisol infusion (10 μg/min). Hypothalamic and pituitary tissues were collected from additional fetuses for assessment of glucocorticoid receptors. During the saline infusion in response to hypotension, plasma ACTH increased over preinfusion mean values in both groups ( P < 0.05). Plasma cortisol concentrations increased in both groups concomitant with increased ACTH secretion. However, peak values in the LTH fetuses were significantly higher compared with controls ( P < 0.05). During the cortisol infusion, the ACTH response was eliminated in both groups, with ACTH levels significantly lower in the LTH group ( P < 0.05). Glucocorticoid receptor binding was not different between groups. These results demonstrate an enhanced cortisol response to hypotension in LTH fetuses that does not appear to be the result of an increase in negative feedback sensitivity of the hypothalamic-pituitary-adrenal axis.
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Garcia-Ispierto, Irina, Irene López-Helguera, Joan Tutusaus, Ramón Mur-Novales, and Fernando López-Gatius. "Effects of long-term vaccination against Coxiella burnetii on the fertility of high-producing dairy cows." Acta Veterinaria Hungarica 63, no. 2 (June 2015): 223–33. http://dx.doi.org/10.1556/004.2015.020.
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The impact of long-term vaccination against Coxiella burnetii on the fertility of cows was studied. Double vaccinations three weeks apart at the start of the third trimester of gestation in each of two consecutive pregnancies were applied. The final study population consisted of 410 cows after the first vaccination round. Based on the odds ratios, the likelihood of early fetal loss (pregnancy loss following a positive pregnancy diagnosis before Day 90 of gestation) was higher in control cows (OR = 1.42) than in vaccinated cows. The final study population consisted of 336 cows after the second round of vaccination. According to the odds ratios, vaccinated C. burnetii seronegative cows were less likely to be subfertile (> 3 AI) (OR = 0.4) compared to non-vaccinated seronegative animals, and the likelihood of early fetal loss was lower in vaccinated C. burnetii seropositive animals (OR = 0.3) compared to non-vaccinated seronegative cows. Seropositivity to C. burnetii was positively related to twin pregnancy after the two rounds of vaccination (OR = 2.1 and 3.5, respectively). These results indicate that two consecutive vaccination rounds against C. burnetii in advanced gestation reduce subfertility and early fetal loss in dairy cows.
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Mayanskaya, S. D., A. V. Ganeeva, and R. I. Gabidullina. "Blood pressure variability in pregnant women with risk factors of preeclempsia." Kazan medical journal 100, no. 3 (June 13, 2019): 426–33. http://dx.doi.org/10.17816/kmj2019-426.
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Aim. To assess the short-term and long-term variability of blood pressure in women, starting from early pregnancy, to predict the development of complications of gestation, including preeclempsia.
Methods. In 131 pregnant women, systolic blood pressure, diastolic blood pressure, as well as short-term (intra-visit) and long-term (inter-visit) blood pressure variability were assessed during the gestation period and 6 weeks after delivery. At the end of gestation period, depending on the identified complications, all study participants were divided into four groups: group 1 - control (healthy); group 2 - pregnant with preeclempsia; group 3 - with placental insufficiency; group 4 - with chronic arterial hypertension. In patients with placental insufficiency the indices of fetal growth retardation were also analyzed.
Results. In group 4, starting from the second trimester, higher values of short-term blood pressure variability were demonstrated, which increased as pregnancy progressed. Long-term blood pressure variability increased in groups 2 and 4, starting from the second trimester. In pregnant women with fetal growth retardation in the first trimester, blood pressure variability was higher than in pregnant controls and in the second trimester it was higher than in the group with the subsequent development of preeclempsia. Thus, during pregnancy complicated by preeclempsia or placental insufficiency with fetal growth retardation, high long-term blood pressure variability was observed. At the same time, the highest values were observed in the third trimester.
Conclusion. The assessment of long-term blood pressure variability from the early gestation seems to be an effective tool for detecting preclinical changes in the body of a pregnant woman, preceding the development of preeclempsia and fetal growth retardation, and in the presence of risk factors of preeclampsia allows narrowing the group of patients for target follow-up and prevention.